Search Results (467)

Objective: This study aimed to explore the association between magnetic resonance imaging (MRI)-derived volumetric parameters and oncological outcomes, and to develop an exploratory predictive model based on these variables in patients treated with radio-chemotherapy followed by interventional radiotherapy (modern brachytherapy). Methods: Between 2021 and 2024, 300 patients with cervical cancer were included. Treatment was pelvic external beam radiotherapy with platinum-based chemotherapy followed by interventional radiotherapy boost. Volumetric MRI variables for each patient were collected. Time-to-event analyses were performed using Cox proportional hazards regression models. Model performance was assessed using Harrell’s concordance index (C-index). Internal validation was performed using bootstrap resampling. Based on the final multivariable Cox models, an interactive web-based nomogram was developed as an exploratory tool to visualize model-derived associations. Results: Median tumor volume decreased from 69.4 cm³ at diagnosis to 2.2 cm³ at the time of pre-interventional radiotherapy MRI, with a median reduction rate of 96.5%. Tumor volume at diagnosis, pre-interventional radiotherapy residual tumor volume, and tumor volume reduction rate were significantly associated with loco-regional relapse and distant metastases in Cox regression analyses. These findings were consistent across univariate and multivariable models. Internal validation confirmed the stability of the model estimates. Conclusions: MRI-derived volumetric parameters are associated with oncological outcomes in patients with locally advanced cervical cancer and may contribute to early risk stratification. The proposed model should be considered exploratory and hypothesis-generating and requires external validation before any potential clinical application. Full article

To identify BKPyV, the VP1 protein sequence was analyzed and classified into genotypes in 246 RTRs before and after RTx from deceased donors during a one-year observation period. Quantitative assessment of BKPyV was conducted via qPCR. Prior to RTx, genotypes I and IV were identified in the urine (7.27 × 10⁶; 1.20 × 10⁵) and in serum (5.75 × 10⁴; 1.12 × 10⁴). After RTx, genotype I was predominant; identification of DNAuria-BKPyV (62.07%) and BKPyV-DNAemia (55.56%) peaked after three months, and the highest DNAuria-BKPyV titer was also observed after three months (6.48 × 10⁹), whereas the BKPyV-DNAemia titer did not peak until after six months (2.21 × 10⁷). The highest number of copies of genotype IV in the urine was observed after six months (9.54 × 10⁹), while the highest titer in the serum was not observed until after 12 months (3.88 × 10⁶). DNAuria-BKPyV precedes BKPyV-DNAemia, affects a larger group of patients, and has a greater and more easily detected viral load, which makes it not only an earlier marker, but the key predictive marker of greater clinical value than later detection of BKPyV-DNAemia alone. Early monitoring of DNAuria-BKPyV should be the basis of classical screening, and not merely an addition to it, and therapeutic interventions should be undertaken early to prevent nephropathy. Full article

Background/Objectives: This review and meta-analysis assessed whether combining transarterial chemoembolization (TACE) with iodine-125 brachytherapy (I-125 brachytherapy) offers greater efficacy and safety than TACE alone in treating hepatocellular carcinoma (HCC). Methods: PubMed, EMBASE, the Cochrane Library, Scopus, and Web of Science were searched for articles published between 1 January 2010 and 30 November 2023. Eligible studies compared TACE with and without I-125 brachytherapy from randomized controlled trials (RCTs) and non-randomized comparative studies published in English. The primary outcome was overall survival (OS) at 1, 2, and 3 years. The secondary outcomes included progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events. ROB-2 and ROBINS-I tools were used to assess study quality. Results: Eighteen studies (n = 1872 patients) were included. All 18 studies originated from China, with the majority being retrospective cohorts (n = 16), one non-randomized prospective study, and one RCT. Compared with TACE alone, TACE + I-125 brachytherapy significantly improved OS at 1 year (OR = 3.64, 95% CI: 2.92–4.55), 2 years (OR = 3.93, 95% CI: 2.29–6.77), and 3 years (OR = 4.12, 95% CI: 2.24–7.56). The tumor response rates, including the ORR and DCR, were also significantly higher in the combination group. Subgroup analysis revealed that the survival benefit was maintained in studies without systemic chemotherapy (OR = 3.68, 95% CI: 2.89–4.70) and in studies with systemic chemotherapy (OR = 4.13, 95% CI: 1.69–10.09). Although larger effect estimates were observed with low-dose I-125 brachytherapy (<80 Gy; OR = 8.55, 95% CI: 4.32–16.92) compared to high-dose (≥100 Gy; OR = 2.87, 95% CI: 2.05–4.00), this finding is hypothesis-generating rather than conclusive and should be interpreted cautiously as it is based on only three studies. Adverse event rates were comparable between groups. GRADE assessment indicated low to very low certainty for all outcomes, primarily due to the retrospective nature of most included studies. Conclusions: TACE combined with I-125 brachytherapy was associated with improved survival and tumor response without a statistically significant increase in adverse events. High-quality, multicenter RCTs are warranted to confirm these results. Full article

