TY - JOUR AB - IMPORTANCE: The interindividual differences in severity of acute radiation dermatitis are not well understood. To date, the pathomechanism and interplay of microbiome and radiodermatitis before and during treatment remain largely unknown. OBJECTIVE: To assess the association of skin microbiome baseline composition and dynamics with severity of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal prospective pilot observational study was conducted between January 2017 and January 2019. Sequencing results were received in March 2021, and the data were analyzed from August 2021 to March 2023. This study was performed at an urban academic university cancer center. A total of 21 female patients with breast cancer after surgery were consecutively approached, of which 1 patient withdrew consent before the study started. EXPOSURE: Adjuvant radiotherapy for breast cancer for 7 weeks. MAIN OUTCOMES AND MEASURES: The main outcome was the association of baseline skin microbiome composition and its dynamics with the severity of radiodermatitis. A total of 360 skin microbiome samples from patients were analyzed, taken before, during, and after radiotherapy, from both the treated and contralateral healthy sides. The skin microbiome samples were analyzed using 16S (V1-V3) amplicon sequencing and quantitative polymerase chain reaction bacterial enumeration. RESULTS: Twenty female patients with breast cancer after surgery who underwent radiotherapy enrolled in the study had a median (range) age of 61 (37-81) years. The median (range) body mass index of the patients was 24.2 (17.6-38.4). The 16S sequencing revealed that low (<5%) relative abundance of commensal skin bacteria (Staphylococcus epidermidis, Staphylococcus hominis, Cutibacterium acnes) at baseline composition was associated with the development of severe radiodermatitis with an accuracy of 100% (sensitivity and specificity of 100%, P < .001). Furthermore, in patients with severe radiodermatitis, quantitative polymerase chain reaction bacterial enumeration revealed a general non-species-specific overgrowth of skin bacterial load before the onset of severe symptoms. Subsequently, the abundance of commensal bacteria increased in severe radiodermatitis, coinciding with a decline in total bacterial load. CONCLUSIONS AND RELEVANCE: The findings of this observational study indicated a potential mechanism associated with the skin microbiome for the pathogenesis of severe radiodermatitis, which may be a useful biomarker for personalized prevention of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer. AU - Hülpüsch, C.* AU - Neumann, A.U. AU - Reiger, M. AU - Fischer, J.C.* AU - De Tomassi, A.* AU - Hammel, G. AU - Gülzow, C.* AU - Fleming, M.* AU - Dapper, H.* AU - Mayinger, M.* AU - Vogel, M.* AU - Ertl, C.* AU - Combs, S.E. AU - Traidl-Hoffmann, C. AU - Borm, K.J.* C1 - 69895 C2 - 55312 TI - Association of skin microbiome dynamics with radiodermatitis in patients with breast cancer. JO - JAMA Oncol. PY - 2024 SN - 2374-2437 ER - TY - JOUR AU - Neumann, A.U. AU - Borm, K.J.* AU - Traidl-Hoffmann, C. C1 - 70931 C2 - 55866 TI - Comprehensive risk stratification to guide an optimal preventive strategy for breast radiation dermatitis-reply. JO - JAMA Oncol. PY - 2024 SN - 2374-2437 ER - TY - JOUR AU - Eitz, K.A. C1 - 60766 C2 - 49973 CY - 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa SP - 1984-1985 TI - Errors in hazard ratios, labels in figures, and text. JO - JAMA Oncol. VL - 6 IS - 12 PB - Amer Medical Assoc PY - 2020 SN - 2374-2437 ER - TY - JOUR AB - IMPORTANCE For brain metastases, the combination of neurosurgical resection and postoperative hypofractionated stereotactic radiotherapy (HSRT) is an emerging therapeutic approach preferred to the prior practice of postoperative whole-brain radiotherapy. However, mature large-scale outcome data are lacking. OBJECTIVE To evaluate outcomes and prognostic