A pooled patient-reported outcomes analysis of moderately hypofractionated proton beam therapy and photon-based intensity modulated radiation therapy for low- or intermediate-risk prostate cancer.

BACKGROUND: We sought to characterize and compare late patient-reported outcomes (PROs) after moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) for localized prostate cancer (PC). METHODS: This multi-institutional analysis included low- or intermediate-risk group PC patients treated with moderately hypofractionated radiation to an intact prostate stratified by treatment modality: IMRT or PBT. The primary outcomes were prospectively collected patient-reported late gastrointestinal (GI) and genitourinary (GU) toxicity assessed by International Prostate Symptom Score (IPSS) and Expanded PC Index Composite (EPIC). Multivariable regression analysis (MVA) controlling for age, race, and risk group tested the effect of time, treatment, and their interaction. RESULTS: 287 IMRT and 485 PBT patients were included. Intermediate risk group (81.2 vs. 68.2%; p < 0.001) and median age at diagnosis (70 vs. 67 years; p < 0.001) were higher in the IMRT group. On MVA, there was no significant difference between modalities. PBT IPSS did not differ from IMRT IPSS at 12 months (odds ratio [OR], 1.19; p = 0.08) or 24 months (OR, 0.99; p = 0.94). PBT EPIC overall GI function at 12 months (OR, 3.68; p = 0.085) and 24 months (OR 2.78; p = 0.26) did not differ from IMRT EPIC overall GI function. At 24 months, urinary frequency was no different between PBT and IMRT groups (OR 0.35; p = 0.096). CONCLUSIONS: This multi-institutional analysis of low- or intermediate-risk PC treated with moderately hypofractionated PBT and IMRT demonstrated low rates of late patient-reported GI and GU toxicities. After covariate adjustment, late GI and GU PROs were not significantly different between PBT or IMRT cohorts.

Local salvage of radiorecurrent prostate cancer.

BACKGROUND: Locally recurrent prostate cancer following primary external beam radiotherapy without distant metastasis is a challenging problem, with no current consensus on the optimal management of these patients. Traditional whole-gland salvage treatments offered up to a 50% 5-year disease-free survival rate but with troubling levels of risk for significant complications. Recent progress in advanced imaging techniques has allowed a more accurate selection of patients with local-only recurrence and a selection of patients that may be suitable for newer partial-gland salvage treatments that may reduce late complications. METHODS: This article reviews advances in patient selection and provides an overview of whole- and partial-gland salvage results from selected recent meta-analyses, multi-institutional series, and studies from centers of excellence for these treatment approaches. RESULTS: Salvage radical prostatectomy produces 5-year relapse-free survival (RFS) rates in the 50%-60% range with severe gastrointestinal (GI) toxicity in < 2% but severe genitourinary (GU) toxicity in 15%-23% of patients. The whole-gland options of high and low dose rate brachytherapy and stereotactic body radiation therapy appear to offer similar 5-year control rates, with low severe GU and GI toxicity rates of 4%-8% and <2%, respectively. Cryotherapy and high-intensity focused ultrasound (HIFU) offer similar 5-year RFS rates but carry significant risks for severe GU and GI toxicity in the range of 10%-27% and <2%, respectively. Early results of partial-gland salvage techniques in selected patients appear promising, with 3-year RFS rates of 48%-72% and rare grade 3 toxicity. CONCLUSION: It is important to understand the relative effectiveness and risks of the various treatment options to effectively counsel patients who face this distressing clinical situation. Whole-gland salvage options offer the possibility of long-term control but with significant risks of severe toxicity. Emerging data for the partial-gland salvage options in appropriately selected patients may offer hope of reasonable control rates with reduced severe toxicity.

Palliative care utilization and racial and ethnic disparities among women with de novo metastatic breast cancer in the United States.

