Hypofractionation For Prostate Cancer Research Articles

Image-guided Hypofractionated Radiotherapy as an Alternative to Radical Prostatectomy in Localized Prostate Cancer in Elderly Patients with Low Life Expectancy.

Radical prostatectomy is appropriate for any patient whose cancer appears clinically localised to prostate. However because of potential perioperative morbidity, radical prostatectomy is generally reserved for patients whose life expectancy is more than ten years. Moderate hypofractionation for localized prostate cancer is safe and effective. There is a growing body of evidence in support of extreme hypofractionation for localized prostate cancer. Hypofractionation for prostate cancer was originally carried out in the pursuit of efficiency and convenience, but has now attracted greatly renewed interest based upon a hypothesis that prostate cancers have a higher sensitivity to fraction size, reflected in a low α/β ratio, then do late responding organs at risk such as the rectum or bladder. From January 2017 to December 2020 we treated 112 patients of localised Prostate Cancer with Image Guided Radiotherapy (IGRT). They were in range of 75-85 years. They were of stage T1-T3, N0 or N1. There were significant comborbidities. ECOG performance status was 0-1. They were given 3 months of Androgen Deprivation Therapy (ADT) before starting IGRT. Patients were immobilised with casts and subject to CT simulation. CBCT was taken daily. Dose was 70 Gy @ 250 cGy per fraction at a frequency of 5 fractions per week. Complete blood counts were done weekly for assessment of haematological toxicity. Androgen Deprivation Therapy was continued post IGRT. All the patients were able to complete the treatment. Evaluation was done at one month, three month and six months post treatment. 104 out of 112 patients achieved complete response. Other 8 had near complete response. There were no acute grade 3-4 toxicities. Grade 1-2 toxicities like skin desquamation, diarrhoea, burning micturition were managed conservatively. Late toxicity was rectal bleeding seen after one year of completion of treatment and was managed with steroid enemas. 23 patients required argon plasma laser therapy. Image guided radiotherapy is well tolerated, easy to implement and an effective alternative to radical prostatectomy in elderly patients with comorbidities and low life expectancy.

265 Early outcome of first Vietnamese series of moderately hypo-fractionated prostate cancer radiotherapy

265 Early outcome of first Vietnamese series of moderately hypo-fractionated prostate cancer radiotherapy

Investigating the use of comprehensive motion monitoring for intrafraction 3D drift assessment of hypofractionated prostate cancer patients on a 1.5T magnetic resonance imaging radiotherapy system

This work investigates the use of a multi-2D cine magnetic resonance imaging-based comprehensive motion monitoring (CMM) system for the assessment of prostate intrafraction 3D drifts. The data of six healthy volunteers were analyzed and the values of a clinically-relevant registration quality factor metric exported by CMM were presented. Additionally, the CMM-derived prostate motion was compared to a 3D-based reference and the 2D-3D tracking agreement was reported. Due to the low quality of SI motion tracking (often >2 mm tracking mismatch between anatomical planes) we conclude that further improvements are desirable prior to clinical introduction of CMM for prostate drift corrections.

2669: Photon vs Proton Hypofractionation in Prostate Cancer: a systematic review and meta-analysis

2669: Photon vs Proton Hypofractionation in Prostate Cancer: a systematic review and meta-analysis

2033: Systematic trends in T2w and ADC in hypofractionated prostate cancer treatments on a 1.5T MR-Linac

2033: Systematic trends in T2w and ADC in hypofractionated prostate cancer treatments on a 1.5T MR-Linac

Does cost minimization of hypofractionated radiation therapy content all health stakeholders?

Does cost minimization of hypofractionated radiation therapy content all health stakeholders?

Hypofractionation Adoption in Prostate Cancer Radiotherapy: Results of an International Survey.

