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

Phase I study of dose escalation to dominant intraprostatic lesions using high-dose-rate brachytherapy.

PurposeRadiation dose escalation for prostate cancer improves biochemical control but is limited by toxicity. Magnetic resonance spectroscopic imaging (MRSI) can define dominant intraprostatic lesions (DIL). This phase I study evaluated dose escalation to MRSI-defined DIL using high-dose-rate (HDR) brachytherapy.Material and methodsEnrollment was closed early due to low accrual. Ten patients with prostate cancer (T2a-3b, Gleason 6-9, PSA < 20) underwent pre-treatment MRSI, and eight patients had one to three DIL identified. The eight enrolled patients received external beam radiation therapy to 45 Gy and HDR brachytherapy boost to the prostate of 19 Gy in 2 fractions. MRSI images were registered to planning CT images and DIL dose-escalated up to 150% of prescription dose while maintaining normal tissue constraints. The primary endpoint was genitourinary (GU) toxicity.ResultsThe median total DIL volume was 1.31 ml (range, 0.67-6.33 ml). Median DIL boost was 130% of prescription dose (range, 110-150%). Median urethra V120 was 0.15 ml (range, 0-0.4 ml) and median rectum V75 was 0.74 ml (range, 0.1-1.0 ml). Three patients had acute grade 2 GU toxicity, and two patients had late grade 2 GU toxicity. No patients had grade 2 or higher gastrointestinal toxicity, and no grade 3 or higher toxicities were noted. There were no biochemical failures with median follow-up of 4.9 years (range, 2-8.5 years).ConclusionsDose escalation to MRSI-defined DIL is feasible. Toxicity was low but incompletely assessed due to limited patients' enrollment

Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials

Càncer de pròstata; Teràpia de privació d'andrògensCáncer de próstata; Terapia de privación de andrógenosProstate cancer; Androgen-deprivation therapyPURPOSE The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer–specific mortality. RESULTS Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer–specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.Funding support for this study comes from the Prostate Cancer Foundation and ASTRO to AUK. AUK also thanks generous donations from the DeSilva, McCarrick, and Bershad families. A.T. acknowledges support from Cancer Research UK (C33589/A28284 and C7224/A28724) the National Institute for Health Research (NIHR) Cancer Research Network. This project represents independent research supported by the National Institute for Health research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. N.G.Z. is supported by the American Cancer Society – Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG‐20‐013‐01‐CCE (2020)

Hypofractionated simultaneous integrated boost (IMRT-SIB) with pelvic nodal irradiation and concurrent androgen deprivation therapy for high-risk prostate cancer: results of a prospective phase II trial

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Studies of alternative nuclear technologies

This report is a summary of tasks performed for the U.S. Arms Control and Disarmament Agency under Contract AC7NC114. The work is directly related to the Agency effort to examine potential alternative fuel cycles that might enhance uranium resource utilization, minimize plutonium production, and reduce the weapons proliferation risk from spent fuel reprocessing or early introduction of fast breeder reactors. Reported herein are summaries of various inter-related task assignments, including: fuel utilization in current light water reactors operating with the uranium fuel cycle; alternate fuel cycles, including the use of denatured fuel in LWRs and of the spectral shift concept for reactivity control; fuel utilization in high temperature graphite moderated reactors using the denatured fuel cycle; fuel utilization in heavy water reactors (CANDU type), including the use of enriched fuel, denatured fuel, and recycle of plutonium and U-233; the tandem fuel cycle (recovery of spent fuel and further irradiation in a CANDU type reactor); issues in the utilization of denatured fuel in LWRs; preliminary conceptual evaluation of a heavy water moderated reactor suitable for use in the United States

Inter-observer variability in contouring the penile bulb on CT images for prostate cancer treatment planning

Several investigations have recently suggested the existence of a correlation between the dose received by the penile bulb (PB) and the risk of erectile dysfunction (ED) after radical radiotherapy for clinically localized prostate carcinoma

Outcomes of hypofractionated stereotactic body radiotherapy boost for intermediate and high-risk prostate cancer

