Technical note: Evaluation of a silicone-based custom bolus for radiation therapy of a superficial pelvic tumor.

PURPOSE: Use of standard-of-care radiation therapy boluses may result in air-gaps between the target surface and bolus, as they may not adequately conform to each patient's unique topography. Such air-gaps can be particularly problematic in cases of superficial pelvic tumor radiation, as the density variation may result in the radiation delivered to the target site being inconsistent with the prescribed dose. To increase bolus fit and thereby dose predictability and homogeneity, we designed and produced a custom silicone bolus for evaluation against the clinical standard. METHODS: A custom bolus was created for the pelvic regions of both an anthropomorphic phantom and a pelvic patient with squamous cell carcinoma of the penile shaft. Molds were designed using computed tomography (CT) scans, then 3D-printed and cast with silicone rubber to yield the boluses. Air-gap measurements were performed on custom and standard-of-care Superflab gel sheet boluses by analyzing total volume between the bolus and target surface, as measured from CT scans. Therapeutic doses of radiation were delivered to both boluses. Radiation dose was measured and compared to the expected dose using nine optically stimulated luminescent dosimeters (OSLDs) placed on the phantom. RESULTS: Mean air-gap volume between the bolus and phantom was decreased from 314 ± 141 cm3 with the standard bolus to 4.56 ± 1.59 cm3 using the custom device. In the case of the on-treatment patient, air-gap volume was reduced from 169 cm3 with the standard bolus to 46.1 cm3 with the custom. Dosimetry testing revealed that the mean absolute difference between expected and received doses was 5.69%±4.56% (15.1% maximum) for the standard bolus and 1.91%±1.31% (3.51% maximum) for the custom device. Areas of greater dose difference corresponded to areas of larger air-gap. CONCLUSIONS: The custom bolus reduced air-gap and increased predictability of radiation dose delivered compared to the standard bolus. The custom bolus could increase the certainty of prescribed dose-delivery of radiation therapy for superficial tumors.

Optimal pathological response after neoadjuvant chemotherapy for muscle-invasive bladder cancer: results from a global, multicentre collaboration.

OBJECTIVES: To evaluate outcomes of patients achieving a post-treatment pathological stage of

Orgasmic Function after Radical Prostatectomy.

PURPOSE: We examined postprostatectomy orgasmic function and assessed for potential predictors. MATERIALS AND METHODS: Between 2005 and 2013, 499 men underwent radical prostatectomy and completed quality of life questionnaires prospectively before surgery and at regular postoperative intervals. We used mixed effects logistic regression models to evaluate average differences in followup measures and interactions with time. RESULTS: At a median followup of 36 months orgasmic function was worse, stable or improved in 300 (60.1%), 152 (30.5%) and 47 men (9.4%), respectively. Orgasmic function recovery plateaued at 15 to 21 months. High postoperative orgasmic function was positively associated with younger age (50 years or younger vs 51 to 60 OR 3.40, 95% CI 1.56-7.41), nerve sparing (bilateral OR 7.11, 95% CI 2.55-19.77, modified 4.34, 95% CI 1.38-13.58 and unilateral OR 3.93, 95% CI 1.17-13.16), erectile function (OR 4.67, 95% CI 3.32-6.57) and sexual desire (OR 5.51, 95% CI 3.95-7.68) but negatively associated with lower urinary tract symptoms (OR 0.58, 95% CI 0.41-0.82) and urinary incontinence (OR 0.38, 95% CI 0.25-0.56). Although robotic status did not influence orgasmic function in the overall cohort, it was associated with faster recovery on subgroup analysis of 356 patients with long followup. On another subgroup analysis of 235 men with long followup and poor erectile function the association of high preoperative orgasmic function and bilateral nerve sparing with high orgasmic function persisted, suggesting an independent effect on orgasmic function apart from that on erectile function. CONCLUSIONS: Orgasmic function recovery after radical prostatectomy is a lengthy process. Predictors of orgasmic function include preoperative orgasmic function, age, nerve sparing status, erectile function, sexual desire and urinary control and function.

Urinary Diversion for Severe Urinary Adverse Events of Prostate Radiation: Results from a Multi-Institutional Study.

