Protecting Caribbean patients diagnosed with cancer from compounding disasters.

Caribbean small island developing states are becoming increasingly vulnerable to compounding disasters, prominently featuring climate-related hazards and pandemic diseases, which exacerbate existing barriers to cancer control in the region. We describe the complexities of cancer prevention and control efforts throughout the Caribbean small island developing states, including the unique challenges of people diagnosed with cancer in the region. We highlight potential solutions and strategies that concurrently address disaster adaptation and cancer control. Because Caribbean small island developing states are affected first and worst by the hazards of compounding disasters, the innovative solutions developed in the region are relevant for climate mitigation, disaster adaptation, and cancer control efforts globally. In the age of complex and cascading disaster scenarios, developing strategies to mitigate their effect on the cancer control continuum, and protecting the health and safety of people diagnosed with cancer from extreme events become increasingly urgent. The equitable development of such strategies relies on collaborative efforts among professionals whose diverse expertise from complementary fields infuses the local community perspective while focusing on implementing solutions.

Beyond Average: α-Particle Distribution and Dose Heterogeneity in Bone Metastatic Prostate Cancer.

α-particle emitters are emerging as a potent modality for disseminated cancer therapy because of their high linear energy transfer and localized absorbed dose profile. Despite great interest and pharmaceutical development, there is scant information on the distribution of these agents at the scale of the α-particle pathlength. We sought to determine the distribution of clinically approved [223Ra]RaCl2 in bone metastatic castration-resistant prostate cancer at this resolution, for the first time to our knowledge, to inform activity distribution and dose at the near-cell scale. Methods: Biopsy specimens and blood were collected from 7 patients 24 h after administration. 223Ra activity in each sample was recorded, and the microstructure of biopsy specimens was analyzed by micro-CT. Quantitative autoradiography and histopathology were segmented and registered with an automated procedure. Activity distributions by tissue compartment and dosimetry calculations based on the MIRD formalism were performed. Results: We revealed the activity distribution differences across and within patient samples at the macro- and microscopic scales. Microdistribution analysis confirmed localized high-activity regions in a background of low-activity tissue. We evaluated heterogeneous α-particle emission distribution concentrated at bone-tissue interfaces and calculated spatially nonuniform absorbed-dose profiles. Conclusion: Primary patient data of radiopharmaceutical therapy distribution at the small scale revealed that 223Ra uptake is nonuniform. Dose estimates present both opportunities and challenges to enhance patient outcomes and are a first step toward personalized treatment approaches and improved understanding of α-particle radiopharmaceutical therapies.

A pooled long-term follow-up after radiotherapy for prostate cancer with and without a rectal hydrogel spacer: impact of hydrogel on decline in sexual quality of life.

Purpose: The purpose of this study was to analyze the impact of prostate rectal spacers on sexual quality of life (QOL) following external beam radiation therapy (RT). Methods and materials: Patient- reported QOL was evaluated using the Expanded Prostate Cancer Index Composite (EPIC). Patients were pooled from two sources: a randomized controlled trial and a non-randomized cohort of patients from a single institution. Both cohorts used the same spacing product and QOL instrument. Analysis was limited to those with good baseline pre-treatment sexual QOL (EPIC >/= 60). Differences in QOL summary score and individual items were assessed compared with baseline and between treatment arms. Results: A total of 128 men had good baseline sexual function and were evaluated (64% with spacer and 36% without) with QOL data available for median 33 months (range: 2.5-69.4 months). Men without spacer were more likely to have declines in sexual function (p < 0.0001), bother (p = 0.0002), and sexual summary score (p < 0.0001). A minimally important difference of 10 points (1xMID) and 20 point (2xMID) was more likely without rectal spacer [10 points: odds ratio 3.53, (95% confidence interval 1.11-11.2), p = 0.032; 20 points: odds ratio 3.29, (95% confidence interval 1.16-9.33), p = 0.025]. Seven of 13 QOL items were statistically superior with hydrogel (six of nine functional and one of four bother), while no items were statistically superior for control. At baseline, more men treated with hydrogel had erections sufficient for intercourse; however, when analyzed only by the men with best baseline erectile potential and excluding those with worse function, the benefit of rectal spacing was maintained with a higher likelihood of preservation of erections sufficient for intercourse in those treated with hydrogel. Conclusion: In this pooled analysis of QOL after prostate RT, the utilization of a hydrogel spacer was associated with better sexual QOL, less men with measurable declines in sexual QOL, and higher rates of adequate erectile function.

