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Assess the testing rates and prognostic significance of human papilloma virus (HPV) status in hypopharynx malignancies.Historical cohort study.National Cancer Database.Review of the National Cancer Database was conducted between 2010 and 2017 for squamous cell carcinomas (SCCs) of the hypopharynx. We investigated how often the tumors were tested for HPV and whether it was associated with survival outcomes.A total of 13,269 patients with hypopharynx malignancies were identified. Most cases were not tested for HPV status (n = 8702, 65.6%). Of those tested, 872 (19.1%) were positive for HPV and 3695 (80.9%) were negative. The proportion of nonoropharyngeal SCCs tested for HPV increased nearly every year during the study, with roughly one-third of cases (31.9%) being tested in 2017. In the facilities classified as high-testing centers of nonoropharyngeal SCCs of the head and neck, 18.7% of hypopharyngeal tumors were HPV positive. HPV-negative status was associated with worse survival on multivariable analysis. In propensity score-matched analysis controlling for all factors significant in multivariable regression, 2-year survival remained higher in the HPV-positive cohort (77.7% vs 63.1%,HPV-positive tumors constitute a sizable minority of hypopharynx tumors and are associated with improved survival. Expansion of HPV testing to hypopharynx malignancies may be warranted.

PURPOSE Malignant fungating wounds (MFWs) afflict up to 14% of patients with advanced cancer. The bacterial community structures of MFW may influence the development and severity of wound symptoms. The purpose of this systematic review was to evaluate existing evidence regarding the relationship between microbiome and symptoms of MFWs. METHODS A systematic review of the published literature from January 1995 to January 2020 was conducted. An established quality assessment tool was used to assess the quality of the included studies. SEARCH STRATEGY We searched 4 major electronic databases and retrieved 724 articles; 7 met inclusion criteria. FINDINGS/CONCLUSIONS Seven studies were included; the overall quality of the included 7 studies was ranked as adequate. Findings from the studies provided an incomplete characterization of the microbiome and metabolome of MFW; none included modern genomic technologies. Twenty different species of aerobes and 14 species of anaerobes were identified, with inconsistent identification of biofilms and multi-drug-resistant bacteria. Symptom occurrence increased with the number of bacteria species (P = .0003) and the presence of at least 1 anaerobe (P = .0006) in malignant wound beds. Cancer wound-derived odor was associated with dimethyl trisulfide and 4 fatty acid volatiles. Periwound and moisture-associated skin damage were associated with higher putrescine levels in exudates. IMPLICATIONS Understanding the role of microbiota of MFW in developing or amplifying the severity of wound symptoms is the first step toward development of more precise and effective topical interventions.

To describe patterns of primary surgical treatments in patients with T4b oral cavity squamous cell carcinoma (OCSCC).Historical cohort study.National Cancer Database.Review of the National Cancer Database between 2004 and 2017 for all T4b OCSCCs. Only patients with curative treatment methods were included in the survival analysis. Surgical and nonsurgical outcomes were compared by multivariable and propensity score matching analysis.A total of 1515 cases of T4b OCSCC were identified. A minority of patients (n = 363, 24.0%) underwent curative treatment; among these, 206 (56.7%) underwent primary surgery. Median length of follow-up was 24 months. The 90-day mortality of patients who underwent surgical treatment was 1.0%. The 2-year survival was higher for patients who underwent surgery + chemoradiotherapy (CRT) as compared with CRT (64.6% vs 45.2%,A minority of patients with T4b OCSCC undergo treatments with curative intent. A subset of patients underwent primary surgical treatment, which was associated with longer survival. The T4b classification might entail a heterogenous group, and further studies in revision of this classification might be justified.

BACKGROUND: We examine the prognostic implications of mid-course nodal response in oropharyngeal cancer (OPX) to radiation therapy. METHODS: In 44 patients with node-positive OPX undergoing concurrent chemoradiation, nodal volumes were measured on cone beam CTs from days 1, 10, 20, and 35. Nodal decrease (ND) was based on percent shrinkage from day 1. RESULTS: At a median follow-up of 17 months, the 2-year disease-free survival (DFS), locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) were 87%, 92%, 89%, and 92%, respectively. Patients with ND ≥43% at D20 had improved LRC (100% vs 78.4%, P = .03) compared to D20 ND

To investigate differences in epidemiology of oropharyngeal squamous cell carcinoma (OPSCC) with regards to human papillomavirus (HPV), race, and socioeconomic status (SES) using the National Cancer Database (NCDB).Population-based cohort study.Racial and socioeconomic disparities in survival of OPSCC have been previously acknowledged. However, the distribution of HPV-related cancers and its influence on survival in conjunction with race and SES remain unclear.All patients with OPSCC in the NCDB with known HPV status from 2010 to 2016 were included. Differences in presentation, HPV status, treatment, and outcomes were compared along racial and socioeconomic lines. Univariable and multivariable Cox regression survival analyses were performed.In total, 45,940 patients met criteria. Most were male (38,038, 82.8%), older than 60 years (23,456, 51.5%), and white (40,156, 87.4%), and lived in higher median income areas ($48,000, 28,587, 62.2%). Two-thirds were HPV positive (31,007, 67.5%). HPV-negative disease was significantly more common in lower SES ($38,000, 2937, 41.5%,Significant differences in HPV status exist between socioeconomic and racial groups, with HPV-negative disease more common among blacks and lower SES. When controlling for HPV status, race and SES still influence outcomes in oropharyngeal cancers.

To analyze the patterns of care and survival of cutaneous angiosarcomas of the head and neck.Retrospective cohort study.National Cancer Database.The National Cancer Database was queried to select patients with cutaneous angiosarcoma of the head and neck between 2004 and 2015. For survival analysis, patients were included only if they received definitive treatment and complete data. Prognostic factors were analyzed by univariate and multivariable Cox regression.We identified 693 patients diagnosed with head and neck angiosarcomas during the study period. The majority were male (n = 489, 70.6%) and elderly (median, 77 years). A total of 421 patients (60.8%) met the criteria for survival analyses. These patients were treated with surgery and radiation (n = 178, 42.3%), surgery alone (n = 138, 32.8%), triple-modality therapy (n = 48, 11.4%), surgery and chemotherapy (n = 29, 6.9%), and chemoradiation (n = 28, 6.7%). With a median follow-up of 29 months, the 3-year survival was 50.1%. Patients undergoing surgery had better median survival than those who did not (38.1 vs 21.0 months,Angiosarcoma of head and neck is a rare malignancy that affects the elderly. Surgical treatment with negative margins is associated with improved survival. Even with curative-intent multimodality treatment, the survival of patients aged ≥75 years is limited.

