European Registration of Cancer Care financed by European Society of Surgical Oncology, Champalimaud Foundation Lisbon, Bas Mulder Award granted by the Alpe d'Huzes Foundation and Dutch Cancer Society, and European Research Council Advanced Grant.
Purpose
Preoperative chemoradiotherapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumour regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumour regression. In the present study we estimated radiation dose-response curves for various grades of tumour regression after preoperative CRT.
Methods and Materials
A total of 222 patients, treated with consistent chemotherapy and radiotherapy techniques, were considered for the analysis. Radiotherapy consisted of a combination of external beam radiotherapy and brachytherapy. Response at the time of operation was evaluated from the histopathological specimen and graded on a five point scale (TRG1-5). The probability of achieving complete, major and partial response was analyzed using ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose response relationship for a specific grade of histopathological tumour regression was parameterized in terms of the dose required for 50% response, D50,i, and the normalized dose-response gradient, γ50,i.
Results
A highly significant dose–response relationship was found (p=0.002). For complete response (TRG1) the dose-response parameters were D50,TRG1=92.0 Gy (95% CI: 79.3 to 144.9 Gy), γ50,TRG1=0.982 (0.533 to 1.429), and for major response (TRG1-2) D50,TRG1&2=72.1 Gy (65.3 to 94.0 Gy), γ50,TRG1&2=0.770 (0.338 to 1.201). Tumour size and N-category both had a significant effect on the dose-response relationships.
Conclusions
This study has demonstrated a significant dose-response relationship for tumour regression after preoperative CRT for locally advanced rectal cancer for tumour dose levels in the range of 50.4 to 70 Gy, which is higher than the dose-range usually considered.
This is a repository copy of Factors affecting local regrowth after watch and wait for patients with a clinical complete response following chemoradiotherapy in rectal cancer (InterCoRe consortium): an individual participant data meta-analysis.
The purpose was to investigate total cell-free DNA (cfDNA) in colorectal cancer (CRC) patients during treatment with secondline chemotherapy and in healthy controls and patients with different comorbidities. Patient treated with second-line irinotecan for metastatic CRC (n 5 100), a cohort of healthy controls with and without comorbidity (n 5 70 and 100, respectively) were included. cfDNA was quantified by an in-house developed quantitative polymerase chain reaction from plasma samples drawn prior to the first cycle of chemotherapy and at time of progression. cfDNA levels were significantly higher in CRC compared to controls, with a clear capability for discriminating between the groups (receiver operation curve analysis; area under the curve 0.82, p < 0.0001). Patients with high levels had a shorter survival from irinotecan compared to those with lover levels. The cohort independent upper normal limit divided patients into high and low risk groups. The progression-free survival (PFS) was 2.1 months [95% confidence interval (CI) 2.0-3.4] and 6.5 (95% CI 4.2-7.2) months [hazard ratio (HR) 2.53; 95% CI 1.57-4.06, p < 0.0001] and overall survival (OS) 7.4 months (95% CI 4.3-8.7) and 13.8 months (95% CI 11.9-18.9; HR 2.52; 95% CI 1.54-4.13, p < 0.0000), respectively. Cox regression multivariate analysis showed a PFS HR of 1.4 (95% CI 1.1-1.7) for each increase in cfDNA quartile, p 5 0.03 and 1.6 (1.3-2.0) for OS, p < 0.0001, respectively. A combined marker analysis with plasma KRAS mutations added further prognostic impact, which was consistent when performed on the samples drawn at time of progression. In conclusion, cfDNA measurement holds important clinical information and could become a useful tool for prediction of outcome from chemotherapy in mCRC.Despite the availability of several effective cytotoxic drugs and new biological agents the prognosis of metastatic colorectal cancer (mCRC) is still poor and the curative options are limited to a subgroup of patients with resectable metastasis. Consequently, the majority of patients will be offered several lines of palliative chemotherapy, which imply a high level of side effects and careful selection of patients and monitoring during therapy is therefore essential. Irinotecan (a semisynthetic analog of camptothecin) is widely used in combination with flouropyrimidines or as monotherapy for mCRC. 1 The major dose limitating toxicities include diarrhea and myelosupression. 2,3 Better selection criteria in terms of predictive and prognostic markers to optimize treatment are needed.The presence of circulating nucleic acids in peripheral circulation was discovered more than 60 years ago by Mandel and Metais 4 followed by Leon et al. 5 in 1971 who later described the importance of circulating tumor DNA in cancer development. A substantial proportion of the circulating cell-free DNA (cfDNA) in cancer patients is believed to originate from tumor cells. 6,7 Recent studies have consequently focused on the multipurpose utility of cfDNA for molecular characterization to aid in...
IntroductionTotal mesorectal excision (TME) is the highly effective standard treatment for rectal cancer but is associated with significant morbidity and may be overtreatment for low-risk cancers. This study is designed to determine the feasibility of international recruitment in a study comparing organ-saving approaches versus standard TME surgery.Methods and analysisSTAR-TREC trial is a multicentre international randomised, three-arm parallel, phase II feasibility study in patients with biopsy-proven adenocarcinoma of the rectum. The trial is coordinated from Birmingham, UK with national hubs in Radboudumc (the Netherlands) and Odense University Hospital Svendborg UMC (Denmark). Patients with rectal cancer, staged by CT and MRI as ≤cT3b (up to 5 mm of extramural spread) N0 M0 can be included. Patients will be randomised to either standard TME surgery (control), organ-saving treatment using long-course concurrent chemoradiation or organ-saving treatment using short-course radiotherapy. For patients treated with an organ-saving strategy, clinical response to (chemo)radiotherapy determines the next treatment step. An active surveillance regime will be performed in the case of a complete clinical regression. In the case of incomplete clinical regression, patients will proceed to local excision using an optimised platform such as transanal endoscopic microsurgery or other transanal techniques (eg, transanal endoscopic operation or transanal minimally invasive surgery). The primary endpoint of this phase II study is to demonstrate sufficient international recruitment in order to sustain a phase III study incorporating pelvic failure as the primary endpoint. Success in phase II is defined as randomisation of at least four cases per month internationally in year 1, rising to at least six cases per month internationally during year 2.Ethics and disseminationThe medical ethical committees of all the participating countries have approved the study protocol. Results of the primary and secondary endpoints will be submitted for publication in peer-reviewed journals.Trial registration number
ISRCTN14240288, 20 October 2016. NCT02945566; Pre-results, October 2016.
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