scholarly journals Prostate cancer tumour control probability modelling for external beam radiotherapy based on multi-parametric MRI-GTV definition

2020 ◽  
Author(s):  
Ilias Sachpazidis ◽  
Panayiotis Mavroidis ◽  
Constantinos Zamboglou ◽  
Christina Marie Klein ◽  
Anca-Ligia Grosu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Logistic Model ◽  
Radiation Treatment ◽  
Prostate Gland ◽  
Biochemical Relapse ◽  
Linear Quadratic ◽  
Tumour Control ◽  
Tumour Control Probability ◽  
Multivariate Logistic Model

Abstract Purpose: To evaluate the applicability and estimate the radiobiological parameters of linear-quadratic Poisson tumour control probability (TCP) model for primary prostate cancer patients for two relevant target structures (prostate gland and GTV). The TCP describes the dose–response of prostate after definitive radiotherapy (RT). Also, to analyse and identify possible significant correlations between clinical and treatment factors such as planned dose to prostate gland, dose to GTV, volume of prostate and mpMRI-GTV based on multivariate logistic regression model.Methods: The study included 129 intermediate and high-risk prostate cancer patients (cN0 and cM0), who were treated with image-guided intensity modulated radiotherapy (IMRT) +/- androgen deprivation therapy with a median follow-up period of 81.4 months (range: 42.0 - 149.0) months. Tumour control was defined as biochemical relapse free survival according to the Phoenix definition (BRFS). MpMRI-GTV was delineated retrospectively based on a pre-treatment multi-parametric MR imaging (mpMRI), which was co-registered to the planning CT. The clinical treatment planning procedure was based on prostate gland, delineated on CT imaging modality. Furthermore, we also fitted the clinical data to TCP model for the two considered targets for the 5-year follow-up after radiation treatment, where our cohort was composed of a total number of 108 patients, of which 19 were biochemical relapse (BR) patients. Results: For the median follow-up period of 81.4 months (range: 42.0 - 149.0) months, our results indicated an appropriate α/β = 1.3 Gy for prostate gland and α/β = 2.9 Gy for mpMRI-GTV. Only for prostate gland, EQD2 and gEUD2Gy were significantly lower in the biochemical relapse (BR) group compared to the biochemical control (BC) group. Fitting results to the linear-quadratic Poisson TCP model for prostate gland and α/β = 1.3 Gy were D50 = 66.8 Gy with 95%CI [64.6 Gy, 69.0 Gy], and γ = 3.81 with 95%CI [2.58, 5.20]. For mpMRI-GTV and α/β = 2.9 Gy, D50 was 68.1 Gy with 95%CI [66.1 Gy, 70.0 Gy], and γ = 4.45 with 95%CI [3.00, 6.12]. The fitness of the model was better for prostate gland. For the multivariate logistic model, the gEUD2Gy for prostate gland showed a very high significant predictive value (p = 0.001), whereas regarding mpMRI-GTV only its volume showed a significance (p = 0.01). Finally, for the 5-year follow-up after the radiation treatment, our results for the prostate gland were: D50=64.6Gy [61.6Gy, 67.4Gy], γ=3.08 [2.03, 4.35], α/β=2.2Gy (95%CI was undefined). For the mpMRI-GTV, the optimizer was unable to deliver any reasonable results for the expected clinical D50 and α/β. The results for the mpMRI-GTV were: D50=50.1Gy [44.6Gy, 56.0Gy], γ=0.84 [0.53, 1.21], α/β=0.0Gy (95%CI was undefined). Conclusion: The linear-quadratic Poisson TCP model was better fit when the prostate gland was considered as responsible target than with mpMRI-GTV. This is compatible with the results of the comparison of the dose distributions among BR and BC groups and with the results achieved with the multivariate logistic model regarding gEUD 2Gy . Probably limitations of mpMRI in defining the GTV explain these results. Another explanation could be the relatively homogeneous dose prescription and the relatively low number of recurrences.

