Intensity-modulated Radiotherapy For Prostate Cancer Research Articles

Does intensity-modulated radiation therapy by helical tomotherapy for prostate cancer increase the subsequent risk of bladder cancer? A propensity score-matched analysis.

This study aimed to evaluate the risk of bladder cancer after intensity-modulated radiation therapy (IMRT) using helical tomotherapy for prostate cancer in comparison to the risk post-radical prostatectomy (RP) using propensity score-matched analysis and to assess the risk factors for bladder cancer. This retrospective study included 2067 patients with non-metastatic prostate cancer treated at our institution between June 2007 and December 2016. Of these, 1547 patients were treated with IMRT and 520 underwent RP. The propensity scores were calculated using age, National Comprehensive Cancer Network risk classification, prostate volume, Brinkman index, and follow-up time as matched covariates. A propensity score-matched patient cohort (n = 718; IMRT: 359, RP: 359) was created, and the risk of bladder cancer after treatment was compared. In total, bladder cancer was detected in 33 patients. Five patients in the IMRT group and one in the RP group died of bladder cancer. In the propensity score-matched analysis, the 5-year bladder cancer-free survival rate was significantly lower in the IMRT group than in the RP group (91.7% and 96.2%, respectively; p < 0.001). Multivariate analysis revealed that IMRT and the Brinkman index were the risk factors for bladder cancer in this cohort (odds ratio = 5.085, 95% confidence interval = 1.436-18.008, p = 0.012 and odds ratio = 1.001, 95% confidence interval = 1.000-1.001, p = 0.010, respectively). IMRT for prostate cancer using helical tomotherapy increases the subsequent risk of bladder cancer compared with RP and is an independent risk factor for bladder cancer similar to smoking.

Impact of prostate position-based image-guidance in intensity-modulated radiation therapy for localized prostate cancer.

The long-term clinical impact of prostate position-based image-guided radiotherapy (IGRT) for localized prostate cancer remains unclear. We retrospectively compared clinical outcomes following intensity-modulated radiation therapy (IMRT) with cone-beam computed tomography-based prostate position-based IGRT (P-IGRT) or without P-IGRT (non-P-IGRT). From June 2011, we applied P-IGRT in IMRT for intermediate-risk (IR) prostate cancer (PCa) (D'Amico risk classification) (76Gy in 38 fractions, with smaller margins). Clinical outcomes of patients who received P-IGRT between June 2011 and June 2019 were retrospectively compared with those of patients with IR PCa who received IMRT without P-IGRT between October 2002 and May 2011 in our institution (74Gy in 37 fractions). A total of 222 consecutive patients were analyzed: 114 in the P-IGRT cohort and 108 in the non-P-IGRT cohort. The median follow-up period after IMRT was 7.1years for the P-IGRT cohort and 10.8years for the non-P-IGRT cohort. The biochemical failure-free rate was significantly better in the P-IGRT cohort (94.9% for the P-IGRT cohort vs 82.7% for the non-P-IGRT cohort at 10years, p = 0.041). The rate of rectal bleeding which needs intervention including the use of suppositories was significantly lower in the P-IGRT cohort (p < 0.001). The use of P-IGRT with higher doses and smaller margins was correlated with significantly better biochemical control, and a lower incidence of rectal bleeding in IMRT for intermediate-risk prostate cancer. The enhanced accuracy using P-IGRT has the potential to independently improve disease control and reduce late rectal bleeding.

Long-term findings of rectal endoscopy and rectal bleeding after moderately hypofractionated, intensity-modulated radiotherapy for prostate cancer

To present rectal endoscopic findings and toxicity after definitive moderately hypofractionated, intensity-modulated radiotherapy (IMRT) for prostate cancer. We retrospectively reviewed patients who underwent IMRT for prostate cancer and underwent post-radiotherapy endoscopies between 2008 and 2018. Endoscopic findings were reviewed and graded using Vienna Rectoscopy Score (VRS). We have analyzed the association between endoscopic findings and rectal bleeding, and investigated risk factors for rectal bleeding. Total 162 patients met the inclusion criteria of this study. There was a trend of VRS worsening during the initial 3 years after radiotherapy followed by recovery. Rectal bleeding was highest at 1 year after radiotherapy and improved thereafter. The 5-year cumulative incidence of grade ≥ 2 rectal bleeding was 14.8%. In the multivariable Cox regression analysis, cardiovascular disease (hazard ratio [HR] 2.732, P = 0.037), rectal wall V65 (HR 1.158, P = 0.027), and VRS ≥ 3 in first post-radiotherapy endoscopy (HR 2.573, P = 0.031) were significant risk factors for rectal bleeding. After IMRT for prostate cancer, VRS and rectal bleeding worsened over 1–3 years after radiotherapy and recovered. Cardiovascular disease, rectal wall V65, and VRS ≥ 3 in first post-radiotherapy endoscopy were significant risk factors for rectal bleeding.

