The Intersection of Prostate Cancer and Hypertension: a Call to Action.

OPINION STATEMENT: With improvements in treatment and survival from prostate cancer, comorbid cardiac conditions will significantly impact overall morbidity and mortality from prostate cancer. Hypertension is a well-established cardiovascular risk factor that increases the risk of heart failure, myocardial infarction, and stroke. Therapies used in the treatment of prostate cancer, including GnRH agonists, GnRH antagonists, enzalutamide, abiraterone, and others, can directly or indirectly increase the risk of hypertension. In this paper, we review the evidence available on the incidence and mechanism of hypertension in prostate cancer patients. In addition, we provide recommendations on the assessment, treatment, and future directions for hypertension management in the prostate cancer population. We propose an individualized goal for blood pressure in prostate cancer patients, balancing the target goal of 130/80 mmHg with common comorbidities of frailty, orthostatic symptoms, and imbalance in this population. The presence of additional comorbidities (myocardial infarction, heart failure, renal disease, diabetes) can assist in preference of anti-hypertensive drugs.

Rapid unpaired CBCT-based synthetic CT for CBCT-guided adaptive radiotherapy.

In this work, we demonstrate a method for rapid synthesis of high-quality CT images from unpaired, low-quality CBCT images, permitting CBCT-based adaptive radiotherapy. We adapt contrastive unpaired translation (CUT) to be used with medical images and evaluate the results on an institutional pelvic CT dataset. We compare the method against cycleGAN using mean absolute error, structural similarity index, root mean squared error, and Frèchet Inception Distance and show that CUT significantly outperforms cycleGAN while requiring less time and fewer resources. The investigated method improves the feasibility of online adaptive radiotherapy over the present state-of-the-art.

Onboard cone-beam CT-based replan evaluation for head and neck proton therapy.

PURPOSE: Quality assurance computed tomography (QACT) is the current clinical practice in proton therapy to evaluate the needs for replan. QACT could falsely indicate replan because of setup issues that would be solved on the treatment machine. Deforming the treatment planning CT (TPCT) to the pretreatment CBCT may eliminate this issue. We investigated the performance of replan evaluation based on deformed TPCT (TPCTdir) for proton head and neck (H&N) therapy. METHODS AND MATERIALS: Twenty-eight H&N datasets along with pretreatment CBCT and QACT were used to validate the method. The changes in body volume were analyzed between the no-replan and replan groups. The dose on the TPCTdir, the deformed QACT (QACTdir), and the QACT were calculated by applying the clinical plans to these image sets. Dosimetric parameters' changes, including ΔD95, ΔDmean, and ΔD1 for the clinical target volumes (CTVs) were calculated. Receiver operating characteristic curves for replan evaluation based on ΔD95 on QACT and TPCTdir were calculated, using ΔD95 on QACTdir as the reference. A threshold for replan based on ΔD95 on TPCTdir is proposed. The specificities for the proposed method were calculated. RESULTS: The changes in the body contour were 95.8 ± 83.8 cc versus 305.0 ± 235.0 cc (p < 0.01) for the no-replan and replan groups, respectively. The ΔD95, ΔDmean, and ΔD1 are all comparable for all the evaluations. The differences between TPCTdir and QACTdir evaluations were 0.30% ± 0.86%, 0.00 ± 0.22 Gy, and -0.17 ± 0.61 Gy for CTV ΔD95, ΔDmean, and ΔD1, respectively. The corresponding differences between the QACT and QACTdir were 0.12% ± 1.1%, 0.02 ± 0.32 Gy, and -0.01 ± 0.71 Gy. CTV ΔD95 > 2.6% in TPCTdir was chosen as the threshold to trigger QACT/replan. The corresponding specificity was 94% and 98% for the clinical practice and the proposed method, respectively. CONCLUSIONS: The replan evaluation based on TPCTdir provides better specificity than that based on the QACT.

Comparing surgical and nonsurgical larynx-preserving treatments with total laryngectomy for locally advanced laryngeal cancer.

