Sahaja Acharya

Online Magnetic Resonance Image Guided Adaptive Radiation Therapy: First Clinical Applications

PURPOSE To demonstrate the feasibility of online adaptive magnetic resonance (MR) image guided radiation therapy (MR-IGRT) through reporting of our initial clinical experience and workflow considerations. METHODS AND MATERIALS The first clinically deployed online adaptive MR-IGRT system consisted of a split 0.35T MR scanner straddling a ring gantry with 3 multileaf collimator-equipped (60)Co heads. The unit is supported by a Monte Carlo-based treatment planning system that allows real-time adaptive planning with the patient on the table. All patients undergo computed tomography and MR imaging (MRI) simulation for initial treatment planning. A volumetric MRI scan is acquired for each patient at the daily treatment setup. Deformable registration is performed using the planning computed tomography data set, which allows for the transfer of the initial contours and the electron density map to the daily MRI scan. The deformed electron density map is then used to recalculate the original plan on the daily MRI scan for physician evaluation. Recontouring and plan reoptimization are performed when required, and patient-specific quality assurance (QA) is performed using an independent in-house software system. RESULTS The first online adaptive MR-IGRT treatments consisted of 5 patients with abdominopelvic malignancies. The clinical setting included neoadjuvant colorectal (n=3), unresectable gastric (n=1), and unresectable pheochromocytoma (n=1). Recontouring and reoptimization were deemed necessary for 3 of 5 patients, and the initial plan was deemed sufficient for 2 of the 5 patients. The reasons for plan adaptation included tumor progression or regression and a change in small bowel anatomy. In a subsequently expanded cohort of 170 fractions (20 patients), 52 fractions (30.6%) were reoptimized online, and 92 fractions (54.1%) were treated with an online-adapted or previously adapted plan. The median time for recontouring, reoptimization, and QA was 26 minutes. CONCLUSION Online adaptive MR-IGRT has been successfully implemented with planning and QA workflow suitable for routine clinical application. Clinical trials are in development to formally evaluate adaptive treatments for a variety of disease sites.

Outcomes of iodine-125 plaque brachytherapy for uveal melanoma with intraoperative ultrasonography and supplemental transpupillary thermotherapy

PURPOSE To assess the impact on local tumor control of intraoperative ultrasonographic plaque visualization and selective application of transpupillary thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125 (I-125) episcleral plaque brachytherapy (EPB). METHODS AND MATERIALS Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal melanoma. Clinical features, dosimetric parameters, TTT treatments, and local tumor control outcomes were recorded. Statistical analysis was performed using Cox proportional hazards and Kaplan-Meier life table method. RESULTS The study included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean, 62 years; range, 16-91 years). Median dose to the tumor apex was 94.4 Gy (mean, 97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range, 124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was detected in 142 cases (27%). Supplemental TTT was performed in 72 patients (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was associated with lower dose to the tumor base (P=.02). CONCLUSIONS Ultrasound-guided plaque localization of I-125 EPB is associated with excellent local tumor control. Detection of plaque tilt by ultrasonography at plaque removal allows supplemental TTT to be used in patients at potentially higher risk for local recurrence while sparing the majority of patients who are at low risk. Most patients require only 1 or 2 TTT sessions.

Brachytherapy Is Associated With Improved Survival in Inoperable Stage I Endometrial Adenocarcinoma: A Population-Based Analysis

PURPOSE To assess the use of brachytherapy (BT) with or without external beam radiation (EBRT) in inoperable stage I endometrial adenocarcinoma in the United States and to determine the effect of BT on overall survival (OS) and cause-specific survival (CSS). METHODS AND MATERIALS Data between 1998 and 2011 from the National Cancer Institutes Surveillance, Epidemiology and End Results database were analyzed. Coarsened exact matching was used to adjust for differences in age and grade between patients who received BT and those who did not. Prognostic factors affecting OS and CSS were evaluated using the Kaplan-Meier product-limit method and a Cox proportional hazards regression model. RESULTS A total of 460 patients with inoperable stage I endometrial adenocarcinoma treated with radiation therapy were identified. Radiation consisted of either EBRT (n=260) or BT with or without EBRT (n=200). The only factor associated with BT use was younger patient age (median age, 72 vs 76 years, P=.001). Patients who received BT had a higher 3-year OS (60% vs 47%, P<.001) and CSS (82% vs 74%, P=.032) compared with those who did not. On multivariate analysis, BT use was independently associated with an improved OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.52-0.87) and CSS (HR 0.61, 95% CI 0.39-0.93). When patients were matched on age, BT use remained significant on multivariate analysis for OS (HR 0.65, 95% CI 0.48-0.87) and CSS (HR 0.52, 95% CI 0.31-0.84). When matched on age and grade, BT remained independently associated with improved OS and CSS (OS HR 0.62, 95% CI 0.46-0.83; CSS HR 0.57, 95% CI 0.34-0.92). CONCLUSION Brachytherapy is independently associated with improved OS and CSS. It should be considered as part of the treatment regimen for stage I inoperable endometrial cancer patients undergoing radiation.

