TP53 structure-function relationships in metastatic castrate-sensitive prostate cancer and the impact of APR-246 treatment.

PURPOSE: Despite well-informed work in several malignancies, the phenotypic effects of TP53 mutations in metastatic castration-sensitive prostate cancer (mCSPC) progression and metastasis are not clear. We characterized the structure-function and clinical impact of TP53 mutations in mCSPC. PATIENTS AND METHODS: We performed an international retrospective review of men with mCSPC who underwent next-generation sequencing and were stratified according to TP53 mutational status and metastatic burden. Clinical outcomes included radiographic progression-free survival (rPFS) and overall survival (OS) evaluated with Kaplan-Meier and multivariable Cox regression. We also utilized isogenic cancer cell lines to assess the effect of TP53 mutations and APR-246 treatment on migration, invasion, colony formation in vitro, and tumor growth in vivo. Preclinical experimental observations were compared using t-tests and ANOVA. RESULTS: Dominant-negative (DN) TP53 mutations were enriched in patients with synchronous (vs. metachronous) (20.7% vs. 6.3%, p < 0.01) and polymetastatic (vs. oligometastatic) (14.4% vs. 7.9%, p < 0.01) disease. On multivariable analysis, DN mutations were associated with worse rPFS (hazards ratio [HR] = 1.97, 95% confidence interval [CI]: 1.31-2.98) and overall survival [OS] (HR = 2.05, 95% CI: 1.14-3.68) compared to TP53 wild type (WT). In vitro, 22Rv1 TP53 R175H cells possessed stronger migration, invasion, colony formation ability, and cellular movement pathway enrichment in RNA sequencing analysis compared to 22Rv1 TP53 WT cells. Treatment with APR-246 reversed the effects of TP53 mutations in vitro and inhibited 22Rv1 TP53 R175H tumor growth in vivo in a dosage-dependent manner. CONCLUSIONS: DN TP53 mutations correlated with worse prognosis in prostate cancer patients and higher metastatic potential, which could be counteracted by APR-246 treatment suggesting a potential future therapeutic avenue.

Metastasis-Directed Therapy for Oligometastatic Castration-Sensitive Prostate Cancer: An Alternative to ADT?

PURPOSE OF REVIEW: The standard treatment of patients with metastatic prostate cancer is systemic treatment with androgen-deprivation therapy (ADT). The spectrum-based model of metastatic disease includes the presence of an oligometastatic state, an intermediary between localized and widespread metastatic disease, in which radical local treatment might improve systemic control. Our purpose is to review the literature on metastasis-directed therapy in the treatment of oligometastatic prostate cancer. RECENT FINDINGS: Several prospective clinical trials have reported improvements in ADT-free survival and progression-free survival with metastasis-directed therapy of oligometastatic prostate cancer. Retrospective studies have found improvements in oncologic outcomes for patients with oligometastatic prostate cancer undergoing metastasis-directed therapy, and several recent prospective clinical trials have confirmed these results. Advancements in imaging as well as an understanding of the genomics of oligometastatic prostate cancer may allow for better patient selection for metastasis-directed therapy and the potential for cure in selected patients.

A flexible approach for causal inference with multiple treatments and clustered survival outcomes.

When drawing causal inferences about the effects of multiple treatments on clustered survival outcomes using observational data, we need to address implications of the multilevel data structure, multiple treatments, censoring, and unmeasured confounding for causal analyses. Few off-the-shelf causal inference tools are available to simultaneously tackle these issues. We develop a flexible random-intercept accelerated failure time model, in which we use Bayesian additive regression trees to capture arbitrarily complex relationships between censored survival times and pre-treatment covariates and use the random intercepts to capture cluster-specific main effects. We develop an efficient Markov chain Monte Carlo algorithm to draw posterior inferences about the population survival effects of multiple treatments and examine the variability in cluster-level effects. We further propose an interpretable sensitivity analysis approach to evaluate the sensitivity of drawn causal inferences about treatment effect to the potential magnitude of departure from the causal assumption of no unmeasured confounding. Expansive simulations empirically validate and demonstrate good practical operating characteristics of our proposed methods. Applying the proposed methods to a dataset on older high-risk localized prostate cancer patients drawn from the National Cancer Database, we evaluate the comparative effects of three treatment approaches on patient survival, and assess the ramifications of potential unmeasured confounding. The methods developed in this work are readily available in the R $$ \mathsf{R}\kern.15em $$ package riAFTBART $$ \mathsf{riAFTBART} $$ .

