Patient-reported outcomes after Low-dose-rate versus High-dose-rate brachytherapy boost in combination with external beam radiation for intermediate and high risk prostate cancer.

PURPOSE: Addition of a brachytherapy boost to external beam radiation therapy (EBRT) reduces prostate cancer (PCa) recurrence at the expense of genitourinary (GU) toxicity. Whether brachytherapy boost technique, specifically low-dose-rate (LDR-BT) versus high-dose-rate (HDR-BT), impacts treatment-related toxicity is unclear. METHODS: Between 2012-2018, 106 men with intermediate/high risk PCa underwent EBRT (37.5-45 Gy in 1.8-2.5 Gy/fraction) plus brachytherapy boost, either with LDR-BT (110 Gy I-125 or 100 Gy Pd-103; n = 51) or HDR-BT (15 Gy x1 Ir-192; n = 55). Patient-reported outcomes (PRO) were assessed by International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC-CP) surveys at 3-6-month intervals for up to three years following treatment, with higher scores indicating more severe toxicity. Provider-reported GU and gastrointestinal (GI) toxicity was graded per CTCAE v5.0 at each follow-up. Linear mixed models comparing PROs between LDR-BT versus HDR-BT were fitted. Stepwise multivariable analysis (MVA) was performed to account for age, gland size, androgen deprivation therapy use, and alpha-blocker medication use. Incidence rates of grade 2+ GU/GI toxicity was compared using Fisher's exact test. RESULTS: Use of LDR-BT was associated with greater change in IPSS (p=0.003) and EPIC-CP urinary irritative score (p = 0.002) compared with HDR-BT, but effect size diminished over time (LDR-BT versus HDR-BT: baseline to 6-/24-month mean IPSS change, +6.4/+1.4 versus +2.7/-3.0, respectively; mean EPIC-CP irritative/obstructive change, +2.5/+0.1 versus +0.9/+0.1, respectively). Results remained significant on MVA. Post-treatment grade 2+ GU toxicity was significantly higher in the LDR-BT group (67.5% versus 42.9% for LDR-BT and HDR-BT, respectively; p <0.001). There were no differences between groups in incontinence, bowel function, and erectile function, or grade 2+ GI toxicity. CONCLUSION: Compared with LDR-BT, HDR-BT was associated with lower acute patient- and provider-reported GU toxicity.

Optimal timing of chemoradiotherapy after surgical resection of glioblastoma: Stratification by validated prognostic classification.

BACKGROUND: Previous studies examining the time to initiate chemoradiation (CRT) after surgical resection of glioblastoma have been conflicting. To better define the effect that the timing of adjuvant treatment may have on outcomes, the authors examined patients within the National Cancer Database (NCDB) stratified by a validated prognostic classification system. METHODS: Patients with glioblastoma in the NCDB who underwent surgery and CRT from 2004 through 2013 were analyzed. Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (III, IV, V) was extrapolated for the cohort. Time intervals were grouped weekly, with weeks 4 to 5 serving as the reference category for analyses. Kaplan-Meier analysis, log-rank testing, and multivariate (MVA) Cox proportional hazards regression were performed. RESULTS: In total, 30,414 patients were included. RPA classes III, IV, and V contained 5250, 20,855, and 4309 patients, respectively. On MVA, no time point after week 5 was associated with a change in overall survival for the entire cohort or for any RPA class subgroup. The periods of weeks 0 to 1 (hazard ratio [HR], 1.18; 95% CI, 1.02-1.36), >1 to 2 (HR, 1.23; 95% CI, 1.16-1.31), and >2 to 3 (HR, 1.11; 95% CI, 1.07-1.15) demonstrated slightly worse overall survival (all P < .03). The detriment to early initiation was consistent across each RPA class subgroup. CONCLUSIONS: The current data provide insight into the optimal timing of CRT in patients with glioblastoma and describe RPA class-specific outcomes. In general, short delays beyond 5 weeks did not negatively affect outcomes, whereas early initiation before 3 weeks may be detrimental.

High-dose-rate prostate brachytherapy appears safe in patients with high baseline International Prostate Symptom Scores.

