The Impact of Serum Glucose, Anti-Diabetic Agents, and Statin Usage in Non-Small Cell Lung Cancer Patients Treated With Definitive Chemoradiation

Introduction: Epidemiologic data indicate diabetes confers an augmented risk of lung cancer development, yet the relationship between hyperglycemia, metabolic agents, and prognosis is unclear. We analyzed the impact of hyperglycemia, anti-diabetic agents, and statins on outcomes in non-small cell lung cancer (NSCLC) patients undergoing chemoradiation. Method and Materials: In total, data from 170 patients with stage III NSCLC treated at the University of Pittsburgh Medical Center between 2001 and 2014 were obtained for analysis. Kaplan-Meier survival analysis was used to estimate time-to-event for overall survival (OS), disease-free survival, distant metastasis (DM), and loco-regional control (LRC). Blood glucose values (n = 2870), statins, and diabetic medications were assessed both continuously and categorically in univariable and multivariable Cox proportional hazard regression models to estimate hazard ratios and identify prognostic factors. Results: Tumor volume was a negative prognostic factor for OS, disease-free survival, DM, and LRC (p = 0.001). Tumor stage and treatment time were associated with increased all-cause mortality. Any glucose measurement ≥ 130 mg/dl during treatment (2-year estimate 49.9 vs. 65.8%, p = 0.095) was borderline significant for decreased LRC, with similar trends on multivariable analysis (HR 1.636, p = 0.126) and for OS (HR 1.476, p = 0.130). Statin usage was associated with improved 2-year LRC (53.4 vs. 62.4%, p = 0.088) but not with improvements in survival. Other glycemic parameters, comorbid diabetes diagnosis, or anti-diabetic medications were not significantly associated with outcomes. Conclusions: There were trends for blood glucose value over 130 mg/dl and statin nonuse being associated with inferior prognosis for LRC in stage III NSCLC patients; glycemic state, statin usage, and glucose-modulating medications were not associated with survival outcomes in multivariable analysis in this retrospective database

The Impact of Serum Glucose, Anti-Diabetic Agents, and Statin Usage in Non-small Cell Lung Cancer Patients Treated With Definitive Chemoradiation

Introduction: Epidemiologic data indicate diabetes confers an augmented risk of lung cancer development, yet the relationship between hyperglycemia, metabolic agents, and prognosis is unclear. We analyzed the impact of hyperglycemia, anti-diabetic agents, and statins on outcomes in non-small cell lung cancer (NSCLC) patients undergoing chemoradiation.Method and Materials: In total, data from 170 patients with stage III NSCLC treated at the University of Pittsburgh Medical Center between 2001 and 2014 were obtained for analysis. Kaplan-Meier survival analysis was used to estimate time-to-event for overall survival (OS), disease-free survival, distant metastasis (DM), and loco-regional control (LRC). Blood glucose values (n = 2870), statins, and diabetic medications were assessed both continuously and categorically in univariable and multivariable Cox proportional hazard regression models to estimate hazard ratios and identify prognostic factors.Results: Tumor volume was a negative prognostic factor for OS, disease-free survival, DM, and LRC (p = 0.001). Tumor stage and treatment time were associated with increased all-cause mortality. Any glucose measurement ≥ 130 mg/dl during treatment (2-year estimate 49.9 vs. 65.8%, p = 0.095) was borderline significant for decreased LRC, with similar trends on multivariable analysis (HR 1.636, p = 0.126) and for OS (HR 1.476, p = 0.130). Statin usage was associated with improved 2-year LRC (53.4 vs. 62.4%, p = 0.088) but not with improvements in survival. Other glycemic parameters, comorbid diabetes diagnosis, or anti-diabetic medications were not significantly associated with outcomes.Conclusions: There were trends for blood glucose value over 130 mg/dl and statin nonuse being associated with inferior prognosis for LRC in stage III NSCLC patients; glycemic state, statin usage, and glucose-modulating medications were not associated with survival outcomes in multivariable analysis in this retrospective database

One- vs. Three-Fraction Pancreatic Stereotactic Body Radiation Therapy for Pancreatic Carcinoma: Single Institution Retrospective Review

