Assessment of Musculoskeletal Impairment in Head-and-Neck Cancer Patients

Volume 88  Number 2  Supplement 2014 published NDII scores after neck dissection, which average 67.8 (17.4) (Taylor et al , Archives of Otolaryngology, Vol 128, pgs 44-49, 2002). Author Disclosure: S.J.M. Burgin: None. M.E. Spector: None. E. Light: None. F.P. Worden: None. A. Eisbruch: None. D.B. Chepeha: None.

212 Survival Analysis of Patients With Advanced-Stage Oropharyngeal Cancer Stratified by Molecular Profile and Treatment Survivorship V.L. Biron,1,2 D.A. O’Connell,2 A.C. Klimowicz,3 L. Puttagunta,2 J. Harris,2 and H. Seikaly2; 1University of California Davis, Davis, CA, 2 University of Alberta, Edmonton, AB, Canada, 3University of Calgary, Calgary, AB, Canada Purpose/Objective(s): To determine differences in survival outcomes in patients with advanced stage oropharyngeal squamous cell carcinoma (OPSCC) when stratified by treatment and molecular profile. Materials/Methods: Demographic, pathologic and survival data was obtained from all patients diagnosed and treated for OPSCC from 1998-2010 at a tertiary care center (University of Alberta). Tissue microarrays (TMAs) were constructed to include all patients treated within this time frame with sufficient pathologic specimen available (nZ334). TMAs were stained by immunohistochemistry for p16, EGFR, Ki-67, Bcl-XL and p53, and digitally quantified in comparison to positive and negative controls. Patients were stratified by molecular profile using standardized expression cutoffs. Molecular profiles were then used to stratify patients who received the following treatment modalities: 1) primary surgery + chemoradiation (S+CRT), 2) primary surgery + post-operative radiation (S+RT) and 3) primary chemoradiation +/- salvage surgery (CRT). Disease-specific (DSS) and overall survival was calculated for each stratum using Kaplan-Meir analysis. Hazard ratios and multivariate analysis was performed using Cox regression. Results: Distinct two- and five-year survival curves were obtained for each treatment stratum. When considering p16 status, 5-year DSS was highest for patients who received S+CRT (84.8% for p16+ and 60.8% for p16-), followed by S+RT (77.5% for p16+ and 54% for p16-) and CRT (55.2% for p16+ and 38.1% for p16-). Remarkably, the 5-year DSS of patients treated with S+CRT with low tumor EGFR levels was 100%. Patients with p53 positivity had improved DSS with surgical modalities. Bcl-XL levels alone were not associated with a significant difference in survival outcome. Elevated Ki-67 levels were associated with improved outcomes in patients receiving radiation therapy but low Ki-67 levels stratified patients into the poorest outcome group with a 5-year DSS of 18%. Conclusions: To our knowledge, this represents the largest cohort of advanced stage OPSCC survival comparing surgical and non-surgical treatment modalities, stratified by clinically significant biomarkers. Triple modality therapy provides optimal survival outcomes for patients with advanced stage OPSCC regardless of molecular profile. Author Disclosure: V.L. Biron: None. D.A. O’Connell: None. A.C. Klimowicz: None. L. Puttagunta: None. J. Harris: None. H. Seikaly: None.

213 Effect of Adjuvant Radiation Therapy on Survival in Head and Neck Osteosarcoma Survivorship A. Jacobson,1 P. Huang,1 E. Choy,1,2 D. Harmon,1,2 T.F. DeLaney,1,2 and Y. Chen1,2; 1Massachusetts General Hospital, Boston, MA, 2Harvard Medical School, Boston, MA Purpose/Objective(s): Osteosarcoma, the most common primary bone cancer, is especially rare in the head and neck region, a location that presents a complex challenge to surgical and radiation treatment. The purpose of this study was to retrospectively analyze the outcomes of patients with head and neck osteosarcoma (HNOS) treated with surgical resection to determine the effect of adjuvant radiation on overall and disease specific survival.

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Materials/Methods: The Surveillance, Epidemiology, and End Result (SEER) Registry was queried to identify patients diagnosed with HNOS as their first primary malignancy who underwent surgical resection. Outcomes of patients with and without adjuvant radiation therapy were compared using Cox proportional hazards regression to account for other covariates. Results: A total of 229 patients who presented with non-metastatic HNOS and underwent surgical resection were identified; 109 male and 120 female, with a median age of 39 (interquartile rangeZ23-52). The most common disease site was the mandible, representing 100 (43.7%) cases, with the remaining cases spread over other bones of the head and neck. Chondroblastic was the most common histological subtype (55 patients, 24.0%) after the “NOS” (not otherwise specified) grouping. 157 (68.6%) patients were treated with surgery only and 72 (31.4%) patients received adjuvant radiation therapy. Factors associated with increased likelihood of receiving radiation therapy post resection were high grade (pZ0.03), regional over localized stage (pZ0.03), larger tumor size (pZ0.09) and site other than the mandible (pZ0.05). Median follow-up time was 45 months; the 5-, 10-, and 20- year overall survival rates were 68%, 62% and 53%, respectively. Multivariate proportional hazards analysis showed that age (hazard ratio (HR) 1.02 / yr. p<0.001), chondroblastic histology (HR 0.42 pZ0.020) had the most significant effect on overall survival. The model showed no statistically significant difference in survival (overall and disease-specific) outcome for patients based on disease site, extent of surgery, or use of adjuvant radiation therapy. Conclusions: Osteosarcoma arising in the head and neck region is rare and particularly difficult to treat. Although we show that overall survival is unaffected by adjuvant radiation therapy there is a need for further studies to determine its effect on other metrics such as local control and toxicity. Author Disclosure: A. Jacobson: None. P. Huang: None. E. Choy: None. D. Harmon: None. T.F. DeLaney: None. Y. Chen: None.

