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

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

BackgroundHigh-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).MethodsWe 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.ResultsOf 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 ConclusionhfIGRT 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

Effects of β-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 β-adrenergic receptors (β-AR) promotes tumor invasion and therapy resistance. We investigated whether β-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 β-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: β-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