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Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer.

Warner A, Pickles T, Crook J, Martin AG, Souhami L, Catton C, Lukka H, Rodrigues G - Cureus (2015)

Bottom Line: Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS.Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates.Future work should be directed at examining the role of additional prognostic factors, comorbidities, and toxicity in predicting survival outcomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Radiation Oncology, London Health Sciences Centre, London, Ontario, CA.

ABSTRACT

Purpose: Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II "Phoenix" definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database.

Methods and materials: Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy  (n=822). Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS. Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates.

Results: Patients receiving LDR brachytherapy had a mean age of 64 ± 7 years, a mean baseline PSA of 6.3 ± 3.0 ng/mL, 75% had a Gleason 6, and 15% had a Gleason 7, whereas patients receiving EBRT had a mean age of 70 ± 6 years, a mean baseline PSA of 11.6 ± 10.7 ng/mL, 30% had a Gleason 6, 55% had a Gleason 7, and 14% had a Gleason 8-10. Nomograms for 5-year BFFS included age, use and duration of androgen deprivation therapy (ADT), baseline PSA, T stage, and Gleason score for LDR brachytherapy and an ADT (months), baseline PSA, Gleason score, and biological effective dose (Gy) for EBRT.

Conclusions: Clinical nomograms examining 5-year BFFS were developed for patients receiving either LDR brachytherapy or conventionally fractionated EBRT and may assist clinicians in predicting an outcome. Future work should be directed at examining the role of additional prognostic factors, comorbidities, and toxicity in predicting survival outcomes.

No MeSH data available.


Related in: MedlinePlus

Summary of patient selection and creation of final analysis cohorts (LDR – Low-Dose Rate (Brachytherapy), HDR – High-Dose Rate (Brachytherapy), EBRT – External Beam Radiation Therapy).
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FIG1: Summary of patient selection and creation of final analysis cohorts (LDR – Low-Dose Rate (Brachytherapy), HDR – High-Dose Rate (Brachytherapy), EBRT – External Beam Radiation Therapy).

Mentions: Patients receiving LDR brachytherapy ≥ 144 Gy alone (n=4,320) or EBRT (n=832) were eligible for analysis. To address EBRT dose heterogeneity across participating institutions and to ensure the nomograms would be relevant to modern radiotherapy practice, only patients identified as receiving sufficient dose escalation, using either three-dimensional conformal therapy or intensity-modulated radiation therapy (defined as ≥ 70 Gy (GUROC low-risk and high-risk) or ≥ 74 Gy (GUROC intermediate risk)) were considered for this analysis [45]. To reduce the risk of survival bias, landmark analysis techniques were applied by manually excluding patients with follow-up durations below an a priori selected landmark threshold [46-49]. Generally, the use of landmark analysis in the development of nomograms for prostate cancer has been absent with the exception of a study published by Roeloffzen, et al. in 2011 examining acute urinary retention in patients receiving LDR brachytherapy [38]. Six months was selected for the present study in order to maintain sufficient statistical power for analysis relative to the primary endpoint of 5-year biochemical failure-free survival [47-48]. Therefore, patients with follow-up durations less than six months were excluded from analysis (LDR brachytherapy (n=112); EBRT (n=10)). This formed two final analysis cohorts of 4,208 patients receiving LDR brachytherapy and 822 patients receiving EBRT. Details of patient selection are shown in Figure 1.


Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer.

Warner A, Pickles T, Crook J, Martin AG, Souhami L, Catton C, Lukka H, Rodrigues G - Cureus (2015)

Summary of patient selection and creation of final analysis cohorts (LDR – Low-Dose Rate (Brachytherapy), HDR – High-Dose Rate (Brachytherapy), EBRT – External Beam Radiation Therapy).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494461&req=5

FIG1: Summary of patient selection and creation of final analysis cohorts (LDR – Low-Dose Rate (Brachytherapy), HDR – High-Dose Rate (Brachytherapy), EBRT – External Beam Radiation Therapy).
Mentions: Patients receiving LDR brachytherapy ≥ 144 Gy alone (n=4,320) or EBRT (n=832) were eligible for analysis. To address EBRT dose heterogeneity across participating institutions and to ensure the nomograms would be relevant to modern radiotherapy practice, only patients identified as receiving sufficient dose escalation, using either three-dimensional conformal therapy or intensity-modulated radiation therapy (defined as ≥ 70 Gy (GUROC low-risk and high-risk) or ≥ 74 Gy (GUROC intermediate risk)) were considered for this analysis [45]. To reduce the risk of survival bias, landmark analysis techniques were applied by manually excluding patients with follow-up durations below an a priori selected landmark threshold [46-49]. Generally, the use of landmark analysis in the development of nomograms for prostate cancer has been absent with the exception of a study published by Roeloffzen, et al. in 2011 examining acute urinary retention in patients receiving LDR brachytherapy [38]. Six months was selected for the present study in order to maintain sufficient statistical power for analysis relative to the primary endpoint of 5-year biochemical failure-free survival [47-48]. Therefore, patients with follow-up durations less than six months were excluded from analysis (LDR brachytherapy (n=112); EBRT (n=10)). This formed two final analysis cohorts of 4,208 patients receiving LDR brachytherapy and 822 patients receiving EBRT. Details of patient selection are shown in Figure 1.

Bottom Line: Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS.Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates.Future work should be directed at examining the role of additional prognostic factors, comorbidities, and toxicity in predicting survival outcomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Radiation Oncology, London Health Sciences Centre, London, Ontario, CA.

ABSTRACT

Purpose: Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II "Phoenix" definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database.

Methods and materials: Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy  (n=822). Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS. Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates.

Results: Patients receiving LDR brachytherapy had a mean age of 64 ± 7 years, a mean baseline PSA of 6.3 ± 3.0 ng/mL, 75% had a Gleason 6, and 15% had a Gleason 7, whereas patients receiving EBRT had a mean age of 70 ± 6 years, a mean baseline PSA of 11.6 ± 10.7 ng/mL, 30% had a Gleason 6, 55% had a Gleason 7, and 14% had a Gleason 8-10. Nomograms for 5-year BFFS included age, use and duration of androgen deprivation therapy (ADT), baseline PSA, T stage, and Gleason score for LDR brachytherapy and an ADT (months), baseline PSA, Gleason score, and biological effective dose (Gy) for EBRT.

Conclusions: Clinical nomograms examining 5-year BFFS were developed for patients receiving either LDR brachytherapy or conventionally fractionated EBRT and may assist clinicians in predicting an outcome. Future work should be directed at examining the role of additional prognostic factors, comorbidities, and toxicity in predicting survival outcomes.

No MeSH data available.


Related in: MedlinePlus