Search

Purpose/objective(s)Radiographic MRI response following prostate radiotherapy, particularly stereotactic body radiotherapy (SBRT), remains poorly understood. Our objective was to describe radiographic changes to the prostate gland and prostate tumor following SBRT of men treated on a prospective, randomized trial.Materials/methodsMIRAGE (NCT04384770) is a single center, randomized phase III trial of patients receiving either CT or MRI guided SBRT for localized prostate cancer. Patients underwent pre-treatment and annual post-treatment MRIs, in addition to routine PSA surveillance. Outcomes reported include percent gland shrinkage, percent PSA response at one year, and presence of residual tumor based on radiographic interpretation. Patient characteristics were compared via two-sample t-test or Fischer's exact test. Both univariate and multivariable logistical analysis were employed to identify potential clinical predictors of residual tumor on 1-year follow up MRI.ResultsThis study cohort included 94 eligible patients with baseline characteristics in Table 1. Residual lesions were seen in 13 patients (14%), 5/27 (18.5%) treated without ADT and 8/67 (12%) with ADT. PSA ablation was deep, with a 79% median decrease without ADT and 98% median decrease with ADT. Patients receiving ADT showed more gland shrinkage (17% vs. 34% shrinkage, p = 0.0001), while radiographic non-responders and responders experienced similar gland shrinkage (median 21% vs 29% shrinkage, p > 0.05). No significant clinical predictors of residual tumor were identified on univariate and multivariate analysis. No patient had any clinical or biochemical evidence of failure.ConclusionA total of 14% of patients were found to have residual tumor detected on MRI one year after SBRT. These data highlight the protracted nature of radiographic tumor response to radiation therapy, even with ablative radiation techniques. The analysis is limited by the lack of biopsy data to quantify whether visualized residual tumor harbor active cancer.

BackgroundIn focused radiotherapy for prostate cancer (PC), a full dose of radiation is delivered to the index lesion while reduced dose is delivered to the remaining prostate to reduce morbidity. As PC is commonly multifocal, we investigated whether baseline clinical characteristics or multiparametric magnetic resonance imaging (mpMRI) may be useful to predict the actual pathologic distribution of PC in men with intermediate- or high-risk PC, which may better inform how to deliver focused radiotherapy.MethodsA retrospective single-institutional study was performed on 71 consecutive men with clinically localized, intermediate- or high-risk PC who underwent mpMRI followed by radical prostatectomy (RP) from January 2012 to December 2012. Logistic regression analysis was performed to evaluate preoperative predictors for satellite lesions. Performance characteristics of mpMRI to detect satellite lesions and the extent of prostate disease (one hemi-gland vs both) were also evaluated.ResultsIn all, 50.7% had satellite lesions on mpMRI. On RP specimen analysis, 66.2% had satellite lesions and 55.3% of these satellite lesions had pathologic Gleason score (pGS)⩾3+4. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for mpMRI detecting a satellite lesion being present in the RP specimen were 59.6%, 66.7%, 77.8%, 45.7% and 62.0%, respectively. The presence of MRI satellite lesions was the only preoperative predictor significantly associated with finding satellite lesions on final pathology (hazard ratio (HR), 2.95, P=0.040). There was agreement in 76.1% of the entire cohort for unilateral vs bilateral disease when incorporating both biopsy and mpMRI information and comparing with the RP specimen.ConclusionsIn intermediate risk or greater PC, only the presence of mpMRI satellite lesions could predict for pathologic satellite lesions. While combining biopsy and mpMRI information may improve preoperative disease localization, the relatively high incidence of bilateral hemi-gland involvement with pGS ⩾7 satellite lesions makes it challenging to appropriately select men eligible for hemi-gland therapy.

Purpose: To determine the utility of ureteral stents in interstitial gynecological brachytherapy. Methods and Materials: We reviewed 289 patients with cervix cancer treated with high-dose-rate interstitial brachytherapy who did not have pretreatment hydronephrosis to determine the relative incidence of benign ureteral strictures after treatment. We also did comparative dosimetry analysis in five cases of high-dose-rate brachytherapy. Bilateral ureteral stents were placed during the procedure. Three dosimetry plans were created to determine the impact of modifying clinical target volume (CTV) and applying ureteral dose constraints. In Plan 1, the ureters were contoured and excluded from the CTV and 120% dose constraints were applied. In Plan 2, the ureters were contoured and excluded, but no dose constraints were applied to the ureter. In Plan 3, the CTV was created as if the location of the ureters was unknown and then ureteral dose was determined. Results: There were 11 ureteral strictures observed in 255 nonstented cases and 0 ureteral strictures in 34 stented cases. Plan 1 reduced the ureter dose (D0.1cc) by a median 22% (7.0-53.8%) compared with Plan 2 and by a median of 30.9% (12.3-65%). compared with Plan3. Conclusions: Placement of stents and ureteral dose constraints facilitates dosimetry and reduces the dose to ureters. Temporary ureteral stents prevent obstruction during interstitial gynecologic brachytherapy and allows the ureters to be addressed as an organ at risk.

The lack of availability of continuing medical education programs on tobacco dependence for psychiatrists and psychiatric nurses is profound. We developed a 2-day curriculum delivered in November 2006 and March 2007 to 71 participants. Ninety-three percent ( n = 66) completed a pretest/posttest, and 91% (n = 65) completed the attitudes and beliefs survey. Scores on the pretest were low (M = 47% correct). Paired t tests found significant increases in raw scores from 6.7 to 13.6, t(65) = --22.8, p < .0001. More than 90% of psychiatrists and nurses indicated that motivating and helping patients to stop smoking and discussing smoking behavior were part of their professional role. Although 80% reported that they usually ask about smoking status, fewer reported recommending nicotine replacement (34%), prescribing pharmacotherapy (29%), or referring smokers to a telephone quit line (26%). Trainings are repeated twice a year because of ongoing demand. Further follow-up should evaluate changes in practices after training. [ABSTRACT FROM AUTHOR]

While the underutilization of psychosocial treatments for tobacco dependence may be problematic in general, it is especially problematic in smokers with schizophrenia who may need more assistance than those in the general population. Psychosocial approaches are important for motivating ambivalent smokers with schizophrenia to make a quit attempt (i.e., via motivational interviewing) and for providing the smoker with the tools necessary for a successful quit attempt. This paper discusses psychosocial treatment approaches available to the general population, those used in published clinical trials of tobacco dependence for smokers with schizophrenia, and an ongoing clinical trial comparing a high vs. moderately intensive psychosocial treatment for tobacco dependence in smokers with schizophrenia. We also discuss a new consumer advocacy program for smokers with schizophrenia and make recommendations for using psychosocial approaches to treat tobacco dependence in smokers with schizophrenia. [ABSTRACT FROM AUTHOR]

