Stereotactic Body Radiotherapy For Prostate Cancer Research Articles

Pencil Beam Scanning Proton Bragg Peak Conformal FLASH in Prostate Cancer Stereotactic Body Radiotherapy.

Bragg peak FLASH radiotherapy (RT) uses a distal tracking method to eliminate exit doses and can achieve superior OAR sparing. This study explores the application of this novel method in stereotactic body radiotherapy prostate FLASH-RT. An in-house platform was developed to enable intensity-modulated proton therapy (IMPT) planning using a single-energy Bragg peak distal tracking method. The patients involved in the study were previously treated with proton stereotactic body radiotherapy (SBRT) using the pencil beam scanning (PBS) technique to 40 Gy in five fractions. FLASH plans were optimized using a four-beam arrangement to generate a dose distribution similar to the conventional opposing beams. All of the beams had a small angle of two degrees from the lateral direction to increase the dosimetry quality. Dose metrics were compared between the conventional PBS and the Bragg peak FLASH plans. The dose rate histogram (DRVH) and FLASH metrics of 40 Gy/s coverage (V40Gy/s) were investigated for the Bragg peak plans. There was no significant difference between the clinical and Bragg peak plans in rectum, bladder, femur heads, large bowel, and penile bulb dose metrics, except for Dmax. For the CTV, the FLASH plans resulted in a higher Dmax than the clinical plans (116.9% vs. 103.3%). For the rectum, the V40Gy/s reached 94% and 93% for 1 Gy dose thresholds in composite and single-field evaluations, respectively. Additionally, the FLASH ratio reached close to 100% after the application of the 5 Gy threshold in composite dose rate assessment. In conclusion, the Bragg peak distal tracking method can yield comparable plan quality in most OARs while preserving sufficient FLASH dose rate coverage, demonstrating that the ultra-high dose technique can be applied in prostate FLASH SBRT.

Relationship between hydrogel spacer distribution and dosimetric parameters in linear-accelerator-based stereotactic body radiotherapy for prostate cancer.

To explore the potential of quantitative parameters of the hydrogel spacer distribution as predictors for separating the rectum from the planning target volume (PTV) in linear-accelerator-based stereotactic body radiotherapy (SBRT) for prostate cancer. Fifty-five patients underwent insertion of a hydrogel spacer and were divided into groups 1 and 2 of the PTV separated from and overlapping with the rectum, respectively. Prescribed doses of 36.25-45Gy in five fractions were delivered to the PTV. The spacer cover ratio (SCR) and hydrogel-implant quality score (HIQS) were calculated. Dosimetric and quantitative parameters of the hydrogel spacer distribution were compared between the two groups. For PTV, D99% in group 1 (n=29) was significantly higher than that in group 2 (n=26), and Dmax , D0.03cc , D1cc , and D10% for the rectum were significantly lower in group 1 than in group 2. The SCR for prostate (89.5±12.2%) in group 1 was significantly higher (p<0.05) than that in group 2 (74.7±10.3%). In contrast, the HIQS values did not show a significant difference between the groups. An area under the curve of 0.822 (95% confidence interval, 0.708-0.936) for the SCR was obtained with a cutoff of 93.6%, sensitivity of 62.1%, and specificity of 100%. The SCR seems promising to predict the separation of the rectum from the PTV in linear-accelerator-based SBRT for prostate cancer.

Five Fractions versus Seven Fractions SBRT for Intermediate- and High-Risk Prostate Cancer: A Propensity Score Matched Pair Analysis.

To compare two stereotactic body radiotherapy (SBRT) regimens in patients with intermediate- or high-risk prostate cancer with regards toxicity and efficacy. We retrospectively collected data from 198 patients treated with SBRT for prostate cancer at two different institutions. Patients received either 35-36.25 Gy in five fractions (group A) using Cyberknife robotic platform or 42.7 Gy in seven fractions (group B) using a C-arm LINAC (image-guided). Propensity score matching was done (2:1 nearest neighbor matching without replacement), resulting in 120 patients (80 patients for group A, 40 patients for group B). Toxicity, PSA nadir, biochemical failure and disease-free survival (DFS) were analyzed. Median follow up of all patients was 13 months (range 1-91 months). Overall, 23.3% of patients had ≥G2 acute GU toxicity (21.1% group A versus 30% group B (p = 0.222)) and 6.6% of patients ≥G2 GI toxicity (2.5% versus 15% (p = 0.010)). There was one acute G3 GU toxicity in arm A and one acute G4 rectal bleeding in group B (anticoagulated patient). Regarding late toxicity, 14.1% of patients had ≥G2 late GU toxicity (17.4% versus 6.6% (p = 0.159)) and 5.0% of patients had ≥G2 late GI toxicity (1.4% versus 13.3% (p = 0.013)). There was one G3 late GU toxicity in arm B and two G3 late GI toxicities, one in each arm. Relative median PSA reduction was 92.4% (-53.9-99.9%) from baseline PSA (93.7% (-53.9-99.9%) in group A versus 87.7% (39.8-99.9%) in group B (p = 0.043). In total, 4.2% of patients had biochemical relapse, 5.0% in group A and 2.5% in group B (p = 0.518). One-year DFS in the overall cohort was 97.3%, 98.8% in group A and 94.3% in group B (p = 0.318). Both SBRT regimens have acceptable acute and late toxicity and good efficacy. There are significantly more GI toxicities in the seven-fraction regimen. Longer follow-up is warranted for better comparison of long-term efficacy.

