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The standard of care for locally advanced non-small-cell lung cancer (NSCLC) is either surgery combined with chemotherapy pre- or postoperatively or concurrent chemotherapy and radiotherapy. However, older and frail patients may not be candidates for surgery and chemotherapy due to the high mortality risk and are frequently referred to radiotherapy alone, which is better tolerated but carries a high risk of disease recurrence. Recently, immunotherapy with immune checkpoint inhibitors (ICIs) may induce a high response rate among cancer patients with positive programmed death ligand 1 (PD-L1) expression. Immunotherapy is also well tolerated among older patients. Laboratory and clinical studies have reported synergy between radiotherapy and ICI. The combination of ICI and radiotherapy may improve local control and survival for NSCLC patients who are not candidates for surgery and chemotherapy or decline these two modalities. The International Geriatric Radiotherapy Group proposes a protocol combining radiotherapy and immunotherapy based on the presence or absence of PD-L1 to optimize the survival of those patients.

The standard of care for non-metastatic muscle invasive bladder cancer is either radical cystectomy or bladder preservation therapy, which consists of maximal transurethral bladder resection of the tumor followed by concurrent chemoradiation with a cisplatin-based regimen. However, for older cancer patients who are too frail for surgical resection or have decreased renal function, radiotherapy alone may offer palliation. Recently, immunotherapy with immune checkpoint inhibitors (ICI) has emerged as a promising treatment when combined with radiotherapy due to the synergy of those two modalities. Transitional carcinoma of the bladder is traditionally a model for immunotherapy with an excellent response to Bacille Calmette-Guerin (BCG) in early disease stages, and with avelumab and atezolizumab for metastatic disease. Thus, we propose an algorithm combining immunotherapy and radiotherapy for older patients with locally advanced muscle-invasive bladder cancer who are not candidates for cisplatin-based chemotherapy and surgery., Competing Interests: VV-H declares stock ownerships in Affluent Medical. Author ME-C was employed by company MVision AI. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Nguyen, Karlsson, Page, Chirila, Vinh-Hung, Gorobets, Arenas, Mohammadianpanah, Javadinia, Giap, Kim, Dutheil, Murthy, Mallum, Tlili, Dahbi, Loganadane, Blanco, Bose, Natoli, Li and Morganti.)

The standard of care for non-metastatic renal cancer is surgical resection followed by adjuvant therapy for those at high risk for recurrences. However, for older patients, surgery may not be an option due to the high risk of complications which may result in death. In the past renal cancer was considered to be radio-resistant, and required a higher dose of radiation leading to excessive complications secondary to damage of the normal organs surrounding the cancer. Advances in radiotherapy technique such as stereotactic body radiotherapy (SBRT) has led to the delivery of a tumoricidal dose of radiation with minimal damage to the normal tissue. Excellent local control and survival have been reported for selective patients with small tumors following SBRT. However, for patients with poor prognostic factors such as large tumor size and aggressive histology, there was a higher rate of loco-regional recurrences and distant metastases. Those tumors frequently carry program death ligand 1 (PD-L1) which makes them an ideal target for immunotherapy with check point inhibitors (CPI). Given the synergy between radiotherapy and immunotherapy, we propose an algorithm combining CPI and SBRT for older patients with non-metastatic renal cancer who are not candidates for surgical resection or decline nephrectomy., Competing Interests: Author ME-C was employed by company MVision AI. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Nguyen, Chirila, Page, Vinh-Hung, Gorobets, Mohammadianpanah, Giap, Arenas, Bonet, Lara, Kim, Dutheil, Lehrman, Montes, Tlili, Dahbi, Loganadane, Blanco, Bose, Natoli, Li, Mallum and Morganti.)

The standard of care for locally advanced rectal cancer is total neoadjuvant therapy followed by surgical resection. Current evidence suggests that selected patients may be able to delay or avoid surgery without affecting survival rates if they achieve a complete clinical response (CCR). However, for older cancer patients who are too frail for surgery or decline the surgical procedure, local recurrence may lead to a deterioration of patient quality of life. Thus, for clinicians, a treatment algorithm which is well tolerated and may improve CCR in older and frail patients with rectal cancer may improve the potential for prolonged remission and potential cure. Recently, immunotherapy with check point inhibitors (CPI) is a promising treatment in selected patients with high expression of program death ligands receptor 1 (PD- L1). Radiotherapy may enhance PD-L1 expression in rectal cancer and may improve response rate to immunotherapy. We propose an algorithm combining immunotherapy and radiotherapy for older patients with locally advanced rectal cancer who are too frail for surgery or who decline surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) NN, VV-H, MM and MA declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Nguyen, Mohammadianpanah, SunMyint, Page, Vinh-Hung, Gorobets, Arenas, Mazibuko, Giap, Vasileiou, Dutheil, Tuscano, Karlsson, Dahbi, Natoli, Li, Kim, Oboite, Oboite, Bose and Vuong.)

