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Purpose: The purpose of this study was to examine factors associated with the presence of secondary external and internal lymphedema in patients with head-and-neck cancer (HNC). Methods and Materials: The sample included 81 patients ≥3 months after HNC treatment. Physical and endoscopic examinations were conducted to determine if participants had external, internal, and/or combined head-and-neck lymphedema. Logistic regression analysis was used to examine the factors associated with the presence of lymphedema. Results: The following factors were statistically significantly associated with presence of lymphedema: (1) location of tumor associated with presence of external (P=.009) and combined lymphedema (P=.032); (2) time since end of HNC treatment associated with presence of external (P=.004) and combined lymphedema (P=.005); (3) total dosage of radiation therapy (P=.010) and days of radiation (P=.017) associated with the presence of combined lymphedema; (4) radiation status of surgical bed was associated with the presence of internal lymphedema, including surgery with postoperative radiation (P=.030) and (salvage) surgery in the irradiated field (P=.008); and (5) number of treatment modalities associated with external (P=.002), internal (P=.039), and combined lymphedema (P=.004). No demographic, health behavior-related, or comorbidity factors were associated with the presence of lymphedema in the sample. Conclusions: Select tumor and treatment parameters are associated with increased occurrence of lymphedema in patients with HNC. Larger and longitudinal studies are needed to identify adjusted effects and causative risk factors contributing to the development of lymphedema in patients with HNC. [Copyright &y& Elsevier]

Purpose: Radiotherapy (RT)/cetuximab (C) demonstrated superiority over RT alone for locally advanced squamous head and neck cancer. We tested this in completely resected, intermediate-risk cancer., Methods: Patients had squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, or larynx, with one or more risk factors warranting postoperative RT. Patients were randomly assigned 1:1 to intensity-modulated RT (60-66 Gy) with once-per-week C or RT alone. The primary hypothesis was that RT + C would improve overall survival (OS) in randomly assigned/eligible patients, with a prespecified secondary plan to test this in the human papillomavirus (HPV)-negative subpopulation. Disease-free survival (DFS) and toxicity were secondary end points. OS and DFS were tested via stratified log-rank test; toxicity was compared via Fisher's exact test., Results: We enrolled 702 patients from November 2009 to March 2018; 577 were randomly assigned/eligible. Most (63.6%) had oral cavity cancer and most (84.6%) had high epidermal growth factor receptor expression. There were fewer deaths (184) than expected. OS (median follow up, 7.2 years) was not significantly improved (hazard ratio [HR], 0.81; one-sided P = .0747; 5-year OS 76.5% v 68.7%), but DFS was (HR, 0.75; one-sided P = .0168; 5-year DFS 71.7% v 63.6%). Benefit of RT + C was only seen in the HPV-negative subpopulation (80.2% of patients in the trial). Grade 3-4 acute toxicity rates were 70.3% (RT + C) versus 39.7% (RT; two-sided P < .0001), mostly skin and/or mucosal effects. Late grade ≥3 toxicity rate was 33.2% (RT + C) versus 29.0% (RT; two-sided P = .3101). There were no grade 5 toxicities in either arm., Conclusion: RT + C significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT + C is an appropriate option for carefully selected patients with HPV-negative disease.

Objective: Anterior capsulotomy (AC) is a therapeutic option for patients with severe, treatment-resistant obsessive-compulsive disorder (OCD). The procedure can be performed via multiple techniques, with stereotactic radiosurgery (SRS) gaining popularity because of its minimally invasive nature. The risk-benefit profile of AC performed specifically with SRS has not been well characterized. Therefore, the primary objective of this study was to characterize outcomes following stereotactic radiosurgical AC in OCD patients., Methods: Studies assessing mean Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores before and after stereotactic radiosurgical AC for OCD were included in this analysis. Inverse-variance fixed-effect modeling was used for pooling, and random-effects estimate of the ratio of means and standard mean differences were calculated at 6 months, 12 months, and the last follow-up for Y-BOCS scores, as well as the last follow-up for the Beck Depression Inventory (BDI)/BDI-II scores. A generalized linear mixed model was used to generate fixed- and random-effects models for categorical outcomes. Univariate random-effects meta-regression was used to evaluate associations between postoperative Y-BOCS scores and study covariates. Adverse events were summed across studies. Publication bias was assessed with Begg's test., Results: Eleven studies with 180 patients were eligible for inclusion. The mean Y-BOCS score decreased from 33.28 to 17.45 at the last-follow up (p < 0.001). Sixty percent of patients were classified as responders and 10% as partial responders, 18% experienced remission, and 4% had worsened Y-BOCS scores. The degree of improvement in the Y-BOCS score correlated with time since surgery (p = 0.046). In the random-effects model, the mean BDI at the last follow-up was not significantly different from that preoperatively. However, in an analysis performed with available paired pre- and postoperative BDI/BDI-II scores, there was significant improvement in the BDI/BDI-II scores postoperatively. Adverse events numbered 235, with headaches, weight change, mood changes, worsened depression/anxiety, and apathy occurring most commonly., Conclusions: Stereotactic radiosurgical AC is an effective technique for treating OCD. Its efficacy is similar to that of AC performed via other lesioning techniques.

