Background: The relevance of next-generation hormone therapies and circulating tumor cells (CTCs) are not elucidated in biochemical recurrence after prostatectomy. Objective: To evaluate the combination of abiraterone acetate plus prednisone (AAP), prostate bed radiotherapy (PBRT), and goserelin in biochemically relapsing men after prostatectomy, and to investigate the utility of CTCs. Design, setting, and participants: In this single-arm multicenter phase 2 trial, 46 biochemically relapsing men were enrolled between December 2012 and January 2019. The median follow-up was 47 mo. Intervention: All patients received AAP 1000 mg daily (but 750 mg during PBRT), salvage PBRT, and goserelin. Outcome measurements and statistical analysis: The primary outcome was 3-yr biochemical recurrence-free survival (bRFS) when prostate-specific antigen (PSA) levels were >= 0.2 ng/ml. The secondary outcomes included alternative bRFS (alt-bRFS) when PSA levels were >= 0.5 ng/ml and safety assessment. CTC count was assessed. Results and limitations: The 3-yr bRFS and alt-bRFS were 81.5% (95% confidence interval or CI [66.4-90.3%]) and 95.6% (95% CI [83.5-98.9%]), respectively. The most common acute radiotherapy-related adverse effect (AE; all grades was pollakiuria (41.3%). The most common late AE (all grades) was urinary incontinence (15.2%). Grade 3-4 acute or late radiotherapy-related AEs were scarce. Most frequent AEs nonrelated to radiotherapy were hot flashes (76%), hypertension (63%), and hepatic cytolysis (50%, of which 20% were of grades 3-4). Of the patients, 11% had a CTC count of >= 5, which was correlated with poorer bRFS (p = 0.042) and alt-bRFS (p = 0.008). The association between CTC count and higher rates of relapse was independent of the baseline PSA level and PSA doubling time (p = 0.42 and p = 0.09, respectively). This study was nonrandomized with a limited number of patients, and few clinical events were reported. Conclusions: Adding AAP to salvage radiation therapy and goserelin resulted in high bRFS and alt-bRFS. AEs remained manageable, although a close liver surveillance is advised. CTC count appears as a promising biomarker for prognosis and predicting response to treatment. Patient summary: Our study was a phase 2 clinical trial that exhibited the efficacy and tolerance of a novel androgen-receptor targeting agent (abiraterone acetate plus prednisone) in patients with prostate cancer who experienced rising prostate-specific antigen after radical prostatectomy, in combination with prostate bed radiotherapy. The results also indicated the feasibility and potential value of circulating tumor cell detection, which constitutes a possible advance in managing prostate cancers. (c) 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Introduction Salvage prostatic bed radiotherapy (PBRT) is a standard in case of biochemical recurrence following radical prostatectomy (RP) for prostate cancer (PC). The management of isolated prostatic bed recurrence following RP and PBRT is debated. Reirradiation within stereotactic body radiotherapy (SBRT) guided by metabolic imaging could be a relevant option in this case. In parallel, metformin, an economically viable and well-tolerated oral antidiabetic agent, has demonstrated its radiosensitising properties. This phase I/II clinical trial aims to (i) determine the optimal dose for SBRT reirradiation, (ii) conduct safety assessments and (iii) evaluate the efficacy of the metformin and SBRT combination.Methods and analysis We conducted a prospective, non-randomised, open-label, multicentre, dose escalation, phase I/II study involving a minimum of 44 patients. Eligible patients must have biochemical recurrence (Prostate Specific Antigen (PSA)>0.2 ng/mL and confirmed ascending trend in at least two successive assays), occurring at least 2 years after PBRT and prior RP for PC (including low, intermediate and high risk with a single risk factor) and no Common Terminology Criteria for Adverse Events (CTCAE) grade>=2 toxicity following PBRT. The recurrence should be visible on MRI and/or Positron Emission Tomography (PET) Choline and/or PET PSMA, without evidence of pelvic lymph node recurrence or metastatic disease. The primary objective of phase I is to determine the optimal SBRT dose (5×6, 6×6, or 5×5 Gy) based on dose-limiting toxicity (DLT). The dose will be chosen using a time-to-event continual reassessment method based on DLT, defined as CTCAE grade ≥3 gastrointestinal or genitourinary toxicity, or any other grade 4 adverse event. The primary outcome of the phase II is to estimate the efficacy of SBRT in combination with metformin in terms of biological relapse-free survival (bRFS) rate at 3 years. Secondary outcomes include 5-year bRFS rate, early/late genitourinary and gastrointestinal toxicities, quality of life, biochemical response rate, clinical progression-free survival and overall survival (OS).Ethics and dissemination Ethical approval has been obtained from the Ethics committee “SUD EST III Bron” Ref.CPP 2020-042B (20.05.07.72735) and the National Agency for the Safety of Medicines (ANSM) Ref. ANSM MEDAECNAT-2020-05-00009. The ethics approval obtained covers all the sites that will take part in this study. The study’s findings will be disseminated through publications and conference presentations.Trial registration number NCT04536805, Registration Date: 2020-08-17

