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Background: Post-treatment surveillance recommendations for oropharyngeal cancer do not vary with p16 status despite the differences in outcomes. The optimal algorithm personalizing follow-up for these patients remains undefined. Here, we evaluate the feasibility and utility of incorporating electronic patient-reported outcomes (ePROs) and circulating tumor DNA (ctDNA) into routine surveillance for patients treated for p16+ oropharynx cancer., Methods: A prospective registry was developed in which ePROs and ctDNA were incorporated into routine surveillance among patients with oropharynx cancer. ePROs were emailed monthly for 1 year and blood HPV ctDNA testing was performed every 3-6 months. The primary objective was to assess patient compliance with ePRO-based surveillance with adequate compliance defined as ≥85% of patients completing monthly ePROs. Sensitivity, specificity, and positive/negative predictive values to detect recurrence were calculated for ePROs, HPV ctDNA, or the combination., Results: Of 122 patients who initially expressed interest, 76 completed the electronic consent process and 44/76 (58%) were compliant with monthly surveys over 1 year; thus adequate compliance was not achieved. Technical difficulties associated with ePRO receipt through email largely limited participation. Provider feedback was significantly associated with heightened ePRO compliance. One hundred and six patients had ctDNA testing with a mean number of three tests per patient. Sensitivity to detect recurrence was 75% for the combination of ePROs and ctDNA., Conclusion: Despite lower than anticipated compliance with ePROs, our findings show promise for incorporation of HPV ctDNA into surveillance paradigms for HPV-related oropharynx cancer with suggestions of methods to optimize ePRO formats for personalized surveillance., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: The impact of monoclonal antibody therapy (mAB) for advanced head and neck cancer on end-of-life health care utilization and costs has yet to be adequately studied., Methods: Retrospective cohort study of patients aged 65 and over with a diagnosis of head and neck cancer between 2007 and 2017 within the SEER-Medicare registry assessing the impact of mAB therapy (i.e., cetuximab, nivolumab, or pembrolizumab) on end-of-life health care utilization (ED visits, inpatient admissions, ICU admissions, and hospice claims) and costs., Results: Of 12 544 patients with HNC, 270 (2.2%) utilized mAB therapy at the end-of-life period. On multivariable analyses adjusting for demographic and clinicopathologic characteristics, there was a significant association between mAB therapy and emergency department visits (OR: 1.38, 95% CI: 1.1-1.8, p = 0.01) and healthcare costs (β: $9760, 95% CI: 5062-14 458, p < 0.01)., Conclusions: mAB use is associated with higher emergency department utilization and health care costs potentially due to infusion-related and drug toxicity expenses., (© 2023 Wiley Periodicals LLC.)

Background: We sought to characterize early changes in CD8 + tumor-infiltrating lymphocytes and tumor transcriptomes after induction cetuximab in a cohort with p16-positive oropharyngeal cancer on a phase II clinical de-escalation trial., Methods: Tumor biopsies were obtained before and 1 week after a single cetuximab loading dose in eight patients enrolled in a phase II trial of cetuximab and radiotherapy. Changes in CD8 + tumor-infiltrating lymphocytes and transcriptomes were assessed., Results: One week after cetuximab, five patients (62.5%) had an increase in CD8 + cell infiltration with a median (range) fold change of +5.8 (2.5-15.8). Three (37.5%) had unchanged CD8 + cells (median [range] fold change of -0.85 [0.8-1.1]). In two patients with evaluable RNA, cetuximab induced rapid tumor transcriptome changes in cellular type 1 interferon signaling and keratinization pathways., Conclusions: Within 1 week, cetuximab induced measurable changes in pro-cytotoxic T-cell signaling and immune content., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Single cycle induction chemotherapy (IC) with platinum and 5-flurouracil (PF) and treatment based on clinical response predicts organ preservation in laryngeal cancer. Other agents offer intriguing alternatives with potentially increased ease of administration, reduced risk for severe toxicities, and increased platinum sensitivity., Methods: We report the results of a phase II bioselection trial in advanced resectable laryngeal cancer utilizing an IC regimen of two cycles of platinum plus docetaxel (TP) with a Bcl-2 inhibitor. The primary endpoint was organ preservation rate at 12 weeks post chemoradiation., Results: Fifty-four patients were enrolled. Response to IC was 72%. The organ preservation rate was 59% with a laryngectomy free survival of 46%. Induction related grade ≥3 toxicities were observed in 56% of patients with two grade 5 events., Conclusions: Two cycles of TP IC plus a Bcl-2 inhibitor did not improve laryngeal preservation compared to a single cycle of PF., (© 2022 Wiley Periodicals LLC.)

