Introduction
Quality assurance methods are incorporated into multicentre radiotherapy clinical trials for ensuring consistent application of trial protocol and quantifying treatment uncertainties. ...The study's purpose was to determine whether post‐treatment disease progression is associated with measures of the quality of radiotherapy treatment.
Methods
The TROG 03.04 RADAR trial tested the impact of androgen deprivation on prostate cancer patients receiving dose‐escalated external beam radiation therapy. The trial incorporated a plan‐review process and Level III dosimetric intercomparison at each centre, from which variables suggestive of treatment quality were collected. Kaplan–Meier statistics and Fine and Gray competing risk modelling were employed to test for associations between quality‐related variables and the participant outcome local composite progression.
Results
Increased ‘dose‐difference’ at the prostatic apex and at the anterior rectal wall, between planned and measured dose, was associated with reduced progression. Participants whose treatment plans included clinical target volume (CTV) to planning target volume (PTV) margins exceeding protocol requirements also experienced reduced progression. Other quality‐related variables, including total accrual from participating centres, measures of target coverage and other variations from protocol, were not significantly associated with progression.
Conclusions
This analysis has revealed the association of several treatment quality factors with disease progression. Increased dose and dose margin coverage in the prostate region can reduce disease progression. Extensive and rigorous monitoring has helped to maximise treatment quality, reducing the incidence of quality‐indicator outliers, and thus reduce the chance of observing significant associations with progression rates.
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.
Repeated surveys of prostate cancer (PCa) patients indicate that their prevalence of depression is well above that for their non-PCa peers. Although standard first-line treatments for depression are ...only about 35% effective, some recent comments have suggested that a focus upon the possible correlates (factors that aggravate or mediate depression) might help improve treatment efficacy. To investigate this issue, 144 10 year PCa survivors were asked about the frequency of urinary incontinence, a common side effect of some PCa treatments. The 53 patients who suffered urinary incontinence had significantly higher depression scores on the Zung Self-rating Depression Scale than those patients who did not report urinary incontinence. Using mediation analysis, patients' psychological resilience (PR) significantly mediated the depressive effects of urinary incontinence, but those effects were confined to just one of the five components of PR-a sense of control over the things that happen to oneself. Implications for treatment models of psychosocial oncology support for PCa survivors are discussed.
In the TROG 96.01 trial 6month neo-adjuvant androgen suppression (NAS) and radiotherapy (RT) for locally advanced prostate cancer prevented distant progressions (DPs) when compared to RT alone, but ...3months did not. We ask why?
Between 1996 and 2000, 802 men with T2-4 N0 M0 prostate cancers received RT alone (0month NAS) to 66Gy, 3months or 6months NAS before RT. Interval hazards and cumulative incidences of DP were compared using competing risks methodology.
In the first 4 follow-up years 39, 40 and 26 DPs were diagnosed in subjects treated with 0, 3 and 6month NAS, respectively. Compared with 0month, significant reductions in PSA doubling time in subjects with DP occurred following 3month NAS (p=0.01), but a significant reduction (p=0.01) and a near significant delay in DPs (p=0.06) occurred after 6month NAS. Subsequently 25, 20 and 11 DPs occurred in the three trial arms. After early secondary therapy for PSA or local progression 34, 19 and 12 DPs were diagnosed after median delays of almost 4years.
The data are consistent with the failure of 3month NAS to prevent the progression of sub-clinical metastatic deposits already present before treatment.
Abstract Purpose In the TROG 96.01 trial 6 month neo-adjuvant androgen suppression (NAS) and radiotherapy (RT) for locally advanced prostate cancer prevented distant progressions (DPs) when compared ...to RT alone, but 3 months did not. We ask why? Methods Between 1996 and 2000, 802 men with T2-4 N0 M0 prostate cancers received RT alone (0 month NAS) to 66 Gy, 3 months or 6 months NAS before RT. Interval hazards and cumulative incidences of DP were compared using competing risks methodology. Results In the first 4 follow-up years 39, 40 and 26 DPs were diagnosed in subjects treated with 0, 3 and 6 month NAS, respectively. Compared with 0 month, significant reductions in PSA doubling time in subjects with DP occurred following 3 month NAS ( p = 0.01), but a significant reduction ( p = 0.01) and a near significant delay in DPs ( p = 0.06) occurred after 6 month NAS. Subsequently 25, 20 and 11 DPs occurred in the three trial arms. After early secondary therapy for PSA or local progression 34, 19 and 12 DPs were diagnosed after median delays of almost 4 years. Conclusions The data are consistent with the failure of 3 month NAS to prevent the progression of sub-clinical metastatic deposits already present before treatment.
Abstract Background and purpose Temporal distributions in PSA levels following therapeutic intervention for prostate cancer are known to contain characteristics prognostic of disease progression. An ...algorithm was developed for extracting such characteristics, specifically in the context of previous observations following radiotherapy. Material and methods Segmented regression methods were investigated for characterising the ‘signatures’ in log(PSA) descent patterns between intervention and nadir. Results The segmented regression method can automatically identify and parameterise features in a PSA distribution including failure points and doubling time patterns following nadir. The method has previously been applied to the analysis of descent patterns on a large clinical data series (Radiother Oncol 2009;90:382–8). Batch-processing of data using the method for all patients in a clinical trial would establish population parameter values and ranges. Subsequent application to an individual patient’s PSA data would determine which resulting prognostic group they fall into. Conclusions As more complete and higher-resolution PSA progression datasets become available, techniques such as presented here will allow flexible definition of the characteristics being examined and rapid extraction of parameters for correlation with clinical progression data.
Another form of subgroup to beware Denham, James W; Lamb, David S; Joseph, David ...
Radiotherapy and oncology,
12/2011, Letnik:
101, Številka:
3
Journal Article
Abstract Background We sought to determine whether inter-patient variations in pattern of PSA changes after radiation exist and, if so, are they prognostically significant. Methods In the ...Trans-Tasman Radiation Oncology Group (TROG) 96.01 randomized controlled trial, patients with T2b,c,3,4 N0 prostate cancer (PC) were randomised to 0, 3 or 6 months maximal androgen deprivation prior to 66 Gy to the prostate and seminal vesicles (XRT). Patterns of anatomical site of failure were one of the trial endpoints. Serial serum PSA’s were mandated at all follow-up visits. Pattern recognition software was developed to characterize PSA response “signatures” (PRS) after therapy in individual patients. Results By 2000, 270 eligible patients were randomised to radiation alone. Individual patient PSA values were observed to descend after radiation according to one of two characteristic “signatures”: single exponential (PRS Type 1), non-exponential (PRS Type 2). Compared to PRS Type 1, men with PRS Type 2 (50% of the group) had lower PSA nadir (nPSA) levels ( p < .0001), longer doubling times on relapse ( p = .006) and significantly lower rates of local (hazard ratio HR: 0.47, 95% confidence interval 0.30–0.75, p = .0014) and distant failure (HR: 0.250.13–0.46, p < .0001), death due to PC (HR: 0.200.10–0.42, p < .0001) and death due to any cause (HR: 0.37 0.23–0.60, p < .0001). PRS retained its powerful prognostic significance in Cox models that incorporated all key pre-treatment covariates and nPSA. Conclusions PRS reflect the presence of tumor phenotypes that vary substantially in their clinical behavior and response to XRT. Molecular characterization is now necessary.
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