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Background Head-and-neck squamous cell carcinoma (HNSCC) is one of the most common malignancies globally, and the number of elderly patients diagnosed with HNSCC is increasing. However, as elderly HNSCC patients are underrepresented in clinical trials, current clinical decision making for this cohort largely lacks clinical evidence. Methods Elderly patients (≥65 years) with HNSCC undergoing (chemo)radiotherapy from 2010 to 2018 at Freiburg University Medical Center were assessed for patterns of care, locoregional control (LRC), progression-free (PFS) and overall survival (OS) regarding definitive and adjuvant treatments. Acute and late therapy-associated toxicities were quantified according to CTCAE v5.0. Results Two hundred forty-six patients were included in this analysis, of whom 166 received definitive and 80 adjuvant treatment. Two-year rates for OS, PFS and LRC were 56.9, 44.9 and 75.5%, respectively. Survival differed significantly between age groups with an OS of 40 and 22 months and a PFS of 23 and 12 months for patients aged 65–74 or ≥ 75 years, respectively ( p  < 0.05). Concomitant chemotherapy resulted in improved OS in patients aged 65–74 years compared to radiotherapy alone ( p  < 0.05) for definitive treatments, while patients ≥75 years did not benefit ( p  = 0.904). For adjuvant chemoradiotherapy, a trend towards superior OS rates was observed for patients aged 65–74 years ( p  = 0.151). Low performance status (HR = 2.584, 95% CI 1.561–4.274; p  < 0.001) and smoking (HR = 1.960, 95% CI 1.109–3.464, p  < 0.05) were the strongest independent prognostic factor in the multivariate analysis for decreased OS. One hundred thirty-eight patients (56.1%) experienced acute grade 3/4 and 45 patients (19.9%) chronic grade 3 toxicities. Conclusion Radiotherapy is a feasible treatment modality for elderly HNSCC patients. The relatively low OS compared to high LRC may reflect age and comorbidities. Concomitant chemotherapy should be critically discussed in elderly HNSCC patients.

PurposePainful osteoarthritis is common in elderly patients, and low-dose radiotherapy has been demonstrated to provide effective symptomatic treatment. We examined the analgesic effects of low-dose radiotherapy for osteoarthritis in the elderly aiming to reveal potential differences in the response rates relating to increasing age.MethodsA retrospective analysis was performed at two university hospitals including elderly patients (≥ 65 years) undergoing radiotherapy for osteoarthritis between 2008 and 2020. Pain intensity and response were quantified using the numerical rating scale (NRS) and the Pannewitz score. Age groups were defined for young old (65–74 years), older old (75–84 years), and oldest old patients (≥ 85 years).ResultsIn all, 970 patients with 1185 treated sites and a median age of 76 years were analyzed. Mean NRS was 66 at baseline (t0), 53 after radiotherapy (t1), and 44 at first follow-up (t2) (p < 0.001 for t0–t1, t1–t2, and t0–t2). At t1, 1.5% exhibited a Pannewitz score of 0 (no pain), 58.5% of 1–2 (less pain), 36.1% of 3 (equal pain), and 3.9% of 4 (worse pain), while at t2, pain response shifted towards 6.9% (0), 58.6% (1–2), 28.1% (3), and 6.3% (4). Pain response did not differ between age groups at t1 (p = 0.172) or t2 (p = 0.684). In addition, pain response after re-irradiation (n = 384 sites) was 61.0% and was comparable between age groups (p = 0.535).ConclusionLow-dose radiotherapy results in pain reduction in about two-thirds of treated sites with no difference relating to increasing age, showing that radiotherapy is an effective analgesic treatment for osteoarthritis even at advanced ages.