Purpose: No standard treatment exists for platinum-refractory, recurrent/metastatic nasopharyngeal cancer (NPC). This phase II study (NCT02605967) evaluated progression-free survival (PFS) of spartalizumab, an antiprogrammed cell death protein-1 (PD-1) monoclonal antibody, versus chemotherapy, in NPC. Patients and Methods: Patients with nonkeratinizing recurrent/metastatic NPC who progressed on/after platinum-based chemotherapy were enrolled. Spartalizumab was dosed 400 mg once every 4 weeks, and chemotherapy was received per investigator's choice. Results: Patients were randomized to receive either spartalizumab (82 patients) or chemotherapy (40 patients). The most common spartalizumab treatment-related adverse events were fatigue (10.3%) and pruritus (9.3%). Median PFS in the spartalizumab arm was 1.9 months versus 6.6 months in the chemotherapy arm (P = 0.915). The overall response rate in the spartalizumab arm was 17.1% versus 35.0% in the chemotherapy arm. Median duration of response was 10.2 versus 5.7 months in the spartalizumab versus chemotherapy arms, respectively. Median overall survival was 25.2 and 15.5 months in the spartalizumab and chemotherapy arms, respectively. Tumor RNA sequencing showed a correlation between response to spartalizumab and IFNγ, LAG-3, and TIM-3 gene expression. Conclusions: Spartalizumab demonstrated a safety profile consistent with other anti–PD-1 antibodies. The primary endpoint of median PFS was not met; however, median overall survival and median duration of response were longer with spartalizumab compared with chemotherapy.

Background: Patients with head and neck cancer (HNC) experience painful, debilitating symptoms and functional limitations that can interrupt cancer treatment, and decrease their health-related quality of life (HRQoL). The Electronic Patient Visit Assessment (ePVA) for head and neck is a web-based mHealth patient-reported measure that asks questions about 21 categories of symptoms and functional limitations common to HNC. This article presents the development and usefulness of the ePVA as a clinical support tool for real-time interventions for patient-reported symptoms and functional limitations in HNC. Methods: Between January 2018 and August 2019, 75 participants were enrolled in a clinical usefulness study of the ePVA. Upon signing informed consent, participants completed the ePVA and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) general (C30) questionnaire v3.0 (scores range from 0 to 100 with 100 representing best HRQoL). Clinical usefulness of the ePVA was defined as demonstration of reliability, convergent validity with HRQoL, and acceptability of the ePVA (i.e., >70% of eligible participants complete the ePVA at two or more visits and >70% of ePVA reports are read by providers). Formal focus group discussions with the interdisciplinary teamthat cared for patients with HNC guided the development of the ePVA as a clinical support tool. Qualitative and quantitative methods were used throughout the study. Descriptive statistics consisting of means and frequencies, Pearson correlation coefficient, and Student���s t-tests were calculated using SAS 9.4 and STATA. Results: The participants were primarily male (71%), White (76%), diagnosed with oropharyngeal or oralcavity cancers (53%), and undergoing treatment for HNC (69%). Data analyses supported the reliability (alpha =0.85), convergent validity with HRQoL scores, and acceptability of the ePVA. Participants with the highest number of symptoms and functional limitations reported significantly worse HRQoL (sumof symptoms: r=���0.50, P

OBJECTIVES The role of locoregional radiotherapy for metastatic oropharyngeal squamous cell cancer (OPSCC) is unclear. We investigated the impact of head and neck radiotherapy on survival in de novo metastatic OPSCC patients who received systemic therapy. METHODS We queried the NCDB from 2004-2015 for metastatic OPSCC patients at diagnosis with known HPV-status who received systemic therapy. The association of head and neck radiotherapy with overall survival was analyzed using the Kaplan-Meier method, Cox proportional hazards model, and propensity score-matched analysis adjusting for demographic and disease-specific prognostic factors. RESULTS Of the 2,139 patients with metastatic OPSCC who presented with metastases and received systemic treatment, we identified 556 patients with known HPV-status. Among these 556 patients, 49% were HPV-positive and 56% received head and neck radiotherapy. With a median follow-up of 17.5 months (IQR 6.0-163.4 months), radiotherapy was associated with significantly improved 1-year OS (67% vs 58%, log-rank P

Objectives/hypothesis To assess patterns of care and outcomes with the use of neoadjuvant chemotherapy followed by definitive radiation in local-regionally advanced nasopharyngeal carcinoma. Study design Retrospective database analysis. Methods We queried the National Cancer Database for patients with T3-4N2 or T1-4N3 nasopharyngeal carcinoma who received concurrent chemoradiotherapy or neoadjuvant chemotherapy followed by radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method, propensity-score matching, and a Cox proportional hazards model adjusting for demographic and disease-specific prognostic factors. Results From 2004 to 2014, a total of 1,731 patients were identified, including 504 patients (27%) who received neoadjuvant chemotherapy. Neoadjuvant chemotherapy was used more frequently in years 2008 to 2010 (34%) and 2011 to 2014 (30%) compared with 2004 to 2007 (22%) (χ2 P = .001). At a median follow-up of 36.6 months, patients had 3-year OS of 66% in the neoadjuvant group compared with 70% in those who received concurrent chemoradiotherapy (log rank P = .29). On subgroup analysis by histology, T stage, and N stage, there remained no differences in OS between the two groups. On multivariable analysis, there was no significant survival difference associated with neoadjuvant chemotherapy (adjusted hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 0.89-1.25, P = .54). In a propensity score-matched population of 1,008 patients (504 with neoadjuvant therapy and 504 without), there was no significant survival difference associated with neoadjuvant chemotherapy (H: 1.13, 95% CI: 0.93-1.38, P = .22). Conclusions Neoadjuvant chemotherapy was used in over 25% of patients, and its use is increasing. However, neoadjuvant chemotherapy was not associated with any differences in survival compared to concurrent chemoradiotherapy. Level of evidence 4 Laryngoscope, 128:2770-2777, 2018.

Purpose/Objective(s) Lacrimal gland cancer is a rare tumor with little data regarding outcomes and optimal management. We performed a large database analysis using the National Cancer Database (NCDB) to elucidate patterns of care and outcomes for this rare malignancy. Materials/Methods Patients with lacrimal gland cancer diagnosed between 2004 and 2016 were included in analysis. All histologies were included with the exception of malignant melanoma and lymphoma; squamous cell carcinoma was also excluded as it is rarely found in the lacrimal gland, and likely reflects lacrimal duct or sac cancer. Patients without recorded follow up or with less than 6 months of follow up were excluded. Patients were stratified by sex, age, race, Charlson-Deyo comorbidity score, facility type, and pathologic T stage. Patterns of care including treatment with surgery, chemotherapy and/or radiation therapy were noted. Outcomes were analyzed using Kaplan-Meier analysis, and Cox proportional hazards regression was used to study the effect of surgery and radiation therapy on overall survival. Results 460 patients with lacrimal gland cancer were included in the database. Median follow up for all patients was 42.7 months. The most common histology was adenoid cystic carcinoma (185 patients, 40.2%), followed by adenocarcinoma (85, 18.5%). Most patients were of unknown T stage (63.9%). 362 patients (78.7%) underwent surgical resection, 104 (22.6%) received chemotherapy, and 292 (63.5%) underwent radiotherapy. Median overall survival for all patients was 106.8 months (95% CI: 85.3 months - not reached). Variables associated with worse overall survival on univariate analysis included age over 60 (P Conclusion The ideal management for lacrimal gland cancer is still unknown due to the rarity of this tumor. Retrospective study of a large national database suggests that patients who undergo surgical resection may have better outcomes than those who do not, although a benefit for radiotherapy is not apparent. Further data collection is required for this unusual tumor.

