Characterizing cardiac contractile motion for noninvasive radioablation of ventricular tachycardia.

Background: Respiratory motion management strategies are used to minimize the effects of breathing on the precision of stereotactic ablative radiotherapy for ventricular tachycardia, but the extent of cardiac contractile motion of the human heart has not been systematically explored. Objective: We aim to assess the magnitude of cardiac contractile motion between different directions and locations in the heart. Methods: Patients with intracardiac leads or valves who underwent 4-dimensional cardiac computed tomography (CT) prior to a catheter ablation procedure for atrial or ventricular arrhythmias at 2 medical centers were studied retrospectively. The displacement of transvenous right atrial appendage, right ventricular (RV) implantable cardioverter-defibrillator, coronary sinus lead tips, and prosthetic cardiac devices across the cardiac cycle were measured in orthogonal 3-dimensional views on a maximal-intensity projection CT reconstruction. Results: A total of 31 preablation cardiac 4-dimensional cardiac CT scans were analyzed. The LV lead tip had significantly greater motion compared with the RV lead in the anterior-posterior direction (6.0 ± 2.2 mm vs 3.8 ± 1.7 mm; P = .01) and superior-inferior direction (4.4 ± 2.9 mm vs 3.5 ± 2.0 mm; P = .049). The prosthetic aortic valves had the least movement of all fiducials, specifically compared with the RV lead tip in the left-right direction (3.2 ± 1.2 mm vs 6.1 ± 3.8 mm, P = .04) and the LV lead tip in the anterior-posterior direction (3.8 ± 1.7 mm vs 6.0 ± 2.2 mm, P = .03). Conclusion: The degree of cardiac contractile motion varies significantly (1 mm to 15.2 mm) across different locations in the heart. The effect of contractile motion on the precision of radiotherapy should be assessed on a patient-specific basis.

Successful Noninvasive 12-Lead ECG Mapping-Guided Radiotherapy of Inaccessible Ventricular Tachycardia Substrate Due to Mechanical Valves.

In patients presenting with refractory ventricular tachycardia (VT) and aortic and mitral mechanical prosthetic valves, traditional catheter ablation is challenging. We describe a case in which a novel noninvasive computational electrocardiogram mapping algorithm localized VT sources originating from substrate near the mechanical valves, in which stereotactic ablative radiotherapy eliminated VT in 1.5-year follow-up. (Level of Difficulty: Advanced.).

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update.

PURPOSE: This updated report on image guided radiation therapy (IGRT) is part of a series of consensus-based white papers previously published by the American Society for Radiation Oncology addressing patient safety. Since the first white papers were published, IGRT technology and procedures have progressed significantly such that these procedures are now more commonly used. The use of IGRT has now extended beyond high-precision treatments, such as stereotactic radiosurgery and stereotactic body radiation therapy, and into routine clinical practice for many treatment techniques and anatomic sites. Therefore, quality and patient safety considerations for these techniques remain an important area of focus. METHODS AND MATERIALS: The American Society for Radiation Oncology convened an interdisciplinary task force to assess the original IGRT white paper and update content where appropriate. Recommendations were created using a consensus-building methodology, and task force members indicated their level of agreement based on a 5-point Likert scale from "strongly agree" to "strongly disagree." A prespecified threshold of ≥75% of raters who selected "strongly agree" or "agree" indicated consensus. SUMMARY: This IGRT white paper builds on the previous version and uses other guidance documents to primarily focus on processes related to quality and safety. IGRT requires an interdisciplinary team-based approach, staffed by appropriately trained specialists, as well as significant personnel resources, specialized technology, and implementation time. A thorough feasibility analysis of resources is required to achieve the clinical and technical goals and should be discussed with all personnel before undertaking new imaging techniques. A comprehensive quality-assurance program must be developed, using established guidance, to ensure IGRT is performed in a safe and effective manner. As IGRT technologies continue to improve or emerge, existing practice guidelines should be reviewed or updated regularly according to the latest American Association of Physicists in Medicine Task Group reports or guidelines. Patient safety in the application of IGRT is everyone's responsibility, and professional organizations, regulators, vendors, and end-users must demonstrate a clear commitment to working together to ensure the highest levels of safety.