Urethra-Sparing Prostate Cancer Stereotactic Body Radiation Therapy: Sexual Function and Radiation Dose to the Penile Bulb, the Crura, and the Internal Pudendal Arteries From a Randomized Phase 2 Trial

PurposeErectile dysfunction (ED) is a common side effect after prostate cancer stereotactic body radiotherapy (SBRT). We aimed to assess the correlation between the dose to the penile bulb (PB), internal pudendal arteries (IPA), and crura with the development of ED after ultra-hypofractionation as part of a phase II clinical trial of urethra-sparing prostate SBRT. Material and methodsAmong the 170 patients with localized prostate cancer from 9 centers included in the trial, 90 men with CTCAE v4.03 grade 0-1 ED (ED-) at baseline treated with 36.25Gy in 5 fractions were selected for the present analysis. Doses delivered to the PB, crura, and IPA were analyzed and correlated with grade 2-3 ED (ED+) development. The impact on QoL assessed by the EORTC PR-25 questionnaire was reported. ResultsAfter a median follow-up of 6.5 years, 43% (n=39) of the patients developed ED+, while 57% (n=51) remained ED-. The dose delivered to the crura was significantly higher in ED+ patients than in ED- patients (7.7 Gy vs 3.6 Gy (p=0.014) for the Dmean and 18.5 Gy vs 7.2 Gy (p=0.015) for the D2%, respectively). No statistically significant difference between ED+ and ED- patients was observed for the dose delivered to the PB and the IPA. The median ED+ free-survival was worse in patients receiving a crura Dmean ≥ 4.7 Gy vs < 4.7 Gy (51.5% vs 71.7%, p=0.005), and a crura D2% >12 Gy vs ≤ 12 Gy (54.9% vs 68.9%, p =0.015). No ED+ free-survival differences were observed for doses delivered to PB and IPA. Decline in EORTC PR-25 sexual functioning was significantly more pronounced in patients with higher doses to the crura. ConclusionsBy keeping a Dmean and D2% to crura below 4.7 Gy and 12 Gy respectively, the risk to develop ED+ following prostate SBRT may be significantly reduced.

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old-Updated Results.

Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports updated outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. Between April 2006 and December 2022, 6,130 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator. Information was available for 4,143 patients. 3568 (86.12%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 575 (13.88%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 1,035 (24.98%) of these cases. The mean age was 67.4 years old. 48 patients were younger than 50 years old (mean age 46.6). 4,095 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 43.75%, 50.00%, 6.25% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 23.88%, 57.05%, 19.07% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 47.92%, 7 in 47.92%, and 8-10 in 4.16%. 44 younger patients were treated with SBRT alone. 4 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.42%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 29.84%, 7 in 54.14%, and 8-10 in 16.02%. 3522 were treated with SBRT alone. 573 patients also received supplemental external beam radiation (median dose 4500cGY) and 1030 patients (25.15%) received Androgen Deprivation Therapy (ADT) as part of their treatment. At 75 months the 6-year biochemical relapse free survival was 95.83% in younger patients compared to 98.41% in older patients using the Phoenix definition of biochemical failure. The 6-year median post treatment PSA was 0.3 in younger patients and 0.2 in the older patients. There were no significant differences in the risk stratification between the 2 groups. This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With updated 6-year follow up, SBRT remains an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

Reduction of Late Urinary Toxicity from Prostate Cancer Radiotherapy via Intrafractional MV-kV Image Guidance