Background: The aim of this study was to evaluate the influence of demographic, clinical and physical factors on the occurrence of ocular complications after ruthenium-106 (Ru-106) brachytherapy, iodine-125 (I-125) brachytherapy and proton therapy of uveal melanoma. Methods: A retrospective analysis of 300 patients’ electronic and paper medical records treated for uveal melanoma at the Department of Ophthalmology and Ocular Oncology, University Hospital in Krakow, Poland, from May 2014 to December 2016 was performed. The created database, which includes numerous parameters characterizing patients, tumors, applied treatments and their effects, with particular emphasis on the occurrence of ocular complications, was subjected to detailed analysis. The influence of selected factors on the occurrence of identified complications was checked by performing a univariable Cox proportional hazards regression analysis, and then the factors that were statistically significant were included in a multivariable Cox proportional hazards regression analysis which gave the final results. Results: Of the 300 patients, 125 (41.67%) were treated with Ru-106 brachytherapy (87 (29%) with CCB plaque and 38 (12.67%) with COB plaque), 102 (34%) with I-125 brachytherapy and 73 (24.33%) with proton therapy. Mean follow-up was 88.63 months (median 89, range: 20–127). The occurrence of cataract was associated with the older age of patients. Maculopathy was associated with female sex, younger age, use of I-125 brachytherapy, tumor location involving the macula and/or optic disc and moderate tumor pigmentation. Diagnosis of systemic hypertension was associated with a lower risk of maculopathy. Retinopathy was associated with younger age, tumor location involving the macula and/or optic disc and the use of I-125 brachytherapy. Optic neuropathy was associated with younger age, greater tumor largest base diameter, tumor location involving the macula and/or optic disc and the use of I-125 brachytherapy. Secondary glaucoma was associated with baseline best corrected visual acuity (BCVA) weaker than 0.5, greater tumor thickness, involvement of the left eye and the use of I-125 brachytherapy. Vitreous hemorrhage was associated with greater tumor thickness, tumor location including the macula and/or optic disc and mushroom-shaped tumor. Conclusions: Our study demonstrated an association between demographic, clinical, and physical factors and the occurrence of ocular complications after radiotherapy for uveal melanoma. Full article

Background/Objectives: Squamous cell carcinoma of the nasal vestibule (SCCNV) represents a rare malignancy traditionally managed by radical surgical resection, frequently at the cost of substantial functional impairment and disfiguring aesthetic consequences. This study investigates an organ-preserving therapeutic strategy integrating high-dose-rate interventional radiotherapy (HDR-IRT; brachytherapy) with organ-preserving surgery. Material and Methods: A retrospective analysis of patients with primary SCCNV treated using HDR-IRT between 2008 and 2022, excluding recurrent disease and cutaneous squamous cell carcinomas. Interstitial HDR-IRT catheters were implanted intraoperatively, with radiation delivered twice daily to a target volume encompassing the tumor and a 10–15 mm safety margin. Results: Fifty-one patients were included, with a median age of 71 years. The median total dose was 40 Gy. Gross total resection was performed in 7 patients, and subtotal resection in 44. The median follow-up was 35 months. The 5-year nose preservation rate was 90%, with local control at 84%, regional failure-free survival at 94%, and overall survival at 82%. In total, 49 acute toxicity events were documented, including two grade 3 events, while 35 chronic toxicity events were reported, including one grade 3 event. At 3 years, 84.3% of cosmetic outcomes were rated as satisfactory, 9.8% as acceptable, and 5.9% as unsatisfactory. Conclusions: The OSIRIS approach, combining HDR-IRT with organ-preserving surgery, is an effective treatment for SCCNV, offering high organ preservation and favorable long-term disease control, with manageable toxicity and positive cosmetic outcomes. Full article