BACKGROUND: The declining 5-year overall survival (OS) of patients with laryngeal cancer has been associated with increased nonsurgical management of stage III/IV disease. To further assess this hypothesis, the authors evaluated recent OS trends and patterns of use between larynx-preserving approaches with chemoradiation (CRT) or partial laryngectomy (PL) and total laryngectomy (TL) stratified by tumor and nodal burden. METHODS: The National Cancer Data Base was used to identify 8703 patients with stage III/IV (excluding T1 tumors) laryngeal squamous cell carcinoma treated between 2003 and 2011 with CRT or upfront PL or TL with or without adjuvant therapy. OS was analyzed using the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: Among patients with non-T4, low nodal burden (T2N1 or T3N0-N1) disease, no survival differences were observed between CRT, PL, and TL. Patients who had non-T4, high nodal burden (T2-T3N2-N3) disease who underwent TL with or without adjuvant treatment had a higher risk of death compared with those who received CRT (hazard ratio, 1.25; 95% CI, 1.04-1.51; P = .016). For T4N0-N3 tumors, TL compared with CRT was associated with improved OS (hazard ratio, 0.80; 95% CI, 0.62-0.92; P = .002). No statistically significant difference in outcome was noted between CRT and PL for all stage groups. The use of CRT has declined and receipt of TL has increased since 2006 for T4 disease, whereas PL rates have remained stably low. CONCLUSIONS: No survival differences were noted between surgical and nonsurgical approaches for patients with non-T4, low nodal burden laryngeal cancer. Patients with non-T4, high nodal burden disease may benefit from definitive CRT. Total laryngectomy remains advantageous in patients with T4 disease.

Surveillance Imaging Patterns and Outcomes Following Radiation Therapy and Radical Resection for Localized Extremity and Trunk Soft Tissue Sarcoma.

BACKGROUND: Optimal surveillance imaging (SI) regimens following radiation therapy (RT) and radical resection for localized soft tissue sarcoma (STS) are unknown and practice patterns vary. METHODS: Between 2006 and 2014, 94 patients with localized STS of the extremity/trunk treated with preoperative RT and radical resection were identified. Timing of local recurrence (LR), distant recurrence (DR), and SI were evaluated. The Kaplan-Meier method was used to determine recurrence-free and overall survival (OS), and the method of recurrence detection (SI or due to signs/symptoms) was determined. RESULTS: Median tumor size was 7.5 cm, and 92% were intermediate/high grade. After a median follow-up of 60 months for surviving patients, 30 patients (32%) recurred, including 5 LRs and 26 DRs. The median time to LR and DR was 36.2 months (range 14.4-65.7) and 10.4 months (range 5.2-76.9), respectively, and the 5-year local recurrence-free survival (RFS), distant RFS, and OS was 95, 71, and 76%, respectively. Local SI was performed for 90% of patients, mostly by magnetic resonance imaging (MRI; 91%). Of the five LRs, two were detected by SI and three had signs/symptoms preceding imaging. All patients underwent distant SI. Of the 26 DRs, 23 (88%) were in the lung. SI detected 22 (85%) DRs, and only 4 of 26 had signs/symptoms prompting imaging. CONCLUSION: Given excellent local control with RT and radical resection for intermediate/high-grade STS of the extremity/trunk, SI of the primary site should be reserved for select patients at high risk of LR. Conversely, due to frequent occurrence of asymptomatic DR in the lungs, periodic lung SI is appropriate. Routine abdominopelvic SI may not be indicated for most histologies.

Cost-Effectiveness of Surveillance for Distant Recurrence in Extremity Soft Tissue Sarcoma.

BACKGROUND: Optimal distant recurrence (DR) surveillance strategies for extremity soft tissue sarcoma (STS) are unknown. We performed a cost-effectiveness analysis of different imaging modalities performed at guideline-specified intervals. METHODS: We developed a Markov model simulating lifetime outcomes for 54-year-old patients after definitive treatment for American Joint Committee on Cancer stage II-III extremity STS using four surveillance strategies: watchful waiting (WW), chest X-ray (CXR), chest computed tomography (CCT), and positron emission tomography-computed tomography (PET/CT). Probabilities, utilities, and costs were extracted from the literature and Medicare claims to determine incremental cost-effectiveness ratios (ICER). RESULTS: CCT was the most effective and most costly strategy with CXR the most cost-effective strategy at a societal willing-to-pay (WTP) of $100,000/quality-adjusted life year (QALY). The ICER was $12,113/QALY for CXR versus $104,366/QALY for CCT while PET/CT was never cost-effective. Sensitivity analyses demonstrated CCT becomes the preferred imaging modality as the lifetime risk of DR increases beyond 33% or as the WTP increases beyond $120,000/QALY. CONCLUSIONS: Optimal DR surveillance imaging for stage II-III extremity STS should be individualized based on patients' risks for DR. These results suggest CXR, or CCT performed at more protracted intervals, may be preferred for lower-risk patients (i.e., DR risk <33%), whereas CCT may be preferred for higher-risk patients (i.e., DR risk >33%). Further study of optimal strategies is needed. In the interim, these findings may help to refine guidelines to reduce resource overutilization during routine surveillance of lower-risk sarcoma patients.