factors after HSRT to the resection cavity in patients with brain metastases. DESIGN, SETTING, AND PARTICIPANTS An international, multi-institutional cohort study was performed in 558 patients with resected brain metastases and postoperative HSRT treated between December 1, 2003, and October 31, 2019, in 1 of 6 participating centers. Exclusion criteria were prior cranial radiotherapy (including whole-brain radiotherapy) and early termination of treatment. EXPOSURES A median total dose of 30 Gy (range, 18-35 Gy) and a dose per fraction of 6 Gy (range, 5-10.7 Gy) were applied. MAIN OUTCOMES AND MEASURES The primary end points were overall survival, local control (LC), and the analysis of prognostic factors associated with overall survival and LC. Secondary end points included distant intracranial failure, distant progression, and the incidence of neurologic toxicity. RESULTS A total of 558 patients (mean [SD] age, 61 [0.50] years; 301 [53.9%] female) with 581 resected cavities were analyzed. The median follow-up was 12.3 months (interquartile range, 5.0-25.3 months). Overall survival was 65% at 1 year, 46% at 2 years, and 33% at 3 years, whereas LC was 84% at 1 year, 75% at 2 years, and 71% at 3 years. Radiation necrosis was present in 48 patients (8.6%) and leptomeningeal disease in 73 patients (13.1%). Neurologic toxic events according to the Common Terminology Criteria for Adverse Events grade 3 or higher occurred in 16 patients (2.8%) less than 6 months and 24 patients (4.1%) greater than 6 months after treatment. Multivariate analysis identified a Karnofsky Performance Status score of 80% or greater (hazard ratio [HR], 0.61; 95% CI, 0.46-0.82; P < .001), 22 to 33 days between resection and radiotherapy (HR, 1.50; 95% CI, 1.07-2.10; P = .02), and a controlled primary tumor (HR, 0.69; 95% CI, 0.52-0.90; P = .007) as prognostic factors associated with overall survival. For LC, a single brain metastasis (HR, 0.57; 95% CI, 0.35-0.93; P = .03) and a controlled primary tumor (HR, 0.59; 95% CI, 0.39-0.92; P = .02) were significant in the multivariate analysis. CONCLUSIONS AND RELEVANCE To date, this cohort study includes one of the largest series of patients with brain metastases and postoperative HSRT and appears to confirm an excellent risk-benefit profile of local HSRT to the resection cavity. Additional studies will help determine radiation dose-volume parameters and provide a better understanding of synergistic effects with systemic and immunotherapies. AU - Eitz, K.A. AU - Lo, S.S.* AU - Soliman, H.* AU - Sahgal, A.* AU - Theriault, A.* AU - Pinkham, M.B.* AU - Foote, M.C.* AU - Song, A.J.* AU - Shi, W.* AU - Redmond, K.J.* AU - Gui, C.* AU - Kumar, A.M.S.* AU - Machtay, M.* AU - Meyer, B.* AU - Combs, S.E. C1 - 60414 C2 - 49448 CY - 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa SP - 1901-1909 TI - Multi-institutional analysis of prognostic factors and outcomes after hypofractionated stereotactic radiotherapy to the resection cavity in patients with brain metastases. JO - JAMA Oncol. VL - 6 IS - 12 PB - Amer Medical Assoc PY - 2020 SN - 2374-2437 ER - TY - JOUR AB - Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Data Sources: Genomewide association studies (GWAS) published up to January 15, 2015. Study Selection: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Data Extraction and Synthesis: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Main Outcomes and Measures: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Results: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). Conclusions and Relevance: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases. AU - The Telomeres Mendelian Randomization Collaboration (Standl, M.) C1 - 50632 C2 - 42649 SP - 636-651 TI - Association between telomere length and risk of cancer and non-neoplastic diseases: A mendelian randomization study. JO - JAMA Oncol. VL - 3 IS - 5 PY - 2017 SN - 2374-2437 ER -