Background: Of interest is the long-term neck and shoulder impairment of patients treated with primary chemoradiotherapy (CRT). This is important for counseling patients regarding treatment decisions when discussing primary CRT., Methods: A cross-sectional study to identify factors that contribute to neck and shoulder dysfunction in patients treated with primary CRT. We utilized the neck dissection impairment index (NDII). Eighty-seven patients treated between 2003 and 2010, who were free of disease, responded; 24 of these 87 underwent post-CRT neck dissection. Mean interval since completion of CRT was over 5 years (62.7 months). Mean age, 63.5 years, male:female 75:12., Results: Mean NDII score was 87.4 (SD 22.1, range 5-100). Multiple linear regression revealed worse NDII scores for patients with larger pre-CRT gross tumor nodal volume (GTVnodal), controlled for age, sex, body mass index (BMI), and the presence of neck dissection (p = 0.02). There were significant associations with increasing GTVnodal and "low" scores for components of the NDII that assessed neck pain (p = 0.02), neck stiffness (p = 0.01), lifting heavy objects (p = 0.02), reaching overhead (p = 0.02), and ability to do work (p = 0.02). Physical therapy (PT) was evaluated as an "anchor" but it was prescribed "as needed." Regression revealed participation in PT was associated with higher GTVnodal, lower BMI, presence of neck dissection, and female sex (p = 0.00007)., Conclusion: GTVnodal was an independent predictor of neck and shoulder impairment. High GTVnodal was associated with increased pain and stiffness, and increased difficulty lifting heavy objects, reaching overhead, overall ability to perform work-related tasks and was associated with participation in post-treatment PT., (© 2021 Wiley Periodicals LLC.)

Background: Alternative therapeutic strategies are needed for localized oropharyngeal carcinoma. Cetuximab represents a potential option for those ineligible for cisplatin or, until recently, an agent for de-escalation in low risk HPV+ oropharyngeal carcinoma (OPSCC). Our objective was to define the toxicity and efficacy of cetuximab-radiotherapy., Methods: We conducted paired phase II trials evaluating cetuximab-radiotherapy in two cohorts (a) low risk HPV+ OPSCC and (b) cisplatin ineligible. The mean follow-up was 48 months., Results: Forty-two patients were enrolled in cohort A with a 2-year disease free survival (DFS) of 81%. Twenty-one patients were enrolled in cohort B prior to closure due to adverse outcomes with a 2-year DFS of 37%. Severe toxicities were seen in 60% of patients, 30% required enteral nutrition., Conclusion: Among cisplatin ineligible patients, cetuximab treatment engendered poor outcomes. Rates of severe toxicities were on par with platinum-based regimens suggesting that cetuximab is not a benign treatment., (© 2020 Wiley Periodicals, Inc.)

Background: The purpose of this study was to evaluate the AJCC eighth edition clinical staging system for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma and to further understand how clinical stage and smoking history affect oncologic outcomes. The purpose of this study was to present the understanding of how clinical stage and smoking history affect oncologic outcomes in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) is critical for selecting patients for treatment deintensification., Methods: Kaplan-Meier and Cox regression were used to evaluate overall survival (OS), locoregional recurrence-free survival (LRFS), and distant recurrence-free survival (DRFS). Concordance statistics (C-indices) were used to compare discriminating ability., Results: The OS and DRFS but not LRFS were significantly distributed using the American Joint Committee on Cancer (AJCC) seventh and eighth editions criteria. The C-indices for OS, LRFS, and DRFS were 0.57, 0.54, and 0.60, respectively, using the AJCC seventh edition, and 0.63, 0.53, and 0.65, respectively, using the AJCC eighth edition. On multivariate analysis, 1 + pack-year smoking history correlated with OS (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.2-3.1; P < .01) but not LRFS or DRFS., Conclusion: These results support implementation of the AJCC eighth edition for HPV-associated oropharyngeal SCC. Clinical stage may be more important than smoking history in selection for deintensification., (© 2018 Wiley Periodicals, Inc.)