PURPOSE: The potential disparities in palliative care delivery for underrepresented minorities with breast cancer are not well known. We sought to determine whether race and ethnicity impact the receipt of palliative care for patients with metastatic breast cancer (MBC). METHODS: We retrospectively reviewed the National Cancer Database for female patients diagnosed with stage IV breast cancer between 2010 and 2017 who received palliative care following diagnosis of MBC to assess the proportion of patients who received palliative care, including non-curative-intent local-regional or systemic therapy. Multivariable logistic regression analysis was performed to identify variables associated with receiving palliative care. RESULTS: 60,685 patients were diagnosed with de novo MBC. Of these, only 21.4% (n = 12,963) received a palliative care service. Overall, there was a positive trend in palliative care receipt from 18.2% in 2010 to 23.0% in 2017 (P < 0.001), which persisted when stratified by race and ethnicity. Relative to non-Hispanic White women, Asian/Pacific Islander women (aOR 0.80, 95% CI 0.71-0.90, P < 0.001), Hispanic women (adjusted odds ratio [aOR] 0.69, 95% CI 0.63-0.76, P < 0.001), and non-Hispanic Black women (aOR 0.94, 95% CI 0.88-0.99, P = 0.03) were less likely to receive palliative care. CONCLUSIONS: Fewer than 25% of women with MBC received palliative care between 2010 and 2017. While palliative care has significantly increased for all racial/ethnic groups, Hispanic White, Black, and Asian/Pacific Islander women with MBC still receive significantly less palliative care than non-Hispanic White women. Further research is needed to identify the socioeconomic and cultural barriers to palliative care utilization.

Heterogeneity in Radiotherapeutic Parameter Assumptions in Cost-Effectiveness Analyses in Prostate Cancer: A Call for Uniformity.

OBJECTIVES: Cost-effectiveness analyses (CEAs) may provide useful data to inform management decisions depending on the robustness of a model's input parameters. We sought to determine the level of heterogeneity in health state utility values, transition probabilities, and cost estimates across published CEAs assessing primarily radiotherapeutic management strategies in prostate cancer. METHODS: We conducted a systematic review of prostate cancer CEAs indexed in MEDLINE between 2000 and 2018 comparing accepted treatment modalities across all cancer stages. Search terms included "cost effectiveness prostate," "prostate cancer cost model," "cost utility prostate," and "Markov AND prostate AND (cancer OR adenocarcinoma)." Included studies were agreed upon. A Markov model was designed using the parameter estimates from the systematic review to evaluate the effect of estimate heterogeneity on strategy cost acceptability. RESULTS: Of 199 abstracts identified, 47 publications were reviewed and 37 were included; 508 model estimates were compared. Estimates varied widely across variables, including gastrointestinal toxicity risk (0%-49.5%), utility of metastatic disease (0.25-0.855), intensity-modulated radiotherapy cost ($21 193-$61 996), and recurrence after external-beam radiotherapy (1.5%-59%). Multiple studies assumed that different radiotherapy modalities delivering the same dose yielded varying cancer control rates. When using base estimates for similar parameters from included studies, the designed model resulted in 3 separate acceptability determinations. CONCLUSIONS: Significant heterogeneity exists across parameter estimates used to perform CEAs evaluating treatment for prostate cancer. Heterogeneity across model inputs yields variable conclusions with respect to the favorability and cost-effectiveness of treatment options. Decision makers are cautioned to review estimates in CEAs to ensure they are up to date and relevant to setting and population.

Five- and seven-year outcomes for image-guided moderately accelerated hypofractionated proton therapy for prostate cancer.

