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Differences in sex hormone recovery profile after cessation of 12-week gonadotropin-releasing hormone antagonist versus agonist therapy.
Sasaki, H, Miki, K, Tashiro, K, Mori, K, Urabe, F, Fukuokaya, W, Kimura, T, Sato, S, Takahashi, H, Aoki, M, et al
Andrology. 2022;(2):270-278
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Abstract
BACKGROUND Pharmacobiological behavior differs between gonadotropin-releasing hormone (GnRH) antagonists and GnRH agonists. However, reliable evidence clarifying the difference between them is limited. OBJECTIVES We aimed to elucidate the difference in recovery profile between GnRH antagonist (degarelix) and GnRH agonist (leuprorelin acetate or goserelin acetate) as short-term (12 weeks) neoadjuvant androgen deprivation therapy (ADT) prior to 125I-transperineal prostate brachytherapy (TPPB) for localized prostate cancer. MATERIALS AND METHODS This study was initially designed as a single-center, prospective, open-label, randomized controlled trial. The primary endpoint was a serum testosterone level above the castration range (>50 ng/dl) after the cessation of 12-week neoadjuvant ADT (GnRH antagonist or GnRH agonists). All patients underwent 12 weeks of neoadjuvant ADT. The recovery profiles of hormones, prostate-specific antigen, total prostate volume (TPV), bone mineral density, and quality of life scores were investigated. RESULTS Testosterone recovery duration after the last injection was significantly longer in the GnRH antagonist arm than in the GnRH agonist arm (median, 27.3 vs. 4.8 weeks, p < 0.001). The serum levels of luteinizing hormone and follicle-stimulating hormone in the GnRH antagonist arm also remained significantly lower than those in the GnRH agonist arm between 16 and 24 weeks (p < 0.01). Meanwhile, reduction in TPV at the time of TPPB was comparable between both arms (p = 0.128). There were also no significant between-arm differences in the International Prostate Symptom Score and the International Index of Erectile Function scores. DISCUSSION AND CONCLUSION The recovery patterns of hormonal profiles after short-term (12 weeks) neoadjuvant ADT differ between GnRH antagonists and GnRH agonists. The choice between these drugs matters and may have a clinical impact depending on the primary objective of ADT.
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[18F]-JK-PSMA-7 PET/CT Under Androgen Deprivation Therapy in Advanced Prostate Cancer.
Dietlein, F, Mueller, P, Kobe, C, Endepols, H, Hohberg, M, Zlatopolskiy, BD, Krapf, P, Heidenreich, A, Neumaier, B, Drzezga, A, et al
Molecular imaging and biology. 2021;(2):277-286
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Abstract
PURPOSE PSMA imaging is frequently used for monitoring of androgen deprivation therapy (ADT) in prostate cancer. In a previous study, [18F]-JK-PSMA-7 exhibited favorable properties for tumor localization after biochemical recurrence. In this retrospective study, we evaluated the performance of [18F]-JK-PSMA-7 under ADT. PROCEDURES We examined the performance of [18F]-JK-PSMA-7 in 70 patients (first cohort) with increasing or detectable PSA values under ADT (PSA < 2 ng/ml for 21/70 patients). We further analyzed 58 independent patients with PSA levels < 2 ng/ml under ADT, who were imaged with [68Ga]PSMA-11 or [18F]DCFPyL (second cohort). Finally, we compared detection rates between [18F]-JK-PSMA-7, [68Ga]PSMA-11, and [18F]DCFPyL. RESULTS In the first cohort, we detected [18F]-JK-PSMA-7-positive lesions in 63/70 patients. In patients with PSA levels ≥ 2 ng/ml, the detection rate was 100 % (49/49). In patients with PSA < 2 ng/ml, the detection rate was significantly lower (66.7 %, 14/21, p = 9.7 × 10-5) and dropped from 85.7 % (12/14, PSA levels between 0.3 and 2.0 ng/ml) to 28.6 % (2/7) for PSA levels < 0.3 ng/ml (p = 1.73 × 10-2). In the second cohort (PSA < 2 ng/ml), the detection rate was 79.3 % (46/58) for [68Ga]PSMA-11 or [18F]DCFPyL. Again, the detection rate was significantly higher (p = 1.1 × 10-2) for patients with PSA levels between 0.3 and 2.0 ng/ml (87.0 %, 40/46) relative to those with PSA levels < 0.3 ng/ml (50 %, 6/12). No significant difference was found between [18F]-JK-PSMA-7 and [68Ga]PSMA-11 or [18F]DCFPyL in patients with PSA levels < 2 ng/ml (p = 0.4295). CONCLUSION [18F]-JK-PSMA-7 PET showed a high detection rate in patients with PSA levels ≥ 0.3 ng/ml under ADT. The lower PSA threshold of 0.3 ng/ml for high detection rates was consistent across the three PSMA ligands. Thus, PSMA imaging is suitable for clinical follow-up of patients with increasing PSA levels under ADT.
