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Guideline Post-prostatectomy radiation therapy: consensus guidelines of the Australian and New Zealand Radiation Oncology Genito-Urinary Group. 2008
Sidhom MA, Kneebone AB, Lehman M, Wiltshire KL, Millar JL, Mukherjee RK, Shakespeare TP, Tai KH. · Cancer Therapy Centre, Liverpool Hospital, NSW, Australia. · Radiother Oncol. · Pubmed #18514340 No free full text.
Abstract: BACKGROUND AND PURPOSE: Three randomised trials have demonstrated the benefit of adjuvant post-prostatectomy radiotherapy (PPRT) for high risk patients. Data also documents the effectiveness of salvage radiotherapy following a biochemical relapse post-prostatectomy. The Radiation Oncology Genito-Urinary Group recognised the need to develop consensus guidelines on to whom, when and how to deliver PPRT. MATERIALS AND METHODS: Draft guidelines were developed and refined at a consensus conference in June 2006 attended by 63 delegates where urological, radiotherapy and diagnostic imaging experts spoke on aspects of PPRT. Unresolved issues were further developed by working parties and redistributed until consensus was reached. RESULTS: Central to the recommendations is that patients with positive surgical margins, seminal vesicle invasion and/or extracapsular extension have a high risk of residual local disease and should be informed of the options of either immediate adjuvant radiotherapy or active surveillance with early salvage in the event of biochemical recurrence. Salvage radiotherapy should be instituted at the earliest confirmation of biochemical recurrence. Detailed contouring guidelines have been developed, defining the regions at risk of residual microscopic disease which should be included in the clinical target volume. The recommended doses are 60-64Gy for adjuvant, and 60-66Gy for salvage radiotherapy. The role of hormone therapy in conjunction with PPRT is yet to be defined. CONCLUSIONS: These consensus guidelines have been developed to give clinical and technical guidance to radiation oncologists and urologists in the management of high risk post-prostatectomy patients.
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Review Australian and New Zealand three-dimensional conformal radiation therapy consensus guidelines for prostate cancer. 2004
Skala M, Berry M, Duchesne G, Gogna K, Tai KH, Turner S, Kneebone A, Rolfo A, Haworth A. · Cancer Therapy Centre, Liverpool Health Service, Sydney, New South Wales, Australia. · Australas Radiol. · Pubmed #15601330 No free full text.
Abstract: Three-dimensional conformal radiation therapy (3DCRT) has been shown to reduce normal tissue toxicity and allow dose escalation in the curative treatment of prostate cancer. The Faculty of Radiation Oncology Genito-Urinary Group initiated a consensus process to generate evidence-based guidelines for the safe and effective implementation of 3DCRT. All radiation oncology departments in Australia and New Zealand were invited to complete a survey of their prostate practice and to send representatives to a consensus workshop. After a review of the evidence, key issues were identified and debated. If agreement was not reached, working parties were formed to make recommendations. Draft guidelines were circulated to workshop participants for approval prior to publication. Where possible, evidence-based recommendations have been made with regard to patient selection, risk stratification, simulation, planning, treatment delivery and toxicity reporting. This is the first time a group of radiation therapists, physicists and oncologists representing professional radiotherapy practice across Australia and New Zealand have worked together to develop best-practice guidelines. These guidelines should serve as a baseline for prospective clinical trials, outcome research and quality assurance.
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Clinical Conference Planning and implementing an implanted fiducial programme for prostate cancer radiation therapy. 2008
Thompson A, Fox C, Foroudi F, Styles C, Tai KH, Owen R, Laferlita M. · Department of Radiation Therapy Services, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. · J Med Imaging Radiat Oncol. · Pubmed #18811768 No free full text.
