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Background: Radiation for patients with head and neck cancer (HNC) is associated with painful mucositis that impacts the delivery of treatment and contributes to high symptom burden. Methods: This was a prospective, randomized pilot trial. Eligible patients received primary or adjuvant chemoradiation. Patients were randomized to usual care vs usual care plus gabapentin titrated to drug tolerance during radiation. Patients completed a symptom survey at baseline and weekly during therapy. Results: Seventy‐nine patients were enrolled in the study (38 control, 41 treatment). At interim analysis, gabapentin use resulted in a decrease in pain (P =.004), with the biggest decreases being in the latter weeks of therapy. By week 7, the median pain score in the treatment group was below the 0.25 quantile of the control group. Conclusion: Prophylactic use of gabapentin during chemoradiation for HNC patients resulted in a decrease in pain, neurosensory symptoms, and general systemic symptoms. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to describe the types of musculoskeletal impairment in head and neck cancer survivors and to evaluate objective and subjective measures of musculoskeletal impairment and identify areas of need in future studies.Methods: This is a cross-sectional pilot study of 29 head and neck cancer patients who were treated with resection and reconstruction. Subjective measures of musculoskeletal impairment (Neck Disability Index, Shoulder Pain and Disability Index, Vanderbilt Head and Neck Symptom Survey, General Symptom Survey) were collected and compared to objective measures (Cervical Range of Motion Device, Inter-incisal Distance). Digital photography was used to assess the severity of postural abnormalities. Findings were summarized using descriptive statistical and graphical methods.Results: The majority of patients in this cohort suffered from neck disability (69%). Thirty-five percent of patients had shoulder pain and disability. Cervical range of motion deficits were observed in all directions. Inter-incisal distance averaged 33.4 mm and inversely correlated with self-reported jaw and trismus symptoms. Digital photography identified shoulder misalignment in 93% of subjects, head tilt in 89% of subjects, and postural deviation in 68% of subjects.Conclusion: Musculoskeletal impairment is a significant side effect in head and neck cancer survivors that results in chronic neck pain, shoulder disability, trismus, and postural deficits. Tools to describe postural deficits are needed. [ABSTRACT FROM AUTHOR]

Background Constitutive activation of nuclear factor κB (NF-κB) is associated with poor prognosis. Irinotecan demonstrates single-agent activity in head and neck cancer but activates NF-κB, promoting cell survival and resistance. Bortezomib is a proteasome inhibitor that inactivates NF-κB. Patients and Methods We performed a randomized phase II trial of bortezomib on days 1, 4, 8, and 11 and irinotecan on days 1 and 8 of each 21-day cycle or single-agent bortezomib on days 1, 4, 8, and 11 on a 21-day cycle. The addition of irinotecan to bortezomib was allowed in patients who progressed on bortezomib alone. Results The response rate of bortezomib and irinotecan was 13%. One patient had a partial response to bortezomib alone (response rate 3%). No responses were seen in patients with addition of irinotecan at time of progression on bortezomib. Conclusions The bortezomib-based regimens evaluated in this study have minimal activity in recurrent or metastatic head and neck cancer. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

Background Lymphedema may disrupt local function and affect quality of life (QOL) in patients with head and neck cancer. The purpose of this study was to examine the associations among severity of internal and external lymphedema, symptoms, functional status, and QOL in patients with head and neck cancer. Methods The sample included 103 patients who were ≥3 months after head and neck cancer treatment. Variables assessed included severity of internal and external lymphedema, physical/psychological symptoms, functional status, and QOL. Results Severity of internal and external lymphedema was associated with physical symptoms and psychological symptoms. Patients with more severe external lymphedema were more likely to have a decrease in neck left/right rotation. The combined effects of external and internal lymphedema severity were associated with hearing impairment and decreased QOL. Conclusions Lymphedema severity correlates with symptom burden, functional status, and QOL in patients after head and neck cancer treatment. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