Purpose/Objective(s) In locally advanced rectal cancer (LARC), which is relatively radioresistant, dose escalation increases clinical and histological tumor response and improves local control 1-2. However, radiation-induced toxicity is a major limiting factor for dose-escalation. Additionally, the new 64Cu-ATSM PET-CT tracer allows for dose-painting RT since it is a potential cellular redox witness of oxidative stress, responsible for radioresistance and tumor aggressiveness 3-4. The machine is a biology-guided radiotherapy (BgRT)-capable machine that is also cleared for image-guided radiation therapy. This study compares a dose-painting and escalation IMRT plan on the X1 treatment planning system (TPS) based on a 64Cu-ATSM biological target volume (BTV), with a conventional VMAT plan for LARC. Materials/Methods Pelvic dose distributions were retrospectively calculated for 14 patients who underwent neoadjuvant chemoradiotherapy (CRT) for LARC and had prior-CRT diagnostic 64Cu-ATSM PET-CT, 18FDG PET-CT and MRI. They were planned using two different boost definition and dose-escalation RT techniques: 64Cu-ATSM PET-CT-based BTV on the TPS and GTV based on 18FDG PET-CT and MRI for VMAT with the medical technology company's Halcyon. High-risk planning target volume (PTV HR) was defined as BTV or GTV with 10 mm isotropic margin except 7 mm laterally for both plans. Low-risk PTV (PTV LR) was defined as mesorectum and lymph node drainage area according to the recommendations of Valentini et al 5. The delineated organs at risk (OARs) were small bowel, large bowel, bladder, left and right femoral head and penile bulb or vagina. The prescribed PTV HR and PTV LR doses were 25Gy in 5 fractions and 45Gy in 25 fractions respectively, with homogeneous target dose. Dose constraints from preRADAR trial were used 6. The summed EQD2 OARs dose distributions were compared. Results The BTV (mean: 4.7cc [min: 0.9cc – max: 18.6cc]) was on average eleven times smaller than the GTV (mean: 52.7cc [min: 10.9cc – max: 253.7cc]). The 2 plans met the V95% requirement with slightly better coverage for IMRT plans compared to VMAT plans (98.8% and 97.6% respectively). A medical technology company's plans resulted in lower dose to OARs compared to VMAT plans. Conclusion This dosimetry study is an encouraging precursor to allow clinical dose-painting and dose-escalation for LARC on the medical technology company's system. The benefit has the potential for further increase by the future incorporation of online adaptive BgRT capabilities.

Hepatocellular carcinoma (HCC) is a disease with a poor prognosis, often diagnosed at an advanced stage. Therapeutic options have developed considerably in recent years, particularly with trans-arterial treatments. Systemic treatments have also evolved significantly, with the rise of immune checkpoint inhibitors (ICI) as first-line treatment for advanced HCC. The combination of loco-regional treatments and ICI is opening up new prospects and is the subject of numerous clinical trials. Recently, two global phase 3 trials investigating ICI-based adjuvant combinations have demonstrated improvements in recurrence-free survival or progression-free survival in patients treated with resection, ablation, or trans-arterial chemoembolization. However, mature data and overall survival results are still awaited but will be difficult to interpret. We are at the start of a new era of combinations of loco-regional treatments and immunotherapy. The identification of the best therapeutic strategies and predictive biomarkers is a crucial issue for future standards in clinical practice.

