Proton Therapy For Prostate Cancer Research Articles

Dosimetric Features of Ultra-Hypofractionated Intensity Modulated Proton Therapy for Prostate Cancer

PurposeTo report clinical and dosimetric characteristics of five-fraction stereotactic ablative radiotherapy (SABR) using intensity modulated proton therapy (IMPT) for localized prostate cancer. Materials and MethodsAll patients receiving IMPT SABR from 2017 to 2021 for localized prostate cancer at our institution were included. Five fractions were delivered every other day to the prostate +/- seminal vesicles [clinical target volume (CTV)] with 3 mm/3% robustness. A four-field arrangement with two anterior oblique and two opposed lateral beams was used in most patients (97%), and most (99%) had a retroprostatic hydrogel spacer. ResultsA total of 534 patients with low (14%), favorable intermediate (45%), unfavorable intermediate (36%), high (4.0%), or very high-risk (0.6%) disease are evaluated. Prescription dose was 36.25 Gy (31%), 38 Gy (38%), or 40 Gy (31%) was prescribed. Median volume percentage of CTV receiving at least 100% of prescription dose [V100% (%)] was 100% [interquartile range: 99.99 - 100]. Rectum V50% (%), V80% (%), and V90% (%) were significantly lower in patients who had spacer, with a mean difference of -9.70%, -6.59%, and -4.42%, respectively, compared to those who did not have spacer. Femoral head dose was lower with a four-field arrangement. Mean differences in left and right femoral head V40% (%) were -6.99% and -10.74%, respectively. ConclusionWe provide a large, novel report of patients treated with IMPT SABR for localized prostate cancer. Four-field IMPT with hydrogel spacer provides significant sparing of rectum and femoral heads without compromising target coverage.

Evaluation of Delivered Doses in Proton Beam Therapy for Prostate Cancer Using Positron Emission Tomography/Computed Tomography Imaging

AimsProton beams deposit energy along their paths and stop abruptly without penetrating the opposite side, making it difficult to detect their actual paths. However, confirming the path may lead to evaluating the actual doses to organs at risk in proton therapy for prostate cancer. As proton beams produce positron emitters through nuclear fragmentation reactions, theoretically, proton beam paths can be measured by positron emission tomography/computed tomography (PET/CT). Therefore, this study investigated whether conducting PET/CT examinations immediately after proton beam therapy helps to assess the doses delivered to the rectal and urinary bladder walls, which are the major sites of radiation-related toxicity. Materials and methodsBetween June 2022 and June 2023, 51 consecutive patients with prostate cancer who underwent proton beam therapy were enrolled and imaged with PET/CT to measure these radioactive particles and validate the actual dose delivered to the rectal and urinary bladder walls. ResultsThe delivered doses assessed using PET/CT after proton beam therapy strongly correlated with the planned volume for proton beam treatment. ConclusionsPET/CT exhibited potential as a valuable tool for validating the irradiated dose to organs at risk.

The Role of Proton Therapy for Prostate Cancer in the Setting of Hip Prosthesis.

Given that the current standard of proton therapy (PT) for prostate cancer is through bilateral beams, this modality is typically avoided when it comes to treatment of patients with hip prosthesis. The purpose of this study was to evaluate whether novel PT methods, i.e., anterior proton beams and proton arc therapy (PArc), could be feasible options to treat this patient subpopulation. We evaluate PT methods in the context of dosimetry and robustness and compare with standard of practice volumetric modulated arc therapy (VMAT) to explore any potential benefits. Two PT and one VMAT treatment plans were retrospectively created for 10 patients who participated in a clinical trial with a weekly repeat CT (rCT) imaging component. All plans were robustly optimized and featured: (1) combination anterior oblique and lateral proton beams (AoL), (2) PArc, and (3) VMAT. All patients had hydrogel spacers in place, which enabled safe application of anterior proton beams. The planned dose was 70 Gy (RBE) to the entire prostate gland and 50 Gy (RBE) to the proximal seminal vesicles in 28 fractions. Along with plan dose-volume metrics, robustness to setup and interfractional variations were evaluated using the weekly rCT images. The linear energy transfer (LET)-weighted dose was evaluated for PArc plans to ensure urethra sparing given the typical high-LET region at the end of range. Both PT methods were dosimetrically feasible and provided reduction of some key OAR metrics compared to VMAT except for penile bulb, while providing equally good target coverage. Significant differences in median rectum V35 (22-25%), penile bulb Dmean (5 Gy), rectum V61 (2%), right femoral head Dmean (5 Gy), and bladder V39 (4%) were found between PT and VMAT. All plans were equally robust to variations. LET-weighted dose in urethra was equivalent to the physical dose for PArc plans and hence no added urethral toxicity was expected. PT for treatment of prostate cancer patients with hip prosthesis is feasible and equivalent or potentially superior to VMAT in quality in some cases. The choice of radiotherapy regimen can be personalized based on patient characteristics to achieve the best treatment outcome.