Long-term outcomes and late effects for childhood and young adulthood intracranial germinomas

BACKGROUND Pediatric and young adult central nervous system (CNS) germinomas have favorable cure rates. However, long-term follow-up data are limited because of the rarity of this tumor. We report the long-term overall survival (OS) and causes of late mortality for these patients. METHODS Data between 1973 and 2005 from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Kaplan Meier survival analysis was performed on 5-year survivors of childhood CNS germinomatous germ cell tumors (GGCTs) and nongerminomatous germ cell tumors (NGGCTs). Standardized mortality ratios (SMRs) were calculated using US population data to compare observed versus expected all-cause death and death from stroke. Cumulative incidence was calculated using a competing risk model. RESULTS Four hundred five GGCTs and 94 NGGCTs cases were eligible. OS at 20 and 30 years for GGCTs was 84.1% and 61.9%, respectively, and was 86.7% for NGGCTs at both time points. Five-year survivors of GGCTs and NGGCTs experienced a 10-fold increase in mortality risk compared with their peers (SMR, 10.41; 95% confidence interval [CI], 7.71-13.76 vs SMR, 10.39;95% CI, 4.83-19.73, respectively). Five-year survivors GGCTs also experienced a nearly 59-fold increase in risk of death from stroke (SMR, 58.93; 95% CI, 18.72-142.10). At 25 years, the cumulative incidence of death due to cancer and subsequent malignancy was 16% and 6.0%, respectively. CONCLUSION Although CNS germinomas have favorable cure rates, late recurrences, subsequent malignancies, and stroke significantly affect long-term survival. Close attention to long-term follow-up with assessment of stroke risk factors is recommended.

Effects of Race/Ethnicity and Socioeconomic Status on Outcome in Childhood Acute Lymphoblastic Leukemia.

With modern therapy, overall survival (OS) for children with acute lymphoblastic leukemia approaches 90%. However, inferior outcomes for minority children have been reported. Data on the effects of ethnicity/race as it relates to socioeconomic status are limited. Using state cancer registry data from Texas and Florida, we evaluated the impact of neighborhood-level poverty rate and race/ethnicity on OS for 4719 children with acute lymphoblastic leukemia. On multivariable analysis, patients residing in neighborhoods with the highest poverty rate had a 1.8-fold increase in mortality compared with patients residing in neighborhoods with the lowest poverty rate (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.41-2.30). Hispanic and non-Hispanic black patients also had increased risk of mortality compared with non-Hispanic white patients (Hispanic: HR, 1.18; 95% CI, 1.01-1.39; non-Hispanic black: HR, 1.31; 95% CI, 1.03-1.66). On subgroup analysis, there was a 21.7% difference in 5-year OS when comparing non-Hispanic white children living in the lowest poverty neighborhoods (5-year OS, 91.2%; 95% CI, 88.6-93.2) to non-Hispanic black children living in the highest poverty neighborhoods (5-year OS, 69.5%; 95% CI, 61.5-76.1). To address such disparities in survival, further work is needed to identify barriers to cancer care in this pediatric population.

Comparison of stereotactic body radiation therapy for biopsy-proven versus radiographically diagnosed early-stage non-small lung cancer: a single-institution experience.