Background Polymorphism of the serotonin transporter gene, 5-HTTLPR (short allele) has been associated with depression. The purpose of this study was to show the evaluated depression in patients with head and neck cancer and a possible association with the 5-HTTLPR. Methods The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID for DSM-IV) was administered to 94 patients with head and neck cancer, of which 33 patients were genotyped for 5-HTTLPR. We also evaluated the prevalence of 5-HTTLPR polymorphism in 121 patients with head and neck cancer and 97 controls. Results Forty-three percent of the patients met the criteria for a depressive diagnosis, 19% of which was new onset. In depressed patients, 85.7% ( n = 12 of 14) had at least 1 short allele versus 68.4% ( n = 13 of 19) of the patients without depressive diagnosis ( p < .04). No difference was noted in the prevalence of the short allele in head and neck cancer cases versus controls (odds ratio = 0.8; p = .490). Conclusion Despite the high rate of depressive diagnosis, patients with head and neck cancer did not demonstrate a higher prevalence of this short allele of the 5-HTTLPR compared with a control population.© 2011 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

BACKGROUND: This phase 2 trial evaluated the tolerability and clinical efficacy of the combination of oxaliplatin and pemetrexed as an induction chemotherapy regimen in locally advanced head and neck squamous cell carcinoma (HNSCC). METHODS: Forty-two patients were enrolled in the study. Patients received pemetrexed 300 mg/m2 intravenously (IV) and oxaliplatin 85 mg/m2 IV every 14 days for a total of 4 cycles. A subset of patients consented to correlative studies including tumor tissue for human papillomavirus (HPV) detection and expression of DNA repair genes that may be predictive of response or resistance to oxaliplatin or pemetrexed. RESULTS: Response data were available for 40 patients. Eighteen had a partial response, and 1 had a complete response, for a response rate of 47.5%. Patients with HPV+ disease demonstrated superior response rates, progression-free survival, and overall survival. The regimen was well tolerated, with predominantly grade 1 or 2 alanine aminotransferase/aspartate aminotransferase elevation. One patient had grade 5 toxicity with neutropenia and sepsis. The authors did not identify genes predictive of response or toxicity, although HPV+ tumors demonstrated a unique gene expression signature. CONCLUSIONS: Although the response rate of oxaliplatin and pemetrexed proved less than anticipated, the combination remains an active induction regimen in HNSCC. This regimen should be evaluated further in combination with targeted agents, such as cetuximab, especially in the HPV+ patient population. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that chronic inhibition of epidermal growth factor receptor (EGFR) by cetuximab, a monoclonal anti-EGFR antibody, induces up-regulation of its ligands resulting in resistance and that microRNAs (miRs) play an important role in the ligand regulation in head and neck squamous cell carcinoma (HNSCC). Methodology/Principal Findings: Genome-wide changes in gene and miR expression were determined in cetuximab-sensitive cell line, SCC1, and its resistant derivative 1Cc8 using DNA microarrays and RT-PCR. The effects of differentially expressed EGFR ligands and miRs were examined by MTS, colony formation, ELISA, and western blot assays. Heparin-binding EGF-like growth factor (HB-EGF) and its regulator, miR-212, were differentially expressed with statistical significance when SCC1 and 1Cc8 were compared for gene and miR expression. Stimulation with HB-EGF induced cetuximab resistance in sensitive cell lines. Inhibition of HB-EGF and the addition of miR-212 mimic induced cetuximab sensitivity in resistant cell lines. MicroRNA-212 and HB-EGF expression were inversely correlated in an additional 33 HNSCC and keratinocyte cell lines. Six tumors and 46 plasma samples from HNSCC patients were examined for HB-EGF levels. HB-EGF plasma levels were lower in newly diagnosed HNSCC patients when compared to patients with recurrent disease. Conclusions/Significance: Increased expression of HB-EGF due to down-regulation of miR-212 is a possible mechanism of cetuximab resistance. The combination of EGFR ligand inhibitors or miR modulators with cetuximab may improve the clinical outcome of cetuximab therapy in HNSCC. [ABSTRACT FROM AUTHOR]