Early-stage rectal cancer: clinical and pathologic prognostic markers of time to local recurrence and overall survival after resection.

BACKGROUND: Resection without adjuvant therapy results in a low recurrence rate for patients with stage I (T1/2 N0) rectal cancer in the range of 4% to 16% at 5 years. There are limited data, however, regarding clinical or pathologic prognostic markers for recurrence in this population. OBJECTIVE: The aim of this study is to assess the clinical and pathologic factors associated with local recurrence and overall survival in patients with early-stage rectal cancer after resection. DESIGN: This is a retrospective study. SETTING: This study was conducted at 2 tertiary care centers in Boston, Massachusetts. PATIENTS: From 2000 to 2008, 175 patients with stage I rectal cancer treated with local or total mesorectal excision without adjuvant therapy were identified. MAIN OUTCOME MEASURES: Time to local recurrence after resection and overall survival were evaluated for all patients with complete follow-up data. Perioperative data were reviewed to identify staging method, preoperative CEA, type of surgery, tumor size, number of lymph nodes resected, histological grade, circumferential resection margin, perineural invasion, lymphovascular invasion, and tumor ulceration. Data were analyzed by using a Cox proportional hazards regression model. RESULTS: Of the eligible cohort, 137 patients had complete follow-up data for analysis of time to local recurrence, and only 23 (16.8%) patients had local recurrence. Among these 23 patients, the median time to recurrence was 1.1 years (0.1-7.8). On multivariate analysis, male sex, current alcohol use, and tumor ulceration were associated with heightened risk of local recurrence. Of the original cohort, 173 patients had complete follow-up for overall survival analysis. Among these patients, the median overall survival was 12 years. On multivariable analysis, age at diagnosis >65 years and T2 pathologic stage were associated with decreased survival. LIMITATIONS: As in any retrospective study, there is a potential for selection bias. Several patients were excluded from the analysis due to inadequate follow-up data. These results from two academic medical centers with specialized colorectal surgeons may not be generally applicable. The relatively small number of events, ie, recurrences, suggest the findings should be validated in a larger study. CONCLUSIONS: For patients with stage I rectal cancer treated with resection alone, these results provide important prognostic information and may help identify those who could benefit from additional therapy.

Physician Assessment of ChatGPT and Bing Answers to American Cancer Society's Questions to Ask About Your Cancer.

OBJECTIVES: Artificial intelligence (AI) chatbots are a new, publicly available tool for patients to access health care-related information with unknown reliability related to cancer-related questions. This study assesses the quality of responses to common questions for patients with cancer. METHODS: From February to March 2023, we queried chat generative pretrained transformer (ChatGPT) from OpenAI and Bing AI from Microsoft questions from the American Cancer Society's recommended "Questions to Ask About Your Cancer" customized for all stages of breast, colon, lung, and prostate cancer. Questions were, in addition, grouped by type (prognosis, treatment, or miscellaneous). The quality of AI chatbot responses was assessed by an expert panel using the validated DISCERN criteria. RESULTS: Of the 117 questions presented to ChatGPT and Bing, the average score for all questions were 3.9 and 3.2, respectively ( P < 0.001) and the overall DISCERN scores were 4.1 and 4.4, respectively. By disease site, the average score for ChatGPT and Bing, respectively, were 3.9 and 3.6 for prostate cancer ( P = 0.02), 3.7 and 3.3 for lung cancer ( P < 0.001), 4.1 and 2.9 for breast cancer ( P < 0.001), and 3.8 and 3.0 for colorectal cancer ( P < 0.001). By type of question, the average score for ChatGPT and Bing, respectively, were 3.6 and 3.4 for prognostic questions ( P = 0.12), 3.9 and 3.1 for treatment questions ( P < 0.001), and 4.2 and 3.3 for miscellaneous questions ( P = 0.001). For 3 responses (3%) by ChatGPT and 18 responses (15%) by Bing, at least one panelist rated them as having serious or extensive shortcomings. CONCLUSIONS: AI chatbots provide multiple opportunities for innovating health care. This analysis suggests a critical need, particularly around cancer prognostication, for continual refinement to limit misleading counseling, confusion, and emotional distress to patients and families.

