|
1
|
van den Berg K, Banken E, van Rees JM, Coolen LM, de Vries M, Voogt ELK, Rothbarth J, Rutten HJT, Nederend J, van Hellemond IEG, Creemers GJM, Verhoef C, Burger JWA. Neoadjuvant chemotherapy and chemoradiotherapy versus chemoradiotherapy alone in high-risk locally advanced rectal cancer: A retrospective comparison of two Dutch tertiary referral centres. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109699. [PMID: 39987817 DOI: 10.1016/j.ejso.2025.109699] [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: 10/27/2024] [Revised: 01/02/2025] [Accepted: 02/12/2025] [Indexed: 02/25/2025]
Abstract
INTRODUCTION The effect of neoadjuvant chemotherapy and chemoradiotherapy in patients with locally advanced rectal cancer, at increased risk of failing current treatment regimens, is unknown. This study compared the complete response rate and long-term survival of these patients treated with or without neoadjuvant chemotherapy prior to chemoradiotherapy. MATERIALS AND METHODS Patients with high-risk locally advanced rectal cancer, who were surgically treated or entered a watch and wait approach after neoadjuvant chemoradiotherapy with or without neoadjuvant chemotherapy in Erasmus Medical Centre or Catharina Hospital between 2016 and 2020, were retrospectively identified. High-risk was defined as the presence of tumour invasion into the mesorectal fascia, grade 4 extramural venous invasion, enlarged lateral lymph nodes, or tumour deposits. The primary endpoint was complete response rate, which was defined as a histopathological complete response or a sustained (during 12 months) clinical complete response. Long-term oncological outcomes were evaluated based on Kaplan-Meier and Cox regression survival analyses. RESULTS The neoadjuvant chemotherapy group consisted of 64 patients, of whom 61 (95.3 %) were treated with chemotherapy prior to chemoradiotherapy, the chemoradiotherapy group of 194 patients. The complete response rates were 25.0 % and 9.8 %, respectively (P = 0.002). The estimated 3-year overall survival was 92.2 % in the neoadjuvant chemotherapy group versus 66.9 % in the chemoradiotherapy group. CONCLUSION Excellent oncological outcomes were observed in patients with high-risk locally advanced rectal cancer selected during a multidisciplinary team (MDT) meeting for neoadjuvant chemotherapy and chemoradiotherapy. The actual difference with patients treated with chemoradiotherapy alone should be investigated in prospective trials. Pretreatment referral to expert MDTs is encouraged.
Collapse
Affiliation(s)
- K van den Berg
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands; Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
| | - E Banken
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands; Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - J M van Rees
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, University Hospital Rotterdam, the Netherlands
| | - L M Coolen
- Department of Radiology, Catharina Hospital, Eindhoven, the Netherlands
| | - M de Vries
- Department of Radiology, Erasmus MC Cancer Institute, University Hospital Rotterdam, the Netherlands
| | - E L K Voogt
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - J Rothbarth
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, University Hospital Rotterdam, the Netherlands
| | - H J T Rutten
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands; GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
| | - J Nederend
- Department of Radiology, Catharina Hospital, Eindhoven, the Netherlands
| | - I E G van Hellemond
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - G J M Creemers
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - C Verhoef
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, University Hospital Rotterdam, the Netherlands
| | - J W A Burger
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| |
Collapse
|
|
2
|
Kubota S, Wakiya T, Morohashi H, Miura T, Kanda T, Matsuzaka M, Sasaki Y, Sakamoto Y, Hakamada K. Prediction of the Therapeutic Response to Neoadjuvant Chemotherapy for Rectal Cancer Using a Deep Learning Model. J Anus Rectum Colon 2025; 9:202-212. [PMID: 40302856 PMCID: PMC12035344 DOI: 10.23922/jarc.2024-085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 12/08/2024] [Indexed: 05/02/2025] Open
Abstract
Objectives Predicting the response to chemotherapy can lead to the optimization of neoadjuvant chemotherapy (NAC). The present study aimed to develop a non-invasive prediction model of therapeutic response to NAC for rectal cancer (RC). Methods A dataset of the prechemotherapy computed tomography (CT) images of 57 patients from multiple institutions who underwent rectal surgery after three courses of S-1 and oxaliplatin (SOX) NAC for RC was collected. The therapeutic response to NAC was pathologically confirmed. It was then predicted whether they were pathologic responders or non-responders. Cases were divided into training, validation and test datasets. A CT patch-based predictive model was developed using a residual convolutional neural network and the predictive performance was evaluated. Binary logistic regression analysis of prechemotherapy clinical factors showed that none of the independent variables were significantly associated with the non-responders. Results Among the 49 patients in the training and validation datasets, there were 21 (42.9%) and 28 (57.1%) responders and non-responders, respectively. A total of 3,857 patches were extracted from the 49 patients. In the validation dataset, the average sensitivity, specificity and accuracy was 97.3, 95.7 and 96.8%, respectively. Furthermore, the area under the receiver operating characteristic curve (AUC) was 0.994 (95% CI, 0.991-0.997; P<0.001). In the test dataset, which included 750 patches from 8 patients, the predictive model demonstrated high specificity (89.9%) and the AUC was 0.846 (95% CI, 0.817-0.875; P<0.001). Conclusions The non-invasive deep learning model using prechemotherapy CT images exhibited high predictive performance in predicting the pathological therapeutic response to SOX NAC.
Collapse
Affiliation(s)
- Shunsuke Kubota
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Taiichi Wakiya
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Hajime Morohashi
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Takuya Miura
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Taishu Kanda
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Masashi Matsuzaka
- Department of Medical Informatics, Hirosaki University Hospital, Hirosaki, Japan
| | - Yoshihiro Sasaki
- Department of Medical Informatics, Hirosaki University Hospital, Hirosaki, Japan
| | - Yoshiyuki Sakamoto
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Kenichi Hakamada
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| |
Collapse
|
|
3
|
Ofluoğlu CB, Mülküt F, Aydın İC, Başdoğan MK, Aydın İ. Prognostic Nutritional Index as a Predictor of Surgical Morbidity in Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer. J Clin Med 2025; 14:1937. [PMID: 40142744 PMCID: PMC11943409 DOI: 10.3390/jcm14061937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 02/28/2025] [Accepted: 03/05/2025] [Indexed: 03/28/2025] Open
Abstract
Background: The management of locally advanced rectal cancer (LARC) has seen the emergence of total neoadjuvant therapy (TNT) as a promising approach. TNT has shown potential in enhancing tumor regression, increasing pathological complete response (pCR) rates, and improving the control of systemic disease. However, the impact of TNT on complications during and after surgery remains uncertain. This research aimed to assess surgical complications linked to TNT in comparison with conventional neoadjuvant chemoradiotherapy (nCRT). Additionally, this study explored the potential of the Prognostic Nutritional Index (PNI) as a predictor of surgical outcomes. Methods: A retrospective cohort study was conducted at Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, including patients with LARC who underwent either TNT or nCRT followed by curative excision (TME). Demographic data, perioperative complications, and tumor-related variables were also analyzed. The prognostic value of the PNI in predicting surgical complications was assessed using multivariate logistic regression analysis. Statistical significance was set at p < 0.05. Results: A total of 103 patients with LARC were included, of whom 38 (36.9%) received TNT and 65 (63.1%) underwent nCRT. TNT was associated with significantly higher rates of anastomotic leakage (13.2% vs. 6.2%, p = 0.04) and wound infections (23.7% vs. 9.2%, p = 0.02). The mean tumor size was significantly smaller in the TNT group (3.22 ± 1.10 cm) than in the nCRT group (3.65 ± 1.26 cm, p = 0.02). The PNI was significantly lower in the TNT group (38.96 ± 5.54) than in the nCRT group (41.31 ± 4.65, p = 0.03). Multivariate logistic regression analysis demonstrated that a lower PNI was independently associated with increased surgical complications (β = -1.09, p = 0.028, 95% CI: -2.06--0.12). Conclusions: Although TNT demonstrates clear oncological benefits in LARC, it is associated with increased perioperative morbidity. Our findings suggest that the PNI is a valuable predictive biomarker of surgical complications in patients treated with TNT. Preoperative nutritional assessment and optimization may improve perioperative outcomes and mitigate the risks associated with TNT. Future prospective studies should explore targeted interventions to enhance the safety profile of TNT while preserving its oncological advantages.
Collapse
Affiliation(s)
- Cem Batuhan Ofluoğlu
- Department of Gastrointestinal Surgery, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences, Istanbul 34785, Turkey
| | - Fırat Mülküt
- Department of General Surgery, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences, Istanbul 34785, Turkey; (F.M.); (M.K.B.); (İ.A.)
| | - İsa Caner Aydın
- Department of Gastrointestinal Surgery, Ministry of Health Zonguldak Ataturk State Hospital, Zonguldak 67100, Turkey;
| | - Mustafa Kağan Başdoğan
- Department of General Surgery, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences, Istanbul 34785, Turkey; (F.M.); (M.K.B.); (İ.A.)
| | - İbrahim Aydın
- Department of General Surgery, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences, Istanbul 34785, Turkey; (F.M.); (M.K.B.); (İ.A.)