BACKGROUND AND PURPOSE: Treatment of intermediate and high-risk prostate cancer with a high BED has been shown to increase recurrence free survival (RFS). While high dose rate (HDR) brachytherapy, given as a boost is effective in delivering a high BED, many patients are not candidates for the procedure or wish to avoid an invasive procedure. We evaluated the use of stereotactic body radiotherapy (SBRT) as a boost, with dosimetry modeled after HDR-boost. MATERIAL AND METHODS: Fifty patients were treated with two fractions of SBRT (9.5-10.5 Gy/fraction) after 45 Gy external-beam radiotherapy, with 48 eligible for analysis at a median follow-up of 42.7 months. RESULTS: The Kaplan-Meier estimates of biochemical control post-radiation therapy (95 % Confidence Interval) at 3, 4 and 5 years were 95 % (81–99 %), 90 % (72–97 %) and 90 % (72–97 %), respectively (not counting 2 patients with a PSA bounce as failures). RFS (defined as disease recurrence or death) estimates at 3, 4 and 5 years were 92 % (77–97 %), 88 % (69–95 %) and 83 % (62–93 %) if patients with PSA bounces are not counted as failures, and were 90 % (75–96 %), 85 % (67–94 %) and 75 % (53–88 %) if they were. The median time to PSA nadir was 26.2 months (range 5.8–82.9 months), with a median PSA nadir of 0.05 ng/mL (range <0.01–1.99 ng/mL). 2 patients had a “benign PSA bounce”, and 4 patients recurred with radiographic evidence of recurrence beyond the RT fields. Treatment was well tolerated with no acute G3 or higher GI or GU toxicity and only a single G3 late GU toxicity of urinary obstruction. CONCLUSIONS: SBRT boost is well-tolerated for intermediate and high-risk prostate cancer patients with good biochemical outcomes and low toxicity

Distribution of hydrated minerals in the north polar region of Mars

The previous discovery of extensive deposits of hydrated minerals in Olympia Planum in the north polar region of Mars by the Mars Express OMEGA instrument raises important questions about the origin and subsequent redistribution of these hydrated minerals. Here we present a new map of the distribution of hydrated minerals within the north polar region of Mars by applying both standard and new spectral analysis techniques to near-infrared spectral data from OMEGA. Our results are in agreement with the previous OMEGA observations but also show more extensive detections of hydrated minerals throughout the circumpolar plains, as well as new detections of hydrated minerals on the surface of Planum Boreum and within the polar troughs. We find that while the circumpolar plains hydration signatures appear to be correlated with the dark dunes of the north polar erg, hydration signatures in Planum Boreum instead appear to be correlated with the north polar veneers and their sources within the polar layered deposits. By applying laboratory-derived empirical models of the dependence of gypsum spectra on grain size and abundance, we provide approximate abundance estimates for the hydrated minerals we have identified in Observatoire pour la Minéralogie, l’Eau, les Glaces et l’Activité (OMEGA) and Compact Reconnaissance Imaging Spectrometer (CRISM) data. We find that the presence of hydrated minerals throughout the north polar region suggests (1) a complex cycle of sediment exchange between the Olympia Planum dunes and the other polar units; (2) an earlier origin for the hydrated minerals than originally postulated; and (3) the occurrence of significant water activity in this region during the Amazonian.This work was supported by grants from the Mars Data Analysis Program under contracts from NASA, the Mars Odyssey Participating Scientist program under contracts from the Jet Propulsion Laboratory, and the Canadian Space Agency.https://agupubs.onlinelibrary.wiley.com/doi/abs/10.1029/2008JE00318

High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series

BACKGROUND: The use of minimally invasive ablative therapies in localised prostate cancer offer potential for a middle ground between active surveillance and radical therapy. METHODS: An analysis of men with organ-confined prostate cancer treated with transrectal whole-gland HIFU (Sonablate 500) between 1 February 2005 and 15 May 2007 was carried out in two centres. Outcome data (side-effects using validated patient questionnaires, biochemical, histology) were evaluated. RESULTS: A total of 172 men were treated under general anaesthetic as day-case procedures with 78% discharged a mean 5 h after treatment. Mean follow-up was 346 days (range 135-759 days). Urethral stricture was significantly lower in those with suprapubic catheter compared with urethral catheters (19.4 vs 40.4%, P = 0.005). Antibiotics were given to 23.8% of patients for presumed urinary tract infection and the rate of epididymitis was 7.6%. Potency was maintained in 70% by 12 months, whereas mild stress urinary incontinence (no pads) was reported in 7.0% (12 out of 172) with a further 0.6% (1 out of 172) requiring pads. There was no rectal toxicity and no recto-urethral fistulae. In all, 78.3% achieved a PSA nadir <= 0.5 mu g ml(-1) at 12 months, with 57.8% achieving <= 0.2 mu g ml(-1). Then, 8 out of 13 were retreated with HIFU, one had salvage external beam radiotherapy and four chose active surveillance for small-volume low-risk disease. Overall, there was no evidence of disease (PSA <0.5 mu g ml(-1) or negative biopsy if nadir not achieved) after one HIFU session in 92.4% ( 159 out of 172) of patients. CONCLUSION: HIFU is a minimally invasive, day-case ablative technique that can achieve good biochemical outcomes in the short term with minimal urinary incontinence and acceptable levels of erectile dysfunction. Long-term outcome needs further evaluation and the inception of an international registry for cases treated using HIFU will significantly aid this health technology assessment. British Journal of Cancer (2009) 101, 19-26. doi: 10.1038/sj.bjc.6605116 www.bjcancer.com Published online 9 June 2009 (C) 2009 Cancer Research U