Prostate cancer localization during radiotherapy is difficult and introduces positional variability during treatment. Here we evaluate the impact on treatment toxicities of an in-house system that uses MV and kV imaging guidance (MKIG) to track implanted fiducials during stereotactic body radiotherapy (SBRT) for localized prostate cancer. A 3D MKIG platform that tracks prostate implanted fiducials in real-time was built and clinically translated to replace a prior commercial approach called intrafraction motion review (IMR), which tracks thefiducials in 2D kV view only. MKIG has been shown to correct both superior-inferior and anterior-posterior (AP) motions that are harmful to critical organs and is superior to IMR for intrafractional motion management, which is less sensitive to AP motions. From 2017 to 2019, 150 patients with localized prostate cancer were treated with SBRT to 40 Gy in 5 fractions. During the delivery of volumetric modulated arc therapy, orthogonal MV-kV pairs were simultaneously acquired at every 20° gantry rotation and rigidly registered to the reference image templates created from the planning CT. Calculated 3D translations of implanted fiducials were used to localize the prostate and alert the therapist to interrupt and reposition the prostate when exceeding a 1.5-2 mm threshold. A comparison cohort of 121 prostate patients was treated from 2015 to 2016 with the same prescription dose and treatment technique but instead managed by IMR, where the therapist interrupted treatment based on a 2mm expansion of the fiducial contours superimposed on the kV images. Statistics of intrafractional interruptions, patient shifts, and overall delivery time were collected to evaluate the efficacy of the clinical workflow. The incidence of late grade ≥2 toxicities was analyzed to assess clinical complications. The median follow-up time was 5.5 years (range of 3.6 to 8.0 years). The MKIG cohort had more interruptions per fraction (1.09 vs. 0.28) and longer average delivery time per fraction (579±205s vs. 357±117s) than IMR. 75% of shifts resulting from MKIG were less than 3mm, compared to 51% in IMR, indicating that MKIG tended to detect and correct smaller deviations (p<0.001). The baseline International Prostate Symptom Score was 7.9 in the MKIG cohort vs. 8.4 in IMR (p = 0.41). The incidence of late grade ≥2 urinary toxicity was lower in the MKIG than IMR cohort: 10.7% vs. 19.8% (p = 0.05). One grade ≥2 rectal toxicity was observed in the IMR cohort but none in MKIG. Wehave demonstrated that MKIG is a clinically practical and effective method for monitoring and correcting prostate positional deviations during SBRT of prostate cancer. MKIG is better suited than 2D IMR to localize the prostate and trigger patient repositioning during treatment. A statistically and clinically significant reduction in urinary toxicity was observed. The potential expansion of MKIG to other clinical sites and translation to other centers should be considered.

Stereotactic Body Radiation Therapy in Prostate Cancer: Where Do We Stand?

Stereotactic body radiotherapy (SBRT) is an important option for prostate cancer treatment. It involves the delivery of a high dose of radiation to the malignant tissue without affecting the neighboring healthy tissue to achieve a high therapeutic index. As the cells of prostate cancer are radiobiologically similar to a late-responding tissue with a low 𝛼/𝛽 ratio, the dose escalation approach has a better disease control probability than conventional dose fractionation. Therefore, considering the availability of intensity-modulated RT and possibility of dose escalation (&gt;70 Gy), ultrahypofractionated SBRT is now being recommended in select patients with prostate cancers of low and intermediate risk. Although adverse events following SBRT are a concern, acute toxicity can be limited to a certain extent by adjusting the overall length of treatment time by spacing out RT over multiple fractions. Modern radiation planning and delivery methods used in conjunction with cutting-edge imaging techniques have led to the increased adoption of SBRT in prostate cancer. Thus, from a practical standpoint, it is noninvasive and effective for treating prostate cancer, leading to increased access and higher patient satisfaction.

Every-Other-Day Versus Once-a-Week Urethra-Sparing Prostate Stereotactic Body Radiation Therapy: 5-Year Results of a Randomized Phase 2 Trial

To present the 5-year results from a prospective multicenter phase II randomized trial of every-other-day (EOD) vs. once-a-week (QW) urethra-sparing stereotactic body radiotherapy (SBRT) for localized prostate cancer. Between 2012 and 2015, 170 patients from nine European institutions with cT1c-3aN0M0 prostate cancer were randomized to 36.25 Gy in 5 fractions (6.5 Gy/fraction to the urethra) delivered either EOD (arm A, n=84), or QW (arm B, n=86). The median follow-up was 78 months (interquartile range, IQR 23 months) and 77 months (IQR 16 months) for arms A and B, respectively. Among the 165 patients treated and retained for the final analysis (arm A, n=82; arm B= 83), acute toxicity (CTCAE v4.03 scale) was mild or absent with no differences between arms. The 5-year ≥ grade-2 genitourinary (GU) toxicity-free survival was 75.9% and 76.1% for arms A and B, respectively (p=0.945), while the 5-year ≥ grade-2 gastrointestinal (GI) toxicity-free survival was 89% and 92% for arms A and B, respectively (p=0.596). No changes in EORTC QLQ-PR25 scores were observed in both arms for GU, GI, and sexual domains at 5-year follow-up compared to baseline. At the last follow-up, biochemical failure was observed in 14 patients in the EOD arm and in 7 patients in the QW arm with a 5-year biochemical relapse-free survival rate of 92.2% and 93% for arms A and B, respectively (p=0.13). Prostate cancer SBRT with a 10% dose reduction to urethra was associated with a minimal impact on urinary function and quality of life regardless of a EOD or QW fractionation schedule. Biochemical control so far, has been encouraging and much alike in both study arms, though longer follow-up is probably needed to assess the true value of overall treatment time on disease outcome.