Background Unilateral radiotherapy (RT) of oropharyngeal carcinomas is accepted for patients with lateralized primary and low-volume nodal disease. Utilizing prospectively defined criteria of laterality and staging positron emission tomography (PET)/CT, we studied outcomes in patients with advanced-stage oropharyngeal cancer undergoing unilateral RT. Methods Thirty-seven patients with oropharyngeal tumors >1 cm from midline regardless of node status underwent unilateral RT and were followed prospectively. Patient characteristics: T1 = 11; T2 = 22; T3 = 4; N0 = 3; N1 = 9; N2a = 3; N2b = 21; and Nx = 1. Dosimetry were determined and weekly National Comprehensive Cancer Network (NCCN) distress thermometer data were collected. Results At median follow-up of 32 months, 3-year locoregional control, contralateral regional failure, distant metastasis-free survival, and disease-free survival were 96%, 0%, 7%, and 93%, respectively. Conclusion Low rates of contralateral neck failure are demonstrated utilizing prospectively defined criteria for unilateral RT. The tolerances of contralateral organs are respected and patients report low to moderate levels of distress throughout treatment.

OBJECTIVE To investigate and improve compliance of thyroid function monitoring in head and neck cancer patients who received radiotherapy to the cervical region before and after instituting quality improvement interventions. METHODS Using the Plan, Do, Study, Act (PDSA) methodology, patients with head and neck malignancies who received radiotherapy to the cervical region from 2013-2015 were identified at a tertiary medical center. The status of the patients' thyroid monitoring and related characteristics were recorded. A quality improvement project was subsequently implemented by data sharing and providing feedback to practitioners involved in head and neck cancer care and creating a tracking database for all patients who received radiotherapy to the neck. After implementation of these interventions, data was collected on patients meeting the inclusion criteria from 2015-2017. RESULTS One hundred fifty-six patients met criteria pre-intervention and ninety-eight patients met criteria post-intervention. Compliance of thyroid monitoring went up from 34% to 80% after interventions (P

Background: Research on the patterns of use of medical cannabis among cancer patients is lacking. Objective: To describe patterns of medical cannabis use by patients with cancer, and how patterns differ from patients without cancer. Design/Measurements: We performed secondary data analysis using data from a medical cannabis licensee in New York State, analyzing demographic information, qualifying conditions, and symptoms, and the medical cannabis product used, including tetrahydrocannabinol (THC) to cannabidiol (CBD) ratios. Setting/Subjects: Adults age ≥18 who used New York State medical cannabis licensee products between January 2016 and December 2017. Results: There were a total of 11,590 individuals with 1990 (17.2%) having cancer who used at least one cannabis product. Patients with cancer using cannabis were older and more likely to be female. The most common qualifying symptom for both cancer and noncancer patients was severe or chronic pain. Cancer patients were more likely to use the sublingual tincture form of cannabis (n = 1098, 55.2%), while noncancer patients were more likely to use the vaporization form (n = 4222, 44.0%). Over time, across all patients, there was an increase in the THC daily dose by a factor of 0.20 mg/week, yielding a corresponding increase in the THC:CBD daily ratio. Compared with noncancer patients, these trends were not different in the cancer group for THC daily dose, but there were less pronounced increases in the THC:CBD daily ratio over time among cancer patients. Conclusions: Our study found some key differences in demographics and medical cannabis product use between patients with cancer and without cancer.

Background: Annually, over 65,000 persons are diagnosed with head and neck cancer in the United States. During treatment, up to 50% of patients become severely symptomatic with pain, fatigue, mouth sores, and inability to eat. Long term complications are lymphedema, fibrosis, dysphagia, and musculoskeletal impairment. Patients��� ability to perform daily activities and to interact socially may be impaired, resulting in poor quality of life. A pragmatic, clinically useful assessment is needed to ensure early detection and intervention for patients to report symptoms and functional limitations over time. We developed the Electronic Patient Visit Assessment (ePVA) that enables patients to report 42 symptoms related to head and neck cancer and 17 limitations of functional status. This manuscript reports (I) the development of the ePVA, (II) the content validity of the ePVA, and (III) the usability and reliability of the ePVA. Methods: Usability was evaluated using the ���Think Aloud��� technique to guide the iterative process to refine the ePVA based on participants��� evaluations. After signing the informed consent, 30 participants with head and neck cancer completed the ePVA using digital tablet devices while thinking aloud about ease of use. All patient conversations were recorded and professionally transcribed. Reliability of the ePVA symptom and functional limitation measures was estimated using the Kuder-Richardson test. Convergent validity of the ePVA was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global QoL/health scale. Transcribed qualitative data were analyzed using directed content analysis approach. Quantitative analyses consisted of descriptive statistics and correlation analyses. Results: Among participants, 90% strongly agreed or agreed that the ePVA system was easy to use and 80% were very satisfied. Only minor usability problems were reported due to formatting and software ���bugs���. Reporting of usability problems decreased in frequency over the study period and no usability problems were reported by the last 3 participants who completed the ePVA. Based on participants��� suggestions during the iterative process, refinement of the ePVA included increased touch sensitivity of the touch screen technology and customized error messages to improve ease of use. The ePVA also recorded patient reported symptoms (mouth symptoms: 93%, fibrosis: 60%, fatigue: 60%). The ePVA demonstrated acceptable reliability (alpha =0.82���0.85) and convergent validity (ePVA total number of reported symptoms and function limitations was negatively correlated with EORTC QLQ-C30 global QOL/health scale: r=���0.55038, P

