Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer.

Purpose Men with localized prostate cancer often are treated with external radiotherapy (RT) over 8 to 9 weeks. Hypofractionated RT is given over a shorter time with larger doses per treatment than standard RT. We hypothesized that hypofractionation versus conventional fractionation is similar in efficacy without increased toxicity. Patients and Methods We conducted a multicenter randomized noninferiority trial in intermediate-risk prostate cancer (T1 to 2a, Gleason score ≤ 6, and prostate-specific antigen [PSA] 10.1 to 20 ng/mL; T2b to 2c, Gleason ≤ 6, and PSA ≤ 20 ng/mL; or T1 to 2, Gleason = 7, and PSA ≤ 20 ng/mL). Patients were allocated to conventional RT of 78 Gy in 39 fractions over 8 weeks or to hypofractionated RT of 60 Gy in 20 fractions over 4 weeks. Androgen deprivation was not permitted with therapy. The primary outcome was biochemical-clinical failure (BCF) defined by any of the following: PSA failure (nadir + 2), hormonal intervention, clinical local or distant failure, or death as a result of prostate cancer. The noninferiority margin was 7.5% (hazard ratio, < 1.32). Results Median follow-up was 6.0 years. One hundred nine of 608 patients in the hypofractionated arm versus 117 of 598 in the standard arm experienced BCF. Most of the events were PSA failures. The 5-year BCF disease-free survival was 85% in both arms (hazard ratio [short v standard], 0.96; 90% CI, 0.77 to 1.2). Ten deaths as a result of prostate cancer occurred in the short arm and 12 in the standard arm. No significant differences were detected between arms for grade ≥ 3 late genitourinary and GI toxicity. Conclusion The hypofractionated RT regimen used in this trial was not inferior to conventional RT and was not associated with increased late toxicity. Hypofractionated RT is more convenient for patients and should be considered for intermediate-risk prostate cancer.

Corrigendum to "The Current Practice of Screening, Prevention, and Treatment of Androgen-Deprivation-Therapy Induced Osteoporosis in Patients with Prostate Cancer".

[This corrects the article DOI: 10.1155/2012/958596.].

You are how you recruit: a cohort and randomized controlled trial of recruitment strategies.

BACKGROUND: Recruitment is a challenge in developing population-representative pregnancy and birth cohorts. METHODS: We developed a collaborative recruitment infrastructure (CRI) to recruit pregnant women for 4 pregnancy cohorts using: faxes from obstetrical offices, in-clinic recruiters, university and funder-driven free-media events, paid-media, and attendance at relevant tradeshows. Recruitment rates and demographic differences were compared between recruitment methods. RESULTS: We received 5008 referrals over 40 months. Compared to fax, free-media referrals were 13 times more likely to be recruited (OR 13.0, 95% CI 4.2, 40.4: p < 0.001) and paid-media referrals were 4 times more likely to be recruited (OR 4.6, 95% CI 2.1, 10.3: p < 0.001). Among paid-media advertisements, free-to-read print (e.g. Metro) was the most effective (OR 3.3, 95% CI 2.3, 4.5: p < 0.05). Several demographic differences were identified between recruitment methods and against a reference population. Between recruitment methods, media recruits had a similar proportion families with incomes ≥ $40,000 (paid-media: 94.4%; free-media: 93.3%) compared to fax recruits (95.7%), while in-clinic recruits were less likely to have family incomes ≥ $40,000 (88.8%, p < 0.05). Maternal recruits from fax and in-clinic were more likely to attend university (Fax: 92.6%, in-clinic 89.8%) versus the reference population (52.0%; p < 0.05 for both) and both were less likely to smoke (Fax: 6.8%, in-clinic 4.2%) versus reference (18.6%; p < 0.05 for both). However, while fax referrals were more likely to be Caucasian (85.9% versus reference 77.5%; p < 0.05), in-clinic referrals were not significantly different (78.2%; P > 0.05). CONCLUSION: Recruitment methods result in different recruitment rates and participant demographics. A variety of methods are required to recruit a generalizable sample.

