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PURPOSE We sought to investigate whether enzalutamide (ENZA), without concurrent androgen deprivation therapy, increases freedom from prostate-specific antigen (PSA) progression (FFPP) when combined with salvage radiation therapy (SRT) in men with recurrent prostate cancer after radical prostatectomy (RP). PATIENTS AND METHODS Men with biochemically recurrent prostate cancer after RP were enrolled into a randomized, double‐blind, phase II, placebo-controlled, multicenter study of SRT plus ENZA or placebo (ClinicalTrials.gov identifier: NCT02203695 ). Random assignment (1:1) was stratified by center, surgical margin status (R0 v R1), PSA before salvage treatment (PSA ≥ 0.5 v < 0.5 ng/mL), and pathologic Gleason sum (7 v 8‐10). Patients were assigned to receive either ENZA 160 mg once daily or matching placebo for 6 months. After 2 months of study drug therapy, external-beam radiation (66.6‐70.2 Gy) was administered to the prostate bed (no pelvic nodes). The primary end point was FFPP in the intention-to-treat population. Secondary end points were time to local recurrence within the radiation field, metastasis‐free survival, and safety as determined by frequency and severity of adverse events. RESULTS Eighty-six (86) patients were randomly assigned, with a median follow-up of 34 (range, 0-52) months. Trial arms were well balanced. The median pre-SRT PSA was 0.3 (range, 0.06-4.6) ng/mL, 56 of 86 patients (65%) had extraprostatic disease (pT3), 39 of 86 (45%) had a Gleason sum of 8-10, and 43 of 86 (50%) had positive surgical margins (R1). FFPP was significantly improved with ENZA versus placebo (hazard ratio [HR], 0.42; 95% CI, 0.19 to 0.92; P = .031), and 2-year FFPP was 84% versus 66%, respectively. Subgroup analyses demonstrated differential benefit of ENZA in men with pT3 (HR, 0.22; 95% CI, 0.07 to 0.69) versus pT2 disease (HR, 1.54; 95% CI, 0.43 to 5.47; Pinteraction = .019) and R1 (HR, 0.14; 95% CI, 0.03 to 0.64) versus R0 disease (HR, 1.00; 95% CI, 0.36 to 2.76; Pinteraction = .023). There were insufficient secondary end point events for analysis. The most common adverse events were grade 1-2 fatigue (65% ENZA v 53% placebo) and urinary frequency (40% ENZA v 49% placebo). CONCLUSION SRT plus ENZA monotherapy for 6 months in men with PSA-recurrent high-risk prostate cancer after RP is safe and delays PSA progression relative to SRT alone. The impact of ENZA on distant metastasis or survival is unknown at this time.

In the era of dose-escalated prostate radiation therapy (RT), the use of androgen deprivation therapy (ADT) is undefined for intermediate-risk (IR) prostate cancer. There is growing concern of the risk of ADT to be detrimental to quality of life. This single-institution retrospective analysis aimed to evaluate outcomes of IR patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with or without concurrent/adjuvant short-term ADT.Data was collected from 260 consecutive patients treated with dose-escalated IMRT with daily image-guided RT for newly diagnosed IR prostate cancer. Biochemical recurrence-free survival (BCRFS), distant metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were calculated using Kaplan-Meier methodology.Median follow-up was 93 months. A total of 181 patients had unfavorable IR disease, and 36.2% (N=94) received ADT, with median ADT duration of 6 months. Seven-year BCRFS was 94.1% vs. 86.2% (P=0.067), for ADT and no ADT, respectively, and no difference in distant metastasis-free survival or prostate cancer-specific survival was observed. ADT was associated with significantly worse 7-year OS (80.0% vs. 91.3%, P=0.010). Analysis of the unfavorable IR cohort alone, showed similar results; 7-year BCRFS and 7-year OS in patients who received ADT versus no ADT were 93.7% vs. 85.9% (P=0.093), and 79.0% vs. 90.6% (P=0.019), respectively.In our 15-year experience treating IR prostate cancer with dose-escalated IMRT with daily image-guided RT, short-term concurrent ADT was associated with a statistically significant worse OS. Additional studies are needed to determine if ADT is beneficial or detrimental for patients with IR prostate cancer treated with dose-escalated radiation.

Please see the Editorial Comment by Joanna Kee-Sampson discussing this article. BACKGROUND. Transarterial chemoembolization (TACE) has synergistic properties when combined with ablative therapies f...

PURPOSE: To study longitudinal changes in retinal capillary circulation in eyes treated with iodine 125 (I(125)) plaque brachytherapy for uveal melanoma using OCT angiography (OCTA). DESIGN: Longitudinal prospective study of 21 patients undergoing treatment for uveal melanoma with I(125) plaque brachytherapy. Eyes with melanoma were imaged with OCTA before treatment and at 12-month intervals until 2 years after brachytherapy. PARTICIPANTS: After institutional review board approval, participants were enrolled prospectively from an academic ocular oncology clinic. METHODS: Peripapillary (4.5 × 4.5-mm) and macular (3 × 3-mm) OCTA scans were acquired with AngioVue (Optovue, Inc, Fremont, CA). MAIN OUTCOME MEASURES: The peripapillary nerve fiber layer plexus capillary density (NFLP_CD), macular superficial vascular complex vessel density (mSVC_VD), and foveal avascular zone (FAZ) area were calculated. RESULTS: Before treatment, no significant difference was found in the NFLP_CD, mSVC_VD, or FAZ area between eyes with melanoma and normal fellow eyes. By 24 months, 11 eyes had developed clinical signs of radiation retinopathy, radiation optic neuropathy, or both. In treated eyes, the NFLP_CD (48.4 ±.44.1%) was reduced at 12 months (46.7±5.0%; P = 0.04, Wilcoxon signed-rank test) and 24 months (44.5±6.1%; P < 0.001). Similarly, the mSVC_VD (48.4 2±3.6%) was reduced in treated eyes at 12 months (43.5±5.9%; P = 0.01) and 24 months (37.4±9.1%; P < 0.001). The FAZ area (0.26±0.11 mm(2)) increased in treated eyes at 12 months (0.35±0.22 mm(2); P = 0.009) and 24 months (0.81±1.03 mm(2); P = 0.001). When only eyes with clinically evident radiation changes were evaluated, the changes in NFLP_CD, mSVC_VD, and FAZ area were more pronounced. OCT angiography measurements correlated with both radiation dose and visual acuity. The mSVC_VD measured at 12 months was found to predict the development of clinically apparent radiation retinopathy within 1 year. CONCLUSIONS: OCT angiography demonstrated early emergence of peripapillary and macular capillary vasculature changes after I(125) plaque brachytherapy. OCT angiography provided a quantitative measurement of retinal capillary changes associated with ischemia that correlated with visual acuity and radiation dose and may predict future development of radiation-induced retinal toxicity.