PURPOSE: We evaluated the short and long-term surgical outcomes of urinary diversion done for urinary adverse events arising from prostate radiation therapy. We hypothesized that patient characteristics are associated with complications after urinary diversion. MATERIALS AND METHODS: We performed a retrospective cohort study of 100 men who underwent urinary diversion (urinary conduit or continent catheterizable pouch) due to urinary adverse events after prostate radiotherapy from 2007 to 2016 from 9 academic centers in the United States. Outcome measurements included predictors of short and long-term complications, and readmission after urinary diversion of patients who had prostate cancer treated with radiotherapy. The data were summarized using descriptive statistics and univariate associations with complications were identified with logistic regression controlling for center. RESULTS: Mean patient age was 71 years and median time from radiotherapy to urinary diversion was 8 years. Overall 81 (81%) patients had combined modality therapy (radical prostatectomy plus radiotherapy or various combinations of radiotherapy). Grade 3a or greater Clavien-Dindo complications occurred in 31 (35%) men, including 4 deaths (4.5%). Normal weight men had more short-term complications compared to overweight (OR 4.9, 95% CI 1.3-23.1, p=0.02) and obese men (OR 6.3, 95% CI 1.6-31.1, p=0.009). Hospital readmission within 6 weeks of surgery occurred for 35 (38%) men. Surgery was needed to treat long-term complications after urinary diversion in 19 (22%) patients with a median followup of 16.3 months. CONCLUSIONS: Urinary diversion after prostate radiotherapy has a considerable short and long-term surgical complication rate. Urinary diversion most often cannot be avoided in these patients but appreciation of the risks allows for informed shared decision making between surgeons and patients.

Management of Radiation Therapy Oncology Group grade 4 urinary adverse events after radiotherapy for prostate cancer.

OBJECTIVE: To describe the management of Radiation Therapy Oncology Group (RTOG) grade 4 urinary adverse events (UAEs) after radiotherapy (RT) for prostate cancer (PCa). METHODS: We conducted a single-centre retrospective review, over a 6-year period (2010-2015), to identify men with RTOG grade 4 UAEs after RT for PCa. RT was classified as combined therapy (radical prostatectomy [RP] followed by external beam radiotherapy [EBRT], EBRT + low-dose-rate [LDR] brachytherapy, EBRT + high-dose-rate [HDR] brachytherapy or other combinations of RT) or monotherapy RT. UAEs were classified as outlet (urethral stricture, bladder neck contracture, prostate necrosis, or recto-urethral fistula) or bladder (contraction, necrosis, fistula, ureteric stricture or haemorrhage) UAEs. RESULTS: We identified 73 men with a mean age of 73 years. Of these, 44 (60%) received combined therapy, consisting of RP + EBRT (n = 19), HDR brachytherapy + EBRT (n = 19), LDR brachytherapy + EBRT (n = 5), and other combined RT (n = 1). Twenty-nine (40%) patients had monotherapy consisting of EBRT (n = 4), HDR brachytherapy (n = 11), LDR brachytherapy (n = 12), or proton beam therapy (n = 2). UAEs were isolated to the bladder in six men (8%), the outlet in 52 men (71%), and to both in 15 men (21%). UAE management included: conservative in 21 (29%), indwelling catheters in 12 (16%), reconstructive in 19 (26%), and urinary diversion (UD) in 23 men (32%). Reconstruction included: ureteric (n = 4), recto-urethral fistula repair (n = 2), and posterior urethroplasty (n =13), of which 14/16 surgeries (88%) with follow-up >90 days were successful. CONCLUSIONS: Although the incidence of RTOG grade 4 UAEs after PCa radiation treatment is not well defined, their associated morbidity is significant, and approximately one third of patients with these high-grade complications require UD. Conversely, only about a quarter of patients can be managed with conservative strategies or local surgeries. Reconstruction is successful in selected patients.

Climacturia after definitive treatment of prostate cancer.

PURPOSE: Prostate cancer treatment results in several sexually related side effects beyond the well studied erectile dysfunction. Climacturia (leakage of urine during orgasm) has been reported after prostatectomy but studies have been limited by multiple factors. In this study we examine the prevalence, causes and impact on orgasm function of climacturia after definitive treatment of prostate cancer with surgery or radiation. MATERIALS AND METHODS: A total of 906 anonymous surveys were sent to patients with prostate cancer treated with surgery and/or radiation. Respondents were asked about the presence of urinary leakage, climacturia and various elements related to sexual and orgasmic function. We estimated the prevalence of climacturia, evaluated the differences between those with and without climacturia, and assessed the impact of climacturia on orgasmic function. RESULTS: Overall 412 surveys were returned and available for analysis, and of these respondents 75.2% were sexually active or experiencing orgasms. Climacturia was reported by 22.6% of these respondents, and by 28.3%, 5.2% and 28.6% of those treated with surgery, radiation, or both, respectively (p <0.001). The use of aides to obtain an erection (OR 2.24, 95% CI 1.08-4.93, p = 0.035) and the presence of urinary incontinence (OR 3.09, 95% CI 1.66-5.88, p <0.001) were also associated with climacturia in a multivariate logistic regression model. Climacturia had no significant impact on orgasmic function and satisfaction. CONCLUSIONS: Climacturia is experienced by a substantial proportion of men after undergoing definitive treatment of prostate cancer. We found a complex relationship between stress urinary incontinence and climacturia, and noted that the presence of climacturia does not necessarily negatively impact sexual satisfaction.

Patterns of care with brachytherapy for cervical cancer.

OBJECTIVE: Concurrent chemotherapy with external beam radiotherapy (EBRT) and brachytherapy (BT) is critical to the curative treatment of locally advanced cervical cancer. Patterns of care and the use of EBRT and BT for locally advanced cervical cancer in the United States were analyzed with an emphasis on regional variation across the United States. METHODS/MATERIALS: A retrospective analysis was performed using the Surveillance, Epidemiology, and End Results Program database from 1988 to 2010 to identify women with locally advanced cervical carcinoma treated with definitive radiotherapy. RESULTS: Twelve thousand three hundred women were identified who met the inclusion criteria. From 1988 to 2010, percent use of EBRT and BT decreased from 68% to 45%; specifically, between 1988 and 2000, there was a decrease of 12% (P = 0.0003), and between 2000 and 2010, there was another decrease of 11% (P < 0.0001). When examined individually, 15 of the 16 registries displayed a decline in use of EBRT and BT with a significant decrease in 11 of the registries. No registry displayed an increased use of EBRT and BT, but the use of EBRT alone increased from 1988 to 2000 by 8% (P = 0.0055) and from 2000 to 2010 by 6% (P = 0.0095). CONCLUSIONS: Combination of EBRT and BT for locally advanced cervical cancer continues to decline, despite guidelines indicating the appropriateness of BT. This decline was seen for most regions across the United States, with a concomitant rise in the use of EBRT. EBRT alone is an inferior therapy and must be used in conjunction with BT to realize maximal patient benefit.

Validation of the Combined Clinical Cell-Cycle Risk Score to Prognosticate Early Prostate Cancer Metastasis From Biopsy Specimens and Comparison With Other Routinely Used Risk Classifiers.

PURPOSE: We aim to independently validate the prognostic utility of the combined cell-cycle risk (CCR) multimodality threshold to estimate risk of early metastasis after definitive treatment of prostate cancer and compare this prognostic ability with other validated biomarkers. METHODS: Patients diagnosed with localized prostate cancer were enrolled into a single-institutional registry for the prospective observational cohort study. The primary end point was risk of metastasis within 3 years of diagnostic biopsy. Secondary end points included time to definitive treatment, time to subsequent therapy, and metastasis after completion of initial definitive treatment. Multivariable cause-specific Cox proportional hazards regression models were produced accounting for competing risk of death and stratified on the basis of the CCR active surveillance and multimodality (MM) thresholds. Time-dependent areas under the receiver operating characteristic curve were calculated. RESULTS: The cohort consisted of 554 men with prostate cancer and available CCR score from biopsy. The CCR score was prognostic for metastasis (hazard ratio [HR], 2.32 [95% CI, 1.17 to 4.59]; P = .02), with scores above the MM threshold having a higher risk than those below the threshold (HR, 5.44 [95% CI, 2.72 to 10.91]; P < .001). The AUC for 3-year risk of metastasis on the basis of CCR was 0.736. When men with CCR above the MM threshold received MM therapy, their 3-year risk of metastasis was significantly lower than those receiving single-modality therapy (3% v 14%). Similarly, a CCR score above the active surveillance threshold portended a faster time to first definitive treatment. CONCLUSION: CCR outperforms other commonly used biomarkers for prediction of early metastasis. We illustrate the clinical utility of the CCR active surveillance and multimodality thresholds. Molecular genomic tests can inform patient selection and personalization of treatment for localized prostate cancer.