Despite its clinical use and investigation in other countries, low dose radiation therapy (LDRT) in the treatment of osteoarthritis (OA) is minimally used in the United States (US). Numerous recent studies published outside the US have shown moderate to long-term pain relief and improvement of mobility after treatment with LDRT for joints affected by OA. Here, we review the most recent literature published on the use of LDRT in OA. We provide a brief outline on the epidemiology, pathophysiology, current treatments, and health care burden of OA within the US. We provide a brief history of the historic use of LDRT in the US as well as a history of LDRT within the modern era of radiation oncology, discuss criticisms of LDRT including recently published randomized trials questioning its benefit as well as the risk of secondary malignancy from LDRT, and provide an outline of treatment planning considerations and recommendations regarding dose and fractionation, energy, beam arrangements, and immobilization techniques. LDRT has been shown to be a cost-effective, noninvasive treatment with minimal side effects. Further investigation into the potential role in the treatment of OA with modern LDRT is recommended., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Acute oropharyngeal hemorrhage is a serious complication for patients with oropharyngeal squamous cell carcinoma (OPSCC), particularly in patients with a history of radiation therapy (RT)., Methods: Retrospective case series from at a tertiary care center for treated patients with HPV-positive OPSCC presenting with oropharyngeal hemorrhage., Results: Median time from completion of chemoradiation to first hemorrhagic event was 186 days (range 66-1466 days). Seven patients (58%) required intervention to secure their airway. All patients were evaluated for endovascular intervention, six (50%) were embolized. Eight patients (67%) had a second hemorrhagic event; median time to second bleed was 22 days (range 3-90 days)., Conclusions: Acute oropharyngeal hemorrhage is a sequelae following treatment for HPV-positive OPSCC. The majority of bleeds occurred within a year of completion of treatment. While more research is needed to determine optimal treatment paradigms, endovascular intervention should be considered, even if noninvasive imaging does not demonstrate active bleeding., (© 2022 Wiley Periodicals LLC.)

