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Saad SS, Forones N, Lopes G, Waisberg J, Caetano E, Artigiani-Neto R, Matos D. Analysis of clinical and pathological prognostic factors of survival in rectal adenocarcinoma treated with preoperative radiochemotherapy. Acta Cir Bras 2025; 40:e401125. [PMID: 39936724 PMCID: PMC11810072 DOI: 10.1590/acb401125] [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: 06/24/2024] [Accepted: 11/14/2024] [Indexed: 02/13/2025] Open
Abstract
PURPOSE To identify the prognostic variables related to the survival of patients operated on for adenocarcinoma of the rectum who underwent preoperative radiochemotherapy (RCT). METHODS We studied 70 patients from the Discipline of Surgical Gastroenterology at Escola Paulista de Medicina from 2000 to 2019, with rectal cancer located up to 10 cm from the anal verge and with stages II or III, submitted to preoperative RCT and curative surgery (R0) and with follow-up of at least 12 months. Clinical restaging was performed four to six weeks after the end of neoadjuvant treatment to characterize the degree of clinical tumor regression. Surgery by laparotomy or videolaparoscopy was performed six to 12 weeks after RCT. Primary endpoint were: overall survival (OS), disease-free survival (DFS), metastasis-free survival (MSS), and neoplasm-specific survival (SEN). These were compared with gender, age, carcinoembryonic antigen (CEA) dosage, distance from the tumor to the anal verge, radiation dose, radiotherapy-surgery interval, clinical regression, type of surgery, pT and pN TNM stage tumor, number of nodes, circumferential resection margin, and complete pathological response. Survival was assessed by Kaplan-Meier curves. Univariate and multivariate Cox analyses were calculated to identify factors associated with survival outcomes. RESULTS The mean follow-up time was 62 months. The pathological complete response rate was 18.6%. Univariate cox regression showed a significant relationship of CEA equal to or greater than 4 ng/mL with DFS and MFS, pT3/pT4 staging with DFS, MFS and SEN, pN1/N2 with DFS, MFS and SEN and stages II and III with DFS and MFS. Multivariate regression found that CEA, pT, and pN staging are independent prognostic factors for DFS, MFS, and SEN. CONCLUSION Carcinoembryonic antigen level prior to radiotherapy, pT staging and pN staging were independent prognostic factors for survival in patients with rectal adenocarcinoma who are treated with preoperative radiochemotherapy.
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Affiliation(s)
- Sarhan Sydney Saad
- Universidade Federal de São Paulo – Escola Paulista de Medicina – Departamento Cirurgia – São Paulo (SP) – Brazil
| | - Nora Forones
- Universidade Federal de São Paulo – Escola Paulista de Medicina – Departamento Medicina – São Paulo (SP) – Brazil
| | - Gaspar Lopes
- Universidade Federal de São Paulo – Escola Paulista de Medicina – Departamento Cirurgia – São Paulo (SP) – Brazil
| | - Jaques Waisberg
- Universidade Federal de São Paulo – Escola Paulista de Medicina – Departamento Cirurgia – São Paulo (SP) – Brazil
| | - Elesiario Caetano
- Universidade Federal de São Paulo – Escola Paulista de Medicina – Departamento Cirurgia – São Paulo (SP) – Brazil
| | - Ricardo Artigiani-Neto
- Universidade Federal de São Paulo – Escola Paulista de Medicina – Departamento Patologia – São Paulo (SP) – Brazil
| | - Delcio Matos
- Universidade Federal de São Paulo – Escola Paulista de Medicina – Departamento Cirurgia – São Paulo (SP) – Brazil
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De Lacavalerie PA, Lord SJ, Morgan MJ, Caldon CE, Kohonen-Corish MR. Molecular biomarkers for predicting complete response to preoperative chemoradiation in people with locally advanced rectal cancer. Cochrane Database Syst Rev 2024; 11:CD014718. [PMID: 39611427 PMCID: PMC11605794 DOI: 10.1002/14651858.cd014718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2024]
Abstract
OBJECTIVES This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: Primary objectives To identify and estimate the prognostic value of molecular biomarkers as predictors of pathological complete response to neoadjuvant chemoradiotherapy in people with locally advanced rectal cancer. summarises the review question in population, index prognostic factor, comparator prognostic factor(s), outcome, timing, and setting (PICOTS) format. [Table: see text] [Figure: see text] Secondary objectives To explore the following biomarker measurement, treatment, and study design factors as possible sources of heterogeneity in the association between the prognostic factor and pathological response: type of assay/measurement method, biomarker positivity criteria or cut-off point, chemotherapy regimen, and radiotherapy regimen.
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Affiliation(s)
- Penelope A De Lacavalerie
- Cancer Theme, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
- St Vincent's Clinical School, UNSW Medicine, UNSW Sydney, Darlinghurst, NSW, Australia
- Department of Surgery, Northern Beaches Hospital, Sydney, NSW, Australia
- Department of Surgery, Prince of Wales Private Hospital, Sydney, NSW, Australia
| | - Sarah J Lord
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
- School of Medicine, University of Notre Dame, Darlinghurst, NSW, Australia
| | - Matthew J Morgan
- Department of Surgery, Bankstown Hospital, Sydney, NSW, Australia
- Southwest Clinical School, UNSW Sydney, Bankstown, NSW, Australia
| | - Catherine E Caldon
- Cancer Theme, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
- St Vincent's Clinical School, UNSW Medicine, UNSW Sydney, Darlinghurst, NSW, Australia
| | - Maija Rj Kohonen-Corish
- Cancer Theme, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
- Woolcock Institute of Medical Research, Sydney, NSW, Australia
- Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia
- School of Medicine, Western Sydney University, Sydney, NSW, Australia
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Shahabi F, Ansari M, Najafi Ghobadi K, Ghahramani A, Parandeh A, Saberi‐Karimian M, Orafaie A, Abdollahi A. Significant Pathologic Response Following Neoadjuvant Therapy and Curative Resection in Patients With Rectal Cancer: Surgical and Oncological Outcomes From a Retrospective Cohort Study. Cancer Rep (Hoboken) 2024; 7:e70041. [PMID: 39506816 PMCID: PMC11541061 DOI: 10.1002/cnr2.70041] [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: 06/11/2024] [Revised: 09/24/2024] [Accepted: 10/14/2024] [Indexed: 11/08/2024] Open
Abstract
AIM This study evaluated surgical complication rates, recurrence-free survival, overall survival (OS), and stoma status of patients with rectal cancer after significant pathologic response following neoadjuvant treatment and curative resection. Pathologic complete response (pCR) and near-pCR patients constitute patients in our study. METHODS Included was a retrospective cohort study of patients with rectal cancer who were diagnosed between July 2011 and September 2022 and who underwent neoadjuvant therapy and surgical resection. RESULTS Of 696 patients with rectal cancer, 149 (21.4%) cases achieved significant pathologic response. During the 64 (70.5) months of follow-up, recurrence occurred in 16.1% of patients and distant metastases account for the majority of them. Age (p = 0.014) and receiving adjuvant chemotherapy (p = 0.016) were significantly related to the occurrence of recurrence. The five-year recurrence-free survival (RFS) and OS rates were obtained at 83% and 87%, respectively. Although age and surgical technique were significant factors in univariate Cox regression analysis, none of the candidate variables were significant prognostic factors for RFS in the multiple models. The risk of surgical complications remained in these patients. The most frequent complication attributed to infection (20.8%). Despite the 24.8% presence of permanent stoma at primary surgery, more than 50% of our patients lived without stoma at the last follow-up. CONCLUSION Our recurrence rate was about 16%, and it was related to age and adjuvant chemotherapy. These patients achieved over 80% rates of five-year RFS and OS. No significant prognostic factors were found on RFS in the multivariable model. As a matter of course, the risk of surgical complications and permanent stoma has still remained in these patients.
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Affiliation(s)
- Fatemeh Shahabi
- Endoscopic and Minimally Invasive Surgery Research CenterMashhad University of Medical SciencesMashhadIran
| | - Majid Ansari
- Endoscopic and Minimally Invasive Surgery Research CenterMashhad University of Medical SciencesMashhadIran
| | | | - Abolfazl Ghahramani
- Endoscopic and Minimally Invasive Surgery Research CenterMashhad University of Medical SciencesMashhadIran
| | - Amiresmaeil Parandeh
- Endoscopic and Minimally Invasive Surgery Research CenterMashhad University of Medical SciencesMashhadIran
| | - Maryam Saberi‐Karimian
- Endoscopic and Minimally Invasive Surgery Research CenterMashhad University of Medical SciencesMashhadIran
| | - Ala Orafaie
- Endoscopic and Minimally Invasive Surgery Research CenterMashhad University of Medical SciencesMashhadIran
| | - Abbas Abdollahi
- Endoscopic and Minimally Invasive Surgery Research CenterMashhad University of Medical SciencesMashhadIran
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Smithson M, Diffalha SA, Irwin RK, Williams G, McLeod MC, Somasundaram V, Bellis SL, Hardiman KM. ST6GAL1 is associated with poor response to chemoradiation in rectal cancer. Neoplasia 2024; 51:100984. [PMID: 38467087 PMCID: PMC11026834 DOI: 10.1016/j.neo.2024.100984] [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: 11/06/2023] [Revised: 02/26/2024] [Accepted: 02/27/2024] [Indexed: 03/13/2024]
Abstract
INTRODUCTION Colorectal cancer is the third most common cause of cancer death. Rectal cancer makes up a third of all colorectal cases. Treatment for locally advanced rectal cancer includes chemoradiation followed by surgery. We have previously identified ST6GAL1 as a cause of resistance to chemoradiation in vitro and hypothesized that it would be correlated with poor response in human derived models and human tissues. METHODS Five organoid models were created from primary human rectal cancers and ST6GAL1 was knocked down via lentivirus transduction in one model. ST6GAL1 and Cleaved Caspase-3 (CC3) were assessed after chemoradiation via immunostaining. A tissue microarray (TMA) was created from twenty-six patients who underwent chemoradiation and had pre- and post-treatment specimens of rectal adenocarcinoma available at our institution. Immunohistochemistry was performed for ST6GAL1 and percent positive cancer cell staining was assessed and correlation with pathological grade of response was measured. RESULTS Organoid models were treated with chemoradiation and both ST6GAL1 mRNA and protein significantly increased after treatment. The organoid model targeted with ST6GAL1 knockdown was found to have increased CC3 after treatment. In the tissue microarray, 42 percent of patient samples had an increase in percent tumor cell staining for ST6GAL1 after treatment. Post-treatment percent staining was associated with a worse grade of treatment response (p = 0.01) and increased staining post-treatment compared to pre-treatment was also associated with a worse response (p = 0.01). CONCLUSION ST6GAL1 is associated with resistance to treatment in human rectal cancer and knockdown in an organoid model abrogated resistance to apoptosis caused by chemoradiation.
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Affiliation(s)
- Mary Smithson
- Department of Surgery, University of Alabama at Birmingham, Birmingham, Al 35294, USA
| | - Sameer Al Diffalha
- Department of Pathology, University of Alabama at Birmingham, Birmingham, Al 35294, USA
| | - Regina K Irwin
- Department of Surgery, University of Alabama at Birmingham, Birmingham, Al 35294, USA
| | - Gregory Williams
- Department of Surgery, University of Alabama at Birmingham, Birmingham, Al 35294, USA
| | - M Chandler McLeod
- Department of Surgery, University of Alabama at Birmingham, Birmingham, Al 35294, USA
| | - Vivek Somasundaram
- Department of Surgery, University of Alabama at Birmingham, Birmingham, Al 35294, USA
| | - Susan L Bellis
- Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Al 35294, USA
| | - Karin M Hardiman
- Department of Surgery, University of Alabama at Birmingham, Birmingham, Al 35294, USA; Department of Surgery, Birmingham Veterans Affairs Medical Center, Birmingham, Al 35294, USA.
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Ding Y, Liu Z, Li J, Niu W, Li C, Yu B. Predictive effect of the systemic inflammation response index (SIRI) on the efficacy and prognosis of neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. BMC Surg 2024; 24:89. [PMID: 38481180 PMCID: PMC10935841 DOI: 10.1186/s12893-024-02384-5] [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: 07/11/2023] [Accepted: 03/06/2024] [Indexed: 03/17/2024] Open
Abstract
BACKGROUND Inflammation is a part of tumours, and inflammatory cells can affect the proliferation, invasion, and development of tumour cells. An increasing number of peripheral blood inflammatory markers have been found to play very important roles in the treatment and prognosis of cancer patients. The systemic inflammatory response index (SIRI) is a newer inflammatory marker, and its role in colorectal cancer, especially in locally advanced rectal cancer, is still unclear. METHODS From 2015 to 2020, 198 patients with locally advanced rectal cancer (LARC) who underwent surgery following neoadjuvant chemoradiotherapy (Neo-CRT) were analysed. Patients were categorized into good- and poor- response groups according to their pathological results, and clinical characteristics and baseline parameters were compared between the two groups. The optimal cutoff values for inflammatory indicators were determined using receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using the Cox proportional hazard model. Survival analysis was performed via the Kaplan‒Meier method. RESULTS After patients were grouped into good and poor response groups, indicator differences were found in CEA, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and SIRI. According to the ROC analysis, the NLR (P = 0.015), SII (P = 0.001), and SIRI (P = 0.029) were significant prognostic factors. After univariate and multivariate analyses of the Cox proportional hazards regression model, only the SIRI was found to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Finally, Kaplan‒Meier survival curves also confirmed the ability of the SIRI to predict survival. CONCLUSION The preoperative SIRI can be used to predict the response to Neo-CRT in LARC patients and is an independent predictor of OS and DFS in postoperative patients. A high SIRI was associated with poor radiotherapy response and predicted poor OS and DFS.
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Affiliation(s)
- Yuanyi Ding
- The Second General Surgery, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumour Hospital, Hebei, 050011, China
| | - Zining Liu
- The Second General Surgery, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumour Hospital, Hebei, 050011, China
| | - Jing Li
- The Second General Surgery, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumour Hospital, Hebei, 050011, China
| | - Wenbo Niu
- The Second General Surgery, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumour Hospital, Hebei, 050011, China
| | - Chenhui Li
- The Second General Surgery, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumour Hospital, Hebei, 050011, China
| | - Bin Yu
- The Second General Surgery, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumour Hospital, Hebei, 050011, China.