Using the Cell-Cycle Risk Score to Predict the Benefit of Androgen-Deprivation Therapy Added to Radiation Therapy in Patients With Newly Diagnosed Prostate Cancer.

PURPOSE: Guidelines recommend adding androgen-deprivation therapy (ADT) to radiation therapy (RT) in certain patients with localized prostate cancer. Individualized genomic testing may improve the prognostic accuracy of risk assessments. Herein, we describe a mathematical model of the benefit of adding ADT to RT as a function of the personalized clinical cell-cycle risk (CCR) score to inform 10-year metastasis risk. METHODS: A model of absolute risk reduction (ARR) was built using a retrospective cohort of men tested with Prolaris who received RT alone (N = 467). The relative benefit of ADT added to RT to reduce distant metastasis was estimated at 41% on the basis of a meta-analysis of randomized trials. The ARR and number needed to treat (NNT) were computationally derived in patients clinically tested with Prolaris between January 1, 2020, and October 31, 2022 (N = 56,485). Risks were predicted using a cause-specific Cox proportional hazards model with CCR score predicting time to metastasis. A CCR score of 2.112 represents the validated multimodal treatment (MMT) threshold. RESULTS: The ARR from ADT increased from almost zero at low CCR scores to 17.1% at CCR = 3.690 with the corresponding NNT = 6, indicating that adding ADT to RT would prevent metastasis within 10 years for one of every six treated individuals. In the clinical cohort, the average ARR was 0.86% in individuals under the MMT threshold (NNT = 116). The average ARR was 8.19% in individuals above the MMT threshold (NNT = 12). Broad ranges of ADT benefit were observed within National Comprehensive Cancer Network risk categories. CONCLUSION: The precise and personalized risk estimate of metastasis provided by the CCR score can help inform patients and physicians when considering treatment intensification.

Secondary malignancies in non-Hodgkin lymphoma survivors: 40 years of follow-up assessed by treatment modality.

BACKGROUND: Survivors of non-Hodgkin lymphoma (NHL) have increased secondary malignancy (SM) risk. We quantified this risk by patient and treatment factors. METHODS: Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio) were assessed in 142,637 NHL patients diagnosed from 1975 to 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Comparisons were made between subgroups in terms of their SIRs relative to respective endemic populations. RESULTS: In total, 15,979 patients developed SM, more than the endemic rate (O/E 1.29; p < 0.05). Compared with white patients, relative to respective endemic populations, ethnic minorities had a higher risk of SM (white O/E 1.27, 95% CI 1.25-1.29; black O/E 1.40, 95% CI 1.31-1.48; other O/E 1.59, 95% CI 1.49-1.70). Relative to respective endemic populations, patients who received radiotherapy had similar SM rates to those who did not (O/E 1.29 each), but irradiated patients had increased breast cancer (p < 0.05). Patients who received chemotherapy had higher SM rates than those who did not (O/E 1.33 vs. 1.24, p < 0.05) including more leukemia, Kaposi sarcoma, kidney, pancreas, rectal, head and neck, and colon cancers (p < 0.05). CONCLUSIONS: This is the largest study to examine SM risk in NHL patients with the longest follow-up. Treatment with radiotherapy did not increase overall SM risk, while chemotherapy was associated with a higher overall risk. However, certain subsites were associated with a higher risk of SM, and they varied by treatment, age group, race and time since treatment. These findings are helpful for informing screening and long-term follow-up in NHL survivors.

