Faculty Bibliography

PURPOSE:To investigate predictors associated with post-treatment biopsy outcomes after stereotactic body radiotherapy (SBRT) for localized prostate cancer. MATERIALS AND METHODS:257 patients treated with prostate SBRT to dose levels of 32.5 Gy to >40 Gy in 5-6 fractions underwent a post-treatment biopsy performed approximately two years after treatment to evaluate local control status. 73 had% intermediate-risk disease (n = 187) and the remaining 17% (n = 43) and 10% (n = 27) had low-risk and high-risk disease, respectively. RESULTS:The incidence of positive, negative, and treatment-effect post-treatment biopsies were 15.6%, 57.6%, and 26.8%, respectively. The incidence of a positive biopsy according to dose was 37.5% (n = 9/24), 21.4% (n = 6/28), 19.4% (n = 6/31), and 10.9% (n = 19/174) for 32.5 Gy, 35 Gy, 37.5 Gy, and >40 Gy, respectively. In a multivariable model, patients treated with SBRT doses of <40 Gy and those with unfavorable-intermediate-risk or high-risk disease had higher likelihood of a positive post-treatment biopsy. A positive post-SBRT biopsy was associated with a significantly higher likelihood of subsequent PSA relapse at five years (Positive biopsy: 57%, 95% CI: 29-77% compared to negative biopsy: 7%, 95% CI: 3-14%; p < 0.001). CONCLUSION:Based on two-year post-SBRT biopsies, excellent tumor control was achieved when dose levels of 40 Gy or higher were used. Standard SBRT dose levels of 35-37.5 Gy were associated with a higher likelihood of a positive post-treatment biopsy. Two-year positive post-treatment biopsies pre-dated the development of PSA failure in the majority of patients.

BACKGROUND AND PURPOSE:Artificial intelligence advances have stimulated a new generation of autosegmentation, however clinical evaluations of these algorithms are lacking. This study assesses the clinical utility of deep learning-based autosegmentation for MR-based prostate radiotherapy planning. MATERIALS AND METHODS:Data was collected prospectively for patients undergoing prostate-only radiation at our institution from June to December 2019. Geometric indices (volumetric Dice-Sørensen Coefficient, VDSC; surface Dice-Sørensen Coefficient, SDSC; added path length, APL) compared automated to final contours. Physicians reported contouring time and rated autocontours on 3-point protocol deviation scales. Descriptive statistics and univariable analyses evaluated relationships between the aforementioned metrics. RESULTS:Among 173 patients, 85% received SBRT. The CTV was available for 167 (97%) with median VDSC, SDSC, and APL for CTV (prostate and SV) 0.89 (IQR 0.83-0.95), 0.91 (IQR 0.75-0.96), and 1801 mm (IQR 1140-2703), respectively. Physicians completed surveys for 43/55 patients (RR 78%). 33% of autocontours (14/43) required major "clinically significant" edits. Physicians spent a median of 28 min contouring (IQR 20-30), representing a 12-minute (30%) time savings compared to historic controls (median 40, IQR 25-68, n = 21, p < 0.01). Geometric indices correlated weakly with contouring time, and had no relationship with quality scores. CONCLUSION:Deep learning-based autosegmentation was implemented successfully and improved efficiency. Major "clinically significant" edits are uncommon and do not correlate with geometric indices. APL was supported as a clinically meaningful quantitative metric. Efforts are needed to educate and generate consensus among physicians, and develop mechanisms to flag cases for quality assurance.

PURPOSE:We investigated whether T2-weighted magnetic resonance imaging findings could improve upon established prognostic indicators of metastatic disease and prostate cancer specific survival. MATERIALS AND METHODS:For a cohort of 3,406 consecutive men who underwent prostate magnetic resonance imaging before prostatectomy (2,160) or radiotherapy (1,246) between 2001 and 2006, T2-weighted magnetic resonance imaging exams were retrospectively interpreted and categorized as I) no focal suspicious lesion, II) organ confined focal lesion, III) focal lesion with extraprostatic extension or IV) focal lesion with seminal vesicle invasion. Clinical risk was recorded based on European Association of Urology (EAU) guidelines and the Cancer of the Prostate Risk Assessment (CAPRA) scoring system. Survival probabilities and c-indices were estimated using Cox models and inverse probability censoring weights, respectively. RESULTS:The median followup was 10.8 years (IQR 8.6-13.0). Higher magnetic resonance imaging categories were associated with a higher likelihood of developing metastases (HR 3.5-18.1, p <0.001 for all magnetic resonance imaging categories) and prostate cancer death (HR 3.1-29.7, p <0.001-0.025); these associations were statistically independent of EAU risk categories, CAPRA scores and treatment type (surgery vs radiation). Combining EAU risk or CAPRA scores with magnetic resonance imaging categories significantly improved prognostication of metastases (c-indices: EAU: 0.798, EAU + magnetic resonance imaging: 0.872; CAPRA: 0.808, CAPRA + magnetic resonance imaging: 0.877) and prostate cancer death (c-indices: EAU 0.813, EAU + magnetic resonance imaging: 0.889; CAPRA: 0.814, CAPRA + magnetic resonance imaging: 0.892; p <0.001 for all). CONCLUSION:Magnetic resonance imaging findings of localized prostate cancer are associated with clinically relevant long-term oncologic outcomes. Combining magnetic resonance imaging and clinicopathological data results in more accurate prognostication, which could facilitate individualized patient management.

