Background: Platinum-based chemotherapy (PBC) followed by avelumab maintenance is a treatment option for patients with advanced urothelial carcinoma (aUC) patients. However, the optimal treatment sequencing in the era of antibody–drug conjugates (ADCs) is yet to be determined. Recent studies suggest that the timing of immune checkpoint inhibitor (ICI) administration may impact patient outcomes, with a potential benefit from morning infusions. Methods: This retrospective study included 105 patients with aUC treated with avelumab in Portugal and intended to assess the safety and clinical outcomes (progression-free survival (PFS), overall survival (OS), and overall response rate (ORR)) and evaluate the impact of treatment timing (morning vs. afternoon) on patient outcomes. Results: The median follow-up from the start of avelumab was 17.7 months, the median PFS (mPFS) was 9.8 months (95% CI 4.9–14.7), and the median OS (mOS) was 39.5 months (95% CI 13.2–65.7). Immune-related adverse events (irAEs) were reported in 65.8% of patients, with 6.7% experiencing G3 irAEs. Among those who received a subsequent-line ADC upon disease progression (43%), the mOS from the start of avelumab was 23.1 months (95% CI 9.2–37.0). Multivariate analysis showed significant improvement in mOS with morning avelumab infusions (HR 0.35, 95% CI: 0.12–0.97, p = 0.042) and a trend towards improved mPFS (HR 0.43, 95% CI: 0.179–1.02, p = 0.055). Conclusions: This study confirms the clinical efficacy and safety of avelumab, showing improved outcomes over JAVELIN Bladder 100 and suggesting that morning infusions may offer a survival benefit in this context. Further research is needed to optimize treatment sequencing and explore the impact of infusion timing in ICI strategies.

Medullary thyroid carcinoma (MTC) is a rare type of neuroendocrine tumor, accounting for 3%-4% of all thyroid cancers. Seventy-five percent are sporadic, of which 60% have pathogenic REarranged during Transfection (RET) somatic mutations. The sporadic RET-mutated MTC poses novel challenges for targeted treatment. The authors present a case of a 60-year-old male diagnosed in 2018 with MTC who underwent total thyroidectomy with sternotomy and bilateral cervical lymph node dissection - pT3N1b R1 L1 V1 Pn0 cM1 (hepatic and lung metastasis). According to the decisions made by the multidisciplinary tumor board, the patient received multiple palliative systemic treatments. Despite an initial response, vandetanib was accompanied by grade 3 high blood pressure and progression after 14 months of treatment. The patient also received cabozantinib, which led to an initial response, but with grade 3 hypertension and skin toxicity. The patient progressed, including symptomatic bone metastasis, after 15 months of treatment. Following the next sequencing genome result, which showed a somatic mutation in the RET M918T gene, the patient was treated with selpercatinib, a highly selective and potent RET inhibitor. The treatment led to clinical and radiological responses without significant toxicities. The objective of this case report is to highlight the impact of innovative treatment and precision medicine on the management of cancer patients, which not only has a direct effect on their survival but also on their quality of life.

Introduction Geriatrics is a discipline that covers all adult healthcare, and oncology is no exception. The global geriatric assessment process plays a crucial role, impacting research, funding, resource allocation, as well as therapeutic decision-making. Thus, greater knowledge of the epidemiology of the frailty and functionality of elderly patients with cancer will allow for the development of a global care strategy. This study aimed to assess the prevalence of geriatric conditions in elderly cancer patients admitted to a medical geriatric unit following unplanned hospitalisation. Methods A retrospective, single-centre cohort study was conducted of patients aged ≥ 75 with an active oncological disease who were admitted to a geriatric medicine unit over a two-year period. Results A total of 65 patients were included. The median age was 85 (IQR 81-88), and 86% were aged ≥ 80. A moderate-to-high functional dependence was found: 67.7% on ≥ 3 basic activities of daily living (Katz ≥ D), with the majority classified as severely dependent based on the Barthel Index (mean 49.0 ± 33.7). Frailty was found in 90.7%. A high prevalence of geriatric syndromes was observed: malnutrition (84.6%), polypharmacy (64.6%), urinary incontinence (58.5%) and pressure ulcers (33.8%). The mortality rate was 36.9% during hospitalisation and 13.8%, 30 days post-discharge. Conclusions The study revealed a high prevalence of geriatric conditions, emphasising the importance of comprehensive assessment in managing elderly patients at different stages of the disease. This multidimensional and multidisciplinary approach optimises patient care throughout admission, hospitalisation and discharge.

Comprehensive genomic profiling (CGP) is a tool used in precision oncology to identify genomic alterations and match them with targeted therapies across several tumor types. However, real-world data on its clinical utility and impact remains limited. The FRONTAL study (Foundation Medicine Real wOrld evideNce in porTugAL) is a multicenter academic initiative that established a national registry of Portuguese patients with solid tumors who underwent CGP with FoundationOne CDx, Liquid CDx or FoundationOne Heme assays. Methods: Eligible patients had advanced solid tumors not suitable for curative treatment at the time of recruitment. Prior CGP testing was permitted if taken within 12 months before study initiation. Genomic profiling data were extracted from FoundationOne Medicine reports, and clinical information was extracted from medical records. Actionable alterations were defined as those associated with approved treatments or with clinical evidence of benefit in other cancers, per NCCN guidelines. Variant interpretation was also reviewed according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) guidelines. The primary outcome was disease control at 16 weeks, defined by the absence of progression. Results: The study included 205 patients between 2020 and 2025 across 10 sites, with colorectal (40, 19.5%), sarcomas (28, 13.7%), and other gastrointestinal tumors (22, 10.7%) being the most common pathologies. Actionable alterations were identified in 104 cases (50.7%). Genomic findings guided therapy decisions in 50 patients (24.4%), of whom 30 achieved disease control at 16 weeks (14.6%). Conclusions: The FRONTAL study highlighted the clinical relevance of CGP in advanced solid tumors. Over half of the patients had actionable alterations, a quarter had therapy changes based on CGP results, and improved disease outcome was observed in approximately 15% of the cohort.