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Mediterranean-style dietary pattern improves cancer-related fatigue and quality of life in men with prostate cancer treated with androgen deprivation therapy: A pilot randomised control trial.
Baguley, BJ, Skinner, TL, Jenkins, DG, Wright, ORL
Clinical nutrition (Edinburgh, Scotland). 2021;(1):245-254
Abstract
BACKGROUND & AIMS Cancer-related fatigue (CRF) is a prevalent and persistent symptom from androgen deprivation therapy (ADT) in prostate cancer. The Mediterranean-style dietary pattern (MED-diet) offers a plausible mechanism to mitigate CRF through reducing inflammation and improving body composition. This study aimed to evaluate the effects of a 12-week MED-diet, compared to usual care, on CRF and quality of life in men with prostate cancer treated with ADT. METHODS Twenty-three men (65.9 ± 7.8 years; body mass index: 29.6 ± 2.7 kg/m2; ADT duration: 33.8 ± 35.6 months) receiving ADT for ≥3 months were randomly assigned (1:1) to 12-weeks of usual care or the MED-diet involving six individualised nutrition consults. Primary outcomes included CRF [Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (FACIT-F) and quality of life [FACIT-General (FACIT-G)], secondary outcomes included body mass/composition and interleukin (IL)-6 and IL-8 concentrations measured at baseline, 8-weeks and 12 weeks. Intervention feasibility was measured by intervention safety, study completion rate, consult attendance, and adherence to the MED-diet through the Mediterranean-diet adherence screener (MEDAS). Intention to treat linear mixed models were used to determine changes in outcomes between the MED-diet and usual care at baseline, 8-weeks and 12-weeks. RESULTS The MED-diet improved CRF (FACIT-F) at 8-weeks [+4.8 (0.0, 9.8); P = 0.05] and 12-weeks [+7.2 (2.2, 12.0); P = 0.005], quality of life (FACIT-G) at 12-weeks [+9.2 (2.7, 15.8); P = 0.006], reduced total body mass at 8-weeks [-2.51 kg (-4.25, -0.78); P = 0.005] and 12-weeks [-2.97 kg (-4.71, -1.25); P = 0.001], lean mass at 8-weeks [-1.50 kg (-2.91, -0.10); P = 0.036], and IL-8 at 8-weeks [-0.18 ng/ml (-0.34, -0.02); P = 0.029] compared to usual care. The MED-diet demonstrated zero adverse events, 91% study completion, 100% attendance, and 81% adherence to the MEDAS. CONCLUSION The MED-diet is safe and feasible, and has the potential to improve CRF and quality of life in overweight men treated with ADT compared to usual care. Further exploration of the MED-diet is warranted in a larger powered sample size to consolidate these findings.
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Toxicity Index, Patient-Reported Outcomes, and Early Discontinuation of Endocrine Therapy for Breast Cancer Risk Reduction in NRG Oncology/NSABP B-35.
