Dataset Information

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

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 ?/??=?1.3 Gy for prostate gland and ?/??=?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 ?/??=?1.3 Gy were D₅₀?=?66.8 Gy with 95% CI [64.6 Gy, 69.0 Gy], and ??=?3.8 with 95% CI [2.6, 5.2]. For mpMRI-GTV and ?/??=?2.9 Gy, D₅₀ was 68.1 Gy with 95% CI [66.1 Gy, 70.0 Gy], and ??=?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], ??=?3.1 [2.0, 4.4], ?/??=?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 ?/?. The results for the mpMRI-GTV were D₅₀?=?50.1 Gy [44.6 Gy, 56.0 Gy], ??=?0.8 [0.5, 1.2], ?/??=?0.0 Gy (95% CI was undefined). For a follow-up time of 5 years and a fixed ?/??=?1.6 Gy, the TCP fitting results for prostate gland were D₅₀?=?63.9 Gy [60.8 Gy, 67.0 Gy], ??=?2.9 [1.9, 4.1], and for mpMRI-GTV D₅₀?=?56.3 Gy [51.6 Gy, 61.1 Gy], ??=?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 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. The failure to identify any benefit for considering mpMRI-GTV as the target responsible for the clinical response is confirmed when considering a fixed ?/??=?1.6 Gy, a fixed follow-up time for biochemical response at 5 years or Gleason score differentiation.

SUBMITTER: Sachpazidis I

PROVIDER: S-EPMC7574270 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Sachpazidis Ilias I Mavroidis Panayiotis P Zamboglou Constantinos C Klein Christina Marie CM Grosu Anca-Ligia AL Baltas Dimos D

Radiation oncology (London, England) 20201020 1

<h4>Purpose</h4>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, volum ...[more]

PMID: 33081804

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Project description:BackgroundPre-treatment magnetic resonance imaging (MRI) can give patient-specific evaluation of suspected pathologically involved volumes in the seminal vesicles (SV) in prostate cancer patients. By targeting this suspicious volume we hypothesize that radiotherapy is more efficient without introducing more toxicity. In this study we evaluate the concept of using MRI-defined target volumes in terms of tumor control probability (TCP) and rectal normal tissue complication probability (NTCP).Material and methodsTwenty-one high-risk prostate cancer patients were included. Pre-treatment CT images, T2 weighted (T2w) MRI and two multi-parametric MRI were acquired. Overlap between a suspicious volume in the SV observed on T2w images and a suspicious volume observed on either multi-parametric MRI was assumed to reflect a true malignant region (named 'MRI positive'). In addition the entire SV on the CT-scan was delineated. Three treatment plans of 2 Gy ×39 fractions were generated per patient: one covering the MRI positive volume in SV and prostate with margin of 11 mm to the MRI positive in the SV and two plans covering prostate and SV using 11 and 7 mm SV margin, respectively. All plans were prescribed the same PTV mean dose. Rectal NTCP grade ≥2 was evaluated with the Lyman-Kutcher-Burman model and TCP was estimated by a logistic model using the combined MRI positive volume in SV and prostate as region-of-interest.ResultsFourteen of twenty-one patients were classified as MRI positive, six of which had suspicious volumes in all three MRI modalities. On average TCP for the plan covering prostate and the MRI positive volume was 3% higher (up to 11%) than the two other plans which was statistically significant. The increased TCP was obtained without increasing rectal NTCP grade ≥2.ConclusionsUsing functional MRI for individualized target delineation in the SV may improve the treatment outcome in radiotherapy of prostate cancer without increasing the rectal toxicity.

Project description:To compare the outcomes of localized prostate cancer treatment with high-dose-rate brachytherapy (HDR-BT) and low-dose-rate brachytherapy (LDR-BT), we examined 924 patients treated with HDR-BT + external beam radiotherapy (EBRT) and 500 patients treated with LDR-BT ± EBRT using multi-institutional retrospective data. The HDR-BT treated advanced disease with more hormonal therapy than LDR-BT. To reduce background selection bias, we performed inverse probability of treatment weighting (IPTW) analysis using propensity scores and excluded patients with T3b-4 disease/ initial prostate-specific antigen (PSA) levels > 50 ng/ml. The actuarial 5-year biochemical control rates (5y-bNED) were 96.3% and 95.7% in the HDR-BT and LDR-BT groups, respectively. The corresponding values were 100% and 96.5% in the low-risk group; 97.4% and 97.1% in the intermediate-risk group (97.2% and 97% in the higher titer group and 97.5% and 94.6% in the lower titer group, respectively); and 95.7% and 94.9% in the selected high-risk group, respectively. IPTW correction indicated no significant difference among the groups. The 5y-bNED in the HDR-BT + EBRT, LDR-BT + EBRT, and LDR-BT alone groups were 96.3%, 95.5%, and 97%, respectively (P = 0.3011). The corresponding values were 97.4%, 94.7%, and 96.6% (P = 0.1004) in the intermediate-risk group (97.5%, 100%, and 94.5% in the lower titer group [P = 0.122] and 97.2%, 96.2%, and 100% [P = 0.664] in the higher titer group, respectively) and 95.7%, 95.5%, and 100% (P = 0.859) in the high-risk group, respectively. The HDR-BT group showed a lower incidence of acute grade ≥ 2 genitourinary toxicities; the incidence of other early and late grade ≥ 2 toxicities were similar between the HDR-BT and LDR-BT groups. Acute genitourinary toxicity predicted the occurrence of late genitourinary toxicity. EBRT increased the risk of grade ≥ 2 gastrointestinal toxicity. HDR-BT + EBRT is a good alternative to LDR-BT ± EBRT for low-, intermediate-, and selected high-risk patients.