Hypofractionation is noninferior to conventional fractionation in the treatment of localized prostate cancer. Using results from the European Society of Radiation Oncology's (ESTRO) Global Impact of Radiotherapy in Oncology (GIRO) initiative survey on hypofractionation, this study identifies rates of adoption, facilitating factors, and barriers to adoption of hypofractionation in prostate cancer across World Bank income groups. The ESTRO-GIRO initiative administered an international, anonymous, electronic survey to radiation oncologists from 2018 to 2019. Physician demographics, clinical practice characteristics, and hypofractionation regimen use (if any) for several prostate cancer scenarios were collected. Responders were asked about specific justifications and barriers to adopting hypofractionation, and responses were stratified by World Bank income group. Multivariate logistic regression models were used to analyze variables associated with hypofractionation preference. A total of 1,157 physician responses were included. Most respondents (60%) were from high-income countries (HICs). In the curative setting, hypofractionation was most often preferred in low- and intermediate-risk prostate cancers, with 52% and 47% of respondents reporting hypofractionation use in ≥50% of patients, respectively. These rates drop to 35% and 20% in high-risk prostate cancer and where pelvic irradiation is indicated. Most respondents (89%) preferred hypofractionation in the palliative setting. Overall, respondents from upper-middle-income countries and lower-middle- and low-income countries were significantly less likely to prefer hypofractionation than those from HICs (P < .001). The most frequently cited justification and barrier were availability of published evidence and fear of worse late toxicity, respectively. Hypofractionation preference varies by indication and World Bank income group, with greater acceptance among providers in HICs for all indications. These results provide a basis for targeted interventions to increase provider acceptance of this treatment modality.

PO-2095 In silico identification of dose equivalences in hypofractionated prostate cancer radiotherapy

PO-2095 In silico identification of dose equivalences in hypofractionated prostate cancer radiotherapy

Moderate hypofractionation in prostate cancer: experience from Regional Hospital ISSSTE, Morelos

Moderate hypofractionation in prostate cancer: experience from Regional Hospital ISSSTE, Morelos

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.

Evaluation of the dosimetric influence of interfractional 6D setup error in hypofractionated prostate cancer treated with IMRT and VMAT using daily kV-CBCT

IntroductionProstate cancer is one of the most common malignant tumors in men and is usually treated with advanced intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Significant uncorrected interfractional 6-Dimensional setup errors could impact the delivered dose. The aim of this study was to assess the dosimetric impact of 6D interfractional setup errors in hypofractionated prostate cancer using daily kilovoltage cone-beam computed tomography (kV-CBCT). MethodsThis retrospective study comprised twenty prostate cancer patients treated with hypofractionated IMRT (8) and VMAT (12) with daily kV-CBCT image guidance. Interfraction 6D setup errors along lateral, longitudinal, vertical, pitch, roll, and yaw axes were evaluated for 400 CBCTs. For targets and organs at risk (OARs), the dosimetric impact of rotational error (RError), translational error (TError), and translational plus rotational error (T+RError) were evaluated on kV-CBCT images. ResultsThe single fraction maximum TError ranged from 12–20 mm, and the RError ranged from 2.80–3.00. The maximum mean absolute dose variation ΔD in D98% (dose to 98% volume) of CTV-55 and PTV-55 was -0.66±0.82 and -5.94±3.8 Gy, respectively, in the T+RError. The maximum ΔD (%) for D98% and D0.035cc in CTV-55 was -4.29% and 2.49%, respectively, while in PTV-55 it was -24.9% and 2.36%. The mean dose reduction for D98% in CTV-55 and D98% and D95% in PTV-55 was statistically significant (p<0.05) for TError and T+RError. The mean dose variation for Dmean and D50% in the rectum was statistically significant (p<0.05) for TError and T+RError. ConclusionThe uncorrected interfractional 6D setup error results in significant target underdosing and OAR overdosing in prostate cancer. This emphasizes the need to correct interfractional 6D setup errors daily in IMRT and VMAT.

