Rectal Hydrogel Spacer Improves Late Gastrointestinal Toxicity Compared to Rectal Balloon Immobilization After Proton Beam Radiation Therapy for Localized Prostate Cancer: A Retrospective Observational Study.

PURPOSE: Our purpose was to compare dosimetric parameters and late gastrointestinal outcomes between patients treated with proton beam therapy (PBT) for localized prostate cancer with rectal balloon immobilization versus a hydrogel rectal spacer. METHODS AND MATERIALS: Patients with localized, clinical stage T1-4 prostate adenocarcinoma were treated at a single institution using conventionally fractionated, dose-escalated PBT from 2013 to 2018. Patient-reported gastrointestinal toxicity was prospectively collected, and the incidence of rectal bleeding was retrospectively reviewed from patient records. RESULTS: One hundred ninety-two patients were treated with rectal balloon immobilization, and 75 were treated with a rectal spacer. Rectal hydrogel spacer significantly improved rectal dosimetry while maintaining excellent target coverage. The 2-year actuarial rate of grade 2+ late rectal bleeding was 19% and 3% in the rectal balloon and hydrogel spacer groups, respectively (P = .003). In univariable analysis, the probability of grade 2+ rectal bleeding was significantly correlated with increasing rectal dose. In multivariable analysis, only receipt of spacer hydrogel (hazard ratio, 0.145; P = .010) and anticoagulation use (hazard ratio, 5.019; P < .001) were significantly associated with grade 2+ bleeding. At 2-year follow-up, patient-reported Expanded Prostate Cancer Index Composite bowel quality of life composite scores were less diminished in the hydrogel spacer group (absolute mean difference, 5.5; P = .030). CONCLUSIONS: Use of rectal hydrogel spacer for prostate PBT is associated with a significantly lower incidence of clinically relevant, late rectal bleeding and lower decrement in long-term, patient-reported bowel quality of life compared with rectal balloon immobilization. Our results suggest that hydrogel spacer may improve rectal sparing compared with rectal balloon immobilization during PBT for prostate cancer.

Analysis of Gastrointestinal Toxicity in Patients Receiving Proton Beam Therapy for Prostate Cancer: A Single-Institution Experience.

PURPOSE: We characterized both physician- and patient-reported rates of gastrointestinal (GI) toxicity in patients treated with proton beam therapy (PBT) at our institution for prostate adenocarcinoma and identified factors associated with toxicity. METHODS AND MATERIALS: We treated 192 patients with PBT between July 2013 and July 2016. Included patients had ≥1 year of follow-up. Potential preexisting clinical and treatment-related risk factors for GI toxicity were recorded. Common Terminology Criteria for Adverse Events version 4.0 was used to score toxicity. Expanded Prostate Cancer Index Composite (EPIC) bowel domain questionnaires assessed patient-reported quality of life. Associations between grade (GR) 2+ toxicity and clinical, treatment, and dosimetric factors were assessed using Cox models and corresponding hazard ratios. RESULTS: The median follow-up was 1.7 years. Most of the observed GI toxicity (>90%) was in the form of rectal bleeding (RB). GR2+ GI toxicity and RB actuarial rates specifically at 2 years were 21.3% and 20.4%, respectively. GR3 toxicity was rare, with only 1 observed RB event. No GR4/5 toxicity was seen. The EPIC bowel domain median score was 96 (range, 61-100) pretreatment, 93 (range, 41-100) at 1 year, 89 (range, 57-100) at 1.5 years, and 89 (range, 50-100) at 2 years. Anticoagulation use was the only factor selected during multivariate analysis for predicting GR2+ RB, with a resulting concordance index of 0.59 (95% confidence interval, 0.48-0.68; P = .088). Type of proton technology (pencil beam scanning vs uniform scanning) and number of fields treated per day (1 vs 2) showed no significant difference in toxicity rate. CONCLUSIONS: PBT was associated with acceptable rates of GR2+ transient GI toxicity, mostly in the form of RB, which correlated with anticoagulation use. High EPIC bowel domain quality of life was maintained in the 2 years after treatment.

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes.