Acute Gastrointestinal and Genitourinary Toxicity from Stereotactic Body Radiotherapy for Prostate Cancer following Continuous Tumour Tracking with the Micropos Medical RayPilot and RayPilot HypoCath System®

Purpose: Stereotactic body radiotherapy (SBRT) for prostate cancer is delivered over a shorter period than standard fractionation, with similar levels of post-treatment toxicity [1]. However, the greater dose per fraction delivered increases the significance of inter-fraction variability. The use of prostate tracking devices in planning and during treatment may help reduce variability and help develop more personalised radiotherapy plans. Here, we present acute toxicity data for patients treated with SBRT for prostate cancer where on-treatment prostate tracking was carried out.

Contour similarity and its implication on inverse prostate SBRT treatment planning.

Success of auto-segmentation is measured by the similarity between auto and manual contours that is often quantified by Dice coefficient (DC). The dosimetric impact of contour variability on inverse planning has been rarely reported. The main aim of this study is to investigate whether automatically generated organs-at-risk (OARs) could be used in inverse prostate stereotactic body radiation therapy (SBRT) planning and whether the dosimetric parameters are still clinically acceptable after radiation oncologists modify the OARs. Planning computed tomography images from 10 patients treated with SBRT for prostate cancer were selected and automatically segmented by commercially available atlas-based software. The automatically generated OAR contours were compared with the manually drawn contours. Two volumetric modulated arc therapy (VMAT) plans, autoRec-VMAT (where only automatically generated rectums were used in optimization) and autoAll-VMAT (where automatically generated OARs were used in inverse optimization) were generated. Dosimetric parameters based on the manually drawn PTV and OARs were compared with the clinically approved plans. The DCs for the rectum contours varied from 0.55 to 0.74 with a mean value of 0.665. Differences of D95 of the PTV between autoRec-VMAT and manu-VMAT plans varied from 0.03% to -2.85% with a mean value of -0.64%. Differences of D0.03cc of manual rectum between the two plans varied from -0.86% to 9.94% with a mean value of 2.71%. D95 of PTV between autoAll-VMAT and manu-VMAT plans varied from 0.28% to -2.9% with a mean value -0.83%. Differences of D0.03cc of manual rectum between the two plans varied from -0.76% to 6.72% with a mean value of 2.62%. Our study implies that it is possible to use unedited automatically generated OARs to perform initial inverse prostate SBRT planning. After radiation oncologists modify/approve the OARs, the plan qualities based on the manually drawn OARs are still clinically acceptable, and a re-optimization may not be needed.

Correlation between Obesity and Treatment Failure Following Stereotactic Body Radiation Therapy (SBRT) for Clinically Localized Prostate Cancer

<h3>Purpose/Objective(s)</h3> Cancer control outcomes are significantly worse in obese prostate cancer patients. Over the past decade, stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for localized prostate cancer. Accurate delivery of external beam radiation could be adversely affected by increased pelvic adipose tissue and result in worse biochemical control. Data reporting on the efficacy of SBRT stratified by BMI is limited. This single-institution study sought to evaluate oncologic outcomes following SBRT for prostate cancer in men based on BMI. <h3>Materials/Methods</h3> A retrospective chart review was performed on all patients with localized prostate cancer treated with SBRT at a single institution between 2006 to 2021. Treatment was delivered using robotic SBRT with doses of 35-36.25 Gy in 5 fractions, per institutional protocol. Biochemical recurrence was defined by the Phoenix definition (PSA rise ≥ 2 ng/mL above nadir). Multiple regression Cox proportional hazard analysis was performed. <h3>Results</h3> 1306 patients were identified, with a mean follow-up of 47 months. The patients were elderly (Median age = 70 years) and overweight (Median BMI = 27.6 kg/m²). The majority were low to intermediate risk (88%) according to the D'Amico classification. Median pre-treatment PSA was 7.4 ng/mL. 23.7% received neoadjuvant ADT. BMI (kg/m²) was calculated prior to initiation of treatment and patients were stratified as thus: BMI < 25, 25 – 29.9, 30 – 34.9, ≥ 35. There was no statistically significant difference between pre-treatment PSA or Gleason's score between BMI groups. A multiple regression Cox proportional hazard analysis was performed, with BMI < 25 set as the reference. There was no statistically significant difference in biochemical disease-free survival, distant metastasis-free survival, or disease-specific survival between BMI subgroups. <h3>Conclusion</h3> In the general population, cancer control following prostate SBRT is equivalent to other standard radiation options. In this analysis, increased BMI did not portend worse oncologic outcomes following SBRT when analyzing bDFS, DMFS, or DSS. Thus, in the opinion of the authors, obesity should not be considered a contraindication to prostate SBRT.

