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      Timing of Adjuvant Chemotherapy and Survival in Colorectal, Gastric, and Pancreatic Cancer. A Systematic Review and Meta-Analysis

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          Abstract

          (1) Background: The optimal timing of adjuvant chemotherapy (CT) in gastrointestinal malignancies is still a matter of debate. For colorectal cancer, it is recommended to start post-operative treatment within eight weeks. The objective of this study was to assess the clinical effects of starting adjuvant CT within or after 6–8 weeks post-surgery in colorectal, gastric, and pancreatic cancer. (2) Methods: MEDLINE, EMBASE, and the Cochrane Library were searched in December 2018. Publications comparing the outcomes of patients treated with adjuvant CT administered before (early) or after (delayed) 6–8 weeks post-surgery for colorectal, gastric, and pancreatic cancer were identified. The primary endpoint was overall survival (OS). (3) Results: Out of 8752 publications identified, 34 comparative studies assessing a total of 141,853 patients were included. Meta-analysis indicated a statistically significant increased risk of death with delayed CT (>6–8 weeks post-surgery) in colorectal cancer (hazard ratio (HR) = 1.27, 95% confidence interval (CI) 1.21–1.33; p <0.001). Similarly, for gastric cancer, delaying adjuvant CT was associated with inferior overall survival (HR = 1.2, 95% CI 1.04–1.38; p = 0.01). Conversely, the benefit of earlier CT was not evident in pancreatic cancer (HR = 1, 95% CI 1–1.01; p = 0.37). Conclusions: Starting adjuvant CT within 6–8 weeks post-surgery is associated with a significant survival benefit for colorectal and gastric cancer, but not for pancreatic cancer.

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          Most cited references39

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          Laparoscopic versus open distal gastrectomy for gastric cancer: a meta-analysis of randomized controlled trials and high-quality nonrandomized studies.

          To perform a meta-analysis of high-quality published trials, randomized and observational, comparing laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) for gastric cancer. Controversy persists about the clinical utility of minimally invasive techniques for the treatment of gastric cancer. Prospective data is limited to a few small randomized trails. : Studies published from January 1992 to March 2010 that compare LDG and ODG were identified. No restrictions in pathologic stage were applied. All randomized controlled trials (RCTs) were included. Selection of high-quality, nonrandomized comparative studies (NRCTs) was based on a validated tool (Methodological Index for Nonrandomized Studies). Mortality, complications, harvested lymph nodes, operative time, blood loss, and hospital stay were compared using weighted mean differences (WMDs) and odds ratios (ORs). Twenty-five studies were included in the analyses, 6 RCTs and 19 NRCTs, compromising 3055 patients (1658 LDG, 1397 ODG). LDG was associated with longer operative times (WMD 48.3 minutes; P < 0.001) and lower overall complications (OR 0.59; P < 0.001), medical complications (OR 0.49; P = 0.002), minor surgical complications (OR 0.62; P = 0.001), estimated blood loss (WMD -118.9 mL; P < 0.001), and hospital stay (WMD -3.6 days; P < 0.001). Mortality and major complications were similar. Patients in the ODG group had a significantly higher number of lymph nodes harvested (WMD 3.9 nodes; P < 0.001), although the estimated proportion of patients with less than 15 retrieved nodes was similar (OR 1.26, P = 0.09). LDG can be performed safely with a shorter hospital stay and fewer complications than open surgery. The long-term significance of a difference of less than 5 nodes in the number of harvested lymph nodes remains unclear. Lymph node staging appears to be unaffected. These results need to be validated in Western patients with advanced gastric cancer.
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            A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate.

            A mathematic model has been developed relating the drug sensitivity of a tumor to its own spontaneous mutation rate towards phenotypic drug resistance. The proportion as well as the absolute numbers of resistant cells will increase with time and the fraction of resistant cells within tumor colonies of the same size with vary depending on whether mutation occurs as an early or late event. Analysis of the model indicates that the probability of the appearance of a resistant phenotype increases with the mutation rate. Furthermore, for any population of tumors with a non-zero mutation rate the likelihood of there being at least one resistant cell will go from a condition of low to high probability over a very short interval in the tumor's biologic history.
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              Association of Delayed Adjuvant Chemotherapy With Survival After Lung Cancer Surgery.

              Adjuvant chemotherapy offers a survival benefit to a number of staging scenarios in non-small-cell lung cancer. Variable recovery from lung cancer surgery may delay a patient's ability to tolerate adjuvant chemotherapy, yet the urgency of chemotherapy initiation is unclear.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                17 April 2019
                April 2019
                : 11
                : 4
                : 550
                Affiliations
                [1 ]Oncology Unit, ASST Bergamo Ovest, 24047 Treviglio, Italy
                [2 ]Oncology Unit, Fondazione Poliambulanza, 25124 Brescia, Italy; azaniboni@ 123456alice.it (A.Z.); michela.libertini@ 123456poliambulanza.it (M.L.)
                [3 ]Oncology Unit, Casa di Cura Igea, 20129 Milano, Italy; antonioghidini@ 123456hotmail.com
                [4 ]Oncology Unit, ASST Cremona, 26100 Cremona, Italy; micheleghidini@ 123456outlook.com (M.G.); claupizz1987@ 123456gmail.com (C.P.); margherita.ratti@ 123456studenti.unipr.it (M.R.); gianluca.tomasello@ 123456gmail.com (G.T.)
                [5 ]Surgical Oncology Unit, ASST of Bergamo, 24100 Bergamo Ovest, Italy; luca_turati@ 123456ospedale.treviglio.bg.it
                Author notes
                [* ]Correspondence: faupe@ 123456libero.it ; Tel.: +39-0363-424420
                Author information
                https://orcid.org/0000-0002-6142-2018
                https://orcid.org/0000-0002-6958-6682
                Article
                cancers-11-00550
                10.3390/cancers11040550
                6520704
                30999653
                50549866-90ed-4f18-a71b-5b1a2c6a9c9d
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 April 2019
                : 15 April 2019
                Categories
                Review

                colorectal cancer,gastric cancer,pancreatic cancer,adjuvant chemotherapy,timing,meta-analysis

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