Benjamin W. Fischer-Valuck

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.

SIFT-based dense pixel tracking on 0.35 T cine-MR images acquired during image-guided radiation therapy with application to gating optimization

PURPOSE To first demonstrate the viability of applying an image processing technique for tracking regions on low-contrast cine-MR images acquired during image-guided radiation therapy, and then outline a scheme that uses tracking data for optimizing gating results in a patient-specific manner. METHODS A first-generation MR-IGRT system-treating patients since January 2014-integrates a 0.35 T MR scanner into an annular gantry consisting of three independent Co-60 sources. Obtaining adequate frame rates for capturing relevant patient motion across large fields-of-view currently requires coarse in-plane spatial resolution. This study initially (1) investigate the feasibility of rapidly tracking dense pixel correspondences across single, sagittal plane images (with both moderate signal-to-noise and spatial resolution) using a matching objective for highly descriptive vectors called scale-invariant feature transform (SIFT) descriptors associated to all pixels that describe intensity gradients in local regions around each pixel. To more accurately track features, (2) harmonic analysis was then applied to all pixel trajectories within a region-of-interest across a short training period. In particular, the procedure adjusts the motion of outlying trajectories whose relative spectral power within a frequency bandwidth consistent with respiration (or another form of periodic motion) does not exceed a threshold value that is manually specified following the training period. To evaluate the tracking reliability after applying this correction, conventional metrics-including Dice similarity coefficients (DSCs), mean tracking errors (MTEs), and Hausdorff distances (HD)-were used to compare target segmentations obtained via tracking to manually delineated segmentations. Upon confirming the viability of this descriptor-based procedure for reliably tracking features, the study (3) outlines a scheme for optimizing gating parameters-including relative target position and a tolerable margin about this position-derived from a probability density function that is constructed using tracking results obtained just prior to treatment. RESULTS The feasibility of applying the matching objective for SIFT descriptors toward pixel-by-pixel tracking on cine-MR acquisitions was first retrospectively demonstrated for 19 treatments (spanning various sites). Both with and without motion correction based on harmonic analysis, sub-pixel MTEs were obtained. A mean DSC value spanning all patients of 0.916 ± 0.001 was obtained without motion correction, with DSC values exceeding 0.85 for all patients considered. While most patients show accurate tracking without motion correction, harmonic analysis does yield substantial gain in accuracy (defined using HDs) for three particularly challenging subjects. An application of tracking toward a gating optimization procedure was then demonstrated that should allow a physician to balance beam-on time and tissue sparing in a patient-specific manner by tuning several intuitive parameters. CONCLUSIONS Tracking results show high fidelity in assessing intrafractional motion observed on cine-MR acquisitions. Incorporating harmonic analysis during a training period improves the robustness of the tracking for challenging targets. The concomitant gating optimization procedure should allow for physicians to quantitatively assess gating effectiveness quickly just prior to treatment in a patient-specific manner.

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.

Assessment of the treatment approach and survival outcomes in a modern cohort of patients with atypical teratoid rhabdoid tumors using the National Cancer Database

Atypical teratoid rhabdoid tumors (ATRTs) are rare brain tumors that occur primarily in children under the age of 3 years. This report evaluates the treatment approach and survival outcomes in a large cohort of patients treated in the United States.

Hydrogel spacer distribution within the perirectal space in patients undergoing radiotherapy for prostate cancer: Impact of spacer symmetry on rectal dose reduction and the clinical consequences of hydrogel infiltration into the rectal wall

PURPOSE Hydrogel prostate-rectum spacers, biomaterials placed between the prostate and rectum, continue to gain interest as a method to reduce or limit rectal dose during dose escalated prostate cancer radiation therapy. Because the spacer is initially injected into the perirectal space as a liquid, the final distribution can vary. The purpose of this study was to evaluate hydrogel spacer (SpaceOAR system) implantation and distribution from a recent prospective randomized control trial and correlate spacer symmetry with rectal dose reduction as well as rectal wall infiltration (RWI) to acute and late toxicity. METHODS AND MATERIALS T2-weighted magnetic resonance imaging sets of 149 patients enrolled in a prospective clinical trial who received transperineal spacer injection were assessed for hydrogel spacer midline symmetry and RWI using a semiqualitative scoring system. Symmetry was then correlated to rectal dose reduction using a Student t test (1-tailed, paired), whereas a Fisher exact test was used to correlate RWI with acute and late rectal toxicity. All patients had control treatment plans created before spacer injection. RESULTS Hydrogel spacer was symmetrically placed at midline for 71 (47.7%) patients at the prostate midgland as well as 1 cm superior and inferior to midgland. The remaining 78 (50.9%) patients had some level of asymmetry, with only 2 (1.3%) having far lateral distribution (ie, >2 cm) of hydrogel spacer. As the hydrogel spacer became more asymmetric, the level of rectal dose reduction relative to their control plans decreased. However, all but the most asymmetrical 1.3% had significant rectal dose reduction (P < .05). Rectal wall hydrogel spacer infiltration was seen in 9 (6.0%) patients. There was no correlation between RWI and procedure-related adverse events or acute/late rectal toxicity. CONCLUSIONS Significant reduction of rectal dose can still be achieved even in the setting of asymmetric hydrogel spacer placement. RWI does not correlate with patient complications.