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Project description:Background and purposeApparent diffusion coefficient (ADC) reflects micro-enviromental changes and therefore might be useful in predicting recurrence prior to brachytherapy. The purpose of this study is to evaluate change in ADC of the primary tumour and pathologic lymph nodes during treatment and to correlate this with clinical outcome.Material and methodsTwenty patients were included who received chemoradiation for locally advanced cervical cancer between July 2016 and November 2017. All patients underwent magnetic resonance imaging (MRI) prior to treatment, and three MRIs in weeks 1/2, 3 and 4 of treatment, including T2 and diffusion weighted imaging (b-values 0, 200, 800 s/mm2) for determining an ADC-map. Primary tumour was delineated on T2 and ADC-map and pathologic lymph nodes were delineated only on ADC-map.ResultsAt time of analysis median follow-up was 15 (range 7-22) months. From MRI one to four, primary tumour on ADC-map showed a significant signal increase of 0.94 (range 0.74-1.46) × 10-3 mm2/s to 1.13 (0.98-1.49) × 10-3 mm2/s (p < 0.001). When tumour was delineated on T2, ADC-value signal increase (in tumour according to T2) was similar. All 46 delineated pathologic lymph nodes showed an ADC-value increase on average from 0.79 (range 0.33-1.12) × 10-3 mm2/s to 1.14 (0.59-1.75) × 10-3 mm2/s (p < 0.001). The mean tumour/suspected lymph node volumes decreased respectively 51/40%. Four patients developed relapse (one local and three nodal), without clear relation with ΔADC. However, the median volume decrease of the primary tumour was substantially lower in the failing patients compared to the group without relapse (19 vs. 57%).ConclusionsADC values can be acquired using T2-based tumour delineations unless there are substantial shifts between ADC-mapping and T2 acquisition. It remains plausible that ΔADC is a predictor for response to EBRT. However, the correlation in this study was not statistically significant.

Project description:Importance:The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective:To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants:Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures:Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. Main Outcomes and Measures:The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Results:Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Conclusions and Relevance:Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

Project description:PurposeTo evaluate the interobserver variability of gross tumor volume (GTV) - delineation of Dominant Intraprostatic Lesions (DIPL) in patients with prostate cancer using published MRI criteria for multiparametric MRI at 3 Tesla by 6 different observers.Material and methods90 GTV-datasets based on 15 multiparametric MRI sequences (T2w, diffusion weighted (DWI) and dynamic contrast enhanced (DCE)) of 5 patients with prostate cancer were generated for GTV-delineation of DIPL by 6 observers. The reference GTV-dataset was contoured by a radiologist with expertise in diagnostic imaging of prostate cancer using MRI. Subsequent GTV-delineation was performed by 5 radiation oncologists who received teaching of MRI-features of primary prostate cancer before starting contouring session. GTV-datasets were contoured using Oncentra Masterplan® and iplan® Net. For purposes of comparison GTV-datasets were imported to the Artiview® platform (Aquilab®), GTV-values and the similarity indices or Kappa indices (KI) were calculated with the postulation that a KI > 0.7 indicates excellent, a KI > 0.6 to < 0.7 substantial and KI > 0.5 to < 0.6 moderate agreement. Additionally all observers rated difficulties of contouring for each MRI-sequence using a 3 point rating scale (1 = easy to delineate, 2 = minor difficulties, 3 = major difficulties).ResultsGTV contouring using T2w (KI-T2w = 0.61) and DCE images (KI-DCE = 0.63) resulted in substantial agreement. GTV contouring using DWI images resulted in moderate agreement (KI-DWI = 0.51). KI-T2w and KI-DCE was significantly higher than KI-DWI (p = 0.01 and p = 0.003). Degree of difficulty in contouring GTV was significantly lower using T2w and DCE compared to DWI-sequences (both p < 0.0001). Analysis of delineation differences revealed inadequate comparison of functional (DWI, DCE) to anatomical sequences (T2w) and lack of awareness of non-specific imaging findings as a source of erroneous delineation.ConclusionsUsing T2w and DCE sequences at 3 Tesla for GTV-definition of DIPL in prostate cancer patients by radiation oncologists with knowledge of MRI features results in substantial agreement compared to an experienced MRI-radiologist, but for radiotherapy purposes higher KI are desirable, strengthen the need for expert surveillance. DWI sequence for GTV delineation was considered as difficult in application.

Dataset Information

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

Purpose

Methods

Results

Conclusion

Publications

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

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