Abstract Although salvage external-beam radiation therapy (EBRT) is an attractive treatment option for pelvic lymph nodal recurrence (PeNR) in patients with prostate cancer (PCa), limited data are available regarding its long-term efficacy. This study examined the long-term clinical outcomes of patients who underwent salvage pelvic radiation therapy (sPRT) for oligo-recurrent pelvic lymph nodes after definitive EBRT for non-metastatic PCa. Patients who developed PeNR after definitive EBRT and were subsequently treated with sPRT at our institution between November 2007 and December 2015 were retrospectively analyzed. The prescribed dose was 45–50.4 Gy (1.8–2 Gy per fraction) to the upper pelvis, with up to 54–66 Gy (1.8–2 Gy per fraction) for recurrent nodes. Long-term hormonal therapy was used as neoadjuvant and/or adjuvant therapy. The study population consisted of 12 consecutive patients with PeNR after definitive EBRT (median age: 73 years). The median follow-up period was 58.9 months. The 5-year overall survival, PCa-specific survival, biochemical failure-free, clinical failure-free, and castration-resistant PCa-free rates were 82.5, 100.0, 62.3, 81.8, and 81.8%, respectively. No grade 2 or higher sPRT-related late toxicities occurred. In conclusion, more than half of the study patients treated with sPRT had a long-term disease-free status with acceptable morbidities. Moreover, most of the patients maintained hormonal sensitivity. Therefore, this approach may be a promising treatment method for oligo-recurrent pelvic lymph nodes.

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Background Although immune checkpoint inhibitors (ICIs) are promising in the treatment of advanced cancer, their use is associated with immune-related adverse events (irAEs) that affect endocrine organ systems. Although development of irAEs was associated with improved cancer-specific survival, the risk of irAEs is unclear. We investigated the association of pre-ICI comorbidities—including diabetes—with irAEs, overall survival (OS), and progression-free survival (PFS) in advanced lung cancer. Methods Patients with lung cancer who were treated with ICIs during the period from September 1, 2015 through July 31, 2018 were retrospectively enrolled. All data were collected from the NEPTUNE database of university patients. Hazard ratios were estimated by using Cox regression weighted for propensity scores. Odds ratios were calculated by logistic regression and adjusted for unbalanced variables. The Kaplan–Meier method was used to compare OS, and the generalized Wilcoxon test was used to compare median survival. Results Among the 88 patients identified, 22 (25.0%) had diabetes (DM) before ICI treatment and 57 (75.0%) did not (non-DM); irAEs developed in 12.2% of patients with DM and in 9.1% of patients in non-DM (p=0.87). Diabetes status was not associated with irAE risk in relation to baseline characteristics (age, sex, TNM staging, thyroid and renal function) or in propensity score–matched analysis (age, TNM staging). During a mean follow-up of 30 months, OS and cancer-specific PFS were significantly higher in patients who developed irAEs (Kaplan–Meier estimates, p=0·04 and 0·03, respectively). In propensity score–matched analysis, diabetes was significantly associated with lower OS (multivariate hazard ratio, 0·36; 95% CI, 0·13–0·98) unrelated to irAEs. Irrespective of irAEs, PFS was also lower among patients with DM than among non-DM patients (Kaplan–Meier estimate, p=0·04). Conclusion Pre-existing diabetes was associated with higher mortality in advanced lung cancer, regardless of irAE development during treatment with ICI.

The effects of irradiation on tumor tissue and the host immune system are interrelated. The antitumor effect of irradiation is attenuated in the immunocompromised hosts. In addition, radiation alone positively and negatively influences the host immune system. The positive effects of radiation are summarized by the ability to help induce and enhance tumor-antigen-specific immune responses. The cancer-immunity cycle is a multistep framework that illustrates how the tumor-antigen-specific immune responses are induced and how the induced antigen-specific immune cells exert their functions in tumor tissues. Irradiation affects each step of this cancer-immunity cycle, primarily in a positive manner. In contrast, radiation also has negative effects on the immune system. The first is that irradiation has the possibility to kill irradiated effector immune cells. The second is that irradiation upregulates immunosuppressive molecules in the tumor microenvironment, whereas the third is that irradiation to the tumor condenses immunosuppressor cells in the tumor microenvironment. When used in conjunction with radiotherapy, immune checkpoint inhibitors can further leverage the positive effects of radiation on the immune system and compensate for the negative effects of irradiation, which supports the rationale for the combination of radiotherapy and immune checkpoint inhibitors. In this review, we summarize the preclinical evidence for the reciprocal effects of radiation exposure and the immune system, and up-front topics of the combination therapy of immune checkpoint inhibitors and radiotherapy.

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