title: A Novel Computational Tool for Mining Real-Life Data: Application in the Metastatic Colorectal Cancer Care Setting.
abstract: Randomized clinical trials constitute the gold-standard for evaluating new anti-cancer therapies; however, real-life data are key in complementing clinically useful information. We developed a computational tool for real-life data analysis and applied it to the metastatic colorectal cancer (mCRC) setting. This tool addressed the impact of oncology/non-oncology parameters on treatment patterns and clinical outcomes.
  
  
  
  The developed tool enables extraction of any computerized information including comorbidities and use of drugs (oncological/non-oncological) per individual HMO member. The study in which we evaluated this tool was a retrospective cohort study that included Maccabi Healthcare Services members with mCRC receiving bevacizumab with fluoropyrimidines (FP), FP plus oxaliplatin (FP-O), or FP plus irinotecan (FP-I) in the first-line between 9/2006 and 12/2013.
  
  
  
  The analysis included 753 patients of whom 15.4% underwent subsequent metastasectomy (the Surgery group). For the entire cohort, median overall survival (OS) was 20.5 months; in the Surgery group, median duration of bevacizumab-containing therapy (DOT) pre-surgery was 6.1 months; median OS was not reached. In the Non-surgery group, median OS and DOT were 18.7 and 11.4 months, respectively; no significant OS differences were noted between FP-O and FP-I, whereas FP use was associated with shorter OS (12.3 month; p <0.002; notably, these patients were older). Patients who received both FP-O- and FP-I-based regimens achieved numerically longer OS vs. those who received only one of these regimens (22.1 [19.9-24.0] vs. 18.9 [15.5-21.9] months). Among patients assessed for wild-type KRAS and treated with subsequent anti-EGFR agent, OS was 25.4 months and 18.7 months for 124 treated vs. 37 non-treated patients (non-significant). Cox analysis (controlling for age and gender) identified several non-oncology parameters associated with poorer clinical outcomes including concurrent use of diuretics and proton-pump inhibitors.
  
  
  
  Our tool provided insights that confirmed/complemented information gained from randomized-clinical trials. Prospective tool implementation is warranted.
authors.affiliation: Department of Professional Medicine, Maccabi Healthcare Services, Tel Aviv, Israel.
authors.forename: Nava
authors.initials: N
authors.lastname: Siegelmann-Danieli
authors.affiliation: Department of Biomedical Informatics, IBM Research-Haifa, Haifa University Campus, Haifa, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Farkash
authors.affiliation: Department of Pharmacology, Maccabi Healthcare Services, Tel Aviv, Israel.
authors.forename: Itzhak
authors.initials: I
authors.lastname: Katzir
authors.affiliation: Department of Pharmacology, Maccabi Healthcare Services, Tel Aviv, Israel.
authors.forename: Janet
authors.initials: J
authors.lastname: Vesterman Landes
authors.affiliation: Department of Pharmacology, Maccabi Healthcare Services, Tel Aviv, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Rotem Rabinovich
authors.affiliation: Department of Pharmacology, Maccabi Healthcare Services, Tel Aviv, Israel.
authors.forename: Yossef
authors.initials: Y
authors.lastname: Lomnicky
authors.affiliation: Department of Biomedical Informatics, IBM Research-Haifa, Haifa University Campus, Haifa, Israel.
authors.forename: Boaz
authors.initials: B
authors.lastname: Carmeli
authors.affiliation: Department of Biomedical Informatics, IBM Research-Haifa, Haifa University Campus, Haifa, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Parush-Shear-Yashuv
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000556:secondary* / Q000628:therapy*; D003131:Combined Modality Therapy; D019295:Computational Biology; D057225:Data Mining / Q000379:methods*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011743:Pyrimidines / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D011743:Pyrimidines; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin