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These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (HN the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.

Purpose This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa). Methods and Materials The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm. Results A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% ( P =.42), local-regional progression-free survival was 31.5% versus 37.6% ( P =.20), and overall survival was 36.9% versus 38.2% ( P =.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms. Conclusions This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.

A 76-year-old woman presented with 8 years of progressive right hand tremor. Initial examination demonstrated mild head tremor, voice tremor, right arm mild rest tremor, and moderate postural and kinetic tremor exacerbated by writing, and left hand mild postural tremor with no rest or kinetic components. Fahn-Tolosa-Marin (FTM) score was 35. Multiple medication trials, including β-blocker, primidone, and topiramate, were ineffective or associated with adverse effects. Deep brain stimulation (DBS) was offered, but the patient felt it was too invasive. She elected to undergo stereotactic radiosurgery (SRS), receiving 14,500 cGy to the left ventral intermediate (VIM) thalamic nucleus via linear accelerator-based SRS.

Summary Background Panitumumab is a fully human monoclonal antibody that targets EGFR. We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy alone in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. Methods In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 41 sites in nine countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0–1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m 2 ) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9·0 mg/kg every 3 weeks plus cisplatin 75 mg/m 2 ) using stratified randomisation with a block size of five. All patients received 70 Gy to gross tumour and 50 Gy to areas at risk for subclinical disease with standard fractionation. The primary endpoint was local-regional control at 2 years, analysed in all randomised patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00500760. Findings Between Oct 26, 2007, and March 26, 2009, 153 patients were enrolled and 150 received treatment (63 in the chemoradiotherapy group and 87 in the panitumumab plus chemoradiotherapy group). Local-regional control at 2 years was 68% (95% CI 54–78) in the chemoradiotherapy group and 61% (50–71) in the panitumumab plus chemoradiotherapy group. The most frequent grade 3–4 adverse events were dysphagia (17 [27%] of 63 patients in the chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37 (43%) of 87 patients in the panitumumab plus chemoradiotherapy group. Interpretation In patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit, and the role of EGFR inhibition in these patients needs to be reassessed. Funding Amgen.

Summary Background We aimed to compare panitumumab, a fully human monoclonal antibody against EGFR, plus radiotherapy with chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. Methods In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 22 sites in eight countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0–1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m 2 during radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9 mg/kg every 3 weeks administered with radiotherapy) using a stratified randomisation with a block size of five. All patients received 70–72 Gy to gross tumour and 54 Gy to areas of subclinical disease with accelerated fractionation radiotherapy. The primary endpoint was local-regional control at 2 years, analysed in all randomly assigned patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This study is registered with ClinicalTrials.gov, number NCT00547157. Findings Between Nov 30, 2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab group). Local-regional control at 2 years was 61% (95% CI 47–72) in the chemoradiotherapy group and 51% (40–62) in the radiotherapy plus panitumumab group. The most frequent grade 3–4 adverse events were mucosal inflammation (25 [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30 (34%) of 89 patients in the radiotherapy plus panitumumab group. Interpretation Panitumumab cannot replace cisplatin in the combined treatment with radiotherapy for unresected stage III–IVb squamous-cell carcinoma of the head and neck, and the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the head and neck needs to be reassessed. Funding Amgen.

Purpose The optimal treatment strategy following local recurrence after stereotactic radiosurgery (SRS) remains unclear. While upfront SRS has been extensively studied, few reports focus on outcomes after retreatment. Here, we report the results following a second course of SRS for local recurrence of brain metastases previously treated with SRS. Methods Using institutional database, patients who received salvage SRS (SRS2) following in-field failure of initial SRS (SRS1) for brain metastases were identified. Radionecrosis and local failure were defined radiographically by MRI following SRS2. The primary endpoint was defined as the time from SRS2 to the date of all-cause death or last follow-up [overall survival (OS)]. The secondary endpoints included local failure-free survival (LFFS) and radionecrosis-free survival, defined as the time from SRS2 to the date of local failure or radionecrosis, or last follow-up, respectively. Results Twenty-eight patients with 32 brain metastases were evaluated between years 2004 and 2015. The median interval between SRS1 and SRS2 was 9.7 months. Median OS was 22.0 months. Median LFFS time after SRS2 was 13.6 months. The overall local control rate following SRS2 was 84.4%. The 1- and 2-year local control rates are 88.3% (95% CI, 76.7–100%) and 80.3% (95% CI, 63.5–100%), respectively. The overall rate of radionecrosis following SRS2 was 18.8%. On univariate analysis, higher prescribed isodose line (p = 0.033) and higher gross tumor volume (p = 0.015) at SRS1 were associated with radionecrosis. Although not statistically significant, there was a trend toward lower risk of radionecrosis with interval surgical resection, fractionated SRS, lower total EQD2 (

