Faculty Bibliography

PURPOSE/UNASSIGNED:Screening colonoscopies (CS) performed before prostate stereotactic body radiation therapy (SBRT) allow for identifying synchronous malignancies and comorbid gastrointestinal (GI) conditions. Performing these procedures prior to radiation precludes the necessity of post-SBRT pelvic instrumentation, which may lead to severe toxicity and fistulization. We review compliance of CSs, incidence of GI pathology, and the impact of pretreatment CS findings on subsequent physician-reported toxicity and patient-reported quality of life (QoL). METHODS AND MATERIALS/UNASSIGNED:We reviewed an institutional database of patients treated for prostate cancer with SBRT including toxicity and QoL outcomes. A detailed review of pretreatment CS findings was reviewed including identification of diverticulosis, location of polyp resection, and presence of hemorrhoids. Pretreatment CS findings were then correlated with outcomes following SBRT. RESULTS/UNASSIGNED:Identification of comorbid GI conditions was a common event, with the presence of diverticulosis in 49.5% (n = 100), hemorrhoids in 67% (n = 136), and polyps in 48% (n = 98). More than half of patients with polyps removed had at least 1 removed from the rectosigmoid. Pretreatment CS did not introduce a delay in SBRT start date. Grade 1 toxicity was significantly lower in patients who underwent CS closer to the initiation of SBRT. There was no increased risk of physician-graded toxicity in the presence of diverticulosis, hemorrhoids, or polyps. Patient-reported GI QoL pattern in our screening cohort mimicked that seen in the previously published nonscreened population. There was no overt QoL detriment observed in patients who had GI pathology identified before SBRT. CONCLUSIONS/UNASSIGNED:GI pathology identified in our elderly patient population was commonly identified on pretreatment CS. Screening CS may optimize bowel health for patients heading into radiation therapy. Toxicity and QoL for patients with GI pathologies identified on pretreatment CS do not preclude the delivery of prostate SBRT. We advocate for pretreatment CS in patients eligible prior to SBRT.

PURPOSE/OBJECTIVE:We hypothesized that an in-house developed system using megavoltage and kilovoltage image guidance (MKIG) to ensure correct prostate positioning during stereotactic body radiation therapy (SBRT) could potentially avoid unwanted doses to nontarget tissues, leading to reduced toxicities. METHODS AND MATERIALS/METHODS:We built a 3-dimensional MKIG platform that accurately tracks prostate implanted fiducials in real time and clinically translated the system to replace a commercial approach, intrafraction motion review (IMR), which only tracks fiducials in the 2-dimensional kilovoltage views. From 2017 to 2019, 150 patients with prostate cancer were treated with SBRT and monitored using MKIG. The motion trace of the fiducials alerts therapists to interrupt and reposition the prostate when displacement exceeds a 1.5 mm threshold. A comparison cohort of 121 patients was treated with the same dose regimen and treatment technique but managed by IMR. Statistics of intrafractional patient shifts and delivery time were collected to evaluate the workflow efficacy. The incidence of grade ≥2 urinary toxicities was analyzed to assess clinical complications. The median follow-up time was 3.7 years (0.2-8.2 years). RESULTS:MKIG treatments had more treatment shifts (1.09 vs 0.28) and a longer average delivery time per fraction (579 ± 205 seconds vs 357 ± 117 seconds) than IMR treatments. Three-quarters (75%) of shifts resulting from MKIG were ≤3 mm, versus 51% in IMR, indicating that MKIG detected and corrected smaller deviations. The incidence of grade ≥2 urinary toxicity was lower in the MKIG than the IMR cohort: 10.7% versus 19.8% (P = .047). On multivariate analysis of late urinary toxicity, only high (>7) preradiation therapy international prostate symptom score (P < .043) and the use of MKIG were selected (P < .029). CONCLUSIONS:Automated and quantitative MKIG introduced minimal workflow impact and was superior to IMR in localizing the prostate during SBRT, which correlated with a clinically significant reduction in late urinary toxicity. Further clinical testing using randomized trials will be required to validate the impact on outcomes.