Introduction Prostate cancer can negatively impact the health of patients and their spouse, particularly early on in the cancer trajectory. Purpose To determine the feasibility and acceptability of dyadic exercises during radiation therapy and preliminary efficacy on physical, mental, and relational outcomes for men and their spouses. Exercising Together©, originally designed as a 6-month dyadic resistance training program for couples post-treatment, was adapted for the radiation setting. Methods We conducted a single-group pilot feasibility study of Exercising Together© in men scheduled for radiation therapy for prostate cancer and their spouse. Couples attended supervised exercise sessions thrice weekly throughout radiation treatment and were followed up 8 weeks later. Primary outcomes were feasibility and acceptability with secondary outcomes of changes in physical (physical functioning (short physical performance battery (sPPB)), gait speed (m/s), functional capacity (400-m walk (min), physical activity (min/week)), mental (depressive symptoms (CES-D), and anxiety (SCL-90 ANX)), and relationship (Dyadic Coping, Role Overload, and Physical Intimacy Behavior Scales) health outcomes for each partner. Participants completed an evaluation post-intervention. Results Ten couples enrolled and 8 completed the intervention, attending 83% of scheduled sessions. Couple satisfaction with the intervention was high (patients: mean difference (MD) = 9.4 ± 1.9 and spouses: MD = 10.0 ± 0.0, on a 1–10 scale). At post-intervention, gait speed (MD = 0.1; 95%CI: 0.1, 0.2; p = 0.003; d = 0.94) and functional capacity (MD = −0.6; 95%CI: −0.9, 0.3; p = 0.002; d = −0.42) improved in patients and sPPB in spouses (MD = 1.3; 95%CI: 0.3, 2.2; p = 0.02; d = 0.71). Total physical activity increased non-significantly for patients and significantly for spouses at post-intervention and decreased at follow-up (MD = 179.6; 95%CI: 55.4, 303.7; p = 0.01; d = 1.35 and MD = −139.9; 95%CI: −266.5, 13.3; p = 0.03; d=1.06). Among patients, anxiety and active engagement significantly improved post-intervention (MD = −2.3; 95%CI: −3.8, 0.7; p = 0.01; d = −0.43 and MD = 2.5; 95%CI: 0.7, 4.3; p = 0.01; d = 0.98, respectively). There were modest effects on other physical, mental, and relationship health domains in patients and spouses. Conclusion A modified version of Exercising Together© is a feasible and acceptable program during radiation therapy for prostate cancer and shows preliminary evidence for improvements on physical, mental, and relational health in both patient and spouse. A larger, fully powered randomized controlled trial is warranted and could help shift the landscape toward dyadically targeted interventions. Trial registration This study was registered on ClinicalTrials.gov on February 18th, 2018 (NCT03418025).

Background: Treatment planning for I-125 plaque therapy for uveal melanoma has advanced significantly since the Collaborative Ocular Melanoma Study trial, with more widely available image-guided planning and improved dosimetry. Objective: We evaluated real-world practice patterns for I-125 plaque brachytherapy in the United States by studying practice patterns at centers that comprise the Ocular Oncology Study Consortium (OOSC). Methods: The OOSC database and responses to a treatment practice survey were evaluated. The database contains treatment information from 9 institutions. Patients included in the database were treated between 2010 and 2014. The survey was conducted in 2018 and current treatment planning methods and prescriptions were queried. Results: Examination of the OOSC database revealed that average doses to critical structures were highly consistent, with the exception of one institution. Survey responses indicated that most centers followed published guidelines regarding dose and prescription point. Dose rate ranged from 51 to 118 cGy/h. As of 2018, most institutions use pre-loaded plaques and fundus photographs and/or computed tomography or magnetic resonance imaging in planning. Conclusions: While there were differences in dosimetric practices, overall agreement in plaque brachytherapy practices was high among OOSC institutions. Clinical margins and planning systems were similar among institutions, while prescription dose, dose rates, and dosimetry varied.

Background Many prostate cancer survivors are treated with androgen deprivation therapy (ADT), but these therapies may increase frailty, worsen physical functioning, and increase fall risk. While exercise may counter functional declines associated with ADT, no studies have tested whether and which type of exercise may reduce falls and frailty. The purpose of this trial is to compare the relative efficacy of strength training versus tai ji quan training against each other and to a stretching control group on falls, frailty, and physical functioning in men expose to ADT for prostate cancer. Methods Prostate cancer survivors treated with ADT (N = 360) who have fallen in the past year or are at risk of a fall based on validated risk factors will be recruited to participate in this single-blind, parallel group, randomized trial. Participants will be randomized to one of three supervised, group training programs: (i) strength training, (ii) tai ji quan training, or (iii) stretching (control), that train 3×/week for 6 months. Outcomes are assessed at baseline, 3 (mid-intervention), 6 (immediately post-intervention), and 12 (follow-up) months. The primary outcome is falls assessed by monthly self-report. Secondary outcomes include the following: frailty (low lean body mass (by bioelectrical impedance analysis), exhaustion (by SF-36 vitality scale), low activity (by CHAMPS physical activity survey), slowness (by 4 m usual walk speed), and weakness (by chair stand time)); objective and subjective measures of physical function will also be collected. Negative binomial regression models will be used to assess differences in falls between groups, while mixed effects modeling will be used to compare the relative efficacy of training group on secondary outcomes. Discussion Exercise represents a non-pharmacologic approach to mitigate the problem of falls experienced among men treated with ADT. By engaging in appropriate exercise, men may be able to avoid or delay falls, frailty, and disability associated with their cancer treatment. Findings of the trial are expected to inform clinical practice about how exercise could be prescribed as part of cancer care for prostate cancer survivors prescribed ADT. Trial registration ClinicalTrials.gov NCT03741335. Registered on November 18, 2018.

PURPOSE/OBJECTIVE(S) To assess the performance of commercially available autosegmentation solutions of pelvic anatomy in edge cases of anatomic variation among patients receiving definitive radiotherapy (RT) for prostate cancer. MATERIALS/METHODS In a single institution retrospective cohort of 830 patients with prostate cancer receiving definitive RT between 2011 and 2019, we identified 112 patients with anatomic variations seen on simulation CT imaging which may present challenging cases for precise delineation of anatomy, including reasons such as arthroplasty metal artifacts, extensive median lobe hypertrophy, "droopy" seminal vesicles, presence of urinary catheter, and history of transurethral resection of prostatic tissue. Three commercially available solutions for pelvic anatomy autosegmentation (AS) employing deep learning and model-based segmentation were applied to treatment planning CT scans to generate segmented volumes of the prostate, rectum, bladder and femoral heads in DICOM-RT format. To quantify the accuracy of software-generated contours, Dice similarity coefficients (DSC) and Hausdorff distances (HD) were calculated for each AS contour with a comparator manually segmented reference contour. Calculations were performed in R using the RadOnc package and manually segmented contours were approved by an expert radiation oncologist with 19 years of experience. RESULTS A total of 112 patients were identified for inclusion after manual review of treatment planning CTs. Contours were generated using two atlas/model-based segmentation products and a deep learning segmentation method. The mean DSC for the prostate, bladder, rectum was calculated for each segmentation method (Table 1). Deep learning segmentation outperformed model-based methods for all structures with the highest mean DSC but still had significant disagreement with manually segmented structures. Hip arthroplasty in particular reduced overall performance more than other anatomical edge cases, followed by prostatic hypertrophy. CONCLUSION Anatomic edge cases present a challenging and relevant consideration in clinical implementation of autosegmentation software.