The world’s first single-room proton therapy facility: Two-year experience

PURPOSE This is a review of our 2-year experience with the first single-gantry proton therapy (PT) system. METHODS AND MATERIALS All patients were consented to participate on an institutional review board-approved prospective patient registry between December 2013 and December 2015. PT was delivered in a single-room facility using a synchrocyclotron with proton beam energy of 250 MeV. The dataset was interrogated for demographics, diagnosis, treatment modality, and clinical trial involvement. Cases were classified as simple or complex based on fields used and immobilization. The volume of photon patients treated in our department was collected between January 2011 and December 2015 to evaluate the impact of PT on our photon patient volume. RESULTS A total of 278 patients were treated with PT, including 228 (82%) adults and 50 (18%) pediatric cases. PT patients traveled a mean distance of 83.3 miles compared with 47.4 miles for photon patients queried in 2015. Rationale for treatment included reirradiation (20%), involvement in prospective clinical trial (14%), and proximity to critical structures to maximally spare organs at risk (66%). Forty patients were enrolled on 5 adult and 3 pediatric prospective clinical trials. The most common histologies treated were glioma (27%) and non-small cell lung cancer (18%) in adults, and medulloblastoma (22%) and low-grade glioma (24%) in pediatric patients. Prostate cancer composed 6% of PT. Complex cases composed 45% of our volume. Our photon patient volume increased yearly between 2011 and 2015, with 2780 patients completing photon treatment in 2011 and 3385 patients in 2015. PT composed 4% of overall patients treated with external beam radiation. CONCLUSIONS The installation of our single-gantry proton facility has expanded the treatment options within our cancer center, helping to increase the number of patients we see. Patients travel from twice as far away to receive this treatment, many for typical PT indications such as pediatrics or to participate in prospective clinical trials.

An integrated model-driven method for in-treatment upper airway motion tracking using cine MRI in head and neck radiation therapy.

PURPOSE For the first time, MRI-guided radiation therapy systems can acquire cine images to dynamically monitor in-treatment internal organ motion. However, the complex head and neck (H&N) structures and low-contrast/resolution of on-board cine MRI images make automatic motion tracking a very challenging task. In this study, the authors proposed an integrated model-driven method to automatically track the in-treatment motion of the H&N upper airway, a complex and highly deformable region wherein internal motion often occurs in an either voluntary or involuntary manner, from cine MRI images for the analysis of H&N motion patterns. METHODS Considering the complex H&N structures and ensuring automatic and robust upper airway motion tracking, the authors firstly built a set of linked statistical shapes (including face, face-jaw, and face-jaw-palate) using principal component analysis from clinically approved contours delineated on a set of training data. The linked statistical shapes integrate explicit landmarks and implicit shape representation. Then, a hierarchical model-fitting algorithm was developed to align the linked shapes on the first image frame of a to-be-tracked cine sequence and to localize the upper airway region. Finally, a multifeature level set contour propagation scheme was performed to identify the upper airway shape change, frame-by-frame, on the entire image sequence. The multifeature fitting energy, including the information of intensity variations, edge saliency, curve geometry, and temporal shape continuity, was minimized to capture the details of moving airway boundaries. Sagittal cine MR image sequences acquired from three H&N cancer patients were utilized to demonstrate the performance of the proposed motion tracking method. RESULTS The tracking accuracy was validated by comparing the results to the average of two manual delineations in 50 randomly selected cine image frames from each patient. The resulting average dice similarity coefficient (93.28%  ±  1.46%) and margin error (0.49  ±  0.12 mm) showed good agreement between the automatic and manual results. The comparison with three other deformable model-based segmentation methods illustrated the superior shape tracking performance of the proposed method. Large interpatient variations of swallowing frequency, swallowing duration, and upper airway cross-sectional area were observed from the testing cine image sequences. CONCLUSIONS The proposed motion tracking method can provide accurate upper airway motion tracking results, and enable automatic and quantitative identification and analysis of in-treatment H&N upper airway motion. By integrating explicit and implicit linked-shape representations within a hierarchical model-fitting process, the proposed tracking method can process complex H&N structures and low-contrast/resolution cine MRI images. Future research will focus on the improvement of method reliability, patient motion pattern analysis for providing more information on patient-specific prediction of structure displacements, and motion effects on dosimetry for better H&N motion management in radiation therapy.