Introduction Stereotactic radiosurgery (SRS) is increasingly used as an alternative to whole brain radiotherapy (WBRT) following surgical resection of brain metastases. We analyzed the outcomes of postoperative frameless fractionated stereotactic radiosurgery (fSRS) cases for surgically resected brain metastases at our institution. Materials and Methods We performed a retrospective review of 85 patients who underwent fSRS to 87 resection beds from 2006 - 2014 with a median follow-up of 6.4 months. Clinically relevant outcomes were assessed with analysis to determine predictors of these outcomes. Results The median target volume was 9.8 cm­3 (1.1 - 43.1 cm­3). The most frequently used fractionation scheme was 3,000 cGy in five fractions. The rates of local control (LC), distant brain failure (DBF), and overall survival (OS) at one-year were 87%, 52%, and 52%, respectively. Five patients (5.9%) experienced Grade >2 toxicity related to fSRS, including seizures (two), symptomatic radionecrosis (two), and potential treatment-related death (one). A multivariable analysis revealed that tumor volume (p < 0.001) and number of fractions (p < 0.001) were associated with LC, while recursive partitioning analysis (RPA) class (p < .0001), tumor volume (p = .0181), and the number of fractions (p = .0181) were associated with OS. Conclusions Postoperative fSRS for surgically resected brain metastases is well-tolerated and achieves durable LC. Further studies are needed to determine the optimal dose and fractionation for fSRS as well as to compare outcomes with WBRT.

Copyright © 2014 by the National Comprehensive Cancer Network. All rights reserved. This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."

Long-term outcomes and sequalae of pediatric stereotactic radiosurgery (SRS) for benign neurologic disease are poorly understood. We sought to explore the efficacy and late effects of SRS in pediatric patients treated our institution. After institutional review board approval, we performed a retrospective analysis of patients age 21 or younger treated between 1990 and 2016. Covariates were summarized with descriptive statistics. 56 consecutive patients were enrolled. Patients were primarily Caucasian (n=51, 93%) males (n=30, 54%). Diagnoses included arterio-venous malformation (n=41, 73%) and functional pituitary adenoma (n=9, 16%) as well as vestibular schwannoma, craniopharyngioma, meningioma, papilloma, and ganglioglioma. Average age was 14 years (95% CI 13–16 years). SRS was often the first intervention (n=22, 44%); treatments prior to SRS included embolization (n=18, 36%) and surgery (n=10, 20%). SRS was typically single fraction (n=45, 94%) with a median total dose of 16 Gy (IQR 15–18 Gy). Most patients had no acute side effects of SRS (n=40, 87%). Median follow-up time after SRS was 12 years (IQR 6–18 years, max 26 years). 91% of patients had no late sequelae of SRS. One patient was diagnosed with radionecrosis one year after repeat SRS for residual malformation. Two patients had malformation hemorrhage. One patient with brainstem malformation developed focal weakness after ischemia from treatment effect; another patient with malformation developed seizures related to SRS edema. Over 673 patient-years following SRS, no patient developed radiation-induced malignancy or malignant transformation. Median disease-free survival after SRS was 6 years (IQR 3–13) with 66% overall local control; 84% of local failures occurred within 5 years of SRS. At last follow-up, 95% of patients remained without evidence of disease with 100% overall survival. These data support the long-term safety and efficacy of pediatric SRS.