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Wang G, Yao K, Yang Y, Chen H, Tang Z, Ye J, Fu M, Xue X, Shen Q, Tang H, Guo Y, Huang Y. Local resection versus radical resection after neoadjuvant chemoradiotherapy for patients with locally advanced rectal cancer: a propensity-score matched cohort analysis. BMC Gastroenterol 2023; 23:205. [PMID: 37312044 DOI: 10.1186/s12876-023-02809-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 05/09/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND We aimed to address the shortage of evidence regarding the safety of the local resection approach by comparing long-term oncological outcomes between patients managed by local resection and those who underwent radical resection. METHODS This was a propensity-score matched cohort analysis study that included patients of all ages diagnosed with locally advanced rectal cancer (LARC) who had received neoadjuvant chemoradiotherapy (nCRT) at the Fujian Medical University Union Hospital and Fujian Medical University Affiliated Zhangzhou Hospital, China, between Jan 10, 2011, to Dec 28, 2021. Partial patients with a significant downstage of the tumor were offered management with the local resection approach, and most of the rest were offered radical resection if eligible. FINDINGS One thousand six hundred ninety-three patients underwent radical resection after nCRT, and another 60 patients performed local resection. The median follow-up times were 44.0 months (interquartile range = 4-107 months). After propensity-core matching (PSM), in the Kaplan-Meier curves, local resection (n = 56) or radical resection (n = 211) was not significantly associated with 1-, 3-, and 5-year cumulative incidence of overall survival (OS) (HR = 1.103, 95% CI: 0.372 ~ 3.266), disease-free survival (DFS) ((HR = 0.972, 95% CI: 0.401 ~ 2.359), local recurrence (HR = 1.044, 95% CI: 0.225 ~ 4.847), and distant metastasis (HR = 0.818, 95% CI: 0.280 ~ 2.387) (all log-rank P > 0.05). Similarly, multivariate Cox regression analysis indicates that local excision still was not an independent risk factor for OS (HR = 0.863, 95% CI: 0.267 ~ 2.785, P = 0.805) and DFS (HR = 0.885, 95% CI: 0.353 ~ 2.215, p = 0.794). CONCLUSION Local resection can be a management option in selected patients with middle-low rectal cancer after nCRT for LARC and without loss of oncological safety at five years.
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Affiliation(s)
- Guancong Wang
- Department of Colorectal and Anal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China
| | - Kaiyuan Yao
- Department of Colorectal and Anal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China
| | - Yugang Yang
- Department of Colorectal and Anal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China
| | - Hongying Chen
- Department of Colorectal and Anal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China
| | - Zihan Tang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Jiahong Ye
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Muhai Fu
- Department of Colorectal and Anal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China
| | - Xiajuan Xue
- Department of Colorectal and Anal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China
| | - Qiyuan Shen
- Department of Colorectal and Anal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China
| | - Haiwen Tang
- Department of Colorectal and Anal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China
| | - Yincong Guo
- Department of Colorectal and Anal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China.
| | - Ying Huang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
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Koëter T, Jongen G, Hanrath-Vos E, Smit E, Fütterer J, Maas M, Scheenen T. Reducing Acquisition Time of Diffusion Weighted MR Imaging of the Rectum with Simultaneous Multi-Slice Acquisition: A Reader Study. Acad Radiol 2022; 29:1802-1807. [PMID: 35256274 DOI: 10.1016/j.acra.2022.02.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/03/2022] [Accepted: 02/05/2022] [Indexed: 01/26/2023]
Abstract
RATIONALE AND OBJECTIVES To assess the acquisition time and image quality of simultaneous multislice-accelerated diffusion-weighted imaging (SMS-DWI) versus conventional DWI (C-DWI) of the rectum. MATERIALS AND METHODS In patients scheduled for a magnetic resonance imaging of the rectum, both SMS-DWI and C-DWI were performed on a 3T whole body magnetic resonance scanner. Image quality of the DWI sequences was reviewed by two independent radiologists who were blinded to the method of imaging using a five-point Likert scale: (score ranging from 1 (non-diagnostic) to 5 (excellent). The mean scores of SMS-DWI versus C-DWI were compared for the individual readers using a nonparametric test (Wilcoxon signed ranks). RESULTS The SMS-DWI protocol acquisition time was 4:08 min vs. 7:24 min per patient, which led to a reduction of 44.1% for the C-DWI protocol, both excluding time for sequence specific adjustments (shimming). No statistical differences between the conventional-, and SMS- diffusion weighted images were seen for both readers. Mean overall image quality of the SMS-DWI TRACE images was 3.5 (SD: 1.3) and 3.3 (SD: 1.0) for reader 1 and reader 2, respectively. Mean overall image quality of the C-DWI TRACE images was 3.4 (SD: 1.3) and 3.2 (SD: 1.1) for reader 1 and reader 2, respectively. CONCLUSION Optimized SMS-DWI compared to C-DWI in imaging of the rectum showed similar image quality while a significant acquisition time reduction was achieved.
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Affiliation(s)
- Tijmen Koëter
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands; Department of Surgery, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands.
| | - Germaine Jongen
- Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Eline Hanrath-Vos
- Department of Radiology, Elisabeth-TweeSteden Ziekenhuis (ETZ), Tilburg, The Netherlands
| | - Ewoud Smit
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands
| | - Jurgen Fütterer
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands
| | - Marnix Maas
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands
| | - Tom Scheenen
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands
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Yan L, Weifeng Z, Qin W, Jinping W. A model based on endorectal ultrasonography predicts lateral lymph node metastasis in low and middle rectal cancer. JOURNAL OF CLINICAL ULTRASOUND : JCU 2022; 50:705-712. [PMID: 35322883 PMCID: PMC9313894 DOI: 10.1002/jcu.23204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/04/2022] [Accepted: 02/10/2022] [Indexed: 06/14/2023]
Abstract
PURPOSE To investigate the risk factors for lymph node (LN) metastasis in low and middle rectal tumors, construct a predictive model and test the model's diagnostic efficacy. METHODS The clinical and pathological data of 172 patients with rectal cancer confirmed by surgery were retrospectively evaluated, among whom 61 patients were finally included in this study. Patients were divided into positive groups and negative groups based on LN metastasis, and risk factors that might affect LN metastasis were analyzed. Finally, a risk predictive model was constructed based on the weights of each risk factor. RESULTS Compared with pathology, the efficacy of diagnosing LN metastasis only according to conventional endorectal ultrasonography (ERUS) features of LN was not high, with sensitivity 67%, specificity 86%, positive predictive value 76%, negative predictive value 80%, and accuracy 79%. Univariate analysis showed that circumferential angle of the tumor, ultrasonic T- stage (UT stage), conventional ultrasound features diagnosis of LN metastasis, strain ratio (SR) of tumor were risk factors for LN metastasis, while vascular resistance index of rectal tumor was protective factor. Multivariate analysis showed that UT stage (OR = 7.188, p = 0.049), conventional ultrasound features diagnosis of LN metastasis (OR = 8.010, p = 0.025) and SR (OR = 5.022, p = 0.031) were independent risk factors for LN metastasis. These risk factors were included in logistic regression analysis and the model was established, Y = -7.3 + 1.9 X10 + 2.1 X11 + 1.6 X13 (Y = Logit[P], P: LN metastasis rate, X10: UT stage, X11: conventional ultrasound features diagnosis of LN metastasis, X13: SR). The receiver operating characteristic (ROC) curve was used to test the model's predictive efficacy, the area under the curve was 0.95, sensitivity: 95%, specificity: 87%. Hosmer-Lemeshow goodness of fit test showed X2 = 6.015, p = 0.65 (p > 0.05), indicating that the model had a high predictive value. CONCLUSION Evaluation of perirectal LN metastasis only based on conventional ERUS features of LN was not effective enough. UT stage of tumor, conventional ultrasound features diagnosis of LN metastasis and SR were independent risk factors for LN metastasis. The predictive model had good assessment efficacy and had certain clinical application value.
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Affiliation(s)
- Li Yan
- Department of UltrasoundThe first affiliated hospital of Anhui University of Traditional Chinese MedicineAnhuiChina
| | - Zhou Weifeng
- Department of UltrasoundThe first affiliated hospital of Anhui University of Traditional Chinese MedicineAnhuiChina
| | - Wang Qin
- Department of UltrasoundThe first affiliated hospital of Anhui University of Traditional Chinese MedicineAnhuiChina
| | - Wang Jinping
- Department of UltrasoundThe first affiliated hospital of Anhui University of Traditional Chinese MedicineAnhuiChina
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Hayes IP, Milanzi E, Pelly RM, Gibbs P, Reece JC. T‐stage downstaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy is not associated with reduced recurrence after adjusting for tumour characteristics. J Surg Oncol 2022; 126:728-739. [PMID: 35635190 PMCID: PMC9543614 DOI: 10.1002/jso.26932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 05/16/2022] [Indexed: 11/05/2022]
Affiliation(s)
- Ian P. Hayes
- Colorectal Surgery Unit, Royal Melbourne Hospital Melbourne Victoria Australia
- Department of Surgery The University of Melbourne Melbourne Victoria Australia
| | - Elasma Milanzi
- Neuroepidemiology Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health The University of Melbourne Carlton Victoria Australia
- Australasian Kidney Trials Network University of Queensland Brisbane Australia
| | - Rachel M. Pelly
- Health Services Research Unit, The Royal Children's Hospital Melbourne Victoria Australia
- Health Services, Murdoch Children's Research Institute Melbourne Victoria Australia
| | - Peter Gibbs
- Personalised Oncology Division The Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
- Faculty of Medicine, Dentistry and Health Sciences The University of Melbourne Melbourne Victoria Australia
- Department of Medical Oncology Western Health Melbourne Victoria Australia
| | - Jeanette C. Reece
- Neuroepidemiology Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health The University of Melbourne Carlton Victoria Australia
- Centre for Cancer Research The University of Melbourne Melbourne Victoria Australia
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Kim J, Sohn KA, Kwak JH, Kim MJ, Ryoo SB, Jeong SY, Park KJ, Kang HC, Chie EK, Jung SH, Kim D, Park JW. A Novel Scoring System for Response of Preoperative Chemoradiotherapy in Locally Advanced Rectal Cancer Using Early-Treatment Blood Features Derived From Machine Learning. Front Oncol 2021; 11:790894. [PMID: 34912724 PMCID: PMC8666428 DOI: 10.3389/fonc.2021.790894] [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: 10/08/2021] [Accepted: 11/05/2021] [Indexed: 11/25/2022] Open
Abstract
Background Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer (LARC). However, individual responses to preoperative CRT vary from patient to patient. The aim of this study is to develop a scoring system for the response of preoperative CRT in LARC using blood features derived from machine learning. Methods Patients who underwent total mesorectal excision after preoperative CRT were included in this study. The performance of machine learning models using blood features before CRT (pre-CRT) and from 1 to 2 weeks after CRT (early-CRT) was evaluated. Based on the best model, important features were selected. The scoring system was developed from the selected model and features. The performance of the new scoring system was compared with those of systemic inflammatory indicators: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and the prognostic nutritional index. Results The models using early-CRT blood features had better performances than those using pre-CRT blood features. Based on the ridge regression model, which showed the best performance among the machine learning models (AUROC 0.6322 and AUPRC 0.5965), a novel scoring system for the response of preoperative CRT, named Response Prediction Score (RPS), was developed. The RPS system showed higher predictive power (AUROC 0.6747) than single blood features and systemic inflammatory indicators and stratified the tumor regression grade and overall downstaging clearly. Conclusion We discovered that we can more accurately predict CRT response by using early-treatment blood data. With larger data, we can develop a more accurate and reliable indicator that can be used in real daily practices. In the future, we urge the collection of early-treatment blood data and pre-treatment blood data.
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Affiliation(s)
- Jaesik Kim
- Department of Computer Engineering, Ajou University, Suwon, South Korea.,Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.,Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, United States
| | - Kyung-Ah Sohn
- Department of Computer Engineering, Ajou University, Suwon, South Korea.,Department of Artificial Intelligence, Ajou University, Suwon, South Korea
| | - Jung-Hak Kwak
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Min Jung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea.,Cancer Research Institute, Seoul National University, Seoul, South Korea
| | - Seung-Bum Ryoo
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Seung-Yong Jeong
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea.,Cancer Research Institute, Seoul National University, Seoul, South Korea
| | - Kyu Joo Park
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Hyun-Cheol Kang
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, South Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, South Korea.,Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, South Korea
| | - Sang-Hyuk Jung
- Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.,Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, United States.,Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea
| | - Dokyoon Kim
- Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.,Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, United States
| | - Ji Won Park
- Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.,Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, United States.,Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea.,Cancer Research Institute, Seoul National University, Seoul, South Korea
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11
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Marchegiani F, Palatucci V, Capelli G, Guerrieri M, Belluco C, Rega D, Morpurgo E, Coco C, Restivo A, De Franciscis S, Aschele C, Perin A, Bonomo M, Muratore A, Spinelli A, Ramuscello S, Bergamo F, Montesi G, Spolverato G, Del Bianco P, Gambacorta MA, Delrio P, Pucciarelli S. Rectal Sparing Approach After Neoadjuvant Therapy in Patients with Rectal Cancer: The Preliminary Results of the ReSARCh Trial. Ann Surg Oncol 2021; 29:1880-1889. [PMID: 34855063 DOI: 10.1245/s10434-021-11121-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 10/12/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND Rectum-preservation for locally advanced rectal cancer has been proposed as an alternative to total mesorectal excision (TME) in patients with major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The purpose of this study was to report on the short-term outcomes of ReSARCh (Rectal Sparing Approach after preoperative Radio- and/or Chemotherapy) trial, which is a prospective, multicenter, observational trial that investigated the role of transanal local excision (LE) and watch-and-wait (WW) as integrated approaches after neoadjuvant therapy for rectal cancer. METHODS Patients with mid-low rectal cancer who achieved mCR or cCR after neoadjuvant therapy and were fit for major surgery were enrolled. Clinical response was evaluated at 8 and 12 weeks after completion of chemoradiotherapy. Treatment approach, incidence, and reasons for subsequent TME were recorded. RESULTS From 2016 to 2019, 160 patients were enrolled; mCR or cCR at 12 weeks was achieved in 64 and 96 of patients, respectively. Overall, 98 patients were managed with LE and 62 with WW. In the LE group, Clavien-Dindo 3+ complications occurred in three patients. The rate of cCR increased from 8- to 12-week restaging. Thirty-three (94.3%) of 35 patients with cCR had ypT0-1 tumor. At a median 24 months follow-up, a tumor regrowth was found in 15 (24.2%) patients undergoing WW. CONCLUSIONS LE for patients achieving cCR or mCR is safe. A 12-week interval from chemoradiotherapy completion to LE is correlated with an increased cCR rate. The risk of ypT > is reduced when LE is performed after cCR.
