|
1
|
Roesel R, Strati F, Basso C, Epistolio S, Spina P, Djordjevic J, Sorrenti E, Villa M, Cianfarani A, Mongelli F, Galafassi J, Popeskou SG, Facciotti F, Caprera C, Melle F, Majno-Hurst PE, Franzetti-Pellanda A, De Dosso S, Bonfiglio F, Frattini M, Christoforidis D, Iezzi G. Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer. Oncoimmunology 2025; 14:2465015. [PMID: 39992705 PMCID: PMC11853554 DOI: 10.1080/2162402x.2025.2465015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 12/15/2024] [Accepted: 02/05/2025] [Indexed: 02/26/2025] Open
Abstract
Locally advanced rectal cancer (LARC) is treated with neoadjuvant chemo-radiotherapy (nCRT) followed by surgery. A minority of patients show complete response (CR) to nCRT and may avoid surgery and its functional consequences. Instead, most patients show non-complete response (non-CR) and may benefit from additional treatments to increase CR rates. Reliable predictive markers are lacking. Aim of this study was to identify novel signatures predicting nCRT responsiveness. We performed a combined analysis of tumor-associated microbiome and immune gene expression profiling of diagnostic biopsies from 70 patients undergoing nCRT followed by rectal resection, including 16 with CR and 54 with non-CR. Findings were validated by an independent cohort of 49 patients, including 7 with CR and 42 with non-CR. Intratumoral microbiota significantly differed between CR and non-CR groups at genus and species level. Colonization by bacterial species of Ruminococcus genera was consistently associated with CR, whereas abundance of Fusobacterium, Porhpyromonas, and Oscillibacter species predicted non-CR. Immune gene profiling revealed a panel of 59 differentially expressed genes and significant upregulation of IFN-gamma and -alpha response in patients with CR. Integrated microbiome and immune gene profiling analysis unraveled clustering of microbial taxa with each other and with immune cell-related genes and allowed the identification of a combined signature correctly identifying non-CRS in both cohorts. Thus, combined intratumoral microbiome-immune profiling improves the prediction of response to nCRT. Correct identification of unresponsive patients and of bacteria promoting responsiveness might lead to innovative therapeutic approaches based on gut microbiota pre-conditioning to increase nCRT effectiveness in LARC.
Collapse
Affiliation(s)
- Raffaello Roesel
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Francesco Strati
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
| | - Camilla Basso
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Samantha Epistolio
- Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland
| | - Paolo Spina
- Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland
| | - Julija Djordjevic
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Elisa Sorrenti
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Martina Villa
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Agnese Cianfarani
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Francesco Mongelli
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Jacopo Galafassi
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Sotirios G. Popeskou
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Federica Facciotti
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
| | - Cecilia Caprera
- Division of Hematopathology, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Federica Melle
- Division of Hematopathology, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Pietro Edoardo Majno-Hurst
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | | | - Sara De Dosso
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
- Department of Medical Oncology, Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Ferdinando Bonfiglio
- Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy
- CEINGE Advanced Biotechnology Franco Salvatore, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Milo Frattini
- Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland
| | - Dimitrios Christoforidis
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
- Department of Visceral Surgery, CHUV, University of Lausanne, Lausanne, Switzerland
| | - Giandomenica Iezzi
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| |
Collapse
|
|
2
|
Liu Q, Meng C, Cao S, Liu X, Tian Y, Li Z, Zhong H, Sun Y, Yu J, Zhou Y. Comparison of short- and long-term outcomes of robotic versus laparoscopic gastrectomy for locally advanced gastric cancer after neoadjuvant therapy: a high-volume center retrospective study with propensity score matching. Surg Endosc 2025; 39:2814-2827. [PMID: 40064692 DOI: 10.1007/s00464-025-11626-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 02/18/2025] [Indexed: 05/01/2025]
Abstract
BACKGROUND Although neoadjuvant therapy (NAT) for advanced gastric cancer (AGC) can benefit patient survival, few studies have compared the short- and long-term outcomes of robotic and laparoscopic gastrectomy for AGC after NAT. METHODS The clinical data of 321 AGC patients who received NATs and who underwent robotic gastrectomy (RG, n = 109) or laparoscopic gastrectomy (LG, n = 212) between May 2017 and September 2022 were collected and analyzed retrospectively at our center. After propensity score matching (PSM) for 1:1 matching to eliminate bias, both groups had 106 cases. Short-term clinical outcomes and long-term survival-related indicators were compared between the two groups of patients. RESULTS A total of 212 patients were included in the groups after matching. There were fewer overall complications (13.2% vs. 28.3%, P = 0.007) and surgical complications (8.5% vs. 17.9%, P = 0.043) in the RG group than in the LG group. Compared with the LG group, the RG group had more harvested overall lymph nodes (35.25 ± 4.99 vs. 31.45 ± 6.31, P < 0.001) and more suprapancreatic lymph nodes (13.12 ± 4.38 vs. 10.05 ± 4.13, P < 0.001). Patients in the RG group had significantly shorter surgery times (217.62 ± 47.49 vs. 267.25 ± 70.68, P < 0.001) and less blood loss (46.51 ± 27.02 vs. 70.75 ± 37.25, P < 0.001) than patients in the LG group. The RG group had significantly faster bowel function recovery, earlier liquid diet, and shorter hospital stay. Compared with LG, RG had a better 3-year RFS (75.5% vs. 62.3%, P = 0.017). CONCLUSION Compared with laparoscopic surgery, robotic surgery significantly increased the number of lymph node dissected, reduced intraoperative blood loss, and postoperative surgical complications rate. Although RG did not statistically improve 3-year overall survival, there was a significant improvement in RFS and could be an alternative surgical method for GC patients after NAC.
Collapse
Affiliation(s)
- Qi Liu
- Department of General Surgery, Affiliated Hospital of Qingdao University, 16# Jiangsu Road, Qingdao, 266000, Shandong Province, People's Republic of China
- Gastrointestinal Tumor Translational Medicine Research Institute of Qingdao University, Qingdao, Shandong Province, China
| | - Cheng Meng
- Department of General Surgery, Affiliated Hospital of Qingdao University, 16# Jiangsu Road, Qingdao, 266000, Shandong Province, People's Republic of China
- Gastrointestinal Tumor Translational Medicine Research Institute of Qingdao University, Qingdao, Shandong Province, China
| | - Shougen Cao
- Department of General Surgery, Affiliated Hospital of Qingdao University, 16# Jiangsu Road, Qingdao, 266000, Shandong Province, People's Republic of China
- Gastrointestinal Tumor Translational Medicine Research Institute of Qingdao University, Qingdao, Shandong Province, China
| | - Xiaodong Liu
- Department of General Surgery, Affiliated Hospital of Qingdao University, 16# Jiangsu Road, Qingdao, 266000, Shandong Province, People's Republic of China
- Gastrointestinal Tumor Translational Medicine Research Institute of Qingdao University, Qingdao, Shandong Province, China
| | - Yulong Tian
- Department of General Surgery, Affiliated Hospital of Qingdao University, 16# Jiangsu Road, Qingdao, 266000, Shandong Province, People's Republic of China
- Gastrointestinal Tumor Translational Medicine Research Institute of Qingdao University, Qingdao, Shandong Province, China
| | - Zequn Li
- Department of General Surgery, Affiliated Hospital of Qingdao University, 16# Jiangsu Road, Qingdao, 266000, Shandong Province, People's Republic of China
- Gastrointestinal Tumor Translational Medicine Research Institute of Qingdao University, Qingdao, Shandong Province, China
| | - Hao Zhong
- Department of General Surgery, Affiliated Hospital of Qingdao University, 16# Jiangsu Road, Qingdao, 266000, Shandong Province, People's Republic of China
- Gastrointestinal Tumor Translational Medicine Research Institute of Qingdao University, Qingdao, Shandong Province, China
| | - Yuqi Sun
- Department of General Surgery, Affiliated Hospital of Qingdao University, 16# Jiangsu Road, Qingdao, 266000, Shandong Province, People's Republic of China
- Gastrointestinal Tumor Translational Medicine Research Institute of Qingdao University, Qingdao, Shandong Province, China
| | - Junjian Yu
- Department of General Surgery, Affiliated Hospital of Qingdao University, 16# Jiangsu Road, Qingdao, 266000, Shandong Province, People's Republic of China
- Gastrointestinal Tumor Translational Medicine Research Institute of Qingdao University, Qingdao, Shandong Province, China
| | - Yanbing Zhou
- Department of General Surgery, Affiliated Hospital of Qingdao University, 16# Jiangsu Road, Qingdao, 266000, Shandong Province, People's Republic of China.
- Gastrointestinal Tumor Translational Medicine Research Institute of Qingdao University, Qingdao, Shandong Province, China.
| |
Collapse
|
|
3
|
Serra F, Valerio F, Pedrazzoli P, Viganò J, Caccialanza R, Cicognini D, Pagani A, Corallo S. Real-life effectiveness of FLOT in resectable gastric cancer: existing challenges. Drugs Context 2025; 14:2024-10-7. [PMID: 40017727 PMCID: PMC11867168 DOI: 10.7573/dic.2024-10-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 12/27/2024] [Indexed: 03/01/2025] Open
Abstract
Background Gastric cancer has a high mortality rate. Therapeutic management must be multidisciplinary to offer the patient the best, personalized strategy. Patients and methods We performed an observational study to evaluate the pathological response, survival and nutritional status in patients with resectable gastric cancer and candidates for perioperative chemotherapy with the fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) regimen versus other regimens. The primary endpoints were pathological response rate, care continuity rate and survival outcomes. A total of 96 patients attending the Hospital "Policlinico San Matteo" in Pavia (Italy) between January 2012 and August 2022 were selected for the study. Results Regarding pathological response rates, the best rate (TRG-0) was recorded in the FLOT group with a percentage of 6.2% compared with 4.7% in the NO-FLOT arm (p=0.052). The highest failure rate to complete the post-operative phase was 75% in the NO-FLOT group and only 25% in the FLOT group (p=0.007). Survival outcomes were better in the FLOT group with a median disease-free survival of 30 versus 22.2 months (p=0.586). Conclusions Despite the limitations, the results obtained were consistent with the medical literature and confirmed the effectiveness of the FLOT chemotherapy in real life. Nevertheless, some questions remain: the application in elderly patients, the addition of immunotherapy in patients with microsatellite instability or with high PD-L1 levels, comparison with chemoradiotherapy in junctional cancers and real cure rates. The FLOT regimen has revolutionized the treatment of resectable gastric cancer, but caution is needed before considering it an absolute standard of care.
Collapse
Affiliation(s)
- Francesco Serra
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Federica Valerio
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Paolo Pedrazzoli
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Jacopo Viganò
- General Surgery Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Riccardo Caccialanza
- Dietetics and Clinical Nutrition Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Daniela Cicognini
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Anna Pagani
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Salvatore Corallo
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| |
Collapse
|
|
4
|
Tinsley N, O'Dwyer ST, Nagaraju R, Chakrabarty B, Braun M, Mullamitha S, Kamposioras K, Marti Marti FE, Saunders M, Clouston H, Selvasekar C, Wild J, Wilson M, Renehan A, Aziz O, Barriuso J. Preoperative chemotherapy response and survival in patients with colorectal cancer peritoneal metastases. J Surg Oncol 2024; 130:1422-1432. [PMID: 39011877 PMCID: PMC11826003 DOI: 10.1002/jso.27776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 06/26/2024] [Accepted: 07/01/2024] [Indexed: 07/17/2024]
Abstract
Treatment guidelines provided by PRODIGE-7 recommend perioperative systemic chemotherapy before cytoreductive surgery (CRS) for colorectal cancer peritoneal metastases (CRPM). Toxicity with multimodal treatment needs to be better defined. Chemotherapy response and impact on survival have not been reported. We assessed CRPM patients who received systemic oxaliplatin/irinotecan before CRS (preoperative) with Mitomycin C (35 mg/m2, 90 min) or Oxaliplatin (368 mg/m2, 30 min) heated intraperitoneal chemotherapy (HIPEC). Secondary analysis was performed from a prospective database. Overall survival (OS) in chemotherapy responders (R) and nonresponders (NR) was compared. Toxicity was assessed by rate of adverse events (AEs). From April 2005 to April 2021, 436 patients underwent CRS + HIPEC; 125 (29%) received preoperative chemotherapy. The 112 (90%) received oxaliplatin (64, 57%) or irinotecan (48, 43%). R, defined as complete (CR) or partial response on preoperative imaging and/or postoperative histology, was seen in 71, 63% (53.8-72.3); 16, 14% (8.4-22.2) had CR. Median OS in R versus NR was 43.7 months (37.9-49.4) versus 23.9 (16.3-31.4) p = 0.007, HR 0.51 (0.31-0.84). OS multivariable analysis showed HR 0.48 (0.25-0.95), p = 0.03 for chemotherapy response corrected by peritoneal cancer index, completeness of cytoreduction score. CRS led to 21% grade 3-4 AEs versus 4% for preoperative chemotherapy. HIPEC grade 3-4 AEs were 0.5%. Preoperative chemotherapy response is an independent predictor for OS in CRPM.
Collapse
Affiliation(s)
- Nadina Tinsley
- Division of Cancer Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Sarah T. O'Dwyer
- Division of Cancer Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Raghavendar Nagaraju
- Division of Cancer Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Bipasha Chakrabarty
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Michael Braun
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Saifee Mullamitha
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | | | - F. E. Marti Marti
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Mark Saunders
- Division of Cancer Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Hamish Clouston
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Chelliah Selvasekar
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Jonathan Wild
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Malcolm Wilson
- Division of Cancer Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Andrew Renehan
- Division of Cancer Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Omer Aziz
- Division of Cancer Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| | - Jorge Barriuso
- Division of Cancer Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK
- Christie Peritoneal Oncology Centre (CPOC) at The Christie NHS Foundation TrustManchesterUK
| |
Collapse
|
|
5
|
Drago SG, Maino C, Giandola TP, Franco PN, Corso R, Talei Franzesi C, Pecorelli A, Ippolito D. Correlations between Apparent Diffusion Coefficient (ADC) and Prognosis in Patients with Locally Advanced Rectal Cancer. Life (Basel) 2024; 14:1282. [PMID: 39459582 PMCID: PMC11509644 DOI: 10.3390/life14101282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/28/2024] [Accepted: 10/04/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND the aim of this study is to assess the performance of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values in predicting the response to neoadjuvant chemoradiation therapy (CRT) and outcome in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS ninety-four patients with magnetic resonance imaging (MRI) pre- and post-neoadjuvant treatment were retrospectively enrolled. Three regions of interest (ROIs) were manually drawn on three different slices of the tumor for every DWI sequence. ROIs were positioned to include only high signal areas and avoid artifacts or necrotic areas. ROIs were automatically copied onto the corresponding ADC maps and the system derived three different ADC values, distinguishing between mean, maximum, and minimum values, and the standard deviation (SD). Only mean ADC values were considered. After surgical intervention, pTNM and the Mandard tumor regression grade (TRG) were obtained. Patients with a TRG of 1-2 were classified as responders, while patients with a TRG from 3 to 5 were classified as non-responders. RESULTS no correlation was found between pre-ADC values and TRG classes, while post-ADC and ΔADC values showed a significant correlation with TRG classes (r = -0.285, p = 0.002 and r = -0.290, p = 0.019, respectively). Post-ADC values were statistically different between responders and non-responders (p = 0.019). When considering the relation between overall survival (OS) and ADC values, pre-ADC showed a negative correlation with OS (r = -0.381, p = 0.001), while a positive correlation was found between ΔADC values and OS (r = 0.323, p = 0.013). According to ΔADC values, the mean OS time between responders and non-responders showed a significant difference (p = 0.030). A statistical difference was found between TRG classes and OS (p = 0.038) and by dividing patients in responders and non-responders (p = 0.019). CONCLUSIONS the pre-ADC and ΔADC values could be used as useful predictors for patient prognosis, thus helping the treatment planning. On the other hand, the post-ADC values, thanks to their relationship with the TRG classes, could be the ideal tool to predict the histopathological response and plan a conservative approach to the treatment of rectal cancer.
Collapse
Affiliation(s)
- Silvia Girolama Drago
- Department of Diagnostic Radiology, IRCCS Fondazione San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, MB, Italy; (S.G.D.); (C.M.); (T.P.G.); (P.N.F.); (R.C.); (C.T.F.); (D.I.)
| | - Cesare Maino
- Department of Diagnostic Radiology, IRCCS Fondazione San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, MB, Italy; (S.G.D.); (C.M.); (T.P.G.); (P.N.F.); (R.C.); (C.T.F.); (D.I.)
| | - Teresa Paola Giandola
- Department of Diagnostic Radiology, IRCCS Fondazione San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, MB, Italy; (S.G.D.); (C.M.); (T.P.G.); (P.N.F.); (R.C.); (C.T.F.); (D.I.)
| | - Paolo Niccolò Franco
- Department of Diagnostic Radiology, IRCCS Fondazione San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, MB, Italy; (S.G.D.); (C.M.); (T.P.G.); (P.N.F.); (R.C.); (C.T.F.); (D.I.)
| | - Rocco Corso
- Department of Diagnostic Radiology, IRCCS Fondazione San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, MB, Italy; (S.G.D.); (C.M.); (T.P.G.); (P.N.F.); (R.C.); (C.T.F.); (D.I.)
| | - Cammillo Talei Franzesi
- Department of Diagnostic Radiology, IRCCS Fondazione San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, MB, Italy; (S.G.D.); (C.M.); (T.P.G.); (P.N.F.); (R.C.); (C.T.F.); (D.I.)
| | - Anna Pecorelli
- Radiologia Addomino Pelvica Diagnostica e Interventistica IRCCS Azienda Ospedaliera Universitaria di Bologna Policlinico di Sant’Orsola, Via Pietro Albertoni 15, 40138 Bolonga, BO, Italy
| | - Davide Ippolito
- Department of Diagnostic Radiology, IRCCS Fondazione San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, MB, Italy; (S.G.D.); (C.M.); (T.P.G.); (P.N.F.); (R.C.); (C.T.F.); (D.I.)