6059 Background: Preliminary data suggest that gabapentin (G) administered during HNC radiation may decrease treatment associated pain. To confirm this, we undertook a prospective, randomized trial in HNC patients undergoing CCR. Primary outcomes: pain severity (scale of 0-10) and opioid use. Exploratory outcomes: local and systemic symptoms measured by the Vanderbilt Head and Neck Symptom Survey version 2 plus the general symptom survey (VHNSSv2/GSS). We report results of the exploratory endpoints from the interim analysis. Methods: Measures: VHNSSv2 - 50 items, demonstrated reliability/validated, captures acute/chronic local HNC specific symptoms; GSS – 11 item checklist, demonstrated content validity, captures acute/chronic systemic symptoms. Population: HNC patients (≥ stage 2) undergoing primary or adjuvant CCR. Procedures: Randomized to standard pain management (SPM) or SPM + G dose escalated to 900mg tid. VHNSSv2/GSS completed weekly during treatment beginning week 1 and ending the last week of radiation therapy. Results were analyzed using a mixed-effects regression analysis adjusting for baseline levels of each symptom. Results: 71 patients completed a mean of 5.5 surveys. Patients on G experienced a reduction in overall systemic symptoms as measured by the GSS (11-items, p = 0.0073), fatigue (two-items, p = 0.013 ) sleep disturbance (five items, p < 0.0001) , neurosensory eating (3 items, p = 0.026), phlegm-related symptoms (4 items, p = 0.004), and trend to better smell (2 items, p = 0.055). No impact on swallow, xerostomia, voice, dental or musculoskeletal symptoms was noted. Conclusions: This exploratory analysis suggests that G may moderate neurological and neuropsychiatric toxicities in HNC patients undergoing CCR. Further studies are warranted.

Image segmentation has become a vital and often rate-limiting step in modern radiotherapy treatment planning. In recent years, the pace and scope of algorithm development, and even introduction into the clinic, have far exceeded evaluative studies. In this work we build upon our previous evaluation of a registration driven segmentation algorithm in the context of 8 expert raters and 20 patients who underwent radiotherapy for large space-occupying tumours in the brain. In this work we tested four hypotheses concerning the impact of manual segmentation editing in a randomized single-blinded study. We tested these hypotheses on the normal structures of the brainstem, optic chiasm, eyes and optic nerves using the Dice similarity coefficient, volume, and signed Euclidean distance error to evaluate the impact of editing on inter-rater variance and accuracy. Accuracy analyses relied on two simulated ground truth estimation methods: simultaneous truth and performance level estimation and a novel implementation of probability maps. The experts were presented with automatic, their own, and their peers' segmentations from our previous study to edit. We found, independent of source, editing reduced inter-rater variance while maintaining or improving accuracy and improving efficiency with at least 60% reduction in contouring time. In areas where raters performed poorly contouring from scratch, editing of the automatic segmentations reduced the prevalence of total anatomical miss from approximately 16% to 8% of the total slices contained within the ground truth estimations. These findings suggest that contour editing could be useful for consensus building such as in developing delineation standards, and that both automated methods and even perhaps less sophisticated atlases could improve efficiency, inter-rater variance, and accuracy.

Treatment of locally advanced head and neck squamous cell carcinomas requires a multidisciplinary approach to be able to offer patients definitive therapy while aiming to preserve organ function and minimize acute and long-term toxicities. Advances in surgical techniques will be reviewed for both primary sites and the neck and also in the salvage settings. Recent data on concurrent versus sequential chemoradiotherapy in these patients will be reviewed, with emphasis on identification of appropriate patients for sequential chemoradiotherapy. Finally, advances in modern radiotherapy modalities that have resulted in improved dosimetry and quality of life following treatment will be reviewed.

Chemotherapies Utilized in Sequential Boost Cohort. Table S2. Acute toxicity in sequential and integrated boost cohorts among patients who received 5 or more cycles of concurrent chemotherapy. (DOCX 12 kb)

