In recent years, cancer chemotherapy has been administered in an outpatient setting; therefore, patient self-management of adverse events is an important issue. Pharmaceutical interventions were performed by pharmacists at the following 3 time points: before the physician consultation, after the physician consultation, and during multidisciplinary conferences at the Ibaraki Prefectural Central Hospital Cancer Chemotherapy Center. In this study, prescription proposals and their effectiveness for adverse events, were investigated. Of the 338 cases in which pharmaceutical interventions were performed, 280 were accepted by physicians, and the acceptance rates were 77% in conference, 89% before physician consultations, and 85% after physician consultations. Pharmaceutical interventions for the management of nausea and vomiting were most frequently accepted (96 cases), with improvement observed in 58 cases (60%). Improvement rates for hypertension and skin disorders were 76% and 56%, respectively, and improvement rates for peripheral neuropathy and dysgeusia were 33% and 22%, respectively. Of all interventions made by pharmacists, 68% were for the 1st 5 courses, with proposals continuing beyond the 6th course, suggesting that there is demand for long-term intervention. Pharmacists collecting patient information and implementing pharmaceutical interventions may contribute to the management of adverse events. As the degree of improvement varies according to the type of adverse event, it will be necessary to establish optimal pharmaceutical interventions in the future.

Metastatic castration-resistant prostate cancer (mCRPC) remains an aggressive disease with limited response to systemic therapies despite androgen deprivation. Immune-excluded prostate tumors are typically resistant to immunotherapy. STAR0602 is a selective bifunctional T-cell agonist composed of an antibody targeting Vβ6 and Vβ10 T-cell receptor chains fused to human interleukin-2 that selectively expands Vβ6⁺ CD8⁺ memory T cells and has demonstrated clinical activity as a monotherapy in anti-programmed death-ligand 1-resistant tumors (NCT05592626). We hypothesized that combining poly ADP-ribose polymerase (PARP) inhibition with Vβ-directed T-cell activation would enhance antitumor immunity and promote polyclonal T-cell responses in immune-excluded prostate cancer.

The antitumor activity of the PARP inhibitor olaparib combined with mSTAR1302, the murine surrogate of STAR0602, was evaluated in TRAMP-C2 and RM-1 prostate tumor models. Tumor growth, survival, and immune responses were assessed by flow cytometry and functional depletion studies. The role of tumor-intrinsic TRAIL-R2 signaling was evaluated using a TRAIL-R2 knockout TRAMP-C2 model, and clinical relevance was explored by assessing TRAIL-R2 expression in tumor samples from patients treated with olaparib in a Phase 2 clinical trial (NCT02484404).

Combination therapy with olaparib and mSTAR1302 induced significant tumor regression and improved survival compared with either agent alone. Treatment increased tumor-infiltrating lymphocytes, expanded activated Vβ13⁺ CD4⁺ and Vβ13⁺ CD8⁺ T cells, reduced immunosuppressive populations, and enriched stem-like progenitor exhausted CD8⁺ T cells. Depletion studies demonstrated that Vβ13⁺ CD4⁺ T cells, Vβ13⁺ CD8⁺ T cells, natural killer cells, and interferon-γ were required for therapeutic efficacy. TRAIL-R2 knockout experiments demonstrated that tumor-intrinsic TRAIL-R2 signaling contributes to the antitumor activity of the combination. Mechanistically, these findings support a model in which PARP inhibition sensitizes tumors while mSTAR1302-mediated Vβ13⁺ T-cell expansion initiates a broader polyclonal antitumor immune response associated with antigen spreading and recognition of multiple tumor antigens and neoepitopes.

These findings suggest that combining tumor-sensitizing therapies with selective T-cell activation may represent a broader strategy to overcome immune exclusion in solid tumors. Together, these results provide mechanistic rationale for clinical evaluation of olaparib in combination with STAR0602 in patients with mCRPC who have progressed on androgen deprivation therapy.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with poor prognosis and limited curative treatment options. While chimeric antigen receptor (CAR) T cells have shown some promise in solid tumors, ACC remains largely unexplored in this context. Here, we used patient-derived xenograft (PDX) models of ACC to identify immunotherapeutic targets and develop novel CAR T-cell strategies.

Target identification and tumor microenvironment (TME) profiling were conducted using publicly available bulk and single-cell RNA sequencing data from patients with ACC samples. Surface proteomic analysis and flow cytometry of PDXs were conducted to validate antigen candidates. CAR T cells were engineered and tested for cytotoxicity in vitro and in vivo and profiled using flow cytometry and cytokine analysis.

We identified ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3) as a shared immunotherapy target in 4/7 (57%) ACC PDXs. ENPP3-targeted CAR T-cells eradicated >85% of ENPP3⁺ ACC cells in vitro but showed attenuated efficacy in PDX mouse models. Restrained ENPP3 CAR T-cell activity correlated with immunosuppressive features of the TME, particularly the presence of CD206⁺ tumor-associated macrophages (TAMs). Co-treatment with an agent modulating CD206⁺ TAMs restored CAR T-cell function and improved antitumor responses in ENPP3^high and ENPP3^low PDX models (difference between mean tumor weights -270.1 mg±117.4; p<0.05).