scholarly journals Prostate cancer tumour control probability modelling for external beam radiotherapy based on multi-parametric MRI-GTV definition

2020 ◽  
Author(s):  
Ilias Sachpazidis ◽  
Panayiotis Mavroidis ◽  
Constantinos Zamboglou ◽  
Christina Marie Klein ◽  
Anca-Ligia Grosu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Radiation Treatment ◽  
Prostate Gland ◽  
Multivariate Logistic Regression Model ◽  
Biochemical Relapse ◽  
Linear Quadratic ◽  
Tumour Control ◽  
Tumour Control Probability

Abstract Purpose: To evaluate the applicability and estimate the radiobiological parameters of linear-quadratic Poisson tumour control probability (TCP) model for primary prostate cancer patients for two relevant target structures (prostate gland and GTV). The TCP describes the dose–response of prostate after definitive radiotherapy (RT). Also, to analyse and identify possible significant correlations between clinical and treatment factors such as planned dose to prostate gland, dose to GTV, volume of prostate and mpMRI-GTV based on multivariate logistic regression model. Methods: The study included 129 intermediate and high-risk prostate cancer patients (cN0 and cM0), who were treated with image-guided intensity modulated radiotherapy (IMRT) +/- androgen deprivation therapy with a median follow-up period of 81.4 months (range: 42.0 - 149.0) months. Tumour control was defined as biochemical relapse free survival according to the Phoenix definition (BRFS). MpMRI-GTV was delineated retrospectively based on a pre-treatment multi-parametric MR imaging (mpMRI), which was co-registered to the planning CT. The clinical treatment planning procedure was based on prostate gland, delineated on CT imaging modality. Furthermore, we also fitted the clinical data to TCP model for the two considered targets for the 5-year follow-up after radiation treatment, where our cohort was composed of a total number of 108 patients, of which 19 were biochemical relapse (BR) patients.Results: For the median follow-up period of 81.4 months (range: 42.0 - 149.0) months, our results indicated an appropriate α/β=1.3 Gy for prostate gland and α/β=2.9 Gy for mpMRI-GTV. Only for prostate gland, EQD2 and gEUD2Gy were significantly lower in the biochemical relapse (BR) group compared to the biochemical control (BC) group. Fitting results to the linear-quadratic Poisson TCP model for prostate gland and α/β=1.3 Gy were D50=66.8 Gy with 95%CI [64.6 Gy, 69.0 Gy], and γ=3.8 with 95%CI [2.6, 5.2]. For mpMRI-GTV and α/β=2.9 Gy, D50 was 68.1 Gy with 95%CI [66.1 Gy, 70.0 Gy], and γ=4.5 with 95%CI [3.0, 6.1]. Finally, for the 5-year follow-up after the radiation treatment, our results for the prostate gland were: D50=64.6Gy [61.6Gy, 67.4Gy], γ=3.1 [2.0, 4.4], α/β=2.2Gy (95%CI was undefined). For the mpMRI-GTV, the optimizer was unable to deliver any reasonable results for the expected clinical D50 and α/β. The results for the mpMRI-GTV were D50=50.1Gy [44.6Gy, 56.0Gy], γ=0.8 [0.5, 1.2], α/β=0.0Gy (95%CI was undefined). For a follow-up time of 5 years and a fixed α/β=1.6Gy, the TCP fitting results for prostate gland were D50=63.9Gy [60.8Gy, 67.0Gy], γ=2.9 [1.9, 4.1], and for mpMRI-GTV D50=56.3Gy [51.6Gy, 61.1Gy], γ=1.3 [0.8, 1.9].Conclusion: The linear-quadratic Poisson TCP model was better fit when the prostate gland was considered as responsible target than with mpMRI-GTV. This is compatible with the results of the comparison of the dose distributions among BR and BC groups and with the results achieved with the multivariate logistic model regarding gEUD2Gy. Probably limitations of mpMRI in defining the GTV explain these results. Another explanation could be the relatively homogeneous dose prescription and the relatively low number of recurrences. The failure to identify any benefit for considering mpMRI-GTV as the target responsible for the clinical response is confirmed when considering a fixed α/β=1.6Gy, a fixed follow-up time for biochemical response at 5 years or Gleason score differentiation.