Objectives: This cross-sectional study examined the relationship between motivation to quit smoking and symptoms of depression and anxiety among 216 smokers seeking outpatient substance abuse treatment. Methods: Subjects were administered the Beck Depression Inventory, the Beck Anxiety Inventory, a Likert scale of readiness to quit smoking, the Smoking Stages of Change Algorithm, the Addiction Severity Index and the Fagerstrom Test for Nicotine Dependence. Results: There was a relationship between anxiety and motivation to quit smoking, with subjects reporting higher anxiety also reporting greater motivation to quit smoking. This relationship held up after controlling for the effects of substance use severity, race, gender, and cigarettes smoked per day. However, there was no relationship between depression and motivation to quit smoking. Conclusions: This is one of the few studies examining the role of anxiety and depression on motivation to quit smoking among smokers attending a substance abuse treatment program. The findings help to clarify the relationship between mental health symptoms and motivation to quit smoking in a substance abuse treatment setting. [ABSTRACT FROM AUTHOR]

BACKGROUND: The relationship between preference for stronger sweet solutions and propensity to excessive alcohol drinking is supported by both animal and human studies. This study was designed to test the hypothesis that sweet preference is associated with the genetic risk of alcoholism as measured by a paternal history of alcoholism. METHODS: Participants were 180 patients admitted to a residential treatment program for the treatment of alcoholism, drug dependence, or psychiatric conditions. In addition to a routine medical examination, patients completed the standard sweet preference test twice (on the 9th and 24th days after admission), and the family history of alcoholism was evaluated. RESULTS: Sweet preference was shown to be stable over time. It was strongly associated with a paternal history of alcoholism, with family history-positive patients approximately 5 times more likely to prefer stronger sweet solutions than family history-negative subjects. Such factors as dependence on alcohol, cocaine, opiates, cannabis, other drugs (including prescription drugs), and tobacco smoking, as well as demographics (gender and age), did not significantly interfere with association between sweet preference and paternal history of alcoholism. CONCLUSIONS: These findings provide some support for the hypothesis that preference for stronger sweet solutions is associated with a genetic predisposition to alcoholism as measured by a paternal history of alcoholism. [ABSTRACT FROM AUTHOR]

The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies. [ABSTRACT FROM AUTHOR]

Background and Objective: Time to testosterone recovery (TR) following androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonists varies widely. We evaluate TR kinetics and the oncological impact of an effective castration period in patients receiving definitive radiotherapy and ADT for prostate cancer., Methods: We obtained individual patient data from randomized controlled trials of radiotherapy with ADT and prospectively collected serial testosterone data from the MARCAP Consortium. We estimated the times to noncastrate TR (>1.7 nmol/l) and nonhypogonadal TR (>8.0 nmol/l) were estimated for each prescribed ADT duration, and developed corresponding nomograms. The association between effective castration period and metastasis-free survival (MFS) for any given ADT duration was evaluated via multivariable Cox regression. We conducted cubic spline analyses to assess nonlinear associations., Key Findings and Limitations: We included 1444 men from five trials in the analysis, of whom 115 received 4 mo, 880 received 6 mo, 353 received 18 mo, 36 received 28 mo, and 60 received 36 mo of ADT. Times to noncastrate TR and to nonhypogonadal TR varied considerably by ADT duration. Higher baseline testosterone and lower age were associated with a higher likelihood of TR (p < 0.001 for both). Effective castration period was not linearly associated with MFS for any ADT duration on Cox regression. Cubic spline analysis revealed that the optimal effective castration period for an MFS benefit was 10.6 mo for men who received 6 mo of ADT and 18 mo for men who received 18 mo of ADT., Conclusions and Clinical Implications: Time to TR varies according to the ADT duration, baseline testosterone, and age. The relationship between effective castration period and MFS may be nonlinear, with a longer effective castration period being helpful for men receiving 6 mo of ADT., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Systemic treatments for metastatic castration-resistant prostate cancer (mCRPC) include androgen deprivation therapy, androgen receptor pathway inhibitors, chemotherapy, and radiopharmaceuticals, all of which have associated toxicity. Prostate-specific membrane antigen (PSMA) PET/CT allows for higher sensitivity in detecting metastatic disease than is possible with conventional imaging. We hypothesized that PSMA PET/CT-guided, metastasis-directed radiotherapy may offer durable disease control with low toxicity rates in patients with mCRPC who have a limited number of metastases. Methods: We retrospectively screened 5 prospective PSMA PET/CT studies for patients with mCRPC who had up to 5 sites of oligorecurrent or oligoprogressive disease on PSMA PET/CT and subsequently received definitive-intent, metastasis-directed radiotherapy to all new or progressing sites with concurrent androgen deprivation therapy. Progression-free survival, freedom from new lines of systemic therapy, and overall survival (OS) were calculated from the start of metastasis-directed radiotherapy using Kaplan-Meier analysis. Biochemical response was defined as at least a 50% decrease in prostate-specific antigen 6 mo after the start of treatment. Toxicity was graded using the Common Terminology Criteria for Adverse Events, version 5. Results: Twenty-four patients met the inclusion criteria with a median follow-up of 33.8 mo (interquartile range, 27.6-45.1 mo). Between October 2017 and April 2023, 11 patients (45.8%) had 1 treated site, 10 patients (41.7%) had 2, and 3 patients (12.5%) had 3. Five sites were prostate or prostate bed, 15 were nodal, 19 were osseous, and 1 was visceral. Seventeen patients (70.8%) continued their preexisting systemic therapy, whereas 7 (29.2%) started a new systemic therapy. Median progression-free survival was 16.4 mo (95% CI, 9.8-23.0 mo). The biochemical response rate was 66.7%. Median freedom from a new line of systemic therapy was 29.0 mo (95% CI, 7.6-50.4 mo). Median OS was not reached. The 2- and 4-y OS rates were 91.1% (95% CI, 79.3%-100%) and 68.8% (95% CI, 45.1%-92.5%), respectively. Grade 2 and grade 3 or higher toxicity rates were 4.2% and 0%, respectively. Conclusion: PSMA PET/CT-guided, metastasis-directed radiotherapy appears to offer durable disease control with low toxicity rates for oligometastatic castration-resistant prostate cancer. Further prospective studies are needed to compare metastasis-directed radiotherapy with systemic therapy versus systemic therapy alone and PSMA PET/CT-guided versus conventional imaging-guided radiotherapy., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: Present knowledge of patient setup and alignment errors in image guided radiation therapy (IGRT) relies on voluntary reporting, which is thought to underestimate error frequencies. A manual retrospective patient-setup misalignment error search is infeasible owing to the bulk of cases to be reviewed. We applied a deep learning-based misalignment error detection algorithm (EDA) to perform a fully automated retrospective error search of clinical IGRT databases and determine an absolute gross patient misalignment error rate., Methods and Materials: The EDA was developed to analyze the registration between planning scans and pretreatment cone beam computed tomography scans, outputting a misalignment score ranging from 0 (most unlikely) to 1 (most likely). The algorithm was trained using simulated translational errors on a data set obtained from 680 patients treated at 2 radiation therapy clinics between 2017 and 2022. A receiver operating characteristic analysis was performed to obtain target thresholds. DICOM Query and Retrieval software was integrated with the EDA to interact with the clinical database and fully automate data retrieval and analysis during a retrospective error search from 2016 to 2017 and from 2021 to 2022 for the 2 institutions, respectively. Registrations were flagged for human review using both a hard-thresholding method and a prediction trending analysis over each individual patient's treatment course. Flagged registrations were manually reviewed and categorized as errors (>1 cm misalignment at the target) or nonerrors., Results: A total of 17,612 registrations were analyzed by the EDA, resulting in 7.7% flagged events. Three previously reported errors were successfully flagged by the EDA, and 4 previously unreported vertebral body misalignment errors were discovered during case reviews. False positive cases often displayed substantial image artifacts, patient rotation, and soft tissue anatomy changes., Conclusions: Our results validated the clinical utility of the EDA for bulk image reviews and highlighted the reliability and safety of IGRT, with an absolute gross patient misalignment error rate of 0.04% ± 0.02% per delivered fraction., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To characterize the relationship between Decipher genomic classifier scores and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-based metastatic spread., Materials and Methods: We identified patients from four institutions who underwent PSMA PET/CT scans pretreatment for primary staging or postradical prostatectomy (RP) for suspected recurrence and had Decipher transcriptomic data available from biopsy or RP specimens. PSMA PET/CT-based patterns of spread were classified as localized (miT + N0M0) or nonlocalized (miN1M0 or miM1a-c). We calculated the association between Decipher scores and the risk of nonlocalized disease on PSMA PET/CT using multivariable logistic regression for pretreatment patients and multivariable Cox regression for post-RP patients. We also compared select transcriptomic signatures between patients with localized and nonlocalized diseases., Results: Five hundred eighty-six patients were included (pretreatment: n = 329; post-RP: n = 257). Higher Decipher scores were associated with nonlocalized disease on PSMA PET/CT both pretreatment (odds ratio, 1.18 [95% CI, 1.03 to 1.36] per 0.1 increase in Decipher score, P = .02) and post-RP (hazard ratio, 1.15 [95% CI, 1.05 to 1.27] per 0.1 increase in Decipher score, P = .003). In the pretreatment setting, nonlocalized disease was associated with higher rates of TP53 mutations and lower rates of PAM50 luminal A subtype compared with localized disease. In the post-RP setting, overexpression of signatures related to metabolism, DNA repair, and androgen receptor signaling were associated with higher rates of nonlocalized disease., Conclusion: Higher Decipher scores were associated with nonlocalized disease identified on PSMA PET/CT both pretreatment and post-RP. There were several transcriptomic differences between localized and nonlocalized diseases in both settings.