Purpose Previous analysis of this Intergroup trial demonstrated that with a median follow-up among surviving patients of 45.9 months, the concurrent postoperative administration of cisplatin and radiation therapy improved local-regional control and disease-free survival of patients who had high-risk resectable head-and-neck carcinomas. With a minimum of 10 years of follow-up potentially now available for all patients, these results are updated here to examine long-term outcomes. Methods and Materials A total of 410 analyzable patients who had high-risk resected head-and-neck cancers were prospectively randomized to receive either radiation therapy (RT: 60 Gy in 6 weeks) or identical RT plus cisplatin, 100 mg/m 2 i.v. on days 1, 22, and 43 (RT + CT). Results At 10 years, the local-regional failure rates were 28.8% vs 22.3% ( P =.10), disease-free survival was 19.1% vs 20.1% ( P =.25), and overall survival was 27.0% vs 29.1% ( P =.31) for patients treated by RT vs RT + CT, respectively. In the unplanned subset analysis limited to patients who had microscopically involved resection margins and/or extracapsular spread of disease, local-regional failure occurred in 33.1% vs 21.0% ( P =.02), disease-free survival was 12.3% vs 18.4% ( P =.05), and overall survival was 19.6% vs 27.1% ( P =.07), respectively. Conclusion At a median follow-up of 9.4 years for surviving patients, no significant differences in outcome were observed in the analysis of all randomized eligible patients. However, analysis of the subgroup of patients who had either microscopically involved resection margins and/or extracapsular spread of disease showed improved local-regional control and disease-free survival with concurrent administration of chemotherapy. The remaining subgroup of patients who were enrolled only because they had tumor in 2 or more lymph nodes did not benefit from the addition of CT to RT.

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.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.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.Lymphedema severity correlates with symptom burden, functional status, and QOL in patients after head and neck cancer treatment.

Background The prevalence, severity, and functional implications of adverse oral health outcomes attributed to head and neck cancer therapy are largely undefined. We report development of an oral health outcome subscale for the Vanderbilt Head and Neck Symptom Survey (VHNSS). Methods Oral health outcome questions were formulated through literature review and consultation with an expert panel. Questions were incorporated into the VHNSS resulting in a 50-item survey, scored 0 (none) to 10 (severe). The tool was administered to 70 subjects who completed radiation to assess for feasibility. Results Patient acceptance was high with a completion time

The purpose of this work was to characterize expert variation in segmentation of intracranial structures pertinent to radiation therapy, and to assess a registration-driven atlas-based segmentation algorithm in that context. Eight experts were recruited to segment the brainstem, optic chiasm, optic nerves, and eyes, of 20 patients who underwent therapy for large space-occupying tumors. Performance variability was assessed through three geometric measures: volume, Dice similarity coefficient, and Euclidean distance. In addition, two simulated ground truth segmentations were calculated via the simultaneous truth and performance level estimation algorithm and a novel application of probability maps. The experts and automatic system were found to generate structures of similar volume, though the experts exhibited higher variation with respect to tubular structures. No difference was found between the mean Dice similarity coefficient (DSC) of the automatic and expert delineations as a group at a 5% significance level over all cases and organs. The larger structures of the brainstem and eyes exhibited mean DSC of approximately 0.8-0.9, whereas the tubular chiasm and nerves were lower, approximately 0.4-0.5. Similarly low DSCs have been reported previously without the context of several experts and patient volumes. This study, however, provides evidence that experts are similarly challenged. The average maximum distances (maximum inside, maximum outside) from a simulated ground truth ranged from (-4.3, +5.4) mm for the automatic system to (-3.9, +7.5) mm for the experts considered as a group. Over all the structures in a rank of true positive rates at a 2 mm threshold from the simulated ground truth, the automatic system ranked second of the nine raters. This work underscores the need for large scale studies utilizing statistically robust numbers of patients and experts in evaluating quality of automatic algorithms.

Synovial sarcoma is typically an aggressive malignant tumor of the soft tissues, usually in the extremities, that affects young adults. Tumors of the head and neck are rare. Reported head and neck sites have included the hypopharynx (the most common site), the oropharynx, the larynx, and the soft tissues of the neck; only 4 cases of orbital involvement have been previously reported. We describe a case of synovial sarcoma of the medial canthus, which we discovered during a review of a tumor registry. The patient, an 18-year-old woman, underwent conservative excision and postoperative radiation therapy. Long-term follow-up detected no evidence of recurrence. Because there is no established, consistent approach to the treatment of synovial sarcoma of the head and neck, we also present a consensus management plan based on our review of the literature.