The clinical impact of removing rectal gas on high-dose-rate brachytherapy dose distributions for gynecologic cancers.

PURPOSE: To evaluate the impact of gas removal on bladder and rectal doses during intracavitary and interstitial high-dose-rate brachytherapy (HDRB) for gynecologic cancers. MATERIAL AND METHODS: Fifteen patients treated with definitive external beam radiation followed by HDRB for gynecologic cancers for a total of 21 fractions, presented with a significant amount of rectal gas at initial CT imaging (CTGAS ) after implantation. The gas was removed via rectal tubing followed by subsequent scan acquisition (CTCLINICAL ), which was used for planning and treatment delivery. To assess the effect of gas removal on dosimetry, both bladder and rectum volumes were recontoured on CTGAS . In order to evaluate the clinical impact on the total Equivalent-Dose-in-2Gy-fraction (EQD2 ), each fraction was also replanned to maintain clinically delivered target coverage (HRCTV D90). EQD2 D2cm3 for bladder and rectum were compared between plans. The Wilcoxon signed rank test was performed to evaluate statistically significant differences for all comparisons (P < 0.05). RESULTS: Mean rectum and bladder Dmax , D0.1cm3 , D1cm3 , D2cm3 , and D5cm3 were significantly different between CTGAS and CTCLINICAL . The mean percent increases on CTGAS for bladder were 12.3, 8.4, 9.9, 10.2, and 9.5% respectively and for rectum were 27.0, 19.6, 18.1, 18.5, and 19.4%, respectively. After replanning with CTGAS to maintain HRCTV D90 EQD2 , bladder and rectum EQD2 D2 cm3 resulted in significantly higher doses. The mean EQD2 D2 cm3 difference was 2.4 and 4.1 Gy for bladder and rectum, revealing a higher impact of gas removal on rectal DVH. CONCLUSION: Rectal gas removal resulted in statistically significant differences for both bladder and rectum. The resulting larger EQD2 D2 cm3 for bladder and rectum demonstrates that if patients were treated without removing gas, target coverage would need to be sacrificed to satisfy the rectum constraints and prevent toxicities. Therefore, this study demonstrates the importance of gas removal for gynecologic HDRB patients.

Immortal Time Bias in Observational Studies of Time-to-Event Outcomes: Assessing Effects of Postmastectomy Radiation Therapy Using the National Cancer Database.

The objectives of this study are to illustrate the effects of immortal time bias (ITB) using an oncology outcomes database and quantify through simulations the magnitude and direction of ITB when different analytical techniques are used. A cohort of 11 626 women who received neoadjuvant chemotherapy and underwent mastectomy with pathologically positive lymph nodes were accrued from the National Cancer Database (2004-2008). Standard Cox regression, time-dependent (TD), and landmark models were used to compare overall survival in patients who did or did not receive postmastectomy radiation therapy (PMRT). Simulation studies showing ways to reduce the effect of ITB indicate that TD exposures should be included as variables in hazard-based analyses. Standard Cox regression models comparing overall survival in patients who did and did not receive PMRT showed a significant treatment effect (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.88-0.99). Time-dependent and landmark methods estimated no treatment effect with HR: 0.97, 95% CI: 0.92 to 1.03 and HR: 0.98, 95% CI, 0.92 to 1.04, respectively. In our simulation studies, the standard Cox regression model significantly overestimated treatment effects when no effect was present. Estimates of TD models were closest to the true treatment effect. Landmark model results were highly dependent on landmark timing. Appropriate statistical approaches that account for ITB are critical to minimize bias when examining relationships between receipt of PMRT and survival.

Prophylactic sildenafil citrate improves select aspects of sexual function in men treated with radiotherapy for prostate cancer.