227 Assessment of Musculoskeletal Impairment in Head-and-Neck Cancer Patients Survivorship K. Mannion, K. Stevens, B. Murphy, J. Gilbert, J. Deng, M.S. Dietrich, M. Adair, and S.H. Ridner; Vanderbilt University Medical Center, Nashville, TN Purpose/Objective(s): Head and neck cancer (HNC) patients develop musculoskeletal impairment (MSI) due to surgical and non-surgical therapy. Most studies have assessed MSI using self-report measures. Studies using objective measures are limited and have focused primarily on trismus or shoulder dysfunction. We undertook a cross sectional, pilot study to compare MSI of two reconstructive technique (regional pedicled flap-RPF and free tissue transfer-FTF). The secondary aim compared selfreport and objective measures of MSI to determine optimal measurement methods for future studies. Materials/Methods: Patients were age  21, previously resected HNC with either RPF or FTF for reconstruction, completed therapy > 3 months prior to enrollment, and free of disease. Patients completed the following self-report validated measures: 1) Neck Disability Index (NDI), 2) Shoulder Pain and Disability Index (SPADI) and 3) the Vanderbilt Head and Neck Symptom Survey (VHNSS). In addition, the following objective measures were performed: 1) Cervical Range of Motion (CROM), 2) digital postural analysis, 3) Inter-incisal distance (IID) and 4) Pulmonary Function Tests (PFTs). Demographic, tumor and treatment related information was obtained by chart review. Results: 25 patients were recruited: average age 60, 64% male, 88% white, and 55% stage 3 or 4 disease. 8 patients underwent RPF and 17 FTF reconstruction. The NDI indicated 8 of 25 patients had moderate to severe function loss: average score was 11. Using a score cut off of 30, 40% and 24% of patients reported high levels of pain and disability respectively on the SPADI. Objective data from the CROM indicated impaired neck ROM in all directions which was statistically significant for left and right neck

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rotation. Average neck rotation in either direction was 49.9 degrees (normal - 80 degrees in either direction). Self-report of trismus using the VHNSS trismus item correlation with objective measure of IID. Digital photos in front of a posture grid revealed subjective postural abnormalities and asymmetries. Too few patients underwent PFTs to characterize the findings. Conclusions: Our data revealed both subjective and objective evidence of MSI in post-surgical HNC patients; however, self-report measures may only partially capture the scope and impact of HNC treatment on musculoskeletal integrity. Furthermore, validated grading systems for documenting MSI are lacking. This hampers the ability of investigators to study the severity, trajectory and impact of MSI. Furthermore, it impairs the ability to test interventions. This was particularly relevant to postural abnormalities with little prior identified in the literature. Further development and validation of measurement tools and grading systems for MSI are needed. Author Disclosure: K. Mannion: None. K. Stevens: None. B. Murphy: None. J. Gilbert: None. J. Deng: None. M.S. Dietrich: None. M. Adair: None. S.H. Ridner: None.

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229 Cervical Osteoradionecrosis: A New Syndrome Affecting Survivors of Head-and-Neck Cancer Years After Chemoradiation Survivorship A.J. Rosko, S. Lynn, G. Griffin, C.R. Bradford, M.E. P. Prince, J.S. Moyer, F. Worden, A. Eisbruch, and D.B. Chepeha; University of Michigan, Ann Arbor, MI Purpose/Objective(s): Cervical ORN can present as subtle neck pain that rapidly progress to quadriplegia in patients with a history of chemoradiation (CXRT), salvage surgery and disruption of the pharyngeal mucosa. We have assembled a cohort of patients to help define the syndrome to assist in early detection and treatment in long term survivors of laryngeal/hypopharyngeal Squamous Cell Carcinoma (SCCa). Materials/Methods: Retrospective case series of 6 patients who developed neurologic changes associated with cervical ORN. All patients had a history laryngeal or hypopharyngeal SCCa and underwent CXRT with curative intent followed by salvage laryngectomy for recurrent disease or chondroradionecrosis. A chart review was performed. Results: Six patients developed new onset neck or shoulder pain that progressed to focal neurological findings with in a range of 1-60 days. All patients had a mucosal disruption, from recent dilation of a stricture (4/6) or postsurgical dehiscence (2/6). All patients presented with a history of head neck, back, or shoulder pain. 50% of patients were febrile at presentation and all but one had a leukocytosis. ESR and CRP were elevated in all patients. Neurological symptoms included motor weakness with hemiplegia (1/6) or quadriplegia (2/6), upper limb weakness (1/6) and bowel and bladder symptoms (2/6). All but 1 patient required urgent neurosurgical cervical decompression with cervical fusion. 2 patients experienced neurological improvement. Infections were polymicrobial and consistent with contamination from the pharynx. MRI was essential for the diagnosis of this syndrome. Thickening of the epidural space was the critical radiologic sign. The disease specific mortality was 50%. Conclusions: Cervical osteoradionecrosis is a life threatening late complication of CRT and salvage surgery. Patients who present with new onset neck and/or shoulder pain after mucosal disruption from stricture dilation or breakdown of the pharyngeal closure are at risk. Signs of cord compression rapidly develops and often progresses to hemiplegia or quadriplegia. A high index of suspicion is required and cross sectional imaging along with coordination between infectious disease and neurosurgery. Treatment includes surgical drainage stabilization of the cervical spine and a prolonged course of broad spectrum antibiotics. Author Disclosure: A.J. Rosko: None. S. Lynn: None. G. Griffin: None. C.R. Bradford: None. M.E.P. Prince: None. J.S. Moyer: None. F. Worden: None. A. Eisbruch: None. D.B. Chepeha: None.