scholarly journals Prostate cancer tumour control probability modelling for external beam radiotherapy based on multi-parametric MRI-GTV definition

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Ilias Sachpazidis ◽  
Panayiotis Mavroidis ◽  
Constantinos Zamboglou ◽  
Christina Marie Klein ◽  
Anca-Ligia Grosu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Radiation Treatment ◽  
Prostate Gland ◽  
Multivariate Logistic Regression Model ◽  
Biochemical Relapse ◽  
Linear Quadratic ◽  
Tumour Control ◽  
Tumour Control Probability

Abstract Purpose To evaluate the applicability and estimate the radiobiological parameters of linear-quadratic Poisson tumour control probability (TCP) model for primary prostate cancer patients for two relevant target structures (prostate gland and GTV). The TCP describes the dose–response of prostate after definitive radiotherapy (RT). Also, to analyse and identify possible significant correlations between clinical and treatment factors such as planned dose to prostate gland, dose to GTV, volume of prostate and mpMRI-GTV based on multivariate logistic regression model. Methods The study included 129 intermediate and high-risk prostate cancer patients (cN0 and cM0), who were treated with image-guided intensity modulated radiotherapy (IMRT) ± androgen deprivation therapy with a median follow-up period of 81.4 months (range 42.0–149.0) months. Tumour control was defined as biochemical relapse free survival according to the Phoenix definition (BRFS). MpMRI-GTV was delineated retrospectively based on a pre-treatment multi-parametric MR imaging (mpMRI), which was co-registered to the planning CT. The clinical treatment planning procedure was based on prostate gland, delineated on CT imaging modality. Furthermore, we also fitted the clinical data to TCP model for the two considered targets for the 5-year follow-up after radiation treatment, where our cohort was composed of a total number of 108 patients, of which 19 were biochemical relapse (BR) patients. Results For the median follow-up period of 81.4 months (range 42.0–149.0) months, our results indicated an appropriate α/β = 1.3 Gy for prostate gland and α/β = 2.9 Gy for mpMRI-GTV. Only for prostate gland, EQD2 and gEUD2Gy were significantly lower in the biochemical relapse (BR) group compared to the biochemical control (BC) group. Fitting results to the linear-quadratic Poisson TCP model for prostate gland and α/β = 1.3 Gy were D50 = 66.8 Gy with 95% CI [64.6 Gy, 69.0 Gy], and γ = 3.8 with 95% CI [2.6, 5.2]. For mpMRI-GTV and α/β = 2.9 Gy, D50 was 68.1 Gy with 95% CI [66.1 Gy, 70.0 Gy], and γ = 4.5 with 95% CI [3.0, 6.1]. Finally, for the 5-year follow-up after the radiation treatment, our results for the prostate gland were: D50 = 64.6 Gy [61.6 Gy, 67.4 Gy], γ = 3.1 [2.0, 4.4], α/β = 2.2 Gy (95% CI was undefined). For the mpMRI-GTV, the optimizer was unable to deliver any reasonable results for the expected clinical D50 and α/β. The results for the mpMRI-GTV were D50 = 50.1 Gy [44.6 Gy, 56.0 Gy], γ = 0.8 [0.5, 1.2], α/β = 0.0 Gy (95% CI was undefined). For a follow-up time of 5 years and a fixed α/β = 1.6 Gy, the TCP fitting results for prostate gland were D50 = 63.9 Gy [60.8 Gy, 67.0 Gy], γ = 2.9 [1.9, 4.1], and for mpMRI-GTV D50 = 56.3 Gy [51.6 Gy, 61.1 Gy], γ = 1.3 [0.8, 1.9]. Conclusion The linear-quadratic Poisson TCP model was better fit when the prostate gland was considered as responsible target than with mpMRI-GTV. This is compatible with the results of the comparison of the dose distributions among BR and BC groups and with the results achieved with the multivariate logistic model regarding gEUD2Gy. Probably limitations of mpMRI in defining the GTV explain these results. Another explanation could be the relatively homogeneous dose prescription and the relatively low number of recurrences. The failure to identify any benefit for considering mpMRI-GTV as the target responsible for the clinical response is confirmed when considering a fixed α/β = 1.6 Gy, a fixed follow-up time for biochemical response at 5 years or Gleason score differentiation.