PURPOSE: We studied adjuvant daily sildenafil citrate during and after radiotherapy for prostate cancer for erectile function preservation. MATERIALS AND METHODS: We performed a randomized, prospective trial of 279 patients with localized prostate cancer treated with radiotherapy who received sildenafil citrate (50 mg daily) or placebo (2:1 randomization). Medication/placebo was initiated 3 days before treatment and continued daily for 6 months. Before therapy and 3, 6, 9, 12, 18 and 24 months after radiotherapy patients completed the IIEF questionnaire, including the erectile function domain, the I-PSS questionnaire and the RAND SF-36®. All IIEF domains were scored. RESULTS: At 12 months erectile function scores were better for sildenafil citrate than placebo (p = 0.018), 73% of patients on sildenafil citrate vs 50% on placebo had mild/no erectile dysfunction (p = 0.024) and the sildenafil citrate arm had superior overall satisfaction (p = 0.027) and IIEF total scores (p = 0.043). At 24 months erectile function and IIEF scores were no longer significantly better for sildenafil citrate (p = 0.172 and 0.09, respectively) and yet overall satisfaction scores were higher (p = 0.033). Sexual desire scores in patients who received sildenafil citrate were higher at 24 months although they had completed drug therapy 18 months previously (p = 0.049). At 24 months 81.6% of patients on sildenafil citrate and 56.0% of those on placebo achieved functional erection with or without erectile dysfunction medication (p = 0.045). CONCLUSIONS: Daily sildenafil citrate during and after radiotherapy for prostate cancer was associated with improved overall sexual function compared with placebo for various sexual function domains. To our knowledge this is the largest randomized, prospective, controlled trial to show the usefulness of a phosphodiesterase-5 inhibitor as a rehabilitation strategy in patients with prostate cancer who received radiation therapy.

Prostate-Specific Membrane Antigen PET Response Associates with Metastasis-Free Survival After Stereotactic Ablative Radiation in Oligometastatic Prostate Cancer.

Purpose: Emerging data suggest that metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can detect occult metastatic disease, and PSMA response has been proposed as a biomarker for treatment response. Herein, we identify and validate a PSMA-PET biomarker for metastasis-free survival (MFS) following MDT in omCSPC. Methods and Materials: We performed an international multi-institutional retrospective study of patients with omCSPC, defined as ≤3 lesions, treated with metastasis-directed stereotactic ablative radiation who underwent PSMA-PET/computed tomography (CT) before and after (median, 6.2 months; range, 2.4-10.9 months) treatment. Pre- and post-MDT PSMA-PET/CT maximum standardized uptake value (SUVmax) was measured for all lesions, and PSMA response was defined as the percent change in SUVmax of the least responsive lesion. PSMA response was both evaluated as a continuous variable and dichotomized into PSMA responders, with a complete/partial response (at least a 30% reduction in SUVmax), and PSMA nonresponders, with stable/progressive disease (less than a 30% reduction in SUVmax). PSMA response was correlated with conventional imaging-defined metastasis-free survival (MFS) via Kaplan-Meier and Cox regression analysis. Results: A total of 131 patients with 261 treated metastases were included in the analysis, with a median follow-up of 29 months (IQR, 18.5-41.3 months). After stereotactic ablative radiation, 70.2% of patients were classified as PSMA responders. Multivariable analysis demonstrated that PSMA response as a continuous variable was associated with a significantly worse MFS (hazard ratio = 1.003; 95% CI, 1.001-1.006; P = .016). Patients classified as PSMA responders were found to have a significantly improved median MFS of 39.9 versus 12 months (P = .001) compared with PSMA nonresponders. Our study is limited as it is a retrospective review of a heterogenous population. Conclusions: After stereotactic ablative radiation, PSMA-PET response appears to be a radiographic biomarker that correlates with MFS in omCSPC. This approach holds promise for guiding clinical management of omCSPC and should be validated in a prospective setting.

A case of radiation-induced bullous pemphigoid in a vulvar cancer patient.

•Radiation-induced bullous pemphigoid is a rare autoimmune disease.•There is only one prior documented case of radiation-induced bullous pemphigoid in a vulvar cancer patient.•A multidisciplinary approach is critical to identify and treat bullous pemphigoid.

Integrating innovative therapeutic strategies into the management of renal cell carcinoma.

Three emerging trends have occurred recently in renal cell carcinoma (RCC). First, over the last several decades there has been a marked increase in the diagnosis of RCC, with a corresponding decrease in the typical tumor size, resulting in an increased interest in less invasive approaches to primary tumor treatment. Second, while conventional radiotherapy plays a limited palliative role due to the relative radio-resistance of RCC, advances in immobilization and image guidance have led several investigators to consider stereotactic radiotherapy techniques (SRT) to overcome this resistance, with impressive results in the metastatic setting. In addition, preliminary use of SRT to treat the primary RCC tumor is underway. Thirdly, although RCC is resistant to conventional chemotherapy agents, exciting recent advances have emerged in the treatment of clear cell RCC, with the development of targeted agents in addition to immunotherapy-based treatments. In the current critical review we discuss these emerging trends in localized and systemic treatment as well as possible interesting combinations of the two modalities. Finally, we discuss the role of the new systemic agents in non-clear cell RCC.

A Flexible Approach for Assessing Heterogeneity of Causal Treatment Effects on Patient Survival Using Large Datasets with Clustered Observations.

Personalized medicine requires an understanding of treatment effect heterogeneity. Evolving toward causal evidence for scenarios not studied in randomized trials necessitates a methodology using real-world evidence. Herein, we demonstrate a methodology that generates causal effects, assesses the heterogeneity of the effects and adjusts for the clustered nature of the data. This study uses a state-of-the-art machine learning survival model, riAFT-BART, to draw causal inferences about individual survival treatment effects, while accounting for the variability in institutional effects; further, it proposes a data-driven approach to agnostically (as opposed to a priori hypotheses) ascertain which subgroups exhibit an enhanced treatment effect from which intervention, relative to global evidence-average treatment effects measured at the population level. Comprehensive simulations show the advantages of the proposed method in terms of bias, efficiency and precision in estimating heterogeneous causal effects. The empirically validated method was then used to analyze the National Cancer Database.

Modern Management of Localized Renal Cell Carcinoma- Is Ablation Part of the Equation?

While the gold-standard for management of localized renal cell carcinoma (RCC) is partial nephrectomy, recent ablative strategies are emerging as alternatives with comparable rates of complications and oncologic outcomes. Thermal ablation, in the form of radiofrequency ablation and cryoablation, is being increasingly accepted by professional societies, and is particularly recommended in patients with a significant comorbidity burden, renal impairment, old age, or in those unwilling to undergo surgery. Maturation of long-term oncologic outcomes has further allowed increased confidence in these management strategies. New and exciting ablation technologies such as microwave ablation, stereotactic body radiotherapy, and irreversible electroporation are emerging. In this article, we review the existing management options for localized RCC, with specific focus on the oncologic outcomes associated with the various ablation modalities.

Radiation Oncology Alternative Payment Model and Large Urban Academic Centers: Future Implications for Patients and Providers.

The radiation oncology alternative payment model (RO-APM) was developed by the Center for Medicare and Medicaid Innovation, a part of the Centers for Medicare & Medicaid Services, as a vehicle to optimize value for patients undergoing radiation therapy. By shifting reimbursement away from fee-for-service and toward a prospective bundled payment system, the RO-APM is intended to bend the cost curve in radiation oncology while preserving or even enhancing outcomes. As with prior large-scale policy initiatives, the nature and magnitude of the RO-APM's impact on care delivery will vary substantially depending on a host of local factors, including practice setting. Urban academic centers play a key role in radiation oncology by spearheading innovation, managing the most complicated cases, training the next generation of radiation oncologists, and often caring for vulnerable patient populations. Thus, to protect patients' access to this high-quality cancer care, it will be crucial to characterize the RO-APM's projected impact on large urban academic institutions before its implementation, including possible unintended adverse consequences. Here, we provide an overview of this seismic change in radiation oncology reimbursement and discuss its unique potential implications for large urban academic institutions as a means to facilitate necessary preparations and inform future revisions to the model.

A Framework for Patient-Centered Pathways of Care for Radiopharmaceutical Therapy: An ASTRO Consensus Document.

