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i-Move, a personalised exercise intervention for patients with advanced melanoma receiving immunotherapy: a randomised feasibility trial protocol.
Hyatt, A, Gough, K, Murnane, A, Au-Yeung, G, Dawson, T, Pearson, E, Dhillon, H, Sandhu, S, Williams, N, Paton, E, et al
BMJ open. 2020;(2):e036059
Abstract
INTRODUCTION There is increasing evidence demonstrating the benefits of exercise in counteracting cancer treatment-related fatigue. Immunotherapy is an established treatment for advanced melanoma, and is associated with fatigue in a third of patients. The safety and efficacy of exercise in counteracting treatment-related fatigue in patients with advanced melanoma receiving immunotherapy are yet to be determined. This study aims to assess the safety, adherence to and acceptability of a mixed-methods parallel-group, pilot randomised controlled trial of a personalised, 12-week semi-supervised exercise programme prescribed by an exercise physiologist (iMove) in 30 patients with stage IV melanoma scheduled to commence immunotherapy: single agent ipilimumab, nivolumab or pembrolizumab, or combination ipilimumab and nivolumab. The trial will be used to provide preliminary evidence of the potential efficacy of exercise for managing fatigue. METHODS AND ANALYSIS Thirty participants will be recruited from a specialist cancer centre between May and September, 2019. Participants will be randomised 1:1 to receive iMove, or usual care (an information booklet about exercise for people with cancer). Feasibility data comprise: eligibility; recruitment and retention rates; adherence to and acceptability of exercise consultations, personalised exercise programme and study measures; and exercise-related adverse events. Patient-reported outcome measures assess potential impact of the exercise intervention on: fatigue, role functioning, symptoms and quality of life. Follow-up will comprise five time points over 24 weeks. Physical assessments measure physical fitness and functioning. ETHICS AND DISSEMINATION This study was reviewed and approved by the Peter MacCallum Cancer Centre Human Research Ethics Committee (HREC/48927/PMCC-2019). The findings from this trial will be disseminated via conference presentations and publications in peer-reviewed journals, and by engagement with clinicians, media, government and consumers. In particular, we will promote the outcomes of this work among the oncology community should this pilot indicate benefit for patients. TRIAL REGISTRATION NUMBER ACTRN12619000952145; Pre-results.
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Peptide vaccine with glucopyranosyl lipid A-stable oil-in-water emulsion for patients with resected melanoma.
Grewal, EP, Erskine, CL, Nevala, WK, Allred, JB, Strand, CA, Kottschade, LA, McWilliams, RR, Dronca, RS, Yakovich, AJ, Markovic, SN, et al
Immunotherapy. 2020;(13):983-995
Abstract
Aim: We tested the safety and immunogenicity of a novel vaccine in patients with resected high-risk melanoma. Patients & methods: HLA-A2-positive patients with resected Stage II-IV melanoma were randomized to receive up to three vaccinations of melanoma-associated peptide (MART-1a) combined with a stable oil-in-water emulsion (SE) either with the Toll-like receptor 4 agonist glucopyranosyl lipid A (GLA-SE-Schedule 1) or alone (SE-Schedule 2). Safety and immunogenicity of the vaccines were monitored. Results: A total of 23 patients were registered. No treatment-related grade 3 or higher adverse events were observed. Increases in MART-1a-specific T cells were seen in 70 and 63% of Schedule 1 and Schedule 2 patients, respectively. Conclusion: Both vaccine schedules were well-tolerated and resulted in an increase in MART-1a-specific T cells. Clinical Trial registration: NCT02320305 (ClinicalTrials.gov).
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Randomized Trial of Monthly Versus As-Needed Intravitreal Ranibizumab for Radiation Retinopathy-Related Macular Edema: 1-Year Outcomes.