Objectives: During the COVID-19 pandemic, maintenance of safe and timely oncologic care has been challenging. The goal of this study is to compare presenting symptoms, staging, and treatment of head and neck mucosal squamous cell carcinoma during the pandemic with an analogous timeframe one year prior., Materials and Methods: Retrospective cohort study at a single tertiary academic center of new adult patients evaluated in a head and neck surgical oncology clinic from March -July 2019 (pre-pandemic control) and March - July 2020 (COVID-19 pandemic)., Results: During the pandemic, the proportion of patients with newly diagnosed malignancies increased by 5%, while the overall number of new patients decreased (n = 575) compared to the control year (n = 776). For patients with mucosal squamous cell carcinoma (SCC), median time from referral to initial clinic visit decreased from 11 days (2019) to 8 days (2020) (p = 0.0031). There was no significant difference in total number (p = 0.914) or duration (p = 0.872) of symptoms. During the pandemic, patients were more likely to present with regional nodal metastases (adjusted odds ratio (OR) 2.846, 95% CI 1.072-3.219, p = 0.028) and more advanced clinical nodal (N) staging (p = 0.011). No significant difference was seen for clinical tumor (T) (p = 0.502) or metastasis (M) staging (p = 0.278). No significant difference in pathologic T (p = 0.665), or N staging (p = 0.907) was found between the two periods., Conclusion: Head and neck mucosal SCC patients presented with more advanced clinical nodal disease during the early months of the COVID-19 pandemic despite no change in presenting symptoms., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Management of jugular paragangliomas (PGL) has evolved toward subtotal resection (STR). The purpose of this study is to analyze neural preservation and adjuvant treatment for long-term local control., Study Design: Retrospective chart review., Settings: Tertiary neurotology practice., Subjects and Methods: Adults undergoing surgical treatment of jugular PGL between 2006 and 2019. Patients, disease, and treatment variables were collected retrospectively. Single predictor logistic regression was used to ascertain predictors of regrowth or need for salvage radiation., Results: A total of 41 patients (median age, 47 years; 76% female) were identified. Most patients presented with advanced-stage disease (Glasscock-Jackson stage III-IV = 76%). Subtotal resection (STR) was performed in 32 (78%) patients. Extended STR (type 1) was the most commonly performed conservative procedure (n = 19, 59%). Postoperative new low cranial neuropathy (LCN) involving CN X and XII was rare (n = 3 and n = 1, respectively). Seventeen patients (41%) underwent postsurgical therapy for tumor regrowth or recurrence, including 15 patients who underwent adjuvant (n = 4) or salvage (n = 11) radiation. Overall tumor control of 94.7% was achieved at a mean follow-up of 35 months. All patients treated with combined modality treatment had local control at last follow-up. Logistic regression identified no single predictor for postsurgical radiation treatment or salvage-free survival., Conclusion: Management of jugular PGL with a conservative approach is safe and effective with a low rate of new LCN deficit. Active surveillance of residual tumor with salvage radiation for growth results in excellent long-term tumor control.

Background: We conducted a correlative study for E2399, a function preservation trial for resectable locally advanced oropharynx and larynx cancer, to prospectively assess effects of chemoradiation (CCR) on quality of life (QOL), swallowing and voice. We correlated the results of swallow assessments done via questionnaires and objective assessments by modified barium swallow (MBS)., Methods: The Functional Assessment of Cancer-HN (FACT-HN), the Performance Status Scale - Head and Neck (PSS-HN), swallow assessments (including modified barium swallow studies), and voice assessments: Voice Handicap Index (VHI), the Voice Disability Assessment (VDA), and American Speech-Language Hearing Association's Functional Communication Measure (FCM) were conducted at baseline and periodically post-treatment for 2 years., Results: Baseline QOL and swallowing function predicted overall survival. Patients experienced a marked decrease in QOL, swallowing, and speech post CCR although the decrease in vocal function was modest. Function and QOL returned towards baseline in the majority of patients by 12 months post treatment. Less than 10% of patients had severe dysphagia and were PEG dependent at 12 months post treatment. There was a high degree of correlation between the FACT-HN and PSS-HN swallow items. Statistically significant correlations were found between subjective and objective measures of swallow function., Conclusions: Patients experience marked loss in swallowing function post CCR which returned to baseline in the majority of patients. The correlations between the FCM and self-report swallow items on the PSS and FACT-HN appear to be sufficiently strong to justify their use as a surrogate marker for swallowing disability in large therapeutic trials.

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., (© 2020 Wiley Periodicals LLC.)

Background: The purpose of this study was to determine the prevalence and nature of internal, external, and combined lymphedema and fibrosis in patients with head and neck cancer (HNC)., Materials and Methods: We obtained consent from 100 patients newly diagnosed with having cancer of the head and neck for a 4-year, prospective, longitudinal descriptive study. Recruitment began in August 23, 2010, and the study was completed in April 24, 2014. Eighty-three were evaluated at regular intervals from preradiation therapy to 18 months post-treatment. Percentage developing external, internal, or both types of lymphedema and/or fibrosis and trajectories of the severity of external, internal, or both types of lymphedema and/or fibrosis were determined., Results: Before treatment, lymphedema rates were the following: external: 62.7%, internal: 41.7%, or combined: 29.2%, and/or fibrosis: 42.2%. Ranges of lymphedema late-effect rates were even higher: external: 81.9%-90.1%, internal: 80.4%-89.4%, combined: 70.6%-80.9%, and fibrosis: 66.7%-77.4%. Approximately 75% had a late-effect trajectory characterized by moderate to severe external or internal lymphedema; ∼47% had moderate to severe fibrosis., Conclusion: Lymphatic and soft tissue complications of HNC occur not only post-treatment but also before treatment. They are ubiquitous throughout the first 18 months post-treatment, with greater than 90% of patients in our study experiencing some form of internal, external, or combined lymphedema, and over half of those patients developing fibrosis. Further research regarding these conditions is indicated., Competing Interests: Author Disclosure Statement No competing financial interests exist.

