MRI assessment and outcomes in patients receiving neoadjuvant chemotherapy only for primary rectal cancer: long-term results from the GEMCAD 0801 trial

Patel, Uday; Brown, Gina; Machado, Isabel; Santos-Corés, Jesús; Pericay, Carles; Ballesteros, Eva; Salud, Antonieta; Isabel-Gil, M.; Montagut, Clara; Maurel, Joan; Ramón-Ayuso, J.; Martin, Neil E.; Estevan, Rafael; Fernández-Martos, Carlos

doi:10.1093/annonc/mdw616

Cited by 75 publications

(72 citation statements)

References 19 publications

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“…In the present study, mrEMVI at baseline was a strong predictor of DFS. This is concordant with previous studies that found mrEMVI to be associated with poor prognosis. In a large meta‐analysis including 1262 patients, those with mrEMVI developed metastases more frequently than those with mrEMVI‐negative tumours (odds ratio 5·68; P < 0·001).…”

Section: Discussionsupporting

confidence: 90%

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Early MRI predictors of disease-free survival in locally advanced rectal cancer from the GRECCAR 4 trial

Nougaret

Castan

Forges

et al. 2019

British Journal of Surgery

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Background: Tailored neoadjuvant treatment of locally advanced rectal cancer (LARC) may improve outcomes. The aim of this study was to determine early MRI prognostic parameters with which to stratify neoadjuvant treatment in patients with LARC.Methods: All patients from a prospective, phase II, multicentre randomized study (GRECCAR4; NCT01333709) were included, and underwent rectal MRI before treatment, 4 weeks after induction chemotherapy and after completion of chemoradiotherapy (CRT). Tumour volumetry, MRI tumour regression grade (mrTRG), T and N categories, circumferential resection margin (CRM) status and extramural vascular invasion identified by MRI (mrEMVI) were evaluated.Results: A total of 133 randomized patients were analysed. Median follow-up was 41⋅4 (95 per cent c.i. 36⋅6 to 45⋅2) months. Thirty-one patients (23⋅3 per cent) developed tumour recurrence. In univariable analysis, mrEMVI at baseline was the only prognostic factor associated with poorer outcome (P = 0⋅015). After induction chemotherapy, a larger tumour volume on MRI (P = 0⋅019), tumour volume regression of 60 per cent or less (P = 0⋅002), involvement of the CRM (P = 0⋅037), mrEMVI (P = 0⋅026) and a poor mrTRG (P = 0⋅023) were associated with poor outcome. After completion of CRT, the absence of complete response on MRI (P = 0⋅004), mrEMVI (P = 0⋅038) and a poor mrTRG (P = 0⋅005) were associated with shorter disease-free survival. A final multivariable model including all significant variables (baseline, after induction, after CRT) revealed that Eastern Cooperative Oncology Group performance status (P = 0⋅011), sphincter involvement (P = 0⋅009), mrEMVI at baseline (P = 0⋅002) and early tumour volume regression of 60 per cent or less after induction (P = 0⋅007) were associated with relapse.Conclusion: Baseline and early post-treatment MRI parameters are associated with prognosis in LARC. Future preoperative treatment should stratify treatment according to baseline mrEMVI status and early tumour volume regression.

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Section: Discussionsupporting

confidence: 90%

“…The mrTRG was also evaluated to determine the degree of tumour replacement by fibrotic or mucinous changes. Favourable mrTRG was defined as grades 1 and 2, and unfavourable mrTRG as grades 3, 4 and 5.…”

Section: Methodsmentioning

confidence: 99%

Early MRI predictors of disease-free survival in locally advanced rectal cancer from the GRECCAR 4 trial

Nougaret

Castan

Forges

et al. 2019

British Journal of Surgery

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“…This evaluation can be performed within days to weeks of the start of the intervention and prior to surgery by assessing volume effects using RECIST criteria with CT or MRI [4,5], MRI based tumour regression grading [6], and mapping macroscopic and microscopic details about tumour architecture [7,8]. Results of prospective trials showed clinical complete response (cCR) or TNM down-staging after CRT is a biomarker of more favourable oncological outcomes in LARC [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

How to measure tumour response in rectal cancer? An explanation of discrepancies and suggestions for improvement

