Search

Background: Understanding biological differences between different racial groups of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) patients, who have differences in terms of incidence, survival, and tumor morphology, can facilitate accurate prognostic biomarkers, which can help develop personalized treatment strategies., Methods: This study evaluated whether there were morphologic differences between HPV-associated tumors from Black and White patients in terms of multinucleation index (MuNI), an image analysis-derived metric that measures density of multinucleated tumor cells within epithelial regions on hematoxylin-eosin images and previously has been prognostic in HPV-associated OPSCC patients. In this study, the authors specifically evaluated whether the same MuNI cutoff that was prognostic of overall survival (OS) and disease-free survival in their previous study, T TR , is valid for Black and White patients, separately. We also evaluated population-specific cutoffs, T B for Blacks and T W for Whites, for risk stratification., Results: MuNI was statistically significantly different between Black (mean, 3.88e-4; median, 3.67e-04) and White patients (mean, 3.36e-04; median, 2.99e-04), with p = .0078. Using T TR , MuNI was prognostic of OS in the entire population with hazard ratio (HR) of 1.71 (p = .002; 95% confidence interval [CI], 1.21-2.43) and in White patients with HR of 1.72 (p = .005; 95% CI, 1.18-2.51). Population-specific cutoff, T W , yielded improved HR of 1.77 (p = .003; 95% CI, 1.21-2.58) for White patients, whereas T B did not improve risk-stratification in Black patients with HR of 0.6 (p = .3; HR, 0.6; 95% CI, 0.2-1.80)., Conclusions: Histological difference between White and Black patient tumors in terms of multinucleated tumor cells suggests the need for considering population-specific prognostic biomarkers for personalized risk stratification strategies for HPV-associated OPSCC patients., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: We sought to determine whether detection of cartilage invasion (CI) by computed tomography predicts oncologic outcomes after primary total laryngectomy., Methods: Retrospective cohort study comparing oncologic outcomes between radiologic versus pathologic diagnosis., Results: Assessment of clear CI versus gestalt CI resulted in 84% versus 48% specificity, 90.9% versus 80.3% positive predictive value (PPV), 60.6% versus 80.3% sensitivity, 44.7% versus 48% negative predictive value (NPV), respectively. Disease-free survival (DFS) was similar between cT4a and cT3/cT2 patients (p = 0.87). DFS trended towards superiority among pT3/pT2 versus pT4a patients (p = 0.18). DFS was similar among patients with CI on radiologist gestalt versus no CI (p = 0.94). Histologically confirmed CI was associated with a hazard ratio (HR) of 1.46 (p = 0.27), gestalt CI 1.13 (p = 0.70), and clear CI 1.61 (p = 0.10) for DFS., Conclusion: Gestalt determination of CI results in high sensitivity but low specificity, while clear determination of CI results in moderate sensitivity and high specificity., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background/aim: Definitive treatment for locally advanced head and neck squamous cell carcinoma (LAHNSCC) is often compromised in older adults due to concerns about potential treatment toxicity intolerance. We reviewed our institutional experience with definitive management of older adults with LAHNSCC., Patients and Methods: From our Institutional Review Board-approved registry, we identified patients aged >60 years with stage III-IV, M0 LAHNSCC (seventh/earlier editions of the American Joint Committee on Cancer classification) treated with definitive radiotherapy from 1993-2019. Indications for concurrent chemotherapy included T3-4 or N2-3 disease. Multivariable analysis using Fine and Gray regression was performed to identify risk factors associated with recurrence. The cumulative incidence method was used to calculate recurrence rates., Results: Overall, 350 patients were identified: 223 aged 60-69, 82 aged 70-74, and 45 aged ≥75 years. Median follow-up was 36.3 months. Two-year recurrence rates were 13.7%, 20.2% and 34.8%, respectively; human papillomavirus-positive disease was present in 190 (85%), 44 (54%), and 25 (56%), respectively; and systemic therapy was given to 194 (87%), 64 (88%), and 23 (56%) patients, respectively. Factors significantly associated with increased risk of recurrence included age ≥75 years, Karnofsky performance status 70-80, clinical N2c-N3, and Charlson score 2-3., Conclusion: Patients aged ≥75 years received less aggressive therapy and experienced increased recurrence compared to younger patients. Outcomes for those aged 70-74 years were similar to younger patients treated with aggressive therapy, despite their inferior performance status/comorbidity, and such patients should not routinely be excluded from standard-of-care therapy. Further study is needed to optimize therapy for a redefined older adult (age ≥75 years) population., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: To explore the influence of treatment package time(TPT) in high-risk oral cavity squamous cell carcinoma(OCSCC) receiving adjuvant radiotherapy with concurrent chemotherapy(CRT)., Materials and Methods: We queried our multi-institutional OCSCC collaborative database for cases diagnosed between 2005 and 2015 who underwent surgery followed by adjuvant CRT. All patients had high-risk features: extranodal extension(ENE) and/or positive surgical margin(PM). TPT was days between surgery to last radiotherapy fraction. Kaplan-Meier curves, log-rank p-values and multivariate analysis(MVA) were used to investigate the impact of TPT on overall(OS), disease-free(DFS), locoregional failure-free(LRFS) and distant metastases-free(DMFS) survival., Results: We identified 187 cases: median age 58 (range, 24-87 years), males 66%, and ever smokers 69%. ENE and PM were detected in 85% and 32%, and oral tongue and floor of the mouth constituted 49% and 18%, respectively. Median radiotherapy and cisplatin doses received were 66 Gy and 200 mg/m2. Overall, median TPT was 98 (range, 63-162 days). OS was worse for TPT > 90-days (n = 134) than TPT ≤ 90 (n = 53) at two-(65% vs. 71%) and five-years (45% vs. 62%); p = 0.05, with similar results for DFS. No influence on LRFS or DMFS was noted. More lymph nodes(LN) dissected(P = 0.039), T3-4 disease(P = 0.017), and unplanned reoperations(P = 0.037) occurred with TPT > 90-days. On MVA, TPT in 10-day increments was independently detrimental for OS (Hazard Ratio: 1.14; 95 %Confidence Interval [1-1.28]; P = 0.043), perineural invasion, age and positive LN (p < 0.05 for all)., Conclusion: In one of the largest multi-institutional cohorts, TPT > 90-days predicted worse OS for high-risk OCSCC receiving adjuvant CRT. All efforts are needed to optimize perioperative care and baseline conditions for favorable outcomes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m 2 cisplatin dose ( p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m 2 ) vs. 20.8 months (≥200 mg/m 2 ). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m 2 was associated with improved DFS in high-risk resected OCSCC pts.