BACKGROUND Cancer is prevalent in the rapidly growing Chinese American community, yet little is known about the symptom experience to guide comprehensive treatment planning. This study evaluated symptom prevalence and patient subgroups with symptom distress in a large sample of Chinese American cancer patients. METHODS Patients were consecutively recruited from 4 oncology practices, and they completed a translated cancer symptom scale. Latent class cluster analysis was used to identify subgroups of patients with distinct symptom distress profiles. RESULTS There were 1436 patients screened; 94.4% were non–English-speaking, and 45.1% were undergoing cancer therapy. The cancers included breast (32.6%), lung (14.8%), head and neck (12.5%), and hematologic cancer (10.1%). Overall, 1289 patients (89.8%) had 1 or more symptoms, and 1129 (78.6%) had 2 or more. The most prevalent symptoms were a lack of energy (57.0%), dry mouth (55.6%), feeling sad (49.3%), worrying (47.5%), and difficulty sleeping (46.8%). Symptoms causing “quite a bit” or “very much” distress included difficulty sleeping (37.9%), a lack of appetite (37.2%), feeling nervous (35.8%), pain (35.2%), and worrying (34.0%). Four patient subgroups were identified according to the probability of reporting moderate to high symptom distress: very low physical and psychological symptom distress (49.5%), low physical symptom distress and moderate psychological symptom distress (25.2%), moderate physical and psychological symptom distress (17.4%), and high physical and psychological symptom distress (7.8%). CONCLUSIONS Symptom prevalence is high in community-dwelling Chinese American cancer patients, and nearly half experience severe distress (rated as “quite a bit” or “very much” distressing) from physical symptoms, psychological symptoms, or both. These data have important implications for the development of effective symptom control interventions. Cancer 2015. © 2015 American Cancer Society. Cancer 2015;121:3352–3359. © 2015 American Cancer Society.

PURPOSE: To retrospectively review our single institution experience of patients with tonsillar squamous cell carcinoma. MATERIAL AND METHODS: Between 1999 and 2005, a total of 79 patients were identified. Stage distribution was as follows: stages I-II, III, IVA, and IVB were in 6, 14, 43, and 16 patients, respectively. Sixty-three patients (80%) were male. Median age was 55.5 years. Treatment generally consisted of external beam radiation therapy (RT) (median dose, 70 Gy), concomitant chemotherapy (CCRT) (cisplatin 100 mg/m on days 1, 22, and 43), and neck dissection (ND), and was administered as follows: stages I/II, 6 patients received RT alone; stages III/IVA, 20, 5, and 32 patients received RT alone, CCRT, and CCRT followed by ND, respectively; stage IVB, 9 and 7 patients received CCRT and CCRT plus ND, respectively. RESULTS: After a median follow-up of 56 months (range, 12 to 122 mo), the 5-year local control (LC), regional control (RC), distant control (DC), and overall survival (OS) by stage were as follows: stage I-II 100%, 100%, 100%, 100%; stage III-IVA 98%, 96%, 95%, and 88%; stage IVB 100%, 100%, 69%, and 66%, respectively. Among stage IVB patients, DC was significantly lower (P=0.01) and a trend toward lower OS was noted (P=0.08). Long-term percutaneous endoscopic gastrostomy dependence was noted in 3% of them who had received CCRT. The effect of both chemotherapy and ND on treatment outcomes was analyzed; in stage III/IVA patients treated with or without chemotherapy, LC was 97% and 100% (P=0.43); RC was 92% and 100%(P=0.27); and DC was 91% and 94% (P=0.92), respectively. In stage III/IVA, patients treated with CCRT with or without ND, RC was 100% and 88%, respectively (P=0.087). CONCLUSIONS: Primary radiotherapy with or without CCRT followed by ND provides excellent tumor control with acceptable toxicity in treating squamous cell carcinoma of the tonsil.

Background: GSK3359609 (GSK609) is an inducible T cell co-stimulator (ICOS) agonist antibody and tremelimumab (treme) is a cytotoxic T-lymphocyte-antigen 4 (CTLA-4) antagonist antibody. Nonclinical and clinical studies have shown that ICOS expression on T cells is upregulated after anti-CTLA-4 treatment (tx). ICOS+ T cells have a positive association with overall survival (OS) in treme treated chemotherapy-resistant malignant mesothelioma and melanoma patients (pts). Therefore, the combination of these 2 drugs may provide greater antitumoral response than either drug alone (Coutzac C: AACR 2019 meeting abstract). Methods: This is a Phase I/II, open-label, 2-part study. In Part 1, N=~24 pts will be enrolled. The study is designed to assess treme starting at 75 mg followed by GSK609 starting at 8 mg. At dose level (DL) 1, one pt who will receive the lowest doses of both drugs will be enrolled. If no dose limiting toxicity (DLT) is observed in the DLT observation period of 28 days, then 1-3 pts will be enrolled in DL2 - DL6 in a zone-based fashion (zones include the DLs with the next highest dose of one of the two drugs - 2DL are included in each zone in this study) with different dose combinations of the drugs being evaluated. The dose of 1 of the 2 drugs will be escalated with each new DL up to the highest dose of each. If ≥ grade 2 tx-related AEs occur at DL1 or 2, additional pts will be enrolled to collect more safety information. If DLTs are observed, the bivariate Continual Reassessment Method (CRM) model will be used to guide dose recommendations. The primary objective of Part 1 will be to assess safety. Additional pts may be enrolled in Part 1 to further evaluate pharmacokinetics/pharmacodynamics (PK/PD). Part 2 is a randomized expansion enrolling recurrent/metastatic head and neck squamous cell carcinoma pts who have disease progression after platinum chemotherapy and anti-programmed death receptor protein-1 (PD-1)/anti-programmed death-ligand 1 (PD-L1) therapy, in combination or separately. Pts may not have had ≥4 lines of prior tx in either Part 1 or 2. In Part 2, pts will be randomized 2:1 to the doses of GSK609 and treme (n=60) selected from Part 1 or to the Investigator’s choice of SOC single-agent therapy (paclitaxel, docetaxel or cetuximab) (n=30). The primary objective in Part 2 is to evaluate overall survival and the primary analysis is to perform Bayesian predictive probability of success for a future hypothetical Phase III study based on survival data. Secondary endpoints include safety, ORR, PFS, DOR, and PK while pharmacodynamic and other biomarker analyses constitute exploratory endpoints. Pts will be treated for up to 2 years with survival follow-up for up to 2 years post-tx. This study has enrolled 1 pt. Study NCT03693612 funded by GSK. Citation Format: Aaron Hansen, Raghad Abdul-Karim, Naiyer Rizvi, Danny Rischen, John Hilton, Zujun Li, Patrick Ott, Natalie Karpinich-Fedoriw, Sapna Yadavilli, Xiaowei Wang, Laurel Adams, Melody Wyres, Charles Ferte, Marc Ballas, Axel Hoos, Daniel Zandberg. A Phase I/II, open-label, two part study of GSK3359609 in combination with tremelimumab in participants with selected, advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT166.