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.

Effect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial.

PURPOSE: To determine whether addition of external beam radiation therapy (EBRT) to brachytherapy (BT) (COMBO) compared with BT alone would improve 5-year freedom from progression (FFP) in intermediate-risk prostate cancer. METHODS: Men with prostate cancer stage cT1c-T2bN0M0, Gleason Score (GS) 2-6 and prostate-specific antigen (PSA) 10-20 or GS 7, and PSA < 10 were eligible. The COMBO arm was EBRT (45 Gy in 25 fractions) to prostate and seminal vesicles followed by BT prostate boost (110 Gy if 125-Iodine, 100 Gy if 103-Pd). BT arm was delivered to prostate only (145 Gy if 125-Iodine, 125 Gy if 103-Pd). The primary end point was FFP: PSA failure (American Society for Therapeutic Radiology and Oncology [ASTRO] or Phoenix definitions), local failure, distant failure, or death. RESULTS: Five hundred eighty-eight men were randomly assigned; 579 were eligible: 287 and 292 in COMBO and BT arms, respectively. The median age was 67 years; 89.1% had PSA < 10 ng/mL, 89.1% had GS 7, and 66.7% had T1 disease. There were no differences in FFP. The 5-year FFP-ASTRO was 85.6% (95% CI, 81.4 to 89.7) with COMBO compared with 82.7% (95% CI, 78.3 to 87.1) with BT (odds ratio [OR], 0.80; 95% CI, 0.51 to 1.26; Greenwood T P = .18). The 5-year FFP-Phoenix was 88.0% (95% CI, 84.2 to 91.9) with COMBO compared with 85.5% (95% CI, 81.3 to 89.6) with BT (OR, 0.80; 95% CI, 0.49 to 1.30; Greenwood T P = .19). There were no differences in the rates of genitourinary (GU) or GI acute toxicities. The 5-year cumulative incidence for late GU/GI grade 2+ toxicity is 42.8% (95% CI, 37.0 to 48.6) for COMBO compared with 25.8% (95% CI, 20.9 to 31.0) for BT (P < .0001). The 5-year cumulative incidence for late GU/GI grade 3+ toxicity is 8.2% (95% CI, 5.4 to 11.8) compared with 3.8% (95% CI, 2.0 to 6.5; P = .006). CONCLUSION: Compared with BT, COMBO did not improve FFP for prostate cancer but caused greater toxicity. BT alone can be considered as a standard treatment for men with intermediate-risk prostate cancer.

Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma.

Head and neck squamous cell carcinoma (HNSCC) includes a subset of cancers driven by human papillomavirus (HPV). Here we use single-cell RNA-seq to profile both HPV-positive and HPV-negative oropharyngeal tumors, uncovering a high level of cellular diversity within and between tumors. First, we detect diverse chromosomal aberrations within individual tumors, suggesting genomic instability and enabling the identification of malignant cells even at pathologically negative margins. Second, we uncover diversity with respect to HNSCC subtypes and other cellular states such as the cell cycle, senescence and epithelial-mesenchymal transitions. Third, we find heterogeneity in viral gene expression within HPV-positive tumors. HPV expression is lost or repressed in a subset of cells, which are associated with a decrease in HPV-associated cell cycle phenotypes, decreased response to treatment, increased invasion and poor prognosis. These findings suggest that HPV expression diversity must be considered during diagnosis and treatment of HPV-positive tumors, with important prognostic ramifications.

The Association of Radiation Dose With Overall Survival for Patients Treated With Prostate Stereotactic Body Radiation Therapy.