Dosimetry Impact of Bladder Volume Changes and Rectum Filling/Emptying at Proton Therapy of Prostate Cancer; A Simulation Study

Purpose: In the recent decade, proton therapy facilities are increasing worldwide. This study aimed to analyze the influence of volumetric changes in bladder and rectum filling on the dose received by normal surrounding tissues at prostate cancer proton therapy. In this work, an anthropomorphic phantom dedicated to the prostate organs and nearby tissues has been developed using the FLUKA simulation code.
 Materials and Methods: The geometry of the prostate and normal nearby tissues, bladder volumetric changes, and rectum filling/emptying status were simulated according to a database of real patients to mimic actual treatment, assuming the prostate as the target receives the prescribed dose uniformly with no over- and under dosage at each treatment session. Furthermore, the dosimetric effect of air- and water-filled balloons as prostate fixation tools was considered on the rectum, during our simulation process.
 Results: Final analyzed results showed that the overall dose received by normal nearby organs with be decreased at proton therapy of prostate cancer if the bladder is full, although this dose reduction is not remarkable. Moreover, rectum filling/emptying and also implementation of balloons with different matters have no significant effect on the amount of dose received by this organ.
 Conclusion: The dosimetric impact of bladder volumetric variations onto normal nearby organs will not be a crucial issue in proton therapy of prostate cancer if the prescribed high dose is delivered on the target with proper uniformity laterally and in-depth. Based on the obtained results, a full bladder is recommended while target bombarding by a proton beam.

Phase II Clinical Trial of Hypofractionated Image-Guided Proton Therapy with 12 Fractions for Prostate Cancer.

Towards hypofractionated proton therapy for prostate cancer for improving convenience for patients to receive treatment and improving therapeutic efficacy, image-guided technique with hydrogel spacer solved the late gastrointestinal toxicity, but it is unclear whether acute genitourinary (GU) toxicity is acceptable. The aim of this phase II study was to evaluate the safety and efficacy of hypofractionated image-guided proton therapy (IGPT) with 12 fractions for prostate cancer. Eligibility criteria were as follows: (1) histologically confirmed primary prostate cancer; (2) T1-T3bN0M0 staged by (UICC TNM8th); (3) ECOG-PS ≤ 2; (4) age ≥ 20 years; (5) no serious underlying disease or other cancers; (6) technically capable of proton therapy, and (7) written informed consent. Primary endpoint was the ratio of grade 2 or more acute genitourinary toxicity. We used the modified CTCAE grading of grade 2 GU toxicities, in which prescribing two and more types of drugs for dysuria within 3 months of the start of radiation was considered to indicate grade 2 GU toxicity. A phase II trial was planned based on the minimax Simon's two-stage design with a significance level of 0.05 and a power of 90%. The acceptable incidence is considered to be less than 5%, and the unacceptable incidence is considered to be more than 15%. A total of 83 patients is required for completion of the trial (7 patients or fewer). After evaluating the primary endpoint in 83 patients, 217 additional patients were registered and a total of 300 patients were registered in order to further examine the safety and efficacy. The prescribed dose to the isocenter was 51.6 GyRBE in 12 fractions (4 days a week). From January 2020 to March 2021, 30, 53, and 217 patients (total 300) were enrolled. The patient characteristics were as follows: median age, 70 (48-83) years; low/intermediate/high risk, 44/132/124. Forty-nine and 38 patients had benign prostatic hyperplasia and diabetes mellitus, respectively. Grade 2 acute GU toxicities were observed in 1, 5 and 13 patients, respectively (total 6.3%). No grade 3 or higher acute GU toxicities were observed. However, urinary retention during IGPT, which was not previously observed, was observed in 3 cases, and temporary urethral catheterization was performed (Grade 2). Most of the acute GU toxicity tended to improve at 1 month after IGPT, and almost improved at 3 months. Mean score deteriorations beyond the minimum clinically important difference threshold (1/2 SD) were observed only at 1 month in the following scales: summary (-6.0), bother (-7.0), and irritative/obstructive (-6.3). Hypofractionated IGPT with 12 fractions for prostate cancer is well tolerated in acute GU toxicities. Longer follow-up is necessary to evaluate the efficacy and late toxicities. Further investigation of hypofractionated IGPT with 12 fractions for prostate cancer is warranted. Since April 2021, an additional 1000 cases of prospective registration study have been conducted.