scholarly journals Prostate cancer tumour control probability modelling for external beam radiotherapy based on multi-parametric MRI-GTV definition

2020 ◽  
Author(s):  
Ilias Sachpazidis ◽  
Panayiotis Mavroidis ◽  
Constantinos Zamboglou ◽  
Christina Marie Klein ◽  
Anca-Ligia Grosu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Logistic Model ◽  
External Beam Radiotherapy ◽  
Prostate Gland ◽  
Biochemical Relapse ◽  
Linear Quadratic ◽  
Tumour Control ◽  
Tumour Control Probability ◽  
Multivariate Logistic Model

Abstract Purpose: To evaluate the applicability and estimate the radiobiological parameters of linear-quadratic Poisson tumour control probability (TCP) model for primary prostate cancer patients for two relevant target structures (prostate gland and GTV). The TCP describes the dose–response of prostate after definitive radiotherapy (RT). Also, to analyse and identify possible significant correlations between clinical and treatment factors such as planned dose to prostate gland, dose to GTV, volume of prostate and mpMRI-GTV based on multivariate logistic regression model.Methods: The study included 129 intermediate and high-risk prostate cancer patients (cN0 and cM0), who were treated with image-guided intensity modulated radiotherapy (IMRT) +/- androgen deprivation therapy with a median follow-up period of 81.4 months (range: 42.0 - 149.0) months. Tumour control was defined as biochemical relapse free survival according to the Phoenix definition (BRFS). MpMRI-GTV was delineated retrospectively based on a pre-treatment multi-parametric MR imaging (mpMRI), which was co-registered to the planning CT. The clinical treatment planning procedure was based on prostate gland, delineated on CT imaging modality.Results: Our results indicated an appropriate α/β = 1.3 Gy for prostate gland and α/β = 2.9 Gy for mpMRI-GTV. Only for prostate gland, EQD2 and gEUD 2Gy were significantly lower in the biochemical relapse (BR) group compared to the biochemical control (BC) group. Fitting results to the linear-quadratic Poisson TCP model for prostate gland and α/β = 1.3 Gy were D 50 = 66.8 Gy with 95%CI [64.6 Gy, 69.0 Gy], and γ = 3.81 with 95%CI [2.58, 5.20]. For mpMRI-GTV and α/β = 2.9 Gy, D 50 was 68.1 Gy with 95%CI [66.1 Gy, 70.0 Gy], and γ = 4.45 with 95%CI [3.00, 6.12]. The fitness of the model was better for prostate gland. For the multivariate logistic model, the gEUD 2Gy for prostate gland showed a very high significant predictive value ( p = 0.001), whereas regarding mpMRI-GTV only its volume showed a significance ( p = 0.01).Conclusion: The linear-quadratic Poisson TCP model was better fit when the prostate gland was considered as responsible target than with mpMRI-GTV. This is compatible with the results of the comparison of the dose distributions among BR and BC groups and with the results achieved with the multivariate logistic model regarding gEUD 2Gy . Probably limitations of mpMRI in defining the GTV explain these results. Another explanation could be the relatively homogeneous dose prescription and the relatively low number of recurrences.

