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PURPOSE: To identify an optimal afterloading technique for high-dose-rate brachytherapy treat- ments in patients with medically inoperable uterine cancer. METHODS AND MATERIALS: Eighteen treatment plans were generated using point and volume-based techniques for three patients using a single, dual, and triple tandem. Dosimetric parameters of the target and critical structures were evaluated. RESULTS: Similar target coverage was achieved for each patient using volume-based planning; however, differences were evident when comparing point-based plans for the three applicators. In Patient 1, with a cylindrical uterus (8 cm by 4.5 cm), similar results were achieved with all three applicators (V95 (Single)590.6%, V95 (Dual) 5 90.6%, and V95 (Triple) 591.5%). In Patient 2, who had a more spherical uterus (5 cm by 5.4 cm), the dual tandem was inferior to the others (V95 565.9% vs. 83.7% with triple and 85.8% with single tandem). Analysis of isodose distribu- tions showed that the dual tandem failed to achieve adequate coverage of the central portion of the fundus. In Patient 3, who had a uterus (6 cm by 5.5 cm) in close proximity to the bladder (0.5 cm) and bowel, both the triple and dual tandem point-based plans achieved better coverage than the single tandem, given dose constraints on the bladder and bowel, with uterus V95 of 83.4% (Triple), 84.9% (Dual), and 73.7% (Single), respectively. CONCLUSIONS: For inoperable uterine cancer, optimal high-dose-rate applicator selection depends on the anatomy and location of the uterus and critical organs. The triple tandem applicator provides greater latitude in dose and anatomic uterus coverage as compared with either single or dual tandem applicators. 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Purpose: To date, lung CT-ventilation imaging has been based on quantification of local breathing-induced changes in Hounsfield Units (HU) or volume. This work investigates the use of a stress map resulting from a biomechanical deformable image registration (DIR) algorithm as a metric of the ventilation function. Method: Eight lung cancer patients presenting different kinds of ventilation defects were retrospectively analyzed. Additionally, to the 4DCT acquired for radiotherapy planning, five of them had PET and three had SPECT imaging following inhalation of Ga-68 and Tc-99m, respectively. For each patient, the inhale phase of the 4DCT was registered to the exhale phase using Morfeus, a biomechanical DIR algorithm based on the determination of boundary conditions on the lung surfaces and vessel tree. To take into account the heterogeneity of the tissue stiffness in the stress map estimation, each tetrahedral element of the finite-element model was assigned a Young's modulus ranging from 60kPa to 12MPa, as a function of the HU in the inhale CT. The node displacements and element stresses resulting from the numerical simulation were used to generate three CT-ventilation maps based on: (i) volume changes (Jacobian determinant), (ii) changes in HU, (iii) the maximum principal stress. The voxel-wise correlation between each CT-ventilation map and the PET or SPECT V image was computed in a lung mask. Results: For patients with PET, the mean (min-max) Spearman correlation coefficients r were: 0.33 (0.19–0.45), 0.36 (0.16–0.51) and 0.42 (0.21–0.59) considering the Jacobian, changes in HU and maximum principal stress, respectively. For patients with SPECT V, the mean r were: 0.12 (−0.12–0.43), 0.29 (0.22–0.45) and 0.33 (0.25–0.39). Conclusion: The maximum principal stress maps showed a stronger correlation with the ventilation images than the previously proposed Jacobian or change in HU maps. This metric thus appears promising for CT-ventilation imaging. This work was funded in part by NIH P01CA059827.

