Curtis Bryant

Five-Year Biochemical Results, Toxicity, and Patient-Reported Quality of Life After Delivery of Dose-Escalated Image Guided Proton Therapy for Prostate Cancer

PURPOSE To report clinical outcomes in patients treated with image guided proton therapy (PT) for localized prostate cancer. METHODS AND MATERIALS The medical records of 1327 men were reviewed. Each man was enrolled on an outcomes tracking study. Dual enrollment on a prospective clinical trial was allowed. Each patient was treated for localized prostate cancer with PT at our institution between 2006 and 2010. Ninety-eight percent of patients received 78 Gy (radiobiological equivalent [RBE]) or higher; 18% received androgen deprivation therapy (ADT). The 5-year freedom from biochemical progression (FFBP), distant metastasis-free survival, and cause-specific survival rates are reported for each risk group. Data on patient-reported quality of life and high-grade toxicities were prospectively collected and reported. A multivariate analysis was performed to identify clinical predictors of biochemical failure and urologic toxicity. RESULTS The median follow-up time was 5.5 years. The 5-year FFBP rates were 99%, 94%, and 74% in low-risk, intermediate-risk, and high-risk patients, respectively. The actuarial 5-year rates of late grade 3+ Common Terminology Criteria for Adverse Events, version 4.0, gastrointestinal (GI) and genitourinary (GU) toxicity were 0.6% and 2.9%, respectively. Multivariate analysis showed a significant correlation between grade 3+ GU toxicity and pretreatment prostate reductive procedures (P<.0001), prostate volume (P=.0085), pretreatment α-blockers (P=.0067), diabetes (P=.0195), and dose-volume histogram parameters (P=.0208). The median International Prostate Symptom Scores pretreatment scores and scores at 5 years after treatment were 7 and 7, respectively. The mean Expanded Prostate Cancer Index Composite (EPIC) scores significantly declined for sexual summary for patients not receiving ADT (from 67 to 53) between baseline and 5 years. CONCLUSIONS Image guided PT provided excellent biochemical control rates for patients with localized prostate cancer. The actuarial rates of high-grade toxicity were low after PT. From pretreatment to 5 years of follow-up, a significant decline was found only in mean EPIC sexual summary scores. Prospective clinical studies are needed to determine the comparative effectiveness of PT and other radiation treatment strategies.

Low-kilovoltage, single-dose intraoperative radiation therapy for breast cancer: results and impact on a multidisciplinary breast cancer program.

BACKGROUND The Intrabeam (Carl Zeiss) brachytherapy device (IB) is an electronic brachytherapy device that can be used to deliver low energy x-rays (50 kV) to a lumpectomy cavity at the time of lumpectomy for breast cancer. Reported experience with IB for breast cancer in the United States has been extremely limited. Here we describe our experience and analyze the impact of IB on our multidisciplinary breast cancer program. STUDY DESIGN This is a retrospective review of a prospectively collected breast cancer database. Patient characteristics, treatment characteristics, recurrence, and cosmesis were analyzed. Cost data were also analyzed to determine the impact of IB on the breast cancer program. RESULTS Seventy-eight patients underwent 80 IB treatments in this series between November 2010 and October 2012. Most patients had invasive ductal carcinoma. Mean total operative time for patients receiving lumpectomy, sentinel node biopsy, and IB was 132 minutes (range 79 to 243 minutes). Intrabeam brachytherapy was the only adjuvant radiation required in 81% of patients, and only 15% of patients required additional operation after the index lumpectomy procedure. At 12 months of follow-up, cosmesis was good to excellent in 92% of patients. There have been no local recurrences in patients treated in this series. Intrabeam brachytherapy is associated with considerably lower costs (

Rectal Toxicity After Proton Therapy For Prostate Cancer: An Analysis of Outcomes of Prospective Studies Conducted at the University of Florida Proton Therapy Institute

1,857) than conventional whole breast radiation therapy (

Outcomes of Sinonasal Cancer Treated With Proton Therapy

9,653). CONCLUSIONS Implementation of IB impacts treatment planning and operating room use in a multidisciplinary breast cancer program. The safety profile, ease of administration, and reduced costs of IB favor its more widespread use in selected patients with early-stage breast cancer.

