Interval to biochemical failure as a biomarker for cause‐specific and overall survival after dose‐escalated external beam radiation therapy for prostate cancer

BACKGROUND: After external beam radiation therapy (EBRT) for prostate cancer, a short interval to biochemical failure of <18 months has been proposed as a surrogate for cause‐specific survival. Because EBRT dose influences biochemical failure, the authors investigated the interval to biochemical failure in a cohort of patients treated with dose‐escalated EBRT. METHODS: From 1998 to 2008, 710 patients were treated with EBRT (≥75 grays) ± androgen deprivation therapy (ADT) at the University of Michigan. Biochemical failure was defined using the Phoenix consensus definition (nadir + 2 ng/mL). A short interval to biochemical failure was defined as <18 months after completing radiotherapy and/or ADT. The associations between biochemical failure, the interval to biochemical failure, and clinical factors with cause‐specific survival (CSS) and overall survival (OS) were evaluated. RESULTS: There were 149 biochemical failures (21%), and short interval to biochemical failure accounted for 14% and 40% of biochemical failures in those with intermediate‐risk or high‐risk disease, respectively. Biochemical failure impacted CSS ( P < .0001) but not OS ( P = .36). However, a short interval to biochemical failure predicted decreased CSS ( P < .0001; hazard ratio [HR], 5.6; 95% confidence interval [CI], 2.4‐13.0) and OS ( P < .0001; HR, 4.8; 95% CI, 2.3‐10.3) when compared with a long interval to biochemical failure. The 8‐year OS was 78% without biochemical failure, compared with 87% with a long interval to biochemical failure ( P = .1; HR, 0.7; 95% CI, 0.4‐1.1) and 38% with a short interval to biochemical failure ( P < .0001; HR, 3.7; 95% CI, 2.3‐5.9). On multivariate analysis, a short interval to biochemical failure increased the risk of prostate cancer death ( P < .0001; HR, 18.1; 95% CI, 8.4‐39) and all cause mortality ( P = .0027; HR, 1.5; 95% CI, 1.2‐2.1), whereas a long interval to biochemical failure did not. CONCLUSIONS: The relation between the interval to biochemical failure, CSS, and OS was independently validated in patients treated with dose‐escalated EBRT. Further evaluation of the interval to biochemical failure as a surrogate endpoint is warranted. Cancer 2012. © 2011 American Cancer Society. Because biochemical failure does not predict for overall survival after radiotherapy (RT) in prostate cancer, a short interval to biochemical failure (defined as <18 months after finishing therapy) is tested as a biomarker for both cause‐specific and overall survival. Among 710 patients treated with dose‐escalated RT at the University of Michigan, a short interval to biochemical failure is found to be prognostic of both cause‐specific and overall survival.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91158/1/26498_ftp.pd

The use of hormonal therapy with radiotherapy for prostate cancer: analysis of prospective randomised trials

In 1901, Wilhelm Conrad Röntgen won the Nobel prize in Physics for his discovery of the Röntgen rays or, as he himself called them, X-rays. In 1966, Dr Charles Brenton Higgins won the Nobel Prize in Medicine for his breakthroughs concerning hormonal treatment of prostatic cancer. After 31 years, in 1997, the first prospective randomised trials of the combination of hormonal therapy and radiation therapy were published, showing increased survival when compared to radiation therapy alone for patients with prostate cancer. Since 1997, many investigators have published trials combining hormonal and radiation therapy for prostate cancer. This minireview will address the largest and most influential of these trials, and attempt to guide physicians in selecting the appropriate patients for this combined approach

Comparative efficacy and safety of treatments for localised prostate cancer: an application of network meta-analysis.

CONTEXT: There is ongoing uncertainty about the optimal management of patients with localised prostate cancer. OBJECTIVE: To evaluate the comparative efficacy and safety of different treatments for patients with localised prostate cancer. DESIGN: Systematic review with Bayesian network meta-analysis to estimate comparative ORs, and a score (0-100%) that, for a given outcome, reflects average rank order of superiority of each treatment compared against all others, using the Surface Under the Cumulative RAnking curve (SUCRA) statistic. DATA SOURCES: Electronic searches of MEDLINE without language restriction. STUDY SELECTION: Randomised trials comparing the efficacy and safety of different primary treatments (48 papers from 21 randomised trials included 7350 men). DATA EXTRACTION: 2 reviewers independently extracted data and assessed risk of bias. RESULTS: Comparative efficacy and safety evidence was available for prostatectomy, external beam radiotherapy (different types and regimens), observational management and cryotherapy, but not high-intensity focused ultrasound. There was no evidence of superiority for any of the compared treatments in respect of all-cause mortality after 5 years. Cryotherapy was associated with less gastrointestinal and genitourinary toxicity than radiotherapy (SUCRA: 99% and 77% for gastrointestinal and genitourinary toxicity, respectively). CONCLUSIONS: The limited available evidence suggests that different treatments may be optimal for different efficacy and safety outcomes. These findings highlight the importance of informed patient choice and shared decision-making about treatment modality and acceptable trade-offs between different outcomes. More trial evidence is required to reduce uncertainty. Network meta-analysis may be useful to optimise the power of evidence synthesis studies once data from new randomised controlled studies in this field are published in the future