BACKGROUND:Radiation therapy is one of the most commonly used cancer therapeutics but genetic determinants of clinical benefit are poorly characterized. Pathogenic germline variants in ATM are known to cause ataxia-telangiectasia, a rare hereditary syndrome notable for marked radiosensitivity. In contrast, somatic inactivation of ATM is a common event in a wide variety of cancers, but its clinical actionability remains obscure. METHODS:We analyzed 20 107 consecutively treated advanced cancer patients who underwent targeted genomic sequencing as part of an institutional genomic profiling initiative and identified 1085 harboring a somatic or germline ATM mutation, including 357 who received radiotherapy (RT). Outcomes of irradiated tumors harboring ATM loss-of-function (LoF) mutations were compared with those harboring variants of unknown significance. All statistical tests were 2-sided. RESULTS:Among 357 pan-cancer patients who received 727 courses of RT, genetic inactivation of ATM was associated with improved radiotherapeutic efficacy. The 2-year cumulative incidence of irradiated tumor progression was 13.2% vs 27.5% for tumors harboring an ATM LoF vs variant of unknown significance allele, respectively (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.77, P = .001). The greatest clinical benefit was seen in tumors harboring biallelic ATM inactivation (HR = 0.19, 95% CI = 0.06 to 0.60, P = .005), with statistically significant benefit also observed in tumors with monoallelic ATM inactivation (HR = 0.57, 95% CI = 0.35 to 0.92, P = .02). Notably, ATM LoF was highly predictive of outcome in TP53 wild-type tumors but not among TP53-mutant tumors. CONCLUSIONS:We demonstrate that somatic ATM inactivation is associated with markedly improved tumor control following RT. The identification of a radio-sensitive tumor phenotype across multiple cancer types offers potential clinical opportunities for genomically guided RT.

Among 84,447 radiotherapy (RT) courses for Medicare beneficiaries age ≥ 65 with prostate cancer treated with external beam RT (EBRT), brachytherapy, or both, 42,608 (51%) were delivered in hospital-affiliated and 41,695 (49%) in freestanding facilities. Freestanding centers were less likely to use EBRT + brachytherapy than EBRT (OR 0.84 [95%CI 0.84-0.84]; p < .001). Treatment was more costly in freestanding centers (mean difference $2,597 [95%CI $2,475-2,719]; p < .001). Adjusting for modality and fractionation, RT in hospital-affiliated centers was more costly (mean difference $773 [95%CI $693-853]; p < .001). Freestanding centers utilized more expensive RT delivery, but factors unrelated to RT modality or fractionation rendered RT more costly at hospital-affiliated centers.

PURPOSE:The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. METHODS AND MATERIALS:The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. RESULTS:LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure. CONCLUSIONS:LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.

PURPOSE/OBJECTIVE:There are limited data regarding high-dose stereotactic body radiation therapy (SBRT) for prostate cancer in patients with poor baseline urinary function. The purpose of this study was to evaluate genitourinary (GU) toxicity and changes in patient-reported symptom severity scores after prostate SBRT in men with a high pretreatment International Prostate Symptom Score (IPSS). METHODS AND MATERIALS/METHODS:Seven hundred fifty-three patients treated with prostate SBRT at our institution from 2012 to 2019 were identified, of whom 72 consecutive patients with baseline IPSS ≥15 were selected for this study. GU toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and IPSS were prospectively documented at each follow-up visit. Univariable logistic regression was used to evaluate for potential predictors of GU toxicity. RESULTS:= .001). CONCLUSIONS:In men with baseline IPSS ≥15 managed with prostate SBRT, the rate of severe GU toxicity was low and patient-reported symptoms generally improved over time. Thus, high pretreatment IPSS should not deter clinicians from offering prostate SBRT.