BACKGROUND. Patients with recurrent or metastatic HNC have a poor response and survival with currently available chemotherapy agents. Thus, new agents are needed. The authors report the results of a phase II trial of irinotecan and cisplatin in patients with metastatic or recurrent HNC. METHODS. Patients were treated with irinotecan 65 mg/m2 IV over 90 minutes and cisplatin 30 mg/m2 were administered intravenously weekly for four weeks, followed by a two week rest. However, after 17 patients were treated with weekly irinotecan at a dose of 65 mg/m2, toxicity analysis demonstrated the poor tolerance of that dose in this patient population. Thus, the protocol was amended, and irinotecan was dose reduced to a starting dose of 50 mg/m2. Twenty-three additional patients were treated with this dose. RESULTS. Forty patients were enrolled on study between February 2002 and April 2006, 17 patients at the first dose level and 23 patients at the amended dose level. Overall, 12 of 17 patients (71%) treated with irinotecan 65 mg/m2 experienced clinically significant grade 3 or 4 toxicity. Twelve patients required dose reductions. Toxicity was reduced but 17% of patients still experienced grade 3 or 4 toxicity on the lower irinotecan dose. The response rate was 35% for patients treated at irinotecan 65 mg/m2 and 22% for patients treated at 50 mg/m2. No complete responses were noted. CONCLUSIONS. The combination of irinotecan and cisplatin is efficacious in a poor prognosis group of patients but toxicity is substantial. Cancer 2008. © 2008 American Cancer Society.

Background The improved prognosis for patients with human papillomavirus (HPV) – positive head and neck squamous cell carcinoma (HNSCC) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospective clinical trial. Methods We prospectively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group (ECOG) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and standard fractionation radiation therapy. The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction (PCR) and in situ hybridization. Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan – Meier analysis. The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age, ECOG performance status, stage, and other covariables was estimated by use of a multivariable Cox proportional hazards model. All statistical tests were two-sided. Results Genomic DNA of oncogenic HPV types 16, 33, or 35 was located within tumor cell nuclei of 40% (95% confidence interval [CI] = 30% to 50%) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR. Compared with patients with HPV-negative tumors, patients with HPV-positive tumors had higher response rates after induction chemotherapy (82% vs 55%, difference = 27%, 95% CI = 9.3% to 44.7%, P = .01) and after chemoradiation treatment (84% vs 57%, difference = 27%, 95% CI = 9.7% to 44.3%, P = .007). After a median follow-up of 39.1 months, patients with HPV-positive tumors had improved overall survival (2-year overall survival = 95% [95% CI = 87% to 100%] vs 62% [95% CI = 49% to 74%], difference = 33%, 95% CI = 18.6% to 47.4%, P = .005, log-rank test) and, after adjustment for age, tumor stage, and ECOG performance status, lower risks of progression (hazard ratio [HR] = 0.27, 95% CI = 0.10 to 0.75), and death from any cause (HR = 0.36, 95% CI = 0.15 to 0.85) than those with HPV-negative tumors. Conclusion For patients with HNSCC of the oropharynx, tumor HPV status is strongly associated with therapeutic response and survival.

Purpose To determine whether the addition of recombinant human erythropoietin (Epo) could improve the outcomes of anemic patients receiving definitive radiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Methods and Materials Eligible patients had SCCHN, with a plan for continuous-course definitive radiotherapy (66–72 Gy) with or without chemotherapy. Patients with Stage III or IV SCCHN were required to undergo concurrent chemoradiotherapy and/or accelerated fractionation radiotherapy. Preradiotherapy hemoglobin was required to be between 9.0 g/dL and 13.5 g/dL (12.5 g/dL for women). Patients randomized to Epo received 40,000 U once weekly, starting 7–10 days before start of radiotherapy. Results A total of 148 patients were enrolled; 141 were evaluable. Median pretreatment hemoglobin was 12.1 g/dL. Hemoglobin levels at 4 weeks rose by an average of 1.66 g/dL in the Epo arm, compared with an average 0.24 g/dL decrease in the control arm (p = 0.0001). Median follow-up was 2.5 years (3.1 years for surviving patients). There was no statistically significant difference in the primary endpoint of local–regional failure (LRF) rate between the treatment arms. The 3-year LRF rate was 36% for control and 44% for Epo (p = 0.56). There were also no significant differences in local–regional progression-free survival (LRPFS), patterns of failure, overall survival, or toxicity. The 3-year LRPFS rate was 52% for control and 47% for Epo. The overall survival rate was 57% and 56%, respectively. Conclusions The addition of Epo to definitive radiotherapy for SCCHN did not improve outcomes. The study was not specifically designed to detect a potential negative association between Epo and tumor progression/survival.