Radiopharmaceutical therapy (RPT) is an area of projected growth and importance with several agents in clinical use, new agents in late-phase clinical trials, and many others under testing and development. This article proposes a framework for developing pathways of care that can be broadly applied to all RPTs, representing the current status of RPT. It suggests foundational elements for many pathways of care for patients with cancer and concludes with areas in active development and the future horizon for RPT treatment centers. Developing a framework for patient-centered pathways of care is a critical step in establishing RPT as standard therapy for patients with a diverse spectrum of cancers. This expected increase in RPT treatment options will affect a much larger population of patients with complex cancer. It will also require enhanced coordination and collaboration among appropriately qualified personnel with diverse expertise in image acquisition, image interpretation, quantitative imaging, dosimetry calculation, radiation quality assurance and safety as well as oncology care and RPT-induced sequelae and response assessment. The essential role of this evolving RPT care team within multidisciplinary oncology care is a cornerstone of this framework for a patient-centered pathway of care for RPT. Given the status of current RPT practice and the horizon for future applications, this patient-centered pathway of care guidance is timely and should help inform future clinical RPT practice paradigms. A task force was recruited from the Theranostic Working Group of the American Society for Radiation Oncology (ASTRO) in May 2019 with equal representation from the nuclear medicine community. The task force expanded on a framework that was originally conceived by the Working Group for patient-centered care. This framework was developed to incorporate the strengths of both radiation oncologists and nuclear medicine physicians. The manuscript was then developed by the task force and posted on the ASTRO website for a 6-week public comment period ending in July 2020. Comments were adjudicated, and the draft was sent to external organizations for potential endorsement. This document was sent to the ASTRO Board of Directors in October 2020 for approval.

Drivers of Medicare Spending: A 15-Year Review of Radiation Oncology Charges Allowed by the Medicare Physician/Supplier Fee-for-Service Program Compared With Other Specialties.

PURPOSE: In 2019, the Centers for Medicare and Medicaid Services proposed a new radiation oncology alternative payment model aimed at reducing expenditures. We examined changes in aggregate physician Medicare charges allowed per specialty to provide contemporary context to proposed changes and hypothesize that radiation oncology charges remained stable through 2017. METHODS AND MATERIALS: Medicare physician/supplier utilization, program payments, and balance billing for original Medicare beneficiaries, by physician specialty, were analyzed from 2002 to 2017. Total allowed charges under the physician/supplier fee-for-service program, inflation-adjusted charges, and percent of total charges billed per specialty were examined. We adjusted for inflation using the consumer price index for medical care from the US Bureau of Labor Statistics. RESULTS: Total allowed charges increased from $83 billion in 2002 to $138 billion in 2017. The specialties accounting for the most charges billed to Medicare were internal medicine and ophthalmology. Radiation oncology charges accounted for 1.2%, 1.6%, and 1.4% of total charges allowed by Medicare in 2002, 2012, and 2017, respectively. Radiation oncology charges allowed increased 44% from 2002 to 2012 ($987.6 million to $1.42 billion) but decreased by 19% from 2012 to 2017 ($1.15 billion), adjusted for inflation. Total charges allowed by internal medicine decreased 2% from 2002 to 2012 ($8.53 to $8.36 billion), adjusted for inflation, and decreased 16% from 2012 to 2017 ($7.05 billion). When adjusting for inflation, ophthalmology charges increased 18% from 2002 to 2012 ($4.53 to $5.36 billion) and increased 3% from 2012 to 2017 ($5.5 billion). CONCLUSIONS: Radiation oncology physician charges represent a small fraction of total Medicare expenses and are not a driver for Medicare spending. Aggregate inflation-adjusted charges by radiation oncology have dramatically declined in the past 5 years and represent a stable fraction of total Medicare charges. The need to target radiation oncology with cost-cutting measures may be overstated.

US Radiation Oncologists (Re)Defined: An American Society for Radiation Oncology Scope of Practice Study.

