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Despite Immune-Oncology (IO) combinations, bone metastases (BM) remain a clinical challenge, occurring in ~30% of metastatic renal cell carcinoma (mRCC) patients and leading to skeletal-related events (SREs). Bone-targeted therapies (BTT), denosumab (Dmab) and zoledronic acid (ZOL AC), reduce SREs but are associated with a risk of Medication-Related Osteonecrosis of the Jaw (MRONJ), especially when combined with Vascular Endothelial Growth Factor Receptor - Tyrosine Kinase Inhibitors (VEGFR-TKIs). We retrospectively collected data from mRCC patients with BM who received IO alone or in combinations and VEGFR-TKIs concurrent or sequential with BTT from January 2013 to January 2025. We identified 104 mRCC patients who received BTT (Dmab: 86/104; ZOL AC: 18/104; switch: 4/104). MRONJ occurred in 12/104 (11.5%) patients, with a median BTT exposure of 13.8 months vs. 11.6 months in the overall cohort. At ONJ diagnosis, 10/12 patients were on VEGFR-TKI, one on IO (previously on pazopanib), and one off therapy (previously on tivozanib). Notably, patients on IO-IO or IO-TKI combinations (10) did not develop MRONJ. This study represents one of the largest real-world cohorts assessing MRONJ incidence in mRCC patients treated with VEGFR-TKIs and IO-combo with concomitant BTT. Our findings confirm an MRONJ rate consistent with prior reports (10-17%) of patients treated with TKIs monotherapy and BTT.

Objective: This study aims to unravel the relationship between apolipoprotein C1 (APOC1) levels, prognostic nutritional index (PNI), and clinicopathological characteristics in patients with diffuse large B-cell lymphoma (DLBCL) and their prognostic predictive value.

Methods: This study retrospectively analyzed clinical data from 55 DLBCL patients and 50 healthy screening volunteers. APOC1 levels and the PNI were compared between groups, along with their association with DLBCL's clinicopathological features. Patients were stratified into favorable and poor prognosis groups based on the International Prognostic Index (IPI), with APOC1 and PNI compared between subgroups. Kaplan-Meier curves were used to analyze the impact of high and low expression levels of APOC1 and PNI on progression-free survival (PFS) and overall survival (OS) in DLBCL patients. Multivariate logistic regression identified risk factors for poor prognosis, while Receiver Operating Characteristic (ROC) curves assessed the predictive value of APOC1 and PNI for DLBCL outcomes.

Results: DLBCL patients had higher APOC1 levels and lower PNI than controls. Patients with advanced-stage (III-IV) disease showed significantly increased APOC1 and decreased PNI compared to early-stage (I-II) cases. DLBCL patients with high APOC1 expression and low PNI showed left-shifted PFS and OS curves (P < 0.05). Both elevated APOC1 and reduced PNI were independent risk factors for poor prognosis, with Area Under the Curve (AUC)s of 0.836 and 0.779, respectively. Their combined predictive value improved, suggesting potential utility in prognosis assessment.

Conclusion: APOC1 levels and PNI are significantly correlated with higher disease risk in DLBCL, and their combined evaluation may help improve risk assessment.

Breast cancer (BC) is the leading cause of cancer-related mortality among women, with early BC (EBC) comprising most cases. Advancements in neo(adjuvant) therapies have significantly improved outcomes, although they are often associated with cancer treatment-induced bone loss, which increases the risk of fractures and negatively impacts quality of life. Bone-modifying agents (BMAs), such as bisphosphonates and denosumab can mitigate this adverse effect. By reviewing and summarizing the most recent evidence published on BMAs use in EBC, an expert Italian Panel, composed of the authors of the Italian Association of Medical Oncology (AIOM) guidelines, offers an extended clinical interpretation and updated overview of key questions and recommendation, including the optimal timing of BMAs initiation, appropriate treatment duration, and the most effective agents for fracture risk reduction. Additionally, a critical and previously unaddressed topic is also discussed: BMAs impact on survival outcomes in EBC scenario. This paper offers practical insights into bone health management for EBC patients, explores the potential survival benefits offered by BMAs, and highlights differences among international guidelines regarding their recommended use.

Introduction: An indirect approach was applied to the case-study of thyroid cancer (TC) and melanoma of the skin (MS) in Italy to identify health services (HS) for cancer patients and to enable cost estimation.

Materials and methods: Within the Epicost-2 project, a self-controlled crossover design analysed TC and MS 2018 prevalent cases from Italian cancer registries. Controls (1:1) were matched to cases 18-6 months prior to diagnosis; increases between cases and controls in potentially cancer-related HS claims (P⩽5%) were identified.