Sarcopenia is associated with reduced survival and increased toxicity in malignant diseases. The prevalence of sarcopenia increases with age and is an important cause of functional decline. We analyzed sarcopenia and sarcopenia dynamics in elderly head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiation. Skeletal muscle mass of 280 elderly HNSCC-patients (>65 yrs) receiving curative (chemo)radiation was manually outlined and quantified on CT scans at the level of the C3 (C3MA). Cross-sectional muscle area at L3 (L3MA) was calculated and normalized to height (L3MI). Frequency distributions of clinical parameters as well as overall survival (OS), progression-free survival (PFS) and locoregional control (LRC) were calculated regarding sarcopenia. Calculated L3MA correlated with pretherapeutic hemoglobin-levels (ρ = 0.280) bodyweight (ρ = 0.702) and inversely with patient-age (ρ = −0.290). Sarcopenic patients featured larger tumors (T3/4 69.0% vs. 52.8%, p < 0.001), a higher burden of comorbidity (age-adjusted Charlson Comorbidity Index 4.8 vs. 4.2, p = 0.015) and more severe chronic toxicities (CTCAE grade 3/4 24.0% vs. 11.8%, p = 0.022). OS was significantly deteriorated in sarcopenic patients with a median of 23 vs. 91 months (logrank p = 0.002) (HR 1.79, CI 1.22–2.60, p = 0.003) and sarcopenia remained an independent prognostic factor for reduced OS in the multivariate analysis (HR 1.64, CI 1.07–2.52, p = 0.023). After therapy, 33% of previously non-sarcopenic patients developed sarcopenia, while 97% of pre-treatment sarcopenic remained sarcopenic. Median bodyweight decreased by 6.8%, whereas median calculated L3MA decreased by 2.4%. In contrast to pretherapeutic, post-therapeutic sarcopenia is no prognosticator for reduced OS. Pretherapeutic sarcopenia is a significant prognostic factor in elderly HNSCC patients undergoing (chemo-)radiation and should be considered in pretherapeutic decision-making. Its role as a predictive marker for tailored supportive interventions merits further prospective evaluation.

Background Treatment for local and locoregional recurrence or second head-and-neck (H&N) cancers after previous radiotherapy is challenging, and re-irradiation carries a significantly increased risk for radiotherapy-related normal tissue toxicities and treatment failure due to a radioresistant tumor phenotype. Here, we analyzed re-irradiation management and outcomes in patients with recurrent or second primary H&N carcinoma using state-of-the-art diagnostic procedures and radiotherapy techniques. Methods Between 2010 and 2019, 48 patients with recurrent or second primary H&N carcinoma received re-radiotherapy at the University of Freiburg Medical Center and were included in this study. Overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method, and univariate Cox-regression analyses were performed to assess the effects of clinico-pathological factors on treatment outcomes. Acute and chronic treatment-related toxicities were quantified using the Common Terminology Criteria for Adverse Events (CTCAE v4.03). Results Thirty-one patients (64.6%) received definitive and 17 (35.4%) adjuvant radiotherapy. Simultaneous chemotherapy was administered in 28 patients (58.3%) with cetuximab as the most commonly used systemic agent ( n  = 17, 60.7%). After a median time of 17 months (range 4 months to 176 months) between first and second radiotherapy, patients were re-irradiated with a median of 58.4 Gy and a treatment completion rate of 87.5% ( n  = 42). Median OS was 25 months with a 1-year OS amounting to 62.4%, and median PFS was 9 months with a 1-year PFS of 37.6%. Univariate analyses demonstrated that both a lower rT-status and a radiotherapy boost were associated with improved OS ( p  < 0.05). There was a trend towards superior OS for patients who received > 50 Gy ( p  = 0.091) and who completed the prescribed radiotherapy ( p  = 0.055). Five patients (10.4%) suffered from at least one grade 3 toxicities, while 9 patients (27.3%) experienced chronic higher-grade toxicities (≥ grade 3) with one (3.0%) grade 4 carotid blowout and one (3.0%) grade 4 osteoradionecrosis. Conclusion Re-irradiation of recurrent or second primary H&N cancer with modern radiation techniques such as intensity-modulated radiotherapy resulted in promising survival rates with acceptable toxicities compared to historical cohorts. Increased re-irradiation doses, utilization of a radiotherapy boost and completion of the re-irradiation treatment were found to result in improved survival.