Treatment Patterns and Overall Survival Outcomes of Octogenarians with Muscle Invasive Cancer of the Bladder: An Analysis of the National Cancer Database

Purpose: Elderly patients with muscle invasive bladder cancer can pose a therapeutic dilemma, given multiple comorbidities which may preclude surgery. In this registry based analysis we investigated treatment patterns and survival outcomes in this group of patients. Materials and Methods: We queried the National Cancer Database for muscle invasive (cT2‐T4aN0M0) bladder cancer in patients 80 years old or older who were diagnosed from 2004 to 2013. Patients included in study underwent transurethral resection of bladder tumor followed by radical cystectomy, radical cystectomy plus chemotherapy, radiation therapy alone, chemotherapy alone, chemoradiation or no treatment. We performed Kaplan‐Meier, log rank and multivariate Cox proportional hazards regression and propensity score matching. Results: A total of 9,270 patients were identified with a median followup of 12.8 months. Median overall survival in patients treated with radical cystectomy alone was 23.2 months (95% CI 19.8–26.6), which was superior to that of chemotherapy alone or radiation therapy alone (p <0.0001). Those treated with chemoradiation had a median overall survival of 27.3 months (95% CI 25.0–29.7), which did not statistically differ from that of radical cystectomy alone (p = 0.39). Surgery plus chemotherapy showed the longest median overall survival of 34.5 months (95% CI 22.2–46.7, vs chemoradiation and radical cystectomy alone p <0.0001). On multivariate analysis and propensity score matching the best overall survival was seen in patients treated with surgery plus chemotherapy and there was no difference in overall survival between chemoradiation and radical cystectomy alone. Conclusions: In elderly patients with muscle invasive bladder cancer chemoradiation is an alternative definitive treatment strategy with survival equal to that of surgery alone and superior to that of chemotherapy alone or radiation therapy alone. If a patient was able to receive neoadjuvant or adjuvant chemotherapy with surgery, additional survival was observed in this nonrandomized study.

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.

Treatment Patterns and Survival Outcomes for Patients with Small Cell Carcinoma of the Bladder

BACKGROUND Small cell carcinoma of the bladder (SCCaB) is a rare tumor without a standard treatment algorithm. Treatment patterns and survival outcomes from the National Cancer Database (NCDB) may provide insight into optimal treatment strategies. OBJECTIVE To investigate the relationship between overall survival (OS) and treatment strategy. DESIGN, SETTING, AND PARTICIPANTS This was an observational study of treatment-naïve patients who received treatment from 2004 to 2013. Patients with cT1-4aN0M0 SCCaB were identified from the NCDB, a hospital-based tumor registry that captures >70% of incident cancer cases in the USA. INTERVENTION Treatment strategies included local therapy alone, chemotherapy (CT), radiation therapy (RT), chemoradiation therapy (CRT), radical cystectomy (RC), and RC plus chemotherapy (RC+C). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS OS was analyzed as a function of treatment modality adjusting for patient, demographic, and tumor-related factors. The Kaplan-Meier survival method, and the log-rank test and Cox regression were used for univariable and multivariable analyses. RESULTS AND LIMITATIONS We identified 856 patients with median follow-up of 18.3 mo. The median OS for the entire cohort was 20.7 mo (95% confidence interval [CI] 18.3-23.2) and estimated 3-yr and 5-yr OS were 37.5% and 28.2%, respectively. The most common treatment modality was CT (225 patients; 26.3%) followed by CRT (203 patients; 23.7%) and RC+C (201 patients; 23.5%). The median OS was 18.4 mo (95% CI 15.2-21.5) for CT, 34.1 mo (95% CI 22.5-45.8) for CRT, and 32.4 mo (95% CI 20.8-44.1) for RC+C. OS did not significantly differ between CRT and RC+C (p=0.42). On multivariable analysis, the best OS was associated with CRT (hazard ratio [HR] 0.41, 95% CI 0.32-0.53; p<0.0001) and RC+C (HR 0.45, 95% CI 0.34-0.59; p<0.0001). CONCLUSIONS RC+C and CRT are associated with better OS compared to monotherapy among patients with SCCaB. PATIENT SUMMARY Small cell carcinoma of the bladder is a rare and highly aggressive cancer. According to National Cancer Database data, radical cystectomy plus chemotherapy and chemoradiation therapy are associated with better overall survival compared to monotherapy.