Validation: Oncology and clinical experts validated cancer-related HS lists using statistical, clinical, and economic criteria.

Results: The approach identified 202 and 333 cancer-related HS codes for TC and MS, respectively, aligned with clinical pathways.

Discussion: The indirect approach reduced validation workload by 75% versus direct one.

Conclusion: The approach identifies the costs of cancer care that could also be reproduced in other countries with consistent results, and the approach applied to other cancers.

Background: Women carriers of BRCA1/2 mutations face a very high lifetime risk (penetrance) of developing breast and/or ovarian cancer. A sizeable proportion of carriers, however, does not develop cancer at all or develop it only late in life, thus suggesting a potential modulation of this risk. Epidemiological studies have suggested that other genetic (polymorphisms) and environmental factors (lifestyle) affect penetrance. However, data regarding these associations mainly come from retrospective case-control analyses and the results are likely to be distorted by bias.

Aims: The e-BRAVE (Brca, ReseArch, Virtual, Education) study aims to create a web-based prospective cohort and biological bank of unaffected women carriers of BRCA1/2 mutations to investigate the role of polymorphisms and environmental factors, and their interaction, in the occurrence of primary BRCA-related cancers.

Methods: An innovative digital platform (including a mobile App) will be used to empower the synergy between participants and researchers, supporting engagement with women, adherence to intervention plan, self-empowerment, flanked by activities tracking and monitoring.

Results: Based on the incidence data in previous studies, we estimate to observe an overall incidence of ~3.7% year.

Conclusion: The success of this study will ensure the definition of further predictive risk models and comprehensive recommendations aimed at improving management and health of BRCA women.

Background: As part of the improvement plan of the Organisation of European Cancer Institutes at the Fondazione IRCCS Istituto Nazionale dei Tumori of Milan (INT) a Committee composed of patients, caregivers, and representatives of patient associations has been established to actively participate in the planning and organization of both hospital services and research initiatives. The potential impact of implementation of the Committee could ensure a patient-centered care environment.

Aim: To determine whether there is consensus among INT staff on key aspects of the Committee.

Method: Selected INT staff (experts) were invited to participate in a Delphi study. Each expert was asked to rate their agreement on 13 statements and give a brief explanation for their answers. Only the statements that failed to reach an 80% consensus were reintroduced in the second round, following the same procedures.

Results: Ninety experts responded to Round I (55.21% response rate). Eight statements reached the 80% consensus threshold, while five did not meet the predefined threshold and were therefore re-proposed in the second round. These statements concerned the Committee's role (advisory vs decision-making), the perceived value of the Committee in research (improvement vs no involvement), and participant compensation (voluntary vs paid). In Round II, 69 experts participated (79.31% response rate), but none of the reintroduced statements reached the required consensus threshold.

Conclusion: Although a Committee is a topic of theoretical interest and aligns with respondents' values, the establishment of a Committee in INT is currently difficult to implement. Training and awareness initiatives are necessary, as requested by respondents.

Background: Recent advancements in identifying druggable molecular drivers in lung adenocarcinoma (LUAD), have transformed treatment paradigms. In recent years, Next Generation Sequencing (NGS) has gained momentum as an essential tool for in-depth simultaneous analysis of multiple genes, thereby streamlining the diagnostic process in LUAD. Despite this, the implementation of NGS testing in both the US and Europe remains suboptimal.

Aims: In compliance with a decree issued by the Italian Ministry of Health, Lombardy Region recently launched an initiative to implement NGS testing in patients with advanced LUAD. In this context, a real-world prospective observational study was planned to assess the efficacy of the regional network of molecular laboratories in testing nine biomarkers (KRAS p.G12C, EGFR, BRAF, HER2, MET mutations; ALK, ROS1, NTRK1-3, RET rearrangements), for on-label molecularly targeted drugs.

Results: In 2023, out of the 2784 advanced/metastatic LUAD patients expected in Lombardy, 2343 (84.2%) were successfully evaluated with an NGS panel including all the nine biomarkers for on-label drugs. Actionable aberrations were identified in 45.5% of the patients (1068/2343), predominantly involving EGFR, KRAS, and ALK genes.

Conclusion: Our data provide evidence that establishing a structured network of NGS hubs is mandatory to ensure access of advanced LUAD patients to molecularly targeted treatments.

Objective: To analyze the central lymph node metastasis (CLNM) rates of patients who underwent prophylactic central lymph node dissection (pCLND) with total thyroidectomy for cT1-2N0 papillary thyroid cancer in our clinic, to evaluate the conditions associated with lymph node metastasis, and to examine the necessity of pCLND in these patient groups.