Henry, NL, Kim, S, Hays, RD, Diniz, MA, Luu, M, Cecchini, RS, Yothers, G, Rogatko, A, Ganz, PA
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021;(34):3800-3812
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Abstract
PURPOSE The US National Cancer Institute Moonshot initiative calls for improving analysis and reporting of toxicity to inform treatment tolerability. We used existing clinician-reported adverse event (AE) and patient-reported outcome (PRO) questionnaire data from the randomized, double-blind NSABP B-35 clinical trial to explore reasons for anastrozole and tamoxifen discontinuation. METHODS Postmenopausal women with ductal carcinoma in situ treated with breast-conserving therapy were randomly assigned to anastrozole or tamoxifen for 5 years. The primary outcome for this analysis was time to treatment discontinuation. AEs were collected every 6 months post-random assignment from all 3,104 participants and summarized using the Toxicity Index (TI). PRO data were collected at baseline and every 6 months from 1,194 participants. Univariate and multivariable analyses of time to treatment discontinuation were performed using Cox regression models with TIs and PROs as time-dependent covariates. RESULTS Of 3,046 analyzed participants, 869 (28.5%) discontinued treatment prematurely. In multivariable analysis, when both baseline PROs and on-treatment AEs were considered, thrombosis and arthralgia AEs were associated with discontinuation of both tamoxifen and anastrozole; additional AEs associated with discontinuation varied by drug. In addition, baseline pain interference, hot flashes, and unhappiness were associated with tamoxifen discontinuation (n = 589; overall Harrell's C-statistic 0.686 [95% CI, 0.640 to 0.732]); no baseline PROs were associated with anastrozole discontinuation (n = 589; overall Harrell's C-statistic 0.656 [95% CI, 0.630 to 0.681]). When only baseline PROs were examined, pain interference, hot flashes, and unhappiness were associated with shorter time to discontinuation of tamoxifen; only hot flashes were associated with discontinuation of anastrozole. CONCLUSION Analysis of AEs using the TI yielded important insights into reasons for discontinuation of endocrine therapy that was enhanced by the addition of PRO baseline and treatment-emergent symptoms.
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The Clinical Significance of Bone Mineral Density Changes Following Long-Term Androgen Deprivation Therapy in Localized Prostate Cancer Patients.
Khriguian, J, Tsui, JMG, Vaughan, R, Kucharczyk, MJ, Nabid, A, Bettahar, R, Vincent, L, Martin, AG, Jolicoeur, M, Yassa, M, et al
The Journal of urology. 2021;(6):1648-1654
Abstract
PURPOSE Long-term androgen deprivation therapy has been associated with decreased bone mineral density in men with prostate cancer. Some evidence suggests that there is no impact on fracture risk despite this bone mineral density loss. Our study aimed to quantify changes in bone mineral density in men with high risk prostate cancer on long-term androgen deprivation therapy and calcium and vitamin D supplementation. MATERIALS AND METHODS Bone mineral density analysis was conducted for localized high risk prostate cancer patients enrolled in the phase III randomized trial PCS-V (Prostate Cancer Study 5), comparing conventional and hypofractionated radiation therapy. Patients received 28 months of luteinizing hormone-releasing hormone agonist and calcium and vitamin D supplementation (500 mg calcium BID+400 IU vitamin D3 BID). The areal density and T-scores (spine, femoral neck and total femur) at baseline and 30 months of followup were extracted, and the absolute change was calculated. Clinical bone density status (normal, osteopenia, osteoporosis) was monitored. RESULTS The lumbar spine, femoral neck and total femoral bone mineral density were measured for 226, 231, and 173 patients, respectively. The mean percent change in bone mineral density was -2.65%, -2.76% and -4.27% for these respective sites (p <0.001 for all). The average decrease in bone mineral density across all sites was -3.2%, with no decline in bone mineral density category in most patients (83%). Eight patients (4%) became osteoporotic. CONCLUSIONS Despite a mild decline in bone mineral density, the change in clinical bone mineral density category remained low with long-term androgen deprivation therapy. Consequently, calcium and vitamin D supplementation alone may suffice for most localized prostate cancer patients on long-term androgen deprivation therapy.
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The effect of exercise training on cardiometabolic health in men with prostate cancer receiving androgen deprivation therapy: a systematic review and meta-analysis.