The addition of low‐dose‐rate brachytherapy and androgen‐deprivation therapy decreases biochemical failure and prostate cancer death compared with dose‐escalated external‐beam radiation therapy for high‐risk prostate cancer

BACKGROUND: The objective of this study was to determine whether the addition of low‐dose‐rate brachytherapy or androgen‐deprivation therapy (ADT) improves clinical outcome in patients with high‐risk prostate cancer (HiRPCa) who received dose‐escalated radiotherapy (RT). METHODS: Between 1995 and 2010, 958 patients with HiRPCa were treated at Schiffler Cancer Center (n = 484) or at the University of Michigan (n = 474) by receiving either dose‐escalated external‐beam RT (EBRT) (n = 510; minimum prescription dose, 75 grays [Gy]; median dose, 78 Gy) or combined‐modality RT (CMRT) consisting of 103 Pd implants (n = 369) or 125 I implants (n = 79) both with pelvic irradiation (median prescription dose, 45 Gy). The cumulative incidences of biochemical failure (BF) and prostate cancer‐specific mortality (PCSM) were estimated by using the Kaplan‐Meier method and Fine and Gray regression analysis. RESULTS: The median follow‐up was 63.2 months (interquartile range, 35.4‐99.0 months), and 250 patients were followed for >8 years. Compared with CMRT, patients who received EBRT had higher prostate‐specific antigen levels, higher tumor classification, lower Gleason sum, and more frequent receipt of ADT for a longer duration. The 8‐year incidence BF and PCSM among patients who received EBRT was 40% (standard error, 38%‐44%) and 13% (standard error, 11%‐15%) compared with 14% (standard error, 12%‐16%; P < .0001) and 7% (standard error 6%‐9%; P = .003) among patients who received CMRT. On multivariate analysis, the hazard ratios (HRs) for BF and PCSM were 0.35 (95% confidence interval [CI], 0.23‐0.52; P < .0001) and 0.41 (95% CI, 0.23‐0.75; P < .003), favoring CMRT. Increasing duration of ADT predicted decreased BF ( P = .04) and PCSM ( P = .001), which was greatest with long‐term ADT (BF: HR, 0.33; P < .0001; 95% CI, 0.21‐0.52; PCSM: HR, 0.30; P = .001; 95% CI, 0.15‐0.6) even in the subgroup that received CMRT. CONCLUSIONS: In this retrospective comparison, both low‐dose‐rate brachytherapy boost and ADT were associated with decreased risks of BF and PCSM compared with EBRT. Cancer 2013. © 2012 American Cancer Society. The authors retrospectively analyze the impact of combined‐modality radiation therapy on clinical outcomes in 958 patients with high‐risk prostate cancer. The addition of an interstitial brachytherapy boost and long‐term androgen suppression significantly decreases the rates of biochemical failure and prostate cancer death compared with dose‐escalated radiotherapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96383/1/27784_ftp.pd

Impact of hormonal treatment duration in combination with radiotherapy for locally advanced prostate cancer: Meta-analysis of randomized trials

<p>Abstract</p> <p>Background</p> <p>Hormone therapy plus radiotherapy significantly decreases recurrences and mortality of patients affected by locally advanced prostate cancer. In order to determine if difference exists according to the hormonal treatment duration, a literature-based meta-analysis was performed.</p> <p>Methods</p> <p>Relative risks (RR) were derived through a random-effect model. Differences in primary (biochemical failure, BF; cancer-specific survival, CSS), and secondary outcomes (overall survival, OS; local or distant recurrence, LR/DM) were explored. Absolute differences (AD) and the number needed to treat (NNT) were calculated. Heterogeneity, a meta-regression for clinic-pathological predictors and a correlation test for surrogates were conducted.</p> <p>Results</p> <p>Five trials (3,424 patients) were included. Patient population ranged from 267 to 1,521 patients. The longer hormonal treatment significantly improves BF (with significant heterogeneity) with an absolute benefit of 10.1%, and a non significant trend in CSS. With regard to secondary end-points, the longer hormonal treatment significantly decrease both the LR and the DM with an absolute difference of 11.7% and 11.5%. Any significant difference in OS was observed. None of the three identified clinico-pathological predictors (median PSA, range 9.5-20.35, Gleason score 7-10, 27-55% patients/trial, and T3-4, 13-77% patients/trial), did significantly affect outcomes. At the meta-regression analysis a significant correlation between the overall treatment benefit in BF, CSS, OS, LR and DM, and the length of the treatment was found (p≤0.03).</p> <p>Conclusions</p> <p>Although with significant heterogeneity (reflecting different patient' risk stratifications), a longer hormonal treatment duration significantly decreases biochemical, local and distant recurrences, with a trend for longer cancer specific survival.</p