Rapid Unpaired CBCT-Based Synthetic CT for CBCT-Guided Adaptive Radiotherapy

Quantitative cone beam CT (CBCT) is the foundation for image-guided radiation therapy, improving treatment setup, tumor delineation and dose calculation. However, CBCT images suffer from severe artifacts, limiting clinical utility. Deep learning can overcome these limitations, boosting radiographic and dosimetric quality critical for online adaptive radiotherapy (ART). We hypothesize adapted contrastive unpaired translation (CUT), a recent method for image-to-image translation of photographic images, can improve CBCT quality while reducing compute time, demonstrating utility for ART. Same-day CBCT and quality assurance CT (QACT) images acquired from 79 patients receiving proton therapy for prostate cancer between 2019 and 2020 at a single institution were retrospectively collected. QACT images were acquired for quality assurance in accordance with institutional policy. Seventy-nine patients yielded 102 non-contrast CBCT-QACT image sets. Each QACT image was rigidly registered to the corresponding CBCT and resampled to 1 × 1 × 2 mm to establish uniform voxel size and spacing. CBCT images were randomly shuffled prior to input to the CUT model for unsupervised training and QACT-quality synthetic CT images were generated as outputs. We compared mean absolute error (MAE), structural similarity index measure (SSIM), and Fréchet inception distance (FID) against same-day QACT. MAE, SSIM, and FID were compared for the CycleGAN and CUT data relative to input QACT and are reported as the mean across five-fold cross-validation ± standard error. CUT achieved superior performance in MAE (19.5 ± 3.9 HU vs. cycleGAN 47.1 ± 25.4) and FID (31.5 ± 6.6 vs cycleGAN 75.9 ± 41.3). MAE indicates pixel-level correspondence to QACT HU intensity values, making the synthetic outputs of CUT useful for dose calculations during ART. FID further demonstrates perceptual visual similarity. SSIM for CycleGAN (0.7 ± 0.2) and CUT (0.8 ± 0.0) were similar, indicating acceptable reproducibility of global structure. CUT was faster and lighter than CycleGAN. CycleGAN contained a total of 28,286,000 parameters; CUT contained 14,703,000, approximately half that of CycleGAN. As a result, CycleGAN computes on a single CT image slice over 0.33s while CUT requires just 0.18s. The contrastive method investigated here was demonstrated to be faster and more accurate than CycleGAN, requiring fewer networks and parameters to achieve superior performance. We demonstrated anatomic boundary preservation and HU fidelity superior to cycleGAN while significantly reducing compute time. We plan to investigate the use of these synthetic CT images in automated segmentation prior to exploration of CUT in a prospective setting.

Dose evaluation of inter- and intra-fraction prostate motion in extremely hypofractionated intensity-modulated proton therapy for prostate cancer.

Inter- and intra-fractional prostate motion can deteriorate the dose distribution in extremely hypofractionated intensity-modulated proton therapy. We used verification CTs and prostate motion data calculated from 1024 intra-fractional prostate motion records to develop a voxel-wise based 4-dimensional method, which had a time resolution of 1s, to assess the dose impact of prostate motion. An example of 100 fractional simulations revealed that motion had minimal impact on planning dose, the accumulated dose in 95% of the scenarios fulfilled the clinical goals for target coverage (D95>37.5Gy). This method can serve as a complementary measure in clinical setting to guarantee plan quality.

Acute genitourinary toxicity of pencil beam scanning proton therapy for localized prostate cancer: utility of the transition zone index and average urinary flow rate in predicting acute urinary retention.