Background: There is currently no standard treatment for patients (pts) with platinum refractory, recurrent metastatic (R/M) NPC. Spartalizumab, a humanized anti-PD-1 IgG4 mAb, blocks interaction with PD-L1 and PD-L2. This is the first randomized phase II study to evaluate efficacy and safety of spartalizumab vs CT in NPC. Methods: This phase II open-label study recruited pts with non-keratinizing locally advanced R/M NPC who progressed on/after platinum-based CT and received up to 2 systemic therapies. Pts were randomized (2:1) to receive spartalizumab or CT, per investigator’s choice. Spartalizumab was dosed 400 mg every 4 weeks intravenously. Pts in CT arm could cross over to receive spartalizumab if progression confirmed by RECIST v1.1, based on independent central review. Primary endpoint was progression free survival (PFS); secondary endpoints were overall response rate (ORR), based on central review by RECIST v1.1, duration of response (DOR), overall survival, safety and pharmacokinetics. Correlation between efficacy and expression of immunologic biomarkers and immune-related genes was also studied. Results: In total, 76 pts in spartalizumab arm and 37 pts in CT arm were randomized (median age 51 years, ECOG performance status 0-2). As of Jan 31, 2018, 18/76 (23.7%) spartalizumab-treated pts, 8/37 (21.6%) CT-treated pts and 4/20 (20.0%) pts in crossover group were ongoing. Discontinuation rates were similar between arms, mainly due to progressive disease in spartalizumab arm (67.0%) and CT arm (68.0%). Median PFS (95% CI) was 1.9 mo (1.8;3.5) in spartalizumab arm vs 6.6 mo (3.7;9.2) in CT arm; primary endpoint was not met, with hazard ratio of 1.53 (95% CI 1.02;2.27). ORR (95% CI) was 18.4% (10.5;29.0) vs 32.4% (18.0;49.8) in spartalizumab vs CT arm, respectively, and 5.0% (0.1;24.9) in crossover group. ORR for pts treated with monotherapy CT was 19.2% (5/26) and for pts treated with CT doublet/triplet was 63.3% (7/11). The Kaplan-Meier estimate of DOR rate at 12 mo in responding spartalizumab-treated pts was 61.0% (95% CI 20.2;85.8). In CT arm, 11/12 pts either progressed or discontinued at 12 mo; at data cut-off, 1 pt remained responding for 3.61 mo. Safety profile of spartalizumab was largely consistent with results obtained from other spartalizumab single-agent studies. Overall, treatment-related grade 3/4 adverse events were reported in 18.4% of spartalizumab-treated pts and 40.5% of CT-treated pts. No treatment-related deaths occurred. RNA sequencing analyses of tumors revealed a correlation between response to spartalizumab and IFN-γ signature, TIM3 and LAG3 gene expression; this correlation was not observed in pts treated with CT. Conclusions: Spartalizumab was well tolerated and despite the study not reaching its primary endpoint, long-lasting tumor responses were observed in a subset of spartalizumab-treated pts with NPC. Biomarker analysis is ongoing. Citation Format: Darren Wan-Teck Lim, Hung-Ming Wang, Shau-Hsuan Li, Roger Ngan, Arunee Dechaphunkul, Li Zhang, Chia Jui Yen, Po Chung Chan, Somvilai Chakrabandhu, Brigette Ma, Suebpong Tanasanvimon, Victor Lee, Pei-Jen Lou, Zujun Li, Alexander Spira, Ammar Sukari, Joël Guigay, Steven McCune, Yongjian Sun, Sebastian Szpakowski, Yao Yao, Xueqiang Fan, Luigi Manenti, Caroline Even. Phase II study of spartalizumab (PDR001) vs chemotherapy (CT) in patients with recurrent/metastatic nasopharyngeal cancer (NPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT150.

Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive malignancy with optimal management remains unclear. We performed a review of the impact of trimodality approach on SNUC outcome.This is a single-institution retrospective study of 18 patients, who were managed between 1997 and 2009. The median age at presentation was 52 years (28 to 82). Nine patients (50%) were female. Three patients had stage II disease and underwent surgery alone, 12 had stages III and IVa and underwent surgery combined with chemoradiation, and 3 had stage IVb and underwent definitive chemoradiation. Patients who underwent preoperative, postoperative, and definitive chemoradiation received 60, 66, and 70 Gy of radiation, respectively. In all patients receiving concurrent chemoradiation, cisplatin was used, at a dose of 100 mg/m every 3 weeks for 3 cycles. Neoadjuvant chemotherapy included docetaxel, cisplatin, and 5-fluorouracil (TPF) every 3 weeks for 2 to 3 cycles.After a median follow-up of 26 months (16 to 120), a total of 8 patients (44%) have experienced the following: 1 persistent disease (5.5%), 4 local failure (22%), and 3 distant metastases (DM, 16.5%). Five of the 8 patients had preexisting cranial nerve deficits or gross cranial invasion. The 2-, 3-, and 4-year local control (LC), disease-free survival (DFS), and overall survival (OS) were 78%, 72%, and 56%; 75%, 65%, and 52%; and 75%, 50%, and 48%, respectively. Trimodality approach provided 83% LC and 92% DM-free survival, whereas other modalities provided 50% LC and 33% DM-free survival. The causes of death for the entire cohort were DM and local invasion. Acute chemoradiotherapy toxicity was 100% grades 1 and 2 dermatitis, mucositis, and fatigue, 55% developed grades 1 and 2 dysphagia, and 6% had grade 3 mucositis. Long-term toxicity was 28% grade 1 xerostomia, 11% retinopathy and optic neuropathy, and 6% orbital exenteration and grade 3 peripheral neuropathy.SNUC is an aggressive neoplasm that frequently presents at an advanced stage. Our data show that trimodality approach in the form of surgery combined with chemoradiation seems to offer better LC and lower DM compared with other modalities.

Purpose Squamous cell carcinoma of unknown primary (SCCHNUP) is commonly treated with comprehensive radiation to the laryngopharynx and bilateral necks. In 1998, we established a departmental policy to treat SCCHNUP with radiation directed to the oropharynx and bilateral neck. Methods From 1998–2011, 60 patients were treated – N1: 18%, N2: 75% and N3: 7%. 82% underwent neck dissection. 55% received IMRT and 62% underwent concurrent chemoradiotherapy. Results At median follow-up of 54 months, 5 patients failed regionally and 4 emerged with a primary (tongue base, hypopharynx and thoracic esophagus). Five-year rates of regional control, primary emergence, distant metastasis, disease-free survival and overall survival were 90%, 10%, 20%, 72% and 79%, respectively. The 5 year rate of primary emergence in a non-oropharynx site was 3%. Conclusion This is the first demonstration that an oropharynx-directed approach yields low rates of primary emergence in SCCHNUP with excellent oncologic outcomes.