Background/introductionEarly reports of stereotactic body radiation therapy (SBRT) for pancreatic ductal adenocarcinoma (PDAC) used single fraction, but eventually shifted to multifraction regimens. We conducted a single institution review of our patients treated with single- or multifraction SBRT to determine whether any outcome differences existed.Methods and materialsPatients treated with SBRT in any setting for PDAC at our facility were included, from 2004 to 2014. Overall survival (OS), local control (LC), regional control (RC), distant metastasis (DM), and late grade 3 or greater radiation toxicities from the time of SBRT were calculated using Kaplan–Meier estimation to either the date of last follow-up/death or local/regional/distant failure.ResultsWe identified 289 patients (291 lesions) with pathologically confirmed PDAC. Median age was 69 (range, 33–90) years. Median gross tumor volume was 12.3 (8.6–21.3) cm3 and planning target volume 17.9 (12–27) cm3. Single fraction was used in 90 (30.9%) and multifraction in 201 (69.1%) lesions. At a median follow-up of 17.3 months (IQR 10.1–29.3 months), the median survival for the entire cohort 17.8 months with a 2-year OS of 35.3%. Univariate analysis showed multifraction schemes to have a higher 2-year OS 30.5% vs. 37.5% (p = 0.019), it did not hold significance on MVA. Multifractionation schemes were found to have a higher LC on MVA (HR = 0.53, 95% CI, 0.33–0.85, p = 0.009). At 2 years, late grade 3+ toxicity was 2.5%. Post-SBRT CA19-9 was found on MVA to be a prognostic factor for OS (HR = 1.01, 95% CI, 1.01–1.01, p = 0.009), RC (HR = 1.01, 95% CI 1.01–1.01, p = 0.02), and DM (HR = 1.01, 95% CI, 1.01–1.01, p = 0.001).ConclusionOur single institution retrospective review is the largest to date comparing single and multifraction SBRT and the first to show multifraction regimen SBRT to have a higher LC than single fractionation. Additionally, we show low rates of severe late toxicity with SBRT

MRI-guided high-dose-rate intracavitary brachytherapy for treatment of cervical cancer: the University of Pittsburgh experience

Image-based brachytherapy is increasingly used for gynecologic malignancies. We report early outcomes of magnetic resonance imaging (MRI)-guided brachytherapy. Consecutive patient cases with FIGO stage IB1 to IVA cervical cancer treated at a single institution were retrospectively reviewed. All patients received concurrent cisplatin with external beam radiation therapy along with interdigitated high-dose-rate intracavitary brachytherapy. Computed tomography or MRI was completed after each application, the latter acquired for at least 1 fraction. High-risk clinical target volume (HRCTV) and organs at risk were identified by Groupe Européen de Curiethérapie and European SocieTy for Radiotherapy and Oncology guidelines. Doses were converted to equivalent 2-Gy doses (EQD2) with planned HRCTV doses of 75 to 85 Gy. From 2007 to 2013, 128 patients, median 52 years of age, were treated. Predominant characteristics included stage IIB disease (58.6%) with a median tumor size of 5 cm, squamous histology (82.8%), and no radiographic nodal involvement (53.1%). Most patients (67.2%) received intensity modulated radiation therapy (IMRT) at a median dose of 45 Gy, followed by a median brachytherapy dose of 27.5 Gy (range, 25-30 Gy) in 5 fractions. At a median follow up of 24.4 months (range, 2.1-77.2 months), estimated 2-year local control, disease-free survival, and cancer-specific survival rates were 91.6%, 81.8%, and 87.6%, respectively. Predictors of local failure included adenocarcinoma histology (P<.01) and clinical response at 3 months (P<.01). Among the adenocarcinoma subset, receiving HRCTV D90 EQD2 ≥84 Gy was associated with improved local control (2-year local control rate 100% vs 54.5%, P=.03). Grade 3 or greater gastrointestinal or genitourinary late toxicity occurred at a 2-year actuarial rate of 0.9%. This study constitutes one of the largest reported series of MRI-guided brachytherapy in North America, demonstrating excellent local control with acceptable morbidity. Dose escalation may be warranted when feasible for adenocarcinomas to offset the risk of local failure