Faculty Bibliography

[This corrects the article DOI: 10.3389/fonc.2023.1132777.].

INTRODUCTION/UNASSIGNED:Brain metastases are the most common intracranial tumor diagnosed in adults. In patients treated with stereotactic radiosurgery, the incidence of post-treatment radionecrosis appears to be rising, which has been attributed to improved patient survival as well as novel systemic treatments. The impacts of concomitant immunotherapy and the interval between diagnosis and treatment on patient outcomes are unclear. METHODS/UNASSIGNED:This single institution, retrospective study consisted of patients who received single or multi-fraction stereotactic radiosurgery for intact brain metastases. Exclusion criteria included neurosurgical resection prior to treatment and treatment of non-malignant histologies or primary central nervous system malignancies. A univariate screen was implemented to determine which factors were associated with radionecrosis. The chi-square test or Fisher's exact test was used to compare the two groups for categorical variables, and the two-sample t-test or Mann-Whitney test was used for continuous data. Those factors that appeared to be associated with radionecrosis on univariate analyses were included in a multivariable model. Univariable and multivariable Cox proportional hazards models were used to assess potential predictors of time to local failure and time to regional failure. RESULTS/UNASSIGNED:A total of 107 evaluable patients with a total of 256 individual brain metastases were identified. The majority of metastases were non-small cell lung cancer (58.98%), followed by breast cancer (16.02%). Multivariable analyses demonstrated increased risk of radionecrosis with increasing MRI maximum axial dimension (OR 1.10, p=0.0123) and a history of previous whole brain radiation therapy (OR 3.48, p=0.0243). Receipt of stereotactic radiosurgery with concurrent immunotherapy was associated with a decreased risk of local failure (HR 0.31, p=0.0159). Time interval between diagnostic MRI and first treatment, time interval between CT simulation and first treatment, and concurrent immunotherapy had no impact on incidence of radionecrosis or regional failure. DISCUSSION/UNASSIGNED:An optimal time interval between diagnosis and treatment for intact brain metastases that minimizes radionecrosis and maximizes local and regional control could not be identified. Concurrent immunotherapy does not appear to increase the risk of radionecrosis and may improve local control. These data further support the safety and synergistic efficacy of stereotactic radiosurgery with concurrent immunotherapy.

Purpose/UNASSIGNED:Whole gland cryoablation is a guideline-approved definitive treatment for localized prostate cancer, and is being explored for partial gland ablation. However, there is limited data regarding management of cryoablation failures. Stereotactic body radiation therapy (SBRT) is a well-established method of primary treatment for prostate cancer. Here we review salvage SBRT after cryoablation failures. Methods and Materials/UNASSIGNED:A large database of patients treated with definitive SBRT was interrogated to identify those who underwent primary cryoablation. All patients were determined to have progressive disease based on a rising prostate specific antigen and/or postcryoablation biopsy. All patients were treated with SBRT over 5 treatment fractions using a robotic radiosurgical platform. Baseline cryoablation characteristics and pre- and posttreatment Expanded Prostate Cancer Index Composite questionnaires were analyzed. Acute and late toxicity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Cancer outcomes after salvage SBRT were stratified by disease and treatment characteristics. Results/UNASSIGNED:A total of 51 patients were identified who underwent cryoablation followed by salvage SBRT. The majority (47%) were found to have intermediate-risk disease at the time of SBRT salvage and most commonly were treated with 3500 cGy in 5 fractions to the prostate and seminal vesicles. Only 1 grade 3+ toxicity was identified. Patient-reported quality of life metrics after SBRT salvage followed prior patterns observed in the de novo SBRT setting. With a median follow-up of 40 months, 76% of the cohort demonstrated disease control. Median time to prostate cancer recurrence was 57.5 months, and recurrence was predominantly seen in patients with underlying high-risk disease. Conclusions/UNASSIGNED:This is the largest cohort of patients treated with any radiation therapy salvage after cryoablation and the first institution to report SBRT as a modality of salvage. Salvage SBRT after cryoablation results in low rates of high-grade toxicity, acceptable changes in patient-reported quality of life, and durable rates of long-term oncologic control.