Abdominal Aorto-Iliac Calcification Burden Assessment Using Deep Convolutional Neural Networks for Prediction of Cardiovascular Risk Among Prostate Cancer Patients Undergoing Stereotactic Body Radiotherapy (SBRT)

<h3>Purpose/Objective(s)</h3> Cardiovascular (CV) disease is among the leading causes of death for patients with prostate cancer. One novel strategy for automated screening for CV disease is the use of opportunistic imaging biomarkers derived from CT simulation scans. This study aims to investigate association of abdominal aorto-iliac calcification burden as measured qualitatively by physicians and quantitatively using a deep learning approach, and occurrence of major adverse CV events (MACE) among prostate cancer patients undergoing SBRT. <h3>Materials/Methods</h3> A retrospective study was conducted of 146 patients undergoing SBRT for localized prostate cancer (median age 68.9 years [interquartile range, IQR, 63.6-74.0]; 23.2% low risk, 35.1% intermediate risk, 11.6% high risk) between June 2007 and August 2018. MACE was collected from review of the medical chart, defined as a composite event of stroke, myocardial infarction, hospitalization for new onset heart failure, and CV death. Two physicians who were blinded to outcomes (WCC, JDB) independently reviewed non-contrast CT simulation scans to assess aorto-iliac calcification burden by a pre-defined 5-point scale (weighted Kappa: 0.72). Next, the abdominal aorta and common iliac arteries were contoured for 50 scans which served as a training dataset. A multi-stage UNet was trained to delineate aorto-iliac contours, achieving a mean dice score of 0.87±0.08 and Hausdorff distance of 1.9±0.6mm. Calcification burden was quantified using a per-voxel threshold of >130 Houndsfield units. <h3>Results</h3> 20 patients (13.7%) experienced MACE during a cohort-wide median clinical follow up of 5.9 years (IQR 4.7-6.4), and 5 patients (3.4%) died of CV disease and 10 patients (6.8%) of other causes (1 prostate cancer related). 49 patients (33.5%) had moderate to severe CaBS of 3 or higher. CaBS was significantly positively correlated with MACE in a dose dependent manner (P<0.0001, Cochran-Armitage test for trend), increasing from 6.2% for patients with mild/absent CaBS, to 20.6%, 37.5%, and 57.1%, for CaBS of 3, 4 and 5, respectively. Quantitative calcification burden (CaQ)derived from auto-segmentation was correlated with CaBS (Pearson r=0.79, P<0.0001) and achieved a similar area under the curve (AUC 0.74 vs 0.73 for CaBS) for MACE, resulting in a sensitivity of 78%, specificity of 63%, negative predictive value of 94.8%, and positive predictive value of 24.6%, using a cut-off of 1650 mm^3. Finally, both CaBS and CaQ remained significantly associated with MACE after adjusting for age on Cox regression (P=0.04, CaQ: HR 1.15 per 1000mm^3, 95% CI 1.005-1.33). <h3>Conclusion</h3> Abdominal aorto-iliac calcification burden was strongly associated with cardiovascular risk among patients undergoing SBRT for prostate cancer. A deep learning approach to quantify calcification burden on non-contrast pelvic CT simulation scans identified patients at elevated cardiovascular risk and may facilitate automated screening.

Quality of life after definitive linear accelerator-based stereotactic radiotherapy for prostate cancer: a longitudinal study

BackgroundProstate cancer is the second most common malignancy worldwide, and the majority of patients are diagnosed with localized disease. We examined patients’ quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer.MethodsWe included patients who were treated between 2016 and 2020. Inclusion criteria were adenocarcinoma of the prostate; class risk of low, intermediate, and high; and a World Health Organization performance status of 0–2. Quality of life was measured using the Functional Assessment of Cancer Therapy-Prostate (FACT-P).ResultsA total of 439 patients were treated with SBRT, with a median age of 73 years old. The median follow-up period was 34 months. FACT-P Trial Outcome Index (p < 0.0001), FACT-General (p = 0.0003), and FACT-P-Total (p < 0.0001) scores declined at 1 month post-SBRT, then recovered and returned to the same level as before treatment at 3–4 months post-SBRT. The decrease in quality of life in the first month was particularly remarkable in patients who received long-term hormone injections (36%). One month after the end of SBRT, about 22% of patients experienced "quite a bit” or more troubling side effects.ConclusionsThis study showed longitudinal changes in quality of life by FACT-P after SBRT for prostate cancer. Overall, prostate SBRT was well tolerated.

