PSA decay during salvage radiotherapy for prostate cancer as a predictor of disease outcome - 5 year follow-up of a prospective observational study.

BACKGROUND AND PURPOSE: Biochemical recurrence after prostatectomy is commonly treated with salvage radiotherapy (SRT). In this prospective observational study we investigated the PSA decay rate, determined by predefined serial PSA measurements during SRT, as a predictor for treatment outcome. MATERIALS AND METHODS: Between 2013 and 2016, 214 patients were included in the study. The prescribed dose to the prostate bed was 70 Gy in 35 fractions (7 weeks) without hormonal treatment. PSA was measured weekly during SRT. Assuming first order kinetics, a PSA decay-rate constant (k) was calculated for 196 eligible patients. The ability of k to predict disease progression was compared with known clinical prediction parameters using Cox regression, logistic regression and ROC analyses. Disease progression was defined as continuously rising PSA after SRT, PSA increase by ≥0.2 ng/ml above nadir after SRT, hormonal treatment or clinical progression. RESULTS: After a median follow up of 4.7 years the estimated failure-free survival at 5 years was 56%. The PSA decay-rate constant (k) was found to be the strongest predictor of disease progression in both uni-and multivariable analyses. CONCLUSION: The addition of k to established clinical variables significantly improves the possibility to predict treatment outcome after SRT and could be used to personalize future therapies.

Mindfulness-Based Program for Children with Autism Spectrum Disorder and Their Parents: Direct and Long-Term Improvements.

A combined mindfulness-based program for children and their parents (MYmind) was beneficial for adolescents with autism spectrum disorder (ASD). In this study, we investigated whether this program is also beneficial for younger children with ASD, whether effects last on the long-term, and whether it reduces common comorbid problems. Forty-five children referred with ASD aged 8 until 19 years old, and their parents participated. Repeated measures of children's and parents' social communication problems, emotional and behavioral functioning, mindful awareness, and of parenting were conducted pre-intervention, post intervention, 2-month follow-up, and 1-year follow-up. While children did not report significant changes in mindful awareness, their social communication problems decreased, and their emotional and behavioral functioning improved. Results were not consistent at each occasion; improvements reported by children were most substantial at a 2-month follow-up and only partly remained at a 1-year follow-up, while all children's improvements as reported by parents were present on all occasions. Parents themselves reported improved emotional and behavioral functioning, improved parenting, and increased mindful awareness on all occasions. Parents' social communication problems reduced only directly after the intervention. Most improvements were supported by the qualitative investigation of children's and parents' experienced change as reported on open-ended questions. This study suggests that children, including adolescents, with ASD and their parents can benefit from a mindfulness-based program with parallel sessions for children and parents.

Bone-targeted Novel Cytotoxic Polybisphosphonate Conjugate in Castration-resistant Prostate Cancer: A Multicenter Phase 1 Study.

BACKGROUND: Osteodex (ODX) is a cytotoxic bone-targeting polybisphosphonate, intended for treatment of bone metastasis from castration-resistant prostate cancer (CRPC). The primary objective of this study was to describe the tolerability and toxicity of such treatment by defining its maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). PATIENTS AND METHODS: Twenty-eight patients with castration-resistant prostate cancer and confirmed bone metastasis were assigned to seven infusions of ODX every third week, divided in seven ascending dose cohorts. RESULTS: No DLT's were observed and as pre-specified, the highest dose administered was defined as MTD. In total, 206 adverse events (AE) were recorded and 13,6% were classified as treatment-related, while none were serious or severe (SAE). No cumulative toxicity and no renal toxicity were recorded. CONCLUSION: ODX was well tolerated, with few and mild side-effects and with apparent treatment efficacy in the highest dose cohort. Further clinical development is currently in progress.

Low-dose rate brachytherapy with I-125 seeds has an excellent 5-year outcome with few side effects in patients with low-risk prostate cancer.

BACKGROUND: Low-dose rate brachytherapy (LDR-BT) has been used in Sweden for more than a decade for treatment of low-risk prostate cancer. This study presents the outcome for patients treated with LDR-BT at a single institution with focus on the association between dose and biochemical failure-free survival (BFFS). METHODS: In total 195 patients were treated with LDR-BT between 2004 and 2008. The patients were followed systematically for side effects for at least one year. PSA levels were followed regularly from three months and for at least five years. Outcome was analyzed in relation to clinical variables at baseline and to radiotherapy data. RESULTS: Kaplan-Meier estimated BFFS at five years was 95.7%. Dose to the prostate in terms of D90% was significantly associated with BFFS [HR 0.90 (95%CI 0.83-0.96), p = 0.002]. CONCLUSION: Out data confirmed that absorbed dose is a predictive factor for BFFS for low-risk patients without androgen deprivation therapy. With our treatment routines and dosimetry, a D90% in the range of 170-180 Gy gives excellent outcomes with acceptable toxicity for patients with low-risk prostate cancer.

