Central venous catheters-related-thrombosis and risk factors in oncological patients: A retrospective evaluation of recent risk scores.

BACKGROUND: Insertions of central venous catheters (CVC) has become a common practice in Onco-Hematologic Units to administer systemic treatments. Unfortunately they can cause complications influencing patient's care-pathway significantly. Oncological patients have a higher thrombotic risk than the general population, therefore specific recent risk scores are spreading through the clinical practice, such as Khorana, Protecht, COMPASS-CAT, and Michigan scores. METHODS: A retrospective cohort of 177 out of a total of 3046 outpatients accessing the Medical Day Hospital of Istituto Nazionale Tumori di Milano from March 2019 to February 2021 aged ⩾ 18 years who developed CVC complications was analyzed extracting clinical data from their medical records. Focusing on the risk factors, especially through recent risk scores to estimate the thrombotic risk we used Wilcoxon-test for continuous variables and the Pearson-Chi-Square test for categorical variables. RESULTS: Anticoagulants resulted a protective factor mostly for partial CVC occlusion (p = 0.0001), preventing CVC occlusions. CVC occlusions were significantly associated with epitelial tumor histotype, (p = 0.0061). Complete CVC occlusions were significantly associated with peripherical inserted central venous catheters (PICC) (p < 0.0001). Catheter-related-thrombosis (CRT) was significantly associated with peripherical-inserted-central-venous-catheter, both when it was diagnosed clinically (p = 0.0121) and radiographically (p = 0.0168).There was a strong association between CRT and a high grade of Khorana Score (p = 0.0195), Protecht Score (p = 0.0412), COMPASS-CAT Score (p = 0.0027). A positive statistical trend was observed between the Michigan Score and CRT in patients carrying PICC (p = 0.053). CONCLUSIONS: There are many different and various factors associated with higher or lower risk of CVC thrombotic complications, so it could be useful to test the recent risk scores to estimate thrombotic risk in oncological patients in clinical practice.

Comparison of outcomes of central venous catheters in patients with solid and hematologic neoplasms: an Italian real-world analysis.

INTRODUCTION: Although many reports have analyzed the outcomes of central venous catheters (CVCs) in oncologic and oncohematologic patients, current guidelines do not routinely recommend a specific type of CVC over the other. METHODS: We retrospectively evaluated the outcomes of 178 patients with CVCs referred to an Italian specialized cancer center between January 2016 and December 2018. The analysis compares midterm peripherally inserted central venous catheters (PICCs) with long-term centrally inserted catheters, including totally implanted ports and tunneled catheters with central insertion (tCVCs). RESULTS: A total of 130 PICCs (73%) and 48 tCVCs (27%) were analyzed. The overall complication rate was significantly increased in the PICC cohort compared to the tCVC cohort (43.1% vs 25%, respectively; p = 0.037), leading to complication-related device removal in 30.8% of PICCs vs 12.5% of tCVCs (p = 0.013). No significant differences in terms of catheter-related thromboses (p = 0.676) or catheter-related infections (p = 0.140) were detected. Nonthrombotic obstructions were significantly higher in the PICC group compared to the tCVC cohort (p = 0.006). Overall complication-free survival was significantly longer for tCVCs compared to PICCs (hazard ratio [HR], 0.262; 95% confidence interval [CI], 0.128-0.536; p < 0.0001), as well as obstruction-free survival (HR, 0.082; 95% CI, 0.018-0.372; p < 0.0001). In multivariable analysis, the type of CVC was independently correlated with the occurrence of any complication (HR, 0.273; 95% CI, 0.135-0.553; p < 0.0001). CONCLUSIONS: This Italian real-world experience suggests that PICCs are associated with a higher risk of overall complications compared with tCVCs. Catheter choice in oncologic patients should be guided by treatment type and duration, risk-benefit assessment, patient preferences, and compliance.

Dose-Dense Temozolomide in Patients with MGMT-Silenced Chemorefractory Colorectal Cancer.

BACKGROUND: In a phase II study, we showed that temozolomide (TMZ) was tolerable and active in heavily pre-treated patients with advanced colorectal cancer (CRC) and MGMT methylation. A schedule of dose-dense TMZ may have enhanced activity due to the higher cumulative dose and induction of MGMT depletion, even in resistant tumors. METHODS: Thirty-two patients with chemorefractory MGMT-methylated CRC were treated with TMZ at a daily dose of 75 mg/m(2) for 21 consecutive days every 4 weeks, for up to six cycles or until the occurrence of progressive disease/unacceptable toxicity. The primary endpoint was treatment activity in terms of objective response rate (ORR). MGMT protein expression was tested by immunohistochemistry (IHC) on two pooled cohorts: patients from the previous study of standard-dose TMZ and those from the current investigation. RESULTS: From November 2013 to December 2014, 32 patients were treated at Fondazione IRCCS Istituto Nazionale dei Tumori. We observed only three episodes of grade 3 asthenia and no significant myelotoxicity. The ORR was 16 % (all partial responses occurring in RAS-BRAF-mutated tumors). Median progression-free survival (PFS) and overall survival (OS) were 2.3 and 6.7 months, respectively. Patients with MGMT-low expression by IHC had a significantly higher ORR (p < 0.0001) and PFS (p = 0.001) compared to those with MGMT-high expression, while no difference was observed in OS. CONCLUSIONS: Our data confirm the encouraging activity of TMZ in chemorefractory CRC patients selected for MGMT silencing, even in the RAS-BRAF-mutated population. The role of MGMT IHC as a biomarker for improving patient selection warrants further prospective confirmation.

