Stereotactic Body Radiation Therapy for Central Early-Stage NSCLC: Results of a Prospective Phase I/II Trial.

INTRODUCTION: We report results from a prospective phase I/II trial for patients with centrally located, early-stage NSCLC receiving stereotactic body radiation therapy. METHODS: Eligible patients were medically inoperable with biopsy-proven NSCLC within 2 cm of the proximal bronchial tree or 5 mm of the mediastinal pleura or parietal pericardium. Phase I had four dose levels using 5 fractions: 9, 10, 11, and 12 Gy per fraction. The primary phase II objective was to determine if the maximum tolerated dose in phase I achieved local control greater than 80% at 2 years. RESULTS: Seventy-four patients were enrolled; 23 to phase I and 51 to phase II. Two phase I patients treated with 10 Gy × 5 fractions developed unrelated acute grade 3 lung toxicities which resolved. The phase II dose level selected was 11 Gy × 5 fractions. The median follow-up for living phase II patients was 27 months (range, 9 to 58 months). Two-year local control using 11 Gy × 5 fractions was 85% (95% confidence interval [CI]: 62%-95%). Two-year overall survival was 43% (95% CI: 28%-57%). Three patients (6%, 95% CI: 1%-17%) experienced acute grade 3 and 4 cardiac or pulmonary toxicities. Of the 41 patients evaluable for late cardiac and pulmonary toxicity, 11 (27%, 95% CI: 14%-43%) developed grade 3, 5 (12%, 95% CI: 4%-26%) developed grade 4, and 1 (4%, 95% CI: 0%-13%) died of grade 5 toxicity. CONCLUSION: Stereotactic body radiation therapy for central NSCLC using 11 Gy × 5 fractions is tolerable and has excellent local control, but is associated severe late toxicity in some patients.

In Silico Trial of MR-Guided Midtreatment Adaptive Planning for Hypofractionated Stereotactic Radiation Therapy in Centrally Located Thoracic Tumors.

PURPOSE: Hypofractionated (>5 fraction) stereotactic radiation therapy (HSRT) may allow for ablative biologically equivalent dose to tumors with a lower risk of organ-at-risk (OAR) toxicity in central thoracic tumors. Adaptive planning may further improve OAR sparing while maintaining planning target volume (PTV) coverage. We hypothesized that midtreatment adaptive replanning would offer dosimetric advantages during HSRT for central thorax malignancies using magnetic resonance imaging (MRI)-guided radiation therapy. METHODS AND MATERIALS: Twelve patients with central thorax tumors received HSRT using MRI-guided radiation therapy. Clinically delivered regimens were 60 Gy in 12 fractions or 62.5 Gy in 10 fractions, with low-field magnetic resonance (0.35 T) volumetric setup imaging acquired at each fraction. Daily gross tumor volume (GTV) and OARs were retrospectively redefined on fraction 1, 6, and 10 MRIs, and GTV response was recorded. Simulated initial plans prescribed a dose of 60 Gy in 12 fractions based on fraction 1 MRI. Midtreatment adaptive plans were created based on fraction 6 anatomy-of-the-day. All plans were created using an isotoxicity approach with a goal of 95% PTV coverage, subject to hard OAR constraints, to represent clinically ideal OAR sparing. Plans were then compared for projected OAR sparing and PTV coverage. RESULTS: Patients demonstrated significant on-treatment MRI-defined GTV reduction (median 41.8%; range 16.7%-65.7%). At fraction 6, median reduction was 26.7%. All initial plans met OAR constraints. Initial plan application to fraction 6 and fraction 10 anatomy resulted in 8 OAR violations (5 of 13 patients) and 10 OAR violations (6 of 13 patients). All fraction 6 violations persisted at fraction 10. Midpoint adaptive planning reversed 100% of midpoint OAR violations and tended to reduce the magnitude of OAR violations incurred at fraction 10. In 40% of fractions (2 of 5) in which OAR violation resulted from initial plan application to fraction 6 anatomy, PTV coverage was increased concomitant with violation reversal. CONCLUSIONS: Midtreatment adaptive planning based on tumor response may be dosimetrically advantageous for sparing of surrounding critical structures in HSRT for central thorax malignancies and could be applied using either an online or offline paradigm.

Treatment Patterns and Overall Survival Outcomes of Octogenarians with Muscle Invasive Cancer of the Bladder: An Analysis of the National Cancer Database.

PURPOSE: Elderly patients with muscle invasive bladder cancer can pose a therapeutic dilemma, given multiple comorbidities which may preclude surgery. In this registry based analysis we investigated treatment patterns and survival outcomes in this group of patients. MATERIALS AND METHODS: We queried the National Cancer Database for muscle invasive (cT2-T4aN0M0) bladder cancer in patients 80 years old or older who were diagnosed from 2004 to 2013. Patients included in study underwent transurethral resection of bladder tumor followed by radical cystectomy, radical cystectomy plus chemotherapy, radiation therapy alone, chemotherapy alone, chemoradiation or no treatment. We performed Kaplan-Meier, log rank and multivariate Cox proportional hazards regression and propensity score matching. RESULTS: A total of 9,270 patients were identified with a median followup of 12.8 months. Median overall survival in patients treated with radical cystectomy alone was 23.2 months (95% CI 19.8-26.6), which was superior to that of chemotherapy alone or radiation therapy alone (p <0.0001). Those treated with chemoradiation had a median overall survival of 27.3 months (95% CI 25.0-29.7), which did not statistically differ from that of radical cystectomy alone (p = 0.39). Surgery plus chemotherapy showed the longest median overall survival of 34.5 months (95% CI 22.2-46.7, vs chemoradiation and radical cystectomy alone p <0.0001). On multivariate analysis and propensity score matching the best overall survival was seen in patients treated with surgery plus chemotherapy and there was no difference in overall survival between chemoradiation and radical cystectomy alone. CONCLUSIONS: In elderly patients with muscle invasive bladder cancer chemoradiation is an alternative definitive treatment strategy with survival equal to that of surgery alone and superior to that of chemotherapy alone or radiation therapy alone. If a patient was able to receive neoadjuvant or adjuvant chemotherapy with surgery, additional survival was observed in this nonrandomized study.