What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer in a pooled analysis of EORTC 22921 and FFCD 9203 trials: Surrogacy in question?

Bonnetain, Franck; Bosset, J.F.; Gérard, Jean Pierre; Calais, G.; Conroy, Thierry; Mineur, Laurent; Bouché, Olivier; Maingon, P.; Chapet, O.; Radošević-Jelić, Ljiljana; Methy, N.; Collette, Laurence

doi:10.1016/j.ejca.2012.03.016

Cited by 94 publications

(60 citation statements)

References 31 publications

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“…Moreover, the eligibility of poor-risk rectal cancer is the most important limitation, because there are no previous studies of neoadjuvant chemotherapy alone for patients with poor-risk rectal cancer, and we cannot compare the efficacy and feasibility. It has been mentioned that a short-term outcome such as the pCR rate or local relapse rate does not qualify as a surrogate for overall survival in patients treated by preoperative FU/RT (40). Although this study showed that neoadjuvant chemotherapy alone is effective in some patients with poor-risk rectal cancer from the viewpoint of short-term outcome, it is essential to develop predictive markers of response.…”

Section: Neoadjuvant Chemotherapy For Rectal Cancermentioning

confidence: 98%

Neoadjuvant Oxaliplatin and Capecitabine and Bevacizumab without Radiotherapy for Poor-risk Rectal Cancer: N-SOG 03 Phase II Trial

Uehara

Hiramatsu

Maeda

et al. 2013

Japanese Journal of Clinical Oncology

117

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Objective: This Phase II trial was designed to evaluate the safety and efficacy of neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy in patients with poor-risk rectal cancer. Methods: Patients with magnetic resonance imaging-defined poor-risk rectal cancer received neoadjuvant oxaliplatin and capecitabine and bevacizumab followed by total mesorectal excision or more extensive surgery. Results: Between February 2010 and December 2011, 32 patients were enrolled in this study. The completion rate of the scheduled chemotherapy was 91%. Reasons for withdrawal were refusal to continue therapy in two patients and disease progression in one, with two of these three patients not undergoing surgery. Among the 29 patients who completed the scheduled chemotherapy, one refused surgery within 8 weeks after the completion of chemotherapy, which was the period stipulated by the protocol, and another had rectal perforation, requiring urgent laparotomy. As a result, the completion rate of this experimental treatment was 84%. Of the 30 patients who underwent surgery, the R0 resection rate was 90% and a postoperative complication occurred in 43%. A pathological complete response was observed in 13% and good tumor regression was exhibited in 37%. Conclusions: Neoadjuvant oxaliplatin and capecitabine plus bevacizumab for poor-risk rectal cancer caused a high rate of anastomotic leakage and experienced a case with perforation during chemotherapy, both of which were bevacizumab-related toxicity. Although the shortterm results with the completion rate of 84.4% and the pathological complete response rate of 13.3% were satisfactory, we have to reconsider the necessity of bevacizumab in neoadjuvant chemotherapy (UMIN number, 000003507).

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Section: Neoadjuvant Chemotherapy For Rectal Cancermentioning

confidence: 98%

Neoadjuvant Oxaliplatin and Capecitabine and Bevacizumab without Radiotherapy for Poor-risk Rectal Cancer: N-SOG 03 Phase II Trial

Uehara

Hiramatsu

Maeda

et al. 2013

Japanese Journal of Clinical Oncology

117

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“…El coeficiente de concordancia de la RP es similar al encontrado en otros estudios que han empleado una categorización diferente de la RP 9 . El valor pronóstico de la RP no logra superar la fortaleza de la etapificación definitiva luego de RQT en esta serie, hecho que tiene defensores 9 y retractores 4 , lo que amerita mayor estudio 13,14 .…”

Section: Discussionunclassified

Valor pronóstico de la respuesta patológica a la radioquimioterapia preoperatoria en el cáncer de recto bajo localmente avanzado

et al. 2013

Rev Chil Cir

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Prognostic value of pathological response to chemo radiotherapy of locally advanced low rectal cancer Background: Preoperative chemo radiotherapy improves the prognosis of locally advanced low rectal cancer and induces a pathological response in the tumor, which may have prognostic value. Aim: To assess the results of rectal cancer treatment according to the degree of pathological response of the tumor after chemo radiotherapy. Patients and Methods: All patients with a locally advanced rectal cancer located within 11 cm of the rectal margin, subjected to preoperative chemo radiotherapy followed by surgical treatment in a period of 13 years, were included. Pathological response was classified as complete, intermediate and poor. The tumor was staged according to TNM 2002 classification. Survival was analyzed with Kaplan Meier curves and Cox regression. Results: Patients were followed for a mean of 50 months (range 18-156). Exclusive and global local relapse was observed in 3 and 9.6% of patients, respectively. Pathological response was complete in 13 patients (none died), intermediate in 23 (three died) and poor in 68 (22 died). Global five years survival was 74%. There was a concordance of 0.64 between survival and pathological response. The concordance between survival and TNM classification was 0.69. Conclusions: The pathological response of the tumor to chemo radiotherapy has a good concordance with prognosis, although it is not superior to the final pathological status.

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“…Collectively, these studies indicate that the number of patients with good response to CRT may be optimized by escalating the radiation dose to the tumour. It is worth noting, though, that pCR does not work well as a surrogate endpoint for evaluation of pre-operative treatment strategies [21][22][23], i.e. increased rates of pCR do not appear to translate into clinical benefit for patients who subsequently undergo surgery.…”

Section: Rationale For Dose-escalationmentioning

confidence: 98%

Radiation Techniques for Increasing Local Control in the Non-Surgical Management of Rectal Cancer

Appelt

Jakobsen

2015

Curr Colorectal Cancer Rep

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A fraction of patients with rectal cancer can achieve clinical complete response following longcourse chemoradiotherapy (CRT), and there is accumulating clinical evidence that these patients can be managed non-surgically with acceptable oncological outcome. Consequently, strategies for increasing the proportion of complete responders are actively being explored. Some, although limited, experience with high-dose radiotherapy indicates that there might exist a dose-response relationship for local tumour control after radiotherapy alone. Thus, tumour dose escalation could be indicated for selected patients, particularly in cases with small tumours and limited local disease. This report discusses several radiotherapy techniques for tumour boosting, focusing on technical challenges and clinical experiences with each technique. Specifically, external beam radiotherapy, brachytherapy and contact X-ray treatment for dose escalation are considered. Ultimately, no technique provides definitive advantage over others, and the choice in clinical practice will have to depend on the patient population treated as well as the technical capabilities of the treating department.

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What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer in a pooled analysis of EORTC 22921 and FFCD 9203 trials: Surrogacy in question?

Cited by 94 publications

References 31 publications

Neoadjuvant Oxaliplatin and Capecitabine and Bevacizumab without Radiotherapy for Poor-risk Rectal Cancer: N-SOG 03 Phase II Trial

Neoadjuvant Oxaliplatin and Capecitabine and Bevacizumab without Radiotherapy for Poor-risk Rectal Cancer: N-SOG 03 Phase II Trial

Valor pronóstico de la respuesta patológica a la radioquimioterapia preoperatoria en el cáncer de recto bajo localmente avanzado

Radiation Techniques for Increasing Local Control in the Non-Surgical Management of Rectal Cancer

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