Background: The purpose of this study was to evaluate the predictive value of positron emission tomography (PET)-CT in identifying occult nodal metastasis in clinically and radiographically N0 patients with recurrent laryngeal cancer undergoing salvage laryngectomy., Methods: Retrospective review of 46 clinically and radiographically N0 patients with recurrent laryngeal cancer who underwent a PET-CT examination before salvage laryngectomy with neck dissection from January 1, 2002, to December 31, 2014, was performed., Results: Two patients (16.7%) had true-positive PET-CT results, whereas 10 patients (83.3%) had false-negative scans, 1 patient (2.9%) had a false-positive result and 33 patients (97.1%) had a true-negative PET-CT. The sensitivity of PET-CT was 16.7% (95% confidence interval [CI], 3.5% to 46.0%) with a specificity of 97.1% (95% CI, 83.8% to 99.9%), positive predictive value (PPV) of 66.7% (95% CI, 20.2% to 94.4%), and negative predictive value (NPV) of 76.7% (95% CI, 62.1% to 87.0%)., Conclusion: PET-CT has poor sensitivity and NPV making PET-CT an imperfect predictor of nodal disease in recurrent laryngeal cancer. © 2017 Wiley Periodicals, Inc. Head Neck 39: 980-987, 2017., (© 2017 Wiley Periodicals, Inc.)

The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Here, we present the Appropriateness Criteria for cancers arising in the nasal cavity and paranasal sinuses (maxillary, sphenoid, and ethmoid sinuses). This includes clinical presentation, prognostic factors, principles of management, and treatment outcomes. Controversies regarding management of cervical lymph nodes are discussed. Rare and unusual nasal cavity cancers, such as esthesioneuroblastoma and sinonasal undifferentiated carcinomas, are included. © 2016 American College of Radiology. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 39: 407-418, 2017., (© 2016 Wiley Periodicals, Inc.)

Background: There are no level I studies to guide treatment for resectable oropharyngeal squamous cell carcinoma (SCC). Treatment toxicities influence management recommendations. Ongoing investigations are examining deintensified treatments for human papillomavirus (HPV)-associated oropharyngeal SCC., Methods: The Appropriateness Criteria panel, using modified Delphi methodology, produced a literature summary, an assessment of treatment recommendations, and cases to illustrate their use., Results: A multidisciplinary team produces optimum results. Based on HPV status, smoking history, and staging, patients are divided into groups at low, intermediate, and high-risk of death. In the future, treatment recommendations may be influenced by HPV status, which has changed the epidemiology of oropharyngeal SCC., Conclusion: T1 to T2N0M0 resectable oropharyngeal SCC can be treated with surgery or radiation without chemotherapy. Patients with T1-2N1-2aM0 disease can receive radiation, chemoradiation, or transoral surgery with neck dissection and appropriate adjuvant therapy. Patients with T1-2N2b-3M0 disease should receive chemoradiation or transoral surgery with neck dissection and appropriate adjuvant therapy. Concurrent chemoradiation is preferred for T3 to T4 disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1299-1309, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: Delayed nonspecific posterior neck pain after pharyngeal instrumentation can be associated with a syndrome of rapidly progressive neurologic embarrassment. We present this cohort to help define the syndrome and aid in early detection., Methods: We conducted a retrospective case series of 6 patients presenting from 2003 to 2012 with a history of laryngeal or hypopharyngeal squamous cell carcinoma (SCC) who underwent radiotherapy (RT) or chemoradiotherapy (CRT) followed by salvage laryngectomy., Results: Posterior neck and upper back pain developed a mean of 27.5 days after instrumentation of the pharynx (reconstruction after laryngectomy or pharyngeal dilation). Myelopathy developed an average of 21.5 days after the onset of posterior neck pain. Five patients required urgent decompression. Three patients developed quadriplegia. The disease-specific mortality was 50%., Conclusion: There is a syndrome of late neurological effects after RT, salvage surgery, and pharyngeal instrumentation that is associated with high morbidity and mortality. © 2016 Wiley Periodicals, Inc. Head Neck 38:1187-1193, 2016., Competing Interests: None, (© 2016 Wiley Periodicals, Inc.)

