A Contemporary Report of Low-Dose-Rate Brachytherapy for Prostate Cancer Using MRI for Risk Stratification: Disease Outcomes and Patient-Reported Quality of Life.

PURPOSE: We examined a prospective consecutive cohort of low dose rate (LDR) brachytherapy for prostate cancer to evaluate the efficacy of monotherapy for unfavorable-intermediate risk (UIR) disease, and explore factors associated with toxicity and quality of life (QOL). METHODS: 149 men with prostate cancer, including 114 staged with MRI, received Iodine-125 brachytherapy alone (144-145 Gy) or following external beam radiation therapy (110 Gy; EBRT). Patient-reported QOL was assessed by the Expanded Prostate Index Composite (EPIC) survey, and genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively recorded (CTC v4.0). Global QOL scores were assessed for decline greater than the minimum clinically important difference (MCID). Univariate analysis (UVA) was performed, with 30-day post-implant dosimetry covariates stratified into quartiles. Median follow-up was 63 mo. RESULTS: Men with NCCN low (n = 42) or favorable-intermediate risk (n = 37) disease were treated with brachytherapy alone, while most with high-risk disease had combined EBRT (n = 17 of 18). Men with UIR disease (n = 52) were selected for monotherapy (n = 42) based on clinical factors and MRI findings. Freedom from biochemical failure-7 yr was 98%. Of 37 men with MRI treated with monotherapy for UIR disease, all 36 men without extraprostatic extension were controlled. Late Grade 2+/3+ toxicity occurred in 55/3% for GU and 8/2% for GI, respectively. Fifty men were sexually active at baseline and had 2 yr sexual data; 37 (74%) remained active at 2 yr. Global scores for urinary incontinence (UC), urinary irritation/obstruction (UIO), bowel function, and sexual function (SF) showed decreases greater than the MCID (p < 0.05) in UC at 2 mo, UIO at 2 and 6 mo, and SF at 2-24 mo, and >5 yr. Analysis did not reveal any significant associations with any examined rectal or urethral dosimetry for late toxicity or QOL. CONCLUSION: Disease outcomes and patient-reported QOL support LDR brachytherapy, including monotherapy for UIR disease.

STK11 Inactivation Predicts Rapid Recurrence in Inoperable Early-Stage Non-Small-Cell Lung Cancer.

PURPOSE: Molecular factors predicting relapse in early-stage non-small-cell lung cancer (ES-NSCLC) are poorly understood, especially in inoperable patients receiving radiotherapy (RT). In this study, we compared the genomic profiles of inoperable and operable ES-NSCLC. MATERIALS AND METHODS: This retrospective study included 53 patients with nonsquamous ES-NSCLC (stage I-II) treated at a single institution (University of Chicago) with surgery (ie, operable; n = 30) or RT (ie, inoperable; n = 23) who underwent tumor genomic profiling. A second cohort of ES-NSCLC treated with RT (Stanford, n = 39) was included to power clinical analyses. Prognostic gene alterations were identified and correlated with clinical variables. The primary clinical end point was the correlation of prognostic genes with the cumulative incidence of relapse, disease-free survival, and overall survival (OS) in a pooled RT cohort from the two institutions (N = 62). RESULTS: Although the surgery cohort exhibited lower rates of relapse, the RT cohort was highly enriched for somatic STK11 mutations (43% v 6.7%). Receiving supplemental oxygen (odds ratio [OR] = 5.5), 20+ pack-years of tobacco smoking (OR = 6.1), and Black race (OR = 4.3) were associated with increased frequency of STK11 mutations. In the pooled RT cohort (N = 62), STK11 mutation was strongly associated with inferior oncologic outcomes: 2-year incidence of relapse was 62% versus 20% and 2-year OS was 52% versus 85%, remaining independently prognostic on multivariable analyses (relapse: subdistribution hazard ratio = 4.0, P = .0041; disease-free survival: hazard ratio, 6.8, P = .0002; OS: hazard ratio, 6.0, P = .022). STK11 mutations were predominantly associated with distant failure, rather than local. CONCLUSION: In this cohort of ES-NSCLC, STK11 inactivation was associated with poor oncologic outcomes after RT and demonstrated a novel association with clinical hypoxia, which may underlie its correlation with medical inoperability. Further validation in larger cohorts and investigation of effective adjuvant systemic therapies may be warranted.

