Efficacy and cost of high-frequency IGRT in elderly stage III non-small-cell lung cancer patients.

BACKGROUND: High-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC). METHODS: We selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods. RESULTS: Of the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86-1.09), ETFS (HR 1.05; 95% CI 0.93-1.18), CSS (HR 0.94; 95% CI 0.84-1.04), or OS (HR 0.95; 95% CI 0.87-1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively. CONCLUSION: hfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost. hfIGRT deserves further scrutiny through a randomized controlled trial.

Increased rates of immunosuppressive treatment and hospitalization after checkpoint inhibitor therapy in cancer patients with autoimmune disease.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are important new therapeutic options for the treatment of malignancy. Existing data on the relative safety of ICI treatment in patients with pre-existing autoimmune disease (AID) are limited. METHODS: In this retrospective study utilizing an oncology medical claims database, we determined the rates of treatment with immunosuppressive agents and hospitalization within 180 days of treatment with ICIs (pembrolizumab, nivolumab, and ipilimumab) in patients both with and without AID. Patients had diagnoses of either malignant melanoma or lung cancer. Immunosuppressive agents evaluated included oral prednisone and intravenous methylprednisolone. RESULTS: 124 cancer patients with AID and 1896 cancer patients without AID met inclusion criteria for oral prednisone analysis, while 284 patients with AID and 3230 patients without AID met inclusion criteria for all other analyzes. Following treatment with PD-1 inhibitors, rates of treatment with both oral prednisone and intravenous methylprednisolone within 180 days of ICI treatment were significantly increased in the AID group relative to the control group (oral prednisone: 16.7% treatment in AID vs 8.3% in non-AID, p=0.0048; intravenous methylprednisolone: 8.4% treatment in AID vs 3.7% in non-AID, p=0.0012). Rates of hospitalization were significantly increased in melanoma patients with AID relative to melanoma patients without AID following treatment with PD-1 inhibitors (24.1% in AID vs 5.8% in non-AID, p<0.0001). CONCLUSION: Cancer patients with AID have higher rates of hospitalization and treatment with immunosuppressive agents following treatment with ICI therapy compared with patients with no AID. This suggests that patients with AID may have increased toxicity risk while being treated with checkpoint inhibitor therapy. Further prospective clinical trials are needed to determine safety.

Effects of ß-Adrenergic Antagonists on Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: Locally advanced non-small cell lung cancer (NSCLC) is highly resistant to chemoradiotherapy, and many cancer patients experience chronic stress. Studies that suggest stimulation of ß-adrenergic receptors (ß-AR) promotes tumor invasion and therapy resistance. We investigated whether ß-AR inhibition with beta-blockers acts as a chemotherapy and radiation sensitizer in vitro and in patients treated with chemoradiation for locally advanced NSCLC. METHODS: We investigated the effects of the non-selective beta-blocker propranolol on two human lung adenocarcinoma cell lines (PC9, A549) treated with radiation or cisplatin. We retrospectively evaluated 77 patients with Stage IIIA NSCLC who received induction chemoradiation followed by surgery. Pathological and imaging response, metastatic rate, and survival were analyzed using SPSS v22.0 and PrismGraphpad6. RESULTS: Propranolol combined with radiation or cisplatin decreased clonogenic survival of PC9 and A549 cells in vitro (p < 0.05). Furthermore, propranolol decreased expression of phospho-protein kinase A (p-PKA), a ß-adrenergic pathway downstream activation target, in both cell lines compared to irradiation or cisplatin alone (p < 0.05). In patients treated for Stage IIIA NSCLC, 16 took beta-blockers, and 61 did not. Beta-blockade is associated with a trend to improved overall survival (OS) at 1 year (81.3% vs 57.4%, p = 0.08) and distant metastasis-free survival (DMFS) (2.6 years vs. 1.3 years, p = 0.16). Although beta-blocker use was associated with decreased distant metastases (risk ratio (RR) 0.19; p = 0.03), it did not affect primary tumor pathological response (p = 0.40) or imaging response (p = 0.36). CONCLUSIONS: ß-AR blockade enhanced radiation and cisplatin sensitivity of human lung cancer cells in vitro. Use of beta-blockers is associated with decreased distant metastases and potentially improved OS and DMFS. Additional studies are warranted to evaluate the role of beta-blockers as a chemoradiation sensitizer in locally advanced NSCLC.

Impact of estrogen monotherapy on survival in women with stage III-IV non-small cell lung cancer.