Background and Objective: Both imaging and several prognostic factors inform the planning of salvage radiotherapy (SRT). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can localize disease unseen by other imaging modalities. The main objective of the study was to evaluate the impact of PSMA-PET on biochemical recurrence-free survival rate after SRT., Methods: This prospective randomized, controlled, phase 3 clinical trial randomized 193 patients with biochemical recurrence of prostate cancer after radical prostatectomy to proceed with SRT (control arm, n = 90) or undergo a PSMA-PET/computed tomography (CT) scan prior to SRT planning (investigational arm, n = 103) from June 2018 to August 2020. Any other approved imaging modalities were allowed in both arms (including fluciclovine-PET). This is a secondary endpoint analysis: impact of PSMA-PET on SRT planning. Case-report forms were sent to referring radiation oncologists to collect the management plans before randomization and after completion of SRT. The relative frequency (%) of management changes within each arm were compared using chi-square and Fisher's exact tests., Key Findings and Limitations: The delivered SRT plan was available in 178/193 patients (92.2%;76/90 control [84.4%] and 102/103 PSMA-PET [99%]). Median prostate-specific antigen levels at enrollment was 0.30 ng/ml (interquartile range [IQR] 0.19-0.91) in the control arm and 0.23 ng/ml (IQR 0.15-0.54) in the PSMA-PET arm. Fluciclovine-PET was used in 33/76 (43%) in the control arm. PSMA-PET localized recurrence(s) in 38/102 (37%): nine of 102 (9%) outside of the pelvis (M1), 16/102 (16%) in the pelvic LNs (N1, with or without local recurrence), and 13/102 (13%) in the prostate fossa only. There was a 23% difference (95% confidence interval [CI] 9-35%, p = 0.002) of frequency of major changes between the control arm (22% [17/76]) and the PSMA-PET intervention arm (45%[46/102]). Of the major changes in the intervention group, 33/46 (72%) were deemed related to PSMA-PET. There was a 17.6% difference (95% CI 5.4-28.5%, p = 0.005) of treatment escalation frequency between the control arm (nine of 76 [12%]) and the intervention arm (30/102 [29%]). Treatment de-escalation occurred in the control and intervention arms in eight of 76 (10.5%) and 12/102 (11.8%) patients, and mixed changes in zero of 76 (0%) and four of 102 (3.9%) patients, respectively., Conclusions and Clinical Implications: In this prospective randomized phase 3 study, PSMA-PET findings provided information that initiated major management changes to SRT planning in 33/102 (33%) patients. The final readout of the primary endpoint planned in 2025 may provide evidence on whether these changes result in improved outcomes., Patient Summary: Prostate-specific membrane antigen positron emission tomography leads to management changes in one-third of patients receiving salvage radiotherapy for post-radical prostatectomy biochemical recurrence of prostate cancer., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: A suboptimal prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) among men who go on to receive definitive radiation therapy for prostate cancer might suggest the existence of castration-resistant disease or altered androgen receptor signaling. This in turn may portend worse long-term clinical outcomes, especially in men with high-risk disease. We set out to evaluate the prognostic impact of poor PSA response to neoadjuvant ADT in men with high-risk prostate cancer., Methods and Materials: This was a post hoc analysis of the multicenter TROG 03.04 RADAR and PCS IV randomized clinical trials. Inclusion criteria for this analysis were patients with high-risk prostate cancer (defined as Gleason score ≥8, initial PSA ≥20 ng/mL, or cT3a disease or higher) who received definitive radiation therapy, at least 18 months of ADT, and had a preradiation therapy PSA level drawn after at least 3 months of neoadjuvant ADT. Poor PSA response was defined as PSA >0.5 ng/mL. Cox regression and Fine-Gray models were used to test whether poor PSA response was associated with metastasis-free survival, biochemical recurrence, prostate-cancer specific mortality, and overall survival., Results: Nine hundred thirty men met inclusion criteria for this analysis. Median follow-up was 130 months (interquartile range [IQR], 89-154 months). After a median of 3 months (IQR, 3-4.2 months) of neoadjuvant ADT, the median PSA was 0.60 ng/mL (IQR, 0.29-1.59). Overall, 535 men (57%) had a PSA >0.5 ng/mL. Poor PSA response was associated with significantly worse metastasis-free survival (hazard ratio [HR], 3.93; P = .02), worse biochemical recurrence (subdistribution HR, 2.39; P = .003), worse prostate-cancer specific mortality (subdistribution HR, 1.50; P = .005), and worse overall survival (HR, 4.51; P = .05)., Conclusions: Patients with PSA >0.5 mg/mL after at least 3 months of neoadjuvant ADT had worse long-term clinical outcomes and should be considered for treatment intensification., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: P.E.W. previously served as an Associate Executive Director for Radiation Oncology of the American Board of Radiology (ABR) and represented the ABR as an ex officio member of the Accreditation Council for Graduate Medical Education (ACGME) Radiation Oncology Review Committee (RO RC). M.L.S. currently serves as chair of the ACGME RO RC. J.B. serves as chair of the ABR RO Medical Physics Committee. P.D. currently serves as vice-chair of the ACGME RO RC. B.J.D. is a trustee of the ABR and member of the ACGME RO RC. B.G.H. previously served as a trustee and president of the ABR and chair of the ACGME RO RC. B.M. currently serves as chair of the ABR RO Radiation and Cancer Biology Committee. A.L.Z. previously served on the ACGME RO RC and as a trustee of the ABR. The other author declares no conflicts of interest.