The purpose of this study was to evaluate the incidence of acute genitourinary toxicities in patients undergoing pencil beam scanning proton therapy for prostate cancer and investigate predictive factors associated with acute urinary retention. A total of 227 patients treated between 2018 and 2021 were divided into the normo-fractionated proton therapy group (n=107) and the moderately hypo-fractionated proton therapy group (n=120), with prescribed doses of 76-78Gy relative biological effectiveness in 38-39 fractions and 60-63Gy relative biological effectiveness in 20-21 fractions, respectively. Uroflowmetry parameters and the transition zone index were prospectively evaluated. Forty-five patients (42%) in the normo-fractionated proton therapy and 33 (28%) in the moderately hypo-fractionated proton therapy developed acute grade 2 genitourinary toxicities (P=0.02). The most common acute genitourinary toxicity was acute urinary retention. Thirty-nine patients (36%) treated with normo-fractionated proton therapy and 27 (23%) treated with moderately hypo-fractionated proton therapy developed grade 2 acute urinary retention (P=0.02). No patients developed grade≥3 toxicity. Univariate analysis showed the transition zone index, prostate volume, international prostate symptom score, voided volume, maximum flow rate and average flow rate were associated with grade 2 acute urinary retention. Multivariate analysis in both groups revealed the transition zone index (P=0.025 and 0.029) and average flow rate (P=0.039 and 0.044) were predictors of grade 2 acute urinary retention. The incidence of acute genitourinary toxicities was lower in the moderately hypo-fractionated proton therapy compared with the normo-fractionated proton therapy. Lower pretreatment average flow rate and a higher transition zone index were useful predictors of grade 2 acute urinary retention.

Initial Experience with Real-Time Gated Proton Therapy (RGPT) in the Definitive Treatment of Prostate Cancer

<h3>Purpose/Objective(s)</h3> RGPT has the potential to provide instantaneous feedback for intrafraction target motion to maximize patient safety and inform optimal treatment planning. Our purpose was to report our early experience with RGPT and to summarize intrafraction target motion and implications on treatment delivery, including added time, for a pilot population of prostate cancer patients before expansion to other sites with greater motion. <h3>Materials/Methods</h3> RGPT with a proton beam therapy system was commissioned and implemented at our proton center, representing the first experience in the United States. Patients being treated definitively with proton therapy to the prostate ± seminal vesicles-only and who had successful placement of platinum fiducial markers and hydrogel spacer were assessed on a prospective IRB-approved registry. Orthogonal fluoroscopic imaging was taken at a pulse rate of one image per second during fractionated proton therapy to assess positioning of a pre-selected fiducial marker. Thresholds to guide beam-on and beam-off gating were determined for a matching score component (based on quality of the image tracking and the guiding template) and for a shift tolerance component (based on our typical set-up uncertainty robustness of 3mm). The shift tolerances were defined as 2mm for left-right and anterior-posterior, and 3mm for superior-inferior. Each patient was treated with single-field optimization planning and a two lateral beam setup. <h3>Results</h3> To date, 8 prostate cancer patients have been treated with a total of 152 RGPT-guided fields. The table details the mean, maximum, standard deviation, and estimated upper 90^th percentile of directional shifts for the entire dataset for 1) the total RGPT-tracked treatment time and 2) the beam-on time as gated by RGPT tracking. On average, the initial imaging to set up the RGPT system required 2.5 seconds per field. The average total treatment time during RGPT guidance, including periods of both "on" and "off" gating, was 41.3 seconds per field. RGPT tracking triggered "beam-off" for an average of 7.8 seconds per field, increasing the total treatment delivery time by 20.2% across the 152 fields. <h3>Conclusion</h3> RGPT successfully tracked intrafraction fiducial marker motion during proton therapy for prostate cancer, while having minimal impact on total treatment time. Further aggregated RGPT-derived data may help to inform optimal treatment planning parameters such as robust optimization.

Technical note: Investigation of dose and LETd effect to rectum and bladder by using non-straight laterals in prostate cancer receiving proton therapy.