Examining the Effect of Direct Patient Care for Medical Physicists: A Randomized Prospective Phase III Trial.

PURPOSE: Our purpose was to investigate the effect of physicist-patient consults on patient anxiety and patient satisfaction with a randomized prospective phase III clinical trial. METHODS AND MATERIALS: Sixty-six patients were randomly assigned to the physics direct patient care (PDPC) arm or the control arm of the trial. Patients assigned to the PDPC arm received 2 physicist-patient consults to educate them on the technical aspects of their radiation therapy, while patients assigned to the control arm received the standard of care (ie, standard radiation therapy workflow without any additional physicist-patient consults). Questionnaires were administered to all patients at 4 time points (after enrollment, after the simulation, after the first treatment, and after the last treatment) to assess anxiety and satisfaction. RESULTS: The decrease in anxiety for the PDPC arm, compared with the control arm, was statistically significant at the first treatment (P = .027) time point. The increase in technical satisfaction for the PDPC arm, compared with the control arm, was statistically significant at the simulation (P = .005), first treatment (P < .001), and last treatment (P = .002) time points. The increase in overall satisfaction for the PDPC arm, compared with the control arm, was statistically significant at the first treatment (P = .014) and last treatment (P = .001) time points. CONCLUSIONS: Physicist-patient consults improved the patient experience by decreasing anxiety and increasing satisfaction. Future work is needed to modify current radiation oncology workflows and medical physics responsibilities to allow all patients to benefit from this advancement in patient care.

Improved survival in cervical cancer patients receiving care at National Cancer Institute-designated cancer centers.

BACKGROUND: Locally advanced cervical cancer (CC) remains lethal in the United States. We investigate the effect of receiving care at an National Cancer Institute-designated cancer center (NCICC) on survival. METHODS: Data for women diagnosed with CC from 2004 to 2016 who received radiation treatment were extracted from the California Cancer Registry (n = 4250). Cox proportional hazards regression models assessed whether (1) receiving care at NCICCs was associated with risk of CC-specific death, (2) this association remained after multivariable adjustment for age, race/ethnicity, and insurance status, and (3) this association was explained by receipt of guideline-concordant treatment. RESULTS: Median age was 50 years (interquartile range [IQR] 41-61 years), with median follow-up of 2.7 years (IQR 1.3-6.0 years). One-third of patients were seen at an NCICC, and 29% died of CC. The hazard of CC-specific death was reduced by 20% for those receiving care at NCICCs compared with patients receiving care elsewhere (HR = .80; 95% CI, 0.70-0.90). Adjustment for guideline-concordant treatment and other covariates minimally attenuated the association to 0.83 (95% CI, 0.74-0.95), suggesting that the survival advantage associated with care at NCICCs may not be due to receipt of guideline-concordant treatment. CONCLUSIONS: This study demonstrates survival benefit for patients receiving care at NCICCs compared with those receiving care elsewhere that is not explained by differences in guideline-concordant care. Structural, organizational, or provider characteristics and differences in patients receiving care at centers with and without NCI designation could explain observed associations. Further understanding of these factors will promote equality across oncology care facilities and survival equity for patients with CC.

Impact of age on treatment response in men with prostate cancer treated with radiotherapy.