Biochemical Relapse-Free Survival in Post-Prostatectomy Patients Receiving 18F-Fluciclovine-Guided Prostate Bed Only Radiation: Post-Hoc Analysis of a Prospective Randomized Trial.

PURPOSE: Whole pelvis (WP) radiation therapy (radiation) improved biochemical relapse free survival (bRFS) compared to prostate-bed (PB)-only radiation in RTOG 0534 but was performed in an era prior to PET staging. Separately, 18F-fluciclovine PET/CT (PET)-guided post-prostatectomy radiation improved 3-year bRFS versus radiation guided by conventional imaging alone. We hypothesized that patients who were changed from WP to PB-only radiation after PET would have bRFS3 that was (a) no higher than patients initially planned for PB-only radiation & (b) lower than patients planned for WP radiation without PET guidance. METHODS AND MATERIALS: We conducted a post-hoc analysis of a prospective, randomized, trial comparing conventional (Arm 1) v. PET-guided (Arm 2) post-prostatectomy radiation. In Arm 2, pre-PET treatment field decisions were recorded & post-PET fields were defined per protocol: pathologic node negative (pN0) without pelvic or extrapelvic PET uptake received PB-only radiation. Three-year bRFS was compared in patients planned for WP with change to PB-only radiation [Arm 2 (WP:PB)] v Arm 2 patients planned for PB-only with final radiation to PB-only [Arm 2(PB:PB)] & Arm 1 pN0 patients treated with WP radiation [Arm 1(WP)] using Z test and log-rank test. Demographics were compared using Chi-square test, Fisher's exact test, or ANOVA as appropriate. RESULTS: We identified 10 Arm 2(WP:PB), 31 Arm 2(PB:PB) and 11 Arm 1(WP) patients. Androgen deprivation was used in 50.0% of Arm 2(WP:PB) & 3.2% of Arm 2(PB:PB) patients, p<0.01. Median pre-radiation PSA was higher in Arm 2(WP:PB) vs Arm 2(PB:PB) patients (0.4 v 0.2 ng/mL, p=0.03), however, there were no significant differences in T-stage, Gleason score, or margin positivity. Three-year bRFS was 80% in Arm 2(WP:PB) vs 87.4% in Arm 2(PB:PB), p=0.47, respectively. Arm 1(WP) patients had significantly worse three-year (23%) bRFS vs Arm 2(WP:PB), p<0.01. CONCLUSIONS: Patients initially planned for WP radiation with field decision change to PB-only radiation after PET showed (a) no significant difference in 3-year bRFS compared to patients initially planned for PB-only radiation and (b) improved bRFS compared with patients receiving WP radiation without PET guidance. PET-guided volume de-escalation in selected patients may be one approach to mitigating toxicity without compromising outcomes.

Impact of Rectal Spacer on Toxicity Reduction in Men Treated With Proton Versus Photon Therapy.

Purpose: Rectal toxicity after prostate cancer (PCa) radiation therapy (RT) may be greater with protons compared with photon intensity-modulated RT, perhaps due to lateral penumbra and end-of-range uncertainty. Rectal spacers (RSs) have been shown to mitigate RT-associated acute/late rectal toxicity in men treated with photons. The relative benefit of RS in men treated with protons versus photons is unknown. We hypothesize that RS will confer greater bowel toxicity benefits in PCa treated with protons versus photons. Materials and Methods: We conducted a single institution, retrospective review of men receiving photon intensity-modulated RT or pencil-beam scanning proton RT for localized PCa. Four cohorts were compared: photon with or without RS, and proton with or without RS. Acute (<3 months), late (≥3 months), and most recent toxicity were compared among the 4 cohorts. The cumulative incidence of physician-reported grade 1 to 2 gastrointestinal (GI) toxicity (common terminology criteria for adverse events V5.0) was compared using χ2 or Fisher exact test. Patient-reported toxicity was evaluated using the International Prostate Expanded Prostate Composite Index-Clinical Practice and compared using linear mixed modeling. Results: In total, 164 patients were eligible for analysis: 38 photons without RS, 50 photons with RS, 26 protons without RS, and 50 protons with RS. The median follow-up was 17.6 months. In proton patients, acute (6.12% vs 30.77%, P = .009) and most recent (4.26% vs 26.09%, P = .01) G1-2 GI toxicity was lower with versus without RS. In photon patients, there were no significant differences in toxicity with versus without RS. No significant differences in patient-reported outcomes were observed with versus without RS in photon or proton groups. Conclusion: The rectal spacer was associated with lower G1-2 acute and most recent GI toxicity in men treated with protons; this difference was not observed in men treated with photons. While this study is limited by sample size, a relatively greater benefit of RS with proton versus photon therapy was observed.

