Search

Background: We evaluate the impact of post-operative 18-fluorodeoxyglucose positron emission tomography with computed tomography (PET/CT) for radiation planning on the detection of early recurrence (ER) and treatment outcomes in oral squamous cell carcinoma (OSCC)., Methods: We retrospectively reviewed the records of patients treated with post-operative radiation between 2005 and 2019 for OSCC at our institution. Extracapsular extension and positive surgical margins were classified as high risk features; pT3-4, node positivity, lymphovascular invasion, perineural invasion, tumor thickness >5 mm, and close surgical margins were considered intermediate risk features. Patients with ER were identified. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances between baseline characteristics., Results: 391 patients with OSCC were treated with post-operative radiation. 237 (60.6%) patients underwent post-operative PET/CT planning vs. 154 (39.4%) who were planned with CT only. Patients screened with post-operative PET/CT were more likely to be diagnosed with ER than those planned with CT only (16.5 vs. 3.3%, p < 0.0001). Among patients with ER, those with intermediate features were more likely than those high risk features to undergo major treatment intensification, including re-operation, the addition of chemotherapy, or intensification of radiation by ≥ 10 Gy (91% vs. 9%, p < 0.0001). Post-operative PET/CT was associated with improved disease-free and overall survival for patients with intermediate risk features (IPTW log-rank p = 0.026 and p = 0.047, respectively) but not high risk features (IPTW log-rank p = 0.44 and p = 0.96)., Conclusions: Use of post-operative PET/CT is associated with increased detection of early recurrence. Among patients with intermediate risk features, this may translate to improved disease-free survival., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yao Yu: Travel: Elekta. Heiko Schoder: None. Kaveh Zakeri: None. Linda Chen: None. Jung Kang: None. Sean McBride: Consulting or Advisory: Janssen, Astra Zeneca; Research Funding: Genentech, AstraZeneca. C. Jillian Tsai: Honoraria: Varian Medical Inc; Consulting or Advisory: Varian Medical Systems. Daphna Gelblum: None. Jay Boyle: None. Jennifer R Cracchiolo: None. Marc A Cohen: None. Bhuvanesh Singh: None. Ian Ganly: None. Snehal Patel: Patent PCT/US2016/026717; equity in Summit Biomedical Imaging; patent US 10,016,238 B2 Apparatus; equity in ColdSteel Laser Inc; patent PCT/US2014/073053; patent PCT/US2015/065816 ; Patent PCT/US2016/066969. Loren Michel: Research Funding: Exelixis; Travel: Immunomedics. Lara Dunn: Consulting: Regeneron, CUE Biopharma, Merck; Research Funding: Regeneron, Eisai, CUE-101. Eric Sherman: Consulting: Cota Healthcare, Goldilocks, Eisai, Regeneron, UpToDate, Lilly, Blueprint Medicines; Research Funding: Plexxikon, Regeneron. David Pfister: Consulting or Advisory: Boehringer Ingelheim, Incyte; Research Funding: AstraZeneca, Atara Biotherapeutics, Bayer, Boehringer Ingelheim, Eisai, Exelixis, Genentech/Roche, Hoopika Pharma, Lilly, Medimmune, MeiraGtx, Merck, Novartis, Regeneron. Richard Wong: None. Nadeem Riaz: Honoraria: PeerView; Consulting or Advisory: Mirati Therapeutics, Repare Therapeutics; Speakers Bureau: Illumina; Research Funding: Bristol Myers Squibb, Pfizer, Repare Therapeutics; Travel, Accommodations, Expenses: Varian Medical Systems. Nancy Lee: Consulting or Advisory: Merck, Pfizer, Merck Serono, Sanofi, Mirati Therapeutics, Roche/Genentech; Research Funding: AstraZeneca, Pfizer., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Importance: Use of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret., Objective: To evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma., Design, Setting, and Participants: This retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and grade early and late toxic effects., Exposures: Proton therapy reirradiation., Main Outcomes and Measures: Follow-up was defined from the start of PT-ReRT. The Kaplan-Meier method was used for outcomes of interest, including local control (LC), locoregional control, distant metastatic control, progression-free survival, and overall survival (OS). Cox proportional hazards regression modeling was used to assess associations of covariates with