BRACHYTHERAPY FOR PATIENTS WITH PROSTATE CANCER: American Society of Clinical Oncology/Cancer Care Ontario Joint Guideline Update Table of Contents Data Supplement 1: Additional Evidence Table(s) Table 1: Characteristics of Studies Identified in the Search of the Literature Table 2: Study Quality Assessment Data Supplement 2: Search Strategy String and Dates Data Supplement 3: QUOROM Diagram Data Supplement 4: Clinical Questions Data Supplement 5: MCC table Data Supplement 6: Original recommendations compared with updated recommendations References
Data Supplement 1: Additional Evidence Table(s) Table 1: Characteristics of Studies Identified in the Search of the Literature Trial ID: RTOG 0232 NCT Number: 00063882 Title: A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy With Brachytherapy Alone for Selected Patients With Intermediate Risk Prostatic Carcinoma Randomized, open-label, phase III study Experimental agent: Interstitial brachytherapy only (iodine 125 and palladium 103 given as interstitial seeds) EBRT (3DCRT or IMRT) 5 days a week for 5 weeks + interstitial brachytherapy only (iodine 125 and palladium 103 given as interstitial seeds) Planned Enrollment: 588 Active, not recruiting Radiation Therapy Oncology Group Trial ID: ASCENDE-RT NCT Number: 00175396 Title: A Randomized Phase III Study Comparing Androgen Suppression and Elective Pelvic Nodal Irradiation Followed by High Dose 3-D Conformal Boost Versus Androgen Suppression and Elective Pelvic Nodal Irradiation Followed by 125- Iodine Brachytherapy Implant Boost for Patients With Intermediate and High Risk Localized Prostate Cancer Randomized, open-label, phase III study Experimental agent: Androgen suppression, radiotherapy, iodine 125 brachytherapy Androgen suppression, radiotherapy Planned Enrollment: 400 Active, not recruiting University of British Columbia Trial ID: Hoskin et al, 2007 NCT Number: N/A Title: High dose rate brachytherapy in combination with external beam radiotherapy in the radical treatment of prostate cancer: initial results of a randomised phase three trial Randomized phase III study Experimental agent: EBRT + HDR Brachytherapy EBRT Actual recruitment: 200 Closed UK Department of Health and Cancer Research UK Trial ID: Sathya et al, 2005 NCT Number: N/A Title: Randomized Trial Comparing Iridium Implant Plus External-Beam Radiation Therapy With External-Beam Radiation Therapy Alone in Node-Negative Locally Advanced Cancer of the Prostate Randomized phase III study Experimental agent: EBRT + HDR Brachytherapy EBRT Actual recruitment: 104 Closed Ontario Clinical Oncology Group (OCOG) Trial ID: GMOR_HDR Monotherapy RCT NCT Number: 01890096
Title: A Randomized Phase II Trial of High Dose-Rate Brachytherapy as Monotherapy in Low and Intermediate Risk Prostate Cancer Randomized, open-label, phase 2 study Experimental agent: HDR Brachytherapy 1 fraction HDR Brachytherapy 2 fractions Planned Enrollment: 174 Ongoing, not recruiting Sunnybrook Health Sciences Centre Table 2: Study Quality Assessment Author Year Reference Prestidge BR, 2016 1 RTOG 0232 2003-2012 [Abstract] Morris JW, 2015 2,3 ACENDE-RT 2002-2011 Hoskin PJ, 2007 4 1997-2005 Sathya JR, 2005 5 Adequate Randomization Concealed Allocation Sufficient Sample Size Similar Groups Blinded Validated and Reliable Measures Adequate Followup Intention to Treat Analysis Insignificant COIs Overall Potential Risk of Bias a + - + + - + +? + Low + + + + - + + + + Low +? + +? + + +? Low 1992-1997 +? + + + + +? + Low Morton G, 2016 6 2013-2015 + - + + - + +? + Intermediate Note: +, indicates criteria was met; -, indicates criteria was not met;?, indicates insufficient detail, not reported, and/or uncertain if the criteria was met; NA, indicates not applicable. a Ratings are based on the estimation of whether the criterion was met and the extent of potential bias, not simply on reporting.