Adaptive Proton Therapy Using CBCT-Guided Digital Twins.

This study aims to develop a digital twin (DT) framework to enhance adaptive proton stereotactic body radiation therapy (SBRT) for prostate cancer. Prostate SBRT has emerged as a leading option for external beam radiotherapy due to its effectiveness and reduced treatment duration. However, interfractional anatomy variations can impact treatment outcomes. This study seeks to address these uncertainties using DT concept, with the goal of improving treatment quality, potentially revolutionizing prostate radiotherapy to offer personalized treatment solutions. Our study presented a pioneering approach that leverages DT technology to enhance adaptive proton SBRT. The framework improves treatment plans by utilizing patient-specific CTV setup uncertainty, which is usually smaller than conventional clinical setups. This research contributes to the ongoing efforts to enhance the efficiency and efficacy of prostate radiotherapy, with ultimate goals of improving patient outcomes and life quality.

An optimized framework for cone-beam computed tomography-based online evaluation for proton therapy.

BACKGROUND: Clinical evidence has demonstrated that proton therapy can achieve comparable tumor control probabilities compared to conventional photon therapy but with the added benefit of sparing healthy tissues. However, proton therapy is sensitive to inter-fractional anatomy changes. Online pre-fraction evaluation can effectively verify proton dose before delivery to patients, but there is a lack of guidelines for implementing this workflow. PURPOSE: The purpose of this study is to develop a cone-beam CT-based (CBCT) online evaluation framework for proton therapy that enables knowledge transparency and evaluates the efficiency and accuracy of each essential component. METHODS: Twenty-three patients with various lesion sites were included to conduct a retrospective study of implementing the proposed CBCT evaluation framework for the clinic. The framework was implemented on the RayStation 11B Research platform. Two synthetic CT (sCT) methods, corrected CBCT (cCBCT), and virtual CT (vCT), were used, and the ground truth images were acquired from the same-day deformed quality assurance CT (dQACT) for the comparisons. The evaluation metrics for the framework include time efficiency, dose-difference distributions (gamma passing rates), and water equivalent thickness (WET) distributions. RESULTS: The mean online CBCT evaluation times were 1.6 ± 0.3 min and 1.9 ± 0.4 min using cCBCT and vCT, respectively. The dose calculation and deformable image registration dominated the evaluation efficiency, and accounted for 33% and 30% of the total evaluation time, respectively. The sCT generation took another 19% of the total time. Gamma passing rates were greater than 91% and 97% using 1%/1 mm and 2%/2 mm criteria, respectively. When the appropriate sCT was chosen, the target mean WET difference from the reference were less than 0.5 mm. The appropriate sCT method choice determined the uncertainty for the framework, with the cCBCT being superior for head-and-neck patient evaluation and vCT being better for lung patient evaluation. CONCLUSIONS: An online CBCT evaluation framework was proposed to identify the use of the optimal sCT algorithm regarding efficiency and dosimetry accuracy. The framework is extendable to adopt advanced imaging methods and has the potential to support online adaptive radiotherapy to enhance patient benefits. It could be implemented into clinical use in the future.

Disparities in time to prostate cancer treatment initiation before and after the Affordable Care Act.