Parallel-opposed lateral beams are the conventional beam arrangements in proton therapy for prostate cancer. However, when considering linear energy transfer (LET) and RBE effects, alternative beam arrangements should be investigated. To investigate the dose and dose averaged LET (LETd ) impact of using new beam arrangements rotating beams 5°-15° posteriorly to the laterals in prostate cancer treated with pencil-beam-scanning (PBS) proton therapy. Twenty patients with localized prostate cancer were included in this study. Four proton treatment plans for each patient were generated utilizing 0°, 5°, 10°, and 15° posterior oblique beam pairs relative to parallel-opposed lateral beams. Dose-volume histograms (DVHs) from posterior oblique beams were analyzed. Dose-LETd -volume histogram (DLVH) was employed to study the difference in dose and LETd with each beam arrangement. DLVH indices, , defined as the cumulative absolute volume that has a dose of at least d (Gy[RBE]) and a LETd of at least l (keV/µm), were calculated for both the rectum and bladder to the whole group of patients and two-sub groups with and without hydrogel spacer. These metrics were tested using Wilcoxon signed-rank test. Rotating beam angles from laterals to slightly posterior by 5°-15° reduced high LETd volumes while it increased the dose volume in the rectum and increased LETd in bladders. Beam angles rotated five degrees posteriorly from laterals (i.e., gantry in 95° and 265°) are proposed since they achieved the optimal balance of better LETd sparing and minimal dose increase in the rectum. A reduction of V(50 Gy[RBE], 2.6 keV/µm) from 7.41 to 3.96 cc (p < 0.01), and a slight increase of V(50 Gy[RBE], 0 keV/µm) from 20.1 to 21.6 cc (p < 0.01) were observed for the group without hydrogel spacer. The LETd sparing was less effective for the group with hydrogel spacer, which achieved the reduction of V(50 Gy[RBE], 2.6 keV/µm) from 4.28 to 2.10 cc (p < 0.01). Posterior oblique angle plans improved LETd sparing of the rectum while sacrificing LETd sparing in the bladder in the treatment of prostate cancer with PBS. Beam angle modification from laterals to slightly posterior may be a strategy to redistribute LETd and perhaps reduce rectal toxicity risks in prostate cancer patients treated with PBS. However, the effect is reduced for patients with hydrogel spacer.

PO-1682 Visibility, artifacts and dose degradations around gold markers in proton therapy of prostate cancer

PO-1682 Visibility, artifacts and dose degradations around gold markers in proton therapy of prostate cancer

Proton Therapy for Prostate Cancer: Challenges and Opportunities.

Simple SummaryReported clinical outcomes of proton therapy (PT) for localized prostate cancer are similar to photon-based external beam radiotherapy. Apparently, the dosimetric advantages of PT have yet to be translated to clinical benefits. The suboptimal clinical outcomes of PT might be attributable to inadequate dose prescription, as indicated by the ASCENDE-RT trial. Moreover, uncertainties involved in the treatment planning and delivery processes, as well as technological limitations in PT treatment systems, may lead to discrepancies between planned doses and actual doses delivered to patients. In this article, we reviewed the current status of PT for prostate cancer and discussed different clinical implementations that could potentially improve the clinical outcome of PT for prostate cancer. Various technological advancements under which uncertainties in dose calculations can be minimized, including MRI-guided PT, dual-energy photon-counting CT and high-resolution Monte Carlo-based treatment planning systems, are highlighted.The dosimetric advantages of proton therapy (PT) treatment plans are demonstrably superior to photon-based external beam radiotherapy (EBRT) for localized prostate cancer, but the reported clinical outcomes are similar. This may be due to inadequate dose prescription, especially in high-risk disease, as indicated by the ASCENDE-RT trial. Alternatively, the lack of clinical benefits with PT may be attributable to improper dose delivery, mainly due to geometric and dosimetric uncertainties during treatment planning, as well as delivery procedures that compromise the dose conformity of treatments. Advanced high-precision PT technologies, and treatment planning and beam delivery techniques are being developed to address these uncertainties. For instance, external magnetic resonance imaging (MRI)-guided patient setup rooms are being developed to improve the accuracy of patient positioning for treatment. In-room MRI-guided patient positioning systems are also being investigated to improve the geometric accuracy of PT. Soon, high-dose rate beam delivery systems will shorten beam delivery time to within one breath hold, minimizing the effects of organ motion and patient movements. Dual-energy photon-counting computed tomography and high-resolution Monte Carlo-based treatment planning systems are available to minimize uncertainties in dose planning calculations. Advanced in-room treatment verification tools such as prompt gamma detector systems will be used to verify the depth of PT. Clinical implementation of these new technologies is expected to improve the accuracy and dose conformity of PT in the treatment of localized prostate cancers, and lead to better clinical outcomes. Improvement in dose conformity may also facilitate dose escalation, improving local control and implementation of hypofractionation treatment schemes to improve patient throughput and make PT more cost effective.

Dosimetric Effects of the Supine and Prone Positions in Proton Therapy for Prostate Cancer.