Introduction Stereotactic body radiation therapy (SBRT) for prostate adenocarcinoma (PCa) has demonstrated excellent biochemical recurrence-free survival, with studies showing improved BRFS with higher-dose SBRT. However, current studies have been underpowered to evaluate the relationship of SBRT dose to overall survival (OS). In this retrospective study using the National Cancer Database (NCDB), we hypothesize that, given the low alpha/beta ratio of PCa, a relatively small increase in the dose-per-fraction would be associated with improved survival outcomes for intermediate-risk PCa (IR-PCa) comparing 36.25 Gy/5 fx [biologically equivalent dose (BEDα/ß = 1.5 = 211.46 Gy vs. 35 Gy (BED1.5 = 198.33 Gy)]. Materials and methods We queried records from the NCDB from 2005 to 2015 for men receiving prostate SBRT for IR-PCa (n=2673). 82% were treated using either 35 Gy/5 fx or 36.25 Gy/5 fx. We compared OS in men receiving 35 Gy versus 36.25 Gy. Inverse probability of treatment weighting (IPTW) was used to adjust for covariable imbalances. Unweighted- and weighted-multivariable analysis (MVA) using Cox regression was used to compare OS hazard ratios, accounting for age, race, Charlson-Deyo comorbidity score, treatment facility type, prostate-specific antigen (PSA), clinical T-stage, Gleason Score, and use of androgen deprivation therapy (ADT). Kaplan-Meier analysis was performed. Results Seven hundred and eighty men (35%) were treated with 35 Gy/5 fx and 1434 men (65%) were treated with 36.25 Gy/5 fx (n=2214). Compared to 35 Gy, treatment with 36.25 Gy was associated with significantly improved OS (hazard ratio [HR]: 0.61 [95% CI: 0.43-0.89], P=0.009) on MVA. On Kaplan-Meier analysis, 36.25 Gy was associated with improved survival (p=0.034), with a five-year OS of 92% and 88%, respectively. Conclusions In a multi-institutional retrospective database of 2,214 IR patients treated with prostate SBRT, a prescription dose of 36.25 Gy/5 fx was associated with improved OS vs. 35 Gy/5 fx. Results are hypothesis-generating but do lend support to the current National Comprehensive Cancer Network (NCCN) guidelines that the minimum recommended dose for prostate SBRT is 36.25 Gy/5 fx.

Remote Global Radiation Oncology Education and Training: A Pathway to Increase Access to High-Quality Radiation Therapy Services in Low- and Middle-Income Countries.

Purpose: There is a vital need to train radiation therapy professionals in low- and middle-income countries (LMICs) to develop sustainable cancer treatment capacity and infrastructure. LMICs have started to introduce intensity modulated radiation therapy (IMRT), which is the standard of care in high-income countries, because of improved outcomes and reduced toxicities. This work reports the efficacy of a complementary asynchronous plus synchronous virtual-training approach on improving radiation therapy professions' self-confidence levels and evaluating participants' attitudes toward asynchronous and synchronous didactic hands-on learning in 3 LMICs. Methods and Materials: Training was provided to 37 participants from Uganda, Guatemala, and Mongolia, which included 4 theoretical lectures, 4 hands-on sessions, and 8 self-guided online videos. The 36-day training focused on IMRT contouring, site-specific target/organ definition, planning/optimization, and quality assurance. Participants completed pre- and postsession confidence surveys on a 0 to 10 scale, which was converted to a 5-point Likert rating scale to evaluate the training outcomes. The pros and cons of the 3 different training formats were compared. Results: The participants included 15 (40.5%) radiation oncologists, 11 (29.7%) medical physicists, 6 (16.2%) radiation therapists, and 5 (13.5%) dosimetrists. Approximately 50% had more than 10 years of radiation therapy experience, 70.8% had no formal IMRT training, and only 25% had IMRT at their institutions. The average experience and confidence levels in using IMRT at baseline were 3.2 and 2.9, which increased to 5.2 and 4.9 (P < .001) after the theoretical training. After the hands-on training, the experience and confidence levels further improved to 5.4 and 5.5 (P < .001). After the self-guided training, the confidence levels increased further to 6.9 (P < .01). Among the 3 different training sessions, hands-on trainings (58.3%) were most helpful for the development of participants' IMRT skills, followed by theoretical sessions with 25%. Conclusions: After completing the training sessions, Uganda and Mongolia started IMRT treatments. Remote training provides an excellent and feasible e-learning platform to train radiation therapy professionals in LMICs. The training program improved the IMRT confidence levels and treatment delivery. The hands-on trainings were most preferred.