Purpose: Adding high-dose-rate brachytherapy (BT) boost to external beam radiation therapy (EBRT) improves biochemical control but may affect patient-reported quality of life (QOL). We sought to determine long-term QOL outcomes for EBRT+BT versus EBRT alone., Methods and Materials: This was a post hoc analysis of the Trans-Tasman Radiation Oncology Group 03.04 Randomized Androgen Deprivation and Radiotherapy (TROG 03.04 RADAR) trial. Only patients who received 74 Gy conventionally fractionated EBRT (n = 260) or 46 Gy conventionally fractionated EBRT plus 19.5 Gy in 3 fractions high-dose-rate BT boost (n = 237) were included in this analysis. The primary endpoint was patient-reported QOL measured using the European Organisation for Research and Treatment of Cancer QOL (EORTC QLQ-C30) and prostate-specific QOL module (EORTC QLQ-PR25) questionnaires. We evaluated temporal changes in QOL scores, rates of symptom resolution, and the proportion of men who had decrements from baseline of >2 × the threshold for minimal clinically important change (2 × MCIC) for each domain., Results: At 5, 17, and 29 months after radiation therapy, the EBRT+BT group had 2.5 times (95% confidence interval [CI], 1.4-4.2; P < .001), 2.9 times (95% CI, 1.7-4.9; P < .001), and 2.6 times (95% CI, 1.4-4.6; P = .002) greater odds of reporting 2 × MCIC in urinary QOL score compared with EBRT. There were no differences beyond 29 months. EBRT+BT led to a slower rate of urinary QOL symptom score resolution up to 17 months after radiation therapy compared with EBRT (P < .001) but not at later intervals. In contrast, at the end of the radiation therapy period and at 53 months after radiation therapy, the EBRT+BT group had 0.65 times (95% CI, 0.44-0.96; P = .03) and 0.51 times (95% CI, 0.32-0.79; P = .003) the odds of reporting 2 × MCIC in bowel QOL symptom scores compared with EBRT. There were no significant differences in the rate of bowel QOL score resolution. There were no significant differences in global health status or sexual activity scores between the 2 groups., Conclusions: There were no persistent differences in patient-reported QOL measures between EBRT alone and EBRT+BT. BT boost does not appear to negatively affect long-term, patient-reported QOL., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This multicenter randomized phase III trial (NCT04457245) evaluated the effect of performing prostate-specific membrane antigen (PSMA) PET/CT before definitive radiotherapy. Methods: Men with unfavorable intermediate- or high-risk prostate cancer were randomized 1.08:1 between receiving and not receiving a PSMA PET/CT scan before definitive radiotherapy. All other imaging modalities were allowed in the control arm. The primary endpoint was 5-y progression-free survival. Results: Fifty-four men were randomized between November 2020 and December 2021 (PSMA PET/CT, n = 25; control, n = 29). The trial closed early after approval and insurance coverage of PSMA PET/CT. In the PSMA PET/CT arm, 14 patients had localized disease (miT2b-cN0M0), 6 had locally advanced disease (miT3a-bN0M0), 3 had regional metastasis (miN1M0), and 1 had distant metastasis (miM1b). Four patients were upstaged. Conclusion: PSMA PET/CT upstaged 17% of patients, which allowed for more accurate radiotherapy planning. Unfortunately, this trial closed early before completion of target enrollment (54/316, 17%) and was underpowered to assess the effect of PSMA PET/CT on progression-free survival., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Nearly all men with metastatic hormone-sensitive prostate cancer treated with intermittent androgen deprivation therapy (ADT) experience recurrence within 6 mo of testosterone recovery. We conducted a single-arm phase 2 trial to evaluate whether addition of dual androgen receptor pathway inhibitors (ARPIs) and metastasis-directed stereotactic body radiotherapy (SBRT) to intermittent ADT improves recurrence rates for men with between one and five nonvisceral, extrapelvic metastases on prostate-specific membrane antigen positron emission tomography/computed tomography after prior radical prostatectomy. Patients received 6 mo of androgen annihilation therapy (AAT; leuprolide, abiraterone acetate plus prednisone, and apalutamide) and metastasis-directed SBRT. The primary endpoint was the percentage of patients with prostate-specific antigen (PSA) <0.05 ng/ml 6 mo after testosterone recovery (≥150 ng/dl), with the study powered to detect an improvement from 1% to 12%. We enrolled 28 men between March 2021 and June 2022. Median follow-up was 20 mo (interquartile range 16-22). Twenty-six patients (93%) completed SBRT with 6 mo of hormone therapy, of whom six discontinued at least one ARPI; two patients withdrew prematurely. At 6 mo after testosterone recovery, PSA was maintained at <0.05 ng/ml in 13/26 patients (50%, 95% confidence interval 32-67%). Rates of grade 2 and 3 AAT toxicity were 21% and 21%. The results confirm that addition of metastasis-directed SBRT to highly potent systemic therapy can maintain low PSA after testosterone recovery, although further studies are needed to clarify the optimal systemic therapy regimen. PATIENT SUMMARY: We tested a combination of intensified hormone therapy (called androgen annihilation therapy) and radiotherapy targeted at metastases in men with recurrence of metastatic prostate cancer. We found that half of patients were recurrence-free 6 months after their testosterone level recovered, and that less than a quarter of patients experienced a severe drug-related side effect. Overall, this appears to be an effective therapy with acceptable side effects. This trial is registered on ClinicalTrials.gov as NCT03902951., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Real-time intrafraction tracking/gating is an integral component of magnetic resonance imaging-guided radiation therapy (MRgRT) and may have contributed to the acute toxicity reduction during prostate stereotactic body radiation therapy observed on the MRgRT-arm of the MIRAGE (MAGNETIC RESONANCE IMAGING-GUIDED Stereotactic Body Radiotherapy for Prostate Cancer) randomized trial (NCT04384770). Herein we characterized intrafraction prostate motion and assessed gating effectiveness., Methods and Materials: Seventy-nine patients were treated on an MR-LINAC. Real-time cine imaging was acquired at 4Hz in a sagittal plane. If >10% of the prostate area moved outside of a 3-mm gating boundary, an automatic beam hold was initiated. An in-house tool was developed to retrospectively extract gating signal for all patients and identify the tracked prostate in each cine frame for a subgroup of 40 patients. The fraction of time the prostate was within the gating window was defined as the gating duty cycle (GDC)., Results: A total of 391 treatments from 79 patients were analyzed. Median GDC was 0.974 (IQR, 0.916-0.983). Fifty (63.2%) and 24 (30.4%) patients had at least 1 fraction with GDC ≤0.9 and GDC ≤0.8, respectively. Incidence of low GDC fractions among patients appeared stochastic. Patients with minimum GDC <0.8 trended toward more frequent grade 2 genitourinary toxicity compared with those with minimum GDC >0.8 (38% vs 18%, P = .065). Prostate intrafraction motion was mostly along the bladder-rectum axis and predominantly in the superior-anterior direction. Motion in the inferior-posterior direction was associated with significantly higher rate of acute grade 2 genitourinary toxicity (66.7% vs 13.9%, P = .001). Gating limited mean prostate motion during treatment delivery in fractions with a GDC <0.9 (<0.8) to 2.9 mm (2.9 mm) versus 4.1 mm (4.7 mm) for ungated motion., Conclusions: Fractions with large intrafraction motion were associated with increased toxicity and their occurrence among patients appears stochastic. Real-time tracking/gating effectively mitigated this motion and is likely a major contributing factor of acute toxicity reduction associated with MRgRT., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: Magnetic Resonance Imaging (MRI)-guided Stereotactic body radiotherapy (SBRT) treatment to prostate bed after radical prostatectomy has garnered growing interests. The aim of this study is to evaluate intra-fractional anatomic and dose/volume metric variations for patients receiving this treatment., Materials and Methods: Nineteen patients who received 30-34 Gy in 5 fractions on a 0.35T MR-Linac were included. Pre- and post-treatment MRIs were acquired for each fraction (total of 75 fractions). The Clinical Target Volume (CTV), bladder, rectum, and rectal wall were contoured on all images. Volumetric changes, Hausdorff distance, Mean Distance to Agreement (MDA), and Dice similarity coefficient (DSC) for each structure were calculated. Median value and Interquartile range (IQR) were recorded. Changes in target coverage and Organ at Risk (OAR) constraints were compared and evaluated using Wilcoxon rank sum tests at a significant level of 0.05., Results: Bladder had the largest volumetric changes, with a median volume increase of 48.9 % (IQR 28.9-76.8 %) and a median MDA of 5.1 mm (IQR 3.4-7.1 mm). Intra-fractional CTV volume remained stable with a median volume change of 1.2 % (0.0-4.8 %). DSC was 0.97 (IQR 0.94-0.99). For the dose/volume metrics, there were no statistically significant changes observed except for an increase in bladder hotspot and a decrease of bladder V 32.5 Gy and mean dose. The CTV V 95% changed from 99.9 % (IQR 98.8-100 %) to 99.6 % (IQR 93.9-100 %)., Conclusion: Despite intra-fractional variations of OARs, CTV coverage remained stable during MRI-guided SBRT treatments for the prostate bed., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Kishan reports consulting fees and speaking honoraria from Varian Medical Systems, ViewRay, and Intelligent Automation; equity in ViewRay; and serving on the Janssen advisory board and Boston Scientific; received research funds from Janssen and Point Biopharma and ViewRay. Dr. Low reports corporate grant with Varian, consulting and presentation travel and fees from ViewRay, SAB for TAE Life Sciences, and founder of Pulmonum LLC. Dr. Ma and Dr. Steinberg reports honorarium from ViewRay. Dr. Cao reports corporate grant with Varian, honorarium and consulting fees from Varian and ViewRay. All other authors do not have any potential conflicts of interest to disclose. Funding support for the SCIMITAR trial was partially provided by ViewRay, Inc., but ViewRay, Inc. has no role in the conduct of this analysis., (© 2024 The Authors.)