- School of Medicine, University of Milano Bicocca, Via Cadore 33, 20090 Monza, MB, Italy
| |
Collapse
|
|
6
|
Surov A, Diallo-Danebrock R, Radi A, Kröger JR, Niehoff JH, Michael AE, Gerdes B, Elhabash S, Wienke A, Borggrefe J. Photon Counting Computed Tomography in Rectal Cancer: Associations Between Iodine Concentration, Histopathology and Treatment Response: A Pilot Study. Acad Radiol 2024; 31:3620-3626. [PMID: 38418345 DOI: 10.1016/j.acra.2024.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 01/29/2024] [Accepted: 02/04/2024] [Indexed: 03/01/2024]
Abstract
RATIONALE AND OBJECTIVES Common computed tomography (CT) investigation plays a limited role in characterizing and assessing the response of rectal cancer (RC) to neoadjuvant radiochemotherapy (NARC). Photon counting computed tomography (PCCT) improves the imaging quality and can provide multiparametric spectral image information including iodine concentration (IC). Our purpose was to analyze associations between IC and histopathology in RC and to evaluate the role of IC in response prediction to NARC. MATERIALS AND METHODS Overall, 41 patients were included into the study, 14 women and 27 men, mean age, 65.5 years. PCCT in a portal venous phase of the abdomen was performed. In every case, a polygonal region of interest (ROI) was manually drawn on iodine maps. Normalized IC (NIC) was also calculated. Tumor stage, grade, lymphovascular invasion, circumferential resection margin, and tumor markers were analyzed. Tumor regression grade (absence/presence of tumor cells) after NARC was analyzed. NIC values in groups were compared to Mann-Whitney-U tests. Sensitivity, specificity, and area under the curve values were calculated. Intraclass correlation coefficient (ICC) was calculated. RESULTS ICC was 0.93, 95%CI= (0.88; 0.96). Tumors with lymphovascular invasion showed higher NIC values in comparison to those without (p = 0.04). Tumors with response grade 2-4 showed higher pretreatment NIC values in comparison to lesions with response grade 0-1 (p = 0.01). A NIC value of 0.36 and higher can predict response grade 2-4 (sensitivity, 73.9%; specificity, 91.7%; area under the curve, 0.85). CONCLUSION NIC values showed an excellent interreader agreement in RC. NIC can predict treatment response to NARC.
Collapse
Affiliation(s)
- Alexey Surov
- Department of Radiology, Neuroradiology and Nuclear Medicine, Johannes Wesling University Hospital Minden, Ruhr University Bochum, Hans-Nolte-Str. 1, Minden 32429, Germany.
| | - Raihanatou Diallo-Danebrock
- Department of Pathology, Johannes Wesling University Hospital Minden, Ruhr University Bochum, Hans-Nolte-Str. 1, Minden 32429, Germany
| | - Amin Radi
- Department of Radiology, Neuroradiology and Nuclear Medicine, Johannes Wesling University Hospital Minden, Ruhr University Bochum, Hans-Nolte-Str. 1, Minden 32429, Germany
| | - Jan Robert Kröger
- Department of Radiology, Neuroradiology and Nuclear Medicine, Johannes Wesling University Hospital Minden, Ruhr University Bochum, Hans-Nolte-Str. 1, Minden 32429, Germany
| | - Julius Henning Niehoff
- Department of Radiology, Neuroradiology and Nuclear Medicine, Johannes Wesling University Hospital Minden, Ruhr University Bochum, Hans-Nolte-Str. 1, Minden 32429, Germany
| | - Arwed Elias Michael
- Department of Radiology, Neuroradiology and Nuclear Medicine, Johannes Wesling University Hospital Minden, Ruhr University Bochum, Hans-Nolte-Str. 1, Minden 32429, Germany
| | - Berthold Gerdes
- Department of General Surgery, Johannes Wesling University Hospital Minden, Ruhr University Bochum, Hans-Nolte-Str. 1, Minden 32429, Germany
| | - Saleem Elhabash
- Department of General Surgery, Johannes Wesling University Hospital Minden, Ruhr University Bochum, Hans-Nolte-Str. 1, Minden 32429, Germany
| | - Andreas Wienke
- Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany
| | - Jan Borggrefe
- Department of Radiology, Neuroradiology and Nuclear Medicine, Johannes Wesling University Hospital Minden, Ruhr University Bochum, Hans-Nolte-Str. 1, Minden 32429, Germany
| |
Collapse
|
|
7
|
Soni A, Chandola S, Das CJ, Sharma R, Pathy S, Bhattacharjee HK, Chandrashekhara SH, Sharma A, Kumar R. Role of [18F]FDG-PET/CT in Evaluation of Tumor Response to Chemoradiation Therapy for Advanced Colorectal Cancer. Indian J Nucl Med 2024; 39:279-285. [PMID: 39790821 PMCID: PMC11708798 DOI: 10.4103/ijnm.ijnm_60_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/28/2024] [Accepted: 07/29/2024] [Indexed: 01/12/2025] Open
Abstract
Objectives The objective is to evaluate the efficacy of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) computed tomography (CT) in the evaluation of tumor response to preoperative/palliative chemoradiotherapy (CRT) for advanced colorectal cancer; including metastatic cancer at primary presentation and recurrent cancers with local and/or distant metastasis. Materials and Methods Fifty patients with advanced rectal cancer underwent two point imaging with 18 FDG PET-CT before and after 3 weeks of completion of preoperative/palliative CRT in between 2016 and 2022. Patients with locally recurrent cancer also underwent radical surgery. The assessment consisted of the evaluation of the following metabolic PET parameters: Maximum standardized uptake value (SUVmax), SUVratio, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Response was assessed among the followed patients using RECIST 1.1 criteria. Observations and Results There was a significant decline in the mean post therapy SUVmax and SUVratio as compared to baseline (P = 0.0001). Twenty-six out of 50 (52%) patients were classified as responders. A significant decrease in all parameters (SUVmax, SUVratio, TLG, and MTV) from baseline was observed in responders of the study when comparing with nonresponders (P < 0.05). Besides SUVmax and SUVratio, the mean posttherapy TLG was significantly reduced in responders than nonresponders (P = 0.0065). Conclusion PET-CT is a useful combined anatomic and functional imaging modality in monitoring tumor response to preoperative/palliative CRT in advanced rectal cancer, whether primary or recurrent, including metastatic cancers at presentation. Posttherapy SUV and TLG in particular are significantly associated with treatment response.
Collapse
Affiliation(s)
- Abhishek Soni
- Department of Radio-Diagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Stuti Chandola
- Department of Radio-Diagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Chandan Jyoti Das
- Department of Radio-Diagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Raju Sharma
- Department of Radio-Diagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Sushmita Pathy
- Department of Radiation Oncology, BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | | | | | - Atul Sharma
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Rakesh Kumar
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| |
Collapse
|
|
8
|
Yanagawa S, Tanabe K, Kano M, Hotta R, Saeki Y, Fujikuni N, Ohdan H. Clinicopathological features of hepatoid adenocarcinoma of the stomach: A multicenter retrospective study. Cancer Rep (Hoboken) 2024; 7:e2101. [PMID: 38831124 PMCID: PMC11147685 DOI: 10.1002/cnr2.2101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 04/20/2024] [Accepted: 05/05/2024] [Indexed: 06/05/2024] Open
Abstract
BACKGROUND Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive subtype of gastric cancer (GC), accounting for less than 1% of all cases. It is characterized by frequent liver metastasis recurrence and a poorer prognosis than conventional GC. However, established treatment guidelines for HAS are currently not available.In this report, we present the results of a clinicopathological study of 19 patients diagnosed with HAS, including seven patients with liver metastasis, conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO) between 2016 and 2018. AIMS The aim of the study was to retrospectively observe the outcomes of HAS with gastrectomy and hepatectomy for liver metastasis and determine relevant prognostic factor. We also examined the criteria and outcomes of hepatectomy for liver metastasis and aimed to suggest the optimal treatment for HAS, including chemotherapy. METHODS AND RESULTS A total of 2147 patients underwent gastrectomy for GC at HiSCO-affiliated institutions during the study period; 19 patients, all male with a mean age of 70.9 years, were diagnosed with HAS by hematoxylin-eosin and immunohistochemical staining. Patients underwent gastrectomy at varying pathological stages: six at Stage I, three at Stage II, seven at Stage III, and three at Stage IV. Ten patients received postoperative chemotherapy and the 5-year survival rate was 67.7% after gastrectomy. Among the seven patients with pre or postoperative liver metastasis, five patients underwent hepatectomy. Although one patient had recurrence, the 3-year survival rate was 100% after hepatectomy. CONCLUSION Contrary to previous reports suggesting a 3-year survival rate of approximmately 30% for HAS, our findings indicate that the prognosis for HAS may not be as poor as reported previously. This study contributes valuable insights into the management and potential treatment strategies for HAS.
Collapse
Affiliation(s)
| | - Kazuaki Tanabe
- Department of Perioperative and Critical Care Management, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Mikihiro Kano
- Department of Surgery, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan
| | - Ryuichi Hotta
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Japan
| | - Yoshihiro Saeki
- Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
| | - Nobuaki Fujikuni
- Department of Digestive Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
| |
Collapse
|
|
9
|
Piozzi GN, Khobragade K, Shin SH, Choo JM, Kim SH. Treatment of side limb full-thickness prolapse of the side-to-end coloanal anastomosis following intersphincteric resection: a case report and review of literature. Ann Coloproctol 2024; 40:S38-S43. [PMID: 36751014 PMCID: PMC11162843 DOI: 10.3393/ac.2022.00829.0118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 12/29/2022] [Accepted: 12/29/2022] [Indexed: 02/09/2023] Open
Abstract
Intersphincteric resection (ISR) with coloanal anastomosis is an oncologically safe anus-preserving technique for very low-lying rectal cancers. Most studies focused on oncological and functional outcomes of ISR with very few evaluating long-term postoperative anorectal complications. Full-thickness prolapse of the neorectum is a relatively rare complication. This report presents the case of a 70-year-old woman presenting with full-thickness prolapse of the side limb of the side-to-end coloanal anastomosis occurring 2 weeks after the stoma closure and 2 months after a robotic partial ISR performed with the Da Vinci single-port platform. The anastomosis was revised through resection of the side limb and conversion of the side-to-end anastomosis into an end-to-end handsewn anastomosis with interrupted stitches. This study describes the first case of full-thickness prolapse of the side limb of the side-to-end handsewn coloanal anastomosis following ISR. Moreover, a revision of all reported cases of post-ISR full-thickness and mucosal prolapse was performed.
Collapse
Affiliation(s)
- Guglielmo Niccolò Piozzi
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Krunal Khobragade
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
- Department of Surgical Oncology, Alexis Multispecialty Hospital, Nagpur, India
| | - Seon Hui Shin
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Jeong Min Choo
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Seon Hahn Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| |
Collapse
|
|
10
|
Demir D, Parvizi M, Pehlivanoglu B, Ergin E, Ayhan S, Doganavsargil B. The Association of the Epidermal Growth Factor Receptor (EGFR) Immunoexpression With Prognostic Parameters in Adenocarcinoma Patients Receiving Neoadjuvant Treatment. Cureus 2024; 16:e56763. [PMID: 38650801 PMCID: PMC11034285 DOI: 10.7759/cureus.56763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2024] [Indexed: 04/25/2024] Open
Abstract
The epidermal growth factor receptor (EGFR) expression is considered to play an essential role in the pathogenesis of colorectal adenocarcinoma. This study assessed the expression and predictive/prognostic value of EGFR expression in pre-op biopsy and post-op resection specimens in patients receiving neoadjuvant radiotherapy/neoadjuvant chemoradiotherapy (NRT/NCRT). Thirty-four consecutive patients were included in this study. The association between the prognostic features and EGFR immunohistochemical expression was analyzed in pre- (n=34) and post-treatment (n=22) tissue samples in cases with available tissue blocks. Of 34, 23 (67.6%) were men. The median age was 60.50 ± 10.69 (range, 31-84) years. EGFR expression was detected in 88.2% of biopsy specimens and in 91.2% of surgical specimens. There was only slight agreement between pre-op and post-op EGFR expression scores (kappa value 0.11). There was no significant correlation between pre-op and post-op EGFR expression scores (p>0.05). Although pre-op EGFR positivity and higher pre-op EGFR scores seemed to indicate a worse prognosis, this association between pre-op EGFR expression and overall survival (OS) or disease-specific survival (DSS) did not reach statistical significance (p>0.05). The only case with a post-op EGFR score of three who died of the disease experienced local recurrence and had distant metastasis. In conclusion, EGFR positivity in pre-op biopsy samples seems to be associated with shorter survival, and increased EGFR expression in post-treatment resection specimens predicts aggressive behavior in patients with rectal adenocarcinoma who received NRT/NCRT. However, due to the molecular heterogeneity, EGFR expression status should be evaluated in resection specimens rather than in pre-op biopsy samples for optimal prognosis prediction.
Collapse
Affiliation(s)
| | | | | | - Erhan Ergin
- Internal Medicine, Manisa City Hospital, Manisa, TUR
| | - Semin Ayhan
- Pathology, Manisa Celal Bayar University, Manisa, TUR
| | | |
Collapse
|
|
11
|
MOSTAFAVI SAMANEH, HASSAN ZUHAIRMOHAMMAD. The anti-neoplastic effects of metformin modulate the acquired phenotype of fibroblast cells in the breast cancer-normal fibroblast co-culture system. Oncol Res 2024; 32:477-487. [PMID: 38361760 PMCID: PMC10865743 DOI: 10.32604/or.2023.043926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 11/06/2023] [Indexed: 02/17/2024] Open
Abstract
Intracellular communications between breast cancer and fibroblast cells were reported to be involved in cancer proliferation, growth, and therapy resistance. The hallmarks of cancer-fibroblast interactions, consisting of caveolin 1 (Cav1) and mono-carboxylate transporter 4 (MCT4) (metabolic coupling markers), along with IL-6, TGFβ, and lactate secretion, are considered robust biomarkers predicting recurrence and metastasis. In order to promote a novel phenotype in normal fibroblasts, we predicted that breast cancer cells could be able to cause loss of Cav1 and increase of MCT4, as well as elevate IL-6 and TGFβ in nearby normal fibroblasts. We created a co-culture model using breast cancer (4T1) and normal fibroblast (NIH3T3) cell lines cultured under specific experimental conditions in order to directly test our theory. Moreover, we show that long-term co-culture of breast cancer cells and normal fibroblasts promotes loss of Cav1 and gain of MCT4 in adjacent fibroblasts and increase lactate secretion. These results were validated using the monoculture of each group separately as a control. In this system, we show that metformin inhibits IL-6 and TGFβ secretion and re-expresses Cav1 in both cells. However, MCT4 and lactate stayed high after treatment with metformin. In conclusion, our work shows that co-culture with breast cancer cells may cause significant alterations in the phenotype and secretion of normal fibroblasts. Metformin, however, may change this state and affect fibroblasts' acquired phenotypes. Moreover, mitochondrial inhibition by metformin after 8 days of treatment, significantly hinders tumor growth in mouse model of breast cancer.
Collapse
Affiliation(s)
- SAMANEH MOSTAFAVI
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - ZUHAIR MOHAMMAD HASSAN
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| |
Collapse
|
|
12
|
Katdare AN, Baheti AD, Pangarkar SY, Mistry KA, Ankathi SK, Haria PD, Choudhari AJ, Guha A, Gala K, Shetty N, Kulkarni S, Ramadwar M, Bal M. Evaluation of an Objective MRI-Based Tumor Regression Grade (mrTRG) Score and a Subjective Likert Score for Assessing Treatment Response in Locally Advanced Rectal Cancers-A Retrospective Study. Indian J Radiol Imaging 2024; 34:69-75. [PMID: 38106857 PMCID: PMC10723953 DOI: 10.1055/s-0043-1772695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2023] Open
Abstract
Purpose: Magnetic resonance imaging (MRI) with the help of MRI-based tumor regression grade (mrTRG) score has been used as a tool to predict pathological tumor regression grade (pTRG) in patients of rectal cancer post-neoadjuvant chemoradiation. Our study aims to evaluate the ability of MRI in assessing treatment response comparing an objective mrTRG score and a subjective Likert score, with a focus on the ability to predict pathologic complete response (pCR). Methods: Post-treatment MRI studies were retrospectively reviewed for 170 consecutive cases of histopathologically proven rectal cancer after receiving neoadjuvant chemoradiation and prior to surgery by two oncoradiologists blinded to the eventual postoperative histopathology findings. An objective (mrTRG) and a subjective Likert score were assigned to all the cases. Receiver operating characteristic curves were constructed to determine the ability of Likert scale and mrTRG to predict pCR, with postoperative histopathology being the gold standard. The optimal cutoff points on the scale of 1 to 5 were obtained for mrTRG and Likert scale with the greatest sum of sensitivity and specificity using the Youden Index. Results: The most accurate cutoff point for the mrTRG to predict complete response was 2.5 (using Youden index), with a sensitivity of 69.2%, specificity of 69.6%, positive predictive value (PPV) of 85.6%, negative predictive value (NPV) of 46.4%, and accuracy of 69.3%. The most accurate cutoff for the Likert scale to predict complete response was 3.5, with a sensitivity of 47.5%, specificity of 89.1%, PPV of 91.9%, NPV of 39.4%, and accuracy of 59%. mrTRG had a lower cutoff and was more accurate in predicting pCR compared to Likert score. Conclusion: An objective mrTRG was more accurate than a subjective Likert scale to predict complete response in our study.
Collapse
Affiliation(s)
- Aparna N Katdare
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Akshay D Baheti
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sayali Y Pangarkar
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Kunal A Mistry
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Suman K Ankathi
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Purvi D Haria
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Amit J Choudhari
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Amrita Guha
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Kunal Gala
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Nitin Shetty
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Suyash Kulkarni
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Mukta Ramadwar
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
- Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Munita Bal
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
- Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| |
Collapse
|
|
13
|
Verheij FS, Kuhlmann KFD, Silliman DR, Soares KC, Kingham TP, Balachandran VP, Drebin JA, Wei AC, Jarnagin WR, Cercek A, Kok NFM, Kemeny NE, D'Angelica MI. Combined Hepatic Arterial Infusion Pump and Systemic Chemotherapy in the Modern Era for Chemotherapy-Naive Patients with Unresectable Colorectal Liver Metastases. Ann Surg Oncol 2023; 30:7950-7959. [PMID: 37639032 DOI: 10.1245/s10434-023-14073-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 07/14/2023] [Indexed: 08/29/2023]
Abstract
PURPOSE Chemotherapy-naive patients with unresectable colorectal liver metastases (CRLM) have been the best responders to hepatic arterial infusion (HAI) therapy. The current treatment paradigm has drifted away from HAI in the first-line setting. We aimed to analyze outcomes of combined first-line systemic therapy with HAI therapy (HAI+SYS) in the modern era. METHODS We conducted a retrospective study of consecutive chemotherapy-naive patients with unresectable CRLM who received HAI+SYS between 2003 and 2019. Patients were selected from a prospectively maintained database. Outcomes included radiological response rate, conversion to resection (CTR) rate, and overall survival (OS). RESULTS Fifty-eight chemotherapy-naive patients were identified out of 546 patients with unresectable CRLM managed with HAI. After induction treatment, 4 patients (7%) had a complete radiological response, including two durable responses. In total, 32 patients (55%) underwent CTR. CTR or complete response without resection was achieved after seven cycles of systemic therapy and four cycles of HAI therapy. Median OS for the whole cohort was 53.0 months (95% confidence interval 23.0-82.9). Three- and 5-year OS in patients who achieved CTR or complete response versus patients who did not was 88% and 72% versus 27% and 0% respectively. Of patients who underwent CTR, complete and major pathological response (no and <10% viable tumor cells, respectively) was observed in 7 (22%) and 12 patients (38%). CONCLUSIONS Combined HAI+SYS in chemotherapy-naive patients resulted in durable and substantial response in a large proportion of patients. Nearly two-thirds of patients achieved a complete response or proceeded to conversion surgery, which was associated with prolonged survival.