Schefler, AC, Fuller, D, Anand, R, Fuller, T, Moore, C, Munoz, J, Kim, RS, ,
American journal of ophthalmology. 2020;:165-173
Abstract
PURPOSE To assess efficacy of intravitreal ranibizumab injections and targeted panretinal photocoagulation (TRP) for radiation retinopathy-related macular edema. DESIGN Phase IIb, prospective, randomized clinical trial. METHODS Setting: Multicenter. SUBJECTS Forty eyes in 40 treatment-naïve patients with radiation-induced macular edema and a resulting decrease in visual acuity ranging between 20/25 and 20/400 (Snellen equivalent). INTERVENTION Patients either received intravitreal 0.5 mg ranibizumab monthly, monthly ranibizumab with TRP, or 3 monthly ranibizumab (loading doses) followed by as-needed (PRN) injections and TRP. After week 52, all subjects entered a treat-and-extend protocol for ranibizumab. MainOutcomeMeasures: Mean Early Treatment Diabetic Maculopathy Study (ETDRS) BCVA change from baseline. RESULTS Mean patient age was 57 years (range, 22-80 years), ETDRS BCVA was 56.7 letters (20/74 Snellen equivalent), and central macular thickness (CMT) was 423 μm (range, 183-826 μm). Thirty-seven patients completed the month 12 visit (92.5%), at which time the change in mean BCVA was +4.0 letters, -1.9 letters, and +0.9 letters in the monthly, monthly plus laser, and PRN plus laser cohorts, respectively. There was a significant difference in mean BCVA at 1 year among all 3 cohorts (P < .001), as well as between cohorts in pairwise comparisons, with the most significant gains in the monthly group. A total of 82.5% of the patients retained visual acuity of 20/200 or better, and 20.0% improved 10 or more ETDRS letters. CONCLUSIONS Ranibizumab may improve vision and anatomy in patients with radiation retinopathy-related macular edema and prevent vision loss through 48 weeks of therapy. Monthly injections were more effective than as-needed approach, and the addition of TRP yielded no therapeutic benefits.
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Reducing perceived pain levels during nonbreast lymphoscintigraphy.
Johnston, MJ, Ntambi, JA, Hilliard, N, Spencer, HJ, Vaughn, R, Owens, SS, Myrick, RS, Parker, LD, Garner, DA, Yarbrough, TL
Clinical nuclear medicine. 2015;(12):945-9
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Abstract
PURPOSE The aim of this study was to quantify the reduction of perceived pain levels during lymphoscintigraphy for melanoma by altering the pH of the Tc-sulfur colloid to near the physiologic value of 7.40. PATIENTS AND METHODS This is an institutional review board- and Food and Drug Administration-approved randomized, double-blinded, prospective crossover trial, registered with clinicaltrials.org. Before beginning the procedure and after signing informed consent, 60 serial enrollees presenting for sentinel lymph node imaging of melanoma of the thorax and appendicular structures completed a questionnaire addressing background information, administered by a research support nurse.An investigator (N.H.) prepared the injections to be used and labeled them such that no one else could discover which injections contained standard-of-care solution and which contained the pH-altered solution (buffered to near pH 7.40 using sodium bicarbonate).After each injection, the enrollee was asked by a research support nurse to quantify the pain of each injection using a scale of 0 to 10. The injection site location (head, thorax, appendicular structures, and other) was also recorded. RESULTS Sixty subjects were enrolled in the study, of which 57 had complete data. On average, there was a significant mean (SD) decrease of 1.42 (2.17) points (95% confidence interval, 0.85-2.00) on a pain scale of 0 to 10 when the buffered injections were used as compared with the standard-of-care injections (P < 0.0001). Ordering of injections did not significantly affect perceived pain scores. CONCLUSIONS The use of sodium bicarbonate to buffer the pH of Tc-sulfur colloid to near the physiologic value of 7.40 significantly reduced perceived pain levels during nonbreast lymphoscintigraphy.
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Periocular triamcinolone for prevention of macular edema after plaque radiotherapy of uveal melanoma: a randomized controlled trial.
