The mammalian target of rapamycin (mTOR) pathway inhibitors are key drugs for the treatment of many tumor types, however, there are no predictive biomarkers in clinical use. Here, we performed a molecular and immunohistochemical characterization of key mTOR pathway components in a series of 105 renal cell carcinoma patients treated with rapalogs, aimed at identifying markers of treatment response. Mutational analysis in MTOR, TSC1 and TSC2 was performed through targeted next‐generation sequencing (NGS), and immunohistochemistry (IHC) was performed for PTEN, pAKT, pS6K1, pS6 and p21. Among patients with NGS data, 11 of 87 (13%) had mTOR pathway mutations (8 in MTOR, 1 in TSC1 and 2 in TSC2). When comparing the molecular data to the response of the patients, we found that partial response was more frequent in cases with mTOR pathway mutations than in those without mutations (odds ratio [OR] = 0.08, 95% confidence interval [CI] = 0.008–0.79, p = 0.030 univariate; p = 0.038 multivariable). Regarding IHC, negative PTEN staining was detected in 58% of the tumors, and it was more frequent in rapalog responder patients (OR = 0.24, 95% CI = 0.065–0.86, p = 0.029 univariate; p = 0.029 multivariable). Mutations and PTEN IHC were not mutually exclusive events and its combination improved response prediction (OR = 0.16, 95% CI = 0.04–0.62, p = 0.008 univariate; p = 0.013 multivariable). The staining of other proteins did not show and association with response and no association with PFS was observed in unselected patients. In conclusion, our findings suggest that mTOR pathway mutations, negative PTEN IHC and their combination are potential markers of rapalog response.

Desmoid tumors (DTs), also known as aggressive fibromatosis, are rare neoplasms characterized by local invasiveness and a high risk of recurrence, despite their lack of metastatic potential. The management of these tumors remains challenging due to their unpredictable behavior and heterogeneous presentations. In this two-part study, we first provide a comprehensive review of the scientific evidence on diagnosis and emerging therapeutic strategies for DT. In the second part, we will present a retrospective analysis of our experience at a national reference center for sarcoma treatment, focusing on diagnostic strategies, therapeutic interventions, and clinical outcomes.

Background: Non-AIDS defining malignancies present a growing challenge for persons with human immunodeficiency virus (HIV, PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish IMPAC-Neo protocol was designed to compare two comprehensive cancer screening strategies integrated into routine HIV care. This study reports baseline data on the prevalence and types of precancerous lesions and early-stage cancer among participants at enrolment. Acceptability of the procedure was additionally assessed. Methods: Cross-sectional analysis of a comprehensive screening protocol to detect precancer and cancer. The readiness of healthcare providers to implement the protocol was evaluated using a validated 4-item survey. Results: Among the 1430 enrolled PWH, 1172 underwent 3181 screening tests, with positive findings in 29.4% of cases, leading to further investigation in 20.7%. Adherence to the protocol was 84%, with HIV providers expressing high acceptability (97.1%), appropriateness (91.4%), and feasibility (77.1%). A total of 145 lesions were identified in 109 participants, including 60 precancerous lesions in 35 patients (3.0%), 9 early-stage cancers in 9 patients (0.8%), and 76 low-risk lesions in 65 subjects (5.5%). Adverse events related to screening occurred in 0.8% of participants, all mild. The overall prevalence of cancer precursors or early-stage cancer was 3.8% (95% confidence interval [CI], 2.74%–5.01%), with highest rates observed in individuals screened for anal and colorectal cancers. Conclusions: The baseline comprehensive cancer screening protocol of the IMPAC-Neo study successfully identified a significant proportion of PWH with precancerous lesions and early-stage cancer. High adherence rates and positive feedback from providers suggest effective implementation potential in real-world healthcare settings.