PURPOSE/OBJECTIVE:This guideline presents evidence-based consensus recommendations for high-dose-rate (HDR) brachytherapy boost in combination with external beam radiotherapy (EBRT) for the primary treatment of localized prostate cancer. METHODS AND MATERIALS/METHODS:The American Brachytherapy Society convened a task force for addressing key questions concerning prostate HDR brachytherapy boost with EBRT for the primary treatment of localized prostate cancer. A comprehensive literature search was conducted to identify prospective and large retrospective studies involving HDR brachytherapy combined with EBRT. Outcomes of interest included biochemical and/or disease control, toxicity, patient-reported quality of life, and the role of androgen deprivation therapy. RESULTS:HDR brachytherapy using Ir-192 in combination with EBRT is an appropriate treatment option for men with intermediate- and high-risk prostate cancer. CT, ultrasound, and/or MRI are imaging platforms that may be utilized for treatment planning and delivery. A single implant/fraction of 15 Gy or 2 implants/fractions of 9.5-11 Gy each are acceptable regimens in combination with EBRT at a dose equivalent of 45-50.4 Gy in 1.8-2.0 Gy fractions. The addition of HDR brachytherapy is expected to improve biochemical control compared with dose escalated EBRT alone. HDR brachytherapy boost is expected to achieve similar biochemical control outcomes as a low dose rate (LDR) brachytherapy boost. Androgen deprivation therapy is recommended for men with unfavorable intermediate and high-risk disease, with varying duration dependent on cancer risk. Use of an HDR brachytherapy technique, as opposed to LDR permanent seeds, has been shown to have less acute genitourinary (GU) and gastrointestinal (GI) toxicity following treatment. CONCLUSIONS:For men with intermediate- and high-risk prostate cancer, HDR brachytherapy boost is a safe and effective technique for dose-escalation that can achieve superior biochemical control compared with EBRT alone, possibly with an improved GU and GI side effect profile compared with an LDR brachytherapy technique.

PURPOSE/OBJECTIVE:This systematic review provides an overview of the available literature regarding the efficacy and safety of implantable rectal spacers (IRS) in reducing rectal dose and gastrointestinal (GI) toxicity during prostate cancer (PC) radiotherapy (RT). METHODS AND MATERIALS/METHODS:A comprehensive literature search was conducted in December 2024. Results included prospective research in humans and were limited to the English language. The 30 included studies, all published between 2007 and 2024, were randomized controlled trials (RCTs) or clinical trials which focused on adverse events (AEs), rectal dose reduction, GI toxicity, or bowel quality of life (QOL). Secondly, IRS implantation technique, safety, and spacing distance were assessed. RESULTS:RCT data was available for hydrogel (HG), hyaluronic acid (HA) and rectal balloon implant (RBI) spacers, while only one pilot study is available for HC. Prospective clinical research on IRS in brachytherapy is limited. One centimeter of spacing between rectum and prostate sufficed to spare the rectum, the primary dose-limiting organ. Findings indicate a favorable safety profile, with an overall complication rate of 0,96% when using hydrogel (HG) spacers. There was no grade 4-5 GI toxicity reported in clinical trials. The use of an IRS was associated with improved long-term bowel QOL. CONCLUSIONS:The integration of IRS into clinical practice offers potential to enhance the therapeutic landscape for PC patients. However, its use should be guided by careful consideration of individual patient needs to determine those who benefit most from IRS, as not all patients may benefit equally.

OBJECTIVES/UNASSIGNED:To evaluate the incidence and degree of rectal wall infiltration (RWI) of spacer gel used during prostate radiotherapy among two practitioners experienced in using rectal spacers. MATERIALS AND METHODS/UNASSIGNED:Consecutive patients with prostate cancer who received prostate radiotherapy after hydrogel rectal spacer insertion in August 2023-August 2024 by two experienced practitioners were retrospectively included. Post-implant magnetic resonance imaging examinations were evaluated by two radiologists for RWI: 0 (no abnormality), 1 (rectal wall edema), 2 (superficial RWI), and 3 (deep RWI). Scores 2-3 were considered positive for RWI and their location and degree of RWI (radial, longitudinal, and circumferential) were also categorized. Inter-reader agreement was assessed with Cohen's Kappa. RESULTS/UNASSIGNED:215 men were included. Agreement was substantial between the radiologists for RWI scores (Kappa, 0.697; 95% confidence interval, 0.594-0.800). RWI scores were 0 in 80.5% (173/215), 1 in 7.9% (17/215), 2 in 10.7% (23/215), and, 3 in 0.9% (2/215) of the men. Altogether, RWI was present (scores 2-3) in 11.6% (25/215), most commonly in the mid-gland and apex with median radial, longitudinal, and circumferential involvement of 3.2 mm, 8.6 mm, and 11.5%. None of these patients demonstrated any significant rectal toxicity. CONCLUSION/UNASSIGNED:RWI was very uncommon for experienced practitioners. The degree of RWI was focal and not associated with increased complications.