PURPOSE: The purpose of the study was to report our institutional quality of life data for those undergoing high-dose-rate brachytherapy with an International Prostate Symptom Score (IPSS) ≥15 compared with those with an IPSS <15. METHODS AND MATERIALS: The charts of 95 patients with localized adenocarcinoma of the prostate treated with high-dose-rate as monotherapy or as a boost after external beam radiation therapy at a single institution between 2012 and 2015 were reviewed. All patients completed the IPSS and Expanded Prostate Index for Prostate Cancer-Clinical Practice quality of life assessments before treatment and at least one followup survey. Linear mixed models were performed to test for significant changes and differences in each outcome over time. RESULTS: Median followup in the IPSS <15 group was 23 months and 16 months in the IPSS ≥15 group. Median prostate volume was 46.3 cc and 45.4 cc, respectively (p = 0.901). IPSS, incontinence, and urinary irritation/obstruction scores were significantly higher in the IPSS ≥15 group compared with the IPSS <15 group at baseline (all p ≤ 0.05). By the >24 months time point, these scores had decreased below baseline and were not significantly different from those with a baseline IPSS <15 (all p > 0.1). 12.5% in the IPSS ≥15 group developed a new Grade 2 genitourinary toxicity requiring an alpha blocker compared with 26.5% in the IPSS <15 group (p = 0.34). No patients required emergency placement of a foley catheter within 30 days of treatment. CONCLUSIONS: Given the low rates of genitourinary toxicity, this technique appears appropriate even for those with high baseline urinary symptoms.

Fractionated Radiotherapy Is Associated with Lower Rates of Treatment-Related Edema than Stereotactic Radiosurgery in Magnetic Resonance Imaging-Defined Meningiomas.

OBJECTIVE: Both stereotactic radiosurgery (SRS) and fractionated radiation therapy (FRT) techniques are used for treatment of intracranial meningiomas with excellent local control (LC) rates. Although SRS techniques are convenient, toxicity including treatment-related edema can significantly impact patient quality of life. The long-term clinical outcomes of patients with magnetic resonance imaging (MRI)-defined meningiomas treated with radiation therapy (RT) alone are reported. METHODS: The charts of 211 patients with meningiomas diagnosed by contrast-enhanced MRI treated with either SRS or FRT between 1991 and 2012 at a single institution were reviewed. Actuarial rates for LC and development of treatment-related radiographic edema (TRE) were determined by the Kaplan-Meier method. RESULTS: There were 211 patients who received radiation therapy for 223 lesions. Median follow-up was 5.7 years. Eleven patients experienced a local failure; of these, 2 were ultimately found to have pathologically proven metastatic carcinoma. Two- and 5-year LC was 97.8% and 94.6%, respectively, with no significant difference based on modality of therapy. Actuarial rate for development of TRE at 1 and 2 years was 30.1% and 34.6% for the SRS group and 1.6% and 2.5% for the FRT group, respectively (P < 0.001). CONCLUSIONS: RT alone using a limited margin is an effective treatment option for MRI-defined meningiomas and should be considered even without biopsy if surgery will present significant morbidity. Although LC with SRS versus FRT was comparable, FRT was associated with a significantly decreased risk of TRE.

Patient-reported health-related quality of life outcomes after HDR brachytherapy between small (<60 cc) and large (≥60 cc) prostate glands.

PURPOSE: Patients with large prostate glands are underrepresented in clinical trials incorporating brachytherapy due to concerns for excessive toxicity. We sought to compare health-related quality of life (HRQOL) outcomes between small (<60 cc) and large (≥60 cc) prostates treated with high-dose-rate brachytherapy (HDR-B). METHODS AND MATERIALS: One hundred thirty patients at Emory University were treated with HDR-B monotherapy (n = 75) or HDR-B in combination with external beam radiation therapy (n = 55). American Urologic Association Symptom Score (AUASS) and expanded prostate cancer index composite for clinical practice (EPIC-CP) scores were recorded. A linear mixed model was performed dichotomizing prostate volume (<60 and ≥ 60 cc) with AUASS, individual EPIC-CP domains (urinary incontinence, urinary irritation/obstruction [UIO], bowel function, sexual function, and vitality/hormonal function), and overall EPIC-CP HRQOL scores. RESULTS: Median followup was 22.6 months (range 2.2-55.8). The median gland volume for the entire cohort (n = 130), <60 cc cohort (n = 104), and ≥60 cc cohort (n = 26) was 44 cc, 41.1 cc, and 68.0 cc, respectively. There were no baseline differences in HRQOL scores between cohorts. At 2 months, AUASS and UIO scores increased similarly between cohorts (AUASS p = 0.807; UIO p = 0.539), then decreased (longitudinal effect p < 0.001 and p = 0.005, respectively) to remain not significantly different at 12 months (AUASS p = 0.595; UIO p = 0.673). Overall, prostate volume was not significantly associated with change in AUASS (p = 0.403), urinary incontinence (p = 0.322), UIO symptoms (p = 0.779), bowel symptoms (p = 0.757), vitality/hormonal symptoms (p = 0.503), or overall HRQOL (p = 0.382). CONCLUSIONS: In appropriately selected patients, HDR-B appears well tolerated in patients with ≥60 cc prostate glands without an increase in patient-reported toxicity. Volume should not be a strict contraindication in those with adequate baseline function.

Hypofractionated external beam radiation therapy in combination with HDR boost for localized prostate cancer: patient reported quality of life outcomes.

PURPOSE: There is limited data to support the use of hypofractionated external beam radiation (HypoF) in combination with high-dose-rate brachytherapy (HDR). We report our quality of life (QOL) outcomes when treating intermediate and high-risk prostate cancer patients with external beam radiation (EBRT) plus HDR. MATERIAL AND METHODS: The charts of 54 patients with localized adenocarcinoma of the prostate treated with standard fractionation (SF) or HypoF EBRT plus HDR boost at a single institution between 2012 and 2015 were reviewed. All patients completed the American Urological Association Symptom Score (AUASS) and Expanded Prostate Index for Prostate Cancer - Clinical Practice (EPIC-CP) quality of life assessments prior to treatment and completed at least one follow-up survey. Linear mixed models were performed to test for significant changes and differences in each outcome over time. RESULTS: There was no significant difference in AUA score (p = 0.98), incontinence (urge) and urinary irritation/obstruction scores (p = 0.81 and p = 0.62, respectively), and bowel QOL (p = 0.97) between the two dosing groups over time or at any discrete time point. For both groups, AUA scores peaked at 0-2 months before improving. Likewise, sexual function, vitality score, and QOL scores were also not significantly different between the dose groups over time (p = 0.59, p = 0.37, and p = 0.71, respectively). All QOL categories, except sexual function, trended toward baseline with increasing time from intervention. CONCLUSIONS: Our study suggests HypoF EBRT can be delivered in combination with HDR for patients with ntermediate-risk and high-risk adenocarcinoma of the prostate without increasing toxicity compared to SF with an HDR boost.

Does size matter? Investigating the optimal planning target volume margin for postoperative stereotactic radiosurgery to resected brain metastases.

OBJECTIVE: The optimal margin size in postoperative stereotactic radiosurgery (SRS) for brain metastases is unknown. Herein, the authors investigated the effect of SRS planning target volume (PTV) margin on local recurrence and symptomatic radiation necrosis postoperatively. METHODS: Records of patients who received postoperative LINAC-based SRS for brain metastases between 2006 and 2016 were reviewed and stratified based on PTV margin size (1.0 or > 1.0 mm). Patients were treated using frameless and framed SRS techniques, and both single-fraction and hypofractionated dosing were used based on lesion size. Kaplan-Meier and cumulative incidence models were used to estimate survival and intracranial outcomes, respectively. Multivariate analyses were also performed. RESULTS: A total of 133 patients with 139 cavities were identified; 36 patients (27.1%) and 35 lesions (25.2%) were in the 1.0-mm group, and 97 patients (72.9%) and 104 lesions (74.8%) were in the > 1.0-mm group. Patient characteristics were balanced, except the 1.0-mm cohort had a better Eastern Cooperative Group Performance Status (grade 0: 36.1% vs 19.6%), higher mean number of brain metastases (1.75 vs 1.31), lower prescription isodose line (80% vs 95%), and lower median single fraction-equivalent dose (15.0 vs 17.5 Gy) (all p < 0.05). The median survival and follow-up for all patients were 15.6 months and 17.7 months, respectively. No significant difference in local recurrence was noted between the cohorts. An increased 1-year rate of symptomatic radionecrosis was seen in the larger margin group (20.9% vs 6.0%, p = 0.028). On multivariate analyses, margin size > 1.0 mm was associated with an increased risk for symptomatic radionecrosis (HR 3.07, 95% CI 1.13-8.34; p = 0.028), while multifraction SRS emerged as a protective factor for symptomatic radionecrosis (HR 0.13, 95% CI 0.02-0.76; p = 0.023). CONCLUSIONS: Expanding the PTV margin beyond 1.0 mm is not associated with improved local recurrence but appears to increase the risk of symptomatic radionecrosis after postoperative SRS.

Whole lung irradiation in stage IV Wilms tumor patients: Thyroid dosimetry and outcomes.

PURPOSE: To report the thyroid dosimetry and long-term follow-up of childhood cancer survivors treated with whole lung irradiation (WLI) for Wilms tumor. METHODS: Twenty-eight patients with pulmonary metastases from Wilms tumor who underwent WLI from 2000 TO 2012 at a single institution were reviewed. Radiation dose to the thyroid gland in each case was calculated. Postradiation thyroid function test (TFT) results and management of thyroid function abnormalities were extracted from the medical records. RESULTS: Median age at treatment was 5 years (range: 1-9 years), and median follow-up time was 74.1 months (7.2-198.4). The male/female ratio was 1:1.8. Complete dosimetry data were available for 22 of the 28 patients receiving WLI. Mean thyroid volume was 3.3 cc (range: 1-6.8). The average mean and median mean dose to the thyroid was 6.7 and 7.1 Gy, respectively (range: 1.3-11.7 Gy). Average max dose to the thyroid was 12.4 Gy (range: 7.8-20.3 Gy). Two patients were found to have a thyroid stimulating hormone (TSH) above the normal range, managed with levothyroxine. Another patient was found to have an isolated elevation of TSH which normalized without treatment. A fourth patient was found to have an enlarged thyroid on examination with no palpable nodules or abnormal TFTs. CONCLUSIONS: Average mean dose to the thyroid gland was 6.7 Gy for this population of stage IV Wilms tumor patients. There was a low rate of thyroid dysfunction, but limited follow-up. Attention to blocking the thyroid gland as much as possible when designing radiation fields can potentially mitigate the risks of long-term thyroid effects.

Brachytherapy for localized prostate cancer in the modern era: a comparison of patient-reported quality of life outcomes among different techniques.

PURPOSE: To report our institutional quality of life (QOL) data for low-dose-rate (LDR) monotherapy (LDR mono), high-dose-rate (HDR) monotherapy (HDR mono), and EBRT with an HDR brachytherapy boost (HDR boost). MATERIAL AND METHODS: The charts of 165 patients with localized adenocarcinoma of the prostate treated with LDR monotherapy (LDR mono), HDR monotherapy (HDR mono), and EBRT with an HDR brachytherapy boost (HDR boost) at a single institution between 2012 and 2015 were reviewed. All patients completed the American Urological Association symptom score (AUASS) and Expanded Prostate Index for Prostate Cancer - Clinical Practice (EPIC-CP) quality of life assessments prior to treatment and at least one follow-up survey. Time points included baseline, ≤ 2 months, 2-≤ 6 months, 6-≤ 12 months, 12-≤ 18 months, 18-≤ 24 months, 24-≤ 30 months, and > 30 months. Linear mixed models were performed to test for significant changes and differences in each outcome over time. RESULTS: Mean follow-up was 19.5 months. All major functional QOL domains were affected after treatment with brachytherapy for localized prostate cancer. All domains improved over time, with the exception of sexual function scores for all groups and urinary incontinence scores for the HDR mono group. Patients treated with LDR did have higher AUA, irritability/obstructive symptoms, incontinence, bowel, and QOL scores acutely compared to the HDR and HDR + boost groups. Vitality scores were significantly worse in the HDR boost group both acutely and at the > 30-month time point. CONCLUSIONS: Patients receiving HDR brachytherapy had lower acute urinary and rectal toxicity compared to the patients receiving LDR, even when combined with EBRT. However, long-term toxicity was similar.