BACKGROUND: To report 5- and 7-year outcomes after image-guided moderately accelerated hypofractionated proton therapy (AHPT) for prostate cancer. MATERIAL AND METHODS: We reviewed the first 582 prostate cancer patients enrolled on prospective outcomes tracking trial and treated with double-scattered moderately AHPT between 2008 and 2015. 269 patients had low-risk (LR) and 313 had intermediate-risk (IR) disease, including 149 with favorable intermediate-risk (FIR) and 164 with unfavorable intermediate-risk (UIR) disease. LR patients received a median 70.0GyRBE (2.5GyRBE/fraction) and IR patients received a median of 72.5 GyRBE. Seventeen patients (UIR, n = 12) received androgen deprivation therapy (ADT) for a median of 6 months. Toxicities were graded per the CTCAE, v4.0, and patient-reported quality-of-life data were reviewed. RESULTS: Median follow-up was 8.0 years (0.9-12.2). The 5- and 7-year rates of freedom from biochemical progression (FFBP) overall and in the LR and IR subsets, respectively, were 96.8/95.2%, 98.8/98.8%, and 95.0/91.9%. For the FIR and UIR subsets, they were 97.2/95.2% and 93.1/88.8%. Actuarial 5- and 7-year rates of late CTCAE, v4.0, grade 2 gastrointestinal (GI), grade 3 GI, and grade 3 genitourinary (GU) toxicities were 9.9%/11.2%, 1.4/1.4% and 1.3/2.1%, respectively. No grade ≥4 GI or GU toxicities occurred. The mean (standard deviation, SD) IPSS and EPIC Composite bowel function and bother scores were 7 (SD = 5), 97 (SD = 7), and 94 (SD = 6), respectively at baseline, 7 (SD = 5), 92 (SD = 13), and 92 (SD = 9) at the 5-year follow-up, and 7 (SD = 5), 93 (SD = 12), and 92 (SD = 10) at the 7-year follow-up. CONCLUSION: Image-guided AHPT 5- and 7-year outcomes show high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes in this cohort.

Intraoperative radiation therapy for early-stage breast cancer: a single-institution experience.

Background: To assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC). Materials and methods: We reviewed patients with unilateral ESBC treated with breast-conserving surgery and 50-kV IORT at our institution. Patients were prescribed 20 Gy to the surface of the spherical applicator, fitted to the surgical cavity during surgery. Patients who did not meet institutional guidelines for IORT alone on final pathology were recommended adjuvant treatment, including additional surgery and/or external-beam radiation therapy (EBRT). We analyzed ipsilateral breast tumor recurrence, overall survival, recurrence-free survival and toxicity. Results: Among 201 patients (median follow-up, 5.1 years; median age, 67 years), 88% were Her2 negative and ER positive and/or PR positive, 98% had invasive ductal carcinoma, 87% had grade 1 or 2, and 95% had clinical T1 disease. Most had pathological stage T1 (93%) N0 (95%) disease. Mean IORT applicator dose at 1-cm depth was 6.3 Gy. Post-IORT treatment included additional surgery, 10%; EBRT, 11%; adjuvant chemotherapy, 9%; and adjuvant hormonal therapy, 74%. Median total EBRT dose was 42.4 (range, 40.05-63) Gy and median dose per fraction was 2.65 Gy. At 5 years, the cumulative incidence of ipsilateral breast tumor recurrence was 2.7%, the overall survival rate was 95% with no breast cancer-related deaths, and the recurrence-free survival rate was 96%. For patients who were deemed unsuitable for postoperative IORT alone and did not receive recommended risk-adapted EBRT, the IBTR rate was 4.7% versus 1.7% (p = 0.23) for patients who were either suitable for IORT alone or unsuitable and received adjuvant EBRT. Cosmetic toxicity data was available for 83%, with 7% experiencing grade 3 breast toxicity and no grade 4-5 toxicity. Conclusions: IORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.

Five-Year Breast Surgeon Experience in LYMPHA at Time of ALND for Treatment of Clinical T1-4N1-3M0 Breast Cancer.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a source of postoperative morbidity for breast cancer survivors. Lymphatic microsurgical preventive healing approach (LYMPHA) is a technique used to prevent BCRL at the time of axillary lymph node dissection (ALND). We report the 5-year experience of a breast surgeon trained in LYMPHA and investigate the outcomes of patients who underwent LYMPHA following ALND for treatment of cT1-4N1-3M0 breast cancer. METHODS: A retrospective review of patients with cT1-4N1-3M0 breast cancer was performed in patients who underwent ALND with and without LYMPHA. Diagnosis of BCRL was made by certified lymphedema therapists. Descriptive statistics and lymphedema surveillance data were analyzed using results of Fisher's exact or Wilcoxon rank-sum tests. Logistic regression and propensity matching were performed to assess the reduction of BCRL occurrence following LYMPHA. RESULTS: In a 5-year period, 132 patients met inclusion criteria with 76 patients undergoing LYMPHA at the time of ALND and 56 patients undergoing ALND alone. Patients who underwent LYMPHA at the time of ALND were significantly less likely to develop BCRL than those who underwent ALND alone (p = 0.045). Risk factors associated with BCRL development were increased patient age (p = 0.007), body mass index (BMI) (p = 0.003), and, in patients undergoing LYMPHA, number of positive nodes (p = 0.026). CONCLUSIONS: LYMPHA may be successfully employed by breast surgeons trained in lymphatic-venous anastomosis at the time of ALND. While research efforts should continue to focus on prevention and surveillance of BCRL, LYMPHA remains an option to reduce BCRL and improve patient quality of life.