Collapse
Affiliation(s)
- Floris S Verheij
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Koert F D Kuhlmann
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Danielle R Silliman
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kevin C Soares
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jeffrey A Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Niels F M Kok
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Nancy E Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| |
Collapse
|
|
14
|
Stanojevic A, Samiotaki M, Lygirou V, Marinkovic M, Nikolic V, Stojanovic-Rundic S, Jankovic R, Vlahou A, Panayotou G, Fijneman RJA, Castellví-Bel S, Zoidakis J, Cavic M. Data-Independent Acquisition Mass Spectrometry Analysis of FFPE Rectal Cancer Samples Offers In-Depth Proteomics Characterization of the Response to Neoadjuvant Chemoradiotherapy. Int J Mol Sci 2023; 24:15412. [PMID: 37895091 PMCID: PMC10607861 DOI: 10.3390/ijms242015412] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/30/2023] [Accepted: 10/03/2023] [Indexed: 10/29/2023] Open
Abstract
Locally advanced rectal cancer (LARC) presents a challenge in identifying molecular markers linked to the response to neoadjuvant chemoradiotherapy (nCRT). This study aimed to utilize a sensitive proteomic method, data-independent mass spectrometry (DIA-MS), to extensively analyze the LARC proteome, seeking individuals with favorable initial responses suitable for a watch-and-wait approach. This research addresses the unmet need to understand the response to treatment, potentially guiding personalized strategies for LARC patients. Post-treatment assessment included MRI scans and proctoscopy. This research involved 97 LARC patients treated with intense chemoradiotherapy, comprising radiation and chemotherapy. Out of 97 LARC included in this study, we selected 20 samples with the most different responses to nCRT for proteome profiling (responders vs. non-responders). This proteomic approach shows extensive proteome coverage in LARC samples. The analysis identified a significant number of proteins compared to a prior study. A total of 915 proteins exhibited differential expression between the two groups, with certain signaling pathways associated with response mechanisms, while top candidates had good predictive potential. Proteins encoded by genes SMPDL3A, PCTP, LGMN, SYNJ2, NHLRC3, GLB1, and RAB43 showed high predictive potential of unfavorable treatment outcome, while RPA2, SARNP, PCBP2, SF3B2, HNRNPF, RBBP4, MAGOHB, DUT, ERG28, and BUB3 were good predictive biomarkers of favorable treatment outcome. The identified proteins and related biological processes provide promising insights that could enhance the management and care of LARC patients.
Collapse
Affiliation(s)
- Aleksandra Stanojevic
- Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia; (A.S.); (R.J.)
| | - Martina Samiotaki
- Institute for Bioinnovation, Biomedical Sciences Research Center “Alexander Fleming”, Fleming 34, 166 72 Vari, Greece; (M.S.); (G.P.)
| | - Vasiliki Lygirou
- Department of Biotechnology, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece; (V.L.); (A.V.); (J.Z.)
| | - Mladen Marinkovic
- Clinic for Radiation Oncology and Diagnostics, Department of Radiation Oncology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia; (M.M.); (S.S.-R.)
- Faculty of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia
| | - Vladimir Nikolic
- Clinic for Medical Oncology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia;
| | - Suzana Stojanovic-Rundic
- Clinic for Radiation Oncology and Diagnostics, Department of Radiation Oncology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia; (M.M.); (S.S.-R.)
- Faculty of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia
| | - Radmila Jankovic
- Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia; (A.S.); (R.J.)
| | - Antonia Vlahou
- Department of Biotechnology, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece; (V.L.); (A.V.); (J.Z.)
| | - George Panayotou
- Institute for Bioinnovation, Biomedical Sciences Research Center “Alexander Fleming”, Fleming 34, 166 72 Vari, Greece; (M.S.); (G.P.)
| | - Remond J. A. Fijneman
- Department of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands;
| | - Sergi Castellví-Bel
- Gastroenterology Department, Fundació Clínic per la Recerca Biomèdica-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), C/del Rosselló, 149, 08036 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Almagro, 3, 28029 Madrid, Spain
- Hospital Clínic, University of Barcelona, C/del Villarroel, 170, 08036 Barcelona, Spain
| | - Jerome Zoidakis
- Department of Biotechnology, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece; (V.L.); (A.V.); (J.Z.)
- Department of Biology, National and Kapodistrian University of Athens, Panepistimíou 30, 106 79 Athens, Greece
| | - Milena Cavic
- Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia; (A.S.); (R.J.)
| |
Collapse
|
|
15
|
Withey SJ, Owczarczyk K, Grzeda MT, Yip C, Deere H, Green M, Maisey N, Davies AR, Cook GJ, Goh V. Association of dynamic contrast-enhanced MRI and 18F-Fluorodeoxyglucose PET/CT parameters with neoadjuvant therapy response and survival in esophagogastric cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:106934. [PMID: 37183047 PMCID: PMC10769883 DOI: 10.1016/j.ejso.2023.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 04/17/2023] [Accepted: 05/09/2023] [Indexed: 05/16/2023]
Abstract
INTRODUCTION Better predictive markers are needed to deliver individualized care for patients with primary esophagogastric cancer. This exploratory study aimed to assess whether pre-treatment imaging parameters from dynamic contrast-enhanced MRI and 18F-fluorodeoxyglucose (18F-FDG) PET/CT are associated with response to neoadjuvant therapy or outcome. MATERIALS AND METHODS Following ethical approval and informed consent, prospective participants underwent dynamic contrast-enhanced MRI and 18F-FDG PET/CT prior to neoadjuvant chemotherapy/chemoradiotherapy ± surgery. Vascular dynamic contrast-enhanced MRI and metabolic 18F-FDG PET parameters were compared by tumor characteristics using Mann Whitney U test and with pathological response (Mandard tumor regression grade), recurrence-free and overall survival using logistic regression modelling, adjusting for predefined clinical variables. RESULTS 39 of 47 recruited participants (30 males; median age 65 years, IQR: 54, 72 years) were included in the final analysis. The tumor vascular-metabolic ratio was higher in patients remaining node positive following neoadjuvant therapy (median tumor peak enhancement/SUVmax ratio: 0.052 vs. 0.023, p = 0.02). In multivariable analysis adjusted for age, gender, pre-treatment tumor and nodal stage, peak enhancement (highest gadolinium concentration value prior to contrast washout) was associated with pathological tumor regression grade. The odds of response decreased by 5% for each 0.01 unit increase (OR 0.95; 95% CI: 0.90, 1.00, p = 0.04). No 18F-FDG PET/CT parameters were predictive of pathological tumor response. No relationships between pre-treatment imaging and survival were identified. CONCLUSION Pre-treatment esophagogastric tumor vascular and metabolic parameters may provide additional information in assessing response to neoadjuvant therapy.
Collapse
Affiliation(s)
- Samuel J Withey
- Department of Radiology, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom
| | - Kasia Owczarczyk
- Department of Clinical Oncology, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom
| | - Mariusz T Grzeda
- School of Biomedical Engineering & Imaging Sciences, King's College London, United Kingdom
| | - Connie Yip
- Department of Radiation Oncology, National Cancer Centre, Singapore
| | - Harriet Deere
- Department of Pathology, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom
| | - Mike Green
- Department of Pathology, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom
| | - Nick Maisey
- Department of Medical Oncology, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom
| | - Andrew R Davies
- Department of Surgery, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom
| | - Gary J Cook
- School of Biomedical Engineering & Imaging Sciences, King's College London, United Kingdom; The King's College London and Guy's and St Thomas' PET Centre, St Thomas' Hospital, London, United Kingdom
| | - Vicky Goh
- Department of Radiology, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom; School of Biomedical Engineering & Imaging Sciences, King's College London, United Kingdom.
| |
Collapse
|
|
16
|
Almuradova E, Yalcin S, Arıkan R, Ayhan M, Demir H, Cevik GT, Karaca M, Petekkaya I, Karabulut B. Survival of Patients With Metastatic Rectum Cancer Who Underwent Metastasectomy Following Conversion Chemotherapy Sans Pelvic Radiotherapy: A Turkish Oncology Group Study. Cureus 2023; 15:e39119. [PMID: 37216135 PMCID: PMC10195643 DOI: 10.7759/cureus.39119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/17/2023] [Indexed: 05/24/2023] Open
Abstract
BACKGROUND The management of early rectal cancer is different from that of colon cancer in terms of radiotherapy (RT) requirements or neoadjuvant treatment. It is not clear how the course of rectal cancer differs from that of the colon in a metastatic setting or how it should be approached differently. This study aimed to evaluate outcomes after combining downsizing chemotherapy (CTx) with rescue surgery. METHODS Eighty-nine patients (57 men and 32 women) diagnosed with metastatic rectal cancer with resectable disease after systemic CTx were included in the study. All patients underwent surgery for the primary mass and metastasis, but none received radiation therapy before or after surgery. Survival curves for overall survival (OS) and progression-free survival (PFS) were generated using the Kaplan-Meier method and compared with the log-rank test for subgroups. RESULTS The median follow-up time was 28.8 (17.6-39.4) months. During the follow-up, 54 (60.7%) patients died and 78 (87.6%) patients had a PFS event. Cancer relapsed in 72 (80.9%) patients. Median OS was 35.2 (95% CI: 28.5-41.8) months, and median PFS was 17.7 (95% CI: 14.4-21) months. The five-year OS and PFS were 19% and 3.5%, respectively. Male sex (p=0.04) and a better Mandard score (p=0.021) were associated with a longer OS, while obesity was associated with a shorter PFS (p<0.001). CONCLUSION Our study is the first to evaluate the effects of metastasectomy after conversion therapy in metastatic rectal cancer independent of colon cancer. As a result of the study, it was seen that the survival after metastasectomy in rectal cancer is worse than the colon cancer data known from previous studies.
Collapse
Affiliation(s)
| | - Suayib Yalcin
- Medical Oncology, Hacettepe University Medical School, Ankara, TUR
| | - Rukiye Arıkan
- Medical Oncology, Marmara University School of Medicine, Istanbul, TUR
| | - Murat Ayhan
- Medical Oncology, Dr. Lutfi Kırdar Kartal Education and Research Hospital, Istanbul, TUR
| | - Hacer Demir
- Medical Oncology, Afyonkarahisar University of Health and Science, Afyonkarahisar, TUR
- Medical Oncology, Afyon Kocatepe University School of Medicine, Afyonkarahisar, TUR
| | | | - Mustafa Karaca
- Medical Oncology, Antalya Education and Research Hospital, Antalya, TUR
| | | | | |
Collapse
|
|
17
|
Bádon ES, Beke L, Mokánszki A, András C, Méhes G. Carbonic Anhydrase IX Expression and Treatment Response Measured in Rectal Adenocarcinoma Following Neoadjuvant Chemo-Radiotherapy. Int J Mol Sci 2023; 24:ijms24032581. [PMID: 36768903 PMCID: PMC9916425 DOI: 10.3390/ijms24032581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/16/2023] [Accepted: 01/24/2023] [Indexed: 01/31/2023] Open
Abstract
The overexpression of the pH regulator carbonic anhydrase IX (CAIX) due to hypoxic/metabolic stress was reported in various tumors as an adverse prognostic feature. Our retrospective study aimed to investigate the general pattern and dynamics of CAIX expression in rectal adenocarcinoma following preoperative neoadjuvant therapy (NAT) in matched initial biopsy and surgical resection samples. A total of 40/55 (72.72%) of the post-treatment samples showed partial CAIX expression, frequently in the proximity of hypoxic tumor areas. CAIX expression showed a significant increase in post-treatment tumors (mean% 21.8 ± 24.9 SD vs. 39.4 ± 29.4 SD, p < 0.0001), that was not obvious in untreated tumors (mean% 15.0 ± 21.3 SD vs. 20 ± 23.02, p = 0.073). CAIXhigh phenotype was associated with mutant KRAS status and lack of pathological regression (WHO Tumor Regression Grade 4 and 5). However, the adverse effect of CAIX on overall or progression-free survival could not be statistically confirmed. In conclusion, the dynamic upregulation of CAIX expression is a general feature of rectal adenocarcinoma following neoadjuvant chemo-radiotherapy indicating therapy-induced metabolic reprogramming and cellular adaptation. A synergism of the CAIX-associated regulatory pathways and the mutant KRAS oncogenic signaling most likely contributes to therapy resistance and survival of residual cancer.
Collapse
Affiliation(s)
- Emese Sarolta Bádon
- Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Lívia Beke
- Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Attila Mokánszki
- Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Csilla András
- Department of Oncology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Gábor Méhes
- Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Correspondence: ; Tel.: +36-5-2411-600
| |
Collapse
|
|
18
|
Rosário MIVD, Barbosa JP, Gullo I, Barbosa J. DOES NEOADJUVANT CHEMORADIOTHERAPY FOR ESOPHAGEAL AND GASTROESOPHAGEAL JUNCTION CANCER PATIENTS AFFECT POSTOPERATIVE OUTCOMES? A STUDY USING THE BECKER TUMOR REGRESSION GRADE SYSTEM AND LYMPH NODE REGRESSION. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2023; 36:e1724. [PMID: 37162100 PMCID: PMC10168664 DOI: 10.1590/0102-672020230002e1724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 10/30/2022] [Indexed: 05/11/2023]
Abstract
BACKGROUND The effect of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal cancer can be determined by assessing the Becker tumor regression grade in the primary tumor, as well as in lymph nodes. AIMS The aim of this study was to investigate the anatomopathological changes caused by neoadjuvant chemoradiotherapy and their impact on clinical parameters. Specifically, we analyzed the Becker tumor regression grade, lymph node status, and regression changes and evaluated their association with the Clavien-Dindo classification of surgical complications and overall patient survival. METHODS This is a retrospective and observational study including 139 patients diagnosed with adenocarcinoma or squamous cell carcinoma of the esophagus and treated with either neoadjuvant chemoradiotherapy followed by surgery or surgery alone. For the 94 patients who underwent neoadjuvant chemoradiotherapy, we evaluated tumor regression by Becker tumor regression grade in primary tumors. We also analyzed lymph node status and regression changes on lymph nodes with or without metastases. Overall survival analysis was performed using Kaplan-Meier curves. RESULTS Becker tumor regression grade is associated with lower lymphatic permeation (p<0.01) and vascular invasion (p<0.001), but not with lymph node regression rate (p=0.10). Clavien-Dindo classification was associated neither with lymph node regression rate (odds ratio=0.784, p=0.795) nor with tumor regression grade (p=0.68). Patients who presented with lymphatic permeation and vascular invasion had statistically significantly lower median survival (17 vs. 30 months, p=0.006 for lymphatic permeation, and 14 vs. 29 months, p=0.024 for vascular invasion). CONCLUSION In our series, we were unable to demonstrate an association between Becker tumor regression grade and lymph node regression rate with any postoperative complications. Patients with lower lymphatic permeation and vascular invasion have higher overall survival, correlating with a better response in the Becker tumor regression grade system.
Collapse
Affiliation(s)
| | - José Pedro Barbosa
- Universidade do Porto, Faculty of Medicine - Porto, Portugal
- Universidade do Porto, Faculty of Medicine, Information and Decision in Health, Department of Community Medicine - Porto, Portugal
| | - Irene Gullo
- Universidade do Porto, Faculty of Medicine - Porto, Portugal
- Universidade do Porto, Faculty of Medicine, Information and Decision in Health, Department of Community Medicine - Porto, Portugal
- Centro Hospitalar Universitário de São João, Department of Pathology - Porto, Portugal
| | - José Barbosa
- Universidade do Porto, Faculty of Medicine - Porto, Portugal
- Centro Hospitalar Universitário de São João, Department of General Surgery - Porto, Portugal
| |
Collapse
|
|
19
|
Carbonara R, Surgo A, Ciliberti MP, Gregucci F, Bonaparte I, Nicosia L, Meldolesi E, Caliandro M, Ferraro V, Inchingolo R, Memeo R, Ludovico E, Calbi R, Lavalle M, Gambacorta MA, Alongi F, Fiorentino A. Impact of preoperative chemoradiation with higher dose intensity modulated radiotherapy on pathological complete response for locally advanced rectal cancer: a systematic review. Expert Rev Anticancer Ther 2022; 22:1249-1259. [PMID: 36174658 DOI: 10.1080/14737140.2022.2130895] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 08/25/2022] [Accepted: 09/27/2022] [Indexed: 01/12/2023]
Abstract
INTRODUCTION Neoadjuvant chemoradiation (CRT) followed by total mesorectal excision is the current standard-of-care for locally advanced UICC II-III stage rectal cancer (LARC). A pathological complete response (pCR) correlates with survival. Improvements of pCR, including dose escalation, should be explored. The aim of this explorative analysis is to assess the impact on pCR of intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB). AREAS COVERED A literature search via PICO (Population, Intervention, Comparison, Outcome) in MEDLINE/PubMed and EMBASE and a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Metanalysis) methodology were performed. Studies that reported pCR rate in patients with LARC in clinical stage T2N+M0 or cT3/4 N0/+M0 treated with preoperative CRT with SIB-IMRT/VMAT (Volumetric Modulated Arc Therapy) were included. Sixty-two studies were identified, but only eight clinical trials with a total of 311 patients were included . Median follow-up was 16-61 months. pCR reached the value of 38%. Good survival outcomes were observed with a mild toxicity profile. EXPERT OPINION Radiotherapy dose intensification in LARC showed a slight increase of pCR compared to historical studies. Prospective evaluations are necessary to define which patients would benefit most.