Abstract: Using implanted gold seeds as fiducial markers to verify the position of the prostate in radiation therapy is well accepted and is becoming the standard of practice and requirement for international multicentre trials. In 2006 the decision was made at the Peter MacCallum Caner Centre (Peter Mac) to plan for and implement this process as standard clinical practice for radical dose prostate treatments (74-78 Gy). Before this, programme verification of field placement for prostate cancer radiation treatment was routinely carried out using regular off-line electronic portal imaging with matching of bony anatomy. A small multidisciplinary team investigated and assisted in the implementation of this new practice across the Peter Mac sites at East Melbourne and our three satellite centres. Issues considered included seed size, number and position in the prostate, implant equipment, imaging equipment and procedure and consent and information forms. The use of a custom made fiducial pack, comprehensive patient information and a daily on-line imaging process was implemented. The experience of the first 28 patients at Peter Mac from January 2007 to May 2007 inclusive is reported on.
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Clinical Conference Patterns of toxicity following high-dose-rate brachytherapy boost for prostate cancer: mature prospective phase I/II study results. 2007
Duchesne GM, Williams SG, Das R, Tai KH. · Division of Radiation Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria, Australia. · Radiother Oncol. · Pubmed #17561293 No free full text.
Abstract: BACKGROUND: To examine the long-term morbidity of high dose rate brachytherapy boost (HDRBB) in prostate cancer. PATIENTS AND METHODS: A phase I/II HDRBB dose escalation protocol recruited 108 men up to November 1999. Treatment combined 46 Gy external beam radiation to the prostate with four fractions of HDR totalling 16 or 20 Gy. Morbidity data were collected prospectively regarding urological, bowel and erectile dysfunction (ED) symptoms using a validated clinician completed instrument. Actuarial incidence and prevalence of symptoms were estimated; the latter to account for potential recovery. RESULTS: The median follow-up was 78 months, with 880 questionnaires completed. The respective actuarial cumulative incidence and point prevalence rates of any grade 2 or higher symptom score at 5 years were 24.9% (95% confidence intervals [CI] 16.8-33.5%) and 7.7% (95% CI 1.8-14.5%) for urinary toxicity; and 11.3% (95% CI 5.6-17.1%) and 3.0% (0-7.6%) for rectal toxicity, meaning that most symptom sub-domains showed substantial recovery with time. Corresponding erectile function toxicity figures for the subgroup of men (n=53) with normal erectile function prior to treatment and no androgen deprivation therapy were 77.0% (95% CI 64.9-88.1%) and 45.3% (95% CI 27.2-64.6%). Some late toxicity profiles developed after twelve months, typically with low grade bowel and urinary urgency. These peaked at 12-24 months and stayed relatively stable subsequently. Paradoxically, grade 1 or more nocturia symptoms settle with time, despite the accumulation of grade 2 or more toxicity beyond 24 months. CONCLUSIONS: HDRBB as a means of dose escalation in prostate cancer is associated with low and relatively stable rates of long-term bowel and urinary morbidity, and compares favourably with external beam results. Actuarial incidence methods overstate the burden of toxicity with substantial recovery noted in most domains.
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Clinical Conference A prospective dose escalation trial of high-dose-rate brachytherapy boost for prostate cancer: Evidence of hypofractionation efficacy? 2006
Tang JI, Williams SG, Tai KH, Dean J, Duchesne GM. · Department of Radiation Oncology, The Cancer Institute, National University Hospital, Singapore. · Brachytherapy. · Pubmed #17118320 No free full text.