Cryotherapy is an ablative therapy that can be used to treat localized prostate cancer. In case of recurrence, treatment options are not well-defined, and their outcomes are unknown. We therefore collected all patients treated with radiotherapy after cryotherapy for prostate cancer recurrence in Nantes (France) between 2012 and 2019. We identified ten patients. After a median follow-up of 5 years, two patients presented late grade 3 toxicities; one patient presented a grade 3 rectal hemorrhage, and one had a grade 3 hematuria. Two patients relapsed at 61 and 62 months, and three patients died of other causes. Radiotherapy to treat local prostate cancer recurrence after cryotherapy seems feasible and effective in local control. These results do not allow us to recommend this technique in current practice but are encouraging for the conduct of prospective trials.

Background: As in other solid tumors, increasing evidence indicates that patients diagnosed with a limited number of prostate cancer metastases, so-called oligometastases, have a better prognosis than patients with extensive metastatic disease. Stereotactic body radiotherapy (SBRT) is now considered an option in this population.Programmed death-1 (PD-1) and its ligands (PD-L1) are targeted by immune checkpoint inhibitors. Preclinical studies have shown that the tumor immune microenvironment changes when combining radiotherapy with immunotherapy, especially with hypofractionated radiotherapy.The oligometastatic setting appears to be the most relevant clinical situation for evaluating the immune response generated by radiotherapy and immune checkpoint inhibitors in patients with an intact immune system.We hypothesize that durvalumab will enhance the immune response following SBRT targeting oligometastatic lesions. Our purpose is to demonstrate, via a randomized 2:1 phase II trial, that SBRT (3 fractions) with durvalumab in oligometastatic hormone-sensitive prostate cancer patients would improve progression-free survival in patients with prostate cancer with up to 5 metastases compared to patients who exclusively received SBRT. Methods: This is a multicentric randomized phase II study in French academic hospitals. Patients with prostate cancer and up to 5 metastases (lymph node and/or bone) were randomized into a 2:1 ratio between Arm A (experimental group), corresponding to durvalumab and SBRT to the metastases, and Arm B (control group), corresponding to SBRT alone to the metastases. The study aims to accrue a total of 96 patients within 3 years. The primary endpoint is two-year progression-free survival and secondary endpoints include androgen deprivation therapy-free survival, quality of life, toxicity, prostate cancer specific survival, overall survival, and immune response. Discussion: The expected benefit for the patients in the experimental arm is longer life expectancy with acceptable toxicity. We also expect our study to provide data for better understanding the synergy between immunotherapy and radiotherapy in oligometastatic prostate cancer.

BACKGROUND:Given the potential cardiovascular risks of androgen deprivation therapy (ADT), it is essential to identify patients who may be at an increased risk for coronary artery disease (CAD). Despite the recent ESC recommendations, there is no consensus on when to refer a patient to a cardiologist for further evaluation.OBJECTIVE:To report on new diagnoses of CAD in patients with prostate cancer (PCa) requiring ADT who underwent a systematic cardio-onco evaluation with an assessment of their coronary status.DESIGN, SETTING, AND PARTICIPANTS:This is a retrospective, monocentric study that included patients with PCa who had completed a cardio-onco evaluation with an assessment of their coronary status in the cardio-oncology department at the Western Cancer Institute, Nantes, between January 2019 and August 2022.INTERVENTION:The baseline cardio-onco evaluation included a physical exam, transthoracic echography, and electrocardiogram, followed with a systematic evaluation of their coronary status.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The primary objective was to determine the incidence of newly diagnosed CAD. The secondary objective was to evaluate the number of changes in cardiovascular treatment.RESULTS AND LIMITATIONS:Among the 34 patients who underwent cardio-onco evaluation, 7 (20.6%) were diagnosed with CAD, with a median time to diagnosis of 5 months. Most patients were asymptomatic, with one who experienced a myocardial infarction. Of the 27 patients without CAD, 44.4% underwent a therapeutic intervention by the cardiologist, with no cardiac deaths during follow-up. Overall, 55.9% of patients had a therapeutic intervention after the cardio-onco evaluation.CONCLUSIONS:The high incidence of newly diagnosed CAD in asymptomatic patients supports the need for screening for CAD in this population. Further research is needed to determine whether routine screening for CAD in patients receiving ADT would result in significant clinical benefits.

