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1.
The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma: IV. Local Treatment Failure and Enucleation in the First 5 Years after Brachytherapy. COMS Report No. 19.
Jampol, LM, Moy, CS, Murray, TG, Reynolds, SM, Albert, DM, Schachat, AP, Diddie, KR, Engstrom, RE, Finger, PT, Hovland, KR, et al
Ophthalmology. 2020;(4S):S148-S157
Abstract
OBJECTIVE To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I125) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial. DESIGN Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial. PARTICIPANTS Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension. METHODS I125 brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis. MAIN OUTCOME MEASURES Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation. RESULTS As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [CI], 10.0%-15.6%); the risk of treatment failure was 10.3% (95% CI, 8.0%-13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P = 0.08). CONCLUSIONS Local treatment failure and enucleation were relatively infrequent events after I125 brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe.
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2.
Tumor burden and liver function in HCC patient selection for selective internal radiation therapy: SARAH post-hoc study.
Palmer, DH, Hawkins, NS, Vilgrain, V, Pereira, H, Chatellier, G, Ross, PJ
Future oncology (London, England). 2020;(1):4315-4325
Abstract
Aim: To determine whether a liver tumor burden ≤25% and well-preserved liver function (albumin-bilirubin grade 1) are appropriate criteria for identifying patients with unresectable hepatocellular carcinoma who may benefit from selective internal radiation therapy (SIRT) using 90yttrium resin microspheres versus sorafenib. Patients & methods: Post-hoc analysis of patients in the intention-to-treat population of the SARAH trial (SIRT vs sorafenib) with ≤25% tumor burden and albumin-bilirubin grade 1. Primary end point: overall survival. Results: Median overall survival was 21.9 months (95% CI: 15.2-32.5, n = 37) with SIRT and 17.0 months (11.6-20.8, n = 48) with sorafenib (hazard ratios: 0.73; 95% CI: 0.44-1.21; p = 0.22). Conclusion: A combination of good liver function and low tumor burden may be relevant for selection of hepatocellular carcinoma patients for SIRT.
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3.
Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma.
Ricke, J, Klümpen, HJ, Amthauer, H, Bargellini, I, Bartenstein, P, de Toni, EN, Gasbarrini, A, Pech, M, Peck-Radosavljevic, M, Popovič, P, et al
Journal of hepatology. 2019;(6):1164-1174
Abstract
BACKGROUND & AIMS Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safety of a combination of sorafenib and selective internal radiation therapy (SIRT) - with yttrium-90 (90Y) resin microspheres - to sorafenib alone in patients with advanced HCC. METHODS SORAMIC is a randomised controlled trial comprising diagnostic, local ablation and palliative cohorts. Based on diagnostic study results, patients were assigned to local ablation or palliative cohorts. In the palliative cohort, patients not eligible for TACE were randomised 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. The primary endpoint was overall survival (OS; Kaplan-Meier analysis) in the intention-to-treat (ITT) population. RESULTS In the ITT cohort, 216 patients were randomised to SIRT + sorafenib and 208 to sorafenib alone. Median OS was 12.1 months in the SIRT + sorafenib arm, and 11.4 months in the sorafenib arm (hazard ratio [HR] 1.01; 95% CI 0.81-1.25; p = 0.9529). Median OS in the per protocol population was 14.0 months in the SIRT + sorafenib arm (n = 114), and 11.1 months in the sorafenib arm (n = 174; HR 0.86; p = 0.2515). Subgroup analyses of the per protocol population indicated a survival benefit of SIRT + sorafenib for patients without cirrhosis (HR 0.46; 0.25-0.86; p = 0.02); cirrhosis of non-alcoholic aetiology (HR 0.63; p = 0.012); or patients ≤65 years old (HR 0.65; p = 0.05). Adverse events (AEs) of Common Terminology Criteria for AE Grades 3-4 were reported in 103/159 (64.8%) patients who received SIRT + sorafenib, 106/197 (53.8%) patients who received sorafenib alone (p = 0.04), and 8/24 (33.3%) patients who only received SIRT. CONCLUSION Addition of SIRT to sorafenib did not result in a significant improvement in OS compared with sorafenib alone. Subgroup analyses led to hypothesis-generating results that will support the design of future studies. LAY SUMMARY Sorafenib given orally is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). In selective internal radiation therapy (SIRT), also known as radioembolisation, microscopic, radioactive resin or glass spheres are introduced into the blood vessels that feed the tumours in the liver. This study found that the addition of SIRT with 90yttrium-loaded resin microspheres to sorafenib treatment in people with advanced HCC did not significantly improve overall survival compared with sorafenib treatment alone. However, the results give an indication of how future studies using this combination therapy in people with advanced HCC could be designed. STUDY REGISTRATION EudraCT 2009-012576-27, NCT0112 6645.
