Clinical impact of postoperative interval until adjuvant chemotherapy following curative gastrectomy for advanced gastric cancer

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Abstract

Background: Adjuvant chemotherapy (AC) following curative gastrectomy for stage II/III gastric cancer (GC) is recommended in Japan. However, for various reasons, patients cannot always start AC at the appropriate time. This study was designed to investigate the effect of the postoperative interval until adjuvant chemotherapy (PIAC) and cumulative S-1 dose on prognosis.

Methods: Between 2008 and 2014, consecutive 81 GC patients who underwent postoperative S-1 monotherapy were enrolled in this study.

Results: Postoperative complications of Clavien-Dindo grade II or higher and postoperative peak C-reactive protein of 8.1 mg/dl or higher were significantly associated with delayed AC. The cut-off value of PIAC selected to most effectively stratify prognosis was 7 weeks. For relapse-free survival (RFS), patients with PIAC ≥ 7 weeks had an insignificantly poorer prognosis than those with PIAC < 7 weeks. A multivariate analysis showed that PIAC ≥ 7 weeks [ p = 0.024; hazard ratio (HR) 2.45] and the cumulative S-1 dose/body surface area (BSA) ≥ 12,000 mg/m ² [ p = 0.004; HR 3.27] were independent prognostic factors. In patients with the cumulative S-1 dose/BSA ≥ 12,000 mg/m ², there were no prognostic differences between patients with and without PIAC ≥ 7 weeks.

Conclusions: Seven weeks after surgery could be a limit indicator starting AC. A cumulative S-1 dose/BSA of more than 12,000 mg/m ² might be a key dose for diminishing the poor prognostic effects of delaying AC.

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Most cited references 35

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Lindsey A Torre, Freddie Bray, Rebecca Siegel … (2015)

Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.

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Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial.

Yung-Jue Bang, Young-Woo Kim, Han-Kwang Yang … (2012)

D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II-IIIB gastric cancer. The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II-IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m(2) twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m(2) on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov (NCT00411229). 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4-41·7) in the chemotherapy and surgery group and 34·3 months (25·6-41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69-79) in the chemotherapy and surgery group and 59% (53-64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44-0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294). Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer. F Hoffmann-La Roche and Sanofi-Aventis. Copyright © 2012 Elsevier Ltd. All rights reserved.

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Excess deaths associated with underweight, overweight, and obesity.

Katherine Flegal (2005)

As the prevalence of obesity increases in the United States, concern over the association of body weight with excess mortality has also increased. To estimate deaths associated with underweight (body mass index [BMI] or =30) in the United States in 2000. We estimated relative risks of mortality associated with different levels of BMI (calculated as weight in kilograms divided by the square of height in meters) from the nationally representative National Health and Nutrition Examination Survey (NHANES) I (1971-1975) and NHANES II (1976-1980), with follow-up through 1992, and from NHANES III (1988-1994), with follow-up through 2000. These relative risks were applied to the distribution of BMI and other covariates from NHANES 1999-2002 to estimate attributable fractions and number of excess deaths, adjusted for confounding factors and for effect modification by age. Number of excess deaths in 2000 associated with given BMI levels. Relative to the normal weight category (BMI 18.5 to or =30) was associated with 111,909 excess deaths (95% confidence interval [CI], 53,754-170,064) and underweight with 33,746 excess deaths (95% CI, 15,726-51,766). Overweight was not associated with excess mortality (-86,094 deaths; 95% CI, -161,223 to -10,966). The relative risks of mortality associated with obesity were lower in NHANES II and NHANES III than in NHANES I. Underweight and obesity, particularly higher levels of obesity, were associated with increased mortality relative to the normal weight category. The impact of obesity on mortality may have decreased over time, perhaps because of improvements in public health and medical care. These findings are consistent with the increases in life expectancy in the United States and the declining mortality rates from ischemic heart disease.

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Author and article information

Journal

Journal ID (nlm-ta): J Cancer

Journal ID (iso-abbrev): J Cancer

Journal ID (publisher-id): jca

Title: Journal of Cancer

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1837-9664

Publication date Collection: 2021

Publication date (Electronic): 13 August 2021

Volume: 12

Issue: 19

Pages: 5960-5966

Affiliations

Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.

Author notes

✉ Corresponding author: Shuhei Komatsu, MD, PhD, FACS, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. E-mail: skomatsu@ 123456koto.kpu-m.ac.jp , Telephone: +81-75-2515527, Fax: +81-75-2515522.

*These two authors contributed equally to this work.

Competing Interests: The authors have declared that no competing interest exists.

Article

Publisher ID: jcav12p5960

DOI: 10.7150/jca.58154

PMC ID: 8408116

PubMed ID: 34476010

SO-VID: 93d331b5-bb86-4588-88bf-a6d728903442

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This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Clinical impact of postoperative interval until adjuvant chemotherapy following curative gastrectomy for advanced gastric cancer

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Karger: Oncology

Most cited references 35

Global cancer statistics, 2012.

Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial.

Excess deaths associated with underweight, overweight, and obesity.

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