M.A. Thomas

Changes in Cervical Cancer FDG Uptake During Chemoradiation and Association With Response

PURPOSE Previous research showed that pretreatment uptake of F-18 fluorodeoxyglucose (FDG), as assessed by the maximal standardized uptake value (SUVmax) and the variability of uptake (FDGhetero), predicted for posttreatment response in cervical cancer. In this pilot study, we evaluated the changes in SUVmax and FDGhetero during concurrent chemoradiation for cervical cancer and their association with post-treatment response. METHODS AND MATERIALS Twenty-five patients with stage Ib1-IVa cervical cancer were enrolled. SUVmax, FDGhetero, and metabolic tumor volume (MTV) were recorded from FDG-positron emission tomography (PET)/computed tomography (CT) scans performed pretreatment and during weeks 2 and 4 of treatment and were evaluated for changes and association with response assessed on 3-month post-treatment FDG-PET/CT. RESULTS For all patients, the average pretreatment SUVmax was 17.8, MTV was 55.4 cm3, and FDGhetero was -1.33. A similar decline in SUVmax was seen at week 2 compared with baseline and week 4 compared with week 2 (34%). The areas of highest FDG uptake in the tumor remained relatively consistent on serial scans. Mean FDGhetero decreased during treatment. For all patients, MTV decreased more from week 2 to week 4 than from pretreatment to week 2. By week 4, the average SUVmax had decreased by 57% and the MTV had decreased by 30%. Five patients showed persistent or new disease on 3-month post-treatment PET. These poor responders showed a higher average SUVmax, larger MTV, and greater heterogeneity at all 3 times. Week 4 SUVmax (P=.037), week 4 FDGhetero (P=.005), pretreatment MTV (P=.008), and pretreatment FDGhetero (P=.008) were all significantly associated with post-treatment PET response. CONCLUSIONS SUVmax shows a consistent rate of decline during treatment and declines at a faster rate than MTV regresses. Based on this pilot study, pretreatment and week 4 of treatment represent the best time points for prediction of response.

Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound

BACKGROUND Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era in which tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesized that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. STUDY DESIGN Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (arm 1) vs SLNB (arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. RESULTS Sixty-eight subjects were enrolled in the pilot phase of the trial (34 subjects in arm 1, no further staging; 32 subjects in arm 2, SLNB; and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40 to 80 years) in arm 1 and 59 years (range 31 to 81 years) in arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1 to 32 months). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (>2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. CONCLUSIONS Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial.

Managing breast cancer in younger women: challenges and solutions

Breast cancer in young women is relatively rare compared to breast cancer occurring in older women. Younger women diagnosed with breast cancer also tend to have a more aggressive biology and consequently a poorer prognosis than older women. In addition, they face unique challenges such as diminished fertility from premature ovarian failure, extended survivorship periods and its attendant problems, and the psychosocial impact of diagnosis, while still raising families. It is therefore imperative to recognize the unique issues that younger women face, and plan management in a multidisciplinary fashion to optimize clinical outcomes. This paper discusses the challenges of breast cancer management for young women, as well as specific issues to consider in diagnosis, treatment, and follow-up of such patients.

Lymphovascular space invasion and lack of downstaging after neoadjuvant chemotherapy are strong predictors of adverse outcome in young women with locally advanced breast cancer

