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Simple Summary: Identification of the optimal treatment strategy is challenging in elderly with non-small cell lung cancer (NSCLC). Outcomes (1) in elderly vs. younger patients and (2) with low-dose cisplatin vs. cisplatin/vinorelbine were studied. Elderly included more males, had a lower Karnofsky index, more comorbidities, and lower stages. Low-dose cisplatin patients had higher age, more comorbidities, and lower stages. We observed reduced dermatitis and dysphagia and increased anemia and thrombocytopenia in elderly, without increased ≥grade 3 toxicities. Low-dose cisplatin was less toxic than cisplatin/vinorelbine. Survival was lower in elderly vs. younger and comparable between both chemotherapy protocols. In elderly, gender, Karnofsky index, stage, and multimodal treatment (including additional surgery/systemic therapy) were prognostic factors. In elderly, we found acceptable toxicities with radiotherapy but the need for the improvement of outcomes. Multimodal strategies showed a favorable prognosis and can reasonably be considered. Low-dose cisplatin should be discussed on an individual basis due to favorable toxicity and outcomes. Identification of the optimal treatment strategy is challenging in elderly with localized non-small cell lung cancer (NSCLC). Concurrent chemotherapy with low-dose cisplatin represents an option for elderly. Outcomes (1) in elderly (≥70 years, n = 158) vs. younger patients (n = 188) and (2), independently of age, in definitive radiochemotherapy, with low-dose cisplatin (n = 125) vs. cisplatin/vinorelbine (n = 76) were studied. Elderly included more males, had a lower Karnofsky index, more comorbidities, and lower stages. Low-dose cisplatin patients (vs. cisplatin/vinorelbine) had higher age, more comorbidities, and lower stages. We observed reduced dermatitis and dysphagia and increased anemia and thrombocytopenia in elderly vs. younger patients, without increased ≥grade 3 toxicities. Low-dose cisplatin was less toxic than cisplatin/vinorelbine. Survival outcomes were lower in elderly vs. younger and comparable between low-dose cisplatin and cisplatin/vinorelbine. In elderly, gender, Karnofsky index, stage, and multimodal treatment (including additional surgery/systemic therapy) were identified as prognostic factors. In conclusion, we found evidence for an acceptable toxicity profile and the need for improvement of outcomes in elderly with localized NSCLC. Multimodal strategies (including additional surgery/systemic treatment) showed favorable outcomes and should be reasonably considered in elderly who are deemed fit enough. Low-dose cisplatin should be discussed on an individual basis due to favorable toxicity and outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Locally advanced head and neck squamous cell carcinomas (HNSCC) are often managed with surgery and postoperative radiochemotherapy (RCT). Until now, a deeper understanding of specific management strategies for elderly patients was lacking. In the present study, we compared patients ≥70 years of age and younger patients treated with postoperative RCT for HNSCC. All patients were treated with modern radiotherapy techniques (IMRT/VMAT). Elderly patients had more comorbidities. In addition, they less frequently received concomitant systemic treatment. The rates of mucositis and dermatitis were lower in patients ≥70 years. Elderly patients had significantly worse overall survival and progression-free survival. Locoregional and distant control were comparable in elderly and younger patients. In conclusion, postoperative radiochemotherapy is a safe and effective treatment option in patients ≥70 years. In light of comorbidities and poor survival rates, potential benefits and harms of radiotherapy and concomitant systemic treatment should be weighed carefully for this age group. Locally advanced head and neck squamous cell carcinomas (HNSCC) are often managed with surgery followed by postoperative radiochemotherapy (RCT). With the general increase in life expectancy, the proportion of elderly patients with HNSCC is expected to grow rapidly. Until now, a deeper understanding of specific management strategies for these patients in clinical routine was lacking. In the present study, we compared elderly patients (≥70 years, n = 52) and younger patients (n = 245) treated with postoperative RCT for HNSCC at our tertiary cancer center. All patients were irradiated with modern radiotherapy techniques (IMRT/VMAT). Patients ≥70 years of age had more comorbidities. Additionally, elderly patients less frequently received concomitant systemic treatment. The rates of mucositis and dermatitis were lower in patients ≥70 years. Elderly patients had significantly worse overall and progression-free survival. Locoregional and distant control were comparable in elderly and younger patients. In conclusion, postoperative RCT is a safe and effective treatment option in patients ≥70 years. In light of comorbidities and poor overall survival rates, benefits and harms of radiotherapy and concomitant systemic treatment should be weighed carefully. When exclusively applying up-to-date radiotherapy techniques with, at the same time, careful use of concomitant systemic therapy, favorable acute toxicity profiles are achieved. [ABSTRACT FROM AUTHOR]