Purpose A second intensification is an option at first relapse in multiple myeloma (MM) after more than 36 months of initial remission. Many conditioning regimens have been tested, with or without total body irradiation (TBI). Recently, it was found that TBI could be replaced by total marrow irradiation (TMI) using helical tomotherapy, with promising results. Methods and Materials This study was a prospective multicenter phase 1 trial that aimed to determine the maximum tolerated dose (MTD) of TMI administered in association with melphalan 140 mg/m², followed by autologous stem cell transplantation as consolidation at first relapse in MM. Four dose levels were explored: 8 Gy, 10 Gy, 12 Gy, and 14 Gy. The dose-limiting toxicity (DLT) was defined as grade 4 neutropenia >15 days, grade 4 thrombopenia >28 days, and all other grade 4 nonhematologic toxic effects except nausea, vomiting, alopecia, mucositis, and reaction to autologous stem cell infusion. Results Thirteen patients were included; only 1 DLT at the third escalated dose level (12 Gy) was observed, whereas 1 patient was treated at 14 Gy with no adverse events. The MTD was not reached. The rate of acute toxicity was low: 38% of grade 3-4 diarrhea, mucositis, or unexplained fever. Regarding the lungs, the mean dose administered was systematically less than 8 Gy. After a median follow-up of 55 months, 70% of participants were alive. Of these 13 patients, 38.5% were in very good partial response and 30.8% were in complete response. Three of them were progression-free. Six patients were long survivors, still alive after 55 months of follow-up. Conclusions Total marrow irradiation provides good results with a good tolerance profile at first relapse in MM and makes it possible to increase the dose delivered to the planning target volume while sparing organs at risk. This technique could be discussed for all regimens before auto- or allo-stem cell rescue when TBI is required.

Purpose. - Haematologic malignancies are particular in that they can generally be cured, even when distant metastases are present at diagnosis, unlike solid malignancies. Systemic treatments, including chemotherapy, targeted therapies, and immunotherapy, are the standard of care with excellent results. The considerable progress made in the management of these diseases in the last 20 years has redefined the role of radiation therapy as minor in many clinical situations. We propose a literature review of data, showing that radiation therapy still has a role in curative, salvage, and palliative therapy situations. Material and methods. - A document and literature search was carried out in the following databases: Medline and ClinicalTrial.gov, for the terms "radiotherapy", "haematologic malignancies", "Hodgkin lymphoma", "non-Hodgkin lymphoma", "CAR T cells", "multiple myeloma", "solitary plasmocytoma", "intensity-modulated radiotherapy", "extracranial stereotactic body radiation therapy" and "proton therapy references". Results. - Haemopathological malignancies include a wide range of diseases and radiation therapy indications have been assessed over the past 20 years. Currently, radiation therapy is indicated for localized disease (solitary plasmocytoma), as an adjuvant (Hodgkin lymphoma), in palliative settings, or after systemic treatment in relapsed patients (chimeric antigen receptor [CAR] T-cells) with a low recurrence burden, which can therefore be considered "oligorecurrence". Radiation therapy, through total body irradiation, has important indications, thanks to its immunomodulatory and/or myeloablative effects. Moreover, recent technological developments have made possible significant improvement in safety, contributing to radiation therapy being positioned in the treatment strategy of several indications. Conclusions. - Given the effectiveness of systemic treatments in hematologic malignancies, the oligometastasis stage is of little importance. A curative intent after local radiation therapy, even advanced stage, is possible, both with residual disease for advanced Hodgkin lymphoma, aggressive non-Hodgkin lymphoma, or solitary plasmocytoma, and even without evidence of disease after chemotherapy

The treatment of local prostate cancer recurrence after cryotherapy is challenging since the optimal management is unknown. We collected the available evidence to date to better define the risk and benefit of salvage radiotherapy (SRT) after cryotherapy failure for localized prostate cancer. This review confirms the feasibility of SRT in terms of biochemical control and late toxicity rate. However, the absence of comparative trials or prospective studies, coupled with the heterogeneity of patients treated and the variations in treatments delivered across the analyzed studies, highlights the need for cautious consideration when opting for salvage radiotherapy. Therefore, we highly recommend the inclusion of patients in dedicated clinical trials to comprehensively assess the efficacy and safety of this approach.