Laura D’Alimonte

Prostate high dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: Early toxicity and quality-of life results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy

BACKGROUND AND PURPOSE Multi-fraction high dose-rate (HDR) brachytherapy as monotherapy is safe and effective for low and intermediate risk prostate cancer. Two or single fraction regimens have some radiobiological rationale. The purpose is to determine toxicity and effect on health related quality of life (HRQOL) of single fraction 19Gy or 13.5Gy×2. MATERIALS AND METHODS Eligible patients had low or intermediate risk prostate cancer, prostate volume <60cc, and no androgen deprivation use. 170 patients were randomized to receive either a single 19Gy or two fractions of 13.5Gy 1week apart. HRQOL was measured using the Expanded Prostate Index Composite (EPIC), toxicity with Common Terminology for Adverse Events (CTCAE) v4.0 and urinary symptoms with the International Prostate Symptom Score (IPSS). RESULTS Median follow-up is 20months. Grade 2 urinary toxicity occurred in 51% within the first 3months and in 31% thereafter with no significant difference between treatment arms. Ten patients (6%) developed urinary retention in the acute phase, although only 4 (2.4%) required a catheter for more than 48h. One Grade 3 acute (⩽3months) and late (>3months) urinary toxicity occurred. No more than 1% had any Grade 2 GI toxicity. The 2-fraction arm had a higher occurrence of grade 2 erectile dysfunction (29% vs. 11.5%, p=0.0249) and higher IPSS scores for the first year. Mean EPIC urinary scores at 12months decreased by 4.0 and 4.6, and sexual scores decreased by 8 and 15.9 (p=0.035) in the single and 2-fraction arms, respectively. No change occurred in the bowel or hormonal domains. CONCLUSIONS Single 19Gy and 13.5Gy×2 are both well tolerated. During the first 12months, urinary symptoms and erectile dysfunction are more common in the 2-fraction arm.

High dose-rate brachytherapy boost for intermediate risk prostate cancer: Long-term outcomes of two different treatment schedules and early biochemical predictors of success

BACKGROUND AND PURPOSE To report long-term cancer control rates following high dose-rate (HDR) brachytherapy boost for intermediate risk prostate cancer and explore early biochemical predictors of success. MATERIAL AND METHODS Results of two sequential phase II trials are updated and compared: (1) Single 15 Gy HDR-boost followed by external beam radiotherapy (EBRT) 37.5 Gy/15fractions, (2) Two HDR fractions of 10 Gy followed by EBRT 45 Gy/25fractions. Patients were followed prospectively for clinical and biochemical outcomes. Nadir PSA (nPSA) and PSA at 3-years were analyzed as continuous variables, and ROC analysis was used to identify the optimal cutoff values. Kaplan-Meier bDFS curves were generated and the log-rank test used to compare different groups RESULTS 183 patients were accrued; 123 to the single fraction trial and 60 to the standard fractionation trial, with a median follow-up of 74 months and 99 months, respectively. The 5-year biochemical relapse-free survival was 97.4% and 92.7%, respectively (p=0.995). Median nPSA was 0.08 ng/ml. Failure to achieve a nPSA <0.4 ng/ml was associated with a significantly higher rate of biochemical relapse (5-year bDFS: 100% vs. 72%; p<0.0001). CONCLUSION HDR boost with single fraction 15 Gy provides durable long-term biochemical disease-free survival. PSA nadir <0.4 ng/ml is associated with very low risk of biochemical failure.

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy

BACKGROUND AND PURPOSE Initial results of Stereotactic Ablative Body Radiotherapy (SABR) in the treatment of localized prostate cancer appear promising however long-term quality of life (QOL) outcomes and dosimetric correlates are necessary. MATERIAL AND METHODS A phase I/II study was performed where low risk prostate cancer patients received SABR 35 Gy in 5 fractions, once weekly. Patient self-reported QOL was measured using the Expanded Prostate Cancer Index Composite (EPIC) at baseline and q6 month up to 5 years. Urinary, bowel and sexual domains were analyzed. A minimally clinical important change (MCIC) was defined as 0.5∗standard deviation of the baseline. Univariate and multivariate logistic regression were used to identify dosimetric predictors of MCIC. RESULTS 84 patients were included. The median follow-up was 50.8 months (interquartile range [IQR], 44.7-56.3). 17.9%, 26.2% and 37.5% of patients reported worse QOL on follow up in the urinary, bowel and sexual domains respectively. On univariate analysis Rectal V31.8>10%, D1cc>35 Gy were associated with bowel MCIC, penile bulb (PB) V35>4%, V20>40% with sexual MCIC. Of these factors only rectal D1cc and PB V35 were predictors of worse QOL on multivariate analysis. CONCLUSIONS Long-term single-institution QOL outcomes are encouraging. Rigorous dosimetric constraints are needed to keep bothersome side effects low.