Background: Nasopharyngeal carcinoma (NPC) presents mostly with locally advanced disease and is treated with multimodal therapy; however, consensus is lacking for different clinical scenarios., Methods: The American College of Radiology (ACR) Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment., Results: The ACR Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for guiding management of nasopharyngeal carcinoma., Conclusion: Multidisciplinary evaluation is essential to guiding the optimal use of surgery, radiation, and systemic therapy in this disease. © 2015 Wiley Periodicals, Inc. Head Neck 38: 979-986, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: The purpose of this study was to determine whether matted nodes uniquely identify patients with human papillomavirus (HPV)-positive oropharyngeal cancer at disproportionately high distant failure risk who may benefit from intensified systemic therapy., Methods: One hundred seventy-eight patients with stage III/IV HPV-positive oropharyngeal cancer who completed definitive chemoradiotherapy were stratified by risk group (low-risk = T1-3/N0-2c/<10 pack-years; intermediate-risk = T1-3/N0-2c/≥10 pack-years; and high-risk = T4 or N3). Prognostic impact of matted nodes was assessed., Results: At the 52-month median follow-up, event rates with and without matted nodes were: locoregional failure: 23.3% versus 12.8% (p = .16), distant failure: 50.0% versus 1.4% (p < .01), any failure: 73.3% versus 14.2% (p < .01); cause-specific mortality: 56.7% versus 5.4% (p < .01), and death: 56.7% versus 13.5% (p < .01). In multivariate analyses, including risk group and individual risk factors, matted nodes were the strongest predictor for all endpoints except locoregional failure. Among patients without matted nodes, risk-group discriminated locoregional failure (at 3 years: low-risk = 2.0%; intermediate-risk = 14.4%; and high-risk = 24.2%; p < .01), but not distant failure (low-risk = 0.0%; intermediate-risk = 2.1%; and high-risk = 3.8%; p = .53)., Conclusion: Matted nodes portended dramatically increased distant failure and death risks in HPV-positive oropharyngeal cancer, identifying a candidate population for consideration of chemo-intensification. © 2015 Wiley Periodicals, Inc. Head Neck 38: E805-E814, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Concurrent chemoradiotherapy (concurrent CRT) to treat head and neck cancer is associated with significant reductions of weight, mobility, and quality of life (QOL). An intervention focusing on functional exercise may attenuate these losses., Methods: We allocated patients to a 14-week functional resistance and walking program designed to maintain physical activity during cancer treatment (MPACT group; n = 11), or to usual care (control group; n = 9). Outcomes were assessed at baseline, and 7 and 14 weeks., Results: Compared to controls, the MPACT participants had attenuated decline or improvement in several strength, mobility, physical activity, diet, and QOL endpoints. These trends were statistically significant (p < .05) in knee strength, mental health, head and neck QOL, and barriers to exercise., Conclusion: In this pilot study of patients with head and neck cancer undergoing concurrent CRT, MPACT training was feasible and maintained or improved function and QOL, thereby providing the basis for larger future interventions with longer follow-up. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1086-E1096, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined., Methods: The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols versus radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for nonnasopharyngeal HNSCC was extracted. In the case of nonrandomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses., Results: Eleven randomized trials and 7 nonrandomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association (p = .027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses., Conclusion: Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocols for HNSCC has a significant positive correlation with survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2151-E2158, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: We recently described the imaging characteristics of multiple confluent regional metastases (matted nodes) and found that this characteristic was associated with distant metastasis in patients with oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was to determine if matted nodes are a predictive marker for distant metastasis., Methods: Radiologic lymph node characteristics on 205 patients with untreated stage III/IV with oropharyngeal SCC of whom 192 had known human papillomavirus (HPV) status underwent weekly carboplatin and paclitaxel with concomitant intensity-modulated radiation therapy (IMRT) between 2003 and 2010 with a minimum of 2-year of follow-up., Results: The 3-year disease-specific survival (DSS) for patients with matted nodes was 58% versus 97% with nonmatted nodes (p = .0001). The prevalence of matted nodes in the population was 20%. The positive predictive value of matted nodes for distant metastasis was 66%, and the negative predictive value was 99%., Conclusion: Matted nodes are a predictive marker for distant disease and can be used for planning new clinical interventions., (© 2014 Wiley Periodicals, Inc.)

Background: Aggressive nonmelanomatous skin cancer (NMSC) of the head and neck presents an increasingly common therapeutic challenge for which prospective clinical trials are lacking., Methods: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment., Results: The American College of Radiology Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for guiding management of aggressive NMSC., Conclusion: Multidisciplinary assessment is vital to guiding the ideal use of surgery, radiation, and systemic therapy in this disease., (Copyright © 2015 Wiley Periodicals, Inc.)

