Lymph nodes (LN) serve a crucial role in host defense against cancer. Oral cancer commonly metastasizes to the LN, which is a marker for poor prognosis. The mechanisms behind tumor metastasis in oral squamous cell carcinoma (OSCC) remain elusive despite the study of cellular and molecular tumor characteristics. We hypothesize that tumor-draining LN develop alterations in their infrastructure and inflammatory cell populations prior to establishment of tumor cells. We examined the LN microenvironment of patients both with and without LN metastasis. For those patients with metastasis, we compared LN with involvement to those without involvement.

To evaluate the incidence of second primary malignancies in patients diagnosed with head and neck cancers in the United States. The SEER registry was used to identify patients with primary head and neck cancers from 1973-2005. Patients’ data were retrieved using ICD-3-O topography codes for all head and neck sites (C00.0-C14.8) (C30.0-C32.9) (C44.2) (C69.0-C69.9) (C73.9). Individuals were stratified by age, race, sex, stage, surgery and radiation. Pooled overall survival (OS) and disease specific survival (DSS) were calculated using univariate Cox Proportional Hazards models. Overall and site-specific relative risks of second malignancies (SMs) were evaluated using standardized incidence ratios (SIRs) to determine the ratio of observed to the expected number of cases among the cohort population. P <0.05 was used to determine the required level of significance. For all ages, 190,468 patients were found to have 34266 second primary malignant tumors observed in this patient cohort. Among these cases, 111,469 individuals were male (58%), 161,325 were white (84%), 23,319 were 60-64 years (12.2%), and 96,883 received radiation therapy (50%). 5 year OS and DSS was 36% and 63%, respectively. Among this cohort, OS was improved in females (P<0.0005), non-white or African American race (P<0.0005), age 0-20 (P<0.001), localized stage (P<0.0003), surgical treatment (P<0.0002) and radiation treatment (P<0.0003). Evaluation of all sites identified that patients are at higher risk of second primary malignancies in all sites (SIR 1.56), The most significant risk was located in head and neck region; oral cavity and pharynx (SIR 8.68), tongue (SIR 11.2), floor of mouth (SIR 12.25), gum (SIR 13.7), oropharynx (SIR 10.27), hypopharynx (SIR 8.95), tonsil (SIR 6.92), pharynx (SIR 7.85), other oral cavity and pharynx (SIR 12.70) and trachea (SIR 11.64). Evaluation of the latency to development of second primary malignancies revealed this increased risk remained significant at multiple time frames from 6 months to greater than 60 months. On Multivariate Cox Proportional Hazards analysis, both age and surgery significantly reduced risk of SMs, (CI = 0.625-0.753, P<0.0005) and (CI = 0.762-0.812, P<0.001), respectively. This remained true on subgroup analysis performed on non-radiation and radiation groups were associated with less risk of SMs (CI = 0.576-0.689, P = 0.0004) and (CI = 0.514-0.630, P = 0.002), respectively. Head and neck cancer patients are at a significant risk for second primary malignancies, most notably in the head and neck region. Radiation therapy improves OS and does not increase risk of SMs, suggesting that elevated risk is attributable to factors other than radiation.

Normal tissue sparing strategies are becoming the standard for modern radiation therapy; without organ preservation the toxicity associated with external beam radiation therapy, such as xerostomia, adversely affects a patient’s long-term quality of life (QOL). Recently, clinicians have come to understand that there are significant changes to the head and neck (H&N) anatomic compartments induced by radiation therapy, despite efforts to spare normal structures. Herein, we propose an investigation of the anatomic and volume changes of the major salivary (parotid and submandibular) glands during treatment with concurrent chemoradiation. We further assess the volume changes of the deep and superficial parotid glands during our IMRT treatment. Our ultimate goal is to identify the timing at which radiation-induced changes to the salivary glands occur, the effects on saliva quality, and assess QOL, with the future goal to design an adaptive radiation therapy paradigm to maximize the quality of life of H&N patients. We retrospectively investigated 20 patients with recurrent or newly diagnosed squamous cell carcinoma of the H&N carcinoma treated with concurrent chemoradiation therapy. Assessed, were the volume and anatomic positions of the parotid and submandibular glands at the time of CT simulation, the 12th, 25th, and final fraction of image guided radiation therapy. We compared the total gland volumes, and then measured position translation to a bony reference (C2 dens). We utilized the embedded volume, distance, and dosing tools within the treatment planning software package. Cohort median age was 61 (3:1 male:female ratio). Fifteen patients were diagnosed with stage IVa H&N squamous cell carcinoma. There was a balance of left vs. right-sided disease. Patients received a minimum of 66 Gy, with a median dose of 70 Gy. Mean treatment package time was 44d; 85% of patients received concurrent chemotherapy. Median weight loss was 7.4%. CCRT vs. no chemotherapy resulted in a trend towards significant mean parotid gland volume loss (41.9 ± 19.4% vs. 35.2 ± 20.1%; P = 0.18). Volume loss was greatest by the first 12 fractions of treatment. For submandibular glands, our sample small sample size suggested a trend increased volume loss with CCRT. The glands exhibited a medial displacement of 5-8mm during the course of treatment. No differences in unstimulated/stimulated saliva output or pH were seen between the two groups. Our data suggests a connection with use of CCRT and salivary gland changes. Due to a small sample size, these differences were not statistically significant, however, we are increasing our study size in light of this important result. We wish to identify timing of gland changes, dose effect on saliva chemistry, and assess QOL to design an adaptive CCRT paradigm to maximize QOL.

