Comparative analysis of plan quality and delivery efficiency: ZAP-X vs. CyberKnife for brain metastases treatment.

Purpose/Objectives: ZAP-X, a novel and dedicated radiosurgery (SRS) system, has recently emerged, while CyberKnife has solidified its position as a versatile solution for SRS and stereotactic body radiation therapy over the past two decades. This study aims to compare the dosimetric performance and delivery efficiency of ZAP-X and CyberKnife in treating brain metastases of varying target sizes, employing circular collimation. Methods and materials: Twenty-three patients, encompassing a total of 47 brain metastases, were included in the creation of comparative plans of ZAP-X and CyberKnife for analysis. The comparative plans were generated to achieve identical prescription doses for the targets, while adhering to the same dose constraints for organs at risk (OAR). The prescription isodose percentage was optimized within the range of 97-100% for each plan to ensure effective target-volume coverage. To assess plan quality, indices such as conformity, homogeneity, and gradient (CI, HI, and GI) were computed, along with the reporting of total brain volumes receiving 12Gy and 10Gy. Estimated treatment time and monitor units (MUs) were compared between the two modalities in evaluating delivery efficiency. Results: Overall, CyberKnife achieved better CI and HI, while ZAP-X exhibited better GI and a smaller irradiated volume for the normal brain. The superiority of CyberKnife's plan conformity was more pronounced for target size less than 1 cc and greater than 10 cc. Conversely, the advantage of ZAP-X's plan dose gradient was more notable for target sizes under 10 cc. The homogeneity of ZAP-X plans, employing multiple isocenters, displayed a strong correlation with the target's shape and the planner's experience in placing isocenters. Generally, the estimated treatment time was similar between the two modalities, and the delivery efficiency was significantly impacted by the chosen collimation sizes for both modalities. Conclusion: This study demonstrates that, within the range of target sizes within the patient cohort, plans generated by ZAP-X and CyberKnife exhibit comparable plan quality and delivery efficiency. At present, with the current platform of the two modalities, CyberKnife outperforms ZAP-X in terms of conformity and homogeneity, while ZAP-X tends to produce plans with a more rapid dose falloff.

Prognostic utility of biopsy-based PTEN and ERG status on biochemical progression and overall survival after SBRT for localized prostate cancer.

Introduction/background: Phosphatase and tensin homolog (PTEN) genomic deletions and transmembrane protease, serine 2/v-ets avian erthyroblastosis virus E26 oncogene homolog (ERG) rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies have demonstrated these alterations portend worse clinical outcomes. Our objective is to evaluate the impact of biopsy-determined PTEN losses and TMPRSS2-ERG fusion on biochemical progression-free survival (bPFS) and overall survival (OS) in patients who receive SBRT for localized prostate cancer. Methods/materials: Patients received SBRT for localized prostate cancer on a prospective quality-of-life (QoL) and cancer outcomes study. For each patient, the single biopsy core with the highest grade/volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and χ2 for categorical groupings. bPFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bPFS and OS were identified using the Cox proportional hazards method. For all analyses, p <0.05 was considered statistically significant. Results: Ninety-nine consecutive patients were included in the analysis with a median follow-up of 72 months. A statistically significant improvement in bPFS (p = 0.018) was observed for wild type ERG patients with an estimated 5-year bPFS of 94.1% vs. 72.4%. Regarding PTEN mutational status, significant improvements in were observed in both bPFS (p = 0.006) and OS (p < 0.001), with estimated 5-year bPFS rates of 91.0% vs. 67.9% and 5-year OS rates of 96.4% vs. 79.4%. When including both ERG and PTEN mutational status in the analysis, there were statistically significant differences in both bPFS (p = 0.011) and OS (p < 0.001). The estimated 5-year bPFS rates were 100%, 76.6%, 72.9%, and 63.8% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. The estimated 5-year OS rates were 93.9%, 100%, 80.0%, and 78.7% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. Conclusion: ERG rearrangements and PTEN deletions detected on biopsy samples are associated with poorer oncologic outcomes in prostate cancer patients treated with SBRT and merit further study in a dedicated prospective trial.

Intensity modulated radiation therapy with stereotactic body radiation therapy boost for unfavorable prostate cancer: five-year outcomes.