Sarcomas are a group of diverse, rare tumors originating in the bone and connective tissue. They comprise approximately 1% of adult malignancies and 12% of pediatric malignancies. Eighty percent of sarcomas are soft tissue sarcomas which arise in the extremities, trunk and retroperitoneum, and head and neck in order of decreasing frequency. The World Health Organization recognizes over 100 different histologies. Sarcoma treatment primarily involves a high-quality oncologic resection. Based on prognostic factors, treatment includes adjuvant or neoadjuvant treatment with radiation and/or chemotherapy. This chapter reviews the management of soft tissue and bone sarcomas, pertinent literature, and radiation therapy guidelines. Radiation oncologists most often treat soft tissue sarcomas of the extremity so a deeper focus is given to this group.

Purpose: Most men with stage I testicular seminoma are cured with surgery alone, which is a preferred strategy per national guidelines. The current pattern of practice among US radiation oncologists (ROs) is unknown. Materials and Methods: We surveyed practicing US ROs via an online questionnaire. Respondent's characteristics, self-rated knowledge, perceived patient compliance rates with observation were analyzed for association with treatment recommendations. Results: We received 353 responses from ROs, of whom 23% considered themselves experts. A vast majority (84%) recommend observation as a default strategy, however this rate drops to 3% if the patient is believed to be noncompliant. 33% of respondents believe that survival is jeopardized in case of disease recurrence, and among these respondents only 5% support observation. 22% of respondents over-estimate the likelihood of noncompliance with observation to be in the 50-80% range. Responders with a higher perceived noncompliance rate are more likely to recommend adjuvant therapy (Fisher's exact p

The purpose of our study was to show the feasibility and potential benefits of using 68Ga-PSMA-PET/CT imaging for radiation therapy treatment planning of patients with primary prostate cancer using either integrated boost on the PET-positive volume or localized treatment of the PET-positive volume. The potential gain of such an approach, the improvement of tumor control, and reduction of the dose to organs-at-risk at the same time was analyzed using the QUANTEC biological model. Twenty-one prostate cancer patients (70 years average) without previous local therapy received 68Ga-PSMA-PET/CT imaging. Organs-at-risk and standard prostate target volumes were manually defined on the obtained datasets. A PET active volume (PTV_PET) was segmented with a 40% of the maximum activity uptake in the lesion as threshold followed by manual adaption. Five different treatment plan variations were calculated for each patient. Analysis of derived treatment plans was done according to QUANTEC with in-house developed software. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was calculated for all plan variations. Comparing the conventional plans to the plans with integrated boost and plans just treating the PET-positive tumor volume, we found that TCP increased to (95.2 ± 0.5%) for an integrated boost with 75.6 Gy, (98.1 ± 0.3%) for an integrated boost with 80 Gy, (94.7 ± 0.8%) for treatment of PET-positive volume with 75 Gy, and to (99.4 ± 0.1%) for treating PET-positive volume with 95 Gy (all p

Background In men with a rising PSA following radical prostatectomy, salvage radiation therapy (SRT) offers a second chance for cure. Hormonal therapy can be combined with SRT in order to increase prostate tumor control, albeit with associated higher rates of treatment side effects. This trial studies the effectiveness of SRT combined with hormonal therapy using a more potent anti-androgen with a favorable side effect profile. Enzalutamide, a next generation selective androgen receptor antagonist, is approved by the Food and Drug Administration for the treatment of metastatic castrate-resistant prostate cancer (CRPC) where it has been shown to improve overall survival in combination with androgen deprivation therapy. The primary objective of this study is to evaluate the efficacy of combination SRT and enzalutamide for freedom-from-PSA-progression. Secondary objectives include time to local recurrence within the radiation field, metastasis-free survival and safety as determined by frequency and severity of adverse events. Methods/design This is a randomized, double-blind, phase II, prospective, multicenter study in adult males with biochemically recurrent prostate cancer following radical prostatectomy. Following registration, enzalutamide 160 mg or placebo by mouth (PO) once daily will be administered for 6 months. Following two months of study drug, external beam radiotherapy to 66.6–70.2 Gray (Gy) will be administered to the prostate bed over 7–8 weeks while continuing daily placebo/enzalutamide. This is followed by two additional months of placebo/enzalutamide. Discussion The SALV-ENZA trial is the first phase II placebo-controlled double-blinded randomized study to test SRT in combination with a next generation androgen receptor antagonist in men with high-risk recurrent prostate cancer after radical prostatectomy. The primary hypothesis of this study is that clinical outcomes will be improved by the addition of enzalutamide compared to standard-of-care SRT alone and pave the path for phase III evaluation of this combination. Trial registrations ClinicaltTrials.gov Identifier: NCT02203695 Date of Registration: 06/16/2014. Date of First Participant Enrollment: 04/16/2015.

Medical image segmentation is typically performed manually by a physician to delineate gross tumor volumes for treatment planning and diagnosis. Manual segmentation is performed by medical experts using prior knowledge of organ shapes and locations but is prone to reader subjectivity and inconsistency. Automating the process is challenging due to poor tissue contrast and ill-defined organ/tissue boundaries in medical images. This paper presents a genetic algorithm for combining representations of learned information such as known shapes, regional properties and relative position of objects into a single framework to perform automated three-dimensional segmentation. The algorithm has been tested for prostate segmentation on pelvic computed tomography and magnetic resonance images.

Soft tissue sarcomas are highly diverse mesenchymal malignancies of muscle, peripheral nerves, and adipose or fibrous connective tissues. Sarcoma classification had been entirely based on resemblance to various tissue types. More recently, classifications have been revised to include molecular features and genetic profiles of sarcoma. While our treatment paradigms for soft tissue sarcomas were developed on, what we know now to be oversimplified, histologic classifications, the addition of specific karyotyping and biomarkers has not changed our overall approach to these tumors in the majority. The local therapy paradigms are still based on surgery and radiation for the vast majority of these tumors.

INTRODUCTION AND OBJECTIVE:The 18F-Fluciclovine (FACBC, Axumin) PET/CT scan has higher sensitivity than traditional imaging modalities for the detection of prostate cancer (PCa) recurrence. We aim ...

