Search Results (114)

Background/Objectives: Clinical studies of prostate cancer treated with radically hypofractionated high-dose-rate brachytherapy (HDR-BT) have reported a significant loss of tumor control that contradicts the standard linear-quadratic (LQ) and low-$\alpha /\beta$-ratio paradigm for prostate cancer. In a previous study by our group, we showed that the linear–quadratic–linear (LQL) model could describe this response, but the underlying biological drivers remained unclear. In this follow-up study, we further investigate whether the interplay between hypoxia and reoxygenation kinetics can explain the poor response to extreme hypofractionation. Methods: We analyzed a large dataset of 3239 patients (44 schedules) using a three-compartment reoxygenation model (the MSK model) that simulates the dynamics of oxic, intermediate, and hypoxic cell populations. Results: The results show that the MSK model achieves an excellent fit to the clinical data ($p>0.99$) while maintaining a biologically plausible low $\alpha /\beta$ ratio (≤8 Gy). The reoxygenation model provided a performance comparable to the LQL model for low-risk prostate cancer and slightly inferior for intermediate-risk. Conclusions: This suggests that the observed reduction in tumor control may not necessarily be a failure of the LQ formalism but, rather, a consequence of oxygen dynamics associated with ultra-hypofractionated schedules. Nonetheless, neither this nor our previous work can provide insight into the driving mechanism and should only be interpreted as showing that both hypotheses are compatible with the clinical data. Full article

Background/Objectives: Prostate cancer is one of the most common malignancies diagnosed in men worldwide. Brachytherapy (BT), particularly low-dose rate (LDR)-BT, has been shown to be a successful treatment. The aim of this study was to evaluate the effectiveness of BT treatment in localized prostate cancer patients from a single-center Portuguese cohort. Methods: This was a retrospective study that evaluated prostate cancer patients followed up at the Center for the Treatment of Urological Diseases, Coimbra, Portugal, who underwent LDR-BT between November 2007 and March 2024. Overall survival (OS), biochemical recurrence-free survival (BRFS) and complications post-LDR BT treatment were evaluated during patients’ follow-up time. Results: A total of 1343 patients treated with LDR-BT were recruited. Global OS and BRFS rates were 98.4% and 87.7%, respectively. A reduced frequency of complications such as lower urinary tract symptoms, erectile dysfunction, acute urinary retention, radiation proctitis and stress urinary incontinence were described. High OS (>98%) and BRFS rates were observed particularly in low and intermediate disease risk. Prostate-specific antigen (PSA) serum levels > 20 ng/mL, Gleason score (GS) ≥ 8 and clinical tumor stage (cT) ≥ T2c were identified as the strongest predictors of death and/or biochemical recurrence. Conclusions: BT is an effective treatment in localized prostate cancer patients, with comparable outcomes and consistent with the OS and BRFS rates reported in the current literature for radical prostatectomy and external beam radiotherapy approaches, and with a reduced frequency of complications. PSA serum levels > 20 ng/mL, GS ≥ 8 and cT stage ≥ T2c can be used as strong predictors of death and/or biochemical recurrence during patients’ follow-up. 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/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

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: 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: 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

Background: This study aimed to analyse treatment outcomes, determine prognostic factors and assess the toxicity of reirradiation using high-dose-rate (HDR) brachytherapy for liver metastases in the oligometastatic stage of disease. Materials and Methods: The study included 59 patients who had previously undergone SBRT (stereotactic body radiation therapy) or HDR brachytherapy and experienced progression within (type 1) or outside (type 2) the irradiated area, but in a different location within the liver. Patients were divided according to the type of reirradiation and the reason for treatment. Local control (LC), progression-free survival (PFS) and overall survival (OS) were analysed in relation to the following factors: age; gender; performance status; tumour type; line of systemic treatment; location of extrahepatic metastases; type of reirradiation; time since previous irradiation; indication for treatment; size and number of metastases; dose; and degree of response to treatment. Treatment toxicity and the influence of dose, irradiation volume, number of metastases, time since previous radiotherapy and dose to the non-irradiated part of the liver on hepatic toxicity were also assessed. Results: With a median follow-up period of 13 months, the median LC, PFS and OS were 9, 8 and 13 months, respectively. The respective rates of partial regression (PR), stable disease (SD) and progressive disease (PD) were 32%, 44% and 12%. The most significant factors influencing LC were the degree of tumour shrinkage, with PFS influenced by the degree of tumour shrinkage and a low number of metastases, and OS influenced by the degree of tumour shrinkage, a low number of metastases and one to two lines of systemic therapy. Treatment toxicity was low, and there was no strong correlation between the dosimetric parameters of the treatment plan and the biochemical parameters of liver function. Conclusions: Brachytherapy is a safe and effective method of re-irradiating liver metastases. However, due to the limitations of the study, further investigation is required. Full article

Background/Objectives: The anatomical complexity of the auricular region poses a unique challenge for contact interventional radiotherapy (IRT, modern brachytherapy), especially in maintaining close conformity between the applicator and skin surface. Air gaps can arise due to the irregular shape of the ear, potentially compromising dose coverage. This study evaluates the dosimetric impact of air gaps in HDR IRT for non-melanoma skin cancer (NMSC) of the ear. Methods: Ten patients treated with contact IRT using alginate as supporting material were retrospectively analyzed. Treatment plans were recalculated using both the TG-43 and the TG-186 formalism. CTV coverage and organ-at-risk dose parameters were evaluated within the two formalisms. Results: CTV coverage was comparable between algorithms (mean V95% 96.2% vs. 94.4%, V100% 89.6% vs. 86.7%, and V150% 2.6% vs. 2.5% for TG-43 vs. TG-186; p > 0.05), while the ipsilateral eye D2cc decreased from 4.0% (TG-43) to 3.2% (TG-186). In silico simulations showed that increasing air gaps reduced skin dose progressively (up to ~15% at 5 mm), whereas alginate thickness produced only a mild dose increase (<5%) across the tested range. Overall, small air pockets (<1 mm) did not substantially alter global dosimetric metrics, although local underdosage may occur at gap locations. Conclusions: This study underscores the importance of accounting for material heterogeneities and geometric uncertainties in anatomically complex regions through advanced dose calculation algorithms. Full article

