SS 04 - Lung 2 - Stage III/IV
32 - Phase I Study of Accelerated Hypofractionated Proton Therapy and Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)
Sunday, October 21
5:05 PM - 5:15 PM
Location: Room 301
Clifford Robinson, MD
Siteman Cancer Center/Washington University School of Medicine in St. Louis
Washington University in St Louis: Assistant Professor: Employee
DFINE: Speaker's Bureau, Travel Expenses; Elekta: Research Grants; Radialogica: Advisory Board; Varian Medical Systems: Research Grants, Speaker's Bureau, Travel Expenses
Radialogica: Stock Options
Phase I Study of Accelerated Hypofractionated Proton Therapy and Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)
C. G. Robinson1, J. Contreras2, T. A. DeWees3, S. Jenkins3, S. Waqar3, R. Govindan3, M. Q. Baggstrom3, D. Morgensztern3, B. A. Bottani3, D. Przybysz Jr3, M. C. Roach Jr3, and J. D. Bradley3; 1Washington University School of Medicine, Department of Radiation Oncology, St. Louis, MO, 2Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 3Washington University School of Medicine, St. Louis, MO
Purpose/Objective(s): Locoregional control for LA-NSCLC can be improved with hypofractionated RT, but potentially at the expense of increased toxicity particularly when combined with chemotherapy. We hypothesized that protons would facilitate safe delivery of hypofractionated RT and concurrent chemotherapy for LA-NSCLC.
Materials/Methods: A phase I trial was designed using the Time to Event – Continuous Reassessment Method (TITE-CRM). Maximum tolerated dose was defined as the dose associated with a 20% probability of CTCAE v4.0 protocol-specified serious adverse events (SAEs; G3+ cardiac, bleeding, neurologic, pulmonary; G4+ GI, skin; any G5) within 6 mo. Starting dose was 3.5 Gy/fx x 15 fx, bracketed by 2 potential escalation and de-escalation levels in 0.25 Gy/fx increments. GTV was gross disease on PET/CT with variable CTV expansion (0 mm nodes, 5 mm tumor) and beam-specific PTV margins planned with a passive-scattering technique. Target coverage could be compromised for spinal cord and brachial plexus, but otherwise coverage was prioritized over protocol-specified organ at risk (OAR) dose constraints with a hard limit of <= 105% Rx. Chemotherapy was weekly carboplatin/paclitaxel with 2 cycles of optional consolidation q3wk carboplatin/paclitaxel.
Results: From 5/2015-9/2016, 23 patients enrolled at a single institution. Of 20 evaluable, median age was 66.5 years (range, 54-89) and 12 (60%) were male. Histology was squamous cell in most (n=14, 70%), and 15 (75%) were stage IIIA. Most (n=19, 95%) completed all 3 cycles of concurrent chemotherapy, and 16 (80%) received at least one cycle (2 – 1 cycle, 14 – 2 cycles) of consolidation chemotherapy. Within the 6 mo TITE-CRM assessment window, no SAEs were reported and most patients were treated at the highest dose level. Dose-level assignment was 52.5 Gy (n=2), 56.25 Gy (n=4), and 60 Gy (n=14). The TITE-CRM posterior probability of dose-limiting toxicity for 60 Gy was 5.3% (95% CI, 1-18.1%). Select acute (<=6 mo) non-heme AEs not categorized as SAEs included G2 esophagitis (n=2, 10%), G2 dysphagia (n=5, 25%), and G2 pneumonitis (n=1, 5%). At a median follow-up of 17.6 mo for all and 22.4 mo for living patients, late (> 6 mo) AEs included G2 dysphagia (n=1, 5%), G2/3 pneumonitis (n=2, 10%), G2/3 vocal cord paralysis (n=2, 10%), G2 pericardial effusion (n=1, 5%), G2 pleural effusion (n=1, 5%), G2 chest wall pain (n=1, 5%), G2 bronchopleural fistula (n=1, 5%, 22 mo), and G3 pleurocutaneous fistula (n=1, 5%, 27 mo). Median overall survival was 27.4 mo. 2-year local, regional, and distant control was 93.3%, 77.1%, and 74.1%, respectively.
Conclusion: Accelerated hypofractionated proton therapy and chemotherapy is well tolerated, with high rates of locoregional control and overall survival. Two patients developed late non-life threatening fistulas. Data from this trial will further inform OAR dose limits for hypofractionated RT.
Author Disclosure: C.G. Robinson: Research Grant; Varian Medical Systems, Elekta. Speaker's Bureau; Varian Medical Systems, DFINE. Advisory Board; Radialogica. Stock Options; Radialogica. J. Contreras: None. T.A. DeWees: Consultant; Traxxsson. S. Jenkins: None. S. Waqar: None. R. Govindan: Consultant; Boehringer, GSK, Pfizer, Merck, Bayer, Covidien, BMS, Genentech, Mallinckrodt. Chair; IASLC. Co-Chair; TCGA. M.Q. Baggstrom: Employee; St. Alexius Hospital. D. Morgensztern: Honoraria; Boerhimger, Celgene. D. Przybysz: None. M.C. Roach: Travel Expenses; BTG, Varian, Elekta.