Clinical utility of a 1.5 T magnetic resonance imaging-guided linear accelerator during conventionally fractionated and hypofractionated prostate cancer radiotherapy.

PurposeTo report our initial experience with 1.5 T magnetic resonance imaging (MRI) linear accelerator (LINAC) in prostate cancer radiotherapy in terms of its use in a radiation oncology clinic.MethodsThe medical records of 14 prostate cancer patients treated with MRI-guided radiotherapy were retrospectively evaluated. The fraction time, adapt-to-position (ATP):adapt-to-shape (ATS) usage rate, machine-associated treatment interruption rate, median gamma pass rate, the percentage of planning target volume receiving at least 95% of the prescription dose coverage value of each ATS fraction, the effect of the learning curve on the fraction time and radiation-related acute gastrointestinal and genitourinary toxicities were evaluated.ResultsFourteen patients have completed their treatment receiving a total of 375 fractions. Six patients (42%) were treated with the moderately hypofractionated regimen, five patients (36%) with conventionally fractionated, and three patients (22%) with the ultra-hypofractionated radiotherapy regimens. The ATP : ATS usage ratio was 3:372. The median fraction time was 46 min (range, 24-81 min). For the 3%/3 mm criterion, median gamma pass rate was 99.4% (range, 94.6–100%). Machine-related treatment interruptions were observed in 11 (2.9%) of 375 fractions, but this interruption rate decreased from 4.1% to 0.8%, after an upgrade. Three patients (22%) had gastrointestinal and five patients (36%) had genitourinary toxicity. No ≥grade 3 toxicity was observed.Conclusion1.5 T MRI-LINAC device could be used as a conventional LINAC device, when the conditions of the radiotherapy center are appropriate. MRI-guided prostate radiotherapy is safe and feasible, and high-quality studies with a larger number of patients and long-term results are needed to better evaluate this new technology.

PO-1382 Moderate hypofractionation for prostate cancer with fiducials markers

PO-1382 Moderate hypofractionation for prostate cancer with fiducials markers

Urethra Sparing With Target Motion Mitigation in Dose-Escalated Extreme Hypofractionated Prostate Cancer Radiotherapy: 7-Year Results From a Phase II Study.

PurposeTo explore whether the rectal distension-mediated technique, harnessing human physiology to achieve intrafractional prostate motion mitigation, enables urethra sparing by inverse dose painting, thus promoting dose escalation with extreme hypofractionated stereotactic ablative radiotherapy (SABR) in prostate cancer.Materials and MethodsBetween June 2013 and December 2018, 444 patients received 5 × 9 Gy SABR over 5 consecutive days. Rectal distension-mediated SABR was employed via insertion of a 150-cm3 air-inflated endorectal balloon. A Foley catheter loaded with 3 beacon transponders was used for urethra visualization and online tracking. MRI-based planning using Volumetric Modulated Arc Therapy - Image Guided Radiotherapy (VMAT-IGRT) with inverse dose painting was employed in delivering the planning target volume (PTV) dose and in sculpting exposure of organs at risk (OARs). A 2-mm margin was used for PTV expansion, reduced to 0 mm at the interface with critical OARs. All plans fulfilled Dmean ≥45 Gy. Target motion ≥2 mm/5 s motions mandated treatment interruption and target realignment prior to completion of the planned dose delivery.ResultsPatient compliance to the rectal distension-mediated immobilization protocol was excellent, achieving reproducible daily prostate localization at a patient-specific retropubic niche. Online tracking recorded ≤1-mm intrafractional target deviations in 95% of treatment sessions, while target realignment in ≥2-mm deviations enabled treatment completion as scheduled in all cases. The cumulative incidence rates of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicities were 5.3% and 1.1%, respectively. The favorable toxicity profile was corroborated by patient-reported quality of life (QOL) outcomes. Median prostate-specific antigen (PSA) nadir by 5 years was 0.19 ng/ml. The cumulative incidence rate of biochemical failure using the Phoenix definition was 2%, 16.6%, and 27.2% for the combined low/favorable–intermediate, unfavorable intermediate, and high-risk categories, respectively. Patients with a PSA failure underwent a 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) scan showing a 20.2% cumulative incidence of intraprostatic relapses in biopsy International Society of Urological Pathology (ISUP) grade ≥3.ConclusionThe rectal distension-mediated technique is feasible and well tolerated. Dose escalation to 45 Gy with urethra-sparing results in excellent toxicity profiles and PSA relapse rates similar to those reported by other dose-escalated regimens. The existence of intraprostatic recurrences in patients with high-risk features confirms the notion of a high α/β ratio in these phenotypes resulting in diminished effectiveness with hypofractionated dose escalation.