OBJECTIVE: To study peripapillary retinal capillary circulation in eyes treated with I-125 plaque brachytherapy for uveal melanoma using optical coherence tomography angiography (OCTA). DESIGN: Cross-sectional study of 10 subjects imaged with OCTA prior to uveal melanoma treatment and 15 subjects imaged after development of radiation retinopathy and/or optic neuropathy. PARTICIPANTS: Following IRB approval, subjects were enrolled from an academic ocular oncology clinical practice. All subjects had uveal melanoma in one eye and treatment with I-125 plaque brachytherapy was planned or had previously taken place. Patients with low vision at baseline and uncontrolled hypertension were excluded. In the post-treatment group, seven subjects were male and eight were female; age range 38 to 81 years. Visual acuities in the irradiated eyes ranged from 20/20 to counting fingers. Visual acuities in the untreated fellow eyes were 20/25 or better. METHODS: Peripapillary retinal capillary circulation was measured by OCTA (Optovue, Inc). 4.5×4.5 mm optic disc scans were obtained. 10 subjects were imaged prior to brachytherapy treatment and 15 subjects were imaged after development of clinically apparent radiation retinopathy and/or radiation optic neuropathy post-brachytherapy. MAIN OUTCOME MEASURES: The relationship of the peripapillary retinal capillary density (PPCD) as measured by OCTA to the calculated dose to the optic nerve (D50, the dose to 50% of the disc) and the LogMAR vision was evaluated. RESULTS: No significant difference was seen in the PPCD as measured by OCTA when comparing the eye with melanoma to the fellow eye prior to brachytherapy; however the PPCD was significantly lower in treated eyes (52.9% +/− 22.4%) than in fellow eyes that did not receive radiation (73.3% +/− 13.7%, p = 0.004). There was an inverse linear correlation between D50 and the PPCD (Pearson’s; r= −0.528, P=0.043) and between visual acuity and the PPCD (Pearson’s; r= −0.564, P=0.028). CONCLUSIONS: Among patients with clinically apparent radiation retinopathy and/or radiation optic neuropathy, PPCD was lower in the treated eye and correlated with the radiation dose to the optic nerve and the visual acuity. OCTA provides a measure of capillary changes following radiation, and may serve as a quantitative endpoint to address visual prognosis.

Purpose Radiation oncology curriculum development is challenging because of limited numbers of trainees at any single institution. The goal of this project is to implement and evaluate a standardized medical student clerkship curriculum following the multi-institutional cooperative group research model. Methods During the 2013 academic year, a standardized curriculum was implemented at 11 academic medical centers consisting of three 1-hour lectures and a hands-on radiation treatment planning workshop. After the curriculum, students completed anonymous evaluations using Likert-type scales (1 = "not at all" to 5 = "extremely") and free responses. Evaluations asked students to rate their comfort, before and after the curriculum, with radiation oncology as a specialty, knowledge of radiotherapy planning methods, and ability to function as a radiation oncology resident. Nonparametric statistical tests were used in the analysis. Results Eighty-eight students at 11 academic medical centers completed the curriculum de novo, with a 72.7% (64 of 88) survey response rate. Fifty-seven students (89.1%) reported intent to pursue radiation oncology as their specialty. Median (interquartile range) student ratings of the importance of curricular content were as follows: overview, 4 (4-5); radiation biology/physics, 5 (4-5); practical aspects/emergencies, 5 (4-5); and planning workshop, 4 (4-5). Students reported that the curriculum helped them better understand radiation oncology as a specialty (5 [4-5]), increased specialty decision comfort (4 [3-5]), and would help the transition to radiation oncology residency (4 [4-5]). Students rated their specialty decision comfort significantly higher after completing the curriculum (4 [4-5] versus 5 [5-5]; P Conclusions A national standardized curriculum was successfully implemented at 11 academic medical centers, providing proof of principle that curriculum development can follow the multi-institutional cooperative group research model.

Mechanisms of fatigue reported during radiotherapy are poorly defined but may include inflammatory cytokines and/or sleep disturbances. This prospective, longitudinal, phase II study assessed fatigue, sleep, and serum cytokine levels during radiotherapy for early-stage prostate cancer (PCa).Twenty-eight men undergoing radiotherapy for early-stage PCa wore an Actiwatch Score to record fatigue level, sleep time, onset latency, efficiency and wake after sleep onset. Serum levels of IL-1α, IL-1β, TNF-α, IL-6, IL-8, IL-10 and VEGF were measured weekly during radiotherapy. Patient reported quality of life (QOL) metrics were collected before and after treatment. Linear mixed effects models examined trajectories across treatment weeks.Fatigue increased across treatment weeks (P.01), and fatigue was associated with decreased patient-reported QOL. Sleep efficiency increased across treatment weeks (rate of change over time=.29, P=.03), and sleep onset latency decreased (rate of change over time=.86, P=.06). IL-6 tended to increase during treatment (P=0.09), but none of the cytokine levels or sleep variables were significantly related to fatigue trajectories.Despite increased sleep efficiency across treatment weeks, fatigue significantly increased. Although IL-6 increased during the course of radiotherapy, cytokines levels were not associated with fatigue scores or sleep disturbance. Further studies are needed to define the mechanisms for fatigue during radiotherapy.

Patients with testicular seminoma may face fertility issues because of their underlying disease as well as treatments they undergo. The current patterns of practice among U.S. radiation oncologists aimed at assessing and preserving fertility in patients with Stage I seminoma are unknown.We surveyed practicing U.S. radiation oncologists via an Institutional Review Board-approved online questionnaire. Respondents' characteristics and perceived patient infertility rates were analyzed for association with treatment recommendations.We received 353 responses, of whom one quarter (23%) consider themselves experts. A vast majority (84%) recommend observation as a default strategy. Fifty-two percent routinely advise fertility assessment for patients before observation or chemotherapy, and 74% routinely do so before adjuvant radiation therapy (RT). Forty-one percent and 43% believe that 10% and 30% of patients are infertile following orchiectomy, respectively. Thirty-seven percent and 22% believe infertility rates following para-aortic RT to be 30% and 50%, respectively. Eighty percent routinely use clamshell scrotal shielding. Responders with higher perceived infertility rates are more likely to recommend fertility assessment/sperm banking (Fisher's exact p 0.0001). Responders who routinely advised fertility assessment were more likely to use clamshell shielding (Cochran-Armitage trend test p = 0.0007). Clamshell use was positively correlated with higher perceived infertility rates following para-aortic RT (Spearman's correlation coefficient = 0.006).Despite a clear knowledge of fertility issues in men diagnosed with seminoma, there is no universal adoption of fertility assessment among U.S. radiation oncologists.

The optimal treatment of high-risk soft tissue sarcomas (STS) of the extremities remains controversial. We report follow-up from a phase II study of dose-intense chemotherapy with preoperative hypofractionated radiation in this population supplemented with subsequent data from an extensive institutional experience using this regimen. Patients with localized, intermediate- or high-grade STS of the extremity or body wall measuring > 5 cm were treated with epirubicin 30 mg/m2/day and ifosfamide 2.5 g/m2/day on days 1–4 every 21 days for 3 preoperative and 3 postoperative cycles. During cycle 2 of preoperative therapy, epirubicin was omitted, and a total of 28 Gy of radiation (8 fractions) was delivered. Twenty-five patients were treated on the phase II study (2002–2005). Fifty-one additional patients were identified from a retrospective chart review (2005–2014). The 5-year rates for overall survival, distant disease-free survival, and freedom from local regional failure were 70.4% (95% CI 59.2–83.7%), 55.9% (95% CI 44.5–70.2%), and 87.2% (95% CI 77.9–96.5%) respectively. Thirty-eight percent of tumors (29/76) demonstrated ≥ 90% pathologic response. Wound complications occurred in 32% (24/76) of patients. Treatment with preoperative radiation and pre- and post-operative epirubicin and ifosfamide was associated with favorable clinical outcomes. Survival and recurrence rates were comparable to those reported with other preoperative chemotherapy regimens in high-risk extremity sarcomas. Use of trimodality therapy should be considered for appropriate high-risk STS patients.