Collapse
Affiliation(s)
- Roberta Carbonara
- Radiation Oncology Department, General Regional Hospital F. Miulli, Acquaviva delle Fonti, Bari, Italy
| | - Alessia Surgo
- Radiation Oncology Department, General Regional Hospital F. Miulli, Acquaviva delle Fonti, Bari, Italy
| | - Maria Paola Ciliberti
- Radiation Oncology Department, General Regional Hospital F. Miulli, Acquaviva delle Fonti, Bari, Italy
| | - Fabiana Gregucci
- Radiation Oncology Department, General Regional Hospital F. Miulli, Acquaviva delle Fonti, Bari, Italy
| | - Ilaria Bonaparte
- Radiation Oncology Department, General Regional Hospital F. Miulli, Acquaviva delle Fonti, Bari, Italy
| | - Luca Nicosia
- IRCCS, Advanced Radiation Oncology Department, Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
| | - Elisa Meldolesi
- Radiation Oncology Department, Fondazione Policlinico Universitario A.Gemelli, IRCCS, Rome, Italy
| | - Morena Caliandro
- Radiation Oncology Department, General Regional Hospital F. Miulli, Acquaviva delle Fonti, Bari, Italy
| | - Valentina Ferraro
- Hepatobiliary and Pancreatic Surgery Unit, General Regional Hospital F. Miulli, Acquaviva delle Fonti, Bari, Italy
| | - Riccardo Inchingolo
- Hepatobiliary and Pancreatic Surgery Unit, General Regional Hospital F. Miulli, Acquaviva delle Fonti, Bari, Italy
| | - Riccardo Memeo
- Hepatobiliary and Pancreatic Surgery Unit, General Regional Hospital F. Miulli, Acquaviva delle Fonti, Bari, Italy
| | - Elena Ludovico
- Radiology Department, General Regional Hospital F. Miulli, Acquaviva delle Fonti (BA), Bari, Italy
| | - Roberto Calbi
- Radiology Department, General Regional Hospital F. Miulli, Acquaviva delle Fonti (BA), Bari, Italy
| | - Mariadea Lavalle
- Nuclear Medicine Department, General Regional Hospital F. Miulli, Acquaviva delle Fonti (BA), Bari, Italy
| | | | - Filippo Alongi
- IRCCS, Advanced Radiation Oncology Department, Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
- Medicine Faculty, University of Brescia, Brescia, Italy
| | - Alba Fiorentino
- Radiation Oncology Department, General Regional Hospital F. Miulli, Acquaviva delle Fonti, Bari, Italy
| |
Collapse
|
|
20
|
Roesel R, Epistolio S, Molinari F, Saletti P, De Dosso S, Valli M, Franzetti-Pellanda A, Deantonio L, Biggiogero M, Spina P, Popeskou SG, Cristaudi A, Mongelli F, Mazzucchelli L, Stefanini FM, Frattini M, Christoforidis D. A Pilot, Prospective, Observational Study to Investigate the Value of NGS in Liquid Biopsies to Predict Tumor Response After Neoadjuvant Chemo-Radiotherapy in Patients With Locally Advanced Rectal Cancer: The LiBReCa Study. Front Oncol 2022; 12:900945. [PMID: 35837093 PMCID: PMC9274270 DOI: 10.3389/fonc.2022.900945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/23/2022] [Indexed: 11/13/2022] Open
Abstract
IntroductionCirculating tumor DNA (ctDNA) correlates with the response to therapy in different types of cancer. However, in patients with locally advanced rectal cancer (LARC), little is known about how ctDNA levels change with neoadjuvant chemoradiation (Na-ChRT) and how they correlate with treatment response. This work aimed to explore the value of serial liquid biopsies in monitoring response after Na-ChRT with the hypothesis that this could become a reliable biomarker to identify patients with a complete response, candidates for non-operative management.Materials and MethodsTwenty-five consecutive LARC patients undergoing long-term Na-ChRT therapy were included. Applying next-generation sequencing (NGS), we characterized DNA extracted from formalin-fixed paraffin embedded diagnostic biopsy and resection tissue and plasma ctDNA collected at the following time points: the first and last days of radiotherapy (T0, Tend), at 4 (T4), 7 (T7) weeks after radiotherapy, on the day of surgery (Top), and 3–7 days after surgery (Tpost-op). On the day of surgery, a mesenteric vein sample was also collected (TIMV). The relationship between the ctDNA at those time-points and the tumor regression grade (TRG) of the surgical specimen was statistically explored.ResultsWe found no association between the disappearance of ctDNA mutations in plasma samples and pathological complete response (TRG1) as ctDNA was undetectable in the majority of patients from Tend on. However, we observed that the poor (TRG 4) response to Na-ChRT was significantly associated with a positive liquid biopsy at the Top.ConclusionsctDNA evaluation by NGS technology may identify LARC patients with poor response to Na-ChRT. In contrast, this technique does not seem useful for identifying patients prone to developing a complete response.
Collapse
Affiliation(s)
- Raffaello Roesel
- Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland
- *Correspondence: Raffaello Roesel, ; Samantha Epistolio,
| | - Samantha Epistolio
- Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland
- *Correspondence: Raffaello Roesel, ; Samantha Epistolio,
| | - Francesca Molinari
- Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland
| | - Piercarlo Saletti
- Clinical Research Unit, Clinica Luganese Moncucco, Lugano, Switzerland
- Medical Oncology Clinic, Clinica Luganese Moncucco, Lugano, Switzerland
- Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland
| | - Sara De Dosso
- Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland
- Istituto Oncologico della Svizzera Italiana, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Mariacarla Valli
- Radiation Oncology Clinic, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | | | - Letizia Deantonio
- Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland
- Radiation Oncology Clinic, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Maira Biggiogero
- Clinical Research Unit, Clinica Luganese Moncucco, Lugano, Switzerland
| | - Paolo Spina
- Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland
- Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
| | - Sotirios Georgios Popeskou
- Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland
| | - Alessandra Cristaudi
- Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland
| | - Francesco Mongelli
- Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland
| | - Luca Mazzucchelli
- Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland
- Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland
| | | | - Milo Frattini
- Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland
| | - Dimitri Christoforidis
- Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland
- Department of Visceral Surgery, Lausanne University Hospital, Lausanne, Switzerland
| |
Collapse
|
|
21
|
Shahzadi I, Zwanenburg A, Lattermann A, Linge A, Baldus C, Peeken JC, Combs SE, Diefenhardt M, Rödel C, Kirste S, Grosu AL, Baumann M, Krause M, Troost EGC, Löck S. Analysis of MRI and CT-based radiomics features for personalized treatment in locally advanced rectal cancer and external validation of published radiomics models. Sci Rep 2022; 12:10192. [PMID: 35715462 PMCID: PMC9205935 DOI: 10.1038/s41598-022-13967-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/17/2022] [Indexed: 11/21/2022] Open
Abstract
Radiomics analyses commonly apply imaging features of different complexity for the prediction of the endpoint of interest. However, the prognostic value of each feature class is generally unclear. Furthermore, many radiomics models lack independent external validation that is decisive for their clinical application. Therefore, in this manuscript we present two complementary studies. In our modelling study, we developed and validated different radiomics signatures for outcome prediction after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) based on computed tomography (CT) and T2-weighted (T2w) magnetic resonance (MR) imaging datasets of 4 independent institutions (training: 122, validation 68 patients). We compared different feature classes extracted from the gross tumour volume for the prognosis of tumour response and freedom from distant metastases (FFDM): morphological and first order (MFO) features, second order texture (SOT) features, and Laplacian of Gaussian (LoG) transformed intensity features. Analyses were performed for CT and MRI separately and combined. Model performance was assessed by the area under the curve (AUC) and the concordance index (CI) for tumour response and FFDM, respectively. Overall, intensity features of LoG transformed CT and MR imaging combined with clinical T stage (cT) showed the best performance for tumour response prediction, while SOT features showed good performance for FFDM in independent validation (AUC = 0.70, CI = 0.69). In our external validation study, we aimed to validate previously published radiomics signatures on our multicentre cohort. We identified relevant publications on comparable patient datasets through a literature search and applied the reported radiomics models to our dataset. Only one of the identified studies could be validated, indicating an overall lack of reproducibility and the need of further standardization of radiomics before clinical application.
Collapse
Affiliation(s)
- Iram Shahzadi
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Alex Zwanenburg
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany
| | - Annika Lattermann
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Annett Linge
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Christian Baldus
- Department of Radiology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Jan C Peeken
- German Cancer Consortium (DKTK) partner site Munich, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, München, Germany.,Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Neuherberg, Germany
| | - Stephanie E Combs
- German Cancer Consortium (DKTK) partner site Munich, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, München, Germany.,Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Neuherberg, Germany
| | - Markus Diefenhardt
- Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Frankfurt am Main, Germany.,German Cancer Consortium (DKTK) partner site Frankfurt, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Frankfurt Cancer Institute, Frankfurt, Germany
| | - Claus Rödel
- Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Frankfurt am Main, Germany.,German Cancer Consortium (DKTK) partner site Frankfurt, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Frankfurt Cancer Institute, Frankfurt, Germany
| | - Simon Kirste
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK) partner site Freiburg, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Anca-Ligia Grosu
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK) partner site Freiburg, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Baumann
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Mechthild Krause
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, Dresden, Germany
| | - Esther G C Troost
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, Dresden, Germany
| | - Steffen Löck
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. .,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany. .,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
| |
Collapse
|
|
22
|
Redegalli M, Schiavo Lena M, Cangi MG, Smart CE, Mori M, Fiorino C, Arcidiacono PG, Balzano G, Falconi M, Reni M, Doglioni C. Proposal for a New Pathologic Prognostic Index After Neoadjuvant Chemotherapy in Pancreatic Ductal Adenocarcinoma (PINC). Ann Surg Oncol 2022; 29:3492-3502. [PMID: 35230580 PMCID: PMC9072515 DOI: 10.1245/s10434-022-11413-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 01/16/2022] [Indexed: 01/03/2023]
Abstract
BACKGROUND Limited information is available on the relevant prognostic variables after surgery for patients with pancreatic ductal adenocarcinoma (PDAC) subjected to neoadjuvant chemotherapy (NACT). NACT is known to induce a spectrum of histological changes in PDAC. Different grading regression systems are currently available; unfortunately, they lack precision and accuracy. We aimed to identify a new quantitative prognostic index based on tumor morphology. PATIENTS AND METHODS The study population was composed of 69 patients with resectable or borderline resectable PDAC treated with preoperative NACT (neoadjuvant group) and 36 patients submitted to upfront surgery (upfront-surgery group). A comprehensive histological assessment on hematoxylin and eosin (H&E) stained sections evaluated 20 morphological parameters. The association between patient survival and morphological variables was evaluated to generate a prognostic index. RESULTS The distribution of morphological parameters evaluated was significantly different between upfront-surgery and neoadjuvant groups, demonstrating the effect of NACT on tumor morphology. On multivariate analysis for patients that received NACT, the predictors of shorter overall survival (OS) and disease-free survival (DFS) were perineural invasion and lymph node ratio. Conversely, high stroma to neoplasia ratio predicted longer OS and DFS. These variables were combined to generate a semiquantitative prognostic index based on both OS and DFS, which significantly distinguished patients with poor outcomes from those with a good outcome. Bootstrap analysis confirmed the reproducibility of the model. CONCLUSIONS The pathologic prognostic index proposed is mostly quantitative in nature, easy to use, and may represent a reliable tumor regression grading system to predict patient outcomes after NACT followed by surgery for PDAC.
Collapse
Affiliation(s)
- M Redegalli
- Pathology Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - M Schiavo Lena
- Pathology Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - M G Cangi
- Pathology Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - C E Smart
- Pathology Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - M Mori
- Medical Physics, San Raffaele Scientific Institute, Milan, Italy
| | - C Fiorino
- Medical Physics, San Raffaele Scientific Institute, Milan, Italy
| | - P G Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
| | - G Balzano
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - M Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - M Reni
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Pancreas Translational and Clinical Research Centre, Milan, Italy.
| | - C Doglioni
- Pathology Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| |
Collapse
|
|
23
|
Inzani F, Arciuolo D, Angelico G, Santoro A, Travaglino A, D'Alessandris N, Scaglione G, Valente M, Cianfrini F, Raffone A, Zannoni GF. Assessing Post-Treatment Pathologic Tumor Response in Female Genital Tract Carcinomas: An Update. Front Oncol 2022; 12:814989. [PMID: 35223496 PMCID: PMC8866564 DOI: 10.3389/fonc.2022.814989] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 01/05/2022] [Indexed: 01/05/2023] Open
Abstract
In the last decades, several new therapeutic strategies have been introduced in the field of gynecologic oncology. These include neoadjuvant chemotherapy for high-grade serous tubo-ovarian carcinoma, hormonal fertility-sparing strategies for endometrial cancer, pressurized intraperitoneal aerosol chemotherapy (PIPAC) for surgically incurable peritoneal metastasis, and neoadjuvant treatments for locally advanced cervical carcinomas. All these recent advances lead to the development of novel scoring systems for the evaluation of pathological response related to specific treatments. In this regard, pathological evaluation of the morphological modifications related to these treatments and the definition of a tumor regression grading score have been introduced in clinical practice in order to achieve a more efficient prognostic stratification of patients affected by gynecological malignancies. The aim of the present paper is to provide a detailed review on the post-treatment pathological scoring systems in patients affected by gynecological malignancies.
Collapse
Affiliation(s)
- Frediano Inzani
- Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Damiano Arciuolo
- Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Giuseppe Angelico
- Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Angela Santoro
- Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Travaglino
- Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Nicoletta D'Alessandris
- Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Giulia Scaglione
- Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Michele Valente
- Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Federica Cianfrini
- Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Raffone
- Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.,Division of Gynaecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC), IRCCS Azienda Ospedaliero-Univeristaria di Bologna. S. Orsola Hospital, University of Bologna, Bologna, Italy
| | - Gian Franco Zannoni
- Unità di Ginecopatologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Rome, Italy
| |
Collapse
|
|
24
|
Piozzi GN, Kim JS, Choo JM, Shin SH, Kim JS, Lee TH, Baek SJ, Kwak JM, Kim J, Kim SH. Da Vinci SP robotic approach to colorectal surgery: two specific indications and short-term results. Tech Coloproctol 2022; 26:461-470. [PMID: 35182278 DOI: 10.1007/s10151-022-02597-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 02/04/2022] [Indexed: 01/17/2023]
Abstract
BACKGROUND Da Vinci® Single Port (dvSP) was recently developed. Its application in colorectal surgery is under investigation. The aim of this study was to explore the safety and feasibility of dvSP for intersphincteric (dvSP-ISR), right colectomy (dvSP-RC), and transverse colectomy (dvSP-TC). Surgical indication and short-term results were analyzed. METHODS All consecutive patients from a prospective database of patients who underwent dvSP-ISR, dvSP-RC, and dvSP-TC at Korea University Anam Hospital from November 2020 to December 2021, were analyzed. Perioperative, pathological, and oncological short-term outcomes were analyzed. RESULTS A total of 7 dvSP-ISR, 5 dvSP-RC, and 1 dvSP-TC were performed. Median age was 56.0 (55.0-61.0) years for the dvSP-ISR and 54.0 (44.7-63.5) years for the dvSP-RC/TC. Median body mass index was 22.8 (17.1-24.8) kg/m2 for the dvSP-ISR and 23.6 (20.8-26.9) kg/m2 for the dvSP-RC/TC. All dvSP-ISR patients received neoadjuvant long-course chemoradiotherapy, including one patient with squamocellular carcinoma who was treated with 5-fluorouracil (5-FU)/mitomycin. All other patients, excluding one dvSP-RC patient with Crohn's disease, had an adenocarcinoma. Median operation time was 280 (240-370) minutes for the dvSP-ISR and 220 (201-270) minutes for the dvSP-RC/TC. Estimated blood loss was insignificant. No intraoperative complications or conversions to multiport/open surgery was reported. Median post-operative stay was 7.0 (6.0-10.0) days for the dvSP-ISR and 5.0 (4.0-6.7) days for the dvSP-RC/TC. Quality of mesorectum was complete for six patients, and nearly complete for one. Median number of retrieved lymph nodes were 21 (17-25) for the dvSP-ISR and 28 (24-49) for the dvSP-RC/TC. Proximal and distal resection margins were tumor free. Four patients experienced post-operative complications not related to the platform which were: ileus, voiding dysfunction, infected pelvic hematoma, and wound infection. Median follow-up was 9 (6-11) months and 11 (7-17) months for the dvSP-ISR and dvSP-RC/TC, respectively. Two patients had systemic recurrence; all others were tumor free. CONCLUSIONS The dvSP platform is safe and feasible for intersphincteric resection with right lower quadrant access, and right/transverse colectomy with suprapubic access. Further studies are needed to evaluate benefit differences compared to multiport robotic platform.
Collapse
Affiliation(s)
- G N Piozzi
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - J-S Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - J M Choo
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - S H Shin
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - J S Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - T-H Lee
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - S-J Baek
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - J-M Kwak
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - J Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - S H Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73 Goryodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
| |
Collapse
|
|
25
|
Zylstra J, Whyte GP, Beckmann K, Pate J, Santaolalla A, Gervais-Andre L, Russell B, Maisey N, Waters J, Tham G, Lagergren J, Green M, Kelly M, Baker C, Van Hemelrijck M, Goh V, Gossage J, Browning M, Davies A. Exercise prehabilitation during neoadjuvant chemotherapy may enhance tumour regression in oesophageal cancer: results from a prospective non-randomised trial. Br J Sports Med 2022; 56:402-409. [PMID: 35105604 DOI: 10.1136/bjsports-2021-104243] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/06/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND There is increasing evidence for the use of exercise in cancer patients and data supporting enhanced tumour volume reduction following chemotherapy in animal models. To date, there is no reported histopathological evidence of a similar oncological benefit in oesophageal cancer. METHODS A prospective non-randomised trial compared a structured prehabilitation exercise intervention during neoadjuvant chemotherapy and surgery versus conventional best-practice for oesophageal cancer patients. Biochemical and body composition analyses were performed at multiple time points. Outcome measures included radiological and pathological markers of disease regression. Logistic regression calculated ORs with 95% CI for the likelihood of pathological response adjusting for chemotherapy regimen and chemotherapy delivery. RESULTS Comparison of the Intervention (n=21) and Control (n=19) groups indicated the Intervention group had higher rates of tumour regression (Mandard TRG 1-3 Intervention n=15/20 (75%) vs Control n=7/19 (36.8%) p=0.025) including adjusted analyses (OR 6.57; 95% CI 1.52 to 28.30). Combined tumour and node downstaging (Intervention n=9 (42.9%) vs Control n=3 (15.8%) p=0.089) and Fat Free Mass index were also improved (Intervention 17.8 vs 18.7 kg/m2; Control 16.3 vs 14.7 kg/m2, p=0.026). Differences in markers of immunity (CD-3 and CD-8) and inflammation (IL-6, VEGF, INF-y, TNFa, MCP-1 and EGF) were observed. CONCLUSION The results suggest improved tumour regression and downstaging in the exercise intervention group and should prompt larger studies on this topic. TRIAL REGISTRATION NUMBER NCT03626610.