Ejaculatory Function Following Stereotactic Body Radiation Therapy for Prostate Cancer

Ejaculatory dysfunction is an important male quality of life issue which has not yet been studied in the setting of prostate stereotactic body radiation therapy (SBRT). The purpose of this study is to evaluate ejaculatory function following SBRT for prostate cancer. Two hundred and thirty-one patients on a prospective quality of life study with baseline ejaculatory capacity treated with prostate SBRT from 2013 to 2019 were included in this analysis. Ejaculation was assessed via the Ejaculation Scale (ES-8) from the Male Sexual Health Questionnaire. Patients completed the questionnaire at 1, 3, 6, 9, 12, 18, and 24 months post-SBRT. Elderly patients (Age > 70) and those who received hormonal therapy were excluded from analysis. Patients were treated to 35-36.25 Gy in 5 fractions delivered with theCyberKnifeRadiosurgical System (Accuray). Ejaculatory function was assessed by ES-8 scores (range 4-40) with lower values representing increased interference or annoyance. Median age at the time of treatment was 65 years. Median follow up was 24 months (IQR 19-24.5 months). 64.5% of patients had ED at baseline (SHIM < 22). The 2-year anejaculation rate was 15%. Mean composite ES-8 scores showed a decline in the first month following treatment then stabilized: 30.4 (start of treatment); 26.5 (1 month); 27.6 (3 month); 27.0 (6 month); 26.2 (9 month); 25.4 (12 month); 25.0 (18 month) and 25.4 (24 month). White race, higher pre-treatment SHIM (≥22), and higher ES-8 (≥31) at treatment start were significantly associated with a decreased probability of a clinically significant decline. Patient-reported ejaculate volume was significantly reduced at all time points post-SBRT. Ejaculatory discomfort peaked at 1 month and 9 months post-SBRT. Prior to treatment, 8.0% of men reported that they were very to extremely bothered by their ejaculatory dysfunction. The number of patients reporting this concern increased to 14.4% at one year and dropped to 11% at 24-months post-SBRT. Patients undergoing prostate SBRT may experience meaningful changes in ejaculatory function and should be counseled on the trajectory of these side effects. This was a retrospective analysis of a prospectively maintained database. Subjective questionnaire responses captured limited aspects of ejaculatory function in this cohort. The high incidence of moderate to extreme bother in ejaculatory function before and after SBRT suggests a need for novel approaches to improving ejaculation. Sholklapper T, Creswell M, Cantalino J, etal. Ejaculatory Function Following Stereotactic Body Radiation Therapy for Prostate Cancer. J Sex Med 2022;19:771-780.

Discordance of patient- and physician-reported toxicities in two prospective trials of stereotactic body radiotherapy (SBRT) for localized prostate cancer.

245 Background: SBRT for localized prostate cancer (PCa) is the focus of several ongoing and reported high-impact trials, which often focus on physician-reported toxicity (P-Tox) when comparing regimens. Patient-reported quality of life (PR-QoL) may differ and provide a more sensitive comparative metric of treatment burden, especially with fewer provider interactions during SBRT than during protracted RT courses. We evaluated the concordance of prospective genitourinary (GU) and gastrointestinal (GI) P-Tox and PR-QOL in men receiving SBRT for PCa. Methods: Data from two concurrently-enrolled prospective trials of SBRT in high-risk (Phase I Safety Endpoint, NCT01896271) and low-intermediate risk (Phase II GI Toxicity Endpoint, NCT02353832) PCa were used. Matching standardized schedules of collected PR-QoL [Expanded Prostate Cancer Index Composite (EPIC)] and P-Tox (CTCAE v5.0) were analyzed over the first 18 months of follow up, where symptoms are most pronounced. We assessed concordance of Grade≥2 GU/GI physician reported toxicity with PR-QoL declines exceeding anchor based minimal clinically important difference (MCID) thresholds (-6 urinary and -5 bowel summary scores, respectively) for each patient at each time point. Patients without baseline PR-QoL data were excluded in full, while time points with missing PR-QoL or P-Tox were excluded individually without imputation. Concordance was evaluated by Cohen’s kappa statistic. Results: From 101 patients, there were 256 (64%) follow up observations through 18 months with both PR-QoL and P-Tox at the time point and baseline. Concordance of PR-QoL and P-Tox was low at all time points for both GU and GI toxicity domains (mean kappa 0.093; Table). MCID was more often reported by patients than Grade≥2 toxicity by physicians (38% vs 17% for GU and 44% vs 10% for GI). There was little overlap of PR-QoL and P-Tox reporting: Grade≥2 P-Tox reported in 17% of observations with MCID in PR-QoL, while MCID in PR-QoL reported in 54% of observations of Grade ≥2 P-Tox. Mean concordance was similarly low when analyzing sub-groups of trial, investigator, and an alternative 2xMCID threshold. Conclusions: P-Tox and PR-QoL differed dramatically in two prospective studies of SBRT despite toxicity primary endpoints. This may reflect subjective and varying intervention thresholds driving P-Tox reporting, rather than actual patient burden. These data strongly support use of PR-QoL rather than P-Tox for SBRT comparative study endpoints and guidelines in this rapidly evolving space. [Table: see text]