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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.

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.

Introduction: The neurovascular and anatomic relationships surrounding craniopharyngiomas, and their tending to recur despite any method of primary treatment, has characterized this tumor as an exigent and frustrating clinical entity. Various strategies have been developed to deal with recurrences which include radical re-resection, stereotactic or localized radiotherapy, cyst fenestration, marsupialization or stent placement, and intracavitary therapies such as bleomycin or radionucleotides., Case Report: We present a case where the patient had previously experienced a transsphenoidal resection followed by a pterional, microsurgical resection of her craniopharyngioma at an outside hospital. The second recurrence was cystic, and confined to the sella. We elected to proceed with a minimally invasive, transnasal endoscopic approach for the instillation of phosphorus 32 radionucleotide into the cyst. There were no complications, and the patient was discharged home on postoperative day one. At six months, there was no progression of the cyst., Conclusion: While intracystic adionucleotide therapies have been utilized for primary and secondary treatment of craniopharyngioma, to our knowledge, this is the first report of the delivery of this therapy by an endoscopic transsphenoidal route., (Copyright Georg Thieme Verlag KG Stuttgart. New York.)

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., ((Copyright) 2008 American Cancer Society.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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].)., (Copyright 2007 Massachusetts Medical Society.)

Combined-modality treatment of head and neck cancers, though linked to improved outcomes over earlier treatment methods, can be associated with acute and late adverse effects. These toxicities may lead to significant morbidity, increased mortality, and decreased quality of life. It is necessary to provide patients with adequate supportive-care measures in order to lessen suffering while maintaining the ability to deliver necessary doses of anticancer agents. The current review describes the pathology, assessment, and treatment options for cases of mucositis, impaired swallowing, nutritional and metabolic changes, xerostomia, radiation dermatitis, lymphedema, taste alterations, and pain, all of which may be associated with treatment of patients with head and neck cancers. Additionally, the pretreatment and during-treatment evaluation of dental health, as well as posttreatment dental care, are described.

Purpose: High epidermal growth factor receptor (EGFR) gene copy number is associated with poor prognosis in lung cancer, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC., Patients and Methods: EGFR status was analyzed in 86 tumor samples from 82 HNSCC patients by fluorescent in situ hybridization (FISH) to determine EGFR gene copy number, by polymerase chain reaction and direct sequencing for activating mutations, and by DNA microarray and immunohistochemistry for RNA and protein expression. The results were associated with patient characteristics and clinical end points., Results: Forty-three (58%) of 75 samples with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH positive). The FISH-positive group did not differ from the FISH-negative group with respect to age, sex, race, tumor grade, subsites and stage, or EGFR expression by analyses of RNA or protein. No activating EGFR mutations were found. However, the FISH-positive group was associated with worse progression-free and overall survival (P < .05 and P < .01, respectively; log-rank test). When microarray data were interrogated using the FISH results as a supervising parameter, ECop (which is known to coamplify with EGFR and regulate nuclear factor-kappa B transcriptional activity) had higher expression in FISH-positive tumors., Conclusion: High EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.

Traditionally, the role of chemotherapy in the treatment of squamous carcinoma of the head and neck has been confined to patients with recurrent or metastatic disease who are deemed incurable with surgery or radiation therapy. Over the past decade, however, the role of chemotherapy has changed dramatically. The use of primary combined chemoradiation to preserve function or to enhance survival in patients with unresectable disease has become a standard approach. As the use of chemotherapy in squamous carcinoma of the head and neck has expanded, investigators have been interested in identifying new active agents. Topoisomerase I inhibitors, a new class of drugs, have been found to be active in a number of solid and hematologic malignancies. Three topoisomerase I inhibitors have been investigated in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: 9-aminocamptothecin (9-AC), topotecan (Hycamtin), and irinotecan (CPT-11, Camptosar). Neither 9-AC nor topotecan has demonstrated clinically significant activity in the treatment of metastatic or recurrent squamous carcinoma of the head and neck. In contrast, irinotecan has demonstrated a modest overall response rate of 21.2% (95% confidence interval [CI] = 9%-38.9%), with a median survival of 214 days and a 1-year survival rate of 30.2%. The response and toxicity appear to be dose dependent. Further investigation of irinotecan in combination with other active agents and radiotherapy is warranted.

