Ross Halperin

Predictive Factors for Acute and Late Urinary Toxicity After Permanent Prostate Brachytherapy: Long-Term Outcome in 712 Consecutive Patients

PURPOSE To describe the frequency of acute and late Radiation Therapy Oncology Group (RTOG) urinary toxicity, associated predictive factors, and resolution of International Prostate Symptom Score (IPSS) in 712 consecutive prostate brachytherapy patients. METHODS AND MATERIALS Patients underwent implantation between 1998 and 2003 (median follow-up, 57 months). The IPSS and RTOG toxicity data were prospectively collected. The patient, treatment, and implant factors were examined for an association with urinary toxicity. The time to IPSS resolution was examined using Kaplan-Meier curves, and multivariate modeling of IPSS resolution was done using Cox proportional hazards regression analysis. Logistic regression analysis was used to examine the factors associated with urinary toxicity. RESULTS The IPSS returned to baseline at a median of 12.6 months. On multivariate analysis, patients with a high baseline IPSS had a quicker resolution of their IPSS. Higher prostate D90 (dose covering 90% of the prostate), maximal postimplant IPSS, and urinary retention slowed the IPSS resolution time. The rate of the actuarial 5-year late urinary (>12 months) RTOG Grade 0, 1, 2, 3, and 4 was 32%, 36%, 24%, 6.2%, and 0.1%, respectively. At 7 years, the prevalence of RTOG Grade 0-1 was 92.5%. Patients with a larger prostate volume, greater number of needles, greater baseline IPSS, and use of hormonal therapy had more acute toxicity. On multivariate analysis, the significant predictors for late greater than or equal to RTOG toxicity 2 were a greater baseline IPSS, maximal postimplant IPSS, presence of acute toxicity, and higher prostate V150 (volume of the prostate covered by 150% of the dose). More recently implanted patients had less acute urinary toxicity and patients given hormonal therapy had less late urinary toxicity (all p < 0.02). CONCLUSION Most urinary symptoms resolved within 12 months after prostate brachytherapy, and significant long-term urinary toxicity was very low. Refined patient selection and greater technical experience in prostate brachytherapy were associated with less urinary toxicity.

Rectal toxicity and rectal dosimetry in low-dose-rate 125I permanent prostate implants: A long-term study in 1006 patients

OBJECTIVE To describe the acute and late rectal toxicity in 1006 prostate brachytherapy patients implanted 1998-2003. To determine whether rectal dose-volume histogram as well as patient and treatment factors were associated with rectal toxicity. METHODS AND MATERIALS Median followup was 60.7 months. Rectal dosimetry was calculated as dose-volume histogram of the rectum using Day 28 CT-based dosimetry and expressed as volume of the rectum in cc receiving 50%, 100%, and 150% of the prescription dose (VR(50cc), VR(100cc), and VR(150cc), respectively). Univariate and multivariate analyses were performed to examine the influence of patient, implant, dosimetry, and learning curve factors on the development of acute and late toxicities using a modified Radiation Therapy Oncology Group (RTOG) scale. Acute toxicity was analyzed using logistic regression and late toxicity using Cox proportional hazards regression. Analysis of variance was used to examine the association between rectal toxicity and rectal dose. RESULTS Rectal dosimetry in 93.5% and rectal toxicity in 96.2% have been recorded. Median VR(100)=1.05cc. Late RTOG Grades 0, 1, 2, 3, and 4 were recorded in 68%, 23%, 7.3%, 0.9%, and 0.2% patients, respectively. On multivariate analysis, acute RTOG ≥2 rectal toxicity was associated with urinary retention (p=0.036) and learning curve (p=0.015); late RTOG ≥2 was associated with the presence of acute toxicity (p=0.0074), higher VR(100) (p=0.030) and learning curve (p=0.027). CONCLUSIONS Late rectal RTOG ≥2 rectal toxicity in this cohort was 8%. Increased VR(100), presence of acute rectal toxicity, and learning curve were associated with higher rate of late RTOG ≥2 toxicity. Severe late rectal toxicity after prostate brachytherapy was rare.