Objective: To analyse the effect of age at diagnosis on clinical outcomes of localized prostate cancer (PCa) treated with radiation therapy. Subjects and methods: We identified 12 784 patients with intermediate- or high-risk localized PCa treated with radiation therapy (RT) and neoadjuvant androgen deprivation therapy (ADT) between 2000 and 2015 from nationwide Veterans Affairs data. Patients were grouped into three age categories (≤59, 60-69, and ≥70 years old). Outcomes included immediate PSA response (3-month post-RT PSA and 2-year PSA nadir, grouped into <0.10 ng/ml, 0.10-0.49 ng/ml, and ≥0.50 ng/ml), biochemical recurrence, and PCa-specific mortality. Multivariable regression models included ordinal logistic regression for short-term PSA outcomes, Cox regression for biochemical recurrence, and Fine-Gray competing risks regression for PCa-specific mortality. Results: A total of 2136 patients (17%) were ≤59 years old at diagnosis, 6107 (48%) were 60-69 years old, and 4541 (36%) were ≥70 years old. Median follow-up was 6.3 years. Younger age was associated with greater odds of higher 3-month PSA group (≤59 vs. ≥70: adjusted odds ratio [aOR] 1.90, 95% CI 1.64-2.20; p < 0.001) and higher 2-year PSA nadir group (≤59 vs. ≥70: aOR 1.89, 95% CI 1.62-2.19, p < 0.001). Younger age was associated with greater risk of biochemical recurrence (≤59 vs. ≥70: adjusted hazard ratio 1.45, 95% CI 1.26-1.67, p < 0.001) but not PCa-specific mortality (p = 0.16). Conclusion: In a large nationwide sample of US veterans treated with ADT and RT for localized PCa, younger age was associated with inferior short-term PSA response and higher risk of biochemical recurrence.

Volumetric de-escalation and improved acute toxicity with proton craniospinal irradiation using a vertebral body-sparing technique.

PURPOSE: In growing children, craniospinal irradiation (CSI) has historically treated the entire vertebral body (VB) to avoid potential long-term spinal abnormalities. Vertebral body-sparing proton craniospinal irradiation (VBSpCSI) is a technique that spares the majority of the VB from significant irradiation, and long-term safety outcomes have been reported previously. This retrospective study reviews the acute toxicity profile of children treated with VBSpCSI in a cohort comparison with photon-based craniospinal radiotherapy (3DCRT). METHODS: Thirty-eight pediatric CSI patients treated between 2008 and 2018 were retrospectively evaluated for treatment-related toxicity. Acute toxicity outcomes and acute hematologic profiles were compared according to treatment modality, either VBSpCSI or 3DCRT. Statistical analysis was performed using Fisher's exact test for toxicity. RESULTS: Twenty-five patients received VBSpCSI and 13 patients received photon CSI. Mean patient age at treatment was 7.5 years (range 2-16). The cohorts were well matched with respect to gender, age, and CSI dose. Patients receiving VBSpCSI had lower rates of grade 2+ gastrointestinal (GI) toxicity (24% vs. 76.5%, p = .005), grade 2+ nausea (24% vs. 61.5%, p = .035), and any-grade esophagitis (0% vs. 38%, p = .0026). Patients treated with VBSpCSI had lower red blood cell transfusion rates (21.7% vs. 60%, p = .049) and grade 4+ lymphopenia (33.3% vs. 77.8%, p = .046). CONCLUSIONS: VBSpCSI in children is a volumetric de-escalation from traditional volumes, which irradiate the entire VB to full or intermediate doses. In our study, VBSpCSI was associated with lower rates of acute GI and hematologic toxicities. Long-term growth outcomes and disease control outcomes are needed for this technique.

Positron Emission Tomography-Guided Bone Marrow-Sparing Radiation Therapy for Locoregionally Advanced Cervix Cancer: Final Results From the INTERTECC Phase II/III Trial.

PURPOSE: To test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer. METHODS AND MATERIALS: In an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS. RESULTS: In total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ2P = .048) and in the combined cohort (13% vs 35%, χ2P = .01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P = .216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group. CONCLUSIONS: PET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS.

Computational ECG mapping and respiratory gating to optimize stereotactic ablative radiotherapy workflow for refractory ventricular tachycardia.