Background/aim: Satellitosis/in-transit metastasis (S-ITM) has prognostic value in melanoma and Merkel cell carcinoma, but is not incorporated into cutaneous squamous cell carcinoma (cSCC) staging., Patients and Methods: From our IRB-approved registry, patients with high-risk cSCC, including patients with S-ITM, were identified. Univariate (UVA) and multivariate (MVA) analyses were performed to compare disease progression (DP) and overall survival (OS). Cumulative incidence of DP and OS analyses were performed using Fine-Gray and Kaplan-Meier methods, respectively., Results: A total of 18 S-ITM subjects were compared to 247 high risk subjects including T3N0 (n=143), N1-N3 without extranodal extension (ENE) (n=56), N1-N3 with ENE (n=26) and M1 disease (n=22). Median follow up was 16.5 months. Three-year rates of DP were 22% for T3N0, 42% for S-ITM, 48% for T4 bone invasion, 50% for N1-N3 without extranodal extension (ENE), 53% for N1-N3 with ENE, and 66% for M1. Patients with S-ITM did not experience significantly worse DP compared to those with T3N0 (HR=1.96, 95%CI=0.8-4.9; p=0.14)., Conclusion: Cutaneous SCC patients with S-ITM experienced outcomes similar to locally advanced non-metastatic cSCC patients. Larger studies are needed to guide incorporation into staging systems., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To investigate the association between tumor volume and locoregional failure (LRF) after concurrent chemoradiation (CCRT) for locally advanced larynx cancer (LC)., Methods: This is a retrospective cohort study from 2009 to 2014 identified from an institutional review board-approved registry. Fifty-nine of 68 patients with locally advanced larynx cancer treated with definitive CCRT who had available imaging for review were identified. The main endpoint to be assessed was the association between gross tumor volumes (GTV; T = total, P = primary, N = nodal) and LRF. Receiver operative characteristic (ROC) curves were used to investigate diagnostic accuracy., Results: Twenty LRFs were observed, resulting in a 2-year LRF rate of 39% (95% CI, 23-52%). On UVA, the GTV-T (P = .01), GTV-P (P = .05), and GTV-N (P = .04) were statistically significant predictors of LRF. Furthermore, age, smoking status, N-stage, larynx subsite, and tracheostomy/feeding tube dependence were potentially associated with LRF (P < .3), whereas T-stage (T3-4 vs. T2) was not (HR 1.05, 95% CI, 0.38-2.91, P = .92). In the multivariable model, GTV-P (HR 1.022, 95% CI, 0.999-1.046, P = .07) and GTV-N (HR 1.053, 95% CI, 1.0004-1.108, P = .05) were the two most impactful covariates on the model's R 2 . ROC analysis suggested an optimal cut point of 12 cc in the GTV-T. The 2-year LRF for GTV-T > 12 cc was 64.2% and ≤ 12 cc was 16.4%, P = .006., Conclusion: GTV is associated with LRF after definitive CCRT for LC. Patients with bulky primary and/or nodal tumors may be better served with upfront surgical resection regardless of T-stage. Further investigation into the safety of larynx preservation for low-volume T4 tumors can be considered., Level of Evidence: 4 Laryngoscope, 130:2372-2377, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: We investigated the impact of level I lymph node involvement (LNI) on survival for patients with oropharyngeal squamous cell carcinoma (OPSCC)., Methods: We performed a cohort study of patients with OPSCC who underwent resection with known human papillomavirus (HPV) status in the National Cancer Database (2010-2014)., Results: Among 5591 patients with OPSCC, 599 (10.7%) had level I LNI. Predictors of level I LNI included pT classification (pT3 vs pT1; odds ratio [OR], 1.95; P < 0.001), pN classification (pN3 vs pN1; OR, 1.63; P = 0.05), and level III LNI (OR, 6.05; P < 0.001). Among included patients, 4035 had known survival status. Level I LNI predicted inferior overall survival (OS) while adjusting for covariates (HR, 1.64; P < 0.001). Subset analyses revealed association between level I LNI and inferior OS among patients with base of tongue cancer, pT/pN classification greater than 1, and HPV-negative cancer., Conclusions: Level I LNI predicts inferior OS, particular among patients with at least pT2 or pN2 OPSCC., (© 2019 Wiley Periodicals, Inc.)