Purpose: To develop a method for generating female pelvic synthetic CT (MRCT) images from a single MR scan and evaluate its utility in radiotherapy. Methods: Under IRB-approval, an imaging sequence (T1_VIBE_Dixon) was acquired for 10 patients. This sequence yields 3 useful image volumes of different contrast (“in-phase” T1-weighted, fat and water). A previously published pelvic bone shape model was used to generate a rough bone mask for each patient. A modified fuzzy c-means classification was performed on the multi spectral MR data, with a regularization term that utilizes the prior knowledge provided by the bone mask and addresses the intensity overlap between different tissue types. A weighted sum of classification probabilities with attenuation values yielded MRCT volumes. The mean absolute error (MAE) between MRCT and real CT on various regions was calculated following deformable alignment (Velocity). Intensity modulated Treatment plans based on actual CT and MRCT were made and compared. Results: The average/standard deviation of MAE across 10 patients was 10.1/6.7 HU for muscle, 6.7/4.6 HU for fat, 136.9/53.5 HU for bony tissues under 850 HU (97% of total bone volume), 188.9/119.3 HU for bony tissues above 850 HU and 17.3/13.3 HU for intrapelvic soft tissues. Calculated doses were comparable for plans generated on CT and calculated using MRCT densities or vice versa, with differences in PTV D99% (mean/σ) of (–0.1/0.2 Gy) and (0.3/0.2 Gy), PTV D0.5cc of (–0.3/0.2 Gy) and (–0.4/1.7 Gy). OAR differences were similarly small for comparable structures, with differences in bowel V50Gy of (–0.3/0.2%) and (0.0/0.2%), femur V30Gy of (0.7/1.2%) and (0.2/1.2%), sacrum V20GY of (0.0/0.1%) and (–0.1/1.1%) and mean pelvic V20Gy of (0.0/0.1%) and (0.6/1.8%). Conclusion: MRCT based on a single imaging sequence in the female pelvis is feasible, with acceptably small variations in attenuation estimates and calculated doses to target and critical organs. Work supported by NIHR01EB016079

6071Background: We designed a single arm phase II trial to determine the efficacy and toxicity of concurrent cetuximab (C) radiotherapy (RT) in patients non-eligible for standard chemotherapy. Non-...

Patients facing head and neck cancer treatment are profoundly vulnerable to physiologic and functional disability. Exercise and nutrition have been shown to have many benefits in cancer patients, but much of this work has been performed in groups of breast, colon, and prostate cancer patients. Limited data exists regarding the role of exercise and nutrition in the management of head and neck cancer patients given their unique set of challenges relating to the cancer as well as its treatment. In this paper, we review the existing literature about general or recreational physical exercise as well as nutrition in this patient population as it pertains to lean muscle body composition, functional well-being, and overall quality of life.

The epidermal growth factor receptor (EGFR) has been targeted for inhibition using tyrosine kinase inhibitors and monoclonal antibodies, with improvement in outcome in subsets of patients with head and neck, lung, and colorectal carcinomas. We have previously found that EGFR stability plays a key role in cell survival after chemotherapy and radiotherapy. Heat shock protein 90 (HSP90) is known to stabilize mutant EGFR and ErbB2, but its role in cancers with wild-type (WT) WT-EGFR is unclear. In this report, we demonstrate that fully mature, membrane-bound WT-EGFR interacts with HSP90 independent of ErbB2. Further, the HSP90 inhibitors geldanamycin (GA) and AT13387 cause a decrease in WT-EGFR in cultured head and neck cancer cells. This decrease results from a significantly reduced half-life of WT-EGFR. WT-EGFR was also lost in head and neck xenograft specimens after treatment with AT13387 under conditions that inhibited tumor growth and prolonged survival of the mice. Our findings demonstrate that WT-EGFR is a client protein of HSP90 and that their interaction is critical for maintaining both the stability of the receptor as well as the growth of EGFR-dependent cancers. Furthermore, these findings support the search for specific agents that disrupt HSP90's ability to act as an EGFR chaperone.

Purpose Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to variations in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance. Methods and Materials A detailed cardiac computed tomography scan atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart, left main and left anterior descending interventricular branches, and right coronary arteries on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard atlas volumes. The concordance index was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac structures were calculated and compared with gold standard contour doses. Pre- and post-atlas values were analyzed using a paired t test. Results The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and concordance index of observer-contoured cardiac and gold standard volumes were 2.3-fold improved for all structures ( p 0.002). After application of the atlas, reported mean doses to the whole heart, left main artery, left anterior descending interventricular branch, and right coronary artery were within 0.1, 0.9, 2.6, and 0.6 Gy, respectively, of gold standard doses. Conclusions This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart.