scholarly journals Derivation of the Tumour Control Probability (TCP) from a Cell Cycle Model

2006 ◽  
Vol 7 (2-3) ◽  
pp. 121-141 ◽  
Author(s):  
A. Dawson ◽  
T. Hillen
Keyword(s):  
Cell Cycle ◽  
Radiation Treatment ◽  
Malignant Cell ◽  
Time Dependent ◽  
Death Process ◽  
Linear Quadratic ◽  
Tumour Control ◽  
Tumour Control Probability ◽  
A Cell ◽  
General Time

In this paper, a model for the radiation treatment of cancer which includes the effects of the cell cycle is derived from first principles. A malignant cell population is divided into two compartments based on radiation sensitivities. The active compartment includes the four phases of the cell cycle, while the quiescent compartment consists of theG0state. Analysis of this active-quiescent radiation model confirms the classical interpretation of the linear quadratic (LQ) model, which is that a larger α/β ratio corresponds to a fast cell cycle, while a smaller ratio corresponds to a slow cell cycle. Additionally, we find that a large α/β ratio indicates the existence of a significant quiescent phase. The active-quiescent model is extended as a nonlinear birth–death process in order to derive an explicit time dependent expression for the tumour control probability (TCP). This work extends the TCP formula from Zaider and Minerbo and it enables the TCP to be calculated for general time dependent treatment schedules.

scholarly journals A proof-of-concept study on the use of prostate artery embolization prior to definitive radiotherapy in prostate cancer

2020 ◽  
Author(s):  
Jeffrey Peacock ◽  
Dhiraj Sikaria ◽  
Laura Maun-Garcia ◽  
Khosrow Javedan ◽  
Kosj Yamoah ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Treatment ◽  
Organs At Risk ◽  
Statistical Significance ◽  
Volume Reduction ◽  
Proof Of Concept ◽  
Artery Embolization ◽  
Definitive Radiotherapy ◽  
Prostate Artery Embolization

Abstract Backgrounds: Prostatic artery embolization (PAE) has been well studied as a clinically effective therapy for alleviating lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). We demonstrate a proof of concept for PAE prior to definitive radiotherapy in patients with prostate cancer.Methods: From 12/2017 to 07/2019, 57 patients underwent PAE for LUTS and BPH. Nine of these patients had PAE for LUTS in the setting of localized prostate cancer prior to receiving radiation. Five of the nine patients received their entire radiotherapy course at our institution and had clinical follow up were included in the analysis. Median follow up was 18 months from the time of PAE. LUTS improvement quantified by IPSS was the primary endpoint and a two tail students T test was used to compare statistical significance. Side effects during radiation were quantified using the CTCAE scoring system. Pre- and post- PAE plans were compared in the five patients that by performing an isovolumetric expansion of the post PAE plan (treated plan) equivalent to the measured volume reduction after PAE. Patient 1 and 2 had prostate and seminal vesicle RT alone while patients 3-5 had prostate with elective nodal coverage. Mean doses to organs at risk were compared between the two plans.Results: The average IPSS score pre-PAE was 17.40 compared to post-PAE of 3.6 (p=0.02). The average IPSS score reduction after PAE was 13.8 (5-30). The average prostatic volume reduction after PAE was 23.14% (7.2% - 47.7%). There were no CTCAE grade 3 (severe) or higher during radiation treatment. Post-PAE plans in patient 1 and 2 had on average 16.7% and 39.8% decrease in mean dose across the bladder, rectum, and penile bulb compared to the pre-PAE plans. There were no appreciable differences in dosimetry in the patients 3-5 who had nodal coverage. There was no biochemical failure in any of the patients.Conclusion: We demonstrate a proof of concept that prostate artery embolization is useful as an adjunctive procedure to alleviate LUTS, achieve significant volume reduction prior to radiation therapy, and decrease radiation related toxicity in the treatment of prostate cancer.