Collapse
Affiliation(s)
- Janine Zylstra
- Gastrointestinal Medicine and Surgery, Guy's and St Thomas' Hospitals NHS Trust, London, UK.,School of Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK
| | - Greg P Whyte
- School of Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK.,Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK.,Centre for Health and Human Performance, London, UK
| | - Kerri Beckmann
- School of Cancer and Pharmaceutical Studies, King's College London, London, UK
| | - James Pate
- Centre for Health and Human Performance, London, UK
| | - Aida Santaolalla
- School of Cancer and Pharmaceutical Studies, King's College London, London, UK
| | | | - Beth Russell
- School of Cancer and Pharmaceutical Studies, King's College London, London, UK
| | - Nick Maisey
- Oncology, Guy's and St Thomas' Hospitals NHS Trust, London, UK
| | - Justin Waters
- Oncology, Maidstone and Tunbridge Wells NHS Trust, Maidstone, UK
| | - Gemma Tham
- Physiotherapy, Guy's and St Thomas' Hospitals NHS Trust, London, UK
| | - Jesper Lagergren
- School of Cancer and Pharmaceutical Studies, King's College London, London, UK
| | - Michael Green
- Pathology, Guy's and St Thomas' Hospitals NHS Trust, London, UK
| | - Mark Kelly
- Gastrointestinal Medicine and Surgery, Guy's and St Thomas' Hospitals NHS Trust, London, UK
| | - Cara Baker
- Gastrointestinal Medicine and Surgery, Guy's and St Thomas' Hospitals NHS Trust, London, UK
| | | | - Vicky Goh
- Clinical Cancer Imaging, King's College London, London, UK
| | - James Gossage
- Gastrointestinal Medicine and Surgery, Guy's and St Thomas' Hospitals NHS Trust, London, UK
| | - Mike Browning
- Anaesthesia and Intensive Care Medicine, Maidstone and Tunbridge Wells Hospital NHS Trust, Maidstone, UK
| | - Andrew Davies
- Gastrointestinal Medicine and Surgery, Guy's and St Thomas' Hospitals NHS Trust, London, UK .,School of Cancer and Pharmaceutical Studies, King's College London, London, UK
| |
Collapse
|
|
26
|
Immunotherapy for Esophageal Cancer: State-of-the Art in 2021. Cancers (Basel) 2022; 14:cancers14030554. [PMID: 35158822 PMCID: PMC8833794 DOI: 10.3390/cancers14030554] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/19/2022] [Accepted: 01/20/2022] [Indexed: 02/01/2023] Open
Abstract
The management of esophageal cancer (EC) has experienced manifold changes during the last decades. Centralization of EC treatment has been introduced in many countries, subsequently allowing the development of specialized high-volume centers. Minimal invasive surgery has replaced open surgery in many centers, whereas more potent systemic treatments have been introduced in clinical practice. Newer chemotherapy regimens increase long-term survival. Nevertheless, the overall survival of EC patients remains dismal for advanced tumor stages. In this direction, a wide range of targeted biologic agents (immunotherapy) is currently under assessment. Anti- Human Epidermal Growth Factor Receptor-2 (HER-2) monoclonal antibodies are used in HER2 (+) tumors, predominantly well-differentiated adenocarcinomas, and are currently assessed in the neoadjuvant setting (TRAP, INNOVATION trials). Immune checkpoint inhibitors Nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181), have demonstrated a survival benefit compared with conventional chemotherapy in heavily pre-treated progressive disease. More recently, CheckMate-577 showed very promising results for nivolumab in a curative adjuvant setting, improving disease-free survival mainly for esophageal squamous cell carcinoma. Several ongoing trials are investigating novel targeted agents in the preoperative setting of locally advanced EC. In addition, other immunomodulatory approaches such as peptide vaccines and tumor infiltrating lymphocytes (TILs) are currently under development and should be increasingly integrated into clinical practice.
Collapse
|
|
27
|
Kim S, Yeo MK, Kim JS, Kim JY, Kim KH. Elevated CXCL12 in the plasma membrane of locally advanced rectal cancer after neoadjuvant chemoradiotherapy: a potential prognostic marker. J Cancer 2022; 13:162-173. [PMID: 34976180 PMCID: PMC8692683 DOI: 10.7150/jca.64082] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 11/10/2021] [Indexed: 02/07/2023] Open
Abstract
Background: Neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) has been shown to improve sphincter preservation and local pelvic control, but the efficacy of nCRT plateaus due to metastasis. CXC chemokine ligand 12 (CXCL12) has a critical impact on cancer development and metastasis. Methods: By investigating public databases containing LARC patient data, CXCL12, CXCR4 and FAPα expression was analyzed via the Tumor Immune Estimation Resource (TIMER) and GSEA. Immunohistochemistry was applied to a total of 121 surgically resected specimens consisting of 61 LARCs after nCRT and 60 LARCs with no nCRT and 16 cases with endoscopic resection of high-grade colorectal adenoma. Results: By investigating public databases containing LARC patient data, CXCL12 expression is correlated with poor prognosis, immune cell infiltration, epithelial- mesenchymal transition, and angiogenesis in LARC. Furthermore, radiation selectively induced CXCL12, CXCR4 and FAPα expression in tumor tissues. Immunohistochemistry results showed that the levels of CXCL12, CXCR4, and FAPα in LARC cells after nCRT were higher than in LARC cells untreated with nCRT (p < 0.001 for each). Elevated levels of CXCL12 in the plasma membrane of LARC cells after nCRT demonstrated an association with the period of freedom from recurrence (FFR) in univariate and multivariate survival analyses (p = 0.005 and p = 0.031, respectively). Conclusions: The expression of CXCL12 may influence the survival and invasive properties of LARC cells during nCRT and promote cancer recurrence. We suggest that CXCL12 expression in the plasma membrane of radioresistant LARC cells may be a predictive factor of recurrence and a viable therapeutic strategy to control radioresistant LARC recurrence.
Collapse
Affiliation(s)
- Sup Kim
- Department of Radiation Oncology, Chungnam National University School of Medicine, 288 Munhwa Street, Daejeon 35015, Korea.,Department of Radiation Oncology, Chungnam National University Hospital, 282 Munwha-ro, Daejeon 35015, Korea
| | - Min-Kyung Yeo
- Department of Pathology, Chungnam National University School of Medicine, 266 Munhwa Street, Daejeon 35015, Korea.,Department of Pathology, Chungnam National University Hospital, 282 Munwha-ro, Daejeon 35015, Korea
| | - Jun-Sang Kim
- Department of Radiation Oncology, Chungnam National University School of Medicine, 288 Munhwa Street, Daejeon 35015, Korea.,Department of Radiation Oncology, Chungnam National University Hospital, 282 Munwha-ro, Daejeon 35015, Korea
| | - Ji-Yeon Kim
- Department of Surgery, Division of Colorectal Surgery, Chungnam National University School of Medicine, Daejeon, Republic of Korea
| | - Kyung-Hee Kim
- Department of Pathology, Chungnam National University School of Medicine, 266 Munhwa Street, Daejeon 35015, Korea.,Department of Pathology, Chungnam National University Sejong Hospital, 20 Bodeum 7-ro, Sejong-si 30099, Korea
| |
Collapse
|
|
28
|
Lutsyk M, Turgeman I, Bar-Sela G. Rapid Initiation of Neoadjuvant Chemoradiotherapy After Diagnosis is Associated With Improved Pathologic Response in Locally Advanced Rectal Cancer. Am J Clin Oncol 2022; 45:1-8. [PMID: 34857697 DOI: 10.1097/coc.0000000000000872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
INTRODUCTION In rectal cancer, neoadjuvant chemoradiation (NCRT) is preferred because of toxicity profile, improved resectability and sphincter preservation, although with no impact on overall survival. Pathologic complete response (pCR) to NCRT has been linked with longer disease-free survival (DFS). The study purpose was to evaluate an association between clinical factors and treatment schedule with tumor response and treatment outcome, among patients with locally advanced rectal cancer. PATIENTS AND METHODS In this single-center retrospective study, conducted over 9 years (2011 to 2020), patients with stage II to III rectal cancer who had received NCRT were enrolled. The standard radiotherapy was 45 Gy to the pelvis, with a simultaneous integrated 50 Gy boost to the primary tumor. Continuous 5-Fluorouracil or oral capecitabine was administered concurrently. Surgery was preplanned within 6 to 8 weeks. Multinomial logistic regressions for evaluation of clinical factors, Kaplan-Meier method for DFS estimation, and receiver operating characteristic analysis for determination of the optimal timeframe were used. RESULTS Of 279 cases, pCR was observed in 72 (25.8%). In 207 cases, pTis-4N-negative was obtained in 137 (66.2%), pT0N-positive in 6 (2.9%), and pTis-4N-positive in 64 (30.9%). The pCR group had shorter diagnosis-NCRT time (P<0.01) and on-treatment time (P=0.05). DFS was longer for pCR and partial responders with clinical stage II and III (P<0.0001). Diagnosis-NCRT time was shown different between pCR and non-pCR groups. receiver operating characteristic analysis (P<0.01) showed that a diagnosis-NCRT time of <4.5 weeks predicts pCR with a sensitivity of 88% and specificity of 81% accuracy. CONCLUSION The time elapsed between rectal cancer diagnosis and NCRT initiation is significantly associated with pCR. Reducing this time may increase the probability of achieving pCR.
Collapse
Affiliation(s)
| | | | - Gil Bar-Sela
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa
- Cancer Center, Emek Medical Center, Afula, Israel
| |
Collapse
|
|
29
|
Evans RP, Kamarajah SK, Kunene V, Zardo D, Elshafie M, Griffiths EA. Impact of neoadjuvant chemotherapy on nodal regression and survival in oesophageal adenocarcinoma. Eur J Surg Oncol 2021; 48:1001-1010. [PMID: 34974947 DOI: 10.1016/j.ejso.2021.12.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 11/02/2021] [Accepted: 12/17/2021] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND The prognostic value of lymph node regression (LNR) following neoadjuvant chemotherapy (nCT) for oesophageal and gastro-oeosphageal adenocarcinoma remains unclear. This study aimed to characterise the long-term survival outcomes of LNR in patients having resectional surgery after nCT. METHODS This study included patients undergoing oesophagectomy or extended total gastrectomy for oesophageal and junctional tumours (Siewert types 1,2,3) at the Queen Elizabeth Hospital Birmingham from 2012 to 2018. Lymph nodes retrieved at surgery were examined for evidence of a response to chemotherapy. Patients were classified as lymph node-negative (either negative nodes with no evidence of previous tumour involvement or negative with evidence of complete regression) or positive with either partial or no response. RESULTS This study identified 183 patients who received nCT, of which 71% (130/183) had positive lymph nodes. Of these 130 patients, 44% (57/130) had a lymph node response and 56% (73/130) did not. The remaining 53 patients (29.0%) had negative lymph nodes with no evidence of tumour. Lymph node responders had a significant survival benefit compared to patients without lymph node response, but shorter than those with negative lymph nodes (median: 27 vs 18 vs NR months, p < 0·001). On multivariable analysis, lymph node responders had an improved overall (Hazard ratio (HR): 0.86, 95% CI: 0.80-0.92, p < 0.001) and recurrence-free (HR: 0.90, 95% CI: 0.82-0.98, p = 0.030) survival. CONCLUSION Lymph node regression is an important prognostic factor, warranting closer evaluation over primary tumour response to help with planning further adjuvant therapy in these patients.
Collapse
Affiliation(s)
- Richard Pt Evans
- Department of Upper Gastrointestinal Surgery, University Hospitals Birmingham NHS Foundation Trust, UK; Institute of Immunology and Immunotherapy, University of Birmingham, UK
| | - Sivesh K Kamarajah
- Department of Upper Gastrointestinal Surgery, University Hospitals Birmingham NHS Foundation Trust, UK; Institute of Cancer and Genomic Science, University of Birmingham, UK
| | - Victoria Kunene
- Department of Oncology, University Hospitals Birmingham NHS Foundation Trust, UK
| | - Davide Zardo
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Department of Pathology, San Bortolo Hospital, Vicenza, Italy
| | - Mona Elshafie
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Ewen A Griffiths
- Department of Upper Gastrointestinal Surgery, University Hospitals Birmingham NHS Foundation Trust, UK; Institute of Cancer and Genomic Science, University of Birmingham, UK.
| |
Collapse
|
|
30
|
Shi C, Badgwell BD, Grabsch HI, Gibson MK, Hong SM, Kumarasinghe P, Lam AK, Lauwers G, O'Donovan M, van der Post RS, Tang L, Ushiku T, Vieth M, Selinger CI, Webster F, Nagtegaal ID. Data Set for Reporting Carcinoma of the Stomach in Gastrectomy. Arch Pathol Lab Med 2021; 146:1072-1083. [DOI: 10.5858/arpa.2021-0225-oa] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/19/2021] [Indexed: 11/06/2022]
Abstract
Context.—
A standardized detailed surgical pathology report is the cornerstone of gastric cancer management.
Objective.—
To guide management and prognostication for patients with gastric carcinomas globally, the International Collaboration on Cancer Reporting aimed to produce an evidence-based international pathology reporting data set with a panel of globally recognized expert pathologists and clinicians.
Design.—
Based on published guidelines/data sets for gastric carcinomas, a working draft was developed by the chair of the expert panel of pathologists and clinicians. The draft was then circulated to the panel and discussed in a series of teleconferences and email communications until consensus was achieved. The draft data set was uploaded on the International Collaboration on Cancer Reporting Web site for public comment. The data set was reviewed in consideration of the feedback, and a final version was approved by the panel.
Results.—
This data set was developed for gastrectomy specimens for primary gastric carcinomas, including neuroendocrine carcinomas and mixed neuroendocrine-nonneuroendocrine neoplasms. Well-differentiated neuroendocrine tumors, nonepithelial malignancies, and secondary tumors were excluded from this data set. The final data set contains 15 core (required) elements and 8 noncore (recommended) elements. A commentary is provided for each element.
Conclusions.—
The International Collaboration on Cancer Reporting has published freely available, evidence-based data sets for gastric cancer reporting. Standardized reporting has been shown to improve patient care and facilitates data exchange and analysis for quality assurance, cancer epidemiology, and clinical and basic research.
Collapse
Affiliation(s)
- Chanjuan Shi
- From the Department of Pathology, Duke University School of Medicine, Durham, North Carolina (Shi)
| | - Brian D. Badgwell
- The Division of Surgery, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston (Badgwell)
| | - Heike I. Grabsch
- The Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands (Grabsch)
- The Division of Pathology & Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom (Grabsch)
| | - Michael K. Gibson
- The Division of Hematology and Oncology, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee (Gibson)
| | - Seung-Mo Hong
- The Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (Hong)
| | - Priyanthi Kumarasinghe
- PathWest Laboratory Medicine, PathWest QEII Medical Center, Perth, Australia (Kumarasinghe)
| | - Alfred K. Lam
- Pathology, School of Medicine, Gold Coast Campus, Griffith University, Gold Coast, Australia (Lam)
- Pathology Queensland, Gold Coast University Hospital, Southport, Australia (Lam)
- Faculty of Medicine, The University of Queensland, Herston, Australia (Lam)
| | - Gregory Lauwers
- The Department of Pathology, Moffitt Cancer Center, Tampa, Florida (Lauwers)
| | - Maria O'Donovan
- The Histopathology Department, Cambridge University Hospitals NHS Foundation Trust Addenbrookes Hospital, Cambridge, United Kingdom (O'Donovan)
| | - Rachel S. van der Post
- The Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands (van der Post and Nagtegaal)
| | - Laura Tang
- The Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, New York, (Tang)
| | - Tetsuo Ushiku
- The Department of Pathology and Diagnostic Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan (Ushiku)
| | - Michael Vieth
- The Institute of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, Klinikum Bayreuth, Germany (Vieth)
| | | | - Fleur Webster
- The International Collaboration on Cancer Reporting, Sydney, Australia (Webster)
| | - Iris D. Nagtegaal
- The Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands (van der Post and Nagtegaal)
| |
Collapse
|
|
31
|
Tsekrekos A, Vieth M, Ndegwa N, Bateman A, Flejou JF, Grabsch HI, Mastracci L, Meijer SL, Saragoni L, Sheahan K, Shetye J, Yantiss R, Lundell L, Detlefsen S. Interobserver agreement of a gastric adenocarcinoma tumor regression grading system that incorporates assessment of lymph nodes. Hum Pathol 2021; 116:94-101. [PMID: 34284051 DOI: 10.1016/j.humpath.2021.07.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 07/08/2021] [Accepted: 07/10/2021] [Indexed: 02/06/2023]
Abstract
Perioperative chemotherapy is increasingly used in combination with surgery for the treatment of patients with locally advanced, resectable gastric cancer. Histologic tumor regression grade (TRG) has emerged as an important prognostic factor; however, a common standard for its evaluation is lacking. Moreover, the clinical significance of regressive changes in metastatic lymph nodes (LNs) remains unclear. We conducted an international study to examine the interobserver agreement of a TRG system that is based on the Becker system for the primary tumors and additionally incorporates regression grading in LNs. Twenty observers at different levels of experience evaluated the TRG in 60 histologic slides (30 primary tumors and 30 LNs) based on the following criteria: for primary tumors, grade 1 represented complete response (no residual tumor), grade 2 represented <10%, grade 3 represented 10-50%, and grade 4 represented >50% residual tumor, as described by Becker et al. For LNs, grade "a" represented complete, grade "b" represented partial, and grade "c" represented no regression. The interobserver agreement was estimated using the Kendall's coefficient of concordance (W). Regarding primary tumors, agreement was good irrespective of the level of experience, reaching a W-value of 0.70 overall, 0.71 among subspecialized, and 0.71 among nonsubspecialized observers. Regarding LNs, interobserver agreement was moderate to good, with W-values of 0.52 overall, 0.64 among subspecialized, and 0.45 among nonsubspecialized observers. These findings indicate that the combination of the Becker TRG system with a three-tiered grading of regression in LNs generates a system that is reproducible. Future studies should investigate whether the additional information of TRG in LNs adds to the prognostic value of histologic regression grading in gastric cancer specimens.
