-
Oncological efficacy, functional outcomes and safety of MR-guided ultrasound ablation (MRgFUS/TULSA) for localized prostate cancer: a scoping review.5 days agoMR-guided focused ultrasound (MRgFUS) and transurethral ultrasound ablation (TULSA) have emerged as MRI-guided, minimally invasive options for men with localized prostate cancer who seek tissue-preserving alternatives to radical therapy. This scoping review mapped and synthesized clinical studies published since 2015 on MRgFUS and TULSA in primary and recurrent disease, focusing on indications, oncologic efficacy, functional outcomes, and safety. A systematic search of PubMed and Scopus identified 34 eligible studies, mostly single-arm series in men with organ-confined, low- to intermediate-risk cancer, with smaller cohorts including high-risk and post-radiotherapy patients. Across whole-gland TULSA series, 12-24‑month biopsy‑negative rates ranged roughly from two thirds to almost all patients, with marked PSA declines, while focal MRgFUS consistently achieved very high in‑field control but showed relevant rates of out‑of‑field recurrence on systematic biopsy in multifocal disease. Urinary continence was generally preserved (pad‑free rates close to 100%), and erectile function was maintained in most men, particularly after focal treatments, clearly outperforming historical radical prostatectomy series in functional terms. Adverse events were predominantly mild and transient, with serious complications concentrated in salvage procedures after radiotherapy. Overall, MRgFUS and TULSA appear safe and effective for carefully selected patients, but heterogeneity of study designs, short follow‑up, and limited comparative data underscore the need for randomized trials and longer-term outcomes to define their precise role in prostate cancer management.CancerCare/Management
-
B-cell and plasma cell proliferations associated with T follicular helper cell lymphomas: clinical-pathological and genetic features.5 days agoNodal T-follicular helper cell lymphomas (nTFHL) are aggressive peripheral T-cell lymphomas with unique clinical-biological features. B-cell and/or plasma cell proliferations (B/PCP) are frequently reported in nTFHL, yet their histological spectrum remains incompletely defined. This study aims to delineate the clinical, pathological and molecular features of a retrospective series of nTFHL-associated B/PCP, with particular emphasis on recurrent disease patterns. To this aim, we retrospectively analyzed 39 nTFHL with 45 synchronous and/or metachronous B/PCP, collected from five Italian referral centers for hematological disorders. Multiple B/PCP were documented in 5/39 (12.8%) patients. All diagnoses were established according to the 2022 WHO/ICC criteria, using the nomenclature proposed by the 2023 SH/EA4HP Workshop on T-cell lymphomas. Clinical and pathological data were collected, and recurrent histological patterns were categorized. RHOAG17V, TET2, DNMT3A, and IDH2 mutations were tested in 16 cases. The cohort included 20 males and 19 females (median age: 73.3 years). B/PCP clustered into six diagnostic categories: (i) diffuse large B-cell lymphoma (DLBCL)-like proliferations associated with nTFHL (19/45 [42.2%]), (ii) nodular large B-cell proliferations associated with nTFHL (5/45 [11.1%]), (iii) secondary DLBCL without co-localization of nTFHL (3/45 [6.7%]); (iv) EBV-positive polymorphic B-cell proliferations (10/45 [22.2%]), (v) monotypic plasma cell proliferations (5/45 [11.1%]), and (vi) small B-cell lymphoma-like proliferations with plasma cell differentiation (3/45 [6.7%]). TET2 mutations were detected in 10/16 (62.5%) cases with high allelic burden, whereas DNMT3A and IDH2 mutations were rare. The RHOAG17V mutation was detected in 3 cases, most likely representing contamination by minor nTFHL clones. In conclusion, TFHL-associated B/PCP are a heterogeneous group of lymphoproliferative and plasma cell disorders, displaying recurrent histological patterns and frequent clonal hematopoiesis-associated mutations. Further studies on larger cohorts of patients are warranted to elucidate their biological and clinical implications.CancerCare/ManagementPolicy
-
UBA3 reduction sensitizes cancer cells to NAE inhibitors.5 days agoThe NEDD8-activating enzyme (NAE), comprising NAE1 and UBA3, is an anticancer target. The relative contribution of each of these subunits toward NAE inhibitor (NAEi) efficacy remains unclear. We demonstrated a profound interdependence of NAE1 and UBA3 expression. UBA3 reduction augmented NAEi sensitivity, whereas its overexpression led to decreased sensitivity. UBA3 deficiency enhanced RKO xenograft sensitivity to SOMCL-19-133 (NAEi), which was reversed by UBA3 restoration. Cells with naturally low UBA3 expression were highly NAEi-sensitive. The criticality of UBA3 in NAEi sensitivity is not completely unexpected given that the ability of NAEi to directly bind to UBA3 is known. TCGA data showed that rectum adenocarcinoma patients with low UBA3 mRNA had poorer prognoses, and 27.16% of tumors expressed low UBA3 mRNA. We propose that low UBA3 expression may serve as a NAEi sensitivity biomarker, particularly given that MLN4924 (NAEi) phase 3 failures may be due to a lack of patient stratification. Therefore, our key findings, on the criticality of UBA3 in NAEi sensitivity, underpin future clinical evaluations.CancerCare/ManagementPolicy