BACKGROUND: Stereotactic ablative radiotherapy (SAbR) is an emerging therapy for refractory ventricular tachycardia (VT). However, the current workflow is complicated, and the precision and safety in patients with significant cardiorespiratory motion and VT targets near the stomach may be suboptimal. OBJECTIVE: We hypothesized that automated 12-lead electrocardiogram (ECG) mapping and respiratory-gated therapy may improve the ease and precision of SAbR planning and facilitate safe radiation delivery in patients with refractory VT. METHODS: Consecutive patients with refractory VT were studied at 2 hospitals. VT exit sites were localized using a 3-D computational ECG algorithm noninvasively and compared to available prior invasive mapping. Radiotherapy (25 Gy) was delivered at end-expiration when cardiac respiratory motion was ≥0.6 cm or targets were ≤2 cm from the stomach. RESULTS: In 6 patients (ejection fraction 29% ± 13%), 4.2 ± 2.3 VT morphologies per patient were mapped. Overall, 7 out of 7 computational ECG mappings (100%) colocalized to the identical cardiac segment when prior invasive electrophysiology study was available. Respiratory gating was associated with smaller planning target volumes compared to nongated volumes (71 ± 7 vs 153 ± 35 cc, P < .01). In 2 patients with inferior wall VT targets close to the stomach (6 mm proximity) or significant respiratory motion (22 mm excursion), no GI complications were observed at 9- and 12-month follow-up. Implantable cardioverter-defibrillator shocks decreased from 23 ± 12 shocks/patient to 0.67 ± 1.0 (P < .001) post-SAbR at 6.0 ± 4.9 months follow-up. CONCLUSIONS: A workflow including computational ECG mapping and protocol-guided respiratory gating is feasible, is safe, and may improve the ease of SAbR planning. Studies to validate this workflow in larger populations are required.

End of treatment cone-beam computed tomography (CBCT) is predictive of radiation response and overall survival in oropharyngeal squamous cell carcinoma.

BACKGROUND: Image guidance in radiation oncology has resulted in significant improvements in the accuracy and precision of radiation therapy (RT). Recently, the resolution and quality of cone beam computed tomography (CBCT) for image guidance has increased so that tumor masses and lymph nodes are readily detectable and measurable. During treatment of head and neck squamous cell carcinoma (HNSCC), on-board CBCT setup imaging is routinely obtained; however, this CBCT imaging data is not utilized to predict patient outcomes. Here, we analyzed whether changes in CBCT measurements obtained during a course of radiation therapy correlate with responses on routine 3-month follow-up diagnostic imaging and overall survival (OS). MATERIALS/METHODS: Patients with oropharyngeal primary tumors who received radiation therapy between 2015 and 2018 were included. Anatomical measurements were collected of largest nodal conglomerate (LNC) at CT simulation, end of radiation treatment (EOT CBCT), and routine 3-month post-RT imaging. At each timepoint anteroposterior (AP), mediolateral (ML) and craniocaudal (CC) measurements were obtained and used to create a 2-dimensional (2D) maximum. RESULTS: CBCT data from 64 node positive patients were analyzed. The largest nodal 2D maximum and CC measurements on EOT CBCT showed a statistically significant correlation with complete response on 3-month post-RT imaging (r = 0.313, p = 0.02 and r = 0.318, p = 0.02, respectively). Furthermore, patients who experienced a 30% or greater reduction in the CC dimension had improved OS (Binary Chi-Square HR 4.85, p = 0.028). CONCLUSION: Decreased size of pathologic lymph nodes measured using CBCT setup imaging during a radiation course correlates with long term therapeutic response and overall survival of HNSCC patients. These results indicate that CBCT setup imaging may have utility as an early predictor of treatment response in oropharyngeal HNSCC.

Brachytherapy utilization for cervical cancer in Western United States border counties: seeking to understand referral patterns for outcome improvement.