Background/aim: There are limited data regarding survival, failure patterns, and factors associated with disease recurrence in patients with cutaneous squamous cell cancer of the head and neck (cSCC-HN) with nodal metastases., Patients and Methods: A retrospective analysis of patients with cSCC-HN metastatic to cervical and/or parotid lymph nodes treated with surgery and post-operative radiation therapy was performed., Results: This study included 76 patients (57 immunocompetent and 18 immunosuppressed) with a median follow-up of 18 months. Overall survival, disease-free survival (DFS), and disease recurrence (DR) at 2 years was 60%, 49%, and 40%, respectively. Immunosuppressed patients had significantly lower 2-year DFS (28% vs. 55%; p=0.003) and higher DR (61% vs. 34%; p=0.04) compared to immunocompetent patients. Analysis of immunocompetent patients demonstrated extracapsular extension (ECE) as the only factor associated with DR (p<0.0001)., Conclusion: Patients with nodal metastases from cSCC-HN have suboptimal outcomes. ECE and immunosuppression were significantly associated with DR., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives/hypothesis: Patients with human papillomavirus (HPV)-induced cancer of unknown primary (CUP) are generally excluded from clinical trials, despite surgical series reporting detection rates of occult oropharynx primaries of >80%. We performed a matched-pair analysis to compare outcomes between T0N1-3M0 HPV+ CUP and T1-2N1-3M0 HPV+ oropharynx known primary (OPX)., Study Design: Retrospective cohort study at a single institution., Methods: Patients with early T stage, node positive HPV+ OPX or CUP treated with curative intent between 1998 and 2016 were identified. For a subgroup of CUP patients with an unknown HPV status, we imputed HPV status and included patients with a >80% probability of being HPV+. Cohorts were matched based on patient demographics using a nearest neighbor propensity technique. After matching, patients were grouped according to either a favorable or unfavorable risk stratification designations per current NRG Oncology clinical trial enrollment criteria. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier analysis., Results: Of 298 patients with T1-2N1-3 OPX, 48 were matched to 48 HPV+ CUP patients (32 with confirmed and 16 imputed HPV status). Median follow-up for CUP (34.1 months) and OPX (27.8 months) patients were similar (P = .23).There were no significant differences between the CUP and OPX groups for 3-year DFS (89% vs. 85%, P = .44), and 3-year OS (91% vs. 91%, P = .11), respectively., Conclusions: Patients with T0N+M0 HPV-induced CUP have similar survival outcomes to matched patients with T1-2N+M0 HPV+ OPX. These patients can reasonably be included in clinical trials investigating the role of treatment deintensification and risk stratified similar to patients with early-stage known primary OPX cancer., Level of Evidence: 4. Laryngoscope, 128:1379-1385, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Background/aim: Definitive chemoradiation (CRT) is a common approach for locally advanced hypopharyngeal squamous cell carcinoma (SCC) with the goal of organ preservation. Reports on long-term oncologic and functional outcomes have been limited. This study reports on outcomes utilizing this approach at a single institution over 30 years., Materials and Methods: Medical records for patients with stage III-IVB SCC of the hypopharynx were retrospectively reviewed. Patient and disease-related factors were identified and analyzed for impact on overall survival (OS), cancer-specific survival (CSS), disease-free survival, distant failure, and locoregional failure., Results: A total of 54 patients were identified who were treated with definitive CRT to a mean dose of 72 Gy. With a median follow-up period of 49.8 months, 5- and 10-year OS was 62% and 43% respectively. Five and 10-year CSS were 74% and 72% respectively. Ten-year local control was 78%. Of the 37 patients with no treatment failure, 29% experienced a grade 3 or higher late toxicity, with the majority resolving during continued long-term follow-up., Conclusion: This study demonstrates good outcomes with long-term follow-up with acceptable rates of late toxicities. The findings here represent the longest published median follow-up in this population and validate the strategy of organ preservation., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Time to treatment initiation (TTI) is increasing and is associated with worsening survival. In the current study, the authors sought to identify a mechanism for this relationship by assessing the effect of TTI on clinical-to-pathologic upstaging in patients with head and neck squamous cell carcinoma (HNSCC)., Methods: Using the National Cancer Data Base, the authors analyzed patients receiving definitive surgery for SCC of the oral cavity, oropharynx, larynx, and hypopharynx from 2005 through 2014. The primary outcome was T, N, or stage group upstaging, defined as higher pathologic stage than clinical stage. TTI was defined as the time between diagnosis and surgery. Multivariable logistic and Cox proportional hazards regression modeled upstaging and survival, respectively., Results: Cohorts of 60,194 patients, 51,380 patients, and 52,980 patients, respectively, with complete T, N, and stage group data were included. N upstaging was most common (18.6%), followed by stage group (17.4%) and T (12.1%) upstaging; all types were predicted by TTI. Compared with a TTI of 1 to 6 days, TTIs as short as 7 to 13 days (odds ratio, 1.20; P = .038) or ≥ 70 days (odds ratio, 2.04; P < .001) were found to predict T upstaging, a finding that is consistent for N and stage group upstaging. Using restricted cubic splines, relative odds of T and stage group upstaging escalated to 2.25 and 1.93, respectively, at a TTI of 365 days. In survival analyses, T (hazard ratio [HR], 1.53), N (HR, 1.88), and stage group (HR, 1.69) upstaging all predicted mortality (P < .001), whereas TTI only predicted mortality after 70 days (HR, 1.11; P = .023)., Conclusions: Tumor progression, measured by clinical-to-pathologic upstaging, increases mortality for patients with HNSCC experiencing treatment delays. Cancer 2018;124:1400-14. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Purpose The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy in oropharyngeal squamous cell carcinoma (OPSCC) that was determined to be relevant to the American Society of Clinical Oncology (ASCO) membership. After applying standard critical appraisal policy and endorsement procedures, ASCO chose to endorse the ASTRO guideline. Methods The ASTRO guideline was reviewed by ASCO content experts for clinical accuracy and by ASCO methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened to review the guideline contents and recommendations. The ASCO guideline approval body, the Clinical Practice Guidelines Committee, approved the final endorsement. Results The ASCO Expert Panel determined that the ASTRO guideline recommendations, published in July 2017, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the ASTRO guideline and added minor qualifying statements. Recommendations Recommendations for the addition of systemic therapy to definitive radiotherapy in the treatment of OPSCC, postoperative radiotherapy with and without systemic therapy following primary surgery of OPSCC, induction chemotherapy in the treatment of OPSCC, and the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC are outlined for a variety of disease stages and clinical scenarios. ASCO Endorsement Panel qualifying statements and minor modifications were made to the ASTRO recommendations. The staging system that is referenced in these guidelines is the American Joint Committee on Cancer Staging Manual, 7th edition. Additional information is available at: www.asco.org/head-neck-cancer-guidelines and www.asco.org/guidelineswiki .