Minimum non-isotropic and asymmetric margins for taking into account intrafraction prostate motion during moderately hypofractionated radiotherapy

PurposeTo investigate the impact on dose distribution of intrafraction motion during moderate hypofractionated prostate cancer treatments and to estimate minimum non-isotropic and asymmetric (NI-AS) treatment margins taking motion into account. MethodsProstate intrafraction 3D displacements were recorded with a transperineal ultrasound probe and were evaluated in 46 prostate cancer patients (876 fractions) treated by moderate hypofractionated radiation therapy (60 Gy in 20 fractions). For 18 patients (346 fractions), treatment plans were recomputed increasing CTV-to-PTV margins from 0 to 6 mm with an auto-planning optimization algorithm. Dose distribution was estimated using the voxel shifting method by displacing CTV structure according to the retrieved movements. Time-dependent margins were finally calculated using both van Herk’s formula and the voxel shifting method. ResultsMean intrafraction prostate displacements observed were −0.02 ± 0.52 mm, 0.27 ± 0.78 mm and −0.43 ± 1.06 mm in left–right, supero-inferior and antero-posterior directions, respectively. The CTV dosimetric coverage increased with increased CTV-to-PTV margins but it decreased with time. Hence using van Herk’s formula, after 7 min of treatment, a margin of 0.4 and 0.5 mm was needed in left and right, 1.5 and 0.7 mm in inferior and superior and 1.1 and 3.2 mm in anterior and posterior directions, respectively. Conversely, using the voxel shifting method, a margin of 0 mm was needed in left–right, 2 mm in superior, 3 mm in inferior and anterior and 5 mm in posterior directions, respectively. With this latter NI-AS margin strategy, the dosimetric target coverage was equivalent to the one obtained with a 5 mm homogeneous margin. ConclusionsNI-AS margins would be required to optimally take into account intrafraction motion.

Simultaneous integrated boost (SIB) to dominant intra-prostatic lesions during extreme hypofractionation for prostate cancer: the impact of rectal spacers

PurposeBoosting dominant intra-prostatic lesions (DILs) has the potential to increase the therapeutic ratio in prostate cancer radiotherapy. In this study, employing 5-fraction stereotactic ablative radiotherapy (SABR) volumetric modulated arc therapy (VMAT) to deliver 40 Gy to the prostate clinical target volume (CTV) while boosting the DIL up to 50 Gy was evaluated for patients before and after rectal spacer insertion.Materials and methods24 Computed Tomography (CT) scans of 12 prostate cancer patients with unfavourable intermediate or high risk prostate cancer were employed in this study. At least two treatment plans were generated for each patient to compare pre- and post-spacer insertion plans. Plans were evaluated for target coverage, organs-at-risk doses, and the achievable boost dose level.ResultsThe CTV coverage was significantly better in plans with a spacer, V40Gy 98.4% versus 97.0% (p = 0.012). Using spacers significantly reduced rectal dose in all 12 patients in this study. It was possible to boost DIL to 50 Gy to without violating dose constraints in 6 of 12 patients and to 47.5 Gy in 3 patients post-spacer insertion. For 3 patients (25%) it was not possible to boost DIL above 45 Gy even with a spacer in situ. Without a spacer, for 6 patient (50%) clinically acceptable plan were only achieved when the DIL dose was lowered to 45 Gy. In five of these 6 patients the dose limiting structure was the urethra (urethra planning risk volume V45Gy [cc] ≤ 0.1 cc constraint).ConclusionsClinically acceptable plans for 5 fraction SABR, 40 Gy to the prostate CTV, with a SIB to DIL (45–50 Gy) were achieved. The boost dose achieved was DIL location dependent and primarily affected by DIL’s proximity to the urethra. Compared to plans before spacer insertion, higher DIL dose were achieved with spacer in situ for 25% of the patients. Moreover, significant reduction in rectal dose and better target coverage were also achieved for all patients with spacers in situ.