OS., Results: A total of 242 patients (median [range] age, 63 [21-96] years; 183 [75.6%] male) were included. Of these patients, 231 (95.9%) had a Karnofsky performance status score of 70 or higher, and 145 (59.9%) had at least a 10-pack-year smoking history. Median (range) follow-up was 12.0 (5.8-26.0) months for all patients and 24.5 (13.8-37.8) months for living patients. A total of 206 patients (85.1%) had recurrent disease vs second primary or residual disease. The median (range) interval between radiation courses was 22 (1-669) months. Median PT-ReRT dose was 70 cobalt gray equivalents (CGE) for the fractionated cohort and 44.4 CGE for the quad shot cohort. For the fractionated cohort, the 1-year LC was 71.8% (95% CI, 62.8%-79.0%) and the 1-year OS was 66.6% (95% CI, 58.1%-73.8%). For the quad shot cohort, the 1-year LC was 61.6% (95% CI, 46.4%-73.6%) and the 1-year OS was 28.5% (95% CI, 19.4%-38.3%). Higher Karnofsky performance status scores (hazard ratio [HR], 0.50; 95% CI, 0.25-0.99; P = .046) and receipt of salvage surgery prior to PT-ReRT (HR, 0.57; 95% CI, 0.39-0.84; P = .005) were associated with improved OS, whereas receipt of quad shot (HR, 1.97; 95% CI, 1.36-2.86; P < .001) was associated with worse OS. There were a total of 73 grade 3 and 6 grade 4 early toxic effects. There were 79 potential grade 3, 4 grade 4, and 5 grade 5 late toxic effects., Conclusions and Relevance: The findings of this cohort study suggest that, compared with previous reports with photon-based reirradiation, patients are living longer with aggressive PT-ReRT; however, surviving patients remain at risk of early and late complications.

Because of the national emergency triggered by the coronavirus disease 2019 (COVID-19) pandemic, government-mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in-person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard-of-care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high-volume cancer center at the domestic epicenter of the COVID-19 crisis., (© 2020 American Cancer Society.)

Objectives: Patients with prior irradiated head and neck cancer (HNC) who are ineligible for definitive retreatment have limited local palliative options. We report the largest series of the use of the Quad Shot (QS) regimen as a last-line local palliative therapy., Materials and Methods: We identified 166 patients with prior HN radiation therapy (RT) treated with QS regimen (3.7 Gy twice daily over 2 consecutive days at 4 weeks intervals per cycle, up to 4 cycles). Palliative response defined by symptom(s) relief or radiographic tumor reduction, locoregional progression free survival (LPFS), overall survival (OS) and radiation-related toxicity were assessed., Results: Median age was 66 years. Median follow-up for all patients was 6.0 months and 9.7 months for living patients. Overall palliative response rate was 66% and symptoms improved in 60% of all patients. Predictors of palliative response were > 2 year interval from prior RT and 3-4 QS cycles. Median LPFS was 5.1 months with 1-year LPFS 17.7%, and median OS was 6.4 months with 1-year OS 25.3%. On multivariate analysis, proton RT, KPS > 70, presence of palliative response and 3-4 QS cycles were associated with improved LPFS and improved OS. The overall Grade 3 toxicity rate was 10.8% (n = 18). No Grade 4-5 toxicities were observed., Conclusion: Palliative QS is an effective last-line local therapy with minimal toxicity in patients with previously irradiated HNC. The administration of 3-4 QS cycles predicts palliative response, improved PFS, and improved OS. KPS > 70 and proton therapy are associated with survival improvements., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives/hypothesis: We used the National Cancer Database to identify the patterns of care and prognostic factors in adult patients with head and neck soft-tissue sarcoma (HNSTS)., Study Design: Retrospective cohort analysis., Methods: Using the National Cancer Database, we identified patients age ≥ 18 years who were diagnosed with HNSTS between 2004 and 2013. Both χ 2 and multivariate logistic regression were used to identify factors associated with radiation therapy (RT) utilization. Kaplan-Meier methods were used to estimate overall survival (OS) and Cox proportional regression was used to determine