Purpose: Treatment intensification of external beam radiotherapy (EBRT) plays a crucial role in the treatment of high-risk prostate cancer., Methods: We performed a critical narrative review of the relevant literature and present new developments in evidence-based treatment intensification strategies., Results: For men with high-risk prostate cancer, there is strong evidence to support prolonging androgen deprivation therapy (ADT) to 18-36 months and escalating the dose to the prostate using a brachytherapy boost. A potentially less toxic alternative to a brachytherapy boost is delivering a focal boost to dominant intraprostatic lesions using EBRT. In patients who meet STAMPEDE high-risk criteria, there is evidence to support adding a second-generation anti-androgen agent, such as abiraterone acetate, to long-term ADT. Elective pelvic lymph node irradiation may be beneficial in select patients, though more prospective data is needed to elucidate the group of patients who may benefit the most. Tumor genomic classifier (GC) testing and advanced molecular imaging will likely play a role in improving patient selection for treatment intensification as well as contribute to the evolution of treatment intensification strategies for future patients., Conclusion: Treatment intensification using a combination of EBRT, advanced hormonal therapies, and brachytherapy may improve patient outcomes and survival in men with high-risk prostate cancer. Shared decision-making between patients and multidisciplinary teams of radiation oncologists, urologists, and medical oncologists is essential for personalizing care in this setting and deciding which strategies make sense for individual patients., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: Emerging data suggest that trigone dosimetry may be more associated with poststereotactic body radiation therapy (SBRT) urinary toxicity than whole bladder dosimetry. We quantify the dosimetric effect of interfractional displacement and deformation of the whole bladder and trigone during prostate SBRT using on-board, pretreatment 0.35T magnetic resonance images (MRI)., Methods and Materials: Seventy-seven patients treated with MRI-guided prostate SBRT (40 Gy/5 fractions) on the MRI arm of a phase 3 single-center randomized trial were included. Bladder and trigone structures were contoured on images obtained from a 0.35T simulation MRI and 5 on-board pretreatment MRIs. Dice similarity coefficient (DSC) scores and changes in volume between simulation and daily treatments were calculated. Dosimetric parameters including D max , D 0.03 cc , D mean , V 40 Gy , V 39 Gy , V 38 Gy , and V 20 Gy for the bladder and trigone for the simulation and daily treatments were collected. Both physician-scored (Common Terminology Criteria for Adverse Events, version 4.03 scale) as well as patient-reported (International Prostate Symptom Scores and the Expanded Prostate Cancer Index Composite-26 scores) acute genitourinary (GU) toxicity outcomes were collected and analyzed., Results: The average treatment bladder volume was about 30% smaller than the simulation bladder volume; however, the trigone volume remained fairly consistent despite being positively correlated with total bladder volume. Overall, the trigone accounted for <2% of the bladder volume. Median DSC for the bladder was 0.79, whereas the median DSC of the trigone was only 0.33. No statistically significant associations between our selected bladder and trigonal dosimetric parameters and grade ≥2 GU toxicity were identified, although numerically, patients with GU toxicity (grade ≥2) had higher intermediate doses to the bladder (V 20 Gy and D mean ) and larger volumes exposed to higher doses in the trigone (V 40 Gy , V 39 Gy , and V 38 Gy )., Conclusions: The trigone exhibits little volume change, but considerable interfractional displacement/deformation. As a result, the relative volume of the trigone receiving high doses during prostate SBRT varies substantially between fractions, which could influence GU toxicity and may not be predicted by radiation planning dosimetry., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Intrathoracic progression remains the predominant pattern of failure in patients treated with concurrent chemoradiation followed by a consolidation immune checkpoint inhibitor for locally advanced, unresectable non-small cell lung cancer (NSCLC)., Objective: To determine the maximum tolerated dose (MTD) and use of hypofractionated concurrent chemoradiation with an adaptive stereotactic ablative radiotherapy (SABR) boost., Design, Setting, and Participants: This was an early-phase, single-institution, radiation dose-escalation nonrandomized controlled trial with concurrent chemotherapy among patients with clinical stage II (inoperable/patient refusal of surgery) or III NSCLC (American Joint Committee on Cancer Staging Manual, seventh edition). Patients were enrolled and treated from May 2011 to May 2018, with a median patient follow-up of 18.2 months. Patients advanced to a higher SABR boost dose if dose-limiting toxic effects (any grade 3 or higher pulmonary, gastrointestinal, or cardiac toxic effects, or any nonhematologic grade 4 or higher toxic effects) occurred in fewer than 33% of the boost cohort within 90 days of follow-up. The current analyses were conducted from January to September 2023., Intervention: All patients first received 4 Gy × 10 fractions followed by an adaptive SABR boost to residual metabolically active disease, consisting of an additional 25 Gy (low, 5 Gy × 5 fractions), 30 Gy (intermediate, 6 Gy × 5 fractions), or 35 Gy (high, 7 Gy × 5 fractions) with concurrent weekly carboplatin/paclitaxel., Main Outcome and Measure: The primary outcome was to determine the MTD., Results: Data from 28 patients (median [range] age, 70 [51-88] years; 16 [57%] male; 24 [86%] with stage III disease) enrolled across the low- (n = 10), intermediate- (n = 9), and high- (n = 9) dose cohorts were evaluated. The protocol-specified MTD was not exceeded. The incidences of nonhematologic acute and late (>90 days) grade 3 or higher toxic effects were 11% and 7%, respectively. No grade 3 toxic effects were observed in the intermediate-dose boost cohort. Two deaths occurred in the high-dose cohort. Two-year local control was 74.1%, 85.7%, and 100.0% for the low-, intermediate-, and high-dose cohorts, respectively. Two-year overall survival was 30.0%, 76.2%, and 55.6% for the low-, intermediate-, and high-dose cohorts, respectively., Conclusions and Relevance: This early-phase, dose-escalation nonrandomized controlled trial showed that concurrent chemoradiation with an adaptive SABR boost to 70 Gy in 15 fractions with concurrent chemotherapy is a safe and effective regimen for patients with locally advanced, unresectable NSCLC., Trial Registration: ClinicalTrials.gov Identifier: NCT01345851.

