Using multiparametric Magnetic Resonance Imaging and Prostate Specific Membrane Antigen Positron Emission Tomography to detect and delineate the gross tumour volume of intraprostatic lesions - A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Radiation therapy is used frequently for patients with prostate cancer. Dose escalation to intraprostatic lesions (IPLs) has been shown to improve oncologic outcomes, without increasing toxicity. Both multiparametric MRI (mpMRI) and PSMA PET can be used to identify IPLs. MATERIALS AND METHODS: A systematic review was conducted to determine the ability of mpMRI, PSMA PET and their combination to detect IPLs prior to radical prostatectomy (RP) as correlated with the histology. Trials included patients that had mpMRI, PSMA PET, or both, prior to RP. The quality of the histopathological-radiological co-registration was assessed as high or low for each study. Recorded outcomes include sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). A meta-analysis was conducted using a bivariate model to determine the pooled sensitivity and specificity for each imaging modality. This systematic review was registered through PROSPERO (CRD42023389092). RESULTS: Altogether, 42 studies were included in the systematic review. Of these, 20 could be included in the meta-analysis. The pooled sensitivity (95 % CI), specificity (95 % CI) and AUROC for mpMRI (n = 13 studies) were 64.7 % (50.2 % - 76.9 %), 86.4 % (79.7 % - 91.1 %), and 0.852; the pooled outcomes for PSMA PET (n = 12) were 75.7 % (64.0 % - 84.5 %), 87.1 % (80.2 % - 91.9 %), and 0.889; for their combination (n = 5), the pooled outcomes were 70.3 % (64.1 % - 75.9 %), 81.9 % (71.9 % - 88.8 %), and 0.796. When reviewing studies with a high-quality histopathological-radiological co-registration, IPL delineation recommendations varied by study and the imaging modality used. CONCLUSION: All of mpMRI, PSMA PET or their combination were found to have very good diagnostic outcomes for detecting IPLs. Recommendations for delineating IPLs varied based on the imaging modalities used and between research groups. Consensus guidelines for IPL delineation would help with creating consistency for focal boost radiation treatments in future studies.

Is Ultrahypofractionated Whole Pelvis Radiation Therapy (WPRT) as Well Tolerated as Conventionally Fractionated WPRT in Patients With Prostate Cancer? Early Results From the HOPE Trial.

OBJECTIVE: The aim of this work was to evaluate the acute toxicity and quality-of-life (QOL) impact of ultrahypofractionated whole pelvis radiation therapy (WPRT) compared with conventional WPRT fractionation after high-dose-rate prostate brachytherapy (HDR-BT). METHODS AND MATERIALS: The HOPE trial is a phase 2, multi-institutional randomized controlled trial of men with prostate-confined disease and National Comprehensive Cancer Network unfavorable intermediate-, high-, or very-high-risk prostate cancer. Patients were randomly assigned to receive conventionally fractionated WPRT (standard arm) or ultrahypofractionated WPRT (experimental arm) in a 1:1 ratio. All patients underwent radiation therapy with 15 Gy HDR-BT boost in a single fraction followed by WPRT delivered with conventional fractionation (45 Gy in 25 daily fractions or 46 Gy in 23 fractions) or ultrahypofractionation (25 Gy in 5 fractions delivered on alternate days). Acute toxicities measured during radiation therapy and at 6 weeks posttreatment were assessed using the clinician-reported Common Terminology Criteria for Adverse Events version 5.0, and QOL was measured using the Expanded Prostate Cancer Index Composite (EPIC-50) and International Prostate Symptom Score (IPSS). RESULTS: A total of 80 patients were enrolled and treated across 3 Canadian institutions, of whom 39 and 41 patients received external radiation therapy with conventionally fractionated and ultrahypofractionated WPRT, respectively. All patients received androgen deprivation therapy except for 2 patients treated in the ultrahypofractionated arm. The baseline clinical characteristics of the 2 arms were similar, with 51 (63.8%) patients having high or very-high-risk prostate cancer disease. Treatment was well tolerated with no significant differences in the rate of acute adverse events between arms. No grade 4 adverse events or treatment-related deaths were reported. Ultrahypofractionated WPRT had a less detrimental impact on the EPIC-50 bowel total, function, and bother domain scores compared with conventional WPRT in the acute setting. By contrast, more patients treated with ultrahypofractionated WPRT reached the minimum clinical important difference on the EPIC-50 urinary domains. No significant QOL differences between arms were noted in the sexual and hormonal domains. CONCLUSIONS: Ultrahypofractionated WPRT after HDR-BT is a well-tolerated treatment strategy in the acute setting that has less detrimental impact on bowel QOL domains compared with conventional WPRT.

The use of Lutetium-177 PSMA radioligand therapy with high dose rate brachytherapy for locally recurrent prostate cancer after previous definitive radiation therapy: a randomized, single-institution, phase I/II study (ROADSTER).

BACKGROUND: Isolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues. METHODS: ROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment. DISCUSSION: ROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy. TRIAL REGISTRATION: NCT05230251 (ClinicalTrials.gov).

Stereotactic Body Radiation Therapy (SBRT) for a Patient with a Myocardial Metastasis: A Case Report.

Metastatic lesions of the heart are rare but have the potential to cause significant morbidity. We describe the case of a patient with renal cell carcinoma who presented with shortness of breath and palpitations and was found to have a metastatic myocardial lesion causing arrythmia. He received stereotactic body radiation therapy (SBRT) to alleviate symptoms and provide local control. SBRT planning was executed using a four-dimensional computed tomography (4DCT) scan to account for respiratory and cardiac motion. Images from a planning magnetic resonance imaging (MRI) scan and a gated diagnostic MRI scan of the heart were fused with the 4DCT to assist with delineating the tumour. A dose of 30 Gy in five fractions was delivered without incident. The patient's cardiac MRI at two months post-treatment showed stability of his cardiac lesion. He subsequently died of distant disease progression, without any recurrence of his cardiac symptoms. SBRT may be considered for patients who present with a symptomatic metastatic cardiac lesion.