Tumori最新文献

IntroductionDesmoplastic small round cell tumor (DSRCT) is a rare and aggressive mesenchymal malignancy driven by the EWS-WT1 gene fusion. Prognosis remains poor despite intensive multimodal therapy. Preclinical studies indicate that trabectedin combined with irinotecan exerts synergistic antitumor effects in translocation-driven sarcomas.Case descriptionWe report a case series of eight young patients (age range 11-23 years) with advanced and relapsed DSRCT treated between 2021 and 2024 at five Italian pediatric oncology centers. The trabectedin-irinotecan combination (given on compassionate grounds) was administered as second-line therapy in six cases, and third-line in two. The regimen included trabectedin at 1.3 mg/m², 24-hour infusion, day 1, and irinotecan at 20 mg/m², days 8-12. Observed outcomes included: one complete remission, three partial responses, two minor responses, one mixed response, one progressive disease. The chemotherapy combination was overall well tolerated, with good preservation of patients' quality of life, and no life-threatening adverse events reported.Conclusions:This descriptive case series of trabectedin-irinotecan in DSRCT supports preclinical evidence of synergistic activity. The regimen was well tolerated and showed potential clinical benefit even in heavily pre-treated patients, providing a rationale for further studies to optimize dosing and explore early integration.

IntroductionMultilocus Inherited Neoplasia Allele Syndrome (MINAS) is a condition defined by the presence of germline pathogenic variants in more than one Cancer Susceptibility Gene (CSG). MINAS is still underreported in the literature and public databases. Since MINAS-related phenotypes are difficult to predict, case descriptions may contribute to risk assessment, treatment, and personalized surveillance for proband and relatives.Case Description:Here we report a unique case of early onset, bifocal, non-Triple Negative breast cancer in a 31-year-old woman. Fast metastatic dissemination involving the brain caused the death of the patient in a few months. Her multigene panel testing showed the co-occurrence of pathogenic variants in PALB2 (c.1221del; p.Thr408fs*40), ATM (c.8545C>T; p.Arg2849*), PMS2 (c.1919C>A; p.Ser640*), and MUTYH (c.1103G>A; p.Gly368Asp). The patient inherited the ATM and MUTYH variants from the mother, and PALB2 and PMS2 variants from the father. The brother inherited the maternal ATM and paternal PMS2 variants. A baseline imaging-based family screening excluded malignancies in both parents and in the brother. Tailored monitoring is ongoing based on the risk predicted by pathogenic variants identified in family members.Conclusions:Currently, there are no predictive tools available to determine organ-specific cancer risk in MINAS patients. Given the uncertainty in predicting the phenotypic effect of multiple variants in CSGs, ongoing clinical surveillance and sharing data from complex cases are crucial for improving risk stratification in this condition.

Introduction: The association of acute lymphoblastic leukaemia (ALL) and cystic fibrosis (CF) is rare. We present the case of a paediatric patient affected by CF and refractory B-cell precursor (BCP) ALL, who was treated with combined chimeric antigen receptor T-cells (CAR-T) and allogeneic haematopoietic stem cell transplantation (HSCT).

Case description: Autologous-CD19 targeting CAR-T allowed to achieve molecular remission and spare chemo-related toxicity. As B-cell aplasia was not achieved, the patient underwent HSCT after total body irradiation (TBI)-based conditioning. The course after HSCT was complicated by veno-occlusive disease, status epileptic and pulmonary invasive fungal infection which showed progressive radiological worsening despite aggressive treatment. Five months after HSCT a left upper lobe lobectomy was successfully performed. Thirteen months after HSCT the patient is in complete disease remission with normal lung function.

Conclusions: CAR-T cell therapy bridge-to-HSCT may be an effective approach in paediatric refractory ALL in the context of multiple comorbidities as observed in CF.