Bigaran, A, Zopf, E, Gardner, J, La Gerche, A, Murphy, DG, Howden, EJ, Baker, MK, Cormie, P
Prostate cancer and prostatic diseases. 2021;(1):35-48
Abstract
BACKGROUND Growing evidence suggests that men exposed to androgen deprivation therapy (ADT) have an increased risk of cardiovascular disease. While exercise has shown to attenuate some adverse effects of ADT, the effects on cardiometabolic health have not been systematically evaluated. OBJECTIVE To evaluate the effect of exercise on cardiometabolic health in men with prostate cancer (PCa) receiving ADT. METHODS A systematic literature search of MEDLINE, EMBASE, CINHAL, SCOPUS, WEB OF SCIENCE and SPORTSDICUS from database inception to April 2020 was performed. A quantitative synthesis using Cohens d effect size and a meta-analysis using random-effects models were conducted. RESULTS Overall, fourteen randomised controlled trials (RCTs) and four non-randomised studies were included. Eleven RCTs (n = 939 patients) were included in the meta-analysis. Exercise training improved the 400-m-walk test (MD -10.11 s, 95% CI [-14.34, -5.88]; p < 0·00001), diastolic blood pressure (-2.22 mmHg, [-3.82, -0.61]; p = 0.007), fasting blood glucose (-0.38 mmol/L, [-0.65, -0.11]; p = 0.006), C-reactive protein (-1.16 mg/L, [-2.11, -0.20]; p = 0.02), whole-body lean mass (0.70 kg, [0.39, 1.01]; p < 0.0001), appendicular lean mass (0.59 kg, [0.43, 0.76]; p < 0.00001), whole-body fat mass (-0.67 kg, [-1.08, -0.27]; p = 0.001), whole-body fat percentage (-0.79%, [-1.16, -0.42]; p < 0.0001), and trunk fat mass (-0.49 kg, [-0.87, -0.12]; p = 0.01), compared to usual care. No significant effects on systolic blood pressure or blood lipid metabolism were detected. CONCLUSIONS In a small subset of evaluated studies, exercise may favourably improve some but not all markers of cardiometabolic health. Future exercise intervention trials with cardiometabolic outcomes as primary endpoints are needed to confirm these initial findings.
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Lifestyle and quality of life in patients with early-stage breast cancer receiving adjuvant endocrine therapy.
Di Meglio, A, Soldato, D, Presti, D, Vaz-Luis, I
Current opinion in oncology. 2021;(6):553-573
Abstract
PURPOSE OF REVIEW A comprehensive approach to survivorship care for women with early-stage, hormone-receptor positive breast cancer should systematically include the proactive assessment and adequate management of endocrine therapy-associated symptoms, in order to assure optimal balance between preserving quality of life (QOL) and maximizing treatment adherence. We reviewed the recent literature focused on lifestyle factors, including physical activity, diet and nutrition, weight management, smoke, and alcohol behavior, and their link with symptomatology and QOL among women receiving adjuvant endocrine therapy. RECENT FINDINGS Recent studies confirm the safety, feasibility, and effectiveness of lifestyle interventions in mitigating several common endocrine therapy-related effects, including musculoskeletal pain, fatigue, and insomnia, and in improving physical and emotional wellbeing as well as overall health-related QOL among women with early-stage breast cancer. SUMMARY Healthy lifestyle behaviors have the potential to modulate the downstream impact of endocrine therapy and improve QOL among women with early-stage breast cancer. Considerations for real-world clinical care implementation emerged, including a need to evaluate the long-term uptake of healthy behaviors and facilitate the postintervention maintenance of an improved lifestyle. Some facilitators to health promotion in breast cancer survivors were also suggested, such as individualized and one-to-one supervised programs, and digital solutions providing real-time feedback, building on personalized, direct patient engagement.
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Somatostatin Analogs in Clinical Practice: a Review.
Gomes-Porras, M, Cárdenas-Salas, J, Álvarez-Escolá, C
International journal of molecular sciences. 2020;(5)
Abstract
Somatostatin analogs are an invaluable therapeutic option in the diagnosis and treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. They should also be considered an effective and safe therapeutic alternative to corticotropinomas, gonadotropinomas, and prolactinomas resistant to dopamine agonists. Somatostatin analogs have also shown to be useful in the treatment of other endocrine diseases (congenital hyperinsulinism, Graves' orbitopathy, diabetic retinopathy, diabetic macular edema), non-endocrine tumors (breast, colon, prostate, lung, and hepatocellular), and digestive diseases (chronic refractory diarrhea, hepatorenal polycystosis, gastrointestinal hemorrhage, dumping syndrome, and intestinal fistula).