The clonality of ipsilateral breast tumor recurrences (IBTR) after breast-conserving therapy (BCT) was established using a polymerase chain reaction-based allelic imbalance assay of microsatellite loci to compare tumor suppressor gene alteration patterns.The clonality of IBTRs relative to the initial invasive carcinomas were analyzed using a polymerase chain reaction-based allelic imbalance assay in 57 patients treated with BCT, including both whole breast irradiation and accelerated partial breast irradiation.Thirty-four IBTRs (60%) were clonally related to the initial carcinoma and 23 (40%) were clonally different. Clonally related IBTRs were more frequently higher grade (70% vs. 32%, P = 0.019) and developed sooner after initial treatment (mean time interval to IBTR was 5.1 years in clonally related versus 9.3 years in clonally different cases [P = 0.002]). Twelve patients subsequently developed distant metastases, of which 9 (75%) had clonally related IBTRs. Clinical IBTR classification and molecular clonality assay results differed in 44% of all cases. The proportion of IBTRs that were clonally related at 5, 10, and 15 years after BCT were 82%, 48%, and 33%, respectively.This analysis demonstrates the inaccuracy of clinically establishing the clonality of most IBTRs. Clonally related IBTRs occurred sooner than clonally different IBTRs, were more frequently associated with the development of distant metastases and had a worse prognosis. Molecular clonality assays provide a reliable means of identifying patients who may benefit from aggressive systemic therapy at the time of IBTR and provide an accurate assessment of the efficacy of various forms of local therapy.

While several recent studies have demonstrated excellent fi ve-year results using accelerated partial breast irradiation (APBI), the optimal clinical target volume (CTV) to be used in these patients has not been clearly defi ned (Vicini et al. 2003; Wallner et al. 2004). The CTV, which refers to the volume of breast tissue around the lumpectomy cavity requiring radiotherapy (RT), is crucial in determining the effi cacy of adjuvant PBI in comparison to whole breast RT. It is important to consider whether PBI treats the appropriate volume of breast tissue at risk of harboring residual disease. There are three bodies of data that can be used to help defi ne the optimal CTV for APBI. These data include (1) mastectomy studies in which the distribution of cancer in the breast is correlated with the site of the initial tumor, (2) re-excision studies in which the presence, amount, and distance of residual disease is correlated with the initial tumor, and (3) published results with APBI in which the actual CTV used is correlated with the local recurrence rates.

87 Background: Following radiation therapy (RT), gynecologic oncology patients report high rates of sexual dysfunction. However, little is known regarding communication of sexual health among these patients and their healthcare providers. The aim of this study was to assess the beliefs/attitudes of patients regarding sexual history taking. Methods: Survey results were obtained from 75 women who presented for follow up care for gynecologic cancers in the radiation oncology department. The surveys assessed patient beliefs about sexual health and its impact on overall quality of life, the role practitioners should play in obtaining an accurate sexual history, and preferences and level of embarrassment regarding sexual history collection. Overall level of sexual functioning was assessed using the Female Sexual Function Index (FSFI). Chi-squared tests were used to analyze categorical variables and logistic regression modeling was used to predict agreement with survey statements. Results: Most subjects were white and married with a mean FSFI score of 9.9 [(SD = 10.3) sexual dysfunction is defined as < 26.5]. 78.7% agreed that sexual function is an important component of overall health, and only 12.0% reported embarrassment about discussing their sexual health with healthcare providers. 62.79% agreed that medical providers should take a sexual history on a regular basis. However, 58.7% and 22.7% of women report never or almost never being asked about their sexual health by their primary care physician or Ob/Gyn, respectively. Approximately two-thirds of women expressed a preference to have a female provider obtain their sexual health history. Conclusions: Gynecologic cancer patients s/p RT report low sexual function scores. A majority agree that sexual function is essential to overall health. They report little embarrassment regarding discussions of sexual health, yet, note limited discussion about the topic with their healthcare providers. This work highlights the need for improvements in communication about sexual health. We suggest that healthcare providers caring for women with gynecologic cancers should more regularly inquire about their patients’ sexual health and function.

e20606 Background: Concurrent chemotherapy and radiation (CCRT) to treat head and neck cancer (HNCa) is associated with significant reductions of weight, mobility and quality of life (QoL). Support...