Multi-Institutional Analysis of Cancer Patient Exposure, Perceptions, and Trust in Information Sources Regarding Complementary and Alternative Medicine.

PURPOSE: Complementary and alternative medicine (CAM) use during cancer treatment is controversial. We aim to evaluate contemporary CAM use, patient perceptions and attitudes, and trust in various sources of information regarding CAM. METHODS: A multi-institutional questionnaire was distributed to patients receiving cancer treatment. Collected information included respondents' clinical and demographic characteristics, rates of CAM exposure/use, information sources regarding CAM, and trust in each information source. Comparisons between CAM users and nonusers were performed with chi-squared tests and one-way analysis of variance. Multivariable logistic regression models for trust in physician and nonphysician sources of information regarding CAM were evaluated. RESULTS: Among 749 respondents, the most common goals of CAM use were management of symptoms (42.2%) and treatment of cancer (30.4%). Most CAM users learned of CAM from nonphysician sources. Of CAM users, 27% reported not discussing CAM with their treating oncologists. Overall trust in physicians was high in both CAM users and nonusers. The only predictor of trust in physician sources of information was income >$100,000 in US dollars per year. Likelihood of trust in nonphysician sources of information was higher in females and lower in those with graduate degrees. CONCLUSION: A large proportion of patients with cancer are using CAM, some with the goal of treating their cancer. Although patients are primarily exposed to CAM through nonphysician sources of information, trust in physicians remains high. More research is needed to improve patient-clinician communication regarding CAM use.

Artificial Intelligence Predictive Model for Hormone Therapy Use in Prostate Cancer.

Background: Androgen deprivation therapy (ADT) with radiotherapy can benefit patients with localized prostate cancer. However, ADT can negatively impact quality of life and there remain no validated predictive models to guide its use. Methods: Digital pathology image and clinical data from pre-treatment prostate tissue from 5,727 patients enrolled on five phase III randomized trials treated with radiotherapy +/- ADT were used to develop and validate an artificial intelligence (AI)-derived predictive model to assess ADT benefit with the primary endpoint of distant metastasis. After the model was locked, validation was performed on NRG/RTOG 9408 (n = 1,594) that randomized men to radiotherapy +/- 4 months of ADT. Fine-Gray regression and restricted mean survival times were used to assess the interaction between treatment and predictive model and within predictive model positive and negative subgroup treatment effects. Results: In the NRG/RTOG 9408 validation cohort (14.9 years of median follow-up), ADT significantly improved time to distant metastasis (subdistribution hazard ratio [sHR] = 0.64, 95%CI [0.45-0.90], p = 0.01). The predictive model-treatment interaction was significant (p-interaction = 0.01). In predictive model positive patients (n = 543, 34%), ADT significantly reduced the risk of distant metastasis compared to radiotherapy alone (sHR = 0.34, 95%CI [0.19-0.63], p < 0.001). There were no significant differences between treatment arms in the predictive model negative subgroup (n = 1,051, 66%; sHR = 0.92, 95%CI [0.59-1.43], p = 0.71). Conclusions: Our data, derived and validated from completed randomized phase III trials, show that an AI-based predictive model was able to identify prostate cancer patients, with predominately intermediate-risk disease, who are likely to benefit from short-term ADT.