Background: Although typically associated with a favorable prognosis, a minority of human papillomavirus (HPV)-related (+) oropharyngeal cancers recur after chemoradiation. We postulated that a minor HPV-negative tumor subfraction may be responsible for recurrences of HPV+ oropharyngeal cancer., Methods: Paired untreated primary and recurrent tumor specimens were identified for 37 patients with oropharyngeal cancer who received definitive chemoradiotherapy at our institution. Concordance in HPV/p16 expression between primary and recurrent tumors was assessed., Results: Among 31 patients with HPV+/p16+ primary tumors, 30 (97%) retained evidence of both HPV and p16 expression at recurrence (27 HPV+/p16+; 3 HPV+/p16-partial). One (3%) initially HPV+/p16+ patient developed an HPV-negative/p16-negative lung squamous cell carcinoma (SCC), representing either a discordant oropharyngeal cancer metastasis or second primary tumor., Conclusion: HPV-related oropharyngeal cancers retain HPV+/p16+ expression at recurrence. Our results fail to provide evidence that a minor HPV-negative tumor subfraction is responsible for biologically aggressive behavior of HPV+ oropharyngeal cancer that recurs after chemoradiation., (© 2014 Wiley Periodicals, Inc.)

Background: A phase I study and an institutional pilot study in patients with metastatic/recurrent squamous cell carcinoma of the head and neck (SCCHN) utilizing biweekly gemcitabine and paclitaxel (GEMTAX), showed an overall response rate of 53%. 1 This phase II trial was conducted to determine the feasibility, tolerability, and efficacy of this combination., Methods: Patients with metastatic/recurrent SCCHN were treated with gemcitabine (3000 mg/m2) and paclitaxel (150 mg/m2) on days 1 and 15 of every 28-day cycle., Results: In 57 patients with measurable disease, median progression-free survival (PFS) was 4 months and median overall survival (OS) was 8 months. Overall response rate of 28% and disease stabilization in 19% were seen. There were no treatment-related deaths with grade 3/4 hematologic toxicity seen in 20% of the patients., Conclusion: Biweekly GEMTAX is feasible, well tolerated, and demonstrated reasonable efficacy. This may be an alternative for patients who are not candidates for platinum-based chemotherapy., (© 2014 Wiley Periodicals, Inc.)

Background: Management of head and neck carcinoma from unknown primary (HNCUP) remains controversial, with neck dissection and radiotherapy (RT) or definitive RT both commonly used. The purpose of this study was to characterize HNCUP and retrospectively compare outcomes for patients treated with neck dissection + RT versus definitive RT., Methods: From 1994 to 2009, 41 patients with HNCUP underwent either neck dissection + RT (n = 22) or definitive RT ± concurrent chemotherapy (n = 19) at our institution. Treatment outcomes were compared using Kaplan-Meier methods and log-rank test., Results: There were no differences between patients treated with neck dissection + RT and definitive RT in overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), freedom from locoregional failure (FFLRG), or freedom from distant failure (FFDF). Among 17 patients who underwent neck dissection + RT for whom human papillomavirus (HPV) status could be determined, HPV(+) patients trended toward improved OS (p = .06) and PFS (p = .15)., Conclusion: Neck dissection and postoperative RT resulted in similar outcomes as definitive RT. The prognostic implications of HPV(+) nodes in HNCUP are similar to those in oropharyngeal primary cancers., (© 2013 Wiley Periodicals, Inc.)

Background: The current American Joint Committee on Cancer (AJCC) staging system may not accurately reflect survival in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was to develop a system that more precisely predicts survival., Methods: CT scans from 156 patients who underwent chemoradiation for advanced-stage oropharyngeal SCC with >2 years follow-up were reviewed. We modeled patterns of nodal metastasis associated with different survival rates. We defined HPV+ N1 as a single node <6 cm, ipsilaterally, contralaterally, or bilaterally. HPV+ N2 was defined as a single node ≥6 cm or ≥2 nodes ipsilaterally/contralaterally or ≥3 nodes bilaterally. HPV+ N3 was defined as matted nodes., Results: There was no significant difference in disease-specific survival (DSS; p = .14) or overall survival (OS; p = .16) by AJCC classification. In patients grouped by HPV+ N1, HPV+ N2, and HPV+ N3 nodal classification, significant differences in DSS (100%, 92%, and 55%, respectively; p = .0001) and OS (100%, 96%, and 55%, respectively; p = .0001) were found., Conclusion: A staging system with reclassification of size, bilaterality, and matted nodes more accurately reflects survival differences in this cohort of patients. Review of the AJCC staging system with these criteria should be considered for HPV-positive oropharyngeal SCC., (Copyright © 2014 Wiley Periodicals, Inc.)

