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IMPORTANCEThe benefit of internal mammary node irradiation (IMNI) for treatment outcomes in node-positive breast cancer is unknown.OBJECTIVE To investigate whether the inclusion of IMNI in regional nodal irradiation improves disease-free survival (DFS) in women with node-positive breast cancer.

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Background Immunotherapy is currently being examined as a treatment modality for glioblastoma. Maintaining an optimal total lymphocyte count (TLC) after radiotherapy (RT) and using temozolomide may be beneficial in optimizing immunotherapy. However, conventional temozolomide-based chemoradiation is known to induce immunosuppressive effects, including lymphopenia. Therefore, this study aimed to identify potential clinical predictors of acute severe lymphopenia (ASL) in patients receiving chemoradiation for glioblastoma. Methods We identified patients with glioblastoma treated with RT plus temozolomide from 2006 to 2017. ASL was defined as a TLC of < 500/μL within 3 months after initiating RT. Independent predictors of ASL were determined using logistic regression. Results A total of 336 patients were evaluated. Three-dimensional conformal RT (3D-CRT) and intensity-modulated RT (IMRT) were used in 186 (55.4%) and 150 patients (44.6%), respectively. TLC decreased during RT and remained persistently low during the 1-year follow-up, whereas the levels of other blood cell types recovered. In total, 118 patients (35.1%) developed ASL. During a median follow-up of 19.3 months, patients with ASL showed significantly worse overall survival than did those without ASL (median, 18.2 vs. 22.0 months; P = .028). Multivariable analysis revealed that increased planning target volume (PTV) was independently associated with increased ASL incidence (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00–1.03; P = .042), while IMRT was independently associated with decreased ASL incidence (HR, 0.48; 95% CI, 0.27–0.87; P = .015). A propensity-matched comparison showed that the incidence of ASL was lower with IMRT than with 3D-CRT (20% vs. 37%; P = .005). Conclusions IMRT and low PTV were significantly associated with decreased ASL incidence after RT plus temozolomide for glioblastoma. An IMRT-based strategy is necessary to enhance treatment outcomes in the immune-oncology era. Electronic supplementary material The online version of this article (10.1186/s13014-019-1256-6) contains supplementary material, which is available to authorized users.

Purpose/Objective(s): Lymphedema is a serious long-term complication in breast cancer patients post-surgery; however, the influence of trimodality treatments including surgery, systemic therapy, and radiotherapy (RT) on its occurrence remains unclear despite the rapid development of each modality. We sought to identify the comprehensive risk factors of lymphedema using two large patient databases, thereby enabling more informed multidisciplinary treatment decision-making. Materials/Methods: We retrospectively collected data from 5,549 breast cancer patients who underwent surgery, systemic therapy, and RT between 2007 and 2015 at our institution. Individual RT plans were reviewed for regional nodal irradiation (RNI) field design and fractionation type. Patients were categorized according to the RT field (no RNI [n Z 3,969]; RNI excluding axilla IeII [n Z 478]; and RNI including axilla IeII [n Z 1,102]) and RT fractionation (hypofractionation [n Z 927] and conventional fractionation [n Z 3,100]). The primary end-point was the lymphedema, which was defined based on objective (difference in arm circumference 2 cm) and subjective (patient perception of arm edema) methods. All patients underwent assessment by experts in Oncological Rehabilitation. We identified lymphedema risk factors using Cox's regression and used them to construct predictive nomograms that were validated internally using 1,000 bootstrap samples and externally using a separate dataset of 1,877 patients. Results: In total, 639 patients (11.5%) developed lymphedema over a median follow-up of 60 months. The 3-year lymphedema incidence was 10.5%; this rate increased with larger irradiation volumes (no RNI vs. RNI excluding axilla IeII vs. RNI including axilla IeII: 5.7% vs. 16.8% vs. 24.1%; P <.001) and when using conventional fractionation instead of hypofractionation (6.8% vs. 13.5%; P <.001). On multivariate analysis, a higher body mass index, a larger number of dissected nodes, using a taxane-based regimen, undergoing total mastectomy, a larger irradiation field, and conventional fractionation were strongly associated with the development of lymphedema (all P<.001). Nomograms constructed based on these variables to predict 2-, 3-, and 5-year lymphedema risk of the individual patients. These nomograms showed good discrimination internally (C-index: 0.77; 95% CI, 0.76e0.79) and externally (C-index: 0.83; 95% CI, 0.81e0.86). Conclusion: Factors associated with trimodality breast cancer treatments interact to promote lymphedema development, the risk of which may be decreased by modifying the RNI field and/or selecting a hypofractionated regimen. De-escalation strategy to minimize lymphedema risk should be discussed in a multidisciplinary team.