OBJECTIVES: Women with lung cancer have better survival than men. The reasons are unknown, but estrogen is hypothesized to improve survival. Our objective was to examine the association between estrogen monotherapy and cancer-specific and overall survival in elderly women with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We used the SEER-Medicare database to identify women ≥65 years old who were diagnosed with stage III or IV NSCLC. Estrogen monotherapy (EM) was defined as at least one estrogen claim without any progesterone claims 6 months prior to diagnosis. To assess cancer-specific survival and overall survival, we used Kaplan-Meier and multivariate Cox modeling with propensity score adjustments. As an exploratory analysis, we also examined the effect of combined estrogen and progesterone hormonal therapy on survival using Cox modeling. RESULTS: We identified 6958 women in our initial cohort: 283 used EM (4%) and 6675 (96%) did not. The median follow-up time was 46.5 months in the EM patients and 49.5 months in the non-EM patients. In a Kaplan-Meier analysis, median overall survival was 8.2 months in patients who receive EM and 6.2 months in those who did not (p = 0.004). In our 1:4 propensity-matched cohort, median follow-up was 46.5 in the EM group and 50.6 in the non-EM group; median overall survival was 8.0 months in the EM group and 6.4 months in the non-EM group (p = 0.02). In a multivariate Cox regression of the matched cohort, EM was significantly associated with overall survival (HR 0.84; 95% CI 0.73 - 0.97). All results were similar for cancer-specific survival. In our exploratory analysis, combined Estrogen-Progesterone did significantly impact overall survival (HR 0.84; 95% CI 0.71-0.99, p = 0.04) but did not appear to effect cancer-specific survival (HR 0.91; 95% CI 0.77-1.09, p = 0.30). CONCLUSION: EM was associated with a significant improvement in cancer-specific survival and overall survival in women with late stage NSCLC.

Survival Benefit of Adjuvant Radiation Therapy in Node-positive Vulvar Cancer.

BACKGROUND: Adjuvant radiation therapy improves overall survival in patients with vulvar cancer with 2+ positive lymph nodes, but its benefit remains uncertain for 1 positive lymph node. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified node-positive, American Joint Committee on Cancer version 6-staged women with squamous cell vulvar carcinoma treated with and without radiation following surgery. The Kaplan-Meier approach assessed overall and cause-specific survival. Propensity score-based, multiply imputed Cox modeling accounted for missing data and selection bias. RESULTS: From 2004 to 2013, 488 versus 206 women did and did not receive adjuvant radiation after surgery. Patient characteristics were well balanced, including home county, index tumor diameter, number of nodes excised, provider type, race, and surgery type (P>0.05). Unbalanced covariates-including median age, grade, number of positive nodes, N-stage-were adjusted using Cox regression. At a median follow-up of 36 months, adjuvant radiation was associated with improved median overall survival across all node-positive patients (54 vs. 24 mo; P<0.01). This survival benefit persisted in women with just one (not reached vs. 39 mo; P<0.01) and 2+ (26 vs. 16 mo; P<0.01) positive lymph nodes. Likewise, all node-positive groups saw a cause-specific survival benefit with adjuvant radiation (all P<0.02). On multivariable Cox regression, adjuvant radiation, age, tumor diameter, number of positive nodes, race, and N-stage associated with survival (P<0.05). CONCLUSIONS: All node positive vulvar cancer patients should benefit from and thus should receive adjuvant radiation, including those with one positive node.

Glenoid component loosening associated with increased critical shoulder angle at midterm follow-up.

BACKGROUND: Glenoid component loosening is a common failure mode of total shoulder arthroplasty (TSA). A larger critical shoulder angle (CSA) may cause superior glenoid component loading and more rapid component loosening. The purpose of this study was to define the relationship between the CSA and glenoid component loosening in midterm follow-up after TSA. METHODS: We conducted a retrospective study of 61 primary TSAs for osteoarthritis with an average follow-up of 5.0 ± 2.2 years without surgical revision. Standard true anteroposterior radiographs postoperatively and at longest follow-up were graded in a blinded and repetitive nature for pegged glenoid radiolucent lines and measured for the CSA. An "at-risk" glenoid was defined as grade 3 or higher lucency. RESULTS: The average CSA was 32° ± 5°, median midterm lucency grade was 2 (range, 0-5), and median progression of lucency grade was 1 (range, -1 to 4). At midterm follow-up, 20% of TSAs were grade 3 or higher mean glenoid lucency, with an average CSA of 36°. There was a statistically significant correlation between CSA and both glenoid lucency grade (odds ratio, 1.20 per degree CSA) and progression of lucency grade (odds ratio, 1.24). An increase in CSA of 10° was associated with a 6.2-fold increased odds of having an at-risk glenoid. CONCLUSION: This study identifies the CSA as a risk factor for glenoid component loosening after TSA. Our findings suggest that the CSA may be a modifiable factor during surgery to improve glenoid component outcomes.