Abstract: PURPOSE: The study aimed to evaluate mature outcomes of a Phase I/II high-dose-rate brachytherapy (HDRB) boost protocol. METHODS AND MATERIALS: We analyzed data from 88 patients with T1a-T3a, N0, M0 prostate adenocarcinoma treated on a prospective Phase I/II HDRB boost protocol of 16 (n = 47) or 20 Gy (n = 41) in four fractions, without planned androgen deprivation therapy. HDRB was added to 46 Gy of external beam radiotherapy (EBRT). Outcomes were compared to a contemporaneous retrospective cohort of 104 patients receiving 66 Gy EBRT monotherapy. The primary endpoint was freedom from biochemical failure, defined as a 2 ng/mL rise above the lowest prostate-specific antigen (PSA) (FFbFn2), whereas the American Society of Therapeutic Radiology and Oncology consensus definition (ACD) was used for comparative purposes. RESULTS: For the HDRB cohort, the overall actuarial 5-year FFbFn2 was 67.4% (95% CI: 58.2-75.5%). For the HDRB doses of 16 and 20 Gy, the 5-year FFbFn2 rates were 58.8% (95% CI: 41.9-72.5%) and 77.3% (95% CI: 64.4-88.3%), respectively (log-rank test p = 0.07). Compared to men treated with 66 Gy EBRT, using multivariate analysis, there was no significant benefit to using HDRB with the FFbFn2 outcome (p = 0.52), yet the ACD suggested a significant advantage (hazard ratio 0.50, 95% CI: 0.29-0.86, p = 0.011). There was a trend to better FFbFn2 outcomes with increasing biologically effective doses (p = 0.09), which was significant using the ACD (p = 0.0003). CONCLUSIONS: The data support HDRB boost as a potential means of dose escalation in prostate cancer. Significant findings using the ACD need to be validated with contemporary biochemical failure definitions. Prospective trials to optimize fractionation and evaluate outcomes in comparison to contemporary EBRT techniques are warranted.
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Clinical Conference Acceptability of short term neo-adjuvant androgen deprivation in patients with locally advanced prostate cancer. 2003
Lamb DS, Denham JW, Mameghan H, Joseph D, Turner S, Matthews J, Franklin I, Atkinson C, North J, Poulsen M, Kovacev O, Robertson R, Francis L, Christie D, Spry NA, Tai KH, Wynne C, Duchesne G. · Wellington Cancer Centre, Wellington, New Zealand. · Radiother Oncol. · Pubmed #13129633 No free full text.
Abstract: PURPOSE: To determine the acceptability of short term neo-adjuvant maximal androgen deprivation (MAD) to patients treated with external beam radiation for locally advanced prostate cancer. METHODS: Between 1996 and 2000, 818 patients with locally advanced, but non-metastatic, prostate cancer were entered into a randomised clinical trial (TROG 96.01), which compared radiation treatment alone with the same radiation treatment and 3 or 6 months neo-adjuvant MAD with goserelin and flutamide. Relevant symptoms, and how troublesome they were to the patient, were scored using a self-assessment questionnaire. This was completed by the patient at registration, and at specified times during and after treatment. Patients taking flutamide had liver function tests checked at regular intervals. RESULTS: All patients have completed at least 12 months follow-up after treatment. Nearly all patients completed planned treatment with goserelin, but 27% of patients in the 6-month MAD treatment arm, and 20% in the 3-month arm, had to stop flutamide early. This was mainly due to altered liver function (up to 17% patients) and bowel side effects (up to 8% patients). However, although flutamide resulted in more bowel symptoms for patients on MAD, there was significant reduction in some urinary symptoms on this treatment. Acute bowel and urinary side effects at the end of radiation treatment were similar in all treatment arms. Side effect severity was unrelated to radiation target volume size, which was reduced by MAD, but symptomatology prior to any treatment was a powerful predictor. Of the 36% of patients who were sexually active before any treatment, the majority became inactive whilst on MAD. However, sexual activity at 12 months after radiation treatment was similar in all treatment arms, indicating that the effects of short term MAD on sexual function are reversible. CONCLUSION: Despite temporary effects on sexual activity, and compliance difficulties with flutamide, short-term neo-adjuvant MAD was not perceived by patients to be a major inconvenience. If neo-adjuvant MAD in the way tested can be demonstrated to lead to improved biochemical control and/or survival, then patients would view these therapeutic gains as worthwhile. Compliance with short-term goserelin was excellent, confirming that LH-RH analogues have a potential role in more long-term adjuvant treatment. However, for more protracted androgen deprivation, survival advantages and deleterious effects need to be assessed in parallel, in order to determine the optimal duration of treatment.