Purpose: Intensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost. Materials and methods: Between 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) according to an institutional protocol. For the first year, the patient's PSA level was monitored every 3 months, biannually for 2 years, and annually thereafter. Failure was defined as nadir + 2 ng/mL or a rising PSA with imaging suggestive of recurrence. Detection of recurrence also included digital rectal examination and imaging studies, such as MRI, CT, PET/CT, and/or bone scans. PFS and PCSS were calculated using the Kaplan-Meier method. Results: The median follow-up period was 71 months. According to the NCCN risk classification, 5% (13/255) of the patients had favorable intermediate-risk disease, 23% (57/255) had unfavorable intermediate-risk disease, 40% (102/255) had high-risk disease, and 32% (83/255) had very high-risk disease. Androgen deprivation therapy was administered to 80% (204/255) of the patients. Elective pelvic lymph node IMRT was performed in 28 (10%) patients. The PFS for all patients at 5 years was 81% (favorable intermediate risk, 91%; unfavorable intermediate risk, 89%; high-risk, 78%; and very-high risk, 72%). The PCSS for all patients at 5 years was 97% (favorable intermediate risk, 100%; unfavorable intermediate risk, 100%; high risk, 100%; and very high risk, 89%). Conclusion: The incidence of failure following IMRT plus SBRT for unfavorable prostate cancer remains low at 5 years.

Testosterone as a Biomarker for Quality of Life (QOL) Following Androgen Deprivation Therapy (ADT) and Stereotactic Body Radiotherapy (SBRT).

BACKGROUND: Androgen deprivation therapy (ADT) causes fatigue and sexual dysfunction. The time to testosterone recovery depends on patient and treatment-specific characteristics. The kinetics of testosterone recovery in men treated with neoadjuvant ADT and stereotactic body radiotherapy (SBRT) is not well established. This study seeks to characterize testosterone recovery and evaluate its relationship with the improvement in patient-reported hormonal and sexual function. METHODS: Institutional review board (IRB) approval was obtained for retrospective review of prospectively collected data. All patients with localized prostate cancer treated with short-course ADT (3-6 months of Leuprolide) and robotic SBRT (35-36.25 Gy in five fractions) at a single institution were included in this analysis. Testosterone levels were measured at the start of radiation, every 3 months for the first year, and every 6 months thereafter. Total testosterone recovery was defined as a serum level of >230 ng/dL. Sexual and hormonal function was recorded using the Expanded Prostate Index Composite (EPIC)-26 prior to ADT initiation, the first day of SBRT, and at each follow-up. The EPIC-26 subdomain scores were transformed to a 0-100 scale with higher scores reflecting less bother. RESULTS: Between January 2009 and May 2018, 122 men with a median age of 72 years (range: 55-89 years) received ADT followed by SBRT. Thirty-two percent (N=39) were black and 27% [N=39 were obese (BMI > 30)]. The median pre-SBRT testosterone level was 15 ng/dL (range: 3-89 ng/dL). Around 77% (N=94) of patients received 3 months of ADT. The median pre-ADT EPIC-26 Hormone and Sexual Domain Scores were 94 and 41, respectively. At 12 months, 71% (N=87) of patients recovered to a eugonadal state with a mean recovery time of 4 months post-SBRT. Hormonal and sexual subdomain scores declined significantly following ADT but recovered to within the minimally important difference (MID) for sexual and hormonal domain scores by 12 months post-SBRT. CONCLUSIONS: Testosterone recovery following short-course ADT with leuprolide and SBRT occurs rapidly in the majority of patients within one year after treatment. Quality of life domain improvements followed the testosterone recovery trend closely. Testosterone testing at follow-up appointments would allow for anticipatory counseling that may limit the bother associated with temporary quality of life decrements.

Stereotactic Partial Breast Irradiation: What Does the Future Hold?

Breast irradiation has evolved significantly over the last several decades. Accelerated partial breast and stereotactic breast irradiation have evolved as strategies to reduce irradiated volumes, preserve appropriate oncologic control, and improve cosmetic outcome. The sequencing and/or combination of stereotactic partial breast irradiation with novel systemic agents is of great interest to the oncologic community. Here we explore the landscape of modern trials and opine on the future of partial breast irradiation.

High-Risk Non-Small Cell Lung Cancer Treated With Active Scanning Proton Beam Radiation Therapy and Immunotherapy.

Purpose: Non-small cell lung cancer (NSCLC) is a deadly malignancy that is frequently diagnosed in patients with significant medical comorbidities. When delivering local and regional therapy, an exceedingly narrow therapeutic window is encountered, which often precludes patients from receiving aggressive curative therapy. Radiation therapy advances including particle therapy have been employed in an effort to expand this therapeutic window. Here we report outcomes with the use of proton therapy with curative intent and immunotherapy to treat patients diagnosed with high-risk NSCLC. Methods and Materials: Patients were determined to be high risk if they had severe underlying cardiopulmonary dysfunction, history of prior thoracic radiation therapy, and/or large volume or unfavorable location of disease (eg, bilateral hilar involvement, supraclavicular involvement). As such, patients were determined to be ineligible for conventional x-ray-based radiation therapy and were treated with pencil beam scanning proton beam therapy (PBS-PBT). Patients who demonstrated excess respiratory motion (ie, greater than 1 cm in any dimension noted on the 4-dimensional computed tomography simulation scan) were deemed to be ineligible for PBT. Toxicity was reported using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Overall survival and progression-free survival were calculated using the Kaplan-Meier method. Results: A total of 29 patients with high-risk NSCLC diagnoses were treated with PBS-PBT. The majority (55%) of patients were defined as high risk due to severe cardiopulmonary dysfunction. Most commonly, patients were treated definitively to a total dose of 6000 cGy (relative biological effectiveness) in 30 fractions with concurrent chemotherapy. Overall, there were a total of 6 acute grade 3 toxicities observed in our cohort. Acute high-grade toxicities included esophagitis (n = 4, 14%), dyspnea (n = 1, 3.5%), and cough (n = 1, 3.5%). No patients developed grade 4 or higher toxicity. The majority of patients went on to receive immunotherapy, and high-grade pneumonitis was rare. Two-year progression-free and overall survival was estimated to be 51% and 67%, respectively. COVID-19 was confirmed or suspected to be responsible for 2 patient deaths during the follow-up period. Conclusions: Radical PBS-PBT treatment delivered in a cohort of patients with high-risk lung cancer with immunotherapy is feasible with careful multidisciplinary evaluation and rigorous follow-up.

Chest CT for Breast Cancer Diagnosis.

Background: We report the results of our retrospective analysis of the ability of standard chest CT scans to correctly diagnose cancer in the breast. Methods: Four hundred and fifty-three consecutive women with chest CT scans (contrast and non-contrast) preceding mammograms within one year comprise the study population. All chest CT images were reviewed by an experienced fellowship-trained chest radiologist and mammograms by an experienced fellowship-trained mammographer without the benefit of prior or ancillary studies; only four mammographic views were included for analysis. The size, location, and shape of breast masses were documented; on CT, the average Hounsfield units were measured. On both imaging modalities, the presence of lymphadenopathy, architectural distortion, skin thickening, and microcalcifications were recorded. Ultimately, the interpreting radiologist was asked to decide if a biopsy was indicated, and these recommendations were correlated with the patient's outcome. Findings: Nineteen of four hundred and fifty-three patients had breast cancer at the time of the mammography. Breast masses were the most common finding on chest CT, leading to the recommendation for biopsy. Hounsfield units were the most important feature for discerning benign from malignant masses. CT sensitivity, specificity, and accuracy of CT for breast cancer detection was 84.21%, 99.3%, and 98.68% compared to 78.95%, 93.78%, and 93.16% for four-view mammography. Chest CT scans with or without contrast had similar outcomes for specificity and accuracy, but sensitivity was slightly less without contrast. Chest CT alone, without the benefit of prior exams and patient recall, correctly diagnosed cancer with a p-value of <0.0001 compared to mammography with the same limitations. Conclusion: Chest CT accurately diagnosed breast cancer with few false positives and negatives and did so without the need for patient recall for additional imaging.

Highly Oriented Direct-Spun Carbon Nanotube Textiles Aligned by In Situ Radio-Frequency Fields.

Carbon nanotubes (CNTs) individually exhibit exceptional physical properties, surpassing state-of-the-art bulk materials, but are used commercially primarily as additives rather than as a standalone macroscopic product. This limited use of bulk CNT materials results from the inability to harness the superb nanoscale properties of individual CNTs into macroscopic materials. CNT alignment within a textile has been proven as a critical contributor to narrow this gap. Here, we report the development of an altered direct CNT spinning method based on the floating catalyst chemical vapor deposition process, which directly interacts with the self-assembly of the CNT bundles in the gas phase. The setup is designed to apply an AC electric field to continuously align the CNTs in situ during the formation of CNT bundles and subsequent aerogel. A mesoscale CNT model developed to simulate the alignment process has shed light on the need to employ AC rather than DC fields based on a CNT stiffening effect (z-pinch) induced by a Lorentz force. The AC-aligned synthesis enables a means to control CNT bundle diameters, which broadened from 16 to 25 nm. The resulting bulk CNT textiles demonstrated an increase in the specific electrical and tensile properties (up to 90 and 460%, respectively) without modifying the quantity or quality of the CNTs, as verified by thermogravimetric analysis and Raman spectroscopy, respectively. The enhanced properties were correlated to the degree of CNT alignment within the textile as quantified by small-angle X-ray scattering and scanning electron microscopy image analysis. Clear alignment (orientational order parameter = 0.5) was achieved relative to the pristine material (orientational order parameter = 0.19) at applied field intensities in the range of 0.5-1 kV cm-1 at a frequency of 13.56 MHz.