MYmind: Mindfulness training for Youngsters with autism spectrum disorders and their parents.

BACKGROUND: Despite the dramatic increase in autism spectrum disorder in youth and the extremely high costs, hardly any evidence-based interventions are available. The aim of this study is to examine the effects of mindfulness training for adolescents with autism spectrum disorder, combined with Mindful Parenting training. METHOD: A total of 23 adolescents with autism spectrum disorder, referred to a mental health clinic, received nine weekly sessions of mindfulness training in group format. Their parents (18 mothers, 11 fathers) participated in parallel Mindful Parenting training. A pre-test, post-test, and 9-week follow-up design was used. Data were analyzed using multi-level analyses. RESULTS: Attendance rate was 88% for adolescents and fathers and 86% for mothers. Adolescents reported an increase in quality of life and a decrease in rumination, but no changes in worry, autism spectrum disorder core symptoms, or mindful awareness. Although parents reported no change in adolescent's autism spectrum disorder core symptoms, they reported improved social responsiveness, social communication, social cognition, preoccupations, and social motivation. About themselves, parents reported improvement in general as well as in parental mindfulness. They reported improved competence in parenting, overall parenting styles, more specifically a less lax, verbose parenting style, and an increased quality of life. DISCUSSION: Mindfulness training for adolescents with autism spectrum disorder combined with Mindful Parenting is feasible. Although the sample size was small and no control group was included, the first outcomes of this innovative training are positive.

Low rate of lymphedema after extended pelvic lymphadenectomy followed by pelvic irradiation of node-positive prostate cancer.

BACKGROUND: The aim of the present study was to evaluate the prevalence and severity of lower limb lymphedema after pelvic lymphadenectomy and radiotherapy to the pelvic lymph nodes in patients with prostate cancer. METHODS: Twenty-six patients underwent combined treatment for high-risk node-positive prostate cancer at Skåne University Hospital between April 2008 and March 2011. The treatment consisted of extended pelvic lymphadenectomy followed by androgen deprivation therapy and radiotherapy. The pelvic lymphnodes, prostate and seminal vesicles were treated with external beam radiotherapy (EBRT) to an absorbed dose of 50 Gy followed by a brachytherapy (BT) boost of 2x10 Gy to the prostate only. Twenty-two patients accepted an invitation to a clinical examination with focus on lower limb swelling. The median time between the end of radiotherapy and examination was 2.2 years (range 1.2-4.1). RESULTS: Six patients (27%) experienced grade 1 lymphedema and two patients (9%) grade 2 while none had grade 3 or 4 according to the CTC Common Toxicity Criteria scale 4.0. Three patients required treatment with compression stockings. CONCLUSION: Brachytherapy and pelvic EBRT have a low incidence of lymphedema (at median 2.2 y after treatment) in patients with high-risk node-positive prostate cancer that have undergone pelvic lymph node dissection.

Two-year survival follow-up of the randomized, double-blind, placebo-controlled phase II study of radium-223 chloride in patients with castration-resistant prostate cancer and bone metastases.

BACKGROUND: This phase II randomized, placebo-controlled study was conducted to evaluate efficacy and safety of radium-223 in patients with castration-resistant prostate cancer (CRPC) and painful bone metastases. Twelve- and 18-month survival results were reported previously. Here we report 24-month overall survival (OS) and safety data from the period 12 to 24 months after the first injection of study medication. METHODS: Patients with CRPC and bone pain were randomized 1:1 to receive 4 injections of radium-223 (50 kBq/kg [n = 33]) or placebo (n = 31) after external-beam radiotherapy; each injection was given every 4 weeks. Endpoints for this report were 24-month OS, long-term safety, and treatment-related adverse events (AEs) occurring in the 12- to 24-month period. RESULTS: After 24 months, 10 (30%) patients were alive in the radium-223 group compared with 4 patients (13%) in the placebo group. Patients who received at least 1 dose of study medication had a median OS of 65 weeks in the radium-223 group vs. 46 weeks in the placebo group (log-rank P = .056). The hazard ratio (HR) for OS, adjusted for baseline covariates, was 0.476 (95% confidence interval [CI], 0.258-0.877; Cox regression P = .017). The most frequent cause of death for both arms was disease progression. There were no reports of treatment-related AEs or long-term hematologic toxicity during the 12- to 24-month follow-up. CONCLUSION: Radium-223 had a highly favorable safety profile, with no evidence of second malignancies at 24-month follow-up. The significant improvement in OS observed in patients receiving radium-223 vs. placebo suggests that treatment of bone disease with radium-223 has survival benefits.

Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study.

BACKGROUND: The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of (223)Ra. METHODS: Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat. FINDINGS: Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued (223)Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression). INTERPRETATION: (223)Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers.