Future of Radiotherapy Delivery in Rectal Cancer—European and US Approaches

2015 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Jordan A Torok ◽  
Brian G Czito ◽  
Christopher G Willett ◽  
Manisha Palta ◽  
◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Radiation Therapy ◽  
Randomized Clinical Trials ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Significant Difference ◽  
Long Course

Neoadjuvant radiation therapy is integral in the management of patients with localized rectal cancer. In parts of Europe, patients with operable rectal cancer are treated with short-course radiation therapy delivered in five daily, 5 Gy fractions to a total dose of 25 Gy, followed by surgery within 1 week. In the US, the standard for locally advanced rectal cancer is neoadjuvant chemoradiotherapy. This approach is principally based on the results of the German Rectal Cancer Study Group trial evaluating preoperative compared with postoperative chemoradiation. Surgery is typically performed at 4–8 weeks following completion of long-course chemoradiotherapy, facilitating tumor downstaging, and potential sphincter sparing surgery. No significant difference in clinical outcomes has been observed between these two approaches in two randomized clinical trials; however, further follow-up of these studies and new results from ongoing trials are anticipated to further clarify the optimal neoadjuvant treatment strategy.

scholarly journals Future of Radiotherapy Delivery in Rectal Cancer— European and US Approaches

2014 ◽  
Vol 10 (02) ◽  
pp. 139
Author(s):  
Jordan A Torok ◽  
Brian G Czito ◽  
Christopher G Willett ◽  
Manisha Palta ◽  
◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Radiation Therapy ◽  
Randomized Clinical Trials ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Significant Difference ◽  
Long Course

Neoadjuvant radiation therapy is integral in the management of patients with localized rectal cancer. In parts of Europe, patients with operable rectal cancer are treated with short-course radiation therapy delivered in five daily, 5 Gy fractions to a total dose of 25 Gy, followed by surgery within 1 week. In the US, the standard for locally advanced rectal cancer is neoadjuvant chemoradiotherapy. This approach is principally based on the results of the German Rectal Cancer Study Group trial evaluating preoperative compared with postoperative chemoradiation. Surgery is typically performed at 4–8 weeks following completion of long-course chemoradiotherapy, facilitating tumor downstaging, and potential sphincter sparing surgery. No significant difference in clinical outcomes has been observed between these two approaches in two randomized clinical trials; however, further follow-up of these studies and new results from ongoing trials are anticipated to further clarify the optimal neoadjuvant treatment strategy.

scholarly journals Adding Three Cycles of CAPOX after Neoadjuvant Chemoradiotherapy Increases the Rates of Complete Response for Locally Advanced Rectal Cancer

2021 ◽  
Vol 28 (1) ◽  
pp. 283-293
Author(s):  
Zhiwei Zhai ◽  
Kunning Zhang ◽  
Chen Wang ◽  
Tian Zhang ◽  
Lixia Wang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Distant Metastases ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Consolidation Chemotherapy ◽  
Significant Difference

Background and Objectives: the total neoadjuvant chemoradiotherapy (TNT) includes different strategies, but the most appropriate model remains uncertain. The purpose of this retrospectively study was to evaluate the safety and pathological response in the consolidation chemotherapy model. Methods: patients with cT3/T4 or TxN + M0 rectal cancer that were receiving neoadjuvant chemoradiotherapy (CRT) (50 Gy with oral capecitabine)/TNT (CRT followed by three cycles of CAPOX) during September 2017 to September 2019 in our department were included. All of the patients were recommended to receive radical surgery. Results: a total of 197 patients were included. Eighty-one patients received CRT, while one hundred and sixteen patients received TNT. Nine patients did not undergo surgery because of the distant metastases (one patient (1.2%) in CRT group, two patients (1.7%) in TNT group) or a refusal of resection (two patients in CRT group, four patients in TNT group). The pathological complete response (pCR) rate was 32.7% in TNT compared with 12.8% in CRT (p = 0.002). There was no statistically significant difference in grade 3 acute toxicities of neoadjuvant treatment and surgical complications between the two groups. Conclusions: the consolidation chemotherapy model is safe for patients with locally advanced rectal cancer and it has a high pCR rate. The long-term follow-up is necessary to be evaluated in a future prospective, randomized trial.

scholarly journals Total neoadjuvant chemoradiotherapy (consolidation chemotherapy during the interval after chemoradiotherapy) for distal rectal cancer increases the rates of complete response

2020 ◽  
Author(s):  
Zhiwei Zhai ◽  
Kunning Zhang ◽  
Chen Wang ◽  
Jiagang Han ◽  
Tian Zhang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Consolidation Chemotherapy ◽  
Significant Difference