Considered a significant acute and long-term morbidity, lymphedema within head and neck carcinoma (HNC) patients completing high-dose radiotherapy is an under-diagnosed and under-treated concern. At risk for these patients are considerable quality of life detriments, ranging from cosmetic disfigurement to functional impairments, and may include psychosocial difficulties. Presently, composite index scoring (CIS) is used for objective determination of facial and/or neck swelling and treatment-related edema. Unfortunately, in current practice, there is limited correlation of these objective measures with subjective quality of life (QOL) assessments. Herein, we report our institutional experience of a pilot program designed to identify, assess, intervene, and quantify measures to reduce Lymphedema present within our locally advanced HNC patients. With institutional review board approval, 21 patients diagnosed and treated for HNC were identified to have treatment-related lymphedema; 5 patients were eligible for study. CIS of the face and neck were utilized to quantify facial and neck edema. In addition, a Lymphedema severity rating scale was employed for tissue quality staging. The cohort was status post multi-modality treatment, which included surgery and chemoradiation. Patients were evaluated after definitive cancer treatment, but prior to lymphedema intervention. All therapeutic intervention was carried out by a certified lymphedema therapist. Treatment included an outpatient evaluation of lymphedema severity, shoulder and cervical ROM, and upper extremity strength. Patients then received a combination of therapist administered treatment and daily self-administered home-based program. Median age was 68 years (52-96). Four of 5 patients were stage IV squamous cell carcinoma and 4 patients received either concurrent or neoadjuvant chemotherapy. A median XRT dose of 70 Gy was delivered. 4 of 5 patients had stage 2 head and neck lymphedema upon initial evaluation. Clinical response of lymphedema was seen in 100% of the patients. Treatment response ranged from 2.9% to 10% in facial/neck CIS reduction; significant minimal clinical improvement is a difference of ≥ 2%. Median lymphedema treatment duration was 68 days (20-156 days). Our preliminary data shows that with adequate screening, assessment, and intervention, symptom burden associated with lymphedema as a result of HNC treatment can be reduced. These efforts represent a grassroots effort to increase awareness of lymphedema as a HNC treatment sequelae to our referring physicians and provide an opportunity to improve the clinical outcomes and QOL of this vulnerable patient population. We will continue this paradigm to expand our outreach and improve outcomes for this underserved patient population.

Unintended toxicity remains a practice-limiting concern for head and neck (H&N) radiation therapy (RT). Radiation oncologists understand there are significant changes to the H&N anatomic compartments induced by RT, despite our efforts to spare normal structures. In correlation to this, dose becomes heterogeneous across organs at risk as these anatomic changes occur. Here, we report how the parotid gland anatomic position and volume changes during CCRT and compare the dose delivered at the beginning and end of a nonadapted definitive RT course. Our ultimate goal is to identify the timing at which significant changes occur, with the purpose to design an adaptive RT paradigm to maximize the quality of life of H&N patients. This is a pilot study of 20 patients with recurrent or newly diagnosed H&N squamous cell carcinoma, treated with daily image guided intensity modulated RT and concurrent chemotherapy. The mean dose delivered to the comprehensive parotid gland, the superficial and deep parotid lobes, as well as the max dose delivered to these were assessed. The baseline dose calculations were made on the initial planning CT, then at the completion of RT, the final fraction cone beam CT (CBCT) was fused to the planning CT and parotid structures were contoured. The delivered dose was then calculated across the parotid glands at the first and last fraction. Hounsfield unit correction was manually input to account for CBCT nonuniformity. Cohort median age was 61 years, with a 3:1 male:female ratio. Fifteen patients were diagnosed with stage IVa H&N squamous cell carcinoma; the remainder were stage II or greater. There was a balance of left- versus right-sided disease. Patients received a minimum of 66 Gy to the disease/postoperative site, with a median dose of 70 Gy. Mean treatment package time was 44d; 85% of patients received concurrent chemotherapy. The total parotid gland planned at simulation, compared to the final fraction, received a mean dose of 3069.8±1035.4 cGy versus 3634.7±1449.5 cGy (P=0.04). This difference can be attributed to the change in position and volume of the parotid gland during RT. Comparing the mean dose to the superficial versus deep parotid lobes, there was a significant dose increase delivered to the superficial parotid glands (124%; P=0.03 vs 111%; P=0.13) by the final fraction, compared to that delivered in the original plan. Overall, the parotid glands were found to translate medially by a mean of 5.5 mm. Here, we have investigated the dose response of the parotid glands during definitive RT. We wish to further our understanding of when gland changes occur, the clinical relevance, and the patient subjective experience to define an adaptive CCRT paradigm to maximize quality of life.