Objective: This study aims to report the early safety outcomes from an ongoing single-center, non-randomized phase 2 trial on focal salvage stereotactic radiotherapy (s-SBRT) for local prostate cancer recurrence. Materials and methods: This prospective phase 2 study includes patients with local recurrence after conventional or hypofractionated radiotherapy, ultrahypofractionated radiotherapy, or post-prostatectomy radiotherapy. The present analysis includes an initial subset of 21 out of 55 planned patients. All patients undergo mpMRI and PSMA-PET; biopsy is not required if imaging results are unambiguous. Focal s-SBRT is delivered to the recurrent lesion with a dose of 5 × 6.75 Gy. The primary endpoint is the rate of treatment-related CTCAE v5.0 grade ≥ 3 genitourinary (GU) or gastrointestinal (GI) toxicity. Secondary endpoints include early biochemical response (BR), defined as any PSA decline at 3 months. Results: With a median follow-up of 14 months (range: 4.5–25), one patient (4.8%) experienced both early and persistent late Grade 3 GU toxicity (bladder bleeding). Late Grade 2 GU and GI toxicities occurred in five (23.8%) and one (4.8%) patients, respectively. In exploratory univariable analysis, PTV volume 13 cc was identified as a marginal predictor for increased GU/GI radiation reactions (p < 0.1). Regarding efficacy, all 21 patients (100%) demonstrated an early biochemical response, with 15 patients (71.4%) achieving a PSA reduction of 50%. Conclusions: Focal s-SBRT demonstrates a favorable early safety profile and consistent biochemical response, supporting the preliminary safety of this ongoing study. Full article

Background/Objectives: Cervical cancer remains a leading cause of cancer morbidity and mortality worldwide. Although chemoradiation followed by brachytherapy is the curative-intent standard for locally advanced disease, outcomes remain heterogeneous and recurrence and distant metastasis persist. In parallel, immune checkpoint inhibitors (ICIs) and antibody–drug conjugates (ADCs) have expanded systemic options in recurrent or metastatic settings and created new opportunities for multimodality. This review aims to integrate treatment-relevant cervical cancer biology and biomarkers to clarify how chemoradiation, immunotherapy, and ADCs can be optimally selected, sequenced, and combined across disease states. Methods: We conducted a structured narrative, evidence-based literature synthesis focusing on cervical cancer management. The review encompassed: (i) the molecular and immune mechanisms underlying human papillomavirus (HPV)-driven carcinogenesis; (ii) contemporary diagnostic and staging approaches, including advanced imaging modalities and histopathological evaluation; and (iii) clinical and translational evidence supporting the optimization of chemoradiation, immune checkpoint inhibition, and antibody–drug conjugates, with emphasis on clinically validated or emerging biomarkers that are relevant to patient stratification and mechanistically rational combination or sequencing strategies. A systematic search of PubMed/MEDLINE, Embase, and major oncology conference proceedings was performed. Priority was given to peer-reviewed original research articles, high-impact clinical trials (Phase II–III), meta-analyses, and consensus guidelines published within the past 10 years to ensure contemporary relevance. Articles published prior to this period were generally excluded to maintain clinical currency; however, seminal studies that established foundational therapeutic standards, mechanistic paradigms, or landmark treatment milestones were intentionally retained due to their enduring influence on current practice. Exclusion criteria included non-peer-reviewed sources, case reports with limited generalizability, non-English publications, and studies lacking methodological rigor or clinical relevance to cervical cancer management. Preclinical studies were included selectively when directly informing therapeutic mechanisms, biomarker development, or translational rationale. This approach was designed to balance historical context with up-to-date clinical applicability, ensuring both scientific rigor and contemporary relevance. Results: Chemoradiation and brachytherapy remain essential for local control, while ICIs can restore antitumor T-cell activity in biomarker-enriched contexts. ADCs enable target-directed delivery of potent cytotoxins and may promote immunogenic cell death, supporting immunotherapy and radiation. However, key challenges include resistance mechanisms, toxicity management, and patient identification for the most beneficial combined multimodality. Conclusions: A biology- and biomarker-informed framework can guide more rational integration of multimodality therapy in cervical cancer. Future progress will depend on validated predictive biomarkers, optimized sequencing/combination strategies, and trials that balance efficacy with short- and long-term toxicity. Full article

