Faculty Bibliography

PURPOSE/OBJECTIVE:Curative-intent radiotherapy for locally advanced and select early stage cervical cancer in the US includes external beam radiotherapy (EBRT) with brachytherapy. Although there are guidelines for brachytherapy dose and fractionation regimens, there are limited data on practice patterns. This study aims to evaluate the contemporary utilization of cervical cancer brachytherapy in the US and its association with patient demographics and facility characteristics. METHODS:We retrospectively analyzed clinical covariates of cervical cancer patients diagnosed and treated in 2018-2020 with curative-intent radiotherapy from the 2020 National Cancer Database. Associations between patient and institutional factors with the number of brachytherapy fractions were identified with logistic regression. Factors with association (p < 0.10) were then included in a multivariable logistic regression model. All tests were two-sided with significance <0.05 unless specified otherwise. RESULTS:Among the eligible 2517 patients, 97.3% received HDR or LDR and is further analyzed. More patients received HDR than LDR brachytherapy (98.9% vs 1.1%) and intracavitary than interstitial brachytherapy (86.4% vs 13.6%). The most common number of HDR fractions prescribed were 5 (51.0%), 4 (32.9%), and 3 (8.6%). After adjusting for the other variables in the model, ethnicity, private insurance status, overall insurance status, and facility type were the only factors that were significantly associated with the number of brachytherapy factions (p < 0.0001, p = 0.028, p = 0.001, and p < 0.0001, respectively, n = 2184). CONCLUSIONS:In the US, various HDR brachytherapy regimens are utilized depending on patient and institutional factors. Future research may optimize cervical cancer brachytherapy by correlating specific dose and fractionation regimens with patient outcomes.

PURPOSE:Given the limited data using an interstitial approach with 3D-based planning for definitive cervical cancer utilizing the GEC-ESTRO defined high-risk clinical target volume (HR-CTV), we reviewed our institutional experience of cervical cancer patients with HR-CTVs ≥ 30 cc to determine whether our clinical and toxicity outcomes are acceptable. METHODS:of 87.44 Gy was achieved. Kaplan-Meier method was used to evaluate local control (LC), distant control, and overall survival (OS), with stratification by overall treatment time (OTT) ≤ 7 or >7 weeks. RESULTS:Median followup was 17 months. The estimated 2-year LC, distant control, and OS were 77.6% (confidence interval [CI]: 63.8-94.5%), 56.8% (CI: 41.3-78.1%), and 54.4% (CI: 39.4-75%), respectively. The 2-year LC for OTT ≤7 weeks and >7 weeks were 100% and 58.3%, respectively (p = 0.026). The 2-year OS for OTT ≤7 weeks and >7 weeks were 77.8% and 38%, respectively (p = 0.021). DISCUSSIONS:to the HR-CTV even in the setting of large-volume disease and results in a favorable LC and toxicity profile. OTT > 7 weeks is associated with significant decrease in LC and OS. CONCLUSIONS:Efforts should be made to complete whole treatment within 7 weeks as this is associated with improved clinical outcomes.

PURPOSE:To determine whether pretreatment 3T multiparametric MRI (mpMRI) staging impacts biochemical recurrence-free survival (BRFS) or distant metastasis-free survival (DMFS) for men with high-risk prostate cancer treated with combination high-dose-rate (HDR) brachytherapy and external beam radiation therapy (EBRT). MATERIALS AND METHODS:This institutional review board-approved retrospective study included a cohort of 37 men with high-risk prostate cancer treated with HDR brachytherapy and EBRT after 3T mpMRI. Kaplan-Meier analysis was used to evaluate whether mpMRI evidence of extracapsular extension or seminal vesicle invasion (SVI) resulted in differences in BRFS or DMFS. Pretreatment and treatment-related variables were evaluated for association with biochemical failure (Phoenix definition) and distant metastatic failure using univariate Cox regression analysis. RESULTS:The median prostate-specific antigen at diagnosis was 9 ng/mL (range 2-100). Biopsy Gleason score (bGS) was ≤8 in 38% and nine in 62%. Clinical T-category was T1-T2 in 89%, T3a in 8%, and T3b in 3%. With a median followup of 30.6 months, actuarial 3-year BRFS and DMFS were 76% and 86%, respectively. Kaplan-Meier analysis revealed that mpMRI evidence of extracapsular extension or SVI resulted in significantly higher rates of both biochemical recurrence and distant failure. Using Cox regression analysis, only mpMRI evidence of SVI vs. no SVI predicted for biochemical failure (hazard ratio 13.98, p = 0.0055). CONCLUSIONS:For high-risk prostate cancer treated with combination HDR brachytherapy and EBRT, mpMRI evidence of SVI predicted for biochemical failure, whereas traditional pretreatment variables did not. Therefore, pretreatment 3T mpMRI appears useful for identifying men who may benefit from treatment intensification.