Background. We describe the development and validation of the Vanderbilt Head and Neck Symptom Survey (VHNSS), which was designed to screen for tumor- and treatment-specific symptoms in patients with head and neck cancer undergoing concurrent chemoradiation (CCR). Methods. Using a 2-step card sort method, we identified high-impact and high-frequency toxicities in patients with head and neck cancer treated with CCR. This resulted in a 28-item questionnaire which scores symptoms on a 0 to 10 scale (none to severe). The tool was validated using data collected from 5 supportive care studies comprising a total sample of 332 patients with head and neck cancer. Results. Responses to the VHNSS items demonstrated a very consistent pattern (Cronbach's alpha = 0.943) with each item contributing substantially to the global index. Five symptom subscales were identified including “Nutrition,” “Pain,” “Voice,” “Swallow,” and “Mucous/Dry Mouth.” Each of the cluster scores demonstrated good internal consistency. The pattern of associations between the VHNSS and established tools indicated appropriate convergence and divergence. Comparison of global and subscale scores and objective measure were also in the expected direction providing further evidence of validity. Conclusions. The findings provide support that the VHNSS is a valid and reliable tool to assess head and neck–specific symptom burden and function loss. Further research to evaluate this screening tool as a part of a systems approach to supportive care is warranted. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

Purpose: Lymphedema and fibrosis (LEF) are common yet overlooked late effects of head and neck cancer and its therapy. Lack of reliable and valid measures of head and neck LEF is a critical barrier to the timely identification and management of head and neck LEF. To fill this gap, we developed and pilot tested a 64-item patient-reported outcome measure ( Lymphedema Symptom Intensity and Distress Survey-Head and Neck, LSIDS-H&N). This article aims to report the process of further validation and refinement of the tool.Methods and Materials: A prospective, longitudinal study was conducted, and 120 patients with oral cavity and oropharyngeal cancer were recruited. Participants completed the LSIDS-H&N at pretreatment, end of treatment, and every 3 months up to 12 months after treatment. SAS PROC VARCLUS was used to generate preliminary clusters of item responses. Internal consistency of the item responses within each cluster was assessed using Cronbach's alpha.Results: A total of 117 patients completed the study. The participants reported that the LSIDS-H&N was easy to understand and captured their symptoms and medical conditions. However, >50% of participants indicated that the survey was burdensome due to length. Thus, we proceeded with item reduction, and the shortened tool (33-item) was named Head and Neck Lymphedema and Fibrosis Symptom Inventory (HN-LEF Symptom Inventory). The subsequent exploration of symptom clusters identified 7 symptom domain clusters (eg, soft tissue and neurologic toxicity), all of which demonstrated good internal consistency.Conclusions: The HN-LEF Symptom Inventory has been carefully developed and refined to allow clinicians and researchers to capture LEF-associated symptom burden and function impairments. Additional rigorous psychometric testing of the tool is ongoing to further validate the strength and internal validity of this tool. [ABSTRACT FROM AUTHOR]

Purpose: To conduct a retrospective review of 168 consecutively treated locally advanced head-and-neck cancer (LAHNC) patients treated with intensity-modulated radiotherapy (IMRT)/chemotherapy, to determine the rate and risk factors for developing hypothyroidism. Methods and Materials: Intensity-modulated radiotherapy was delivered in 33 daily fractions to 69.3 Gy to gross disease and 56.1 Gy to clinically normal cervical nodes. Dose–volume histograms (DVHs) of IMRT plans were used to determine radiation dose to thyroid and were compared with DVHs using conventional three-dimensional radiotherapy (3D-RT) in 10 of these same patients randomly selected for replanning and with DVHs of 16 patients in whom the thyroid was intentionally avoided during IMRT. Weekly paclitaxel (30 mg/m2) and carboplatin area under the curve-1 were given concurrently with IMRT. Results: Sixty-one of 128 evaluable patients (47.7%) developed hypothyroidism after a median of 1.08 years after IMRT (range, 2.4 months to 3.9 years). Age and volume of irradiated thyroid were associated with hypothyroidism development after IMRT. Compared with 3D-RT, IMRT with no thyroid dose constraints resulted in significantly higher minimum, maximum, and median dose (p < 0.0001) and percentage thyroid volume receiving 10, 20, and 60 Gy (p < 0.05). Compared with 3D-RT, IMRT with thyroid dose constraints resulted in lower median dose and percentage thyroid volume receiving 30, 40, and 50 Gy (p < 0.005) but higher minimum and maximum dose (p < 0.005). Conclusions: If not protected, IMRT for LAHNC can result in higher radiation to the thyroid than with conventional 3D-RT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT are achievable and recommended. [Copyright &y& Elsevier]