Chemotherapy with Preoperative Radiotherapy in Rectal Cancer

Bosset, Jean-François; Collette, Laurence; Calais, G.; Mineur, Laurent; Maingon, P.; Radošević-Jelić, Ljiljana; Daban, A.; Bardet, É.; Beny, Alexander; Ollier, Jean-Claude

doi:10.1056/nejmoa060829

Cited by 2,420 publications

(1,652 citation statements)

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“…Using the pCRT approach, the rate of local recurrence at 5-year ranges from 6 to 8%, 1,2 and the rate of complete pathological response ranges from 4 to 44% of cases, as reported in single institution series trials, 3,4 in phase II studies [5][6][7] and in randomized trials. 2,8 For patients with good pathologic response to pCRT, the oncological outcome has been reported to be better for 'responders' than for 'nonresponders'.…”

Section: Introductionmentioning

confidence: 93%

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

et al. 2010

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The aim of the study was the identification of a pharmacogenetic profile predictive of the tumor regression grade (TRG), considered as tumor response parameter, after neo-adjuvant treatment in rectal cancer patients. A total of 238 rectal cancer patients treated in a neo-adjuvant setting by a fluoropyrimidines-based chemo-radiotherapy (RT) were genotyped for 25 genetic polymorphisms in 16 genes relevant for treatment-associated pathways. Two polymorphisms were associated with TRG in a multivariate analysis: hOGG1-1245C4G, which can affect radiosensitivity and MTHFR-677C4T, which is involved in fluoropyrimidines action. Patients bearing at least one variant allele had a lower chance to get TRGp2 (OR ¼ 0.46 95% CI 0.23-0.90, P ¼ 0.024; and OR ¼ 0.48 95% CI 0.24-0.96, P ¼ 0.034; respectively). An association trend was observed for ABCB1-3435C4T, which is responsible for the multi-drug resistance (odds ratio (OR) ¼ 1.96, 95% confidence interval (CI) 0.98-3.95, P ¼ 0.057). Exploratory classification and regression tree (CART) analysis highlighted high-order gene-gene and gene-environment interactions and a genetic signature associated with differential response, with hOGG1-1245C4G as the most predictive factor. Other significant variables were: ABCB1-3435C4T, MTHFR-677C4T, ERCC1-8092C4A, ABCC2-1249G4A, XRCC1-28152G4A, XRCC3-4541A4G and patients gender. On the basis of CART results, patients were categorized into three groups according to tumor response probability: intermediate and high profiles had a higher probability to get TRGp2 as compared with low profiles (OR ¼ 4.12 95% CI 1. Po0.001 and OR ¼ 12.44, Po0.0001, respectively). This study evidences a major role of hOGG1-1245C4G and MTHFR-677C4T polymorphisms in the tumor response of rectal cancer patients treated with chemo-RT in neo-adjuvant setting, and shows the relevance of gene-gene and gene-environment interactions for complex phenotypes as tumor response.

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Section: Introductionmentioning

confidence: 93%

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

et al. 2010

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“…[41] Many individuals exhibit poor tolerance of this package of treatment due to morbidity from radiotherapy and pelvic surgery resulting in failure to start AC or dose reductions [42]. Of 506 rectal cancer patients due to receive AC post LCPCRT in one study, only 43% tolerated the full course and 27% never started treatment [4,42].…”

Section: Rationale For Neoadjuvant Chemotherapy In Rectal Cancermentioning

confidence: 99%

“…However, improvements in pre-operative assessment and surgical quality, including the widespread adoption total mesorectal excision (TME) [1].and optimal surgery for low rectal cancers [2], together with the selective use of pelvic radiotherapy, has markedly reduced pelvic LR from historically approx 25% [3], to approximately 5-10% [4,5,6,7]. However, this has not reduced the rate of distant metastatic relapse, which is now the major cause of rectal cancer death.…”

Section: Introductionmentioning

confidence: 99%

“…Pre-operative RT is used as either SCPRT of 25 Gy in 5 daily fractions over 1 week, followed by surgery within a week [6,7]. Alternatively LCPCRT is used, typically with 45-50.4 Gy in 1.8 Gy fractions over approximately 5 weeks with a concurrent fluoropyrimidine (either 5-Fluorouracil (FU) or capecitabine), followed by a gap of 8-10 weeks before surgery [4,5,9]. Both LCPCRT and SCPRT approximately halve the risk of pelvic LR and LCPCRT and SCPRT are equivalent in their ability to reduce LR in phase III trials of resectable rectal cancer [10.11].…”

Section: Introductionmentioning

confidence: 99%

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Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

Gollins

Sebag‐Montefiore

2016

Clinical Oncology

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Improved surgical technique plus selective pre-operative radiotherapy, has decreased rectal cancer pelvic local recurrence (LR) from historically 25%, down to approximately 5-10%. However, this improvement has not reduced distant metastatic relapse, the main cause of death and a key issue in rectal cancer management.The current standard is local pelvic treatment (surgery +/-pre-operative radiotherapy) followed by adjuvant chemotherapy (AC), depending on resection histology. For circumferential resection margin (CRM)-threatened cancer on baseline MRI, downstaging long-course pre-operative chemoradiation (LCPCRT) is generally used. However, for non-CRM threatened disease, varying approaches are currently adopted in the UK, including straight to surgery (STS), short-course pre-operative radiotherapy (SCPRT) and LCPCRT.Clinical trials are investigating intensification of concurrent chemoradiation. There is also increasing interest in investigating pre-operative neoadjuvant chemotherapy (NAC) as a way of exposing micro-metastatic disease to full dose systemic chemotherapy as early as possible and potentially reducing metastatic relapse.Phase II trials suggest that this strategy is feasible, with promising histological response and low rates of tumour progression during NAC. Phase III trials are needed to determine the benefit of NAC when added to standard therapy and also to determine if it can be used instead of neoadjuvant radiotherapy based schedules.

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“…In den Studien zur präoperativen Kurzzeit-Radiotherapie mit 5 × 5 Gy wurde generell keine adjuvante Chemotherapie appliziert. Eine aktuelle holländische Phase-III-Studie randomisiert derzeit nach 5 × 5 Gy und Operation zwischen einer adjuvanten Chemotherapie mit Capecitabin und Beobachtung [813,828]. [548], ein systematisches Review [553], eine prospektive Fallkontrollstudie [549] und eine retrospektive Fallserie [551] identifiziert, die in die Bewertung ebenfalls mit eingegangen sind (Einzelheiten siehe Evidenzbericht).…”

Section: Hintergrundunclassified