Dose-escalation of five-fraction SABR in prostate cancer: Toxicity comparison of two prospective trials

PURPOSE To compare biochemical outcome and toxicities of two prospective 5-fraction stereotactic ablative radiotherapy (SABR) studies in prostate cancer. MATERIALS AND METHODS 84 patients in pHART3 received 35 Gy, 30 patients in pHART6 received 40 Gy in 5-fractions to the prostate alone, once weekly. 4mm and 5mm PTV margins were used, respectively. Biochemical outcome, acute, late and cumulative genitourinary (GU)/gastrointestinal (GI) toxicities were compared. RESULTS Median follow-up was 74 and 36 months, respectively. Median prostate specific antigen nadir was 0.4 ng/ml and 0.3 ng/ml. 2-, 4- and 6-year biochemical relapse-free survival (bRFS-2+nadir) was 100%, 98.7% and 95.9% in pHART3; 100%, 100% and not reached in pHART6 (p=0.91). There was one acute grade 3 GU (retention) and late grade 4 GI (fistula) toxicity in pHART3, none in pHART6. One patient in each study had persisting grade 2+ toxicity at the last follow-up. pHART6 patients had a greater grade 2+ cumulative GU (5% versus 24.2%) and GI (7.6% versus 26.2%) toxicities. CONCLUSIONS Patients receiving dose-escalated SABR had slightly lower PSA nadir and similar bRFS, longer follow-up is needed to better estimate biochemical outcomes. There was a greater risk of grade 2 toxicity in pHART6 but not grade 3+ toxicities. Persisting toxicity at the last follow-up is similar.

Dose-Escalated Stereotactic Body Radiation Therapy for Prostate Cancer: Quality-of-Life Comparison of Two Prospective Trials

Introduction The optimal prostate stereotactic body radiation therapy (SBRT) dose-fractionation scheme is controversial. This study compares long-term quality of life (QOL) from two prospective trials of prostate SBRT to investigate the effect of increasing dose (NCT01578902 and NCT01146340). Material and methods Patients with localized prostate cancer received SBRT 35 or 40 Gy delivered in five fractions, once per week. QOL was measured using the Expanded Prostate Cancer Index Composite at baseline and every 6 months. Fisher’s exact test and generalized estimating equations were used to analyze proportions of patients with clinically significant change and longitudinal changes in QOL. Results One hundred fourteen patients were included, 84 treated with 35 Gy and 30 treated with 40 Gy. Median QOL follow-up was 56 months [interquartile range (IQR) 46–60] and 38 months (IQR 32–42), respectively. The proportion of patients reporting clinically significant declines in average urinary, bowel, and sexual scores were not significantly different between dose levels, and were 20.5 vs. 24.1% (p = 0.60), 26.8 vs. 41.4% (p = 0.16), and 42.9 vs. 38.5% (p = 0.82), respectively. Similarly, longitudinal analysis did not identify significant differences in QOL between treatment groups. Conclusion Dose-escalated prostate SBRT from 35 to 40 Gy in five fractions was not associated with significant decline in long-term QOL.

A comparative study of quality of life in patients with localized prostate cancer treated at a single institution: Stereotactic ablative radiotherapy or external beam + high dose rate brachytherapy boost

PURPOSE To compare the quality of life (QOL) in patients treated with stereotactic ablative radiation therapy (SABR) alone or high dose rate (HDR) brachytherapy+hypofractionated external beam radiotherapy (EBRT). METHODS AND MATERIALS Patient self-reported QOL was prospectively measured among patients from two sequential phase 2 clinical trials: 1-SABR 35Gy/5fractions/5 weeks, 2-15Gy HDR 1 fraction, followed by EBRT 37.5Gy/15 fractions/3 weeks. The expanded prostate cancer index composite was assessed at baseline and q6 monthly up to 5 years. Urinary, bowel and sexual domains were analyzed. A minimally clinical important change (MCIC) was defined as 0.5*standard deviation of the baseline for each domain. Fisher exact test and general linear mixed model were used (p<0.05). RESULTS 84 and 123 patients were treated on the SABR and HDR boost studies, with a median follow up of 51 and 61 months respectively. There was a significant difference in MCIC between treatments in the urinary function and bother (p<0.0001), the bowel function (p=0.0216) and the sexual function (p=0.0419) and bother (p=0.0290) domains in favor of the SABR group. Of patients who reported no problem with their sexual function at baseline, 7% and 23% respectively considered it to be a moderate to big problem on follow up (p=0.0077). CONCLUSION Patients treated with HDR-boost reported deterioration of QOL particularly in sexual domains in comparison with SABR.

Educating our patients collaboratively: a novel interprofessional approach.