Abstract Objective To compare the safety and efficacy between neoadjuvant concurrent chemoradiotherapy (CRT) and total neoadjuvant chemoradiotherapy (TNT) in patients with locally advanced rectal cancer. Methods Patients with cT3/T4 or TxN+M0 rectal cancer were randomized to receive CRT/TNT. In CRT group, we planned pelvic radiotherapy (50.0Gy in 25 fractions) with two cycles of concurrent CAPOX followed by total mesorectal excision (TME). In TNT group, 3 cycles of CAPOX were administered 2 weeks after the completion of CRT before TME. The primary endpoints of my study were pathological complete response (pCR) rates in the two cohorts. Results A total of 197 patients were included in our study. Eighty-one patients received CRT while one hundred and sixteen patients received TNT (consolidation chemotherapy). Nine patients did not undergo surgery because of the distant metastases (1 patient (1.2%) in CRT group, 2 patients (1.7%) in TNT group) or clinical complete response (cCR) (2 patients in CRT group, 4 patients in TNT group). The rate of pathological complete response in TNT was significantly higher than the rate in CRT (32.7% vs12.8%, P =0.002). No grade 4 or serious adverse events were observed. There was no statistically significant difference in the grade 3 acute toxicities of neoadjuvant treatment and surgical complications between the two groups (all P >0.05). Conclusions Our data suggests that total neoadjuvant chemoradiotherapy (consolidation chemotherapy) is effective and safe for patients with locally advanced rectal cancer and is associated with high rates of pathological complete response. The long-term follow-up and survival outcomes for patients are necessary to be evaluated in future prospective randomized trial.

The consensus Immunoscore adapted to biopsies in patients with locally advanced rectal cancer: Potential clinical significance for a “Watch and Wait” strategy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2628-2628
Author(s):  
Carine El Sissy ◽  
Amos Kirilovsky ◽  
Marc Van Den Eynde ◽  
Alfredo Romero ◽  
Florence Marliot ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Reliable Estimate ◽  
Watch And Wait ◽  
Significant Difference

2628 Background: We investigated whether an adaptation to rectal biopsies of the recently validated consensus Immunoscore, could predict the response to neoadjuvant treatment and delineate clinical responders that could benefit from a “Watch and Wait” (W&W) strategy with acceptable outcomes. Methods: Initial biopsies from 273 patients with locally advanced rectal cancer (LARC) treated by neoadjuvant chemoradiotherapy (nCRT) followed by Total Mesorectal Excision (TME), were immunostained for CD3+ and cytotoxic CD8+ T cells and quantified by digital pathology to determine the Immunoscore within pre-treatment Biopsy (ISB). Expression level of 44 immune related genes post-neoadjuvant treatment was investigated by Nanostring technology (n = 64 patients). Results were correlated with response to neoadjuvant treatment, disease free survival (DFS) and time to recurrence (TTR). Prognostic performance of ISB was finally assessed in 73 LARC treated by W&W strategy. Results: ISB Low, Intermediate and High were respectively observed in 23.3, 50.4 and 26.3 % of the cohort. ISB was positively and significantly correlated with the response to nCRT, as evaluated by Dworak classification (P = .0034), ypTNM (P = .0003), down-staging (P = .0014), and neoadjuvant rectal (NAR) score, (P < .0001). ISB status was also positively associated with the degree of local immune activation post-neoadjuvant treatment. ISB High patients were at low risk of relapse, with 5-year DFS rates of 81.1 % (CI, 71.3-92.1 %) as compared to 57.8 % (CI, 45.9-72.9 %) in ISB low patients. In multivariate analysis, ISB was the only significant parameter at presentation associated with DFS (High vs Low: P = .001). Among W&W patients, significant difference was observed for TTR according to ISB status (High vs Low: P = .025). Conclusions: ISB could provide a reliable estimate of the response to nCRT and risk of recurrence in LARC patients' treated by TME or W&W strategy.

scholarly journals Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1539
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Bianca de Cássia Troncarelli Flores ◽  
Alexcia Camila Braun ◽  
Daniela de Jesus Ferreira Costa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Transforming Growth Factor ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

Deferral of rectal surgery following a continued response to preoperative chemoradiotherapy (Watch and Wait) study: A phase II multicenter study in the United Kingdom.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 489-489 ◽  
Author(s):  
S. K. Yu ◽  
G. Brown ◽  
R. J. Heald ◽  
S. Chua ◽  
G. Cook ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Clinical Staging ◽  
Pet Ct