BackgroundThere are currently no data from randomized controlled trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost as part of a breast-conservation approach for breast cancer. This study retrospectively reviewed the safety and efficacy of IORT as a boost treatment at a tertiary cancer center.MethodsFrom 2015 to 2019, patients underwent breast-conserving surgery with axillary lymph node staging and a single dose of 20 Gy IORT with 50-kV photons, followed by whole-breast irradiation (WBI) and adjuvant systemic therapy (if applicable). Patients were followed for assessment of acute and late toxicities (using the Common Terminology Criteria for Adverse Events version 5.0) at 3–6-month intervals. Outcomes included ipsilateral (IBTR) and contralateral breast progression-free survival (CBE), distant metastasis-free survival (DMFS), and overall survival (OS).ResultsMedian follow-up for the 214 patients was 28 (range 2–59) months. Most patients had T1 disease (n = 124) and were clinically node negative. Only few patients had high-grade and/or triple-negative disease. The vast majority of patients underwent sentinel node biopsy, and 32 (15%) required re-resection for initially positive margins. Finally, all tumor bed margins were clear. Nine (4.2%) and 48 (22.4%) patients underwent neoadjuvant and adjuvant chemotherapy, respectively. WBI was predominantly performed as conventionally fractionated WBI (n = 187, 87.4%), and the median time from BCS to WBI was 54.5 days. IORT was delivered with a single dose of 20 Gy. The median WBI dose was 50 Gy (range 29.4–50.4 Gy). No patients experienced grade 4 events; acute grade 3 toxicities were limited to 17 (8%) cases of radiation dermatitis. Postoperative toxicities were mild. After WBI only one case of late grade ≥ 2 events was reported. There were two recurrences in the tumor bed and one contralateral breast event.ConclusionThis investigation provides additional preliminary data supporting the using of IORT in the boost setting and corroborates the existing literature. These encouraging results should be prospectively validated by the eventual publication of randomized studies such as TARGIT‑B.

Purpose To examine treatment patterns, oncological outcomes and toxicity rates in elderly patients receiving radiotherapy for cutaneous squamous cell carcinoma (cSCC) of the head-and-neck region. Material and methods In this retrospective single-center analysis, locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) of elderly patients > 65 years with cSCC of the head-and-neck region undergoing radiotherapy between 2010 and 2019 were calculated. The prognostic value of clinicopathological parameters on radiotherapy outcomes was analyzed using the Cox proportional hazards model. In addition, both acute and chronic toxicities were retrospectively quantified according to CTCAE version 5.0. Results A total of 69 elderly patients with cSCC of the head-and-neck region with a median age of 85 years were included in this analysis, of whom 21.7% (15 patients) presented with nodal disease. The majority of patients exhibited a good performance status, indicated by a median Karnofsky performance status (KPS) and Charlson Comorbidity Index (CCI) of 80% and 6 points, respectively. Radiotherapy was administered as primary (48%), adjuvant (32%) or palliative therapy (20%). 55 patients (79.7%) completed treatment and received the scheduled radiotherapy dose. Median EQD2 radiation doses were 58.4 Gy, 60 Gy and 51.3 Gy in the definitive, adjuvant and palliative situation, respectively. 2-year LRC, PFS and OS ranged at 54.2%, 33.5 and 40.7%, respectively. Survival differed significantly between age groups with a median OS of 20 vs. 12 months ( p  < 0.05) for patients aged 65–80 or above 80 years. In the multivariate analysis, positive lymph node status remained the only significant prognostic factor deteriorating OS (HR 3.73, CI 1.54–9.03, p  < 0.01). Interestingly, neither KPS nor CCI impaired survival in this elderly patient cohort. Only 3 patients (4.3%) experienced acute CTCAE grade 3 toxicities, and no chronic CTCAE grade 2–5 toxicities were observed in our cohort. Conclusion Radiotherapy was feasible and well-tolerated in this distinct population, showing the general feasibility of radiotherapy for cSCC of the head-and-neck region also in the older and oldest olds. The very mild toxicities may allow for moderate dose escalation to improve LRC.