significant contributors to OS., Results: Our final cohort included 1,282 patients (682 treated with surgery only, 199 treated with RT only, and 401 treated with surgery and RT). Patients with younger age, poor tumor grade, rhabdomyosarcoma histology, and chemotherapy treatment were more likely to receive RT alone without surgery. Among the 1,083 surgical patients, RT utilization was associated with positive margins (odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.36-3.48), poor grade (OR: 2.92, 95% CI: 1.95-4.38), and chemotherapy use (OR: 1.78, 95% CI: 1.15-2.76). Radiotherapy utilization among surgical patients was not affected by demographic factors (age, sex, or ethnicity) or treatment institution (academic or community). For surgical patients, poor grade, large tumor size, and rhabdomyosarcoma histology were associated with worse OS on multivariate analysis., Conclusions: In this analysis of HNSTS, younger patients with poor tumor grade and rhabdomyosarcoma histology were more likely to receive RT without surgery. Among surgical patients, adjuvant RT was more likely to be used for positive margins and poor grade, with no demographic disparities identified. Poor grade and rhabdomyosarcoma histology were negative prognostic factors for surgical patients., Level of Evidence: NA Laryngoscope, 130:120-127, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Even though 15% to 50% of patients with head and neck squamous cell carcinoma (HNSCC) experience recurrence, relatively little is known regarding patterns of treatment failure and postrecurrence outcomes after chemoradiotherapy using modern radiation techniques (intensity-modulated radiotherapy [IMRT]). Recurrence patterns are significantly affected by variations in the quality of radiotherapy, which may confound findings from multicenter trials., Objective: To assess patterns of treatment failure and postrecurrence outcomes for patients with HNSCC treated with contemporary radiotherapy techniques., Design, Setting, and Participants: This large single-institution cohort study reviewed the outcomes of 1000 consecutive patients with stage III to IVB oropharyngeal carcinoma (n = 703), laryngeal carcinoma (n = 126), or hypopharyngeal carcinoma (n = 46) treated with definitive IMRT with or without concurrent chemotherapy, as well as patients with oral cavity carcinoma (n = 125) treated with postoperative IMRT with or without concurrent systemic therapy, from December 1, 2001, to December 31, 2013, with a median follow-up of 65.1 months among surviving patients. Data analysis was performed from January 31, 2016, to February 17, 2017., Main Outcomes and Measures: Patterns of treatment failure and overall survival following locoregional failure or distant metastasis., Results: Among the 1000 patients (186 women and 814 men; mean [SD] age, 59.3 [10.8] years), there were no marginal or isolated out-of-radiation-field failures. Among subsites, the cumulative incidence of local failure was highest among patients with oral cavity carcinoma vs those with oropharyngeal carcinoma (hazard ratio, 5.2; 95% CI, 3.1-8.6; P < .001). Furthermore, patients with oral cavity carcinoma experienced significantly shorter survival following distant metastasis (hazard ratio, 3.66; 95% CI, 1.98-6.80; P < .001). Patients with oropharyngeal carcinoma positive for human papillomavirus or p16 lived longer after locoregional failure compared with patents with oropharyngeal carcinoma negative for human papillomavirus or p16 (median survival, 36.5 vs 13.6 months; P = .007) but not after distant metastasis. Salvage surgery was associated with improved overall survival following locoregional failure (hazard ratio, 0.51; 95% CI, 0.34-0.77; P = .001); oligometastatic disease (1 vs ≥2 lesions: hazard ratio, 0.32; 95% CI, 0.16-0.63; P = .001) was associated with improved overall survival following distant metastasis., Conclusions and Relevance: Overall survival after recurrence of HNSCC is influenced by the HNSCC subsite and human papillomavirus or p16 status, as well surgical and systemic interventions. An oligometastatic phenotype characterizes patients with solitary metastasis after chemoradiotherapy. These findings have important implications for clinical trial designs for HNSCC in the recurrent and oligometastatic setting.

