Anupama Chundury

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.

Intensity modulated radiation therapy for recurrent ovarian cancer refractory to chemotherapy

OBJECTIVE To evaluate local control, survival outcomes, and toxicity after intensity modulated radiotherapy (IMRT) for recurrent chemorefractory ovarian cancer. METHODS Between 2006 and 2014, 33 patients were treated with IMRT for recurrent ovarian cancer. Patients received a median of 3 chemotherapy regimens prior to IMRT (range, 1-12) with 11 (33%) undergoing concurrent therapy. Local control (LC), recurrence free survival (RFS), and overall survival (OS) were calculated via Kaplan-Meier method. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Impact of patient characteristics on outcomes was evaluated via Coxs proportional hazard model. RESULTS Median follow up was 23.7 months. Forty-nine sites were treated to a median dose of 5040cGy (range, 4500-7000). Nine (18%) of the 49 sites had in-field failures. Two year actuarial LC, RFS, and OS were 82%, 11%, and 63%, respectively. Seventeen patients had both a pre and post-treatment FDG-PET/CT; 6 (35%) had a complete metabolic response while 11 (65%) had a partial metabolic response. Acute ≥ grade 3 gastrointestinal (GI) toxicities occurred in 2 (6%) patients, late ≥ grade 3 GI toxicities occurred in 12 (36%), acute ≥ grade 3 hematological toxicities occurred in 5 (15%) and late ≥ grade 3 hematological toxicities occurred in 14 (42%). CONCLUSIONS IMRT for recurrent chemorefractory ovarian cancer is associated with excellent local control and limited radiation related toxicity. Future studies will be required to determine which subpopulation will benefit most from IMRT and whether alternative techniques such as stereotactic body radiotherapy may be feasible.

Intensity modulated radiation therapy for squamous cell carcinoma of the vulva: Treatment technique and outcomes

Objective The objective of this study was to present the treatment technique and evaluate clinical outcomes after intensity modulated radiation therapy (IMRT) for vulvar cancer. Methods and materials This retrospective study included 39 patients with squamous cell carcinoma of the vulva treated with IMRT from 2005 to 2015. There were 21 patients treated with postoperative IMRT, 13 with definitive IMRT, and 5 with preoperative IMRT. Tumor staging was Federation of Gynecology and Obstetrics stage I in 6, stage II in 7, stage III in 19, and stage IV in 7 patients. Concurrent chemotherapy was administered to 14 patients. Brachytherapy was delivered in 8 patients. Results The median follow-up was 34 months (range, 3.3-71). Median IMRT dose to patients receiving pre- or postoperative IMRT was 5040 cGy (range, 5040-6080). Median combined IMRT and brachytherapy dose to gross tumor was 7000 cGy (range, 5040-7520) in those treated with definitive RT. The 3-year locoregional control (LRC) and overall survival for those receiving postoperative RT were 89% and 67%, respectively. The 3-year LRC and overall survival for those receiving definitive IMRT were 42% and 49%, respectively. In patients receiving definitive or neoadjuvant IMRT, 69% had complete clinical response and 44% had complete pathologic response. The actuarial 3-year inguinal recurrence rate was 7%. There were no acute grade 3-4 hematological, gastrointestinal, or genitourinary toxicities. There were no late grade 3-4 gastrointestinal or genitourinary toxicities. Conclusions IMRT for vulvar cancer is associated with high rates of LRC in the postoperative setting and limited radiation-related toxicity. Durable LRC of disease after definitive IMRT remains challenging, and several refinements to our treatment technique are suggested.

Association of post-treatment positron emission tomography with locoregional control and survival after radiation therapy for squamous cell carcinoma of the vulva.

BACKGROUND/PURPOSE The aim of this study was to investigate the use of post-treatment F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for vulvar cancer and compare metabolic response to clinical outcomes. MATERIALS/METHODS This retrospective study included 21 patients with vulvar squamous cell carcinoma treated with curative-intent radiation between 2007 and 2015. All patients received intensity-modulated radiation treatment (IMRT), a pre-treatment FDG/PET-CT, and a post-treatment FDG-PET/CT performed at a median time of 3months post-IMRT. RESULTS Median follow-up time was 28months. Post-treatment FDG-PET/CT demonstrated no evidence of disease (NED) in 12 patients and residual or progressive disease (PD) in 9. FDG-PET/CT response significantly correlated with biopsy-proven locoregional failure (p=0.02) and was the only significant factor associated with overall survival (OS) (p=0.049). Patients with NED on FDG-PET had a 2-year locoregional control (LRC) of 89% versus 25% for those with PD (p<0.01). Patients with NED on FDG-PET/CT had a 2-year OS of 100% versus 42% for those with PD (p=0.02). FDG-PET/CT evaluation had a sensitivity of 100% and a specificity of 71% for detecting pathologically proven residual disease in patients receiving neoadjuvant or definitive radiation. CONCLUSION In this single-institution study of women with vulvar cancer, post-treatment response on FDG-PET/CT was associated with LRC and OS.