231 Background: The 18F-Fluciclovine (FACBC) PET/CT scan has higher sensitivity than traditional imaging modalities for detection of prostate cancer (PCa) recurrence. We aim to identify the PSA characteristics as predictors of positive FACBC scan. Methods: Seventy-eight patients who underwent FACBC scan in 2018 at our institution were identified. Patient demographics, prior PSA, clinical information including prior treatment was recorded. Scans were deemed positive if definitive lesions were noted at the prostate bed, pelvic lymph nodes, or skeletal level. Detection rate was the ratio of positive over total scans and was calculated for PSA ranges. PSA velocity (PSAV) was calculated for patients who did not initiate androgen-deprivation therapy 12 months prior to the scan. The baseline PSA and PSAV were modeled as predictors of having a positive scan using logistic regression. Results: The median baseline PSA is 2.7 (range 0.2 - 226.5). The rates of positivity increased with increasing baseline PSA (Table 1). Positive scans had higher median baseline PSA (3.0, range 0.2-226.5 vs. 1.2, range 0.2-26.0; p = 0.0015) and higher PSAV (median 2.3, range -0.6-1478.7 vs. 1.0, range -0.5-31.9; p = 0.025). Baseline PSA (AUC = 0.712) was better predictor than PSAV (AUC = 0.656) of a positive scan. Combining the two variables does not improve their predictive ability (AUC = 0.719). There is a 50% detection rate in post-radical prostatectomy (RP) patients (Table 2). Conclusions: FACBC PET’s detection rate increases with increasing baseline PSA. While higher PSAV is associated with higher rate of positive scan, it did not increase the predictive ability of baseline PSA for a positive scan in prostate cancer recurrence patients. [Table: see text][Table: see text]

Purpose: We conducted a phase I trial of the addition of sorafenib to a chemoradiotherapy regimen in patients with high-risk (intermediate/high grade, >5 cm) extremity soft tissue sarcoma undergoing limb salvage surgery. We conducted a correlative study of quantitative dynamic contrast-enhanced MRI (DCE-MRI) to assess response to treatment. Experimental Design: Patients were treated at increasing dose levels of sorafenib (200 mg daily, 400 mg daily, 400 mg twice daily) initiated 14 days before three preoperative and three postoperative cycles of epirubicin/ifosfamide. Radiation (28 Gy) was administered during cycle 2 with epirubicin omitted. The primary objective was to determine the maximum tolerated dose (MTD) of sorafenib. DCE-MRI was conducted at baseline, after 2 weeks of sorafenib, and before surgery. The imaging data were subjected to quantitative pharmacokinetic analyses. Results: Eighteen subjects were enrolled, of which 16 were evaluable. The MTD of sorafenib was 400 mg daily. Common grade 3–4 adverse events included neutropenia (94%), hypophosphatemia (75%), anemia (69%), thrombocytopenia (50%), and neutropenic fever/infection (50%). Of note, 38% developed wound complications requiring surgical intervention. The rate of ≥95% histopathologic tumor necrosis was 44%. Changes in DCE-MRI biomarker ΔKtrans after 2 weeks of sorafenib correlated with histologic response (R2 = 0.67, P = 0.012) at surgery. Conclusion: The addition of sorafenib to preoperative chemoradiotherapy is feasible and warrants further investigation in a larger trial. DCE-MRI detected changes in tumor perfusion after 2 weeks of sorafenib and may be a minimally invasive tool for rapid assessment of drug effect in soft tissue sarcoma. Clin Cancer Res; 19(24); 6902–11. ©2013 AACR.

Few data exist regarding irradiation for prostate adenocarcinoma after cryotherapy failure. In this study, we summarized our results of postcryotherapy high-dose intensity-modulated radiotherapy for biochemically recurrent prostate adenocarcinoma. Nine patients were treated to a median dose of 79.2 Gy (range, 72-81 Gy). At a median of 31 months of follow-up, 7 patients experienced biochemical control, and no patients experienced grade 3 or higher toxicities. Background: To summarize our results of intensity-modulated radiation therapy (IMRT) for prostate adenocarcinoma after cryotherapy failure. Materials and Methods: Patients underwent IMRT with curative intent for biochemically recurrent prostate cancer after cryotherapy. Radiation was delivered to a minimum dose of 72 Gy (range, 72-81 Gy). Acute and late treatment-related gastrointestinal and genitourinary effects were scored according to Common Toxicity Criteria version 3.0. Prostate-specific antigen failure was defined by Radiation Therapy Oncology GroupAmerican Society for Therapeutic Radiology and Oncology 2006 consensus definition. Results: Nine patients were treated from 2008 to 2010. The median follow-up was 31 months (range, 15-40 months). The mean preradiotherapy prostate-specific antigen was 4.3 ng/mL (range, 1.07-15.6 ng/mL). The median elapsed time between cryotherapy and IMRT was 20.5 months (range, 8.5-56.5 months). Biochemical control was achieved in 7 patients. Two patients developed distant metastases shortly after completion of radiotherapy. No patients experienced grade 3 or higher toxicities. Conclusions: Our results suggest that high-dose IMRT after cryotherapy failure is well tolerated, without severe morbidity. The results also showed that IMRT can render a significant number of patients biochemically free of disease after initial cryotherapy. High-dose IMRT should be considered as a treatment option for these potentially salvageable cases.

This study aims to assess the utility of quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters in comparison with imaging tumor size for early prediction and evaluation of soft tissue sarcoma response to preoperative chemoradiotherapy. In total, 20 patients with intermediate- to high-grade soft tissue sarcomas received either a phase I trial regimen of sorafenib + chemoradiotherapy (n = 8) or chemoradiotherapy only (n = 12), and underwent DCE-MRI at baseline, after 2 weeks of treatment with sorafenib or after the first chemotherapy cycle, and after therapy completion. MRI tumor size in the longest diameter (LD) was measured according to the RECIST (Response Evaluation Criteria In Solid Tumors) guidelines. Pharmacokinetic analyses of DCE-MRI data were performed using the Shutter-Speed model. After only 2 weeks of treatment with sorafenib or after 1 chemotherapy cycle, Ktrans (rate constant for plasma/interstitium contrast agent transfer) and its percent change were good early predictors of optimal versus suboptimal pathological response with univariate logistic regression C statistics values of 0.90 and 0.80, respectively, whereas RECIST LD percent change was only a fair predictor (C = 0.72). Post-therapy Ktrans, ve (extravascular and extracellular volume fraction), and kep (intravasation rate constant), not RECIST LD, were excellent (C &gt, 0.90) markers of therapy response. Several DCE-MRI parameters before, during, and after therapy showed significant (P &lt, 05) correlations with percent necrosis of resected tumor specimens. In conclusion, absolute values and percent changes of quantitative DCE-MRI parameters provide better early prediction and evaluation of the pathological response of soft tissue sarcoma to preoperative chemoradiotherapy than the conventional measurement of imaging tumor size change.