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.

Logistical, technical, and radiation safety aspects of establishing a radiopharmaceutical therapy program: A case in Lutetium-177 prostate-specific membrane antigen (PSMA) therapy.

Prostate-specific membrane antigen (PSMA) is a cell surface protein highly expressed in nearly all prostate cancers, with restricted expression in some normal tissues. The differential expression of PSMA from tumor to non-tumor tissue has resulted in the investigation of numerous targeting strategies for therapy of patients with metastatic prostate cancer. In March of 2022, the FDA granted approval for the use of lutetium-177 PSMA-617 (Lu-177-PSMA-617) for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. Therefore, the use of Lu-177-PSMA-617 is expected to increase and become more widespread. Herein, we describe logistical, technical, and radiation safety considerations for implementing a radiopharmaceutical therapy program, with particular focus on the development of operating procedures for therapeutic administrations. Major steps for a center in the U.S. to implement a new radiopharmaceutical therapy (RPT) program are listed below, and then demonstrated in greater detail via examples for Lu-177-PSMA-617 therapy.

A clinical and time savings evaluation of a deep learning automatic contouring algorithm.

Automatic contouring algorithms may streamline clinical workflows by reducing normal organ-at-risk (OAR) contouring time. Here we report the first comprehensive quantitative and qualitative evaluation, along with time savings assessment for a prototype deep learning segmentation algorithm from Siemens Healthineers. The accuracy of contours generated by the prototype were evaluated quantitatively using the Sorensen-Dice coefficient (Dice), Jaccard index (JC), and Hausdorff distance (Haus). Normal pelvic and head and neck OAR contours were evaluated retrospectively comparing the automatic and manual clinical contours in 100 patient cases. Contouring performance outliers were investigated. To quantify the time savings, a certified medical dosimetrist manually contoured de novo and, separately, edited the generated OARs for 10 head and neck and 10 pelvic patients. The automatic, edited, and manually generated contours were visually evaluated and scored by a practicing radiation oncologist on a scale of 1-4, where a higher score indicated better performance. The quantitative comparison revealed high (> 0.8) Dice and JC performance for relatively large organs such as the lungs, brain, femurs, and kidneys. Smaller elongated structures that had relatively low Dice and JC values tended to have low Hausdorff distances. Poor performing outlier cases revealed common anatomical inconsistencies including overestimation of the bladder and incorrect superior-inferior truncation of the spinal cord and femur contours. In all cases, editing contours was faster than manual contouring with an average time saving of 43.4% or 11.8 minutes per patient. The physician scored 240 structures with > 95% of structures receiving a score of 3 or 4. Of the structures reviewed, only 11 structures needed major revision or to be redone entirely. Our results indicate the evaluated auto-contouring solution has the potential to reduce clinical contouring time. The algorithm's performance is promising, but human review and some editing is required prior to clinical use.

Learning-based Cancer Treatment Outcome Prognosis using Multimodal Biomarkers.

Predicting early in treatment whether a tumor is likely to be responsive is a difficult yet important task to support clinical decision-making. Studies have shown that multimodal biomarkers could provide complementary information and lead to more accurate treatment outcome prognosis than unimodal biomarkers. However, the prognosis accuracy could be affected by multimodal data heterogeneity and incompleteness. The small-sized and imbalance datasets also bring additional challenges for training a designed prognosis model. In this study, a modular framework employing multimodal biomarkers for cancer treatment outcome prediction was proposed. It includes four modules of synthetic data generation, deep feature extraction, multimodal feature fusion, and classification to address the challenges described above. The feasibility and advantages of the designed framework were demonstrated through an example study, in which the goal was to stratify oropharyngeal squamous cell carcinoma (OPSCC) patients with low- and high-risks of treatment failures by use of positron emission tomography (PET) image data and microRNA (miRNA) biomarkers. The superior prognosis performance and the comparison with other methods demonstrated the efficiency of the proposed framework and its ability of enabling seamless integration, validation and comparison of various algorithms in each module of the framework. The limitation and future work was discussed as well.