Deformable image registration (DIR) and interobserver variation inevitably intro-duce uncertainty into the treatment planning process. The purpose of the current work was to measure deformable image registration (DIR) errors and interobserver variability for regions of interest (ROIs) in the head and neck and pelvic regions. Measured uncertainties were combined to examine planning margin adequacy for contours propagated for adaptive therapy and to assess the trade-off of DIR and interobserver uncertainty in atlas-based automatic segmentation. Two experi-enced dosimetrists retrospectively contoured brainstem, spinal cord, anterior oral cavity, larynx, right and left parotids, optic nerves, and eyes on the planning CT (CT1) and attenuation-correction CT of diagnostic PET/CT (CT2) for 30 patients who received radiation therapy for head and neck cancer. Two senior radiation oncology residents retrospectively contoured prostate, bladder, and rectum on the postseed-implant CT (CT1) and planning CT (CT2) for 20 patients who received radiation therapy for prostate cancer. Interobserver variation was measured by calculating mean Hausdorff distances between the two observers' contours. CT2 was deformably registered to CT1 via commercially available multipass B-spline DIR. CT2 contours were propagated and compared with CT1 contours via mean Hausdorff distances. These values were summed in quadrature with interobserver variation for margin analysis and compared with interobserver variation for sta-tistical significance using two-tailed t-tests for independent samples (α = 0.05). Combined uncertainty ranged from 1.5-5.8 mm for head and neck structures and 3.1-3.7 mm for pelvic structures. Conventional 5 mm margins may not be adequate to cover this additional uncertainty. DIR uncertainty was significantly less than interobserver variation for four head and neck and one pelvic ROI. DIR uncertainty was not significantly different than interobserver variation for four head and neck and one pelvic ROI. DIR uncertainty was significantly greater than interobserver variation for two head and neck and one pelvic ROI. The introduction of DIR errors may offset any reduction in interobserver variation by using atlas-based automatic segmentation.

PURPOSE/OBJECTIVE:To investigate the effects of cholinergic blockade on inflammatory cell infiltration and cytokine production in the mouse lacrimal gland (LG). METHODS:C57BL/6 mice were untreated (UT) or received subcutaneous injections of either scopolamine hydrobromide (SCOP; 0.5 mg/0.2 mL) or saline (SAL) four times daily for 2 or 5 days (2D, 5D). This was followed by a 7-day rest period in separate groups. Tear volume (cotton thread) and tear epidermal growth factor (EGF, by ELISA) concentrations were measured. Extraorbital LGs were surgically excised and sectioned or lysed for gene expression analysis. Immunohistochemistry evaluated immunophenotype of infiltrating cells. Expression of EGF and T helper (Th)-1, -2, and -17-associated cytokines in LGs was evaluated by real-time PCR. Goblet cell density was evaluated in periodic acid Schiff-stained conjunctival sections. RESULTS:Tear volume and EGF protein levels were significantly reduced in SCOP5D mice compared with controls, indicating that cholinergic blockade decreased LG secretory function. LGs of SCOP2D and SCOP5D mice showed an increased density of CD4(+), CD11c+, CD11b+, and myeloperoxidase+ cells compared with UT controls. At day 5, these cells were significantly elevated compared with SAL-treated counterparts. Elevated levels of IL-17A, IL-17R, IFN-γ, IL-12Rβ1, IL-2, IL-13, IL-6, IL-1β, and TNF-α transcripts were noted in SCOP2D mice and IFN-γ, TGF-β1, and IL-18R transcripts in SCOP5D mice. CONCLUSIONS:Pharmacological blockade of lacrimal secretion induced a significant CD4(+) infiltration in the LG, mimicking Sjögren's syndrome. The mRNA expression profile revealed elevations of a mix of inflammatory cytokines and Th-1-associated factors.

Asian-Indians have high rates of coronary artery disease (CAD), which also occurs at an earlier age, with 50% of all heart attacks occurring in patients <55 years old and 25% in those <40 years old. Previous studies have cited structural factors in Asian-Indians, specifically smaller coronary arteries, as the cause of increased CAD in this population. We found that Asian-Indian patients have smaller coronary arteries, with a statistically significant difference in the mean diameter even after correction for body surface area