BACKGROUND: Delayed access to care may contribute to disparities in prostate cancer (PCa). The Affordable Care Act (ACA) aimed at increasing access and reducing healthcare disparities, but its impact on timely treatment initiation for PCa men is unknown. METHODS: Men with intermediate- and high-risk PCa diagnosed 2010-2016 and treated with curative surgery or radiotherapy were identified in the National Cancer Database. Multivariable logistic regression modeled the effect of race and insurance type on treatment delay >180 days after diagnosis. Cochran-Armitage test measured annual trends in delays, and joinpoint regression assessed if 2014, the year the ACA became fully operationalized, was significant for inflection in crude rates of major delays. RESULTS: Of 422,506 eligible men, 18,720 (4.4%) experienced >180-day delay in treatment initiation. Compared to White patients, Black (OR 1.79, 95% CI 1.72-1.87, p < 0.001) and Hispanic (OR 1.37, 95% CI 1.28-1.48, p < 0.001) patients had higher odds of delay. Compared to uninsured, those with Medicaid had no difference in odds of delay (OR 0.94, 95% CI 0.84-1.06, p = 0.31), while those with private insurance (OR 0.57, 95% CI 0.52-0.63, p < 0.001) or Medicare (OR 0.64, 95% CI 0.58-0.70, p < 0.001) had lower odds of delay. Mean time to treatment significantly increased from 2010 to 2016 across all racial/ethnic groups (trend p < 0.001); 2014 was associated with a significant inflection for increase in rates of major delays. CONCLUSIONS: Non-White and Medicaid-insured men with localized PCa are at risk of treatment delays in the United States. Treatment delays have been consistently rising, particularly after implementation of the ACA.

Bladder only versus bladder plus pelvic lymph node chemoradiation for muscle-invasive bladder cancer.

BACKGROUND: Bladder-sparing chemoradiation therapy (CRT) is a definitive first-line treatment for muscle-invasive bladder cancer. The optimal radiotherapy target volume, either bladder-only (BO) or bladder plus pelvic lymph nodes (BPN), remains unclear. METHODS: We identified 2,104 patients in the National Cancer Database with cT2-4N0M0 urothelial cell carcinoma of the bladder treated with CRT following maximal transurethral resection of bladder tumor from 2004 to 2016. The exposure of interest was BO vs. BPN treatment volume. The primary outcome was overall survival (OS), compared between groups using Kaplan-Meier and multivariable Cox proportional hazards. Sensitivity analysis tested an interaction term for clinical T stage (T2 vs. T3-4) and radiation modality (3-dimensional conformal radiotherapy vs. intensity modulated radiotherapy or proton therapy). Annual use of BO vs. BPN from 2004 to 2016 was compared using Cochran-Armitage test. RESULTS: A total of 578 patients were treated with BO and 1,526 patients treated with BPN CRT. There was a significant increase in BPN use from 2004 to 2016 (66.9%-76.8%, P < 0.0001). With a median follow-up of 6.2 years, there was no survival difference between groups: 5- and 10-year OS 27.4% (95% CI 23.4%-31.4%) in the BO group vs. 31.9% (95% CI 29.3%-34.6%) in the BPN group, and 13.1% (95% CI 9.7%-17.1%) in the BO group vs. 13.2% (95% CI 10.6%-16.0%) in the BPN group, respectively (log-rank P = 0.10). On multivariable analysis, there was no significant association between BPN and OS (adjusted HR 0.90, 95% CI 0.81-1.02, P = 0.09). On sensitivity analysis, we found no differential effect by T stage or radiation modality. CONCLUSION: Use of pelvic lymph node radiation has risen in the US but may not impact long-term survival outcomes for patients with node-negative muscle-invasive bladder cancer (MIBC). Optimizing radiation treatment volumes for CRT for MIBC will be important to study under prospective trials, such as the SWOG/NRG 1806.

Association of Brachytherapy Boost with Overall Survival for Gleason 9-10 Prostate Cancer: The Impact of Primary versus Secondary Pattern 5.

PURPOSE: The addition of a brachytherapy (BT) boost to external beam radiotherapy (EBRT) reduces recurrence risk in men with high-risk prostate cancer (PCa) and may reduce PCa-mortality for Gleason grade group 5 (GG5). Whether the extent of pattern five, a risk factor for distant metastases, impacts the benefit of a BT boost is unclear. METHODS: Men with localized GG5 PCa treated with (1) EBRT or (2) EBRT+BT between 2010 and 2016 were identified in the National Cancer Database. EBRT monotherapy group received conventionally fractionated (1.8-2.0 Gy per fraction) ≥74 Gy or moderately hypofractionated (2.5-3.0 Gy per fraction) ≥60 Gy. EBRT + BT group received conventionally fractionated ≥45 Gy or moderately hypofractionated ≥37.5 Gy, and either LDR or HDR BT. All patients received concomitant ADT; none received chemotherapy, immunotherapy, or surgery. OS was compared using Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards in the overall cohort, followed by subgroups based on primary versus secondary pattern 5. Propensity score- and exact-matching was used to corroborate results. RESULTS: A total of 8260 men were eligible: EBRT alone (89%) versus EBRT + BT (11%). 5-year OS for EBRT versus EBRT + BT was 76.3% and 85.0%, respectively (p = 0.002; multivariable adjusted HR 0.84, 95% CI 0.65-0.98; p = 0.04). These results remained consistent after propensity score and exact matching. The OS advantage of a BT boost was more prominent in men with Gleason 4 + 5 PCa (p = 0.001) and not observed in men with Gleason 5 + 5 or 5 + 4 PCa. CONCLUSIONS: Extent of pattern five may be useful in appropriately selecting men for EBRT+BT and should be considered as a pre-randomization stratification variable for future clinical trial design.