Background: Optimal treatment for locally advanced squamous cell carcinoma of the oropharynx (SCCOP) is not well defined. Here we retrospectively compare survival and toxicities from 2 different organ preservation protocols., Methods: The matched dataset consisted of 35 patients from each trial matched for age, stage, smoking, and tumor human papillomavirus (HPV) status. Patients in the University of Michigan Cancer Center (UMCC) trial 9921 were treated with induction chemotherapy (IC) followed by high-dose cisplatin and radiation in responders or surgery in nonresponders. Patients in the UMCC trial 0221 were treated with weekly carboplatin and paclitaxel and radiation., Results: Survival was comparable for both studies and did not differ significantly across each trial after stratifying by HPV status. Grade 3 and 4 toxicities were more frequent in UMCC 9921. At 6 months posttreatment, gastrostomy tube (G-tube) dependence was not statistically different., Conclusion: These data suggest that survival outcomes in patients with locally advanced SCCOP are not compromised with weekly chemotherapy and radiation therapy, and such treatment is generally more tolerable., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Little is known about the determinants of postradiation neck spasms in patients with head and neck cancer., Methods: Patients with head and neck cancer treated with radiation therapy (RT) from 2004 to 2010 who experienced neck spasms werereviewed. Radiation doses were generated for their sternocleidomastoid (SCM) muscles bilaterally. Unaffected SCMs were used as controls., Results: Thirty-four patients reported neck spasms. Thirty had received definitive chemoradiation, and 4 had RT alone. Seven also had an ipsilateral neck dissection. Median time to onset was 23 months (range, 6-67 months). There were significantly higher radiation doses to the affected SCMs with a median of the mean dose to the affected and unaffected SCM of 62.3 Gy (range, 29-71 Gy) and 53.7 Gy (range, 27-65 Gy), respectively (p < .0001). Other dosimetric variables were also statistically significant but were highly correlated with the mean SCM dose. Neck dissection did not affect our results., Conclusion: Neck spasms after chemotherapy intensity-modulated radiation therapy (IMRT) shows a strong dose-response relationship., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Controversy surrounds the appropriate therapy for T1 glottic cancer. Both transoral endolaryngeal resection and radiation offer excellent local control and voice quality; some lesions are best addressed with resection and others with radiation., Methods: The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guideline development includes an analysis of current literature from peer reviewed journals and the well-established "modified Delphi" consensus methodology to rate the appropriateness of treatment. Where evidence is not definitive, expert opinion informed recommendations., Results: The ACR Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for treatment of T1 glottic cancer. Treatment planning is complex and decisions nuanced., Conclusion: Best treatment for a particular cancer cannot be defined without consideration of the lesion's location, extent, depth of invasion, and quality of surgical exposure during direct laryngoscopy., (© 2013 American College of Radiology. Head & Neck © 2013 Wiley Periodicals, Inc.)