Horgan, N, Shields, CL, Mashayekhi, A, Salazar, PF, Materin, MA, O'Regan, M, Shields, JA
Ophthalmology. 2009;(7):1383-90
Abstract
OBJECTIVE To determine the efficacy and safety of periocular triamcinolone acetonide (40 mg) for the prevention of macular edema in patients undergoing plaque radiotherapy for uveal melanoma. DESIGN Prospective, randomized, controlled clinical trial. PARTICIPANTS AND CONTROLS One-hundred sixty-three patients with newly diagnosed uveal melanoma undergoing iodine 125 plaque radiotherapy were entered into the study. Fifty-five patients were randomized to the control group and 108 to the triamcinolone group. Eighteen-month data were available for 143 (88%) of the 163 patients. INTERVENTION Periocular injection of triamcinolone acetonide (40 mg in 1 ml) at the time of plaque radiotherapy and 4 months and 8 months later. Optical coherence tomography was performed at each patient evaluation. MAIN OUTCOME MEASURES Optical coherence tomography-evident macular edema, moderate vision loss, and poor final visual acuity. RESULTS Optical coherence tomography-evident macular edema occurred significantly less often in the triamcinolone group compared with the control group up to 18 months after plaque radiotherapy (hazard estimate, 0.45; 95% confidence interval, 0.19-0.70; P = 0.001). At the 18-month follow-up, moderate vision loss (loss of 3 lines or more of best-corrected visual acuity [BCVA]) and severe vision loss (BCVA <5/200 Snellen) occurred significantly less frequently in the triamcinolone group than in the control group (31% vs. 48% [P = 0.039] and 5% vs. 15% [P = 0.048], respectively). Rates of elevated intraocular pressure and cataract progression were similar in both groups. CONCLUSIONS Periocular triamcinolone is beneficial in reducing the risk of macular edema up to 18 months after plaque radiotherapy for uveal melanoma and significantly reduces the risk of moderate vision loss and poor visual acuity in these patients.
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Long-term choroidal vascular changes after iodine brachytherapy versus transpupillary thermotherapy for choroidal melanoma.
Pilotto, E, Vujosevic, S, De Belvis, V, Parrozzani, R, Boccassini, B, Midena, E
European journal of ophthalmology. 2009;(4):646-53
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Abstract
PURPOSE To compare long-term choroidal vascular changes after iodine-125 brachytherapy (IBT) versus transpupillary thermotherapy (TTT) used as primary treatment of small choroidal melanoma. METHODS Ninety-five small choroidal melanomas were randomized: 49 eyes with TTT and 46 eyes with IBT alone. Fluorescein and indocyanine green angiography (ICGA) were performed at 3-month intervals during the first year, and every 6 months thereafter. RESULTS Mean follow-up was 56.2 months (range, 24-118 months; SD, 22.6). Tumor regressed in 45 (92%) TTT-treated vs 45 (98%) IBT-treated eyes (p=0.397). Four TTT-treated and one IBT-treated tumor recurred. Occlusion of choriocapillaris was present in all TTT and IBT cases. Closure of medium and large choroidal vessels was observed in 17 (35%) TTT-treated vs 44 (96%) IBT-treated eyes (p<0.001). Choroidal vascular remodeling was detected in 20 (41%) TTT-treated and 16 (35%) IBT-treated eyes (p=0.693). Retinochoroidal anastomosis was present in 4 of the 37 (11%) TTT-treated eyes with patency of medium and large choroidal vessels, but never observed in the IBT-treated eyes, and was associated with tumor recurrence. Among IBT-treated eyes, segments of choroidal vascular wall ICG staining and choroidal aneurysmal changes were detected in 30 (65%) and 7 (15%), respectively. These changes were never detected in TTT-treated cases (p<0.0001 and p=0.015, respectively). CONCLUSIONS The pattern of tumor choroidal vascular changes following IBT and TTT differs. TTT is less effective in closing all tumor vasculature. The role of long-term choroidal vascular remodeling observed after these two treatments needs longer follow-up.