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Affiliation(s)
- Francesco Marchegiani
- Department of Surgical, Oncological and Gastroenterological Sciences, First Surgical Clinic, University of Padova, Padua, Italy
| | - Valeria Palatucci
- Department of Surgical, Oncological and Gastroenterological Sciences, First Surgical Clinic, University of Padova, Padua, Italy
| | - Giulia Capelli
- Department of Surgical, Oncological and Gastroenterological Sciences, First Surgical Clinic, University of Padova, Padua, Italy
| | - Mario Guerrieri
- Surgery Clinic, Marche Polytechnic University, Ancona, Italy
| | - Claudio Belluco
- Oncological Surgery Department, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
| | - Daniela Rega
- National Cancer Institute, IRCCS Fondazione "G.Pascale", Naples, Italy
| | - Emilio Morpurgo
- Department of Surgery, Regional Center for Laparoscopic and Robotic Surgery, Camposampiero Hospital, Padua, Italy
| | - Claudio Coco
- Department of Surgical Sciences, Catholic University of Rome, Rome, Italy
| | - Angelo Restivo
- Department of Surgery, Colorectal Surgery Center, University of Cagliari, Cagliari, Italy
| | | | | | - Alessandro Perin
- Department of Surgical, Oncological and Gastroenterological Sciences, First Surgical Clinic, University of Padova, Padua, Italy
| | | | - Andrea Muratore
- Division of General Surgery, E. Agnelli Hospital, Pinerolo, Turin, Italy
| | - Antonino Spinelli
- Colon and Rectal Surgery Unit, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | | | | | - Giampaolo Montesi
- Radiation Oncology Unit, Santa Maria della Misericordia Hospital, Rovigo, Italy
| | - Gaya Spolverato
- Department of Surgical, Oncological and Gastroenterological Sciences, First Surgical Clinic, University of Padova, Padua, Italy.
| | | | | | - Paolo Delrio
- National Cancer Institute, IRCCS Fondazione "G.Pascale", Naples, Italy
| | - Salvatore Pucciarelli
- Department of Surgical, Oncological and Gastroenterological Sciences, First Surgical Clinic, University of Padova, Padua, Italy
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12
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Yang Y, Luo D, Zhang R, Cai S, Li Q, Li X. Tumor Regression Grade as a Prognostic Factor in Metastatic Colon Cancer Following Preoperative Chemotherapy. Clin Colorectal Cancer 2021; 21:96-106. [PMID: 34895989 DOI: 10.1016/j.clcc.2021.10.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/26/2021] [Accepted: 10/19/2021] [Indexed: 11/11/2022]
Abstract
BACKGROUND The prognostic value of tumor regression grade (TRG) in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy has been explored extensively. However, whether TRG is predictive of outcome in colon cancer following preoperative chemotherapy has not been reported. MATERIALS AND METHODS A total of 276 colon cancer patients who had undergone preoperative chemotherapy and surgery in Fudan University Shanghai Cancer Center during the period March 2014 through November 2019 were recruited in this study. 113 (40.9%) and 163 (59.1%) patients were diagnosed with locally advanced colon cancer (LACC) and metastatic colon cancer (mCC) before preoperative chemotherapy, respectively. The TRG was divided into TRG0 (complete response), TRG1 (good response), TRG2 (moderate response), and TRG3 (poor response). RESULTS Of the 276 patients 4.0% were TRG0, 5.4% were TRG1, 29.3% were TRG2, 61.2% were TRG3. TRG0 and TRG1 or TRG0, TRG1 and TRG2 were combined to simplify analysis due to limited sample size. In entire cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 80.0%, 68.8% and 43.3% (P = .003). In LACC cohort, TRG was not associated with patients' prognosis, which largely resulted from limited outcome events. In mCC cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 74.3%, 62.8% to 28.1% (P<0.001). Multivariate analysis demonstrated that TRG was an independent prognostic factor for overall survival in both entire cohort and mCC cohort (TRG3 vs. TRG0-2). CONCLUSION TRG is a prognostic factor in predicting long-term outcomes of mCC patients treated with preoperative chemotherapy.
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Affiliation(s)
- Yufei Yang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Dakui Luo
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ruoxin Zhang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Sanjun Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qingguo Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Xinxiang Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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13
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Intratumoral Budding and Tumor Microenvironment in Pretreatment Rectal Cancer Biopsies Predict the Response to Neoadjuvant Chemoradiotherapy. Appl Immunohistochem Mol Morphol 2021; 30:1-7. [PMID: 34369419 DOI: 10.1097/pai.0000000000000966] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Accepted: 07/09/2021] [Indexed: 11/27/2022]
Abstract
Tumor budding at the invasive tumor front (peritumoral budding) is an established prognostic factor in colorectal cancer. However, the significance of intratumoral budding (ITB) in pretreatment biopsies is still uncertain. Our study aims to investigate the association of ITB and tumor microenvironment in pretreatment rectal cancer biopsies with pathologic response to neoadjuvant chemoradiotherapy. Pretreatment biopsies of low-grade rectal cancer from 37 patients who underwent resection after neoadjuvant chemoradiotherapy were retrospectively reviewed to evaluate ITB, type of tumor stroma, and intraepithelial lymphocytes. ITB was counted on a single hotspot in 1 HPF upon pan-keratin immunohistochemical staining. Intraepithelial lymphocytes was graded semiquantitatively as "absent" (≤2/HPF) or "present" (>2/HPF). The tumor stroma was classified as either immature type or maturing type. In pretreatment biopsies, ITB was observed in 34/37 patients (92%). High-grade ITB was significantly associated with a poor pathologic response to neoadjuvant chemoradiotherapy (tumor regression score 2 to 3, P<0.001; and higher posttreatment T stage, P=0.002). Immature type of stroma was significantly associated with both high-grade ITB in biopsies (P=0.02) and a poor pathologic response to neoadjuvant chemoradiotherapy (tumor regression score 2 to 3, P=0.005). In multivariate analysis, ITB and the type of stroma remained the significant parameters for prediction of response to neoadjuvant treatment. Our study indicates that ITB and tumor microenvironment in pretreatment biopsies are strong predictors of response to neoadjuvant chemoradiotherapy, which may assist risk stratification and clinical management in rectal cancer patients.
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14
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Association Between Pathological Complete Response and Tumor Location in Patients with Rectal Cancer After Neoadjuvant Chemoradiotherapy, a Prospective Cohort Study. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2021. [DOI: 10.5812/ijcm.113135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Colorectal cancers are the third common malignancies after lung and breast neoplasms. Some contributing factors for pathological complete response (pCR) to neoadjuvant therapy of rectal cancer have been defined. Despite various studies in this era, there are few studies on the location of tumors. Objectives: Regarding the high prevalence of colorectal cancer in Iran and the importance of neoadjuvant chemoradiation for survival and morbidity, this study was carried out to determine the association between pathologic complete response and tumor location in patients with rectal cancer after neoadjuvant chemoradiotherapy. Methods: In this prospective cohort, 100 cases with rectal adenocarcinoma from 2017 to 2019 were enrolled. Distance between anal verge and tumor was measured by clinical examination, colonoscopy, endo-sonography, and MRI. Tumors were defined as distal (less than 5 cm from the anal verge) and none distal (more than 5 cm from the anal verge). Another subdivision was inferior (0 - 4.99 cm), middle (5 - 9.99 cm), and superior (10 - 15 cm). The pathological response was compared across the groups. Results: In this study, the pCR was seen in 30%. In univariate analysis body mass index (BMI), grade, N-stage, and distance from anal verge were related to pCR. In cases with BMI over 25 kg/m2 and in tumors with low to medium grade N0/N1, and distance less than 5 cm from the anal verge (low lying tumors) the pCR to neoadjuvant treatment was higher. In multivariate analysis tumor grade, N stage, and distance from anal verge were still related to pCR. Conclusions: According to the obtained results in this study, there may be some association between rectal tumor location and pathologic complete response.
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15
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Huang Y, Wei W, Wang Z, Liang T, Tian S, Fu G. Neoadjuvant Chemoradiotherapy Does Not Contribute to Worse Survival in Pathological Node-Negative Rectal Cancer. Front Oncol 2021; 11:649313. [PMID: 33763379 PMCID: PMC7982457 DOI: 10.3389/fonc.2021.649313] [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: 01/04/2021] [Accepted: 02/11/2021] [Indexed: 12/24/2022] Open
Abstract
Purpose: The prognostic significance of ypN0 rectal cancer with comparison to pN0 disease still remains poorly defined. This study aimed to compare the prognosis of ypN0 and pN0 rectal cancer. Methods: Eligible patients were identified from the SEER18 registries research database (the latest data up to date was on April 15, 2019). Propensity score (PS) matching was usually performed to reduce the imbalance and potential confounding that were introduced by inherent differences between the groups. The cause-specific survival (CSS) was analyzed to evaluate the prognostic prediction of ypN0 and pN0 groups using the Kaplan–Meier method with the log-rank test. Cox proportional hazard model was also used to identify independent prognostic variables. Results: In total, 26,832 patients diagnosed with pN0 or ypN0 rectal cancer were confirmed as the final cohort, including 7,237 (27.0%) patients with radiation and 19,595 (73.0%) patients without radiation prior to surgery. The median follow-up time was up to 81 months. After adjusting for other prognostic factors, neoadjuvant radiotherapy was not an independent prognostic variable of CSS (HR = 1.100, 95%CI = 0.957–1.265, P = 0.180, using pN0 group as the reference). Conclusions: ypN0 rectal cancer was strongly associated with worse pathological diagnoses compared with pN0 rectal cancer, contributing to worse oncologic outcomes. However, the receipt of neoadjuvant chemoradiotherapy was not an independent prognostic factor of worse prognosis in pathological node-negative patients. Our study could give guidance to the treatment of ypN0 rectal cancer.
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Affiliation(s)
- Yong Huang
- Department of General Surgery, Jiangdu People' s Hospital Affiliated to Yangzhou University Medical School, Yangzhou, China
| | - Wei Wei
- Department of General Surgery, Jiangdu People' s Hospital Affiliated to Yangzhou University Medical School, Yangzhou, China
| | - Zhenguang Wang
- Department of General Surgery, Jiangdu People' s Hospital Affiliated to Yangzhou University Medical School, Yangzhou, China
| | - Tao Liang
- Department of General Surgery, Jiangdu People' s Hospital Affiliated to Yangzhou University Medical School, Yangzhou, China
| | - Shuyun Tian
- Department of General Surgery, Jiangdu People' s Hospital Affiliated to Yangzhou University Medical School, Yangzhou, China
| | - Guangshun Fu
- Department of General Surgery, Jiangdu People' s Hospital Affiliated to Yangzhou University Medical School, Yangzhou, China
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16
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Sakin A, Sahin S, Karyagar SS, Karyagar S, Atci M, Akboru MH, Cihan S. The Predictive Value of Baseline Volumetric PET/CT Parameters on Treatment Response and Prognosis in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy. J Gastrointest Cancer 2021; 53:341-347. [PMID: 33651265 DOI: 10.1007/s12029-021-00608-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2021] [Indexed: 10/22/2022]
Abstract
PURPOSE To investigate the prognostic effects of baseline volumetric PET/CT parameters including the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG) on treatment response and prognosis in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (NACRT). METHODS Between 2015 and 2018, 51 patients with LARC treated with NACRT followed by surgery were included in this retrospective study. Patients were divided into 2 groups by tumor regression grade (TRG) as follows: group I = TRG 1 (no detectable cancer cells) + TRG 2 (single cells and/or small groups of cancer cells) and group II = TRG3 (residual tumor outgrown by fibrosis) + TRG 4 (remarkable fibrosis outgrown by tumor cells) + TRG 5 (no fibrosis with extensive residual cancer). RESULTS Of the 51 patients, 34 (66.7%) were male. The median age was 55 (range, 37-78) years. According to TRG status, 14 (27.4%) patients were in group I and 37 (72.6%) patients were in group II. The area under the curve (95% CI) was 0.749 (0.593-0.905) in the ROC curve plotted for MTV. The cut-off value for MTV was 12, with 70% sensitivity and 65% specificity. MTV was ≥ 12 in 32 (62.8%) patients. MTV and TLG values were significantly different between groups I and II, whereas there was no significant difference between the groups in terms of SUVmax values (p = 0.006, p = 0.033, and p = 0.673, respectively). The disease-free survival was not reached in patients with MTV < 12 vs. 20 months in those with MTV ≥ 12 (p = 0.323). In multivariate analysis, MTV (OR, 95% Cl, 5.00 [1.17-21.383]) was found to be the factor that affected pathological complete response. CONCLUSION In LARC treated with NACRT, MTV prior to treatment can help predict the response to treatment.
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Affiliation(s)
- Abdullah Sakin
- Department of Medical Oncology, Yuzuncu Yil University Medical School, 65030, Van, Turkey.
| | - Suleyman Sahin
- Department of Medical Oncology, University of Health Sciences, Van Training and Research Hospital, Van, Turkey
| | - Sevda Saglampınar Karyagar
- Department of Nuclear Medicine, University of Health Sciences, Prof. Dr Cemil, Tascıoglu City Hospital, İstanbul, Turkey
| | - Savas Karyagar
- Department of Nuclear Medicine, University of Health Sciences, Prof. Dr Cemil, Tascıoglu City Hospital, İstanbul, Turkey
| | - Mustafa Atci
- Department of Medical Oncology, University of Health Sciences, Prof. Dr Cemil, Tascıoglu City Hospital, 34384, Istanbul, Turkey
| | - Mustafa Halil Akboru
- Department of Radiation Oncology, University of Health Sciences, Prof. Dr Cemil, Tascıoglu City Hospital, 34384, Istanbul, Turkey
| | - Sener Cihan
- Department of Medical Oncology, University of Health Sciences, Prof. Dr Cemil, Tascıoglu City Hospital, 34384, Istanbul, Turkey
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17
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Hemmings C, Connor S. Pathological assessment of tumour regression following neoadjuvant therapy in pancreatic carcinoma. Pathology 2020; 52:621-626. [PMID: 32800331 DOI: 10.1016/j.pathol.2020.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 06/29/2020] [Accepted: 07/06/2020] [Indexed: 12/20/2022]
Abstract
Pancreatic carcinoma is a relatively common malignancy with an overall poor prognosis which is somewhat improved in those patients for whom resection and adjuvant therapy is feasible. In recent years there has been a trend to administering neoadjuvant therapy (combination chemotherapy and/or chemoradiotherapy), followed by resection in patients who remain surgical candidates at the completion of this treatment. Advantages of a neoadjuvant approach may include greater likelihood of achieving complete resection with negative surgical margins, reduced treatment toxicity and greater cost effectiveness, as well as potentially sparing patients with rapidly progressive disease from major surgery. To gauge the tumour's response to preoperative therapy, and to compare the efficacy of different regimens, there is a need for a robust and reproducible system of assessing tumour regression in resection specimens. Several such systems have been proposed, but there is generally a lack of consensus as to which system is the 'best'. This review describes the evolution of a number of tumour regression grading systems which have been proposed, and discusses the relative merits and shortfalls of several of the most frequently applied schemata. Some problems common to many of these include poorly defined criteria, low interobserver reproducibility and a reliance on fibrosis as a surrogate for tumour kill, which may not be valid. Despite that, recent evidence suggests that the Dworak grading system (first developed for rectal cancer) may be useful in terms of both interobserver concordance and correlation with survival.
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Affiliation(s)
- Chris Hemmings
- Department of Anatomic Pathology, Canterbury Health Laboratories, Christchurch Central, New Zealand; Department of Pathology and Biomedical Science, University of Otago Medical School, Christchurch Central, New Zealand.
| | - Saxon Connor
- Department of Surgery, Christchurch Hospital, Christchurch Central, New Zealand
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18
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Nguyen TNQ, Maguire A, Mooney C, Jackson N, Lynam‐Lennon N, Weldon V, Muldoon C, Maguire AA, O'Toole D, Ravi N, Reynolds JV, O'Sullivan J, Meade AD. Prediction of pathological response to neo‐adjuvant chemoradiotherapy for oesophageal cancer using vibrational spectroscopy. TRANSLATIONAL BIOPHOTONICS 2020. [DOI: 10.1002/tbio.202000014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
- Thi N. Q. Nguyen
- Centre for Radiation and Environmental Science, Focas Research Institute Technological University Dublin Dublin Ireland
- School of Physics and Clinical and Optometric Sciences Technological University Dublin Dublin Ireland
| | - Adrian Maguire
- Centre for Radiation and Environmental Science, Focas Research Institute Technological University Dublin Dublin Ireland
| | - Catherine Mooney
- School of Computer Science University College Dublin Dublin Ireland
| | - Naomi Jackson
- Centre for Radiation and Environmental Science, Focas Research Institute Technological University Dublin Dublin Ireland
| | - Niamh Lynam‐Lennon
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin St James's Hospital Dublin Ireland
| | - Vicki Weldon
- Centre for Radiation and Environmental Science, Focas Research Institute Technological University Dublin Dublin Ireland
- School of Physics and Clinical and Optometric Sciences Technological University Dublin Dublin Ireland
| | - Cian Muldoon
- Department of Histopathology St. James's Hospital Dublin Ireland
| | - Aoife A. Maguire
- Department of Histopathology St. James's Hospital Dublin Ireland
| | - D. O'Toole
- Department of Histopathology St. James's Hospital Dublin Ireland
| | - Narayanasamy Ravi
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin St James's Hospital Dublin Ireland
| | - John V. Reynolds
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin St James's Hospital Dublin Ireland
| | - Jacintha O'Sullivan
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin St James's Hospital Dublin Ireland
| | - Aidan D. Meade
- Centre for Radiation and Environmental Science, Focas Research Institute Technological University Dublin Dublin Ireland
- School of Physics and Clinical and Optometric Sciences Technological University Dublin Dublin Ireland
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19
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Izzotti A, Ceccaroli C, Geretto M, Ruggieri FG, Schenone S, Di Maria E. Predicting Response to Neoadjuvant Therapy in Colorectal Cancer Patients the Role of Messenger-and Micro-RNA Profiling. Cancers (Basel) 2020; 12:cancers12061652. [PMID: 32580435 PMCID: PMC7352797 DOI: 10.3390/cancers12061652] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 06/12/2020] [Accepted: 06/17/2020] [Indexed: 12/19/2022] Open
Abstract
Colorectal cancer patients' responses to neoadjuvant therapy undergo broad inter-individual variations. The aim of this systematic review is to identify a molecular signature that is predictive of colon cancer downstaging and/or downgrading after neoadjuvant therapy. Among the hundreds analysed in the available studies, only 19 messenger-RNAs (mRNAs) and six micro-RNAs (miRNAs) were differentially expressed in responders versus non-responders in two or more independent studies. Therefore, a mRNA/miRNA signature can be designed accordingly, with limitations caused by the retrospective nature of these studies, the heterogeneity in study designs and the downgrading/downstaging assessment criteria. This signature can be proposed to tailor neoadjuvant therapy regimens on an individual basis.
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Affiliation(s)
- Alberto Izzotti
- Department of Experimental Medicine, University of Genova, 16132 Genova, Italy;
- IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy;
- Correspondence: ; Tel.: +39-010-353-8522
| | | | - Marta Geretto
- Department of Experimental Medicine, University of Genova, 16132 Genova, Italy;
| | | | - Sara Schenone
- Department of Health Sciences, University of Genova, 16132 Genova, Italy; (S.S.); (E.D.M.)
| | - Emilio Di Maria
- Department of Health Sciences, University of Genova, 16132 Genova, Italy; (S.S.); (E.D.M.)
- Unit of Medical Genetics, Galliera Hospital, 16128 Genoa, Italy
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20
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Sakin A, Sahin S, Sengul Samanci N, Yasar N, Demir C, Geredeli C, Erhan SS, Akboru MH, Cihan S. The impact of tumor regression grade on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy. J Oncol Pharm Pract 2020; 26:1611-1620. [PMID: 32046577 DOI: 10.1177/1078155219900944] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE The aim of this study is to investigate the prognostic effect of tumor regression grade (TRG) on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy. METHODS Medical records of 182 patients with locally advanced rectal cancer, who were treated with preoperative chemoradiotherapy followed by surgery between 2002 and 2016, were retrospectively reviewed. TRG was classified into five categories based on the pathological response as follows - TRG1: no viable cancer cell, TRG2: single cancer cell or small groups of cancer cells, TRG3: residual tumor outgrown by fibrosis, TRG4: residual tumor outgrowing fibrosis, TRG5: diffuse residual tumor without regression. TRG1, (TRG2+TRG3), and (TRG4+TRG5) were grouped as complete response, intermediate response, and no response, respectively. RESULTS Of the 182 patients with locally advanced rectal cancer, 112 (61.5%) were male. The mean age was 54.4 (range, 25-87) years. The total number of patients in complete response, intermediate response, and no response group was 24 (13.2%), 105 (57.7%), and 53 (29.1%), respectively. The corresponding five-year relapse-free survival and overall survival rates were 79.8%-92.3%, 74.7%-79.4%, and 55.7%-55.8%, respectively (p < 0.05 for relapse-free survival, p < 0.05 for overall survival). According to ypTNM stage, there was no significant difference in relapse-free survival among TRG groups in ypStage I and II patients (p > 0.05). In ypStage III patients, relapse-free survival was 62 months in no response group vs. not reached in intermediate response group (p < 0.05). According to the ypTNM, there was no significant difference in overall survival among TRG groups in ypStage I, II, and III patients (p > 0.05). In the multivariate analysis, pathological complete response was found to be an independent variable for relapse-free survival and overall survival (hazard ratio (95% confidence interval), 0.34 (0.17-6.77), 0.39 (0.18-0.83), respectively). CONCLUSION This study showed that patients with pathological complete response to preoperative chemoradiotherapy had longer relapse-free survival and overall survival rates than those with residual disease.
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Affiliation(s)
- Abdullah Sakin
- Department of Medical Oncology, Yuzuncu Yil University Faculty of Medicine, Van, Turkey
| | - Suleyman Sahin
- Department of Medical Oncology, University of Health Sciences, Van Training and Research hospital, Van, Turkey
| | - Nilay Sengul Samanci
- Department of Medical Oncology, Cerrahpasa University Faculty of Medicine, Istanbul, Turkey
| | - Nurgul Yasar
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Cumhur Demir
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Caglayan Geredeli
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Selma Sengiz Erhan
- Department of Patology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Mustafa Halil Akboru
- Department of Radiation Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Sener Cihan
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
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21
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Fanelli GN, Loupakis F, Smyth E, Scarpa M, Lonardi S, Pucciarelli S, Munari G, Rugge M, Valeri N, Fassan M. Pathological Tumor Regression Grade Classifications in Gastrointestinal Cancers: Role on Patients' Prognosis. Int J Surg Pathol 2019; 27:816-835. [PMID: 31416371 DOI: 10.1177/1066896919869477] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Preoperative chemotherapy or combined radiotherapy and chemotherapy (CRT), followed by surgery, represents the standard approach for locally advanced esophageal, gastric, and rectal carcinomas. To adequately evaluate the effects of neoadjuvant CRT in the resection specimens, several histopathologic tumor regression grade (TRG) scoring systems have been introduced into clinical practice. The primary goal of these TRG systems relies on a correct prognostic stratification of patients in the attempt to help clinical decision-making and influence surgical strategies, postoperative adjuvant therapies, and surveillance intensity. However, most TRG systems suffer from poor reproducibility and low interobserver concordance rates. Many efforts have been made in the identification of alternative, robust, simple, and universally accepted TRG scoring systems, which would help in the comparison of different treatment strategies and in the standardization of multimodal therapies. The aim of this review is to analyze the most commonly used TRG systems in gastrointestinal cancers highlighting their pitfalls and usefulness, depending on the tumor type.
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Affiliation(s)
| | | | | | - Marco Scarpa
- Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | - Sara Lonardi
- Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | | | | | | | - Nicola Valeri
- Royal Marsden Hospital, London and Sutton, UK
- The Institute of Cancer Research, London and Sutton, UK
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22
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Hayes IP, Milanzi E, Gibbs P, Reece JC. Neoadjuvant Chemoradiotherapy and Tumor Recurrence in Patients with Early T-Stage Cancer of the Lower Rectum. Ann Surg Oncol 2019; 27:1570-1579. [PMID: 31773520 DOI: 10.1245/s10434-019-08105-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND The role neoadjuvant chemoradiotherapy (nCRT) plays in oncological outcomes in early T-stage rectal cancer is uncertain. The present work aims to clarify prognostic outcomes by estimating the effect of nCRT on tumor recurrence prior to major surgery compared with major surgery alone. PATIENTS AND METHODS Prospectively collected data were retrospectively analyzed for patients diagnosed with localized rectal adenocarcinoma ≤ 8 cm from the anal verge, with final histopathology ≤ T2 (≤ ypT2/≤ pT2), regardless of magnetic resonance imaging staging, between 1990 and 2017. As the effect of nCRT on recurrence varied over time, thereby violating the Cox proportional hazards assumption, the effect of nCRT on recurrence hazards was estimated using a time-varying multivariate Cox model over two separate time intervals (≤ 1 year and > 1 year postsurgery) by nCRT. RESULTS Long-course nCRT was associated with a 5.6-fold increase in the hazard of recurrence ≤ 1 year postsurgery [hazard ratio (HR) 5.6; 95% confidence interval (CI) 1.2-24.9; P = 0.02], but there was no increase in recurrence hazards > 1 year (HR 0.84; 95% CI 0.4-2.0; P = 0.70). In subgroup analysis restricted to ≤ mrT2/≤ ypT2 and ≤ pT2 tumors (omitting > mrT2 tumors), the effect of nCRT on recurrence no longer varied over time, indicating that tumor heterogeneity was responsible for the observed increased recurrence hazards ≤ 1 year postsurgery; That is, > mrT2 tumors that were downstaged to ≤ ypT2 after nCRT were responsible for the time-varying effects of nCRT and increased recurrence hazards ≤ 1 year postsurgery. Subsequently, no difference was found in prognostic outcomes either with or without nCRT before surgery in the homogeneous population of ≤ mrT2/≤ ypT2 and ≤ pT2 tumors. CONCLUSIONS No evidence was found to indicate that nCRT prior to surgery reduces tumor recurrence in early T-stage lower rectal cancer compared with surgery alone.
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Affiliation(s)
- Ian P Hayes
- Colorectal Surgery Unit, Suite 2, Private Medical Centre, Royal Melbourne Hospital, Parkville, VIC, Australia. .,Department of Surgery, The University of Melbourne, Parkville, VIC, Australia.
| | - Elasma Milanzi
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, VIC, Australia.,Victorian Centre for Biostatistics, Melbourne, VIC, Australia
| | - Peter Gibbs
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.,Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.,Department of Medical Oncology, Western Health, Melbourne, VIC, Australia
| | - Jeanette C Reece
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, VIC, Australia.,The University of Melbourne Centre for Cancer Research, The University of Melbourne, Parkville, VIC, Australia
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23
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Nahas SC, Nahas CSR, Cama GM, de Azambuja RL, Horvat N, Marques CFS, Menezes MR, Junior UR, Cecconello I. Diagnostic performance of magnetic resonance to assess treatment response after neoadjuvant therapy in patients with locally advanced rectal cancer. Abdom Radiol (NY) 2019; 44:3632-3640. [PMID: 30663025 DOI: 10.1007/s00261-019-01894-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE Our study aimed to evaluate the diagnostic performance of rectal magnetic resonance imaging (MRI) for local restaging in patients with non-metastatic locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT) using surgical histopathology of total mesorectal excision as the reference standard. METHODS Ninety-five patients with LARC who underwent rectal MRI after CRT between January 2014 and December 2016 were included. Accuracy, sensitivity, specificity, positive, and negative predictive value for local staging regarding T-stage, N-stage, circumferential resection margin, and MRI tumor regression grade (ymriTRG) were calculated, and inter-test agreements were assessed. RESULTS 22/95 (23.2%) patients had radiological complete response (rCR), whereas 20/95 (21.1%) had pathological complete response (pCR). Among the patients with pCR, 11/20 (55%) had rCR. Fair agreement was demonstrated between ymriTRG and pathological TRG (ypTRG) (κ = 0.255). The sensitivity and specificity for detection of pCR were 61.1% (95% CI 35.7-82.7) and 89.6% (95% CI 80.6-95.4). For the detection of ypTRG grades 1 and 2, the corresponding values were 67.2% (95% CI 54.3-78.4) and 51.6 (95% CI 33.1-69.8). The accuracy of ymriTRG was 24.2% (95% CI 15.6-32.8). Inter-test agreement in TRG between MRI and pathology was overall fair (κ = 0.255) and slight (κ = 0.179), if TRG 1 + 2. CONCLUSION Qualitative assessment on MRI for diagnosing pCR showed moderate sensitivity and high specificity, whereas the diagnosis of TRG had moderate sensitivity and low specificity with slight to fair inter-test agreement when compared with pathological specimens.