PURPOSE: To assess US radiation oncologists' views on practice scope and the ideal role of the radiation oncologist (RO), the American Society for Radiation Oncology (ASTRO) conducted a scope of practice survey. METHODS AND MATERIALS: In spring 2019, ASTRO distributed an online survey to 3822 US RO members. The survey generated 984 complete responses (26% response rate) for analysis. Face validity testing confirmed respondents were representative of ASTRO's RO membership. RESULTS: Nearly all respondents agreed that "ROs should be leaders in oncologic care." Respondents indicated the ideal approach to patient care was to provide "an independent opinion on radiation therapy and other treatment options" (82.5%) or "an independent opinion on radiation therapy but not outside of it" (16.1%), with only 1.4% favoring provision of "radiation therapy at the request of the referring physician" as the ideal approach. Actual practice fully matched the ideal approach in 18.2% of respondents. For the remaining majority, actual practice did not always match the ideal and comprised a mix of approaches that included providing radiation at the referring physician's request 24.0% of the time on average. Reasons for the mismatch included fear of alienating referring physicians and concern for offering an unwelcome opinion. One-fifth of respondents expressed a desire to expand the scope of service though interspecialty politics and insufficient training were potential barriers. Respondents interested in expanding scope of practice were on average earlier in their career (average years in practice 13.3) than those who were not interested (average years in practice 17.2, P < .001). Radiopharmaceuticals administration, medical marijuana and anticancer medications prescribing, and RO inpatient service represented areas of interest for expansion but also knowledge gaps. CONCLUSIONS: These results provide insight regarding US ROs' scope of practice and attitudes on the ideal role of the RO. For most ROs, to provide an independent opinion on treatment options represented the ideal approach to care, but barriers such as concern of alienating referring physicians prevented many from fully adhering to their ideal in practice. Actual practice commonly comprised a mixed approach, including the least favored scenario of delivering radiation at the referring physician's request one-quarter of the time, highlighting the influence of interspecialty politics on practice behavior. Advocacy for open communication and meaningful interdisciplinary collaboration presents an actionable solution toward a more balanced relationship with other specialties as ROs strive to better fulfill the vision of being leaders in oncologic care and being our best for our patients. The study also identified interest in expanding into nontraditional domains that offer opportunities to address unmet needs in the cancer patient's journey and elevate radiation oncology within the increasingly value-based US health care system.

A Statewide Multi-Institutional Study of Asymptomatic Pretreatment Testing of Radiation Therapy Patients for SARS-CoV-2 in a High-Incidence Region of the United States.

PURPOSE: Our purpose was to establish the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in asymptomatic patients scheduled to receive radiation therapy and its effect on management decisions. METHODS AND MATERIALS: Between April 2020 and July 2020, patients without influenza-like illness symptoms at four radiation oncology departments (two academic university hospitals and two community hospitals) underwent polymerase chain reaction testing for SARS-CoV-2 before the initiation of treatment. Patients were tested either before radiation therapy simulation or after simulation but before treatment initiation. Patients tested for indications of influenza-like illness symptoms were excluded from this analysis. Management of SARS-CoV-2-positive patients was individualized based on disease site and acuity. RESULTS: Over a 3-month period, a total of 385 tests were performed in 336 asymptomatic patients either before simulation (n = 75), post-simulation, before treatment (n = 230), or on-treatment (n = 49). A total of five patients tested positive for SARS-CoV-2, for a pretreatment prevalence of 1.3% (2.6% in north/central New Jersey and 0.4% in southern New Jersey/southeast Pennsylvania). The median age of positive patients was 58 years (range, 38-78 years). All positive patients were white and were relatively equally distributed with regard to sex (2 male, 3 female) and ethnicity (2 Hispanic and 3 non-Hispanic). The median Charlson comorbidity score among positive patients was five. All five patients were treated for different primary tumor sites, the large majority had advanced disease (80%), and all were treated for curative intent. The majority of positive patients were being treated with either sequential or concurrent immunosuppressive systemic therapy (80%). Initiation of treatment was delayed for 14 days with the addition of retesting for four patients, and one patient was treated without delay but with additional infectious-disease precautions. CONCLUSIONS: Broad-based pretreatment asymptomatic testing of radiation oncology patients for SARS-CoV-2 is of limited value, even in a high-incidence region. Future strategies may include focused risk-stratified asymptomatic testing.

Impact of the Coronavirus Disease of 2019 Pandemic on Radiation Oncology Clinical Decision Making in a High-Prevalence Environment.