Novel Radiotherapy Techniques for Breast Cancer.

During the early decades of radiation therapy for breast cancer, local control of disease was documented consistently but, enigmatically, an anticipated impact on breast cancer survival was not observed, leading to confusion in our understanding of the natural history of breast cancer and radiation effects. Now, almost 90 years after its first use in breast cancer, technology developments in diagnostic imaging and radiation therapy have elucidated parts of this enigma. The data now available demonstrate a significant impact of radiation therapy on survival as well as disease control and treatment-related mortality, opening a doorway to understanding the powerful impact of radiation therapy on both breast cancer and critical organs. Efforts are focused on leveraging novel techniques to maximize the benefits of radiation for breast cancer patients.

Serum Testosterone 60 Months after Passive-Scatter Proton Therapy for Localized Prostate Cancer.

Studies demonstrate a decline of ∼10% in serum testosterone (ST) level after X-ray radiotherapy for prostate cancer. We evaluated changes in ST for patients with low- and intermediate-risk prostate cancer receiving 70-82Gy(RBE) using passive-scatter proton therapy (PT). ST was checked at baseline (n = 358) and at 60+ months after PT (n = 166). The median baseline ST was 363.3 ng/dl (range, 82.0-974.0). The median ST 5 years after PT was 391.5 ng/dl (range, 108.0-1061.0). The difference was not statistically significant (p = 0.9341). Passive-scatter PT was not associated with testosterone suppression at 5 years, suggesting that protons may cause less out-of-field scatter radiation than X-rays.

Radiotherapy for Orbital Pseudotumor: The University of Florida Experience.

BACKGROUND: To evaluate outcomes after definitive radiotherapy for orbital pseudotumor. METHODS: We reviewed adult patients treated between 1971 and 2012. RESULTS: 20 patients with 8.0-year median follow-up were analyzed. Symptoms improved in 75% of patients: 40% showed a complete response, 35% partial response, and 20% had stable disease. The disease progressed in 1 and recurred in 8 patients. Local control rates were 63% and 53% at 5 and 10 years, respectively. The most common toxicities were cataracts (10%) and dry eye (10%). CONCLUSIONS: Radiotherapy for orbital pseudotumor is well-tolerated and results in long-term control in most patients, with local control in over half.

Long-term outcomes following proton therapy for prostate cancer in young men with a focus on sexual health.

BACKGROUND: We investigated long-term outcomes for men ≤60 years old treated with proton therapy (PT). METHODS: Of 254 men ≤60 years old were treated with proton therapy alone for prostate cancer. Risk stratification included 56% with low-, 42% with intermediate- and 2% with high-risk disease. Patients received 76-82 Gy at 2 Gy/fraction or 70-72.5 Gy at 2.5 Gy/fraction. Before treatment and every 6-12 months for 5 years, patients were evaluated by a physician, answered health-related quality of life surveys, including the EPIC, IIEF and IPSS, and had PSA evaluated. RESULTS: Median follow-up for the cohort was 7.1 years; 7-year biochemical-free survival was 97.8%. Eight men (one high-risk; five intermediate-risk and two low-risk) experienced biochemical progression, including one who died of disease 9 years after treatment. Potency (erections firm enough for sexual intercourse) was 90% at baseline and declined to 72% at the first-year follow-up, but declined to only 67% at 5 years. Only 2% of patients developed urinary incontinence requiring pads. The bowel habits mean score declined from a baseline of 96 to 88 at 1 year, which improved over the following years to 93 at 5 years. CONCLUSIONS: Young men with prostate cancer continue to have excellent results with respect to 7-year biochemical control and 5-year erectile function, without clinically significant urinary incontinence 5 years after proton therapy. Comparative effectiveness studies of proton therapy with surgery and IMRT are needed.