Does Chemo-Radiotherapy Improve Survival Outcomes vs. Radiotherapy Alone for High-Grade cT1 Urothelial Carcinoma of the Bladder?

BACKGROUND: Non-muscle invasive bladder cancer (non-MIBC) that is high-grade and confined to the lamina propria (HGT1) often has an aggressive clinical course. Currently, there is limited data on the comparative effectiveness of RT vs. CRT for HGT1 non-MIBC. We hypothesized that CRT would be associated with improved overall survival (OS) vs. RT in HGT1 bladder cancer. METHODS: Patients diagnosed with HGT1 non-MIBC, and treated with transurethral resection of bladder tumor followed by either treatment with RT alone or CRT, were identified in the National Cancer Database. Inverse probability of treatment weighting (IPTW) was employed and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. OS was the primary endpoint, and was estimated using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 259 patients with HGT1 UC were treated with: (i) RT alone (n = 123) or (ii) CRT (n = 136). Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone (Hazard Ratio [HR]: 0.62, 95% Confidence Interval (95% CI): 0.44-0.88, P = .007). Four-year OS for the CRT vs. RT alone was 36% and 19%, respectively (log-rank P <.008). CONCLUSION: For patients with HGT1 bladder cancer, concurrent CRT was associated with improved OS compared with radiation alone in a retrospective cohort. These results are hypothesis-generating. The NRG is currently developing a phase II randomized clinical trial comparing CRT to other novel, bladder preservation strategies.

Radiation Facility Volume and Survival for Men With Very High-Risk Prostate Cancer Treated with Radiation and Androgen Deprivation Therapy.

Importance: Very high-risk (VHR) prostate cancer is an aggressive substratum of high-risk prostate cancer, characterized by high prostate-specific antigen levels, high Gleason score, and/or advanced T category. Contemporary management paradigms involve advanced molecular imaging and multimodal treatment with intensified prostate-directed or systemic treatment-resources more readily available at high-volume centers. Objective: To examine radiation facility case volume and overall survival (OS) in men with VHR prostate cancer. Design, Setting, and Participants: A retrospective cohort study was performed from November 11, 2022, to March 4, 2023, analyzing data from US facilities reporting to the National Cancer Database. Patients included men diagnosed with nonmetastatic VHR prostate cancer by National Comprehensive Cancer Network criteria (clinical T3b-T4 category, primary Gleason pattern 5, >4 cores with grade group 4-5, and/or 2-3 high-risk features) and treated with curative-intent radiotherapy and androgen deprivation therapy between January 1, 2004, to December 31, 2016. Exposures: Treatment at high- vs low-average cumulative facility volume (ACFV), defined as the total number of prostate radiotherapy cases at an individual patient's treatment facility from 2004 until the year of their diagnosis. The nonlinear association between a continuous ACFV and OS was examined through a Martingale residual plot; an optimal ACFV cutoff was identified that maximized the separation between high vs low ACFV via a bias-adjusted log rank test. Main Outcomes and Measures: Overall survival was assessed between high vs low ACFV using Kaplan-Meier analysis with and without inverse probability score weighted adjustment and multivariable Cox proportional hazards. Results: A total of 25 219 men (median age, 71 [IQR, 64-76] years; 78.7% White) with VHR prostate cancer were identified, 6438 (25.5%) of whom were treated at high ACFV facilities. Median follow-up was 57.4 (95% CI, 56.7-58.1) months. Median OS for patients treated at high ACFV centers was 123.4 (95% CI, 116.6-127.4) months vs 109.0 (95% CI, 106.5-111.2) months at low ACFV centers (P < .001). On multivariable analysis, treatment at a high ACFV center was associated with lower risk of death (hazard ratio, 0.89; 95% CI, 0.84-0.95; P < .001). These results were also significant after inverse probability score weighted-based adjustment. Conclusions and Relevance: In this cohort study of patients with VHR prostate cancer who underwent definitive radiotherapy and androgen deprivation therapy, facility case volume was independently associated with longer OS. Further studies are needed to identify which factors unique to high-volume centers may be responsible for this benefit.

