{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:30:44Z","timestamp":1760146244891,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: This retrospective study investigates the impact of various treatment strategies on progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), a significant global health issue. Methods: We employed the restricted mean survival time (RMST) to evaluate how different treatments affect PFS over a defined period. The study included 225 patients with mCRC who were treated between 2015 and 2023 at the Oncology Department of Col\u021bea Clinical Hospital in Bucharest. To assign KRAS status, mutation data from exons 2, 3, and 4 of the KRAS gene were required. Eligibility criteria included a confirmed histopathological diagnosis of colorectal adenocarcinoma, a valid RAS mutation test from a solid biopsy, radiological confirmation of stage IV disease by computed tomography, and at least one line of systemic treatment in the metastatic setting. Results: Our analysis revealed a small difference in PFS based on KRAS status, but this difference was not statistically significant. Neither sex nor the urban versus rural environment impacted PFS; however, the data indicated that educational level affected survival outcomes. Conclusions: Consistent with existing literature, our findings showed no survival benefit from locoregional treatments such as surgery of the primary tumor or curative radiotherapy at diagnosis. In contrast, resection of hepatic metastases was associated with improved survival outcomes.<\/jats:p>","DOI":"10.3390\/jcm13206174","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T03:49:34Z","timestamp":1729136974000},"page":"6174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Treatment Strategies\u2019 Impact on Progression-Free Survival According to RMST Function in Metastatic Colorectal Cancer Patients: A Retrospective Study from Romania"],"prefix":"10.3390","volume":"13","author":[{"given":"Edvina Elena","family":"Pirvu","sequence":"first","affiliation":[{"name":"Department of Genetics, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Medical Oncology, \u201cColtea\u201d Clinical Hospital, 030167 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-615X","authenticated-orcid":false,"given":"Emilia","family":"Severin","sequence":"additional","affiliation":[{"name":"Department of Genetics, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raluca Ileana","family":"Patru","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u201cColtea\u201d Clinical Hospital, 030167 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Nita","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Medicover Hospital, 020331 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania Andreea","family":"Toma","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ponderas Academic Hospital, 014142 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca Elena","family":"Croitoru","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u201cColtea\u201d Clinical Hospital, 030167 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana Estefa","family":"Munoz Groza","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u201cColtea\u201d Clinical Hospital, 030167 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Marinescu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u201cColtea\u201d Clinical Hospital, 030167 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","unstructured":"WHO (2024, August 04). Cancer. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cancer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101174","DOI":"10.1016\/j.tranon.2021.101174","article-title":"Global colorectal cancer burden in 2020 and projections to 2040","volume":"14","author":"Xi","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hossain, M.S., Karuniawati, H., Jairoun, A.A., Urbi, Z., Ooi, D.J., John, A., Lim, Y.C., Kibria, K.M.K., Mohiuddin, A.K.M., and Ming, L.C. (2022). Colorectal Cancer: A Review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk Factors, Preventive and Treatment Strategies. Cancers, 14.","DOI":"10.3390\/cancers14071732"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1136\/gutjnl-2015-310912","article-title":"Global patterns and trends in colorectal cancer incidence and mortality","volume":"66","author":"Arnold","year":"2017","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.prp.2009.07.010","article-title":"Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer","volume":"205","author":"Neumann","year":"2009","journal-title":"Pathol. Res. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1200\/JCO.2007.14.7116","article-title":"Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer","volume":"26","author":"Amado","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1200\/JCO.2008.19.8168","article-title":"KRAS Mutations and Sensitivity to Epidermal Growth Factor Receptor Inhibitors in Colorectal Cancer: Practical Application of Patient Selection","volume":"27","author":"Jimeno","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_9","first-page":"308","article-title":"Markers of resistance to anti-EGFR therapy in colorectal cancer","volume":"4","author":"Shaib","year":"2013","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.coph.2008.06.006","article-title":"KRAS mutations predict response to EGFR inhibitors","volume":"8","author":"Raponi","year":"2008","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1097\/COC.0000000000000191","article-title":"Factors associated with guideline-recommended KRAS testing in colorectal cancer patients: A population-based study","volume":"40","author":"Charlton","year":"2017","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.annonc.2022.10.003","article-title":"Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"34","author":"Cervantes","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"P\u00eervu, E.E., Severin, E., P\u0103tru, R.I., Ni\u021b\u0103, I., Toma, S.A., Macarie, R.R., Cocioab\u0103, C.E., Florescu, I., and Coniac, S. (2023). Correlations between demographic, clinical, and paraclinical variables and outcomes in patients with KRAS-mutant or KRAS wild-type metastatic colorectal cancer: A retrospective study from a tertiary-level center in Romania. Diagnostics, 13.","DOI":"10.3390\/diagnostics13182930"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clcc.2014.11.002","article-title":"A review of the evolution of systemic chemotherapy in the management of colorectal cancer","volume":"14","author":"Gustavsson","year":"2015","journal-title":"Clin. Colorectal Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/s13046-021-02130-2","article-title":"Resistance to anti-EGFR therapies in metastatic colorectal cancer: Underlying mechanisms and reversal strategies","volume":"40","author":"Zhou","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0140-6736(12)61900-X","article-title":"Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomized, placebo-controlled, phase 3 trial","volume":"381","author":"Grothey","year":"2013","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1056\/NEJMoa0805019","article-title":"Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer","volume":"360","author":"Hitre","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1007\/s11605-006-0061-3","article-title":"Surgical therapy for colorectal metastases to the liver","volume":"11","author":"Pawlik","year":"2007","journal-title":"J. Gastrointest. Surg."