Tumour control probability of a UK cohort of lung SABR patients

2020 ◽  
pp. 1-3
Author(s):  
J. E. Marsden
Keyword(s):  
The Other ◽  
Stereotactic Ablative Radiotherapy ◽  
Linear Quadratic ◽  
Planning Techniques ◽  
Tumour Control ◽  
Tumour Control Probability ◽  
The Uk

Abstract Aims: The aim of this work is to report on the tumour control probability (TCP) of a UK cohort of lung stereotactic ablative radiotherapy patients (n = 198) for a range of dose and fractionations common in the UK. Materials and methods: TCP values for 3 (54 Gy), 5 (55 and 60 Gy) and 8 (50 Gy) fraction (#) schemes were calculated with the linear-quadratic Marsden TCP model using the Biosuite software. Results: TCP values of 100% were computed for the 3 # and for 5 # (α/β = 10 Gy) cohorts; reduced to 99% (range 97–100) for the 5 # cohort only when an α/β of 20 Gy was used. The average TCP value for the 50 Gy in 8 # regime was 97% (range 92–99, α/β = 10 Gy) and 64% (range 48–79, α/β = 20 Gy). Statistical significant differences were observed between the α/β of 10 Gy versus 20 Gy groups and between all data grouped by fraction. Conclusion: TCPs achievable with current planning techniques in the UK have been presented. The ultra-conservative 50 Gy in 8 # scheme returns a significantly lower TCP than the other regimes.

Radiation Treatment for Localized Prostate Cancer and the Risk of Developing Myelodysplastic Syndromes (MDS)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 120-120
Author(s):  
Sudipto Mukherjee ◽  
Chandana Reddy ◽  
Jay Ciezki ◽  
Ramon V. Tiu ◽  
Edward A. Copelan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Treatment ◽  
Previous History ◽  
World Health ◽  
Localized Prostate Cancer ◽  
Control Group ◽  
Surgery Group ◽  
Increased Risk ◽  
Secondary Mds

