A Clinical-Genetic Risk Score for Predicting Cancer-Associated Venous Thromboembolism: A Development and Validation Study Involving Two Independent Prospective Cohorts.

PURPOSE: Venous thromboembolism (VTE) is a leading cause of death among patients with cancer. The Khorana score was developed for assessing the risk of VTE in outpatients with cancer receiving chemotherapy, but its accuracy in identifying patients at high risk has been questioned. The aim of this study was to develop and validate a clinical-genetic score that improves the assessment of VTE risk in oncology outpatients within 6 months of diagnosis. METHODS: The new score was developed using the data of 364 outpatients belonging to the Spanish ONCOTHROMB 12-01 population. In this cohort, clinical data associated with the risk of VTE were collected at the time of diagnosis, including the Khorana score. These patients were also genotyped for the 51 genetic variants known to be associated with VTE. Multivariate logistic regression was performed to determine the weight of each genetic and clinical variable in relation to VTE risk, allowing a clinical-genetic risk score (the ONCOTHROMB score) to be developed. The Khorana and the ONCOTHROMB scores were then compared via the area under the receiver operating characteristic curve (AUC), calibration, and the number of patients needed to treat. The new score was then validated in a study of 263 patients in the Vienna Cancer and Thrombosis Study population. RESULTS: Nine genetic variants, tumor site, TNM stage, and a body mass index of > 25 kg/m2 were found to be associated with VTE and were used to build the ONCOTHROMB score, which better predicted the overall risk of VTE than did the Khorana score (AUC, 0.781 v 0.580; P < .001). Similar AUC results were recorded in the validation study the Vienna Cancer and Thrombosis Study cohort involving patients with the same type of tumor (AUC for the ONCOTHROMB score v the Khorana score: 0.686 v 0.577; P < .001) and with all type of tumors (AUC for the ONCOTHROMB score v the Khorana score: 0.720 v 0.561; P < .0001). CONCLUSION: The ONCOTHROMB score for VTE risk in outpatients with cancer, which takes into account both clinical and genetic variables, better identifies patients who might benefit from primary thromboprophylaxis than does the Khorana score.

Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patients with cancer.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death among patients with cancer. Outpatients with cancer should be periodically assessed for VTE risk, for which the Khorana score is commonly recommended. However, it has been questioned whether this tool is sufficiently accurate at identifying patients who should receive thromboprophylaxis. The present work proposes a new index, TiC-Onco risk score to be calculated at the time of diagnosis of cancer, that examines patients' clinical and genetic risk factors for thrombosis. METHODS: We included 391 outpatients with a recent diagnosis of cancer and candidates for systemic outpatient chemotherapy. All were treated according to standard guidelines. The study population was monitored for 6 months, and VTEs were recorded. The Khorana and the TiC-Onco scores were calculated for each patient and their VTE predictive accuracy VTEs was compared. RESULTS: We recorded 71 VTEs. The TiC-Onco risk score was significantly better at predicting VTE than the Khorana score (AUC 0.73 vs. 0.58, sensitivity 49 vs. 22%, specificity 81 vs. 82%, PPV 37 vs. 22%, and NPV 88 vs. 82%). CONCLUSIONS: TiC-Onco risk score performed significantly better than Khorana score at identifying cancer patients at high risk of VTE who would benefit from personalised thromboprophylaxis.

Nab-paclitaxel plus gemcitabine as first-line palliative chemotherapy in a patient with metastatic pancreatic cancer with Eastern Cooperative Oncology Group performance status of 2.

Metastatic pancreatic cancer (PC) has been associated with a considerably poor prognosis. Due to its toxicity, first-line combination chemotherapy is limited to patients with a good performance status (PS). Previously nab-paclitaxel plus gemcitabine has been demonstrated to improve the overall survival rate in patients with advanced pancreatic cancer with a good PS. The present study reports a case of a patient with metastatic PC with a poor PS (Eastern Cooperative Oncology Group 2) and a complex set of comorbidities treated with nab-paclitaxel plus gemcitabine as a first-line palliative therapy. Adjusted doses of nab-paclitaxel plus gemcitabine reached a favourable clinical, radiological and biochemical response in the present patient, which increased the quality of life for the patient. Eventually, the patient succumbed to acute cholangitis. Based on the results of the present study, nab-paclitaxel plus gemcitabine appears to be a favourable treatment as first-line palliative chemotherapy for patients with metastatic PC, comorbidities and poor PS.

Evaluation of a heredofamilial cancer unit in increasing family history collection and genetic counseling referrals among Spanish oncologists at a university hospital.

A comprehensive family history is essential to identify patients at risk for hereditary cancer who could benefit from genetic counseling (GC). In a previous study, we observed a low occurrence of family history record (FHR) collection rate and GC referral among oncologists at our institution. The present work analyzes whether the implementation of a heredofamilial cancer unit (HFCU) would improve these parameters. We retrospectively compared the FHR rate in clinical records, National Cancer Institute (NCI) general criteria for hereditary cancer suspicion, GC referrals and FHR quality in two cohorts: cohort 1 (patients diagnosed before HFCU creation) and cohort 2 (after HFCU creation). Of 1,175 patients (590 cohort 1 and 585 cohort 2), FHRs were consigned in 27.3 % and 52.5 % of patients, respectively (p < 0.001). The GC referral of patients with any NCI criterion was 13.6 % xin cohort 1 vs. 40.5 % in cohort 2 (p < 0.001). FHR quality improved in terms of the total number of relatives (164 vs. 314, p = 0.1, N.S.) and number of healthy relatives consigned (80 vs. 191, p < 0.01). Nine mutations (6 BRCA, 1 MEN1, 2 Lynch), 4 unknown significance variants (all in BRCA) and 2 with no mutation were identified among patients referred from cohort 2. We conclude that the creation of a heredofamilial cancer unit has changed both FHR and GC referrals among oncologists at our institution, although continuous educational efforts are required.