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24
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Yokoyama Y, Sakatani T, Wada R, Ishino K, Kudo M, Koizumi M, Yamada T, Yoshida H, Naito Z. In vitro and in vivo studies on the association of long non‑coding RNAs H19 and urothelial cancer associated 1 with the susceptibility to 5‑fluorouracil in rectal cancer. Int J Oncol 2019; 55:1361-1371. [PMID: 31638183 DOI: 10.3892/ijo.2019.4895] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 08/29/2019] [Indexed: 11/06/2022] Open
Abstract
There is no predictive biomarker for response to 5‑fluorouracil (5FU)‑based neoadjuvant chemotherapy (NAC) in rectal cancer. In the present study, we examined potential long non‑coding RNAs (lncRNAs) linked to the susceptibility to 5FU in cultured colorectal cancer cells, and in biopsy and resected tissues of 31 human rectal cancer cases treated with NAC. Candidate lncRNAs for the prediction of susceptibility to 5FU were investigated by comprehensive analysis of expression profiles of 84 lncRNAs in cultured cells using PCR array. Bioinformatic analysis identified H19 and urothelial cancer associated 1 (UCA1) as candidate biomarkers for 5FU susceptibility. Quantitative PCR of H19 and UCA1 in cultures of colorectal cancer cells demonstrated the notable variation in expression. The ratios of changes of H19 and UCA1 expression in response to 5FU were low in cells resistant to 5FU, whereas ratios were high in cells susceptible to 5FU. In 5FU‑susceptible cells, cell proliferation was inhibited by 5FU. Upregulation of H19 and UCA1 were associated with the reduction in target molecule expression, including retinoblastoma and p27kip1. In 31 cases of rectal cancer, H19 and UCA1 expression levels in biopsy and resected tissue were comparable. The ratios of H19 and UCA1 expression in resected tissue compared with biopsy samples were low in 17 cases, whereas the ratios were high in 14 cases; 11 of the 17 cases (65%) with low ratios exhibited poor response to NAC, whereas 4 of the 14 cases (29%) with high ratios showed poor response (P=0.045). The increase in H19 and UCA1 expression may represent the response to impaired cell cycle in cells susceptible to 5FU. Our results indicate that changes in H19 and UCA1 expression may be considered for predicting the susceptibility to 5FU‑based NAC in rectal cancer.
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Affiliation(s)
- Yasuyuki Yokoyama
- Department of Integrated Diagnostic Pathology, Nippon Medical School Hospital, Tokyo 113‑8602, Japan
| | - Takashi Sakatani
- Department of Integrated Diagnostic Pathology, Nippon Medical School Hospital, Tokyo 113‑8602, Japan
| | - Ryuichi Wada
- Department of Integrated Diagnostic Pathology, Nippon Medical School Hospital, Tokyo 113‑8602, Japan
| | - Kousuke Ishino
- Department of Integrated Diagnostic Pathology, Nippon Medical School Hospital, Tokyo 113‑8602, Japan
| | - Mitsuhiro Kudo
- Department of Integrated Diagnostic Pathology, Nippon Medical School Hospital, Tokyo 113‑8602, Japan
| | - Michihiro Koizumi
- Department of Gastrointestinal and Hepato‑Biliary‑Pancreatic Surgery, Nippon Medical School Hospital, Tokyo 113‑8602, Japan
| | - Takeshi Yamada
- Department of Gastrointestinal and Hepato‑Biliary‑Pancreatic Surgery, Nippon Medical School Hospital, Tokyo 113‑8602, Japan
| | - Hiroshi Yoshida
- Department of Gastrointestinal and Hepato‑Biliary‑Pancreatic Surgery, Nippon Medical School Hospital, Tokyo 113‑8602, Japan
| | - Zenya Naito
- Department of Integrated Diagnostic Pathology, Nippon Medical School Hospital, Tokyo 113‑8602, Japan
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25
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Vandendorpe B, Durot C, Lebellec L, Le Deley MC, Sylla D, Bimbai AM, Amroun K, Ramiandrisoa F, Cordoba A, Mirabel X, Hoeffel C, Pasquier D, Servagi-Vernat S. Prognostic value of the texture analysis parameters of the initial computed tomographic scan for response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer. Radiother Oncol 2019; 135:153-160. [DOI: 10.1016/j.radonc.2019.03.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 02/28/2019] [Accepted: 03/11/2019] [Indexed: 12/21/2022]
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26
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Kim SM, Yoon G, Seo AN. What are the most important prognostic factors in patients with residual rectal cancer after preoperative chemoradiotherapy? Yeungnam Univ J Med 2019; 36:124-135. [PMID: 31620624 PMCID: PMC6784638 DOI: 10.12701/yujm.2019.00157] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 03/15/2019] [Accepted: 03/18/2019] [Indexed: 01/01/2023] Open
Abstract
Background We aimed to establish robust histoprognostic predictors on residual rectal cancer after preoperative chemoradiotherapy (CRT). Methods Analyzing known histoprognostic factors in 146 patients with residual disease allows associations with patient outcome to be evaluated. Results The median follow-up time was 77.8 months, during which 59 patients (40.4%) experienced recurrence and 41 (28.1%) died of rectal cancer. On univariate analysis, residual tumor size, ypT category, ypN category, ypTNM stage, downstage, tumor regression grade, lymphatic invasion, perineural invasion, venous invasion, and circumferential resection margin (CRM) were significantly associated with recurrence free survival (RFS) or/and cancer-specific survival (CSS) (all p<0.005). On multivariate analysis, higher ypTNM stage and CRM positivity were identified as independent prognostic factors for RFS (ypTNM stage, p=0.024; CRM positivity, p<0.001) and CSS (p=0.022, p=0.017, respectively). Furthermore, CRM positivity was an independent predictor of reduced RFS and CSS, irrespective of subgrouping according to downstage (non-downstage, p<0.001 and p<0.001; downstage, p=0.002 and p=0.002) or lymph node metastasis (non-metastasis, p<0.001 and p=0.001; metastasis, p<0.001 and p<0.001). Conclusion CRM status may be as powerful as ypTNM stage as a prognostic indicator for patient outcome in patients with residual rectal cancer after preoperative CRT.
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Affiliation(s)
- Sol-Min Kim
- Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Ghilsuk Yoon
- Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea.,Department of Pathology, Kyungpook National University Chilgok Hospital, Daegu, Korea
| | - An Na Seo
- Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea.,Department of Pathology, Kyungpook National University Chilgok Hospital, Daegu, Korea
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27
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Ichikawa N, Homma S, Funakoshi T, Hattori M, Sato M, Kamiizumi Y, Omori K, Nomura M, Yokota R, Koike M, Kon H, Takeda K, Ishizu H, Hirose K, Kuraya D, Ishikawa T, Murata R, Iijima H, Kawamata F, Yoshida T, Ohno Y, Minagawa N, Takahashi N, Taketomi A. Preoperative FOLFOX in resectable locally advanced rectal cancer can be a safe and promising strategy: the R-NAC-01 study. Surg Today 2019; 49:712-720. [DOI: 10.1007/s00595-019-01788-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Accepted: 02/07/2019] [Indexed: 12/31/2022]
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28
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Frambach P, Pucciarelli S, Perin A, Zuin M, Toppan P, Maretto I, Urso EDL, Spolverato G. Metastatic pattern and new primary tumours after neoadjuvant therapy and surgery in rectal cancer. Colorectal Dis 2018; 20:O326-O334. [PMID: 30230157 DOI: 10.1111/codi.14427] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Accepted: 09/05/2018] [Indexed: 01/13/2023]
Abstract
AIM Current follow-up guidelines for distant tumour recurrence after rectal cancer surgery are not defined or agreed. The aim was to elucidate the pattern of recurrence over time and provide information that could help direct a strategy for surveillance. METHOD In all, 378 patients with locally advanced rectal cancer were treated with preoperative chemoradiotherapy and surgery with curative intent. Patients were followed up with a standard protocol, and data were prospectively collected in a dedicated database. Disease-free survival and overall survival were calculated. RESULTS Within a median follow-up time of 75 months, rates of local and distant recurrence were 2.6% and 21.7%, respectively. Risk factors for recurrence were a baseline carcinoembryonic antigen > 5.0 ng/ml, a distance from the anal verge ≤ 5 cm, R1 resection margins, G3 grading, ypT staging > 2, positive lymph node status and a tumour regression grade of 3-5. Disease-free survival did not vary significantly between patients with lung and extra-pulmonary metastases (P = 0.59). The only factor associated with increased risk of lung metastases was a distance of the tumour from the anal verge of ≤ 5 cm (P = 0.01). Most recurrences occurred within the first 3 years after surgery (74.4%). The first site of recurrence was most frequently the lung (52.0%). The most frequent new primary malignancy was lung cancer (22.5%). CONCLUSIONS Patients undergoing curative therapy for rectal cancer often experience distant recurrence; the majority of recurrences occur within the first 3 years after surgery and lung metastases are the most common. A predictive factor for pulmonary recurrence is a tumour in the lower rectum.
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Affiliation(s)
- P Frambach
- Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padova, Italy
| | - S Pucciarelli
- Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padova, Italy
| | - A Perin
- Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padova, Italy
| | - M Zuin
- Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padova, Italy
| | - P Toppan
- Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padova, Italy
| | - I Maretto
- Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padova, Italy
| | - E D L Urso
- Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padova, Italy
| | - G Spolverato
- Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padova, Italy
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29
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Abstract
The management of locally-advanced rectal cancer involves a combination of chemotherapy, chemoradiation, and surgical resection to provide excellent local tumor control and overall survival. However, aspects of this multimodality approach are associated with significant morbidity and long-term sequelae. In addition, there is growing evidence that patients with a clinical complete response to chemotherapy and chemoradiation treatments may be safely offered initial non-operative management in a rigorous surveillance program. Weighed against the morbidity and significant sequelae of rectal resection, recognizing how to best optimize non-operative strategies without compromising oncologic outcomes is critical to our understanding and treatment of this disease.
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Affiliation(s)
- Iris H Wei
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering, New York, NY, USA -
| | - Julio Garcia-Aguilar
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering, New York, NY, USA
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30
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Model predicting the ypN0 status after good response to chemoradiotherapy in rectal cancer. Am J Surg 2018; 216:438-443. [PMID: 29656991 DOI: 10.1016/j.amjsurg.2018.03.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Revised: 03/14/2018] [Accepted: 03/29/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND The purpose of this study was to identify the predictive factors for ypN0 status in tumors with good pathologic response to chemoradiotherapy (CRT). METHODS A retrospective chart review was conducted on patients at two tertiary cancer center who underwent rectal resection after good response to CRT between 2000 and 2013. RESULTS No preoperative treatment (oxaliplatin use, radiotherapy boost of 5,4 Gy, delay CRT-surgery) impacted on the ypN status. In the multivariate analysis, only a ypT<3 (HR 7.5 [2,9-19.5]) was significant and no lymphovascular invasion (HR 8,9 [1.6-49.8]) was limited to significance.The best model predicting the ypN0 status used only the ypT status<3. The major part (92.2%) of patients with ypT0-2 tumors had no LN invasion. CONCLUSION The risk of lymph node involvement metastases was only 7.8% for the patients with an ypT0-2 status. A fullthickness transanal resection coud be the futur treatment of these patients.
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31
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Rampazzo E, Del Bianco P, Bertorelle R, Boso C, Perin A, Spiro G, Bergamo F, Belluco C, Buonadonna A, Palazzari E, Leonardi S, De Paoli A, Pucciarelli S, De Rossi A. The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients. Br J Cancer 2018; 118:878-886. [PMID: 29449673 PMCID: PMC5877438 DOI: 10.1038/bjc.2017.492] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 12/13/2017] [Accepted: 12/18/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. METHODS 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT=T0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4-8 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. RESULTS Plasma levels of TERT were significantly lower at T2 (P<0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73-0.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10-4.11)-fold and 4.55 (95% CI 1.48-13.95)-fold higher, respectively, than those with undetectable plasma TERT levels. CONCLUSIONS Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy.
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Affiliation(s)
- Enrica Rampazzo
- Section of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Gattamelata 64, Padova 35128, Italy
| | - Paola Del Bianco
- Clinical Trials and Biostatistic Unit, Istituto Oncologico Veneto (IOV)-IRCCS, Via Gattamelata 64, Padova 35128, Italy
| | - Roberta Bertorelle
- Immunology and Molecular Oncology Unit, IOV- IRCCS, Via Gattamelata 64, Padova 35128, Italy
| | - Caterina Boso
- Radiotherapy and Nuclear Medicine Unit, IOV-IRCCS, Via Gattamelata 64, 35128 Padova, Italy
| | - Alessandro Perin
- Section of Surgery, Department of Surgery, Oncology and Gastroenterology, Via Giustiniani 1, University of Padova, Padova 35128, Italy
| | - Giovanna Spiro
- Section of Surgery, Department of Surgery, Oncology and Gastroenterology, Via Giustiniani 1, University of Padova, Padova 35128, Italy
| | - Francesca Bergamo
- Medical Oncology Unit 1, IOV-IRCCS, Via Gattamelata 64, Padova 35128, Italy
| | - Claudio Belluco
- Department of Surgical Oncology, Centro di Riferimento Oncologico (CRO)-IRCCS, Aviano, Italy
| | | | | | - Sara Leonardi
- Medical Oncology Unit 1, IOV-IRCCS, Via Gattamelata 64, Padova 35128, Italy
| | | | - Salvatore Pucciarelli
- Section of Surgery, Department of Surgery, Oncology and Gastroenterology, Via Giustiniani 1, University of Padova, Padova 35128, Italy
| | - Anita De Rossi
- Section of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Gattamelata 64, Padova 35128, Italy
- Immunology and Molecular Oncology Unit, IOV- IRCCS, Via Gattamelata 64, Padova 35128, Italy
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32
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Yan H, Wang R, Zhu K, Zhao W, Jiang S, Feng R, Xu X, Meng X, Sun H, Zhang H, Mu D, Xu Z. Predictors of Sensitivity to Preoperative Chemoradiotherapy of Rectal Adenocarcinoma. TUMORI JOURNAL 2018; 97:717-23. [DOI: 10.1177/030089161109700607] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Objectives The purpose of the study was to identify predictive factors of tumor response to preoperative chemoradiotherapy for rectal adenocarcinoma. Methods Ninety-eight patients with nonmetastatic rectal adenocarcinoma received preoperative concurrent chemoradiotherapy and underwent mesorectal excision. After treatment, tumor response according to tumor regression grade were evaluated. The correlation of clinicopathologic factors to tumor response was analyzed. Results The results from a univariate analysis indicated that pretreatment carcinoembryonic antigen level ≤3.0 ng/ml (P = 0.002), non-fixed tumor (P = 0.001), and tumor circumferential extent ≤50% (P = 0.001) were associated significantly with a good tumor response. They also indicated that pretreatment positive lymph nodes (P = 0.032) were associated significantly with a poor tumor response. In multivariate analysis, the results indicated that pretreatment carcinoembryonic antigen level (hazard ratio, 2.930; P = 0.003), tumor mobility (hazard ratio, 2.651; P = 0.002) and circumferential extent of tumor (hazard ratio, 2.394; P = 0.019) independently predicted a good pathologic response rate. Pretreatment positive lymph nodes were not significantly associated with a good response (hazard ratio, 0.361; P = 0.191). Conclusions Pretreatment carcinoembryonic antigen level, tumor mobility and circumferential extent of tumor may be helpful in predicting responsiveness in rectal adenocarcinoma to preoperative chemoradiotherapy, although the results should be confirmed in larger, more homogeneous studies.