Assessing the impact of brachytherapy boost and androgen deprivation therapy on survival outcomes for patients with unfavorable intermediate-risk prostate cancer patients treated with external beam radiotherapy.

BACKGROUND: Current recommendations regarding radiotherapy treatment for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost (BT) ± androgen deprivation therapy (ADT). The ideal radiotherapy treatment approach for UIR-PCa has not been well-defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to EBRT±ADT in men with UIR-PCa. MATERIALS AND METHODS: The National Cancer Database (NCDB) was used to retrospectively identify 32,246 men diagnosed between 2004 and 2015 with UIR-PCa who received EBRT (n = 13,265), EBRT+ADT (n = 13,123), EBRT+BT (n = 3440), or EBRT+BT+ADT (n = 2418). OS was the primary outcome. Inverse probability of treatment weighting was used to adjust for covariable imbalances and weight-adjusted multivariable analysis using Cox regression modeling was used to compare OS hazard ratios. RESULTS: Median follow-up was 60 months (range: 3-168 months). EBRT+ADT correlated with improved OS relative to EBRT alone on multivariable analysis (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87-0.98], p = 0.005). Compared to EBRT+ADT, EBRT+BT (HR: 0.77 [0.69-0.85], p = 3 × 10-7) and EBRT+BT+ADT (HR: 0.75 [0.67-0.83], p = 6 × 10-8) were associated with improved OS. Eight-years OS for the EBRT+ADT versus EBRT+BT+ADT was 70% and 78% (p < 0.0001), which is similar to historical clinical trials (ASCENDE-RT 9-year OS: 74% vs. 78%, p = 0.29). Relative to EBRT+BT, EBRT+BT+ADT was not associated with improved OS (HR: 0.99 [0.87-1.11], p = 0.82). CONCLUSIONS: In a large retrospective cohort, the addition of brachytherapy to EBRT correlated with improved survival in men with UIR-PCa. Men receiving EBRT+ADT+BT had improved OS relative to EBRT+ADT. The addition of ADT to EBRT, but not to EBRT+BT, correlated with improved OS.

Treatment Patterns and Overall Survival Outcomes Among Patients Aged 80 yr or Older with High-risk Prostate Cancer.

BACKGROUND: Elderly patients diagnosed with high-risk prostate cancer (PCa) present a therapeutic dilemma of balancing treatment of a potentially lethal malignancy with overtreatment of a cancer that may not threaten life expectancy. OBJECTIVE: To investigate treatment patterns and overall survival outcomes in this group of patients. DESIGN SETTING AND PARTICIPANTS: A retrospective cohort study was conducted. We queried the National Cancer Database for high-risk PCa in patients aged 80 yr or older diagnosed during 2004-2016. INTERVENTION: Eligible patients underwent no treatment following biopsy (ie, observation), androgen deprivation therapy (ADT) alone, radiation therapy (RT) alone, RT + ADT, or surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier, log rank, and multivariate Cox proportional hazard regression was performed to compare overall survival (OS). RESULTS AND LIMITATIONS: A total of 19 920 men were eligible for analysis, and the most common treatment approach was RT + ADT (7401 patients; 37.2%). Observation and ADT alone declined over time (59.3% in 2004 vs 47.5% in 2016). There was no observed difference in OS between observation and ADT alone (adjusted hazard ratio [HR] 1.04, 95% confidence interval [CI], 0.99-1.09; p = 0.105). Definitive local treatment was associated with improved OS compared with ADT alone (RT alone, HR 0.54, 95% CI, 0.50-0.59, p < 0.0001; ADT + RT, HR 0.48, 95% CI, 0.46-0.50, p < 0.0001; surgery, HR 0.50, 95% CI, 0.42-0.59, p < 0.0001). CONCLUSIONS: This analysis demonstrates that the use of definitive local therapy, including surgery or RT ± ADT, is increasing and is associated with a 50% reduction in overall mortality compared with observation or ADT alone. While prospective validation is warranted, elderly men with high-risk disease eligible for definitive management should be counseled on the risks, including a possible compromise in OS, with deferring definitive management. PATIENT SUMMARY: Elderly men are more often diagnosed with higher-risk prostate cancer but are less likely to receive curative treatment options than younger men. Our analysis demonstrates that for men ≥80 yr of age with high-risk prostate cancer, definitive local therapy, including surgery or radiation therapy and/or androgen deprivation therapy, is associated with a 50% reduction in overall mortality compared with observation or androgen deprivation therapy alone. We therefore recommend that life expectancy (ie, physiologic age) be taken into account, over chronologic age, and that elderly men with good life expectancy (eg, >5 yr; minimal comorbidity) should be offered definitive, life-prolonging therapy.

