Background: Unresectable cholangiocarcinoma prognosis can be extremely variable due to different symptoms and sites of disease involvement at diagnosis and unpredictable chemotherapy response rates. Most patients will usually receive 1st line palliative chemotherapy with platinum compounds and Gemcitabine or Gemcitabine alone. Only a few patients maintain adequate performance status after first-line treatment failure: second-line treatment with FOLFOX or FOLFIRI chemotherapy has been used in this setting with modest overall survival improvement. There is a lack of data concerning whether laboratory findings might help clinicians in identifying those patients with the highest likelihood of benefiting from 2nd line treatment. The aim of this analysis is to assess the prognostic role of a series of easily available laboratory tests in patients with bile duct cancer who received 2nd line chemotherapy. Patients and Methods: Patients with unresectable bile duct cancer treated in 2nd-line setting with platinum-based chemotherapy doublet or FOLFIRI were enrolled. The primary objective of the analysis was to assess overall survival (OS) differences among patients based on the results of lab tests. Serum hemoglobin, neutrophil, lymphocyte, monocyte, platelet absolute count, creatinine, total bilirubin, albumin, LDH, circulating CEA and CA19.9 values were collected at the start of 2nd line treatment. Cut-off values for all lab tests were set by ROC curve analysis. Survival was calculated by the Kaplan–Meier method and differences in survival among stratification factors were assessed by Log-rank test. Cox-proportional-hazard regression was used for multivariate analysis. Level of statistical significance p was set at 0.05 for all tests. Correction for false discovery error rate was performed by Holm’s stepdown procedure. Results: A total of 46 patients were eligible. Median overall survival of the entire cohort was 8.98 months (95%CI: 6.68–13.93) while mean OS was 17.10 months (standard error: 3.16). Using 6.2 months OS landmark as classification variable for ROC curve analysis, only serum hemoglobin (cut-off: >10 g/dL), albumin (cut-off: >3.5 mg/dL), CA19.9 (cut-off: ≤668 UI/mL), monocyte (cut-off: ≤510/mmc) and neutrophil count (cut-off: ≤5140/mmc) were significantly associated with the chosen end-point. Multivariate analysis confirmed an independent statistically significant impact on overall survival only for hemoglobin (Exp(b): 0.12, p = 0.0023) and neutrophil count (Exp(b): 0.30, p = 0.0039). Based on these results, using both hemoglobin and neutrophil count, three prognostic groups were defined: patients with both favorable factors had 12.63 months median OS vs. 6.75 months of patients with only one favorable factor vs. 1.31 months of those with neither. The difference between these three groups of patients was statistically significant (p < 0.0001). Discussion: Second-line palliative chemotherapy can be a potentially useful option for a few patients with unresectable/metastatic bile duct cancer. Even though assessment of patients’ prognosis might be difficult due to the complex behavior of this disease, a series of easily available laboratory tests might be used for these means: serum hemoglobin and neutrophil count we0re able to define subsets of patients with entirely different prognoses. It is hoped that this score will be prospectively validated in a larger group of patients in order to improve treatment decisions in patients with unresectable bile duct cancer candidate to receive palliative 2nd line chemotherapy.

Aim: During the coronavirus disease 2019 (COVID-19) pandemic two needs have overlapped: on one hand continuing to provide the best care for patients with lung cancer and preventing the spread of the virus between patients and healthcare professionals on the other hand. Due to the pandemic’s unpredictable duration, physicians had to evaluate the risk/benefit ratio of anti-cancer therapeutic strategy to do the best for their patients and to protect patients themselves, as well as healthcare workers. Methods: Systematic literature research was performed with the aim to assess the available guidelines for the management of lung cancer patients during the COVID-19 pandemic. Thirteen potentially relevant articles were selected and recommendations have been divided into three main categories: dos, don’ts and don’t knows. Results: All guidelines and recommendations highlighted the relevance of being able to delay, if possible and based on risk stratification, and curative interventions. The selected recommendations should be considered adaptable and flexible because they might be contextualized on the basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prevalence and the availability of diagnostic-therapeutic resources. Conclusions: It remains of fundamental importance to discuss each diagnostic and therapeutic decision with the patient taking into account risks and benefits that might vary from case to case.