Given shifting trends of religious identities in the USA, better understanding the impact of patients’ religious identities on health-related quality of life (QOL) may help tailor the use of psychological interventions. Men with prostate cancer (N = 43) completed measures of quality of life (QOL), spiritual well-being in two domains (i.e., Faith and Meaning/Peace), psychological state, and psychological trait before undergoing radiotherapy. We hypothesized that (1) higher existential Meaning/Peace would correlate with higher QOL and psychological trait protective factors (e.g., Agreeableness) and that (2) higher existential Meaning/Peace would correlate with lower depression, anxiety, and Neuroticism (i.e., a psychological trait risk factor). We did not anticipate similar relationships between religious Faith and QOL, depression, anxiety, or psychological traits and consider related analyses to be exploratory in nature. Meaning/Peace was indeed negatively associated with depression, anxiety, and Neuroticism. Meaning/Peace was positively correlated with Physical, Social, Functional, and Emotional well-being, as well as Extraversion. Religious Faith was positively associated with Functional well-being, but not the other state, trait, or QOL domains. In sum, prostate cancer patients’ sense of existential Meaning/Peace prior to radiotherapy was associated with well-being in many domains, whereas religious Faith appeared less so.

Purpose To report the toxicities and outcomes for stereotactic body radiation therapy (SBRT) and accelerated hypofractionated radiation therapy (AHRT) in patients with Child-Pugh (CP) class A, B, or C and albumin-bilirubin (ALBI) score 1, 2, or 3 hepatocellular carcinoma. Methods and Materials We retrospectively reviewed the data from 146 patients with hepatocellular carcinoma who had undergone SBRT (50 Gy in 5 fractions) or AHRT (45 Gy in 18 fractions). The primary endpoint was liver toxicity, defined as an increase in the CP score of ≥2 within 6 months of radiation therapy. The secondary endpoints of ALBI change, overall survival, and local control were also calculated. Results The median follow-up was 23 months (range 1-59). Most received SBRT (72%), and 28% received AHRT. Of all 146 patients, 45 (31%) had a CP score elevation of ≥2 within 6 months of radiation therapy (RT) (27 patients [28%] with baseline CP-A/B7 and 18 [35%] with baseline CP-B8/B9/C cirrhosis; P = .45). On multivariate analysis, neither baseline CP nor ALBI score was predictive of toxicity. No patient with a decline in liver functionality of CP ≥2 within 6 months of RT returned to baseline at later time points. Eleven grade 4 toxicities were observed. The mean change in the raw ALBI score at ∼6 months was similar for all baseline ALBI groups. Twenty-two patients underwent orthotopic liver transplantation after RT, 13 of whom had baseline CP-B8/B9/C liver functionality. For all patients, the 1- and 2-year treated-lesion local control was greater for SBRT than for AHRT (2-year 94% vs 65%, P Conclusions The tolerability of SBRT or AHRT as measured by a CP score decline of ≥2 within 6 months of RT was similar across baseline liver functionality groups. Compared with AHRT, SBRT was associated with superior local control. Because the true tolerability of limited-volume RT for patients with CP-B or CP-C cirrhosis is unknown, prospective trials validating its safety and efficacy are warranted.

443 Background: To assess the relative efficacy and toxicity associated with TACE+Ablation (Ablation) or TACE+SBRT (SBRT) in a large cohort of patients with unresectable HCC. Methods: Patients with HCC undergoing Ablation or SBRT from 2006-2016 with available follow up were included. Treatment groups were different at baseline regarding tumor stage (BCLC A, B and C: 96%, 4%, 0% (Ablation) vs. 73%, 14% and 13% (SBRT), P < 0.001) and severity of liver disease (CTP A, B, and C: 55%, 45% and 0% (Ablation) vs. 50%, 41%, and 9% (SBRT), P = 0.007). Propensity scores were calculated with age, sex, BCLC stage, CTP class, etiology of liver disease, tumor number, and diameter to balance the cohorts. Average treatment effects on survival with multivariable propensity score-weighted competing risk Cox regression models were evaluated, with BCLC stage, number of treated tumors and liver transplant as additionally controlled variables. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), local tumor control and hepatotoxicity. Treatment-related hepatotoxicity was defined as a two point change in CTP within six months after treatment. Results: 192 subjects were included (101 Ablation, 91 SBRT; median age=60 years, 75% men). Liver disease included HCV (78%), alcohol (35%) and NASH (8%). Liver transplant-adjusted 1- and 2-year OS rates were significantly greater for Ablation vs SBRT (88% vs. 75% and 77% vs. 50%, P

Radiation therapy (RT) for prostate cancer has made huge strides over the past two decades. The addition of image guidance has allowed radiation oncologists to ensure accurate delivery of increasingly precise radiation treatment plans using newer conformal therapy methods such as three-dimensional conformal RT, intensity-modulated RT, and proton beam RT. Regardless of the specific treatment technique, patients can depend on the treatment to target the moving prostate effectively while significantly sparing adjacent tissues, thereby reducing the morbidity of having to undergo prostate cancer therapy. This review summarizes the recent technical advances made in radiation dose delivery, including target volume definition, treatment planning, treatment delivery methods, and positional verification methods during RT.

Medical students applying for radiation oncology residency rated “perceived quality of didactics” within the top 5 factors in ranking programs (1). However, according to a 2013 national survey, only 27% of radiation oncology clerkships included didactic components specifically for medical students (2). In 2012, a pilot radiation oncology clerkship curriculum was developed at two institutions using the six-step conceptual framework for medical education curriculum development by Kern et al (3). Eighteen students completed the pilot curriculum. Students rated the curriculum highly and reported improved comfort with their decision to pursue radiation oncology as a specialty (4). Using the cooperative group research model, the curriculum was expanded to 11 selected academic medical centers within the United States in 2013 with the goal of increasing the number of participating students to provide more robust feedback for further curriculum development. Here, we describe the structure of the curriculum with corollary student feedback that can be used by other institutions to design or enhance their medical student curriculum. The curriculum consisted of three 1-hour lectures delivered by a senior resident or faculty member; topics included: (1) an overview of radiation oncology, including a history of the specialty, types of treatments, and basic clinic flow; (2) fundamentals of radiation biology and radiation physics; and (3) practical aspects of radiation treatment simulation and planning and radiation emergencies. Ideally, one session was conducted per week with all students present. The lecture format was open, and students were encouraged to ask questions. In addition, a 1-hour hands-on radiation treatment workshop facilitated by a senior resident, faculty, physicist, or dosimetrist was implemented to teach students the fundamentals of radiation treatment planning (5). While using a radiation treatment planning workstation, each student was provided with a step-by-step guide to delineating a radiation target, selecting appropriately directed radiation beams, and modifying various beam parameters to achieve an optimal plan. Individual institutions were encouraged to adapt the lectures according to institutional treatment or practice patterns, but all institutions retained the core curriculum format (3 lectures, 1 planning session). All participating institutions obtained institutional review board exemption. A total of 94 students participated in the curriculum in the 2013 academic year, allowing both wide dissemination and robust feedback. Upon completion of the clerkship, students were invited to complete an anonymous internet-based survey to rate the curriculum components, which yielded a 73% response rate. Qualitative analysis of the evaluations was undertaken by two authors (P.M. and J.C.Y.). Evaluation-free responses were reviewed independently and divided into positive and negative “consistent” themes (Table 1). These themes reflected the students' subjective overall feeling that the course laid an excellent knowledge foundation for transition to residency and their concern that they might not retain the knowledge during the two years prior to beginning residency. Future directions for curriculum development include expansion to additional institutions while using these constructive comments to enhance the learning experience. For example, one negative theme was that lectures should be scheduled earlier in the rotation to ensure that students have a good knowledge base for the remainder of the clinical rotation. This and other constructive feedback will be considered in the future when implementing the curriculum. Table 1 Consistent positive and negative feedback themes for individual curriculum components and how the curriculum will or will not be useful for transition to residency and for the overall curriculum This successful implementation of a standardized curriculum piloted at multiple institutions provides proof-of-principle that curriculum development can follow the multi-institutional cooperative group model. In the process, we identified areas of positive and negative needs as perceived by the students, who represent the most important stakeholders. Additional data are being collected to assess the impact of this curriculum on the students' decision to apply for radiation oncology residency. In the interim, the current data can help individual departments enhance their ongoing curriculum for rotating medical students.