ENPP3 is a novel target for CAR T-cell therapy in ACC. ENPP3 CAR T cells, when combined with CD206 modulation to overcome immune suppression within the TME, have therapeutic efficacy in ACC by mediating robust tumor growth suppression. This combinatorial strategy, which includes CAR T cells alongside therapies that recalibrate immunosuppressive CD206⁺ TAMs, may be a novel approach for improved immunotherapy of solid cancers beyond ACC.

A man in his 60s with metastatic Merkel cell carcinoma was treated with avelumab. After 8 months, he achieved complete resolution of cutaneous lesions. At 13.5 months, he developed erythematous chest papules with biopsy-proven non-necrotising granulomas. Imaging revealed bilateral hilar and mediastinal lymphadenopathy, and serum calcium was elevated at 3.02 mmol/L. This is consistent with a sarcoid-like reaction to avelumab. High-dose prednisolone resolved sarcoid lesions and normalised calcium. However, avelumab rechallenge triggered recurrent hypercalcaemia and renal deterioration, raising concern for immunotherapy-related sarcoid nephritis. Avelumab was permanently discontinued after 2 years, and the sarcoid-like reaction remained inactive thereafter.

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm arising from follicular dendritic cells, with a predilection for extranodal sites. FDCS of the tonsil is exceptionally uncommon, and no standardized treatment exists for patients with locally advanced or inoperable disease, particularly when conventional therapies are contraindicated.

We report the case of an 80-year-old woman with localized FDCS of the left palatine tonsil who was ineligible for surgery or systemic therapy due to severe comorbidities. Electrochemotherapy (ECT) with bleomycin was administered under general anesthesia following ESOPE guidelines. The treatment was well tolerated without complications. At two weeks post-treatment, marked tumor reduction and necrosis were observed, and a complete clinical and radiological response was documented at 2 months, and maintained at 12 months of follow-up.

To our knowledge, this is the first documented case of tonsillar FDCS treated with ECT. This experience suggests that ECT may represent a valuable local treatment option for selected patients with inoperable FDCS, warranting further investigation of its role in managing rare soft tissue sarcomas.

Eukaryotic translation initiation factor 3 subunit F (eIF3f) is a critical component of the eIF3 complex and plays a pivotal role in diverse biological processes, including cell proliferation, apoptosis, adhesion, and transcriptional regulation. Recent studies have revealed that eIF3f is aberrantly expressed in multiple malignancies and exhibits a striking context-dependent functional profile. In solid tumors such as hepatocellular carcinoma (HCC), colorectal cancer (CRC), and prostate cancer (PCa), elevated eIF3f expression correlates with poor patient prognosis, indicating an oncogenic role. Conversely, in pancreatic cancer (PC) and melanoma (MM), reduced or absent eIF3f expression promotes tumor progression, suggesting a tumor-suppressive function. This functional plasticity indicates that eIF3f is not a simple oncogenic driver but rather a molecular hub that integrates diverse cellular signals. This review systematically delineates the structural characteristics and biological functions of eIF3f, summarizing its expression patterns and underlying molecular mechanisms across various malignancies. Building on this, we propose an integrated mechanistic framework that attributes the functional plasticity of eIF3f to differential upstream signaling networks, heterogeneity in post-translational modification profiles, and the remodeling status of the tumor microenvironment (TME). Furthermore, we critically evaluate the strength of evidence supporting eIF3f as a diagnostic and prognostic biomarker, identify methodological bottlenecks and translational challenges in current targeting strategies, and outline priority research directions, including elucidating the structural biological basis of its functional plasticity and developing context-specific intervention strategies. By integrating mechanistic insights with clinical relevance, this review aims to establish a conceptually coherent and mechanistically testable theoretical framework for eIF3f research, guiding the design of precision stratified therapeutic approaches and facilitating its substantive translation from basic research to clinical application.

Anastomosing hemangioma is a benign vascular neoplasm originally described in the genitourinary tract, but subsequently reported in a variety of anatomic sites. Although ovarian involvement has been documented, bilateral localization has not yet been reported in the English literature. Here, we describe the case of a 67-year-old woman with a strong clinical suspicion of advanced ovarian carcinoma, in whom histologic examination revealed bilateral ovarian anastomosing hemangioma. Frozen section evaluation did not allow a definitive diagnosis; however, on permanent sections, characteristic diagnostic features-such as foci of extramedullary hematopoiesis and scattered fibrin thrombi-became evident, enabling the correct classification. This report highlights the peculiar presentation of bilateral ovarian anastomosing hemangioma, aiming to increase awareness of this rare entity and to emphasize the diagnostic challenges it may pose, particularly during intraoperative consultation.

Stereotactic ablative radiotherapy (SABR) represents a new era of treatment for polymetastatic extracranial disease but introduces unique challenges in isocenter selection and margin optimization to balance treatment efficiency and normal tissue sparing.

Develop an end-to-end method to simultaneously cluster M tumor targets and optimize isocenter number (N) and position to minimize the additional margins required to maintain target coverage as tumor-to-isocenter distance increases.

K-means clustering identified candidate isocenters ranging from one to one per target. Margins required for 95% coverage probability were determined based on tumor-to-isocenter distance, accounting for translational (5 mm) and rotational (1°, 2°, 3°) uncertainties modeled as three-dimensional normal distributions. K-means total margin volume was compared versus isotropic 5- and 10-mm margins and benchmarked against a derivative-free hybrid optimization method. The method was evaluated on 20 clinical lung cases with 2-21 targets per patient, target-to-target distances of 3.8-32.4 cm, and volumes of 0.07-41.05 cm³.

The total margin volume determined by k-means showed no significant differences (p = 0.94) relative to the hybrid optimization method, with median differences of 0.03% (0.01 cm³), 0.14% (0.06 cm³), and 0.19% (0.15 cm³) for 1°, 2°, and 3° rotational uncertainties, respectively. Significant (p < 0.0167) differences in total margin were observed versus fixed margins of 5 or 10 mm. Increasing the number of isocenters for a given patient reduced the median total margin volume by 31.0% for N = 2 versus N = 1 and 15.7% for N = 3 versus N = 2, but diminishing returns were observed as additional isocenters were added (N = 4 to N = 6: -6.6%, -5.4%, and -3.7%, respectively). Median run time was 0.19 s for k-means versus 306.9 s for the reference method.

K-means clustering offers an efficient method for selecting the number and locations of isocenters to reduce the total margin volume in multi-target extracranial SABR.

Tissue biopsy specimens, both remnant diagnostic specimens and those collected for ancillary study, are an invaluable resource for clinical oncology research. However, using biopsy specimens for molecular research is associated with innate challenges, such as insufficient tissue and/or tumor content, and low nucleic acid yields as well as analyte degradation due to suboptimal preanalytical workflows.

The National Cancer Institute's Biorepositories and Biospecimen Research Branch convened a meeting that included expert-guided discussions that centered on strategies to mitigate these challenges and their effects on molecular analysis.

Participants, who included medical oncologists, interventional radiologists, pathologists, and molecular biologists, offered best practice guidance on biopsy collection, preservation, storage, and extraction techniques. Their recommendations were largely based on the optimized workflows that were implemented at their respective institutions, which improved the likelihood of producing reproducible molecular data. Pre- and postcollection techniques, such as clear cross-team communication, prebiopsy scoring based on lesion- and patient-specific criteria, biopsy collection and handling practices, and tumor enrichment options, were also discussed.

The proceedings revealed that increasing awareness of the challenges associated with research use of tissue biopsies is key to developing assay-specific strategies that ensure sufficient tumor specimens are available for molecular oncology research. The lessons shared here from large-scale and multicenter trials will, ideally, inform the design of new cancer research studies, thereby harnessing the full potential of valuable clinical biopsy specimens.

Intermediate-risk neuroblastoma patients older than 18 months, with non-MYCN amplified, International Neuroblastoma Risk Group Staging System localized, unresectable or International Neuroblastoma Staging System stage 3 tumors, and unfavorable histology have inferior outcomes compared with other intermediate-risk patients. This study aimed to identify genetic prognostic biomarkers within this rare subgroup.

We conducted a large, international study including chromosomal copy number in all cases, next-generation DNA sequencing in most, and telomere maintenance mechanisms and gene expression in a subset, and correlated results with patient survival.

Among 98 tumors, 9/98 (9.2%) had oncogene amplifications (CDK4/MDM2/TERT coamplification (n = 1), CDK4/MDM2 coamplification (n = 4), CDK4 (n = 2), TERT (n = 1), and MYC (n = 1)), while 63/98 (64.3%) had typical segmental chromosomal aberrations (tSCAs). Patients with tumors with oncogene amplification had the worst 5-year event-free survival (EFS; 0%; P < .0001 log-rank test) and 5-year overall survival (OS; 44.4% [95% CI, 21.4 to 92.3]; P < .01 log-rank test). Patients with tumors harboring tSCAs had inferior EFS compared with those with numerical chromosomal aberrations only (51.7% [95% CI, 40.6 to 65.8] v 93.3% [95% CI, 81.5 to 100]; P < .01). Patients with p53 pathway tumor alterations (n = 10) had worse EFS than those without (0% v 61.1% [95% CI, 50.3 to 74.3]; P < .0001, log-rank test) and worse OS (26.7% [95% CI, 8.9 to 80.3] v 80.9% [95% CI, 71.8 to 91.3]; P < .001 log-rank test). Multivariable analysis identified tSCAs as an independent prognostic variable for EFS and oncogene amplification or p53 pathway abnormalities as independent prognostic variables for EFS and OS.

Oncogene amplification and/or p53 pathway abnormalities and/or typical SCAs identify patients with intermediate-risk neuroblastoma with inferior outcome for whom intensified or alternative treatments should be considered.