Brachytherapy

This is a multi-center clinical study enrolling up to 28 participants. The primary objectives are to determine the objective response rate (ORR) established by the confirmed best overall response (BOR) following intratumoral administration of DaRT - Diffusing Alpha-Emitters Radiation Therapy. Secondary objectives are to: 1. Determine Progression Free Survival (PFS) up to 12 months after Alpha DaRT sources insertion. 2. Assess Overall Survival (OS) of patients treated with DaRT up to 12 months. 3. Assess Local control up to 12 months after DaRT insertion.

The goal of this open label, randomized, controlled clinical trial is to assess the benefits of providing Reiki therapy to subjects receiving their first brachytherapy treatment for gynecological malignancies. Participants will either receive a session of Reiki therapy or usual care during the standard wait time between the placement of the brachytherapy device and brachytherapy treatment. Questionnaires will be administered at various time points on the day of the participant's first brachytherapy treatment as well as at the three month follow-up time point. Researchers will compare the intervention (Reiki therapy) and control (usual care) groups to assess the impact of the Reiki therapy on anxiety, pain, state anxiety, depression, and physiological measurements.

Patients with prostate cancer and pelvic lymph node involvement (cN1M0) identified on PSMA PET imaging represent a biologically aggressive yet potentially curable disease population. Contemporary management relies on multimodality treatment combining definitive radiotherapy to the prostate and pelvic lymph nodes with long-term androgen deprivation therapy (ADT), often intensified with androgen receptor pathway inhibitors. Despite these advances, a substantial proportion of patients still develop distant metastatic disease, highlighting the need to optimize local-regional treatment strategies in the era of molecular imaging. The introduction of PSMA PET has fundamentally altered staging accuracy in prostate cancer, enabling earlier and more precise detection of pelvic nodal disease. However, most existing evidence guiding radiotherapy dose prescription in node-positive prostate cancer originates from the pre-PSMA era. As a result, it remains unclear how best to integrate prostate-directed and nodal-directed dose escalation strategies when disease extent is defined by modern molecular imaging. In particular, it is unknown whether long-term disease control is primarily driven by durable intraprostatic tumor eradication, by aggressive treatment of involved lymph nodes, or by a combination of both. PRO-BOOST-N is a prospective, multicenter, randomized phase II/III clinical trial designed to address this critical evidence gap. The trial evaluates prostate-first versus combined prostate and nodal dose escalation strategies in patients with PSMA PET-staged node-positive (cN1M0) prostate cancer treated within a standardized ultrahypofractionated whole-pelvis radiotherapy framework. All enrolled patients indicated for definitive treatment undergo mandatory baseline PSMA PET/CT to confirm pelvic lymph node involvement and exclude distant metastatic disease. All patients receive a uniform radiotherapy backbone consisting of ultrahypofractionated whole-pelvis radiotherapy delivered in five fractions, combined with long-term ADT. Use of androgen receptor pathway inhibitors is permitted and encouraged according to contemporary clinical practice and local availability, ensuring the relevance of the trial to real-world treatment settings. Using a 2×2 factorial randomized design, PRO-BOOST-N evaluates two independent treatment factors. The primary randomized comparison assesses whether ablative prostate dose escalation improves oncologic outcomes compared with contemporary SBRT-based definitive prostate radiotherapy without additional boost. Prostate dose escalation may be delivered using one of three protocol-defined modalities-high-dose-rate brachytherapy, low-dose-rate brachytherapy, or single-fraction SBRT-according to institutional expertise. This comparison directly tests the hypothesis that durable intraprostatic disease control is the dominant determinant of long-term systemic disease suppression in node-positive prostate cancer. The key secondary, hierarchically tested comparison evaluates the role of nodal dose escalation by comparing two predefined dose levels delivered to PSMA PET-positive pelvic lymph nodes. These dose levels reflect intermediate versus higher nodal boost strategies based on biologically effective dose concepts specific to prostate cancer radiobiology. To ensure patient safety and protocol feasibility, organ-at-risk-driven nodal dose de-escalation is permitted within the higher-dose arm, without altering randomization assignment. The primary endpoint of the trial is metastasis-free survival. Secondary endpoints include overall survival, radiographic progression-free survival assessed primarily using PSMA PET imaging, intraprostatic and regional nodal control, time to castration-resistant prostate cancer, time to next systemic therapy, treatment-related toxicity graded according to CTCAE version 5.0, and patient-reported outcomes assessing urinary, bowel, sexual, and global quality of life. By prospectively and hierarchically evaluating prostate and nodal dose escalation strategies within a modern PSMA PET-guided and ultrahypofractionated radiotherapy platform, PRO-BOOST-N aims to define the optimal radiotherapy intensification approach for patients with node-positive prostate cancer. The results of this study are expected to directly inform clinical practice, guideline development, and future treatment individualization in the PSMA PET era.