Apixaban and rivaroxaban are two direct-acting oral anticoagulants (DOACs) recommended for thromboprophylaxis in cancer patients treated with chemotherapy in an ambulatory setting. We aimed to assess the cost-utility of thromboprophylaxis with apixaban and rivaroxaban vs no thromboprophylaxis in ambulatory cancer patients starting chemotherapy with an intermediate-to-high risk of venous thromboembolism (VTE), Khorana score ≥ 2 points. A cost-effectiveness analysis was performed from the perspective of Spain´s National Health System (NHS) using an analytical decision model in the short term (180 days) and a Markov model in the long term (5 years). Transition probabilities were obtained from randomized, double-blind, placebo-controlled clinical trials of apixaban and rivaroxaban in adult ambulatory patients with cancer at risk for VTE, treated with chemotherapy (AVERT and CASSINI trials). The costs (€2021) were taken from Spanish sources. The utilities of the model were obtained through the EQ-5D questionnaire. Deterministic (base case) and probabilistic (second-order Monte Carlo simulation) analyses were conducted. In the probabilistic sensitivity analysis, apixaban generated a cost per patient of €1,082 ± 187 with a 95% confidence intervals (CI) of €713;1,442, while no prophylaxis produced a cost per patient of €1,146 ± 218 with a 95% CI of €700; 1491, with a saving of €64 per patient and a gain of 0.008 QALYs. Likewise, rivaroxaban provided a cost per patient of €993 ± 133 with a 95% CI of €748; 1,310, while no prophylaxis produced a cost per patient of €872 ± 152 with a 95% CI of €602; 1,250, with an additional expense of €121 per patient and a gain of 0.008 QALYs. In thromboprophylaxis of cancer patients, the use of apixaban and rivaroxaban generated similar cost compared to non-prophylaxis, without the difference found being statistically significant, with a clinically insignificant QALY gain.

Background/Objectives: Primary cardiac sarcomas are rare and aggressive tumors. Management is often guided by evidence from other sarcoma types due to limited disease-specific data. This study aimed to analyze the clinical characteristics, pathology, treatment, and outcomes of primary cardiac sarcomas at a national referral center in Spain. Methods: We conducted a retrospective, observational, single-center study from February 2017 to December 2024. Patient data were collected from medical records, and a descriptive analysis was performed. Results: Twelve patients were identified (58% female; median age 43 years, range 13–76). Dyspnea was the most common symptom (8/12, 67%), and the right atrium was the most frequent tumor site (6/12, 50%). Angiosarcoma was the predominant histologic subtype (6/12, 50%). Seven patients had localized disease at diagnosis. Surgery was performed in six patients, with complete (R0) resection in two. Two patients received adjuvant chemotherapy, one underwent cardiac transplantation, and one received sequential chemo- and radiotherapy. All patients experienced tumor recurrence, with a median recurrence-free survival of 5 months (95% CI, 1.5–8.6). Median overall survival for localized disease was 22 months (95% CI, 16–28). Five patients were metastatic at diagnosis, and 11 of 12 developed metastases. Median progression-free survival for first-line therapy was 5.9 months (95% CI, 1.8–9.9), and median overall survival for advanced disease was 12 months (95% CI, 10–13.6). Conclusions: Complete surgical resection was rarely achieved, and recurrence was universal. Outcomes remained poor even for localized disease, highlighting the limited efficacy of current therapies and the need for improved multimodal treatment strategies.

Background: Desmoid tumors (DTs) are rare, locally aggressive fibroblastic neoplasms with highly heterogeneous clinical behavior. The present work constitutes the second part of a two-part project, following our previously published multidisciplinary review of the diagnostic and therapeutic landscape of DTs. It provides a comprehensive analysis of our institutional experience as a national reference center for sarcoma. We aim to describe real-world diagnostic pathways, management strategies, and clinical outcomes in a high-volume cohort. Methods: We conducted a retrospective cohort study that included patients diagnosed with DT at our center between 2014 and 2024. Demographic, clinical, molecular, treatment, and outcome data were collected. Management strategies were analyzed according to tumor location, symptoms, progression patterns, and multidisciplinary decision-making. Outcomes included response rates, event-free survival (EFS), need for active treatment, response to systemic therapy, and recurrence after local treatments. Results: A total of 109 patients were included (median age 36.8 years; 56.9% women). Somatic CTNNB1 mutations were identified in 23 of 29 tested patients, predominantly T41A, while germline alterations were found in 18 patients, mainly in APC. Initial management was conservative in 40.4% of patients and active in 59.6%, primarily through surgery. After a median follow-up of 41.5 months, 44.9% of patients experienced disease progression. Among patients managed with active surveillance, spontaneous regression occurred in 22.2%, and 58% remained treatment-free. Surgical relapse occurred in 35.8% of patients undergoing upfront resection, with major postoperative complications limited to externally operated cases. Cryoablation achieved radiological responses in most evaluable patients, while systemic therapies showed clinical activity but relevant toxicity, particularly with tyrosine kinase inhibitors. The median EFS for the whole cohort was 57 months. Conservative initial management and R1/2 surgical margins were independently associated with worse EFS. Conclusions: Our results support a personalized, multidisciplinary management strategy for DTs, prioritizing conservative approaches when appropriate and reserving active treatments for progressive or symptomatic disease. Outcomes achieved in a specialized referral center are comparable to those reported in large international retrospective series, underscoring the value of expert multidisciplinary care in optimizing DT management.