Outcomes following proton therapy for pediatric ependymoma.

BACKGROUND: Proton therapy can reduce the low and intermediate radiation dose to uninvolved brain tissue in children with intracranial ependymomas, which may improve functional outcomes and reduce second malignancies in survivors. Accordingly, ependymoma has become the most common pediatric tumor treated with proton therapy, yet data on efficacy and toxicity are limited. MATERIAL AND METHODS: Between June 2007 and February 2017, 179 children (≤21 years old) with nonmetastatic grade II/III intracranial ependymoma received proton therapy at our institution. Median age, 3.5 years (range, 0.7-21); 58% were male. Most (66%) tumors were in the posterior fossa and classified as WHO grade III (67%). 27% underwent multiple operations to maximize the extent of resection; ultimately 85% had a gross total or near total tumor resection before radiotherapy. 33% received preradiation chemotherapy. Median radiation dose in children ≤3 years old, 54 Gy(RBE). Most (>90%) children over 3 years old received 59.4 Gy(RBE). Patient and treatment variables were assessed for correlation with disease control. RESULTS: Median follow-up, 3.2 years. 3-year local control, progression-free survival, and overall survival rates were 85%, 76%, and 90%, respectively. First site of progression was local, metastatic, or simultaneous in 14, 17 and 6 patients, respectively. On multivariate analysis, subtotal resection was associated with inferior local control (67% vs. 88%; p ≤ .01) and progression-free survival (59% vs. 79%; p < .05). Male sex was associated with inferior progression-free (67% vs. 87%; p< .05) and overall survival (84% vs. 99%; p < .01). The 3-year CTCAE grade 2 + brainstem toxicity rate was 5.5% (95% CI: 2.9-10.2), including 1 grade 5 toxicity. CONCLUSIONS: This series of proton therapy for pediatric intracranial ependymoma demonstrates disease control comparable to photon series without unexpected toxicity. Subtotal resection and male sex were associated with inferior disease control. Additional follow-up to quantify the expected reductions in late toxicity with proton therapy is ongoing.

Five-year outcomes from a prospective trial of image-guided accelerated hypofractionated proton therapy for prostate cancer.

PURPOSE: To report 5-year outcomes of a prospective trial of image-guided accelerated hypofractionated proton therapy (AHPT) for prostate cancer. PATIENTS AND METHODS: 215 prostate cancer patients accrued to a prospective institutional review board-approved trial of 70Gy(RBE) in 28 fractions for low-risk disease (n = 120) and 72.5Gy(RBE) in 29 fractions for intermediate-risk disease (n = 95). This trial excluded patients with prostate volumes of ≥60 cm3 or International Prostate Symptom Scores (IPSS) of ≥15, patients on anticoagulants or alpha-blockers, and patients in whom dose-constraint goals for organs at risk (OAR) could not be met. Toxicities were graded prospectively according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. This trial can be found on ClinicalTrials.gov (NCT00693238). RESULTS: Median follow-up was 5.2 years. Five-year rates of freedom from biochemical and clinical disease progression were 95.9%, 98.3%, and 92.7% in the overall group and the low- and intermediate-risk subsets, respectively. Actuarial 5-year rates of late radiation-related CTCAE v3.0 grade 3 or higher gastrointestinal and urologic toxicities were 0.5% and 1.7%, respectively. Median IPSS before treatment and at 4+ years after treatment were 6 and 5 for low-risk patients and 4 and 6 for intermediate-risk patients. CONCLUSIONS: Image-guided AHPT 5-year outcomes show high efficacy and minimal physician-assessed toxicity in selected patients. These results are comparable to the 5-year results of our prospective trials of standard fractionated proton therapy for patients with low-risk and intermediate-risk prostate cancer. Longer follow-up and a larger cohort are necessary to confirm these findings.

Sperm preservation and neutron contamination following proton therapy for prostate cancer study.