Background: Although smoking rates have declined over time, this decline has not been observed among those with mental health concerns. It is therefore important to develop effective messaging to support quitting in this population., Methods: We conducted an online experiment with 419 adults who smoke cigarettes daily. Participants with, or without a lifetime history of anxiety and/or depression were randomized to view a message focused on the benefits of quitting smoking on mental or physical health. Participants then reported motivation to quit smoking, mental health concerns about quitting, and perceived effectiveness of the message., Results: Participants with a lifetime history of anxiety and/or depression who saw the message focused on the benefits of quitting smoking on mental health reported greater motivation to quit than when they saw a message focused on the benefits to physical health. This was not replicated when examining current symptoms instead of lifetime history. Pre-existing beliefs that smoking improves one's mood were greater in those experiencing current symptoms and in those with a lifetime history of anxiety and/or depression. There was no main or interaction (message type X mental health status) effect of message type received on mental health related concerns about quitting., Conclusions: This study is one of the first to evaluate a smoking cessation message with content specifically targeted to those with mental health concerns about quitting smoking. Additional work is needed to determine how to best target those with mental health concerns with messages focused on the benefits of quitting on mental health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

MRI-guided radiation therapy (MRgRT) is an emerging, innovative technology that provides opportunities to transform and improve the current clinical care process in radiation oncology. As with many new technologies in radiation oncology, careful evaluation from a healthcare economic and policy perspective is required for its successful implementation. In this review article, we describe the current evidence surrounding MRgRT, framing it within the context of value within the healthcare system. Additionally, we highlight areas in which MRgRT may disrupt the current process of care, and discuss the evidence thresholds and timeline required for the widespread adoption of this promising technology., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Asynchronous podcast education is a popular supplementary tool, with up to 88% of medical residents reporting its use. Radiation oncology podcasts remain scarce. The authors analyzed the early performance, listenership, and engagement of the first education-specific radiation oncology medical podcast., Methods: Episode data and listener demographics were gathered from Spotify and Apple Podcasts. Episodes were case based, categorized by disease subsite, and reviewed by a board-certified radiation oncologist. Listenership was defined by the number of plays per day (ppd) on unique devices, averaged up to 60 days from publication. Episode engagement was defined as a percentage of plays on unique devices playing >40% of an episode within a single session. Quantitative end points included episode engagement and listenership. Pearson's correlation coefficient calculations were used for analysis., Results: From July 2022 to March 2023, 20 total episodes had 13,078 total plays over 227 days. The median episode length was 13.8 min (range, 9.2-20.1 min). Listener demographics were as follows: 54.4% men, 44.0% women, 1.3% not specified, and 0.3% nonbinary, with ages 18 to 22 (1%), 23 to 27 (13%), 28 to 34 (58%), 35 to 44 (22%), 45 to 59 (4%), and ≥60 (2%) years. Episodes were played in 53 countries, with the most plays in North America (71.5%), followed by Asia (10.2%), Europe (8.2%), Oceania (8.0%), Africa (1.5%), and South America (0.5%). There was a 585.2% increase in listenership since initiation, with median growth of 46.0% per month. Median listenership and engagement were 11.3 ppd (interquartile range, 10.3-13.8 ppd) and 81.4% (interquartile range, 72.0%-84.2%) for all episodes, respectively. A significant negative relationship between episode length and engagement was observed (r[20] = -0.51, P = .02). There was no statistically significant relationship between ppd and episode length (r[20] = -0.19, P = .42)., Conclusions: The significant rise in listenership, high episode engagement, and large international audience support a previously unmet need in radiation oncology medical education that may be supplemented by podcasts., (Published by Elsevier Inc.)