| |
Collapse
|
|
4
|
Rencuzogullari A, Karahan SN, Selcukbiricik F, Lacin S, Taskin OC, Saka B, Karahacioglu D, Gurses B, Ozoran E, Uymaz DS, Ozata IH, Saglam S, Bugra D, Balik E. The New Era of Total Neoadjuvant FLOT Therapy for Locally Advanced, Resectable Gastric Cancer: A Propensity-Matched Comparison With Standard Perioperative Therapy. J Surg Oncol 2025; 131:417-426. [PMID: 39400342 PMCID: PMC12044282 DOI: 10.1002/jso.27934] [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: 06/07/2024] [Revised: 08/28/2024] [Accepted: 09/17/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND The FLOT 4-AIO trial established the docetaxel-based regimen's superiority over epirubicin-based triplet therapy in terms of survival rates and acceptable toxicity for locally advanced resectable gastric (LARGC). Yet, fewer than half of the patients achieved completion of eight prescribed FLOT cycles. We proposed that administering all FLOT cycles in the form of total neoadjuvant therapy may improve completion rates and downstaging. This study contrasted total neoadjuvant therapy (FLOT x8) with standard neoadjuvant therapy (FLOT 4+4) for patients LARGC adenocarcinoma who underwent curative resection with routine D2 lymphadenectomy, focusing on histopathological outcomes, toxicity, and survival outcomes. METHODS We reviewed patients with histologically confirmed advanced clinical stage cT2 or higher, nodal positive stage (cN+), or both, with resectable gastric tumors and no distant metastases (January 2017 to July 2023). We divided patients into two groups, FLOT 4+4 and FLOT x8; FLOT 4+4 patients underwent four preoperative and four postoperative bi-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil, while FLOT x8 patients received all eight cycles preoperatively after a gradual practice change starting from January 2020. Propensity score matching adjusted for age, clinical stage, tumor location, and histology. RESULTS Of the 77 patients in the FLOT x8 group, 37 were propensity-matched to an equal number in the FLOT 4+4 group. Demographics, duration of surgery, and hospital stay showed no significant differences between the groups. The FLOT x8 group exhibited a significantly higher all-cycle completion rate at 89.1% compared to FLOT 4+4's 67.6% (p < 0.01). Both groups demonstrated comparable hematological and non-hematological toxicity rates, Clavien-Dindo ≥ 3 complications, and CAP tumor regression grades. The mean number of harvested lymph nodes was 42.5 and 41.2 in the FLOT 4+4 and FLOT x8 groups, respectively. Similar rates of disease-free survival and overall survival were noted in both groups, despite a trend toward a higher pathological complete response rate, albeit not statistically significant (8.1% vs. 18.9%, p = 0.29), in the FLOT x8 group at a median follow-up of 36 months. CONCLUSION Total neoadjuvant therapy with the FLOT x8 protocol corresponds to higher treatment completion rates, a safety profile similar to standard perioperative therapy, and a twofold increase in complete pathological response. Further research on long-term oncological outcomes is needed to confirm the effectiveness of total neoadjuvant therapy.
Collapse
Affiliation(s)
| | - Salih Nafiz Karahan
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
| | - Fatih Selcukbiricik
- Department of Medical Oncology, School of MedicineKoç UniversityIstanbulTurkey
| | - Sahin Lacin
- Department of Medical Oncology, School of MedicineKoç UniversityIstanbulTurkey
| | - Orhun Cig Taskin
- Department of Pathology, School of MedicineKoç UniversityIstanbulTurkey
| | - Burcu Saka
- Department of Pathology, School of MedicineKoç UniversityIstanbulTurkey
| | | | - Bengi Gurses
- Department of Radiology, School of MedicineKoç UniversityIstanbulTurkey
| | - Emre Ozoran
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
| | - Derya Salim Uymaz
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
| | - Ibrahim Halil Ozata
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
| | - Sezer Saglam
- Department of Medical OncologyDemiroglu Bilim UniversityIstanbulTurkey
| | - Dursun Bugra
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
- Department of General SurgeryAmerican HospitalIstanbulTurkey
| | - Emre Balik
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
| |
Collapse
|
|
5
|
Salah T, Aboziada M, Buhlaiaqh T, Mass NA, Bukhari N, Alwhaibi B, Makhali AM, Mahrous M, Mohamed S, Abd El-Aziz N, Mokhtar H. Efficacy of Neoadjuvant Short-Course Radiation Therapy Followed by Oxaliplatin-Based Chemotherapy for Locally Advanced Rectal Adenocarcinoma: A Single-Center Experience From Saudi Arabia. Cureus 2025; 17:e77604. [PMID: 39963619 PMCID: PMC11832227 DOI: 10.7759/cureus.77604] [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: 01/17/2025] [Indexed: 02/20/2025] Open
Abstract
Background The 5-fluorouracil (5-FU), capecitabine-based long-course or short-course radiotherapy (SCRT) eventually preceded or followed by induction or consolidation chemotherapy (CT) and resection represents the preferred regimen for the treatment of locally advanced rectal cancer (LARC). This study aims to report our experience as a large medical center in Saudi Arabia, with the efficacy of short-course radiation therapy followed by oxaliplatin-based CT in achieving a pathologic complete response (pCR) in patients with LARC. Materials and methods This retrospective analysis encompassed 57 patients diagnosed with LARC at a large tertiary center in Riyadh, Saudi Arabia, from June 2020 to December 2022. All participants underwent short-term radiotherapy (25 Grays (Gy) over fractions within one week) followed by CT with 5-FU, leucovorin, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX), constituting the total neoadjuvant therapy (TNT). Surgical intervention and total mesorectal excision were performed six to eight weeks post-preoperative treatment. The primary endpoint was the pCR rate. Results Of the study participants, 34 (60%) were males, with a mean age of 57.6 ± 13.9 years. Two-thirds (n = 37,65%) were classified as T3. The overall response rates were 12 (21%), 12 (21%), 24 (42%), and nine (16%), for complete response (CR), near-complete response (nCR), partial response (PR), and progressive disease (PD), respectively. The multivariable logistic regression model identified five independent predictors for overall CR after adjusting for disease-related factors: N-stage, the circumferential resection margin (CRM), average vascularity (AV), surgical procedure, and postoperative tumor size. Patients with N2 disease had an 18% lower chance of achieving CR (OR = 0.824; 95% CI: 0.634-0.974; p = 0.035). Positive CRM was linked to a 71% reduction in the probability of CR (OR = 0.268; 95% CI: 0.087-0.823; p = 0.021). Each 1 cm increase in AV corresponded to a 28.5% increase in the likelihood of complete response (OR = 1.285; 95% CI: 1.029-1.605; p = 0.027). Patients who underwent AR had 2.8 times greater chances of achieving CR than those who underwent abdominoperineal resection (APR) (OR = 2.801; 95% CI: 1.057-9.324; p = 0.044). Lastly, each 1 cm increase in postoperative tumor size was associated with a 92.5% reduction in the odds of CR (OR = 0.074; 95% CI: 0.017-0.330; p = 0.001). Conclusions The current study supports the efficacy of TNT for treating LARC, with a pCR rate of 21% and near-complete response in nearly half of the patients with LARC. Significant predictors of pCR included N-stage, CRM status, AV size, and surgical approach. These insights could refine patient selection for TNT and inform future strategies to optimize treatment outcomes in rectal cancer. Prospective multicenter studies are warranted.
Collapse
Affiliation(s)
- Tareq Salah
- Oncology Department, Prince Sultan Military Medical City, Riyadh, SAU
- Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Assiut University, Asyut, EGY
| | - Mohamed Aboziada
- Oncology Department, Prince Sultan Military Medical City, Riyadh, SAU
- Radiation Oncology Department, South Egypt Cancer Institute, Asyut, EGY
| | - Taleb Buhlaiaqh
- Oncology Department, Prince Sultan Military Medical City, Riyadh, SAU
| | - Nada A Mass
- Oncology Department, Prince Sultan Military Medical City, Riyadh, SAU
| | - Nedal Bukhari
- Oncology Department, Prince Sultan Military Medical City, Riyadh, SAU
| | - Bader Alwhaibi
- Oncology Department, Prince Sultan Military Medical City, Riyadh, SAU
| | | | - Mervat Mahrous
- Oncology Department, Faculty of Medicine, Minia University, Minia, EGY
- Oncology Department, Prince Sultan Military Medical City, Riyadh, SAU
| | - Sherif Mohamed
- Internal Medicine Department, Sultan Bin Abdulaziz Humanitarian City, Riyadh, SAU
| | - Nashwa Abd El-Aziz
- Medical Oncology Department, South Egypt Cancer Institute, Asyut, EGY
- Medical Oncology Department, Blood and Cancer Center, Riyadh, SAU
| | - Hoda Mokhtar
- Oncology Department, Prince Sultan Military Medical City, Riyadh, SAU
- Clinical Oncology Department, Faculty of Medicine, Minia University, Minia, EGY
| |
Collapse
|
|
6
|
Williams H, Lee C, Garcia-Aguilar J. Nonoperative management of rectal cancer. Front Oncol 2024; 14:1477510. [PMID: 39711959 PMCID: PMC11659252 DOI: 10.3389/fonc.2024.1477510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 11/21/2024] [Indexed: 12/24/2024] Open
Abstract
The management of locally advanced rectal cancer has changed drastically in the last few decades due to improved surgical techniques, development of multimodal treatment approaches and the introduction of a watch and wait (WW) strategy. For patients with a complete response to neoadjuvant treatment, WW offers an opportunity to avoid the morbidity associated with total mesorectal excision in favor of organ preservation. Despite growing interest in WW, prospective data on the safety and efficacy of nonoperative management are limited. Challenges remain in optimizing multimodal treatment regimens to maximize tumor regression and in improving the accuracy of patient selection for WW. This review summarizes the history of treatment for rectal cancer and the development of a WW strategy. It also provides an overview of clinical considerations for patients interested in nonoperative management, including restaging strategies, WW selection criteria, surveillance protocols and long-term oncologic outcomes.