Nagtegaal

Glynne‐Jones

2020

Cancer Treatment Reviews

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Various methods categorize tumour response after neoadjuvant therapy, including down-staging and tumour regression grading. Response categories allow comparison of different treatments within clinical trials and predict outcome. A reproducible response categorization could identify subgroups with high or low risk for the most appropriate subsequent treatments, like watch and wait. Lack of standardization and interpretation difficulties currently limit the usability of these approaches. In this review we describe these difficulties for the evaluation of chemoradiation in rectal cancer. An alternative approach of tumour response is based on patterns of residual disease, including fragmentation. We summarise the evidence behind this alternative method of response categorisation, which explains a number of very relevant clinical discrepancies. These issues include differences between downstaging and tumour regression, high local regrowth in advanced tumours during watchful waiting procedures, the importance of resection margins, the limited value of post-treatment biopsies and the relatively poor outcome of patients with a near complete pathological response. Recognition of these patterns of response can allow meaningful development of novel biomarkers in the future.

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“…Therefore, the European Society for Medical Oncology guidelines suggest that mrEMVI indicates high risk; CRT followed by TME is recommended in such cases [24]. Moreover, several studies have shown that the presence of ymrEMVI, which was evaluated after the neoadjuvant treatment, and not only mrEMVI, had prognostic impact [23,[25][26][27]. Our study revealed that mrEMVI remained after NAC except for 2 patients.…”

Section: Discussionmentioning

confidence: 58%

Predicting prognosis according to preoperative chemotherapy response in patients with locally advanced lower rectal cancer

Shiraishi

Sasaki²,

Ikeda

et al. 2019

Preprint

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Background: Neoadjuvant chemoradiotherapy is regarded as the standard of treatment for locally advanced lower rectal cancer, although some of these cases are systemic, and distant control may be inadequate. Neoadjuvant chemotherapy could compensate for such shortcomings, potentially yielding better survival outcomes. We aimed to stratify patients into prognostic groups on the basis of preoperative factors, including response to neoadjuvant chemotherapy. Methods: We retrospectively analyzed patients with locally advanced lower rectal adenocarcinoma (clinical stage II/III with high-risk features of distant metastasis) who were treated with neoadjuvant chemotherapy (without radiotherapy) followed by curative resection between 2010 and 2017. Reduction in tumor volume (before vs. after neoadjuvant chemotherapy) was measured using magnetic resonance imaging, and a reduction above 60% was defined as a good response. Recurrence and overall survival were evaluated. Results: The cohort comprised 102 patients. Good response to neoadjuvant chemotherapy was associated with better 5-year recurrence-free survival (good responders: 81.1%, poor responders: 49.0%; p =0.001) and 5-year overall survival (good responders: 94.9%, poor responders: 80.6%; p =0.06). In a multivariate analysis, extramural venous invasion on magnetic resonance imaging after neoadjuvant chemotherapy and a tumor volume reduction rate <60 were found to be significantly and independently associated with worse recurrence-free survival (hazard ratio: 2.74, 95% confidence interval: 1.36–5.50, p =0.005 and hazard ratio: 3.48, 95% confidence interval: 1.57–7.72, p =0.002, respectively). Good responders without extramural venous invasion had the best 5-year recurrence-free and overall survival (89.0% and 93.8%, respectively). Poor responders with extramural venous invasion had the worst 5-year recurrence-free and overall survival (21.4% and 50.0%, respectively). Conclusions: Reductions in tumor volume after neoadjuvant chemotherapy were associated with a better prognosis in patients with locally advanced lower rectal cancer. Extramural venous invasion was a preoperative prognostic factor.

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MRI assessment and outcomes in patients receiving neoadjuvant chemotherapy only for primary rectal cancer: long-term results from the GEMCAD 0801 trial

Cited by 75 publications

References 19 publications

Early MRI predictors of disease-free survival in locally advanced rectal cancer from the GRECCAR 4 trial

Early MRI predictors of disease-free survival in locally advanced rectal cancer from the GRECCAR 4 trial

How to measure tumour response in rectal cancer? An explanation of discrepancies and suggestions for improvement

Predicting prognosis according to preoperative chemotherapy response in patients with locally advanced lower rectal cancer

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