Brain arteriovenous malformation flow after stereotactic radiosurgery: Role of quantitative MRA.

BACKGROUND: Stereotactic radiosurgery (SRS) is a current therapeutic option for treatment of arteriovenous malformations (AVMs) located in deep or eloquent brain regions. Obliteration usually occurs in a delayed fashion, with an expected latency of 3-5 years. Here, we assess how AVM flow correlates with volume before and after SRS treatment. METHODS: Patients with supratentorial AVM treated with SRS at our institution between 2012-2022 were retrospectively reviewed. Patients were included if Quantitative Magnetic Resonance Angiography (QMRA) study was performed at baseline and at least at the first follow-up. Correlation between AVM flow and volume before and after treatment was evaluated. AVM flow and volume were additionally assessed for obliteration using the non-parametric receiver operating characteristic (ROC) curve. RESULTS: Twelve patients with radiologic follow-up imaging were included. Eight patients presented AVM rupture, one of which occurred after radiosurgical treatment. Three patients underwent embolization prior SRS. Mean AVM initial volume was 3.8 cc (0.1-12.4 cc), mean initial flow 174 ml/min (11-604 ml/min), both variables showed progressive reduction at follow-up (range 3-57 months); and flow decreased with volume reduction (p < 0.001). Area under the ROC was 0.914 for both AVM flow and volume with obliteration (p = 0.019). CONCLUSIONS: AVM flow significantly decreased after SRS treatment, reflecting volume reduction. Baseline AVM flow and volume both predicted obliteration. QMRA provides additional non-invasive information to monitor patients after radiosurgical treatment.

Decreased overall survival in patients with locally advanced head and neck cancer receiving definitive radiotherapy and concurrent cetuximab: National Cancer Database analysis.

BACKGROUND: Recently, randomized trials have questioned the efficacy of cetuximab-based bioradiotherapy compared to chemoradiation for patients with squamous cell carcinoma of the oropharynx, larynx, and hypopharynx (HNSCC). We compared the OS of patients treated with radiotherapy alone (RTonly), chemoradiotherapy (chemoRT), and bioradiotherapy (cetuxRT). METHODS: Patients with stage III-IVB HNSCC treated with RTonly, chemoRT, or cetuxRT were identified in the National Cancer Database. OS was estimated using Cox proportional hazards. Analyses were conducted on the overall cohort and propensity matched cohorts. RESULTS: 31 014 patients were treated with RTonly (22%), chemoRT (72%), or cetuxRT (6%) from 2013 to 2016. The 2-year OS was 69% for RTonly, 79% for chemoRT, and 66% for cetuxRT (p < 0.001). In the overall and propensity-matched cohorts, chemoRT and RTonly were associated with improved OS as compared to cetuxRT (p ≤ 0.001). CONCLUSION: Compared to chemoRT or RTonly, cetuxRT is associated with decreased OS for patients with HNSCC, suggesting minimal benefit of bioradiotherapy in this population.

Combined radio-immunotherapy: An opportunity to increase the therapeutic ratio of oligometastasis-directed radiotherapy.

The utility of radiotherapy as a means of palliating symptoms due to metastatic cancer is well-accepted. A growing body of literature suggests that radiotherapy may play a role beyond palliation in some patients with low-burden metastatic disease. Recent data suggest that oligometastasis-directed radiotherapy may improve progression-free and even overall survival in select patients. Immunotherapy also has a growing role in the management of patients with metastatic cancer and, like radiotherapy, appears to be most effective in the setting of low-volume disease. Thus, the addition of immunotherapy may be a feasible means of increasing the therapeutic ratio of metastasis-directed radiotherapy, particularly among patients with oligometastatic cancer.

Hematuria following Post-Prostatectomy Radiotherapy: Incidence Increases with Long-Term Followup.