Purpose: To determine the patterns of adjuvant chemoradiotherapy use in elderly patients treated with definitive surgical resection for squamous cell carcinoma of the head and neck with extracapsular extension (ECE) or positive margins and determine whether an association with overall survival (OS) exists with adjuvant concurrent chemoradiotherapy (CRT)., Methods and Materials: The National Cancer Database was queried to identify patients with SCC of the oral cavity, oropharynx, larynx, and hypopharynx who were treated with primary definitive surgery and adjuvant radiation therapy between 2004 and 2012. For elderly patients (aged >70 years) with pathology revealing ECE or positive margin, the benefit of concurrent chemotherapy was explored using multivariable Cox proportional hazards modeling., Results: A total of 7349 patients were identified meeting study criteria, of whom 1187 were elderly (aged >70 years) with a median follow-up of 30.6 months. Of these elderly patients, 445 had ECE or positive margin and represent the study population, of whom 187 (42%) received CRT. Delivery of CRT in this cohort increased over the study period, and intensity modulated radiation therapy was associated with increased use of CRT (odds ratio 2.07; P=.004). Increasing age was associated with reduced use of CRT (odds ratio 0.88; P<.001). Chemoradiotherapy was associated with a significant improvement in OS on multivariable analysis (hazard ratio 0.74; P=.04) and a trend toward significance on inverse propensity score analysis (hazard ratio 0.78; P=.051). Three-year OS was 53.8% in the CRT group, compared with 44.6% in the adjuvant radiation therapy-alone patients., Conclusions: The use of adjuvant CRT is increasing among elderly patients with resected squamous cell carcinoma of the head and neck exhibiting ECE or positive margins. Chemoradiotherapy was associated with an improvement in OS on multivariable analysis but not propensity-weighted analysis. Among fit elderly patients with ECE or positive margins after definitive surgical resection, concurrent chemotherapy can be carefully considered., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To present evidence-based guidelines for the treatment of oropharyngeal squamous cell carcinoma (OPSCC) with definitive or adjuvant radiation therapy (RT)., Methods and Materials: The American Society for Radiation Oncology convened the OPSCC Guideline Panel to perform a systematic literature review investigating the following key questions: (1) When is it appropriate to add systemic therapy to definitive RT in the treatment of OPSCC? (2) When is it appropriate to deliver postoperative RT with and without systemic therapy following primary surgery for OPSCC? (3) When is it appropriate to use induction chemotherapy in the treatment of OPSCC? (4) What are the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC?, Results: Patients with stage IV and stage T3 N0-1 OPSCC treated with definitive RT should receive concurrent high-dose intermittent cisplatin. Patients receiving adjuvant RT following surgical resection for positive surgical margins or extracapsular extension should be treated with concurrent high-dose intermittent cisplatin, and individuals with these risk factors who are intolerant of cisplatin should not routinely receive adjuvant concurrent systemic therapy. Induction chemotherapy should not be routinely delivered to patients with OPSCC. For patients with stage IV and stage T3 N0-1 OPSCC ineligible for concurrent chemoradiation therapy, altered fractionation RT should be used., Conclusion: The successful management of OPSCC requires the collaboration of radiation, medical, and surgical oncologists. When high-level data are absent for clinical decision-making, treatment recommendations should incorporate patient values and preferences to arrive at the optimal therapeutic approach., (Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Aim: The purpose of the present study was to identify variables associated with high risk of failure in patients with locally advanced squamous cell carcinoma of the oral cavity (SCC-OC)., Patients and Methods: This retrospective study included 191 patients with stage III-IVb SCC-OC treated with post-operative radiotherapy (RT) or chemoradiotherapy (CRT) between 1995 and 2013. Disease-free (DFS) and overall survival (OS) were analyzed; variables associated with inferior DFS were identified., Results: Seventy-five patients (39%) recurred. DFS and five-year OS were 52% and 54%, respectively. Poorly differentiated tumors (p=0.03), recurrent tumors (p=0.02) and high nodal ratio (p=0.02) were associated with an increased risk of recurrence. CRT was associated with improved DFS in patients with positive margins and/or extracapsular extension (p=0.021)., Conclusion: Tumors that are recurrent, high grade, or have high nodal ratio are at risk of recurrence. Presence of these disease features should be taken into consideration for better risk stratification., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objectives: To analyze a cohort of patients with HPV positive, oropharyngeal squamous cell carcinoma (OPSCC) treated with lower radiation dose to clinically involved lymph nodes., Materials and Methods: We retrospectively identified patients with HPV positive, OPSCC treated with definitive chemoradiotherapy (70-74.4Gy) to the primary site and, since a post-radiation neck dissection was planned, 54Gy to the involved nodal areas. Neck dissection was ultimately omitted in all cases due to complete response. All patients were treated with a 3 field approach with sequential boost plans. Composite plans were generated retrospectively and primary tumor and lymph node GTVs were contoured and nodes were expanded by 5mm to form a CTV. Mean dose, dose to 95% (D95) and dose to 99% (D99) were determined., Results: Fifty patients treated from 2008 to 2010 with 113 involved nodes were identified. The median age was 57years, and 6%, 46%, and 48% were current, former, and never smokers. Ninety percent of patients received concurrent cisplatin based chemotherapy. Median D95 and D99 to involved nodes were 59.8Gy and 55.9Gy respectively. At a median follow up of 54.1months, two patients developed nodal failure and four developed metastatic disease. Five year loco-regional control, disease free survival and overall survival were 96%, 81% and 86% respectively., Conclusion: In this exploratory analysis, regional lymph node control in HPV positive oropharyngeal cancer was not compromised by dose de-escalated radiotherapy to involved nodes in the setting of concurrent cisplatin based chemotherapy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Importance: Nonsurgical treatment of advanced supraglottic laryngeal cancer is widely used as part of a larynx preservation protocol. However, recent studies have suggested that nonsurgical treatment may be associated with inferior survival. Furthermore, it is not clear whether preservation of the larynx provides superior voice or swallowing function in the long term., Objective: To test the hypothesis that surgical treatment of advanced-stage squamous cell carcinoma of the supraglottic larynx is associated with superior overall survival (OS), freedom from recurrence (FFR), and noninferior voice and swallowing function., Design, Setting, and Participants: Retrospective medical record review of patients treated for stage III or IV squamous cell carcinoma of the supraglottic larynx between January 1990 and June 2013 at a tertiary referral center: 97 patients underwent surgical treatment and 138, nonsurgical treatment. Exclusion criteria included prior definitive treatment for laryngeal cancer or evidence of distant metastatic disease at presentation. The median follow-up for all 235 patients was 63 months., Interventions: Surgical or nonsurgical therapy., Main Outcomes and Measures: Freedom from recurrence (FFR), OS, larynx preservation, voice graded from 1 to 5, and swallowing graded from 1 to 6 using our voice and swallowing function scales., Results: Surgical treatment was associated with superior FFR (5-year FFR: 75% vs 55%; P = .006) but not OS (5-year OS: 52% vs 52%; P = .61). The larynx was preserved in 83% of patients in the nonsurgical group vs 42% of patients in the surgical group (P < .001). Voice function was superior in the nonsurgical group at all time points through 5 years after treatment (mean voice score, 3.8 vs 2.6; P < .001). Swallowing function was comparable between surgical and nonsurgical groups. Multivariable analysis revealed that advanced age (hazard ratio [HR], 1.43 per 10-year increment; 95% CI, 1.19-1.72) and clinical N stage (HR, 1.17 per 1-level increment; 95% CI, 1.05-1.30) were associated with worse OS, while treatment with chemotherapy was associated with superior OS (HR, 0.61; 95% CI, 0.41-0.92)., Conclusions and Relevance: Compared with surgical treatment, nonsurgical treatment as part of a larynx preservation protocol is associated with a higher likelihood of recurrence but has similar OS and should continue to be viewed as a viable alternative for the treatment of advanced supraglottic laryngeal cancer.

Background: Chemoradiotherapy results in excellent outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC). This trial compared 2 chemoradiotherapy regimens., Methods: Patients with locally advanced HNSCC were treated with radiation (70-74.4 Gy), and randomized to arm A: cisplatin 100 mg/m(2) on radiotherapy (RT) days 1, 22, and 43, or arm B: cisplatin (20 mg/m(2) /day) and 5-fluorouracil (5-FU; 1000 mg/m(2) /day) continuous 96-hour infusions on RT weeks 1 and 4. The primary endpoint was relapse-free survival (RFS)., Results: Between February 2008 and October 2011, 69 patients were enrolled in this study. The study prematurely closed when a scheduled interim analysis showed superior outcomes in both arms and futility of continuation. Eighty-three percent of patients had oropharyngeal cancer, of these, 86% were human papillomavirus (HPV)/p16+. The 3-year Kaplan-Meier outcome estimates (median follow-up, 41 months) for arms A and B were: RFS 87% versus 80% (p = .24), overall survival 97% versus 85% (p = .013), locoregional control 96% versus 94% (p = .52), and distant metastatic control 91% versus 87% (p = .9)., Conclusion: Multiagent was not superior to single-agent chemoradiotherapy. Overrepresentation of HPV/p16+ patients resulted in better than expected outcomes., (© 2014 Wiley Periodicals, Inc.)