Collapse
Affiliation(s)
| | | | - Julio Garcia-Aguilar
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer
Center, New York, NY, United States
| |
Collapse
|
|
7
|
Ghalehtaki R, Kolahdouzan K, Piozzi GN, Rezaei S, Shaka Z, Darzikolaee NM, Bayani R, Behboudi B, Aghili M, Couñago F, Sharifian A, Bagheri F, Nazari R, Nabian N, Babaei M, Tafti MA, Fazeli M, Farhan F. Outcomes of neoadjuvant chemoradiotherapy in T4 rectal cancer patients: a real-world single institution experience. Radiat Oncol J 2024; 42:273-280. [PMID: 39748528 PMCID: PMC11701469 DOI: 10.3857/roj.2024.00136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 02/21/2024] [Accepted: 02/26/2024] [Indexed: 01/04/2025] Open
Abstract
PURPOSE Treatment outcomes of locally advanced rectal cancer have improved significantly in recent decades. This retrospective study aimed to assess the efficacy of neoadjuvant chemoradiotherapy (nCRT) followed by surgery in patients with T4 rectal cancer and the different outcomes between T4a and T4b patients. MATERIALS AND METHODS A total of 60 clinically T4 rectal cancer patients who underwent nCRT were included in the analysis. Patient characteristics, treatment regimens, down-staging rates, pathological response, and overall survival (OS) were evaluated. RESULTS Both T4a and T4b patients experienced down-staging following nCRT (36.6% and 6.2% respectively; p = 0.021). T4a patients exhibited a higher rate of pathological complete response (pCR) than T4b patients (13.3% in T4a vs. 0% in T4b; p = 0.122). After a median follow-up of 36 months, the OS and recurrence-free survival (RFS) of T4a patients were significantly higher compared to T4b patients (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.05-6.05, p = 0.038 for OS; HR = 2.32, 95% CI 1.09-4.92, p = 0.025 for RFS). CONCLUSION This study provides valuable insights into the effectiveness of nCRT in T4 rectal cancer patients. Although down-staging was observed in both T4a and T4b subgroups, achieving a pCR remains a challenge, particularly in T4b patients. Further research is needed to optimize treatment strategies and enhance pCR rates in T4 rectal cancer patients to improve oncologic outcomes.
Collapse
Affiliation(s)
- Reza Ghalehtaki
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Kasra Kolahdouzan
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Saeid Rezaei
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Zoha Shaka
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Nima Mousavi Darzikolaee
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reyhaneh Bayani
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Behnam Behboudi
- Division of Colorectal Surgery, Department of Surgery, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdi Aghili
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Felipe Couñago
- Department of Radiation Oncology, San Francisco de Asís Hospital, Madrid, Spain
- Department of Radiation Oncology, La Milagrosa Hospital, Madrid, Spain
- National Chair of Research, GenesisCare Madrid, Madrid, Spain
| | - Azadeh Sharifian
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farzaneh Bagheri
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Nazari
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Naeim Nabian
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Babaei
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Ahmadi Tafti
- Division of Colorectal Surgery, Department of Surgery, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammadsadegh Fazeli
- Division of Colorectal Surgery, Department of Surgery, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Farshid Farhan
- Department of Radiation Oncology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
8
|
Montroni I, Di Candido F, Taffurelli G, Tamberi S, Grassi E, Corbelli J, Mauro F, Raggi E, Garutti A, Ugolini G. Total neoadjuvant therapy followed by total mesorectal excision for rectal cancer in older patients real world data and proof of concept. Front Surg 2024; 11:1448073. [PMID: 39628921 PMCID: PMC11611805 DOI: 10.3389/fsurg.2024.1448073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 11/04/2024] [Indexed: 12/06/2024] Open
Abstract
Background Rectal cancer (RC) commonly affects older patients. Total Neoadjuvant Therapy (TNT) has been introduced to improve local and systemic control of RC. The aim was to present real-world data of older patients receiving TNT followed by surgery after a frailty assessment and verify feasibility and safety of this approach. Methods This was a single-center retrospective study which enrolled all patients ≥70 years of age with RC who underwent TNT followed by surgery between November 2017 and April 2022. Data regarding cancer characteristics, neoadjuvant chemoradiotherapy (CRT), and toxicity were recorded. All patients underwent surgery 12-16 weeks after the end of therapy. Intra- and postoperative outcomes were recorded. Pre- and postoperative functional evaluation was carried out. Results Fifteen patients were enrolled. Mean age was 74 (70-81) years. Mean distance of the tumor from the anal verge was 5.2 cm. Fourteen patients had positive nodes (93.3%), 11 (73.3%) showed involvement of the circumferential margin (CRM+) and 10 (66.6%) had extramural vascular invasion (EMVI+). Ten patients (66.6%) received mFOLFOX-6 and 5 CAPOX (33.3%) followed by CRT. After CRT, positive nodes were reported in 4 cases (26.6%), CRM+ in 4 (26.6%), and EMVI+ in 1 (6.6%). Transanal total mesorectal excision (taTME) was performed in all cases. Median operative time was 280 min (110-420). Median length of stay was 4 days (3-29). One Clavien-Dindo grade 4 complication, no readmissions, and no variations in pre- and postoperative functional status within 30 days from surgery were reported. No positive distal or CRMs were detected. Three pathologic complete responses were reported (20%). Conclusions TNT followed by TME is feasible and safe in older patients, with good clinical and oncologic outcomes. Patient evaluation is crucial for maximizing cancer care in fit older patients.
Collapse
Affiliation(s)
- Isacco Montroni
- General Surgery Unit, Ospedale Santa Maria Delle Croci - AUSL Romagna, Ravenna, Italy
| | | | - Giovanni Taffurelli
- General Surgery Unit, Ospedale Santa Maria Delle Croci - AUSL Romagna, Ravenna, Italy
| | - Stefano Tamberi
- Medical Oncology Unit, Ospedale per gli Infermi - AUSL Romagna, Faenza, Italy
- Medical Oncology Unit, Ospedale Santa Maria Delle Croci - AUSL Romagna, Ravenna, Italy
| | - Elisa Grassi
- Medical Oncology Unit, Ospedale Santa Maria Delle Croci - AUSL Romagna, Ravenna, Italy
| | - Jody Corbelli
- Medical Oncology Unit, Ospedale per gli Infermi - AUSL Romagna, Faenza, Italy
| | - Floranna Mauro
- Department of Radiation Oncology, Maria Cecilia Hospital, Cotignola, Italy
| | - Enrico Raggi
- Department of Radiation Oncology, Maria Cecilia Hospital, Cotignola, Italy
| | - Anna Garutti
- Medical Oncology Unit, Ospedale Santa Maria Delle Croci - AUSL Romagna, Ravenna, Italy
| | - Giampaolo Ugolini
- General Surgery Unit, Ospedale Santa Maria Delle Croci - AUSL Romagna, Ravenna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| |
Collapse
|
|
9
|
Chong CXZ, Koh FH, Tan HL, Sivarajah SS, Ng JL, Ho LML, Aw DKL, Koo WH, Han S, Koo SL, Yip CSP, Wang FQ, Foo FJ, Tan WJ. The impact of short-course total neoadjuvant therapy, long-course chemoradiotherapy, and upfront surgery on the technical difficulty of total mesorectal excision: an observational study with an intraoperative perspective. Ann Coloproctol 2024; 40:451-458. [PMID: 39477330 PMCID: PMC11532385 DOI: 10.3393/ac.2023.00899.0128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 03/05/2024] [Accepted: 03/31/2024] [Indexed: 11/06/2024] Open
Abstract
PURPOSE Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery. METHODS Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to. RESULTS The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01). CONCLUSION TNT does not appear to increase the surgical difficulty of TME.
Collapse
Affiliation(s)
- Cheryl Xi-Zi Chong
- Colorectal Service, Department of General Surgery, Sengkang General Hospital, Singapore
| | - Frederick H. Koh
- Colorectal Service, Department of General Surgery, Sengkang General Hospital, Singapore
| | - Hui-Lin Tan
- Colorectal Service, Department of General Surgery, Sengkang General Hospital, Singapore
| | - Sharmini Su Sivarajah
- Colorectal Service, Department of General Surgery, Sengkang General Hospital, Singapore
| | - Jia-Lin Ng
- Colorectal Service, Department of General Surgery, Sengkang General Hospital, Singapore
| | - Leonard Ming-Li Ho
- Colorectal Service, Department of General Surgery, Sengkang General Hospital, Singapore
| | - Darius Kang-Lie Aw
- Colorectal Service, Department of General Surgery, Sengkang General Hospital, Singapore
| | - Wen-Hsin Koo
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Shuting Han
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Si-Lin Koo
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Connie Siew-Poh Yip
- Department of Radiation Oncology, National Cancer Centre Singapore, Singapore
| | - Fu-Qiang Wang
- Department of Radiation Oncology, National Cancer Centre Singapore, Singapore
| | - Fung-Joon Foo
- Colorectal Service, Department of General Surgery, Sengkang General Hospital, Singapore
| | - Winson Jianhong Tan
- Colorectal Service, Department of General Surgery, Sengkang General Hospital, Singapore
| |
Collapse
|
|
10
|
Malik YG, Benth JŠ, Hamre HM, Færden AE, Schultz JK. Effect of radiotherapy on long-term quality of life in recurrence-free rectal cancer survivors (LaTE study): nationwide inverse probability of treatment-weighted registry-based cohort study and survey. BJS Open 2024; 8:zrae091. [PMID: 39240223 PMCID: PMC11378401 DOI: 10.1093/bjsopen/zrae091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 06/11/2024] [Accepted: 07/06/2024] [Indexed: 09/07/2024] Open
Abstract
BACKGROUND Radiotherapy reduces local recurrence in locally advanced rectal cancer, but may cause harm in patients who do not experience recurrence. The aim was to investigate the impact of radiotherapy on long-term quality of life after curative treatment for rectal cancer, i.e. in patients without a recurrence during the follow-up. METHODS All patients operated on for rectal cancer in Norway under 75 years of age between 30 September 2007 and 1 October 2020 were identified using the Cancer Registry of Norway. Exclusion criteria were distant metastasis, recurrence and dementia. The primary outcome measure was the Gastrointestinal Quality of Life Index. Secondary outcome measures included the 36-item Short Form Survey. Inverse probability weights based on a multiple logistic regression model were used to balance prechosen covariates between the radiotherapy and no radiotherapy groups when assessing differences in outcomes. RESULTS Of 5014 invited patients, 2142 (43%) eligible patients answered the questionnaires. Of these 762 (36%) were treated with neoadjuvant radiotherapy plus surgery and 1380 (64%) with surgery alone. The mean follow-up time was 6.4 and 7.4 years respectively. After propensity score matching, the Gastrointestinal Quality of Life Index differed significantly between irradiated and non-irradiated patients ((mean(s.d.), mean score 103.8(19.4) versus 110.8(19.6) respectively, mean difference: -6.96 (95% c.i. -8.72 to -5.19); P < 0.001). Among patients without a stoma the mean difference was -8.1 points, whereas it was -5.7 for patients with a stoma. The radiotherapy group also scored significantly lower in 7 of 8 36-item Short Form Survey domains compared with the surgery alone group. CONCLUSION Long-term quality of life was significantly lower in patients without a recurrence during the follow-up who received radiotherapy compared with patients who did not. These findings warrant a critical re-evaluation of the use of radiotherapy both in traditional neoadjuvant treatment and in modern organ-preserving treatment regimens.