While intensive chemotherapy is recommended for the treatment of non-HIV related adult small non-cleaved lymphoma (SNCL), including Burkitt's and Burkitt-like lymphoma, optimal treatment for patients with HIV-associated SNCL is not known. We assessed remissions and survival in a cohort of 44 consecutive HIV positive patients diagnosed with SNCL at our hospital between June 2000 and November 2001 using chart and pathology data. Median follow-up, survival and survival at the median follow-up time were 4.5 months, 4 months and 49% respectively. Of this cohort 39% were complete responders (CR) and 36% were long-term lymphoma-free survivors. Two patients relapsed from CR. Short course intensive chemotherapy (McMaster) was administered to 23 patients; 17 received less intensive conventional combination chemotherapy; and four received single-agent chemotherapy or no treatment. In the McMaster group, 38% (9/23) achieved CR with no relapses. Seven patients (30%) died of toxicity compared with one (6%) in the less intensively treated group. Of the stage I patients, 75% (6/8) achieved long-term CR with half being treated conventionally. Conventional chemotherapy may be curative for early stage HIV-SNCL. In advanced disease, McMaster chemotherapy was found to be associated with substantial early mortality but was curative in a significant number of patients.

Waldenström's macroglobulinaemia is a rare B-cell malignancy. It is prevalent in the sixth and seventh decades, the median age at diagnosis being 63 years. Conventional treatment has involved alkylator therapy, especially chlorambucil given daily at a low dose or intermittently at a higher dose. Purine analogues, used initially as salvage therapy in refractory disease, are increasingly used for initial therapy. However, purine analogue therapy entails significant complications, including immunosuppression, pancytopenia and autoimmune haemolysis. Moreover, it is unclear whether purine analogues extend survival. All of these need to be considered before initiation of therapy. More recently, anti-CD20 monoclonal antibody and thalidomide have been used with a 30% response in treated patients. High-dose therapy with stem cell support achieves a partial response in a majority of patients receiving this modality of therapy. The median survival of 5 years has not improved considerably since the introduction of purine analogues. Complete response is still uncommon; using all available modalities of therapy may increase the complete response rate and improve survival. Great strides in understanding the malignant cell, the microenvironment and the potential interactions have identified potential targets for therapy in multiple myeloma. These agents may also be useful in Waldenström's macroglobulinaemia. Since this is a rare malignancy, all patients should be treated with well-designed clinical protocols to achieve improvement in outcome.

Targeted therapies have proven beneficial for patients suffering from a number of different malignancies, including cancers of the head and neck. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor has shown benefit in combination with radiation for untreated patients or as a single agent for patients with platinum resistant disease. Cetuximab is the only targeted agent currently approved by the Federal Drug Administration for the treatment of head and neck cancer. A number of other agents have shown promising initial results including intracellular tyrosine kinase inhibitors, agents targeting vascular endothelial growth factor receptor, as well as other classes of novel therapies. Some of the data supporting the use of targeted therapy, including agents not yet approved in head and neck cancer, will be presented in this review. As our understanding of the cancer cell signaling pathways and novel targeted agents increases, the potential for treatment with reduced toxicity and improved clinical outcomes will become a reality.

Lung cancer is the leading cause of cancer deaths world-wide. Recent advances in cancer biology have led to the identification of new targets in neoplastic cells and the development of novel targeted therapies. At this time, two targeted agents are approved by the FDA in advanced non-small cell lung cancer (NSCLC): the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib, and the anitangiogenic bevacizumab. A third agent, cetuximab, which was recently shown to enhance survival when used with cisplatin and vinorelbine as first line therapy for advanced NSCLC, will likely be approved by regulatory agencies. With more than 500 molecularly targeted agents under development, the prospects of identifying novel therapies that benefit individual patients with lung cancer are bright.

27 Background: Cancer is prevalent in the rapidly-growing Chinese-American community, yet little is known about symptom burden to guide comprehensive treatment planning. We evaluated symptom distress and symptom clusters in a large sample of Chinese-American patients with cancer. Methods: Patients were consecutively recruited from four oncology practices and completed a translated cancer symptom scale. Latent class cluster analysis explored symptom distress clusters in patients. Results: Of 1,436 patients screened, 94.4% were non-English speaking and 45.1% were undergoing active cancer therapy. The most common cancer sites were breast (32.6%), lung (14.8%), head and neck (12.5%), and hematologic (10.1%). Overall, 1,289 (89.8%) patients had > 1 symptom and 1,129 (78.6%) patients had > 2. The most prevalent symptoms were lack of energy (57.0%), dry mouth (55.6%), feeling sad (49.3%), worrying (47.5%), and difficulty sleeping (46.8%). Symptoms causing “quite a bit” or “very much” distress included: difficulty sleeping (37.9%), lack of appetite (37.2%), feeling nervous (35.8%), pain (35.2%), and worrying (34.0%). Four symptom distress clusters were identified: very low physical and psychological symptom distress (49.5%); very low physical and moderate psychological symptom distress (25.2%); moderate physical and psychological symptom distress (17.4%), and high physical and psychological symptom distress (7.8%). Patients in the last group reported lack of energy, difficulty sleeping, pain, feeling sad, and worrying. Conclusions: Symptom prevalence is high in community-dwelling, Chinese-American cancer patients and half experience moderate to high distress from clusters of physical symptoms, psychological symptoms, or both. These data have important implications for the development of effective interventions for symptom control.

Phase 1 Clinical Trial of Re-irradiation With Pemetrexed and Erlotinib Followed by Maintenance Erlotinib for Patients With Recurrent and Second Primary Squamous Cell Carcinoma of the Head and Neck Management of Recurrent Head-and-Neck Squamous Cell Carcinoma M. Porosnicu, K.M. Greven, C.A. Sullivan, J.D. Waltonen, R. Plasser Rouchard, and J.D. Browne; Wake Forest University School of Medicine, Winston-Salem, NC