To quantitatively evaluate how much the doses to organs at risk are affected in the prone position compared to the supine position in the proton therapy (PT) for prostate cancer. Fifteen consecutive patients with clinically localized prostate cancer underwent treatment planning computed tomography scans in both the supine and prone positions. The clinical target volume (CTV) consisted of the prostate gland plus the seminal vesicles. The PT plans were designed using the standard lateral opposed fields with passively scattered proton beams for both treatment positions. The prescribed dose for each plan was set to 78 Gy (Relative biological effectiveness)/39 fractions to 50% of the planning target volume. Dose-volume metrics of the rectum and bladder in the two treatment positions were analyzed. It was confirmed that all the parameters of D05, D10, D20, D30, Dmean, and V90 examined in the rectum were significantly reduced in the prone position. There was no significant difference between the two positions in the bladder dose except for Dmean. The distance between the CTV and the rectum tended to increase with the patient in the prone position; at the prostate level, however, the maximum change was approximately 5 mm, and there was significant variation between cases. We confirmed that the rectal doses were significantly lower in the prone compared with the supine position in PT. Although uncertain, the prone position could be an effective method to reduce the rectal dose in PT.

Five- and seven-year outcomes for image-guided moderately accelerated hypofractionated proton therapy for prostate cancer

Background To report 5- and 7-year outcomes after image-guided moderately accelerated hypofractionated proton therapy (AHPT) for prostate cancer. Material and methods We reviewed the first 582 prostate cancer patients enrolled on prospective outcomes tracking trial and treated with double-scattered moderately AHPT between 2008 and 2015. 269 patients had low-risk (LR) and 313 had intermediate-risk (IR) disease, including 149 with favorable intermediate-risk (FIR) and 164 with unfavorable intermediate-risk (UIR) disease. LR patients received a median 70.0GyRBE (2.5GyRBE/fraction) and IR patients received a median of 72.5 GyRBE. Seventeen patients (UIR, n = 12) received androgen deprivation therapy (ADT) for a median of 6 months. Toxicities were graded per the CTCAE, v4.0, and patient-reported quality-of-life data were reviewed. Results Median follow-up was 8.0 years (0.9–12.2). The 5- and 7-year rates of freedom from biochemical progression (FFBP) overall and in the LR and IR subsets, respectively, were 96.8/95.2%, 98.8/98.8%, and 95.0/91.9%. For the FIR and UIR subsets, they were 97.2/95.2% and 93.1/88.8%. Actuarial 5- and 7-year rates of late CTCAE, v4.0, grade 2 gastrointestinal (GI), grade 3 GI, and grade 3 genitourinary (GU) toxicities were 9.9%/11.2%, 1.4/1.4% and 1.3/2.1%, respectively. No grade ≥4 GI or GU toxicities occurred. The mean (standard deviation, SD) IPSS and EPIC Composite bowel function and bother scores were 7 (SD = 5), 97 (SD = 7), and 94 (SD = 6), respectively at baseline, 7 (SD = 5), 92 (SD = 13), and 92 (SD = 9) at the 5-year follow-up, and 7 (SD = 5), 93 (SD = 12), and 92 (SD = 10) at the 7-year follow-up. Conclusion Image-guided AHPT 5- and 7-year outcomes show high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes in this cohort.

Comparative In Silico Analysis of Intensity Modulated Scanning Beam Proton Therapy (IMPT) and Volumetric Modulated Arc Photon Radiotherapy (VMAT) for the Post-Operative Treatment of Prostate Cancer