A phase II trial of hypofractionated radiation therapy over five treatments for prostate cancer with high-risk features after radical prostatectomy: MC1754.

248 Background: Hypofractionated prostate cancer radiation has showed similar results in several prior phase III studies (PCG GU 003, PACE-B, and Hypo PC RT). However, prospective phase II-III clinical trial data testing 5 tx after prostatectomy is scarce. Methods: Between 2018 and 2019, 41 patients were treated after postprostatectomy for high risk features. 5 patients were treated adjuvantly, 36 for salvage including 8 with oligometastatic disease. Indications for adjuvant RT included a PSA &lt; 0.2 and +margins, SVI, or EPE. Salvage RT was offered for PSA ≥0.2. Oligometastatic RT for patients with ≤5 RT targets. Staging included C11 PET for all cases. Total dose to the prostate bed was 30-32 Gy in 5tx QOD with IMRT, conebeam IGRT, and MRI registration. All salvage patients received ADT for 6 months and oligometastatic patients for 18 months. Dose to the metastatic sites was 30 in 5tx QOD. Of the 41 patients 8 also received SBRT to the sites of oligometastatic disease. We looked at clinical outcomes defining biochemical failure as a PSA &gt; 0.2 after treatment, baseline adjusted CTC AE V5.0, baseline adjusted patient reported toxicities (PRO CTC AE), QOL (EPIC, PROMIS), and AUA was used for all cases. Results: Median follow up was 23 months (range 10-37). Pre-RT T stage was T2-T3b, with 47% being T3a-b; Pre RT Median PSA of 0.4 (range &lt; 0.1-1.9); Median GS 8 (6-9); and (+) margins in 48.8%. Sites of oligometastatic disease radiated included the LN and bone. Treatment related AE were grade 0-1 in all cases, except for one patient with G2 GU incontinence. Overall QOL remained high during follow including Promis 10 overall, mental, and physical scores; urinary bother, irritative/obstructive, and AUA scores; bowel overall, bowel bother, and bowel function scores; and overall sexual, sexual function, and sexual bother scores remained at baseline levels during follow up. Only hormonal overall, hormonal function, and hormonal bother had lower scores at 3 months that recovered by 12 months in patients treated with ADT for 6 months and by 24 months in patients treated with ADT for 18 months. A total of 3 clinical failure have been seen; 2 patients with regional failures alone; and one with axial skeleton bony failures for 93% clinical control at median follow up of 23 months. All 3 patients with clinical failure were salvaged successfully with SBRT and all patients remain disease free at last follow up. A total 5 patients with raising PSAs alone have been seen. All patients have been re-staged with C11 PET. No failures in the prostate bed or previously radiated sites have been seen. Conclusions: Toxicity for RT over 5tx is lower than expected with only one case of grade 2 urinary incontinence. QOL scores remained high during follow up, minor changes in hormonal scores were seen during ADT, but recovered after. 30-32 Gy over 5 tx provided 100% control in radiated targets and metastatic sites. Clinical trial information: NCT03570827.