Importance: Important differences exist in the pattern and timing of distant metastases between human papillomavirus-initiated (HPV+) and HPV- oropharyngeal squamous cell carcinoma (OPSCC). However, our understanding of the natural history of distant metastases in HPV+ OPSCC and its implications for surveillance is limited., Objective: To investigate the rate, pattern, and timing of distant metastases in advanced-stage OPSCC treated definitively with concomitant chemoradiotherapy., Design, Setting, and Participants: In a retrospective review, we identified 291 patients with pathologically diagnosed stages III to IVB OPSCC and known HPV status from a tumor registry at the Cleveland Clinic. Patients were treated from January 1, 1996, through December 31, 2013. Details of treatment failure and the natural history of the disease were retrieved from the electronic medical records., Interventions: All patients were treated with definitive concomitant chemoradiotherapy., Main Outcomes and Measures: The primary outcome was the rate and timing of distant metastases. Secondary outcomes included the pattern of distant failure and survival after distant metastases., Results: Thirty-seven patients developed distant metastatic disease after definitive treatment, including 28 of 252 patients with HPV+ disease and 9 of 39 patients with HPV- disease. The 3-year projected distant control rate was higher in the HPV+ group (88% vs 74%; P = .01). The median time to develop distant metastases was also longer after the completion of treatment for HPV+ disease compared with HPV- disease (16.4 vs 7.2 months; P = .008). We detected a trend in patients with HPV+ disease for more distant metastatic sites involved than in those with HPV- disease (2.04 vs 1.33 sites; P = .09). Although the lung was the most common distant site involved in HPV+ and HPV- disease (HPV+ group, 23 of 28 patients [82%]; HPV- group, 7 of 9 patients [78%]), the HPV+ group had metastases to several subsets atypical for head and neck squamous cell carcinoma, including the brain, kidney, skin, skeletal muscle, and axillary lymph nodes in 2 patients each and in the intra-abdominal lymph nodes in 3 patients. The rate of 3-year overall survival was higher in the HPV+ group (89.9% vs 62.0%; P < .001), as was the median survival after the occurrence of distant metastases regardless of additional treatment (25.6 vs 11.1 months; P < .001)., Conclusions and Relevance: This retrospective review suggests that distant metastases in patients with HPV+ OPSCC occurs significantly later after completion of chemoradiotherapy than in patients with HPV- disease. Human papillomavirus-initiated OPSCC also appears to involve a greater number of subsites and metastatic sites infrequently seen in head and neck squamous cell carcinoma. Distant metastatic disease in HPV+ OPSCC has unique characteristics and a natural history that may require alternative surveillance strategies.

Background: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) is associated with high cure rates and distant metastases are rare., Methods and Results: We report a case of a 61-year-old man presenting with acute left-sided weakness. An enhancing dural mass was noted and resected. Histology revealed p16-positive SCC. Further workup revealed a p16-positive right tonsillar primary with ipsilateral nodal disease and was classified as T2N2bM1. The patient underwent whole brain irradiation and definitive chemoradiation with curative intent. Complete clinical response was achieved and the patient continues to be disease-free 6 months posttreatment., Conclusion: HPV-associated oligometastatic oropharyngeal SCC is a rare entity that may have a unique natural history and behavior. Given the excellent treatment response and prognosis of HPV-positive disease in general, these patients may be appropriate for definitive treatment approaches., (© 2014 Wiley Periodicals, Inc.)

Head and neck squamous cell carcinoma is the fifth most common cancer worldwide. Patients who present with locally advanced disease are usually treated with a combined modality approach, often including chemotherapy, and frequently using the platinum agents cisplatin or carboplatin. In locally advanced head and neck squamous cell carcinoma, carboplatin and cisplatin have both been found to produce a survival benefit when added to radiation therapy. Although it appears that cisplatin may be more active, carboplatin is better tolerated. Cisplatin has been given concurrently with radiation every 3 weeks, weekly or daily. There have been no prospective trials comparing the different cisplatin dose schedules, but a dose of 100 mg/m(2) administered every 3 weeks on days 1, 22 and 43 with concurrent standard fractionation radiation therapy is the most widely used and tested regimen. The required total dose of cisplatin is also not known, although a necessary dose threshold of 200 mg/m(2) has been suggested.

Objective: To investigate the effectiveness of salvage partial and total laryngectomy in the treatment of recurrent laryngeal cancer in the setting of initial nonoperative treatment failure and to identify factors influencing long-term survival., Study Design: Case series with planned chart review., Setting: Tertiary medical center., Subjects and Methods: Patients with recurrent squamous cell carcinoma of the larynx initially treated with either radiation or chemoradiation, who underwent salvage laryngectomy at the Cleveland Clinic Foundation from 1997 to 2011, were identified. The cohort was divided into an early-stage group and an advanced-stage group based on initial tumor staging. Survival outcome was evaluated separately in each group against tumor staging, methods of treatment, and nodal status. Secondary endpoints of speech and swallowing were also evaluated., Results: A total of 100 patients were identified, with 72 patients in the early-stage group and 28 patients in the advanced-stage group. The overall postsalvage locoregional control rate was 70%, and the 5-year disease-specific survival was 70% and 55.2% in the early and advanced group, respectively (P = .39). The 5-year disease-specific survival was not significant in either group when compared with recurrent staging, initial treatment, salvage treatment, or nodal disease (P = ns). Using voice prostheses, good to excellent speech function was achieved postoperatively in most patients., Conclusion: Tumor staging, methods of initial and salvage treatment, and nodal disease were not significant predictors of survival. Both salvage partial and total laryngectomy were effective methods in the treatment of recurrent laryngeal cancer in carefully selected patients.

Background: Tumor human papillomavirus (HPV) status has emerged as one of the most powerful prognostic factors for disease control and survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). We reviewed our experience in patients with OPSCC and known tumor HPV status treated with definitive chemoradiotherapy (CRT)., Methods: Patients with stage III-IVb OPSCC and known tumor HPV status treated with CRT between 2006 and 2011 were identified from an IRB approved registry for this retrospective review. Outcomes were estimated using the Kaplan-Meier method and compared between HPV-positive and negative patients using the log-rank test., Results: Of the 121 pts (89% male, 93% Caucasian) included in this study, median age was 57 (range: 40-73) and median follow-up was 21 months (range: 6-63). Ninety-seven (80%) patients were HPV-positive and 24 (20%) were HPV-negative. Primary site was base of tongue (55%), tonsil (44%), and oropharyngeal wall (2%). Two year rates of locoregional recurrence (3% vs. 26%; p = 0.002), disease free survival (93% vs. 64%; p = 0.001) and overall survival (94% vs 73%; p = 0.002) were superior in HPV-positive patients, while rates of distant recurrence were similar (3% vs. 5%; p = 0.98). While acute toxicities were similar between both groups, patients with HPV-positive disease were more likely to resume a normal diet (90% vs. 65%; p = 0.017) at last follow up. Also, no HPV-positive patient required a feeding tube beyond 6 months after treatment, compared with 24% of HPV-negative patients., Conclusions: Definitive CRT produces excellent rates of disease control with minimal late toxicity for patients with HPV-positive OPSCC. Studies of OPSCC should account for tumor HPV status when identifying factors prognostic for outcome.