489 Background: Neoadjuvant chemoradiotherapy (CRT) and surgical resection are standard components of therapy for patients locally advanced rectal cancer (T3,T4 or N+) in UK. In 15%-30% of patients treated pre-operatively with CRT will develop pathological complete response (CR). The time from completion of CRT to maximal tumour response is as yet unknown. This study is the first prospective study to attempt to identify the percentage of patients who can safely omit surgery and the safety of deferred surgery in patients who achieve clinical complete response post CRT. Of the 59 patients required for the study, this provides an update on 19 patients entered. Methods: Patients with locally advanced rectal cancer requiring neoadjuvant treatment are identified in the multidisciplinary meet (MDT). Patients undergo CRT using a minimum of 50.4Gy in 28 # daily conformal CT planned CRT with concomitant Capecitabine at 825mg/m2 BD. MRI pelvis and body CT are repeated 4 weeks post CRT and rediscussed at MDT. If there is a good partial response or CR, patients are considered for Deferral of Surgery Study. Based on the pre treatment clinical staging, patients are considered for adjuvant chemotherapy as per NICE guidance. At any point of the study, if there is histology proven tumour regrowth or progression, patient undergo surgery. Results: 10 (53%) patients remain in CR. 6 (32%) patients underwent surgical resection with clear margin after detection of tumour regrowth at from 2-23 months post CRT. 5 out of 6 of the patients with tumour regrowth underwent PET CT as per protocol, and all tumour regrowth in those 5 patients were detected by PET CT, i.e. FDG avid disease. The pathological stages on these 6 patients were ypT2N0 CRM negative in 5 and ypT3N0 CRM negative in 1. 3 (15%) patients with tumour regrowth refused surgery. Conclusions: In the 19 recruited patients, all the patients with tumour regrowth underwent surgical resection with clear margins. PET CT appears a useful tool for detecting tumour regrowth. The median time for tumour regrowth is 17.5 months post CRT. The trial will be successful if at least 11/59 patients are able to safely omit surgery. Accrual of patients continues. No significant financial relationships to disclose.

scholarly journals Pre-Treatment T2-WI Based Radiomics Features for Prediction of Locally Advanced Rectal Cancer Non-Response to Neoadjuvant Chemoradiotherapy: A Preliminary Study

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1894 ◽  
Author(s):  
Bianca Petresc ◽  
Andrei Lebovici ◽  
Cosmin Caraiani ◽  
Diana Sorina Feier ◽  
Florin Graur ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Imaging Biomarkers ◽  
Tumor Regression Grade ◽  
Pre Treatment

Locally advanced rectal cancer (LARC) response to neoadjuvant chemoradiotherapy (nCRT) is very heterogeneous and up to 30% of patients are considered non-responders, presenting no tumor regression after nCRT. This study aimed to determine the ability of pre-treatment T2-weighted based radiomics features to predict LARC non-responders. A total of 67 LARC patients who underwent a pre-treatment MRI followed by nCRT and total mesorectal excision were assigned into training (n = 44) and validation (n = 23) groups. In both datasets, the patients were categorized according to the Ryan tumor regression grade (TRG) system into non-responders (TRG = 3) and responders (TRG 1 and 2). We extracted 960 radiomic features/patient from pre-treatment T2-weighted images. After a three-step feature selection process, including LASSO regression analysis, we built a radiomics score with seven radiomics features. This score was significantly higher among non-responders in both training and validation sets (p < 0.001 and p = 0.03) and it showed good predictive performance for LARC non-response, achieving an area under the curve (AUC) = 0.94 (95% CI: 0.82–0.99) in the training set and AUC = 0.80 (95% CI: 0.58–0.94) in the validation group. The multivariate analysis identified the radiomics score as an independent predictor for the tumor non-response (OR = 6.52, 95% CI: 1.87–22.72). Our results indicate that MRI radiomics features could be considered as potential imaging biomarkers for early prediction of LARC non-response to neoadjuvant treatment.

scholarly journals Local recurrence after surgery of locally advanced rectal cancer treated with or without preoperative chemoradiotherapy

2020 ◽  
Vol 26 (2) ◽  
pp. 30-34
Author(s):  
Mladen Djuric ◽  
Dejan Lukic ◽  
Zoran Radovanovic ◽  
Aleksandar Ðermanovic ◽  
Milan Ranisavljevic ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Treatment Protocol ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Number Of Patients ◽  
Study Results

Introduction: The ?gold standard? for patients with locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery. Aim: Evaluation of local recurrence after surgery for locally advanced rectal cancer. Methods and patients: Retrospective study included 189 patients, who were operated at Oncology Institute of Vojvodina from January 1st 2012 until December 31st 2017. Patients were divided into two groups. In the first group 73 patients who received chemoradiotherapy were included, while 116 patients without neoadjuvant treatment were in the second group. All patients were diagnosed with locally advanced rectal cancer. The existence of operable metastases in the liver and/or lungs did not exclude patients from the study. Patients who had undergone resection of the rectum by Miles, Hartmann or local tumor excision were excluded from the study. Results: The median follow-up period was 48 months (range 13-84). In total, 23 (12.2%) patients developed local recurrence. In the chemoradiotherapy group, 15.1% (11 of 73 patients) had a local recurrence, as compared with 10.3% (12 of 116 patients) in the group without neoadjuvant treatment. In both groups, there were no correlation between rate of local recurrence with other clinical and pathological parameters such as gender, tumor location, T and N stage, histological differentiation, or lymphovascular and perineural invasion (p>0.05). We confirmed significant association between circumferential resection margin with local recurrence in patients who were treated by preoperative chemoradiation (p=0.014). Conclusion: This study has not shown reduced risk of local recurrence after neoadjuvant therapy most likely due to small number of patients. Despite our results, neoadjuvant treatment followed by surgery remains the best treatment protocol for patients with locally advanced rectal cancer.

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