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Affiliation(s)
- Hongjiang Yan
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, PR China
| | - Renben Wang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, PR China
| | - Kunli Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, PR China
| | - Wei Zhao
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, PR China
| | - Shumei Jiang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, PR China
| | - Rui Feng
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, PR China
| | - Xiaoqing Xu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, PR China
| | - Xiangjiao Meng
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, PR China
| | - Huiying Sun
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, PR China
| | - Haiqin Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, PR China
| | - Dianbin Mu
- Department of Pathology, Shandong Cancer Hospital and Institute, Jinan, PR China
| | - Zhongfa Xu
- Department of General Surgery, Shandong Cancer Hospital and Institute, Jinan, PR China
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von Moos R, Koeberle D, Schacher S, Hayoz S, Winterhalder RC, Roth A, Bodoky G, Samaras P, Berger MD, Rauch D, Saletti P, Plasswilm L, Zwahlen D, Meier UR, Yan P, Izzo P, Klingbiel D, Bärtschi D, Zaugg K. Neoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced KRAS-mutated rectal cancer: A phase I/II trial (SAKK 41/08). Eur J Cancer 2017; 89:82-89. [PMID: 29241084 DOI: 10.1016/j.ejca.2017.11.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Revised: 10/27/2017] [Accepted: 11/01/2017] [Indexed: 12/01/2022]
Abstract
BACKGROUND KRAS mutation occurs in ∼40% of locally advanced rectal cancers (LARCs). The multitarget tyrosine kinase inhibitor sorafenib has radiosensitising effects and might improve outcomes for standard preoperative chemoradiotherapy in patients with KRAS-mutated LARC. METHODS Adult patients with KRAS-mutated T3/4 and/or N1/2M0 LARC were included in this phase I/II study. The phase I dose-escalation study of capecitabine plus sorafenib and radiotherapy was followed by a phase II study assessing efficacy and safety. Primary end-points were to: establish the maximum tolerated dose of the regimen in phase I; determine the pathologic complete response (pCR) rate in phase II defined as Dworak regression grade 3 and 4. RESULTS Fifty-four patients were treated at 18 centres in Switzerland and Hungary; 40 patients were included in the single-arm phase II study. Recommended doses from phase I comprised radiotherapy (45 Gy in 25 fractions over 5 weeks) with capecitabine 825 mg/m2 twice daily × 33 plus sorafenib 400 mg/d. Median daily dose intensity in phase II was radiotherapy 100%, capecitabine 98.6%, and sorafenib 100%. The pCR rate (Dworak 3/4) was 60% (95% CI, 43.3-75.1%) by central independent pathologic review. Sphincter preservation was achieved in 89.5%, R0 resection in 94.7%, and downstaging in 81.6%. The most common grade 3 toxicities during phase II included diarrhoea (15.0%), skin toxicity outside radiotherapy field (12.5%), pain (7.5%), skin toxicity in radiotherapy field, proctitis, fatigue and cardiac ischaemia (each 5%). CONCLUSIONS Combining sorafenib and standard chemoradiotherapy with capecitabine is highly active in patients with KRAS-mutated LARC with acceptable toxicity and deserves further investigation. www.clinicaltrials.gov: NCT00869570.
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Affiliation(s)
| | | | | | | | | | - Arnaud Roth
- University Hospital Geneva, Geneva, Switzerland
| | | | | | | | | | | | - Ludwig Plasswilm
- Kantonsspital St. Gallen, St. Gallen, Switzerland; Inselspital Bern, Bern, Switzerland
| | | | - Urs R Meier
- Kantonsspital Winterthur, Winterthur, Switzerland
| | - Pu Yan
- University Hospital Zürich, Zürich, Switzerland
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Li YH, Li JL, Zhu XG, He JY, Lin LM, Lin XY, Tang LR, Cai Y. Associations of tumor regression grade with outcomes in patients with locally advanced rectal cancer treated with preoperative two-week course of radiotherapy. Oncotarget 2017; 8:100165-100175. [PMID: 29245968 PMCID: PMC5725010 DOI: 10.18632/oncotarget.22118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Accepted: 09/22/2017] [Indexed: 11/25/2022] Open
Abstract
Purpose Studies concerning tumor regression grade (TRG) after two-week course of radiotherapy (RT) are limited. We tried to assess associations of TRG and outcomes in patients with locally advanced rectal cancer (LARC) treated with preoperative two-week course of RT. Methods 356 consecutive LARC patients were retrospectively assessed. Patients with complete/intermediate (TRG1-3) and poor (TRG4-5) regressions were compared for overall survival (OS), disease-free survival (DFS) and metastasis-free survival (MFS). Results By univariate analysis, pretreatment and postoperative factors including TNM stages, ypT, ypN, surgical procedure, pathological grade, and TRG impacted survival outcomes. Complete/intermediate regressions (TRG1-3) had significantly improved survival outcomes compared with poor ones (TRG4-5) (5y-OS, 85.8% vs. 65.8%, P=0.001; 5y-DFS, 76.0% vs. 53.7%, P<0.001; 5y-MFS, 84.2% vs. 66.7%, P<0.001). Multivariate analysis showed that ypN (P<0.001) and pathological grade (P=0.018) were the most important independent prognostic factors for DFS. ypT (P=0.014) and ypN (P=0.001) were the independent prognostic factors for MFS. Meanwhile, ypT (P=0.009), ypN (P=0.001), surgical procedure (p=0.001), and TRG (p=0.019) were the independent prognostic factors for OS. Conclusions Complete/intermediate TRG regressions had a more favorable prognosis than the poor group. When treated with preoperative two-week course of RT; ypT, ypN, surgical procedure, and TRG seem to affect OS.
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Affiliation(s)
- Yong-Heng Li
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education /Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Jin-Luan Li
- Departments of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Xiang-Gao Zhu
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education /Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Jun-Yan He
- Department of Biochemistry and Molecular Biology, University of South China, Hengyang, China
| | - Li-Mei Lin
- Affiliated Xiamen First Hospital of Xiamen University, Xiamen, China
| | | | - Li-Rui Tang
- Departments of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Yong Cai
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education /Beijing), Peking University Cancer Hospital & Institute, Beijing, China
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Modified 3-Point MRI-Based Tumor Regression Grade Incorporating DWI for Locally Advanced Rectal Cancer. AJR Am J Roentgenol 2017; 209:1247-1255. [PMID: 28981353 DOI: 10.2214/ajr.16.17242] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
OBJECTIVE The purpose of this study was to evaluate the prognostic relevance of a modified 3-point MRI-based tumor regression grading system incorporating DWI for patients with locally advanced rectal cancer after preoperative chemoradiotherapy (CRT). MATERIALS AND METHODS Between March 2012 and September 2013, 118 consecutively registered patients with middle or lower locally advanced rectal cancer who underwent CRT followed by surgery were enrolled in this retrospective study. Two radiologists in consensus assessed MRI tumor regression grade (mrTRG) based on T2-weighted images and high b value DW images (0 and 1000 s/mm2) using the following grades: 0, complete regression (no obvious tumor); 1, intermediate regression (dominant fibrosis, regression > 50%); 2, poor regression (dominant tumor, regression ≤ 50%). Multivariate analysis with a Cox regression model was performed to evaluate the association between modified mrTRG and 3-year disease-free survival (DFS) rate. A Kaplan-Meier method with a log-rank test was used to compare the DFS rate between responder (grades 0 and 1) and nonresponder (grade 2) groups. RESULTS Both the accuracy (72.9% vs 38.1%; p < 0.001) and the interreader agreement (κ = 0.580 vs 0.338; p < 0.001) of modified 3-point mrTRG were improved over the established 5-point mrTRG. Modified mrTRG (adjusted hazard ratio, 2.505; 95% CI, 1.231-5.100) was independently associated with 3-year DFS rate (p = 0.011). There was also a significant difference in the 3-year DFS rate between responders (73.8%; 95% CI, 64.2-81.3%) and nonresponders (41.7%; 95% CI, 10.9-70.8%) (p = 0.028). CONCLUSION In patients with middle or lower locally advanced rectal cancer, the modified 3-point mrTRG incorporating DWI was independently associated with the 3-year DFS rate after CRT followed by surgery. The grading scale may be used as a surrogate for expected prognosis of preoperative CRT. Further prospective trials are warranted.
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Applicability of American Joint Committee on Cancer and College of American Pathologists Regression Grading System in Rectal Cancer. Dis Colon Rectum 2017; 60:815-826. [PMID: 28682967 DOI: 10.1097/dcr.0000000000000806] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Different tumor grading systems have been proposed to predict the association between tumor response and clinical outcome after preoperative chemoradiotherapy in patients with rectal cancer. The American Joint Committee on Cancer and College of American Pathologists regression grading system was recommended as the standard tumor regression grading system for rectal adenocarcinoma. OBJECTIVE This study evaluated the clinical applicability of the American Joint Committee on Cancer and College of American Pathologists regression grading system in neoadjuvant-treated patients with rectal cancer. DESIGN This is a retrospective cohort study based on clinical data from a prospectively maintained colorectal cancer database. SETTINGS This study was performed at a single tertiary referral center. PATIENTS A total of 144 patients with primary locally advanced mid-to-low rectal adenocarcinoma who underwent preoperative long-course chemoradiotherapy and total mesorectal excision between 2003 and 2012 were included. MAIN OUTCOMES MEASURES The primary outcome measures were the 5-year overall survival rate, the relapse-free survival rate, the cancer-specific survival rate, and cumulative recurrence rates. RESULTS Of the 144 patients, 16 (11%) were diagnosed as American Joint Committee on Cancer and College of American Pathologists regression grade 0, 43 patients (30%) as grade 1, 61 patients (42%) as grade 2, and 25 patients (17%) as grade 3.After a median follow-up time of 83 months (range, 3 to 147 mo), 5-year survival estimates for grades 0, 1, 2, and 3, were 93%, 77%, 81%, and 54% for overall survival (p = 0.006); 93%, 82%, 75%, and 55% for relapse-free survival (p = 0.03); and 100%, 86%, 89%, and 63% for cancer-specific survival (p = 0.006). The multivariate Cox regression analyses confirmed the American Joint Committee on Cancer and College of American Pathologists regression grading system as a prognostic factor for overall (p = 0.04), relapse-free (p = 0.02), and cancer-specific survival (p = 0.04). LIMITATIONS This was a retrospective study. CONCLUSIONS Our study findings confirm the clinical relevance and applicability of the American Joint Committee on Cancer and College of American Pathologists regression grade system as a predictive factor for patients with rectal cancer. See Video Abstract at http://links.lww.com/DCR/A320.
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Santos MD, Silva C, Rocha A, Nogueira C, Castro-Poças F, Araujo A, Matos E, Pereira C, Medeiros R, Lopes C. Predictive clinical model of tumor response after chemoradiation in rectal cancer. Oncotarget 2017; 8:58133-58151. [PMID: 28938543 PMCID: PMC5601639 DOI: 10.18632/oncotarget.19651] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2017] [Accepted: 07/18/2017] [Indexed: 12/25/2022] Open
Abstract
Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. The ability to predict tumor response before treatment may significantly have impact the selection of patients for nCRT in rectal cancer. The aim is to identify potential predictive pretreatment factors for Mandard response and build a clinical predictive model design. 167 patients with locally advanced rectal cancer were treated with nCRT and curative surgery. Blood cell counts in peripheral blood were analyzed. Pretreatment biopsies expression of cyclin D1, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and protein 21 were assessed. A total of 61 single nucleotide polymorphisms were characterized using the Sequenom platform through multiplex amplification followed by mass-spectometric product separation. Surgical specimens were classified according to Mandard TRG. The patients were divided as: "good responders" (Mandard TRG1-2) and "poor responders" (Mandard TGR3-5). We examined predictive factors for Mandard response and performed statistical analysis. In univariate analysis, distance from anal verge, neutrophil lymphocyte ratio (NLR), cyclin D1, VEGF, EGFR, protein 21 and rs1810871 interleukin 10 (IL10) gene polymorphism are the pretreatment variables with predictive value for Mandard response. In multivariable analysis, NLR, cyclin D1, protein 21 and rs1800871 in IL10 gene maintain predictive value, allowing a clinical model design. CONCLUSION It seems possible to use pretreatment expression of blood and tissue biomarkers, and build a model of tumor response prediction to neoadjuvant chemoradiation in rectal cancer.
