Validation of the ONKOTEV Risk Prediction Model for Venous Thromboembolism in Outpatients With Cancer.

Importance: The assessment of the risk of venous thromboembolism (VTE) among outpatients with cancer represents an unsolved topic. Current international guidelines recommend primary prophylaxis for patients at intermediate to high risk of VTE, indicated by a Khorana score of 2 or more. A previous prospective study developed the ONKOTEV score, a 4-variable risk assessment model (RAM) consisting of a Khorana score of more than 2, metastatic disease, vascular or lymphatic compression, and previous VTE event. Objective: To validate the ONKOTEV score as a novel RAM to assess the risk of VTE among outpatients with cancer. Design, Setting, and Participants: ONKOTEV-2 is a noninterventional prognostic study conducted in 3 European centers located in Italy, Germany, and the United Kingdom among a prospective cohort of 425 ambulatory patients with a histologically confirmed diagnosis of a solid tumor who were receiving active treatments. The total study duration was 52 months, with an accrual period of 28 months (from May 1, 2015, to September 30, 2017) and an overall follow up-period of 24 months (data were censored September 30, 2019). Statistical analysis was performed in October 2019. Exposures: The ONKOTEV score was calculated for each patient at baseline by collecting clinical, laboratory, and imaging data from tests performed for routine practice. Each patient was then observed to detect any thromboembolic event throughout the study period. Main Outcomes and Measures: The primary outcome of the study was the incidence of VTE, including deep vein thrombosis and pulmonary embolism. Results: A total of 425 patients (242 women [56.9%]; median age, 61 years [range, 20-92 years]) were included in the validation cohort of the study. The cumulative incidences for the risk of developing VTE at 6 months were 2.6% (95% CI, 0.7%-6.9%), 9.1% (95% CI, 5.8%-13.2%), 32.3% (95% CI, 21.0%-44.1%), and 19.3% (95% CI, 2.5%-48.0%), respectively, among 425 patients with an ONKOTEV score of 0, 1, 2, and greater than 2 (P < .001). The time-dependent area under the curve at 3, 6, and 12 months was 70.1% (95% CI, 62.1%-78.7%), 72.9% (95% CI, 65.6%-79.1%), and 72.2% (95% CI, 65.2%-77.3%), respectively. Conclusions and Relevance: This study suggests that, because the ONKOTEV score has been validated in this independent study population as a novel predictive RAM for cancer-associated thrombosis, it can be adopted into practice and into clinical interventional trials as a decision-making tool for primary prophylaxis.

Detection of circulating tumor cells in patients with locally advanced rectal cancer undergoing neoadjuvant therapy followed by curative surgery.

PURPOSE: Circulating tumor cells (CTCs) represent an independent prognostic factor in metastatic colorectal cancer, while their significance in early stages is still an open issue. The aim of the study is to investigate the role of CTCs in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (CT-RT). METHODS: In this prospective single institutional study, cT3-4 and/or N+ rectal cancer was treated with neoadjuvant CT-RT. The primary endpoints were as follows: evaluation of CTCs at baseline (t0), after CT-RT (t1), within 7 days after surgery (t2), and at 6 months from surgery (t3) and correlation with main patient/tumor characteristics, CEA, response to neoadjuvant therapy, and disease-free survival (DFS). CTCs were enumerated with the CellSearch System in 22.5 ml peripheral blood. A repeated measure analysis for binary outcome was used to evaluate over time changes in the percentage of CTCs detectable in blood samples. RESULTS: Of the 90 patients enrolled in this study, 85 were eligible consisting of 52 males and 33 females. Median age was 63 years and median follow-up was 38 months. CTCs were available for all patients at t0, for 67 at t1, for 68 at t2, and for 62 at t3. CTCs >0 were reported on 16 (19%) at t0, on 5 (7.5%) at t1, on 6 (9%) at t2, and on 3 (5%) at t3 (P value for trend 0.039). Only for CT-RT responders, CTCs reduced from t0 to t1. No statistically significant association was found between CTCs and main patient/tumor characteristics and DFS. CONCLUSIONS: Sixteen patients (19%) had CTCs ≥1 at t0 with reduction in CTC number in case of objective remissions. The proportion of patients with CTCs ≥1 decreased over the time as the therapeutic course proceeded. Much effort should be oriented toward increasing CTC detection rate by enhancing technical tests and achieving better patient characterization.

Brain metastases from colorectal cancer: main clinical factors conditioning outcome.

BACKGROUND: The aim of our study is to evaluate the outcome of patients affected by brain metastases from colorectal cancer and to correlate the outcome with prognostic factors. METHODS: Patients were retrospectively evaluated. Survival distributions were estimated by using the Kaplan-Meier method. The log-rank test was used to assess the impact on survival of individual factors. RESULTS: Among 41 patients (25M and 16F; median age 58), 58.5 % had rectal cancer and 39 % synchronous metastatic disease; 95 % had extracranial metastases, most common site was lung (87.8 %). Seven patients had synchronous brain metastases. Median overall survival after diagnosis of brain metastases was 5 months [95 % confidence interval 3-12 months]. Median survival from brain metastases diagnosis was 4.2 months in patients treated with radiotherapy (29.3 %), 11.9 months in those with radio- and chemotherapy (21.9 %) and 21.4 months in those with surgery with/without radiotherapy or chemotherapy (29.3 %) (P < 0.0001). On multivariate analysis, no independent prognostic factors were found for disease-free interval from diagnosis to brain metastases and overall survival; amount of chemotherapy before brain metastases have no statistically significant relation to brain-metastases-free-interval even if patients who received more than one line of chemotherapy have a longer median brain-metastases-free-interval than those who received less than one. KRAS was found mutated in 17/28 patients without statistically significant correlation to outcome due to the small sample size. CONCLUSIONS: Prognosis of brain-metastases-patients is poor. An interesting tool is to evaluate the correlation of KRAS status and brain metastases with aim to tailor treatment and follow-up.