Collapse
Affiliation(s)
- Andrianos Tsekrekos
- Department of Upper Abdominal Surgery, Karolinska University Hospital, 141 57 Stockholm, Sweden; Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, 141 57 Stockholm, Sweden.
| | - Michael Vieth
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Klinikum Bayreuth, 95445 Bayreuth, Germany
| | - Nelson Ndegwa
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, 141 57 Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden
| | - Adrian Bateman
- Department of Cellular Pathology, Southampton General Hospital, Southampton SO16 6YD, UK
| | - Jean-François Flejou
- Service d'Anatomie Pathologique, Hôpital Saint-Antoine, AP-HP, Faculté de Médecine Sorbonne Université, 75012 Paris, France
| | - Heike I Grabsch
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, 6200 MD, the Netherlands; Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, LS2 9NL, UK
| | - Luca Mastracci
- Unit of Anatomic Pathology, Ospedale Policlinico San Martino IRCCS & Department of Surgical and Diagnostic Sciences (DISC), University of Genova, 16126 Genova, Italy
| | - Sybren L Meijer
- Department of Pathology, Amsterdam University Medical Center, 1105 AZ Amsterdam, the Netherlands
| | - Luca Saragoni
- Pathology Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy
| | - Kieran Sheahan
- Department of Pathology, St Vincent's University Hospital & UCD School of Medicine, Dublin 4, D04 T6F4, Ireland
| | - Jayant Shetye
- Department of Laboratory Medicine, Division of Pathology, Karolinska University Hospital, 141 57 Stockholm, Sweden
| | - Rhonda Yantiss
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10021, USA
| | - Lars Lundell
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, 141 57 Stockholm, Sweden; Department of Surgery, Odense University Hospital, 5000 Odense C, Denmark
| | - Sönke Detlefsen
- Department of Pathology, Odense University Hospital & Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense C, Denmark
| |
Collapse
|
|
32
|
Lieto E, Auricchio A, Tirino G, Pompella L, Panarese I, Del Sorbo G, Ferraraccio F, De Vita F, Galizia G, Cardella F. Naples Prognostic Score Predicts Tumor Regression Grade in Resectable Gastric Cancer Treated with Preoperative Chemotherapy. Cancers (Basel) 2021; 13:4676. [PMID: 34572903 PMCID: PMC8471422 DOI: 10.3390/cancers13184676] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/29/2021] [Accepted: 09/14/2021] [Indexed: 02/03/2023] Open
Abstract
Despite recent progresses, locally advanced gastric cancer remains a daunting challenge to embrace. Perioperative chemotherapy and D2-gastrectomy depict multimodal treatment of gastric cancer in Europe, shows better results than curative surgery alone in terms of downstaging, micrometastases elimination, and improved long-term survival. Unfortunately, preoperative chemotherapy is useless in about 50% of cases of non-responder patients, in which no effect is registered. Tumor regression grade (TRG) is directly related to chemotherapy effectiveness, but its understanding is achieved only after surgical operation; accordingly, preoperative chemotherapy is given indiscriminately. Conversely, Naples Prognostic Score (NPS), related to patient immune-nutritional status and easily obtained before taking any therapeutic decision, appeared an independent prognostic variable of TRG. NPS was calculated in 59 consecutive surgically treated gastric cancer patients after neoadjuvant FLOT4-based chemotherapy. 42.2% of positive responses were observed: all normal NPS and half mild/moderate NPS showed significant responses to chemotherapy with TRG 1-3; while only 20% of the worst NPS showed some related benefits. Evaluation of NPS in gastric cancer patients undergoing multimodal treatment may be useful both in selecting patients who will benefit from preoperative chemotherapy and for changing immune-nutritional conditions in order to improve patient's reaction against the tumor.
Collapse
Affiliation(s)
- Eva Lieto
- Division of GI Tract Surgical Oncology, Department of Translational Medical Sciences, Vanvitelli University, 80132 Napoli, Italy; (A.A.); (G.D.S.); (G.G.); (F.C.)
| | - Annamaria Auricchio
- Division of GI Tract Surgical Oncology, Department of Translational Medical Sciences, Vanvitelli University, 80132 Napoli, Italy; (A.A.); (G.D.S.); (G.G.); (F.C.)
| | - Giuseppe Tirino
- Division of Medical Oncology, Department of Precision Medicine, Vanvitelli University, 80132 Napoli, Italy; (G.T.); (L.P.); (F.D.V.)
| | - Luca Pompella
- Division of Medical Oncology, Department of Precision Medicine, Vanvitelli University, 80132 Napoli, Italy; (G.T.); (L.P.); (F.D.V.)
| | - Iacopo Panarese
- Division of Pathology, Department of Mental and Physical Health and Rehabilitation Medicine, Vanvitelli University, 80132 Napoli, Italy; (I.P.); (F.F.)
| | - Giovanni Del Sorbo
- Division of GI Tract Surgical Oncology, Department of Translational Medical Sciences, Vanvitelli University, 80132 Napoli, Italy; (A.A.); (G.D.S.); (G.G.); (F.C.)
| | - Francesca Ferraraccio
- Division of Pathology, Department of Mental and Physical Health and Rehabilitation Medicine, Vanvitelli University, 80132 Napoli, Italy; (I.P.); (F.F.)
| | - Ferdinando De Vita
- Division of Medical Oncology, Department of Precision Medicine, Vanvitelli University, 80132 Napoli, Italy; (G.T.); (L.P.); (F.D.V.)
| | - Gennaro Galizia
- Division of GI Tract Surgical Oncology, Department of Translational Medical Sciences, Vanvitelli University, 80132 Napoli, Italy; (A.A.); (G.D.S.); (G.G.); (F.C.)
| | - Francesca Cardella
- Division of GI Tract Surgical Oncology, Department of Translational Medical Sciences, Vanvitelli University, 80132 Napoli, Italy; (A.A.); (G.D.S.); (G.G.); (F.C.)
| |
Collapse
|
|
33
|
Han Y, Xuan Y, Liu X, Zhu H, Zhang M, Xu D, Wang Y, Cai H. Development of a Quantitative Diagnostic Criterion for Gastric Linitis Plastica: Findings From a Large Single-Institutional Study. Front Oncol 2021; 11:683608. [PMID: 34422637 PMCID: PMC8377468 DOI: 10.3389/fonc.2021.683608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 07/15/2021] [Indexed: 01/17/2023] Open
Abstract
Gastric linitis plastica (GLP) is a descriptive term but lacks a quantitative definition. Several relatively quantitative criteria had been proposed, such as tumor involving a limit of one-third or two-thirds of the gastric surface. However, these criteria needed doctors to subjectively judge tumor infiltration area, which made diagnosis difficult to be objective and reproducible. This study aimed to propose a quantitative diagnostic criterion for distinguishing GLP. We performed a retrospective cohort study of 2,907 patients with Borrmann III and IV gastric cancer (GC) who underwent gastrectomy between 2011 and 2018 in our center. The Kaplan–Meier curves showed that patients with an observed tumor size more than 8 cm had obviously lower overall survival (OS) and disease-free survival (DFS) rates than those with a size less than 8 cm(p < 0.001; p < 0.001). However, there was no significantly different prognosis of patients with tumor sizes between more than 8 cm and more than 10 cm (p = 0.248; p = 0.534). Moreover, patients with tumor sizes greater than 8 cm more presented with advanced stage and had extremely poor 3-year OS and DFS (31.4%; 29.3%), with a stronger propensity toward peritoneal metastasis. Therefore, we considered patients’ observed tumor size more than 8 cm as a critical value for distinguishing the prognosis of Borrmann III and IV GC. Furthermore, we proposed an observed tumor size more than 8 cm as a quantitative diagnostic criterion for GLP on the premise of satisfying the originally descriptive and pathological definition regardless of Borrmann type.
Collapse
Affiliation(s)
- Yang Han
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yi Xuan
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiaowen Liu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hui Zhu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Meng Zhang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Dazhi Xu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yanong Wang
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hong Cai
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| |
Collapse
|
|
34
|
Rizvi F, Shaukat L, Azhar A, Jafri A, Aslam U, Imran-ul-Haq H. Preclinical meritorious anticancer effects of Metformin against breast cancer: An In vivo trial. J Taibah Univ Med Sci 2021; 16:504-512. [PMID: 34408607 PMCID: PMC8348326 DOI: 10.1016/j.jtumed.2021.02.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 02/02/2021] [Accepted: 02/08/2021] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE This research aims to evaluate the preclinical meritorious and anticancer effects of Metformin in a Xenograft model of breast cancer. METHODS This interventional trial was conducted during a defined period of 5 months (August 2016 January 2017). We used a Xenograft model of nude BALB/c mice. A sample size of 50 mice, allocated into two groups and designated as Group A and Group B for Metformin and negative control groups, respectively. The anticancer activity of Metformin has been evaluated by comparing the tumour volume, tumour weight, tumour regression ratio, percentage regression, and survival rate. RESULTS Compared with the control group, Metformin can significantly reduce the progression of tumour in the Xenograft model of breast cancer induced by MCF-7. This is reflected by significant differences in tumour volume at the final follow-up (p = <0.001). Our findings are further supported by a significant reduction of the tumour growth rate (p = <0.001) and tumour weight (p = <0.001) in the Metformin group than in the control group. Similarly, the total survival rate and tumour regression are more significantly correlated in the Metformin group. CONCLUSION This study demonstrates that Metformin can significantly reduce the tumour growth and can increase the survival rate in a Xenograft model of breast cancer.
Collapse
Affiliation(s)
- Fatima Rizvi
- Dow International Medical College (DUHS), Department of Pharmacology, Karachi, Pakistan
| | - Lubna Shaukat
- DUHS, Department of Oral and Maxillofacial Surgery, Karachi, Pakistan
| | - Arfa Azhar
- AKUH, Department of Biological and Biomedical Sciences, Karachi, Pakistan
| | - Alia Jafri
- Department of Biochemistry Institute, JSMU, Karachi, Pakistan
| | | | | |
Collapse
|
|
35
|
Liu Z, Wang Y, Shan F, Ying X, Zhang Y, Li S, Jia Y, Miao R, Xue K, Li Z, Li Z, Ji J. Treatment Switch in Poor Responders with Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy. Ann Surg Oncol 2021; 28:8892-8907. [PMID: 34327603 PMCID: PMC8591025 DOI: 10.1245/s10434-021-10087-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 04/10/2021] [Indexed: 11/20/2022]
Abstract
Background Among locally advanced gastric cancer (LAGC) patients, poor response to initial neoadjuvant chemotherapy (NAC) is associated with unfavorable outcomes; however, changing the postoperative therapy regimen in this group of patients is unclear. We compared the poor responders who continued the original protocols with that of patients who switched treatment after NAC plus D2 gastrectomy. Methods Our study included LAGC patients who achieved tumor regression grade 3 according to the American Joint Committee on Cancer/College of American Pathologists system, after NAC, between December 2006 and December 2017 at our institution. Outcomes were overall survival (OS), progression-free survival (PFS), and adverse events during postoperative treatment. The propensity score matching method was used to match patients. Results Overall, 160 patients were enrolled in the final analysis set, including 21 switched cases and 139 non-switched cases. A 1:2 matched cohort (21 switching vs. 42 non-switching) was generated to eliminate all confounding factors. No statistical differences were observed in OS and PFS, either in the whole patients (OS: log-rank p = 0.804; PFS: log-rank p = 0.943) or in the matched cohort (OS: log-rank p = 0.907; PFS: log-rank p = 0.670) between the two groups. Patients with changed regimens had a significantly higher rate of peripheral neurotoxicity (p = 0.045). Contrarily, a lower rate of overall adverse events was observed in the non-switching group with marginal significance (p = 0.069). Conclusion Adjusting to a non-cross-resistant regimen only by post-NAC pathological evaluation may not be sufficient for designing an effective treatment route for LAGC poor responders. Treatment change required a more scrutinized clinical track, which involved a multifaceted assessment. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-021-10087-x.
Collapse
Affiliation(s)
- Zining Liu
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yinkui Wang
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Fei Shan
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Xiangji Ying
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yan Zhang
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Shuangxi Li
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Yongning Jia
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Rulin Miao
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Kan Xue
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhemin Li
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Ziyu Li
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China.
| | - Jiafu Ji
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China.
| |
Collapse
|
|
36
|
Lütken C, Sheikh K, Willemoe GL, Achiam MP, Hasselby JP. Clinical assessment of tumor regression grade systems in gastroesophageal adenocarcinoma following neoadjuvant chemotherapy. Pathol Res Pract 2021; 224:153538. [PMID: 34243107 DOI: 10.1016/j.prp.2021.153538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 06/22/2021] [Indexed: 11/25/2022]
Abstract
BACKGROUND The standard treatment for gastroesophageal cancer is neoadjuvant chemotherapy, followed by surgery, which has been shown to increase survival compared with surgery alone. Evidence is mounting that characterization of the oncologically induced tumor regression is of prognostic importance. However, no consensus regarding the optimal system for describing tumor regression exists. Thus, this study aims to explore three validated/promising tumor regression systems with a focus on their interobserver reliability and usability. METHODS We included 100 consecutive patients with gastroesophageal adenocarcinoma who had undergone neoadjuvant oncological treatment followed by surgery. The tumors underwent tumor regression grade (TRG) assessment according to the Standard Mandard-, Modified Mandard-, and Becker systems to assess the interobserver reliability between two consultant pathologists. The interobserver reliability was determined by both Fleiss kappa and weighted kappa metrics. Besides, a semi-quantitative usability questionary was completed and it was expanded with usability comments. RESULTS The Fleiss kappa interobserver agreement was 0.67 [95% CI, 0.55-0.79], 0.88 [95% CI, 0.73-1.00], and 0.88 [95% CI, 0.73-1.00] for Standard Mandard-, Modified Mandard-, and the Becker systems, respectively. The weighted kappa (linear) was 0.80 [95% CI, 0.72-0.89], 0.91 [95% CI, 0.84-0.98], and 0.91 [95% CI, 0.84-0.98] for the Standard Mandard-, Modified Mandard-, and the Becker systems, respectively. The usability was scored on a scale of 8-24 by both raters. The systems were scored accordingly: 47 (Modified Mandard system), 43 (Becker system), and 37 (Standard Mandard system). CONCLUSION The Modified Mandard- and Becker systems had excellent interobserver reliability and usability. However, the systems could be improved by a better characterization of the different tiers and tumor morphology.
Collapse
Affiliation(s)
- Christian Lütken
- Department of Surgical Gastroenterology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 7, 2100 Copenhagen Ø, Denmark
| | - Kiran Sheikh
- Department of Pathology, Herlev University hospital, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark
| | - Gro Linno Willemoe
- Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 14, 2100 Copenhagen Ø, Denmark
| | - Michael Patrick Achiam
- Department of Surgical Gastroenterology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 7, 2100 Copenhagen Ø, Denmark
| | - Jane Preuss Hasselby
- Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 14, 2100 Copenhagen Ø, Denmark.
| |
Collapse
|
|
37
|
Tapia C, Aung PP, Roy-Chowdhuri S, Xu M, Ouyang F, Alshawa A, Hajjar J, Singh G, Yang V, Castillo L, Le H, Murthy R, Stephen B, Hess KR, Wistuba I, Naing A. Decrease in tumor content assessed in biopsies is associated with improved treatment outcome response to pembrolizumab in patients with rare tumors. J Immunother Cancer 2021; 8:jitc-2020-000665. [PMID: 32303619 PMCID: PMC7204618 DOI: 10.1136/jitc-2020-000665] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/18/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Decreased tumor content (TC) in resection specimens after neoadjuvant therapy is used to predict prognosis. We investigated whether TC assessed in biopsy specimens or the shift in TC from baseline to on-treatment can be used accordingly to predict response in patients with rare tumors who were treated with pembrolizumab. METHODS A total of 57 tumors (represented by 173 baseline and 179 on-treatment biopsies) from 57 patients with rare tumors participating in an ongoing phase II clinical trial of pembrolizumab were evaluated. TC was estimated on H&E-stained slides and tumors were dichotomized into low and high TC according to a cut-off of 10%. Necrosis, proliferative fibrosis (PF) and normal tissue were assessed in on-treatment biopsies. TC at baseline and on-treatment, as well as the shift in TC from baseline to on-treatment, was correlated with clinical response defined according to Response Evaluation Criteria in Solid Tumors. RESULTS A decrease in TC was seen in 14% (n=8); no change in TC was seen in 75% (n=43); and an increase in TC from baseline to on-treatment was seen in 11% (n=6). Objective response was significantly associated with decrease in TC from baseline to on-treatment (38%, 3/8) compared with no change/increase in TC (6%, 3/49) (p=0.031). Patients with a decrease in TC had a significantly increased time to progression (TTP) (75% probability) compared with patients with an increase (20% probability) or no change in TC (19% probability) (p=0.0042). Low TC was seen in 23% (13/57) of the tumors at baseline and in 26% (15/57) on-treatment. High TC was seen in 77% (44/57) of tumors at baseline and in 74% (42/57) on-treatment. No significant associations with response were seen for necrosis, PF or normal tissue in on-treatment biopsies. CONCLUSION Patients with a decrease in TC from baseline to on-treatment had a significant improvement in objective response and a longer TTP. Our data suggest that the shift in TC might be used to predict response to pembrolizumab in rare tumors. However, further investigations in larger cohorts are needed to determine the clinical value of TC, the shift in TC and the cut-off of 10% assessed in biopsies. TRIAL REGISTRATION NUMBER NCT02721732.
Collapse
Affiliation(s)
- Coya Tapia
- Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA .,Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Phyu P Aung
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sinchita Roy-Chowdhuri
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mingxuan Xu
- Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Fengying Ouyang
- Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Anas Alshawa
- Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Joud Hajjar
- Section of Immunology, Allergy and Rheumatology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA
| | - Gopal Singh
- Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Vincent Yang
- Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lilibeth Castillo
- Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hung Le
- Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ravi Murthy
- Department of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bettzy Stephen
- Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kenneth R Hess
- Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ignacio Wistuba
- Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Aung Naing
- Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| |
Collapse
|
|
38
|
Rodríguez-Tomàs E, Arenas M, Gómez J, Acosta J, Trilla J, López Y, Árquez M, Torres L, Araguas P, Hernández-Aguilera A, Baiges-Gaya G, Castañé H, Camps J, Joven J. Identification of potential metabolic biomarkers of rectal cancer and of the effect of neoadjuvant radiochemotherapy. PLoS One 2021; 16:e0250453. [PMID: 33886674 PMCID: PMC8062076 DOI: 10.1371/journal.pone.0250453] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 04/07/2021] [Indexed: 12/16/2022] Open
Abstract
We report a pilot study on the feasibility of determinations of circulating levels of paraoxonase-1 (PON1) and compounds related to energy metabolism as biomarkers for the evaluation of patients with rectal cancer (RC), and the effects produced by neoadjuvant radiochemotherapy (NRCT). We studied 32 patients treated with radiotherapy plus capecitabine concomitant chemotherapy and 48 control subjects. We identified pre-NRCT PON1 and α-ketoglutarate as the parameters that best discriminated between RC patients and the control group. Receiver operating characteristics analysis of the combination of the two parameters showed an area under the curve (AUC) of 0.918. Moreover, patients who presented a pathological complete response (pCR) to treatment had lower plasma pre-NRCT valine concentrations (AUC of 0.826). Patients who had a relapse had lower concentrations of succinate (AUC of 0.833). The results of the present study illustrate the usefulness of investigating alterations in oxidative stress and metabolism in RC. Due to the small number of patients studied, our results must be considered preliminary, but they suggest that the determination of circulating levels of PON1 and α-ketoglutarate might be a valuable tool for the early diagnosis of RC, while the determination of valine and succinate might effectively predict pCR and the appearance of relapse.