2D medical image synthesis using transformer-based denoising diffusion probabilistic model.

Objective. Artificial intelligence (AI) methods have gained popularity in medical imaging research. The size and scope of the training image datasets needed for successful AI model deployment does not always have the desired scale. In this paper, we introduce a medical image synthesis framework aimed at addressing the challenge of limited training datasets for AI models.Approach. The proposed 2D image synthesis framework is based on a diffusion model using a Swin-transformer-based network. This model consists of a forward Gaussian noise process and a reverse process using the transformer-based diffusion model for denoising. Training data includes four image datasets: chest x-rays, heart MRI, pelvic CT, and abdomen CT. We evaluated the authenticity, quality, and diversity of the synthetic images using visual Turing assessments conducted by three medical physicists, and four quantitative evaluations: the Inception score (IS), Fréchet Inception Distance score (FID), feature similarity and diversity score (DS, indicating diversity similarity) between the synthetic and true images. To leverage the framework value for training AI models, we conducted COVID-19 classification tasks using real images, synthetic images, and mixtures of both images.Main results. Visual Turing assessments showed an average accuracy of 0.64 (accuracy converging to50%indicates a better realistic visual appearance of the synthetic images), sensitivity of 0.79, and specificity of 0.50. Average quantitative accuracy obtained from all datasets were IS = 2.28, FID = 37.27, FDS = 0.20, and DS = 0.86. For the COVID-19 classification task, the baseline network obtained an accuracy of 0.88 using a pure real dataset, 0.89 using a pure synthetic dataset, and 0.93 using a dataset mixed of real and synthetic data.Significance. A image synthesis framework was demonstrated for medical image synthesis, which can generate high-quality medical images of different imaging modalities with the purpose of supplementing existing training sets for AI model deployment. This method has potential applications in many data-driven medical imaging research.

Serial Measurement of Global Longitudinal Strain Among Women With Breast Cancer Treated With Proton Radiation Therapy: A Prospective Trial for 70 Patients.

PURPOSE: Conventional photon radiation therapy (RT) for breast cancer is associated with a reduction in global longitudinal strain (GLS) and an increase in troponin, N-terminal pro hormone B-type natriuretic peptide (NT-proBNP), and incident heart failure. The cardiac radiation exposure with proton-RT is much reduced and thus may be associated with less cardiotoxicity. The objective was to test the effect of proton-RT on GLS, troponin, and NT-proBNP. METHODS AND MATERIALS: We conducted a prospective, observational, single-center study of 70 women being treated with proton-RT for breast cancer. Serial measurements of GLS, high-sensitivity troponin I, and NT-proBNP were performed at prespecified intervals (before proton-RT, 4 weeks after completion of proton-RT, and again at 2 months after proton-RT). RESULTS: The mean age of the patients was 46 ± 11 years, and the mean body mass index was 25.6 ± 5.2 kg/m2; 32% of patients had hypertension, and the mean radiation doses to the heart and the left ventricle (LV) were 0.44 Gy and 0.12 Gy, respectively. There was no change in left ventricular ejection fraction (65 ± 5 vs 66 ± 5 vs 64 ± 4%; P = .15), global GLS (-21.7 ± 2.7 vs -22.7 ± 2.3 vs -22.8 ± 2.1%; P = .24), or segmental GLS from before to after proton-RT. Similarly, there was no change in either high-sensitivity troponin or NT-proBNP with proton-RT. However, in a post hoc subset analysis, women with hypertension had a greater decrease in GLS after proton-RT compared with women without hypertension (-21.3 ± 3.5 vs -24.0 ± 2.4%; P = .006). CONCLUSIONS: Proton-RT did not affect LV function and was not associated with an increase in biomarkers. These data support the potential cardiac benefits of proton-RT compared with conventional RT.

External Beam Radiation Therapy With or Without Brachytherapy Boost in Men With Very-High-Risk Prostate Cancer: A Large Multicenter International Consortium Analysis.

PURPOSE: Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear. METHODS AND MATERIALS: This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT + BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT + BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression. RESULTS: Among the entire cohort, 270 underwent EBRT and 101 EBRT + BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT + BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P = .42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P = .45) between EBRT + BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P = .42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P = .38). CONCLUSIONS: In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT + BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted.