Frontiers in Oncology最新文献

Intravascular large B-cell lymphoma (IVLBCL) is a rare and highly aggressive lymphoma, but current knowledge is still inadequate. We retrospectively analyzed 50 IVLBCL patients from five Chinese tertiary hospitals in China between 2017 and 2024. Hemophagocytic variant (HV) patients showed worse performance status, universal B symptoms, more bone marrow infiltration, higher mortality, pancytopenia, elevated inflammatory markers (CRP, LDH, ferritin), hypoglobulinemia and hypogammaglobulinemia. Among 46 treated patients, CR/CRu rate was 71% (27/38). The 2-year OS was 65.5%, significantly worse in HV vs. classical variant (CV) (43.3% vs. 76.4%, P = 0.007). Multivariate analysis identified CNS involvement (HR = 10.86, P < 0.001), HV subtype (HR = 1.91, P = 0.018), and nodal organs involvement (HR = 5.26, P = 0.052) as poor prognostic factors. IVLBCL exhibits marked heterogeneity, with HV and CNS involvement conferring dismal outcomes. This study provides key diagnostic/therapeutic insights for IVLBCL in China, warranting prospective trials to validate prognostic models and optimize therapies.

[This corrects the article DOI: 10.3389/fonc.2025.1675819.].

Purpose: The increased expression of LAT1, an amino acid transporter, in cancer cells makes boronophenylalanine (BPA) uptake higher in cancer vs. healthy tissues: a high LAT1 expression on cancer cells implies a higher sensitivity to boron neutron capture therapy (BNCT). We explored the LAT1 expression in a cohort of head and neck cancer (HNSCC) patients, stratifying them according to a previously published transcriptomic 6-cluster model.

Methods: We analyzed 100 HNSCC patients treated with multimodal treatments including radiotherapy. Transcriptomics of primary tumor specimens was obtained by Affymetrix ClariomD chips and processed using the Transcriptome Analysis Console Software (ThermoFisher). We retrieved normalized and log2 LAT1 from the data matrix. Data were used to analyze: i) the distribution by anatomical subsites and transcriptomic subtypes (assessed by Kruskal-Wallis test); ii) overall survival (OS).

Results: LAT1 expression was high (>2.83) in 13% of cases. At median follow-up of 64.44 months (95% CI: 54.24-66.91), overall median OS was 94.24 months, 22.99 months (95% CI 14.31-NR) in patients with high LAT1 vs. 94.24 months (95% CI 65.1-NR) in those with low LAT1. LAT1 expression did not differ significantly among HNSCC primary sites. Among GE clusters, the highest LAT1 expression was observed in those with the worst prognosis, the lowest in the immune-reactive one (p=.000028).

Conclusion: High LAT1 expression has a negative prognostic role and is associated with transcriptomic clusters with unfavorable and radioresistant biologic features. These results justify the use of BNCT in radioresistant HNSCCs and may guide patient selection for future clinical studies with BNCT.

Patients with cancer-associated venous thromboembolism (VTE) often require prolonged anticoagulation because malignancy and chemotherapy can persist for months to years, sustaining both thrombotic and bleeding risks. While full-dose apixaban (5 mg twice daily) is recommended for secondary prevention, extended use may increase bleeding in this vulnerable population. Reducing the dose to 2.5 mg twice daily after six months of full-dose treatment has been proposed to lower bleeding risk without compromising protection against recurrent VTE. To clarify the safety and efficacy of this strategy, we conducted a meta-analysis of randomized controlled trials comparing reduced- versus standard-dose apixaban for extended therapy in patients with cancer-associated VTE. The study followed PRISMA guidelines and was registered in PROSPERO (CRD420251026337). Hazard ratios and risk ratios with 95% confidence intervals were pooled using a random-effects model, and evidence certainty was assessed with GRADE. Two randomized trials comprising 2,126 patients (EVE, n = 360; API-CAT, n = 1,766) met inclusion criteria. The composite outcome of recurrent VTE with bleeding showed a significantly lower risk with reduced-dose apixaban (risk ratio 0.79, 95% CI 0.65-0.96; I² = 0%), and the composite of major and clinically relevant nonmajor bleeding was also reduced (HR 0.75 (95% CI 0.63-0.88; I² = 0%). No significant differences were observed for recurrent VTE, major bleeding, clinically relevant nonmajor bleeding, mortality, deep-vein thrombosis, or pulmonary embolism. These findings indicate that reduced-dose apixaban after the initial six months of anticoagulation decreases bleeding without loss of efficacy, supporting dose de-escalation as a safe, evidence-based approach for extended anticoagulation in cancer-associated VTE.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO CRD420251026337.