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Endocrine therapy with or without whole breast irradiation in low-risk breast cancer patients after breast-conserving surgery: 10-year results of the Austrian Breast and Colorectal Cancer Study Group 8A trial.
Fastner, G, Sedlmayer, F, Widder, J, Metz, M, Geinitz, H, Kapp, K, Fesl, C, Sölkner, L, Greil, R, Jakesz, R, et al
European journal of cancer (Oxford, England : 1990). 2020;:12-20
Abstract
PURPOSE To investigate long-term results of patients with hormonal receptor-positive breast cancer treated with breast-conserving surgery (BCS) and consecutive endocrine therapy (ET) with or without whole breast irradiation (WBI). METHODS AND MATERIALS Within the 8 A trial of the Austrian Breast and Colorectal Cancer Study Group, a total of 869 patients received ET after BCS which was randomly followed by WBI (n = 439, group 1) or observation (n = 430, group 2). WBI was applied up to a mean total dosage of 50 Gy (+/- 10 Gy boost) in conventional fractionation. RESULTS After a median follow-up of 9.89 years, 10 in-breast recurrences (IBRs) were observed in group 1 and 31 in group 2, resulting in a 10-year local recurrence-free survival (LRFS) of 97.5% and 92.4%, respectively (p = 0.004). This translated into significantly higher rates for disease-free survival (DFS): 94.5% group 1 vs 88.4% group 2, p = 0.0156. For distant metastases-free survival (DMFS) and overall survival (OS), respective 10-year rates amounted 96.7% and 86.6% for group 1 versus 96.4% and 87.6%, for group 2 (ns). WBI (hazard ratio [HR]: 0.27, p < 0.01) and tumour grading (HR: 3.76, p = 0.03) were found as significant predictors for IBR in multiple cox regression analysis. CONCLUSIONS After a median follow-up of 10 years, WBI resulted in a better local control and DFS compared with ET alone. The omission of WBI and tumour grading, respectively, were the only negative predictors for LRFS.
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Timing of exercise for muscle strength and physical function in men initiating ADT for prostate cancer.
Newton, RU, Galvão, DA, Spry, N, Joseph, D, Chambers, SK, Gardiner, RA, Hayne, D, Taaffe, DR
Prostate cancer and prostatic diseases. 2020;(3):457-464
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Abstract
BACKGROUND Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) results in adverse effects, including reduced muscle strength and physical function, potentially compromising daily functioning. We examined whether it was more efficacious to commence exercise at the onset of ADT rather than later in treatment to counter declines in strength and physical function. METHODS One-hundred-and-four men with PCa (68.3 ± 7.0 years) initiating ADT were randomised to immediate exercise (IMX, n = 54) or delayed exercise (DEL, n = 50) for 12 months. IMX comprised 6 months of supervised resistance/aerobic/impact exercise initiated at the onset of ADT with a 6-month follow-up. DEL comprised 6 months of usual care followed by 6 months of resistance/aerobic/impact exercise. Upper and lower body muscle strength and physical function were assessed at baseline, 6 and 12 months. RESULTS There was a significant difference for all strength measures at 6 months favouring IMX (P < 0.001), with net differences in leg press, seated row and chest press strength of 19.9 kg (95% CI, 12.3-27.5 kg), 5.6 kg (3.8-7.4 kg) and 4.3 kg (2.7-5.8 kg), respectively. From 7 to 12 months, DEL increased in all strength measures (P < 0.001), with no differences between groups at 12 months. Similarly, physical function improved (P < 0.001) in IMX compared with DEL at 6 months for the 6-m fast walk (-0.2, 95% CI -0.3 to -0.1 s), 400-m walk (-9.7, -14.8 to -4.6 s), stair climb (-0.4, -0.6 to -0.2 s) and chair rise (-1.0, -1.4 to -0.7 s), with no differences between groups by 12 months, except for the 6-m fast walk (P < 0.001). CONCLUSION Exercise either at the onset or after 6 months of ADT preserves/enhances muscle strength and physical function. However, to avoid initial treatment-related adverse effects on strength and function, exercise therapy should be implemented with initiation of ADT.