Radiation for Prostate Cancer: Intensity Modulated Radiation Therapy versus Proton Beam

PURPOSE Study goals were to characterize gastrointestinal effects of proton therapy (PT) in a large cohort of patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients receiving investigational protocols versus those in outcome-tracking protocols. METHODS AND MATERIALS A total of 1285 consecutive patients were treated with PT between August 2006 and May 2010. Potential pre-existing clinical and treatment-related risk factors for rectal toxicity were recorded. Common Terminology Criteria for Adverse Events version 3.0 was used to score toxicity. RESULTS Transient RB was the predominant grade 2 or higher (GR2+) toxicity after PT, accounting for 95% of gastrointestinal events. GR1 RB occurred in 217 patients (16.9%), GR2 RB in 187 patients (14.5%), and GR3 in 11 (0.9%) patients. There were no GR4 or GR5 events. Univariate analyses showed correlations between GR2+ RB and anticoagulation therapy (P=.008) and rectal and rectal wall dose-volume histogram (DVH) parameters (P<.001). On multivariate analysis, anticoagulation therapy (P=.0034), relative volume of rectum receiving 75 Gy (V75; P=.0102), and relative rectal wall V75 (P=.0017) were significant predictors for G2+ RB. Patients treated with investigational protocols had toxicity rates similar to those receiving outcome-tracking protocols. CONCLUSIONS PT was associated with a low rate of GR2+ gastrointestinal toxicity, predominantly transient RB, which was highly correlated with anticoagulation and rectal DVH parameters. Techniques that limit rectal exposure should be used when possible.

Hemorrhagic radiation cystitis.

PURPOSE To report disease outcomes after proton therapy (PT) for sinonasal cancer. METHODS AND MATERIALS Eighty-four adult patients without metastases received primary (13%) or adjuvant (87%) PT for sinonasal cancers (excluding melanoma, sarcoma, and lymphoma). Common histologies were olfactory neuroblastoma (23%), squamous cell carcinoma (22%), and adenoid cystic carcinoma (17%). Advanced stage (T3 in 25% and T4 in 69%) and high-grade histology (51%) were common. Surgical procedures included endoscopic resection alone (45%), endoscopic resection with craniotomy (12%), or open resection (30%). Gross residual disease was present in 26% of patients. Most patients received hyperfractionated PT (1.2 Gy [relative biological effectiveness (RBE)] twice daily, 99%) and chemotherapy (75%). The median PT dose was 73.8 Gy (RBE), with 85% of patients receiving more than 70 Gy (RBE). Prognostic factors were analyzed using Kaplan-Meier analysis and proportional hazards regression for multiple regression. Dosimetric parameters were evaluated using logistic regression. Serious, late grade 3 or higher toxicity was reported using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The median follow-up was 2.4 years for all patients and 2.7 years among living patients. RESULTS The local control (LC), neck control, freedom from distant metastasis, disease-free survival, cause-specific survival, and overall survival rates were 83%, 94%, 73%, 63%, 70%, and 68%, respectively, at 3 years. Gross total resection and PT resulted in a 90% 3-year LC rate. The 3-year LC rate was 61% for primary radiation therapy and 59% for patients with gross disease. Gross disease was the only significant factor for LC on multivariate analysis, whereas grade and continuous LC were prognostic for overall survival. Six of 12 local recurrences were marginal. Dural dissemination represented 26% of distant recurrences. Late toxicity occurred in 24% of patients (with grade 3 or higher unilateral vision loss in 2%). CONCLUSIONS Dose-intensified, hyperfractionated PT with or without concurrent chemotherapy results in excellent LC after gross total resection, and results in patients with gross disease are encouraging. Patients with high-grade histology are at greater risk of death from distant dissemination. Continuous LC is a major determinant of survival justifying aggressive local therapy in nearly all cases.

Treatment of Small Cell Carcinoma of the Bladder With Chemotherapy and Radiation after Transurethral Resection of a Bladder Tumor.