Shelters are stressful environments for domestic dogs which are known to negatively impact their welfare. The introduction of outside stimuli for dogs in this environment can improve their welfare and life conditions. However, our current understanding of the influence of different stimuli on shelter dogs' welfare is limited and the data is still insufficient to draw conclusions. In this study, we collected 28 days (four weeks) of telemetry data from eight male dogs housed in an Italian shelter for a long period of time. During this period, three types of enrichment were introduced into the dogs' pens for one week each: entertaining objects, intraspecific, and interspecific social enrichment, by means of the presence of female conspecifics and the presence of a human. To quantify their impact, we introduce novel metrics as indicators of sheltered dogs' welfare based on telemetry data: the variation of heart rate, muscle activity, and body temperature from an average baseline day, quality of sleep, and the regularity for cyclicity of the aforementioned parameters, based on the day-night cycle. Using these metrics, we show that while all three stimuli statistically improve the dogs' welfare, the variance between individual dogs is large. Moreover, our findings indicate that the presence of female conspecific is the best stimulus among the three explored options which improves both the quality of sleep and the parameters' cyclicity. Our results are consistent with previous research findings while providing novel data-driven welfare indicators that promote objectivity. Thus, this research provides some useful guidelines for managing shelters and improving dogs' welfare., (© 2024. The Author(s).)

Background: The objective of this study was to assess the impact of age and other patient and treatment characteristics on toxicity in prostate cancer patients receiving adjuvant radiotherapy (RT)., Materials and Methods: This observational study (ICAROS-1) evaluated both acute (RTOG) and late (RTOG/EORTC) toxicity. Patient- (age; Charlson's comorbidity index) and treatment-related characteristics (nodal irradiation; previous TURP; use, type, and duration of ADT, RT fractionation and technique, image-guidance systems, EQD2 delivered to the prostate bed and pelvic nodes) were recorded and analyzed., Results: A total of 381 patients were enrolled. The median EQD2 to the prostate bed (α/β=1.5) was 71.4 Gy. The majority of patients (75.4%) were treated with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Acute G3 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 0.5% and 1.3%, respectively. No patients experienced >G3 acute toxicity. The multivariable analysis of acute toxicity (binomial logistic regression) showed a statistically significant association between older age (> 65) and decreased odds of G≥2 GI acute toxicity (OR: 0.569; 95%CI: 0.329-0.973; p: 0.040) and decreased odds of G≥2 GU acute toxicity (OR: 0.956; 95%CI: 0.918-0.996; p: 0.031). The 5-year late toxicity-free survival rates for G≥3 GI and GU toxicity were 98.1% and 94.5%, respectively. The only significant correlation found (Cox's regression model) was a reduced risk of late GI toxicity in patients undergoing hypofractionation (HR: 0.38; 95% CI: 0.18-0.78; p: 0.008)., Conclusions: The unexpected results of this analysis could be explained by a "response shift bias" concerning the protective effect of older age and by treatment in later periods (using IMRT/VMAT) concerning the favorable effect of hypofractionation. However, overall, the study suggests that age should not be a reason to avoid adjuvant RT and that the latter is well-tolerated even with moderately hypofractionated regimens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Buwenge, Macchia, Cavallini, Cortesi, Malizia, Bianchi, Ntreta, Arcelli, Capocaccia, Natoli, Cilla, Cellini, Tagliaferri, Strigari, Cammelli, Schiavina, Brunocilla, Morganti and Deodato.)

Shelters are stressful environments for domestic dogs ( Canis familiaris ). Evaluating dogs' welfare is crucial to improve their life condition and to promote a better management of shelters. We aimed at verifying which variables improved welfare in 10 shelter dogs ((hosted in the shelter "Centro cinofilo Caerite" in Bracciano (Rome)) by analysing their behavioural responses in different environmental conditions. Furthermore, faecal samples were taken to measure cortisol metabolites (CM), a non-invasive method to evaluate adrenocortical activity in dogs. Dogs were observed for a total of 400 h in 4 different cage conditions: (i) alone in a cage; ii) alone in an enriched cage; (iii) in cage with conspecifics; (iv) in cage with regular interaction with humans outside the cage. Alone in the cage situation showed highest frequencies of displacement activities (Friedman test: χ 2 = 13.32; p = 0.004). In contrast, being in the cage with conspecifics seems to reduce displacement activity frequency, as well as the level of faecal cortisol metabolites (Friedman test: χ 2 = 8.04; p = 0.045). Our results suggest that conspecifics' presence is the best way to reduce stress in shelter dogs. This research could provide some useful guidelines for managing shelters and improving dogs' life condition.

Welfare and management decisions for unowned free-ranging cats in urban environments should no longer be based on knowledge about behavioural ecology of solitary cats living and breeding in more natural 'wild' environments. We provide evidence that urban free-ranging domestic cats in the Anthropocene have responded to rapidly changing environments, such as abundance of food and higher population densities of conspecifics by adapting their behaviour (behavioural plasticity-the ability of a genotype (individual) to express different behaviours according to its environment) and social organisation to living in complex social groups, especially those living in colonies. Urban free-ranging cats are now more social, as demonstrated by different breeding patterns, lower infanticide, more frequent affiliative interactions in general, and different spatial groupings. We argue that this knowledge should be disseminated widely, and inform future research and strategies used to manage free-ranging cats across environments. Understanding behavioural plasticity and other recently evolved traits of domestic cats may lead to management strategies that maximise health and welfare of cats, wildlife, and humans-otherwise domestic cat behaviour may be 'misunderstood'. Importantly, interdisciplinary research using expertise from biological and social sciences, and engaging human communities, should evaluate these management strategies to ensure they maintain optimal welfare of free-ranging domestic cats while preserving biodiversity and protecting wildcats.