Artificial Intelligence Predictive Model for Hormone Therapy Use in Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT) with radiotherapy can benefit patients with localized prostate cancer. However, ADT can negatively impact quality of life, and there remain no validated predictive models to guide its use. METHODS: We used digital pathology images from pretreatment prostate tissue and clinical data from 5727 patients enrolled in five phase 3 randomized trials, in which treatment was radiotherapy with or without ADT, as our data source to develop and validate an artificial intelligence (AI)­derived predictive patient-specific model that would determine which patients would develop the primary end point of distant metastasis. The model used baseline data to provide a binary output that a given patient will likely benefit from ADT or not. After the model was locked, validation was performed using data from NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 (n=1594), a trial that randomly assigned men to radiotherapy plus or minus 4 months of ADT. Fine­Gray regression and restricted mean survival times were used to assess the interaction between treatment and the predictive model and within predictive model­positive, i.e., benefited from ADT, and ­negative subgroup treatment effects. RESULTS: Overall, in the NRG/RTOG 9408 validation cohort (14.9 years of median follow-up), ADT significantly improved time to distant metastasis. Of these enrolled patients, 543 (34%) were model positive, and ADT significantly reduced the risk of distant metastasis compared with radiotherapy alone. Of 1051 patients who were model negative, ADT did not provide benefit. CONCLUSIONS: Our AI-based predictive model was able to identify patients with a predominantly intermediate risk for prostate cancer likely to benefit from short-term ADT. (Supported by a grant [U10CA180822] from NRG Oncology Statistical and Data Management Center, a grant [UG1CA189867] from NCI Community Oncology Research Program, a grant [U10CA180868] from NRG Oncology Operations, and a grant [U24CA196067] from NRG Specimen Bank from the National Cancer Institute and by Artera, Inc. ClinicalTrials.gov numbers NCT00767286, NCT00002597, NCT00769548, NCT00005044, and NCT00033631.)

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.

An evaluation of interference of inflatable penile prostheses with electromagnetic localization and tracking system.

PURPOSE: The Calypso system is stated by the manufacturer to be contraindicated for cases where the patient has been implanted with a penile prosthesis. This is due to concern for potential metal interference-related reduction of spatial localization and tracking accuracy. Here we quantify the localization and tracking accuracy of the Calypso system in the presence of inflatable penile prosthesis devices from three most widely used models which account for, essentially, 100% of implants in North America. METHODS: Phantom studies were first performed to quantify the interference of Calypso localization and tracking accuracy from both varying metal (steel) masses, and from the penile prosthetic devices themselves. The interference of varying steel masses was studied as a function of two factors: (a) the mass and (b) the location of steel material. The Calypso daily quality assurance (QA) phantom with three implanted Beacon(®) transponders was used to measure any aliasing of position that might occur due to metal interference. After confirming the safety of use in phantom, we implanted Calypso Beacon(®) transponders in one patient with a previously implanted AMS Model 700 inflatable penile prosthetic device. For each of the 42 delivered treatment fractions, redundant stereotactic ultrasound (US) image guidance was performed to ensure good agreement between US and Calypso guidance. RESULTS: We observed that a steel mass of less than 18 g did not cause any detectable positional aliasing for the Calypso tracking function. The mass of metal material measured to exist in the three penile prosthetic devices studied here (MP35N alloy) was approximately 1 g for each. No positional aliasing was observed for the three prosthetic devices in phantom, and good agreement between redundant US and Calypso was also observed in patient. CONCLUSIONS: Both phantom and patient evaluations with the penile prosthetic devices showed no measurable interference with the Calypso system, thus indicating that accurate Calypso-based alignments can be performed in the presence of current industry standard inflatable penile prosthetic devices.

Nomograms for Metastasis-Free and Overall Survival for Pathologically Node Positive Prostate Cancer Patients Treated With or Without Radiation Therapy Plus Short-Term ADT.

PURPOSE/OBJECTIVES: We aimed to develop nomograms to predict the risk reduction for metastasis and death in pathologically node-positive (pN +) prostate cancer patients treated with or without radiation therapy (RT). MATERIALS/METHODS: From a prospectively gathered institutional database, we identified patients with pN + M0 prostate cancer after surgery. We evaluated several regression models of known or suspected clinical-pathologic covariates and selected the model with the highest Harrell's concordance-index (c-index) and clinical utility to prognosticate metastasis for inclusion in a nomogram. Covariates in the final, competing-risk adjusted, metastasis model included PSA nadir after surgery, pathologic T-stage, margin status, Gleason score (GS), number of positive lymph nodes, and use of postoperative radiotherapy combined with androgen deprivation therapy (RT + ADT). The overall survival model also included Charlson comorbidity score and age. RESULTS: 336 pN + men with a mean age of 64.9 years and a median follow-up of 4.1 years who had a radical prostatectomy were included in the analysis. 83 men were recommended RT + ADT, of whom 4% refused the ADT and received RT alone. C-index was 0.85 and 0.71 for the MFS and OS models, respectively. On multivariable analysis (MVA) adjusted for competing risks, RT + ADT significantly improved MFS (HR=0.70 P = < .01) with number of nodes positive, GS 8-10, PSA nadir > 1 ng/mL, and pT3b prognostic for metastasis. MVA for OS demonstrates RT+ADT improves survival (HR=0.40, P = .02), with GS8-10 and PSA nadir > 1.0 prognostic for death. CONCLUSION: We developed predictive nomograms for patients with pN+ prostate cancer following radical prostatectomy. These models can discretely quantify an individual's risk of metastasis or death with and without post-prostatectomy radiotherapy.

