Toshikuni Nishikawa1, Shunzo Maetani. 1. Department of Abdominal Surgery, Tenri Institute of Medical Research and Tenri Hospital, , Tenri, Japan.
Abstract
BACKGROUND: The goal of radical cancer surgery with or without adjuvant therapy is to cure disease rather than to delay death. There is concern that the survival benefit of curative treatment may not be properly appreciated by the log-rank test (LRT), which is more sensitive to treatment that delays death than to treatment that achieves cure. To confirm this concern and to evaluate the survival benefit of adjuvant chemotherapy, the data from a previous randomized controlled trial are analyzed using both traditional and new methods. METHODS: In this trial, 1410 gastric cancer patients with serosal or subserosal invasion had been classified by nodal and serosal status into four strata and randomized to receivehigh-dose or low-dose adjuvant regimens (mitomycin and tegafur-uracil) after gastrectomy. The two treatment groups were compared using the LRT as well as the life expectancy (LE) derived from the Boag model and the competing risk model. RESULTS: The LRT showed no significant difference between the two groups, whereas the LE increased significantly with high-dose chemotherapy (1.4-year gain; 95% CI = 0.1-2.8). A greater gain of 4.4 years occurred exclusively in the serosa-negative node-positive stratum, associated with a 21% increase in cure rate. The gain in LE was particularly greater in younger patients. CONCLUSIONS: Parametric LE analysis offers more relevant information about curative treatment than LRT. It suggests that high-dose chemotherapy may achieve cure in a subset of patients, eradicating residual malignancies left behind after gastrectomy and providing greater survival benefit than expected from LRT.
RCT Entities:
BACKGROUND: The goal of radical cancer surgery with or without adjuvant therapy is to cure disease rather than to delay death. There is concern that the survival benefit of curative treatment may not be properly appreciated by the log-rank test (LRT), which is more sensitive to treatment that delays death than to treatment that achieves cure. To confirm this concern and to evaluate the survival benefit of adjuvant chemotherapy, the data from a previous randomized controlled trial are analyzed using both traditional and new methods. METHODS: In this trial, 1410 gastric cancerpatients with serosal or subserosal invasion had been classified by nodal and serosal status into four strata and randomized to receive high-dose or low-dose adjuvant regimens (mitomycin and tegafur-uracil) after gastrectomy. The two treatment groups were compared using the LRT as well as the life expectancy (LE) derived from the Boag model and the competing risk model. RESULTS: The LRT showed no significant difference between the two groups, whereas the LE increased significantly with high-dose chemotherapy (1.4-year gain; 95% CI = 0.1-2.8). A greater gain of 4.4 years occurred exclusively in the serosa-negative node-positive stratum, associated with a 21% increase in cure rate. The gain in LE was particularly greater in younger patients. CONCLUSIONS: Parametric LE analysis offers more relevant information about curative treatment than LRT. It suggests that high-dose chemotherapy may achieve cure in a subset of patients, eradicating residual malignancies left behind after gastrectomy and providing greater survival benefit than expected from LRT.
Authors: Astrid E Slagter; Edwin P M Jansen; Hanneke W M van Laarhoven; Johanna W van Sandick; Nicole C T van Grieken; Karolina Sikorska; Annemieke Cats; Pietje Muller-Timmermans; Maarten C C M Hulshof; Henk Boot; Maartje Los; Laurens V Beerepoot; Frank P J Peters; Geke A P Hospers; Boudewijn van Etten; Henk H Hartgrink; Mark I van Berge Henegouwen; Grard A P Nieuwenhuijzen; Richard van Hillegersberg; Donald L van der Peet; Heike I Grabsch; Marcel Verheij Journal: BMC Cancer Date: 2018-09-10 Impact factor: 4.430