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Affiliation(s)
- Marisa D Santos
- Department of Surgery, Digestive Surgery Service, Hospital Center of Porto, Porto, Portugal.,Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal
| | - Cristina Silva
- Department of Surgery, Digestive Surgery Service, Hospital Center of Porto, Porto, Portugal.,Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal
| | - Anabela Rocha
- Department of Surgery, Digestive Surgery Service, Hospital Center of Porto, Porto, Portugal.,Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal
| | - Carlos Nogueira
- Department of Surgery, Digestive Surgery Service, Hospital Center of Porto, Porto, Portugal.,Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal
| | - Fernando Castro-Poças
- Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.,Gastroenterology Service, Hospital Center of Porto, Porto, Portugal
| | - António Araujo
- Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.,Service of Medical Oncology, Hospital Center of Porto, Porto, Portugal
| | - Eduarda Matos
- Department of Health Community, Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal
| | - Carina Pereira
- Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.,Molecular Oncology and Viral Pathology Group, IPO Research Center, Portuguese Oncologic Institute, Porto, Portugal.,Research Department, Portuguese League Against Cancer, Porto, Portugal
| | - Rui Medeiros
- Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.,Molecular Oncology and Viral Pathology Group, IPO Research Center, Portuguese Oncologic Institute, Porto, Portugal.,Research Department, Portuguese League Against Cancer, Porto, Portugal.,CEBIMED, Faculty of Health Sciences of Fernando Pessoa, University of Porto, Porto, Portugal
| | - Carlos Lopes
- Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.,Department of Pathology, Pathological Anatomy Service, Hospital Center of Porto, Porto, Portugal.,Department of Pathology and Molecular Immunology, Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal
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Suzuki T, Sadahiro S, Tanaka A, Okada K, Saito G, Miyakita H, Akiba T, Yamamuro H. A Modified Classification of Prognostic Factors Based on Pathological Stage and Tumor Regression Grade in Patients with Rectal Cancer Who Receive Preoperative Chemoradiotherapy. Oncology 2017; 93:287-294. [PMID: 28728151 DOI: 10.1159/000478266] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Accepted: 06/02/2017] [Indexed: 12/20/2022]
Abstract
OBJECTIVE The histologic response to neoadjuvant chemoradiotherapy (CRT) has been intimately related to outcomes in locally advanced rectal cancer. However, reliable prognostic factors have yet to be established. SUBJECTS AND METHODS The study group comprised 198 patients with locally advanced rectal cancer who received CRT. A modified classification based on the combination of ypStage and tumor regression grade (TRG) was developed. ypStage II with TRG 2 was classified as ypTRGstage IIA, and ypStage II with TRG 3 or 4 was classified as ypTRGstage IIB. ypStage 0 and ypStage I were classified as ypTRGstage I, and ypStage III was classified as ypTRGstage III. RESULTS The 5-year disease-free survival (DFS) was 83% in ypTRGstage I, 86% in ypTRGstage IIA, 57% in ypTRGstage IIB, and 60% in ypTRGstage III (p = 0.0001). The 5-year DFS in ypTRGstage IIA did not differ significantly from that in ypStage 0 (p = 0.865) or ypStage I (p = 0.585). The 5-year DFS in ypStage IIB did not differ from that in ypStage III (p = 0.912). Multivariate analysis showed that ypTRGstage was an independent risk factor for DFS. CONCLUSION A modified classification allows patients with ypStage II locally advanced rectal cancer to be clearly divided into two groups: responders and nonresponders.
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Affiliation(s)
- Toshiyuki Suzuki
- Department of Surgery, Tokai University School of Medicine, Isehara, Japan
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Xu L, Cai S, Xiao T, Chen Y, Qiu H, Wu B, Lin G, Sun X, Lu J, Zhou W, Xiao Y. Prognostic significance of tumour regression grade after neoadjuvant chemoradiotherapy for a cohort of patients with locally advanced rectal cancer: an 8-year retrospective single-institutional study. Colorectal Dis 2017; 19:O263-O271. [PMID: 28603932 DOI: 10.1111/codi.13757] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 04/12/2017] [Indexed: 12/25/2022]
Abstract
AIM Locally advanced rectal cancer (LARC) is frequently treated with neoadjuvant chemoradiotherapy (NACRT) to reduce the risk of local recurrence and improve survival. Tumour response to NACRT is variable and may influence the prognosis after subsequent surgery. This study compared the prognostic values of tumour regression grade (TRG) and neoadjuvant pathological (ypTNM) downstaging in patients with Stage II and III rectal cancer treated with NACRT followed by curative surgery. METHOD This study included 185 patients with LARC treated with long-course radiotherapy (45 Gy in 25 fractions) plus 5-fluorouracil over 5 weeks between 2005 and 2013. We used multivariate analysis to assess the relationship of Dworak's five-tier TRG, ypTNM stage and ypTNM downstaging with clinicopathological factors, 5-year disease-free survival (DFS) and 5-year overall survival (OS). RESULTS Total regression (TRG4), good regression (TRG3), moderate regression (TRG2), minor regression (TRG1) and no regression (TRG0) were seen in 38 (20.6%), 65 (35.2%), 43 (23.2%), 28 (15.1%) and 11 (5.9%) patients, respectively. TNM downstaging following NACRT occurred in 109 (58.9%) patients. The 5-year DFS rates after NACRT for TRG0, TRG1, TRG2, TRG3 and TRG4 were 0%, 58.5%, 66.4%, 80.4% and 82.6%, respectively (P < 0.001). The ypTNM stage correlated with 5-year DFS (P = 0.004) but not 5-year OS (P = 0.075). Multivariate analysis demonstrated that TRG was related to both DFS and OS (P < 0.001). CONCLUSION TRG measured on a five-tier system was better than ypTNM stage for predicting outcome in patients with LARC treated with NACRT and surgery.
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Affiliation(s)
- L Xu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - S Cai
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - T Xiao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Medical College of Soochow University, Suzhou, Jiangsu, China
| | - Y Chen
- National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China
| | - H Qiu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - B Wu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - G Lin
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - X Sun
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - J Lu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - W Zhou
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Y Xiao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Merx K, Martens UM, Kripp M, Hoehler T, Geissler M, Gaiser T, Mai S, Kienle P, Belle S, Plöger C, Hieber U, Wenz F, Post S, Hofheinz RD. Panitumumab in Combination With Preoperative Radiation Therapy in Patients With Locally Advanced RAS Wild-type Rectal Cancer: Results of the Multicenter Explorative Single-Arm Phase 2 Study NEORIT. Int J Radiat Oncol Biol Phys 2017; 99:867-875. [PMID: 28870789 DOI: 10.1016/j.ijrobp.2017.06.2460] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 06/16/2017] [Accepted: 06/22/2017] [Indexed: 12/31/2022]
Abstract
PURPOSE Studies investigating combinations of anti-epidermal growth factor receptor monoclonal antibodies such as panitumumab or cetuximab with standard chemoradiation therapy protocols in rectal cancer have yielded disappointing results. Because of the supposed negative interaction of epidermal growth factor receptor inhibition and chemoradiation therapy, we conducted a phase 2 study using single-agent panitumumab in combination with radiation therapy in patients with RAS wild-type locally advanced rectal cancer. METHODS AND MATERIALS Patients with RAS wild-type locally advanced (clinical stage II or III) rectal cancer localized 0 to 12 cm from the anus were eligible for study participation. The primary objective of the study was to determine pathologic complete response (pCR). Secondary objectives comprised assessing the safety, surgical morbidity, clinical response, tumor downstaging, and tumor regression grading according to Dworak. RESULTS A total of 54 patients with a median age of 58 years were treated. In 3.7% of patients, pCR was achieved. Downstaging of the primary tumor or lymph nodes was seen in 65% of patients. No grade ≥2 hematologic toxicity was seen. The most common grade ≥3 nonhematologic toxicities were skin toxicity (24%) and diarrhea (10%). CONCLUSIONS Panitumumab in combination with radiation therapy as neoadjuvant treatment for locally advanced rectal cancer showed a favorable toxicity profile but failed to meet the predefined pCR rate to justify further clinical trials.
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Affiliation(s)
- Kirsten Merx
- III Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany.
| | - Uwe M Martens
- Klinik für Innere Medizin III, Tumorzentrum Heilbronn-Franken, Klinikum am Gesundbrunnen, SLK Kliniken Heilbronn, Heilbronn, Germany
| | - Melanie Kripp
- III Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany
| | - Thomas Hoehler
- Medizinische Klinik I, Prosper Hospital Recklinghausen, Recklinghausen, Germany
| | - Michael Geissler
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen, Esslingen, Germany
| | - Timo Gaiser
- Pathologisches Institut, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany
| | - Sabine Mai
- Klinik für Strahlentherapie und Radioonkologie, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany
| | - Peter Kienle
- Chirurgische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany
| | - Sebastian Belle
- II Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany
| | | | | | - Frederik Wenz
- Klinik für Strahlentherapie und Radioonkologie, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany
| | - Stefan Post
- Chirurgische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany
| | - Ralf D Hofheinz
- Tagestherapiezentrum, Interdisziplinäres Tumorzentrum, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany
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Williamson JS, Jones HG, Williams N, Griffiths AP, Jenkins G, Beynon J, Harris DA. Extramural vascular invasion and response to neoadjuvant chemoradiotherapy in rectal cancer: Influence of the CpG island methylator phenotype. World J Gastrointest Oncol 2017; 9:209-217. [PMID: 28567185 PMCID: PMC5434388 DOI: 10.4251/wjgo.v9.i5.209] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 12/20/2016] [Accepted: 03/24/2017] [Indexed: 02/05/2023] Open
Abstract
AIM To identify whether CpG island methylator phenotype (CIMP) is predictive of response to neoadjuvant chemoradiotherapy (NACRT) and outcomes in rectal cancer.
METHODS Patients undergoing NACRT and surgical resection for rectal cancer in a tertiary referral centre between 2002-2011 were identified. Pre-treatment tumour biopsies were analysed for CIMP status (high, intermediate or low) using methylation specific PCR. KRAS and BRAF status were also determined using pyrosequencing analysis. Clinical information was extracted from case records and cancer services databases. Response to radiotherapy was measured by tumour regression scores determined upon histological examination of the resected specimen. The relationship between these molecular features, response to NACRT and oncological outcomes were analysed.
RESULTS There were 160 patients analysed with a median follow-up time of 46.4 mo. Twenty-one (13%) patients demonstrated high levels of CIMP methylation (CIMP-H) and this was significantly associated with increased risk of extramural vascular invasion (EMVI) compared with CIMP-L [8/21 (38%) vs 15/99 (15%), P = 0.028]. CIMP status was not related to tumour regression after radiotherapy or survival, however EMVI was significantly associated with adverse survival (P < 0.001). Intermediate CIMP status was significantly associated with KRAS mutation (P = 0.01). There were 14 (9%) patients with a pathological complete response (pCR) compared to 116 (73%) patients having no or minimal regression after neoadjuvant chemoradiotherapy. Those patients with pCR had median survival of 106 mo compared to 65.8 mo with minimal regression, although this was not statistically significant (P = 0.26). Binary logistic regression analysis of the relationship between EMVI and other prognostic features revealed, EMVI positivity was associated with poor overall survival, advanced “T” stage and CIMP-H but not nodal status, age, sex, KRAS mutation status and presence of local or systemic recurrence.
CONCLUSION We report a novel association of pre-treatment characterisation of CIMP-H with EMVI status which has prognostic implications and is not readily detectable on pre-treatment histological examination.
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Vychnevskaia K, Dumont F, Agostini J, Julié C, Dartigues P, Lazure T, Boige V, Goéré D, Brouquet A, Penna C, Peschaud F, Benoist S. Prognostic Value of Sterilized Lymph Nodes After Preoperative Chemoradiotherapy for Patients with ypN0 Rectal Cancer. Ann Surg Oncol 2017; 24:1304-1311. [DOI: 10.1245/s10434-016-5736-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Organ preservation with local excision or active surveillance following chemoradiotherapy for rectal cancer. Br J Cancer 2016; 116:169-174. [PMID: 27997526 PMCID: PMC5243997 DOI: 10.1038/bjc.2016.417] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 10/27/2016] [Accepted: 11/21/2016] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Organ preservation has been proposed as an alternative to radical surgery for rectal cancer to reduce morbidity and mortality, and to improve functional outcome. METHODS Locally advanced non-metastatic rectal cancers were identified from a prospective database. Patients staged ⩾T3 or any stage N+ were referred for neoadjuvant chemoradiotherapy (CRT) (50-54 Gy and 5-fluorouracil), and were reassessed 6-8 weeks post treatment. An active surveillance programme ('watch and wait') was offered to patients who were found to have a complete endoluminal response. Transanal excision was performed in patients who were found to have an objective clinical response and in whom a residual ulcer measured ⩽3 cm. Patients were followed up clinically, endoscopically and radiologically to assess for local recurrence or disease progression. RESULTS Of 785 patients with rectal cancer between 2005 and 2015, 362 had non-metastatic locally advanced tumours treated with neoadjuvant CRT. Sixty out of three hundred and sixty-two (16.5%) patients were treated with organ-preserving strategies - 10 with 'watch and wait' and 50 by transanal excision. Fifteen patients were referred for salvage total mesorectal excision post local excision owing to adverse pathological findings. There was no significant difference in overall survival (85.6% vs 93.3%, P=0.414) or disease-free survival rate (78.3% vs 80%, P=0.846) when the outcomes of radical surgery were compared with organ preservation. Tumour regrowth occurred in 4 out of 45 (8.9%) patients who had organ preservation. CONCLUSIONS Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve an objective endoluminal response to neoadjuvant CRT. Transanal excision defines the pathological response and refines decision-making.
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Siddiqui MRS, Bhoday J, Battersby NJ, Chand M, West NP, Abulafi AM, Tekkis PP, Brown G. Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales. World J Gastroenterol 2016; 22:8414-8434. [PMID: 27729748 PMCID: PMC5055872 DOI: 10.3748/wjg.v22.i37.8414] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 07/04/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To define good and poor regression using pathology and magnetic resonance imaging (MRI) regression scales after neo-adjuvant chemotherapy for rectal cancer.
METHODS A systematic review was performed on all studies up to December 2015, without language restriction, that were identified from MEDLINE, Cochrane Controlled Trials Register (1960-2015), and EMBASE (1991-2015). Searches were performed of article bibliographies and conference abstracts. MeSH and text words used included “tumour regression”, “mrTRG”, “poor response” and “colorectal cancers”. Clinical studies using either MRI or histopathological tumour regression grade (TRG) scales to define good and poor responders were included in relation to outcomes [local recurrence (LR), distant recurrence (DR), disease-free survival (DFS), and overall survival (OS)]. There was no age restriction or stage of cancer restriction for patient inclusion. Data were extracted by two authors working independently and using pre-defined outcome measures.