BACKGROUND: The present study investigates the impact of scatter dose radiation to the testis on ejaculate and sperm counts from treatment of prostate cancer with passive-scatter proton therapy. MATERIAL AND METHODS: From March 2010 to November 2014, 20 men with low- or intermediate-risk prostate cancer enrolled in an IRB-approved protocol and provided a semen sample prior to passive-scatter proton therapy and 6-12 months following treatment. Men were excluded if they had high-risk prostate cancer, received androgen deprivation therapy, were on alpha blockers (due to retrograde ejaculation) prior to treatment, had baseline sperm count <1 million, or were unable to produce a pre-treatment sample or could not provide a follow-up specimen. Sperm counts of 0 were considered azoospermia and <15 million/ml were classified as oligospermia. RESULTS: Four patients were unable to provide a sufficient quantity of semen for analysis. Among the 16 remaining patients, only one was found to have oligospermia (7 million/ml). There was a statistically significant reduction in semen volume (median, 0.5 ml) and increase in pH (median 0.5). Although not statistically significant, there appeared to be a decline in sperm concentration (median, 16 million/ml), total sperm count (median, 98.5 million), normal morphology (median, 9%), and rapid progressive motility (median, 9.5%). DISCUSSION: Men did not have azoospermia 6-12 months following passive-scatter proton therapy indicating minimal scatter radiation to the testis during treatment. Changes in semen quantity and consistency may occur due to prostate irradiation, which could impact future fertility and/or sexual activity.

Proton Therapy for Pediatric Hodgkin Lymphoma.

BACKGROUND: Compared to X-ray radiation therapy, proton therapy (PT) reduces the radiation dose to organs at risk, which is expected to translate into fewer second cancers and less cardiac morbidity decades after treatment. The Children's Oncology Group high-risk pediatric Hodgkin lymphoma (PHL) protocol, AHOD1331, allows the use of PT, yet limited data exist on the use of PT in PHL. PROCEDURE: Between 2010 and 2014, 22 pediatric patients were treated with PT for PHL at our institution: 7 intermediate-risk patients, 11 high-risk patients, and 4 relapsed patients. The patients' age ranged from 6 to 18 years old. Median follow-up was 36 months. All patients received chemotherapy before PT. RESULTS: The 2-year and 3-year overall survival rates were both 94%, and the progression-free survival rate was 86%. Recurrences occurred in three high-risk patients: one isolated in-field cervical lymph node and two in-field and out-of-field. All recurrences occurred within 5 months of completing PT. No PT-related grade 3 or higher acute or late complications were observed. CONCLUSION: PT for PHL showed no short-term severe toxicity and yields similar short-term control to recently published large multi-institutional clinical trials.

ACR Appropriateness Criteria® Recurrent Hodgkin Lymphoma.

This topic addresses the management of recurrent Hodgkin lymphoma. While autologous stem cell transplantation may be appropriate for select cases of recurrent disease following comprehensive combined-modality therapy, other options exist for patients treated with lower-dose therapy for early-stage disease. Additionally, innovative targeted therapies provide newer salvage options to consider. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. By combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the complex decision-making associated with the management of recurrent Hodgkin lymphoma.

A dosimetric comparison of ultra-hypofractionated passively scattered proton radiotherapy and stereotactic body radiotherapy (SBRT) in the definitive treatment of localized prostate cancer.

BACKGROUND: We compared target and normal tissue dosimetric indices between ultra-hypofractionated passively scattered proton radiotherapy and stereotactic body radiotherapy (SBRT) in the definitive treatment of localized prostate cancer. MATERIAL AND METHODS: Ten patients were treated definitively for localized prostate cancer with SBRT to a dose of 36.25 Gy in 5 fractions prescribed to a volume encompassing the prostate only. Dose-volume constraints were applied to the rectum, bladder, penile bulb, femoral heads, and prostatic and membranous urethra. Three-field passively scattered proton plans were retrospectively generated using target volumes from the same patients. Dosimetric indices were compared between the SBRT and proton plans using the Wilcoxon signed rank test. RESULTS: All dose constraints were achieved using both ultra-hypofractionated passively scattered proton and SBRT planning. Proton plans demonstrated significant improvement over SBRT in mean dose delivered to the penile bulb (5.2 CGE vs. 11.4 Gy; p=0.002), rectum (6.7 CGE vs. 10.6 Gy; p=0.002), and membranous urethra (32.2 CGE vs. 34.4 Gy; p=0.006) with improved target homogeneity resulting in a significant reduction in hot spots and volumes of tissue exposed to low doses of radiation. Compared to proton planning, SBRT planning resulted in significant improvement in target conformality with a mean index of 1.17 versus 1.72 (p=0.002), resulting in a dose reduction to the volume of bladder receiving more than 90% of the PD (V32.6, 7.5% vs. 15.9%; p=0.01) and mean dose to the left (7.1 Gy vs. 10.4 CGE; p=0.004) and right (4.0 Gy vs. 10.9 CGE; p=0.01) femoral heads. CONCLUSION: Target and normal tissue dose constraints for ultra-hypofractionated definitive radiotherapy of localized prostate cancer are readily achieved using both CK SBRT and passively scattered proton-based therapy suggesting feasibility of either modality.