This article has reviewed the current role of radiation in the treatment of gastrointestinal malignancies and discussed the data supporting its use. Radiation treatment in this setting continues to evolve with the increasing implementation of more conformal delivery techniques. Further scientific investigation is needed to establish the optimal role of radiation and to better define its integration with novel systemic and biologic modalities.

To compare CT and transrectal ultrasound (TRUS)-measured prostate volumes in patients with untreated prostate cancer.Between 1995 and 1999, 48 consecutive patients at the Portland Veterans Affairs Medical Center were treated with external beam radiotherapy. In 36 of these patients, TRUS and CT measurements of the prostate volume were obtained before treatment and6 months apart. The TRUS volume was calculated using the prolate ellipsoid formula. The CT volume was calculated from the contours of the prostate drawn by one physician, who was unaware of the TRUS volume calculation, on axial CT images.The TRUS and CT prostate volume measurements correlated strongly (Pearson's correlation coefficient = 0.925, 95% confidence interval 0.856-0.961, p0.0001). The CT volume was consistently larger than the TRUS volume by a factor of approximately 1.5. In men with a TRUS prostate volume less than the median (28 cm(3)), the CT/TRUS volume ratio was 1.7, and it was 1.4 for men whose volume was greater than the median. The CT volumes were correlated similarly with the TRUS volumes regardless of the CT slice interval.A strong correlation was found between CT scan and TRUS measurement of the prostate volume; however, CT consistently overestimated the prostate volume by approximately 50% compared with TRUS.

553 Background: Patients with testicular seminoma may face fertility issues because of their underlying disease as well as treatments they undergo. The current patterns of practice among US radiation oncologists aimed at assessing and preserving fertility in patients with Stage I seminoma are unknown. Methods: We surveyed practicing US radiation oncologists via an IRB-approved online questionnaire. Respondents’ characteristics, and perceived patient infertility rates were analyzed for association with treatment recommendations. Results: We received 353 responses, of whom one quarter (23%) consider themselves experts. A vast majority (84%) recommend observation as a default strategy. 52% routinely advise fertility assessment for patients prior to observation or chemotherapy, and 74% routinely do so prior to adjuvant RT. Nearly two-fifths believe that 10% and 30% of patients are infertile following orchiectomy. Thirty-seven and 22% believe infertility rates following para-aortic RT to be 30 and 50%, respectively. 80% routinely use clamshell scrotal shielding. Responders with higher perceived infertility rates are more likely to recommend fertility assessment/sperm banking (Fisher’s exact p

To report the observation that in-plane post-biopsy T2-weighted MRI often demonstrates the needle track as a transient visible linear tissue distortion during direct MRI-guided biopsy.We retrospectively identified 11 prostatic lesions in 9 men that underwent direct MRI-guided biopsy and in which post-biopsy images were obtained in the plane of the biopsy needle.In 9 of 11 targets, a post-biopsy needle track was visible as a linear tissue distortion on in-plane T2-weighted images obtained at a mean interval of 6 min (range 3-15). In these nine cases, the needle track traversed the intended target, and the biopsy was positive for malignancy in six. Biopsy was positive in one of two cases where the needle track was not visible. In five targets, one or more delayed series were obtained after a mean interval of 21 min (range 8-33), showing the track was no longer visible (n = 3) or was of progressively decreased conspicuity (n = 2).Accurate targeting during direct MRI-guided biopsy of the prostate can be confirmed by obtaining post-biopsy in-plane images, since the needle track is usually visible as a transient linear tissue distortion.

Stage T1c prostate cancer is defined as nonpalpable disease diagnosed by needle biopsy. As more patients are being diagnosed early because of prostate-specific antigen (PSA) screening, the distribution of patients by stage has shifted dramatically. Although this group has traditionally been characterized as having early-stage disease and the best prognosis, on review of these patients, we instead found a very heterogeneous group with a wide spectrum of outcomes that depend on both patient (Gleason grade and pretreatment PSA) and treatment (dose) factors.A retrospective analysis was performed on 353 patients with stage T1c prostate adenocarcinoma who were referred for radiation therapy from 1989-1999. All patients underwent central review of pathology. Patients were treated with external-beam radiation to doses of 60-78 Gy; 66% of the patients were treated with a dose of 70 Gy or higher. Clinical local recurrence, nodal recurrence, distant metastases, and PSA relapse were recorded. Kaplan-Meier methodology was used to determine survival. For evaluation of prognostic variables, the patients were grouped by Gleason score (2-6, 7, 8-10), pretreatment PSA level (10, 10-20,20 ng/mL), and dose delivered to the prostate (or = 70 Gy,70 Gy). The log-rank test was used for univariate analysis, and Cox-regression was used for multivariate analysis.The median age was 69 years, and the median follow-up of surviving patients was 47 months. As a percentage of all patients with prostate cancer, stage T1c continually increased from 6% in 1989 to 47% in 1999. Of the 353 patients with T1c, 66% of the patients were in the Gleason group of 2-6, 27% had a Gleason score of 7, and 7% had a Gleason score of 8-10. Sixty-five percent of the group had a pretreatment PSA level of10 ng/ mL, 31% had a PSA level of 10-20 ng/mL, and 5% had a PSA level of20 ng/mL. For the entire group, the 8-year overall survival was 86%, and PSA relapse-free survival was 78%. By univariate analysis, Gleason score and pretreatment PSA were significant predictors of overall survival and PSA relapse-free survival. For PSA relapse-free survival, a radiation dose of more than 70 Gy was also a significant factor. By multivariate analysis, Gleason score, pretreatment PSA level, and radiation dose over 70 Gy were significant predictors of PSA relapse-free survival. As expected, patients with Gleason scoreor = 6 and pretreatment PSA10 had an 8-year RFS of 90%, whereas patients with Gleason score of 8-9 and pretreatment PSA20 had a relapse-free survival of zero percent.Contrary to general assumption, stage T1c prostate cancer is composed of a very heterogeneous group of patients with varying outcomes. When treatment modalities and institutional data are evaluated, the spectrum of disease must be accounted for by additional prognostic factors and subset analysis. Improvement in prostate imaging and multiple core biopsies may be helpful in better defining the extent of disease in the individual patient.

MR-guided high intensity focused ultrasound (MRg HIFU) is a novel method of tissue ablation that incorporates high energy focused ultrasound for tissue heating and necrosis within an MR scanner that provides simultaneous stereotactic tissue targeting and thermometry. To date, MRg HIFU has been used primarily to treat uterine fibroids, but many additional applications in the pelvis are in development. This article reviews the basic technology of MRg HIFU, and the use of MRg HIFU to treat uterine fibroids, adenomyosis, and prostate cancer.