A Prospective Phase II Dose Escalation Study Using IMRT for High Risk N0M0 Prostate Cancer.

Published data supports the use of very high dose intensity modulated radiotherapy (IMRT) in achieving high efficacy and low toxicity for high-risk prostate cancer (HRPCa). This phase II multi-institutional non-randomized prospective dose escalation study using intensity modulated radiotherapy (IMRT) for high risk N0M0 prostate cancer was designed to investigate dose escalation using 1.8 Gy increments from baseline 75.6 Gy up to maximum 81 Gy, once dose volume constraints were adhered to. Inclusion criteria were patients undergoing a radical course of RT for high and very high-risk disease, defined as one or more of the criteria ≥ T3*, ≥ Gleason 8, Prostate specific antigen (PSA) > 20ng/ml. All patients received Androgen Deprivation Therapy (ADT) and none had radiological evidence of distant metastatic disease. The primary objective was to determine if dose escalated IMRT for high risk localized prostate cancer could provide freedom from biochemical relapse (BR; PSA rising > nadir +2ng/mL or initiation of salvage hormone therapy) similar to that reported in the literature. The Kaplan-Meier method was used to estimate survival times. Secondary objectives included OS, Disease Free Survival (DFS), and the incidence and severity of Genito-urinary (GU), Gastro-intestinal (GI) and erectile dysfunction (ED) toxicities (CTCAE v.3). Toxicities and performance status were collected and graded weekly during RT, 2 months after completing RT, 8 months' post RT, and 6 monthly thereafter to year five and annually thereafter to year nine. A total of 230 evaluable patients were enrolled between April 2009 and June 2016. The median follow-up was 7.3 years. The cumulative proportion of patients surviving without BR at 5 years was 91% (95% Confidence Interval (CI): 86% to 94%). Overall survival at 5 and 7 years was 92% (88% to 95%) and 89% (83% to 92%) respectively, while the cumulative proportion of patients free from disease was 89% (84% to 93%) at 5 years and 81% (75% to 86%) at 7 years. The incidence of acute G2 and G3 toxicities were; GU; 57.8% G2, 12.6% G3, GI; 15.2% G2, 0.4% G3, ED; 30.0% G2 and 61.7% G3. The incidence of late G2, G3 and G4 toxicities were; GU; 40.9% G2, 8.7% G3, GI; 36.5% G2, 2.2% G3, 0.4% G4, ED; 11.7% G2 and 86.1% G3. The percentage of patients receiving each dose level was; 3.5% received 75.6Gy in 42 fractions, 2.2% received 77.4Gy in 43 fractions, 93% received 81Gy in 45 fractions. The findings indicate that high-dose IMRT is well tolerated and is associated with excellent long-term tumor-control outcomes in patients with localized high and very high-risk prostate cancer, with 91% of patients surviving at 5 years without biochemical relapse. The rates of long term G3 GU and GI toxicity were low at 8.7% and 0.4% respectively.

Prostate Advanced Radiation Technologies Investigating Quality of Life (PARTIQoL): A Phase III Randomized Clinical Trial of Proton Therapy vs. IMRT for Low or Intermediate Risk Prostate Cancer.

Prostate cancer is the most common non-cutaneous cancer diagnosed among men in the United States, and the majority of patients are diagnosed with localized disease. Men with localized prostate cancer have several treatment options including external beam radiotherapy with either photons or protons. Proton beam therapy (PBT) has certain dosimetric advantages and the potential to reduce treatment-associated morbidity and improve oncologic outcomes, but current PBT is significantly more costly than intensity-modulated radiotherapy (IMRT). The PARTIQoL trial (NCT01617161) is the first multicenter phase 3 randomized trial comparing protons to photons in the treatment of localized prostate cancer. Patients with low or intermediate risk prostate cancer (Stage T1c-T2c, PSA < 20, Gleason score ≤ 7) are randomized to receive either PBT or IMRT, with targeted recruitment efforts for minority populations. A companion registry study has concurrently enrolled patients who declined randomization or whose insurance denied coverage for PBT. Patients are stratified by clinical site, age, use of rectal spacer, and fractionation schedule (conventional fractionation: 79.2 Gy in 44 fractions vs moderate hypofractionation: 70.0 Gy in 28 fractions). Participants are followed longitudinally to assess patient-reported outcomes (PROs) of bowel, urinary, and erectile function for 60 months after completion of radiotherapy (with an option for additional follow up through 10 years). Participants may also participate in correlative studies, including serial CT imaging during treatment and analyses of biopsy tissue, blood and urine specimens. The primary objective is to compare PROs of bowel function using the EPIC score at 24 months following completion of radiation. Secondary objectives are to assess treatment-related differences in urinary and erectile functions, adverse events, efficacy endpoints (biochemical control, metastasis-free survival, disease-specific survival, and overall survival), health state utilities, perceptions of care, late effects, cost-effectiveness, association between radiotherapy dose distribution and PROs, and to identify biomarkers of radiation response and toxicity. The randomized trial has completed accrual, with 450 patients enrolled at 27 sites between June 2012 and November 2021. 20.3% of patients enrolled are non-white. Accrual on the companion registry is active, with 354 patients enrolled as of February 2023. Follow-up for the primary endpoint on the randomized trial will be reached in 2024. The PARTIQoL randomized clinical trial will rigorously assess the clinical benefits of PBT relative to IMRT and results will inform decision making by patients, providers, policymakers, and payers.