In this review we outline the current evidence for the use of hydrogel rectal spacers in the treatment paradigm for prostate cancer with external beam radiation therapy. We review their development, summarize clinical evidence, risk of adverse events, best practices for placement, treatment planning considerations and finally we outline a framework and rationale for the utilization of rectal spacers when treating unfavorable risk prostate cancer with dose escalated Stereotactic Body Radiation Therapy (SBRT).

PURPOSE/OBJECTIVE(S): Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. MATERIALS/METHODS: Between April 2006 and December 2020, 3626 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator and followed at an academic institution. 3173 (87.51%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 453 (12.49%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 865 (23.86%) of these cases. The mean age was 67.3 years old. 47 patients were younger than 50 years old (mean age 46.6). 3,579 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 44.68%, 48.94%, 6.38% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 24.76%, 56.83%, 18.41% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 48.94%, 7 in 46.81%, and 8-10 in 4.25%. 44 younger patients were treated with SBRT alone. 3 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.6%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 30.57%, 7 in 54.06%, and 8-10 in 15.37%. 3129 were treated with SBRT alone. 450 patients also received supplemental external beam radiation (median dose 4500cGY) and 860 patients (24.03%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen.
RESULT(S): At 64.8 months (range 7 months - 177 months) the 5-year biochemical relapse free survival was 98% in younger patients compared to 99% in older patients using the Phoenix definition of biochemical failure. The 5-year median post treatment PSA was 0.15 in the younger patients and 0.20 in the older patients. There were no significant differences in biochemical relapse free survival between the groups.
CONCLUSION(S): This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With 5-year follow up, SBRT is an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.
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PURPOSE/OBJECTIVE(S): Historically, caution has been warranted when irradiating large target volumes particularly those in close proximity to organs at risk. Prior literature has demonstrated an increased incidence of GI and GU toxicity when men with large prostates were treated with conventionally fractionated radiation therapy. However, there is very limited data regarding the clinical outcomes when SBRT is used as a definitive treatment modality. We explore the long term oncologic, toxicity, and patient reported outcomes of men treated with definitive SBRT with ultra-large prostate glands (>= 100 cc.) MATERIALS/METHODS: From 2006 to 2020, a total of 3,393 patients with low and intermediate risk prostate cancer were treated with definitive robotic-SBRT. We performed a retrospective review to identify all patients in this cohort with pre-treatment prostate volumes >= 100 cc. Prostate volume was measured at the time of treatment regardless of ADT incorporation. All patients were treated to a total dose of 35-36.25 Gy in 5 fractions. All patients had a minimum of 2 years follow-up and were given pre- and post-treatment EPIC questionnaires at defined intervals. Biochemical control was assessed using the Phoenix definition. Late toxicity was defined using CTCAE version 5.0 and was characterized as occurring >= 6 months post treatment.
RESULT(S): A total of 67 patients were identified with >= 100 cc prostate glands. Of these, 18 patients received ADT prior to treatment. Overall, the median prostate volume was 139.37 cc (range 100.1 - 227 cc). The D'Amico risk classification was low (n=19) and intermediate (n=48). The median age was 70 years (range 54 - 87 years) and the median pretreatment PSA was 8.7 ng/ml. The mean pre-treatment EPIC bowel and urinary scores were 87.8 and 79.7, respectively. One-month following SBRT, mean EPIC bowel and urinary scores worsened to 83.6 and 76.5, respectively. Three months following SBRT, mean epic bowel and urinary scores continued to decline to 83.2 and 77.1, respectively. However, bowel and bladder symptomatology improved by 1 year to 86.16 and 77.19, and by 2 years improved above baseline to 90.00 and 85.78, respectively. There were no high grade (3+) GI toxicities observed, though one grade 3 urinary retention was identified. Excellent oncologic outcomes were observed with a 5-year median PSA nadir of 0.6 ng/mL and a biochemical relapse free survival (bRFS) of 100% at 5 years.
CONCLUSION(S): SBRT has been demonstrated to be oncologically effective with minimal toxicity, and has become a more ubiquitous radiation option in men with localized prostate cancer. Although there is a historical reticence for treatment of men with large glands, we report excellent clinical outcomes. Five-year bRFS was 100% and grade 3+ urinary toxicity was 2%. Although EPIC scores transiently dropped at 1 and 3 months following SBRT, resolution was seen by 1 year following treatment. The use of SBRT for the treatment of localized prostate cancer in men with ultra-large prostate gland is feasible with minimal toxicity.
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BACKGROUND:Historically, IBD has been thought to increase the underlying risk of radiation related toxicity in the treatment of prostate cancer. In the modern era, contemporary radiation planning and delivery may mitigate radiation-related toxicity in this theoretically high-risk cohort. This is the first manuscript to report clinical outcomes for men diagnosed with prostate cancer and underlying IBD curatively treated with stereotactic body radiation therapy (SBRT). METHODS:A large institutional database of patients (n = 4245) treated with SBRT for adenocarcinoma of the prostate was interrogated to identify patients who were diagnosed with underlying IBD prior to treatment. All patients were treated with SBRT over five treatment fractions using a robotic radiosurgical platform and fiducial tracking. Baseline IBD characteristics including IBD subtype, pre-SBRT IBD medications, and EPIC bowel questionnaires were reviewed for the IBD cohort. Acute and late toxicity was evaluated using the CTCAE version 5.0. RESULTS:A total of 31 patients were identified who had underlying IBD prior to SBRT for the curative treatment of prostate cancer. The majority (n = 18) were diagnosed with ulcerative colitis and were being treated with local steroid suppositories for IBD. No biochemical relapses were observed in the IBD cohort with early follow up. High-grade acute and late toxicities were rare (n = 1, grade 3 proctitis) with a median time to any GI toxicity of 22 months. Hemorrhoidal flare was the most common low-grade toxicity observed (n = 3). CONCLUSION/CONCLUSIONS:To date, this is one of the largest groups of patients with IBD treated safely and effectively with radiation for prostate cancer and the only review of patients treated with SBRT. Caution is warranted when delivering therapeutic radiation to patients with IBD, however modern radiation techniques appear to have mitigated the risk of GI side effects.