Prostate cancer is a heterogeneous disease with marked variability in its natural progression and response to therapeutic interventions. It is the most commonly diagnosed visceral cancer of men living in western countries, yet it is life-threatening in only a minority of cases. Thus, appropriate patient selection for treatment based on tumor as well as patient characteristics is essential to achieve optimal outcomes. The combination of early cancer detection and technical improvements in local treatment has led to a reduction in disease burden and an increase in cancer survivorship. However, treatment failure remains common among high-risk cases.

418 Background: Most men with Stage I testicular seminoma are cured with surgery alone, now a preferred strategy per national guidelines. The current pattern of practice among US radiation oncologists (RO) is unknown. Methods: We have surveyed practicing US RO via a short online questionnaire. Respondents’ characteristics, self-rated knowledge, perceived patient (pt) compliance rates with observation protocols and expected rate of infertility with and without adjuvant treatments were analyzed for association with treatment recommendations. Results: We received 353 responses from practicing US RO, of whom 23% consider themselves experts. Recommendations are summarized in the table. 34% believe that survival is jeopardized in case of recurrence on observation, but this belief does not impact the recommendation. Over 70% of respondents rate non-compliance with observation at > = 30%. Responders with a higher perceived non-compliance rate are more likely to recommend adjuvant therapy (Fisher’s exact p < 0.01). 52% routinely advise fertility assessment and/or sperm banking for pts who elect observation or chemotherapy, and 74% advise for pts undergoing RT. Respondents are more likely to recommend fertility assessment if they perceive a higher rate of infertility (Mantel-Haenszel Chi-square p < 0.01). 45% administer adjuvant RT in pts with elevated pre-orchiectomy alpha-fetoprotein levels. Conclusions: There is a dramatic uptake of observation as the recommended approach to pts with Stage I seminoma in US RO practices, despite a significant concern among practitioners about pt compliance. Further clinical work must establish best practices to minimize the effect on fertility, as well as guidelines for pts with Stage IS testicular seminoma. [Table: see text]

214 Background: Cancer survivors often experience psychological stress, with impact on quality of life (QOL) and mortality. Religious/spiritual identity and well-being (WB) can also significantly relate to QOL among individuals with cancer. The specific aim of the current study investigates correlates of spiritual (WB), QOL, and psychological state before and after radiotherapy for prostate cancer (PC). We hypothesized that 1) positive correlations between pre-treatment spiritual WB and health-related QOL will be seen both time points and that 2) negative correlations between spiritual WB and depression and anxiety will be seen at both points. Methods: The PHQ-9 and GAD-7 assessed depression and anxiety, respectively. The FACT-P assessed physical, social, emotional, and functional WB. The FACIT-Sp-Ex assessed spiritual WB. Our sample ( N= 65) had mean age of 68 (range 52-81) and education of 16 years (range 10-20). Most participants (82%) identified as European-American. Associations were assessed by Pearson’s correlation coefficients. Results: Pre-treatment spiritual WB positively correlated with social, emotional, and functional well-being (all p < .001). Spiritual and physical WB were not significantly related. Spiritual WB negatively correlated with depression and anxiety (both p < .001). Among a smaller subsample ( N = 39) with pre-, mid-, and post-treatment assessment, spiritual WB significantly increased over time, p < .001. Post-treatment spiritual WB again correlated with social, emotional, and functional WB (all p < .001) and did not correlate with physical WB. Spiritual WB was again negatively correlated with anxiety ( p < 0.05), but it was no longer associated with depression. Conclusions: Assessing and addressing spiritual WB can be helpful in itself, as well as in better understanding QOL and psychological state. Future directions include more fine-grained assessment of pre- and post-treatment spiritual WB in order to better understand which aspects of religious/spiritual identity relate more or less closely to post-treatment QOL for different stages of PC.

403 Background: To report toxicities and outcomes for stereotactic body radiotherapy (SBRT) and accelerated hypofractionated radiotherapy (AHRT) in patients with Child-Pugh (CP) A/B/C and Albumin-Bilirubin (ALBI) score 1/2/3 hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed 151 patients with HCC treated with SBRT (50 Gy in 5 fractions) or AHRT (45 Gy in 18 fractions) between 2007 and 2015. Primary endpoint was incidence of grade 3 or higher toxicities within 6 months of radiotherapy (RT). Patients were censored for toxicity upon local progression, further liver-directed therapy, or if they exhibited grade 3 or higher toxicities prior to RT, unless RT elevated the grading or a new toxicity class was observed. Secondary endpoints of overall survival and local control were calculated. Results: Median follow-up was 11 months (1 – 90 months). Most received SBRT (72%), while 28% received AHRT due to size criteria ( > 5 cm) or proximity to a critical organ-at-risk. Grade 3 or higher hyperbilirubinemia and hypoalbuminemia was greater in the CP-B8/B9/C patients (42% and 22%) or ALBI-3 patients (45% and 31%) compared to patients with CP-A/B7 (11% and 4%, p < 0.001) or ALBI-1/2 (14% and 4%, p < 0.001). For all other toxicity classes, no difference between liver functionality groups was seen. Eleven grade 4 and no grade 5 toxicities were observed. For all pts, 1- and 2-year treated-lesion local control (LC) rates were greater for SBRT as compared to AHRT (2-year LC 95% vs. 66%, p < 0.0001). When excluding patients with planning treatment volumes > 115 cc (equivalent to a 6 cm sphere), SBRT still yielded superior outcomes. Conclusions: Other than higher rates of grade 3+ hypoalbuminemia and hyperbilirubinemia, highly conformal RT appears to be a potentially safe and effective treatment option for HCC patients with advanced liver dysfunction. Compared to AHRT, SBRT is associated with superior local control.

A rare sclerosing variant of rhabdomyosarcoma characterized by prominent hyalinization and pseudovascular pattern has recently been described as a subtype biologically distinct from embryonal, alveolar, and pleomorphic forms. We present cytogenetic and molecular findings as well as experimental studies of an unusual case of sclerosing rhabdomyosarcoma. The primary lesion arose within the plantar subcutaneous tissue of the left foot of an otherwise healthy 23-year-old male who eventually developed pulmonary nodules despite systemic chemotherapy. Two genetic abnormalities identified in surgical and/or autopsy samples of the tumor were introduced into 10T1/2 murine fibroblasts to determine whether these genetic changes cooperatively facilitated transformation and growth. Cytogenetic analysis revealed a complex abnormal hyperdiploid clone, andMDM2gene amplification was confirmed by fluorescence in situ hybridization. Cancer gene mutation screening using a combination of multiplexed PCR and mass spectroscopy revealed aPIK3CAexon 20 H1047R mutation in the primary tumor, lung metastasis, and liver metastasis. However, this mutation was not cooperative withMDM2overexpression in experimental assays for transformation or growth. Nevertheless,MDM2andPIK3CAare genes worthy of further investigation in patients with sclerosing rhabdomyosarcoma and might be considered in the enrollment of these patients into clinical trials of targeted therapeutics.