Impact of Using Audit Data to Improve the Evidence-Based Use of Single-Fraction Radiation Therapy for Bone Metastases in British Columbia

PURPOSE To assess the impact of a population-based intervention to increase the consistency and use of single-fraction radiation therapy (SFRT) for bone metastases. METHODS AND MATERIALS In 2012, an audit of radiation therapy prescriptions for bone metastases in British Columbia identified significant interphysician and -center (26%-73%) variation in the use of SFRT. Anonymous physician-level and identifiable regional cancer center SFRT use data were presented to all radiation oncologists, together with published guidelines, meta-analyses, and recommendations from practice leaders. The use of SFRT for bone metastases from 2007 through 2011 was compared with use of SFRT in 2013, to assess the impact of the audit and educational intervention. Multilevel logistic regression was used to assess the relationship between the usage of SFRT and the timing of the radiation while controlling for potentially confounding variables. Physician and center were included as group effects to account for the clustered structure of the data. RESULTS A total of 16,898 courses of RT were delivered from 2007 through 2011, and 3200 courses were delivered in 2013. The rates of SFRT use in 2007, 2008, 2009, 2010, 2011, and 2013 were 50.5%, 50.9%, 48.3%, 48.5%, 48.0%, and 59.7%, respectively (P<.001). Use of SFRT increased in each of 5 regional centers: A: 26% to 32%; B: 36% to 56%; C: 39% to 57%; D: 49% to 56%; and E: 73% to 85.0%. Use of SFRT was more consistent; 3 of 5 centers used SFRT for 56% to 57% of bone metastases RT courses. The regression analysis showed strong evidence that the usage of SFRT increased after the 2012 intervention (odds ratio 2.27, 95% confidence interval 2.06-2.50, P<.0001). CONCLUSION Assessed on a population basis, an audit-based intervention increased utilization of SFRT for bone metastases. The intervention reversed a trend to decreasing SFRT use, reduced costs, and improved patient convenience. This suggests that dissemination of programmatic quality indicators in oncology can lead to increased utilization of evidence-based practice.

Point: The relationship between postimplant dose metrics and biochemical no evidence of disease following low dose rate prostate brachytherapy: Is there an elephant in the room?

Point: The relationship between postimplant dose metrics and biochemical no evidence of disease following low dose rate prostate brachytherapy: Is there an elephant in the room? W. James Morris*, Ross Halperin, Ingrid Spadinger Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada Department of Radiation Oncology, British Columbia Cancer Agency, Kelowna, BC, Canada

Radiation oncology and medical physicists quality assurance in British Columbia Cancer Agency Provincial Prostate Brachytherapy Program

PURPOSE To describe in detail British Columbia (BC) Cancer Agency (BCCA) Provincial Prostate Brachytherapy (PB) Quality Assurance (QA) Program. METHODS AND MATERIALS The BCCA PB Program was established in 1997. It operates as one system, unified and supported by electronic and information systems, making it a single PB treatment provider for province of BC and Yukon. To date, >4000 patients have received PB (450 implants in 2011), making it the largest program in Canada. The Program maintains a large provincial prospective electronic database with records on all patients, including disease characteristics, risk stratification, pathology, preplan and postimplant dosimetric data, follow-up of prostate-specific antigen, and toxicity outcomes. RESULTS QA was an integral part of the program since its inception. A formal QA Program was established in 2002, with key components that include: unified eligibility criteria and planning system, comprehensive database, physics and oncologist training and mentorship programs, peer review process, individual performance outcomes and feedback process, structured continuing education and routine assessment of the programs dosimetry, toxicity and prostate-specific antigen outcomes, administration and program leadership that promotes a strong culture of patient safety. The emphasis on creating a robust, broad-based network of skilled providers has been achieved by the programs requirements for training, education, and the QA process. CONCLUSIONS The formal QA process is considered a key factor for the success of cancer control outcomes achieved at BCCA. Although this QA model may not be wholly transferable to all PB programs, some of its key components may be applicable to other programs to ensure quality in PB and patient safety.

Implications of CT-imaging for Postplan Quality Assessment in Prostate Brachytherapy

PURPOSE Postplan quality assurance using CT shows considerable interobserver contour variability. We examined CT postplans of four experienced brachytherapists for comparison with MR-determined prostate volumes. METHODS AND MATERIALS Seventy-five patients had CT and MR scans 1 month post-(125)I prostate brachytherapy. CT scans were contoured by the treating physician and dosimetry calculated. The prostate was contoured independently on MR by one observer with extensive MR experience, the scans were fused and dosimetric parameters compared. RESULTS The mean prostate volume on CT was 38.3 cc (17.5-78.6 cc), on MR 33.3 cc (16.3-66.1 cc). On average, the volume on CT was 16.1% larger than on MR (range, 8% smaller to 64% larger). Craniocaudal discordance of the CT vs. MR prostate contours ranged from 4 mm cranial to 10 mm caudal to MR base and from 6 mm cranial to 14 mm caudal to MR apex. The CT prostate volume not only included an average of 90% of the MR prostate (range, 75-99%) but also included normal tissue (mean, 8.3 cc; range, 2.9-17.1 cc). The average difference between the calculated D(90) from CT contours vs. MR contours was 10.0 Gy (standard deviation, 8.8; range, -37.6 to +41.6 Gy). CONCLUSIONS On average, only 90% of the MR-defined prostate is included in CT contours, while a volume of normal tissue is erroneously designated as prostate. Lack of awareness of this deficiency in planning and/or operative technique gives a false sense of appreciation of the true conformality, delays implementation of corrective measures, and risks unnecessary side effects.

A Quantitative Analysis of the Relationship Between Radiation Therapy Use and Travel Time

PURPOSE To model and quantify the relationship between radiation therapy (RT) use and travel time to RT services. METHODS AND MATERIALS Population-based registries and databases were used to identify both incident cancer patient and patients receiving RT within 1 year of diagnosis (RT1y) in British Columbia, Canada, between 1992 and 2011. The effects of age, gender, diagnosis year, income, prevailing wait time, and travel duration for RT on RT1y were assessed. Significant factors from univariate analyses were included in a multivariable logistic regression model. The shape of the travel time-RT1y curve was represented by generalized additive and segmented regression models. Analyses were conducted for breast, lung, and genitourinary cancer separately and for all cancer sites combined. RESULTS After adjustment for age, gender, diagnosis year, income, and prevailing wait times, increasing travel time to the closest RT facility had a negative impact RT1y. The shape of the travel time-RT1y curve varied with cancer type. For breast cancer, the odds of RT1y were constant for the first 2 driving hours and decreased at 17% per hour thereafter. For lung cancer, the odds of RT1y decreased by 16% after 20 minutes and then decreased at 6% per hour. Genitourinary cancer RT1y was relatively independent of travel time. For all cancer sites combined, the odds of RT1y were constant within the first 2 driving hours and decreased at 7% per hour thereafter. CONCLUSIONS Travel time to receive RT has a different impact on RT1y for different tumor sites. The results provide evidence-based insights for the configuration of catchment areas for new and existing cancer centers providing RT.

Delayed Workforce Entry and High Emigration Rates for Recent Canadian Radiation Oncology Graduates

PURPOSE To determine the employment status and location of recent Canadian radiation oncology (RO) graduates and to identify current workforce entry trends. METHODS AND MATERIALS A fill-in-the-blank spreadsheet was distributed to all RO program directors in December 2013 and June 2014, requesting the employment status and location of their graduates over the last 3 years. Visa trainee graduates were excluded. RESULTS Response rate from program directors was 100% for both survey administrations. Of 101 graduates identified, 99 (98%) had known employment status and location. In the December survey, 5 2013 graduates (16%), 17 2012 graduates (59%), and 18 2011 graduates (75%) had permanent staff employment. Six months later, 5 2014 graduates (29%), 15 2013 graduates (48%), 24 2012 graduates (83%), and 21 2011 graduates (88%) had secured staff positions. Fellowships and temporary locums were common for those without staff employment. The proportion of graduates with staff positions abroad increased from 22% to 26% 6 months later. CONCLUSIONS Workforce entry for most RO graduates was delayed but showed steady improvement with longer time after graduation. High emigration rates for jobs abroad signify domestic employment challenges for newly certified, Canadian-trained radiation oncologists. Coordination on a national level is required to address and regulate radiation oncologist supply and demand disequilibrium in Canada.

Provincial development of a patient-reported outcome initiative to guide patient care, quality improvement, and research:

The BC Cancer Agency Radiotherapy (RT) program started the Prospective Outcomes and Support Initiative (POSI) at all six centres to utilize patient-reported outcomes for immediate clinical care, quality improvement, and research. Patient-reported outcomes were collected at time of computed tomography simulation via tablet and 2 to 4 weeks post-RT via either tablet or over the phone by a registered nurse. From 2013 to 2016, patients were approached on 20,150 attempts by POSI for patients treated with RT for bone metastases (52%), brain metastases (11%), lung cancer (17%), gynecological cancer (16%), head and neck cancer (2%), and other pilots (2%). The accrual rate for all encounters was 85% (n = 17,101), with the accrual rate varying between the lowest and the highest accruing centre from 78% to 89% (P < .001) and varying by tumour site (P < .001). Using the POSI database, we have performed research and quality improvement initiatives that have changed practice.

Directly Improving the Quality of Radiation Treatment Through Peer Review: A Cross-sectional Analysis of Cancer Centers Across a Provincial Cancer Program

PURPOSE To describe the outcomes of peer review across all 14 cancer centers in Ontario. METHODS AND MATERIALS We identified all peer-reviewed, curative treatment plans delivered in Ontario within a 3-month study period from 2013 to 2014 using a provincial cancer treatment database and collected additional data on the peer-review outcomes. RESULTS Considerable variation was found in the proportion of peer-reviewed plans across the centers (average 70.2%, range 40.8%-99.2%). During the study period, 5561 curative plans underwent peer review. Of those, 184 plans (3.3%) had changes recommended. Of the 184 plans, the changes were major (defined as requiring repeat planning or having a major effect on planning or clinical outcomes, or both) in 40.2% and minor in 47.8%. For the remaining 12.0%, data were missing. The proportions of recommended changes varied among disease sites (0.0%-7.0%). The disease sites with the most recommended changes to treatment plans after peer review and with the greatest potential for benefit were the esophagus (7.0%), uterus (6.7%), upper limb (6.3%), cervix and lower limb (both 6.0%), head and neck and bilateral lung (both 5.9%), right supraclavicular lymph nodes (5.7%), rectum (5.3%), and spine (5.0%). Although the heart is an organ at risk in left-sided breast treatment plans, the proportions of recommended changes did not significantly differ between the left breast treatment plans (3.0%, 95% confidence interval 2.0%-4.5%) and right breast treatment plans (2.4%, 95% confidence interval 1.5%-3.8%). The recommended changes were more frequently made when peer review occurred before radiation therapy (3.8%) than during treatment (1.4%-2.8%; P=.0048). The proportion of plans with recommended changes was not significantly associated with patient volume (P=.23), peer-review performance (P=.36), or center academic status (P=.75). CONCLUSIONS Peer review of treatment plans directly affects the quality of care by identifying important clinical and planning changes. Provincial strategies are underway to optimize its conduct in radiation oncology.