Introduction Histological confirmation of non-small cell lung cancer (NSCLC) is often required before patients are offered stereotactic body radiation therapy (SBRT) as a treatment option. Many patients, however, are unsuitable to undergo a biopsy procedure because of comorbidity. Our objective is to compare the outcomes of patients with biopsy-proven (BxPr) or clinically/radiographically diagnosed (RadDx) early-stage NSCLC treated with SBRT. Methods Records of 88 patients treated with SBRT at a single institution were reviewed. Sixty-five patients had BxPr early-stage NSCLC. Twenty-three patients were RadDx with early-stage NSCLC based on an FDG-avid chest nodule on PET scan, serial sequential CT-findings compatible with NSCLC, and consensus of a multidisciplinary team. Outcomes of patients with BxPr and RadDx NSCLC were evaluated in regard to local control, regional lymph node metastasis-free and distant metastasis-free rates, and overall survival using Kaplan-Meier survival curves. Results Median follow-up for all patients was 29 months (range, 4–82 months). Cumulative local progression-free rate after 3 years for the BxPr group was 93.1% (95% confidence interval [CI], 85.2%-97.6%) and 94.10% (95% CI, 73.2%-97.6%) for the RadDx group (p = 0.98). No differences regarding regional lymph node metastasis-free and distant metastasis-free rates by subgroup were observed. The overall 3-year survival rate for the BxPr group was 59.9% (95% CI, 44.8%-68.2%) and 58.9% (95% CI, 40.1%-77.8%) for the RadDx group (p = 0.46). Conclusions SBRT is a practical treatment modality for patients with RadDx early-stage NSCLC. Outcomes of patients RadDx with NSCLC mirror the results of patients treated with BxPr disease.

Medically inoperable endometrial cancer in patients with a high body mass index (BMI): Patterns of failure after 3-D image-based high dose rate (HDR) brachytherapy

BACKGROUND AND PURPOSE High BMI is a reason for medical inoperability in patients with endometrial cancer in the United States. Definitive radiation is an alternative therapy for these patients; however, data on patterns of failure after definitive radiotherapy are lacking. We describe the patterns of failure after definitive treatment with 3-D image-based high dose rate (HDR) brachytherapy for medically inoperable endometrial cancer. MATERIALS AND METHODS Forty-three consecutive patients with endometrial cancer FIGO stages I-III were treated definitively with HDR brachytherapy with or without external beam radiation therapy. Cumulative incidence of failures was estimated and prognostic variables were identified RESULTS Mean follow up was 29.7 months. Median BMI was 50.2 kg/m(2) (range: 25.1-104 kg/m(2)). The two-year overall survival was 65.2%. The two-year cumulative incidence of pelvic and distant failures was 8.3% and 13.5%, respectively. Grade 3 disease was associated with a higher risk of all-failures (Hazard Ratio [HR]: 4.67, 95% CI: 1.04-20.9, p=0.044). The incidence of acute Grade 3 GI/GU toxicities was 4.6%. CONCLUSIONS Pelvic failure at two years was less than 10%. Patients with grade 3 disease were more likely to experience disease failure and may warrant closer follow up.

Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents

Purpose Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary endpoint was distant intracranial failure after SRS, which was defined as any new MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using the Kaplan Meier method and Cox proportional hazards. Results A total of 72 patients with melanoma with 233 MBMs were treated between April 2006 and April 2016. The number of MBMs within each treatment group was as follows: SRS: 121; SRS + IMT: 48; and SRS + targeted therapy: 64. The median follow-up was 8.9 months. One-year distant intracranial control rates for SRS, SRS + IMT, and SRS + targeted therapy were 11.5%, 60%, and 10%, respectively (P < .001). On multivariate analysis, after adjusting for steroid use and number of MBMs, SRS + IMT remained associated with a significant reduction in distant intracranial failure compared with SRS (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.80; P = .003) and compared with SRS + targeted therapy (HR, 0.41; 95% CI, 0.25-0.68; P = .001).One-year local control for SRS, SRS + IMT, and SRS + targeted therapy was 66%, 85%, and 72%, respectively (P = .044). On multivariate analysis, after adjusting for dose, SRS + IMT remained associated with a significant reduction in local failure compared with SRS alone (HR, 0.37; 95% CI, 0.14-0.95; P = .04). Conclusions SRS with immunotherapy is associated with decreased distant and local intracranial failure compared with SRS alone. Prospective studies are warranted to validate this result.