Background: Tumor regression after induction chemotherapy (ICT) identifies laryngeal cancers that are responsive to chemoradiation. Patient immune parameters have recently been associated with response to chemotherapy and may identify responding patients. A retrospective analysis was performed to determine if pretreatment, circulating T lymphocyte levels predicted ICT response in patients with advanced laryngeal cancer., Methods: Pretreatment, circulating T lymphocyte subpopulations were correlated with response to therapy and survival. Results were compared with similar data from an identical phase II trial involving patients with oropharyngeal cancer., Results: An increased percentage of CD4+ cells predicted response to ICT and suggested improved survival in patients with laryngeal, but not oropharyngeal, cancer. In the combined group of patients, increased CD4 levels predicted response to ICT., Conclusion: These findings demonstrate the potential importance of the immune system in chemotherapy response and clinical outcome. Differences in findings between patients with advanced laryngeal and oropharyngeal cancer may reflect different cellular immunity function in the patients with human papillomavirus (HPV)-16+ oropharyngeal cancer., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: The purpose of this study was to assess aspiration pneumonia (AsPn) rates and predictors after chemo-irradiation for head and neck cancer., Methods: The was a prospective study of 72 patients with stage III to IV oropharyngeal cancer treated definitively with intensity-modulated radiotherapy (IMRT) concurrent with weekly carboplatin and paclitaxel. AsPn was recorded prospectively and dysphagia was evaluated longitudinally through 2 years posttherapy by observer-rated (Common Toxicity Criteria version [CTCAE]) scores, patient-reported scores, and videofluoroscopy., Results: Sixteen patients (20%) developed AsPn. Predictive factors included T classification (p = .01), aspiration detected on videofluoroscopy (videofluoroscopy-asp; p = .0007), and patient-reported dysphagia (p = .02-.0003), but not observer-rated dysphagia (p = .4). Combining T classification, patient reported dysphagia, and videofluoroscopy-asp, provided the best predictive model., Conclusion: AsPn continues to be an under-reported consequence of chemo-irradiation for head and neck cancer. These data support using patient-reported dysphagia to identify high-risk patients requiring videofluoroscopy evaluation for preventive measures. Reducing videofluoroscopy-asp rates, by reducing swallowing structures radiation doses and by trials reducing treatment intensity in patients predicted to do well, are likely to reduce AsPn rates., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: The purpose of this study was to determine if there are differences in biomarker modulation and epidermal growth factor receptor (EGFR) degradation between the tumor and the normal mucosa after treatment with an EGFR inhibitor, erlotinib, in head and neck cancer., Methods: Patients with primary oral cavity squamous cell cancers received a course of erlotinib, 150 mg every day for 7 days before surgical resection. Tumor and normal mucosa biopsies were obtained both pre-erlotinib and post-erlotinib. Changes in known markers of EGFR activity (phospho, AKT, STAT3) were measured by immunoblotting, whereas changes in tissue distribution were analyzed by immunohistochemical analysis., Results: Twelve patients were enrolled; 7 had evaluable paired tumors and normal mucosa biopsies pretreatment and posttreatment. Expression of EGFR was higher in tumors compared to the normal mucosa (p = .005). Erlotinib administration was associated with marked inhibition of phosphorylated epidermal growth factor receptor (pEGFR) and reduction in total EGFR protein (p = .004, p = .007) in tumors, whereas there was heterogeneity in EGFR inhibition in the normal mucosa (p = .10 [pEGFR], and p = .07 [EGFR]). Reduced levels of pSrc and pSTAT3 and enhanced p27 levels were noted in tumors after erlotinib. Cell culture studies confirmed that EGFR is degraded in tumor cells after prolonged treatment with erlotinib., Conclusion: Our results show that EGFR inhibition by erlotinib led to a marked reduction in EGFR protein levels in patients. Differential effects of erlotinib on tumors compared to the normal mucosa suggest there may be individual patient heterogeneity. These preliminary data suggest EGFR degradation should be further analyzed as a potential biomarker in selecting patients likely to benefit from EGFR inhibitors., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: The purpose of this study was to describe the relationship of p16 and epidermal growth factor receptor (EGFR) expression with survival in surgically treated patients who had oropharyngeal or oral cavity squamous cell carcinoma (SCC)., Methods: Tissue from 36 patients with oropharyngeal SCC and 49 patients with oral cavity SCC treated between 1997 and 2001 was imbedded and immunostained using a tissue microarray., Results: The p16 was positive in 57% and 13% of patients with oropharyngeal SCC and oral cavity SCC, respectively. EGFR was positive in 60% and 63% of patients with oropharyngeal SCC and oral cavity SCC, respectively. In patients with oropharyngeal SCC, p16 expression was associated with improved disease-specific survival (DSS), overall survival (OS), and time to recurrence (TTR) (p < .01, < .01, and <.01, respectively). EGFR expression was associated with poorer DSS, OS, and TTR (p < .01, = .01, and < .01, respectively). For oropharyngeal SCC, when examining both p16 and EGFR expression as combined biomarkers, high p16 expression coupled with low EGFR expression was associated with improved DSS (p p16 = .01; p EGFR = .01). Patients with oral cavity SCC showed no association between biomarker and outcome., Conclusions: For patients with oropharyngeal SCC, high p16 and low EGFR were associated with improved outcome, suggesting a predictive role in surgically treated patients., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: The aim of this study was to investigate oral cancer in pregnant women, a rare but therapeutically challenging patient subset., Methods: After institutional review board approval, an EMERSE search was used to identify all women treated at the University of Michigan from 1998 to 2010 with head and neck squamous cell carcinoma (HNSCC) during pregnancy. This identified 4 patients with tongue cancer. Biomarkers and human papillomavirus (HPV) were assessed by immunohistochemistry and multiplex PCR/mass spectrometry, respectively., Results: Two patients responded well to therapy and are alive more than 10 years after diagnosis; 2 patients died of disease. All tumors overexpressed EGFR and Bcl-xL, 3 of 4 overexpressed c-Met, both tumors that progressed overexpressed p53. All tumors were negative for HPV, p16, estrogen receptor, progesterone receptor, and HER-2., Conclusions: Biomarkers of aggressive tumors (high EGFR, c-Met; high Bcl-xL-low p53) did not correlate with outcome. Additional studies are needed to determine whether perineural invasion, delay in diagnosis, and p53 overexpression are factors in poor survival., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Despite better prognosis, there is a group of oropharyngeal squamous cell carcinoma (SCC) human papillomavirus (HPV)+ patients who experience treatment failure and succumb to distant metastasis., Methods: Seventy-eight previously untreated patients nested in a concurrent chemoradiation protocol were reviewed to correlate patterns of local-regional tumor extent to distant metastasis. Biomarker assessment was: HPV in situ hybridization and epidermal growth factor receptor (EGFR) immunointensity., Results: The 3-year disease-specific survival (DSS) for patients presenting with and without matted nodes was 69% and 94%, respectively (p = .003). Matted nodes were a poor prognostic factor independent of T classification, HPV, EGFR, and smoking status. For patients who were HPV+, 7 of 11 died of distant metastasis and 6 of 7 with distant metastasis had matted nodes., Conclusion: Matted nodes are a novel marker of poor prognosis in oropharyngeal SCC independent of established prognostic factors. Matted nodes may identify patients at risk for the development of distant metastasis who could benefit from systemic therapy, whereas patients without matted nodes may be candidates for de-escalation of therapy., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: For patients with advanced laryngeal cancer, a trial was designed to determine if chemotherapy alone, in patients achieving a complete histologic complete response after a single neoadjuvant cycle, was an effective treatment with less morbidity than concurrent chemoradiotherapy., Methods: Thirty-two patients with advanced laryngeal or hypopharyngeal cancer received 1 cycle of induction chemotherapy, and subsequent treatment was decided based on response., Results: A histologic complete response was achieved in 4 patients and were treated with chemotherapy alone. All 4 patients' cancer relapsed in the neck and required surgery and postoperative radiotherapy (RT). Twenty-five patients were treated with concomitant chemoradiation. Three patients were treated with surgery. Overall survival and disease-specific survival at 3 years were 68% and 78%, respectively., Conclusion: Chemotherapy alone is not feasible for long-term control of regional disease in patients with advanced laryngeal cancer even when they achieve a histologic complete response at the primary site., (2009 Wiley Periodicals, Inc. Head Neck, 2010.)