Feasibility of artificial intelligence-driven interfractional monitoring of organ changes by mega-voltage computed tomography in intensity-modulated radiotherapy of prostate cancer.

High-dose radiotherapy (RT) for localized prostate cancer requires careful consideration of target position changes and adjacent organs-at-risk (OARs), such as the rectum and bladder. Therefore, daily monitoring of target position and OAR changes is crucial in minimizing interfractional dosimetric uncertainties. For efficient monitoring of the internal condition of patients, we assessed the feasibility of an auto-segmentation of OARs on the daily acquired images, such as megavoltage computed tomography (MVCT), via a commercial artificial intelligence (AI)-based solution in this study. We collected MVCT images weekly during the entire course of RT for 100 prostate cancer patients treated with the helical TomoTherapy system. Based on the manually contoured body outline, the bladder including prostate area, and rectal balloon regions for the 100 MVCT images, we trained the commercially available fully convolutional (FC)-DenseNet model and tested its auto-contouring performance. Based on the optimally determined hyperparameters, the FC-DenseNet model successfully auto-contoured all regions of interest showing high dice similarity coefficient (DSC) over 0.8 and a small mean surface distance (MSD) within 1.43 mm in reference to the manually contoured data. With this well-trained AI model, we have efficiently monitored the patient's internal condition through six MVCT scans, analyzing DSC, MSD, centroid, and volume differences. We have verified the feasibility of utilizing a commercial AI-based model for auto-segmentation with low-quality daily MVCT images. In the future, we will establish a fast and accurate auto-segmentation and internal organ monitoring system for efficiently determining the time for adaptive replanning.

Infection after prostatic transrectal fiducial marker implantation for image guided radiation therapy

PurposeThe aim of this retrospective study is to assess the risk of infection after transrectal ultrasound-guided fiducial marker insertion for image-guided radiotherapy of prostate cancer. Material and methodsBetween January 2016 and December 2020, 829 patients scheduled for intensity-modulated radiotherapy for prostate cancer had an intraprostatic fiducial marker transrectal implantation under ultrasound guidance by radiation-oncologists specialized in brachytherapy. Patients received standard oral prophylactic antibiotic with quinolone. If Gram negative bacteria resistant to quinolone were detected at the time of the prostate cancer biopsies, the antibioprophylaxis regimen was modified accordingly. The resistance to quinolone screening test was not repeated before fiducial marker insertion. Infectious complications were assessed with questionnaires at the time of CT-planning and medical record reviewed. Toxicity was evaluated according to CTCAE v5.0. ResultsThe median time between fiducial marker implantation and evaluation was 10 days (range: 0–165 days). Four patients (0.48%) developed urinary tract infection related to the procedure, mostly with Gram-negative bacteria resistant to quinolone (75%). Three had a grade 2 infection, and one patient experienced a grade 3 urosepsis. The quinolone-resistance status was known for two patients (one positive and one negative) and was unknown for the other two patients prior to fiducial marker implantation. ConclusionIntraprostatic transrectal fiducial marker implantation for image-guided radiotherapy is well tolerated with a low rate of infection. With such a low rate of infection, there is no need to repeat the search of Gram-negative bacteria resistant to quinolone before fiducial marker implantation if it was done at the time of prostate biopsies. Optimal antibioprophylaxis should be adapted to the known status of Gram-negative bacteria resistant to quinolone.

Dosimetric evaluation study of IMRT and VMAT techniques for prostate cancer based on different multileaf collimator designs

