Cancers最新文献

Actinium-225 (²²⁵Ac) has emerged as a pivotal alpha-emitter in modern radiopharmaceutical therapy, offering potent cytotoxicity with the potential for precise tumour targeting. Accurate, patient-specific image-based dosimetry for ²²⁵Ac is essential to optimize therapeutic efficacy while minimizing radiation-induced toxicity. Establishing a robust dosimetry workflow is particularly challenging due to the complex decay chain, low administered activity, limited count statistics, and the indirect measurement of daughter gamma emissions. Clinical single-photon emission computed tomography/computed tomography protocols with harmonized acquisition parameters, combined with robust volume-of-interest segmentation, artificial intelligence (AI)-driven image processing, and voxel-level analysis, enable reliable time-activity curve generation and absorbed-dose calculation, while reduced mixed-model approaches improve workflow efficiency, reproducibility, and patient-centred implementation. Cadmium zinc telluride-based gamma cameras further enhance quantitative accuracy, enabling rapid whole-body imaging and precise activity measurement, supporting patient-friendly dosimetry. Complementing these advances, the cerium-134/lanthanum-134 positron emission tomography in vivo generator provides a unique theranostic platform to noninvasively monitor ²²⁵Ac progeny redistribution, evaluate alpha-decay recoil, and study tracer internalization, particularly for internalizing vectors. Together, these technological and methodological innovations establish a mechanistically informed framework for individualized ²²⁵Ac dosimetry in targeted alpha therapy, supporting optimized treatment planning and precise response assessment. Continued standardization and validation of imaging, reconstruction, and dosimetry workflows will be critical to translate these approaches into reproducible, patient-specific clinical care.

Background: Gastric cancer (GC) is one of the most common malignancies, requires aggressive treatment, as has a high incidence of complications. The high prevalence of cachexia and comorbidity among GC patients has led to the development of the "prehabilitation" concept. We aimed to investigate the prognostic value of cachexia in the "Western" patient population with resectable GC and to evaluate its utility as an indicator for a home-based prehabilitation program. Methods: This cohort study included 147 patients who underwent surgical treatment for GC from 2019 to 2023. A multivariable analysis was conducted to study the impact of cachexia on postoperative outcomes in 122 patients with resectable GC. The prehabilitation group included 25 patients with cachexia who underwent a 2-week-long multimodal prehabilitation program prior to surgery. The functional results, as well as the 30-day incidence of postoperative complications and 90-day mortality, were evaluated. Results: There were 76 (51.7%) patients with cachexia. Multivariate analysis revealed that cachexia was a significant predictor of all postoperative complications (OR = 5.48, 95% CI 1.85-18.39, p = 0.001), severe postoperative complications (OR = 15.87, 95% CI 3.05-131.81, p < 0.001) and surgical site infection (SSI) (OR = 8.03, 95% CI 1.89-49.09, p = 0.038). Patients in the prehabilitation group had a lower incidence of SSI than in the control group (8.3% vs. 23.5%, p = 0.049). Conclusions: Preoperative cachexia is a potentially modifiable predictor of complications after gastric cancer surgery, and its identification may help define high-risk patients for proactive multimodal prehabilitation.

HPV-positive OPSCC shows a favourable prognosis, prompting evaluation of de-escalated and adaptive strategies. Quantitative imaging may provide scalable biomarkers to individualise care. Quantitative imaging can support baseline risk stratification, early on-treatment decision-making, and posttreatment surveillance in HPV-positive OPSCC. Real-world translation requires standardised reporting, calibration/harmonisation across centres, rigorous model validation, and workflow integration with radiotherapy planning. Quantitative MRI, CT, and PET, augmented by radiomics and AI, show convergent promise as non-invasive biomarkers to enable safe individualisation of therapy in HPV-positive OPSCC, contingent on methodological rigour and prospective, externally validated studies. Despite this promise, clinical translation faces substantial barriers, including limited external validation, heterogeneous methodologies, and the need for standardised, prospectively validated pipelines.

Background/objectives: Epithelial ovarian cancer (EOC) is often diagnosed at advanced stages, with metastasis driven by spheroid dissemination within the peritoneal cavity. We previously demonstrated that autophagy supports spheroid cell survival and suggest that it contributes to chemoresistance. Unc-51-like autophagy activating kinase 1 (ULK1), a key regulator of autophagy, has emerged as a promising therapeutic target. Here, we evaluated the effects of ULK1 inhibition via MRT68921, alone and in combination with afatinib-a tyrosine kinase inhibitor (TKI) known to induce pro-survival autophagy-in EOC.

Methods: High-grade serous (HGSOC) and ovarian clear cell carcinoma (OCCC) cell lines were cultured under adherent and spheroid conditions. Immunoblotting confirmed on-target effects and modulation of autophagy. Autophagic flux was assessed using mCherry-eGFP-LC3 reporter assays. We assessed 96 dose combinations of MRT68921 and afatinib using drug combination matrices, with synergy evaluated via Synergy Finder. Promising combinations were evaluated across multiple EOC spheroid models and patient ascites-derived organoids.

