Significance of radiation esophagitis:Conditional survival assessment in patients with non-small cell lung cancer

Purpose:This study aimed to examine the effect of radiation esophagitis(RE)and the dynamics of RE on subse-quent survival in non-small cell lung cancer(NSCLC)patients who underwent radiotherapy.Experimental Design:Patients with NSCLC treated with fractionated thoracic radiotherapy enrolled in prospective trials were eligible.RE was graded prospectively according to Common Terminology Criteria for Adverse Events(CTCAE)v3.0 per protocol requirement weekly during-RT and 1 month after RT.This study applied conditional survival assessment which has advantage over traditional survival analysis as it assesses the survival from the event instead of from the baseline.P-value less than 0.05 was considered to be significant.The primary endpoint is overall survival.Results:A total of 177 patients were eligible,with a median follow-up of 5 years.The presence of RE,the maximum RE grade,the evolution of RE and the onset timing of RE events were all correlated with subsequent survival.At all conditional time points,patients first presented with RE grade1(initial RE1)had significant inferior subsequent survival(multivariable HRs median:1.63,all P-values<0.05);meanwhile those with RE progressed had significant inferior subsequent survival than those never develop RE(multivariable HRs median:2.08,all P-values<0.05).Multivariable Cox proportional-hazards analysis showed significantly higher C-indexes for models with inclusion of RE events than those without(all P-values<0.05).Conclusion:This study comprehensively evaluated the impact of RE with conditional survival assessment and demonstrated that RE is associated with inferior survival in NSCLC patients treated with RT.

Tissue-specific Tregs in cancer metastasis:opportunities for precision immunotherapy

Decades of advancements in immuno-oncology have enabled the development of current immunotherapies,which provide longterm treatment responses in certain metastatic cancer patients.However,cures remain infrequent,and most patients ultimately succumb to treatment-refractory metastatic disease.Recent insights suggest that tumors at certain organ sites exhibit distinctive response patterns to immunotherapy and can even reduce antitumor immunity within anatomically distant tumors,suggesting the activation of tissue-specific immune tolerogenic mechanisms in some cases of therapy resistance.Specialized immune cells known as regulatory T cells(Tregs)are present within all tissues in the body and coordinate the suppression of excessive immune activation to curb autoimmunity and maintain immune homeostasis.Despite the high volume of research on Tregs,the findings have failed to reconcile tissue-specific Treg functions in organs,such as tolerance,tissue repair,and regeneration,with their suppression of local and systemic tumor immunity in the context of immunotherapy resistance.To improve the understanding of how the tissue-specific functions of Tregs impact cancer immunotherapy,we review the specialized role of Tregs in clinically common and challenging organ sites of cancer metastasis,highlight research that describes Treg impacts on tissue-specific and systemic immune regulation in the context of immunotherapy,and summarize ongoing work reporting clinically feasible strategies that combine the specific targeting of Tregs with systemic cancer immunotherapy.Improved knowledge of Tregs in the framework of their tissue-specific biology and clinical sites of organ metastasis will enable more precise targeting of immunotherapy and have profound implications for treating patients with metastatic cancer.