Background: Human papillomavirus (HPV) has been detected in keratinizing nasopharyngeal carcinomas (NPCs); however, the relationship between HPV and Epstein-Barr virus (EBV) among whites with nonkeratinizing NPCs remains unclear. The HPV, p16, and EBV status was examined in current University of Michigan patients with NPC., Methods: From 2003 to 2007, 89 patients, 84 with oropharyngeal cancer (OPC) and 5 with NPC, were enrolled in an organ-sparing trial. Biopsy tissues from all 89 patients were evaluated for HPV and p16 expression. A separate HPV analysis of the 84 OPC patients is in progress. Among the patients with NPC, tumor tissue was also analyzed for EBV-encoded RNA (EBER)., Results: Five of 89 patients (5.6%) had NPC, all with nonkeratinizing histology. The 4 white patients with NPC were HPV(+) (subtype-16, subtype-18 [2 patients], and subtype-59)/p16(+)/EBER(-). One Asian patient with NPC had an HPV(-)/p16(-)/EBER(+) NPC tumor that developed distant metastases., Conclusion: We postulate that HPV may be the etiologic factor in some EBV-negative, nonkeratinizing NPCs among whites.

Background: Our aim was to evaluate the acceleration of a hyperfractionated, concurrent chemoradiation regimen (HxCRT) for advanced head and neck squamous cell carcinoma (HNSCC)., Methods: Patients with unresectable HNSCC were treated based on a previously published HxCRT regimen: 1.25 Gy twice daily to 70 Gy concurrent with cisplatin 12 mg/m(2)/day and 5-fluorouracil 600 mg/m(2)/day for 5 days, weeks 1, 5. This regimen was accelerated in this series by shortening the treatment from 7 to 6 weeks by omitting the planned mid-treatment 1-week break., Results: Forty-six patients with T3-4/N3 disease were treated. The main acute toxicity was pharyngeal. Median weight change during therapy in patients with and without enteral feeding tubes was -3.8% and -7.9%, respectively (p = .08). Fifteen percent had late grade III pharyngeal toxicity. Local/regional and distant failure rates were 28% and 17%, respectively; 52% are alive without evidence of disease., Conclusions: In nonresectable HNSCC, acceleration of the HxCRT regimen is feasible, requiring enteral feeding tubes during therapy in most patients.