Ovarian clear cell carcinoma (OCCC) is a rare and chemoresistant histology known for having a poor prognosis and limited treatment options. Novel therapies offer hope, but come at a significant cost, with patients facing financial toxicity, inequitable access, and systemic barriers inherent to our current cancer care infrastructure. Utilizing a case of complete pathologic response to Lenvatinib, pembrolizumab, and spatially fractionated radiotherapy (SFRT) in metastatic OCCC after overcoming numerous individual and systemic barriers, we address the challenges surrounding access and innovation in cancer treatment, while simultaneously adding evidence to support these novel therapies in OCCC treatment. While acknowledging the role of expanded access programs and right-to-try pathways, we address broader issues surrounding restrictive trial criteria, inequitable resource distribution, and cancer as a chronic disease state, asking the question: how do we develop and disseminate novel therapies while addressing toxicities in today's healthcare system?

Objective: To develop and validate a diagnostic nomogram model for predicting atypical endometrial hyperplasia (AEH) and endometrial carcinoma (EC) in women aged 40-60 years with abnormal uterine bleeding (AUB), incorporating detailed bleeding patterns and clinical parameters.

Methods: This retrospective cohort study included 1,920 patients aged 40-60 years with AUB who underwent hysteroscopic evaluation across four hospital branches from 2021 to 2024. Variables were screened via univariate logistic regression followed by LASSO regression. A multivariate logistic regression model was constructed using seven selected predictors, including age, family history of cancer, endometrial thickness, menstrual blood loss, abnormal menstrual duration, intermenstrual bleeding, and postmenopausal bleeding. Internal validation was performed using bootstrap resampling; external validation was conducted using an independent cohort.

Results: The final model demonstrated good discriminatory performance (AUC = 0.814 in the training cohort, 0.762 in external validation). Calibration plots and the Hosmer-Lemeshow test indicated good agreement between predicted and observed probabilities. Decision curve analysis confirmed favorable clinical utility. Patients classified as high-risk (score ≥70.362) had a significantly increased likelihood of AEH/EC (OR = 12.46, 95% CI: 7.56-21.01, P < 0.001).

Conclusion: This study presents a validated, user-friendly nomogram integrating refined AUB patterns and clinical variables to support early risk stratification for AEH/EC in women aged 40-60 years. The model demonstrates robust predictive performance and may assist in guiding individualized diagnostic strategies, particularly in resource-limited settings.

High-grade neuroendocrine carcinoma (NEC) of the rectum is a rare and aggressive malignancy, with limited treatment options and a poor prognosis. We report the successful off-label use of the PARP inhibitor talazoparib in a patient with metastatic, germline BRCA2-mutated rectal NEC who had a contraindication to standard immunotherapy due to underlying autoimmune disease. A 55-year-old man with ongoing severe psoriatic arthritis presented with a two-week history of rectal pain, abdominal distention, and diarrhea. Cross-sectional imaging demonstrated a rectal mass with mesorectal lymphadenopathy and multiple liver metastases. Biopsy of the rectal lesion demonstrated a high-grade, poorly differentiated NEC with a Ki-67 proliferation index of 99%. Comprehensive tumor molecular profiling identified a pathogenic BRCA2 mutation (c.5291C>G; p.Ser1764*, with loss of the wild-type allele), which was confirmed to be a germline alteration through germline testing. There were also biallelic inactivations of APC, TP53, and RB1. The patient received four cycles of induction chemotherapy with carboplatin and etoposide, achieving a partial radiographic response; however, treatment was complicated by cytopenias and significant fatigue. Immunotherapy was considered inappropriate as part of his initial systemic therapy regimen or as maintenance treatment due to the severe underlying autoimmune condition. Based on the germline BRCA2-mutated (gBRCA) status, we requested emergency approval for off-label use of talazoparib, a poly(ADP ribose) polymerase (PARP) inhibitor. At 12.5 months from initial diagnosis, including after 7.5 months on talazoparib, the patient continues to show ongoing radiographic response with excellent tolerability and no adverse effects. This case illustrates the potential role of PARP inhibitors in the management of BRCA2-mutated high-grade rectal NEC. Molecular profiling techniques may uncover actionable genetic targets in rare, aggressive cancers without standard treatment options or in patients with co-morbidities that preclude standard treatment regimens.