Clinical outcomes and differential effects of PI3K pathway mutation in obese versus non-obese patients with cervical cancer

The purpose of this study was to evaluate the effect of obesity and obesity-associated factors on the outcomes of patients with cervical cancer. Outcomes were evaluated in 591 patients with FIGO Ib to IV cervical cancer treated uniformly with definitive radiation. Patients were stratified into 3 groups based upon pretreatment Body Mass Index (BMI): A ≤ 18.5; B 18.6 – 34.9; and C ≥ 35. The 5-year freedom from failure rates were 58, 59, and 73% for BMI groups A, B, and C (p = 0.01). Overall survival rates were 50, 59, and 68%, respectively (p = 0.02). High expression of phosphorylated AKT (pAKT) was associated with poor outcomes only in non-obese patients. Obese patients with PI3K pathway mutant tumors had a trend toward favorable outcomes, while a similar effect was not observed in non-obese patients. Compared to similar tumors from non-obese hosts, PIK3CA and PTEN mutant tumors from obese patients failed to express high levels of phosphorylated AKT and its downstream targets. These results show that patients with obesity at the time of diagnosis of cervical cancer exhibit improved outcomes after radiation. PI3K/AKT pathway mutations are common in obese patients, but are not associated with activation of AKT signaling.

Magnetic resonance image guided radiation therapy for primary splenic diffuse large B-cell lymphoma: A teaching case.

Malignant neoplasms of the spleen are rare and most commonly non-Hodgkin lymphomas.1 The most frequent primary non-Hodgkin lymphoma of the spleen is a marginal zone lymphoma, which accounts for approximately 80% of cases, whereas primary splenic diffuse largeB-cell lymphoma (PS-DLBCL) is much more rare.2 Given the paucity of data regarding PS-DLBCL, optimal workup and management strategies are not well defined.2 Extrapolated from the standard of care from other extranodal sites of DLBCL, patients with limited-stage PS-DLBCL can be treated with combined modality therapy consisting of systemic chemotherapy with rituximab followed by involved site radiation therapy.3 The safety and efficacy of involved-site radiation therapy is heavily dependent on accurate image guidance that is most commonly accomplished using on-board cone beam computed tomography (CBCT). However, treatment of splenic tumors poses a significant challenge for CBCTguided RT because of its significant respiratory motion and poor soft-tissue resolution. We describe, to the best of our knowledge, the first reported case of a patient treated with

Adaptive anatomical preservation optimal denoising for radiation therapy daily MRI

Abstract. Low-field magnetic resonance imaging (MRI) has recently been integrated with radiation therapy systems to provide image guidance for daily cancer radiation treatments. The main benefit of the low-field strength is minimal electron return effects. The main disadvantage of low-field strength is increased image noise compared to diagnostic MRIs conducted at 1.5 T or higher. The increased image noise affects both the discernibility of soft tissues and the accuracy of further image processing tasks for both clinical and research applications, such as tumor tracking, feature analysis, image segmentation, and image registration. An innovative method, adaptive anatomical preservation optimal denoising (AAPOD), was developed for optimal image denoising, i.e., to maximally reduce noise while preserving the tissue boundaries. AAPOD employs a series of adaptive nonlocal mean (ANLM) denoising trials with increasing denoising filter strength (i.e., the block similarity filtering parameter in the ANLM algorithm), and then detects the tissue boundary losses on the differences of sequentially denoised images using a zero-crossing edge detection method. The optimal denoising filter strength per voxel is determined by identifying the denoising filter strength value at which boundary losses start to appear around the voxel. The final denoising result is generated by applying the ANLM denoising method with the optimal per-voxel denoising filter strengths. The experimental results demonstrated that AAPOD was capable of reducing noise adaptively and optimally while avoiding tissue boundary losses. AAPOD is useful for improving the quality of MRIs with low-contrast-to-noise ratios and could be applied to other medical imaging modalities, e.g., computed tomography.