Background: Suicidal ideation (SI) and attempts are increased in Huntington's disease (HD), making risk factor assessment a priority.Objective: To determine whether, hopelessness, irritability, aggression, anxiety, CAG expansion status, depression, and motor signs/symptoms were associated with Suicidal Ideation (SI) in those at risk for HD.Methods: Behavioral and neurological data were collected from subjects in an observational study. Subject characteristics were calculated by CAG status and SI. Logistic regression models were adjusted for demographics. Separate logistic regressions were used to compare SI and non-SI subjects. A combined logistic regression model, including 4 pre-specified predictors, (hopelessness, irritability, aggression, anxiety) was used to assess the relationship of SI to these predictors.Results: 801 subjects were assessed, 40 were classified as having SI, 6.3% of CAG mutation expansion carriers had SI, compared with 4.3% of non-CAGmutation expansion carriers (p = 0.2275). SI subjects had significantly increased depression (p < 0.0001), hopelessness (p < 0.0001), irritability (p < 0.0001), aggression (p = 0.0089), and anxiety (p < 0.0001), and an elevated motor score (p = 0.0098). Impulsivity, assessed in a subgroup of subjects, was also associated with SI (p = 0.0267). Hopelessness and anxiety remained significant in combined model (p < 0.001; p < 0.0198, respectively) even when motor score was included.Conclusions: Behavioral symptoms were significantly higher in those reporting SI. Hopelessness and anxiety showed a particularly strong association with SI. Risk identification could assist in assessment of suicidality in this group.

To be held on Saturday, 16 October, 2010, in the Pavilion Ballroom at the Hyatt Regency La Jolla at

Despite large gaps in evidence-based knowledge, clinical experience supports the use of pharmacologic treatments for many symptoms of Huntington's disease (HD). The project goal is to develop consensus guidelines based on expert clinical experience that will improve the quality of HD care. The Delphi process, which provides an iterative formal strategy to gather expert opinion and form a consensus, was utilized. First steps of this process explored expert prescribing patterns. Step 1: Nine experts from Huntington's Study Group and European HD Network created initial statements for irritability, obsessive/compulsive behaviors (O/Cs), and chorea. Step 2: Statements were submitted via a web survey to a panel of 40 additional experts. Thirty expert neurologists and psychiatrists from Europe and North America responded. For irritability there was lack of consensus in first choice and in sequence of drugs used in combination therapy. For O/Cs there was high agreement (>80%) on SSRI as first choice; however, there was lack of consensus on adjuvant drug therapy. For chorea there was agreement that it should be treated when quality of life or ADL is affected, but there was lack of consensus on drug of first choice. The next round of the Delphi consensus process will begin in November of 2009. Many areas of variability in the treatment for irritability, O/Cs, and chorea in HD, even among expert clinicians, have been identified. Results will guide future rounds of the Delphi process to elicit rational causes for the differences identified. Collection of further data on consensus will begin in November of 2009. When complete, this process will clarify useful treatment paradigms that will improve patient care and identify areas in which clinical trials would be most useful.

Background Despite large gaps in evidence-based knowledge, clinical experience supports the use of pharmacologic treatments for many symptoms of Huntington9s disease (HD). Aims The project goal is to develop consensus guidelines based on expert clinical experience to improve quality of HD care. Methods The survey was developed by 9 international experts, and designed as a highly iterative and systematic method of soliciting expert opinions on the pharmacologic treatment of irritability, perseverative behaviors, and chorea in HD. Fifty-five experts from Australia, Europe and North America responded to at least one of the surveys. Results For irritability, SSRI was first choice of 58%, an antipsychotic was first choice for 22%, a mood stabilizing anticonvulsant 14%, and benzodiazepine 2%. For perseverative behaviors, SSRI was first choice of 75%, an antipsychotic choice of 4%, a mood stabilizing anticonvulsant choice of 6%, and clomipramine 2%. The remaining 13% chose to qualify the response to include 2 first choices. For chorea, an antipsychotic was first choice for 56%, tetrabenazine 15%, amantadine 6%, and benzodiazepines 4%. The remaining 13% chose to qualify the response to include 2 first choices. Drug choice for use as adjunctive therapy was widely variable. Conclusions Many areas of variability in treatment for irritability, perseverative behaviors, and chorea in HD, have been identified. Results will guide future rounds of the Delphi process to elicit rational causes for differences identified. When complete, this process will clarify useful treatment paradigms that will improve patient care and identify areas in which clinical trials would be most useful.