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Controlled hypotension in adults undergoing choroidal melanoma resection: comparison between the efficacy of nitroprusside and magnesium sulphate.
Yosry, M, Othman, IS
European journal of anaesthesiology. 2008;(11):891-6
Abstract
BACKGROUND AND OBJECTIVE To determine whether magnesium sulphate could induce controlled hypotension, reduce choroidal blood flow, provide a 'dry' operative field and could be compared with sodium nitroprusside in the recently raised issue of the use of hypotensive anaesthesia in eye surgery, i.e. for choroidal tumour surgery as the choroid is the most fragile and vascular structure in the eye. METHODS Forty adult patients undergoing choroidal melanoma resection and anaesthetized with 2.5 mg kg(-1) propofol, followed by a constant infusion of 120 microg kg(-1) min(-1), and remifentanil 1 microg kg(-1), followed by a continuous infusion of 0.25 microg kg(-1) min(-1), were randomly assigned to two groups to receive either magnesium sulphate or sodium nitroprusside. RESULTS Controlled hypotension was achieved at the target systolic pressure of 80 mmHg within 107 +/- 16 and 69 +/- 4.4 s for magnesium sulphate and sodium nitroprusside, respectively. Choroidal blood flow decreased by 24 +/- 0.3% and 22 +/- 3.3% for magnesium sulphate and sodium nitroprusside, respectively. Controlled hypotension was sustained in both groups throughout surgery, and the surgical field rating decreased in a range of 80% in both groups. Sodium nitroprusside decreased pH and increased PaCO2. There were no postoperative complications in any of the groups. CONCLUSION Magnesium sulphate controlled hypotension, reduced intraoperative pressure and provided good surgical conditions for choroidal melanoma resection with no need for additional use of a potent hypotensive agent in adults.
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Pegylated interferon-alpha2b treatment in melanoma patients: influence on amino acids, 5-hydroxyindolacetic acid and pteridine plasma concentrations.
Van Gool, AR, van Ojik, HH, Kruit, WH, Bannink, M, Mulder, PG, Eggermont, AM, Stoter, G, Fekkes, D
Anti-cancer drugs. 2004;(6):587-91
Abstract
Our objective was to study the influence of pegylated interferon-alpha2b (PEG-IFN-alpha) on the metabolism of amino acids and pteridines. We used an exploratory study into plasma concentrations of large neutral amino acids, 5-hydroxyindolacetic acid (5-HIAA), total biopterin (BIOP) and neopterin (NEOP) in 40 high-risk melanoma patients. Patients were randomized to treatment with PEG-IFN-alpha once a week in a dose of 6 microg/kg/week s.c. during 8 weeks, followed by a maintenance treatment of 3 microg/kg/week s.c. or to observation only. We found that treatment with PEG-IFN-alpha decreases tryptophan (TRP) concentrations in the first 3 months of treatment to a maximum of 25.3% compared to controls [95% confidence interval (CI): 14.9 to 34.4]. The TRP:LNAA ratio, an index for the availability of TRP to the central nervous system (CNS), decreases during 6 months with 18.8% (95% CI: 11.9 to 25.2). Concentrations of NEOP rose; however, concentrations of BIOP, the sum of tetrahydrobiopterin [BH4] and its oxidative products, did not decrease. The ratio of phenylalanine to tyrosine was increased with 11.7% (95% CI: 1.0 to 23.5) during 6 months. We conclude that, like conventional IFN-alpha, PEG-IFN-alpha lowers TRP concentrations and decreases the availability of TRP to the CNS. PEG-IFN-alpha has a similar influence on pteridine metabolism as standard IFN-alpha. If a lowered availability of TRP and a consequent decrease of serotonergic neurotransmission are indeed a mechanism underlying neuropsychiatric side-effects of IFN-alpha, patients on PEG-IFN-alpha are not at a lower risk of developing neuropsychiatric side-effects as patients on conventional IFN-alpha.