Collapse
Affiliation(s)
- Yasir G Malik
- Department of Digestive Surgery, Akershus University Hospital, Lørenskog, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Jūratė Šaltytė Benth
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway
| | - Hanne M Hamre
- Department of Internal Medicine, Oncology, Akershus University Hospital, Lørenskog, Norway
| | - Arne E Færden
- Department of Digestive Surgery, Akershus University Hospital, Lørenskog, Norway
| | - Johannes K Schultz
- Department of Digestive Surgery, Akershus University Hospital, Lørenskog, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Digestive Surgery, Oslo University Hospital, Oslo, Norway
| |
Collapse
|
|
11
|
Fleming C, Harji D, Fernandez B, François MO, Assenat V, Gilles P, Clément M, Robert G, Denost Q. Feasibility of a tailored operative strategy from organ preservation to pelvic exenteration for cT4 rectal cancer depending on neoadjuvant response. Int J Colorectal Dis 2024; 39:123. [PMID: 39085478 PMCID: PMC11291515 DOI: 10.1007/s00384-024-04675-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/26/2024] [Indexed: 08/02/2024]
Abstract
PURPOSE Improvements in neoadjuvant therapy for locally advanced cT4 rectal cancer have led to improved tumour response and thus a variety of suitable management strategies. The aim of this study was to report management and outcomes of patients with cT4 rectal cancer undergoing a spectrum of treatment strategies from organ preservation (OP) to pelvic exenteration (PE). METHODS Patients who underwent elective treatment for cT4 rectal cancer between 2016 and 2021 were included. All patients were treated with curative intent. Surgical management was adapted to tumour response. Kaplan-Meier curves were generated to compare 3-year overall survival (3y-OS), local recurrence (3y-LR) and distant metastases (3y-DM) between different strategies. RESULTS Among 152 patients included, 13 (8%) underwent OP, 71 (47%) TME and 68 (45%) APR/PE. The median follow-up was 31.3 months. Patients undergoing OP had a lower tumour pretreatment (p < 0.001). Compared to patients with TME, those with APR/PE had a higher rate of ypT4 (p = 0.001) with a lower R0 rate (p = 0.044). The 3y-OS and 3y-DM were 78% and 15.1%, respectively, without significant differences. The 3y-LR was 6.6%, and patients with OP had a significantly worse 3y-local regrowth compared to 3y-LR in patients with TME and APR/PE (30.2% vs. 5.4% vs. 2%, p = 0.008). CONCLUSION cT4 tumours may be suitable for the full spectrum of rectal cancer management from organ preservation to pelvic exenteration depending on tumour response to neoadjuvant therapy. However, careful attention is required in OP as local regrowth in up to 30% of cases reinforces the need for sustained active surveillance in Watch&Wait programmes.
Collapse
Affiliation(s)
- Christina Fleming
- Bordeaux Colorectal Institute, Clinique Tivoli, 220 Rue Mandron, 33000, Bordeaux, France.
- Department of Digestive Surgery, Colorectal Unit, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France.
- Royal College of Surgeons in Ireland, Dublin, Ireland.
| | - Deena Harji
- Bordeaux Colorectal Institute, Clinique Tivoli, 220 Rue Mandron, 33000, Bordeaux, France
- Department of Digestive Surgery, Colorectal Unit, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France
| | - Benjamin Fernandez
- Department of Digestive Surgery, Colorectal Unit, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France
| | - Marc-Olivier François
- Bordeaux Colorectal Institute, Clinique Tivoli, 220 Rue Mandron, 33000, Bordeaux, France
| | - Vincent Assenat
- Bordeaux Colorectal Institute, Clinique Tivoli, 220 Rue Mandron, 33000, Bordeaux, France
| | - Pasticier Gilles
- Department of Urologic Surgery, Clinique Tivoli, Bordeaux, France
| | - Michiels Clément
- Department of Urologic Surgery, Clinique Tivoli, Bordeaux, France
| | - Grégoire Robert
- Department of Urologic Surgery, CHU Bordeaux University Hospital, Bordeaux, France
| | - Quentin Denost
- Bordeaux Colorectal Institute, Clinique Tivoli, 220 Rue Mandron, 33000, Bordeaux, France.
- Department of Digestive Surgery, Colorectal Unit, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France.
| |
Collapse
|
|
12
|
Cai Q, Guo S, Fu F, Luo S, Chen W. Knowledge, attitude, and practice toward total neoadjuvant therapy for rectal cancer among oncologists in China: A survey study. Heliyon 2024; 10:e32957. [PMID: 38988527 PMCID: PMC11234032 DOI: 10.1016/j.heliyon.2024.e32957] [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: 02/05/2024] [Revised: 06/12/2024] [Accepted: 06/12/2024] [Indexed: 07/12/2024] Open
Abstract
This cross-sectional survey study aimed to explore the knowledge, attitude, and practice (KAP) toward total neoadjuvant therapy (TNT) for rectal cancer (RC) among specialists in Hainan Province, China. RC specialists working in Hainan Province (China) were enrolled in this cross-sectional study between March and June 2023. A self-designed questionnaire was used to collect the participants' characteristics and KAP toward TNT for RC. A total of 279 valid questionnaires were collected. The KAP scores were 15.91 ± 6.02 (possible range: 0-24), 34.16 ± 5.11 (possible range: 10-50), and 12.42 ± 1.83 (possible range: 3-15), respectively. The KAP scores of specialists who had applied TNT in clinical practice or research and had evaluated RC patients treated with TNT were significantly higher than those who had not (all P < 0.05). The structural equation model showed that knowledge of TNT directly affected attitude (β = 0.292, P = 0.007) and practice (β = 0.912, P = 0.007), and attitude toward TNT also had a direct effect on practice (β = 1.047, P = 0.008). In conclusion, RC specialists in Hainan (China) had inadequate knowledge, negative attitudes, and sufficient practice toward TNT in Hainan Province, China. It is necessary to enhance education for RC specialists to improve their knowledge and attitude toward TNT.
Collapse
Affiliation(s)
- Qinlei Cai
- Department of Radiology, Hainan General Hospital/Hainan Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, China
| | - Shanxi Guo
- Department of Radiology, Hainan General Hospital/Hainan Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, China
| | - Fangxiong Fu
- Department of Radiology, Hainan General Hospital/Hainan Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, China
| | - Shishi Luo
- Department of Radiology, Hainan General Hospital/Hainan Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, China
| | - Wangsheng Chen
- Department of Radiology, Hainan General Hospital/Hainan Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, China
| |
Collapse
|
|
13
|
Sonal S, Boudreau C, Lee GC, Cauley CE, Kunitake H, Goldstone RN, Francone TD, Bordeianou LG, Ricciardi R, Berger DL. Causes of death in patients operated for colorectal cancer. Surgery 2024; 175:1285-1290. [PMID: 38378348 DOI: 10.1016/j.surg.2024.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Revised: 12/30/2023] [Accepted: 01/04/2024] [Indexed: 02/22/2024]
Abstract
BACKGROUND Colorectal cancer remains the third leading cause of cancer-related mortality in the United States. This study evaluates the causes of death in patients operated on for colorectal cancer and their determinants. METHODS An Instructional Review Board-approved database containing patients who underwent surgical resection for colorectal cancer from 2004 to 2018 (last followed up in December 2020) in a tertiary care institution. Data on the underlying cause of death was extracted from the Registry of Vital Records and Statistics in Massachusetts. RESULTS A total of 576 deaths were recorded in the database, of which 290 (50.35%) patients died of colorectal cancer. Deaths from colorectal cancer gradually decreased over time, whereas deaths from other cancers increased, and deaths from cardiovascular diseases remained stable. Patients who died from colorectal cancer were younger, died earlier in the disease course, had fewer comorbidities, higher rates of stage IV disease, rectal cancer, neoadjuvant therapy, extramural vascular invasion, perineural invasion, R0 resection, and preserved mismatch repair protein status. On multivariate analysis, age (adjusted odds ratio for 10-year increase = 0.79, 95% confidence interval 0.65-0.95), American Society of Anesthesiologists score (adjusted odds ratio = 0.64, confidence interval 0.42-0.98), stage IV disease (adjusted odds ratio = 3.02, confidence interval 1.59-5.9), neoadjuvant therapy (adjusted odds ratio = 7.91, confidence interval 2.64-28.13), extramural vascular invasion (adjusted odds ratio = 2.3, confidence interval 1.36-3.91) & time from diagnosis to death (adjusted odds ratio = 0.76, confidence interval 0.68-0.83) predicted death due to colorectal cancer versus other causes, whereas tumor location, perineural invasion, R0 resection, and mismatch repair protein status did not. CONCLUSION There is a declining trend of deaths from colorectal cancer, presumably reflecting advances in colorectal cancer management strategies and better screening over time. However, younger patients disproportionately contribute to death due to colorectal cancer and need aggressive screening and management strategies.
Collapse
Affiliation(s)
- Swati Sonal
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA. https://twitter.com/Dr_SwatiSonal
| | - Chloe Boudreau
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Grace C Lee
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - Christy E Cauley
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - Hiroko Kunitake
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - Robert N Goldstone
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Newton-Wellesley Hospital, Newton, MA
| | - Todd D Francone
- Department of Surgery, Newton-Wellesley Hospital, Newton, MA; Department of Surgery, Tufts University School of Medicine, Boston, MA
| | - Liliana G Bordeianou
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - Rocco Ricciardi
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - David L Berger
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA.
| |
Collapse
|
|
14
|
Pretta A, Ziranu P, Giampieri R, Pinna G, Randon G, Donisi C, Ravarino A, Loi F, Deias G, Palmas E, Pretta G, Morano F, Semonella F, Mariani S, Deidda MA, Pusceddu V, Puzzoni M, Lai E, Solinas C, Restivo A, Zorcolo L, Barbara R, Berardi R, Faa G, Pietrantonio F, Scartozzi M. Mismatch Repair system protein deficiency as a resistance factor for locally advanced rectal adenocarcinoma patients receiving neoadjuvant chemo-radiotherapy. Br J Cancer 2023; 129:1619-1624. [PMID: 37749283 PMCID: PMC10646038 DOI: 10.1038/s41416-023-02444-2] [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: 03/21/2023] [Accepted: 09/14/2023] [Indexed: 09/27/2023] Open
Abstract
BACKGROUND Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC). METHODS We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS). RESULTS One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively. CONCLUSION Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies.