Capecitabine, oxaliplatin and irinotecan in combination, with bevacizumab (COI-B regimen) as first-line treatment of patients with advanced colorectal cancer. An Italian Trials of Medical Oncology phase II study.

BACKGROUND: A dose-finding phase I/II trial that evaluated the maximum tolerated doses of a combination of three drugs with irinotecan, oxaliplatin and capecitabine (COI regimen) has been conducted in patients with metastatic colorectal cancer (mCRC). In this study the safety and activity of the combination of COI regimen plus bevacizumab (COI-B) were assessed. METHODS: Patients judged to be unresectable for metastatic disease, were enrolled in a phase II, open-label study and treated with the combination of bevacizumab (5mg/kg on day 1) and COI regimen (irinotecan 180mg/mq on day 1, oxaliplatin 85mg/mq on day 2, capecitabine 2000mg d2-6; q14) as first-line treatment. Induction treatment was administered for a maximum of 8 cycles, followed by maintenance treatment with bevacizumab (7.5mg/kg on d1, q21) until progression. RESULTS: Fifty-one patients were enrolled in six Italian centres. The primary end-point of overall response rate was met, reaching the value of 62% in the per-protocol population and 57% in the intent-to-treat population, patients with stable disease were also taken into account, the clinical benefit rate was 94%. In the intention-to-treat population, median progression-free and overall survivals were 10.3 and 22 months, respectively. Toxicity was different from 5-fluorouracil-based triplet regimens, with 31% of severe diarrhoea, but a low incidence of grade 3/4 neutropenia (6%) and mucositis (4%). CONCLUSIONS: Our results show the feasibility and promising activity of the combination of capecitabine, oxaliplatin, irinotecan and bevacizumab.

Circulating biomarkers in advanced colorectal cancer patients randomly assigned to three bevacizumab-based regimens.

The need to identify biomarkers for bevacizumab-based treatment in advanced colorectal cancer is imperative. The aim of this study was to investigate the prognostic role of circulating VEGF, PDGF, SDF-1, osteopontin and CEA in patients randomly assigned to three bevacizumab-based regimens. Plasma samples from 50 patients treated at a single Institution were analysed using the multiplex assay BioPlex™ 2200 (Bio-Rad Laboratories, Inc, Berkeley, CA, USA) at baseline, before first three cycles and subsequently every three cycles until disease progression. Prognostic analyses of baseline values were performed using multivariable Cox models, including disease extension >10 cm or ≤10 cm (measured as the sum of the diameters for all target lesions) as adjustment factor. The association between progression-free and overall survival and biomarkers modulation during treatment was studied using multivariable Cox models, which included summary statistics synthesizing during-treatment modulation together with disease extension. The biomarkers significantly associated with disease extension were baseline CEA (p = 0.012) and SDF-1 (p = 0.030). High values of VEGF and SDF-1 tended to be associated with worse prognosis, especially in terms of overall survival. The negative prognostic trend was more marked for baseline CEA as compared to other biomarkers; increasing values during treatment was significantly related to worse prognosis independently of disease extension (p = 0.007 and 0.016 for progression-free and overall survival, respectively). VEGF is related to bevacizumab pharmacodynamics and is associated to other angiogenic cytokines; some of the proposed biomarkers such as SDF-1 and CEA should be further validated for prognosis assessment and monitoring of bevacizumab-based treatment of advanced colorectal cancer.

Hepatic colorectal cancer metastases showing a distinctive pattern of pathological response after metronomic capecitabine and bevacizumab.

A 48-year-old man was referred to our hospital with the diagnosis of colon cancer with multiple hepatic metastases. After right hemicolectomy, the rapid progression of liver disease was treated with metronomic capecitabine and bevacizumab according to a study protocol. A gradual regression of metastatic lesions was observed during a 9-month treatment period. After conversion of liver disease to resectability, the histological examination disclosed the complete necrosis of all lesions, with the exception of small neoplastic foci inside a single nodule. The comparison of this type of histological findings with the classic sclero-hyaline pathological response, as well as its importance as indicator of response to antiangiogenic treatment, is discussed.