Abstract Abstract 120 Background: Both environmental radiation exposure and use of therapeutic radiation (XRT) in primary solid tumor malignancies increase the risk of secondary MDS. No data exist on the risk of developing secondary MDS in prostate cancer patients (pts) being treated with radiotherapy. Establishing this risk has important clinical implications, as prostate cancer is the leading cancer in men and radiation therapy has increasingly become the preferred modality for treatment of localized prostate cancer. Methods: We performed a prospective case control study of 11,015 pts with localized prostate adenocarcinoma newly diagnosed between 1986 and 2011 at Cleveland Clinic who underwent treatment with either radical prostatectomy (control group) or definitive radiotherapy (external beam radiotherapy [EBRT] or prostate interstitial brachytherapy [PI] – case group), to investigate the risk of radiation-related MDS. Data on demographics, surgery, radiation treatment, and follow-up were collected from merged prostate cancer and MDS databases. Cytogenetic risk groups were per International Prognostic Scoring System (IPSS) for MDS. Univariate and multivariate analyses were performed using the Fine and Gray competing risk model with MDS as a time-dependent endpoint (which incorporates differences in duration of follow-up) and death from any cause as the competing event, comparing radiotherapy groups to the surgical cohort as the reference group, controlling for age and follow-up frequency. Hazard ratios (HR) with 95% confidence intervals (CIs) are reported. Results: For all pts, median age was 64 years (yrs, range, 37 – 88) at the time of prostate cancer diagnosis: 69 yrs in EBRT, 67 yrs in PI, and 60 yrs in surgery pts, respectively (p<0.0001); 5119 (46%) were treated with XRT, 5896 (54%) with prostatectomy. None of the pts had a previous history of another malignancy. Among XRT pts, 2183 (43%) were treated with EBRT, 2936 (57%) with PI. Median follow-up was 3.0 yrs [(range, 0.0 – 25.2): 6.8 yrs in the EBRT group, 2.5 yrs in the PI group and 1.8 yrs in the surgery group, (p<0.0001)] following prostate intervention, longer (4.6 yrs) in pts treated since 1996, when PI was first performed [6.6 yrs in the EBRT group, 3.8 yrs in the PI group and 4.3 yrs in the surgery group, (p<0.0001)]. In the entire cohort, 30 pts developed MDS: 24 in the XRT group and 6 in the surgery group. MDS World Health Organization classification was: RA/RARS (n=12), RCMD (n=3), RAEB-1 (n=3), RAEB-2 (n=3), CMML (n=2), MDS-U (n=3) and unknown (n=4). IPSS cytogenetic risk classification was: good risk (n=17), intermediate risk (n=5), poor risk (n= 4) and unknown (n = 4). For MDS pts within the XRT group, median age at MDS diagnosis was 79 yrs (range, 74 – 89) for EBRT, 80 yrs (range, 64 – 100) for PI. The median time to develop MDS was 8.9 yrs (range, 0.9 – 20.2): 9.1 for EBRT, 8.2 for PI, and 13.0 for prostatectomy pts, respectively (p=0.05). In univariate analyses, older pts (HR=1.14; CI, 1.09 – 1.2; p<0.0001), and those treated with XRT (HR=3.3; CI, 1.35 – 8.08; p=0.009): EBRT (HR=2.6; CI, 1.0 – 6.9; p=0.05), PI (HR=5.87; CI, 2.1 – 16.3; p=0.0007) were significantly more likely to develop MDS. In multivariate analysis though, while advanced age (HR=1.13; CI, 1.0 – 1.2; p < 0.0001) remained significantly associated with MDS development, XRT did not (HR=1.56; CI, 0.56 – 4.38; p=0.4), though a trend remained for PI (HR=2.85; CI, 0.9 – 8.8; p = 0.07). Conclusions: Pts who underwent definitive radiation treatment for localized prostate cancer did not appear to have a significantly increased risk of subsequent MDS, in analyses that controlled for age and incorporated length of follow-up. A trend for MDS development was present for those undergoing XRT with PI. These findings are encouraging for both patients and providers who have concerns about the potential effects of XRT on development of MDS. Disclosures: Maciejewski: Celgene: Membership on an entity's Board of Directors or advisory committees. Sekeres:Celgene: Consultancy, Honoraria, Speakers Bureau.

Risk Of Acute and Chronic Leukemias Following Radiation Treatment For Locoregional Prostate Cancer In The United States Over 35-Years

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2652-2652
Author(s):  
Sudipto Mukherjee ◽  
Chandana A. Reddy ◽  
Jay P. Ciezki ◽  
Ramon V. Tiu ◽  
Anjali S. Advani ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Diagnosis ◽  
Radiation Treatment ◽  
The United States ◽  
Myelogenous Leukemia ◽  
Acute Leukemias ◽  
Prostate Cancer Diagnosis ◽  
Increased Risk ◽  
Secondary Leukemias