OD16 - Dosimetric impact of intrafraction motion during moderate hypo-fractionated prostate cancer radiotherapy treatment

OD16 - Dosimetric impact of intrafraction motion during moderate hypo-fractionated prostate cancer radiotherapy treatment

Dosimetric evaluation of volumetric modulated arc therapy with simultaneous integrated boost hypofractionated radiation based on two types of multileaf collimators for prostate cancer.

For localized prostatic adenocarcinoma, hypo fractionated radiation has been shown to minimize treatment times while producing results that are similar to those of conventionally fractionated radiotherapy; therefore, volumetric modulated arc therapy (VMAT) plans face a real challenge in achieving the dosimetric parameters for planning target volumes (PTVs) and organs at risk (OARs).The aim of this study was to compare the plan quality and dosimetric effects of two different types of multi-leaf collimators (MLCs) on simultaneous integrated boost (SIB) hypo fractionated prostate cancer treatment using VMAT. Using the VMAT procedure, ten patients with prostate cancer were re-planned with two separate MLCs. For each patient, two treatment plans were carried out. The dose volume histogram (DVH) for PTVs and OARs, as well as the conformity index (CI) and homogeneity index (HI) with 5mm vs. 10mm MLC width, were used to examine the dosimetric parameters. The prescribed doses for the prostate gland (PTVp) and the pelvic nodes (PTVn) are 60 Gy/20fractions and 44 Gy/20fractions, respectively. In plans for Agility to MLCi2, HI and CI were improved. For Agility MLC, the p-values for HI and CI were 0.017 and 0.008, respectively. When compared to MLCi2, the dose distribution for PTVs was improved with Agility MLC. When compared to MLCi2, the delivery time with Agility MLC was reduced by 31%. With Agility MLC, the smallest leaf width results in a dosimetric benefit for PTV.

Biologically Effective Dose and Rectal Bleeding in Definitive Proton Therapy for Prostate Cancer.

Purpose and ObjectivesWith increasing use of hypofractionation and extreme hypofractionation for prostate cancer, rectal dose-volume histogram (DVH) parameters that apply across dose fractionations may be helpful for treatment planning in clinical practice. We present an exploratory analysis of biologically effective rectal dose (BED) and equivalent rectal dose in 2 Gy fractions (EQD2) for rectal bleeding in patients treated with proton therapy across dose fractionations.Materials and MethodsFrom 2016 to 2018, 243 patients with prostate cancer were treated with definitive proton therapy. Rectal DVH parameters were obtained from treatment plans, and rectal bleeding events were recorded. The BED and EQD2 transformations were applied to each rectal DVH parameter. Univariate analysis using logistic regression was used to determine DVH parameters that were significant predictors of grade ≥ 2 rectal bleeding. Youden index was used to determine optimum cutoffs for clinically meaningful DVH constraints. Stepwise model-selection criteria were then applied to fit a “best” multivariate logistic model for predicting Common Terminology Criteria for Adverse Events grade ≥ 2 rectal bleeding.ResultsConventional fractionation, hypofractionation, and extreme hypofractionation were prescribed to 117 (48%), 84 (34%), and 42 (17.3%) patients, respectively. With a median follow-up of 20 (2.5-40) months, 10 (4.1%) patients experienced rectal bleeding. On univariate analysis, multiple rectal DVH parameters were significantly associated with rectal bleeding across BED, EQD2, and nominal doses. The BED volume receiving 55 Gy > 13.91% was found to be statistically and clinically significant. The BED volume receiving 55 Gy remained statistically significant for an association with rectal bleeding in the multivariate model (odds ratio, 9.81; 95% confidence interval, 2.4-40.5; P = .002).ConclusionIn patients undergoing definitive proton therapy for prostate cancer, dose to the rectum and volume of the rectum receiving the dose were significantly associated with rectal bleeding across conventional fractionation, hypofractionation, and extreme hypofractionation when using BED and EQD2 transformations.