Limited data exist regarding the dosimetric techniques and potential advantages of modern scanning beam proton therapy relative to conventional photon therapy modalities for prostate cancer patients in the post-operative setting. Our purpose was to evaluate the dosimetric differences in IMPT versus IMRT for the post-operative treatment of prostate cancer.The 3DCT data of 7 consecutive, post-prostatectomy patients treated at our institution with adjuvant or salvage IMPT in 2020 were used to generate VMAT and IMPT plans using 3 different beam arrangements: 2-field (opposed laterals), 3-field (opposed laterals inferiorly matched to posterior beam superiorly), and 4-field (opposed laterals inferiorly matched superiorly to 2 posterior oblique beams). Prescription was 50 Gy in 2 Gy fractions delivered to elective pelvic nodal regions (i.e., whole pelvis) and 20 Gy in 2 Gy fractions delivered to the prostate bed for a total dose of 70 Gy in 35 fractions. PT doses are reported in Gy (RBE) = 1.1 Gy. Dose goals for target and relevant organs at risk (OAR), as well as dose-volume histogram parameters were assessed. The paired 2-sided Wilcoxon signed-rank test was used to compare the 4-field IMPT versus VMAT plans, with P < .05 indicating statistical significance.CTV coverage met pre-specified dose goals for all plans with 99% of CTVs receiving ≥ 100% of the prescription doses. The 2-, 3-, and 4-field IMPT plans showed similar doses to the bladder and bladder minus CTV (bladderless-CTV), while the 4-field IMPT plan showed the lowest mean and low to intermediate doses to the bowel cavity and rectum. For example, mean bowel cavity V15 and V45 for the 2-, 3-, and 4-field IMPT plans were respectively 549.2 ± 282.6 cc and 110.7 ± 39.8 cc, 303.0 ± 102.0 cc and 92.7 ± 32.6 cc, and 263.4 ± 97.3 cc and 90.6 ± 40.6 cc. Mean rectum V50 and V60 for the 2-, 3-, and 4-field IMPT plans were 26.8 ± 8.9% and 18.7 ± 7.4%, 28.9 ± 10.5% and 19.5 ± 8.0%, 24.3 ± 4.8% and 16.7 ± 4.1% respectively. When comparing the 4-field IMPT and VMAT plans, the rectal, bowel, and bladder parameters in Table 1 differed significantly.The 4-field IMPT beam arrangement showed the greatest reductions in dose to the bowel cavity and rectum compared to VMAT and the 2- and 3-field IMPT arrangements. These data can inform the future clinical management and delivery of proton therapy for prostate cancer in the post-prostatectomy setting.

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer.

IntroductionTo confirm the feasibility of hypofractionated proton beam therapy (PBT), we compared the acute adverse event rates and International Prostate Symptom Score (IPSS) in prostate cancer patients treated with hypofractionated versus conventionally fractionated (2.0 Gy relative biological effectiveness (RBE)/fraction) PBT.MethodsWe reviewed 289 patients with prostate cancer, of whom 73, 100, and 116 patients were treated with 2.0, 2.5, and 3.0 Gy (RBE)/fraction, respectively. The endpoints were acute genitourinary and gastrointestinal toxicities and the IPSS, evaluated up to 6 months after PBT initiation.ResultsNo significant differences were found in acute toxicity rates or the IPSS among the fractionation schedules. Diabetes mellitus, age, and androgen deprivation therapy were not identified as factors associated with the IPSS.ConclusionThere were no significant differences in adverse events or quality of life among the three fractionation schedules early after PBT.

Normal tissue complication probability models for prospectively scored late rectal and urinary morbidity after proton therapy of prostate cancer.

Background and purposePhotons and protons have fundamentally different properties, i.e. protons have a reduced dose bath but a higher relative biological effectiveness. Photon-based normal tissue complication probability (NTCP) models may therefore not immediately be applicable to proton therapy (PT). The aim was to derive parameters of the Lyman-Kutcher-Burman (LKB) NTCP model using prospectively recorded late morbidity data from PT, focusing on rectal morbidity and prostate cancer.Materials and methodsProspectively collected data were available for 1151 prostate cancer patients treated with passive scattering PT and prescribed target doses of 78–82 Gy (RBE = 1.1) in 2 Gy fractions. Morbidity data (CTCAE v3.0) consisted of two alternative late grade 2 rectal bleeding endpoints: Medical Grade2A (GR2A) and procedural Grade2B (GR2B), as well as late grade 3 + urinary morbidity. GR2A + 2B were observed in 156/1047 patients (15%), GR2B in 45/1047 patients (4%), and urinary grade 3 + in 51/1151 patients (4%). LKB NTCP model parameters (D50, m, and n) were derived by maximum likelihood estimation.ResultsFor the rectum/rectal wall the volume parameter n was low (0.07–0.14) for both GR2A + 2B and GR2B, as was the m parameter (range: 0.16–0.20). For the bladder/bladder wall both parameters were high (n-range: 0.20–0.36; m-range: 0.32–0.36). D50 parameters were higher for GR2B of the rectum/rectal wall (95.9–98.0 Gy) and bladder/bladder wall (118.1–119.9 Gy), but lower for GR2A2B (71.7–73.6 Gy).ConclusionPT specific LKB NTCP model parameters were derived from a population of more than 1000 patients. The D50 parameter differed for all structures and endpoints and deviated from typical photon-based LKB model values.