Collapse
Affiliation(s)
- Andrea Pretta
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy.
| | - Pina Ziranu
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Riccardo Giampieri
- Medical Oncology Unit, Azienda Ospedaliera Universitaria delle Marche, Ancona, Italy
| | - Giovanna Pinna
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Giovanni Randon
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Clelia Donisi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Alberto Ravarino
- UOC Anatomia Patologica, AOU Cagliari, University of Cagliari, Cagliari, Italy
| | - Francesco Loi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Giulia Deias
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Enrico Palmas
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Gianluca Pretta
- Science Department, King's School Hove, Hangleton Way, Hangleton, East Sussex, BN3 8BN, UK
| | - Federica Morano
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Francesca Semonella
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Stefano Mariani
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | | | - Valeria Pusceddu
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Marco Puzzoni
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Eleonora Lai
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Cinzia Solinas
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Angelo Restivo
- Department of General Surgery, University Hospital and University of Cagliari, Cagliari, Italy
| | - Luigi Zorcolo
- Department of General Surgery, University Hospital and University of Cagliari, Cagliari, Italy
| | - Raffaele Barbara
- UOC Radioterapia Oncologica, Azienda Ospedaliera "Brotzu", Cagliari, Italy
| | - Rossana Berardi
- Medical Oncology Unit, Azienda Ospedaliera Universitaria delle Marche, Ancona, Italy
| | - Gavino Faa
- UOC Anatomia Patologica, AOU Cagliari, University of Cagliari, Cagliari, Italy
| | - Filippo Pietrantonio
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Mario Scartozzi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| |
Collapse
|
|
15
|
Prabhakaran S, Choong KWK, Prabhakaran S, Choy KT, Kong JC. Accuracy of deep neural learning models in the imaging prediction of pathological complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer: a systematic review. Langenbecks Arch Surg 2023; 408:321. [PMID: 37594552 DOI: 10.1007/s00423-023-03039-4] [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: 03/18/2023] [Accepted: 08/01/2023] [Indexed: 08/19/2023]
Abstract
PURPOSE Up to 15-27% of patients achieve pathologic complete response (pCR) following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). Deep neural learning (DL) algorithms have been suggested to be a useful adjunct to allow accurate prediction of pCR and to identify patients who could potentially avoid surgery. This systematic review aims to interrogate the accuracy of DL algorithms at predicting pCR. METHODS Embase (PubMed, MEDLINE) databases and Google Scholar were searched to identify eligible English-language studies, with the search concluding in July 2022. Studies reporting on the accuracy of DL models in predicting pCR were selected for review and information pertaining to study characteristics and diagnostic measures was extracted from relevant studies. Risk of bias was evaluated using the Newcastle-Ottawa scale (NOS). RESULTS Our search yielded 85 potential publications. Nineteen full texts were reviewed, and a total of 12 articles were included in this systematic review. There were six retrospective and six prospective cohort studies. The most common DL algorithm used was the Convolutional Neural Network (CNN). Performance comparison was carried out via single modality comparison. The median performance for each best-performing algorithm was an AUC of 0.845 (range 0.71-0.99) and Accuracy of 0.85 (0.83-0.98). CONCLUSIONS There is a promising role for DL models in the prediction of pCR following neoadjuvant-CRT for LARC. Further studies are needed to provide a standardised comparison in order to allow for large-scale clinical application. PROPERO REGISTRATION PROSPERO 2021 CRD42021269904 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021269904 .
Collapse
Affiliation(s)
- Sowmya Prabhakaran
- Department of General Surgical Specialties, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
| | | | - Swetha Prabhakaran
- Department of Colorectal Surgery, Alfred Hospital, Melbourne, Victoria, Australia
| | - Kay Tai Choy
- Department of Surgery, Austin Health, Melbourne, Victoria, Australia
| | - Joseph Ch Kong
- Department of Colorectal Surgery, Alfred Hospital, Melbourne, Victoria, Australia
- Central Clinical School, Monash University, Melbourne, Victoria, Australia
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| |
Collapse
|
|
16
|
Daprà V, Airoldi M, Bartolini M, Fazio R, Mondello G, Tronconi MC, Prete MG, D’Agostino G, Foppa C, Spinelli A, Puccini A, Santoro A. Total Neoadjuvant Treatment for Locally Advanced Rectal Cancer Patients: Where Do We Stand? Int J Mol Sci 2023; 24:12159. [PMID: 37569532 PMCID: PMC10418822 DOI: 10.3390/ijms241512159] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 07/20/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
The therapeutic landscape in locally advanced rectal cancer (LARC) has undergone a significant paradigm shift in recent years with the rising adoption of total neoadjuvant treatment (TNT). This comprehensive approach entails administering chemotherapy and radiation therapy before surgery, followed by optional adjuvant chemotherapy. To establish and deliver the optimal tailored treatment regimen to the patient, it is crucial to foster collaboration among a multidisciplinary team comprising healthcare professionals from various specialties, including medical oncology, radiation oncology, surgical oncology, radiology, and pathology. This review aims to provide insights into the current state of TNT for LARC and new emerging strategies to identify potential directions for future research and clinical practice, such as circulating tumor-DNA, immunotherapy in mismatch-repair-deficient tumors, and nonoperative management.
Collapse
Affiliation(s)
- Valentina Daprà
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Marco Airoldi
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Michela Bartolini
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Roberta Fazio
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Giuseppe Mondello
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Maria Chiara Tronconi
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Maria Giuseppina Prete
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Giuseppe D’Agostino
- Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Caterina Foppa
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Alberto Puccini
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Armando Santoro
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| |
Collapse
|
|
17
|
Cuicchi D, Castagna G, Cardelli S, Larotonda C, Petrello B, Poggioli G. Restaging rectal cancer following neoadjuvant chemoradiotherapy. World J Gastrointest Oncol 2023; 15:700-712. [PMID: 37275455 PMCID: PMC10237020 DOI: 10.4251/wjgo.v15.i5.700] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 03/01/2023] [Accepted: 03/29/2023] [Indexed: 05/12/2023] Open
Abstract
Correct tumour restaging is pivotal for identifying the most personalised surgical treatment for patients with locally advanced rectal cancer undergoing neoadjuvant therapy, and works to avoid both poor oncological outcome and overtreatment. Digital rectal examination, endoscopy, and pelvic magnetic resonance imaging are the recommended modalities for local tumour restaging, while chest and abdominal computed tomography are utilised for the assessment of distant disease. The optimal length of time between neoadjuvant treatment and restaging, in terms of both oncological safety and clinical effectiveness of treatment, remains unclear, especially for patients receiving prolonged total neoadjuvant therapy. The timely identification of patients who are radioresistant and at risk of disease progression remains challenging.
Collapse
Affiliation(s)
- Dajana Cuicchi
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Giovanni Castagna
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Stefano Cardelli
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Cristina Larotonda
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Benedetta Petrello
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Gilberto Poggioli
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| |
Collapse
|
|
18
|
Baz Y, Rassam M, Rhayem E, Zouein J, Gharios J, Kourie HR. The use of dostarlimab, a safe and efficient monotherapy in MSI-H rectal cancer patients, an alternative to surgery. Immunotherapy 2023. [PMID: 37139962 DOI: 10.2217/imt-2022-0239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/05/2023] Open
Affiliation(s)
- Yara Baz
- Faculty of Medicine, Saint Joseph University of Beirut, Lebanon
| | - Maria Rassam
- Faculty of Medicine, Saint Joseph University of Beirut, Lebanon
| | - Elsa Rhayem
- Faculty of Medicine, Saint Joseph University of Beirut, Lebanon
| | - Joseph Zouein
- Faculty of Medicine, Saint Joseph University of Beirut, Lebanon
| | - Joseph Gharios
- Faculty of Medicine, Saint Joseph University of Beirut, Lebanon
| | | |
Collapse
|
|
19
|
Integrated Intensified Chemoradiation in the Setting of Total Neoadjuvant Therapy (TNT) in Patients with Locally Advanced Rectal Cancer: A Retrospective Single-Arm Study on Feasibility and Efficacy. Cancers (Basel) 2023; 15:cancers15030921. [PMID: 36765878 PMCID: PMC9913523 DOI: 10.3390/cancers15030921] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/16/2023] [Accepted: 01/30/2023] [Indexed: 02/04/2023] Open
Abstract
While surgery is considered the main treatment for early-stage rectal cancer, locally advanced rectal cancer needs to be handled with a multidisciplinary approach. Based on literature data suggesting promising advantages of total neoadjuvant therapy (TNT), we performed a retrospective, single-arm, single-center study on 45 patients affected by histologically and radiologically proven locally advanced rectal cancer, with the aim of analyzing the feasibility and short-term efficacy of an integrated intensified treatment in the setting of TNT. Each analyzed patient performed three cycles of FOLFOX4 or De Gramont induction chemotherapy (iCT), followed by concurrent chemoradiotherapy (CRT) with long course radiotherapy (LCRT) plus concomitant boost and continuous 5-FU infusion, followed by three cycles of FOLFOX4 or De Gramont consolidation chemotherapy (conCT) and then surgery with total mesorectal excision. At a median follow-up of 30 months, this strategy has shown to be feasible and effective in terms of pathological complete response (pCR) and short-term disease-free survival (DFS).