Title: Integration of Multi-modality Imaging Protocols with Emphasis on CT in Image-Guided Adaptive Brachytherapy (IGABT) for Cervical Cancer - EMBRACE III-TRIPLET : IMPACT Study Locally advanced cervical cancer (LACC) remains a major health challenge, particularly in low- and middle-income countries (LMICs), which account for the majority of global cases. The standard curative treatment involves a combination of external beam radiotherapy (EBRT) with concurrent chemotherapy, followed by brachytherapy (BT). Brachytherapy plays a crucial role in achieving high local control by delivering radiation directly to the tumour through internally placed radioactive sources. Historically, BT dose prescription was based on two-dimensional (2D) X-ray images and defined anatomical "points," achieving 5-year local control rates of 60-70%. Over the last decade, magnetic resonance imaging (MRI)-based image-guided adaptive brachytherapy (MR-IGABT) has transformed practice by enabling three-dimensional (3D) target-based dose prescription and adaptation to tumour regression. The landmark EMBRACE I study, involving over 1300 patients, demonstrated over 90% 5-year local control rates with MR-IGABT, establishing it as the international gold standard endorsed by NCG, ICRU, NCCN, and ESGO-ESTRO guidelines. However, MRI-based planning for IGABT remains logistically and financially challenging for many centres, especially in LMICs. CT and transrectal ultrasound (TRUS) have emerged as feasible alternatives, offering broader accessibility. Despite encouraging outcomes from smaller institutional studies, the lack of standardized and validated target delineation concepts for CT-IGABT has led to significant variability in clinical implementation. Recognizing this, the Indian Brachytherapy Society (IBS), American Brachytherapy Society (ABS), and GEC-ESTRO jointly published consensus recommendations in 2020 to standardize CT-IGABT practices across diverse clinical environments. At Homi Bhabha Cancer Hospital and Research Centre, Visakhapatnam, our prior work (RetroLACER Study) demonstrated that CT-based IGABT can achieve outcomes comparable to MR-IGABT, highlighting its feasibility and potential for wider adoption. Building on this foundation, the EMBRACE III-IMPACT Study seeks to evaluate whether CT-IGABT can be systematically and uniformly implemented in a multi-centre setting and to benchmark clinical outcomes against the standards set by MR-IGABT. Study Design: This is a multicentre, prospective, observational study planned to include approximately 1200 participants with locally advanced cervical cancer. All participants will receive standard-of-care treatment, including EBRT, concurrent weekly cisplatin chemotherapy, and brachytherapy with image-guided planning. Objectives: To assess the feasibility of implementing standardized CT-IGABT protocols across diverse clinical environments. To evaluate local control, disease-free survival, and treatment-related toxicity outcomes for CT-IGABT. To compare and benchmark CT-IGABT outcomes with established MR-IGABT benchmarks from prior international studies. Participant Involvement: Participants will undergo standard diagnostic imaging, EBRT with weekly cisplatin, and brachytherapy using CT-based planning. Imaging and treatment data will be collected, anonymized, and submitted to a central database for review. Regular follow-up visits will monitor tumour control and treatment-related side effects. Benefits: Participants receive internationally standardized, quality-assured treatment protocols. Centres gain access to expert review and QA support from international collaborators, potentially improving treatment quality and outcomes. The study supports global efforts to establish CT-IGABT as a cost-effective, accessible alternative to MRI-based IGABT, expanding equitable cancer care access. Risks: The study is observational and involves standard treatment; therefore, risks and costs are comparable to routine cervical cancer care. Confidentiality and Ethics: All data will be anonymized and handled in compliance with ethical and regulatory standards. Participant confidentiality will be strictly maintained. Written informed consent will be obtained before study participation. Significance: By validating standardised CT-based protocols and establishing outcome benchmarks, the study aims to facilitate widespread adoption of IGABT in resource-limited settings, ultimately improving treatment accessibility and survival outcomes.

Phase 1-2 study, comparing ultra-hypofractionnated (UH) to a moderately hypofractionnated (MH) radiation therapy, with image guided HDR prostate brachytherapy. Using iso-equivalent doses, a non-inferiority analysis will be done in order to prove UH non-inferior to MH, toxicity wise. Acceptability, tolerability, acute and late toxicity will be reported. MRI visible dominant intra-prostatic lesion will be outlines and variability between radiation oncologists and radiologists will be reported. As secondary objective, biochemical and clinical failure free survival will be reported at 5 \& 10 years.

The goal of this observational study is to learn about the long-term effects of HDR Brachytherapy in men with isolated local relapses after radical prostatectomy. The main question it aims to answer is: Does HDR Brachytherapy increase control rates and decreases complications compared with conventional External Irradiation? Participants will be asked to receive HDR brachytherapy as part of their regular medical care for isolated local relapses after radical prostatectomy

To evaluate the effectiveness and safety of radioactive particles in combination with the PARP inhibitor fluzoparib in the treatment of advanced inoperable soft tissue sarcoma.

To acquire data during High Dose Rate (HDR) brachytherapy treatments aiming to track the brachytherapy source inside the patient verifying the delivery of the treatment plan. Medical images (CT,MRI and US) combined with software developed by the investigator will be employed to predict the response of the Investigational product during the treatment and will be used as reference.The IP will be placed on the side of the treatment table and will acquire data during the whole treatment, which will be compared against information derived from the treatment plan. The IP based method can detect errors and information about motion and treatment uncertainties that are not currently available.

Brachytherapy for gynecological cancers will be studied retrospectively.