Purpose This study compares the objective American Society of Anesthesiologists (ASA) and Adult Comorbidity Evaluation-27 (ACE-27) scores with the subjective Eastern Cooperative Oncology Group performance status (ECOG PS) for patient outcome prediction. Methods We retrospectively analyzed head and neck squamous cell carcinoma patients treated with adjuvant (chemo)radiotherapy at the LMU Munich from June 2008 to June 2015. The study focused on associations between patient outcomes; treatment failures; known risk factors (including human papillomavirus [HPV] status and tumor stage); and the comorbidity indices ECOG-PS, ASA score, and ACE-27. The Kaplan–Meier method and Cox proportional hazards model were used for survival analysis and identifying independent risk factors. Results A total of 302 patients were analyzed, 175 received concurrent chemotherapy. Median follow-up was 61.8 months, and median age at diagnosis was 61 years. The 3‑ and 5‑year overall survival (OS) and disease-free survival (DFS) rates were 70.5%/60.2% and 64.7%/57.6%, respectively. Both ACE-27 and ASA showed significant correlations with OS in univariate and multivariate analyses, while ECOG-PS was significant only in univariate analysis. ASA and ACE-27 scores were also significantly correlated with local and locoregional recurrence, but only HPV status and tumor stage were significant in multivariate models. Conclusion ACE-27 and ASA score effectively categorize patients’ risks in adjuvant radiotherapy for head and neck cancer, proving more predictive of overall survival than ECOG-PS. These results underscore the importance of objective comorbidity assessment and suggest further prospective studies.

The purpose of this study was to evaluate the value of routine blood markers regarding their predictive potential for treatment outcomes of elderly head-and-neck squamous cell carcinoma (HNSCC) patients. In total, 246 elderly HNSCC patients (≥65 years) undergoing (chemo)radiotherapy from 2010 to 2018 were analyzed for treatment outcomes, depending on their hemoglobin, glomerular filtration rate (GFR), C-reactive protein (CRP) and albumin values, representing anemia, kidney function, inflammation and nutrition status, respectively. Local/locoregional control, progression-free and overall survival (OS) were calculated using the Kaplan–Meier method. Cox analyses were performed to examine the influence of blood parameters on oncological outcomes. In the univariate Cox regression analysis, hemoglobin ≤ 12 g/dL (HR = 1.536, p < 0.05), a GFR ≤ 60 mL/min/1.73 m2 (HR = 1.537, p < 0.05), a CRP concentration > 5 mg/L (HR = 1.991, p < 0.001) and albumin levels ≤ 4.2 g/dL (HR = 2.916, p < 0.001) were significant risk factors for OS. In the multivariate analysis including clinical risk factors, only performance status (HR = 2.460, p < 0.05) and baseline albumin (HR = 2.305, p < 0.05) remained significant prognosticators. Additionally, baseline anemia correlated with the prevalence of higher-grade chronic toxicities. We could show for the first time that laboratory parameters for anemia (and at least partly, tumor oxygenation), decreased renal function, inflammation and reduced nutrition status are associated with impaired survival in elderly HNSCC patients undergoing (chemo)radiotherapy.

The effects of radiotherapy on the long-term quality of life (QoL) of surviving elderly HNSCC patients are not well understood, therefore, we analyzed QoL in this population. A cross-sectional analysis was performed at a tertiary cancer center to assess long-term QoL in elderly HNSCC patients. Eligible patients were ≥65 years at the time of treatment who had to be alive for ≥1 year after radiotherapy and without current anti-cancer treatment. QoL and patient satisfaction were assessed using the EORTC QLQ-C30, QLQ-H&N35 and ZUF-8 questionnaires, respectively, and treatment-related toxicities were graded according to CTCAE (Common Terminology Criteria of Adverse Effects) v.5.0. Seventy-four patients met the inclusion criteria, of which 50 consented to participate. Median time between radiotherapy and QoL assessment was 32 months (range 12–113). The QLQ-C30 global QoL median amounted to 66.7 points (interquartile range (IQR) 50.0–83.3), which was comparable to the age- and gender-adjusted German population (median 65.3). Median global QoL was similar between patients undergoing definitive (75.0, IQR 50.0–83.3) and adjuvant (chemo)radiotherapy (66.7, IQR 41.7–83.3, p = 0.219). HPV-positive HNSCC patients had superior global QoL after radiotherapy than their HPV-negative counterparts (p < 0.05), and concomitant chemotherapy did not influence the long-term QoL (p = 0.966). Median global QoL did not correspond with physician-assessed highest-graded chronic toxicities (p = 0.640). The ZUF-8 ranged at 29 points in median (IQR 27–31), showing high patient satisfaction. Surviving elderly HNSCC patients treated by radiotherapy exhibit a relatively high long-term global QoL which is a relevant information for clinicians treating elderly HNSCC patients.