Minimum Required Interval Between Hydrogel Spacer Injection and Treatment Planning for Stereotactic Body Radiation Therapy for Prostate Cancer

PurposeThe present study evaluated the short-term characteristics (<3 days) of a hydrogel spacer from the time of injection during stereotactic body radiation therapy (SBRT) for prostate cancer. Methods and MaterialsFifteen patients treated with SBRT via the CyberKnife system (36.25 Gy/5 fractions) were enrolled in this retrospective study. Two magnetic resonance (MR) images were obtained with a hydrogel spacer: one on a computed tomography (CT) simulation day (MR pretreatment [MRpre]) and the other on the last treatment day (MR posttreatment [MRpost]). Two medical physicists contoured the hydrogel spacer on each MR image. The changes of the shapes and the volume for the hydrogel spacer between 2 MR images were evaluated. ResultsThe median period between hydrogel spacer injection and CT simulation was 1 day (range, 1-9 days). The median period between CT simulation and the last treatment was 17 days (range, 14-25 days). Regarding the volume change of the hydrogel spacer, the 2 observers observed significant differences between the volumes of the hydrogel spacer on the MRpre and MRpost. However, the average volume difference between them was less than 1 cm3. The average dice similarity coefficient between the MRpre and MRpost to compare the shape was more than 0.83. In addition, no clear correlation was confirmed between the volume change and the period from hydrogel spacer injection to CT simulation. ConclusionsA single day is an acceptable interval between hydrogel spacer injection and treatment planning for SBRT for prostate cancer.

Ejaculatory Function Following Stereotactic Body Radiation Therapy for Prostate Cancer

Ejaculatory dysfunction after prostate radiation therapy is an important quality of life issue with limited management options. Given the high biologically effective doses (BEDs) that are delivered with stereotactic body radiation therapy (SBRT), ejaculatory dysfunction may be more common and/or more severe than with alternative external beam approaches. The purpose of this study is to evaluate ejaculatory preservation following SBRT for prostate cancer.231 patients on a prospective quality of life study (IRB#: 2009-510) with baseline ejaculatory capacity treated with prostate SBRT at a single institution from 2013 to 2019 were included in this analysis. Ejaculatory function was assessed via the validated Ejaculation Scale (ES-8) from the Male Sexual Health Questionnaire (Rosen RC et al, 2004). ES-8 scores range from 3 - 40 with lower values representing increased interference or annoyance. The ES-8 includes questions about ejaculate volume, ejaculatory pain, and bother. Patients completed the questionnaire on the first day of treatment and at 1, 3, 6, 9, 12, 18, and 24 months post-SBRT. Elderly patients (Age > 70) and those who received hormonal therapy were excluded from this analysis. All patients were treated to 35-36.25 Gy in 5 fractions delivered with a frameless robotic radiosurgery system. Data analysis was performed using XLStat. Minimally important differences (MID) were calculated by obtaining half the standard deviation at time of start of treatment.Mean age at treatment was 64.2 years. Minimum follow-up was 24 months. Mean composite ES-8 scores showed a decline in the first month following treatment then stabilized: 30.3 (baseline); 26.7 (1 month); 27.6 (3 month); 26.9 (6 month); 26.0 (9 month); 25.4 (12 month); 25.0 (18 month) and 25.3 (24 month). The decline from baseline to one month was statistically significant (P < 0.0001). A clinically significant decrease (MID = 3.5) was achieved at 1 month (-3.6) and from 9 months (-4.3) through 24 months (-4.9). Ejaculate volume was statistically significantly reduced at all time points post-SBRT. Ejaculate volume reduction was clinically significant (MID = 0.57) from 6-24 months post SBRT. There was a clinically significant increase (MID = 0.53) in pain with ejaculation at 1-month (-0.67), 9-months (-0.63), and 12-months (-0.59). Prior to treatment, 7.6% of men reported that they were very to extremely bothered by their ejaculatory dysfunction. This was significantly increased to 14.5% at one-year (P = 0.01) and to 10.6% at 18-months (P = 0.048) post-SBRT.Men undergoing SBRT monotherapy for prostate cancer have a small decline in their overall ejaculatory function from baseline to one-month post-treatment, but stable function thereafter. Bother with ejaculation peaked at one year then slowly declined. Longer follow-up is required to confirm the durability of these findings.

