Faculty Bibliography

BACKGROUND:To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences. METHODS:Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to maintain a full bladder and empty rectum prior to simulation and each treatment. A single reviewer delineated organs at risk (OARs) on the simulation (Sim-CT) and Cone Beam CTs (CBCT) for analyses. RESULTS:Bladder and rectum volume reductions were observed throughout the course of SBRT, with largest mean reductions of 86.9 mL (19.0%) for bladder and 6.4 mL (8.7%) for rectum noted at fraction #5 compared to Sim-CT (P < 0.01). Higher initial Sim-CT bladder volumes were predictive for greater reduction in absolute bladder volume during treatment (ρ = - 0.69; P < 0.01). Over the course of SBRT, there was a small but significant increase in bladder mean dose (+ 4.5 ± 12.8%; P < 0.01) but no significant change in the D2cc (+ 0.8 ± 4.0%; P = 0.28). The mean bladder trigone displacement was in the anterior direction (+ 4.02 ± 6.59 mm) with a corresponding decrease in mean trigone dose (- 3.6 ± 9.6%; P < 0.01) and D2cc (- 6.2 ± 15.6%; P < 0.01). There was a small but significant increase in mean rectal dose (+ 7.0 ± 12.9%, P < 0.01) but a decrease in rectal D2cc (- 2.2 ± 10.1%; P = 0.04). No significant correlations were found between relative bladder volume changes, bladder trigone displacements, or rectum volume changes with rates of genitourinary or rectal toxicities. CONCLUSIONS:Despite smaller than expected bladder and rectal volumes at the time of treatment compared to the planning scans, dosimetric impact was minimal and not predictive of detrimental clinical outcomes. These results cast doubt on the need for excessively strict bladder filling and rectal emptying protocols in the context of image guided prostate SBRT and prospective studies are needed to determine its necessity.

BACKGROUND:We examine the prognostic implications of mid-course nodal response in oropharyngeal cancer (OPX) to radiation therapy. METHODS:In 44 patients with node-positive OPX undergoing concurrent chemoradiation, nodal volumes were measured on cone beam CTs from days 1, 10, 20, and 35. Nodal decrease (ND) was based on percent shrinkage from day 1. RESULTS:At a median follow-up of 17 months, the 2-year disease-free survival (DFS), locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) were 87%, 92%, 89%, and 92%, respectively. Patients with ND ≥43% at D20 had improved LRC (100% vs 78.4%, P = .03) compared to D20 ND <43%. On multivariate analysis, D20 ≥43% was independently prognostic for LRC (HR 1.17, P = .05). CONCLUSION/CONCLUSIONS:Patients with low-risk oropharynx cancer with ND of ≥43% by treatment day 20 had significantly improved LRC. The prognostic benefit of ND may assist in identifying candidates for treatment de-escalation.

Advances in cancer therapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (IRAEs), which resemble autoimmune disease. In this Review, we describe the current data regarding immune-related endocrinopathies, including hypophysitis, thyroid dysfunction and diabetes mellitus. We discuss the clinical management of these endocrinopathies within the context of our current understanding of the mechanisms of IRAEs.

Post-radiotherapy erectile dysfunction (ED) can significantly impact the quality of life of patients with prostate cancer (PCa). Critical anatomical structures, such as the neurovascular bundle (NVB), internal pudendal arteries (IPA), penile bulb, and corporal tissues track in close proximity to the prostate, making them susceptible to radiation-related damage. This study aimed to evaluate the anatomical patterns of these structures and their relationship with the prostate, and to provide comprehensive illustrative examples on MRI. Consecutive patients with PCa who underwent MRI-linear accelerator (LINAC)-based stereotactic body radiotherapy (SBRT) in January-December 2024 were included. NVB patterns were classified into 3 categories: (1) "classical" with discrete NVB elements, (2) "adherent", dispersed and adherent to prostatic capsule, and (3) "absent". The smallest distance between the IPA and the prostate capsule and membranous urethral length (MUL), serving as a surrogate for distance between corporal tissue and prostatic apex, were also measured. These MRI findings were compared between prostate volumes >40 and <40 ml and between MRI/pathological features of the dominant intraprostatic lesion. A total of 160 men (median age 70 years, interquartile range [IQR] 64-76) were included. The most common NVB pattern was "classic" (80.0-85.0%), followed by the "adherent" NVB pattern (13.8-18.1%). The median smallest distance between the IPA and prostate was 2.3 cm (IQR 1.8-2.8 cm), with 3.1-3.8% less than 1.0 cm. The median MUL was 1.5 cm (IQR, 1.2-1.8 cm), with 2.5% of patients less than 1.0 cm. No significant association was found between these MRI features and prostate volume or other variables (p = 0.09-0.99). In conclusion, most PCa patients demonstrated favorable anatomy for potential dose sparing of critical structures. Comprehensive MRI illustrations are provided to help radiation oncologists recognize the location, trajectory, and relationship of these structures, facilitating their contouring and ultimately aiding in achieving meaningful dose reductions to these erectile function structures.