},{"key":"ref_19","unstructured":"Belinson, S., Chopra, R., Yang, Y., Shankaran, V., and Aronson, N. (2012). Local Hepatic Therapies for Metastases to the Liver from Unresectable Colorectal Cancer."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cirocchi, R., Trastulli, S., Boselli, C., Montedori, A., Cavaliere, D., Parisi, A., Noya, G., and Abraha, I. (2012). Radiofrequency ablation in the treatment of liver metastases from colorectal cancer. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD006317.pub3"},{"key":"ref_21","unstructured":"Therneau, T. (2024, August 04). A Package for Survival Analysis in R. R Package Version 3.2-3. Available online: https:\/\/CRAN.R-project.org\/package=survival."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Therneau, T.M., and Grambsch, P.M. (2000). Modeling Survival Data: Extending the Cox Model, Springer.","DOI":"10.1007\/978-1-4757-3294-8"},{"key":"ref_23","unstructured":"Kassambara, A., Kosinski, M., and Biecek, P. (2024, August 04). survminer: Drawing Survival Curves Using \u2018ggplot2\u2019; R Package Version 0.4.8. Available online: https:\/\/CRAN.R-project.org\/package=survminer."},{"key":"ref_24","unstructured":"Hajime, U., Tian, L., Horiguchi, M., Cronin, A., Battioui, C., and Bell, J. (2024, August 04). survRM2: Comparing Restricted Mean Survival Time; R Package Version 1.0-3. Available online: https:\/\/CRAN.R-project.org\/package=survRM2."},{"key":"ref_25","unstructured":"Sjoberg, D.D., Curry, M., Hannum, M., Larmarange, J., Whiting, K., and Zabor, E.C. (2024, August 04). gtsummary: Presentation-Ready Data Summary and Analytic Result Tables; R Package Version 1.4.2. Available online: https:\/\/CRAN.R-project.org\/package=gtsummary."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3322\/canjclin.55.2.74","article-title":"Global cancer statistics, 2002","volume":"55","author":"Parkin","year":"2005","journal-title":"CA Cancer J. Clin."},{"key":"ref_27","first-page":"3","article-title":"The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials","volume":"10","author":"Royston","year":"2013","journal-title":"Clin. Trials"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1200\/JCO.2014.55.2208","article-title":"Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis","volume":"32","author":"Uno","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Collett, D. (2015). Modeling Survival Data in Medical Research, Chapman and Hall\/CRC. [3rd ed.].","DOI":"10.1201\/b18041"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1634\/theoncologist.2014-0032","article-title":"Targeted therapies in metastatic colorectal cancer: A systematic review and assessment of currently available data","volume":"19","author":"Kirstein","year":"2014","journal-title":"Oncologist"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1053\/j.gastro.2019.12.051","article-title":"Precision therapy in RAS mutant colorectal cancer","volume":"158","author":"Dienstmann","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e981","DOI":"10.1093\/oncolo\/oyad138","article-title":"Prevalence of KRAS G12C mutation and co-mutations and associated clinical outcomes in patients with colorectal cancer: A systematic literature review","volume":"28","author":"Strickler","year":"2023","journal-title":"Oncologist"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.socscimed.2008.09.070","article-title":"The effect of socioeconomic status on survival from colorectal cancer in the Melbourne Collaborative Cohort Study","volume":"68","author":"Kelsall","year":"2009","journal-title":"Soc. Sci. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3892\/mco.2021.2472","article-title":"Inoperable de novo metastatic colorectal cancer with a primary tumour in situ: Evaluating discordant responses to upfront systemic therapy of the primary tumours and metastatic sites and complications arising from primary tumours (experiences from an Irish Cancer Centre)","volume":"16","author":"Hamed","year":"2022","journal-title":"Mol. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.21037\/hbsn.2019.05.14","article-title":"Surgical approach to synchronous colorectal liver metastases: Staged, combined, or reverse strategy","volume":"9","author":"Lillemoe","year":"2020","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_36","first-page":"w14486","article-title":"Treatment strategies and outcome of surgery for synchronous colorectal liver metastases","volume":"147","author":"Reding","year":"2017","journal-title":"Swiss Med. Wkly."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1097\/01.sla.0000128305.90650.71","article-title":"Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection\/ablation for colorectal liver metastases","volume":"239","author":"Abdalla","year":"2004","journal-title":"Ann. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/00000658-199909000-00004","article-title":"Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: Analysis of 1001 consecutive cases","volume":"230","author":"Fong","year":"1999","journal-title":"Ann. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1245\/s10434-021-11017-7","article-title":"Management of colorectal cancer with synchronous liver metastases: An inception cohort study (CoSMIC)","volume":"29","author":"Chan","year":"2022","journal-title":"Ann. Surg. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5390","DOI":"10.1245\/s10434-023-13656-4","article-title":"Hepatectomy before primary tumor resection as preferred approach for synchronous liver metastases from rectal cancer","volume":"30","author":"Maki","year":"2023","journal-title":"Ann. Surg. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1200\/JOP.0852002","article-title":"Chemotherapy treatments for metastatic colorectal cancer: Is evidence-based medicine in practice?","volume":"4","author":"Field","year":"2008","journal-title":"J. Oncol. Pract."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/20\/6174\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:14:49Z","timestamp":1760112889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/20\/6174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,17]]},"references-count":41,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["jcm13206174"],"URL":"https:\/\/doi.org\/10.3390\/jcm13206174","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2024,10,17]]}}}