-
Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): A practical compartment-based review.5 days agoPrimary cutaneous lymphomas are a heterogeneous group of lymphoid neoplasms with predominant skin involvement, among which mycosis fungoides (MF) and Sézary syndrome (SS) are the most frequent and clinically challenging entities. This narrative review provides a multidisciplinary, compartment-oriented approach to the diagnosis, staging and management of MF/SS. We summarize the therapeutic principles across the disease continuum, from early-stage, skin-directed management to advanced-stage systemic therapy, including oral retinoids, methotrexate, extracorporeal photopheresis, mogamulizumab, brentuximab vedotin, chemotherapy and allogeneic stem-cell transplantation. We also address large-cell transformation, response assessment, follow-up strategies, and practical issues surrounding treatment maintenance, spacing and discontinuation in a chronic, relapsing disease. Finally, we highlight the importance of supportive care, particularly pruritus control and palliative integration when no further effective options remain, and provide pragmatic algorithms to facilitate real-world clinical decision-making.CancerCare/Management
-
Malignant transformation in a patient with type 1 neurofibromatosis: A case report.5 days agoNeurofibromatosis is an autosomal dominant disease. The most common skin manifestation of type 1 neurofibromatosis is plexiform neurofibromas. Malignant peripheral nerve sheath tumors are rare and aggressive malignancies that predominantly arise from peripheral nerves and various nerve sheath cells. This report presents the case of a male patient in his late 50s who was diagnosed with malignant transformation of type 1 neurofibromatosis and treated surgically. The clinical manifestations, histopathological characteristics, treatment, and outcomes of this rare clinical case provide insights for subsequent diagnostic evaluation and clinical decision-making.CancerCare/Management
-
The evidence for the use of peripheral blood indices in the diagnosis of breast cancer.5 days agoDiagnosis at early stages is critical for achieving favorable outcomes in patients with breast cancer. However, early breast cancer is characterized by atypical clinical and imaging manifestations, which are misdiagnosed as benign breast disease. This misdiagnosis may affect the choice of treatment, delay the patient's condition, and affect survival. Therefore, identifying an effective and simple screening method to supplement existing screening methods is of considerable importance for improving diagnostic efficacy. Peripheral blood indices are simple, economical, and readily accessible that include routine blood indices, lipid indices, and coagulation indices. With in-depth research on tumor pathogenesis, the relationships between these indices and tumor development have been gradually revealed, suggesting their potential as diagnostic factors for breast cancer. This narrative review explores the development of peripheral blood indices for diagnosing breast cancer and their potential use in early diagnosis.CancerCare/Management
-
Pathogenic mobile element insertion in the MEN1 gene mimicking a deletion in MLPA: characterisation by long-read sequencing.5 days agoMobile element insertions (MEIs) disrupting coding sequences are rare but clinically significant mutations that are often missed by standard next-generation sequencing (NGS) workflows. Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumour predisposition syndrome caused by pathogenic variants in the MEN1 gene.
Patients included in this study were referred for genetic testing of hereditary cancer syndromes. In a validation of our NGS-based copy number variant detection pipeline, four cases showed discrepancies between NGS and multiplex ligation-dependent probe amplification (MLPA) results. Further investigation using soft-clipped read analysis and the MEI detection tool Scramble revealed an Alu insertion in the MEN1 gene. Long-read whole genome sequencing (LR-WGS) was used for validation and complete characterisation of the variant. Additionally, 2014 retrospective NGS samples were analysed with Scramble. Relatives of probands were tested with MLPA and PCR. Positive samples were analysed with Sanger sequencing.
The apparent exon 2 deletion detected by MLPA was shown to be a false positive caused by an Alu insertion within the probe binding site. LR-WGS confirmed the pathogenic variant (MEN1:c.143_144insAlu) and resolved its complete sequence. Screening of the retrospective cohort revealed no additional MEIs. Altogether, we identified 10 affected individuals from two Polish families carrying hereditary MEN1:c.143_144insAlu, which segregates with MEN1 syndrome.
