Preoperative neo-adjuvant therapy for curable rectal cancer - reaching a consensus 2008 (original) (raw)
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Neoadjuvant therapy in the treatment of high risk rectal carcinoma
Surgical Oncology, 1999
The management of rectal cancer remains a challenging and controversial area of surgical oncology. The spectre of local recurrence, with its' poor prognostic and palliative outcomes, is known to be highly dependent on operative technique and to vary widely between surgeons. The roles of radiotherapy and chemotherapy have been the subject of trials for 30 years and yet no consensus on treatment exists. In this review article we will summarise the evolution of radiotherapy and chemoradiation in the treatment of rectal cancer and evaluate the evidence available for the use of`neoadjuvanta chemoradiation. In particular, the role of adjuvant therapies in the setting of total mesorectal excision will be discussed.
Radiotherapy and Oncology, 2013
Purpose: To present an interim analysis of the trial comparing two neoadjuvant therapies for unresectable rectal cancer. Methods: Patients with fixed cT3 or cT4 or locally recurrent rectal cancer without distant metastases were randomized to either 5 Â 5 Gy and 3 courses of FOLFOX4 (schedule I) or 50.4 Gy delivered in 28 fractions given simultaneously with 5-Fu, leucovorin and oxaliplatin (schedule II). Surgery in both groups was performed 12 weeks after the beginning of radiation and 6 weeks after neoadjuvant treatment. Results: 49 patients were treated according to schedule I and 48 according to schedule II. Grade III+ acute toxicity was observed in 26% of patients in group I and in 25% in group II. There were two toxic deaths, both in group II. The microscopically radical resection (primary endpoint) rate was 73% in group I and 71% in group II. Overall and severe postoperative complications were recorded in 27% and 9% of patients vs. 16% and 7%, respectively. Pathological complete response was observed in 21% of the patients in group I and in 9% in group II. Conclusions: The interim analysis revealed no major differences in acute toxicity and local efficacy between the two evaluated strategies. Ó 2013 Elsevier Ireland Ltd. Radiotherapy and Oncology 107 (2013) 171-177
European Journal of Surgical Oncology, 2020
Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006e2009; II) 2010e2013; III)2014e2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14,391 patients,8871 (61.6%) received neoadjuvant treatment. Long-course chemo/ radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%,p ¼ 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p ¼ 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p ¼ 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59e0.87, Cochrane-Mantel-Haenszel P ¼ 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN þ benefited the most.
Neoadjuvant Treatment in Rectal Cancer: Actual Status
Chemotherapy Research and Practice, 2011
Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinomas. The clinical stages II (cT3-4, N0, M0) and III (cT1-4, N+, M0) according to International Union Against Cancer (IUCC) are concerned. It can reduce tumor volume and subsequently lead to an increase in complete resections (R0 resections), shows less toxicity, and improves local control rate. The aim of this review is to summarize actual approaches, main problems, and discrepancies in the treatment of locally advanced rectal adenocarcinomas.
Arquivos de gastroenterologia
The approach of locally advanced extra-peritoneal rectal adenocarcinoma implies a treatment with neoadjuvant chemoradiotherapy associated with total mesorectal excision surgery. However, the tumors respond variably to this neoadjuvant therapy, and the mechanisms for response are not completely understood. Evaluate the variables related to the complete tumor response and the outcomes of patients who underwent surgery, comparing those with partial tumor regression and those with total remission of rectal lesion, at the pathological examination. Retrospective analysis of medical records of 212 patients operated between 2000 and 2010, in which 182 (85.9%) obtained partial remission at neoadjuvant therapy (Group 1) and 30 (14.1%), total remission (Group 2). No difference was found between the groups in relation to gender, ethnicity, age, tumor distance from the anal verge, occurrence of metastases and synchronous lesions on preoperative staging, dose of radiotherapy and performed surgery...
The treatment of early rectal cancer in the era of adjuvant and neo-adjuvant therapy
Mini-invasive Surgery , 2018
The accurate staging of rectal cancer improves the stratification of patients for adjuvant therapy. Staging of tumor with endoluminal ultrasonography (EUS) shows a good correlation with histology (κ = 0.85; 95% confidence interval 0.76-0.95). Overall pT and pN stage accuracy of EUS was 92% and 65% respectively. The staging of local disease can be further augmented by EUS guided fine needle aspiration of extra rectal lesions lying within or outside of the mesorectum. In a systematic review of local excision after neoadjuvant therapy a total of 22 unique studies reporting on 1068 patients were analysed. At a median follow-up of 54 months, ypT0 tumours had a pooled local recurrence rate of 4% and a median disease-free survival rate of 95%. Outcomes for ≥ ypT1 tumours were much worse with pooled local recurrence and disease-free survival of 22% and 68%, respectively. In a review of 22 studies, 804 patients who underwent local excision followed by adjuvant therapy either for unfavourable histology, prohibitive comorbidity or patient choice. the pooled local recurrence was 5.8% for pT1 tumours, 13.8% for pT2 tumours and 33.7% for pT3 tumours. In addition, the response to radiotherapy may be enhanced by aspirin, metformin and statins.
The rational principles of neo-adjuvant therapy for rectal cancer
Acta bio-medica : Atenei Parmensis, 2003
Aim of the study is to analyze rational principles which at present govern the neoadjuvant therapy for rectal cancer and justify his application. First step is definition of targets: cellular replication block, volumetric reduction of rectal cancer, mesorectum and lateral nodes (Down staging), reduction of side-effects on close organs, radiation on more limited tissue volumes, major series of sphincter saving procedures, minor risk of microscopic tumour deposits. Second step regards standards which Protocols strive in order to: patients selection, therapeutic index, restaging before surgery, total mesorectal excision (TME). Further step accounts for evidence of drawbacks, related to Neoadjuvant approach, both Radiotherapy alone (RT) or Radiochemotherapy (CH-RT). Indications for neoadjuvant therapy, basing a difference between the absolute and relative one, are explained. Given that granting role to such therapy still now remain partially unclear, we have outlined the following topic...
International Journal of Cancer, 2014
Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorized into three groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios (HR) for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). One thousand seven hundred and twenty three (1723) (52%) of 3,313 included patients received aCT. Eight hundred and ninety eight (898) patients had a pCR, 966 had a ypT1-2 tumour and 1,302 had a ypT3-4 tumour. For 122 patients response, category was missing and 25 patients had ypT0N1. Median follow-up for all patients was 51 (0-219) months. HR for RFS with 95% CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging.