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https://ahro.austin.org.au/austinjspui/handle/1/26681| Title: | Prognostic and Predictive Impact of Primary Tumor Sidedness for Previously Untreated Advanced Colorectal Cancer. | Austin Authors: | Yin, Jun;Cohen, Romain;Jin, Zhaohui;Liu, Heshan;Pederson, Levi;Adams, Richard;Grothey, Axel;Maughan, Timothy S;Venook, Alan;Van Cutsem, Eric;Punt, Cornelis;Koopman, Miriam;Falcone, Alfredo;Tebbutt, Niall C ;Seymour, Matthew T;Bokemeyer, Carsten;Rubio, Eduardo Diaz;Kaplan, Richard;Heinemann, Volker;Chibaudel, Benoist;Yoshino, Takayuki;Zalcberg, John;Andre, Thierry;De Gramont, Aimery;Shi, Qian;Lenz, Heinz-Josef | Affiliation: | Universidad Complutense Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos, Madrid, Spain Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht University, The Netherlands Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, The Netherlands Department of Oncology, University of Pisa, Italy National Cancer Center Hospital East, Japan NIHR Clinical Research Network, Leeds UK. St James's Hospital, and University of Leeds, Leeds, United Kingdom Monash University, Melbourne, Australia Digestive Oncology, University Hospitals Gasthuisberg Leuven and University of Leuven Leuven, Belgium Department of Oncology, Haematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany University Hospital Grosshadern, Ludwig Maximilian University of Munich, Munich, Germany Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA Department of Oncology, Mayo Clinic, Rochester, MN, USA Department of Gastrointestinal Onocology, Keck School of Medicine at USC, Los Angeles, CA, USA Sorbonne University, Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, F-75012, Paris, France Institut Franco-Britannique, Levallois-Perret, France Hôpital Saint-Antoine, Paris, France Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France Cardiff University and Velindre Cancer Centre, Cardiff, UK CRUK/MRC Oxford Institute for Radiation Oncology, Oxford, United Kingdom St James's Hospital, and University of Leeds, Leeds, UK MRC Clinical Trials Unit at UCL, University College London, London, UK West Cancer Center and Research Institute, OneOncology, Germantown, TN Department of Medicine, The University of California San Francisco, San Francisco, California, United States of America.. Medical Oncology |
Issue Date: | 1-Jun-2021 | Date: | 2021-06-01 | Publication information: | Journal of the National Cancer Institute 2021; 113(12) | Abstract: | Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the impact of PTS on outcomes of mCRC patients. PTS data of 9,277 mCRC patients from 12 first-line randomized trials in the ARCAD database were pooled. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status, prior radiation/chemo, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (cetuximab plus chemotherapy vs. chemotherapy alone). All statistical tests were 2-sided. Compared to right-sided metastatic colorectal cancer patients (n = 2421, 26.1%), left-sided metastatic colorectal cancer patients (n = 6856, 73.9%) had better OS (median = 21.6 v 15.9 months; adjusted hazard ratio [HRadj] = 0.71, 95% confidence interval [CI] = 0.67-0.76, P<.001) and PFS (median = 8.6 v 7.5 months; HRadj = 0.80, 95% CI = 0.75-0.84, P<.001). Interaction between PTS and KRAS mutation was statistically significant (Pinteraction<.001): left-sidedness was associated with better prognosis among KRAS wild-type (WT) (OS HRadj = 0.59, 95% CI = 0.53-0.66; PFS HRadj =0.68, 95% CI = 0.61-0.75), but not among KRAS mutated tumors. Among KRAS-WT tumors, survival benefit from anti-EGFR was confirmed for left-sidedness (OS HRadj = 0.85, 95% CI = 0.75-0.97, P = .01; PFS HRadj = 0.77, 95% CI = 0.67-0.88, P<.001), but not for right-sidedness. The prognostic value of PTS is restricted to the KRAS-WT population. PTS is predictive of anti-EGFR efficacy, with a statistically significant improvement of survival for left-sidedness mCRC patients. These results suggest treatment choice in mCRC should be based on both PTS and KRAS status. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/26681 | DOI: | 10.1093/jnci/djab112 | Journal: | Journal of the National Cancer Institute | PubMed URL: | 34061178 | Type: | Journal Article |
| Appears in Collections: | Journal articles |
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