Data Supplement 2: Search Strategy String and Dates Database: Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) <1946 to Sept 30 2015> Search Strategy: -------------------------------------------------------------------------------- 1 (Cs-137 or 137-Cs or 137Cs or Cs137 or cesium-137 or 137-cesium or cesium137 or 137cesium).mp. (5178) 2 (Cs-131 or 131-Cs or 131Cs or Cs131 or cesium-131 or 131-cesium or cesium131 or 131cesium).mp. (175) 3 (I-125 or 125-I or 125I or I125 or iodine-125 or 125-iodine or iodine125 or 125iodine).mp. (52098) 4 (Pd-103 or 103-Pd or 103Pd or Pd103 or palladium-103 or 103-palladium or pallidum103 or 103palladium).mp. (659) 5 brachytherap$.mp. or brachytherapy/ (18878) 6 (internal radiotherap$ or sealed source radiotherap$ or ((permanent or seed) adj4 implant$) or curietherap$ or endocurietherap$).mp. (5235) 7 or/1-6 (77313) 8 exp prostate cancer/ (95786) 9 (prostat$ adj2 (cancer$ or neoplasm$ or adenocarcinom$ or carcinom$ or malign$ or tumo?r$)).mp. (116277) 10 8 or 9 (116277) 11 (case reports or comment or editorial or historical article or letter or news or newspaper article or patient education handout).pt. (3385784) 12 (7 and 10) not 11 (4093) 13 limit 12 to (english language and humans and yr="2011 -Current") (815) 14 from 13 keep 1-815 (815)
Data Supplement 3: QUOROM Diagram
Data Supplement 4: Clinical Questions 1. In patients with prostate cancer, what is the efficacy of brachytherapy alone for clinical outcomes compared with external beam radiation therapy (EBRT) alone, or radical prostatectomy alone? 2. In patients with prostate cancer, what is the efficacy of brachytherapy combined with EBRT for clinical outcomes compared with brachytherapy alone, EBRT alone, or radical prostatectomy alone? 3. Among the isotopes used for low dose rate brachytherapy (e.g. Iodine-125, Palladium- 103, and Cesium-137), which isotope maximizes clinical outcomes when used in patients with newly diagnosed prostate cancer?
Data Supplement 5: MCC table 10 Most Common Co-occurring Chronic Conditions among Male Medicare Beneficiaries with Prostate Cancer (N = 1,016,617 ), 2011 Beneficiaries less than 65 years (N =26,243 ) Beneficiaries 65 years and older (N =990,374) N % N % Prostate cancer prevalence 0.9 Prostate cancer prevalence 8.8 Top 10 co-morbidities Top 10 co-morbidities Hypertension 17,767 67.7 Hypertension 693,283 70.0 Hyperlipidemia 13,589 51.8 Hyperlipidemia 590,154 59.6 Diabetes 9,982 38.0 Ischemic heart disease 457,844 46.2 Ischemic heart disease 9,291 35.4 Anemia 337,957 34.1 Anemia 8,478 32.3 Diabetes 312,519 31.6 Arthritis 7,833 29.9 Arthritis 308,537 31.2 Chronic kidney disease 6,286 24.0 Chronic kidney disease 239,960 24.2 Depression 6,162 23.5 Cataract 235,241 23.8 COPD 4,646 17.7 Heart failure 203,231 20.5 Heart failure 4,636 17.7 COPD 145,818 14.7 Notes: Prepared by IPG/OIPDA on May 15, 2013. Citation: Unpublished data provided by the Office of Information Products and Data Analytics, Centers for Medicare & Medicaid Services, May 2013 Data Source: CMS administrative claims data, January 2011- December 2011, from the Chronic Condition Warehouse (CCW), ccwdata.org. Population: Male Medicare beneficiaries enrolled in fee-for-service (FFS) coverage of both Parts A and B for the entire year. Beneficiaries who were enrolled at any point during the year in a Medicare Advantage (MA) plan were excluded as were beneficiaries who first became eligible for Medicare after January of the calendar year. Beneficiaries who died during the year were included up to their date of death if they meet the other inclusion criteria. Beneficiaries less than 65 years of age are primarily receiving Medicare due to a disability. Chronic Condition Measures: For these tables, chronic conditions were identified through Medicare administrative claims. Medicare beneficiaries were considered to have a chronic condition if the CMS administrative data had a claim indicating that they were receiving a service or treatment for the specific condition. The data tables include information for beneficiaries with one of twenty-eight chronic conditions identified in the CCW. Detailed information on the identification of chronic conditions in the CCW is available at: http://www.ccwdata.org/chronic-conditions/index.htm. The list of 28 conditions include: Acquired hypothyroidism, Acute myocardial infarction, Alzheimer's Disease (including related Disorders or senile dementia), Anemia, Asthma, Atrial fibrillation, Autism, Benign prostatic hyperplasia, Breast cancer, Colon cancer, Endometrial cancer, Lung cancer, Prostate cancer, Cataract, Chronic kidney disease, COPD, Depression, Diabetes, Glaucoma, Heart failure, Hip/pelvic fracture, Hypertension, Hyperlipidemia, Ischemic heart disease, Osteoporosis, Arthritis (OA and RA), Schizophrenia (and other psychotic disorders) and Stroke.
Data Supplement 6: Original recommendations compared with updated recommendations Original Recommendations For patients with newly diagnosed low-risk or intermediate-risk prostate cancer who require or choose active treatment, LDR-BT alone is a treatment option as an alternative to EBRT alone or RP alone I-125 and Pd-103 are each reasonable isotope options in patients with prostate cancer. No recommendation can be made for or against using Cs-131 or the combination of EBRT and LDR-BT in the target patient population Patients should be encouraged to participate in clinical trials to test novel or targeted approaches to this disease Updated recommendations For low-risk prostate cancer patients who require or choose active treatment low dose rate brachytherapy (LDR) alone, external beam radiotherapy (EBRT) alone or radical prostatectomy (RP) should be offered to eligible patients For intermediate-risk prostate cancer patients choosing external beam radiotherapy with or without androgen deprivation therapy (ADT), brachytherapy boost (LDR or high dose rate (HDR)) should be offered to eligible patients. For low-intermediate risk prostate cancer (Gleason 7, PSA < 10 ng/ml or Gleason 6, PSA 10-20 ng/ml) LDR brachytherapy alone may be offered as monotherapy. For high-risk prostate cancer patients receiving EBRT and ADT, brachytherapy boost (LDR or HDR) should be offered to eligible patients I-125 and Pd-103 are each reasonable isotope options for patients receiving LDR brachytherapy; no recommendation can be made for or against using Cs-131 or HDR monotherapy Patients should be encouraged to participate in clinical trials to test novel or targeted approaches to this disease
References 1. Prestidge B, Winter K, Sanda M, et al: Initial Report of NRG Oncology/RTOG 0232: A Phase 3 Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy With Brachytherapy Alone for Selected Patients With Intermediate-Risk Prostatic Carcinoma. International journal of radiation oncology, biology, physics 96:S4, 2016 2. Morris WJ, Tyldesley S, Pai HH, et al: ASCENDE-RT*: A multicenter, randomized trial of dose-escalated external beam radiation therapy (EBRT-B) versus low-dose-rate brachytherapy (LDR-B) for men with unfavorable-risk localized prostate cancer. ASCO Meeting Abstracts 33:3, 2015 3. Morris WJ, Tyldesley S, Rodda S, et al: ASCENDE-RT: An Analysis of Survial Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose- Escalated External Beam Boost for High- And Intermediate-Risk Prostate Cancer. Int J Radiation Oncol Biol Physics Accepted, in press, 2016 4. Hoskin PJ, Motohashi K, Bownes P, et al: High dose rate brachytherapy in combination with external beam radiotherapy in the radical treatment of prostate cancer: initial results of a randomised phase three trial. Radiother Oncol 84:114-20, 2007 5. Sathya JR, Davis IR, Julian JA, et al: Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in nodenegative locally advanced cancer of the prostate. J Clin Oncol 23:1192-9, 2005 6. Morton G, Chung HT, McGuffin M, et al: 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 19Gy or two fractions of 13.5 Gy. Radiotherapy and Oncology, 2016