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4.
SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma.
Chow, PKH, Gandhi, M, Tan, SB, Khin, MW, Khasbazar, A, Ong, J, Choo, SP, Cheow, PC, Chotipanich, C, Lim, K, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018;(19):1913-1921
Abstract
Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.
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5.
Seed migration after transperineal interstitial prostate brachytherapy by using loose seeds: Japanese prostate cancer outcome study of permanent iodine-125 seed implantation (J-POPS) multi-institutional cohort study.
Nakano, M, Yorozu, A, Saito, S, Sugawara, A, Maruo, S, Kojima, S, Kikuchi, T, Fukushima, M, Dokiya, T, Yamanaka, H
Radiation oncology (London, England). 2015;:228
Abstract
BACKGROUND The incidence and associated factors of loose seed migration were investigated in cohort 1 of the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS). METHODS The study subjects were 2160 patients, consisting of 1641 patients who underwent permanent iodine-125 seed implantation (PI) and 519 patients who underwent PI combined with external beam radiation therapy (PI + EBRT). The presence or absence of seed migration to the chest and abdominal/pelvic region was determined. RESULTS Seed migration was observed in 22.7 % of PI group patients and 18.1 % of PI + EBRT group patients (p = 0.0276). Migration to the lungs and abdominal/pelvic region was observed in 14.6 % and 11.1 % of the patients in the PI group, and 11.2 % and 8.5 % of the patients in the PI + EBRT group, respectively. In the PI group, the number of implanted seeds was associated with the seed migration incidence. Neither the PI nor the PI + EBRT group showed any difference in the volume of the prostate receiving 100 % of the prescribed dose (V100 [%]) or the minimal dose received by 90 % of the prostate volume (D90 [Gy]) between the patients with and without seed migration. CONCLUSIONS This prospective cohort study investigating the largest number of past cases showed no difference in D90 (Gy) or V100 (%) between seed migration or the absence thereof in both the PI group and PI + EBRT group. TRIAL REGISTRATION ClinicalTrials.gov: NCT00534196.
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Outcomes of choroidal melanomas treated with eye physics: a 20-year review.