Younger age diagnosis of breast cancer is a predictor of adverse outcome. Here, we evaluate prognostic factors in young women with locally advanced breast cancer (LABC). We present a retrospective review of 104 patients younger than 40 years with LABC treated with surgery, radiotherapy (RT), and chemotherapy from 2003 to 2014. Patient‐, tumor‐, and treatment‐related factors important for overall survival (OS), local/regional recurrence (LRR), distant metastasis (DM), and recurrence‐free survival (RFS) were evaluated. Mean age at diagnosis was 34 years (23–39 years) with a median follow‐up of 47 months (8–138 months). Breast‐conserving surgery was performed in 27%. Axillary lymph node dissection was performed in 85%. Sixty percent of patients received neoadjuvant chemotherapy with 19% achieving pathologic complete response (pCR), and 61% downstaged. Lymph node positivity was present in 91% and lymphovascular space invasion (LVSI) in 35%. Thirty‐two percent of patients had triple negative tumors (TN, ER‐/PR‐/HER2 nonamplified). Four‐year OS and RFS was 84% and 71%, respectively. Factors associated with worse OS on multivariate analysis include TN status, LVSI, and number of positive lymph nodes. LVSI was also associated with DM and LRR, as well as worse RFS. Downstaging was associated with improved 4 year RFS in patients receiving neoadjuvant chemotherapy (74% vs. 38%, P = 0.002). With high risks of recurrence and inferior OS compared to older women, breast cancer in young women can be difficult to treat. Among additional factors, presence of LVSI and lack of downstaging portends a particularly worse prognosis.

Long-term outcomes of APBI via multicatheter interstitial HDR brachytherapy: Results of a prospective single-institutional registry

PURPOSE Long-term outcome reports of accelerated partial-breast irradiation (APBI) are limited. Here, we report the 10-year outcomes of APBI delivered using multicatheter interstitial implant (ISI) brachytherapy. METHODS AND MATERIALS Patients with early-stage breast cancer treated with APBI via ISI brachytherapy were enrolled in a prospective registry. Selection criteria included age ≥40 years, ductal carcinoma in situ or invasive tumor ≤3 cm, negative margins (≥2 mm), and negative axillary nodes. 34 Gy in 10 twice-daily fractions was administered to 2 cm of breast tissue surrounding the surgical bed. Toxicity and cosmetic outcomes were collected prospectively. RESULTS A total of 175 patients were included. The median followup time was 10.0 years. Ten-year ipsilateral breast tumor control, regional control, freedom from distant metastasis, breast cancer-specific survival, and overall survival were 92.1%, 96.9%, 97.4%, 97.1%, and 81.2%, respectively. High-grade disease was correlated with increase in the rate of ipsilateral breast tumor recurrence. Grade 1 or 2 skin toxicity was present in 44 patients, and Grade 3 skin toxicity was present in only 1 patient. There were no Grade 4 or higher toxicities observed. Thirty-seven patients developed fat necrosis. Dose Homogeneity Index of ≤0.85 and integrated reference air-kerma of >3400 cGycm2/h correlated with higher rates of fat necrosis. There were 115 (66%), 51 (29%), 8 (5%), and 0 (0%) patients having excellent, good, fair, and poor cosmetic outcomes, respectively. CONCLUSIONS APBI using ISI brachytherapy offers excellent clinical outcomes in appropriately selected patients with excellent cosmetic outcomes and low rates of toxicities such as symptomatic fat necrosis.

SU-F-303-11: Implementation and Applications of Rapid, SIFT-Based Cine MR Image Binning and Region Tracking

Purpose: To develop a novel and rapid, SIFT-based algorithm for assessing feature motion on cine MR images acquired during MRI-guided radiotherapy treatments. In particular, we apply SIFT descriptors toward both partitioning cine images into respiratory states and tracking regions across frames. Methods: Among a training set of images acquired during a fraction, we densely assign SIFT descriptors to pixels within the images. We cluster these descriptors across all frames in order to produce a dictionary of trackable features. Associating the best-matching descriptors at every frame among the training images to these features, we construct motion traces for the features. We use these traces to define respiratory bins for sorting images in order to facilitate robust pixel-by-pixel tracking. Instead of applying conventional methods for identifying pixel correspondences across frames we utilize a recently-developed algorithm that derives correspondences via a matching objective for SIFT descriptors. Results: We apply these methods to a collection of lung, abdominal, and breast patients. We evaluate the procedure for respiratory binning using target sites exhibiting high-amplitude motion among 20 lung and abdominal patients. In particular, we investigate whether these methods yield minimal variation between images within a bin by perturbing the resulting image distributions among bins. Moreover, we compare the motion between averaged images across respiratory states to 4DCT data for these patients. We evaluate the algorithm for obtaining pixel correspondences between frames by tracking contours among a set of breast patients. As an initial case, we track easily-identifiable edges of lumpectomy cavities that show minimal motion over treatment. Conclusions: These SIFT-based methods reliably extract motion information from cine MR images acquired during patient treatments. While we performed our analysis retrospectively, the algorithm lends itself to prospective motion assessment. Applications of these methods include motion assessment, identifying treatment windows for gating, and determining optimal margins for treatment.