Background/Objectives: Brachytherapy (BT) is a local radiation treatment method for solid tumors. A single 10 Gy high–dose–rate (HDR) BT acts as an “in situ” vaccination. Tumor microenvironment (TME)–dependent radio–resistance mechanisms, such as increasing immunosuppression and hypoxia, lead to tumor recurrence after radiotherapy. Our study aimed to determine whether adding imiquimod (IMQ) to anticancer therapy would overcome TME–mediated mechanisms of radiotherapy resistance. IMQ, a toll–like receptor 7 (TLR7) agonist, acts as an immunostimulant and a vascular normalizing agent. Methods: Mice with well–developed tumors were treated with IMQ at a vascular–normalized dose of 50 μg, followed 5 days later by a single 10 Gy HDR BT. The dose coverage was planned using Discovery RT computed tomography CT scans. Irradiation was performed with a high–dose–rate afterloader equipped with an iridium–192 radioactive source. Results: In mice treated with a combination of IMQ and BT, we observed significant inhibition of melanoma tumor growth. We also noticed an effective therapeutic effect in mice with breast cancer, resulting in significantly prolonged survival and complete tumor regression in 20% of treated mice. In the blood of treated mice, we observed leukopenia with eosinophilia. In tumors, there was enhanced infiltration by cytotoxic CD8⁺ T lymphocytes. The depletion of CD8⁺ T cells completely abolished the effect of the combined therapy. Conclusions: The combination of IMQ with HDR brachytherapy induces a synergistic effect, improving the therapeutic antitumor effect of brachytherapy. Our data indicate that it is reasonable to use drugs that prevent changes in the TME in combination with radiotherapy. Full article

Background/Objectives: Image-guided adaptive brachytherapy (IGABT) has transformed the standard of care for locally advanced cervical cancer (LACC), enabling volumetric target definition and dose–volume histogram (DVH)-based planning to improve pelvic tumor control while limiting severe late toxicity. Methods: A comprehensive literature search of PubMed/MEDLINE and Embase was done for articles published up to August 2024, using combinations of the following keywords and Medical Subject Heading (MeSH) terms: “cervical cancer”, “endometrial cancer”, “vaginal cancer”, “uterine neoplasms”, “brachytherapy”, “high-dose-rate”, “image-guided”, “MRI-guided”, “3D brachytherapy”, “IGABT”, “interstitial”, “locoregional control”, “toxicity”, “quality of life”, and “patient-reported outcomes”. Results: We summarized the contemporary evidence on IGABT for cervical, endometrial, and primary or recurrent vaginal cancers, focusing on local control, survival, late morbidity, and patient-reported outcomes. We described the key target volume concepts (gross tumor volume, high- and intermediate-risk clinical target volumes), and the role of MRI-, CT-, and ultrasound-based planning with intracavitary, intracavitary–interstitial, and interstitial applicators. Conclusions: Image-guided adaptive brachytherapy has redefined the standard of care for the management of locally advanced cervical cancer. Through the integration of volumetric target concepts, DVH-based dose reporting, and advanced imaging, IGABT has enabled consistent dose escalation to the residual tumor while accounting for organ-at-risk constraints, resulting in high local control rates and reduced severe morbidity compared with historical 2D brachytherapy. Full article