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Article Recognizing false biochemical failure calls after radiation with or without neo-adjuvant androgen deprivation for prostate cancer. 2009
Denham JW, Kumar M, Gleeson PS, Lamb DS, Joseph D, Atkinson C, Matthews J, Tai KH, Spry NA, Christie D, Turner S, Greer PB, D'Este C, Steigler A. · University of Newcastle, New South Wales, Australia. · Int J Radiat Oncol Biol Phys. · Pubmed #19176272 No free full text.
Abstract: PURPOSE: We studied prostate-specific antigen (PSA) changes after radiation with or without neoadjuvant androgen deprivation to determine posttreatment PSA scenarios in which false-positive biochemical failures (FPBF) are most likely to occur. METHODS AND MATERIALS: In the Trans-Tasman Radiation Oncology 96.01 Group trial, patients with T2b, 2c, 3, 4 N0 prostate cancer were randomized to 3 or 6 months goserelin and flutamide (STAD) before and during 66 Gy to the prostate and seminal vesicles (XRT) or to XRT alone. Piecewise longitudinal changes in PSA before relapse were characterized and quantified to determine which might cause FPBF calls. RESULTS: Between 1996 and 2000, 802 eligible patients were randomized. Of these, 492 met the criteria for American Society for Therapeutic Radiology and Oncology (ASTRO) failure and 467 for Phoenix failure. Seventy-seven ASTRO fails and 39 Phoenix fails were deemed false positives (FPs). The majority of FPBFs were associated with the "plateauing" in PSA values that follow posttreatment nadir. FPBFs were particularly common in men treated with STAD, in whom small, consecutive PSA rises before or during this phenomenon triggered 56 FP ASTRO fail calls. In these men, the Phoenix fail criteria triggered only 15 FPBF calls. However, the Phoenix criteria were more vulnerable than ASTRO to short-term isolated PSA rises during plateau, which resulted in 15 Phoenix fail calls but only 3 FP ASTRO fails. CONCLUSIONS: The Phoenix definition avoided 50% of FPBF calls that occurred with the ASTRO definition. Failures should be confirmed by further PSA rises before investigation and treatment is considered.
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Article Is there more than one proctitis syndrome? A revisitation using data from the TROG 96.01 trial. 2009
Capp A, Inostroza-Ponta M, Bill D, Moscato P, Lai C, Christie D, Lamb D, Turner S, Joseph D, Matthews J, Atkinson C, North J, Poulsen M, Spry NA, Tai KH, Wynne C, Duchesne G, Steigler A, Denham JW. · Calvary Mater Newcastle, NSW, Australia. · Radiother Oncol. · Pubmed #18952309 No free full text.
Abstract: PURPOSE: We sought to categorize longitudinal radiation-induced rectal toxicity data obtained from men participating in a randomised controlled trial for locally advanced prostate cancer. MATERIALS AND METHODS: Data from self-assessed questionnaires of rectal symptoms and clinician recorded remedial interventions were collected during the TROG 96.01 trial. In this trial, volunteers were randomised to radiation with or without neoadjuvant androgen deprivation. Characterization of longitudinal variations in symptom intensity was achieved using prevalence data. An integrated visualization and clustering approach based on memetic algorithms was used to define the compositions of symptom clusters occurring before, during and after radiation. The utility of the CTC grading system as a means of identifying specific injury profiles was evaluated using concordance analyses. RESULTS: Seven well-defined clusters of rectal symptoms were present prior to treatment, 25 were seen immediately following radiation and 7 at years 1, 2 and 3 following radiation. CTC grading did not concord with the degree of rectal 'distress' and 'problems' at all time points. Concordance was not improved by adding urgency to the CTC scale. CONCLUSIONS: The CTC scale has serious shortcomings. A powerful new technique for non-hierarchical clustering may contribute to the categorization of rectal toxicity data for genomic profiling studies and detailed patho-physiological studies.
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Article Time to biochemical failure and prostate-specific antigen doubling time as surrogates for prostate cancer-specific mortality: evidence from the TROG 96.01 randomised controlled trial. 2008
Denham JW, Steigler A, Wilcox C, Lamb DS, Joseph D, Atkinson C, Matthews J, Tai KH, Spry NA, Christie D, Gleeson PS, Greer PB, D'Este C, Anonymous00024. · School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia. · Lancet Oncol. · Pubmed #18929505 No free full text.