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old

Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients.Between April 2006 and December 2020, 3626 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator and followed at an academic institution. 3173 (87.51%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 453 (12.49%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 865 (23.86%) of these cases. The mean age was 67.3 years old. 47 patients were younger than 50 years old (mean age 46.6). 3,579 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 44.68%, 48.94%, 6.38% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 24.76%, 56.83%, 18.41% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 48.94%, 7 in 46.81%, and 8-10 in 4.25%. 44 younger patients were treated with SBRT alone. 3 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.6%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 30.57%, 7 in 54.06%, and 8-10 in 15.37%. 3129 were treated with SBRT alone. 450 patients also received supplemental external beam radiation (median dose 4500cGY) and 860 patients (24.03%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen.At 64.8 months (range 7 months - 177 months) the 5-year biochemical relapse free survival was 98% in younger patients compared to 99% in older patients using the Phoenix definition of biochemical failure. The 5-year median post treatment PSA was 0.15 in the younger patients and 0.20 in the older patients. There were no significant differences in biochemical relapse free survival between the groups.This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With 5-year follow up, SBRT is an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

Stereotactic Body Radiotherapy for Prostate Cancer: Where, When, and Who? A Bibliometric Analysis.

To provide an overview of the achievements and future research with stereotactic body radiotherapy (SBRT) in prostate cancer. SBRT publications for prostate cancer were retrieved from the Web of Science and Dimension database. Bibliometric analyses were performed using VOSviewer and Prism graph. Analysis of variance test was used to compare the publication, citation, and the mean citation between specialty journals. Network maps were produced to identify authors' and countries' collaboration clusters. Between 2006 and 2020, 574 publications fulfilling the inclusion criteria were identified, and a significant growth trend in publication (P<0.0001) and citation (P=0.001) number was recognized over the period. The United States was the most productive country with 253 (44.2%) articles. The RED Journal had the highest number of publications (14%) and citations (19%). Urology journals published (P=0.01) and cited significantly less than radiation oncology journals (P=0.01). All open access and non-open access number of publications increased over time, with a significant difference between non-open access and open access journals (P<0.0001). Two author clusters were identified, in the United States with the collaboration of Canadian and British authors, and in Italy with the participation of European authors. The number of publications and citations on SBRT for prostate cancer has grown linearly in the last decades. The United States is the leading country in this research field, and the use of SBRT in oligometastatic disease, reirradiation, and salvage seems to be hot topics in this research field.

Intrafractional stability of MR-guided online adaptive SBRT for prostate cancer

BackgroundMR-guided online adaptive stereotactic body radiation therapy (SBRT) for prostate cancer aims to reduce toxicity by full compensation of interfractional uncertainties. However, the process of online adaptation currently takes approximately 45 min during which intrafractional movements remain unaccounted for. This study aims to analyze the dosimetric benefit of online adaptation and to evaluate its robustness over the duration of one treatment fraction.MethodsBaseline MR-scans at a MR-linear accelerator were acquired for ten healthy male volunteers for generation of mock-prostate SBRT plans with a dose prescription of 5 × 7.25 Gy. On a separate day, online MR-guided adaptation (ViewRay® MRIdian) was performed, and thereafter MR images were acquired every 15 min for 1 h to assess the stability of the adapted plan.ResultsA dosimetric benefit of online MR-guided adaptive re-planning was observed in 90% of volunteers. The median D95CTV- and D95PTV-coverage was improved from 34.8 to 35.5 Gy and from 30.7 to 34.6 Gy, respectively. Improved target coverage was not associated with higher dose to the organs at risk, most importantly the rectum (median D1ccrectum baseline plan vs. adapted plan 33.3 Gy vs. 32.3 Gy). The benefit of online adaptation remained stable over 45 min for all volunteers. However, at 60 min, CTV-coverage was below a threshold of 32.5 Gy in 30% of volunteers (30.6 Gy, 32.0 Gy, 32.3 Gy).ConclusionThe dosimetric benefit of MR-guided online adaptation for prostate SBRT was robust over 45 min in all volunteers. However, intrafractional uncertainties became dosimetrically relevant at 60 min and we therefore recommend verification imaging before delivery of MR-guided online adapted SBRT.