Obesity and mortality in men with locally advanced prostate cancer

BACKGROUND. Greater body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure following radical prostatectomy and radiation therapy (RT). Whether BMI is associated with prostate cancer-specific mortality (PCSM) was investigated in a large randomized trial of men treated with RT and androgen deprivation therapy (ADT) for locally advanced prostate cancer. METHODS. Between 1987 and 1992, 945 eligible men with locally advanced prostate cancer were enrolled in a phase 3 trial (RTOG 85-31) and randomized to RT and immediate goserelin or RT alone followed by goserelin at recurrence. Height and weight data were available at baseline for 788 (83%) subjects. Cox regression analyses were performed to evaluate the relations between BMI and all-cause mortality, PCSM, and nonprostate cancer mortality. Covariates included age, race, treatment arm, history of prostatectomy, nodal involvement, Gleason score, clinical stage, and BMI. RESULTS. The 5-year PCSM rate for men with BMI <25 kg/m 2 was 6.5%, compared with 13.1% and 12.2% in men with BMI ≥25 to <30 and BMI ≥30, respectively (Gray's P = .005). In multivariate analyses, greater BMI was significantly associated with higher PCSM (for BMI ≥25 to <30, hazard ratio [HR] 1.52, 95% confidence interval [CI], 1.02–2.27, P = .04; for BMI ≥30, HR 1.64, 95% CI, 1.01–2.66, P = .04). BMI was not associated with nonprostate cancer or all-cause mortality. CONCLUSIONS. Greater baseline BMI is independently associated with higher PCSM in men with locally advanced prostate cancer. Further studies are warranted to evaluate the mechanism(s) for increased cancer-specific mortality and to assess whether weight loss after prostate cancer diagnosis alters disease course. Cancer 2007. © 2007 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57506/1/23093_ftp.pd

Адъювантная андрогенная блокада после дистанционной лучевой терапии при раке предстательной железы — отдаленные результаты III фазы исследования RTOG 85-31

The RTOG 85-31 study has indicated that adjuvant hormonotherapy is particularly effective in prostate cancer (PC) patients with a high Glisson score. Long-term adjuvant hormonotherapy is not warranted in patients with a total Glisson score of 2-6. Exception is patients with disseminated locally advanced tumors, in whom neoadjuvant androgenic suppression (RTOG 86-10 protocol) considerably improves the results of treatment. Long-term adjuvant hormonotherapy may be the method of choice in treating PC patients with a poor prognosis.

Soft tissue non-Hodgkin lymphoma of shoulder in a HIV patient: a report of a case and review of the literature

The risk of developing lymphoma is greatly increased in HIV infection. Musculoskeletal manifestations of the human immunodeficiency virus (HIV) are common and are sometimes the initial presentation of the disease. Muscle, bone, and joints are involved by septic arthritis, myopathies and neoplasms. HIV-related neoplastic processes that affect the musculoskeletal system include Kaposi's sarcoma and non-Hodgkin's lymphoma, the latter being mainly localized at lower extremities, spine and skull

No supra-additive effects of goserelin and radiotherapy on clonogenic survival of prostate carcinoma cells in vitro

<p>Abstract</p> <p>Background</p> <p>Oncological results of radiotherapy for locally advanced prostate cancer (PC) are significantly improved by simultaneous application of LHRH analoga (e.g. goserelin). As 85% of PC express LHRH receptors, we investigated the interaction of goserelin incubation with radiotherapy under androgen-deprived conditions in vitro.</p> <p>Methods</p> <p>LNCaP and PC-3 cells were stained for LHRH receptors. Downstream the LHRH receptor, changes in protein expression of c-fos, phosphorylated p38 and phosphorylated ERK1/2 were analyzed by means of Western blotting after incubation with goserelin and irradiation with 4 Gy. Both cell lines were incubated with different concentrations of goserelin in hormone-free medium. 12 h later cells were irradiated (0 – 4 Gy) and after 12 h goserelin was withdrawn. Endpoints were clonogenic survival and cell viability (12 h, 36 h and 60 h after irradiation).</p> <p>Results</p> <p>Both tested cell lines expressed LHRH-receptors. Changes in protein expression demonstrated the functional activity of goserelin in the tested cell lines. Neither in LNCaP nor in PC-3 any significant effects of additional goserelin incubation on clonogenic survival or cell viability for all tested concentrations in comparison to radiation alone were seen.</p> <p>Conclusion</p> <p>The clinically observed increase in tumor control after combination of goserelin with radiotherapy in PC cannot be attributed to an increase in radiosensitivity of PC cells by goserelin in vitro.</p