Abstract Background Prostate cancer is the most common cancer diagnosis in men, and one of the leading indications for radiation therapy. The risk of resultant secondary leukemias has not been consistently established. We investigated the risk of all leukemias in a population-based cohort of patients (pts) with locoregional prostate cancer definitively treated with radiotherapy. Methods We queried the Surveillance, Epidemiology, and End Results (SEER) 17 registries to identify a cohort of men >20 years old (n = 183,268) with locoregional prostate adenocarcinoma newly diagnosed between January 1973 and December 2008. Pts who underwent initial treatment with radical prostatectomy (RP) were compared to pts receiving RP with external beam radiotherapy (RP w/EBRT) to investigate the risk of radiation-induced leukemias. These cohorts tend to be well matched regarding age, medical comorbidities and disease characteristics. All new leukemias occurring as a second primary cancer at least one year after the first diagnosis of prostate cancer were identified in SEER using the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) morphology codes. Secondary leukemias included acute myeloid leukemia (AML); chronic myelogenous leukemia (CML); acute and chronic lymphocytic leukemia (ALL & CLL) and other categories as reported in SEER. Pts were observed from date of prostate cancer diagnosis until leukemia occurrence, death, or last date of follow-up. Univariate and multivariate analyses were performed using the Fine and Gray competing risk regression analysis with leukemia as a time-dependent endpoint and death from any cause or the diagnosis of any other second cancer as competing events. RP w/ EBRT group was compared with the RP cohort as the reference group, controlling for age. Hazard ratios (HR) with 95% confidence intervals (CIs) are reported. Results Median age was 67 years (yrs, range 22 – 105) at prostate cancer diagnosis: 67 yrs in RP and 68 yrs in RP w/ EBRT pts (p<0.0001); 158,913 (86.7%) were treated with RP and 24,355 (13.3%) with RP w/EBRT. Median follow-up was 7.6 yrs [(range, 1 – 35.5): 7.5 yrs in the RP group and 8.3 yrs in the RP w/ EBRT group, (p<0.0001)]. In total, 949 (0.5%) leukemia cases were identified: 336 (0.2%) acute leukemias [266 (0.2%) in the RP group and 70 (0.3%) in the RP w/ EBRT]; 538 (0.3%) chronic leukemias [462 (0.3%) in the RP group and 76 (0.3%) in the RP w/ EBRT] and 75 (0.04%) of unspecified histology. Histologic subtypes (per ICD-O-3 codes) were: AML (n=249), acute monocytic leukemia (n=18), ALL (n=24), other acute leukemias (n=45), other myeloid/monocytic/lymphocytic leukemias (n=48), aleukemic/subleukemic/NOS (n=27), CML (n=131) and CLL (n=407). Median age at acute leukemia diagnosis was 77 yrs [(range, 50 – 101): 78 yrs in the RP group and 76 yrs in RP w/EBRT pts, (p=0.0271)] and for chronic leukemias was 76 yrs [(range, 47 – 101): 76 yrs in the RP group and 77 yrs in the RP w/EBRT pts, (p=0.50)].The median time to develop acute leukemias was 6.0 yrs [(range, 1 – 28.2): 6.1 yrs in the RP group and 5.7 yrs in the RP w/EBRT pts, (p=0.20)] and chronic leukemias was 6.9 yrs [(range, 1 – 29.8): 6.7 yrs in the RP group and 8.6 yrs in the RP w/EBRT pts, (p=0.0020)]. The cumulative incidence rate (CIR) at 20 years for acute leukemias was 0.24% for the RP pts vs. 0.32% for the RP w/EBRT pts (p=0.0196). The CIR at 20 years for chronic leukemias was 0.47% for the RP pts vs. 0.36% for the RP w/EBRT pts (p=0.10). In univariate analyses, age >70 yrs (HR=1.40; CI, 1.13 – 1.74; p=0.0023), and those who received RP w/ EBRT (HR=1.49; CI, 1.14 – 1.94; p=0.0033) were significantly more likely to develop acute leukemias. In multivariate analysis, both advanced age (HR=1.40; CI, 1.13 – 1.74; p = 0.0023) and RP w/ EBRT (HR=1.49; CI, 1.14 – 1.94; p=0.0032), remained significantly associated with increased risk of acute leukemias. Radiation treatment was not significantly associated with the risk of developing chronic leukemias among pts treated with RP w/EBRT vs. RP [HR=0.91; CI, 0.72 – 1.16; p=0.45). Conclusions Among the best matched prostate cancer treatment cohorts, those who underwent EBRT following RP had a 49% increased risk of subsequent acute leukemias, although the absolute number of cases was low. Risk assessment in this cohort spans a time frame where radiation technologies have rapidly advanced and hence treatment period effects need to be considered in interpretation of results Disclosures: No relevant conflicts of interest to declare.

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