PURPOSE: Standard of care for definitive treatment of locally advanced cervical cancer (LACC) is concurrent chemoradiation followed by a brachytherapy boost. Only 55.8% of women in the United States receive brachytherapy, with even lower proportions in San Diego and Imperial Counties. The purpose of this study was to investigate brachytherapy practice and referral patterns in Western United States border region. MATERIAL AND METHODS: A short survey was sent to 28 radiation oncologists in San Diego and Imperial Counties, who treat patients with gynecologic malignancies. Descriptive statistics were used for analysis. RESULTS: Seventeen (61%) physicians responded to the survey. All physicians reported some training in cervical cancer brachytherapy during residency, with median 6 months. Only two physicians reported personally treating all cervical cancer patients with brachytherapy; however, 92% of remaining physicians would recommend brachytherapy for patients if given time and access. The most common reason for referral (78%) was patients deemed to require hybrid or interstitial brachytherapy implants. Barriers to referral included patients' preference, insurance status, their resources, or logistics. No changes were reported for brachytherapy practices during the COVID-19 pandemic, except the addition of pre-procedural testing for SARS-CoV-2. Ninety-two percent of physicians identified inadequate maintenance of skills as a barrier to performing brachytherapy, but 77% were not interested in additional training. External beam radiation therapy boosts were rarely recommended in case scenarios describing potentially curable patients. CONCLUSIONS: The importance of brachytherapy is widely recognized for conferring a survival benefit, but barriers to implementation include inadequate training or maintenance of skills, and larger systematic issues related to reimbursement policy, social support, and financial hardship. As most established providers were uninterested in additional brachytherapy training, future approaches to improve patients' access should be multidimensional and reflect the value of brachytherapy in definitive treatment of patients with LACC.

Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration.

BACKGROUND: Population-based studies demonstrate that Black men in the United States have an increased risk of death from prostate cancer. Determinants of racial disparities are multifactorial, including socioeconomic and biologic factors. METHODS: The authors conducted a pooled analysis of patients derived from 152 centers within the Veterans Health Administration. The cohort included men who had nonmetastatic prostate diagnosed between 2001 and 2015 and received definitive radiation therapy. The primary endpoint was prostate cancer-specific mortality (PCSM). Secondary endpoints included all-cause mortality (ACM) and the time from a prostate-specific antigen level ≥4 ng/mL to biopsy and radiation therapy. A Cox regression model was performed to adjust for differences between clinical parameters. RESULTS: Among the 31,131 patients included in the cohort, 9584 (30.8%) were Black. The 10-year cumulative incidence of death from prostate cancer was lower in Black men compared with White men (4.0% vs 4.8%; P = .004). In a competing risk model, Black race was associated with a decreased risk of PCSM (subdistribution hazard ratio, 0.79; 95% CI, 0.69-0.92; P = .002). Similarly, the 10-year cumulative incidence of death from any cause was lower in Black men (27.6% vs 31.8%; P < .001). In multivariable analysis, Black men had a 10% decreased risk of ACM (hazard ratio, 0.90; 95% CI, 0.85-0.95; P < .001). CONCLUSIONS: The current results indicate relatively lower PCSM and ACM among Black men who were included in a large Veterans Health Administration cohort and received radiation therapy as primary treatment for nonmetastatic prostate cancer. There is an ongoing need to continue to understand and mitigate the factors associated with disparities in health care outcomes.

Association Between African American Race and Clinical Outcomes in Men Treated for Low-Risk Prostate Cancer With Active Surveillance.

