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Varying the volume of solution injected, while keeping the dosage the same, does not cause significant changes in the amount and distribution of drug in the tumor. A higher vascular exchange area leads to higher concentrations of drug in the tumor. Lymphatic drainage in the tumor causes negligible reductions in the mean concentrations in all three different zones. Cellular metabolism and DNA binding kinetics decrease the mean concentrations of drug by about 15 to 40%, as compared to the baseline case.

BackgroundDeveloping multiple cancers is an indicator of underlying hereditary cancer predisposition, but there is a paucity of data regarding the clinical genetic testing outcomes of these patients.MethodsWe compared cancer index patients with ≥2 primary malignancies versus 1 primary cancer who underwent clinical evaluation and testing with multi-gene panels comprising up to 49 genes from 1998-2016.ResultsAmong 1191 cancer index patients, 80.6%, 17.2%, and 2.2% respectively had 1, 2, and ≥3 primary malignancies. For patients with 2 primary cancers (n=205), the most common cancer pairs were bilateral breast (37.5%), breast-ovary (11.7%), endometrium-ovary (9.2%), colon-endometrium (3.9%) and colon-colon (3.4%). 42.3% patients underwent gene testing including 110/231 (47.6%) with multiple malignancies. Pathogenic variants were found more frequently in younger patients, in those with a family history of cancer related to the suspected syndrome, and a trend towards significance in those with multiple primary cancers (35.5% vs. 25.6%, p = 0.09). In patients with multiple cancers, pathogenic variants were most commonly identified in BRCA1 (38.5%), BRCA2 (17.9%), and the mismatch repair genes (20.5%), while 23.1% of pathogenic mutations were in other moderate- to high-penetrance cancer predisposition genes including APC, ATM, MUTYH, PALB2, RAD50 and TP53.ConclusionPatients with multiple cancers were more likely to carry pathogenic mutations than those with single cancer. About three-quarters of deleterious mutations in patients with multiple primary cancers were in BRCA1/2 and the mismatch repair genes, but multi-gene panel testing facilitated the detection of mutations in another 6 genes and is warranted in this high-risk population.

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Hepatocellular carcinoma (HCC) is a hypervascular tumour, which overexpresses vascular endothelial growth factor. Thalidomide is an antiangiogenic agent with activity in refractory multiple myeloma. The purpose of this multi-centre phase II study was to evaluate the efficacy and toxicity of thalidomide in patients with advanced HCC. From February 2000 to November 2001, 37 patients with histologically proven, bi-dimensionally measurable advanced, unresectable HCC were enrolled. The starting dose of Thalidomide was 100 mg per day and escalated weekly by 100 mg to a maximum dose of 800 mg/day according to individual patient tolerance. Radiological tumour response and treatment related toxicities were prospectively assessed. Thirty-seven patients were evaluable for toxicity and 24 patients were evaluable for response. The median Thalidomide dose was 400 mg/day. There was no complete response (CR). One patient had a radiological partial response (PR) (3%; 95% confidence interval [95% CI], 0% to 8%) and six (16%) patients had stable disease for more than 6 months. Somnolence and fatigue were the most common side effects, occurring in 84% and 73% of patients respectively. Thalidomide monotherapy is tolerable and associated with modest antitumour activity in advanced HCC.