PURPOSE/OBJECTIVE:To commission a beam model in ClearCalc (Radformation Inc.) for use as a secondary dose calculation algorithm and to implement its use into an adaptive workflow for an MR-linear accelerator. METHODS:A beam model was developed using commissioning data for an Elekta Unity MR-linear accelerator and entered into ClearCalc. The beam model consisted of absolute dose calculation settings, output factors, percent depth-dose (PDD) curves, mutli-leaf collimator (MLC) transmission and dose leaf gap error, and cryostat corrections. Beam profiles were hard-coded by the manufacturer into the beam model and were compared with Monaco-derived profiles. The beam model was tested by comparing point doses in a homogenous phantom obtained through measurements using an ionization chamber in water, Monaco, and ClearCalc for various field sizes, source-surface distances (SSDs), and point locations. Additional testing including point dose verification for test plans using a heterogeneous phantom and patient plans. Post clinical implementation, performance of ClearCalc was evaluated for the first 41 patients treated, which included 215 adaptive plans. RESULTS:PDDs generated using ClearCalc fell within 1.2% of measurements. Field profile comparison between ClearCalc and Monaco showed an average pass rate of 98% using a 3%/3 mm gamma criteria. Measured cryostat corrections used in the beam model showed a maximum deviation from unity of 1.4%. Point dose and field monitor units (MUs) comparisons in a homogenous phantom (N = 22), heterogeneous phantoms (N = 22), and patient plans (N = 57) all passed with a threshold of 5%/5MU. Clinically, ClearCalc was implemented as a physics check post adaptive planning completed prior to beam delivery. Point dose and field MUs showed good agreement at a 5%/5MU threshold for prostate stereotactic body radiation therapy (SBRT), pelvic lymph nodes, rectum, and prostate and lymph node plans. DISCUSSION/CONCLUSIONS:This work demonstrated commissioning and clinical implementation of ClearCalc into an adaptive planning workflow. No primary or adaptive plan failures were reported with proper beam model testing.

PURPOSE/UNASSIGNED:Rectal spacers have gained popularity as a dose-sparing material for prostate cancer radiation therapy (RT). However, the procedure can be associated with unintended rectal wall infiltration (RWI) of the spacer gel. We therefore classified RWI severity as a function of depth and explored its association with rectal toxicity using a data set from prostate cancer patients treated with RT on a prospective randomized clinical trial (RCT). METHODS AND MATERIALS/UNASSIGNED:Postimplant T2-weighted magnetic resonance images of 149 subjects randomized to the hydrogel spacer arm of a published multicenter RCT were assessed for the presence and depth of RWI. All implants were assigned a score of 0 (no rectal wall signal changes), 1 (rectal wall edema/signal change), 2 (partial RWI), or 3 (full-thickness RWI); RWI was defined as a score of 2 or 3. Correlations were made between RWI score and physician-reported procedure, acute, and late rectal toxicity. RESULTS/UNASSIGNED:= .85) rectal toxicity incidence or grade was detected between RWI categories; none of the 6 men with a RWI score of 3 developed late rectal toxicity by 15 months. CONCLUSIONS/UNASSIGNED:Based on data from an RCT, RWI did not contribute to increased rectal toxicity prior and up to 15 months after conventional prostate cancer RT.

PURPOSE/UNASSIGNED:Multiparametric magnetic resonance imaging (MRI) is known to provide predictors for malignancy and treatment outcome. The inclusion of these datasets in workflows for online adaptive planning remains under investigation. We demonstrate the feasibility of longitudinal relaxometry in online MR-guided adaptive stereotactic body radiotherapy (SBRT) to the prostate and dominant intra-prostatic lesion (DIL). METHODS/UNASSIGNED:Fifty patients with intermediate-risk prostate cancer were included in the study. The clinical target volume (CTV) was defined as the prostate gland plus 1 cm of seminal vesicles. The gross tumor volume (GTV) was defined as the DIL identified on multiparametric MRI. Online adaptive radiotherapy was delivered in a 1.5 T MR-Linac using a prescription of 800 cGy/900 cGy × 5 fractions to the CTV + 3 mm/GTV + 2 mm. Relaxometry and diffusion-weighted imaging were implemented using clinically available sequences. Test-retest measurements were performed in eight patients, at each treatment fraction. Bias and uncertainty in relaxometry measurements were also assessed using a reference phantom. RESULTS/UNASSIGNED:The bias in longitudinal/transverse relaxation times was negligible while uncertainty was within 3 %. Test-retest measurements demonstrate that bias/uncertainty in patient T1 and T2 were comparable to bias/uncertainty estimated in the phantom. Mean T1 and T2 relaxation were significantly different between the prostate and DIL. The correlation between T1, T2, and diffusion was significant in the DIL, but not in the prostate. During treatment, mean T1 in the DIL approaches mean T1 in the prostate. CONCLUSIONS/UNASSIGNED:Longitudinal relaxometry for online MR-guided adaptive SBRT is feasible in a high-field MR-Linac and may provide complementary information for target delineation and response assessment.