A deep Boltzmann machine-driven level set method for heart motion tracking using cine MRI images

HighlightsThe DBM needs small‐sized data set to train, but imposes strong modeling ability.A three‐layer DBM can capture both local and global properties of heart contours.An efficient layer‐wise block‐Gibbs sampling is used to infer heart shape priors.The DBM‐induced heart shape priors are used as constraints of DRLSE evolution. Graphical abstract Figure. No caption available. ABSTRACT Heart motion tracking for radiation therapy treatment planning can result in effective motion management strategies to minimize radiation‐induced cardiotoxicity. However, automatic heart motion tracking is challenging due to factors that include the complex spatial relationship between the heart and its neighboring structures, dynamic changes in heart shape, and limited image contrast, resolution, and volume coverage. In this study, we developed and evaluated a deep generative shape model‐driven level set method to address these challenges. The proposed heart motion tracking method makes use of a heart shape model that characterizes the statistical variations in heart shapes present in a training data set. This heart shape model was established by training a three‐layered deep Boltzmann machine (DBM) in order to characterize both local and global heart shape variations. During the tracking phase, a distance regularized level‐set evolution (DRLSE) method was applied to delineate the heart contour on each frame of a cine MRI image sequence. The trained shape model was embedded into the DRLSE method as a shape prior term to constrain an evolutional shape to reach the desired heart boundary. Frame‐by‐frame heart motion tracking was achieved by iteratively mapping the obtained heart contour for each frame to the next frame as a reliable initialization, and performing a level‐set evolution. The performance of the proposed motion tracking method was demonstrated using thirty‐eight coronal cine MRI image sequences.

Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A 4.5-Year Clinical Experience

AIMS Magnetic resonance image-guided radiotherapy (MRIgRT) has been clinically implemented since 2014. This technology offers improved soft-tissue visualisation, daily imaging, and intra-fraction real-time imaging without added radiation exposure, and the opportunity for adaptive radiotherapy (ART) to adjust for anatomical changes. Here we share the longest single-institution experience with MRIgRT, focusing on trends and changes in use over the past 4.5 years. MATERIALS AND METHODS We analysed clinical information, including patient demographics, treatment dates, disease sites, dose/fractionation, and clinical trial enrolment for all patients treated at our institution using MRIgRT on a commercially available, integrated 0.35 T MRI, tri-cobalt-60 device from 2014 to 2018. For each patient, factors including disease site, clinical rationale for MRIgRT use, use of ART, and proportion of fractions adapted were summated and compared between individual years of use (2014-2018) to identify shifts in institutional practice patterns. RESULTS Six hundred and forty-two patients were treated with 666 unique treatment courses using MRIgRT at our institution between 2014 and 2018. Breast cancer was the most common disease, with use of cine MRI gating being a particularly important indication, followed by abdominal sites, where the need for cine gating and use of ART drove MRIgRT use. One hundred and ninety patients were treated using ART in 1550 fractions, 67.6% (1050) of which were adapted. ART was primarily used in cancers of the abdomen. Over time, breast and gastrointestinal cancers became increasingly dominant for MRIgRT use, hypofractionated treatment courses became more popular, and gastrointestinal cancers became the principal focus of ART. DISCUSSION MRIgRT is widely applicable within the field of radiation oncology and new clinical uses continue to emerge. At our institution to date, applications such as ART for gastrointestinal cancers and accelerated partial breast irradiation (APBI) for breast cancer have become dominant indications, although this is likely to continue to evolve.