Background: Little is known regarding anal cancer patients' perspectives on undergoing radiation therapy. Additionally, the stigma surrounding anal cancer diagnosis warrants a better understanding of the barriers to complete disclosure in patient-healthcare team interactions., Methods: Included patients had squamous cell carcinoma of the anus treated with definitive chemoradiation (CRT) from 2009 to 2018. Survey questions were adapted from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and Discrimination and Stigma Scale., Results: A total of 46 anal cancer patients who underwent CRT were surveyed, of which 72% responded. 73% of respondents indicated little to no pre-treatment knowledge of CRT. 70% reported overall short-term effects as worse than expected, most commonly with bowel habits (82%), energy (73%), and interest in sexual activity (64%). 39% reported overall long-term effects to be worse than expected, most commonly with changes to bowel habits (73%), sexual function (67%), and interest in sexual activity (58%). However, 94% agreed they were better off after treatment. Regarding stigma, a subset reported hiding their diagnosis (12%, 24%) and side effects (24%, 30%) from friends/family or work colleagues, respectively, and 15% indicating they stopped having close relationships due to concerns over stigma., Conclusions: Although patients' perceptions of the severity of short-term CRT side effects were worse than expectations, the vast majority agreed they were better off after treatment. Targeted counseling on common concerns may improve the anal cancer treatment experience. A notable subset reported stigma associated with treatment, warranting further evaluation to understand the impact on the patient experience., (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Importance: Novel hormonal therapy (NHT) agents have been shown to prolong overall survival in numerous randomized clinical trials for patients with advanced prostate cancer (PCa). There is a paucity of data regarding the pattern of use of these agents in patients from different racial and ethnic groups., Objective: To assess racial and ethnic disparities in the use of NHT in patients with advanced PCa., Design, Setting, and Participants: This cohort study comprised all men diagnosed with de novo advanced PCa (distant metastatic [M1], regional [N1M0], and high-risk localized [N0M0] per Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy [STAMPEDE] trial criteria) with Medicare Part A, B, and D coverage between January 1, 2011, and December 31, 2017, in a Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database including prescription drug records. Data analysis took place from January through May 2023., Exposures: Race and ethnicity (Black [non-Hispanic], Hispanic, White, or other [Alaska Native, American Indian, Asian, Pacific Islander, or not otherwise specified and unknown]) abstracted from the SEER data fields., Main Outcomes and Measures: The primary outcome was receipt of an NHT agent (abiraterone, enzalutamide, apalutamide, or darolutamide) using a time-to-event approach., Results: The study included 3748 men (median age, 75 years [IQR, 70-81 years]). A total of 312 (8%) were Black; 263 (7%), Hispanic; 2923 (78%), White; and 250 (7%) other race and ethnicity. The majority of patients had M1 disease (2135 [57%]) followed by high-risk N0M0 (1095 [29%]) and N1M0 (518 [14%]) disease. Overall, 1358 patients (36%) received at least 1 administration of NHT. White patients had the highest 2-year NHT utilization rate (27%; 95% CI, 25%-28%) followed by Hispanic patients (25%; 95% CI, 20%-31%) and patients with other race or ethnicity (23%; 95% CI, 18%-29%), with Black patients having the lowest rate (20%; 95% CI, 16%-25%). Black patients had significantly lower use of NHT compared with White patients, which persisted at 5 years (37% [95% CI, 31%-43%] vs 44% [95% CI, 42%-46%]; P = .02) and beyond. However, there was no significant difference between White patients and Hispanic patients or patients with other race or ethnicity in NHT utilization (eg, 5 years: Hispanic patients, 38% [95% CI, 32%-46%]; patients with other race and ethnicity: 41% [95% CI, 35%-49%]). Trends of lower utilization among Black patients persisted in the patients with M1 disease (eg, vs White patients at 5 years: 51% [95% CI, 44%-59%] vs 55% [95% CI, 53%-58%]). After adjusting for patient, disease, and sociodemographic factors in multivariable analysis, Black patients continued to have a significantly lower likelihood of NHT initiation (adjusted subdistribution hazard ratio, 0.76; 95% CI, 0.61-0.94, P = .01)., Conclusions and Relevance: In this cohort study of Medicare beneficiaries with advanced PCa, receipt of NHT agents was not uniform by race, with decreased use observed in Black patients compared with the other racial and ethnic groups, likely due to multifactorial obstacles. Future studies are needed to identify strategies to address the disparities in the use of these survival-prolonging therapies in Black patients.

Purpose: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods., Materials and Methods: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R 2 ). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed., Results: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R 2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively., Conclusion: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.

