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      Progressive Oncological Surgery Is Associated with Increased Curative Resection Rates and Improved Survival in Metastatic Colorectal Cancer

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          Abstract

          Background: Secondary resection rates in first-line chemotherapy trials for metastatic colorectal cancer (mCRC) remain below 15%, representing a clear contrast to reports by specialised surgical centres, where progressive liver, peritoneal-surface, and pulmonary surgery increased access to curative-intent treatment. We present a long-term evaluation of oncosurgical management in a single-centre, analysing the aggregate effect of gradual implementation of surgical subspecialties and systemic treatments on mCRC patients’ resection rates and prognosis. Methods: Patients with newly diagnosed mCRC from 2003 to 2014 were retrospectively categorised into palliative treatment (PAT) and curative intent surgery (CIS) and three time periods were analysed for treatment changes and factors associated with survival. Results: Four hundred-twenty patients were treated (PAT:250/CIS:170). Over time periods, the number of presenting patients remained consistent, whereas curative resection rates increased from 29% to 55%, facilitated by an increment of patients undergoing hepatectomy (21 to 35%), pulmonary surgery (6 to 17%), and peritonectomy/intraoperative chemotherapy (0 to 8%). Also, recently, significantly more multi-line systemic treatments were applied. The median survival markedly improved from 21.9 months (2003–2006; 95% confidence interval (CI) 17.3–26.5) to 36.5 months (2011–2014; 95% CI 26.6–46.4; p = 0.018). PAT was a significant factor of poor survival and diagnosis of mCRC in the latest time period was independently associated with a distinctly lower risk for palliative treatment (odds ratio 0.15). Conclusions: In modern eras of medical oncology, achieving appropriate resection rates through utilization of state-of-the-art oncological surgery by dedicated experts represents a cornerstone for long-term survival in mCRC.

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          Trends in long-term survival following liver resection for hepatic colorectal metastases.

          To examine trends in outcomes of patients undergoing resection at a single tertiary care referral center over a 16-year period. Hepatic resection is considered the treatment of choice in selected patients with colorectal metastasis confined to the liver. Although a variety of retrospective studies have demonstrated improvements in short-term outcomes in recent years, changes in long-term survival over time are less well-established. Data from 226 consecutive patients undergoing potentially curative liver resection for colorectal metastases between 1984 and 1999 were analyzed. Actuarial survival rates related to prognostic determinants were analyzed using the log-rank test. The median survival for the entire cohort was 46 months, with 5- and 10-year survival rates of 40% and 26% respectively. Ninety-three patients operated on between 1984 and 1992 were found to have an overall survival of 31% at 5 years, compared to 58% for the 133 patients operated on during the more recent period (1993-1999). Both overall and disease-free survival were significantly better in the recent time period compared with the earlier period on both univariate and multivariate analyses. Other independent factors associated with improved survival included number of metastatic tumors < or = 3, negative resection margin, and CEA < 100. Comparisons were made between time periods for a variety of patient, tumor and treatment-related factors. Among all parameters studied, only resection type (anatomical versus nonanatomical), use of intraoperative ultrasonography, and perioperative chemotherapy administration differed between the early and recent time periods. Long-term survival following liver resection for colorectal metastases has improved significantly in recent years at our institution. Although the reasons for this survival trend are not clear, contributing factors may include the use of newer preoperative and intraoperative imaging, increased use of chemotherapy, and salvage surgical therapy.
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            PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer.

            To evaluate panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated wild-type (WT) KRAS exon 2 (codons 12 and 13) metastatic colorectal cancer (mCRC). A prespecified secondary objective was to assess treatment effects in an extended RAS analysis that included exons 2, 3, and 4 of KRAS and NRAS.
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              Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE).

              Bevacizumab provides a survival benefit in first- and second-line metastatic colorectal cancer (mCRC). In a large, observational, bevacizumab treatment study (Bevacizumab Regimens: Investigation of Treatment Effects and Safety [BRiTE]) in patients who had mCRC, a longer-than-expected overall survival (OS) of 25.1 months was reported. The association between various pre- and post-treatment factors (including the use of bevacizumab beyond first progression [BBP]) and survival was examined. The 1,445 of 1,953 previously untreated patients with mCRC who were enrolled in BRiTE and who experienced disease progression (PD) were classified into three groups: no post-PD treatment (n = 253), post-PD treatment without bevacizumab (no BBP; n = 531), and BBP (n = 642). Relevant baseline and on-study variables, including BBP, were analyzed with a Cox model with respect to their independent effect on survival beyond first PD. Median OS was 25.1 months (95% CI, 23.4 to 27.5 months), and median progression-free survival was 10.0 months in the overall BRiTE population. Baseline and postbaseline factors were well balanced between the BBP and no-BBP groups. Median OS rates were 12.6, 19.9, and 31.8 months in the no post-PD treatment, no-BBP, and BBP groups, respectively. In multivariate analyses, compared with no BBP, BBP was strongly and independently associated with improved survival (HR, 0.48; P < .001). Hypertension that required medication was the only bevacizumab-related safety event that occurred more frequently in the BBP group (24.6% v 19.2%). These results from a large, prospective, observational study suggest that continued vascular endothelial growth factor inhibition with bevacizumab beyond initial PD could play an important role improving the overall success of therapy for patients who have mCRC.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                14 February 2019
                February 2019
                : 11
                : 2
                : 218
                Affiliations
                [1 ]Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria; florian.primavesi@ 123456tirol-kliniken.at (F.P.); manuel.maglione@ 123456tirol-kliniken.at (M.M.); t.resch@ 123456tirol-kliniken.at (T.R.); dietmar.oefner@ 123456i-med.ac.at (D.Ö.)
                [2 ]Department of Surgery, Paracelsus Medical University, 5020 Salzburg, Austria; ta.jaeger@ 123456salk.at (T.J.); j.presl@ 123456salk.at (J.P.); catherine.toma@ 123456gmail.com (K.T.); s.buchner@ 123456salk.at (S.B.); j.hutter@ 123456salk.at (J.H.); a.dinnewitzer@ 123456salk.at (A.D.)
                [3 ]Department of Medical Statistics, Informatics, and Health Economics, Medical University of Innsbruck, 6020 Innsbruck, Austria; georg.goebel@ 123456i-med.ac.at
                Author notes
                [* ]Correspondence: stefan.staettner@ 123456i-med.ac.at ; Tel.: +43-512-504-22601
                Author information
                https://orcid.org/0000-0003-2707-6307
                https://orcid.org/0000-0002-5226-7597
                https://orcid.org/0000-0002-2390-0226
                Article
                cancers-11-00218
                10.3390/cancers11020218
                6406820
                30769860
                b3ce314a-b426-4808-9149-396585419363
                © 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
                : 10 January 2019
                : 12 February 2019
                Categories
                Article

                colorectal cancer,metastases,surgery,liver resection,pulmonary resection,peritoneal surface surgery,curative intent,resectability,modern chemotherapy,advances in management

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