Purpose/Objective(s): To study the volumetric changes in constrictor muscles during head and neck radiation therapy and to measure their impact on acute dysphagia. Materials/Methods: Data from prospective adaptive radiation therapy trial in oropharyngeal cancer was analyzed for the volumetric and dosimetric parameters related to constrictor muscles using DVH data in Pinnacle TPS. All patients underwent replanning CT scans after 5 weeks of radiation therapy and the target and OARs were re contoured on fusion images after co-registration using Syntegra software. The volumetric variations were measured and compared with acute dysphagia during RT recorded in terms of RTOG acute morbidity score. Also, the Dmax to constrictors prior to replanning were analyzed for any significant association to severity of dysphagia. Statistical analysis was done in SPSS ver.20. Results: 30 patients of oropharyngeal cancers were included in the study. Median age was 50yrs (35-65). 65% received concurrent chemotherapy (mean cumulative dose: 350 mg). There was significant increase in the volumes of constrictors after 5 weeks of RT (44Gy) by 12% in superior, 2% in middle and 5% in inferior constrictors respectively. Grade 2/3 acute dysphagia was 40% and G1/0 was 60%. 20% of patients required nasogastric feeding tube placement. The volume changes in middle constrictor were significantly associated with higher incidence of Grade 2/3 acute dysphagia (pZ0.006). No such association was seen with volumetric changes in superior or inferior constrictors. The Dmax was significantly different between different constrictors (pZ0.00) with middle constrictors getting highest median Dmax of 48 Gy. There was significant association of D max of inferior constrictor muscles with Grade 2/3 acute dysphagia (pZ0.02) and trend towards significant association in case of superior and middle constrictors (p Z0.08). No association of chemotherapy dose to dysphagia was noted (pZNS) but there was higher dysphagia rates in chemotherapy versus non concurrent chemotherapy patients (pZ0.00). Conclusions: There is significant increase in volumes of superior, middle and inferior constrictors during head and neck radiation therapy. This may be due to RT induced edema and superadded infections. Increase in middle constrictor volume is associated with severe dysphagia in oropharyngeal cancers. Higher dose to constrictor muscles can lead onto severe acute dysphagia. Hence, sparing of constrictors should be considered during radiation therapy planning in head and neck cancer. Author Disclosure: M.K. Sujith: None. M.A. Laviraj: None. T. Bindu: None. B.K. Mohanti: None. G.K. Rath: None.

e17030 Background: Patients undergoing concomitant chemoradiotherapy may or may not undergo prophylactic PEG placement, depending on baseline weight, medical status and presence of dysphagia. We examined quality of life, performance status and oral outcomes in patients with or without PEG at baseline and 3 months post-treatment. Methods: Thirty-three patients with head and neck cancer were treated with chemoradiotherapy. All were seen baseline and 3 months post-tx. Assessments included the Performance Status Scale (PSS), Karnofsky Performance Status Scale (KPSS), tongue strength, jaw opening, and saliva weight. Patient-rated QOL utilized the MD Anderson Dysphagia Inventory (MDADI) and Eating Assessment Tool (EAT-10) with significance at p

6091 Background: Many head and neck cancer patients suffer from side effects of chemoradiotherapy that can result in reduced oral intake, and weight loss. To prevent this malnutrition they often undergo preventative percutaneous endoscopic gastrostomy (PEG) placement. We aim to determine whether PEG placement is necessary for successful patient performace during treatment. Methods: We compared 2 groups: patients that underwent PEG (Gp-1=P) (n=20), and those that did not undergo PEG (GP-2=NP) (n=47). All patients were treated with chemoradiotherapy. All were assessed at baseline (BL), and wk 5 of tx. WHO variables including weight loss, mucositis, dysphagia, and odynophagia ratings, along with patient-rated modified “distress thermometers”, were analyzed. Results: Patients with no PEGs had higher weights at BL (NP=193 vs P= 171, p=0.073) and at wk 5 (NP=179 vs P= 160, p=0.056). Weight loss in these groups were 8.09 % - P (p=0.000), 8.25% - NP (p=0.000) respectively from BL - wk 5. The median distress level of each group was 0-P and 1-NP at BL (p=0.302) and 6-P and 3-NP at wk 5 (p=0.086). 27 patients had a distress level of > = 4 at wk 5. Of these 27, 12 were PEG’d and 15 were not (p=0.008). 86 % of patients in the PEG group had distress >=4 and 44 % in the NP group had distress levels >=4. Patients that underwent PEG had slightly higher odds (NS) of associating their distress to nausea, fatigue and/or eating than patients that were not PEG’d. The wk 5 WHO toxicity scale assessment showed 15 PEG’d patients had Grade 1 (n=5), Grade 2 (n=9) & Grade 3 (n=1) dysphagia and 28 NP patients had Grade 1 (n=23) & Grade 2 (n=5) dysphagia (CHI square =11.66, p=0.009). Conclusions: Patients that underwent PEG placement before or during treatment performed worse in every assessment (weight loss, distress thermometer & toxicity scale) as compared to the no PEG group. Patients who have a normal or above average BMI are candidates to be monitored for PEG placement. However, both groups examined were able to complete treatment without significant treatment breaks. Close multidisciplinary monitoring and more intensive supportive care are needed when determining need for PEG placement during treatment.

5559 Background: OP of HNSCC is commonly treated with comprehensive mucosal RT including nasopharynx, OPX, hypopharynx and larynx and bilateral neck. We are reporting the long term outcomes of a conservative mucosal sparing technique consisting of targeting only the OPX mucosa and bilateral necks. Methods: This is a single-institution retrospective study. From January 1998-2010, a total of 68 patients with OP of HNSCC were treated with CCRT (90%) or RT alone (10%), 40% with IMRT. RT fields comprehended OPX mucosa only and bilateral necks. Gross disease in the neck received 70Gy, involved neck 63 Gy, OPX 60 Gy, uninvolved neck and ipsilateral retropharyngeal nodes 54 Gy. All fractions were given at the rate of 1.8-2 Gy/fraction. The median age was 58 (21-87), 80% Caucasian, and 75% males. Stage IVa (N2) was 75% of the population, while stages III (N1), and IVb (N3) were 9, and 16% respectively. 16 patients (9N3+7 bulky N2) underwent neck dissection (ND). The median time interval from diagnosis to RT and RT duration were 60 (13-70) and 50 days (49-63) respectively. The Median number of Chemotherapy cycles was 2 (1-3). Cisplatin was given to 70% of pts, while Carboplatin and Cetuximab were 10 and 20% respectively. Results: With a median follow-up of 5.3 years (1– 13.6), the loco-regional control, (LRC) for all stages is 95.6 %. The median time to LRF is 18 months (12 - 63). Chronic CCRT toxicity was; grade (1) xerostomia (67%), dysphagia (35%), altered taste (28%), neck stiffness (15%), skin toxicity (12%), dysphonia (9%), and trismus (6%). One HIV patient developed grade 4 dysphagia. No patients experienced distant metastases. The emergence of primary was (1.5%) 1 patient developed subglottic SCC 2 years after CCRT, 2 patients failed in the neck (originally N3) all the 3 patients were salvaged successfully by surgery. Kaplan-Meier curve shows the 5-year cause-specific survival to be 100. Conclusions: Our data show that CCRT or definitive RT alone to the OPX and bilateral neck provides excellent oncologic and functional outcomes. Sparing the mucosal surfaces of the nasopharynx, hypopharynx, and larynx seems reasonable and likely reduces toxicity.