Objectives: To report the complications occurring following TORS and to identify the factors predictive of complications., Methods: Following IRB approval a retrospective analysis of all TORS operations at our institution was performed. Postoperative complications within 45days were collected and graded with the Clavien-Dindo system. Complications were categorized into groups: all complications, not related to TORS and TORS related. Unadjusted odds ratios were calculated to test association between patients with and without a complication., Results: 122 TORS operations were carried out between June 2010 and August 2015. 77% were male, with a median age of 57. There were 92 primary tumor resections, 10second head and neck primary resections, 13 salvage procedures and 7 other indications. Surgical resection involved 1, 2 or >3 sub-sites in 36%, 28% and 36% patients, respectively. Overall, there were 107 complications (66 TORS related, 41 non-TORS related) that occurred in 57 patients (47%). A major complication occurred in 23 patients (18%). 19 patients had a TORS related major complication and 6 patients experienced a non-TORS related major complication. There was a temporal trend in TORS related major complication rate decreasing from 33% in 2010 to 10% in 2015. Statistical analysis showed that the odds of having any complication were 3 times greater in patients over 60years old (p=0.017), and 2.5 times greater when there were more than 2 subsites resected (p=0.022)., Conclusions: Age over 60years and a larger extent of resection were the significant factors predictive of major complications., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Although obesity increases risk and negatively affects survival for many malignancies, the prognostic implications in squamous cell carcinoma (SCC) of the oral tongue, a disease often associated with prediagnosis weight loss, are unknown., Methods: Patients with T1-T2 oral tongue SCC underwent curative-intent resection in this single-institution study. All patients underwent nutritional assessment prior to surgery. Body mass index (BMI) was calculated from measured height and weight and categorized as obese (≥ 30 kg/m(2) ), overweight (25-29.9 kg/m(2) ), or normal (18.5-24.9 kg/m(2) ). Clinical outcomes, including disease-specific survival, recurrence-free survival, and overall survival, were compared by BMI group using Cox regression., Results: From 2000 to 2009, 155 patients (90 men, 65 women) of median age 57 years (range, 18-86 years) were included. Baseline characteristics were similar by BMI group. Obesity was significantly associated with adverse disease-specific survival compared with normal weight in univariable (hazard ratio [HR] = 2.65, 95% confidence interval [CI] = 1.07-6.59; P = .04) and multivariable analyses (HR = 5.01; 95% CI = 1.69-14.81; P = .004). A consistent association was seen between obesity and worse recurrence-free survival (HR = 1.87; 95% CI = 0.90-3.88) and between obesity and worse overall survival (HR = 2.03; 95% CI = 0.88-4.65) though without reaching statistical significance (P = .09 and P = .10, respectively) in multivariable analyses., Conclusions: In this retrospective study, obesity was an adverse independent prognostic variable. This association may not have been previously appreciated due to confounding by multiple factors including prediagnosis weight loss., (© 2013 American Cancer Society.)

Objective: To describe an institutional experience conducting an annual free head and neck (H&N) cancer screening clinic. Specific aims included: (1) identifying factors predicting which individuals will have findings suspicious for malignancy; and (2) evaluating potential barriers to subsequent follow-up among patients with suspicious findings., Materials and Methods: This retrospective cohort study involved individuals presenting to an annual H&N cancer screening clinic (2001-2012). Original screening clinic data and electronic medical records were reviewed. Descriptive and comparative statistics were utilized in order to address the study aims., Results: Of 1573 participants, 325 (21%) had abnormal findings on screening, of which 183 (12%) had findings suspicious for cancer. No demographic factors predicted a suspicion for cancer. The presence of patient-reported symptoms (16% vs. 8%; p<0.001) were significantly associated with a suspicion for cancer. Only 20% of individuals with a suspicion for cancer returned to our institution for recommended follow-up. Patients who did not complain of symptoms were less likely to return for follow-up (2% vs. 36%; p<0.001). Of the patients who returned for follow-up evaluation, malignancies were diagnosed in three patients., Conclusion: Few individuals presenting to a H&N cancer screening clinic will have a malignancy detected, and barriers may influence patients' likelihood to present for subsequent evaluation. Due to self-selection among patients presenting for screening, traditional risk factors may not be associated with the likelihood of detecting a suspicion for H&N cancer. Head and neck cancer screening clinics should thus target patients at high risk, and attempt to ensure appropriate follow-up thereafter., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: The optimal type of neck dissection in head and neck squamous cell carcinoma (SCC) with clinical cervical metastases has not been determined. The following study was performed to determine the rate of regional control with selective neck dissection (SND) in these patients., Study Design: Case series with planned data collection., Setting: Single institution, cancer center., Methods and Subjects: Patients with cervical lymph node metastases from mucosal cancers of the head and neck who were treated with SND from 2000 to 2010 were selected. Demographics, tumor characteristics, extent of neck dissection, adjuvant treatments, locoregional control, and survival were recorded. Recurrence in the neck and disease-specific survival (DSS) were primary and secondary end points., Results: One hundred eight patients underwent SND. Sixty-nine (64%) were male. Median age was 62 (20-89) years. The most common primary site was the oral cavity (71.3%). Ninety-five (88%) received adjuvant treatment. Median follow-up was 21 months. Six patients (5.5%) had isolated recurrence in the dissected neck. Patients with N2C disease had poorer neck recurrence-free survival. At the end of study, 64 (59.3%) patients had no evidence of disease, and 23 (21.3%) had died of disease. Two-year DSS was 76.9%. Number of positive nodes (P = .026) and positive surgical margins (P = .001), among others, were predictors of poorer DSS., Conclusion: In a highly selected group of patients with cervical lymph node metastases from head and neck SCC, selective neck dissection is effective in controlling the disease in the neck when performed in the setting of a multimodality treatment, including adjuvant radiotherapy or radiochemotherapy.

