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      About Oncology Research and Treatment: 2.4 Impact Factor I 3.3 CiteScore I 0.495 Scimago Journal & Country Rank (SJR)

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      Predictors of Early Distant Relapse in Rectal Cancer Patients Submitted to Preoperative Chemoradiotherapy

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          Abstract

          Background: Neoadjuvant chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer. CRT leads to a better local control; however, this does not translate into a survival benefit. Long-term survival is mostly affected by the development of distant metastases after surgery. This study aimed to evaluate predictive clinical factors for the development of early metastatic disease after CRT. Methods: Clinical data of patients with stage II/III rectal cancer submitted to CRT between January 2000 and October 2014 were collected from prospectively maintained electronic databases of three Italian institutes. Patients were divided into two groups: those who developed metastasis within 12 months from surgical resection (Group A) and patients without or with late distant relapse (Group B). Results: Among 635 patients, 86 (13.5%) had early distant relapse within 1 year from surgery (Group A), and 549 (86.5%) did not (Group B). A higher rate of early distant relapse was associated with CEA levels above 3 ng/dL (20% vs. 10%; p <0.001), tumor lying under 5 cm from anal verge (20% vs. 9%; p <0.001), and age under 63 years (17% vs. 11%; p = 0.036). Multivariate analysis confirmed these factors to be independently correlated with a higher risk of early metastasis. Conclusions: Younger age, low tumors, and high serum CEA may be associated with unfavorable early oncological outcomes after CRT and surgery for rectal cancer. These clinical factors could be useful to select patients for more aggressive therapeutic strategies.

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          Most cited references22

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          Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2.

          Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin. We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m(2) twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m(2) twice daily 5 days per week and oxaliplatin 50 mg/m(2) once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR). Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02). The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.
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            Sample size determination for logistic regression revisited.

            There is no consensus on the approach to compute the power and sample size with logistic regression. Some authors use the likelihood ratio test; some use the test on proportions; some suggest various approximations to handle the multivariate case. We advocate the use of the Wald test since the Z-score is routinely used for statistical significance testing of regression coefficients. The null-variance formula became popular from early studies, which contradicts modern software, which utilizes the method of maximum likelihood estimation (MLE), when the variance of the MLE is estimated at the MLE, not at the null. We derive general Wald-based power and sample size formulas for logistic regression and then apply them to binary exposure and confounder to obtain a closed-form expression. These formulas are applied to minimize the total sample size in a case-control study to achieve a given power by optimizing the ratio of controls to cases. Approximately, the optimal number of controls to cases is equal to the square root of the alternative odds ratio. Our sample size and power calculations can be carried out online at www.dartmouth.edu/ approximately eugened.
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              Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial†.

              The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes.
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                Author and article information

                Journal
                ORT
                Oncol Res Treat
                10.1159/issn.2296-5270
                Oncology Research and Treatment
                S. Karger AG
                2296-5270
                2296-5262
                2020
                April 2020
                07 February 2020
                : 43
                : 4
                : 146-152
                Affiliations
                [_a] aColorectal Surgery Unit, A.O.U. Cagliari, Department of Surgical Science, University of Cagliari, Cagliari, Italy
                [_b] bGastrointestinal Surgery Unit, Istituto Nazionale Tumori “Fondazione G. Pascale” IRCCS, Naples, Italy
                [_c] cDepartment of Surgical, Oncological, and Gastroenterological Sciences, Section of Surgery, University of Padova, Padua, Italy
                Author notes
                *Simona Deidda, MD, Colorectal Surgery Unit, A.O.U. Cagliari, Department of Surgical Science, University of Cagliari, Monserrato, S.S. 554 Bivio Sestu, IT–09042 Cagliari (Italy), simonadeidda86@gmail.com
                Article
                505668 Oncol Res Treat 2020;43:146–152
                10.1159/000505668
                32036373
                64625b2f-4eb4-4607-8109-1f2998611291
                © 2020 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 18 May 2019
                : 28 December 2019
                Page count
                Figures: 2, Tables: 4, Pages: 7
                Categories
                Research Article

                Oncology & Radiotherapy,Pathology,Surgery,Obstetrics & Gynecology,Pharmacology & Pharmaceutical medicine,Hematology
                Rectal cancer,Predictors,Metastasis

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