The hypofractionated radiotherapy modality was established to reduce treatment durations and enhance therapeutic efficiency, as compared to conventional fractionation treatment. However, this modality is challenging because of rigid dosimetric constraints. This study aimed to assess the impact of multi-leaf collimator (MLC) widths (10 mm and 5 mm) on plan quality during the treatment of prostate cancer. Additionally, this study aimed to investigate the impact of the MLC mode of energy on the Agility flattening filter (FF), MLC Agility-free flattening filter (FFF), and MLCi2 for patients receiving hypofractionated radiotherapy. Two radiotherapy techniques; Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Radiotherapy (VMAT), were used in this research. In the present study, computed tomography simulations of ten patients (six plans per patient) with localized prostate adenocarcinoma were analyzed. Various dosimetric parameters were assessed, including monitor units, treatment delivery times, conformity, and homogeneity indices. To evaluate the plan quality, dose-volume histograms (DVHs) were estimated for each technique. The results demonstrated that the determined dosimetric parameters of planning target volume (PTV)p (such as D mean, conformity, and homogeneity index) showed greater improvement with MLC Agility FF and MLC Agility FFF than with MLCi2. Additionally, the treatment delivery time was reduced in the MLC Agility FF (by 31%) and MLC Agility FFF (by 10.8%) groups compared to the MLCi2 group. It is concluded that for both the VMAT and IMRT techniques, the smaller width (5 mm) MLCs revealed better planning target volume coverage, improved the dosimetric parameters for PTV, reduced the treatment time, and met the constraints for OARs. It is therefore recommended to use 5 mm MLCs for hypofractionated prostate cancer treatment due to better target coverage and better protection of OARs.

Feasibility and Dosimetric Benefits of Adaptive Planning in Prostate Cancer Radiotherapy Using a Novel Treatment Planning Machine with Integrated Dual kVCT/PET Imaging Systems

<h3>Purpose/Objective(s)</h3> Interfraction anatomical changes during intensity-modulated radiotherapy for prostate cancer may lead to suboptimal patients' treatment. This study assessed the dosimetric effects of anatomical changes on pretreatment kilovoltage computed tomography (kVCT) scans of a novel dual on-board kVCT/positiron emission tomography (PET) imaging radiotherapy system. <h3>Materials/Methods</h3> This retrospective study analyzed daily kVCT scans acquired on days 1, 5, 13, 17, and 22 of a post-prostatectomy patient treated with 44 Gy/22 fractions to the prostate bed and lymph nodes. The prostate bed CTV, pelvic lymph nodes, rectum and bladder were re-contoured on the daily kVCT, and treatment plans were subsequently created. The treatment doses were calculated using the HU density table of kVCT. Delineation and treatment plans created on the daily kVCT scans were compared with those created on the planning CT. Interfraction changes of bladder and rectum were analyzed based on median dose (Dmedian), mean dose (Dmean), maximum dose (Dmax), volume receiving 10 Gy (V10), volume receiving 30 Gy (V30), and overall volume. For bladder and rectum, the correlation coefficient between volume and Dmean was analyzed. <h3>Results</h3> For the kVCT days investigated in this study, mean bladder and rectum volume changes were 10.69 cc ± 10.08 cc and 1.31 cc ± 0.64 cc, respectively. Consequentially, the average changes in Dmedian, Dmean, Dmax for the bladder were 0.51 Gy ±0.32 Gy, 0.30 Gy ±0.22 Gy, and 0.75 Gy ±0.44 Gy, respectively. For the rectum, the average changes in Dmedian, Dmean, Dmax were 0.62 Gy ±0.36 Gy, 0.59 Gy ±0.49 Gy, and 0.76 Gy ±0.57 Gy, respectively. The average changes in V10, and V30 were 0.48 % ±0.56 %, and 1.1 %± 0.66 % for bladder and 1.48 % ±1.27 %, and 1.83 %± 1.34 % for rectum. The correlation coefficient (r2) for bladder-Dmean and Rectum-Dmean were 0.765 and 0.002, respectively. <h3>Conclusion</h3> This study showed that with adaptive planning, the interfraction dose variation was minimal because adaptive plans were optimized based on daily kVCT images (this is one primary benefit of adaptive planning). Even with adaptive planning, there is still a correlation between bladder dose and bladder volume. The high-quality kVCT images produced could potentially be used for target and OAR delineation and consequentially for treatment planning. Treatment delivery could further be improved by kVCT adaptive planning, which will account for possible interfraction variations.

Comparison of intensity-modulated radiotherapy with the 5-field technique, helical tomotherapy and volumetric modulated arc therapy for localized prostate cancer.

The outcomes of three methods of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. Between 2010 and 2018, 308 D’Amico intermediate- or high-risk patients were treated with 2.2 Gy daily fractions to a total dose of 74.8 Gy in combination with hormonal therapy. Overall, 165 patients were treated with 5-field IMRT using a sliding window technique, 66 were then treated with helical tomotherapy and 77 were treated with volumetric modulated arc therapy (VMAT). The median age of patients was 71 years. The median follow-up period was 75 months. Five-year overall survival (OS) and biochemical or clinical failure-free survival (FFS) rates were 95.5 and 91.6% in the 5-field IMRT group, 95.1 and 90.3% in the tomotherapy group and 93.0 and 88.6% in the VMAT group, respectively, with no significant differences among the three groups. The 5-year cumulative incidence of late grade ≥2 genitourinary and gastrointestinal toxicities were 7.3 and 6.2%, respectively, for all patients. Late grade ≥2 gastrointestinal toxicities were less frequent in patients undergoing VMAT (0%) than in patients undergoing 5-field IMRT (7.3%) and those undergoing tomotherapy (11%) (P = 0.025), and this finding appeared to be correlated with the better rectal DVH parameters in patients undergoing VMAT. Other toxicities did not differ significantly among the three groups, although bladder dose-volume parameters were slightly worse in the tomotherapy group than in the other groups. Despite differences in the IMRT delivery methods, X-ray energies and daily registration methods, all modalities may be used as IMRT for localized prostate cancer.

