Faculty Bibliography

PURPOSE:The objective response rate (ORR) for single-agent anti-programmed death receptor 1 (anti-PD-1) therapy is modest in patients with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). We aimed to test whether radiotherapy may act synergistically with anti-PD-1 therapy to improve response through the abscopal effect. PATIENTS AND METHODS:We conducted a single-center, randomized, phase II trial of nivolumab (anti-PD-1 therapy) versus nivolumab plus stereotactic body radiotherapy (SBRT) in patients with metastatic HNSCC. Patients had at least two metastatic lesions: one that could be safely irradiated and one measurable by RECIST version 1.1. Patients were randomly assigned (1:1), stratified by human papillomavirus status, to nivolumab (3 mg/kg intravenously every 2 weeks) or nivolumab (same dose) plus SBRT (9 Gy × 3) to 1 lesion. The primary end point was ORR in nonirradiated lesions, which was assessed by RECIST in patients with at least one available set of on-treatment images; safety was assessed in a per-protocol population. RESULTS:= .70). CONCLUSION:We found no improvement in response and no evidence of an abscopal effect with the addition of SBRT to nivolumab in unselected patients with metastatic HNSCC.

PURPOSE: Combination therapy with trabectedin and docetaxel was evaluated in patients with advanced malignancies. METHODS: In this open-label phase 1 study, docetaxel (60 or 75 mg/m(2); 1-h intravenous infusion) was given on day 1 of a 21-day cycle in combination with escalating doses of trabectedin (0.4-1.3 mg/m(2) by 3-h intravenous infusion, 1 h after docetaxel) and prophylactic granulocyte colony-stimulating factor (G-CSF). Maximum tolerated dose (MTD) as primary objective and safety, plasma pharmacokinetics, and antitumor activity as secondary objectives were assessed. RESULTS: Patients (N = 49) received a median of four cycles of treatment. MTD was 1.3 mg/m(2) trabectedin and 60 mg/m(2) docetaxel for patients with limited and 1.1 mg/m(2) trabectedin and 60 mg/m(2) docetaxel for patients with unlimited prior chemotherapy. Dose-limiting toxicities (during cycle 1) included elevated alanine aminotransferase (ALT) and fatigue in patients with limited prior chemotherapy and elevated ALT and febrile neutropenia in those with unlimited prior chemotherapy. The most common drug-related adverse events were nausea (65 %), fatigue (63 %), and neutropenia (53 %). One patient achieved a complete response. Thirty patients had stable disease, and 11 had stable disease for >/=6 months. Pharmacokinetic results for trabectedin plus docetaxel were similar to those previously reported for the single agents. CONCLUSION: In patients with previously treated, advanced malignancies, the combination of therapeutic doses of trabectedin and docetaxel showed clinical activity and was tolerable with prophylactic G-CSF, with no evidence of clinically important drug interactions.

We began implementation of a medical decision support system (MDSS) at the Columbia-Presbyterian Medical Center (CPMC) using the Arden Syntax in 1992. The Clinical Event Monitor which executes the Medical Logic Modules (MLMs) runs on a mainframe computer. Data are stored in a relational database and accessed via PL/I programs known as Data Access Modules (DAMs). Currently we have 18 clinical, 12 research and 10 administrative MLMs. On average, the clinical MLMs generate 50357 simple interpretations of laboratory data and 1080 alerts each month. The number of alerts actually read varies by subject of the MLM from 32.4% to 73.5%. Most simple interpretations are not read at all. A significant problem of MLMs is maintenance, and changes in laboratory testing and message output can impair MLM execution significantly. We are now using relational database technology and coded MLM output to study the process outcome of our MDSS.