Berry, JL, Dandapani, SV, Stevanovic, M, Lee, TC, Astrahan, M, Murphree, AL, Kim, JW
JAMA ophthalmology. 2013;(11):1435-42
Abstract
IMPORTANCE The University of Southern California Eye Physics plaques compare favorably with the Collaborative Ocular Melanoma Study plaques in terms of late adverse effects from radiation, metastasis, and local tumor recurrence. OBJECTIVE To review the University of Southern California experience using Eye Physics plaques and Plaque Simulator software to treat choroidal melanomas and compare the outcomes with published results of the Collaborative Ocular Melanoma Study. DESIGN, SETTING, AND PARTICIPANTS A retrospective case series of 82 patients treated for medium-sized choroidal melanoma from January 1, 1990, through December 30, 2010, using iodine 125 plaques and treatment simulation software developed at the University of Southern California. The dosimetric goal was 85 Gy in 7 days to a conformal volume enclosing the apex and a 2-mm margin surrounding the tumor base. Plaque localization was guided by the Plaque Simulator computer modeling system using preoperative imaging studies. MAIN OUTCOMES AND MEASURES Primary outcome measures were local tumor control, globe preservation, and metastases. Secondary outcome measures were late radiation adverse effects including postoperative vision changes, optic neuropathy, radiation retinopathy, and cataract. RESULTS The median follow-up for 82 patients was 46.8 months (range, 1-171 months). Globe preservation was achieved in 80 patients (97.6%); 2 patients underwent enucleation for local recurrence. Metastatic disease developed in 9 patients (11.0%). Retinopathy was seen in 31 patients (37.8%), optic neuropathy in 12 (14.6%), and cataracts in 26 (31.7%). Postoperatively, 21 patients (25.6%) lost more than 6 lines of Snellen visual acuity. CONCLUSIONS AND RELEVANCE When considering rates of local recurrence, metastases, and late radiation adverse effects, the University of Southern California results for medium-sized choroidal melanomas using Eye Physics plaques compared favorably with Collaborative Ocular Melanoma Study data. The Plaque Simulator 3-dimensional tumor-modeling program developed at the University of Southern California is a reliable method for determining plaque positioning preoperatively and for treating this cohort of patients.
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7.
Comparison of high-dose proton radiotherapy and brachytherapy in localized prostate cancer: a case-matched analysis.
Coen, JJ, Zietman, AL, Rossi, CJ, Grocela, JA, Efstathiou, JA, Yan, Y, Shipley, WU
International journal of radiation oncology, biology, physics. 2012;(1):e25-31
Abstract
PURPOSE To report a case-matched analysis comparing high-dose external-beam radiation (EBRT) for prostate cancer delivered on Proton Radiation Oncology Group (PROG) 95-09, a randomized trial, with permanent prostate brachytherapy over the same era. METHODS From 1996 to 1999, 196 patients were accrued to the high-dose arm (79.2 Gray equivalent (GyE) using photons and protons) of PROG 95-09 at the Massachusetts General Hospital and Loma Linda University Medical Center. Entry criteria specified T1-2 and prostate-specific antigen ≤ 15 ng/mL. When Gleason score >7 was excluded, 177 men were left for case matching. At Massachusetts General Hospital, 203 similar patients were treated by a single brachytherapist from 1997 to 2002. Minimum follow-up was 3 years. Case matching, based on T stage, Gleason score, prostate-specific antigen, and age resulted in 141 matches (282 patients). Median follow-up was 8.6 and 7.4 years for EBRT and brachytherapy, respectively. The primary endpoint was biochemical failure (BF). RESULTS Using the Phoenix definition, the 8-year BF rates were 7.7% and 16.1% for EBRT and brachytherapy, respectively (p = 0.42). A stratified analysis was performed by risk group. In the EBRT group, 113 and 28 patients were low and intermediate risk, respectively. In the brachytherapy group, 118 and 23 were. When stratified by risk group, the BF rates were similar by either technique. CONCLUSIONS High-dose EBRT and brachytherapy result in similar BF rates for men with localized prostate cancer. Comparative quality-of-life and cost-effectiveness studies are warranted.
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8.
Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial.
Konaka, H, Egawa, S, Saito, S, Yorozu, A, Takahashi, H, Miyakoda, K, Fukushima, M, Dokiya, T, Yamanaka, H, Stone, NN, et al
BMC cancer. 2012;:110
Abstract
BACKGROUND Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required. METHODS/DESIGN This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 ((125)I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with (125)I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during (125)I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events. DISCUSSION To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa. TRIAL REGISTRATION UMIN000003992.
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Collaborative ocular melanoma study randomized trial of I-125 brachytherapy.
Hawkins, BS
Clinical trials (London, England). 2011;(5):661-73
Abstract
BACKGROUND Although findings from observational studies published in the 1970s and early 1980s suggested that length of remaining life after a diagnosis of uveal melanoma was similar following enucleation (removal of the eye) and local eye-conserving radiotherapy, the majority of ophthalmologists in the United States were not convinced that "saving the eye" would not compromise survival. PURPOSE The Collaborative Ocular Melanoma Study (COMS) was designed to compare enucleation and radiotherapy among similar patients with respect to survival outcomes. METHODS A multicenter randomized trial of primary treatment with iodine-125 brachytherapy versus enucleation (i.e., a comparative effectiveness trial) was conducted to provide the evidence required to answer the concerns of ophthalmologists and their patients. Eligibility criteria adopted for the trial were intended to apply to the majority of patients diagnosed with choroidal melanoma who would be suitable candidates for either form of primary treatment. RESULTS Accrual to this COMS trial began in 1986 and ended in 1998. Participating patients were followed for 5 to 15 years, depending upon date of enrollment, before all clinical follow-up ended in 2003. No difference in survival outcomes and little difference in quality-of-life outcomes were observed between patients in the brachytherapy arm and those in the enucleation arm. Five-year survival was substantially better than anticipated based on a review of the literature when the trial was designed. LIMITATIONS The choice of brachytherapy for delivery of radiation to the tumor had important advantages but also imposed restrictions regarding eligibility. CONCLUSIONS The multidisciplinary COMS Group not only successfully conducted a randomized trial that answered the primary study questions but also has contributed to clinical and epidemiologic knowledge of choroidal melanoma through numerous publications. As a consequence of the COMS, a standard approach to I-125 brachytherapy for treatment of choroidal melanoma became widely available to affected patients.
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10.
Transperineal prostate brachytherapy, using I-125 seed with or without adjuvant androgen deprivation, in patients with intermediate-risk prostate cancer: study protocol for a phase III, multicenter, randomized, controlled trial.
Miki, K, Kiba, T, Sasaki, H, Kido, M, Aoki, M, Takahashi, H, Miyakoda, K, Dokiya, T, Yamanaka, H, Fukushima, M, et al
BMC cancer. 2010;:572
Abstract
BACKGROUND The optimal protocol for 125I-transperineal prostatic brachytherapy (TPPB) in intermediate-risk prostate cancer (PCa) patients remains controversial. Data on the efficacy of combining androgen-deprivation therapy (ADT) with 125I-TPPB in this group remain limited and consequently the guidelines of the American Brachytherapy Society (ABS) provide no firm recommendations. METHODS/DESIGN Seed and Hormone for Intermediate-risk Prostate Cancer (SHIP) 0804 is a phase III, multicenter, randomized, controlled study that will investigate the impact of adjuvant ADT following neoadjuvant ADT and 125I-TPPB. Prior to the end of March, 2011, a total of 420 patients with intermediate-risk, localized PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from 20 institutions, all of which have broad experience of 125I-TPPB. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will initially undergo 3-month ADT prior to 125I-TPPB. Those randomly assigned to adjuvant therapy will subsequently undergo 9 months of adjuvant ADT. All participants will be assessed at baseline and at the following intervals: every 3 months for the first 24 months following 125I-TPPB, every 6 months during the 24- to 60-month post-125I-TPPB interval, annually between 60 and 84 months post-125I-TPPB, and on the 10th anniversary of treatment.The primary endpoint is biochemical progression-free survival (BPFS). Secondary endpoints are overall survival (OS), clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, acceptability (assessed using the international prostate symptom score [IPSS]), quality of life (QOL) evaluation, and adverse events. In the correlative study (SHIP36B), we also evaluate biopsy results at 36 months following treatment to examine the relationship between the results and the eventual recurrence after completion of radiotherapy. DISCUSSION These two multicenter trials (SHIP0804 & SHIP36B) are expected to provide crucial data regarding the efficacy, acceptability and safety of adjuvant ADT. SHIP36B will also provide important information about the prognostic implications of PSA levels in intermediate-risk PCa patients treated with 125I-TPPB. TRIAL REGISTRATION NCT00664456, NCT00898326, JUSMH-BRI-GU05-01, JUSMH-TRIGU0709.