The Long-Term Effect of Intensity Modulated Radiation Therapy for Prostate Cancer on Testosterone Levels

PurposeConcern about a long-term effect of the delivery of intensity modulated radiation therapy (IMRT) for prostate cancer on serum testosterone levels remains unelucidated. We evaluated how IMRT for localized prostate cancer affects serum testosterone levels during a follow-up period of up to 10 years. Methods and MaterialsWe retrospectively evaluated data from 182 patients with localized prostate cancer who underwent definitive IMRT alone between 2007 and 2014. Serum total testosterone (TT) levels were measured by blood draws between 6 AM and 11 AM before treatment and at every posttreatment follow-up for 10 years. Pretreatment values and each posttreatment testosterone value were compared using a Wilcoxon signed rank test. The data set was stratified into 4 groups based on the pretreatment testosterone (pre-TT) values using quartiles. ResultsThe median absolute or relative changes in TT levels from pretreatment were –0.42 ng/mL or –12.0% at 3 months after radiation therapy (P < .0001). Subsequently, TT levels gradually recovered to nearly the pretreatment levels 24 to 36 months after IMRT. When analyzed according to the pre-TT quartile, median TT levels initially decreased at the 3- to 12-month period in all the quartiles; however, median TT levels increased from the 18-month period in the first and second quartile groups, whereas they were maintained at less than the pretreatment levels in the third and the fourth quartile groups throughout the entire decade after radiation therapy. The proportion of patients with hypogonadal status, defined as TT levels <3.00 ng/mL, did not increase over time. ConclusionsA transient and modest decrease of TT levels after IMRT spontaneously recovered to the pretreatment levels at the 24- to 36-month period except in patients in the higher quartile of pre-TT. This might have been partly owing to a variable sensitivity of individual testicular function to scattered radiation. Patients with lower pre-TT did not demonstrate a progressive overall rate of hypogonadism until 10 years after radiation therapy.

Dosimetric comparison of MR-linac-based IMRT and conventional VMAT treatment plans for prostate cancer

BackgroundThe aim of this study was to evaluate and compare the performance of intensity modulated radiation therapy (IMRT) plans, planned for low-field strength magnetic resonance (MR) guided linear accelerator (linac) delivery (labelled IMRT MRL plans), and clinical conventional volumetric modulated arc therapy (VMAT) plans, for the treatment of prostate cancer (PCa). Both plans used the original planning target volume (PTV) margins. Additionally, the potential dosimetric benefits of MR-guidance were estimated, by creating IMRT MRL plans using smaller PTV margins.Materials and methods20 PCa patients previously treated with conventional VMAT were considered. For each patient, two different IMRT MRL plans using the low-field MR-linac treatment planning system were created: one with original (orig.) PTV margins and the other with reduced (red.) PTV margins. Dose indices related to target coverage, as well as dose-volume histogram (DVH) parameters for the target and organs at risk (OAR) were compared. Additionally, the estimated treatment delivery times and the number of monitor units (MU) of each plan were evaluated.ResultsThe dose distribution in the high dose region and the target volume DVH parameters (D98%, D50%, D2% and V95%) were similar for all three types of treatment plans, with deviations below 1% in most cases. Both IMRT MRL plans (orig. and red. PTV margins) showed similar homogeneity indices (HI), however worse values for the conformity index (CI) were also found when compared to VMAT. The IMRT MRL plans showed similar OAR sparing when the orig. PTV margins were used but a significantly better sparing was feasible when red. PTV margins were applied. Higher number of MU and longer predicted treatment delivery times were seen for both IMRT MRL plans.ConclusionsA comparable plan quality between VMAT and IMRT MRL plans was achieved, when applying the same PTV margin. However, online MR-guided adaptive radiotherapy allows for a reduction of PTV margins. With a red. PTV margin, better sparing of the surrounding tissues can be achieved, while maintaining adequate target coverage. Nonetheless, longer treatment delivery times, characteristic for the IMRT technique, have to be expected.

Improving efficiency of training a virtual treatment planner network via knowledge-guided deep reinforcement learning for intelligent automatic treatment planning of radiotherapy.