Background: Gender medicine is an emerging approach that recognizes how biological sex, gender identity, and sociocultural roles influence health and disease. These factors can significantly affect prevention, screening, diagnosis, and treatment outcomes. In oncology, accumulating evidence highlights sex-based differences in cancer incidence, therapeutic response, and treatment-related adverse events. A comprehensive gender-based approach should also address the specific needs of sexual and gender minority (SGM) populations. Based on the existing literature and the authors’ expertise, this perspective paper provides an overview of this topic, emphasizing its importance, discussing current challenges, and proposing potential future directions for research and clinical practice. The literature discussed in this article was selected through a narrative, rather than a systematic, approach and is intended to provide the scientific context supporting the authors’ perspective and interpretation of the current evidence. Methods: To investigate gender differences in oncology regarding epidemiological data, we queried the AIRTUM and GLOBOCAN databases. Furthermore, we conducted a bibliography search of scientific papers by querying PubMed/MEDLINE to explore gender differences, in particular regarding treatments. The database was searched by looking for papers published between 1 January 2022 and 31 December 2025. Results: Cancers affecting both sexes show higher incidence and mortality rates in men, a trend observed worldwide and confirmed by national data. However, important sex-related differences also emerge in treatment response. Women appear to derive a smaller survival benefit than men from immunotherapy alone but may experience greater benefit when immunotherapy is combined with chemotherapy. These differences may be explained by distinct molecular mechanisms underlying antitumor immune responses in males and females. Furthermore, women experience higher rates of treatment-related toxicities, likely due to sex-specific differences in pharmacokinetics and pharmacodynamics. Conclusions: Integrating sex and gender perspectives into oncology is essential for advancing personalized medicine and improving patient care. Understanding biological differences can help optimize treatment selection and dosing strategies, thereby enhancing efficacy while minimizing adverse effects. At the same time, addressing gender-related factors may improve psychosocial support, patient well-being, and treatment adherence. Achieving these goals requires coordinated efforts, including sex-disaggregated research, gender-sensitive clinical protocols, and healthcare policies aimed at reducing gender disparities in cancer care.

Background & Aims: Anti‐FGFR therapies changed the treatment landscape for patients with previously treated, advanced, or metastatic cholangiocarcinoma (CCA) harbouring FGFR2 fusions/rearrangements. However, primary resistance to FGFR inhibitors remains a key challenge. In the present real‐world study, we aimed to evaluate the prognostic impact of concomitant GAs in patients with FGFR2 ‐positive CCA treated with pemigatinib. Methods: This study included PEMIREAL‐PEMIBIL patients treated with pemigatinib in second or later lines. Only patients who underwent extensive DNA‐ and/or RNA‐based next‐generation sequencing (NGS) analysis were considered. Primary endpoint was progression‐free survival (PFS), with overall response rate, disease control rate and overall survival (OS) as secondary endpoint. OS and PFS were calculated by Kaplan–Meier and log‐rank test. Multivariate analysis used cox‐regression model. Level of statistical significance p was 0.05. Results: Of 72 patients of PEMIREAL‐PEMIBIL, 63 patients had evaluable NGS data, with concomitant GAs identified in 28 patients (44.4%). The most frequently observed concomitant GAs involved BAP1 (7/63, 11.1%), CDKN2A (7/63, 11.1%), TP53 (6/63, 9.5%), CDKN2B (5/63, 7.9%), PTEN (3/63, 4.7%) and IDH1 (1/63, 1.5%). A significantly shorter PFS was observed in patients with CDKN2A mutations compared to CDKN2A wild‐type tumours (4.79 vs. 8.66 months, p = 0.0011, HR: 3.48 95% CI: 0.91–13.24), and similarly in patients with BAP1 mutations compared to BAP1 wild‐type tumours (5.97 vs. 8.52 months, p = 0.025, HR:2.55 95% CI: 0.72–9.00). No significant differences in OS were observed. Conclusions: Our results support the negative prognostic role of BAP1 and CDKN2A GAs on PFS in patients with locally advanced or metastatic CCA with FGFR2 gene fusion/rearrangement treated with pemigatinib in a real‐world setting.