BACKGROUND: We report prospectively captured clinical toxicity and patient reported outcomes in a single institutional cohort of patients treated for prostate cancer with proton beam therapy (PBT). This is the largest reported series of patients treated mostly with pencil beam scanning PBT. METHODS: We reviewed 231 patients treated on an IRB approved institutional registry from 2013 to 2016; final analysis included 192 patients with > 1-year of follow-up. Toxicity incidence was prospectively captured and scored using CTCAE v4.0. International Prostate Symptoms Score (IPSS), Sexual Health Inventory for Men (SHIM) score, and Expanded Prostate Cancer Index Composite (EPIC) bowel domain questionnaires were collected at each visit. Univariate Cox regression was used to explore associations of grade 2+ toxicity with clinical, treatment, and dosimetric variables. RESULTS: Median follow-up was 1.7 years. Grade 3 toxicity was seen in 5/192 patients. No grade 4 or 5 toxicity was seen. Patient reported quality-of-life showed no change in urinary function post-radiation by IPSS scores. Median SHIM scores declined by 3.7 points at 1-year post-treatment without further decrease beyond year 1. On univariate analysis, only younger age (HR = 0.61, p = 0.022) was associated with decreased sexual toxicity. EPIC bowel domain scores declined from 96 at baseline (median) by an average of 5.4 points at 1-year post-treatment (95% CI: 2.5-8.2 points, p < 0.001), with no further decrease over time. Bowel toxicity was mostly in the form of transient rectal bleeding and was associated with anticoagulation use (HR = 3.45, p = 0.002). CONCLUSIONS: Grade 3 or higher toxicity was rare at 2-years after treatment with PBT for localized prostate cancer. Longer follow-up is needed to further characterize late toxicity and biochemical control. TRIAL REGISTRATION: NCT, NCT01255748 . Registered 1 January 2013.

Dosimetric comparison of single-beam multi-arc and 2-beam multi-arc VMAT optimization in the Monaco treatment planning system.

The purpose of this study was to evaluate the dosimetric and practical effects of the Monaco treatment planning system "max arcs-per-beam" optimization parameter in pelvic radiotherapy treatments. We selected for this study a total of 17 previously treated patients with a range of pelvic disease sites including prostate (9), bladder (1), uterus (3), rectum (3), and cervix (1). For each patient, 2 plans were generated, one using an arc-per-beam setting of "1" and another with an arc-per-beam setting of "2" using the volumes and constraints established from the initial clinical treatments. All constraints and dose coverage objects were kept the same between plans, and all plans were normalized to 99.7% to ensure 100% of the planning target volume (PTV) received 95% of the prescription dose. Plans were evaluated for PTV conformity, homogeneity, number of monitor units, number of control points, and overall plan acceptability. Treatment delivery time, patient-specific quality assurance procedures, and the impact on clinical workflow were also assessed. We found that for complex-shaped target volumes (small central volumes with extending arms to cover nodal regions), the use of 2 arc-per-beam (2APB) parameter setting achieved significantly lower average dose-volume histogram values for the rectum V20 (p = 0.0012) and bladder V30 (p = 0.0036) while meeting the high dose target constraints. For simple PTV shapes, we found reduced monitor units (13.47%, p = 0.0009) and control points (8.77%, p = 0.0004) using 2APB planning. In addition, we found a beam delivery time reduction of approximately 25%. In summary, the dosimetric benefit, although moderate, was improved over a 1APB setting for complex PTV, and equivalent in other cases. The overall reduced delivery time suggests that the use of mulitple arcs per beam could lead to reduced patient-on-table time, increased clinical throughput, and reduced medical physics quality assurance effort.

Information Needs of Men with Localized Prostate Cancer During Radiation Therapy.

The purpose of this study was to describe how patient information needs change over the course of receiving radiation therapy for prostate cancer. Convenience sampling was utilized to recruit men with stage I-III prostate cancer. A longitudinal repeated measures design was implemented for this pilot study. Patients were presented with 36 paired comparisons, each asking the participant to choose the most important information topic(s) for today. Following completion of the survey instruments, the clinic nurse delivered the four top-ranked information topic handouts to each patient with brief instruction on how to use the handouts. Over the course of 6 months, we were able to recruit 35 men. The four highest priority topics across all four sessions were prognosis, stage of disease, treatment options, and side effects. Our results suggest trends in the information priorities that men hold over the course of radiation treatment. The information priorities do appear to shift over time, notably prognosis concerns and risk for family members continued to rise over time, while side effect information declined. These findings will extend an already strong foundation of evidence for preparatory information in radiation therapy. Furthermore, these findings will strengthen current evidence that computerized assessment of patient self-report information is feasible and an important adjunct to clinical practice.