Local control of extra-abdominal desmoid tumors: systematic review and meta-analysis.

The local control of desmoid tumors constitutes a continuing treatment dilemma due to its high recurrence rates. The purpose of this systematic review was to critically examine the current treatment of these rare tumors and to specifically evaluate the local failure and response rates of surgery, radiation and systemic therapy. We comprehensively searched the literature for relevant studies across Cinahl, Embase, Medline and the Cochrane databases. Articles were categorized as surgery, radiation, surgery + radiation and systemic therapy (including cytotoxic and non cytotoxic). Methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Pooled odd ratios (OR) for comparative studies and weighted proportions with 95% confidence intervals (CI) are reported. Thirty-five articles were included in the final analysis. Weighted mean local failure rates were 22% [95% CI (16-28%)], 35% [95% CI (26-44%)] and 28% [95% CI (18-39%)] for radiation alone, surgery alone and surgery + radiation respectively. In the analysis of comparative studies, surgery and radiation in combination had lower local failure rates than radiation alone [OR 0.7 (0.4, 1.2)] and surgery alone [OR 0.7 (0.4, 1.0)]. Weighted mean stable disease rates were 91% [95% CI (85-96%)] and 52% [95% CI (38-65%)] for non cytotoxic and cytotoxic chemotherapy respectively. The current evidence suggests that surgery alone has a consistently high rate of local recurrence in managing extra-abdominal desmoid tumors. Radiation therapy in combination with surgery improves local control rates. However, the limited data on systemic therapy for this rare tumor suggests the benefit of using both cytotoxic and non cytotoxic chemotherapy to achieve stable disease.

Randomized, double-blinded, placebo-controlled, trial of risedronate for the prevention of bone mineral density loss in nonmetastatic prostate cancer patients receiving radiation therapy plus androgen deprivation therapy.

PURPOSE: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. METHODS AND MATERIALS: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > -2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. RESULTS: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. CONCLUSIONS: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT.

The current practice of screening, prevention, and treatment of androgen-deprivation-therapy induced osteoporosis in patients with prostate cancer.

Introduction. ADT is used in the management of locally advanced and metastatic disease. The detrimental effect of ADT on bone density is well documented. This study assesses care gaps in screening, prevention and treatment of osteoporosis among prostate cancer patients. Methods. We conducted a retrospective cohort study for patients diagnosed with non-metastatic prostate cancer on ADT. Charts from a tertiary oncology center were assessed for utilization of DXA scan, prescription of calcium, vitamin D, calcitonin and bisphosphonates.Bivariate analysis was used to determine the effect of patient characteristics and likelihood for osteoporosis screening. Results. 149 charts were reviewed, with 3-year mean follow-up. 58.8% of men received a baseline DXA, of which 20.3% had a repeat DXA within their follow-up periods.In all, 28% were appropriately screened and managed for osteoporosis (received repeat DXA, bisphosphonate). In bivariate analysis, the number of ADT injections which correlate with the duration of androgen suppression was significantly associated with the number of DXA scans. Conclusions. Our study found a care gap in the screening, prevention, and treatment of osteoporosis in this population. Patients receiving the most ADT injections were more likely to be screened. Our results suggest healthcare providers treating prostate cancer are insufficiently screening and treating this susceptible population. We suggest baseline measurement of BMD at the initiation of ADT with periodic reassessment during therapy.

A systematic review and meta-analysis of oncologic outcomes of pre- versus postoperative radiation in localized resectable soft-tissue sarcoma.