Collapse
Affiliation(s)
- Elisabet Rodríguez-Tomàs
- Unitat de Recerca Biomèdica, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| | - Meritxell Arenas
- Department of Radiation Oncology, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
- * E-mail: (MA); (JC)
| | - Junior Gómez
- Department of Radiation Oncology, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| | - Johana Acosta
- Department of Radiation Oncology, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| | - Jordi Trilla
- Department of Radiation Oncology, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| | - Yolanda López
- Department of Radiation Oncology, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| | - Miguel Árquez
- Department of Radiation Oncology, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| | - Laura Torres
- Department of Radiation Oncology, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| | - Pablo Araguas
- Department of Radiation Oncology, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| | - Anna Hernández-Aguilera
- Unitat de Recerca Biomèdica, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
- Department of Pathology, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| | - Gerard Baiges-Gaya
- Unitat de Recerca Biomèdica, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| | - Helena Castañé
- Unitat de Recerca Biomèdica, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| | - Jordi Camps
- Unitat de Recerca Biomèdica, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
- * E-mail: (MA); (JC)
| | - Jorge Joven
- Unitat de Recerca Biomèdica, Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain
| |
Collapse
|
|
39
|
Body Composition Changes in Gastric Cancer Patients during Preoperative FLOT Therapy: Preliminary Results of an Italian Cohort Study. Nutrients 2021; 13:nu13030960. [PMID: 33809587 PMCID: PMC7999770 DOI: 10.3390/nu13030960] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/10/2021] [Accepted: 03/12/2021] [Indexed: 01/19/2023] Open
Abstract
Background: The impact of the new chemotherapy, fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) on body composition in gastric cancer (GC) patients remains unknown. We assessed body composition changes of GC patients receiving the FLOT regimen and their impact on treatment outcomes. Methods: Preoperative pre- and post-FLOT computed tomography (CT) scans of advanced GC patients were studied. Lumbar skeletal muscle index (SMI) and adipose indices were calculated before and after FLOT. Results: A total of 26 patients were identified between April 2019 and January 2020. Nineteen patients were sarcopenic at diagnosis. The mean BMI decreased (from 24.4 ± 3.7 to 22.6 ± 3.1; p < 0.0001) as well as the SMI (from 48.74 ± 9.76 to 46.52 ± 9.98; p = 0.009) and visceral adipose index (VAI) (from 49.04 ± 31.06 to 41.99 ± 23.91; p = 0.004) during preoperative FLOT therapy. BMI, SMI, and VAI variations were not associated with toxicity, Response Evaluation Criteria in Solid Tumors (RECIST), response, delay and completion of perioperative FLOT chemotherapy, and the execution of gastrectomy; a decrease of SMI ≥ 5% was associated with a higher Mandard tumor regression grade (p = 0.01). Conclusions: Almost three-quarters (73.1%) of GC patients were sarcopenic at diagnosis. Preoperative FLOT was associated with a further reduction in SMI, BMI, and VAI. These changes were not associated with short-term outcomes.
Collapse
|
|
40
|
McDuff SGR, Hardiman KM, Ulintz PJ, Parikh AR, Zheng H, Kim DW, Lennerz JK, Hazar-Rethinam M, Van Seventer EE, Fetter IJ, Nadres B, Eyler CE, Ryan DP, Weekes CD, Clark JW, Cusack JC, Goyal L, Zhu AX, Wo JY, Blaszkowsky LS, Allen J, Corcoran RB, Hong TS. Circulating Tumor DNA Predicts Pathologic and Clinical Outcomes Following Neoadjuvant Chemoradiation and Surgery for Patients With Locally Advanced Rectal Cancer. JCO Precis Oncol 2021; 5:PO.20.00220. [PMID: 34250394 DOI: 10.1200/po.20.00220] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 10/16/2020] [Accepted: 11/19/2020] [Indexed: 12/13/2022] Open
Abstract
PURPOSE This study was designed to assess the ability of perioperative circulating tumor DNA (ctDNA) to predict surgical outcome and recurrence following neoadjuvant chemoradiation for locally advanced rectal cancer (LARC). MATERIALS AND METHODS Twenty-nine patients with newly diagnosed LARC treated between January 2014 and February 2018 were enrolled. Patients received long-course neoadjuvant chemoradiation prior to surgery. Plasma ctDNA was collected at baseline, preoperatively, and postoperatively. Next-generation sequencing was used to identify mutations in the primary tumor, and mutation-specific droplet digital polymerase chain reaction was used to assess mutation fraction in ctDNA. RESULTS The median age was 54 years. The overall margin-negative, node-negative resection rate was 73% and was significantly higher among patients with undetectable preoperative ctDNA (n = 17, 88%) versus patients with detectable preoperative ctDNA (n = 9, 44%; P = .028). Undetectable ctDNA was also associated with more favorable neoadjuvant rectal scores (univariate linear regression, P = .029). Recurrence-free survival (RFS) was calculated for the subset (n = 19) who both underwent surgery and had postoperative ctDNA available. At a median follow-up of 20 months, patients with detectable postoperative ctDNA experienced poorer RFS (hazard ratio, 11.56; P = .007). All patients (4 of 4) with detectable postoperative ctDNA recurred (positive predictive value = 100%), whereas only 2 of 15 patients with undetectable ctDNA recurred (negative predictive value = 87%). CONCLUSION Among patients treated with neoadjuvant chemoradiation for LARC, patients with undetectable preoperative ctDNA were more likely to have a favorable surgical outcome as measured by the rate of margin-negative, node-negative resections and neoadjuvant rectal score. Furthermore, we have confirmed prior reports indicating that detectable postoperative ctDNA is associated with worse RFS. Future prospective study is needed to assess the potential for ctDNA to assist with personalizing treatment for LARC.
Collapse
Affiliation(s)
- Susan G R McDuff
- Department of Radiation Oncology, Duke Cancer Center, Duke University Medical Center, Duke Medicine Circle, Durham, NC.,Harvard Radiation Oncology Program, Boston, MA
| | - Karin M Hardiman
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL
| | - Peter J Ulintz
- Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI
| | - Aparna R Parikh
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, MA
| | - Hui Zheng
- Biostatistics Center, Massachusetts General Hospital, Boston, MA
| | | | - Jochen K Lennerz
- Department of Pathology, Center for Integrated Diagnostics, Massachusetts General Hospital, Boston, MA
| | | | | | | | - Brandon Nadres
- Massachusetts General Hospital Cancer Center, Boston, MA
| | - Christine E Eyler
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| | - David P Ryan
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, MA
| | - Colin D Weekes
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, MA
| | - Jeffrey W Clark
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, MA
| | - James C Cusack
- The Division of Gastrointestinal and Oncologic Surgery, Massachusetts General Hospital, Boston, MA
| | - Lipika Goyal
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, MA
| | - Andrew X Zhu
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, MA.,Jiahui International Cancer Center, Jiahui Health, Shanghai, China
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| | - Lawrence S Blaszkowsky
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, MA
| | - Jill Allen
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, MA
| | - Ryan B Corcoran
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, MA.,Massachusetts General Hospital Cancer Center, Boston, MA
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| |
Collapse
|
|
41
|
van der Wielen N, Straatman J, Daams F, Rosati R, Parise P, Weitz J, Reissfelder C, Diez Del Val I, Loureiro C, Parada-González P, Pintos-Martínez E, Mateo Vallejo F, Medina Achirica C, Sánchez-Pernaute A, Ruano Campos A, Bonavina L, Asti ELG, Alonso Poza A, Gilsanz C, Nilsson M, Lindblad M, Gisbertz SS, van Berge Henegouwen MI, Fumagalli Romario U, De Pascale S, Akhtar K, Jaap Bonjer H, Cuesta MA, van der Peet DL. Open versus minimally invasive total gastrectomy after neoadjuvant chemotherapy: results of a European randomized trial. Gastric Cancer 2021; 24:258-271. [PMID: 32737637 PMCID: PMC7790799 DOI: 10.1007/s10120-020-01109-w] [Citation(s) in RCA: 90] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 07/17/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Surgical resection with adequate lymphadenectomy is regarded the only curative option for gastric cancer. Regarding minimally invasive techniques, mainly Asian studies showed comparable oncological and short-term postoperative outcomes. The incidence of gastric cancer is lower in the Western population and patients often present with more advanced stages of disease. Therefore, the reproducibility of these Asian results in the Western population remains to be investigated. METHODS A randomized trial was performed in thirteen hospitals in Europe. Patients with an indication for total gastrectomy who received neoadjuvant chemotherapy were eligible for inclusion and randomized between open total gastrectomy (OTG) or minimally invasive total gastrectomy (MITG). Primary outcome was oncological safety, measured as the number of resected lymph nodes and radicality. Secondary outcomes were postoperative complications, recovery and 1-year survival. RESULTS Between January 2015 and June 2018, 96 patients were included in this trial. Forty-nine patients were randomized to OTG and 47 to MITG. The mean number of resected lymph nodes was 43.4 ± 17.3 in OTG and 41.7 ± 16.1 in MITG (p = 0.612). Forty-eight patients in the OTG group had a R0 resection and 44 patients in the MITG group (p = 0.617). One-year survival was 90.4% in OTG and 85.5% in MITG (p = 0.701). No significant differences were found regarding postoperative complications and recovery. CONCLUSION These findings provide evidence that MITG after neoadjuvant therapy is not inferior regarding oncological quality of resection in comparison to OTG in Western patients with resectable gastric cancer. In addition, no differences in postoperative complications and recovery were seen.
Collapse
Affiliation(s)
- Nicole van der Wielen
- Department of Gastro-Intestinal Surgery, Amsterdam University Medical Center, Location VU University, De Boelelaan 1117, ZH 7F020, 1081 HV, Amsterdam, The Netherlands.
| | - Jennifer Straatman
- Department of Gastro-Intestinal Surgery, Amsterdam University Medical Center, Location VU University, De Boelelaan 1117, ZH 7F020, 1081 HV, Amsterdam, The Netherlands
- Department of Clinical Epidemiology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Freek Daams
- Department of Gastro-Intestinal Surgery, Amsterdam University Medical Center, Location VU University, De Boelelaan 1117, ZH 7F020, 1081 HV, Amsterdam, The Netherlands
| | | | - Paolo Parise
- Department of Surgery, San Raffaele Hospital, Milan, Italy
| | - Jürgen Weitz
- Department of Visceral-, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Dresden, Germany
| | - Christoph Reissfelder
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
| | | | - Carlos Loureiro
- Department of Surgery, Hospital Universitario de Basurto, Bilbao, Spain
| | | | - Elena Pintos-Martínez
- Department of Surgery, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | | | | | | | | | - Luigi Bonavina
- Department of Surgery, IRCCS Policlinico San Donato, Milan, Italy
| | | | | | - Carlos Gilsanz
- Department of Surgery, Hospital del Sureste, Madrid, Spain
| | - Magnus Nilsson
- Department of Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Mats Lindblad
- Department of Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Suzanne S Gisbertz
- Department of Gastro-intestinal Surgery, Amsterdam University Medical Center Location AMC, Amsterdam, The Netherlands
| | - Mark I van Berge Henegouwen
- Department of Gastro-intestinal Surgery, Amsterdam University Medical Center Location AMC, Amsterdam, The Netherlands
| | | | | | - Khurshid Akhtar
- Department of Surgery, Salford Royal NHS Foundation Trust, Manchester, UK
| | - H Jaap Bonjer
- Department of Gastro-Intestinal Surgery, Amsterdam University Medical Center, Location VU University, De Boelelaan 1117, ZH 7F020, 1081 HV, Amsterdam, The Netherlands
| | - Miguel A Cuesta
- Department of Gastro-Intestinal Surgery, Amsterdam University Medical Center, Location VU University, De Boelelaan 1117, ZH 7F020, 1081 HV, Amsterdam, The Netherlands
| | - Donald L van der Peet
- Department of Gastro-Intestinal Surgery, Amsterdam University Medical Center, Location VU University, De Boelelaan 1117, ZH 7F020, 1081 HV, Amsterdam, The Netherlands
| |
Collapse
|
|
42
|
Chen Q, Mao R, Zhao J, Bi X, Li Z, Huang Z, Zhang Y, Zhou J, Zhao H, Cai J. From the completion of neoadjuvant chemotherapy to surgery for colorectal cancer liver metastasis: What is the optimal timing? Cancer Med 2020; 9:7849-7862. [PMID: 32886456 PMCID: PMC7643690 DOI: 10.1002/cam4.3283] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 05/21/2020] [Accepted: 06/11/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) has been widely performed in the treatment of colorectal cancer liver metastasis (CRLM) patients, but the optimal timing of surgery after NAC is unclear. The aim of this study was to investigate the optimal timing of surgery. METHODS From December 2010 to May 2018, 101 consecutive patients who received NAC followed by liver resection for CRLM were included in this study. The main outcome parameters were pathological response, progression-free survival (PFS), and overall survival (OS). The effect of time to surgery (TTS) on patient outcomes, defined as a high TTS and a low TTS according to an X-tile analysis, was investigated. To adjust for potential selection bias, propensity score matching at 1:2 was performed with two high TTS patients matched to one low TTS patient. Kaplan-Meier curves, logistic regression analyses, and Cox regression models were used for the data analysis. RESULTS The optimal cut-off value for the TTS was 5 weeks by X-tile analysis. The patients in this study were divided into low (≤5 weeks, n = 27) and high (>5 weeks, n = 74) TTS groups. Patients with a high TTS were more likely to have an unfavorable pathological response (75.7% vs 48.1%, P = .008). In multivariate analysis, a low TTS significantly predicted a better pathological response (OR = 3.397, 95% CI: 1.116-10.344, P = .031). Compared to patients with a high TTS, patients with a low TTS had significantly better PFS (P < .001, mPFS: 16 months vs 7 months) and better OS (P = .037, mOS: not reached vs 36 months). Multivariate analysis revealed that a TTS > 5 weeks was an independent predictor of decreased PFS (HR = 2.041, 95% CI: 1.152-3.616, P = .014) but not OS. After propensity matching, the patients with a low TTS had significantly better PFS (P < .001, mPFS: 18.2 months vs 10 months) and an equivalent OS (P = .115, mOS: not reached vs 41 months). Multivariate analysis revealed that a TTS > 5 weeks was an independent predictor of decreased PFS (HR = 3.031, 95% CI: 1.494-6.149, P = .002) but not OS. CONCLUSION The longer TTS after the completion of NAC may be disadvantageous for a favorable pathological response and long-term PFS. These results should be validated prospectively in a randomized trial.
Collapse
Affiliation(s)
- Qichen Chen
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Rui Mao
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jianjun Zhao
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xinyu Bi
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Zhiyu Li
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Zhen Huang
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Yefan Zhang
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jianguo Zhou
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Hong Zhao
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jianqiang Cai
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| |
Collapse
|
|
43
|
Bae H, Seo N, Han K, Koom WS, Kim MJ, Kim NK, Lim JS. MR prediction of pathologic complete response and early-stage rectal cancer after neoadjuvant chemoradiation in patients with clinical T1/T2 rectal cancer for organ saving strategy. Medicine (Baltimore) 2020; 99:e22746. [PMID: 33080736 PMCID: PMC7571887 DOI: 10.1097/md.0000000000022746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
To evaluate the ability of magnetic resonance imaging (MRI) to predict pathologic complete response (pCR) after neoadjuvant chemoradiation therapy (CRT) in patients with clinical T1/T2 rectal cancer to indicate candidates for organ-saving strategies.Between 2012 and 2016, 38 patients with clinical T1/T2 rectal cancer received neoadjuvant CRT. Radiologic complete response (rCR) was assigned when dense fibrotic tissue without tumor signal intensity was observed on post-CRT MRI. Surgical pathologic assessment was used to evaluate tumor regression. The association between rCR and the mural extent of the primary tumor, pCR, and pathologic T stage were analyzed.In rCR patients, the pCR rate was higher; the odds of achieving pCR were 8.00 times higher than for non-rCR patients (P = .02). rCR patients were also more likely to have early-stage cancer than non-rCR patients (P = 0.01). Patients with partial extent of the primary tumor on post-CRT MRI were more likely to be diagnosed with early-stage cancer than those with transmural extent (P = .01).rCR indicated by post-CRT MRI can be used as a supportive factor to predict pCR after neoadjuvant CRT in patients with clinical T1/T2 rectal cancer and can guide management decisions around organ-saving treatments.
Collapse
Affiliation(s)
- Heejin Bae
- Department of Radiology and Research Institute of Radiological Science
| | - Nieun Seo
- Department of Radiology and Research Institute of Radiological Science
| | - Kyunghwa Han
- Department of Radiology and Research Institute of Radiological Science
| | | | - Myeong-Jin Kim
- Department of Radiology and Research Institute of Radiological Science
| | - Nam Kyu Kim
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Joon Seok Lim
- Department of Radiology and Research Institute of Radiological Science
| |
Collapse
|
|
44
|
Shamseddine A, Zeidan YH, Kreidieh M, Khalifeh I, Turfa R, Kattan J, Mukherji D, Temraz S, Alqasem K, Amarin R, Al Awabdeh T, Deeba S, Jamali F, Mohamad I, Elkhaldi M, Daoud F, Al Masri M, Dabous A, Hushki A, Jaber O, Khoury C, El Husseini Z, Charafeddine M, Al Darazi M, Geara F. Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma. BMC Cancer 2020; 20:831. [PMID: 32873251 PMCID: PMC7466814 DOI: 10.1186/s12885-020-07333-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 08/24/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. METHODS The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. DISCUSSION Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC. TRIAL REGISTRATION Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.