Background: This phase II study tested the addition of the oral epidermal growth factor receptor gefitinib to multiagent concurrent chemoradiotherapy regimen in head and neck squamous cell cancer (HNSCC)., Methods: Patients with stage III-IV HNSCC received hyperfractionated radiation (72-74.4 Gy at 120 cGy twice daily), with concurrent 96-hour infusions of cisplatin 20 mg/m(2) /day and fluorouracil 1000 mg/m(2) /day given during weeks 1 and 4. Daily gefitinib 250 mg was started on day 1 of radiation and continued for 2 years. Results were retrospectively compared with our previous study using identical chemoradiotherapy without gefitinib., Results: Sixty patients were enrolled in the study; 80% had stage IV disease and 68% had oropharyngeal primary tumors. The full course of gefitinib was not tolerated by 42%; there were 5 treatment-related deaths (8%). With a median follow-up of 54 months, 2- and 3-year overall survival estimates were 80% and 71%, respectively. Projected distant metastatic control at 2 and 3 years was 88%. When compared with our historical cohort, acute toxicities including renal dysfunction and unplanned rehospitalization were worse in the study patients. Projected outcome estimates did not differ between the 2 cohorts., Conclusions: Addition of gefitinib to concurrent chemoradiotherapy was difficult to complete, did not improve outcomes, and increased toxicity., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: The reported decreasing benefit with increasing age from concurrent chemoradiotherapy in head and neck cancer patients prompted this retrospective review., Methods: Two courses of cisplatin-based concurrent chemoradiotherapy were given to fit patients ≥70 years with locoregionally advanced cancers. Clinical characteristics, treatment, and outcomes were compared with those for an identically treated cohort <70 years., Results: There were 44 patients ≥70 and 137 patients <70 years. Clinical characteristics, treatment and toxicities were similar except that the elderly were less likely to receive both chemotherapy courses, experienced more myelosuppression, required more unplanned hospitalization, and were feeding-tube dependent longer. Projected 5-year disease-specific survival (71% vs 74%) and freedom from recurrence (69% v. 71%) were nearly identical., Conclusions: Although these selected elderly patients experienced greater myelosuppression and supportive care requirements, outcomes were the same as in younger patients. Age alone should not be considered a contraindication to aggressive chemoradiotherapy for this disease., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: T1 and T2 tonsillar squamous cell cancer with limited neck disease can be managed with single-modality radiation or surgery. Over 11 years, 17 patients underwent radical tonsillectomies; and 33 patients underwent radiation-based treatments for T1 and T2 and N0 to N2a tonsil cancer. Patients were intended to receive single-modality treatment based on presentation; however, some ultimately received adjuvant treatments., Methods: A retrospective chart review to compare overall survival (OS), disease-specific survival (DSS), and locoregional control (LRC) between the groups was used., Results: In surgical group, of 17 patients, 11 underwent surgery alone, 3 underwent surgery and radiation, and 3 underwent surgery with concurrent chemoradiation. Five-year OS for the surgical and radiation groups was 93% and 72%, respectively (no significance achieved). Five-year DSS rates (93% and 80%) and LRC (69% and 89%) similarly did not yield any significant difference., Conclusion: Surgery remains a viable option in the management of T1 and T2 tonsillar cancers with comparable LRC, OS, and DSS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: The aim of the study was to determine the prognostic impact of preepiglottic space (PES) involvement on local failure after concurrent chemoradiation therapy for squamous cell carcinoma., Materials and Methods: Retrospective chart review of patients who underwent concurrent chemoradiation therapy for T3 or T4 laryngeal, T4 hypopharyngeal, and T3 or T4 oropharyngeal squamous cell carcinoma were eligible for inclusion. Patients were then stratified by the presence or absence of PES tumor involvement. A multivariate analysis was performed on the presence of recurrence using the following pretreatment variables: PES involvement, tumor extent, pathologic cell differentiation, lymph node involvement, age, and sex., Results: A total of 102 patients were included in the study. Twenty-seven (28%) patients had documented PES involvement. Mean follow-up for all patients was 46 months. Involvement of the PES was not significantly associated with local tumor persistence or recurrence (P = .69). No other variables significantly impacted tumor recurrence., Conclusion: Preepiglottic space involvement does not negatively impact local tumor control after concurrent chemoradiation therapy., (Published by Elsevier Inc.)

The human papillomavirus (HPV) has recently been identified as an important etiologic agent in the development of squamous cell carcinoma of the oropharynx. The HPV- associated cancers appear to have a different biology than the HPV-negative cancers, and affect a population that is more likely to be young, male, Caucasian, and nonsmoking. More importantly, however, is the recognition that patients with an HPV-associated oropharyngeal cancer have a distinctly better survival after treatment than those patients with HPV-negative tumors, although their prognosis is significantly worse if there is a history of tobacco abuse. HPV-associated oropharynx cancer should be recognized as a new biologic entity and studied separately from HPV-negative cancers in future clinical trials. The potential for disease prevention with the use of the current HPV vaccines is discussed.

Background: The management of initially bulky nodal disease after primary nonsurgical treatment for stage IV head and neck squamous cell carcinoma (HNSCC) continues to be a subject of debate., Methods: A retrospective chart review of neck management in patients after chemoradiation was performed., Results: Of the initially positive necks analyzed, 210/329 (65%) had a complete clinical response to treatment and 161 necks underwent neck surgery. Patients were pathologically positive 13.8% and 39.6% of the time after clinical complete or partial response, respectively. Regional recurrence was more frequent in necks with partial clinical (p = .04) or pathologic responses (p < .01) and with primary site recurrences (p < .01)., Conclusions: It is still safest at our institution to perform selective neck dissection on patients with > or = N2 neck disease when initially observed to prevent unsalvageable regional recurrence until more accurate interval assessment tools are confirmed.

Background: Concurrent chemoradiotherapy (CCRT) for locoregionally advanced esophageal or gastroesophageal junction cancer produces high locoregional control rates but suboptimal distant metastatic control (DMC) and overall survival. This phase II study added gefitinib (G) to our previously tested CCRT regimen in an effort to improve these outcomes., Methods: Eligibility required T3, N1, or M1a esophageal or gastroesophageal junction squamous cell or adenocarcinoma staged by esophageal ultrasound and positron emission tomography/computed tomography. Four-day continuous intravenous infusions of cisplatin (20 mg/m/d) and fluorouracil (1000 mg/m/d) began on day 1 of preoperative radiation (30 Gy and 1.5 Gy bid). Surgery followed in 4 to 6 weeks, and an identical course of CCRT 6 to 10 weeks postoperatively. G 250 mg/d was given with preoperative CCRT for 4 weeks and restarted with postoperative therapy for 2 years. Results were retrospectively compared with our historical series of 93 patients given CCRT without G., Results: Between April 2003 and July 2006, 80 patients were enrolled. Patient and tumor characteristics were similar to our historical series. G did not increase toxicity except for development of rash in 42 (53%) and diarrhea in 44 (55%) 3-year Kaplan-Meier estimates (G versus non-G treated patients) included: overall survival (42% versus 28%, p = 0.06), DMC (40% versus 32%, p = 0.33), and locoregional control (76% versus 77%, p = 0.74). Intolerance for G maintenance occurred in 48% of patients. Patients who experienced G related diarrhea appeared to have improved outcomes., Conclusions: Although G did not worsen CCRT toxicity, maintenance therapy proved difficult. This contemporary cohort of patients enjoyed superior survival, which does not solely reflect a decrease in DMC and merits further investigation.