BACKGROUND: The goal of this study was to determine the oncologic outcomes in localized resectable soft-tissue sarcoma after pre- versus postoperative radiation. METHODS: Literature searches through MEDLINE, EMBASE, CancerLit, and the Cochrane Database were performed with the following search terms: sarcoma, radiation, preoperative, and postoperative. Two reviewers independently assessed all eligible publications with the Detsky Quality Scale for Randomized Trials and the Newcastle-Ottawa Quality Assessment Scale for case-control studies. The primary outcome measure was the pooled odds ratio and 95% confidence intervals (95% CI) for the risk of local recurrence calculated through the fixed- and random-effects methods. Time-dependent survival data were calculated as an average across all studies. RESULTS: Five eligible studies were identified including a total of 1,098 patients. The P value for heterogeneity was 0.259, and the variability (I (2)) in results across studies due to true differences in treatment effect was 25%. The risk for local recurrence was lower in the preoperative group with an odds ratio of 0.61 (95% CI 0.42-0.89) by means of the fixed-effects method, and an odds ratio of 0.67 (95% CI 0.39-1.15) by means of the random-effects method. Average survival was 76% (range 62-88%) in the preoperative group and 67% (range 41-83%) in the post-operative group. CONCLUSIONS: The delay in surgical resection necessary to complete preoperative radiation does not seem to increase the risk of lethal metastatic spread. The risk of local recurrence may be lower after preoperative radiation. These findings must be interpreted with caution because of the heterogeneity and bias in the available studies.

Association of phosphorylated epidermal growth factor receptor with survival in patients with locally advanced non-small cell lung cancer treated with radiotherapy.

INTRODUCTION: The epidermal growth factor receptor (EGFR) and its downstream effector kinases are thought to have important roles in lung cancer cell proliferation and response to treatment. METHODS: In a prospective cohort of patients with locally advanced non-small cell lung cancer (NSCLC) undergoing high-dose radiotherapy with or without chemotherapy, we examined by immunohistochemistry (IHC) the tumor levels of EGFR and phosphorylated/ activated-EGFR (P-EGFR), P-Erk, P-Akt, P-Stat3, and the cell cycle marker Ki67. We examined the relationships among marker expression, at the plasma membrane (M), cytoplasm (C) and nucleus, as well as the radiologic tumor response, and overall survival (OS). RESULTS: Fifty patients were recruited in this study. Their median survival was 18.3 months. No correlation was detected between total EGFR and P-EGFR levels in any subcellular compartment. M P-EGFR correlated positively with C P-Akt (p = 0.01). C P-Erk correlated negatively with radiologic response (p = 0.022), and on univariate regression analysis, this approached significance (p = 0.059). M and C P-EGFR correlated negatively with OS (p = 0.020), and on univariate analysis higher M P-EGFR predicted for poor OS (p = 0.001). Patients with high M P-EGFR levels had median survival of 7.8 months versus 17.7 months for patients with low M P-EGFR. CONCLUSIONS: Our results support a role of activated M P-EGFR, (but not total EGFR), as a predictor of OS in locally advanced-NSCLC. It is suggested that detailed evaluation of the subcellular distribution and activation state of EGFR and its downstream effectors is required to unravel the predictive value of these markers in NSCLC.

GU radiation oncologists consensus on bone loss from androgen deprivation.

The majority of GU radiation oncologists in Canada attended a consensus meeting in November 2004. The topic of osteoporosis in men receiving androgen deprivation therapy (ADT) for prostate cancer was identified as a key theme. A chaired session with keynote speakers and review of the evidence took place followed by open debate. Participants were provided with background information. Osteoporosis was defined as a T-score < or = -2.5, but the importance of risk factors and clinical findings is noted. Dual DEXA is the current standard for assessment of bone density and relates well to fracture risk. The lifetime risk of fracture is 13% for men over the age of 50 years even without the influence of ADT. Lifestyle, dietary and supplementation advice are provided both to prevent and to manage osteoporosis. The role for prophylactic bisphosphonate therapy in men on ADT without osteoporosis has not been established. Follow-up DEXA scans are required to monitor density, risk and response to interventions. Fracture incidence and BMD should be considered in the trial design of studies involving prolonged ADT. Osteoporosis is a treatable condition and the oncologist should employ ADT with this knowledge. A follow-up e-mail survey was carried out regarding the consensus statement. Responses were received from 49 of the 69 attendees (71%), and overall there was an 89% agreement with the consensus statement. This is now adopted as national practice guidelines for radiation oncologists employed prolonged ADT in prostate cancer patients.