PurposeThis project aimed to describe variability of local evaluations of off-label cancer drug requests by submitting a list of identical requests to different Italian centers.MethodsIn October 2024, oncology unit directors listed in the AIOM Libro Bianco were invited to participate, evaluating 11 clinical cases with solid tumors through their internal approval process. Supporting evidence was retrospective in two cases, based on phase II trials in seven, and phase III trials in two. Inter-rater agreement was measured using Fleiss' kappa.ResultsSeven centers completed evaluations. Two cases were approved by all centers, both with a rare cancer with scant alternatives. The mean number of centers approving the individual requests was 5.36/7 (76.6%) with a poor inter-rater agreement (kappa 0.009, 95% CI -0.120 to 0.138). Single centers approved a mean of 8.4 requests (76.6%). The mean number of centers that approved requests was 5.5 for requests based on retrospective studies, 5.3 for those based on phase II trials, and 5.5 for those based on phase III trials. There was no correlation between estimated cost and chance of approval.ConclusionsThere is a significant inter-hospital variability in off-label oncology drug evaluations, leading to potential disparities in patient's access to care.

IntroductionBRCA1/2 testing via liquid biopsy has emerged as a critical, minimally invasive alternative to tissue sampling in metastatic castration-resistant prostate cancer (mCRPC), especially in the context of insufficient, inadequate, or unavailable tumor material.MethodsA multidisciplinary panel of 18 Italian experts from 16 leading academic and clinical institutions convened to develop consensus recommendations on BRCA1/2 testing via liquid biopsy. Through virtual and on-site meetings, technical gaps in pre-analytical, analytical, and post-analytical workflows were identified and addressed. Statements were approved by ⩾80% of panelists and reviewed to reflect both current evidence and expert practice.ResultsThe survey confirmed widespread implementation or imminent adoption of liquid biopsy testing across Italian centers, despite persistent challenges in standardizing sample collection, testing management, preservation, and reporting. Key technical insights included the importance of cfDNA-preserving tubes, optimal storage conditions, assay sensitivity (LoD <1.0%), and bioinformatic integration for detecting low-frequency variants. Next-generation sequencing was unanimously preferred, with BRCA1/2 coverage extended to coding and flanking regions. A harmonized synoptic report structure was proposed to enhance clinical interpretability and facilitate oncologic decision-making.ConclusionsDespite limitations in tissue availability, the integration of liquid biopsy into a diagnostic algorithm, endorsed by both AIOM and ESMO guidelines, enables broader access to BRCA1/2 stratification and supports timely PARP inhibitor therapy. This consensus aims to improve diagnostic consistency and clinical outcomes in the management of mCRPC across Italy.

Introduction: Antibody-drug conjugate (ADC) has become the standard of treatment for metastatic urothelial cancer. Current trials generally test the combination or sequential use of antibody-drug conjugates with different targets and different chemotherapeutic reagents.

Case description: We show that in three patients with metastatic urothelial cancer who have progressed on anti-HER2 antibody-drug conjugates, two showed responses when treated with EV (the same monomethyl auristatin E-containing ADC, but with different targets).

Conclusion: This result showed the therapeutic potential of sequential use of ADC containing the same chemotherapeutic reagents with different targets for metastatic urothelial cancer.

Background: The distinction between a metastatic recurrence and the onset of a second primary malignancy can be diagnostically challenging. Precision medicine can offer valuable support in this context.

Case presentation: A 34-year-old woman was diagnosed in 2012 with hormone-receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer in the left breast, with homolateral axillary node involvement but no distant metastases. Following neoadjuvant chemotherapy, surgery (pathological stage was ypT1b ypN2a M0), adjuvant endocrine therapy and radiotherapy, she remained disease-free until 2021, when a positron emission tomography scan showed a mediastinal mass. Histology revealed a high-grade large cell neuroendocrine carcinoma (LCNEC) lacking breast cancer-specific markers (GATA3-, HR-, HER2-, mammoglobin-, GCDFP15-), with PD-L1 expression at 10% and a tumor mutational burden (TMB) of 9.54 mut/MB. Chemotherapy (cisplatin plus etoposide) led to rapid disease progression, whereas second-line pembrolizumab led to a remarkable and prolonged disease response. Treatment was discontinued in 2023 due to grade 3 immune-related colitis and, as of November 2024, the patient shows no clinical evidence of disease.Molecular analysis:Next-generation sequencing identified shared tumor PIK3CA pathogenic variants in both breast cancer and LCNEC tissues, suggesting a potential relationship as primary tumor and metastasis, rather than two distinct malignancies.

Conclusions: Molecular characterization of cancer enabled the identification of potential causal links between tumors with distinct histologies and locations, offering a deeper insight into an atypical clinical scenario.

In previous reports, we showed the diversity in the epidemiological features of the most prevalent lymphohaematopoietic malignancies (LHM) in Sardinia, Italy. In this paper, we reviewed those findings, aiming to: 1) explore the geographic correlation between the various LHM; 2) estimate the standardised incidence rates up to 2017; 3) compare our estimates with nationwide trends; 4) project such trends up to 2030; and 5) predict the expected LHM cases in the upcoming years by health district to assess the adequacy of the existing Haematology and Healthcare services. We observed a high probability for all LHM combined exceeding the expectation in the central-northern and central-eastern areas of the region. There was a weak, though significant, geographic correlation between non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), but not the other LHM. The estimated incidence of all LHM was higher in Sardinia than nationwide. The chances for the existing Haematology units and Healthcare services to adequately match the expected incident cases appear low. This paper concludes a 50-year journey in the epidemiology of LHM among a genetically peculiar population. We hope our results will promote appreciation of the value of extending the routine registration of incident cancer cases for prevention and healthcare planning.

Purpose: Hospital admission is frequently required in the cancer trajectory. In a context of bed shortage, pressure on Emergency Departments and increasing healthcare costs, promoting actions that contain hospital stay is a priority. We studied the variables able to predict longer hospital stays.

Methods: We retrospectively retrieved data on consecutive admissions in our cancer inpatient unit in a 6-month period and assessed individual and clinical variables potentially related with duration of hospital stay through univariate and multivariate analysis.

Results: Among the 147 included admissions, mean overall duration of hospital stay was 8.46 days (95% I.C. 8.36 to 8.55). Significant differences were shown for two clusters of variables: 1) the clinical condition causing admission: non-controlled disease vs responding disease (10.0 vs 6.8 days, p: 0.006); cancer-related symptoms vs acute events (not directly cancer-related) or toxicity (9.8 - 6.0 - 7.2 days, respectively; p: 0.05). 2) The discharge modality: discharge at home (6.2 days) vs assisted discharge either at home or in a long-term structure or in hospice (11.0 and 12.5 days, respectively; p: 0.0001). Disease control and discharge modality retained statistical significance also in the multivariate analysis.

Conclusions: Admissions for which a long hospital stay is advisable can be anticipated from patients' entry. Actions on faster symptom control and discharge preparedness may have a strong impact on duration of stay and on bed availability.

Aims: This study evaluates the activity of nivolumab plus metformin in pre-treated metastatic renal cell carcinoma (mRCC) patients.

Materials and methods: The NivoMet TWINS-GU002 Study was a prospective, multicentre, single-arm, phase II trial conducted in pre-treated mRCC patients eligible for nivolumab and without diabetes mellitus. Patients received nivolumab (240 mg every two weeks) plus metformin (500 mg orally twice a day) until disease progression. The primary endpoint was the 9-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), overall response rate (ORR), and safety.

Results: Twelve patients from two sites in Italy were enrolled from November 2020 to April 2023. The trial was terminated early due to slow accrual. The median PFS was 2.7 months, and the 9-month PFS rate was 8%. The median OS was 14.9 months. The ORR was 8%, and the disease control rate (DCR) was 25%. Adverse events (AEs) of any grade occurred in 75% of patients, with only one grade 3 AE (fatigue) not related to treatment. No grade 3 or 4 treatment-related AEs occurred.

Conclusions: The combination of nivolumab and metformin showed marginal activity in pre-treated mRCC patients. Further investigations are needed to explore metabolic pathways as potential therapeutic targets.