BACKGROUND:Ultrahypofractionated stereotactic body radiation therapy (SBRT) has become a standard treatment intervention for localized prostate cancer. OBJECTIVE:To report final long-term tumor control outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicities from a single-center phase 1 dose escalation study using SBRT for patients with low- or intermediate-risk prostate cancer. DESIGN, SETTING AND PARTICIPANTS/METHODS:Between 2009 and 2012, 136 patients were enrolled and treated. The initial dose level was 32.5 Gy in five fractions. Doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy in five fractions delivered every other day. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:The primary endpoint was late treatment-related toxicity. Secondary endpoints included prostate-specific antigen (PSA) failure. RESULTS AND LIMITATIONS/CONCLUSIONS:The median follow-up was 10.5 yr for the 32.5-Gy group, 9.9 yr for the 35-Gy group, 8.2 yr for the 37.5-Gy group, and 7.3 yr for the 40-Gy group. The 8-yr cumulative incidence of PSA failure was 26% for 32.5 Gy, 15% for 35 Gy, 3.4% for 37.5 Gy, and 6.6% for 40 Gy. Higher radiation dose (37.5-40 Gy) and favorable intermediate risk (vs unfavorable intermediate risk) were associated with better PSA recurrence rates (p = 0.011 and 0.002, respectively). The 8-yr actuarial probability rates for survival free from late grade ≥2 toxicity were 94% for GI toxicity and 86% for GU toxicity. No grade 4 events were recorded. Higher dose levels were not associated with higher rates of late grade ≥2 GI (p = 0.2) or GU (p > 0.9) toxicity. CONCLUSIONS:SBRT doses ranging from 32.5 to 40 Gy were associated with low incidence of moderate or severe toxicities. Higher doses resulted in superior disease control outcomes 8 yr after treatment. PATIENT SUMMARY/RESULTS:We investigated the association between the radiotherapy dose used and the rate of control of prostate cancer. We found that higher doses resulted in more favorable outcomes without excess toxicity. This trial is registered on ClinicalTrials.gov as NCT00911118.

PURPOSE/OBJECTIVE:The use of magnetic resonance imaging (MRI) in radiotherapy planning is becoming more widespread, particularly with the emergence of MRI-guided radiotherapy systems. Existing guidelines for defining the prostate bed clinical target volume (CTV) show considerable heterogeneity. This study aimed to establish baseline interobserver variability (IOV) for prostate bed CTV contouring on MRI, develop international consensus guidelines, and evaluate its effect on IOV. METHODS AND MATERIALS/METHODS:Participants delineated the CTV on 3 MRI scans, obtained from the Elekta Unity MR-Linac, as per their normal practice. Radiation oncologist contours were visually examined for discrepancies, and interobserver comparisons were evaluated against simultaneous truth and performance level estimation (STAPLE) contours using overlap metrics (Dice similarity coefficient and Cohen's kappa), distance metrics (mean distance to agreement and Hausdorff distance), and volume measurements. A literature review of postradical prostatectomy local recurrence patterns was performed and presented alongside IOV results to the participants. Consensus guidelines were collectively constructed, and IOV assessment was repeated using these guidelines. RESULTS:Sixteen radiation oncologists' contours were included in the final analysis. Visual evaluation demonstrated significant differences in the superior, inferior, and anterior borders. Baseline IOV assessment indicated moderate agreement for the overlap metrics while volume and distance metrics demonstrated greater variability. Consensus for optimal prostate bed CTV boundaries was established during a virtual meeting. After guideline development, a decrease in IOV was observed. The maximum volume ratio decreased from 4.7 to 3.1 and volume coefficient of variation reduced from 40% to 34%. The mean Dice similarity coefficient rose from 0.72 to 0.75 and the mean distance to agreement decreased from 3.63 to 2.95 mm. CONCLUSIONS:Interobserver variability in prostate bed contouring exists among international genitourinary experts, although this is lower than previously reported. Consensus guidelines for MRI-based prostate bed contouring have been developed, and this has resulted in an improvement in contouring concordance. However, IOV persists and strategies such as an education program, development of a contouring atlas, and further refinement of the guidelines may lead to additional improvements.