OC-0277: Brachytherapy improves survival for inoperable stage I endometrial adenocarcinoma: a population-based analysis

Purpose/Objective: To compare the maximum target dimensions and image quality between magnetic resonance imaging (MRI), transrectal ultrasound (TRUS) and computed tomography (CT) in image guided adaptive brachytherapy (IGABT) of locally advanced cervical cancer Materials and Methods: All patients with locally advanced cervical cancer treated with radiochemotherapy and IGABT between 09/2012-05/2013 were included in this study. T2weighted MRI (1.5 tesla), TRUS and CT were performed before (MRIpreBT, TRUSpreBT) and / or after (MRIBT, TRUSBT and CTBT) insertion of the applicator. 3D TRUS image acquisition was done with a customized US stepper device and software. The target was defined on 3D image sequences acquired with different imaging modalities by one blinded observer, in accordance to the GEC-ESTRO recommendations for MRIbased target volume delineation, as the complete cervical mass including the tumour, any suspicious areas of parametrial involvement and the normal cervical stroma. Maximum target width and thickness were measured on transversal planes. Image quality was classified using the following scoring system: Grade 0: not depicted, Grade 1: inability to discriminate, margin not recognizable, Grade 2: fair discrimination, margin indistinct, Grade 3: excellent discrimination, margin distinct. Descriptive statistics, mean differences between the groups, with MRIBT as reference, and a paired t-test were calculated. Results: Images from 21 patients (FIGO IB: 3, IIB: 11, IIIB: 5, IVB: 2) were available for analysis. The mean difference in maximum target width of TRUSBT, TRUSpreBT, MRIpreBT, CTBT to MRIBT was 0.5mm ±5.5 (n.s.), -1.7mm ±5.7 (n.s.), 0.0mm ±5.7 (n.s.) and 12.9mm ±6.1 (p < 0.001) (figure 1). The mean difference in maximum target thickness of TRUSBT, TRUSpreBT, MRIpreBT, CTBT to MRIBT was -3.5mm ±5.5 (p=0.012), -7.6mm ±4.3 (p <0.001), 0.5mm ±6.4 (n.s.) and 11.8mm ±6.3 (p < 0.001). Mean scores of image quality of the target volume was 2.9 for TRUSpreBT, 2.3 for TRUSBT, 2.9 for MRIpreBT, 2.7 for MRIBT and 2.1 for CTBT.

Distance to nearest radiation facility and treatment choice in early stage breast cancer.

73 Background: Breast conserving surgery followed by breast radiation (RT), collectively termed breast conserving therapy (BCT), is a recommended alternative to mastectomy (MT) for early stage breast cancer. Limited access to RT may result in more extensive surgical treatment. The purpose of this study is to assess the association between distance to nearest RT facility and MT use in a modern cohort of BCT eligible women. METHODS Women with Stage 0 - II breast cancer eligible for BCT diagnosed from 2004 - 2010 were identified from a US state registry. Distance from patient census tract to nearest RT facility census tract was calculated. Multivariate logistic regression was used to identify explanatory variables that significantly influenced MT use, adjusting for age, poverty, insurance, race, Hispanic ethnicity, marital status, diagnosis year, distance to nearest RT facility, T stage, N stage, ER/PR status and grade. RESULTS Of the 24,994 eligible women, 25.4% (n = 6,346) underwent MT and 74.6% (n = 18,648) underwent a breast conserving surgery. 32% of patients lived in a census tract that was > 5 miles from a RT facility. MT use increased with increasing distance to RT facility (24.5% at ≤ 5 miles, 26.5% at > 5 to < 15 miles, 29.5% at 15 to < 40 miles and 43% at ≥ 40 miles, p < 0.001). The likelihood of MT was independently associated with increasing distance to RT facility (Odds Ratio [OR]: 1.02 for every mile increase, 95% Confidence Interval [CI]: 1.01 - 1.02, p < 0.001). Compared to patients living ≤ 5 miles away from a RT facility, patients living 15 - < 40 miles away were 1.3 times more likely to be treated with MT (OR: 1.31, 95% CI: 1.15 - 1.51, p < 0.001), and those living ≥ 40 miles away were more than twice as likely to be treated with MT (OR: 2.29, 95% CI: 1.51 - 3.45, p < 0.001). When restricting the sample to women with T1 disease (n = 16,656), distance to RT facility remained a significant explanatory variable for MT use on multivariate analysis (p < 0.001). CONCLUSIONS MT use in a modern cohort of women eligible for BCT is independently associated with increasing distance to RT facility. Measures to improve RT access should be explored to ensure universal opportunity for BCT.