Methods: This study includes a retrospective review of the medical data of patients who underwent bilateral/unilateral central lymph node dissection (CLND) (b/uCLND) with total thyroidectomy in our center between 2013 and 2021, whose fine needle aspiration biopsy result was reported as malignant, who were detected as cT1a-1b-2N0 on thyroid and neck ultrasonography.

Results: Of the 251 patients included in the study, 63 (25%) had CLNM (49 (19.5%) ipsilateral and 14 (5.5%) had contralateral CLNM). Twenty-two (20.1%) of 109 patients with cT1a, 30 (28.3%) of 106 patients with cT1b, and 11 (30.5%) of 36 patients with cT2 had CLNM, and metastasis rates increased with increasing cT category. CLNM rates increased with increasing pT category (p=0.005). CLNM was present in 21 (38.8%) of 54 patients (21.5%) with collision tumors, and metastasis rates increased significantly compared to the presence of a single histopathologic tumor (p=0.006). CLNM rates were higher in patients with multicentric tumor localization than in those with unicentric localization (p=0.006).

Conclusion: Multicentricity, bilaterality, capsule invasion, collision tumors and tumors larger than 1 cm increase the risk of CLNM. uCLND for tumors larger than 1 cm, bCLND for tumors larger than 2 cm can be considered. We believe that patients with unilateral CLNM also have an increased risk of contralateral metastasis.

Introduction: Anti-HER2 drugs are becoming an important therapeutic option for various solid tumors, increasing the need for HER2 status testing. Comprehensive genomic profiling (CGP) panels, including FoundationOne®CDx, are commonly used to assess ERBB2 (encoding for HER2) copy number alterations. We aimed to evaluate the analytical validity of FoundationOne®CDx assay, by comparing ERBB2 copy number data with traditional HER2 status by immunohistochemistry (IHC)/in situ hybridization (ISH) assays in a heterogeneous cohort of solid tumor samples.

Methods: We retrospectively reviewed the 531 cases evaluated by FoundationOne®CDx in our Institution, and HER2 status by IHC/ISH could be internally analyzed in 68 cases, including 31 (45.5%) gastroesophageal, 17 (25.0%) colorectal, four (5.8%) breast and two (2.9%) cholangiocarcinoma patients.Tumors with estimated ERBB2 copy number ⩾ 4 by FoundationOne®CDx, and tumors with strong and complete (3+) membranous staining by IHC and/or a HER2/CEP17 ratio ⩾2 by ISH were considered NGS positive and IHC/ISH positive, respectively.

Results: We identified 21 NGS positive cases (30.9%); IHC/ISH analysis confirming overexpression/amplification in 16 cases (sensitivity: 76.2%), while among the 47 NGS negative cases, 45 were confirmed by IHC/ISH results (specificity: 90%), with a positive predictive value of 76.2% and a negative predictive value of 95.7%.

Conclusions: FoundationOne®CDx provides an accurate evaluation of ERBB2 copy number status and may represent a cost-effective option in metastatic cancer patients for whom NGS testing is recommended.

Introduction: The strategic addition of immune checkpoint inhibitors (ICIs) to chemotherapy (CT) offers a potential paradigm shift in the treatment of elderly cancer patients. This systematic review evaluates the impact of ICIs combined with CT on the overall survival (OS) of patients aged 65 and older.

Material and methods: Using the terms "immune checkpoint inhibitors" and (PD-1 or PD-L1 or CTLA-4) and ("cancer" or "carcinoma") and ("elderly" or "older" or "65 years" or "70 years"), we searched PubMed, Embase, and the Cochrane Library through March 2024. We selected only English language, phase II-III randomized controlled trials comparing first-line CT + ICIs vs. CT alone for metastatic cancers, with subgroups reporting outcomes of elderly patients (according to the authors' cutoff of at least 65 years). Hazard ratios (HR) for OS with relative 95% confidence intervals (95%CI) were extracted from each study. Summary HR was calculated using random- or fixed-effects models, depending on the heterogeneity of the included studiesResults:The study synthesizes data from 46 phase III randomized controlled trials, focusing on first-line treatments for metastatic cancers, where ICIs plus CT are compared against CT. The meta-analysis reveals that the combination therapy significantly improves OS in certain cancer types like lung cancers (HR=0.79, 95%CI 0.73-0.86; P<0.01), esophageal (HR=0.68, 95%CI 0.6-0.77; P<0.01) and gastric carcinomas (HR=0,8, 95%CI 0.63-0.88; P<0.01). In other cancers, evidence is less strong (e.g, gynecological, breast, genitourinary, head and neck, and skin cancers).

Conclusions: These findings suggest that while the addition of ICIs can enhance survival outcomes in a subset of elderly cancer patients, its efficacy is highly contingent upon the cancer type and the specific patient's health profile.