Radiation Therapy in Conjunction With Surgical Stabilization of Impending or Pathologic Fractures Secondary to Metastasis: Is There a Difference Between Single and Multifraction Regimens?

PURPOSE: Patients who undergo surgical stabilization for impending or pathologic fractures secondary to metastasis are often treated with radiation therapy to the involved site. We sought to retrospectively analyze outcomes from single versus multifraction regimens of radiation therapy in this setting. METHODS AND MATERIALS: From our institutional radiation database, we identified 87 patients between 2004 and 2016 who had an impending or pathologic fracture from metastatic disease and who underwent surgical fixation in conjunction with either neoadjuvant (within 5 weeks before surgery) or adjuvant (within 10 weeks after surgery) radiation therapy, representing 99 total treatment sites. Patients were included on the basis of intention to treat with bimodality therapy. Baseline patient characteristics were compared using 2-sided t tests and Fisher's exact tests. Cumulative incidence of local failure, reirradiation, and reoperation were calculated using the Fine-Gray method for competing risks. Freedom from complication was calculated using the Kaplan-Meier method. RESULTS: Baseline characteristics between the single (n = 52) and multifraction (n = 47) cohorts were similar with the exception of higher rates of synchronous bony metastasis (83% vs 60%, P = .01) and female patients (71% vs 43%, P = .004) in the single fraction cohort. There was no significant difference in overall survival between treatment groups. After a median follow-up of 13 months, there was no significant difference in the single and multifraction cohorts, respectively, in the 1-year cumulative incidence rates of local failure (4% vs 7%, P = .58), reirradiation (5% vs 4%, P = .95), reoperation (4% vs 0%, P = .30), or 1-year freedom from complication (90% vs 95%, P = .40). CONCLUSIONS: This is the first study comparing outcomes between single and multifraction radiation therapy in conjunction with surgical stabilization of an impending or pathologic fracture. We found no difference in outcomes between single and multifraction regimens in this setting. Given these findings, single fraction perioperative radiation therapy may be a viable treatment option in appropriately selected patients pending prospective validation of these findings.

Second Primary Malignancies in Diffuse Large B-cell Lymphoma Survivors with 40 Years of Follow Up: Influence of Chemotherapy and Radiation Therapy.

Purpose: Previous studies have shown an increased risk of second primary malignancies (SPMs) in survivors of diffuse large B-cell lymphoma (DLBCL). Survivors live longer due to the intensification of and improvements in therapy; thus, we aimed to characterize SPM patterns in patients with DLBCL by treatment modality. Methods and Materials: Standardized incidence ratio and absolute excess risk of SPMs were assessed in patients with primary DLBCL from 1975 to 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. A subgroup analyses based on, sex, race, age at the time of diagnosis, latency, and treatment modality were performed. Propensity score-adjusted cumulative incidence curves were generated, stratified by treatment and accounting for death as a competing risk. Results: In total, 45,946 patients with DLBCL were identified with a mean follow up of 70 months. Overall, 9.2% of patients developed an SPM with a standardized incidence ratio of 1.23 (95% confidence interval, 1.20-1.27). There was no difference in SPM risk between men and women or Black and White patients. Patients age <25 years were particularly susceptible to the development of SPMs, with a risk 2.5 times greater than patients aged 50 to 74 years. Temporal patterns showed increasing risk of solid malignancies and decreasing risk of hematologic malignancies over time, with bladder cancer posing the greatest absolute excess risk of any cancer type after 15 years. Patients treated with radiation therapy (RT), chemotherapy (CT), and chemoradiation therapy (CRT) all had an increased risk of SPM development compared with the general population. The cumulative incidence of SPMs was the lowest in patients treated with RT and the highest when treated with CRT. In the modern treatment era, the cumulative incidence of SPM for patients treated with CT versus CRT was not significantly different. Conclusions: In this large population-based study, we demonstrate unique SPM risk patterns based on age, latency, and treatment modality that have important implications for the treatment and screening of patients diagnosed with DLBCL.