PURPOSE: This study aimed to define how the coronavirus disease of 2019 (COVID-19) pandemic affected the role, timing, and delivery of radiation therapy (RT) in a high-prevalence region at the height of the initial U.S. outbreak. METHODS AND MATERIALS: We performed a retrospective review of all patients seen at 3 radiation oncology departments within the Rutgers Robert Wood Johnson Barnabas Health system in New Jersey during the initial COVID-19 surge. The primary endpoints were to define and quantify COVID-related, radiation-specific care changes, and identify predictive factors of experiencing COVID-related care changes. RESULTS: A total of 545 patients with cancer were seen during the study period, 99 of whom (18.1%) experienced ≥1 COVID-related care change. RT delays were the most common, accounting for 51.5% of all care changes. Physician-directed delays accounted for 41.2% of RT delays, and patient fears, COVID testing, and access barriers were responsible for 27.5%, 17.6%, and 13.7%, respectively. Patient age (P = .040), intent of treatment (P = .047), and cancer type (P < .001) were significantly associated with experiencing a COVID-related care change, as we found that older, curative intent and patients with rectal cancer were more likely to experience care changes. On multivariate analysis, patient age remained significant when controlling for treatment intent and cancer type. CONCLUSIONS: Our study provides a perspective on how care was adapted to protect patients with cancer during a pandemic while maximizing disease control. The positive correlation between age and likelihood of care changes may reflect extra precaution taken with older patients given their vulnerability to severe COVID illness. The lower observed likelihood of COVID-related care changes among patients undergoing palliative RT may reflect either the more urgent needs addressed by palliative RT or simply be logistical, because palliative radiation is often delivered in short courses with less exposure risk. Assessing adaptations others have implemented and monitoring how they affect patient outcomes will be crucial.

The Impact of COVID-19 on Brachytherapy During the Pandemic: A Rutgers-Robert Wood Johnson Barnabas Health Multisite Experience.

PURPOSE: This study aimed to evaluate whether the coronavirus disease of 2019 (COVID-19) pandemic resulted in treatment delays in patients scheduled for or undergoing brachytherapy. METHODS AND MATERIALS: A retrospective cohort study was conducted across 4 affiliated sites after local institutional review board approval. The eligibility criteria were defined as all patients with cancer whose treatment plan included brachytherapy during the COVID-19 pandemic from February 24, 2020 to June 30, 2020. Treatment delays, cancellations, alterations of fractionation regimens, and treatment paradigm changes were evaluated. RESULTS: A total of 47 patients were eligible for the analysis. Median patient age at the time of treatment was 62 years (interquartile range, 56-70 years). Endometrial, cervical, and prostate cancers were the most common sites included in this analysis. Three patients (6.4%) with cervical cancer were diagnosed with COVID-19 during the course of their treatment. Interruptions of external beam radiation therapy (EBRT), cancellations of EBRT, cancellations of brachytherapy, and treatment delays due to COVID occurred in 5 (10.6%), 3 (6.4%), 8 (17%), and 9 (19%) patients, respectively. The mean and median number of days delayed for patients who experienced treatment interruptions were 16.3 days (standard deviation: 13.9 days) and 14 days (interquartile range, 5.75-23.75 days), respectively. For patients with cervical cancer, the mean and median overall treatment times defined as the time from the start of EBRT to the end of brachytherapy were 56 and 49 days, respectively. CONCLUSIONS: Despite the challenges the health care system faced during the pandemic, most patients with cancer were safely treated with minor treatment delays and interruptions. Long-term follow up is needed to assess the impact of COVID-19 and treatment interruptions on oncologic outcomes.

A feasibility study of novel ultrasonic tissue characterization for prostate-cancer diagnosis: 2D spectrum analysis of in vivo data with histology as gold standard.

This study demonstrates the feasibility of using a novel 2D spectrum ultrasonic tissue characterization (UTC) technique for prostate-cancer diagnosis. Normalized 2D spectra are computed by performing Fourier transforms along the range (beam) and the cross-range directions of the digital radio-frequency echo data, then dividing by a reference spectrum. This 2D spectrum method provides axial and lateral information of tissue microstructures, an improvement over the current 1D spectrum analysis which only provides axial information. A pilot study was conducted on four prostate-cancer patients who underwent radical prostatectomies. Cancerous and noncancerous regions of interest, identified through histology, were compared using four 2D spectral parameters: peak value and 3 dB width of the radially integrated spectral power (RISP), slope and intercept of the angularly integrated spectral power (AISP). For noncancerous and cancerous prostatic tissues, respectively, our investigation yielded 23 +/- 1 and 26 +/- 1 dB for peak value of RISP, 7.8 +/- 0.5 degrees and 7.6 +/- 0.6 degrees for 3 dB of RISP, -2.1 +/- 0.2 and -2.7 +/- 0.4 dB/MHz for slope of AISP, and 92 +/- 5 and 112 +/- 6 dB for intercept of AISP. Preliminary results indicated that 2D spectral UTC has the potential for identifying tumor-bearing regions within the prostate gland.