Michael J. Dohopolski

Stereotactic body radiotherapy for locally-advanced unresectable pancreatic cancer—patterns of care and overall survival

Background Unresectable pancreatic cancer remains a challenging disease to treat. Stereotactic body radiotherapy (SBRT) allows for a higher biologically equivalent dose in an abbreviated course more convenient for patients and the integration of systemic therapy. We sought to investigate utilization trends and survival outcomes for patients treated with pancreatic SBRT versus conventionally fractionated radiotherapy (CFRT). Methods We engaged the National Cancer Database (NCDB) from 1998-2012 and identified locally-advanced unresectable patients with histologically confirmed, non-metastatic, pancreatic adenocarcinoma who received radiotherapy. Patients who received CFRT (1.5-4.0 Gy per fraction to a dose of ≥45 Gy, n=11,879) were compared to those who received SBRT (6-15 Gy per fraction to a dose of ≥20 Gy, n=474). Results Median follow-up was 11.0 months (18.4 months for survivors). SBRT utilization increased from 0.2% to 7.4% from 1998 to 2012 (P<0.05). On multivariable analysis, factors predictive for preferential utilization of SBRT over CFRT were later year of diagnosis, age ≥75 years, increased facility volume, and no chemotherapy in the initial treatment plan. Unadjusted median survival was 11.2 months for CFRT vs. 12.6 months for SBRT (P=0.002). Results were consistent in the propensity matched model. Variables predictive for improved survival on multivariable analysis were diagnosis after 2010, younger age, lower comorbidity score, tumor size <3 cm, nodal stage zero, and receipt of chemotherapy (P<0.05). Conclusions SBRT utilization has increased significantly and is associated with a small absolute improvement in overall survival (OS) compared to CFRT. The decreased treatment time, without apparent compromise in survival, makes SBRT an attractive option for patients with unresectable pancreatic cancer warranting further research.

Stereotactic Body Radiation Therapy for Pulmonary Oligometastases Arising from Non-lung Primaries in Patients Without Extrapulmonary Disease

Purpose Stereotactic body radiation therapy (SBRT) is increasingly used in the management of patients with oligometastatic cancers and is under prospective evaluation by the Radiation Therapy Oncology Group (RTOG). Here we report outcomes from a high-volume institution of patients treated with SBRT for pulmonary oligometastases. Materials and methods We conducted a retrospective review of 105 patients who had one to five pulmonary oligometastases (185 lesions) without extrapulmonary disease treated with SBRT from 2002-2014. Target failure-free survival (TFFS), progression-free survival (PFS), and overall survival (OS) were calculated. Univariate and multivariate Cox regression analyses were performed on factors predictive of outcomes. Results The median age at first SBRT was 68 years and the median follow-up was 29.5 months. The median time from initial diagnosis of primary to SBRT was 42.7 months; 14.3% had synchronous oligometastases and 76.7% had one to two pulmonary lesions at first SBRT. The distribution of primaries was as follows: 36.2% colorectal, 16.2% head/neck, 9.5% genitourinary, 9.5% sarcoma, 7.6% gynecologic, 6.7% other, 5.7% breast, 5% melanoma, and 4% esophageal. The median lesion size was 1.6 cm and the most common regimen was 60 Gy in three fractions (range: 12-60 Gy in one to five fractions). TFFS was 94.4% and 90.8% at two and three years, respectively. Two and three year OS were 87.9% and 60.2%, respectively. Median PFS and OS were 16.2 and 45.3 months, respectively. In multivariate analysis, age at primary cancer diagnosis and biologically effective dose with an alpha-beta ratio of 10 (BED10) were identified as factors significantly affecting OS (p<0.05). Conclusions Comprehensive treatment of pulmonary oligometastases with SBRT in the absence of extrapulmonary disease results in excellent target control and modest survival outcomes.

Thoracic reirradiation with SBRT for residual/recurrent and new primary NSCLC within or immediately adjacent to a prior high-dose radiation field

PURPOSE Local failure following concurrent chemoradiation and in-lobe failures following stereotactic body radiation therapy (SBRT) are common. We evaluated our institutional experience using SBRT as salvage in this setting. METHODS AND MATERIALS Seventy-two patients were reirradiated with SBRT for residual, locally recurrent, or new primary non-small cell lung cancer within or adjacent to a high-dose external beam radiation therapy or SBRT field. Kaplan-Meier analysis with log-rank test were used to estimate endpoints and differentiate cohorts. RESULTS Median follow-up was 17.9 months. Patients had residual or recurrent disease (54.2%); 45.8% had new lung primaries. Median reirradiated T size was 2.5 cm (range, 0.8-7.8 cm). Median pre-retreatment maximum standardized uptake value (SUVmax) was 7.15 (range, 1.2-37.6). The most common SBRT reirradiation regimen was 48 Gy in 4 fractions (range, 17-60 Gy in 1-5 fractions). Median progression-free survival was 15.2 months, and median overall survival was 20.8 months. Two-year local failure was 21.6%. Patients with SUVmax at reirradiation <7.0 had a 2-year local control of 93.1% versus 61.1% above the median (P < .001). The 2-year rate of distant metastases was 10.4% versus 54.1% in patients treated for a new primary versus residual or recurrent disease (P < .001). Median progression-free survival was 31.9 months versus 8.4 months, respectively (P = .037). Median survival of patients treated for new primary was 25.2 months versus 16.2 months with residual or recurrent disease (P = .049), and median survival for patients with reirradiation SUVmax below the median was 42.0 months versus 9.8 months above the median (P < .001). Acute any-grade toxicity was seen in 29.2% of patients, acute grade 3 toxicity in 11.1%, and late grade 3 toxicity in 1.4% with no treatment-related deaths. CONCLUSIONS SBRT appears to be a safe and effective means of salvaging recurrent, residual, or new primary NSCLC in or adjacent to a previous high-dose radiation field.