Simple Summary: In Western countries, the lifetime risk for rectal cancer is around 1.5%. Most patients are diagnosed with locally advanced stages. For these patients, multimodal treatment comprising radiotherapy, chemotherapy, and surgery has become the standard of care. Whereas excellent local control is achieved, still about one out of three dies from this disease. Cytotoxicity of radiochemotherapy substantially involves reactive oxygen species (ROS). In ROS-related genes, we selected eight inherited variants, for which the literature reports functional or medical effects and which occur frequently in the general population. These variants were assessed whether they impact the clinical outcome of patients with rectal cancer. We found that the OGG1 Cys326 variant, which affected 37% of the 287 patients in the sample, was strongly linked with a worse outcome, in particular cancer-specific survival. Screening for this variant may identify a particular risk subgroup of patients who may be considered for more intensified therapy and aftercare. Despite excellent loco-regional control by multimodal treatment of locally advanced rectal cancer, a substantial portion of patients succumb to this disease. As many treatment effects are mediated via reactive oxygen species (ROS), we evaluated the effect of single nucleotide polymorphisms (SNPs) in ROS-related genes on clinical outcome. Based on the literature, eight SNPs in seven ROS-related genes were assayed. Eligible patients (n = 287) diagnosed with UICC stage II/III rectal cancer were treated multimodally starting with neoadjuvant radiochemotherapy (N-RCT) according to the clinical trial protocols of CAO/ARO/AIO-94, CAO/ARO/AIO-04, TransValid-A, and TransValid-B. The median follow-up was 64.4 months. The Ser326Cys polymorphism in the human OGG1 gene affected clinical outcome, in particular cancer-specific survival (CSS). This effect was comparable in extent to the ypN status, an already established strong prognosticator for patient outcome. Homozygous and heterozygous carriers of the Cys326 variant (n = 105) encountered a significantly worse CSS (p = 0.0004 according to the log-rank test, p = 0.01 upon multiple testing adjustment). Cox regression elicited a hazard ratio for CSS of 3.64 (95% confidence interval 1.70–7.78) for patients harboring the Cys326 allele. In a multivariable analysis, the effect of Cys326 on CSS was preserved. We propose the genetic polymorphism Ser326Cys as a promising biomarker for outcome in rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Excellent dosimetric characteristics were demonstrated for volumetric modulated arc therapy (VMAT) in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). In a single-center retrospective analysis, we tested whether these advantages may translate into significant clinical benefits. We compared VMAT to conventional 3D conformal radiotherapy (3DCRT) in patients, homogeneously treated according to the control arm of the CAO/ARO/AIO-04 trial.Methods: CRT consisted of pelvic irradiation with 50.4/1.8Gy by VMAT (n = 81) or 3DCRT (n = 107) and two cycles of 5-fluorouracil. Standardized total mesorectal excision surgery was performed within 4-6 weeks. The tumor regression grading (TRG) was assessed by the Dworak score. Acute and late toxicity were evaluated via the Common Terminology Criteria for Adverse Events and the Late effects of normal tissues scale, respectively. Side effects greater than or equal to grade 3 were considered high-grade.Results: Median follow-up was 18.3 months in the VMAT group and 61.5 months in the 3DCRT group with no differences in TRG between them (p = 0.1727). VMAT treatment substantially reduced high-grade acute and late toxicity, with 5 % versus 20 % (p = 0.0081) and 6 % vs. 22 % (p = 0.0039), respectively. With regard to specific organs, differences were found in skin reaction (p = 0.019) and proctitis (p = 0.0153).Conclusions: VMAT treatment in preoperative CRT for LARC showed the potential to substantially reduce high-grade acute and late toxicity. Importantly, we could demonstrate that VMAT irradiation did not impair short-term oncological results. We conclude, that the reduced toxicity after VMAT irradiation may pave the way for more efficient systemic therapies, and hopefully improved patient survival in the multimodal treatment of LARC. [ABSTRACT FROM AUTHOR]