Collapse
Affiliation(s)
- Ali Shamseddine
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon.
| | - Youssef H Zeidan
- Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Malek Kreidieh
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ibrahim Khalifeh
- Department of pathology and laboratory medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Rim Turfa
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Joseph Kattan
- Department of Medical Oncology, Hôtel Dieu de France, Beirut, Lebanon
| | - Deborah Mukherji
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Sally Temraz
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Kholoud Alqasem
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Rula Amarin
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Tala Al Awabdeh
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Samer Deeba
- Department of General Surgery, American University of Beirut Medical Center, Beirut, Lebanon
| | - Faek Jamali
- Department of General Surgery, American University of Beirut Medical Center, Beirut, Lebanon
| | - Issa Mohamad
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Mousa Elkhaldi
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Faiez Daoud
- Department of Surgical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Mahmoud Al Masri
- Department of Surgical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Ali Dabous
- Department of Surgical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Ahmad Hushki
- Gastroenterology Department, King Hussein Cancer Center, Amman, Jordan
| | - Omar Jaber
- Pathology Department, King Hussein Cancer Center, Amman, Jordan
| | - Clement Khoury
- Department of Radiation Oncology, Hotel-Dieu de France Hospital, Beirut, Lebanon
| | - Ziad El Husseini
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Maya Charafeddine
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Monita Al Darazi
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Fady Geara
- Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| |
Collapse
|
|
45
|
Ippolito D, Drago SG, Pecorelli A, Maino C, Querques G, Mariani I, Franzesi CT, Sironi S. Role of dynamic perfusion magnetic resonance imaging in patients with local advanced rectal cancer. World J Gastroenterol 2020; 26:2657-2668. [PMID: 32523318 PMCID: PMC7265146 DOI: 10.3748/wjg.v26.i20.2657] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 04/30/2020] [Accepted: 05/13/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The management of rectal cancer patients is mainly based on the use of the magnetic resonance imaging (MRI) technique as a diagnostic tool for both staging and restaging. After treatment, to date, the evaluation of complete response is based on the histopathology assessment by using different tumor regression grade (TRG) features (e.g., Dworak or Mandard classifications). While from the radiological point of view, the main attention for the prediction of a complete response after chemotherapy treatment focuses on MRI and the potential role of diffusion-weighted images and perfusion imaging represented by dynamic-contrast enhanced MRI. The main aim is to find a reliable tool to predict tumor response in comparison to histopathologic findings. AIM To investigate the value of dynamic contrast-enhanced perfusion-MRI parameters in the evaluation of the healthy rectal wall and tumor response to chemo-radiation therapy in patients with local advanced rectal cancer with histopathologic correlation. METHODS Twenty-eight patients with biopsy-proven rectal adenocarcinoma who underwent a dynamic contrast-enhanced MR study performed on a 1.5T MRI system (Achieva, Philips), before (MR1) and after chemoradiation therapy (MR2), were enrolled in this study. The protocol included T1 gadolinium enhanced THRIVE sequences acquired on axial planes. A dedicated workstation was used to generate color permeability maps. Region of interest was manually drawn on tumor tissue and normal rectal wall, hence the following parameters were calculated and statistically analyzed: Relative arterial enhancement (RAE), relative venous enhancement (RVE), relative late enhancement (RLE), maximum enhancement (ME), time to peak and area under the curve (AUC). Perfusion parameters were related to pathologic TRG (Mandard's criteria; TRG1 = complete regression, TRG5 = no regression). RESULTS Ten tumors (36%) showed complete or subtotal regression (TRG1-2) at histology and classified as responders; 18 tumors (64%) were classified as non-responders (TRG3-5). Perfusion MRI parameters were significantly higher in the tumor tissue than in the healthy tissue in MR1 (P < 0.05). At baseline (MR1), no significant difference in perfusion parameters was found between responders and non-responders. After chemo-radiation therapy, at MR2, responders showed significantly (P < 0.05) lower perfusion values [RAE (%) 54 ± 20; RVE (%) 73 ± 24; RLE (%): 82 ± 29; ME (%): 904 ± 429] compared to non-responders [RAE (%): 129 ± 45; RVE (%): 154 ± 39; RLE (%): 164 ± 35; ME (%): 1714 ± 427]. Moreover, in responders group perfusion values decreased significantly at MR2 [RAE (%): 54 ± 20; RVE (%): 73 ± 24; RLE (%): 82 ± 29; ME (%): 904 ± 429] compared to the corresponding perfusion values at MR1 [RAE (%): 115 ± 21; RVE (%): 119 ± 21; RLE (%): 111 ± 74; ME (%): 1060 ± 325]; (P < 0.05). Concerning the time-intensity curves, the AUC at MR2 showed significant difference (P = 0.03) between responders and non-responders [AUC (mm2 × 10-3) 121 ± 50 vs 258 ± 86], with lower AUC values of the tumor tissue in responders compared to non-responders. In non-responders, there were no significant differences between perfusion values at MR1 and MR2. CONCLUSION Dynamic contrast perfusion-MRI analysis represents a complementary diagnostic tool for identifying vascularity characteristics of tumor tissue in local advanced rectal cancer, useful in the assessment of treatment response.
Collapse
Affiliation(s)
- Davide Ippolito
- Department of Diagnostic Radiology, H. S. Gerardo Monza, San Gerardo Hospital, University of Milano-Bicocca, Monza 20900, Italy
| | - Silvia Girolama Drago
- Department of Diagnostic Radiology, H. S. Gerardo Monza, San Gerardo Hospital, University of Milano-Bicocca, Monza 20900, Italy
| | - Anna Pecorelli
- Department of Diagnostic Radiology, H. S. Gerardo Monza, San Gerardo Hospital, University of Milano-Bicocca, Monza 20900, Italy
| | - Cesare Maino
- Department of Diagnostic Radiology, H. S. Gerardo Monza, San Gerardo Hospital, University of Milano-Bicocca, Monza 20900, Italy
| | - Giulia Querques
- Department of Diagnostic Radiology, H. S. Gerardo Monza, San Gerardo Hospital, University of Milano-Bicocca, Monza 20900, Italy
| | - Ilaria Mariani
- Department of Diagnostic Radiology, H. S. Gerardo Monza, San Gerardo Hospital, University of Milano-Bicocca, Monza 20900, Italy
| | - Cammillo Talei Franzesi
- Department of Diagnostic Radiology, H. S. Gerardo Monza, San Gerardo Hospital, University of Milano-Bicocca, Monza 20900, Italy
| | - Sandro Sironi
- Department of Diagnostic Radiology, Papa Giovanni XXIII Hospital, University of Milano-Bicocca, Bergamo 20110, Italy
| |
Collapse
|
|
46
|
The paratumoral immune cell signature reveals the potential for the implementation of immunotherapy in esophageal carcinoma patients. J Cancer Res Clin Oncol 2020; 146:1979-1992. [PMID: 32447483 DOI: 10.1007/s00432-020-03258-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Accepted: 05/12/2020] [Indexed: 12/15/2022]
Abstract
PURPOSE Esophageal cancer (EC) is one of the most lethal gastrointestinal malignancies. Immunotherapy is a promising treatment modality for this disease. However, broader implementation of EC immunotherapy has been discouraged because of insufficient understanding of tumor interactions with the immune system. As with other malignancies, the current research on EC focuses on deciphering the immune cell signatures within the tumor microenvironment. However, the disease-elicited immune cell profiles in the paratumoral compartments are largely unknown. METHODS We examined the immune cell signatures in 62 tissue samples from 16 EC patients in different esophageal tissue compartments: tumor tissue, peritumoral tissue, healthy esophageal tissue, and adjacent lymph nodes. We analyzed the proportions and distribution patterns of NK cells and CD4+ and CD8+ T cells as well as their death receptor (FasR, FasR/DR3)-expressing subpopulations. The analyzed data were then compared and correlated with the patients' clinicopathological data. RESULTS We found that the FasR+ NK cells, CD4+ and CD8+ T cells infiltrated lymph nodes at the lowest levels and that the FasR+DR3+ CD4+ T cells were enhanced in tumors. The comparisons with the clinicopathological data revealed a major impact of active smoking on the reduction in paratumoral NK cells and the upregulation of FasR in tumor-infiltrating NK and CD8+ T cells. The lymph node metastatic stage, tumor stage, and Mandard grade correlated with the compartmental proportions of the evaluated immune cells. CONCLUSION The novel association of the disease state with tumoral and paratumoral immune cell signatures suggests new possibilities for personalized immunotherapy for EC patients.
Collapse
|
|
47
|
Wanigasooriya K, Tyler R, Barros-Silva JD, Sinha Y, Ismail T, Beggs AD. Radiosensitising Cancer Using Phosphatidylinositol-3-Kinase (PI3K), Protein Kinase B (AKT) or Mammalian Target of Rapamycin (mTOR) Inhibitors. Cancers (Basel) 2020; 12:E1278. [PMID: 32443649 PMCID: PMC7281073 DOI: 10.3390/cancers12051278] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 05/08/2020] [Accepted: 05/12/2020] [Indexed: 02/07/2023] Open
Abstract
Radiotherapy is routinely used as a neoadjuvant, adjuvant or palliative treatment in various cancers. There is significant variation in clinical response to radiotherapy with or without traditional chemotherapy. Patients with a good response to radiotherapy demonstrate better clinical outcomes universally across different cancers. The PI3K/AKT/mTOR pathway upregulation has been linked to radiotherapy resistance. We reviewed the current literature exploring the role of inhibiting targets along this pathway, in enhancing radiotherapy response. We identified several studies using in vitro cancer cell lines, in vivo tumour xenografts and a few Phase I/II clinical trials. Most of the current evidence in this area comes from glioblastoma multiforme, non-small cell lung cancer, head and neck cancer, colorectal cancer, and prostate cancer. The biological basis for radiosensitivity following pathway inhibition was through inhibited DNA double strand break repair, inhibited cell proliferation, enhanced apoptosis and autophagy as well as tumour microenvironment changes. Dual PI3K/mTOR inhibition consistently demonstrated radiosensitisation of all types of cancer cells. Single pathway component inhibitors and other inhibitor combinations yielded variable outcomes especially within early clinical trials. There is ample evidence from preclinical studies to suggest that direct pharmacological inhibition of the PI3K/AKT/mTOR pathway components can radiosensitise different types of cancer cells. We recommend that future in vitro and in vivo research in this field should focus on dual PI3K/mTOR inhibitors. Early clinical trials are needed to assess the feasibility and efficacy of these dual inhibitors in combination with radiotherapy in brain, lung, head and neck, breast, prostate and rectal cancer patients.
Collapse
Affiliation(s)
- Kasun Wanigasooriya
- College of Medical and Dental Sciences, Institute of Cancer and Genomic Science, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; (J.D.B.-S.); (Y.S.); (A.D.B.)
- The New Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham B15 2TH, UK; (R.T.); (T.I.)
| | - Robert Tyler
- The New Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham B15 2TH, UK; (R.T.); (T.I.)
| | - Joao D. Barros-Silva
- College of Medical and Dental Sciences, Institute of Cancer and Genomic Science, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; (J.D.B.-S.); (Y.S.); (A.D.B.)
| | - Yashashwi Sinha
- College of Medical and Dental Sciences, Institute of Cancer and Genomic Science, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; (J.D.B.-S.); (Y.S.); (A.D.B.)
- The New Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham B15 2TH, UK; (R.T.); (T.I.)
| | - Tariq Ismail
- The New Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham B15 2TH, UK; (R.T.); (T.I.)
| | - Andrew D. Beggs
- College of Medical and Dental Sciences, Institute of Cancer and Genomic Science, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; (J.D.B.-S.); (Y.S.); (A.D.B.)
- The New Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham B15 2TH, UK; (R.T.); (T.I.)
| |
Collapse
|
|
48
|
Pereira MA, Ramos MFKP, Dias AR, Cardili L, Ribeiro RRE, Charruf AZ, de Castria TB, Zilberstein B, Ceconello I, Avancini Ferreira Alves V, Ribeiro U, de Mello ES. Lymph node regression after neoadjuvant chemotherapy: A predictor of survival in gastric cancer. J Surg Oncol 2020; 121:795-803. [PMID: 31773740 DOI: 10.1002/jso.25785] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 11/17/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND OBJECTIVE Neoadjuvant chemotherapy (nCMT) has been increasingly used in advanced gastric cancer (GC). However, the prognostic impact of tumor response remains unclear. This study aimed to evaluate if tumor response at the primary site and lymph nodes (LN) correlate with survival in GC patients after nCMT. METHODS Patients with gastric adenocarcinoma treated with nCMT followed by gastrectomy were evaluated. Residual tumor was graded from 0% to 100%, defining two groups: poor (PR) and major response (MR). LN regression rate (LNRR) was determined based on tumor/fibrosis examination at each LN and a cutoff value established by receiver operating characteristic curve. RESULTS Among 62 cases, 20 (32.2%) had MR and 42 (67.7%) PR. Smaller size, diffuse histology, lower ypT status and less advanced stage were associated with the MR group. Based on cutoff value of 57, 45.6% and 54.4% patients were classified as low-LNRR and high-LNRR. High-LNRR correlated with absence of venous, lymphatic and perineural invasion, and less advanced stage. Survival was equivalent between MR and PR (P = .956). High-LNRR had better disease-free survival (DFS) than low-LNRR (P < .001). In multivariate analysis, only LNRR associated with DFS. CONCLUSION High-LNRR associates with DFS in GC treated with nCMT. Response at the primary site does not correlate with survival.
Collapse
Affiliation(s)
- Marina Alessandra Pereira
- Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Andre Roncon Dias
- Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Leonardo Cardili
- Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Renan Ribeiro E Ribeiro
- Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Amir Zeide Charruf
- Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Tiago Biachi de Castria
- Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Bruno Zilberstein
- Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Ivan Ceconello
- Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Ulysses Ribeiro
- Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Evandro Sobroza de Mello
- Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| |
Collapse
|
|
49
|
Göbel HH, Büttner-Herold MJ, Fuhrich N, Aigner T, Grabenbauer GG, Distel LVR. Cytotoxic and immunosuppressive inflammatory cells predict regression and prognosis following neoadjuvant radiochemotherapy of oesophageal adenocarcinoma. Radiother Oncol 2020; 146:151-160. [PMID: 32169773 DOI: 10.1016/j.radonc.2020.02.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Revised: 01/22/2020] [Accepted: 02/05/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND PURPOSE Tumour infiltrating lymphocytes (TIL) and tumour associated macrophages (TAM) play a key role in anticancer immunosurveillance. We studied their influence on response to neoadjuvant radiochemotherapy (RCT) and prognosis in patients with oesophageal adenocarcinoma (OAC). MATERIALS AND METHODS Between 10/2004 and 06/2018, pre-RCT biopsy-specimens were available from 76 patients with locally advanced, non-metastatic OAC scheduled for trimodality therapy. We evaluated intra- and peritumoural expression of FoxP3+-, CD8+-TIL and CD68+-, CD163+-TAM, contemplating cell density, cell ratios and cell-to-cell distances to determine a possible influence on tumour regression grade (TRG) and survival. Median follow-up time for all patients was 18 months (IQR 9-43), and 54 months (25-97) for surviving patients. Data were analysed using risk analysis, logrank test and Cox regression. RESULTS Poor tumour regression was detected for cN+ (RR 0.77 [95% CI 0.66-0.90], p = 0.001), low intratumoural FoxP3+/CD8+ ratio (RR 0.75 [0.60-0.96], p = 0.020), high peritumoural CD163+/CD68+ ratio (RR 0.77 [0.60-0.99], p = 0.045) and high intratumoural TAM density (RD -0.44 [-0.82 to -0.06], p = 0.023). Apart from poor resection quality and TRG, pretherapeutic high peritumoural CD8+ infiltration (HR 2.36 [1.21-4.61], p = 0.012) and short intratumoural FoxP3+ to CD8+ cell-to-cell distances in middle ranged CD8+ density (HR 2.55 [1.00-6.52], p = 0.050) were significant unfavourable prognostic factors in multivariate analysis. CONCLUSIONS Immunologic parameters, such as CD8+-, FoxP3+-TIL and CD68+-, CD163+-TAM, were identified to be of independent predictive and prognostic value in patients with OAC. Further and independent validation of these biomarkers by a large size dataset may urgently be contemplated.
Collapse
Affiliation(s)
- Holger H Göbel
- Department of Gastroenterology, REGIOMED Klinikum Lichtenfels, Germany; University of Split, School of Medicine, Croatia.
| | - Maike J Büttner-Herold
- Department of Nephropathology, Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany
| | - Nicole Fuhrich
- Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany
| | - Thomas Aigner
- Department of Pathology, REGIOMED Klinikum Coburg, Germany
| | - Gerhard G Grabenbauer
- Department of Radiation Oncology, REGIOMED Klinikum Coburg, Germany; University of Split, School of Medicine, Croatia
| | - Luitpold V R Distel
- Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany
| |
Collapse
|
|
50
|
Cacciato Insilla A, Vivaldi C, Giordano M, Vasile E, Cappelli C, Kauffmann E, Napoli N, Falcone A, Boggi U, Campani D. Tumor Regression Grading Assessment in Locally Advanced Pancreatic Cancer After Neoadjuvant FOLFIRINOX: Interobserver Agreement and Prognostic Implications. Front Oncol 2020; 10:64. [PMID: 32117724 PMCID: PMC7025535 DOI: 10.3389/fonc.2020.00064] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 01/14/2020] [Indexed: 12/21/2022] Open
Abstract
Neoadjuvant therapy represents an increasingly used strategy in pancreatic cancer, and this means that more pancreatic resections need to be evaluated for therapy effect. Several grading systems have been proposed for the histological assessment of tumor regression in pre-treated patients with pancreatic cancer, but issues like practical application, level of agreement and prognostic significance are still debated. To date, a standardized and widely accepted score has not been established yet. In this study, two pathologists with expertise in pancreatic cancer used 4 of the most frequently reported systems (College of American Pathologists, Evans, MD Anderson, and Hartman) to evaluate tumor regression in 29 locally advanced pancreatic cancers previously treated with modified FOLFIRINOX regimen, to establish the level of agreement between pathologists and to determine their potential prognostic value. Cases were additionally evaluated with a fifth grading system inspired to the Dworak score, normally used for colo-rectal cancer, to identify an alternative, relevant option. Results obtained for current grading systems showed different levels of agreement, and they often proved to be very subjective and inaccurate. In addition, no significant correlation was observed with survival. Interestingly, Dworak score showed a higher degree of concordance and a significant correlation with overall survival in individual assessments. These data reflect the need to re-evaluate grading systems for pancreatic cancer to establish a more reproducible and clinically relevant score.
Collapse
Affiliation(s)
- Andrea Cacciato Insilla
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Caterina Vivaldi
- Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy
| | - Mirella Giordano
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Enrico Vasile
- Division of Medical Oncology, Pisa University Hospital, Pisa, Italy
| | - Carla Cappelli
- Diagnostic and Interventional Radiology, Pisa University Hospital, Pisa, Italy
| | - Emanuele Kauffmann
- Department of Transplant and General Surgery, University of Pisa, Pisa, Italy
| | - Niccolò Napoli
- Department of Transplant and General Surgery, University of Pisa, Pisa, Italy
| | - Alfredo Falcone
- Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy
| | - Ugo Boggi
- Department of Transplant and General Surgery, University of Pisa, Pisa, Italy
| | - Daniela Campani
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| |
Collapse
|