Comparative effectiveness study of patient-reported outcomes after proton therapy or intensity-modulated radiotherapy for prostate cancer.

BACKGROUND: Data continue to emerge on the relative merits of different treatment modalities for prostate cancer. The objective of this study was to compare patient-reported quality-of-life (QOL) outcomes after proton therapy (PT) and intensity-modulated radiation therapy (IMRT) for prostate cancer. METHODS: A comparison was performed of prospectively collected QOL data using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. QOL data were collected during the first 2 years after treatment for men who received PT and IMRT. PT was delivered to 1243 men at a single center at doses from 76 grays (Gy) to 82 Gy. IMRT was delivered to 204 men who were included in the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA) study in doses from 75.6 Gy to 79.4 Gy. The Wilcoxon rank-sum test was used to compare EPIC outcomes by modality using baseline-adjusted scores at different time points. Individual questions were assessed by converting to binary outcomes and testing with generalized estimating equations. RESULTS: No differences were observed in summary score changes for bowel, urinary incontinence, urinary irritative/obstructive, and sexual domains between the 2 cohorts. However, more men who received IMRT reported moderate/big problems with rectal urgency (P = 0.02) and frequent bowel movements (P = 0.05) than men who received PT. CONCLUSIONS: There were no differences in QOL summary scores between the IMRT and PT cohorts during early follow-up (up to 2-years). Response to individual questions suggests possible differences in specific bowel symptoms between the 2 cohorts. These outcomes highlight the need for further comparative studies of PT and IMRT.

Angiosarcoma after breast-conserving therapy: long-term disease control and late effects with hyperfractionated accelerated re-irradiation (HART).

BACKGROUND: Secondary angiosarcoma is a malignant cancer that develops in approximately 1% of patients treated with breast-conserving therapy (BCT) for primary breast cancer. Most treatments for secondary angiosarcoma have been unsuccessful and no consensus has been reached on what is the best therapeutic strategy. We report long-term outcomes of patients with secondary angiosarcoma treated with hyperfractionated and accelerated re-irradiation (HART). MATERIAL AND METHODS: We retrospectively reviewed the medical records of, and established direct contact with, 14 consecutive patients with secondary angiosarcoma after BCT with axillary lymph node dissection who were treated at our institution with HART with or without surgery from November 1997 to March 2006. With HART, patients received three radiation therapy treatments each day, with a minimum interfraction interval of four hours, five days a week, at 1 Gy per fraction, to total doses of 45 Gy, 60 Gy, and 75 Gy for areas with a moderate risk for subclinical disease, a high risk for subclinical disease, and gross disease, respectively. The minimum follow-up for these patients was six years. RESULTS: Median survival was 7.0 years (range 0.4-14.7 years), with five- and 10-year overall survival rates of 79% [95% confidence interval (CI), 51-93%] and 63% (95% CI 37-84%), respectively, and five- and 10-year cause-specific survival rates of 79% (95% CI 51-93%) and 71% (95% CI 44-89%), respectively. Toxicity was minimal. CONCLUSION: Our long-term study provides evidence that patients with secondary angiosarcoma after BCT can frequently be cured. Patients treated with HART have higher overall survival, progression-free survival, and cause-specific survival rates than patients who receive only surgery, conventional radiation therapy, or chemotherapy. HART is well tolerated.