Patient-Reported Financial Burden Following Stereotactic Body Radiation Therapy for Localized Prostate Cancer.

Introduction and Objectives: In patients with localized prostate cancer, 5-fraction, stereotactic body radiation therapy (SBRT) has been found to offer comparable oncologic outcomes and potential for improved treatment compliance compared to conventional, 40-plus fraction radiation therapy (RT). Recent studies of oncologic patient experiences have highlighted both the impact of therapy-associated financial toxicity (FT) on treatment adherence and health-related quality of life (HRQOL). Methods: A cross-sectional assessment of FT after SBRT was performed using the 12-item COST questionnaire. The total questionnaire score (range 0-44) was used to evaluate the FT grade (0-3), with a higher COST value representing lower grade. The patient zip code was used to approximate the distance from the index hospital. Univariate and multivariate analyses of the average COST score (0-4) are performed. Results: The response rate was 57.5% (332 of 575 consented patients) with 90.7%, 8.2%, and 1.1% experiencing grade 0, 1, and 2 FT, respectively, with no grade 3. Unemployment or disability, non-white race, low income, and concurrent hormonal therapy were associated with a statistically significant worse FT (lower COST value) on univariate and multivariate analyses (p < 0.05). Education level and insurance status significant were evaluated on univariate analysis only. There was a non-statistically significant difference in age, marital status, time since treatment, and distance from the index hospital. Conclusions: SBRT was associated with low FT. However, statistically significant socioeconomic disparities in FT remain despite ultra-hypofractionated treatment.

Rationale for Utilization of Hydrogel Rectal Spacers in Dose Escalated SBRT for the Treatment of Unfavorable Risk Prostate Cancer.

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).

Ejaculatory Function Following Stereotactic Body Radiation Therapy for Prostate Cancer.

BACKGROUND: Ejaculatory dysfunction is an important male quality of life issue which has not yet been studied in the setting of prostate stereotactic body radiation therapy (SBRT). AIM: The purpose of this study is to evaluate ejaculatory function following SBRT for prostate cancer. METHODS: Two hundred and thirty-one patients on a prospective quality of life study with baseline ejaculatory capacity treated with prostate SBRT from 2013 to 2019 were included in this analysis. Ejaculation was assessed via the Ejaculation Scale (ES-8) from the Male Sexual Health Questionnaire. Patients completed the questionnaire at 1, 3, 6, 9, 12, 18, and 24 months post-SBRT. Elderly patients (Age > 70) and those who received hormonal therapy were excluded from analysis. Patients were treated to 35-36.25 Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). OUTCOMES: Ejaculatory function was assessed by ES-8 scores (range 4-40) with lower values representing increased interference or annoyance. RESULTS: Median age at the time of treatment was 65 years. Median follow up was 24 months (IQR 19-24.5 months). 64.5% of patients had ED at baseline (SHIM < 22). The 2-year anejaculation rate was 15%. Mean composite ES-8 scores showed a decline in the first month following treatment then stabilized: 30.4 (start of treatment); 26.5 (1 month); 27.6 (3 month); 27.0 (6 month); 26.2 (9 month); 25.4 (12 month); 25.0 (18 month) and 25.4 (24 month). White race, higher pre-treatment SHIM (≥22), and higher ES-8 (≥31) at treatment start were significantly associated with a decreased probability of a clinically significant decline. Patient-reported ejaculate volume was significantly reduced at all time points post-SBRT. Ejaculatory discomfort peaked at 1 month and 9 months post-SBRT. Prior to treatment, 8.0% of men reported that they were very to extremely bothered by their ejaculatory dysfunction. The number of patients reporting this concern increased to 14.4% at one year and dropped to 11% at 24-months post-SBRT. CLINICAL TRANSLATION: Patients undergoing prostate SBRT may experience meaningful changes in ejaculatory function and should be counseled on the trajectory of these side effects. STRENGTHS & LIMITATIONS: This was a retrospective analysis of a prospectively maintained database. Subjective questionnaire responses captured limited aspects of ejaculatory function in this cohort. CONCLUSION: The high incidence of moderate to extreme bother in ejaculatory function before and after SBRT suggests a need for novel approaches to improving ejaculation. Sholklapper T, Creswell M, Cantalino J, et al. Ejaculatory Function Following Stereotactic Body Radiation Therapy for Prostate Cancer. J Sex Med 2022;19:771-780.

Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiation therapy (SBRT) is considered standard of care for medically inoperable early stage non-small cell lung cancer (ES-NSCLC). Central tumor location is a known risk factor for severe SBRT related toxicity. Bronchoscopy allows for visualization of the central airways prior to treatment. Five fraction SBRT approaches have been advocated to mitigate treatment induced toxicity. In this report, we examine the mature clinical outcomes of a diverse cohort of ES-NSCLC patients with both peripheral and central tumors treated with a conservative 5 fraction SBRT approach and evaluate the role of lobar gross endobronchial disease (LGED) in predicting overall survival and treatment-related death. METHODS: Medically inoperable biopsy-proven, lymph node-negative ES-NSCLC patients were treated with SBRT. Bronchoscopy was completed prior to treatment in all centrally located cases. The Kaplan-Meier method was used to estimate overall survival (OS), local control (LC), regional control (RC), distant metastasis free survival (DMFS) and disease-free survival (DFS). Overall survival was stratified based on clinical stage, histology, tumor location and LGED. Toxicities were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. RESULTS: From December 2010 to December 2015, 50 consecutive patients were treated uniformly with a 50 Gy in 5 fraction SBRT approach (tumor BED10 ≥ 100 Gy) and followed for a minimum of 5 years or until death. At a median follow up of 42 months for all patients, 3-year OS was 50%. Three-year OS did not statistically differ between stage I and stage II disease (51% vs. 47%; p=0.86), adenocarcinoma and squamous cell carcinoma (50% vs. 45%; p=0.68), or peripheral and central tumors (56% vs. 45%; p=0.46). Five central tumors were found to have LGED, and 3-year OS for this cohort was quite poor at 20%. Cox regression analysis identified LGED as a predictor of OS while controlling for age, stage and location (OR:4.536, p-value=0.038). Despite the relatively low dose delivered, treatment likely contributed to the death of 4 patients with central tumors. Lobar gross endobronchial disease was an independent predictor for grade 5 pulmonary toxicity (n=4, p=0.007). Specifically, 3 of the 5 patients with LGED developed fatal radiation-induced bronchial stricture. Three-year LC, RC, DMFS and DFS results for the group were similar to contemporary studies at 90%, 90%, 82% and 65%. CONCLUSIONS: Central location of ES-NSCLC is a well-established predictor for severe SBRT-related toxicity. Here we identify LGED as a significant predictor of poor overall survival and grade 5 pulmonary toxicity. The relatively high rates of severe treatment-related toxicity seen in patients with central ES-NSCLC may be due in part to LGED. Underlying LGED may cause irreparable damage to the lobar airway, unmitigated by SBRT treatment thus increasing the risk of severe treatment-related toxicity. These findings should be verified in larger data sets. Future prospective central ES-NSCLC clinical trials should require staging bronchoscopy to identify LGED and further assess its clinical significance.

Bleeding Risk Following Stereotactic Body Radiation Therapy for Localized Prostate Cancer in Men on Baseline Anticoagulant or Antiplatelet Therapy.

PURPOSE: Patients on anticoagulant/antiplatelet medications are at a high risk of bleeding following external beam radiation therapy for localized prostate cancer. SBRT may reduce the bleeding risk by decreasing the volume of bladder/rectum receiving high doses. This retrospective study sought to evaluate the rates of hematuria and hematochezia following SBRT in these patients. METHODS: Localized prostate cancer patients treated with SBRT from 2007 to 2017 on at least one anticoagulant/antiplatelet at baseline were included. The minimum follow-up was 3 years with a median follow-up of 72 months. Patients who had a rectal spacer placed prior to SBRT were excluded. Radiotherapy was delivered in 5 fractions to a dose of 35 Gy or 36.25 Gy utilizing the CyberKnife system. Hematuria and hematochezia were prospectively assessed before and after treatment using the Expanded Prostate Cancer Index Composite (EPIC-26). Toxicities were scored using the CTCAE v4. Cystoscopy and colonoscopy findings were retrospectively reviewed. RESULTS: Forty-four men with a median age of 72 years with a history of taking at least one anticoagulant and/or antiplatelet medication received SBRT. Warfarin (46%), clopidogrel (34%) and rivaroxaban (9%) were the most common medications. Overall, 18.2% experienced hematuria with a median time of 10.5 months post-SBRT. Altogether, 38.6% experienced hematochezia with a median time of 6 months post-SBRT. ≥ Grade 2 hematuria and hematochezia occurred in 4.6% and 2.5%, respectively. One patient required bladder neck fulguration and one patient underwent rectal cauterization for multiple non-confluent telangiectasia. There were no grade 4 or 5 toxicities. Cystoscopy revealed bladder cancer (40%) and benign prostatic bleeding (40%) as the most common hematuria etiology. Colonoscopy demonstrated hemorrhoids (54.5%) and radiation proctitis (9.1%) as the main causes of hematochezia. There was no significant change from the mean baseline EPIC-26 hematuria and hematochezia scores at any point during follow up. CONCLUSION: In patients with baseline anticoagulant usage, moderate dose prostate SBRT was well tolerated without rectal spacing. High grade bleeding toxicities were uncommon and resolved with time. Baseline anticoagulation usage should not be considered a contraindication to prostate SBRT.