Collapse
|
|
20
|
Shi L, Xu Y, Feng M. Role of Gut Microbiome in Immune Regulation and Immune Checkpoint Therapy of Colorectal Cancer. Dig Dis Sci 2023; 68:370-379. [PMID: 36575326 DOI: 10.1007/s10620-022-07689-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 09/01/2022] [Indexed: 12/29/2022]
Abstract
Colorectal cancer (CRC) is one of the most frequent gastrointestinal malignant tumors worldwide. Immune checkpoint therapies (ICTs) have been proven to be a reliable treatment for some subtypes of CRC. Gut microbiome is closely involved in intestinal carcinogenesis through the regulation of local immune and inflammation of colonic mucosa. Numerous studies have demonstrated that the immunotherapeutic efficacy of CRC and other kinds of cancer is influenced by the immunosuppressive microenvironment constituted by intestinal microbiome and their metabolites. This Review will discuss the recent advances in how gut microbiome can modify the immune microenvironment and its potential role in ICTs of CRC.
Collapse
Affiliation(s)
- Linsen Shi
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Yumei Xu
- Department of Radiation Oncology Center, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Min Feng
- Department of Gastrointestinal Surgery, The Affiliated Drum Tower Hospital of NanJing Medical University, 321 Zhongshan Road, Nanjing, 210002, People's Republic of China.
| |
Collapse
|
|
21
|
Šemanjski K, Lužaić K, Brkić J. Current Surgical Methods in Local Rectal Excision. Gastrointest Tumors 2023; 10:44-56. [PMID: 39015761 PMCID: PMC11249472 DOI: 10.1159/000538958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 04/10/2024] [Indexed: 07/18/2024] Open
Abstract
Background The treatment of rectal cancer has evolved with the advancement of surgical techniques. Less invasive approaches are becoming more accepted as the primary treatment method. Summary Such methods as transanal excision, transanal endoscopic microsurgery, and transanal minimally invasive surgery can reduce morbidity and mortality rates. However, not all patients are suitable candidates for these procedures, and proper diagnostics are necessary to establish indications. Compared to total mesorectal excision, transanal excision techniques have been shown to have fewer complications and comorbidities while still being able to remove cancerous tissue entirely. Transanal excision is the simplest method, where the operator removes visible rectal lesions. The basic principle of transanal endoscopic microsurgery is to dilate the rectum mechanically and by air insufflation and then use special surgical instruments to remove suspicious lesions under the vision of a telescope. Transanal minimally invasive surgery combines transanal endoscopic microsurgery and single-incision laparoscopic surgery, making the hard-to-reach proximal rectum accessible to classic laparoscopic instruments. Key Message Local excision techniques, when used as a monotherapy for treating patients with rectal cancer, have established themselves as a curative and less radical treatment for strictly selected patients with early rectal carcinoma, leading to improved quality of life. When combined with other modalities such as neoadjuvant chemoradiotherapy, total neoadjuvant therapy, and immunotherapy, transanal surgery can be offered to patients with locally advanced rectal cancer as part of the organ preservation strategy. This review will discuss the patient selection and technical aspects of transanal surgery, showcasing its current role in treating rectal carcinoma.
Collapse
Affiliation(s)
| | - Karla Lužaić
- Institute of Emergency Medicine of Sisak - Moslavina County, Sisak, Croatia
| | - Jure Brkić
- Department of Surgery, Clinical Hospital Sveti Duh, Zagreb, Croatia
| |
Collapse
|
|
22
|
Bedrikovetski S, Fitzsimmons T, Perry J, Vather R, Carruthers S, Selva-Nayagam S, Thomas ML, Moore JW, Sammour T. Personalized total neoadjuvant therapy (pTNT) for advanced rectal cancer with tailored treatment sequencing based on clinical stage at presentation. ANZ J Surg 2023; 93:173-181. [PMID: 36059157 DOI: 10.1111/ans.18021] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 08/21/2022] [Accepted: 08/23/2022] [Indexed: 12/19/2022]
Abstract
BACKGROUND This study aimed to assess short-term outcomes of a personalized total neoadjuvant treatment (pTNT) protocol, with treatment sequencing based on clinical stage at presentation. METHODS A multidisciplinary pTNT protocol was implemented across two metropolitan hospitals. This consists of two-schema based on clinical stage: patients with distant failure risk were offered induction chemotherapy before chemoradiation (nCRT), and patients with locoregional failure risk received nCRT followed by consolidation chemotherapy. Patients underwent surgical resection unless a complete clinical response (cCR) was achieved, in which case non-operative management (NOM) was offered. A prospective cohort analysis of all patients with rectal cancer who underwent pTNT with curative intent between Jan 2019 and Aug 2022 was performed. RESULTS Of 270 patients referred with rectal cancer, 102 received pTNT with curative intent and 79 have completed their treatment thus far. Thirty-three patients (41.8%) received induction chemotherapy and 46 (58.2%) received consolidation chemotherapy per protocol. The percentage of patients with EMVI, resectable M1 disease, cT4 disease, and positive lateral lymph nodes were 54.4%, 36.7%, 27.8% and 15.2%, respectively. Overall, 32 (40.5%) patients had cCR and 4 (5.1%) pCR, and 40 (50.6%) patients had non-operative management. Grade 3 toxicity was reported in 10.1% of patients and only three patients (3.8%) experienced Grade 4 chemotherapy-related toxicity, with no treatment related mortality. CONCLUSION Early results with a defined two-schema pTNT protocol are encouraging and suggest that tailoring sequencing to disease risk at presentation may represent the optimal balance between local and distant disease control, as well as treatment toxicity.
Collapse
Affiliation(s)
- Sergei Bedrikovetski
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.,Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Tracy Fitzsimmons
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.,Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Joanne Perry
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Ryash Vather
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Scott Carruthers
- Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Sudarsha Selva-Nayagam
- Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Michelle L Thomas
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.,Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - James W Moore
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.,Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Tarik Sammour
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.,Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| |
Collapse
|
|
23
|
Zhao X, Han P, Zhang L, Ma J, Dong F, Zang L, He Z, Zheng M. Prolonged neoadjuvant chemotherapy without radiation versus total neoadjuvant therapy for locally advanced rectal cancer: A propensity score matched study. Front Oncol 2022; 12:953790. [PMID: 36185248 PMCID: PMC9523158 DOI: 10.3389/fonc.2022.953790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 08/25/2022] [Indexed: 11/13/2022] Open
Abstract
Background Although neoadjvuant chemoradiotherapy (CRT) improves the local control rate of locally advanced rectal cancer (LARC), it fails to significantly improve disease-free survival (DFS) and overall survival (OS). We explored the efficacy of prolonged neoadjuvant chemotherapy (pNCT) without radiation and compared this schema with total neoadjuvant therapy (TNT). Material and methods Patients diagnosed with LARC and received TNT (4 cycles of induction CapeOX/FOLFOX followed with CRT) or pNCT (6~8 cycles of CapeOX/FOLFOX) between June 2016 and October 2021 were retrospective analyzed. All patients underwent total mesorectal excision (TME). A 1:1 propensity score match was performed to adjust baseline potential confounders. The tumor response, toxicity, recurrence-free survival (RFS) and OS were observed. Results A total of 184 patients with 92 patients in each group were finally enrolled. The median follow-up time was 35 months. TNT showed better pathological complete response (pCR) rate (25.0% vs 16.3%) and objective regression rate (73.9% vs 59.8%) than pNCT. TNT and pNCT produce similar 3-year RFS and OS rates in patients with mid-to-upper rectal cancer. TNT was associated with improved tumor responsiveness in all patients and improved 3-year RFS rates in those with low rectal cancer. Conclusion pNCT is an option for patients with mid-to-upper rectal cancer, but radiation is still necessary for low rectal cancer. To determine optimal schema for neoadjuvant therapy and patient selection, additional randomized controlled studies are needed.
Collapse
Affiliation(s)
- Xuan Zhao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Peiyi Han
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Luyang Zhang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Junjun Ma
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Feng Dong
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Lu Zang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Zirui He
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
- *Correspondence: Minhua Zheng, ; Zirui He,
| | - Minhua Zheng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
- *Correspondence: Minhua Zheng, ; Zirui He,
| |
Collapse
|
|
24
|
The Effect of Continuing Chemotherapy after Chemoradiotherapy during the Time to Surgery on Tumor Response and Survival for Local Advanced Rectal Cancer. JOURNAL OF ONCOLOGY 2022; 2022:4108677. [PMID: 36157223 PMCID: PMC9499766 DOI: 10.1155/2022/4108677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 09/01/2022] [Indexed: 11/17/2022]
Abstract
Aim The current standard treatment of locally advanced rectal carcinoma is total mesorectal excision and postoperative adjuvant chemotherapy after neoadjuvant concurrent chemoradiotherapy (NCRT). Many studies have shown that pathological complete response (pCR) is an important prognostic factor for patients receiving NCRT. Many studies have therefore been conducted to increase pCR rates by changing the perioperative treatment strategies. Prolonging the chemotherapy time may be a reasonable way to increase the effectiveness of NCRT, pCR, and survival rates. We investigated whether neoadjuvant consolidation chemotherapy had an effect on tumor response and survival. Methods The data of 163 patients diagnosed with locally advanced rectal carcinoma were evaluated. The data of 107 patients (Group 1) who were radiologically T3–T4 and/or N+ and received chemotherapy after NCRT until their operations were compared with the data of 56 patients (Group 2) who were operated after NCRT. Results Group 1 patients had tumor and node downstaging. Their pCR was found significantly higher than in Group 2 (p = 0.005). In Group 1 patients with T3, pCR was significantly higher than for those with T4. The elapsed time between NCRT and surgery was significantly longer in patients with pCR (respectively, p = 0.012 and p = 0.008). Conclusion Neoadjuvant consolidation chemotherapy after NCRT is a safe approach that can lead to higher pathological complete response rates. The time until surgery with neoadjuvant consolidation chemotherapy may provide the chance to follow the patient without surgery in addition to increasing pCR.