Results: MRT68921 inhibited ULK1 activity and reduced autophagic flux in a context-dependent manner while afatinib alone induced autophagy. Their combination produced synergistic effects at select concentrations, impairing spheroid reattachment and viability. However, MRT68921 alone significantly reduced viability across multiple EOC models, including patient ascites-derived organoids.

Conclusions: This study is the first to evaluate the combined effects of MRT68921 and afatinib in epithelial ovarian cancer. Our findings demonstrate that ULK1 inhibition via MRT68921 consistently reduces cell viability across multiple ovarian cancer models, supporting ULK1 as a promising therapeutic target. In contrast, combination with afatinib produced limited and context-dependent effects, indicating that further investigation is needed to identify optimal combination strategies for ULK1-targeted therapies.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited treatment options for patients with locally advanced or metastatic disease. Endoscopic ultrasound (EUS)-guided intra-tumoral radioactive implantation has emerged as a minimally invasive approach to enhance local tumor control while minimizing systemic toxicity. Among the available isotopes, phosphorus-32 (³²P) microparticle brachytherapy has demonstrated promising outcomes, including significant tumor regression, reductions in CA 19-9, and higher rates of tumor downstaging and surgical conversion when combined with systemic chemotherapy. Compared with stereotactic body radiotherapy (SBRT), ³²P delivers higher intratumoral radiation doses, spares adjacent healthy tissues, and can be administered during ongoing chemotherapy without treatment interruption. Additionally, preliminary evidence suggests that ³²P may modulate the tumor microenvironment, improving vascularity and enhancing chemotherapy efficacy. The procedure shows high technical success and a favorable safety profile, with minimal serious adverse events. Future directions include prospective randomized trials to validate its impact on survival, optimize dosing, and establish treatment protocols. EUS-guided intra-tumoral ³²P brachytherapy holds potential as a key component of multimodal therapy, bridging local tumor control and systemic disease management in PDAC.

Management of resectable esophageal cancer has evolved into a multidisciplinary paradigm centered on multimodality therapy. Historically, induction chemoradiotherapy followed by surgery, as established by the CROSS trial, became the standard of care for locally advanced disease due to improvements in R0 resection rates and overall survival. More recently, the ESOPEC trial reexamined this paradigm in esophageal adenocarcinoma, demonstrating superior survival and improved systemic disease control with perioperative chemotherapy using the FLOT regimen compared with chemoradiotherapy. In parallel, the MATTERHORN trial further advanced perioperative treatment by showing improved event-free survival with the addition of the immune checkpoint inhibitor durvalumab to FLOT chemotherapy. Alongside these systemic therapy advances, surgical management has transitioned toward minimally invasive and robotic-assisted esophagectomy, offering equivalent oncologic outcomes with reduced perioperative morbidity. This review summarizes the evolving evidence from pivotal clinical trials, highlights ongoing studies integrating immunotherapy, and discusses emerging strategies such as adoptive cell transfer which currently is under investigation for metastatic recurrence, but in the future may provide additional treatment options for resectable esophageal cancer.

Background: The prognostic value of phosphatidylinositol-3-kinase p110α, a key catalytic subunit in the PI3K/AKT pathway, in breast cancer remains controversial. This study evaluated its prognostic significance in stage I-III invasive breast cancer.

Methods: p110α protein expression was detected via immunohistochemistry (IHC) in 161 patient tissue samples. Its association with overall survival (OS) and relapse-free survival (RFS) was analyzed using Kaplan-Meier and Cox proportional hazards models.

Results: p110α positivity was detected in 59.0% of specimens and showed significant correlation with histological grade (p = 0.034). Survival analysis revealed that p110α positivity was associated with worse OS (log-rank p = 0.008) and RFS (log-rank p = 0.018). In multivariate analysis, p110α expression was an independent predictor of poor prognosis for both OS (HR = 2.45, 95%CI: 1.25-4.78) and RFS (HR = 2.12, 95%CI: 1.14-3.94). This association with poor prognosis was particularly pronounced in stage I-II, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative subgroups. Supporting evidence from the PROGgeneV2 database showed that high PIK3CA mRNA levels predicted inferior survival in external cohorts.

Conclusions: p110α protein expression is an independent biomarker for adverse outcomes in stage I-III invasive breast cancer. Its assessment could improve prognostic evaluation and guide personalized therapy.

On behalf of the Editors, we wish to express our sincere gratitude to all authors and reviewers who contributed to the success of this Special Issue, titled "Intraoperative Visualization Techniques and Advanced Imaging in Brain Tumors" [...].

Brain metastases (BMs) represent the most common intracranial malignancy in adults, affecting up to 50% of patients with solid tumours [...].

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.