Impact of Age on Patient-Reported Outcomes Following Stereotactic Body Radiation Therapy for Prostate Cancer.

Purpose Stereotactic body radiation therapy (SBRT) delivers large radiation doses to the prostate while minimizing exposure to adjacent normal tissues. Large fraction sizes may increase the risks of functional decrements. Elderly men may be at an increased risk of these toxicities due to poor baseline function and hence limited reserve. This study describes patient-reported outcomes following SBRT for clinically localized prostate cancer in the elderly. Methods Between 2007 and 2017, 179 hormone-naive elderly patients (≥ 70 years old) and 210 patients under 70 years old with clinically localized prostate cancer were treated with 35-36.25 Gy SBRT in five fractions utilizing the CyberKnife Radiosurgical System (Accuray Inc.). Quality of life (QOL) was assessed using the Expanded Prostate Index Composite-Short Form (EPIC-26) questionnaire at baseline and at 1, 3, 6, 12, 18, 24, 30, and 36 months following the completion of treatment. EPIC scores range from 0 to 100, with lower values representing worsening symptoms. Results EPIC scores in the elderly cohort mirrored those in the younger cohort. EPIC urinary obstructive/irritative scores declined at one month post-SBRT (mean change from baseline ≥70: -7.9; <70: -11.1) before returning to baseline at three months post-SBRT (mean change from baseline ≥70: -0.4; <70: -1.4). The EPIC urinary incontinence scores declined slowly over the three years following treatment without recovery (mean change from baseline ≥70: -6.6; <70: -4.8). EPIC Bowel scores transiently declined at one month post-SBRT (mean change from baseline ≥70: -8.5; <70: -9.1) and then experienced a second more protracted decline over the next three years without recovery (mean change from baseline ≥70: -4.5; <70: -1.8). Hormonal EPIC scores were not impacted by radiation treatment or age. Older men had lower baseline and post-treatment EPIC sexual summary scores at all time points. However, there was no clinically significant difference in the EPIC sexual bother score between younger and older men at baseline and following treatment. Conclusions In the first three years following treatment, the impact of SBRT treatment on patient-reported outcomes was minimal. Our findings suggest that SBRT for clinically localized prostate cancer should not be deferred in older men solely due to concerns of increased morbidity. Further studies should be conducted to evaluate the impact of age on outcomes or morbidity following SBRT.

Treatment Interruptions During Stereotactic Body Radiotherapy for Prostate Cancer.

BACKGROUND: During the course of radiation treatment for prostate cancer, patients may have unintentional interruptions in their treatment course due to a wide variety of factors. Stereotactic body radiation therapy (SBRT) decreases the number of treatments compared to conventionally fractionated radiation; hence, it has the potential to decrease treatment delays and non-completion. This study sought to determine the incidence of treatment delay and characterize the etiology and length in a large cohort of men treated with SBRT for their prostate cancer. METHODS: One thousand three hundred and thirty-six patients treated with SBRT from 2008 to 2021 at the Georgetown University Hospital for prostate cancer were included in this retrospective study. A treatment delay was defined as a patient requiring longer than 14 days to complete 5 fractions of SBRT. Non-completion was defined as patients treated with less than 5 fractions. In the patients who experienced delays, chart review was performed to characterize the length and etiology of each delay. Multivariate analysis was performed via binary logistic regression modeling on PSPP. RESULTS: All individuals in the cohort eventually completed the planned 5-fraction regimen. Thirty-three patients experienced a treatment delay. Median length of time to complete treatment was 11 days (range 5-155 days). In patients who experienced a delay, nearly half (45.5%) experienced only a one-day delay. The most common reason for a delay was a technical issue (48.5%), including the machine maintenance, fiducial misalignment, or inadequate pretreatment bowel preparation. Other reasons included unplanned breaks due to acute side effects (21.2%), logistical issues (18.2%), non-treatment related health issues (9.1%), and inclement weather (3.0%). There were no significant sociodemographic, oncologic, or treatment variables that predicted treatment interruption on multivariate analysis. CONCLUSIONS: The incidence of treatment interruptions in patients undergoing SBRT for their prostate cancer was low. Most treatment delays were short.