PURPOSE: Hematuria following post-prostatectomy radiotherapy (PPRT) is inadequately characterized. We performed a consecutive cohort study of patients treated with PPRT at our institution to characterize this complication including impact on patient-reported quality of life. MATERIALS AND METHODS: Patients with potential followup ≥4 years following PPRT were identified. Freedom from ≥grade 2 hematuria (FFG2H; macroscopic blood) was estimated using the Kaplan-Meier method. Predictors of ≥grade 2 hematuria (G2H) were assessed via log-rank tests and the Cox model. Urinary patient-reported quality of life by EPIC-26 (26-question Expanded Prostate Cancer Index Composite) was compared for patients with/without hematuria using mixed-effects regression. RESULTS: A total of 216 men received PPRT (median 68.4 Gy, IQR 68.0-68.4) from 2007 to 2016 at a median of 20 months (IQR 9-45) after prostatectomy. Median followup was 72 months (IQR 54-99). A total of 85 men developed hematuria, of whom 49 (58%) underwent cystoscopy, 13 (15%) required intervention and 26 (31%) experienced recurrent hematuria. Eight-year FFG2H was 55%. G2H was highest in men treated with anticoagulation/antiplatelet therapy (HR 3.24, p <0.001), men with bladder V65 Gy ≥43% (HR 1.97, p=0.004) and men with medication allergies (HR 1.73, p=0.049). Age <65 years (HR 0.81, p=0.374) and diabetes mellitus (HR 0.49, p=0.098) were not associated with G2H. Change in urinary continence (mean -3.5, 95% CI: 10.1, 3.1) and irritation/obstruction (mean -3.0, 95% CI: 5.8, -0.3) domain scores did not exceed the minimally clinically important difference for men with/without hematuria. CONCLUSIONS: Hematuria following PPRT is common, especially among men with medication allergies and those on anticoagulation/antiplatelet therapy; however, PPRT-related hematuria is typically self-limited. Limiting bladder V65 Gy may reduce PPRT-related hematuria.

Can Pre-treatment Quantitative Multi-parametric MRI Predict the Outcome of Radiotherapy in Patients with Prostate Cancer?

RATIONALE AND OBJECTIVES: To investigate whether pre-treatment quantitative multiparametric MRI can predict biochemical outcome of prostate cancer (PCa) patients treated with primary radiotherapy (RT). MATERIALS AND METHODS: Fifty-one patients with biopsy confirmed PCa underwent prostate multiparametric MRI on 3T MR scanner prior to RT. Thirty-seven men (73%) were treated with external beam RT alone, 12 men (24%) were treated with brachytherapy monotherapy, and two men (4%) were treated with external beam RT with brachytherapy boost. The index lesion was outlined by a radiologist and quantitative apparent diffusion coefficient (ADC), T2 and DCE parameters were measured. Biochemical failure was defined using the Phoenix criteria. RESULTS: After a median follow-up of 65 months, seven patients had biochemical failure. ADC had an area under the receiver operating characteristic curve of 0.71 for predicting RT outcome with significantly lower ADC (0.78 ± 0.17 vs 0.96 ± 0.26 µm2/ms, p = 0.04) of the index lesion in men with biochemical failure. Ideal ADC cutoff point (Youdens index) was 0.96 µm2/ms which had a sensitivity of 100% and specificity of 48% for predicting biochemical failure. Kaplan-Meier analysis showed that lower ADC values were associated with significantly lower freedom from biochemical failure (FFBF, p = 0.03, no failures out of 20 men if ADC ≥ 0.96 µm2/ms; seven of 31 with failures if ADC < 0.96 µm2/ms). On multivariable analysis, ADC was associated with FFBF (HR 0.96 per increase in ADC of 0.01 um2/ms [95% CI, 0.92-1.00]; p = 0.042) after accounting for National Comprehensive Cancer Network risk category (p = 0.064) and receipt of androgen deprivation therapy (p = 0.141). Quantitative T2 and DCE parameters were not associated with biochemical outcome. CONCLUSION: Our results suggest that quantitative ADC values of the index lesion may predict biochemical failure following primary radiotherapy in patients with PCa. Lower ADC values were associated with inferior biochemical control.

CDKN2A loss-of-function predicts immunotherapy resistance in non-small cell lung cancer.

Immune checkpoint blockade (ICB) improves outcomes in non-small cell lung cancer (NSCLC) though most patients progress. There are limited data regarding molecular predictors of progression. In particular, there is controversy regarding the role of CDKN2A loss-of-function (LOF) in ICB resistance. We analyzed 139 consecutive patients with advanced NSCLC who underwent NGS prior to ICB initiation to explore the association of CDKN2A LOF with clinical outcomes. 73% were PD-L1 positive (≥ 1%). 48% exhibited high TMB (≥ 10 mutations/megabase). CDKN2A LOF was present in 26% of patients and was associated with inferior PFS (multivariate hazard ratio [MVA-HR] 1.66, 95% CI 1.02-2.63, p = 0.041) and OS (MVA-HR 2.08, 95% CI 1.21-3.49, p = 0.0087) when compared to wild-type (WT) patients. These findings held in patients with high TMB (median OS, LOF vs. WT 10.5 vs. 22.3 months; p = 0.069) and PD-L1 ≥ 50% (median OS, LOF vs. WT 11.1 vs. 24.2 months; p = 0.020), as well as in an independent dataset. CDKN2A LOF vs. WT tumors were twice as likely to experience disease progression following ICB (46% vs. 21%; p = 0.021). CDKN2A LOF negatively impacts clinical outcomes in advanced NSCLC treated with ICB, even in high PD-L1 and high TMB tumors. This novel finding should be prospectively validated and presents a potential therapeutic target.

Treatment of Cancer with Radio-Immunotherapy: What We Currently Know and What the Future May Hold.

Radiotherapy and immunotherapy are most effective as cancer therapies in the setting of low-volume disease. Although initial studies of radio-immunotherapy in patients with metastatic cancer have not confirmed the efficacy of this approach, the role of radio-immunotherapy in patients with limited metastatic burden is unclear. We propose that further investigation of radio-immunotherapy in metastatic patients should focus upon patients with oligometastatic disease.

Chemoradiation for Anal Cancer: Clinical Outcomes and Strategies to Optimize the Therapeutic Ratio According to HPV Status.

The incidence of anal cancer in the United States has increased in recent years, primarily related to the increasing incidence of HPV-associated anal squamous cell carcinoma, which is estimated to represent 80%-95% of anal cancers. Similar to head and neck cancer, HPV association has been demonstrated to be a strong positive prognostic factor in patients with anal cancer. Encouraging results from a number of studies investigating treatment de-escalation for HPV-associated oropharyngeal cancer support the notion that similar attempts may be feasible in HPV-associated anal cancer; however, the data to support this hypothesis are currently lacking. Studies are needed to determine how, if at all, HPV status should impact the management of patients with anal cancer. This review summarizes the relationship between HPV association and outcomes for patients with anal cancer, and how HPV status may impact the treatment of patients with anal cancer going forward.

Radiotherapy and Immunotherapy Combinations in the Treatment of Patients with Metastatic Disease: Current Status and Future Focus.

Radiotherapy and immunotherapy benefit subsets of patients with metastatic cancer. Here, we review selected laboratory and clinical studies investigating the utility of combining radiotherapy and immunotherapy in metastatic patients. We examine potential approaches to increase the therapeutic ratio of radioimmunotherapy in the treatment of metastatic cancers moving forward.

Impact of anatomic site of distant metastasis on survival in salivary gland cancers.

BACKGROUND: As exemplified in patients with adenoid cystic carcinoma (ACC), metastatic salivary gland cancers display heterogenous behavior. Although anatomic site of metastasis has been suggested to be prognostic for survival in this population, this is not adequately characterized in the current literature. METHODS: Using the National Cancer Database (NCDB), patients with newly diagnosed metastatic salivary gland cancers with distant metastasis to a single organ were identified. RESULTS: Eight hundred and fifty-eight patients (n = 284 bone-only, n = 322 lung-only, n = 252 other-site-only) were identified. Anatomic site of distant metastasis was not associated with survival in the cohort as a whole; however, on pre-planned subgroup analysis, lung-only metastasis, relative to bone-only metastasis, was the only factor associated with improved survival in patients with ACC (HR: 0.52, 95%CI: 0.30-0.93, p = 0.029). CONCLUSIONS: Anatomic site of metastasis is strongly associated with survival in patients with metastatic ACC and should be considered in future studies aiming to optimize therapy in this population.

The role of immunotherapy in combination with oligometastasis-directed therapy: a narrative review.

Metastatic disease is a significant cause of morbidity and mortality among patients with cancer. Patients with oligometastatic cancer represent a subset of the metastatic population with a limited amount of disease that has metastasized distantly and progresses at a slow pace and thus has the potential to be cured with metastasis-directed local therapy. Recent studies examining the role of metastasis-directed therapy in patients with oligometastatic disease have primarily focused upon treatment with ablative doses of radiation, commonly referred to as stereotactic body radiation therapy (SBRT). While the use of SBRT to treat oligometastases has increased considerably in recent years, the benefit of this approach has yet to be confirmed in phase III randomized controlled trials; moreover, distant failure remains a significant problem in patients with oligometastatic disease treated with SBRT. Given the propensity for distant failure in patients with oligometastatic disease treated with SBRT, there is growing interest in the utility of combining SBRT with systemic agents such as immunotherapy. Immunotherapy, and specifically immune checkpoint blockade (ICB), represents a rapidly evolving systemic therapy option with a growing number of indications among patients with metastatic disease; however, despite its promise, only a minority of patients respond to ICB and among those who do, the majority eventually progress. SBRT and ICB are both dependent upon, and have the ability to shift, the balance between antitumor immune surveillance and immunosuppressive states in the tumor and tumor microenvironment. As a result, it has been speculated that SBRT and ICB have the potential to act synergistically when used in combination. SBRT has been demonstrated to be safe in combination with ICB in studies with short-term follow-up and although additional research is needed, preliminary prospective data support the potential efficacy of this approach. In addition to confirming the safety and efficacy of SBRT in combination with immunotherapy, further studies are needed to determine how to maximize the therapeutic ratio of this treatment paradigm for the full potential of immunotherapy in the oligometastatic population to be realized.

Patterns of Care and Survival Outcomes for Odontogenic Cancers.

OBJECTIVES: Our understanding of odontogenic cancers is limited primarily to case studies given the rarity of these head and neck neoplasms. Using the National Cancer Database, we report the treatment patterns and survival outcomes for one of the largest cohorts of patients with odontogenic cancers. METHODS: Patients with odontogenic tumors who did not have metastatic disease and received at least part of their care at the reporting facility were included. Patient and treatment variables were assessed using logistic regression. Survival was assessed using Cox proportional hazard models. RESULTS: We identified 437 patients with odontogenic cancers, the majority of which had malignant ameloblastoma (n = 203) or odontogenic carcinoma (n = 217). Median follow-up was 44.8 months. On multivariate analysis, improved survival was associated with age <57 years (Hazard ratios [HR] 0.44, P = .012), lower comorbidity scores (HR 0.40, P = .008), surgical resection (HR 0.08, P < .001) and absence of lymph node metastasis (HR 0.23, P < .001). The 5-year overall survival was 87.1% for debulking surgery, 88.6% for radical resection and 26.6% for no surgical resection (P < .001). Lymph node metastases were associated with tumor size ≥5 cm (P = .006), malignant odontogenic histology (P = .025), and moderate/poor differentiation (P < .001). CONCLUSION: In this large series of odontogenic cancers, any type of surgical resection was associated with improved survival. Lymph node metastases, although infrequent, were associated with significantly worse survival. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 131:E1496-E1502, 2021.

Physician review of image registration and normal structure delineation.

INTRODUCTION: Image registration and delineation of organs at risk (OARs) are key components of three-dimensional conformal (3DCRT) and intensity-modulated radiotherapy (IMRT) treatment planning. This study hypothesized that image registration and OAR delineation are often performed by medical physicists and/or dosimetrists and are not routinely reviewed by treating physicians. METHODS: An anonymous, internet-based survey of medical physicists and dosimetrists was distributed via the MEDPHYS and MEDDOS listserv groups. Participants were asked to characterize standard practices for completion and review of OAR contouring, target volume contouring, and image registration at their institution along with their personal training in these areas and level of comfort performing these tasks. Likert-type scales are reported as Median [Interquartile range] with scores ranging from 1 = "Extremely/All of the time" to 5 = "Not at all/Never." RESULTS: Two hundred and ninety-seven individuals responded to the survey. Overall, respondents indicated significantly less frequent physician review (3 [2-4] vs 2 [1-3]), and less confidence in the thoroughness of physician review (3 [2-4] vs 2 [1-3], P < 0.01) of OAR contours compared to image registration. Only 19% (95% CI 14-24%) of respondents reported a formal process by which OAR volumes are reviewed by physicians in their clinic. The presence of a formal review process was also associated with significantly higher perceived thoroughness of review of OAR volumes compared to clinics with no formal review process (2 [2-3] vs 3 [2-4], P < 0.01). CONCLUSION: Despite the critical role of OAR delineation and image registration in the 3DCRT and IMRT treatment planning process, physician review of these tasks is not always optimal. Radiotherapy clinics should consider implementation of formal processes to promote adequate physician review of OARs and image registrations to ensure the quality and safety of radiotherapy treatment plans.

PI-RADS score is associated with biochemical control and distant metastasis in men with intermediate-risk and high-risk prostate cancer treated with radiation therapy.

BACKGROUND: Novel methods of risk stratification are needed for men with prostate cancer. The Prostate Imaging Reporting and Data System (PI-RADS) uses multiparametric MRI (mpMRI) to assign a score indicating the likelihood of clinically significant prostate cancer. We evaluated pretreatment mpMRI findings, including PI-RADS score, as a marker for outcome in patients treated with primary radiation therapy (RT). METHODS: One hundred and twenty-three men, 64% and 36% of whom had National Comprehensive Cancer Network (NCCN) intermediate-risk and high-risk disease, respectively, underwent mpMRI prior to RT. PI-RADS score and size of the largest nodule were analyzed with respect to freedom from biochemical failure (FFBF) and freedom from distant metastasis. RESULTS: A PI-RADS score of ≤3, 4, or 5 was defined in 7%, 49%, and 44%; with a median nodule size of 0, 8, and 18 mm, respectively (P < 0.001). Median follow-up was 67 months. Men with PI-RADS ≤ 3, 4, or 5 disease had 7-year FFBF of 100%, 92%, and 65% (P = 0.002), and a 7-year freedom from distant metastasis of 100%, 100%, and 82%, respectively (P = 0.014). PI-RADS (Hazard Ratio 5.4 for PI-RADS 5 vs. 4, P = 0.006) remained associated with FFBF when controlling for NCCN risk category (P = 0.063) and receipt of androgen deprivation therapy (P = 0.535). Nodule size was also associated with FFBF (Hazard Ratio 1.08 per mm, P < 0.001) after controlling for NCCN risk category (P = 0.156) and receipt of androgen deprivation therapy (P = 0.776). CONCLUSION: mpMRI findings, including PI-RADS score and nodule size, may improve risk stratification in men treated with primary RT.

Prostate Cancer Radiotherapy: Increased Biochemical Control and Late Toxicity in Men With Medication Allergies.

BACKGROUND: Given similarities in the mediators of medication allergy (MA) and tissue response to radiotherapy, we assessed whether outcomes following prostate radiotherapy differ in patients with MAs. METHODS: A total 587 men with known MA history and nonmetastatic prostate cancer underwent radiotherapy from 1989 to 2006. Clinicopathologic and treatment variables were analyzed for association with freedom from biochemical failure (FFBF) and late treatment-related, physician-defined Radiation Therapy Oncology Group gastrointestinal (GI) and genitourinary (GU) toxicity. Covariates identified on univariate analysis for toxicity and disease control were examined on multivariable analysis. All statistical tests were 2-sided, and a P less than .05 was considered statistically significant. RESULTS: A total of 155 of 587 men (26.4%) had 1 or more MAs, most commonly to penicillin (n = 71), sulfa (n = 35), and aspirin or nonsteroidal antiinflammatory drugs (n = 28). On univariate analysis, men with MAs had superior 10-y FFBF (71.5% vs 63.5%, P = .02) and higher incidence of late GI grade 2 or higher (G2+; 20.6% vs 13.2%, P = .04) and grade 3 or higher (G3+; 7.5% vs 3.9%, P = .08) as well as late GU G2+ (42.5% vs 33.2%, P = .04) and G3+ (7.5% vs 3.0%, P = .02) toxicity than men without MAs. On multivariable analysis, MA history remained a statistically significant predictor of FFBF (hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.43 to 0.93, P = .02), late G2+ GI (HR = 1.76, 95% CI = 1.06 to 2.90, P=.03), and G3+ GU (HR = 2.69, 95% CI = 1.16 to 6.27, P = .02) toxicity after controlling for corresponding covariates in each model. CONCLUSIONS: Men with MAs had improved FFBF and increased treatment-related toxicity following radiotherapy for prostate cancer. MA history could be a relevant consideration in the management of men with localized prostate cancer.