Interplay Between Duration of Androgen Deprivation Therapy and External Beam Radiotherapy With or Without a Brachytherapy Boost for Optimal Treatment of High-risk Prostate Cancer: A Patient-Level Data Analysis of 3 Cohorts.

IMPORTANCE: Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain. OBJECTIVE: To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTINGS, AND PARTICIPANTS: This was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivación Androgénica y Radio Terapía (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021. EXPOSURES: High-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs). MAIN OUTCOMES AND MEASURES: The primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months). RESULTS: This cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to <6, 6 to <18, and ≥18 months). Natural cubic spline analysis identified minimum duration thresholds of 26.3 months (95% CI, 25.4-36.0 months) for EBRT and 12 months (95% CI, 4.9-36.0 months) for EBRT+BT for optimal effect on DMFS. In RADAR, the prolongation of ADT for patients receiving only EBRT was not associated with significant improvements in DMFS (hazard ratio [HR], 1.01; 95% CI, 0.65-1.57); however, for patients receiving EBRT+BT, a longer duration was associated with improved DMFS (DMFS HR, 0.56; 95% CI, 0.36-0.87; P = .01). For patients receiving EBRT alone (DART), 28 months of ADT was associated with improved DMFS compared with 18 months (RADAR HR, 0.37; 95% CI, 0.17-0.80; P = .01). CONCLUSIONS AND RELEVANCE: These cohort study findings suggest that the optimal minimum ADT duration for treatment with high-dose EBRT alone is more than 18 months; and for EBRT+BT, it is 18 months or possibly less. Additional studies are needed to determine more precise minimum durations.

Primary vaginal cancer and chemoradiotherapy: a patterns-of-care analysis.

INTRODUCTION: No prospective randomized trials exist to delineate the role of combined chemoradiotherapy (CRT) in the treatment of vaginal cancer (VC). We sought to describe the utilization rate of CRT and evaluate the potential survival benefit of CRT over radiotherapy alone in VC. METHODS: A retrospective analysis of the SEER-Medicare-linked database was performed analyzing women with VC treated with external beam radiation and/or brachytherapy and diagnosed between 1991 and 2005. RESULTS: Of the 1709 primary VC patients in the SEER-Medicare database, 326 met inclusion criteria. Most were white (80.1%) and in the 70- to 74-year age group (42.1%). Squamous cell carcinoma was the most predominant histologic diagnosis (80.4%). Brachytherapy was used in 34% of patients, whereas cisplatin was the chemotherapy of choice in 59% of CRT patients. Median follow-up was 21.5 months. Kaplan-Meier estimated that 5-year cause-specific survival (CSS) and overall survival (OS) was 67.6% and 27.1%, respectively. Before 1999, CRT was used in 7.5% of patients compared with 36.1% of patients thereafter (P < 0.001). Chemoradiotherapy was less likely to be used in patients older than 80 years (P < 0.001) but was otherwise balanced in race, stage, grade, histologic diagnosis, comorbidities, and brachytherapy use. Chemoradiotherapy did not correlate with CSS (hazard ratio [HR], 0.91; P = 0.84) or OS (HR, 1.34; P = 0.21) by multivariate analysis. Factors associated with worse CSS include stage IVA disease (HR, 4.2; P = 0.003) and 2 or more comorbidities (HR, 2.89; P = 0.03). Factors associated with worse OS include age older than 80 years (HR, 1.78; P = 0.04), stage IVA disease (HR, 3.35; P < 0.0001), and 2 or more comorbidities (HR, 2.58; P = 0.001). CONCLUSIONS: Chemoradiotherapy utilization for VC has increased since 1999. We failed to delineate a CSS or OS benefit for CRT in this cohort.