We previously proposed an intelligent automatic treatment planning framework for radiotherapy, in which a virtual treatment planner network (VTPN) is built using deep reinforcement learning (DRL) to operate a treatment planning system (TPS) by adjusting treatment planning parameters in it to generate high-quality plans. We demonstrated the potential feasibility of this idea in prostate cancer intensity-modulated radiation therapy (IMRT). Despite the success, the process to train a VTPN via the standard DRL approach with an ϵ-greedy algorithm was time-consuming. The required training time was expected to grow with the complexity of the treatment planning problem, preventing the development of VTPN for more complicated but clinically relevant scenarios. In this study, we proposed a novel knowledge-guided DRL (KgDRL) approach that incorporated knowledge from human planners to guide the training process to improve the efficiency of training a VTPN. Using prostate cancer IMRT as a test bed, we first summarized a number of rules in the actions of adjusting treatment planning parameters of our in-house TPS. During the training process of VTPN, in addition to randomly navigating the large state-action space, as in the standard DRL approach using the ϵ-greedy algorithm, we also sampled actions defined by the rules. The priority of sampling actions from rules decreased over the training process to encourage VTPN to explore new policy on parameter adjustment that were not covered by the rules. To test this idea, we trained a VTPN using KgDRL and compared its performance with another VTPN trained using the standard DRL approach. Both networks were trained using 10 training patient cases and five additional cases for validation, while another 59 cases were employed for the evaluation purpose. It was found that both VTPNs trained via KgDRL and standard DRL spontaneously learned how to operate the in-house TPS to generate high-quality plans, achieving plan quality scores of 8.82 (±0.29) and 8.43 (±0.48), respectively. Both VTPNs outperformed treatment planning purely based on the rules, which had a plan score of 7.81 (±1.59). VTPN trained with eight episodes using KgDRL was able to perform similar to that trained using DRL with 100 epochs. The training time was reduced from more than a week to ~13hrs. The proposed KgDRL framework was effective in accelerating the training process of a VTPN by incorporating human knowledge, which will facilitate the development of VTPN for more complicated treatment planning scenarios.

Standard versus hypofractionated intensity-modulated radiotherapy for prostate cancer: assessing the impact on dose modulation and normal tissue effects when using patient-specific cancer biology

Hypofractionation of prostate cancer radiotherapy achieves tumour control at lower total radiation doses, however, increased rectal and bladder toxicities have been observed. To realise the radiobiological advantage of hypofractionation whilst minimising harm, the potential reduction in dose to organs at risk was investigated for biofocused radiotherapy. Patient-specific tumour location and cell density information were derived from multiparametric imaging. Uniform-dose plans and biologically-optimised plans were generated for a standard schedule (78 Gy/39 fractions) and hypofractionated schedules (60 Gy/20 fractions and 36.25 Gy/5 fractions). Results showed that biologically-optimised plans yielded statistically lower doses to the rectum and bladder compared to isoeffective uniform-dose plans for all fractionation schedules. A reduction in the number of fractions increased the target dose modulation required to achieve equal tumour control. On average, biologically-optimised, moderately-hypofractionated plans demonstrated 15.3% (p-value: <0.01) and 23.8% (p-value: 0.02) reduction in rectal and bladder dose compared with standard fractionation. The tissue-sparing effect was more pronounced in extreme hypofractionation with mean reduction in rectal and bladder dose of 43.3% (p-value: < 0.01) and 41.8% (p-value: 0.02), respectively. This study suggests that the ability to utilise patient-specific tumour biology information will provide greater incentive to employ hypofractionation in the treatment of localised prostate cancer with radiotherapy. However, to exploit the radiobiological advantages given by hypofractionation, greater attention to geometric accuracy is required due to increased sensitivity to treatment uncertainties.

Prospective evaluation of probabilistic dose-escalated IMRT in prostate cancer.

BackgroundCure- and toxicity rates after intensity-modulated radiotherapy (IMRT) of prostate cancer are dose-and volume dependent. We prospectively studied the potential for organ at risk (OAR) sparing and compensation of tumor movement with the coverage probability (CovP) concept.Patients and methodsTwenty-eight prostate cancer patients (median age 70) with localized disease (cT1c–2c, N0, M0) and intermediate risk features (prostate-specific antigen [PSA] < 20, Gleason score ≤ 7b) were treated in a prospective study with the CovP concept. Planning-CTs were performed on three subsequent days to capture form changes and movement of prostate and OARs. The clinical target volume (CTV) prostate and the OARs (bladder and rectum) were contoured in each CT. The union of CTV1–3 was encompassed by an isotropic margin of 7 mm to define the internal target volume (ITV). Dose prescription/escalation depended on coverage of all CTVs within the ITV. IMRT was given in 39 fractions to 78 Gy using the Monte-Carlo algorithm. Short-term androgen deprivation was recommended and given in 78.6% of patients.ResultsLong-term toxicity was evaluated in 26/28 patients after a median follow-up of 7.1 years. At last follow-up, late bladder toxicity (Radiation Therapy Oncology Group, RTOG) G1 was observed in 14.3% of patients and late rectal toxicities (RTOG) of G1 (7.1%) and of G2 (3.6%) were observed. No higher graded toxicity occurred. After 7.1 years, biochemical control (biochemically no evidence of disease, bNED) was 95.5%, prostate cancer-specific survival and the distant metastasis-free survival after 7.1 years were 100% each.ConclusionsCovP-based IMRT was feasible in a clinical study. Dose escalation with the CovP concept was associated by a low rate of toxicity and a high efficacy regarding local and distant control.