55 Background: Palliative care services enhance quality of life in patients with advanced malignancies and are an integral component of multidisciplinary cancer care. They provide symptom control and psychosocial support for patients and family members. A survey in non-VHA cancer centers showed that despite availability of palliative care programs, there was wide variability in the use of these services (Hui et al, JAMA 2010). Palliative care services are a component of the VHA medical benefits package. We sought to determine the ease of access to palliative care services and provider satisfaction among VHA Radiation Oncologists. Methods: VHA-based Radiation Oncologists were identified using the National VHA Radiation Oncology list serve group. All practicing Radiation Oncologists were surveyed to determine the extent of Palliative Care Services available to them and to measure their level of satisfaction with these services. Eighty two surveys were electronically mailed to practitioners at the 38 active VHA Radiation Oncology sites, followed by a reminder phone call.This survey was conducted over a four week period in May of 2014. Results: Sixty four of the 82 surveys distributed over the 4 week period, or 78% were completed. They represent 89% (34/38) of VHA Radiation Oncology Services. All respondents had Palliative Care Services available to them and 98% were happy with the services rendered by the Palliative Care teams. Conclusions: All VHA-based Radiation Oncologists who responded to this survey have access to local VHA based Palliative Care Services. This represented 82% of VHA Radiation Oncology practitioners and 98% were satisfied with the services rendered. Further studies should explore the scope and extent of palliative care involvement including when these services are integrated into the management of patients with advanced malignancies, availability of outpatient palliative care services and variations in care delivery. Radiation therapy is utilized in over 50% of patients with malignancy, often in advanced disease for symptom management and standard guidelines integrating radiotherapy and palliative care should be developed.

52 Background: The rapid evolution of technology in the treatment of cancer has paralleled other technological advancements in modern society. Intensity Modulated Radiotherapy (IMRT), Image Guided Radiotherapy (IGRT), Brachytherapy (BT), Cone Beam Computed Tomography (CBCT), Stereotactic Radiosurgery (SRS), and Stereotactic Body Radiotherapy (SBRT) facilitate treatment with higher, more conformal radiation doses, potentially improving cancer control while reducing normal tissue toxicity. Recent Surveillance, Epidemiology and End Results (SEER) program data and physician surveys indicate prostate BT is declining and the integration of SRS and SBRT is slower compared to IMRT. As utilization of technology increases, an understanding of its availability within the VHA is necessary to ensure quality and patient safety. Methods: An electronic survey was sent to 82 Radiation Oncologists (ROs)at 38 active VHA Radiation Oncology Centers with subsequent follow-up phone calls. The survey occurred from May-June 2014. ROs were queried on the availability of advanced RT technologies including IMRT, IGRT, BT, CBCT, SRS and SBRT at their facility. Practitioner specific details: years in practice, academic appointment and VHA employment status were collected. Results: Responses were obtained from 62 ROs representing 75% of VHA ROs and 34 or 89% of facilities. Full time VHA employees made up 60% of respondents with 35% in practice for 20 years; 71% held an academic appointment. The Table shows on site availability of advanced RT technologies within the 34 VHA sites that responded. Conclusions: For veterans receiving cancer treatment, VHA ROs are able to routinely use IMRT and IGRT with CBCT capabilities. However, stereotactic (SRS and SBRT) and BT services are less available, and may require referrals externally or to other VHA facilities. Limited availability of SRS and SBRT parallels the community experience. Likewise the decreasing utilization of BT is common to the VHA and private sector. SBRT, SRS and BT require significant expertise and technology. [Table: see text]

