Maas M, Nelemans PJ, Valentino V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol.11(9):835-844
Department of Surgery, Maastricht University Medical Centre, Maastricht, Netherlands. The Lancet Oncology
(Impact Factor: 24.69).
09/2010; 11(9):835-44. DOI: 10.1016/S1470-2045(10)70172-8
Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15-27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR.
In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test.
484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0-277). 5-year crude disease-free survival was 83.3% (95% CI 78.8-87.0) for patients with pCR (61/419 patients had disease recurrence) and 65.6% (63.6-68.0) for those without pCR (747/2263; HR 0.44, 95% CI 0.34-0.57; p<0.0001). The Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0.54 (95% CI 0.40-0.73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0.91 (95% CI 0.73-1.12). The effect of pCR on disease-free survival was not modified by other prognostic factors.
Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival.
Available from: Franck Bonnetain
- "This subpopulation is characterized by slow growth and long regression time of rectal cancer. Patients who achieved a pCR are considered to be a more favorable subpopulation with less LR and DM as well as better OS  . While the prediction of early intermediate endpoints (e.g., pCR) is less prone to uncertainties and may therefore be more http://dx.doi.org/10.1016/j.radonc.2015.02.001 0167-8140/Ó 2015 Elsevier Ireland Ltd. "
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ABSTRACT: Personalized treatments based on predictions for patient outcome require early characterization of a rectal cancer patient's sensitivity to treatment. This study has two aims: (1) identify the main patterns of recurrence and response to the treatments (2) evaluate pathologic complete response (pCR) and two-year disease-free survival (2yDFS) for overall survival (OS) and their potential to be relevant intermediate endpoints to predict.
Pooled and treatment subgroup analyses were performed on five large European rectal cancer trials (2795 patients), who all received long-course radiotherapy with or without concomitant and/or adjuvant chemotherapy. The ratio of distant metastasis (DM) and local recurrence (LR) rates was used to identify patient characteristics that increase the risk of recurrences.
The DM/LR ratio decreased to a plateau in the first 2years, revealing it to be a critical follow-up period. According to the patterns of recurrences, three patient groups were identified: 5-15% had pCR and were disease free after 2years (excellent prognosis), 65-75% had no pCR but were disease free (good prognosis) and 15-30% had neither pCR nor 2yDFS (poor prognosis).
Compared with pCR, 2yDFS is a stronger predictor of OS. To adapt treatment most efficiently, accurate prediction models should be developed for pCR to select patients for organ preservation and for 2yDFS to select patients for more intensified treatment strategies.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Radiotherapy and Oncology 02/2015; 114(3). DOI:10.1016/j.radonc.2015.02.001 · 4.36 Impact Factor
Available from: Paul E Wise
- "Patients do not respond uniformly to neoadjuvant chemoradiation. An important minority of patients (8–24 %)58 have a pathological complete response (pCR), with no viable cancer cells in the resected specimen. Patients with pCR are a unique subset with improved oncologic outcomes and the potential to have organ or sphincter-sparing surgery. "
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Rectal cancer management has evolved into a complex multimodality approach with survival, local recurrence, and quality of life parameters being the relevant endpoints. Surgical treatment for low rectal cancer has changed dramatically over the past 100 years.
Abdominoperineal resection, once the standard of care for all rectal cancers, has become much less frequently utilized as surgeons devise and test new techniques for preserving the sphincters, maintaining continuity, and performing oncologically sound ultra-low anterior or local resections. Progress in rectal cancer surgery has been driven by improved understanding of the anatomy and pathophysiology of the disease, innovative surgical technique, improved technology, multimodality approaches, and increased appreciation of the patient’s quality of life. The patient with a low rectal cancer, once almost universally destined for impotence and a colostomy, now has the real potential for improved survival, avoidance of a permanent stoma, and preservation of the normal route of defecation.
Journal of Gastrointestinal Surgery 07/2014; 18(7). DOI:10.1007/s11605-014-2528-y · 2.80 Impact Factor
Available from: Hee Chul Park
- "In addition to improved local control, reduced toxicity, increased sphincter preservation, and tumor downstaging have been demonstrated after neoadjuvant CRT . Complete pathologic response (ypCR) of approximately 15% has been reported after CRT [3,4]. Patients with ypCR after CRT tend to have decreased local or distant recurrence and improved survival [4-6]. "
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The aim of this study was to examine the clinical implications of a pathologically complete response after neoadjuvant chemoradiotherapy (CRT) followed by local excision for patients with cT2 rectal cancer who refused radical surgery.
Materials and Methods
Seventeen patients with cT2 primary rectal cancer within 6 cm from the anal verge who received neoadjuvant CRT and local excision because of patient refusal of radical surgery or poor performance status were included. Two patients had clinical involvement of a regional lymph node. Preoperative radiotherapy was delivered to the whole pelvis at a dose of 44 to 50.4 Gy in 22 to 28 fractions. All patients underwent transanal excision and eight patients (47%) received postoperative chemotherapy.
Ten patients (59%) achieved ypT0. At a median follow-up period of 75 months (range, 22 to 126 months), four (24%) patients developed recurrence (two locoregional and two distant). The 5-year disease-free survival of all patients was 82%, and was higher in patients with ypT0 (90%) than in patients with ypT1-2 (69%, p=0.1643). Decreased disease-free survival was also observed in patients receiving capecitabine compared with 5-fluorouracil (54% vs. 100%, p=0.0298).
Local excision could be a feasible alternative to radical surgery in patients with ypT0 after neoadjuvant CRT for cT2 distal rectal cancer without further radical surgery.
Cancer Research and Treatment 07/2014; 46(3):243-249. DOI:10.4143/crt.2014.46.3.243 · 3.32 Impact Factor
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