S3-Leitlinie – Kolorektales Karzinom

Schmiegel, Wolff; Buchberger, Barbara; Follmann, Markus; Graeven, Ullrich; Heinemann, Volker; Langer, Thomas; Nothacker, Monika; Porschen, Rainer; Rödel, Claus; Rösch, Thomas; Schmitt, Wolfgang; Wesselmann, Simone; Pox, Christian

doi:10.1055/s-0043-121106

Cited by 129 publications

(99 citation statements)

References 1,258 publications

(586 reference statements)

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“…The personalized approach to treat metastatic colorectal cancer (mCRC) as recommended by national (NCCN, German S3guideline) and international (ESMO/ESMO ASIA ) [1][2][3][4] guidelines is limited to the mutational analyses of RAS (rat sarcoma oncogene) and B-ras associated factor and the analysis of microsatellite (MSI) status.…”

Section: Introductionmentioning

confidence: 99%

Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and first-line efficacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial

et al. 2019

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Background: FIRE-3 compared first-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. The consensus molecular subgroups (CMS) are grouping CRC samples according to their gene-signature in four different subtypes. Relevance of CMS for the treatment of mCRC has yet to be defined. Patients and Methods: In this exploratory analysis, patients were grouped according to the previously published tumor CRC-CMSs. Objective response rates (ORR) were compared using chi-square test. Overall survival (OS) and progression-free survival (PFS) times were compared using Kaplan-Meier estimation, log-rank tests. Hazard ratios (HR) were estimated according to the Cox proportional hazard method. Results: CMS classification could be determined in 438 out of 514 specimens available from the intent-to-treat (ITT) population (n ¼ 592). Frequencies for the remaining 438 samples were as follows: CMS1 (14%), CMS2 (37%), CMS3 (15%), CMS4 (34%). For the 315 RAS wild-type tumors, frequencies were as follows: CMS1 (12%), CMS2 (41%), CMS3 (11%), CMS4 (34%). CMS distribution in right-versus (vs) left-sided primary tumors was as follows: CMS1 (27% versus 11%), CMS2 (28% versus 45%), CMS3 (10% versus 12%), CMS4 (35% versus 32%). Independent of the treatment, CMS was a strong prognostic factor for ORR (P ¼ 0.051), PFS (P < 0.001), and OS (P < 0.001). Within the RAS wild-type population, OS observed in CMS4 significantly favored FOLFIRI cetuximab over FOLFIRI bevacizumab. In CMS3, OS showed a trend in favor of the cetuximab arm, while OS was comparable in CMS1 and CMS2, independent of targeted therapy. Conclusions: CMS classification is prognostic for mCRC. Prolonged OS induced by FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab in the FIRE-3 study appears to be driven by CMS3 and CMS4. CMS classification provides deeper insights into the biology to CRC, but at present time has no direct impact on clinical decision-making. The FIRE-3 (AIO KRK-0306) study had been registered at ClinicalTrials.gov: NCT00433927.

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Section: Introductionmentioning

confidence: 99%

Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and first-line efficacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial

et al. 2019

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“…A preoperative radiation or combined chemoradiotherapy is recommended for carcinomas of the lower or middle rectum due to a better local control and reduced rate of extirpation [4][5][6]. The German guidelines for colorectal cancer recommend the oncological resection 6 to 8 weeks after completed preoperative chemoradiotherapy [7]. Recent studies have shown that a prolonged interval leads to higher rates of pathological complete response (pCR) and that this my even take longer than 16 weeks [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Pathological complete response due to a prolonged time interval between preoperative chemoradiation and surgery in locally advanced rectal cancer: analysis from the German StuDoQ|Rectalcarcinoma registry

et al. 2020

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Background: Preoperative chemoradiotherapy is the recommended standard of care for patients with local advanced rectal cancer. However, it remains unclear, whether a prolonged time interval to surgery results in an increased perioperative morbidity, reduced TME quality or better pathological response. Aim of this study was to determine the time interval for best pathological response and perioperative outcome compared to current recommended interval of 6 to 8 weeks. Methods: This is a retrospective analysis of the German StuDoQ|Rectalcarcinoma registry. Patients were grouped for the time intervals of "less than 6 weeks", "6 to 8 weeks", "8 to 10 weeks" and "more than 10 weeks". Primary endpoint was pathological response, secondary endpoint TME quality and complications according to Clavien-Dindo classification. Results: Due to our inclusion criteria (preoperative chemoradiation, surgery in curative intention, M0), 1.809 of 9.560 patients were suitable for analysis. We observed a trend for increased rates of pathological complete response (pCR: ypT0ypN0) and pathological good response (pGR: ypT0-1ypN0) for groups with a prolonged time interval which was not significant. Ultimately, it led to a steady state of pCR (16.5%) and pGR (22.6%) in "8 to 10" and "more than 10" weeks. We were not able to observe any differences between the subgroups in perioperative morbidity, proportion of rectal extirpation (for cancer of the lower third) or difference in TME quality. Conclusion: A prolonged time interval between neoadjuvant chemoradiation can be performed, as the rate of pCR seems to be increased without influencing perioperative morbidity.

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“…2 Given that no exact (positive or negative) precondition for potential resectability can be defined, the repeated case-by-case discussion in multidisciplinary conferences, including experienced specialists, is a key factor for optimal management of mCRC. 2,7 The patient population of the FIRE-3 trial was recruited in more than 100 centres across Germany and Austria. Inclusion into the trial required measurable disease, but selection according to spread of disease was not performed.…”

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confidence: 99%

Factors That Influence Conversion to Resectability and Survival After Resection of Metastases in RAS WT Metastatic Colorectal Cancer (mCRC): Analysis of FIRE-3- AIOKRK0306

et al. 2020

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Background. Tumor assessments after first-line therapy of RAS wild-type mCRC with cetuximab (cet) versus bevacizumab (bev) in combination with FOLFIRI were evaluated for factors influencing resectability, conversion to resectability, and survival after best response. Methods. Conversion to resectability was defined as conversion of initially unresectable to resectable disease at best response as determined by retrospective assessment. Univariate and multivariate logistic models were fitted with resectability at best response as response variable. A Cox model comparing the survival from best response was used to measure the influence of treatment, resectability at best response, and resection. Interaction of resection and treatment arm on survival was tested by likelihood ratio test. Results. Overall, 270 patients were evaluable (127 cetarm, 143 bev-arm). Lung metastases (odds ratio [OR] 0.35, 95% confidence response [CI] 0.19-0.63), BRAF mutation (OR 0.33, 95% CI 0.12-0.82), and elevated alkaline phosphatase (OR 0.42, 95% CI 0.18-0.9) before randomization were associated with less chance of successful conversion and were integrated into a nomogram. Early tumor shrinkage (OR 1.86, 95% CI 1.06-3.3; p 0.034) and depth of response (OR 1.02, 95% CI 1.01-1.03; p \ 0.001) were associated with successful conversion therapy. Resection of metastases improved post-best-response survival (hazard ratio 0.53, 95% CI 0.29-0.97; p = 0.039),

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S3-Leitlinie – Kolorektales Karzinom

Cited by 129 publications

References 1,258 publications

Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and first-line efficacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial

Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and first-line efficacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial

Pathological complete response due to a prolonged time interval between preoperative chemoradiation and surgery in locally advanced rectal cancer: analysis from the German StuDoQ|Rectalcarcinoma registry

Factors That Influence Conversion to Resectability and Survival After Resection of Metastases in RAS WT Metastatic Colorectal Cancer (mCRC): Analysis of FIRE-3- AIOKRK0306

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