Collapse
|
|
25
|
van den Berg K, Schaap DP, Voogt ELK, Buffart TE, Verheul HMW, de Groot JWB, Verhoef C, Melenhorst J, Roodhart JML, de Wilt JHW, van Westreenen HL, Aalbers AGJ, van 't Veer M, Marijnen CAM, Vincent J, Simkens LHJ, Peters NAJB, Berbée M, Werter IM, Snaebjornsson P, Peulen HMU, van Lijnschoten IG, Roef MJ, Nieuwenhuijzen GAP, Bloemen JG, Willems JMWE, Creemers GJM, Nederend J, Rutten HJT, Burger JWA. Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk ("ugly") locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT). BMC Cancer 2022; 22:957. [PMID: 36068495 PMCID: PMC9446695 DOI: 10.1186/s12885-022-09947-w] [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: 06/07/2022] [Accepted: 07/29/2022] [Indexed: 11/14/2022] Open
Abstract
Background The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. Methods This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. Discussion This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. Trial registration Clinicaltrials.gov: NCT04838496, registered on 02–04-2021 Netherlands Trial Register: NL9790. Protocol version Version 3 dd 11–4-2022.
Collapse
Affiliation(s)
- K van den Berg
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands.,Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - D P Schaap
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - E L K Voogt
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - T E Buffart
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.,Department of Medical Oncology, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| | - H M W Verheul
- Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - J W B de Groot
- Department of Medical Oncology, Isala Oncology Centre, Zwolle, the Netherlands
| | - C Verhoef
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - J Melenhorst
- Department of Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - J M L Roodhart
- Department of Medical Oncology, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - J H W de Wilt
- Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands
| | | | - A G J Aalbers
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - M van 't Veer
- Department of Research and Education, Catharina Hospital, Eindhoven, the Netherlands
| | - C A M Marijnen
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.,Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands
| | - J Vincent
- Department of Medical Oncology, Elkerliek Hospital, Helmond, the Netherlands
| | - L H J Simkens
- Department of Medical Oncology, Maxima Medical Centre, Veldhoven, the Netherlands
| | - N A J B Peters
- Department of Medical Oncology, St. Jans Hospital, Weert, the Netherlands
| | - M Berbée
- Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - I M Werter
- Department of Medical Oncology, Rijnstate Hospital, Arnhem, the Netherlands
| | - P Snaebjornsson
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - H M U Peulen
- Department of Radiation Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - I G van Lijnschoten
- Department of Pathology, PAMM Laboratory for Pathology and Medical Microbiology, Eindhoven, the Netherlands
| | - M J Roef
- Department of Nuclear Medicine, Catharina Hospital, Eindhoven, the Netherlands
| | | | - J G Bloemen
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - J M W E Willems
- Department of Medical Oncology, Anna Hospital, Geldrop, the Netherlands
| | - G J M Creemers
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - J Nederend
- Department of Radiology, Catharina Hospital, Eindhoven, the Netherlands
| | - H J T Rutten
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.,GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
| | - J W A Burger
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
| |
Collapse
|
|
26
|
Gevorkian J, Le E, Alvarado L, Davis B, Tyroch A, Chiba S, Konstantinidis IT. Trends and outcomes of minimally invasive surgery for gastrointestinal stromal tumors (GIST). Surg Endosc 2022; 36:6841-6850. [PMID: 35048188 DOI: 10.1007/s00464-022-09014-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 01/03/2022] [Indexed: 11/24/2022]
Abstract
OBJECTIVE Minimally invasive surgery (MIS) is increasingly being utilized for the resection of gastrointestinal cancers. National trends for perioperative and oncologic outcomes of MIS for gastrointestinal stromal tumors (GIST) are unknown. We hypothesized that with increased use of MIS, the perioperative outcomes and survival for GIST are preserved. METHODS The National Cancer Database (2010-2016) was utilized to assess perioperative and oncologic outcomes for GIST of the stomach and small bowel. Kaplan-Meier method and log rank test were used to compare survival outcomes. RESULTS Data from 8923 gastric and 3683 small bowel resections were analyzed. Over the study period, MIS became the prevalent modality for gastrectomies (2010: robotic: 2.4%, laparoscopic: 26.1%, open: 71.5% vs. 2016: robotic: 9.6%, laparoscopic: 48.8%, open: 41.6%; p < 0.001), with a smaller increase in enterectomies (2010: robotic: 1%, laparoscopic: 17.3%, open: 81.6% vs. 2016: robotic: 3.9%, laparoscopic: 27.2%, open: 68.9%; p < 0.001). Age and Charlson comorbidity index were similar among groups. MIS approaches were associated with fewer readmissions and lower 90 day mortality for gastrectomies and similar rates for enterectomies. MIS did not compromise patient survival even in patients who underwent neoadjuvant treatment or harbored tumors ≥ 10 cm. CONCLUSION Minimally invasive surgery is increasingly being utilized for resection of gastric and small bowel GIST, with improved postoperative outcomes. In this retrospective review, overall survival after minimally invasive or open surgery was comparable, even in challenging scenarios of neoadjuvant treatment or large tumors (≥ 10 cm).
Collapse
Affiliation(s)
- Jonathan Gevorkian
- Department of Surgery, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Emily Le
- Department of Surgery, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Luis Alvarado
- Biostatistics and Epidemiology and Consulting Lab, Office of Research, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Brian Davis
- Department of Surgery, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Alan Tyroch
- Department of Surgery, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Shintaro Chiba
- Department of Surgery, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | | |
Collapse
|
|
27
|
Mauri G, Vitiello PP, Sogari A, Crisafulli G, Sartore-Bianchi A, Marsoni S, Siena S, Bardelli A. Liquid biopsies to monitor and direct cancer treatment in colorectal cancer. Br J Cancer 2022; 127:394-407. [PMID: 35264786 PMCID: PMC9346106 DOI: 10.1038/s41416-022-01769-8] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 02/02/2022] [Accepted: 02/17/2022] [Indexed: 12/15/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide. Despite recent improvements in treatment and prevention, most of the current therapeutic options are weighted by side effects impacting patients' quality of life. Better patient selection towards systemic treatments represents an unmet clinical need. The recent multidisciplinary and molecular advancements in the treatment of CRC patients demand the identification of efficient biomarkers allowing to personalise patient care. Currently, core tumour biopsy specimens represent the gold-standard biological tissue to identify such biomarkers. However, technical feasibility, tumour heterogeneity and cancer evolution are major limitations of this single-snapshot approach. Genotyping circulating tumour DNA (ctDNA) has been addressed as potentially overcoming such limitations. Indeed, ctDNA has been retrospectively demonstrated capable of identifying minimal residual disease post-surgery and post-adjuvant treatment, as well as spotting druggable molecular alterations for tailoring treatments in metastatic disease. In this review, we summarise the available evidence on ctDNA applicability in CRC. Then, we review ongoing clinical trials assessing how liquid biopsy can be used interventionally to guide therapeutic choice in localised, locally advanced and metastatic CRC. Finally, we discuss how its widespread could transform CRC patients' management, dissecting its limitations while suggesting improvement strategies.
Collapse
Affiliation(s)
- Gianluca Mauri
- IFOM-FIRC Institute of Molecular Oncology, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Pietro Paolo Vitiello
- Candiolo Cancer Institute, FPO-IRCCS, 10060, Candiolo, TO, Italy
- Department of Oncology, University of Torino, 10060, Candiolo, TO, Italy
| | - Alberto Sogari
- Candiolo Cancer Institute, FPO-IRCCS, 10060, Candiolo, TO, Italy
- Department of Oncology, University of Torino, 10060, Candiolo, TO, Italy
| | - Giovanni Crisafulli
- Candiolo Cancer Institute, FPO-IRCCS, 10060, Candiolo, TO, Italy
- Department of Oncology, University of Torino, 10060, Candiolo, TO, Italy
| | - Andrea Sartore-Bianchi
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy
| | | | - Salvatore Siena
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
- Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy
| | - Alberto Bardelli
- Candiolo Cancer Institute, FPO-IRCCS, 10060, Candiolo, TO, Italy.
- Department of Oncology, University of Torino, 10060, Candiolo, TO, Italy.
| |
Collapse
|
|
28
|
Chen BY, Xie H, Li Y, Jiang XH, Xiong L, Tang XF, Lin XF, Li L, Cai PQ. MRI-Based Radiomics Features to Predict Treatment Response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer: A Single Center, Prospective Study. Front Oncol 2022; 12:801743. [PMID: 35646677 PMCID: PMC9133669 DOI: 10.3389/fonc.2022.801743] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 03/31/2022] [Indexed: 12/22/2022] Open
Abstract
This is a prospective, single center study aimed to evaluate the predictive power of peritumor and intratumor radiomics features assessed using T2 weight image (T2WI) of baseline magnetic resonance imaging (MRI) in evaluating pathological good response to NAC in patients with LARC (including Tany N+ or T3/4a Nany but not T4b). In total, 137 patients with LARC received NAC between April 2014 and August 2020. All patients were undergoing contrast-enhanced MRI and 129 patients contained small field of view (sFOV) sequence which were performed prior to treatment. The tumor regression grade standard was based on pathological response. The training and validation sets (n=91 vs. n=46) were established by random allocation of the patients. Receiver operating characteristic curve (ROC) analysis was applied to estimate the performance of different models based on clinical characteristics and radiomics features obtained from MRI, including peritumor and intratumor features, in predicting treatment response; these effects were calculated using the area under the curve (AUC). The performance and agreement of the nomogram were estimated using calibration plots. In total, 24 patients (17.52%) achieved a complete or near-complete response. For the individual radiomics model in the validation set, the performance of peritumor radiomics model in predicting treatment response yield an AUC of 0.838, while that of intratumor radiomics model is 0.805, which show no statically significant difference between then(P>0.05). The traditional and selective clinical features model shows a poor predictive ability in treatment response (AUC=0.596 and 0.521) in validation set. The AUC of combined radiomics model was improved compared to that of the individual radiomics models in the validation sets (AUC=0.844). The combined clinic-radiomics model yield the highest AUC (0.871) in the validation set, although it did not improve the performance of the radiomics model for predicting treatment response statically (P>0.05). Good agreement and discrimination were observed in the nomogram predictions. Both peritumor and intratumor radiomics features performed similarly in predicting a good response to NAC in patients with LARC. The clinic-radiomics model showed the best performance in predicting treatment response.
