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      Proposal of Two Prognostic Models for the Prediction of 10-Year Survival after Liver Resection for Colorectal Metastases

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          Abstract

          Background

          One-third of 5-year survivors after liver resection for colorectal liver metastases (CLM) develop recurrence or tumor-related death. Therefore 10-year survival appears more adequate in defining permanent cure. The aim of this study was to develop prognostic models for the prediction of 10-year survival after liver resection for colorectal liver metastases.

          Methods

          N=965 cases of liver resection for CLM were retrospectively analyzed using univariable and multivariable regression analyses. Receiver operating curve analyses were used to assess the sensitivity and specificity of developed prognostic models and their potential clinical usefulness.

          Results

          The 10-year survival rate was 15.2%. Age at liver resection, application of chemotherapies of the primary tumor, preoperative Quick's value, hemoglobin level, and grading of the primary colorectal tumor were independent significant predictors for 10-year patient survival. The generated formula to predict 10-year survival based on these preoperative factors displayed an area under the receiver operating curve (AUROC) of 0.716. In regard to perioperative variables, the distance of resection margins and performance of right segmental liver resection were additional independent predictors for 10-year survival. The logit link formula generated with pre- and perioperative variables showed an AUROC of 0.761.

          Conclusion

          Both prognostic models are potentially clinically useful (AUROCs >0.700) for the prediction of 10-year survival. External validation is required prior to the introduction of these models in clinical patient counselling.

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          Most cited references27

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          Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest.

          The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI). Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR). A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032). The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.
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            Surgical resection of hepatic metastases from colorectal cancer: A systematic review of published studies

            No consensus on the indications for surgical resection of colorectal liver metastases exists. This systematic review has been undertaken to assess the published evidence for its efficacy and safety and to identify prognostic factors. Studies were identified by computerised and hand searches of the literature, scanning references and contacting investigators. The outcome measures were overall survival, disease-free survival, postoperative morbidity and mortality, quality of life and cost effectiveness, and a qualitative summary of the trends across all studies was produced. Only 30 of 529 independent studies met all the eligibility criteria for the review, and data on 30-day mortality and morbidity only were included from a further nine studies. The best available evidence came from prospective case series, but only two studies reported outcomes for all patients undergoing surgery. The remainder reported outcomes for selected groups of patients: those undergoing hepatic resection or those undergoing curative resection. Postoperative mortality rates were generally low (median 2.8%). The majority of studies described only serious postoperative morbidity, the most common being bile leak and associated perihepatic abscess. Approximately 30% of patients remained alive 5 years after resection and around two-thirds of these are disease free. The quality of the majority of published papers was poor and ascertaining the benefits of surgical resection of colorectal hepatic metastases is difficult in the absence of randomised trials. However, it is clear that there is group of patients with liver metastases who may become long-term disease- free survivors following hepatic resection. Such survival is rare in apparently comparable patients who do not have surgical treatment. Further work is needed to more accurately define this group of patients and to determine whether the addition of adjuvant treatments results in improved survival.
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              Actual 10-year survival after hepatic resection of colorectal liver metastases: what factors preclude cure?

              Hepatic resection of colorectal liver metastases (CRLM) is associated with long-term survival. This study analyzes actual 10-year survivors following resection of CRLM, reports the observed rate of cure, and identifies factors that preclude cure. A single-institution, prospectively-maintained database was queried for all initial resections for CRLM 1992–2004. Observed cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up. Clinical risk score (CRS) was dichotomized into low (0–2) and high (3–5). Semiparametric proportional hazards mixture cure model was utilized to estimate probability of cure. 1211 patients were included with a median follow-up for survivors of 11 years. Median DSS was 4.9 years (95% CI: 4.4–5.3). 295 patients (24.4%) were actual 10-year survivors. The observed cure rate was 20.6% (n=250). Among 250 cured patients, 192 (76.8%) had no recurrence and 58 (23.2%) had a resected recurrence with at least 3 years of disease-free follow-up. Extrahepatic disease (EHD, n=88), CEA >200 (n=119), positive margin (n=109), and >10 tumors (n=31) had observed cure rates less than 10%. In cure model analysis, patients with both EHD and high CRS (n=31) had an estimated probability of cure of 3.5%. Actual 10-year survival after resection of CRLM is 24% with an observed 20% cure rate. Patients with both high CRS and EHD have an estimated probability of cure less than 5%. When such factors are identified, strong consideration may be given to preoperative strategies, such as neoadjuvant chemotherapy, to help select patients for surgical therapy. Actual 10-year survival after resection of CRLM is 24% with an observed 20% cure. The significance of this report is that no single factor precludes cure, although patients with both a high CRS and EHD had an estimated probability of cure of 3.5%.
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                Author and article information

                Contributors
                Journal
                HPB Surg
                HPB Surg
                HPB
                HPB Surgery
                Hindawi
                0894-8569
                1607-8462
                2018
                21 October 2018
                : 2018
                : 5618581
                Affiliations
                1General, Visceral and Transplantation Surgery, Hannover Medical School, Germany
                2Core Facility Quality Management & Health Technology Assessment in Transplantation, Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Germany
                Author notes

                Academic Editor: Attila Olah

                Author information
                http://orcid.org/0000-0002-7709-838X
                http://orcid.org/0000-0001-5885-0786
                http://orcid.org/0000-0001-7208-1418
                http://orcid.org/0000-0003-3967-8559
                http://orcid.org/0000-0002-5527-7555
                Article
                10.1155/2018/5618581
                6215566
                30420795
                b779bdad-b501-45a3-b612-f524c6b487cc
                Copyright © 2018 Ulf Kulik et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 July 2018
                : 18 July 2018
                : 1 October 2018
                Funding
                Funded by: Bundesministerium für Bildung und Forschung
                Award ID: 01EO1302
                Categories
                Research Article

                Surgery
                Surgery

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