Background: In young women with cervical cancer, fertility preservation remains challenging, as chemoradiotherapy can severely compromise ovarian reserve and endometrial function. Although ovarian transposition prior to pelvic radiotherapy is well established in early-stage disease, evidence regarding ovarian and endometrial outcomes in advanced stages, particularly in the International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1, remains extremely limited. Case Presentation: We report the case of a 31-year-old nulliparous woman with a histopathologically confirmed FIGO IIIC1 cervical squamous cell carcinoma who underwent a lateral ovarian transposition followed by external beam radiotherapy (ERBT) of the pelvis and interstitial high-dose-rate (HDR) brachytherapy combined with five cycles of cisplatin-based chemotherapy. A detailed dosimetrical analysis demonstrated extremely low ovarian radiation exposure (mean dose < 2 Gy bilaterally). Menstruation resumed seven months after treatment completion, with regular 27–30-day cycles. A day-3 hormonal assessment showed a partial preservation of the ovarian reserve, and the pelvic ultrasound confirmed a thickness of 7 mm in the proliferative phase, implying endometrial function despite full-dose pelvic irradiation. Conclusions: To our knowledge, this is a very unique case of preserved menstruation after ovarian transposition and chemoradiotherapy for FIGO IIIC1 cervical carcinoma. This case challenges the conventional assumptions regarding ovarian failure and endometrial destruction in such cases, suggesting that reproductive potential may occasionally be retained. Although fertility remains a challenging point, this case report underscores the need for individualized counseling and prospective oncofertility research. Full article

Background: Re-irradiation in recurrent cervical cancer presents significant therapeutic challenges, particularly in those with a short interval since prior treatment. Brachytherapy is an ideal re-irradiation method, but regular intracavitary brachytherapy combined with interstitial brachytherapy (ISBT) is restricted by some challenging tumor anatomical locations, which can be optimized through a three-dimensional (3D)-printed curved-needle ISBT system. Case Presentation: A 41-year-old woman diagnosed with cervical mucinous adenocarcinoma developed central pelvic relapse, with tumor extension to the uterine fundus, within two years after completing standard concurrent chemoradiotherapy (CCRT). The patient subsequently received 3D-printed individualized curved-needle-based, MRI-guided adaptive ISBT, in combination with external beam radiotherapy (EBRT) and chemotherapy. This comprehensive treatment approach achieved 45 months of overall survival (OS), 37 months of local control (LC) and progression-free survival (PFS) with grade 3 proctitis and grade 3 cystitis and no fistulation or perforation. Conclusions: The 3D-printed individualized curved-needle ISBT is a re-irradiation option that provides satisfactory LC and prolonged survival with acceptable adverse effects for recurrent tumors located in the distal uterine fundus in cervical cancer. This technique is particularly valuable when intracavitary and traditional interstitial applicators are unsuitable due to the unique location of the tumor. Full article