BACKGROUND:Ethnicity and insurance status have been shown to impact odds of presenting with metastatic cancer, however, the interaction of these two predictors is not well understood. We evaluate the difference in odds of presenting with metastatic disease in minorities compared to white patients despite access to the same insurance across three common cancer types. METHODS:Using the National Cancer Database, a multilevel logistic regression model that estimated the odds of metastatic disease was fit, adjusting for covariates including year of diagnosis, ethnicity, insurance, income, and region. We included adults diagnosed with metastatic prostate, non-small cell lung cancer (NSCLC), and breast cancer from 2004 to 2015. RESULTS:The study cohort consisted of 1 191 241 prostate cancer (PCa), 1 310 986 breast cancer (BCa), and 1 183 029 NSCLC patients. Private insurance was the most protective factor against metastatic presentation. Odds of presenting with metastatic disease were 0.190 [95% CI, 0.182-0.198], 0.616 [95% CI, 0.602-0.630], and 0.270 [95% CI, 0.260-0.279] for PCa, NSCLC, and BCa compared to uninsured patients, respectively. Private insurance provided the most significant benefit to non-Hispanic White PCa patients with 81% reduction in odds of metastatic presentation and conferred the least benefit to African-American NSCLC patients at 30.4% reduction in odds of metastatic presentation. CONCLUSIONS:Insurance status provided the single most protective effect against metastatic presentation. This benefit varied for minorities despite similar insurance. Reducing metastatic disease presentation rates requires addressing social barriers to care independent of insurance.