Acute Toxicity and Quality of Life in a Post-Prostatectomy Ablative Radiation Therapy (POPART) Multicentric Trial

Background: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). Methods: Patients with post-radical prostatectomy PSA levels of ≥0.1–2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD21.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. Results: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55–82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18–1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0–0.48 ng/mL). Conclusions: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy

Radiotherapy for oligometastatic cancer: a survey among radiation oncologists of Lombardy (AIRO-Lombardy), Italy

AIMS: To evaluate the use of radiotherapy (RT) for oligometastatic cancer (OMC) among radiation oncologists in Lombardy, Italy. METHODS AND STUDY DESIGN: A survey with 12 items regarding data of 2016 was sent to all 34 Lombardy RT centers. The survey included six general items and six specific items regarding patient/disease/treatment characteristics. RESULTS: Thirteen centers answered the survey (38%). All centers responded to general items and 12 centers submitted patient/disease/treatment data. General items The majority of centers (8/13) consider OMC if metastases number is less than 5. The most commonly prescribed dose/fraction is 5-10 Gy (8/13) using schedules of 3-5 fractions (11/13). Patient data items A total of 15.681 patients were treated in 2016 with external beam RT in 12 responding centers, and 1.087 patients were treated for OMC (7%). Primary tumor included lung, prostate, breast, colorectal and other malignancies in 33%, 21%, 12%, 9% and 25% of all OMC patients, respectively. Brain, lymph node, lung, bone, liver and others were the most common treated sites (24%, 24%, 22%, 17%, 8% and 5%, respectively). One and more than one metastasis were treated in 75 and 25% of patients, respectively. The vast majority of patients (95%) were treated with image-guided intensity-modulated RT or stereotactic RT. CONCLUSIONS: Seven percent of all RT patients in Lombardy are treated for OMC. Extreme hypofractionation and high-precision RT are commonly employed. The initiative of multicenter and multidisciplinary collaboration has been undertaken in order to prepare the platform for prospective and/or observational studies in OMC

Ambroxol as a disease-modifying treatment to reduce the risk of cognitive impairment in GBA-associated Parkinson’s disease: a multicentre, randomised, double-blind, placebo-controlled, phase II trial. The AMBITIOUS study protocol

Background Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme β-glucocerebrosidase (GCase), are the most frequent genetic risk factor for Parkinson’s disease (PD). GBA-related PD (GBA-PD) patients have higher risk of dementia and reduced survival than non-carriers. Preclinical studies and one open-label trial in humans demonstrated that the chaperone ambroxol (ABX) increases GCase levels and modulates α-synuclein levels in the blood and cerebrospinal fluid (CSF).Methods and analysis In this multicentre, double-blind, placebo-controlled, phase II clinical trial, we randomise patients with GBA-PD in a 1:1 ratio to either oral ABX 1.2 g/day or placebo. The duration of treatment is 52 weeks. Each participant is assessed at baseline and weeks 12, 26, 38, 52 and 78. Changes in the Montreal Cognitive Assessment score and the frequency of mild cognitive impairment and dementia between baseline and weeks 52 are the primary outcome measures. Secondary outcome measures include changes in validated scales/questionnaires assessing motor and non-motor symptoms. Neuroimaging features and CSF neurodegeneration markers are used as surrogate markers of disease progression. GCase activity, ABX and α-synuclein levels are also analysed in blood and CSF. A repeated-measures analysis of variance will be used for elaborating results. The primary analysis will be by intention to treat.Ethics and dissemination The study and protocols have been approved by the ethics committee of centres. The study is conducted according to good clinical practice and the Declaration of Helsinki. The trial findings will be published in peer-reviewed journals and presented at conferences.Trial registration numbers NCT05287503, EudraCT 2021-004565-13