Introduction: The aim of the study was to analyse the results and potential complications of local treatment with HDR (high dose-rate) brachytherapy of liver metastases from colorectal cancer, depending on the targeted therapy used and considering RAS gene mutation and chemotherapy in individual treatment lines. Material and methods: The study included 142 patients with oligoprogressive liver metastases who underwent HDR brachytherapy without changing the line of treatment, based on a retrospective analysis of 270 patients treated between 2015 and 2022. The impact of RAS gene mutations, lines of chemotherapy depending on the treatment regimens used, PFS (progression free survival), OS (overall survival), LC (local control) and the degree of radiological response were analysed. The impact of these drugs on hepatotoxicity and the risk of haemorrhagic complications was also analysed. Results: The presence of mutations in KRAS/NRAS genes (exons 2, 3, 4) had a statistically significant impact on PFS in the first, third and fourth lines of treatment, and on OS and LC in the third and fourth lines of treatment. In the third and fourth lines of treatment, patients with a mutation in the RAS gene had a poorer radiological response to treatment regardless of the chemotherapy used. PFS, OS and LC differed depending on the line of treatment and amounted to 17.5, 11, 8.5, 6 and 4 months, 27, 19, 13, 11 and 11 months, and 27, 19, 11, 6 and 6 months, respectively. The greatest benefit in terms of PFS was achieved by patients treated with first-line chemotherapy combined with epidermal growth factor receptor (EGFR) inhibitors, in the absence of RAS gene mutations. In the third line, the greatest benefit was achieved by patients treated with trifluridine/tipiracil in the absence of RAS gene mutations. The greatest percentage reduction in the volume of treated lesions and the highest percentage of control were observed in the first three lines of treatment. The toxicity of the treatment was low; only in the third and fourth lines of treatment were differences in the decrease in albumin levels found depending on the type of treatment used. Conclusions: A mutation in the RAS genes worsens the prognosis, regardless of the line of treatment and the systemic treatment used. The greatest benefit from brachytherapy is seen in patients in the first three lines of treatment without RAS mutations, treated with anti-EGFR chemotherapy in the first line and trifluridine/tipiracil in the third line. Combining brachytherapy of liver metastases with systemic treatment is safe, regardless of the systemic treatment used. Full article

The accurate calibration of radiochromic films is critical for high dose rate (HDR) brachytherapy dosimetry. Conventional workflows frequently rely on manually determined regions of interest (ROIs), which might increase operator variability. In this investigation, Gafchromic EBT3 films were irradiated under clinical settings at nominal doses of 0–10 Gy and evaluated using a MATLAB (R2024b)-based tool that allows for both manual and automated ROI selection. The calibration curves were modeled with a second-order polynomial and rational model, and performance was assessed using statistical measures. The study found that the rational model fits better than the polynomial model. Additionally, the automatic ROI approach outperformed the manual method in both models, resulting in higher calibration accuracy and reproducibility (R² = 0.999, RMSE = 0.118 Gy, MAE = 0.103 Gy vs. R² = 0.986, RMSE = 0.448 Gy, MAE = 0.388 Gy). Although manual ROI occasionally produced greater dose–response slopes at higher doses, it was more susceptible to operator bias and film non-uniformity. In contrast, automatic ROI reduced variability by consistently picking homogeneous sections, resulting in steady curve fitting across the entire dose range. Furthermore, a companion module transformed calibrated films into 2D false-color maps and 3D dosage surfaces, allowing for visual assessment of dose uniformity, detection of scanner-related aberrations, and quantitative verification for quality assurance. These findings demonstrate that automated ROI selection provides a more stable and reproducible foundation for film calibration in HDR brachytherapy, minimizing operator dependency while facilitating routine clinical quality assurance. Full article

Background: We evaluated the long-term treatment outcomes of patients with clinically localized and locally advanced prostate cancer (PC) who underwent high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT). The primary objective was to identify the optimal timing for discontinuing prostate-specific antigen (PSA) monitoring after HDR-BT. Methods: This analysis included 338 patients with PC who received HDR-BT combined with EBRT between 2006 and 2022 and had a minimum follow-up of 5 years. The patients were stratified based on their PSA levels, and factors associated with recurrence were identified. Results: The median observation period was 8.9 years (range, 5.0–19.0 years). The 10-year recurrence-free survival rate was 92.0%, with 26 recurrences. PSA levels at 5 and 7 years were significantly correlated with oncological outcomes after HDR-BT. Multivariate analysis revealed that a PSA level of >0.2 ng/mL at 5 years was an independent poor prognostic factor for recurrence (hazard ratio, 117.57; 95% confidence interval, 6.22–2223.37; p = 0.001). No patient with a PSA level of ≤0.2 ng/mL at 7 years developed recurrences. Conclusions: Based on our long-term data, we propose that PSA monitoring may be safely discontinued in patients with a PSA level of ≤0.2 ng/mL 7 years after HDR-BT because the risk of recurrence beyond this point is exceedingly low. Full article