Image-Guided Hypofractionated Proton Therapy in Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Study.

PURPOSE: Due to the excellent outcomes with image-guided stereotactic body radiotherapy for patients with early-stage non-small cell lung cancer (NSCLC) and the low treatment-related toxicities using proton therapy (PT), we investigated treatment outcomes and toxicities when delivering hypofractionated PT. MATERIALS AND METHODS: Between 2009 and 2018, 22 patients with T1 to T2 N0M0 NSCLC (45% T1, 55% T2) received image-guided hypofractionated PT. The median age at diagnosis was 72 years (range, 58-90). Patients underwent 4-dimensional computed tomography simulation following fiducial marker placement, and daily image guidance was performed. Nine patients (41%) were treated with 48 GyRBE in 4 fractions for peripheral lesions, and 13 patients (59%) were treated with 60 GyRBE in 10 fractions for central lesions. Patients were assessed for CTCAEv4 toxicities with computed tomography imaging for tumor assessment. The primary endpoint was grade 3 to 5 toxicity at 1 year. RESULTS: The median follow-up for all patients was 3.5 years (range, 0.2-8.8 years). The overall survival rates at 3 and 5 years were 81% and 49%, respectively. Cause-specific survival rates at 3 and 5 years were 100% and 75%, respectively. The 3-year local, regional, and distant control rates were 86%, 85%, and 95%, respectively. Four patients experienced in-field recurrences between 18 and 45 months after treatment. One patient (5%) developed a late grade 3 bronchial stricture requiring hospitalization and stent. CONCLUSION: Image-guided hypofractionated PT for early-stage NSCLC provides promising local control and long-term survival with a low likelihood of toxicity. Regional nodal and distant relapses remain a problem.

Image-guided hypofractionated double-scattering proton therapy in the management of centrally-located early-stage non-small cell lung cancer.

BACKGROUND: The treatment of centrally-located early-stage non-small cell lung cancer (NSCLC) with image-guided stereotactic body radiotherapy (SBRT) is challenging due to the proximity of critical normal structures to the tumor target. The purpose of this study was to report the results of our experience in treating centrally-located early-stage NSCLC with hypofractionated proton therapy (PT). MATERIAL AND METHODS: Between 2009 and 2018, 23 patients with T1-T2N0M0 NSCLC (T1, 46%; T2, 54%) were treated with image-guided hypofractionated double-scattering PT. The median age at the time of treatment was 74 years (range, 58-88). Patients underwent 4-dimensional computed tomography (CT) simulation following fiducial marker placement, and daily image guidance was performed. All patients were treated with 60 GyRBE in 10 fractions. Patients were assessed for CTCAEv4 toxicities weekly during treatment, and at regular follow-up intervals with CT imaging for tumor assessment. Overall survival, cause-specific survival, local control, regional control, and metastases-free survival were evaluated using cumulative incidence with competing risks. RESULTS: Median follow-up for all patients was 3.2 years (range, 0.2-9.2 years). Overall survival rates at 3 and 5 years were 81% and 50% (95% CI, 27-79%), respectively. Cause-specific survival rates at 3 and 5 years were 81% and 71% (95% CI, 46-92%). The 3-year local, regional, and distant control rates were 90%, 81%, and 87%, respectively. Three patients (13%) experienced local recurrences as their first recurrence, at a median time of 28 months from completion of radiation (range, 18-61 months). Two patients (9%) experienced late grade 3 toxicities, including 1 patient who developed a bronchial stricture that required stent placement. CONCLUSION: Image-guided hypofractionated PT for centrally-located early-stage NSCLC provides excellent local control with low rates of grade ≥3 toxicities. For tumors in sensitive locations, PT may provide safer treatment than photon-based treatments due to its dosimetric advantages.

Pulmonary Function after Proton Therapy for Hodgkin Lymphoma.

PURPOSE: Acute and late toxicity from chemotherapy, targeted therapy, and radiation therapy can cause significant morbidity among survivors of Hodgkin lymphoma (HL), including pulmonary dysfunction. Improved dosimetry may influence pulmonary function tests (PFTs), an objective and clinically significant measure of pulmonary toxicity. The present study investigates the impact of proton therapy on PFTs among HL survivors. PATIENTS AND METHODS: We monitored 15 patients with mediastinal HL who were enrolled in an institutional HL trial. All patients were treated with combination chemotherapy plus involved-node proton therapy. All patients were to undergo PFTs before starting treatment and at approximately 6 and 12 months after completing proton therapy. RESULTS: Twelve patients were included in the analysis and 3 excluded. The mean forced vital capacity (FVC) was 96.2% ± 16.5% (mean ± SD) predicted at baseline and 98.2% ± 19.4% predicted at 12 months. The mean forced expiratory volume in 1 second (FEV1) was 96.7% ± 17.2% predicted at baseline and 97% ± 15.1% predicted at 12 months. The mean FEV1/FVC ratio was 99.5 ± 8.29 at baseline and 97.8 ± 8.02 at 12 months. The mean diffusing capacity of the lung for carbon monoxide was 81.4% ± 18.4% predicted at baseline and 95.7% ± 23.5% predicted at 12 months. CONCLUSION: No unexpected changes were observed to the lungs as illustrated through follow-up PFTs. Long-term follow-up and validation in a larger cohort are needed.

A Large Pleural Effusion following Abdominal Aortic Surgery.

Chylous ascites and coexistent chylothorax is a rare but important complication following retroperitoneal abdominal surgery. We report a 70-year-old male who developed gradual abdominal distension, chest tightness, and dyspnea five months after having an uncomplicated aortobifemoral bypass performed. Physical examination was consistent with a large right sided effusion and ascites which were confirmed by computed tomography. Thoracentesis yielded an opaque milky fluid with analysis consistent with a chylothorax with a paracentesis revealing fluid that was similar in both appearance and biochemistry. The patient failed initial conservative management so a chest tube was placed followed by chemical pleurodesis. We review the literature of the pathophysiology and treatment approach to such a pleural effusion.