Background: In an effort to optimize nonoperative therapy in patients with locoregionally advanced head and neck squamous cell cancer, the Southwest Oncology Group conducted a phase II trial combining 3-drug taxane-containing induction chemotherapy with accelerated fractionation/concomitant boost radiation and concomitant single-agent cisplatin., Methods: Two induction courses using docetaxel (75 mg/m(2) on day 1), cisplatin (100 mg/m(2) on day 1), and fluorouracil (1000 mg/m(2)/day continuous intravenous infusion days 1-4) were given, with an interval of 21 days. Patients who were stable or responded to the chemotherapy received definitive accelerated fractionation/concomitant boost radiation with concurrent cisplatin (100 mg/m(2)) on days 1 and 22 of radiation., Results: There were 74 eligible and evaluable patients enrolled between March 1, 2003, and August 15, 2004; 52 (70%) had stage IV disease. At least 1 grade 3-4 toxicity was experienced by 63 patients (85%) during induction. A total of 61 patients completed induction and began concurrent chemoradiotherapy; 50 (68%) completed all planned treatment. At least 1 grade 3-4 toxicity was noted in 53 of the 58 patients (91%) evaluated for toxicity from concurrent chemoradiotherapy. Two patients died during induction, and 2 during chemoradiation. With a median follow-up of 36 months (range, 14-50), the 2-year and 3-year overall survival estimates were 70% and 64%, with 2-year and 3-year progression-free survival estimates of 66% and 61%, respectively., Conclusions: Three-drug induction chemotherapy followed by accelerated fractionation/concomitant boost radiation and concurrent cisplatin is toxic but feasible within a cooperative group. In this patient cohort with advanced head and neck squamous cell cancer, overall and progression-free survivals were encouraging, justifying further study of this approach., (Copyright 2009 Wiley Periodicals, Inc.)

Objectives/hypothesis: To determine whether vocal cord fixation precludes nonsurgical management of T3/T4 laryngeal carcinoma., Study Design: A retrospective chart review., Methods: Between 1989 and 2005 patient records with T3/T4 squamous cell carcinoma of the larynx with vocal cord fixation at presentation were reviewed. All were treated with a concomitant cisplatin-based chemoradiotherapy protocol and were part of the institutional head and neck cancer chemoradiotherapy registry. Only patients with adequate pre- and post-treatment fiberoptic evaluations were included. Charts were reviewed for demographics and tumor characteristics; return of vocal cord function; local, regional, or distant recurrence after treatment; and need for salvage surgery. The Kaplan-Meier method was used to estimate outcomes, and the log-rank test was used to compare those patients whose vocal cords remained fixed to those with recovery of function., Results: Twenty-three patients met the inclusion criteria, 19 males and 4 females. The median age was 59 years (range, 39-73). Fourteen patients had T3 and nine had T4 tumors. Twelve patients recovered full range of mobility, three had partial recovery, and eight did not recover motion. The median follow-up was 68 months (range, 34-191). Comparing patients with post-treatment partial or fully mobile cords to those with persistent fixation revealed the following: A projected five-year overall survival of 100% versus 25%, (P < .001), freedom from recurrence of 86.7 versus 25% (P < .001), local control without surgery of 86.7% versus 30% (P = .003), and survival with functional larynx of 86.7% versus 25% (P = .008), respectively., Conclusions: Nonsurgical therapy in patients with pretreatment vocal cord fixation is feasible. However, persistence of vocal cord fixation after definitive chemoradiotherapy is a poor prognostic sign and early surgical intervention should be considered. Laryngoscope, 2009.

Objective: To report our experience using the neck examination, computed tomography (CT), and positron emission tomography (PET) to clinically evaluate node-positive patients with head and neck squamous cell cancer for residual neck node disease after definitive chemoradiotherapy., Design: Retrospective review of all Cleveland Clinic patients with head and neck squamous cell cancer and N2 or N3 neck node involvement at presentation who were treated with definitive concurrent chemoradiotherapy and who underwent clinical restaging after treatment using the neck examination, CT, and PET., Setting: Tertiary care referral institution., Patients: Forty-eight patients with 72 positive necks at diagnosis were followed up for a median of 20 months., Main Outcome Measures: Palpable nodes on examination, nodes larger than 1 cm, nodes with central necrosis on CT, or any hypermetabolic lymph nodes on PET were considered clinical evidence of residual nodal disease. The true rate of pathologic involvement was determined by histologic examination after planned neck dissection or if regional recurrence developed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all 3 clinical assessment tools., Results: Planned neck dissection was performed in 33 necks and was positive for residual neck node disease in 5 necks. A delayed neck dissection was performed in 5 necks and was positive in 3 necks. The positive predictive value was low for all 3 clinical assessment tools. The addition of PET did not significantly improve the negative predictive value or positive predictive value of CT and the clinical examination., Conclusions: Residual neck node disease after definitive chemoradiotherapy was infrequent and was not well predicted by PET. A positive PET finding in this setting is of little utility. Although a negative PET finding was highly predictive for control of neck disease after chemoradiotherapy, it added little to the clinical neck examination and CT.

Background: Concurrent chemoradiation therapy has been demonstrated to be effective as an organ-sparing treatment for select advanced head and neck squamous cell carcinoma (HNSCC). However, this treatment modality is not without side effects. One side effect is the formation of upper esophageal strictures. As concurrent chemoradiation treatment is used more frequently, it is important to identify risk factors associated with stricture formation., Methods: A retrospective chart review of all patients who had undergone definitive concurrent chemoradiation treatment between 1989 and 2002 was performed. Exclusion criteria included death within 1 year or persistent/recurrent disease that required surgical salvage at the primary site. The outcome measure was stricture formation as determined by both objective findings (barium swallow or endoscopy) and the need for dilation after treatment., Results: Of the 222 patients in this cohort, there were enough data for 199 patients to assess for stricture formation. Strictures developed in a total of 41 patients (21%). Significant predictive factors were a twice-daily (BID) radiation fractionation (p = .007), female sex (p = .015), and a hypopharyngeal primary site (p = .01). Age and tumor extent were not significant factors in stricture formation (p = .15 and p = .23, respectively)., Conclusions: Symptomatic strictures occur in 21% of patients undergoing concurrent chemoradiation for HNSCC. Female sex, BID radiation fractionation, and a hypopharyngeal primary site are significant predictive factors for stricture formation., ((c) 2006 Wiley Periodicals, Inc.)