Background: The updated National Comprehensive Cancer Network (NCCN) criteria redefine the very high-risk (VHR) prostate cancer (PC) category, identifying patients with highly aggressive disease. Evidence regarding the outcomes of high-dose-rate brachytherapy (HDR-BT) in these patients, including those with regional disease, is limited. Therefore, the present study focused on analyzing the long-term clinical performance of HDR-BT-based radiotherapy (RT) for patients meeting the NCCN criteria for VHR or regional PC. Methods: A total of 215 patients with VHR (n = 179) or regional disease (n = 36) treated with HDR-BT with external beam RT between 2006 and 2022 were retrospectively reviewed. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using Kaplan–Meier methods, and prognostic factors were analyzed using Cox regression. Results: Recurrence occurred in 19 (8.8%) patients, and 22 (10.2%) died, including 4 PC-specific deaths. The 5-year RFS, CSS, and OS rates were 92.5%, 98.9%, and 96.2%, respectively, and the 8-year rates were 88.5%, 97.8%, and 90.8%, respectively. Multivariate analysis revealed that pre-RT prostate-specific antigen (PSA) > 0.1 ng/mL (HR 3.93; p = 0.010) and cT4 disease (HR 4.49; p = 0.032) were independent predictors of inferior RFS. Grade ≥ 3 genitourinary toxicity was observed in 1.9% of patients, and no Grade ≥ 3 gastrointestinal toxicity occurred. Conclusions: HDR-BT-based RT provides durable disease control and low toxicity in patients with NCCN-defined VHR and regional PC. Pre-RT PSA and T stage may inform risk-adapted treatment strategies. The present findings demonstrate the importance of HDR-BT as an effective component of multimodal therapy for highly aggressive PC. Full article

Background/Objectives: Uveal melanoma (UM) is the most common intraocular malignancy in adults. Although brachytherapy of the primary tumor provides an approximate 80% five-year survival, with time, nearly half of patients experience predominant liver metastases. It was proposed that malignant cells migrate early and stay dormant as they adapt to the liver microenvironment. We propose that cancer vaccine-mediated activation of UM-targeted immunity in primary UM patients could prevent progression of metastatic disease from dormant cells or malignant seeds. Thus, this study explored DNA vaccination as a measure to educate the immune system to recognize the most common UM-associated Q209L tumor driver mutation in GNAQ and GNA11 G-alpha proteins. Methods: Several DNA constructs encoding mutated GNAQ were developed and tested for activation of UM-reactive T cells in HLA-A2/Hd transgenic mice and human T cells ex vivo. Results: Constructs containing immune-enhancing PADRE and VP22-derived epitopes boosted T cell responses against mutant GNAQ, which correlated with reduced experimental lung metastases. Ex vivo dendritic cell-mediated T cell activation with vaccine constructs containing optimized structure produced cytolytic T cells that secreted IFN gamma and killed mutated GNAQ-expressing UM cells in vitro. Conclusions: These findings propose the utility of the fusion DNA vaccines in eliciting T cell immunity against UM cells bearing the Q209L mutation in GNAQ/GNA11 protein to prevent the establishment and progression of metastatic disease. Full article

Background: Kaposi sarcoma (KS) is a multifocal, angioproliferative neoplasm strongly associated with human herpesvirus-8 infection. Radiotherapy(RT) is a well established treatment due to the intrinsic radiosensitivity of KS lesions. High-dose-rate contact brachytherapy allows precise dose delivery with optimal sparing of surrounding tissues; however, its application in KS remains poorly documented. Methods: We conducted a retrospective analysis of 10 patients with histologically confirmed KS treated with c-HDR-BRT between June 2010 and June 2023. A total of 40 cutaneous lesions were treated using Leipzig applicators with hypofractionated regimens: 10 Gy in 1 fraction, 20 Gy in 2 fractions, or 30 Gy in 3 fractions. Treatment parameters were individualized based on lesion size and location. Local control (LC), overall survival (OS), disease-specific survival (DSS), and toxicity (graded by the RTOG criteria) were evaluated. Follow-up assessments were performed every four months during the first year and annually thereafter. Results: At a median follow-up of 10.3 years, the 2-year LC, OS, and DSS rates were 100%. Complete response was achieved in 62.5% of lesions, with a partial response observed in 37.5%. Grade 1–2 acute skin toxicities were recorded in 55% of treated lesions, while grade 3 toxicity occurred in a single case (2.5%) and was managed conservatively. The hypofractionated schedule significantly improved patient compliance, particularly in those with multiple lesions requiring sequential irradiation. Conclusions: Our long-term institutional experience supports c-HDR-BRT as a feasible and well tolerated local treatment option for the management of KS, providing favorable long-term local outcomes. These results support the inclusion of c-HDR-BRT in the multidisciplinary treatment of KS, warranting further prospective evaluation. Full article

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. Full article