Importance: There is concern that African American men with low-risk prostate cancer may harbor more aggressive disease than non-Hispanic White men. Therefore, it is unclear whether active surveillance is a safe option for African American men. Objective: To compare clinical outcomes of African American and non-Hispanic White men with low-risk prostate cancer managed with active surveillance. Design, Setting, and Participants: Retrospective cohort study in the US Veterans Health Administration Health Care System of African American and non-Hispanic White men diagnosed with low-risk prostate cancer between January 1, 2001, and December 31, 2015, and managed with active surveillance. The date of final follow-up was March 31, 2020. Exposures: Active surveillance was defined as no definitive treatment within the first year of diagnosis and at least 1 additional surveillance biopsy. Main Outcomes and Measures: Progression to at least intermediate-risk, definitive treatment, metastasis, prostate cancer-specific mortality, and all-cause mortality. Results: The cohort included 8726 men, including 2280 African American men (26.1%) (median age, 63.2 years) and 6446 non-Hispanic White men (73.9%) (median age, 65.5 years), and the median follow-up was 7.6 years (interquartile range, 5.7-9.9; range, 0.2-19.2). Among African American men and non-Hispanic White men, respectively, the 10-year cumulative incidence of disease progression was 59.9% vs 48.3% (difference, 11.6% [95% CI, 9.2% to 13.9%); P < .001); of receipt of definitive treatment, 54.8% vs 41.4% (difference, 13.4% [95% CI, 11.0% to 15.7%]; P < .001); of metastasis, 1.5% vs 1.4% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .49); of prostate cancer-specific mortality, 1.1% vs 1.0% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .82); and of all-cause mortality, 22.4% vs 23.5% (difference, 1.1% [95% CI, -0.9% to 3.1%]; P = 0.09). Conclusions and Relevance: In this retrospective cohort study of men with low-risk prostate cancer followed up for a median of 7.6 years, African American men, compared with non-Hispanic White men, had a statistically significant increased 10-year cumulative incidence of disease progression and definitive treatment, but not metastasis or prostate cancer-specific mortality. Longer-term follow-up is needed to better assess the mortality risk.

Evaluation of a Patient Communication Skills Training Program for Medical Physicists.

PURPOSE: To evaluate the efficacy of a training program designed to teach medical physicists how to communicate with patients effectively in the clinical environment. METHODS AND MATERIALS: The training program was offered 3 times between 2016 and 2019. Participants were asked to rank their level of confidence in 5 categories relevant to patient communication on a 5-point Likert scale at 3 separate time points over the course of the training program. Participants were also asked to provide written responses to 5 common questions from patients at 2 separate time points, and these responses were numerically scored using the Constant Comparative Method. Competency in patient communication was assessed during simulated patient consults using a 9-element clinical competency assessment form. Changes in participants' stated level of confidence over the course of the training program and differences between faculty and residents were analyzed using the Student t test, and participants' scored responses to common questions were analyzed using analysis of variance. RESULTS: Fifteen medical physicists participated in the training program: 6 resident physicists (4 first year and 2 second year) and 9 faculty physicists. Mean participant-stated level of confidence increased significantly across all categories (P < .05) between the first and second training intervention and between the second and third training intervention. There was no significant difference in mean participant-stated level of confidence between faculty and resident medical physicists. We observed statistically significant improvements in scored responses to common patient questions between the 2 assessment time points (P < .05). Of the 15 participants, 14 met competency assessment goals during simulated patient consults. CONCLUSIONS: The patient communication skills training program increases medical physicists' level of confidence across 5 patient communication categories and improves their responses to common questions from patients. In addition, the program can discern differences in communication competency between physicists.

Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease.

BACKGROUND: The safety of testosterone therapy (TT) after definitive treatment for localized prostate cancer remains undefined. We analyzed the risks of biochemical recurrence and mortality in men receiving TT after treatment for localized prostate cancer. METHODS: Cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure. We identified 69,984 patients with localized prostate cancer diagnosed from 2001 to 2015 treated with surgery or radiation. We coded receipt of TT after treatment as a time-dependent covariate; used the National Death Index to identify cause of death; and defined biochemical recurrence as PSA > 0.2 ng/mL after surgery and nadir + 2 ng/mL after radiation. We analyzed recurrence and mortality using cumulative incidence curves, Fine-Gray competing risk regression, and Cox regression. RESULTS: This cohort included 28,651 surgery patients and 41,333 radiation patients, of whom 469 (1.64%) and 543 (1.31%), respectively, received TT with a median follow-up of 6.95 years. Comparing testosterone users to nonusers, there were no between-group differences in biochemical recurrence, prostate cancer-specific mortality, or overall mortality after surgery [hazard ratios (HR): 1.07; HR: 0.72 (p = 0.43); and HR: 1.11 (p = 0.43), respectively] or radiation [HR: 1.07; HR: 1.02 (p = 0.95); and HR: 1.02 (p = 0.86), respectively]. Limitations included lack of detailed data on TT duration and serum testosterone concentrations. CONCLUSIONS: In this multi-ethnic national cohort, TT did not increase the risks of biochemical recurrence or prostate cancer-specific or overall mortality after surgery or radiation. These data suggest that TT is safe in appropriate men after definitive treatment of localized prostate cancer.