Collapse
Affiliation(s)
- Bi-Yun Chen
- Department of Medical Imaging, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Hui Xie
- Department of Medical Imaging, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yuan Li
- Department of Colorectal, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xin-Hua Jiang
- Department of Medical Imaging, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Lang Xiong
- Department of Medical Imaging, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiao-Feng Tang
- Department of Ultrasound, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiao-Feng Lin
- Department of Medical Imaging, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Li Li
- Department of Medical Imaging, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Pei-Qiang Cai
- Department of Medical Imaging, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| |
Collapse
|
|
29
|
Hamed RA, Korpanty G, Kelly D. Toxicities and outcomes of neoadjuvant treatment in elderly patients with locally advanced rectal cancer: a scoping review protocol. BMJ Open 2022; 12:e061397. [PMID: 35501084 PMCID: PMC9062800 DOI: 10.1136/bmjopen-2022-061397] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 03/25/2022] [Indexed: 11/03/2022] Open
Abstract
INTRODUCTION Colorectal cancer remains the second leading cause of cancer-related death in 60-79 years old and the third leading cause of death in patients aged 80 and above. Rectal cancer accounts for approximately a third of colorectal cancer diagnoses. The current standard of care for managing locally advanced rectal cancer involves a multimodal combined approach with neoadjuvant treatment, surgery with total mesorectal excision and adjuvant chemotherapy. Neoadjuvant treatment can be in the form of short-course radiotherapy, long-course concurrent radiotherapy with chemotherapy or total neoadjuvant chemotherapy with concurrent chemoradiotherapy followed by chemotherapy. This scoping aims to assess the toxicity and outcome of the different neoadjuvant treatment modalities in elderly patients. METHODS AND ANALYSIS We will use Arksey and O'Malley's five scoping review methodology framework stages. Searches will be conducted in Ovid Medline, Embase, Cochrane database and CINAHL. In addition, the researcher will hand search for all registered trials, using a combination of terms such as "locally advanced rectal cancer", "neoadjuvant treatment", and "elderly patients." Two independent reviewers will screen titles and abstracts and then full text based on predefined inclusion and exclusion criteria. Publications will be extracted using a customised data extraction tool to include study characteristics, research topics, exposures and outcomes. ETHICS AND DISSEMINATION Ethics approval is not required as the data will be collected from the existing literature. The findings of this study will help with future clinical research on the topic. We will publish the findings of this review in a peer-reviewed journal and present them at academic conferences targeting geriatric oncology service providers.
Collapse
Affiliation(s)
- Ruba Ahmed Hamed
- School Of Medicine, University of Limerick, Limerick, Ireland
- Medical Oncology, University Hospital Limerick, Limerick, Ireland
| | - Greg Korpanty
- Medical Oncology, University Hospital Limerick, Limerick, Ireland
| | - Dervla Kelly
- School Of Medicine, University of Limerick, Limerick, Ireland
- Health Research Institute, University of Limerick, Limerick, Ireland
| |
Collapse
|
|
30
|
Abstract
The management of localized rectal cancer requires a multidisciplinary approach to optimize outcomes, reduce morbidity and prevent under or overtreatments. While early stages may obtain benefit of local resections without any additional therapies, locally advanced rectal cancer becomes a challenge defining the better sequential strategy of surgery, radiotherapy and chemotherapy. The latest results of international phase III studies have positioned the total neoadjuvant therapy as a potential new standard of care in high risk rectal cancers, however, the best schedule is still not well defined.
Collapse
|
|
31
|
Intraoperative radiation after pelvic short course radiation-based total neoadjuvant therapy for patients with rectal adenocarcinoma at high risk for local recurrence. Clin Colorectal Cancer 2022; 21:204-211. [DOI: 10.1016/j.clcc.2022.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 12/30/2021] [Accepted: 01/03/2022] [Indexed: 11/21/2022]
|
|
32
|
Sclafani F, Corrò C, Koessler T. Debating Pros and Cons of Total Neoadjuvant Therapy in Rectal Cancer. Cancers (Basel) 2021; 13:cancers13246361. [PMID: 34944980 PMCID: PMC8699289 DOI: 10.3390/cancers13246361] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/12/2021] [Accepted: 12/14/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Rectal cancers represent one third of all colorectal tumours. Patients diagnosed with localised colon cancer undergo surgery upfront, likely followed by adjuvant chemotherapy. Those diagnosed with localised rectal cancer, however, frequently benefit from neoadjuvant treatments with either radiotherapy or chemoradiotherapy before undergoing surgery. On the other hand, the benefit of adjuvant chemotherapy in this setting is more controversial. The main challenges in treating patients affected by rectal cancer encompass: decreasing the risks of local relapse and distant metastases, preserving the sphincter and minimising treatment-associated functional sequelae, and improving overall survival. Some of these fuelled the concept of total neoadjuvant therapy, namely giving all available treatments including radiotherapy and systemic chemotherapy before surgery. Here, we critically review the pros and cons of such a treatment strategy, but also discuss the biological rational to support neoadjuvant treatment intensification. Abstract Recently, two large, randomised phase III clinical trials of total neoadjuvant therapy (TNT) in locally advanced rectal cancer were published (RAPIDO and PRODIGE 23). These two trials compared short-course radiotherapy (SCRT) followed by chemotherapy with standard chemoradiotherapy (CRT) and chemotherapy followed by CRT with standard CRT, respectively. They showed improvement in some of the outcomes such as distant recurrence and pathological complete response (pCR). No improvement, however, was observed in local disease control or the de-escalation of surgical procedures. Although it seems lawful to integrate TNT within the treatment algorithm of localised stage II and III rectal cancer, many questions remain unanswered, including which are the optimal criteria to identify patients who are most likely to benefit from this intensive treatment. Instead of providing a sterile summary of trial results, we put these in perspective in a pros and cons manner. Moreover, we discuss some biological aspects of rectal cancer, which may provide some insights into the current decision-making process, and represent the basis for the future development of alternative, more effective treatment strategies.
Collapse
Affiliation(s)
- Francesco Sclafani
- Department of Medical Oncology, Institut Jules Bordet, Rue Meylemeersch 90, 1070 Anderlecht, Belgium;
- Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium
| | - Claudia Corrò
- Translational Research Center in Onco-Hematology, Department of Medicine, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland;
- Swiss Cancer Center Léman, Geneva and Lausanne, 1005 Lausanne, Switzerland
| | - Thibaud Koessler
- Translational Research Center in Onco-Hematology, Department of Medicine, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland;
- Swiss Cancer Center Léman, Geneva and Lausanne, 1005 Lausanne, Switzerland
- Department of Oncology, Geneva University Hospital, 1205 Geneva, Switzerland
- Correspondence:
| |
Collapse
|
|
33
|
Johnson D, Li L, Lee KC, Lam KO, Wong KH, Ho WM, Ma B. Total Neoadjuvant Therapy for High Risk Rectal Cancer in Western and Asian Populations – Current Evidence and Clinical Applications. Clin Colorectal Cancer 2021; 21:45-54. [DOI: 10.1016/j.clcc.2021.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 12/14/2021] [Accepted: 12/21/2021] [Indexed: 11/26/2022]
|
|
34
|
Jiang T, Liu S, Wu X, Liu X, Li W, Yang S, Cai P, Xi S, Zeng Z, Gao Y, Chen G, Xiao W. Nomogram to Predict Distant Metastasis Probability for Pathological Complete Response Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy. Cancer Manag Res 2021; 13:4751-4761. [PMID: 34163249 PMCID: PMC8214524 DOI: 10.2147/cmar.s313113] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 05/26/2021] [Indexed: 01/04/2023] Open
Abstract
Purpose This study aimed to predict the risks of distant metastasis (DM) of locally advanced rectal cancer (LARC) patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME), and to find the association between adjuvant chemotherapy (ACT) and their survival outcomes. Methods and Materials A total of 242 patients with LARC achieving pCR after NACRT were enrolled in this retrospective study. We developed a nomogram model using logistic regression analyses for predicting risk of DM. The model performance was evaluated by the concordance index and calibration curve. Survival was determined using Kaplan–Meier survival curve. Results Age, pre-operative CEA, pre-treatment CEA and distance of tumor to anal verge were identified as significantly associated variables that could be enrolled in the model to predict the risk of DM for pCR patients. The nomogram we created had a bootstrapped-concordance index of 0.731 (95% CI = 0.627 to 0.834) and was well calibrated. The high risk group was more likely to develop DM than low risk group (total score) (95% CI = 1.439 to 6.493, P = 0.0036). The 1-year, 3-year, and 5-year distant metastasis-free survival (DMFS) for the low and high risk groups (total score ≤ 90 vs > 90) was 97.8%, 94.2%, 94.2% and 91.3%, 83.4%, 81.8%, respectively (P = 0.0036). DM occurred within 1 and 2 years after TME surgery was 33.3% and 55.6% for the low risk group, and 47.3% and 84.2% for the high risk group. The value of ACT was assessed among the whole cohort, patients with cT3-4, with cN+ or with either DM risk group, but no significant difference was observed concerning DMFS whether ACT was given or not (all P > 0.05). Active treatment after DM was more beneficial than palliative treatment (P < 0.001). Conclusion The nomogram model, including age, pre-operative CEA, pre-treatment CEA and distance to anal verge, predicted the probability of DM among LARC patients achieving pCR after NACRT. The effects of ACT were not seen in different subgroups, while closer clinical follow-up may have greater contribution to pCR patients in the first 2 years, especially for patients with relatively higher risk to develop DM. It is suggested that timely active treatment can bring survival benefit for pCR patients developing DM after NACRT.
Collapse
Affiliation(s)
- Ting Jiang
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Shuang Liu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Xiaojun Wu
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Xiaoqing Liu
- Department of Radiation Oncology, Guangzhou Concord Cancer Center, Guangzhou, People's Republic of China
| | - Weizhan Li
- Department of Radiation Oncology, Panyu Center Hospital, Guangzhou, People's Republic of China
| | - Shanfei Yang
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Peiqiang Cai
- Department of Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Shaoyan Xi
- Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Zhifan Zeng
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Yuanhong Gao
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Gong Chen
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Weiwei Xiao
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| |
Collapse
|