Abstract: BACKGROUND: Surrogate endpoints for prostate cancer-specific mortality after curative primary treatment are not well established. We sought to assess time to biochemical failure (TTBF) and prostate-specific antigen doubling time (PSADT) after failure of curative treatment as candidates for this endpoint. METHODS: PSA and survival data from the Trans-Tasman Radiation Oncology Group (TROG) 96.01 trial were used to assess surrogate candidates. Between June 28, 1996, and Feb 16, 2000, 802 eligible men with locally advanced prostate cancer were randomly allocated to prostatic irradiation alone, or to 3 or 6 months of maximum short-term androgen deprivation (STAD) before and during radiation. Successful surrogates were required to satisfy the Prentice criteria and to predict the trial finding. The TROG 96.01 trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000237482. FINDINGS: 6 months of STAD was shown to significantly decrease prostate cancer-specific mortality compared with radiation alone, but 3 months of STAD did not result in a decrease. Relative to radiation alone, the hazard ratio of prostate cancer-specific mortality from randomisation was 0.95 (95% CI 0.63-1.41; p=0.79) in the 3-month STAD treatment arm and 0.56 (0.36-0.88; p=0.01) in the 6-month arm. PSADT predicted the trial finding and satisfied all four Prentice criteria at the cutpoints of less than 12 months and less than 15 months, with proportion of treatment effect ratios between 0.36 and 0.56. Time to biochemical failure was better than PSADT at predicting the trial finding and satisfying all four Prentice criteria at cutpoints of less than 1.5, less than 2, and less than 2.5 years, with proportion of treatment effect ratios between 0.45 and 0.64. INTERPRETATION: This study provides proof of principle that TTBF and PSADT can be useful as surrogate endpoints for prostate cancer-specific mortality and offer potential to substantially reduce follow up in clinical trials. These endpoints now require assessment in multi-trial meta-analyses before use in clinical trials.
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Article Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. 2007
D'Amico AV, Denham JW, Crook J, Chen MH, Goldhaber SZ, Lamb DS, Joseph D, Tai KH, Malone S, Ludgate C, Steigler A, Kantoff PW. · Departments of Radiation Oncology and Medicine, Cardiovascular Division, Brigham and Women's Hospital and Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. · J Clin Oncol. · Pubmed #17557956 No free full text.
Abstract: PURPOSE: We evaluated whether the timing of fatal myocardial infarction (MI) was influenced by the administration of androgen suppression therapy (AST). PATIENTS AND METHODS: The study cohort comprised 1,372 men who were enrolled onto three randomized trials between February 1995 and June 2001. In the three trials, the men were randomly assigned to receive radiation therapy with 0 versus 3 versus 6, 3 versus 8, or 0 versus 6 months of AST. Fine and Gray's regression was used to determine the clinical factors associated with the time to fatal MI, and estimates of time to fatal MI were calculated using a cumulative incidence method. When comparing the cumulative incidence estimates using Gray's k-sample P values, increased weight was ascribed to the earlier data because recovery of testosterone is expected for most men within 2 years after short-course AST. RESULTS: Men age 65 years or older who received 6 months of AST experienced shorter times to fatal MIs compared with men in this age group who did not receive AST (P = .017) and men younger than 65 years (P = .016). No significant difference (P = .97) was observed in the time to fatal MIs in men age 65 years or older who received 6 to 8 months of AST compared with 3 months of AST. CONCLUSION: The use of AST is associated with earlier onset of fatal MIs in men age 65 years or older who are treated for 6 months compared with men who are not treated with AST.