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Episcleral plaque 125I radiotherapy with episcleral LCF hyperthermia: a prospective randomized trial.
Girvigian, MR, Astrahan, MA, Lim, JI, Murphree, AL, Tsao-Wei, D, Petrovich, Z
Brachytherapy. 2003;(4):229-39
Abstract
PURPOSE The purpose of this study was to search for an optimal radiation dose in the treatment of patients with uveal melanoma using 125I episcleral plaque radiotherapy (EPRT) and episcleral hyperthermia (HT). METHODS AND MATERIALS From 1991-1998, 35 patients with uveal melanoma were enrolled in a phase II prospective randomized trial of 125I EPRT combined with episcleral HT. Two groups were closely matched for pre-treatment patient and tumor characteristics. Group 1: N = 16, and Group 2: N = 19. The median dose to the tumor apex for Group 1 was 80.0 Gy and 60.8 Gy for Group 2. Episcleral HT was given once for 45 min immediately prior to EPRT with a median temperature of 44 degrees C for both groups. The median follow-up was 5.5 years for Group 1 and 5.3 years for Group 2. RESULTS The median tumor height decreased 1.7 mm for patients of both groups. The 5- and 8-year probability of local recurrence was 33% for Group 1, and 25% for Group 2, p = 0.73. The 5-year probability of DFS was 54% for Group 1 and 67% for Group 2, p = 0.51. The 5- and 8-year overall survival was 68% and 34%, respectively, for Group 1, and 83% and 50%, respectively, for Group 2, p = 0.60. The rate of distant metastasis at 5- and 8-years for Group 1 was 29% and 62%, respectively, and 17% and 17%, respectively, for Group 2, p = 0.18. The incidence of enucleation was 4 (25%) in Group 1 vs. 4 (22%) in Group 2. The incidence of late complications was similar in either treatment group. The ambulatory visual acuity (> 5/200) at last follow-up was slightly better in Group 2 (80%) than Group 1 (64%). CONCLUSIONS Treatment outcomes were similar despite a 25% difference in radiation dose. In view of these findings and in an attempt to reduce the incidence of late treatment toxicity a still lower radiation dose in combination with HT needs to be studied. The reported outcomes need to be evaluated with caution due to the small number of patients in this study.
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Randomized, placebo-controlled trial of dietary supplementation of alpha-tocopherol on mutagen sensitivity levels in melanoma patients: a pilot trial.
Mahabir, S, Coit, D, Liebes, L, Brady, MS, Lewis, JJ, Roush, G, Nestle, M, Fry, D, Berwick, M
Melanoma research. 2002;(1):83-90
Abstract
We evaluated the effects of vitamin E (dl-alpha-tocopherol) on mutagen sensitivity levels in a randomized placebo-controlled pilot trial. In brief, a dietary supplement of 1000 mg/day vitamin E or a placebo was randomly administered for 3 months to melanoma outpatients clinically free of the disease. Plasma vitamin E and mutagen sensitivity levels were measured at baseline and at the end of the trial after 3 months. At baseline, we found no significant differences in plasma vitamin E and mutagen sensitivity levels between the two groups. We also measured dietary intake at baseline and found dietary vitamin E to be a poor predictor of plasma levels of vitamin E. After 3 months of supplementation, we found that plasma levels of alpha-tocopherol increased significantly (P = 0.0005) in the vitamin E compared to the placebo group. We also found a non-significant, but consistent decrease in plasma gamma-tocopherol concentrations in the vitamin E supplemented compared to the placebo group. We did not find any significant difference between the vitamin E and placebo groups in mutagen sensitivity levels either at baseline or after 3 months of supplementation. We conclude that short term vitamin E supplementation, although it causes increased blood levels of alpha-tocopherol, does not provide protection against bleomycin-induced chromosome damage.