External beam radiation therapy and abiraterone in men with localized prostate cancer: safety and effect on tissue androgens.

PURPOSE: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. METHODS AND MATERIALS: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. RESULTS: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. CONCLUSIONS: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression. Preliminary analysis of the clinical data is also promising, with excellent PSA nadir and no relapse to date in this high-risk population.

The Personal Patient Profile-Prostate decision support for men with localized prostate cancer: a multi-center randomized trial.

OBJECTIVE: The purpose of this trial was to compare usual patient education plus the Internet-based Personal Patient Profile-Prostate, vs. usual education alone, on conflict associated with decision making, plus explore time-to-treatment, and treatment choice. METHODS: A randomized, multi-center clinical trial was conducted with measures at baseline, 1-, and 6 months. Men with newly diagnosed localized prostate cancer (CaP) who sought consultation at urology, radiation oncology, or multi-disciplinary clinics in 4 geographically-distinct American cities were recruited. Intervention group participants used the Personal Patient Profile-Prostate, a decision support system comprised of customized text and video coaching regarding potential outcomes, influential factors, and communication with care providers. The primary outcome, patient-reported decisional conflict, was evaluated over time using generalized estimating equations to fit generalized linear models. Additional outcomes, time-to-treatment, treatment choice, and program acceptability/usefulness, were explored. RESULTS: A total of 494 eligible men were randomized (266 intervention; 228 control). The intervention reduced adjusted decisional conflict over time compared with the control group, for the uncertainty score (estimate -3.61; (confidence interval, -7.01, 0.22), and values clarity (estimate -3.57; confidence interval (-5.85,-1.30). Borderline effect was seen for the total decisional conflict score (estimate -1.75; confidence interval (-3.61,0.11). Time-to-treatment was comparable between groups, while undecided men in the intervention group chose brachytherapy more often than in the control group. Acceptability and usefulness were highly rated. CONCLUSION: The Personal Patient Profile-Prostate is the first intervention to significantly reduce decisional conflict in a multi-center trial of American men with newly diagnosed localized CaP. Our findings support efficacy of P3P for addressing decision uncertainty and facilitating patient selection of a CaP treatment that is consistent with the patient values and preferences.

Duration of first off-treatment interval is prognostic for time to castration resistance and death in men with biochemical relapse of prostate cancer treated on a prospective trial of intermittent androgen deprivation.

PURPOSE: This was an exploratory analysis of a trial of intermittent androgen deprivation (IAD) in men with biochemical relapse (BR) to establish first cycle characteristics prognostic for progression to castration-resistant prostate cancer (CRPC) and death. PATIENTS AND METHODS: Men with BR of prostate cancer after radical prostatectomy (RP) or radiation (RT) were treated with androgen deprivation therapy (ADT) comprised of leuprolide and flutamide. After 9 months on treatment, ADT was stopped, and monthly prostate-specific antigen (PSA) levels were observed during the off-treatment interval. When the PSA reached a threshold value (1 ng/mL for RP, 4 ng/mL for RT), ADT was resumed in a new cycle. Patients were treated intermittently in this manner until CRPC, which was defined as > or = two consecutive increasing PSA values while on ADT with castrate testosterone levels. RESULTS: Seventy-two of 100 patients enrolled onto the study met criteria for this analysis. The duration of the first off-treatment interval (< or = v > 40 weeks) was associated with shorter time to CRPC (hazard ratio = 2.9; 95% CI, 1.1 to 7.7; P = .03) and death (hazard ratio = 3.8; 95% CI, 1.1 to 13.6; P = .04) after adjusting for age, stage, grade, and PSA at diagnosis. CONCLUSION: In patients who completed the first cycle of IAD, a duration of the first off-treatment interval of < or = 40 weeks defines a subset of patients at higher risk of CRPC and death. Conversely, patients with an off-treatment interval of more than 40 weeks have a significantly better long-term prognosis.

Treatment options for muscle-invasive urothelial cancer for patients who were not eligible for cystectomy or neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin: report of Southwest Oncology Group Trial 8733.

BACKGROUND: Many patients with invasive urothelial cell cancer are poor candidates for cisplatin-based chemotherapy, and many are high risk for cystectomy. Southwest Oncology Group Trial 8733 was designed to address treatment for such patients. METHODS: Eligible patients had primary or recurrent muscle-invasive disease with transitional cell or squamous cell histology, a performance status from 0 to 2, no extrapelvic disease, a life expectancy >3 months, and adequate hematologic function. The treating clinician assigned patients to operable or inoperable groups. All patients received 2 cycles of 5-fluorouracil (5-FU) at a dose of 1000 mg/m(2) per day x 4 starting concurrently with radiation at a dose of 200 centigrays per day x 10 each cycle. After 2 cycles, operable patients with positive biopsies underwent cystectomy, and patients with negative biopsies received a third cycle of chemoradiotherapy. Patients in the inoperable group received 3 cycles without interim biopsy. RESULTS: Eighteen of 24 eligible patients in the operable group were evaluable for response. Five patients had a complete response (CR), 9 patients had stable disease, 1 patient had progressive disease, and 3 patients were not assessable. The median progression-free survival was 10 months (95% confidence interval [95% CI], 4-14 months), and the median overall survival was 18 months (95% CI, 7-28 months). In the inoperable group, 35 of 37 eligible patients were evaluable for response with 17 CRs (49%; 95% CI, 31%-66%). The median progression-free survival was 13 months (95% CI, 10-17 months), and the median overall survival was 20 months (95% CI, 11-53 months). There were no episodes of grade 4 toxicity. CONCLUSIONS: In the current study, the combination of 5-FU and radiation was found to be tolerated well by patients with numerous comorbidities who could not tolerate cisplatin-based therapy or cystectomy.

Actual use and perceived usefulness of a web-based, decision support program for men with prostate cancer.

The purpose of this pilot study was to develop and test the Personal Patient Profile-Prostate (P4), a customized, Internet-based decision support system for men with localized prostate cancer. In a sample of 30 men, the P4 program was successfully implemented in a clinical setting. Men reported the program useful and web-logs documented a high use rate of menu-driven components of the intervention.

Factors that predict treatment choice and satisfaction with the decision in men with localized prostate cancer.

PURPOSE: Men diagnosed with localized prostate cancer (LPC) often have the opportunity to participate in the treatment choice. The purpose of this study was to evaluate relationships between influential factors on treatment choice and the decision-related outcomes of decisional conflict and satisfaction. PATIENTS AND METHODS: This report presents data from 260 men diagnosed with LPC who were identified by their clinicians as having a choice of treatments. Men completed questionnaires at home within 2 weeks of the informational clinic visit with the clinician, but before treatment. The respondent sample had a mean age of 63.2 years (standard deviation, 8.1 years); the majority were married/partnered (82.7%), working (51.5%), white (93.8%), and educated at the collegiate level (83.8%). Personal factors (information, influential people, and outcomes), treatment choice, and decisional conflict and satisfaction with the decision (SWD) were queried. Relationships between all variables and the outcomes, SWD, and treatment choice were explored using exhaustive chi(2) automatic interaction detector. RESULTS: The strongest predictor partition variable for SWD was the subscale "factors contributing to uncertainty" (adjusted P < 0.0001) followed by the Trait Anxiety score (adjusted P = 0.0388). The strongest predictive partition for the actual treatment choice was age group (adjusted P < 0.0001), followed by interacting marital status (adjusted P = 0.0003), influence of the urologist (adjusted P = 0.0008), and use of the Internet (adjusted P = 0.0479). Men with LPC were more satisfied with their treatment choice when they reported fewer uncertainty factors; these are factors mainly relevant to information needed to understand the pros and cons and to make a decision. Consistent with this finding for treatment choice is the use of the Internet, though this factor interacted with age, the influence of their surgeon, and marital status. CONCLUSION: This study suggests that personally meaningful information communicated between patients and clinicians is paramount.

Induction of complete remission of advanced stage mycosis fungoides by allogeneic hematopoietic stem cell transplantation.

Advanced mycosis fungoides (MF) is incurable with conventional treatments. High-dose chemoradiotherapy with autologous bone marrow transplantation has induced remissions in a small number of patients with MF, but this modality is limited by a high relapse rate. We report induction of complete remission in a 37-year-old woman with rapidly progressive stage IV MF with allogeneic stem cell transplantation (Allo SCT). She remains in continuous complete remission 2 years after transplant. Allo SCT for MF is theoretically attractive, because there is no contamination of the graft by malignant cells, and because of the possibility of graft-versus-tumor effect. Although the results in this patient are encouraging, more patients and longer follow-up are needed to define the usefulness of Allo SCT in the treatment of MF.