Background: The aim of this study was to compare patient perceptions of radiotherapy (RT) before and after treatment to better inform future patients and providers., Methods: Seventy-eight consecutive patients with rectal adenocarcinoma treated with neo- or adjuvant chemoradiation, surgical resection, and adjuvant chemotherapy from 2009 to 2018 and who were without recurrence were included. Patients were surveyed ≥6 months after ileostomy reversal or ≥3 months after adjuvant chemotherapy. The survey assessed patients' baseline knowledge and fears of RT, how their short- and long-term side effects compared with initial expectations, and how their experiences compared for each modality (RT, surgery, and chemotherapy)., Results: Forty patient-responses were received. Before treatment, 70% of patients indicated little to no knowledge of RT, though 43% reported hearing frightening stories about RT. The most commonly top-ranked fears included organ damage (26%), skin burns (14%), and inability to carry out normal daily activities (10%). Eighty percent reported short-term effects of RT to be less than or as expected, with urinary changes (93%), abdominal discomfort (90%), and anxiety (88%) most commonly rated as less than or as expected. 85% reported long-term effects to be less than or as expected, with pain (95%), changes to the appearance of the treated area (85%), and dissatisfaction with body image (80%) most commonly rated as less than or as expected. Surgery was most commonly rated as the most difficult treatment (50%) and most responsible for long-term effects (55%). RT was least commonly rated as the most difficult treatment (13%), and chemotherapy was least commonly rated as most responsible for long-term effects (13%)., Conclusions: The majority of patients indicated short- and long-term side effects of RT for rectal cancer to be better than initial expectations. In the context of trimodality therapy, patients reported RT to be the least difficult of the treatments., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Ultra-hypofractionated regimens for definitive prostate cancer (PCa) radiotherapy are increasingly utilized due in part to promising safety and efficacy data complemented by greater patient convenience from a treatment course requiring fewer sessions. As such, stereotactic body radiation therapy (SBRT) is rapidly emerging as a standard definitive treatment option for patients with localized PCa. The commercially available magnetic resonance linear accelerator (MR-LINAC) integrates MR imaging with radiation delivery, providing several theoretical advantages compared to computed tomography (CT)-guided radiotherapy. MR-LINAC technology facilitates improved visualization of the prostate, real-time intrafraction tracking of prostate and organs-at-risk (OAR), and online adaptive planning to account for target movement and anatomical changes. These features enable reduced treatment volume margins and improved sparing of surrounding OAR. The theoretical advantages of MR-guided radiotherapy (MRgRT) have recently been shown to significantly reduce rates of acute grade ≥ 2 GU toxicities as reported in the prospective randomized phase III MIRAGE trial, which compared MR-LINAC vs CT-based 5 fraction SBRT in patients with localized PCa (Kishan et al. JAMA Oncol 9:365-373, 2023). Thus, MR-LINAC SBRT-utilizing potentially fewer treatments-is warranted and clinically relevant for men with low or intermediate risk PCa electing for radiotherapy as definitive treatment., Methods/design: A total of 136 men with treatment naïve low or intermediate risk PCa will be randomized in a 1:1 ratio to 5 or 2 fractions of MR-guided SBRT using permuted block randomization. Randomization is stratified by baseline Expanded PCa Index Composite (EPIC) bowel and urinary domain scores. Patients undergoing 5 fractions will receive 37.5 Gy to the prostate over 10-14 days and patients undergoing 2 fractions will receive 25 Gy to the prostate over 7-10 days. The co-primary endpoints are GI and GU toxicities as measured by change scores in the bowel and urinary EPIC domains, respectively. The change scores will be calculated as pre-treatment (baseline) score subtracted from the 2-year score., Discussion: FORT is an international, multi-institutional prospective randomized phase II trial evaluating whether MR-guided SBRT delivered in 2 fractions versus 5 fractions is non-inferior from a gastrointestinal (GI) and genitourinary (GU) toxicity standpoint at 2 years post-treatment in men with low or intermediate risk PCa., Trial Registration: Clinicaltrials.gov identifier: NCT04984343 . Date of registration: July 30, 2021., Protocol Version: 4.0, Nov 8, 2022., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Technological advances in MRI-guided radiation therapy (MRIgRT) have improved real-time visualization of the prostate and its surrounding structures over CT-guided radiation therapy. Seminal studies have demonstrated safe dose escalation achieved through ultrahypofractionation with MRIgRT due to planning target volume (PTV) margin reduction and treatment gating. On-table adaptation with MRI-based technologies can also incorporate real-time changes in target shape and volume and can reduce high doses of radiation to sensitive surrounding structures that may move into the treatment field. Ongoing clinical trials seek to refine ultrahypofractionated radiotherapy treatments for prostate cancer using MRIgRT. Though these studies have the potential to demonstrate improved biochemical control and reduced side effects, limitations concerning patient treatment times and operational workflows may preclude wide adoption of this technology outside of centers of excellence. In this review, we discuss the advantages and limitations of MRIgRT for prostate cancer, as well as clinical trials testing the efficacy and toxicity of ultrafractionation in patients with localized or post-prostatectomy recurrent prostate cancer.

There are numerous radiation modalities for the definitive treatment of localized prostate cancer. Classic clinical trials have established the basic tenets of treatment approaches, and emerging data have generated new potential avenues of treatment that optimize the therapeutic ratio by increasing prostate cancer tumor control while minimizing treatment-related toxicity. In the definitive setting, the selection of the optimal radiation therapy approach depends largely on the appropriate up-front risk stratification of men with prostate cancer, with greater intensification of treatment and greater integration of multimodality therapies for men with higher-risk disease. Hormonal therapy should be selectively deployed based on prognostic information derived from the National Comprehensive Cancer Network risk group and biologic tumor aggressiveness informed by genomic classifiers. Moreover, treatment intensification and target volume delineation are increasingly informed by molecular imaging and multiparametric magnetic resonance imaging. Herein, we perform a critical appraisal of the literature focusing on the optimal selection of radiation therapy modality for localized prostate cancer. Collaboration among medical oncologists, surgeons, and radiation oncologists will be critical for coordinating evidence-based radiation therapies when clearly indicated and for supporting shared decision-making when the evidence is incomplete.

Objective: To assess the efficacy of 177 Lu-PNT2002, a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), in combination with stereotactic body radiotherapy (SBRT) to all sites of metastasis, vs SBRT alone, in men with oligorecurrent metastatic hormone-sensitive prostate cancer (mHSPC)., Patients and Methods: The 177 Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR) trial is an open-label, randomized, stratified, two-arm, single-centre, Phase 2 trial to compare the efficacy and safety of neoadjuvant 177 Lu-PNT2002 plus SBRT vs SBRT alone in men with oligorecurrent mHSPC. Key eligibility criteria include one to five lesions identified on a PSMA positron emission tomography (PET)/computed tomography (CT) scan centrally reviewed by a board-certified nuclear medicine physician. Key exclusion criteria include castrate-resistant disease, de novo oligometastatic disease and receipt of androgen deprivation therapy (ADT) within 6 months of trial enrolment. The trial aims to enrol 100 patients who will be centrally randomized to one of the two treatment arms, in a 1:1 ratio. Patients in the control arm receive SBRT to all sites of disease. Patients in the experimental arm receive two cycles of neoadjuvant 177 Lu-PNT2002 (6.8 GBq) 6-8 weeks apart, followed by an interval PSMA PET/CT in 4-6 weeks and dose-adapted SBRT to all sites of disease 1-2 weeks later. The primary endpoint is progression-free survival. Secondary endpoints are radiographic and prostate-specific antigen-based progression, acute and late physician-scored toxicity, patient-reported quality of life, ADT-free survival, time to progression, overall survival, locoregional control, and duration of response. Enrolment in the study commenced in September 2022., Results and Conclusions: The addition of 177 Lu-PNT2002 to metastasis-directed therapy alone may potentially further forestall disease progression. The results of this Phase 2 trial will determine, for the first time in a randomized fashion, the added benefit of 177 Lu-PNT2002 to SBRT in patients with oligorecurrent mHSPC., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)