5581 Background: To report the role of PORT in the management of PGM and to analyze the prognostic factors for optimal locoregional (LRC) and distant control (DC) Methods: This is a single institution retrospective study. From March 2001-2011, a total of 118 patients with PGM were treated with surgery and PORT (100%) of which 75% were treated with IMRT, 20 and 10% received concurrent carboplatin and CDDP respectively. Indications for PORT were: recurrent or gross residual disease, +ve or close margins, nerve invasion and +ve lymph nodes (LN). PORT fields comprehended parotid bed and ipsilateral neck. Median PORT doses delivered were 70, 63, 54 Gy (at 1.8-2 Gy/fraction) for gross, microscopic disease, and ipsilateral neck respectively. All PORT was delivered via 4-6 MV photons with daily 3-5 mm bolus. The median age was 52 (18-89). Females and Caucasian made up 56% and 64% of the population, respectively. Histologic findings were adenoid cystic carcinoma 20%, mucoepidermoid carcinoma 19%, adenocarcinoma 18%, pleomorphic carcinoma 16%, salivary duct carcinoma 9%, acinic cell carcinoma 8%, ex-pleomorphic carcinoma 7%, and sarcoma 3%. Pathological stages I, II, III, IV were 10, 30, 20 and 40% respectively Results: With a median follow up of 56 months (12-124), the LRC and DC for the whole cohort were 96% (5/118) and 93% (8/118) respectively. The median duration of PORT was 45 days (40-60). The median time to LR failure (LRF) and distant metastases were 16 (12 - 30) and 28 months (24-48) respectively. Late RT toxicity was; grade I xerostomia 30%, altered taste 15%, trismus 6%, dysphagia and neck stiffness 2%. Kaplan-Meier curve shows the 5-year cause-specific survival to be 100%. Chi square and regression analysis tests show significant relationship (P=0.001) between salivary duct ca (70%) and distant metastases (DM), also males are at higher risk (17%) to develop LRF and DM, compared to females (6%). Poor prognostic features for DM and LRF were salivary duct ca, stage IV, PNI, and multiple LN involvement. Conclusions: Our data show that surgery followed by PORT to the tumor bed and ipsilateral neck provide excellent long standing oncologic and functional outcomes. Further studies are warranted to optimize the management of patients at higher risk of DM despite LRC and RT ± chemotherapy administered.

5531 Background: SCCHN with HIV is a challenging clinical situation in the medical arena due to limited data. We report our outcomes and the impact of chemotherapy (CT) and HPV on this patient (pt) population Methods: This is a single institution retrospective study of 71 HIV pts with SCCHN treated from 1998-2011. The median age at RT and HIV diagnosis was 51 (32-72) and 34 (25-50) respectively. HIV duration was 11 yrs (6-20). Stage I-II, III and IV were 22, 27 and 51% respectively. Pts treated with RT alone were 37% and CRT 63% {CDDP 91%}. Fifty pts were on HAART during treatment and 50% of pts with SCC of the oropharynx were HPV+. Median dose of 70, 63 and 54 Gy were delivered at 1.8-2 Gy/fraction to gross disease, high and low risk neck respectively. Twelve pts (17%) underwent neck dissection for N3 Results: With a median follow up of 50 months (12-140) the median weight loss was 20 lbs (6-40). Acute skin desquamation and mucositis grades ≤ 2 and 3 were 76 and 24% respectively. Treatment breaks ≥ 10 and 5 days were 7 and 21% respectively. One pt died from induction CT, 1 was hospitalized for grade 4 mucositis and 1 developed osteoradionecrosis during CRT. Late dysphagia grades ≤ 2, 3 and 4 were 74, 15 and 11%. Late xerostomia grades ≤ 2 and 3 were 77 and 23% respectively. The median CD4 count and viral load before, during and after treatment were 370, 135, 100 and 0, 160, 260 respectively. Seven pts (10%) developed second primary malignancy. The 4 yr locoregional control (LRC) and overall survival (OS) were 69% and 55% respectively. Chi-square test shows significant relationship between LRC and RT duration, as well as between CT and lower CD4 counts and higher viral load (P=0.001). Positive trends were observed between (weight loss ≤10% and LRC) and (absence of second malignancy and OS) (P=0.271). There was no significant relationship between HPV +ve or CT on either LRC or OS. Conclusions: The addition of CT to RT yielded higher morbidity and mortality without clear benefit on LRC or OS. HIV per se seems to have a -ve impact on HPV +ve pts outcomes. Comparing observed rates of LRC and OS, our data show that RT±CT administered for HIV +ve pts with SCCHN appears to be less effective than HIV-ve pts. Larger size studies are warranted to optimize the management of this growing patient population.

Thromboembolic disease is common with an annual incidence of 1–3/1000 individuals. Both acquired and genetic risk factors are responsible. A risk factor for thrombosis can now be identified in over 80 percent of patients. Fifty percent of thrombotic events in patients with inherited thrombophilia are associated with an acquired risk factor. Patients with multiple inherited risk factors are at a greater risk. Two common variations of the MTHFR gene (677CàT and 1298AàC) result in amino acid substitutions and enhanced thermolability of the enzyme. The latter, in the presence of folic acid deficiency, results in elevated homocysteine levels. Thrombosis has been observed in these patients, but there is still controversy whether there is a direct association (Bezemer I, et al. Arch Int Med167, 497–501, 2007; den Heijer M et al. J Thromb Haemost3:292–299, 2005). In the present study, we describe the spectrum of thromboembolic disease observed in 39 patients with a variety of MTHFR polymorphisms referred to a specialty center with a personal or family history of thromboses or obstetrical loss, 18 of these patients having no other risk factor other than MTHFR polymorphisms. These polymorphisms include 18 heterozygotes (11 with 677CàT; 7 with 1298AàC), 9 homozygotes (5 with 677CàT; 4 with 1298AàC) and 12 compound heterozygotes (677CàT and 1298AàC). Concomitant risk factors were found in twenty-one patients (factor V Leiden - 6; prothrombin G20210A - 3; protein C deficiency - 1; protein S deficiency - 1; PAI-1 polymorphism - 2; activated protein C resistance - 2; antiphospholipid antibody syndrome - 5; malignancy - 3; coronary artery disease - 1; hemolytic anemia - 1; factor VIII deficiency - 1). Types of thromboembolic manifestations observed in the 39 patients include venous thromboembolism (22), obstetrical loss (7), arterial thrombosis (3), myocardial infarction (3), ischemic CNS lesions (2), and palpable purpura (1), for a total of 38 manifestations. Seven of the patients had a family history of thromboembolic disease. Patients with only MTHFR polymorphisms suffered 16 types of thromboembolic events (16/38=42%). Our observations suggest that MTHFR polymorphisms alone do play a role in clinically relevant thrombotic disease and probably increase the incidence of these diseases in patients harboring other causes of thrombophilia. Therefore, continuing surveillance for this polymorphism as part of a clinical thrombophilia assessment is recommended, particularly if homocysteine levels are elevated.