To the Editor: This opposing views article highlights some of the fundamental differences in how radiation oncologists view the burgeoning (but not new) application of proton beam therapy (PBT) to treat prostate cancer. Hoppe et al articulate the respective arguments of the so-called proton and photon “camps” that have emerged within our specialty. These camps predictably fall along the lines of whether one practices at a center with PBT, and the financial differences between the 2 technologies are the key driver of the debate. Frankly none of us would be arguing against a product or device that delivers less unwanted radiation while maintaining (if not increasing) dose to the targetdif the cost is comparable to the alternatives. But it is different with prostate cancer. Excellent and affordable alternatives do exist, including brachytherapy, which is cheaper and more conformal than PBT and intensity modulated radiation therapy (IMRT). Those who use PBT should ask the important clinical questions, test them, and be given the time and resources to do so. Those who use only photon based techniques should, in turn, support these efforts, recognizing that IMRT was not held to the same standard when it was widely adopted over older and cheaper conventional techniques. Rather than recapitulating conflicting interpretations of the same methodologically flawed study, 1,2 as is done here, the radiation oncology community could look to patient level data on prospectively collected toxicity and quality of life outcomes for a disease as prevalent as prostate cancer. 3 In the spirit of incorporating patient reported outcomes Hoppe and Bryant suggest that the retrospectively observed 6% to 8% difference in bowel quality of life as measured by EPIC (Expanded Prostate Cancer Index Composite) is not only statistically significant, but also clinically relevant. 4 Sandler references the currently open randomized trial of IMRT vs proton therapy in prostate cancer, which has a primary end point of 2-year patient reported bowel quality of life (using EPIC). While this study will examine whether the retrospectively observed difference in bowel quality of life is statistically significant in a phase III setting, will it answer the question of whether it is clinically meaningful? If we do not see a difference for this specific end point, the trial will be negative. But will we truly feel that we answered the question of which is better? The media and payers certainly will, and frankly in many cases they have already decided that cheaper is better, period. The tide against PBT due to its generally greater costs is a foregone conclusion in many parts of the country but we have not afforded it the opportunity to prove itself. The institutional studies that have been reported to date generally all used passive scatter technique, an increasingly outdated and suboptimal form of proton beam delivery. We need to compare the “best” PBT techniques (ie pencil beam scanning) to the best IMRT. This comparison will require patience as centers work to responsibly deploy such capabilities. 5 While time is a rare luxury in the world of “do more with less,” it is necessary if we really want to test the various hypotheses described by the authors. Although there is multidirectional pressure to produce and report trial results quickly, doing so in prostate cancer can give a limited view of a disease with a long natural history involving patients who are at risk for late toxicities and relapses. As Sandler notes, the proton debate in prostate cancer carries great economic importance. But the comparative effectiveness challenges inherent to prostate cancer hopefully will not translate to a general disregard of PBT for other cancers. As a genitourinary radiation oncologist who uses PBT and photon based IMRT, I would like us to focus our efforts on investigating the promise of

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

The optimal management of persistent hemorrhagic radiation cystitis is ill-defined. Various options are available and include oral agents (ie, sodium pentosan polysulfate), intravenous drugs (ie, WF10), topical agents (ie, formalin), hyperbaric oxygen, and endoscopic procedures (ie, electrical cautery, argon plasma coagulation, laser coagulation). In general, it is best to manage patients conservatively and intervene only when necessary with the option least likely to exacerbate the cystitis. More aggressive measures should be employed only when more conservative approaches fail. Bladder biopsies should be avoided, unless findings suggest a bladder tumor, because they may precipitate a complication.

Definitive Radiotherapy for Skin and Adenoid Cystic Carcinoma with Perineural Invasion

Objectives:Small cell carcinoma of the bladder is a rare, aggressive cancer with a high potential for metastases. We analyzed outcomes of patients with small cell carcinoma of the bladder treated curatively with chemotherapy and radiotherapy with bladder preservation. Materials and Methods:We reviewed the medical records of 11 patients treated with radiotherapy at our institution between 1988 and 2010 for biopsy-proven small cell carcinoma of the bladder clinically localized to the true pelvis. Each patient received transurethral resection of the bladder tumor followed by induction chemotherapy and consolidative radiation or concurrent chemoradiation. After completing radiotherapy, cystoscopy was performed to evaluate local response. Overall survival, distant metastasis-free survival, local-regional control, and complete response rates are reported. Results:The median follow-up was 1.1 years for all patients and 10 years for survivors. Nine patients had clinical T3-T4 disease and 3 had node-positive disease. All patients were treated with conventional radiotherapy (median dose, 59 Gy) and cisplatin-based chemotherapy. Eight patients had a cystoscopy after completing chemoradiation, all of whom had a biopsy-proven complete response. The remaining 3 patients developed a distant metastasis before cystoscopy could be performed. The 3-year overall survival rate was 24%; the distant metastasis-free survival rate was 27%; and the local-regional control rate was 78%. All patients who achieved local control maintained functioning bladders. No Common Terminology Criteria for Adverse Events toxicity scale, version 3.0 late grade 3 genitourinary or gastrointestinal toxicities occurred. Conclusions:Primary chemoradiation provides reasonable local-regional control rates with a functioning bladder, even for patients with locally advanced disease, and is an effective alternative to cystectomy when aiming for bladder conservation.

Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound

Abstract 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.