Background and purpose: Bragg peak FLASH proton therapy (FLASH-PT) relies on fast dose delivery (≥ 40 Gy/s) to elicit a normal tissue sparing effect. FLASH-PT beam delivery modifications lead to inferior margin-based FLASH-PT treatment plan quality compared to intensity modulated proton therapy (IMPT). To achieve ultra-high dose rates to regions of interest, dose rate optimisation may need to be utilised as part of the treatment planning process. This study aims to determine the impact of dose rate optimisation and robust optimisation on FLASH-PT treatment plan quality and achievable dose rates. All FLASH-PT plans are also compared to IMPT plans to determine the clinical applicability of the technique.

Materials and methods: FLASH-PT and IMPT treatment plans were generated for bone (n = 3), brain (n = 4) and lung (n = 3) targets for a one-beam-per-fraction and multi-beam-per fraction delivery, respectively. The open-source MIROpt treatment planning system (TPS) was used to generate dose rate optimised FLASH-PT plans, while a research version of the RayStation TPS was used to generate non-dose rate optimised, margin-based, and robust FLASH-PT plans. Dose rate coverage was evaluated for different dose and dose rate thresholds.

Results and conclusion: Dose rate optimised FLASH-PT plans were associated with significantly worse target dose coverage, whilst significantly improving dose rate coverages to organs at risk, compared to non-dose rate optimised plans. The use of dose rate optimisation should be used with caution as it may lead to degraded plan quality. Robust optimisation improved target coverage compared to margin-based plans, without compromising dose rate coverage. FLASH-PT plans struggle to achieve IMPT-equivalent D_95% and is associated with non-significant increases in organ at risk doses compared to IMPT, regardless of TPSs and treatment planning techniques (margin and robust). Future work will focus on improving D_95%, reducing organ at risk doses, and optimising MU/spot delivery to improve plan quality, while further increasing the dose rates.

[This corrects the article DOI: 10.3389/fonc.2020.579561.].

Background: The primary cancer of the urinary system, kidney cancer is becoming more common worldwide and is linked to a high body mass index (BMI). Although 20% of kidney cancer cases are caused by obesity, current research data on the global burden of the disease and its trends across population groups are scarce, especially as predicted by 2040.

Method: We examined age-standardized mortality rates (ASMR), disability-adjusted life years (DALYs), and sociodemographic index (SDI) using Global Burden of Disease (GBD 2021) data from 204 nations and territories. joinpoint regression revealed changes in temporal trends and age-period-cohort (APC) modeling separated the effects of age, period, and cohort. Finally, we project the disease burden to 2040.

Result: From 1990 to 2021, high BMI-related kidney cancer deaths increased by 2.67-fold, and DALYs rose by 66.1%. In 2021, the ASMR for high BMI-associated kidney cancer was 0.38 (95% per 10 0,000 UI: 0.12-0.52) and the ASDR was 8.99 per 100,000 (95% UI: 3.68-14.51). Significant heterogeneity was observed in gender and age, with a significantly higher male burden concentrated in the 55-79 year group. The main burden is concentrated in the high SDI region, including South Latin America, North America, Europe and North Asia. Over 30 years, the burden of high BMI-associated kidney cancer gradually increased, especially in low SDI areas, while high SDI areas showed a decreasing trend after 2016. The global disease burden of high BMI-associated kidney cancer burden grew fastest between 2000 and 2010, began to decline in 2016, and will rebound in 2030.

Conclusion: The global burden of high BMI-associated kidney cancer burden has surged since 1990. Although it showed a downward trend in 2016, it is expected to rebound by 2030. Significant differences exist across regions, genders, and age groups. Policymakers must prioritize obesity prevention, adopt gender-specific strategies, enhance early detection in older populations, and address issues of socioeconomic inequality and unequal distribution of healthcare resources to tackle this public health challenge.