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Article Short- vs long-term androgen suppression plus external beam radiation therapy and survival in men of advanced age with node-negative high-risk adenocarcinoma of the prostate. free! 2007
D'Amico AV, Denham JW, Bolla M, Collette L, Lamb DS, Tai KH, Steigler A, Chen MH. · Department of Radiation Oncology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Boston, Massachusetts, USA. · Cancer. · Pubmed #17397033 links to free full text
Abstract: BACKGROUND: The study evaluated whether the use of 3 years as compared with 6 months of androgen suppression therapy (AST) combined with external beam radiation therapy (RT) in the treatment of high-risk prostate cancer was associated with prolonged survival in advanced age men. METHODS: A pooled analysis of 311 men enrolled in 3 prospective randomized trials between 1987 and 2000 who received 6 months or 3 years of AST and RT for locally advanced or high-grade localized adenocarcinoma of the prostate comprised the study cohort. Cox regression multivariable analysis was performed adjusting for known prognostic factors to determine whether the treatment received was associated with time to death after randomization. The median age and follow-up was 70 and 5.9 years, respectively, during which 82 (26%) deaths occurred. RESULTS: Treatment received was not significantly associated with survival time after randomization (adjusted hazard ratio [AHR]: 1.1; 95% confidence interval [CI]: 0.7, 1.8; P = .70), whereas age at randomization (AHR: 1.05; 95% CI: 1.01, 1.09; P = .02) was. The presence of Gleason score 8 to 10 cancers approached significance (AHR: 1.6; 95% CI: 0.9, 2.6; P = .09). CONCLUSIONS: After adjusting for known prognostic factors, the treatment of node-negative, high-risk prostate cancer using 3 years as compared with 6 months of AST with RT was not associated with prolonged survival in men of advanced age. The European Organization for Research and Treatment of Cancer randomized trial will help answer whether unknown confounding factors affected the results of the study.
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Article Delayed rectal and urinary symptomatology in patients treated for prostate cancer by radiotherapy with or without short term neo-adjuvant androgen deprivation. 2005
Christie D, Denham J, Steigler A, Lamb D, Turner S, Mameghan H, Joseph D, Matthews J, Franklin I, Atkinson C, North J, Poulsen M, Spry NA, Tai KH, Wynne C, Duchesne G, Kovacev O, Francis L, Kramar A, D'Este C, Bill D. · East Coast Cancer Centre, Tugun, Queensland, Australia. · Radiother Oncol. · Pubmed #16271786 No free full text.
Abstract: BACKGROUND AND PURPOSE: To identify contributing factors to delayed rectal and urinary symptoms in a randomised trial comparing different durations of maximal androgen deprivation (MAD), given prior to radiotherapy, for locally advanced prostate cancer. PATIENTS AND METHODS: Between 1996 and 2000, 818 patients with stages T2b,c, 3 and 4 prostate cancer were entered into a trial comparing 0, 3 and 6 months of MAD prior to and during radiotherapy. Their delayed normal tissue effects were recorded by their treating doctors using standardised scales and by the patients using a self-assessment questionnaire regularly. Time to occurrence and prevalence data were analysed. RESULTS: Rectal and urinary symptom levels were observed to vary markedly over time in at least 80% of patients, with some indicating lasting resolution of symptoms. Prevalence rates were found to be substantially lower than actuarial probability rates. Baseline symptom levels and greatest acute symptom levels were both very powerful predictors. Obstructive lower urinary tract symptoms were noted to improve during the first 4 years after radiotherapy in approximately 60% of cases in each treatment arm. However, the treatment arm itself was not shown to influence these improvements in other univariate or multivariate analyses. MAD was shown to reduce both time to occurrence and prevalence of delayed proctopathic symptoms, but this effect was confirmed statistically in the 3 month treatment arm only. Multivariate models indicated that higher levels of haemoglobin prior to any treatment may in some way protect against delayed proctopathic symptoms. CONCLUSIONS: Prevalence data provide more clinically meaningful estimates of risk of delayed effects in normal tissues where assessment relies substantially on reported symptom levels. In these tissues consideration of the impact of baseline symptom levels and pathologies, and greatest acute symptom levels in analyses of delayed effects appears mandatory. Obstructive lower urinary symptoms improve over several years in the majority of patients treated for locally advanced prostate cancer by radiotherapy. Future research could address whether rectal toxicity is affected by initial haemoglobin levels and declines in it due to MAD.