We report a novel pathogenic Alu insertion in the MEN1 gene, which is associated with MEN1 syndrome. Our findings underscore the importance of incorporating MEI detection into routine diagnostics. It also emphasises the necessity of interpreting single-exon MLPA deletions cautiously, as recommended in the MLPA protocol.CancerCare/Management -
Recurrence of glomangiopericytoma in infraorbital region.5 days agoGlomangiopericytomas (GPCs) are rare spindle cell neoplasms that usually develop in the sinonasal tract and possess a low malignant potential. Although rare, most cases have been found in various areas of otolaryngological importance, notably the deep neck spaces, eyes, larynx, tongue and middle ear. However, no cases of recurrence of infraorbital GPC have been reported in the literature. Total surgical resection is the treatment of choice. Nonetheless this condition recurs in cases of incomplete excision. Because of the rarity of the disease and its prevalence, early detection and care are critical, especially in atypical presentations that necessitate a high level of clinical suspicion. Here we present our first case of recurrence of infraorbital GPC, highlighting management protocols and challenges.CancerCare/Management
-
Effectiveness of a Low-Iodine Diet in Post-Thyroidectomy Thyroid Cancer Patients Receiving I-131 Therapy at the Vietnam National Cancer Hospital.5 days agoThe effects of a low-iodine diet intervention in post-thyroidectomy thyroid cancer patients undergoing radioactive iodine (I-131) therapy has been shown to the improve clinical outcomes of patients worldwide. However, studies evaluating the 24-h dietary intake of low-iodine diets for thyroid cancer patients in Vietnam remain limited. Therefore, we conducted a study to assess the effectiveness of the low-iodine diet and to compare the diet between patients who managed it on their own and those who received guidance from nutrition specialists, with the aim of developing a more effective dietary regimen and monitoring intervention. This was a controlled interventional study comparing two groups: the intervention group received a specialized low-iodine diet designed by a team of experts, while the control group followed the standard hospital low-iodine diet protocol. The effectiveness of the intervention was assessed by measuring urinary iodine concentration and 24-h dietary intake. The mean urinary iodine concentration in the intervention group was lower than in the control group (9.2±3.9 vs. 10.3±3.5 μg/dL), though the difference was not statistically significant (p>0.05). Regarding 24-h dietary intake, the proportion of patients meeting energy and protein requirements was higher in the intervention group (p<0.05). Dietary intake of eicosapentaenoic acid (EPA) was also significantly higher in the intervention group (p<0.05). Nutritional intervention helped ensure adequate energy intake and improved the provision of specific nutrients for patients undergoing I-131 therapy after thyroid cancer surgery.CancerCare/Management
-
C-type lectin domain family 5 member A-mediated activation of macrophages via a bispecific antibody enhances anti-HER2 therapy.5 days agoAlthough HER2-targeted therapies have dramatically improved outcomes for patients with HER2-positive breast cancer, the immunosuppressive tumor microenvironment remains a major barrier to effective immunotherapy in this subtype. Therefore, we sought to develop a new bispecific antibody targeting both HER2 and C-type lectin domain family 5 member A (CLEC5A), a pattern recognition receptor on innate immune cells like macrophages, aiming to alter the tumor immune environment.
CLEC5A-HER2 bispecific antibodies were generated and evaluated for binding properties, macrophage activation, and phagocytic activity in vitro. Anti-tumor efficacy was assessed in multiple syngeneic mouse models, including orthotopic breast cancer models, with mechanistic studies and immune checkpoint inhibitor combinations.
The CLEC5A-HER2 bispecific antibody was more effective in anti-tumor activity than either monotherapies or combinations of individual antibodies in various syngeneic models, including an orthotopic breast cancer model. Mechanistically, it converted "cold" tumors into "hot" tumors by promoting macrophage-mediated phagocytosis, repolarizing tumor-associated macrophages toward an M1-like phenotype, and enhancing antigen presentation and T-cell recruitment. This immune remodeling restored the CXCL9/10-CXCR3 axis, increased CD8+ T cell infiltration, reduced regulatory T cells, and underpinned a T cell-dependent anti-tumor response. Interestingly, combination therapy with CTLA-4 and PD-1 blockade exhibited strong synergistic effects without significant toxicity.
These results identify the CLEC5A-HER2 bispecific antibody as a potential immunotherapy for HER2-positive cancers by effectively engaging both innate and adaptive immunity.CancerCare/Management