A review of patient questions from physicist-patient consults.

PURPOSE: To provide insight into the types of questions asked to medical physicists by patients during one-on-one physicist-patient consults at one institution. MATERIALS AND METHODS: Medical physicists trained in patient communication techniques met with patients to provide an overview of the treatment planning and delivery processes, discuss the patient's treatment plan, and answer any technical questions. From August 2016 to December 2019, 152 physicist-patient consults were conducted. In the initial months of the study (August 2016-December 2017), following each physicist-patient consult, all patient questions were documented by the physicists. For the remaining time period (January 2018-December 2019), any newly encountered questions were periodically added to the list. The questions were compiled into a comprehensive list and organized into categories. RESULTS: There were a total of 88 unique patient questions. These questions fit into four topical categories. Fifty-four questions (61.4%) were in the "Treatment Planning and Delivery Questions" category, 15 questions (17.1%) were in the "General Radiation Questions or Concerns" category, 13 questions (14.8%) were in the "Safety and Quality Assurance Questions" category, and 6 questions (6.8%) were in the "Medical Questions" category. Overall, patients were primarily concerned about how radiation works, the treatment planning and delivery processes, and what is being done to keep them safe throughout their treatment. CONCLUSION: Physicist-patient consults provided an opportunity to address the technical aspects of radiation therapy with patients in greater detail. The fact that patient questions could be conveniently grouped into only four topical categories indicates that it may be straightforward for other medical physicists to prepare for effectively addressing technical questions during physicist-patient consults.

Phase 1 Trial of Concurrent Gemcitabine and Cisplatin with Image Guided Intensity Modulated Radiation Therapy for Locoregionally Advanced Cervical Carcinoma.

PURPOSE: The use of concurrent doublet chemotherapy with radiation for locoregionally advanced cervical cancer (LACC) is limited by gastrointestinal and hematologic toxicity. By reducing radiation dose to bowel and bone marrow, image guided intensity modulated radiation therapy (IG-IMRT) may improve chemotherapy tolerance. The goal of this study was to determine whether IG-IMRT could lead to improved tolerance to concurrent cisplatin and gemcitabine for LACC. METHODS AND MATERIALS: We conducted an open-label, nonrandomized, prospective phase 1 dose escalation trial at a tertiary academic cancer center (ClinicalTrials.gov identifier: NCT01554410). We enrolled patients with stage IB-IVA cervical cancer, with either an intact cervix or posthysterectomy with residual/recurrent pelvic or paraortic nodal involvement, undergoing radical pelvic or extended field chemoradiation therapy. Treatment consisted of chemoradiation with IG-IMRT (45-47.6 Gy, 25-28 fractions to the pelvis ± paraortic nodes with simultaneous nodal boost to 53.2-59.4 Gy, 28 fractions) plus 5 cycles of concurrent weekly cisplatin 40 mg/m2 with escalating doses of gemcitabine (50, 75, 100, or 125 mg/m2). Cohorts were separated preregistration according to whether the patient received pelvic or extended field IG-IMRT and whether gemcitabine followed (CG) or preceded (GC) cisplatin delivery. Dose-limiting toxicity (DLT) events were monitored up to 30 days after chemoradiation therapy. The primary endpoint was maximum tolerated dose (MTD) resulting in DLT probability ≤20%. RESULTS: Between February 2011 and June 2019, 35 patients were registered. Overall, 7 patients (20.0%) experienced DLTs. For the pelvic field cohort, the estimated MTD was 100 mg/m2 with GC sequencing, which is higher than the previously reported MTD for this regimen. The extended field cohort was closed after 2 of 3 patients experienced a DLT at the first dose level. CONCLUSIONS: IG-IMRT can permit higher doses of concurrent gemcitabine with cisplatin and pelvic radiation for LACC. However, acute toxicity remains a factor with this regimen, depending on radiation volume and chemotherapy sequencing.