Background: Nonsmall cell lung carcinoma comprises approximately 75% of all lung carcinoma cases in the U.S. Newly evolving strategies have created considerable controversy regarding the optimal treatment for patients diagnosed with this disease., Methods: A 17-item survey was designed to collect demographic data and information regarding practice patterns for nonsmall cell lung carcinoma, including patient assessment, treatment approaches, and roles of chemotherapy and radiotherapy. Surveys were mailed in the summer of 1997 to approximately 9200 oncologists of all types throughout the U.S. Practice settings included private office, private hospital, academic, university-affiliated office, government, and Veterans Administration institutions., Results: Approximately 10% of the oncologists responded (n = 979), including 499 medical oncologists (51%), 464 radiation oncologists (47%), and 16 others (2%). For the adjuvant treatment of surgically resected N1-2 disease, combined modality treatment was preferred over radiation therapy alone by medical oncologists (48% vs. 16%; P<0.001) and radiation therapy alone was preferred over combined modality treatment by radiation oncologists (55% vs. 38%; P<0.001). The combination of paclitaxel and carboplatin was the preferred first-line regimen for all stages of nonsmall cell lung carcinoma by the majority of medical oncologists (55%), whereas the majority of radiation oncologists (58%) chose the combination of etoposide and platinum. With regard to the optimal combined modality approach, respondents were divided evenly between concurrent chemoradiotherapy (34%) and sequential chemoradiotherapy (31%). Overall, respondents reported basing treatment decisions largely on published literature (55%) compared with personal experience (19%), seminars and colleagues (16%), and clinical trial availability (10%) (P<0.001)., Conclusions: This survey confirms many differences in practice patterns among medical oncologists and radiation oncologists in the treatment of patients with nonsmall cell lung carcinoma and suggests the need for the multidisciplinary management of this entity. In addition, the current study demonstrates that reliance on the medical literature as a basis for treatment steadily declines the longer the physician has been in practice., (Copyright 2000 American Cancer Society.)

Obliteration of the tumor vasculature is an effective means of achieving tumor regression. Antiangiogenic agents have begun to enter cancer clinical trials. Ionizing radiation activates the inflammatory cascade and increases the procoagulative state within blood vessels of both tumors and normal tissues. These responses are mediated through oxidative injury to the endothelium, leading to induction of cell-adhesion molecules and exocytosis of stored proteins from the endothelial cytoplasm. Agents that activate homeostatic responses in the endothelium can enhance thrombosis and vasculitis of irradiated tumor blood vessels. Proinflammatory and prothrombotic biological response modifiers given concurrently with ionizing radiation are known to induce vascular obliteration and necrosis of tumors. Other mechanisms of interaction between antiangiogenic agents and ionizing radiation include the direct cytotoxic effects of these agents. Interactions between drugs and radiation therapy might therefore occur at the level of the vascular endothelium. The importance of this paradigm is that the endothelium might not develop resistance to drugs or radiation because of lessened potential for mutagenesis and clonogenesis. The future design of clinical trials must consider the effects of radiation therapy on the vascular endothelium.

Traditionally, treatment for locally advanced resectable head and neck cancer has been surgical resection followed by postoperative radiation. In unresectable patients, primary radiation has been the mainstay of treatment. In an attempt to improve local control and survival, chemotherapy has been investigated as an adjunct to locoregional treatment. Induction or adjuvant chemotherapy in combination with primary surgical resection has failed to demonstrate an improvement in either local control or survival. Induction chemotherapy followed by radiation therapy is an acceptable alternative to surgical resection for organ preservation. A randomized trial in patients with advanced oropharyngeal carcinoma and another in advanced nasopharyngeal carcinoma have shown an improvement in survival with the use of concomitant chemotherapy and radiation compared to radiation alone. Other prospective randomized trials as well as three meta-analyses also demonstrate improved survival with the addition of concomitant chemotherapy for locally advanced disease. Newer chemotherapeutic agents are currently under investigation, particularly those with radiosensitizing properties. Chemotherapy as part of primary therapy, however, should be used judiciously, and should be based on an assessment of the potential risks and benefits to each patient.