Multiparametric MRI and [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging Is a Potential Prognostic Imaging Biomarker in Recurrent Glioblastoma

Purpose/objectives Multiparametric advanced MR and [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging may be important biomarkers for prognosis as well for distinguishing recurrent glioblastoma multiforme (GBM) from treatment-related changes. Methods/materials We retrospectively evaluated 30 patients treated with chemoradiation for GBM and underwent advanced MR and FDG-PET for confirmation of tumor progression. Multiparametric MRI and FDG-PET imaging metrics were evaluated for their association with 6-month overall (OS) and progression-free survival (PFS) based on pathological, radiographic, and clinical criteria. Results 17 males and 13 females were treated between 2001 and 2014, and later underwent FDG-PET at suspected recurrence. Baseline FDG-PET and MRI imaging was obtained at a median of 7.5 months [interquartile range (IQR) 3.7–12.4] following completion of chemoradiation. Median follow-up after FDG-PET imaging was 10 months (IQR 7.2–13.0). Receiver-operator characteristic curve analysis identified that lesions characterized by a ratio of the SUVmax to the normal contralateral brain (SUVmax/NB index) >1.5 and mean apparent diffusion coefficient (ADC) value of ≤1,400 × 10−6 mm2/s correlated with worse 6-month OS and PFS. We defined three patient groups that predicted the probability of tumor progression: SUVmax/NB index >1.5 and ADC ≤1,400 × 10−6 mm2/s defined high-risk patients (n = 7), SUVmax/NB index ≤1.5 and ADC >1,400 × 10−6 mm2/s defined low-risk patients (n = 11), and intermediate-risk (n = 12) defined the remainder of the patients. Median OS following the time of the FDG-PET scan for the low, intermediate, and high-risk groups were 23.5, 10.5, and 3.8 months (p < 0.01). Median PFS were 10.0, 4.4, and 1.9 months (p = 0.03). Rates of progression at 6-months in the low, intermediate, and high-risk groups were 36, 67, and 86% (p = 0.04). Conclusion Recurrent GBM in the molecular era is associated with highly variable outcomes. Multiparametric MR and FDG-PET biomarkers may provide a clinically relevant, non-invasive and cost-effective method of predicting prognosis and improving clinical decision making in the treatment of patients with suspected tumor recurrence.

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-C-207B-02: Maximal Noise Reduction Filter with Anatomical Structures Preservation

PURPOSE All medical images contain noise, which can result in an undesirable appearance and can reduce the visibility of anatomical details. There are varieties of techniques utilized to reduce noise such as increasing the image acquisition time and using post-processing noise reduction algorithms. However, these techniques are increasing the imaging time and cost or reducing tissue contrast and effective spatial resolution which are useful diagnosis information. The three main focuses in this study are: 1) to develop a novel approach that can adaptively and maximally reduce noise while preserving valuable details of anatomical structures, 2) to evaluate the effectiveness of available noise reduction algorithms in comparison to the proposed algorithm, and 3) to demonstrate that the proposed noise reduction approach can be used clinically. METHODS To achieve a maximal noise reduction without destroying the anatomical details, the proposed approach automatically estimated the local image noise strength levels and detected the anatomical structures, i.e. tissue boundaries. Such information was used to adaptively adjust strength of the noise reduction filter. The proposed algorithm was tested on 34 repeating swine head datasets and 54 patients MRI and CT images. The performance was quantitatively evaluated by image quality metrics and manually validated for clinical usages by two radiation oncologists and one radiologist. RESULTS Qualitative measurements on repeated swine head images demonstrated that the proposed algorithm efficiently removed noise while preserving the structures and tissues boundaries. In comparisons, the proposed algorithm obtained competitive noise reduction performance and outperformed other filters in preserving anatomical structures. Assessments from the manual validation indicate that the proposed noise reduction algorithm is quite adequate for some clinical usages. CONCLUSION According to both clinical evaluation (human expert ranking) and qualitative assessment, the proposed approach has superior noise reduction and anatomical structures preservation capabilities over existing noise removal methods. Senior Author Dr. Deshan Yang received research funding form ViewRay and Varian.