Associations among statins, preventive care, and prostate cancer mortality.

BACKGROUND: Increasing evidence indicates an association between statins and reduced prostate cancer-specific mortality (PCSM). However, significant bias may exist in these studies. One particularly challenging bias to assess is the healthy user effect, which may be quantified by screening patterns. We aimed to evaluate the association between statin use, screening, and PCSM in a dataset with detailed longitudinal information. METHODS: We used the Veterans Affairs Informatics and Computing Infrastructure to assemble a cohort of patients diagnosed with prostate cancer (PC) between 2000 and 2015. We collected patient-level demographic, comorbidity, and tumor data. We also assessed markers of preventive care utilization including cholesterol and prostate specific antigen (PSA) screening rates. Patients were considered prediagnosis statin users if they had at least one prescription one or more years prior to PC diagnosis. We evaluated PCSM using hierarchical Fine-Gray regression models and all-cause mortality (ACM) using a cox regression model. RESULTS: The final cohort contained 68,432 men including 40,772 (59.6%) prediagnosis statin users and 27,660 (40.4%) nonusers. Prediagnosis statin users had higher screening rates than nonusers for cholesterol (90 vs. 69%, p < 0.001) and PSA (76 vs. 67%, p < 0.001). In the model which excluded screening, prediagnosis statin users had improved PCSM (SHR 0.90, 95% CI 0.84-0.97; p = 0.004) and ACM (HR 0.96, 95% CI 0.93-0.99; p = 0.02). However, after including cholesterol and PSA screening rates, prediagnosis statin users and nonusers showed no differences in PCSM (SHR 0.98, 95% CI 0.91-1.06; p = 0.59) or ACM (HR 1.02, 95% CI 0.98-1.05; p = 0.25). CONCLUSION: We found that statin users tend to have more screening than nonusers. When we considered screening utilization, we observed no relationship between statin use before a prostate cancer diagnosis and prostate cancer mortality.

Implementation of peer-review quality rounds for gynecologic brachytherapy in a high-volume academic center.

PURPOSE: While peer review is critical for quality and safety in radiotherapy, there are neither formal guidelines nor format examples for brachytherapy (BT) peer review. We report on a gynecologic BT peer-review method implemented at a high-volume academic center. METHODS AND MATERIALS: We analyzed discussions at bimonthly gynecologic BT peer-review rounds between July and December 2018. Rounds consisted of 2-5 attending physicians with gynecologic BT expertise, 1-2 BT physicists, and trainees. Peer-review targets included clinical case review, contours, implant technique, dose/fractionation, and target/organ-at-risk (OAR) dosimetry. The projected/final target and OAR dosimetry were analyzed. RESULTS: 55 separate implants from 44 patients were reviewed. Implants were mostly reviewed after the first BT fraction (n = 16, 29%) or at another time point during BT (n = 20, 36%). One (2%) implant was presented prospectively. The applicator type and BT technique were reviewed for all implants. Dose/fractionation was evaluated for 46 implants (84%); contours were discussed for 21 (38%). Target and OAR dosimetry were reviewed for 54 (98%) and 28 implants (51%), respectively. Six cases (11%) underwent minor changes to the applicator type to improve target and/or OAR dosimetry. One case (2%) had a major change recommended to the dose/fractionation. CONCLUSIONS: Gynecologic BT peer review may enhance BT quality by allowing for implant optimization and formal review of challenging cases, ultimately improving medical decision-making and team communication. Peer review should be implemented in centers offering gynecologic BT.