RESULTS Quantitative data (prevalence) were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. Qualitative data (LR, DR, DFS and OS) were presented as ranges. The overall proportion of poor responders after neo-adjuvant chemo-radiotherapy (CRT) was 37.7% (95%CI: 30.1-45.8). There were 19 different reported histopathological scales and one MRI regression scale (mrTRG). Clinical studies used nine and six histopathological scales for poor and good responders, respectively. All studies using MRI to define good and poor response used one scale. The most common histopathological definition for good response was the Mandard grades 1 and 2 or Dworak grades 3 and 4; Mandard 3, 4 and 5 and Dworak 0, 1 and 2 were used for poor response. For histopathological grades, the 5-year outcomes for poor responders were LR 3.4%-4.3%, DR 14.3%-20.3%, DFS 61.7%-68.1% and OS 60.7-69.1. Good pathological response 5-year outcomes were LR 0%-1.8%, DR 0%-11.6%, DFS 78.4%-86.7%, and OS 77.4%-88.2%. A poor response on MRI (mrTRG 4,5) resulted in 5-year LR 4%-29%, DR 9%, DFS 31%-59% and OS 27%-68%. The 5-year outcomes with a good response on MRI (mrTRG 1,2 and 3) were LR 1%-14%, DR 3%, DFS 64%-83% and OS 72%-90%.
CONCLUSION For histopathology regression assessment, Mandard 1, 2/Dworak 3, 4 should be used for good response and Mandard 3, 4, 5/Dworak 0, 1, 2 for poor response. MRI indicates good and poor response by mrTRG1-3 and mrTRG4-5, respectively.
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Huang SH, Chi P, Lin HM, Lu XR, Huang YW, Xu ZB, Sun YW, Ye DX, Wang XJ, Wang X. Selecting stage ypT0-1N0 for locally advanced rectal cancer following preoperative chemoradiotherapy: implications for potential candidates of organ-sparing management. Colorectal Dis 2016; 18:989-996. [PMID: 26880193 DOI: 10.1111/codi.13297] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2015] [Accepted: 12/01/2015] [Indexed: 12/11/2022]
Abstract
AIM Local excision or a wait-and-see policy may offer the possibility of organ preservation for locally advanced rectal cancer (LARC) after preoperative chemoradiotherapy (CRT). Identifying associated factors of good responders (GR) with stage ypT0-1N0 would probably influence the selection of potential candidates who were theoretically eligible for organ-sparing management. This study was to establish a scoring system to select stage ypT0-1N0 for LARC following preoperative CRT. METHOD Between 2009 and 2014, 262 patients with middle and low LARC were treated with CRT and radical surgery. Clinicopathological data which were found to be significantly associated with GR were incorporated into a scoring system. RESULTS Fifty-seven (21.8%) patients were GR with stage ypT0-1N0 in the operative specimen. Multivariate analyses indicated that a low level of pretreatment carcinoembryonic antigen (CEA) and post-treatment CEA <2.55 ng/ml (P = 0.008 and P = 0.009 respectively) and long-axis diameter of residual tumours (P = 0.006) were independently associated with stage ypT0-1N0. The three factors were incorporated into a scoring system. Using receiver operating characteristic curve analysis, we determined a cutoff value of -0.3 for scores, at which the system's sensitivity was 71.9% and specificity 73.1%. When applied to testing samples, the sensitivity was 74.1% and specificity 76.2%. CONCLUSION We demonstrated that low levels of pretreatment and post-treatment CEA and the long-axis diameter of residual tumours were associated with stage ypT0-1N0 for LARC after CRT. Therefore, the three-factor scoring system may be used to select potential candidates for organ-sparing management.
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Affiliation(s)
- S H Huang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - P Chi
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
| | - H M Lin
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - X R Lu
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Y W Huang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Z B Xu
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Y W Sun
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - D X Ye
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - X J Wang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - X Wang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China
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Li J, Liu H, Hu J, Liu S, Yin J, Du F, Yuan J, Lv B. New tumor regression grade for rectal cancer after neoadjuvant therapy and radical surgery. Oncotarget 2016; 6:42222-31. [PMID: 26540466 PMCID: PMC4747220 DOI: 10.18632/oncotarget.6008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Accepted: 10/09/2015] [Indexed: 11/25/2022] Open
Abstract
In this retrospective study, we defined a new tumor regression grade (NTRG), which we used to evaluate the prognosis of patients with locally advanced rectal cancer who received neoadjuvant therapy and then underwent radical surgery between June 2004 and October 2011. Calculated as the TRG plus a lymph node score, the NTRG was determined for 347 patients: NTRG 0, 46 patients (13.3%); NTRG 1, 63 (18.2%); NTRG 2, 183 (52.7%); NTRG 3, 30 (8.6%); NTRG 4, 25 (7.2%). Among this group, 45 (97.8%) NTRG 0, 56 (88.9%) NTRG 1, 148 (80.9%) NTRG 2, 24 (66.7%) NTRG 3, and 10 (40.0%) NTRG 4 patients experienced 5-year disease-free survival. We also found that NTRG is significantly associated with 5-year local recurrence, distant metastasis and disease-free survival (P = 0.004, 0.007 and 0.039, respectively). The NTRG may thus be an independent prognostic factor for oncologic outcomes in rectal cancer patients after neoadjuvant therapy and radical surgery, but this conclusion must be validated in randomized trials.
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Affiliation(s)
- Jun Li
- General Surgery Department, Affiliated Hospital/Clinical Medical College of Chengdu University, Chengdu, People's Republic of China
| | - Hao Liu
- General Surgery Department, 2nd Affiliated Hospital of Jilin University, Changchun, People's Republic of China
| | - Junjie Hu
- Gastrointestinal Tumor Surgery, Hubei Cancer Hospital, Wuhan, People's Republic of China
| | - Sai Liu
- Surgical Department of Gastrointestinal Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Jie Yin
- General Surgery Department, Xuzhou Central Hospital, Xuzhou, People's Republic of China
| | - Feng Du
- Internal Medicine-Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Jiatian Yuan
- General Surgery Department, Affiliated Hospital/Clinical Medical College of Chengdu University, Chengdu, People's Republic of China
| | - Bo Lv
- General Surgery Department, Affiliated Hospital/Clinical Medical College of Chengdu University, Chengdu, People's Republic of China
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Siddiqui MRS, Gormly KL, Bhoday J, Balyansikova S, Battersby NJ, Chand M, Rao S, Tekkis P, Abulafi AM, Brown G. Interobserver agreement of radiologists assessing the response of rectal cancers to preoperative chemoradiation using the MRI tumour regression grading (mrTRG). Clin Radiol 2016; 71:854-62. [PMID: 27381221 DOI: 10.1016/j.crad.2016.05.005] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 03/13/2016] [Accepted: 05/03/2016] [Indexed: 02/07/2023]
Abstract
AIM To investigate whether the magnetic resonance imaging (MRI) tumour regression grading (mrTRG) scale can be taught effectively resulting in a clinically reasonable interobserver agreement (>0.4; moderate to near perfect agreement). MATERIALS AND METHODS This study examines the interobserver agreement of mrTRG, between 35 radiologists and a central reviewer. Two workshops were organised for radiologists to assess regression of rectal cancers on MRI staging scans. A range of mrTRGs on 12 patient scans were used for assessment. RESULTS Kappa agreement ranged from 0.14-0.82 with a median value of 0.57 (95% CI: 0.37-0.77) indicating good overall agreement. Eight (26%) radiologists had very good/near perfect agreement (κ>0.8). Six (19%) radiologists had good agreement (0.8≥κ>0.6) and a further 12 (39%) had moderate agreement (0.6≥κ>0.4). Five (16%) radiologists had a fair agreement (0.4≥κ>0.2) and two had poor agreement (0.2>κ). There was a tendency towards good agreement (skewness: 0.92). In 65.9% and 90% of cases the radiologists were able to correctly highlight good and poor responders, respectively. CONCLUSIONS The assessment of the response of rectal cancers to chemoradiation therapy may be performed effectively using mrTRG. Radiologists can be taught the mrTRG scale. Even with minimal training, good agreement with the central reviewer along with effective differentiation between good and intermediate/poor responders can be achieved. Focus should be on facilitating the identification of good responders. It is predicted that with more intensive interactive case-based learning a κ>0.8 is likely to be achieved. Testing and retesting is recommended.
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Affiliation(s)
- M R S Siddiqui
- Department of Colorectal Surgery, Croydon University Hospital, Croydon CR7 7YE, UK; Department of Radiology, Royal Marsden Hospital, Sutton, Surrey SM2 5PT, UK; Imperial College London, London, UK
| | - K L Gormly
- Dr Jones and Partners, Adelaide, South Australia, Australia
| | - J Bhoday
- Department of Colorectal Surgery, Croydon University Hospital, Croydon CR7 7YE, UK; Department of Radiology, Royal Marsden Hospital, Sutton, Surrey SM2 5PT, UK; Imperial College London, London, UK
| | - S Balyansikova
- Department of Radiology, Royal Marsden Hospital, Sutton, Surrey SM2 5PT, UK
| | - N J Battersby
- Department of Radiology, Royal Marsden Hospital, Sutton, Surrey SM2 5PT, UK
| | - M Chand
- Department of Surgery, University College London, London, UK
| | - S Rao
- Department of Radiology, Royal Marsden Hospital, Sutton, Surrey SM2 5PT, UK
| | - P Tekkis
- Department of Surgery, Royal Marsden Hospital, Fulham Rd, London SW3 6JJ, UK; Imperial College London, London, UK
| | - A M Abulafi
- Department of Colorectal Surgery, Croydon University Hospital, Croydon CR7 7YE, UK
| | - G Brown
- Department of Radiology, Royal Marsden Hospital, Sutton, Surrey SM2 5PT, UK; Imperial College London, London, UK.
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Sclafani F, Brown G. Extramural Venous Invasion (EMVI) and Tumour Regression Grading (TRG) as Potential Prognostic Factors for Risk Stratification and Treatment Decision in Rectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2016. [DOI: 10.1007/s11888-016-0319-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Pathologic Complete Response in Rectal Cancer: Can We Detect It? Lessons Learned From a Proposed Randomized Trial of Watch-and-Wait Treatment of Rectal Cancer. Dis Colon Rectum 2016; 59:255-63. [PMID: 26953983 DOI: 10.1097/dcr.0000000000000558] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Chemoradiotherapy has the potential to downsize and downstage tumors before surgery, decrease locoregional recurrence, and induce a complete sterilization of tumor cells for middle and low locally advanced rectal cancer. A watch-and-wait tactic has been proposed for patients with clinical complete response. OBJECTIVE The purpose of this study was to verify our ability to identify complete clinical response in patients with rectal cancer based on clinical and radiologic criteria. DESIGN This was a prospective study. SETTINGS The study was conducted at a single institution, in the setting of a watch-and-wait randomized trial. PATIENTS Consecutive patients with stage T3 to T4N0M0 or T(any)N+M0 cancer located within 10 cm from anal verge or T2N0 within 7 cm from anal verge were included in the study. Patients were staged and restaged 8 weeks after completion of chemoradiation (5-fluorouracil, 5040 cGy) by digital examination, colonoscopy, pelvic MRI, and thorax and abdominal CT scans. MAIN OUTCOME MEASURES Clinical and radiologic judgments of tumor response were compared with pathologic response of patients treated by total mesorectal excision or clinical follow-up of patients selected for nonoperative treatment. RESULTS A total of 118 patients were treated. Six patients were considered clinic complete responders (2 randomly assigned for surgery (1 ypT0N0 and 1 ypT2N0) and 4 patients randomly assigned for observation (3 sustained clinic complete response and 1 had tumor regrowth)). The 112 clinic incomplete responders underwent total mesorectal excision, and 18 revealed pathologic complete response. These 18 patients were not considered complete responders at restaging because they presented at least 1 of the following conditions: mucosal ulceration and/or deformity and/or substenosis of rectal lumen at digital rectal examination and colonoscopy (n = 16), ymrT1 to T4 (n = 16), ymrN+ (n = 2), involvement of circumferential resection margin on MRI (n = 3), extramural vascular invasion on MRI (n = 4), MRI tumor response grade 2 to 4 (n = 15), and pelvic side wall lymph node involvement on MRI (n = 1). Sensitivity for identification of ypT0N0 or sustained clinic complete response was 18.2%. LIMITATIONS This study has a short follow-up and small sample size. Radiologists who reviewed the restaging examination were not blinded to the pretreatment stage. Only 1 radiologist read the images of each patient. CONCLUSIONS Evaluation of clinic complete response according to current adopted criteria has low sensitivity because pathologic complete response more frequently presented as clinic incomplete response (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A221).
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Guedj N, Maggiori L, Poté N, Norkowski E, Cros J, Bedossa P, Panis Y. Distal intramural and tumor spread in the mesorectum after neoadjuvant radiochemotherapy in rectal cancer: about 124 consecutive patients. Hum Pathol 2016; 52:164-72. [PMID: 27210028 DOI: 10.1016/j.humpath.2016.01.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 01/15/2016] [Accepted: 01/24/2016] [Indexed: 02/07/2023]
Abstract
This observational prospective study aimed to assess the distribution of intramural and mesorectal tumor spread in mid/low rectal cancer after neoadjuvant radiochemotherapy. Distribution of mesorectal metastatic lymph nodes (MLNs) and mesorectal extranodal cancer tissue (EX), according to the tumor location, were analyzed. Distal intramural tumor spread was also performed. A total of 1676 LNs, 135 MLNs, and 69 EX were detected on 124 consecutive surgical specimens. Forty-two patients (34%) had MLNs. Six patients (4.8%) were classified as ypN1c. Distal viable cancer spread was observed in 3 patients (2.4%), all with mid rectal carcinoma. Two patients (1.6%) presented distal direct intramural extension less than 1 cm; and 1 (0.8%), with EX localized no more than 2 cm from the lower edge of the tumor. MLNs (76%) and EX (94%) were preferentially localized in the peritumoral area and in the first 3 cm just above the tumor. No viable distal intramural or mesorectal spread was observed in low rectal carcinoma. Distal intramural and mesorectal cancer spread is a rare event after neoadjuvant RCT. These results suggest that the 1-cm distal margin recommended in patients with low rectal carcinoma could be reduced with insurance to obtain a negative distal margin. The knowledge of preferential localization of MLNs and EX would help the pathologist to improve patient's lymph node staging.
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Affiliation(s)
- Nathalie Guedj
- Department of Pathology, Beaujon Hospital, 92110 Clichy, France.
| | - Léon Maggiori
- Department of Colo-rectal Surgery, Beaujon Hospital, 92110 Clichy, France
| | - Nicolas Poté
- Department of Pathology, Beaujon Hospital, 92110 Clichy, France
| | - Emma Norkowski
- Department of Pathology, Beaujon Hospital, 92110 Clichy, France
| | - Jérôme Cros
- Department of Pathology, Beaujon Hospital, 92110 Clichy, France
| | - Pierre Bedossa
- Department of Pathology, Beaujon Hospital, 92110 Clichy, France
| | - Yves Panis
- Department of Colo-rectal Surgery, Beaujon Hospital, 92110 Clichy, France
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