TU-AB-BRA-10: Treatment of Gastric MALT Lymphoma Utilizing a Magnetic Resonance Image-Guided Radiation Therapy (MR-IGRT) System: Evaluation of Gating Feasibility

PURPOSE To evaluate the feasibility of real-time, real-anatomy tracking and gating for gastric lymphoma patients treated with magnetic resonance image-guided radiation therapy (MR-IGRT) METHODS: Over the last 2 years, 8 patients with gastric lymphoma were treated with 0.3-T, Co-60 MR-IGRT. Post-treatment analysis of real-time cine imaging in the sagittal plane during each patients treatment revealed significant motion of the stomach. While this motion was accounted for with generous PTV margins, the systems capability for real-time, real-anatomy tracking could be used to reduce treatment margins by gating. However, analysis was needed for the feasibility of gating using only the single available sagittal imaging plane. While any plane may be chosen, if the stomach moves differently where it is not being observed, there may potentially be a mistreatment. To that end, imaging with healthy volunteers was done to ascertain stomach motion over 2-4 min by analyzing multiple parallel sagittal and coronal planes 0.75 cm apart. The stomach was contoured on every slice, and the mean displacement between pairs of contour centroids was used to determine the amount of overall motion. RESULTS The mean displacement of the centroid in the image plane was 4.3 ± 0.7 mm. The greatest observed motion was more medial with respect to the patient, and less motion laterally, which implies that gating on a plane located closer to MRI isocenter will provide the more conservative scenario as it will turn the radiation delivery off when the stomach is observed to move outside a predetermined boundary. CONCLUSION The stomach was observed to move relatively uniformly throughout, with maximum extent of motion closer to where most MRI systems have the best spatial integrity (near isocenter). Analysis of possible PTV margins from the healthy volunteer study (coupled with previous patient data on interfraction volumetric stomach deformation) is pending.

SU-F-BRA-14: Optimization of Dosimetric Guidelines for Accelerated Partial Breast Irradiation (APBI) Using the Strut-Adjusted Volume Implant (SAVI)

Purpose: Treatment planning guidelines for accelerated partial breast irradiation (ABPI) using the strut-adjusted volume implant (SAVI) are inconsistent between the manufacturer and NSABP B-39/RTOG 0413 protocol. Furthermore neither set of guidelines accounts for different applicator sizes. The purpose of this work is to establish guidelines specific to the SAVI that are based on clinically achievable dose distributions. Methods: Sixty-two consecutive patients were implanted with a SAVI and prescribed to receive 34 Gy in 10 fractions twice daily using high dose-rate (HDR) Ir-192 brachytherapy. The target (PTV_EVAL) was defined per NSABP. The treatments were planned and evaluated using a combination of dosimetric planning goals provided by the NSABP, the manufacturer, and our prior clinical experience. Parameters evaluated included maximum doses to skin and ribs, and volumes of PTV_EVAL receiving 90%, 95%, 100%, 150%, and 200% of the prescription (V90, etc). All target parameters were evaluated for correlation with device size using the Pearson correlation coefficient. Revised dosimetric guidelines for target coverage and heterogeneity were determined from this population. Results: Revised guidelines for minimum target coverage (ideal in parentheses): V90≥95%(97%), V95≥90%(95%), V100≥88%(91%). The only dosimetric parameters that were significantly correlated (p<0.05) with device size were V150 and V200. Heterogeneity criteria were revised for the 6–1 Mini/6-1 applicators to V150≤30cc and V200≤15cc, and unchanged for the other sizes. Re-evaluation of patient plans showed 90% (56/62) met the revised minimum guidelines and 76% (47/62) met the ideal guidelines. All and 56/62 patients met our institutional guidelines for maximum skin and rib dose, respectively. Conclusions: We have optimized dosimetric guidelines for the SAVI applicators, and found that implementation of these revised guidelines for SAVI treatment planning yielded target coverage exceeding that required by existing guidelines while preserving heterogeneity constraints and minimizing dose to organs at risk.