Dataset for predicting single-spot proton ranges in proton therapy of prostate cancer

The number of radiotherapy patients treated with protons has increased from less than 60,000 in 2007 to more than 220,000 in 2019. However, the considerable uncertainty in the positioning of the Bragg peak deeper in the patient raised new challenges in the proton therapy of prostate cancer (PCPT). Here, we describe and share a dataset where 43 single-spot anterior beams with defined proton energies were delivered to a prostate phantom with an inserted endorectal balloon (ERB) filled either with water only or with a silicon-water mixture. The nuclear reactions between the protons and the silicon yield a distinct prompt gamma energy line of 1.78 MeV. Such energy peak could be identified by means of prompt gamma spectroscopy (PGS) for the protons hitting the ERB with a three-sigma threshold. The application of a background-suppression technique showed an increased rejection capability for protons hitting the prostate and the ERB with water only. We describe each dataset, document the full processing chain, and provide the scripts for the statistical analysis.

Proton therapy for prostate cancer: current state and future perspectives.

Localized prostate cancer can be treated with several radiotherapeutic approaches. Proton therapy (PT) can precisely target tumors, thus sparing normal tissues and reducing side-effects without sacrificing cancer control. However, PT is a costly treatment compared with conventional photon radiotherapy, which may undermine its overall efficacy. In this review, we summarize current data on the dosimetric rationale, clinical benefits, and cost of PT for prostate cancer. An extensive literature review of PT for prostate cancer was performed with emphasis on studies investigating dosimetric advantage, clinical outcomes, cost-effective strategies, and novel technology trends. PT is safe, and its efficacy is comparable to that of standard photon-based therapy or brachytherapy. Data on gastrointestinal, genitourinary, and sexual function toxicity profiles are conflicting; however, PT is associated with a low risk of second cancer and has no effects on testosterone levels. Regarding cost-effectiveness, PT is suboptimal, although evolving trends in radiation delivery and construction of PT centers may help reduce the cost. PT has several advantages over conventional photon radiotherapy, and novel approaches may increase its efficacy and safety. Large prospective randomized trials comparing photon therapy with proton-based treatments are ongoing and may provide data on the differences in efficacy, toxicity profile, and quality of life between proton- and photon-based treatments for prostate cancer in the modern era. PT provides excellent physical advantages and has a superior dose profile compared with X-ray radiotherapy. Further evidence from clinical trials and research studies will clarify the role of PT in the treatment of prostate cancer, and facilitate the implementation of PT in a more accessible, affordable, efficient, and safe way.

Assessing concordance between patient-reported and investigator-reported CTCAE after proton beam therapy for prostate cancer

PurposeWe report acute patient-reported outcomes using CTCAE (PRO-CTCAE) of proton beam radiotherapy for high-risk or unfavorable intermediate-risk prostate cancer in a prospective clinical trial. PRO-CTCAE were correlated with investigator reported-CTCAE (IR-CTCAE) to assess the degree of concordance. Methods and materials11 PRO-CTCAE questions assessed gastrointestinal (GI), genitourinary (GU), or erectile function side effects. The correlation scheme between PRO-CTCAE and IR-CTCAE was independently developed by two physicians. Analyses of PRO-CTCAE and IR-CTCAE were conducted using both descriptive terms and the converted grade scores. The Kappa statistic described the degree of concordance. Results55 patients were included. IR-CTCAE underestimated diarrhea compared to PRO-CTCAE at the end of treatment (EOT), with a 28% rate of underestimation (11% by ≥ 2 toxicity grades). Similarly, urinary tract pain was underestimated in 45% of cases (17% by ≥ 2 grades) at EOT. Differences were less pronounced at baseline or 3 months after radiotherapy. The incidence of urinary urgency and frequency tended to be overestimated prior to treatment (36% and 24%, respectively) but underestimated at EOT (35% and 31%, respectively). The degree of interference with daily activities was consistently overestimated by investigators (45%-85%). Finally, erectile dysfunction showed a 36–56% rate of discordance by ≥ 2 toxicity grades. ConclusionsOur study shows a low agreement between IR-CTCAE and PRO-CTCAE in the setting of proton therapy for prostate cancer. Compared to patient-reported outcomes, physicians underestimated the frequency and severity of urinary symptoms and diarrhea at the end of treatment. Continued use of PROs should be strongly encouraged.