Quantitative Effects of Lymphedema Therapy in Patients With Head-and-Neck Cancer Survivorship K. Doke,1 L. Bowman,2 L. Shnayder,3 T. Tsue,3 D. Girod,3 P. Neupane,3 and C. Lominska3; 1University of Kansas School of Medicine, Kansas City, KS, 2Overland Park Regional Medical Center, Kansas City, KS, 3Kansas University Medical Center, Kansas City, KS Purpose/Objective(s): Head and neck surgery and radiation cause tissue fibrosis and disrupt lymphatic drainage, leading to functional limitations and lymphedema. The aim of this study is to quantify the effects of lymphedema therapy. Materials/Methods: Eligible patients (nZ30) received definitive or postoperative radiation with or without chemotherapy for squamous cell carcinoma of the oral cavity or oropharynx between 2011 and 2012. Nineteen patients were treated with primary surgery including ipsilateral modified radical neck dissection (nZ10), bilateral modified radical neck dissection (nZ2), or ipsilateral radical neck dissection (nZ3). All patients received radiation to the primary and bilateral neck using intensity modulated radiation therapy with doses ranging from 54 to 70 gray. They were referred to a certified lymphedema therapist with specialty training in head and neck cancer by the radiation oncologist after completion of radiation treatment and healing of acute toxicity (typically 1-3 months), due to development of or high risk for lymphedema. They underwent at least 3 months of manual lymphatic decongestion and skilled fibrotic techniques (range 3 to 9 months). Superior, middle and inferior circumferential neck measurements were taken using the MD Anderson Cancer Center Head and Neck Tape Measurement Protocol. Cervical range of motion was measured. Changes were calculated from beginning to last date of treatment. Institutional review board approved retrospective review of results. Results: Composite neck measurements and cervical range of motion were evaluated. Changes greater than 2% in circumference were considered clinically significant, whereas  2% or less was considered to be stable. Nineteen patients (63%) had a decrease in edema (2-11% or 3 to 16.5 cm) and 8 patients (27%) were stable. Three patients (10%) had an increase in composite neck measurements over time (2 % to 4% or 4.5 to 6 cm). Of the three patients who increased, one had had a radical neck dissection, one a bilateral neck dissection, and the third reoperation on the floor of mouth for recurrent disease before radiation. Nineteen patients had cervical range of motion measured. Baseline ranged from 20 to 75 degrees on the right and 0 to 75 degrees on the left. Mean improvement over a period of three months was 10 degrees on the right (range 0 to 35 degrees) and 13 degrees on the left (range -10 to 40 degrees). Decreased range of motion was seen in the patient with reoperation of the left floor of mouth. Conclusions: Lymphedema therapy produces objective improvements in range of motion and neck circumference in the majority of patients. Prospective comparison with untreated patients is warranted. High risk patients (extensive surgery) may require more intensive treatment. Author Disclosure: K. Doke: None. L. Bowman: None. L. Shnayder: None. T. Tsue: None. D. Girod: None. P. Neupane: None. C. Lominska: None.

251 Clinical Significance of Body Morphomics Changes in Oropharyngeal Cancer Patients Undergoing Chemoradiation Survivorship C. Wang, J. Vainshtein, M. Veksler, P. Rabban, J. Sullivan, S. Wang, A. Eisbruch, and S. Jolly; University of Michigan, Ann Arbor, MI Purpose/Objective(s): Oropharyngeal cancer patients experience significant weight loss during chemoradiation therapy (CRT). Little is known, however, about their body morphomics changes and its clinical significance in this population. Materials/Methods: Stage III-IV oropharyngeal cancer patients were identified from our institutional prospective phase 2 organ sparing chemoIMRT protocols from 2003 to 2011. Using novel body morphomics techniques, detailed body composition analysis of these patients was