Toxicity of Pelvic Lymph Node Irradiation With Intensity Modulated Radiation Therapy for High-Risk and Locally Advanced Prostate Cancer: A National Population-Based Study Using Patient-Reported Outcomes

Little is known about the toxicity of additional pelvic lymph node irradiation in men receiving intensity modulated radiation therapy (IMRT) for prostate cancer. The aim of this study was to compare patient-reported outcomes after IMRT to the prostate only (PO-IMRT) versus the prostate and pelvic lymph nodes (PPLN-IMRT). Patients who received a diagnosis of high-risk or locally advanced prostate cancer in the English National Health Service between April 2014 and September 2016 who were treated with IMRT were mailed a questionnaire at least 18 months after diagnosis. Patient-reported urinary, sexual, bowel, and hormonal functional domains on a scale from 0 to 100, with higher scores indicating better outcomes, and generic health-related quality of life were collected using the Expanded Prostate Cancer Index Composite 26-item version and EQ-5D-5L. We used linear regression to compare PPLN-IMRT versus PO-IMRT with adjustment for patient, tumor, and treatment characteristics. Of the 7017 men who received a questionnaire, 5468 (77.9%) responded; 4196 (76.7%) had received PO-IMRT and 1272 (23.3%) PPLN-IMRT. Adjusted differences in the Expanded Prostate Cancer Index Composite 26-item version domain scores were smaller than 1 (P always >.2), except for sexual function, with men who had PPNL-IMRT reporting a lower mean score (adjusted difference, 2.3; 95% confidence interval, 0.9-3.7; P = .002). This did not represent a clinically relevant difference. There was no significant difference in health-related quality of life (P = .5). Additional pelvic lymph node irradiation does not lead to clinically meaningful increases in the toxicity of IMRT for prostate cancer according to patient-reported functional outcomes and health-related quality of life.

An institutional review: dosimetry comparison between simultaneous integrated boost IMRT and VMAT for prostate cancer

AbstractPurpose:A comparative study was performed about the plan parameters and quality indices between volumetric arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for the treatment of high-risk prostate cancer patients. The aim of this retrospective study was to compare the two methods of external beam radiotherapy IMRT and VMAT in terms of plan quality and efficacy.Material and method:Fifteen high-risk prostate patients were planned for radiotherapy using 6 MV photon. Three dose levels were contoured having Planning Tumour Volume 1 (PTV1 = 48 Gy), Planning Tumour Volume 2 (PTV2 = 57.6 Gy) and Planning Tumour Volume 3 (PTV3 = 60 Gy). Setup margins were given using the CHIP trial method. The prescribed PTV3 dose was 60 Gy in 20 fractions which is biologically equivalent to 74 Gy in 37 fractions using α/β = 3. In case of IMRT, seven fixed beam angles 30, 60, 105, 180, 255, 300 and 330 were used and the dose was optimised using the sliding window method. In case of rapid arc technique, one or two full arcs were used for dose optimisation while keeping all the dose constraints and other planning parameters same used in IMRT. The plan evaluation parameters and Organ at risks (OARs) doses were calculated using a dose volume histogram (DVH).Results:The average D2, D5, D95 and PTVmean for PTV3 were 61.22, 61.13, 58.12, 60.00 Gy and 62.41 62.24 59.53 61.12 Gy for IMRT and VMAT, respectively. The averages V60 for bladder and V30 for rectum were 22.81, 25 and 67, 65% for IMRT and VMAT, respectively. The average homogeneity index (HI), conformity index (CI) and gradient index (GI) were 1.04, 1.4833, 14.79 and 1.04, 1.704, 7.89 for IMRT and VMAT, respectively.Conclusion:VMAT takes less dose-delivery time and lesser number of monitoring units than IMRT, thus it compensates the intrafractional movements during dose delivery. The Dose GI in VMAT was much better than IMRT. This indicates sharper dose fall off near the normal tissue. No other major differences were observed in terms of plan evaluation parameters between IMRT and VMAT techniques. So, we conclude that VMAT technique is more efficient than IMRT in terms of plan quality and dose delivery.

Fully automated dose prediction using generative adversarial networks in prostate cancer patients.