Association Between Local Radiation Therapy to the Primary Bladder Tumor and Overall Survival for Patients with Metastatic Urothelial Cancer Receiving Systemic Chemotherapy.

There are limited data on the role of local therapy for metastatic urothelial carcinoma of the bladder (mUC). In this retrospective cohort analysis, we queried the National Cancer Data Base for patients with newly diagnosed mUC (cT1-4 N0-3 M1). Overall survival (OS) was compared between treatment with chemotherapy (CT) alone (n = 4122) and CT plus bladder-directed radiation therapy (CT + RT; n = 337). Multivariable Cox proportional-hazards analyses and matching and landmark analyses were performed. CT + RT was independently associated with better OS (hazard ratio 0.70, 95% confidence interval 0.62-0.79; p < 0.0001) and this result persisted in matched and landmark analyses. These findings are hypothesis-generating and limited by inherent confounding factors; however, a prospective trial evaluating the impact of bladder RT in mUC is warranted. PATIENT SUMMARY: For patients with bladder cancer that has already spread to other parts of the body, it is unclear if radiation therapy directed at the primary bladder tumor would provide any improvement in survival. In this study, we found that aggressive radiation therapy directed at the bladder combined with chemotherapy may provide a survival benefit in some patients with metastatic bladder cancer compared to chemotherapy alone.

Assessing the role of external beam radiation therapy in combination with brachytherapy versus brachytherapy alone for unfavorable intermediate-risk prostate cancer.

BACKGROUND: Definitive treatment options for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost ± androgen deprivation therapy (ADT). The role of brachytherapy ± ADT in the absence of EBRT is not well defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to BT±ADT for UIR-PCa. METHODS AND MATERIALS: Men with UIR-PCa diagnosed between 2004 and 2015 were identified in the National Cancer Database (NCDB). Inverse propensity of treatment weighting was used to balance covariables that influenced treatment allocation and outcomes, and propensity-weighted multivariable analysis (MVA) using Cox regression modeling was used to compare OS hazard ratios. RESULTS: A total of 11,721 men were stratified into four treatment groups: (1) BT without ADT (n = 4,535), (2) BT+ADT (n = 1,303), (3) EBRT+BT (n = 3,446), or (4) EBRT+BT+ADT (n = 2,437). Relative to patients treated with BT alone, BT+ADT (Hazard Ratio (HR): 0.86 [95% Confidence Interval (CI): 0.76-0.99], p = 0.03), EBRT+BT (HR: 0.79 [0.70-0.88], p = 0.00002), and EBRT+BT+ADT (HR: 0.76 [0.67-0.85], p = 0.000003) were associated with improved OS on MVA. Relative to BT alone, EBRT+BT correlated with improved OS on weight-adjusted MVA (HR: 0.82 [0.75-0.89], p = 0.000005). 10-year OS for BT vs. EBRT+BT was 62.4% [60.1-64.7] vs. 69.3% [67.5-71.2], respectively (p < 0.0001). CONCLUSIONS: EBRT+BT correlated with improved OS relative to BT alone in men with UIR-PCa, reaffirming current NCCN recommendations recommending EBRT+BT over BT alone. While prior studies reported no benefit to adding EBRT to BT with optimal implant dosimetry, this study suggests men benefit from EBRT in a population of variable implant quality.

