7694 Background: In an attempt to improve the poor local control in patients with locally advanced and medically inoperable lung cancer we investigated helical tomotherapy as a means to decrease radiation dose to critical normal structures while escalating tumor dose. Methods: Thirty-six patients with Stage I-IV NSCLC requiring definitive radiotherapy and judged not to be surgical candidates due to medical comorbidities or advanced tumor stage were enrolled in this phase I trial. Chemotherapy was given sequentially but not allowed concurrently. Pts were placed in 1 of 4 dose-per-fraction bins, all treated for 25 fractions, with dose per fraction ranging from 2.28 to 3.22 Gy. Bins were calculated to yield normalized total dose (NTD) equivalents in 2 Gy fractions of 60–100 Gy. Dose escalation limiting constraints included esophageal maximum NTD, lung NTD mean, and esophageal effective volume (Veff). Radiotherapy was limited to the primary site and clinically proven or suspicious nodal regions. Elective nodal irradiation (ENI) was not performed. A graded-response logistic regression analysis was performed to identify dosimetric and clinical factors associated with esophagitis. Results: No grade 3 (CTCAE v3.0 and RTOG) acute esophageal toxicities were observed. Only 6 patients (16.7%) required narcotic analgesia (RTOG gr. 2 toxicity). Average mean NTD dose to the esophagus (Dmean)=15.3 Gy. Average volume of the esophagus receiving NTD 55 Gy (V55)=3.65%. Both Dmean and V55 were significantly associated with the grade of esophagitis, with P- values of 0.018 and 0.010, respectively. In this limited series, there was no significant effect of sequential chemotherapy, in agreement with previous studies. Conclusions: 1) Acute esophageal toxicity was minimal despite dose escalation via helical tomotherapy for inoperable NSCLC cancer. 2) The observed significant associations between V55, Dmean, and grade of esophagitis validate improved dose distribution as a strategy to permit radiation dose escalation. Pending acceptable rates of radiation pneumonitis the addition of concurrent chemotherapy is anticipated. Supported by NIH Grant CA-88960. No significant financial relationships to disclose.
A phase I, open-label, multi-center, dose-escalation study of codrituzumab, an anti-glypican-3 monoclonal antibody, in combination with atezolizumab in patients with locally advanced or metastatic hepatocellular carcinoma