A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy.We randomly assigned 501 patients (all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were candidates for organ preservation) to receive either TPF or PF induction chemotherapy, followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week. The primary end point was overall survival.With a minimum of 2 years of follow-up (or =3 years for 69% of patients), significantly more patients survived in the TPF group than in the PF group (hazard ratio for death, 0.70; P=0.006). Estimates of overall survival at 3 years were 62% in the TPF group and 48% in the PF group; the median overall survival was 71 months and 30 months, respectively (P=0.006). There was better locoregional control in the TPF group than in the PF group (P=0.04), but the incidence of distant metastases in the two groups did not differ significantly (P=0.14). Rates of neutropenia and febrile neutropenia were higher in the TPF group; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group.Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy. (ClinicalTrials.gov number, NCT00273546 [ClinicalTrials.gov].).

Objective To evaluate radiographic tumor control and treatment-related toxicity in glomus jugulare tumors treated with stereotactic radiosurgery (SRS). Study design Retrospective chart review. Setting Tertiary academic referral center. Patients Glomus jugulare tumors treated with SRS between 1998 and 2014 were identified. The data analysis only included patients with at least 18 months of post-treatment follow up (FU). Intervention Patients were treated with either single fraction or fractionated SRS. Main outcome measure Patient demographics and tumor characteristics were assessed. Radiographic control was determined by comparing pre and post treatment MRI, and was categorized as no change, regression, or progression. Results Eighteen patients were treated with SRS, and 14 met inclusion criteria. Median age at treatment was 55 years (range 35–79), and 71.4% of patients were female. 5 patients (35.7%) received single fraction SRS (dose range 15–18 Gy), and 9 (64.3%) fractionated therapy (dose 3–7 Gy × 3–15 fractions). Median tumor volume was 3.78 cm 3 (range 1.15–30.6). Median FU was 28.8 months (range 18.6–56.1), with a mean of 31.7 months. At their last recorded MRI, 7 patients (50%) had tumor stability, 6 (42.9%) had improvement, and 1 (7.1%) had progression. Disease improvement and progression rates in the single fraction group were 40% and 0%, and in the multiple-fraction group, 44.4% and 11.1%, respectively. There was no statistically significant difference in disease improvement (p = 0.88) or progression (p = 0.48) rates between groups (unpaired t-test). Conclusions At a median follow up of 28 months, both single fraction and fractionated SRS appear to have comparable radiographic tumor control outcomes and toxicity profiles.

Summary Introduction Afatinib is an ErbB family receptor inhibitor with efficacy in head and neck squamous cell carcinoma (HNSCC). A phase I trial was conducted to determine the maximally tolerated dose (MTD) of afatinib in combination with carboplatin and paclitaxel as induction chemotherapy (IC). Material and methods Patients with newly diagnosed, locally advanced HPV-negative or HPV-positive HNSCC with a significant smoking history were enrolled. Afatinib alone was given daily for two weeks as lead-in and subsequently given with carboplatin AUC 6 mg/ml min and paclitaxel 175 mg/m 2 every 21 days as IC. Afatinib was started at a dose of 20 mg daily and dose escalated using a modified Fibonacci design. After completion of IC, afatinib was discontinued and patients received concurrent cisplatin 40 mg/m 2 weekly and standard radiation. Toxicity was assessed using CTCAE version 4.0. Results Seven of nine patients completed afatinib lead-in and IC. Five patients had partial response and two patients had stable disease after IC. Dose level 1 (afatinib 20 mg) was well tolerated with one grade 3 (ALT elevation) and one grade 4 (neutropenia) toxicities. However, dose level 2 (afatinib 30 mg) was not well tolerated with nine grade 3 (pneumonia, abdominal pain, diarrhea, pancytopenia, and UTI), two grade 4 (sepsis) and one grade 5 (death) toxicities. Conclusions The MTD of afatinib given with carboplatin AUC 6 mg/ml min and paclitaxel 175 mg/m 2 is 20 mg daily. Combination of afatinib at doses higher than 20 mg with carboplatin and paclitaxel should be administered with caution due to the toxicities.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.