Outcomes of Patients With Unfavorable Intermediate-Risk Prostate Cancer Treated With External-Beam Radiotherapy Versus Brachytherapy Alone.

BACKGROUND: The NCCN Guidelines for Prostate Cancer currently recommend several definitive radiotherapy (RT) options for men with unfavorable intermediate-risk (UIR) prostate cancer: external-beam RT (EBRT) plus androgen deprivation therapy (ADT) or EBRT plus brachytherapy boost with or without ADT. However, brachytherapy alone with or without ADT is not well defined and is currently not recommended for UIR prostate cancer. We hypothesized that men treated with brachytherapy with or without ADT have comparable survival rates to men treated with EBRT with or without ADT. METHODS: A total of 31,783 men diagnosed between 2004 and 2015 with UIR prostate cancer were retrospectively reviewed from the National Cancer Database. Men were stratified into 4 groups: EBRT (n=12,985), EBRT plus ADT (n=12,960), brachytherapy (n=4,535), or brachytherapy plus ADT (n=1,303). Inverse probability of treatment weighting (IPTW) was used to adjust for covariable imbalances, and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios (HRs). RESULTS: Relative to EBRT alone, the following treatments were associated with improved OS: EBRT plus ADT (HR, 0.92; 95% CI, 0.87-0.97; P=.002), brachytherapy alone (HR, 0.90; 95% CI, 0.83-0.98; P=.01), and brachytherapy plus ADT (HR, 0.78; 95% CI, 0.69-0.88; P=.00006). Brachytherapy correlated with improved OS relative to EBRT in men who were not treated with ADT (HR, 0.92; 95% CI, 0.84-0.99; P=.03) and in those receiving ADT (HR, 0.84; 95% CI, 0.75-0.95; P=.004). At 10-year follow-up, 56% and 63% of men receiving EBRT and brachytherapy, respectively, were alive (P<.0001). IPTW was used to determine the average treatment effect of definitive brachytherapy. Relative to EBRT, definitive brachytherapy correlated with improved OS (HR, 0.90; 95% CI, 0.84-0.97; P=.009) on weight-adjusted MVA. CONCLUSIONS: Definitive brachytherapy was associated with improved OS compared with EBRT. The addition of ADT to both EBRT and definitive brachytherapy was associated with improved OS. These results suggest that definitive brachytherapy should be considered as an option for men with UIR prostate cancer.

Assessing Inter-Fraction Changes in The Size and Position of The Penile Bulb During Daily MR-Guided Radiation Therapy to The Prostate Bed: Do We Need to Adjust How We Plan Radiation in The Post-Radical Prostatectomy Setting to Reduce Risk of Erectile Dysfunction?

BACKGROUND: We evaluated inter-fraction penile bulb (PB) changes in prostate cancer (PCa) patients undergoing MR-guided RT in the post-radical prostatectomy (RP) setting. MATERIALS AND METHODS: 10 patients with PCa status-post RP received MR-guided RT from 2017-2019. Patients received daily setup volumetric MRI scans prior to RT delivery for alignment and target localization. Setup MRI datasets from Fx 1, Fx 19, and Fx 37 were fused for each patient based on soft tissue anatomy. The PB was contoured on each MRI. Data on volume (cc), superior/inferior positional change (cm), and mean dose (Gy) was collected. Differences were assessed by Student's t-test (sig. p<0.05). RESULTS: The mean PB volume change from Fx 1→ 19 was +0.34 ± 0.34 cc (p=0.11) and from Fx 1→ 37 was +0.22 ± 0.28 cc (p=0.31). The mean positional change from Fx 1→ 19 was +0.08±0.26 cm (p=0.37) and from Fx 1→ 37 was +0.05 ±0.25 cm (p=0.57). The mean change in mean PB dose from Fx 1→ 19 was +0.19±4.86 Gy (p=0.98) and from Fx 1→ 37 was -1.51≖7.46 Gy (p=0.88). CONCLUSION: We present the first study evaluating inter-fraction changes to the PB during MR-guided RT. We found no clinically meaningful difference in the volume, positional change, or mean dose during RT in the post-prostatectomy setting, suggesting that PB organ motion may not need to be accounted for in radiation treatment planning.