Volume of Disease as a Predictor for Clinical Outcomes in Patients With Melanoma Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Therapy.

PURPOSE/OBJECTIVES: Clinical trials of anti-Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein (CTLA-4) therapies have demonstrated a clinical benefit with low rates of neurologic adverse events in patients with melanoma brain metastases (MBMs). While the combined effect of these immunotherapies (ITs) and stereotactic radiosurgery (SRS) has yielded impressive results with regard to local control (LC) and overall survival (OS), it has also been associated with increased rates of radiation necrosis (RN) compared to historical series of SRS alone. We retrospectively reviewed patients treated with IT in combination with SRS to report on predictors of clinical outcomes. MATERIALS AND METHODS: Patients were included if they had MBMs treated with SRS within 1 year of receiving anti-PD-1 and/or CTLA-4 therapy. Clinical outcomes including OS, LC, intracranial death (ID), and RN were correlated with type and timing of IT with SRS, radiation dose, total volume, and size and number of lesions treated. RESULTS: Twenty-nine patients with 171 MBMs were treated between May 2012 and May 2018. Patients had a median of 5 lesions treated (median volume of 6.5 cm3) over a median of 2 courses of SRS. The median dose was 21 Gy. Most patients were treated with ipilimumab (n = 13) or nivolumab-ipilimumab (n = 10). Most patients underwent SRS concurrently or within 3 months of receiving immunotherapy (n = 21). Two-year OS and LC were 54.4% and 85.5%, respectively. In addition, 14% of patients developed RN; however, only 4.7% of the total treated lesions developed RN. The median time to development of RN was 9.5 months. Patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID (p = 0.05) and RN (p = 0.03). There was no difference in OS, ID, or RN with regard to type of IT, timing of SRS and IT, number of SRS courses, SRS dose, or number of cumulative lesions treated. CONCLUSIONS: In our series, patients treated with SRS and IT for MBMs had excellent rates of OS and LC; however, patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID and RN. Given the efficacy of combined anti-PD-1/CTLA-4 therapy for MBM management, further study of optimal selection criteria for the addition of SRS is warranted.

Arteriovenous Malformations Treated With Frameless Robotic Radiosurgery Using Non-Invasive Angiography: Long-Term Outcomes of a Single Center Pilot Study.

OBJECTIVE: CT-guided, frameless robotic radiosurgery is a novel radiotherapy technique for the treatment of intracranial arteriovenous malformations (AVMs) that serves as an alternative to traditional catheter-angiography targeted, frame-based methods. METHODS: Patients diagnosed with AVMs who completed single fraction frameless robotic radiosurgery at Medstar Georgetown University Hospital between July 20, 2006 - March 11, 2013 were included in the present study. All patients received pre-treatment planning with CT angiogram (CTA) and MRI, and were treated using the CyberKnife radiosurgery platform. Patients were followed for at least four years or until radiographic obliteration of the AVM was observed. RESULTS: Twenty patients were included in the present study. The majority of patients were diagnosed with Spetzler Martin Grade II (35%) or III (35%) AVMs. The AVM median nidus diameter and nidal volume was 1.8 cm and 4.38 cc, respectively. Median stereotactic radiosurgery dose was 1,800 cGy. After a median follow-up of 42 months, the majority of patients (81.3%) had complete obliteration of their AVM. All patients who were treated to a total dose of 1800 cGy demonstrated complete obliteration. One patient treated at a dose of 2,200 cGy developed temporary treatment-related toxicity, and one patient developed post-treatment hemorrhage. CONCLUSIONS: Frameless robotic radiosurgery with non-invasive CTA and MRI radiography appears to be a safe and effective radiation modality and serves as a novel alternative to traditional invasive catheter-angiography, frame-based methods for the treatment of intracranial AVMs. Adequate obliteration can be achieved utilizing 1,800 cGy in a single fraction, and minimizes treatment-related side effects.

Management of Isolated Local Failures Following Stereotactic Body Radiation Therapy for Low to Intermediate Risk Prostate Cancer.

Background: Stereotactic body radiation therapy (SBRT) is a safe and effective treatment option for patients with low to intermediate risk prostate cancer (1). SBRT results in very low PSA nadirs secondary to the delivery of high biologically effective doses. Studies reporting on the diagnosis, confirmation, and management of salvageable isolated local failures (ILF) are limited. This study aims to determine the incidence and management approach of ILF after SBRT in a large single institution cohort. Method: All patients with low or intermediate risk localized prostate cancer treated with SBRT at Georgetown University Hospital were eligible for this study. Treatment was delivered using robotic SBRT with doses of 35-36.25 Gy in five fractions. ILF were diagnosed using multiparametric MRI and/or biopsy prompted by rising PSA levels after achieving long-term nadir. Patient's characteristics were extracted from a prospective institutional quality of life trial (IRB 2009-510). Type of salvage therapy and post-salvage PSA were determined on subsequent follow-up and chart review. Results: Between December 2008 to August 2018, 998 men with low to intermediate risk prostate cancer were eligible for inclusion in this analysis. Twenty-four patients (low risk, n = 5; intermediate risk, n = 19) were found to have ILF within the prostate on either MRI (n = 19) and/or biopsy (n = 20). Median pre-treatment PSA was 7.55 ng/ml. Median time to diagnosis of ILF was 72 months (24-110 months) with median PSA at the time of ILF of 2.8 ng/ml (0.7-33 ng/ml). Median PSA doubling time was 17 months (5-47 months). Thirteen patients with biopsy proven ILF proceeded with salvage therapy (cryotherapy n = 12, HIFU n = 1). Of 12 patients who underwent cryotherapy, 7 had a post-treatment PSA of <0.1 ng/ml. One patient experienced a urethral-cutaneous fistula (grade 3 toxicity). Conclusion: The incidence of isolated local recurrence is rare in our cohort. Diagnosis and management of isolated local failures post-SBRT continues to evolve. Our report highlights the importance of early utilization of MRI and confirmatory biopsy at relatively low PSA levels and long PSA doubling time (1). Additionally, undetectable PSA levels after salvage therapy supports the role of early treatment in ILF (1). Further research is needed to determine appropriate patient selection and salvage modality in this population.

Stereotactic Body Radiation Therapy (SBRT) for Prostate Cancer in Men With a High Baseline International Prostate Symptom Score (IPSS ≥ 15).

Background: Patients with a high pretreatment IPSS may have higher rates of late urinary morbidity after radiation therapy for prostate cancer (1). Stereotactic body radiation therapy (SBRT) delivers fewer high-dose fractions of radiation, which may be radiobiologically favorable to the conventional low-dose external beam fractions. The urinary toxicity associated with SBRT, however, remains unclear in patients with a high IPSS (1). We report our experience using SBRT for localized prostate cancer in patients with pretreatment IPSS ≥ 15. Methods: Localized prostate cancer patients with a pre-treatment IPSS ≥ 15 treated with SBRT at Georgetown University Hospital from 2009 to 2016 were included in this retrospective review of prospectively collected data. These patients were treated to 35-36.25 Gy in five fractions delivered via CyberKnife (Accuray Inc., Sunnyvale, CA). Urinary toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4). Urinary quality of life was assessed using validated questionnaires (IPSS and EPIC-26). Results: 53 patients at a median age of 71 years (range 57-89 years) received SBRT with a minimum follow up of 3 years. The median prostate size was 37 cm3 (range 12-100 cm3) and 30.2% patients received ADT. The 3-years incidence rate of Grade 3 urinary toxicity was 7.5% with median time to toxicity of 2.9 years. There were no Grade 4 or 5 toxicities. A mean baseline IPSS score of 19.8 significantly decreased to 12.9 at 3 months post-SBRT (p = 0.002) and remained stable at 36 months (13.7). A mean baseline EPIC-26 obstructive/irritative score of 64.1 significantly improved to 80.2 at 3 months (p = 0.002). This improvement was maintained to 36 months. There was no significant change from the mean baseline EPIC-26 urinary incontinence score at any point during follow up. Conclusions: SBRT for clinically localized prostate cancer was well-tolerated in men with baseline IPSS ≥ 15 (1). Grade 3 toxicities occurred but resolved with time. Our data suggest that poor baseline urinary function does not worsen following SBRT and may even improve. High baseline IPSS score should not be considered a contraindication to SBRT.