441P Evaluation of conversion therapy in patients undergoing secondary resection of metastases in curative intent within the FIRE-3 (AIO KRK-0306) study

785 Background: Resection of metastases with curative intent is an integral component of mCRC management. However, relapse rates are high and identifying patients most likely to benefit from this approach is of considerable importance. Among patients with mCRC, mutations (mt) in RAS and BRAF genes portent a worse prognosis. Our hypothesis, therefore, is that patients harbouring these mutations may have a higher relapse rate after resection of metastases. We also wished to analyse clinical predictors of relapse, including site of metastases. Methods: We interrogated the TRACC database of patients undergoing resection with curative intent who had mutation status available. The frequency of RAS and BRAF mt was established and their association with clinical parameters determined. Relapse free (RFS) and overall survival (OS), from the date of resection, was estimated for the mt and wild type (wt) groups using the Kaplan Meier method. Multivariate analysis is planned to investigate factors associated with RFS, including stage of the primary tumour, synchronous metastases, site and number of metastases, CEA, peri-operative chemotherapy use, site of the primary (left v right) and RAS and BRAF mutation status. Results: 188 patients were identified. 89 were KRAS/BRAF wt, 92 KRAS mt and 7 BRAF mt. 40% had presented with metastatic disease and 27% had a right sided primary. 76%, 22% and 2% underwent resection of liver, lung or both metastases. Microscopic resection margin was involved in 6%. Resection was performed prior to any chemotherapy in 48%. No difference was seen in relapse free or overall survival between the mt and wt groups. Conclusions: We found no difference in relapse free or overall survival by mutation subgroup suggesting this should not influence suitability for curative intent resection, but analyses is planned on a much larger cohort once data is available. A multivariate analysis, adjusting for important prognostic variables, is planned.

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Utility of surveillance following curative intent resection of metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.6562 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. 6562-6562

Author(s):

Richard M. Lee-Ying ◽

Daniel John Renouf ◽

Howard John Lim ◽

Hagen F. Kennecke ◽

Sharlene Gill ◽

...

Keyword(s):

Curative Intent ◽

Resection Of Metastases

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Kolorektales Karzinom: Resektable Metastasen resezieren!

Karger Kompass Onkologie ◽

10.1159/000519179 ◽

2021 ◽

pp. 138-139

Author(s):

Hans-Rudolf Raab

Keyword(s):

Lung Metastases ◽

Cox Model ◽

Logistic Models ◽

Ratio Test ◽

Conversion Therapy ◽

Elevated Alkaline Phosphatase ◽

Retrospective Assessment ◽

Depth Of Response ◽

Best Response ◽

Resection Of Metastases

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 cet-arm, 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), predominantely in cet-treated patients (interaction test, p = 0.02). Conclusions: Conversion to resectability is significantly associated with baseline characteristics that can be used in a nomogram to predict conversion. Moreover, early efficacy parameters (ETS and DpR) are associated with successful conversion therapy. In FIRE-3, resection of metastases was associated with improved post-best response survival, this effect originated predominantly from the cetuximab-based study arm.

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CONVERSION THERAPY FOR GASTRIC CANCER: EXPANDING THE TREATMENT POSSIBILITIES

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-672020190001e1435 ◽

2019 ◽

Vol 32 (2) ◽

Cited By ~ 4

Author(s):

Marcus Fernando Kodama Pertille RAMOS ◽

Marina Alessandra PEREIRA ◽

Amir Zeide CHARRUF ◽

André Roncon DIAS ◽

Tiago Biachi de CASTRIA ◽

...

Keyword(s):

Gastric Cancer ◽

Neoadjuvant Treatment ◽

Recurrence Free Survival ◽

Conversion Therapy ◽

Curative Intent ◽

Free Survival ◽

Node Metastasis ◽

Therapeutic Possibility ◽

Indication For Treatment

ABSTRACT Background: Conversion therapy in gastric cancer (GC) is defined as the use of chemotherapy/radiotherapy followed by surgical resection with curative intent of a tumor that was prior considered unresectable or oncologically incurable. Aim: To evaluate the results of conversion therapy in the treatment of GC. Methods: Retrospective analysis of all GC surgeries between 2009 and 2018. Patients who received any therapy before surgery were further identified to define the conversion group. Results: Out of 1003 surgeries performed for GC, 113 cases underwent neoadjuvant treatment and 16 (1.6%) were considered as conversion therapy. The main indication for treatment was: T4b lesions (n=10), lymph node metastasis (n=4), peritoneal carcinomatosis and hepatic metastasis in one case each. The diagnosis was made by imaging in 14 cases (75%) and during surgical procedure in four (25%). The most commonly used chemotherapy regimens were XP and mFLOX. Major surgical complications occurred in four cases (25%) and one (6.3%) died. After an average follow-up of 20 months, 11 patients (68.7%) had recurrence and nine (56.3%) died. Prolonged recurrence-free survival over 40 months occurred in two cases. Conclusion: Conversion therapy may offer the possibility of prolonged survival for a group of GC patients initially considered beyond therapeutic possibility.

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Survival benefit of conversion therapy after intensive chemotherapy for unresectable metastatic gastric cancer: A propensity score-matched analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.354 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 354-354

Author(s):

Hiroyuki Ohnuma ◽

Yasushi Sato ◽

Ginji Omori ◽

Naoki Onoyama ◽

Saki Ameda ◽

...

Keyword(s):

Gastric Cancer ◽

Propensity Score ◽

Large Scale ◽

Propensity Score Analysis ◽

Performance Status ◽

R0 Resection ◽

Conversion Therapy ◽

Ecog Performance Status ◽

Curative Intent ◽

Response To Chemotherapy

354 Background: The significance of conversion therapy (CT), whereby patients (pts) with unresectable disease respond to chemotherapy and subsequently receive surgery with curative intent (adjuvant surgery: AS), has been specifically established for metastatic colorectal cancer. However, such a strategy for advanced or recurrent gastric cancer (AGC) remains controversial. This study aims to clarify the clinical significance of CT for AGC. Methods: In this retrospective multi-institution observational study, we analyzed 168 AGC pts who received chemotherapy consisting of docetaxel, cisplatin or oxaliplatin, and S-1 ± trastuzumab between 2003 and 2019. We divided pts into two groups: those who underwent CT (group CT) or chemotherapy only (group C). Propensity score analysis with 1:1 matching minimized confounding bias when comparing efficacy and safety between groups. Results: A tumor response to chemotherapy was observed in 82.4% of all cases, while 34.5% (58/168) underwent AS. Fifty-one of the 58 pts underwent an R0 resection, and 79.3% were deemed histological responders. After matching, 44 pairs of C and CT pts were selected; significant differences in baseline characteristics were not observed. Incidences of adverse events during chemotherapy were similar between groups, with neutropenia and febrile neutropenia as common grade 3–4 events. Compared with group C, group CT had a significantly better median overall survival (OS) (15.5 vs. 46.0 months; hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.18–0.58; p < .001), and a prolonged progression-free survival (6.5 vs.22.6 months; HR 0.33; 95% CI 0.19–0.56; p < .001). Subgroup analysis of OS showed a favorable trend for CT for almost all parameters. In a multivariate analysis, ECOG performance status (HR 0.10; 95% CI 0.03–0.31) and AS (HR 0.20; 95% CI 0.10–0.40) correlated with favorable OS. In the CT group, pathological response was an independent prognostic factor (HR 0.16; 95% CI 0.06–0.39). Conclusions: CT was associated with better outcomes in AGC pts, even after baseline adjustment. Our data warrants further large-scale studies to establish a conversion therapeutic strategy.

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