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Article Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. 2005
Denham JW, Steigler A, Lamb DS, Joseph D, Mameghan H, Turner S, Matthews J, Franklin I, Atkinson C, North J, Poulsen M, Christie D, Spry NA, Tai KH, Wynne C, Duchesne G, Kovacev O, D'Este C, Anonymous00019. · Newcastle Mater Hospital, Newcastle, New South Wales, Australia. · Lancet Oncol. · Pubmed #16257791 No free full text.
Abstract: BACKGROUND: Androgen deprivation is an established treatment regimen for disseminated prostate cancer; however, its role in patients with localised cancer is less clear. We did a large randomised controlled trial to determine whether 3 months or 6 months of androgen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer. METHODS: 818 men with locally advanced prostate cancer were randomly assigned to: no androgen deprivation (ie, radiotherapy alone: 66 Gy in 33 fractions of 2 Gy per day over 6.5-7.0 weeks to the prostate and seminal vesicles); 3 months' androgen deprivation with 3.6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy (same regimen as control group); or 6 months' androgen deprivation, with the same regimen, starting 5 months before radiotherapy (same regimen as control group). Primary endpoints were time to local failure and prostate-cancer-specific survival; secondary endpoints were distant failure, disease-free survival, and freedom from salvage treatment. Analyses were done by intention to treat. FINDINGS: 802 (98%) patients were eligible for analysis. Median follow-up was 5.9 years (range 0.1-8.5). Compared with patients assigned no androgen deprivation, those assigned 3 months' treatment had significantly improved local failure (hazard ratio [HR] 0.56 [95% CI 0.39-0.79], p=0.001), biochemical failure-free survival (0.70 [0.56-0.88], p=0.002), disease-free survival (0.65 [0.52-0.80], p=0.0001), and freedom from salvage treatment (0.73 [0.56-0.96], p=0.025). 6 months' androgen deprivation significantly improved local failure (0.42 [0.28-0.62], p<0.0001), biochemical failure-free survival (0.58 [0.46-0.74], p<0.0001), disease-free survival (0.56 [0.45-0.69], p<0.0001), freedom from salvage treatment (0.53 [0.40-0.71], p<0.0001), distant failure (0.67 [0.45-0.99], p=0.046) and prostate-cancer-specific survival (0.56 [0.32-0.98], p=0.04) compared with no androgen deprivation. INTERPRETATION: 6 months' androgen deprivation given before and during radiotherapy improves the outlook of patients with locally advanced prostate cancer. Further follow-up is needed to estimate precisely the size of survival benefits. Increased radiation doses and additional periods of androgen deprivation might lead to further benefit.
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Article Three-dimensional conformal radiotherapy in the treatment of prostate cancer in Australia and New Zealand: Report on a survey of radiotherapy centres and the proceedings of a consensus workshop. 2004
Tai KH, Duchesne G, Turner S, Kneebone A, See A, Gogna K, Berry M. · Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. · Australas Radiol. · Pubmed #15601331 No free full text.
Abstract: There is an increasing use of 3-D conformal radiotherapy (3DCRT) in the radiotherapeutic management of prostate cancer. The Faculty of Radiation Oncology Genito-Urinary Group carried out a survey of Australian and New Zealand radiotherapy centres in the preparation of a consensus workshop. Of the 19 centres that were represented, there were 24 radiation oncologists, 16 radiation therapists and 12 medical physicists. The survey collected demographic information and data on the practices undertaken at those centres when delivering curative radiotherapy in the treatment of prostate cancer. There was much variation in the delivery of treatment in the areas of patient set-up, contouring of target volumes and organs of interest during computer planning, the techniques and the dose constraints used in these techniques, the use of adjuvant androgen deprivation therapy and the quality assurance processes used in monitoring effects of treatment. This variability reflects the range of data in the published literature. Emerging trends of practices were also identified. This is a first report on a multi-disciplinary approach to the development of guidelines in 3DCRT of prostate cancer.
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