Providing cancer patients with more information regarding their treatments allows them to feel more in control, increases self efficacy, and can decrease anxiety. The aims of the present study were to develop an interprofessional group education session and to evaluate the usefulness and acceptability of this session. In addition, informational distress levels pre- and post-education were evaluated. A prostate radiation therapy (RT) education session was developed and facilitated by an interprofessional team. Topics discussed included how RT works, side effects and management, and support services available. Prior to the education session, participants reported their informational RT distress levels using the validated Distress Thermometer (DT). Post-education session, the DT was readministered. In addition, participants completed an acceptability survey to assess format, structure, and usefulness of the education session. Participants agreed that the session contained valuable and useful information helping them understand expectations during treatment, including resource availability, side effects and management, as well as procedural expectation during treatment. All stated they would recommend the session to other patients. The interprofessional nature of the sessions was deemed useful. Suggested areas for improvement included addition of a dietitian, information on long-term side effects, statistics of radiotherapy side effects, impact of radiotherapy on sexual function, and overall quality of life. The group education session significantly improved informational distress levels (p = 0.04). Educating prostate cancer patients utilizing an interprofessional group format can decrease anxiety and stress related to their RT treatment. Future development of group education sessions for other disease site groups may be valuable.

Opinions from the Experts: Exploring What Prostate Cancer Patients Should Know About Post-Operative Radiotherapy

The present study investigated health professionals’ opinions about important questions that should be discussed with patients who may require post-prostatectomy radiotherapy. A 74-question survey was conducted among radiation oncologists, urologists, nurses, and radiation therapists involved in the care of prostate cancer patients. Survey questions covered six domains: understanding my situation and prostate cancer diagnosis, making a decision, radiotherapy: procedures involved, potential benefits, side effects, and my support network during radiation treatment. Respondents rated the importance of addressing these questions as either essential, important, no opinion, or avoid with a hypothetical post-prostatectomy case. The majority of questions were rated as either essential or important. There was disagreement between professions on essential questions, mostly between nurses and urologists in the side-effects domain. There was agreement between all professions regarding which questions should be avoided.

To prep or not to prep - that is the question: A randomized trial on the use of antiflatulent medication as part of bowel preparation for patients having image guided external beam radiation therapy to the prostate

INTRODUCTION Radiation therapy is a standard treatment option for prostate cancer. With growing use of escalated doses and tighter margins, procedures to limit rectal size variation are needed to reduce prostate motion, increase treatment accuracy, and minimize rectal toxicity. This prospective study was done to determine whether the introduction of an antiflatulent medication would decrease rectal distention at computed tomography (CT) simulation and throughout a course of radiation therapy. METHODS AND MATERIALS Patients undergoing a radical course of radiation therapy to the prostate/prostate bed were eligible to participate. Participants were randomly assigned to the intervention arm (antiflatulent medication) or the control arm (no medication). For each participant, the number of CT simulation rescans was recorded. Rectal diameters were measured on CT simulation and treatment cone beam CT scans. Acute rectal toxicities were assessed at baseline and weekly using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. A χ2 analysis was used to compare the number of participants requiring a rescan in each study arm. Change in rectal diameter over time was assessed using repeated measures analysis of variance. RESULTS A total of 78 patients participated, with equal numbers assigned to each study arm. There was no significant difference between arms in the number of participants requiring a CT simulation rescan (P = .5551). There was no significant variation in rectal diameter between arms (P = .8999); however, there was a significant effect of time (P = .0017) and a significant interaction effect between study arm and time on rectal diameter (P = .0141). No acute rectal toxicities above grade 2 were reported. CONCLUSIONS The addition of antiflatulent medication did not affect the frequency of CT simulation rescans. Both time and the interaction between study arm and time had a statistically significant effect on rectal diameter, although neither finding was clinically significant. Instead, standardized bowel preparation education developed for this study may have been sufficient to limit rectal size variation.

Improving clinical trial accrual through a novel feedback approach: Lessons learned from a single disease site group

PURPOSE Physician participation is critical for the success of clinical trials. Many efforts have been made to aid physicians with accrual. The aim of our study was to determine what impact a new feedback initiative had on clinical trial accrual and recruitment within a large disease site group. METHODS AND MATERIALS A novel feedback initiative was implemented within a large multidisciplinary disease site group. Feedback on trial recruitment by physician and by study for the month and year to date was formally presented at the end of each trial month at weekly tumor board meetings. In addition, the feedback was sent via email. Trial recruitment was assessed both preintervention and postintervention. RESULTS A 9-month reporting period both preintervention and postintervention are reported. Total accruals within each observation window were 79 versus 209 patients, respectively. Preintervention, the mean number of patients accrued per month was 8.44 (range, 2-16). Postintervention, the mean number of patients accrued was 23.2 (range, 14-48). Preintervention, physicians only accrued to trials within their specialty. Postintervention, this improved by 4% monthly. CONCLUSIONS Physicians play a key role in the success of clinical trials. By adopting a simple monthly feedback communication initiative, we were able to improve clinical trial accruals. Long-term assessment is required to understand longitudinal impact on accrual rates.