Purpose: A retrospective review with long-term follow-up is reported from the Cleveland Clinic Foundation studying radiation and concurrent multiagent chemotherapy in patients with locoregionally advanced squamous cell head and neck cancer., Patients and Methods: Between 1989 and 2002, 222 patients were treated with 4-day continuous infusions of fluorouracil (1,000 mg/m2/d) and cisplatin (20 mg/m2/d) during weeks 1 and 4 of either once daily or twice daily radiation therapy. Primary site resection was reserved for patients with residual or recurrent primary site disease after chemoradiotherapy. Neck dissection was considered for patients with N2 or greater disease, irrespective of clinical response, and for patients with residual or recurrent neck disease., Results: With a median follow-up of 73 months, the Kaplan-Meier 5-year projected overall survival rate is 65.7%, freedom from recurrence rate is 74.0%, local control without the need for surgical resection rate is 86.7%, and overall survival rate with organ preservation is 62.2%. Including patients undergoing primary site resection as salvage therapy, the overall local control rate is 92.4%. Regional control rate at 5 years is 92.4%. Among patients with N2-3 disease, regional control was significantly better if a planned neck dissection was performed. Distant control at 5 years was achieved in 85.4% of patients and was significantly worse in patients with hypopharyngeal primary sites and patients with poorly differentiated tumors., Conclusion: Concurrent multiagent chemoradiotherapy can result in organ preservation and cure in the majority of appropriately selected patients with locoregionally advanced, nonmetastatic, squamous cell head and neck cancer. Distant metastatic disease was the most common cause of treatment failure. Late functional outcomes will require further investigation.

Squamous cell head and neck cancer is a relatively uncommon malignancy in North America. Nonetheless, it has been of considerable interest to medical oncologists because of its remarkable sensitivity to systemic chemotherapy. Even in patients with relapsed or metastatic disease, meaningful tumour shrinkage can be achieved with systemic therapy. This has led to the performance of carefully conducted clinical trials exploring the role of systemic chemotherapy, not only in the palliative setting, but as part of definitive multi-modality treatment. Chemotherapy has been used as the initial (or induction) treatment, as an adjuvant treatment after definitive surgery and/or radiation, and concurrent with both definitive and adjuvant radiation therapy. Evidence-based conclusions have been drawn from these clinical trials and have led to significant changes in the current standards of care for this disease. In this article, the available data supporting the use of systemic chemotherapy as palliative treatment, and as part of the definitive management for this disease will be reviewed.

Objective: We sought to evaluate the effectiveness of clinical staging of depth of tumor invasion (cT), the relationship of cT to survival, the benefits of downstaging cT, and the role of cT in treatment decisions., Methods: The accuracy of determining T by means of endoscopic ultrasonography and the relationship of cT to survival were assessed in 209 patients undergoing esophagectomy alone for esophageal carcinoma. The benefit of downstaging cT was assessed in 128 patients undergoing induction therapy and esophagectomy. The role of cT in treatment decisions was determined by integrating these results with the results of previous work., Results: Compared with pathologic T (pT), cT was 87% accurate, 82% sensitive, 91% specific, 89% positively predictive, and 86% negatively predictive of tumors confined to (< or =T2) or invading beyond (>T2) the esophageal wall. In cN0, increasing cT was predictive of progressively poorer survival. For each category of pT N0, cT accurately predicted survival, except for pT3, which was underestimated (P <.0001). In cN0, downstaging by induction therapy was beneficial only if tumors invaded beyond the wall (> or =cT3, P =.0003). In cN1, it was beneficial only when downstaging was synchronous in cT3/T4 (P <.001)., Conclusions: cT should be the principal determinant of treatment in cN0. In cN0, if endoscopic ultrasonography identifies tumors of greater than cT2, multimodality therapy should be considered. However, only when cT3/T4 tumors are downstaged to pT2 or less will patients benefit, but their survival will not equal that of patients with tumors of cT2 or less having esophagectomy alone. If endoscopic ultrasonography identifies tumors of cT2 or less, esophagectomy alone should be used because induction therapy might adversely affect survival.

Objective: Cancer staging is dynamic, reflecting accrual of knowledge and experience in treatment. The objectives of this study were to assess current esophageal cancer staging and to determine whether refinements of classification and stage grouping are necessary., Methods: From 1983 through November 2000, 480 patients underwent esophagectomy without induction therapy. Depth of tumor invasion (T), regional lymph node status (N), distant status (M), number of metastatic regional lymph nodes, and histopathologic type and grade were subjected to survival-tree analysis, multivariable Cox and hazard function analysis, and residual misclassification risk analysis., Results: Inhomogenity of survival was found within and lack of distinction was found between current American Joint Committee on Cancer staging groups, supporting the need for refinement. T1 and N1 were redefined on the basis of survival differences. T1a is intramucosal cancer, T1b is submucosal cancer (P =.008), N1 is 1 or 2 metastatic regional lymph nodes, and N2 is 3 or more metastatic regional lymph nodes (P =.01). Current subclassification of M1 is not warranted (P =.9). Histopathologic type (P =.17) and grade (P =.3) minimally refined staging. Reassignment of staging groups constrained by American Joint Committee on Cancer definitions of stages 0 and IV produced less monotonic, distinctive, and homogeneous survival than free assignment of staging groups., Conclusions: Current American Joint Committee on Cancer staging of esophageal cancer is inadequate. Refinement requires redefinition of T1, N1, and M1 classifications. Stage grouping within the constraints of American Joint Committee on Cancer definitions produces less accurate prognosis than free assignment based on survival data.

Purpose: Results are reported from an aggressive chemoradiotherapy protocol for advanced squamous cell head and neck cancer., Patients and Methods: Patients with advanced squamous cell head and neck cancer were treated with hyperfractionated radiation therapy (72 Gy at 1.2 Gy twice per day) and two courses of concurrent chemotherapy with fluorouracil (1,000 mg/m(2)/d) and cisplatin (20 mg/m(2)/d), both given as 96-hour continuous intravenous infusions during weeks 1 and 4 of radiation therapy. Primary-site resection was reserved for residual or recurrent primary-site disease after chemoradiotherapy. Neck dissection was considered for N2 or greater disease, irrespective of clinical response, and for residual or recurrent neck disease after nonoperative treatment., Results: Forty-one patients with stage IV disease were treated. Toxicity was significant, with grade 3 to 4 mucositis in 98%, dysphagia in 88%, and skin reaction in 85%. Neutropenic fever requiring hospitalization occurred in 51%. Despite feeding tube placement in 35 patients (85%), the mean weight loss during chemoradiotherapy was 13.3% of initial body weight. One patient died during treatment as a result of a pulmonary embolus. At a median follow-up period of 30 months, the 3-year Kaplan-Meier projected overall survival was 59%, disease-specific survival 69%, likelihood of local control without surgical resection 91%, and local control with surgical resection 97%. The likelihood of distant disease control at 3 years was 74%, and distant metastases were present in eight of 13 patients who died., Conclusion: This chemoradiotherapy schedule produces considerable but manageable toxicity. Survival and organ preservation are excellent for this poor-prognosis patient cohort. Distant metastases are the most common cause of treatment failure.