Purpose: To support radiotherapy dose calculation, synthetic CT (MRCT) image volumes need to represent the electron density of tissues with sufficient accuracy. This study compares CT and MRCT for pelvic radiotherapy. Methods: CT and multi-contrast MRI acquired using T1- based Dixon, T2 TSE, and PETRA sequences were acquired on an IRBapproved protocol patient. A previously published method was used to create a MRCT image volume by applying fuzzy classification on T1- weighted and calculated water image volumes (air and fluid voxels were excluded using thresholds applied to PETRA and T2-weighted images). The correlation of pelvic bone intensity between CT and MRCT was investigated. Two treatment plans, based on CT and MRCT, were performed to mimic treatment for: (a) pelvic bone metastasis with a 16MV parallel beam arrangement, and (b) gynecological cancer with 6MV volumetric modulated arc therapy (VMAT) using two full arcs. The CT-calculated fluence maps were used to recalculate doses using the MRCT-derived density grid. The dose-volume histograms and dose distributions were compared. Results: Bone intensities in the MRCT volume correlated linearly with CT intensities up to 800 HU (containing 96% of the bone volume), and then decreased with CT intensity increase (4% volume). There was no significant difference in dose distributions between CT- and MRCTbased plans, except for the rectum and bladder, for which the V45 differed by 15% and 9%, respectively. These differences may be attributed to normal and visualized organ movement and volume variations between CT and MR scans. Conclusion: While MRCT had lower bone intensity in highly-dense bone, this did not cause significant dose deviations from CT due to its small percentage of volume. These results indicate that treatment planning using MRCT could generate comparable dose distributions to that using CT, and further demonstrate the feasibility of using MRI-alone to support Radiation Oncology workflow. NIH R01EB016079

Purpose: To evaluate the accuracy of MR-based vaginal brachytherapy source localization using an in-house MR-visible marker versus the alignment of an applicator model to MR images. Methods: Three consecutive patients undergoing vaginal HDR brachytherapy with a plastic cylinder were scanned with both CT and MRI (including T1- and T2- weighted images). An MR-visible source localization marker, consisting of a sealed thin catheter filled with either water (for T2 contrast) or Gd-doped water (for T1 contrast), was assembled shortly before scanning. Clinically, the applicator channel was digitized on CT with an x-ray marker. To evaluate the efficacy of MR-based applicator reconstruction, each MR image volume was aligned locally to the CT images based on the region containing the cylinder. Applicator digitization was performed on the MR images using (1) the MR visible marker and (2) alignment of an applicator surface model from Varian's Brachytherapy Planning software to the MRI images. Resulting source positions were compared with the original CT digitization. Results: Although the source path was visualized by the MR marker, the applicator tip proved difficult to identify due to challenges in achieving a watertight seal. This resulted in observed displacements of the catheter tip, at times >1cm. Deviations between themore » central source positions identified via aligning the applicator surface model to MR and using the xray marker on CT ranged from 0.07 – 0.19 cm and 0.07 – 0.20 cm on T1- weighted and T2-weighted images, respectively. Conclusion: Based on the current study, aligning the applicator model to MRI provides a practical, current approach to perform MR-based brachytherapy planning. Further study is needed to produce catheters with reliably and reproducibly identifiable tips. Attempts are being made to improve catheter seals, as well as to increase the viscosity of the contrast material to decrease fluid mobility inside the catheter.« less

e20632 Background: Population studies indicate that 40% of cancer patients use CAM. Most are not well informed of their chosen CAM and do not discuss it with their healthcare providers. However, no...

9607 Background: Head and neck cancer (HNCa) treatment results in unfavorable changes in physical function, body composition and quality of life. The ability of these patients to perform physical activity after cancer treatment has not been previously evaluated. To develop clinical models that will guide the care of HNCa survivors, it is important to characterize these physical activity changes. Methods: From 2008 to 2011, as part of an institutional Head and Neck SPORE longitudinal epidemiology project, health survey data including the Physical Activity Scale in the Elderly (PASE) was collected at baseline, 6 months and annually thereafter. The PASE score assesses the hours doing leisure time physical activity, walking, occupational, and household chores over a typical 7-day period. During follow up, subjects deceased, were lost to follow-up, or refused survey completion. Paired t-test was used to compare the mean PASE score at various endpoints from baseline. Results: 294 HNCa patients completed the survey at baseline. Following a mean follow-up of 25.7 (+/-11.9) months, 66%(n=193), 73%(n=215) and 42%(n=124) of patients completed the assessment at 6-months, 1-year and 2-years respectively. Majority (97%) of the HNCa patients had oropharynx, oral cavity or larynx cancer, which were treated by chemoradiation (36%), surgery followed by chemoradiation (23%) or surgery alone (20%). Results of the PASE score revealed the lowest levels of physical activity at baseline with steady statistically significant improvement at each subsequent timepoint (p