PurposeAlthough dose prediction for intensity modulated radiation therapy (IMRT) has been accomplished by a deep learning approach, delineation of some structures is needed for the prediction. We sought to develop a fully automated dose-generation framework for IMRT of prostate cancer by entering the patient CT datasets without the contour information into a generative adversarial network (GAN) and to compare its prediction performance to a conventional prediction model trained from patient contours.MethodsWe propose a synthetic approach to translate patient CT datasets into a dose distribution for IMRT. The framework requires only paired-images, i.e., patient CT images and corresponding RT-doses. The model was trained from 81 IMRT plans of prostate cancer patients, and then produced the dose distribution for 9 test cases. To compare its prediction performance to that of another trained model, we created a model trained from structure images. Dosimetric parameters for the planning target volume (PTV) and organs at risk (OARs) were calculated from the generated and original dose distributions, and mean differences of dosimetric parameters were compared between the CT-based model and the structure-based model.ResultsThe mean differences of all dosimetric parameters except for D98% and D95% for PTV were within approximately 2% and 3% of the prescription dose for OARs in the CT-based model, while the differences in the structure-based model were within approximately 1% for PTV and approximately 2% for OARs, with a mean prediction time of 5 seconds per patient.ConclusionsAccurate and rapid dose prediction was achieved by the learning of patient CT datasets by a GAN-based framework. The CT-based dose prediction could reduce the time required for both the iterative optimization process and the structure contouring, allowing physicians and dosimetrists to focus their expertise on more challenging cases.

Multi-atlas-based auto-segmentation for prostatic urethra using novel prediction of deformable image registration accuracy.

Accurate identification of the prostatic urethra and bladder can help determine dosing and evaluate urinary toxicity during intensity-modulated radiation therapy (IMRT) planning in patients with localized prostate cancer. However, it is challenging to locate the prostatic urethra in planning computed tomography (pCT). In the present study, we developed a multiatlas-based auto-segmentation method for prostatic urethra identification using deformable image registration accuracy prediction with machine learning (ML) and assessed its feasibility. We examined 120 patients with prostate cancer treated with IMRT. All patients underwent temporary urinary catheter placement for identification and contouring of the prostatic urethra in pCT images (ground truth). Our method comprises the following three steps: (a) select four atlas datasets from the atlas datasets using the deformable image registration (DIR) accuracy prediction model, (b) deform them by structure-based DIR, (3) and propagate urethra contour using displacement vector field calculated by the DIR. In (a), for identifying suitable datasets, we used the trained support vector machine regression (SVR) model and five feature descriptors (e.g., prostate volume) to increase DIR accuracy. This method was trained/validated using 100 patients and performance was evaluated within an independent test set of 20 patients. Fivefold cross-validation was used to optimize the hype parameters of the DIR accuracy prediction model. We assessed the accuracy of our method by comparing it with those of two others: Acostas method-based patient selection (previous study method, by Acosta et al.), and the Waterman's method (defines the prostatic urethra based on the center of the prostate, by Waterman et al.). We used the centerlines distance (CLD) between the ground truth and the predicted prostatic urethra as the evaluation index. The CLD in the entire prostatic urethra was 2.09±0.89mm (our proposed method), 2.77±0.99mm (Acosta et al., P=0.022), and 3.47±1.19mm (Waterman et al., P<0.001); our proposed method showed the highest accuracy. In segmented CLD, CLD in the top 1/3 segment was highly improved from that of Waterman et.al. and was slightly improved from that of Acosta et.al., with results of 2.49±1.78mm (our proposed method), 2.95±1.75mm (Acosta et al., P=0.42), and 5.76±3.09mm (Waterman et al., P<0.001). We developed a DIR accuracy prediction model-based multiatlas-based auto-segmentation method for prostatic urethra identification. Our method identified prostatic urethra with mean error of 2.09mm, likely due to combined effects of SVR model employment in patient selection, modified atlas dataset characteristics and DIR algorithm. Our method has potential utility in prostate cancer IMRT and can replace use of temporary indwelling urinary catheters.

Progress towards Patient-Specific, Spatially-Continuous Radiobiological Dose Prescription and Planning in Prostate Cancer IMRT: An Overview.

Advances in imaging have enabled the identification of prostate cancer foci with an initial application to focal dose escalation, with subvolumes created with image intensity thresholds. Through quantitative imaging techniques, correlations between image parameters and tumour characteristics have been identified. Mathematical functions are typically used to relate image parameters to prescription dose to improve the clinical relevance of the resulting dose distribution. However, these relationships have remained speculative or invalidated. In contrast, the use of radiobiological models during treatment planning optimisation, termed biological optimisation, has the advantage of directly considering the biological effect of the resulting dose distribution. This has led to an increased interest in the accurate derivation of radiobiological parameters from quantitative imaging to inform the models. This article reviews the progress in treatment planning using image-informed tumour biology, from focal dose escalation to the current trend of individualised biological treatment planning using image-derived radiobiological parameters, with the focus on prostate intensity-modulated radiotherapy (IMRT).