PURPOSE/OBJECTIVE:To evaluate the degree and rate of bladder filling during magnetic resonance imaging-guided linear accelerator (MRL) prostate stereotactic body radiotherapy (SBRT), and to determine the association of degree of bladder filling with intra-fractional prostatic motion requiring positional shifts during therapy. The impact of bladder filling on post-treatment target and normal tissue dosimetry was also evaluated. METHODS:Sixty-two consecutive prostate SBRT patients treated on the MRL with an empty bladder and a five-fraction regimen were evaluated. Bladder filling patterns during each treatment session and the frequency of required shifts to address intra-fractional prostate motion were studied. During each fraction, three MR image acquisitions were obtained: an immediate baseline T2-weighted sequence, a verification sequence after the plan was generated prior to treatment delivery, and a sequence post-treatment. Bladder filling rates were evaluated at these time points for each fraction and across the five treatment fractions. Multivariate analysis identified variables associated with increased bladder filling rates and the likelihood of positional target adjustments of the prostate during real-time adaptive planning. Post-treatment MR structures were used to recalculate plans for analysis of intra-fractional dosimetric variations in target and normal tissue doses. RESULTS:The median baseline bladder volume at fraction 1 was 88 cc (range 35-245), increasing to 138 cc (range 55-340) at verification MR and 156 cc (range 69-475) post-treatment. Bladder volume increases from baseline to verification MR and from verification MR to post-treatment MR were consistent across the cohort. Multivariate analysis identified the use of alpha receptor blockers during treatment (beta - 17.36 mL; 95 % CI - 32.97, -1.74; p = 0.030) and lower baseline bladder volume (beta 11.62 mL; 95 % CI 4.20, 19.05; p = 0.002) as significant factors in limiting both absolute bladder volume and the rate of bladder filling during adaptive SBRT fractions. Conversely, the need for a positional target shift at verification MR was associated with larger bladder volume (OR 1.20; 95 % CI 0.98, 1.46; p = 0.075) and high International Prostate Symptom Score (OR 5.42; 95 % CI 1.34, 21.89; p = 0.018). Post-treatment dosimetric analysis revealed no notable compromises to prostate target coverage (D95Gy median -0.19 Gy, IQR 0.49) or normal tissue constraints. CONCLUSIONS:This analysis of bladder filling dynamics in patients undergoing prostate SBRT with real-time adaptive planning demonstrated predictable bladder filling patterns using an empty bladder regimen. Dose-volume constraints were consistently achieved for both target volumes and normal tissues. The finding that alpha receptor blockers reduced the rate of bladder filling during treatment fractions may have implications for improving treatment consistency and patient comfort in real-time adaptive planning workflows.

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/OBJECTIVE:Percentage of positive cores involved on a systemic prostate biopsy has been established as a risk factor for adverse oncologic outcomes and is a National Comprehensive Cancer Network (NCCN) independent parameter for unfavorable intermediate-risk disease. Most data from a radiation standpoint was published in an era of conventional fractionation. We explore whether the higher biological dose delivered with SBRT can mitigate this risk factor. METHODS:A large single institutional database was interrogated to identify all patients diagnosed with localized prostate cancer (PCa) treated with 5-fraction SBRT without ADT. Pathology results were reviewed to determine detailed core involvement as well as Gleason score (GS). High-volume biopsy core involvement was defined as ≥ 50%. Weighted Gleason core involvement was reviewed, giving higher weight to higher-grade cancer. The PSA kinetics and oncologic outcomes were analyzed for association with core involvement. RESULTS:From 2009 to 2018, 1590 patients were identified who underwent SBRT for localized PCa. High-volume core involvement was a relatively rare event observed in 19% of our cohort, which was observed more in patients with small prostates (p < 0.0001) and/or intermediate-risk disease (p = 0.005). Higher PSA nadir was observed in those patients with low-volume core involvement within the intermediate-risk cohort (p = 0.004), which was confirmed when core involvement was analyzed as a continuous variable weighted by Gleason score (p = 0.049). High-volume core involvement was not associated with biochemical progression (p = 0.234). CONCLUSIONS:With a median follow-up of over 4 years, biochemical progression was not associated with pretreatment high-volume core involvement for patients treated with 5-fraction SBRT alone. In the era of prostate SBRT and MRI-directed prostate biopsies, the use of high-volume core involvement as an independent predictor of unfavorable intermediate risk disease should be revisited.

INTRODUCTION/UNASSIGNED:As overall survival in prostate cancer increases due to advances in early detection and management, there is a growing need to understand the long-term morbidity associated with treatment, including secondary tumors. The significance of developing radiation-associated secondary cancers in an elderly population remains unknown. METHODS/UNASSIGNED:Patients diagnosed with prostate cancer between 1975 and 2016 in one of 9 Surveillance, Epidemiology, and End Results registries were included in this study. Risk of second primary pelvic malignancies (SPPMs) were assessed with death as a competing risk using the Fine-Gray model. Time-varying Cox proportional hazard models were employed to analyze risk to overall mortality based on secondary tumor status. RESULTS/UNASSIGNED:A total of 569,167 primary prostate cancers were included in analysis with an average follow-up of 89 months. Among all prostate cancer patients, 4956 SPPMs were identified. After controlling for differences in age, year of diagnosis, and surgery at time of prostate cancer treatment, radiation receipt was associated with a significantly higher incidence of SPPMs (1.1% vs 1.8% at 25 years). Among those who received radiation during initial prostate cancer treatment (n = 195,415), developing an SPPM is significantly associated with worse survival (adjusted hazard ratio = 1.76), especially among younger patients (under age 63, adjusted hazard ratio = 2.36). CONCLUSIONS/UNASSIGNED:While developing a secondary malignancy carries a detrimental effect on overall survival, the absolute risk of developing such tumors is exceedingly low regardless of radiation treatment.