Background: Current therapy for intermediate thickness melanoma involves wide local excision with sentinel lymph node biopsy (SLNB). SLNB provides important prognostic information and immediate regional lymphadenectomy for a positive sentinel lymph node (SLN) may improve survival and identifies patients who are candidates for adjuvant therapy and/or clinical trials. The head and neck site is unique because of its complex lymphatic drainage pattern to multiple nodal basins and because of the risk of site-specific morbidity associated with regional lymphadenectomy when compared to other body sites. The goal of this study is to report the results of SLNB for head and neck cutaneous melanoma in locating the sentinel node and to report on the prognostic implications of SLNB for this cohort of patients., Methods: A prospectively entered melanoma database was used to review consecutive patients with head and neck cutaneous melanoma undergoing SLNB at Memorial Sloan-Kettering Cancer Center between 1996 and 2007. The database, along with a retrospective chart review, was used to evaluate the success of SLNB at locating an SLN and the success rate of frozen section and permanent section analysis at diagnosing metastatic disease. Recurrence at all sites including the nodal basin and status at last follow-up was recorded. Characteristics of the patients' primary melanoma were included. Descriptive statistics along with univariate and multivariate survival analysis were performed., Results: Between 1996 and 2007, 234 patients with a diagnosis of head and neck cutaneous melanoma underwent SLNB and had at least 1 month of follow-up. At least 1 SLN was identified in 218 of these patients (93%) by lymphoscintigraphy. In 16 patients, no SLN was found. These patients had a much shorter time to recurrence (4.75 months) than either the SLN-positive group (10.7 months) or the SLN-negative group (26.0 months). They had a disease-specific survival (DSS) in between the SLN-positive and SLN-negative group. Of the patients in whom an SLN was identified, 28 patients (12%) had at least 1 positive SLN. Of these, the SLNs of 14 patients (50%) were identified on frozen section; 14 (50%) could only be identified after further sectioning or immunohistochemical analysis postoperatively. Among 190 patients with a negative SLNB, 12 patients had recurrences in the nodal basin. This resulted in a sensitivity of 70%, a negative predictive value of 94%, and a false-negative rate of 30%. The 3-year disease-free survival for SLN-negative and SLN-positive patients was 84% (p < .031) and 58% (p < .102), respectively. The 3-year melanoma-specific survival was 98% (p < .012) and 75% (p < .201), respectively., Conclusion: The SLN status is an important predictor of survival. The technique, performed in the head and neck is complex and associated with a high false-negative rate.

Cyclooxygenase (COX)-derived prostaglandin E(2) (PGE(2)) plays a role in the development and progression of several tumor types including head and neck squamous cell carcinoma (HNSCC). Measurements of urinary PGE metabolite (PGE-M) can be used as an index of systemic PGE(2) production. In ever smokers, increased levels of urinary PGE-M reflect increased COX-2 activity. In this study, we determined whether baseline levels of urinary PGE-M were prognostic for ever smoker HNSCC patients. A retrospective chart review of ever smoker HNSCC patients treated with curative intent was done. Fifteen of 31 evaluable patients developed progressive disease (recurrence or a second primary tumor) after a median follow-up of 38 months. There were no statistically significant differences between patients with (n = 15) or without disease progression (n = 16) with regard to stage, site, treatment received, smoking status, and aspirin use during follow-up. Median urinary PGE-M levels were significantly higher in HNSCC patients with disease progression (21.7 ng/mg creatinine) compared with patients without (13.35 ng/mg creatinine; P = 0.03). Importantly, patients with high baseline levels of urinary PGE-M had a significantly greater risk of disease progression (hazard ratio, 4.76, 95% CI, 1.31-17.30; P < 0.01) and death (hazard ratio, 9.54; 95% CI, 1.17-77.7; P = 0.01) than patients with low baseline levels of urinary PGE-M. These differences were most evident among patients with early-stage disease. Taken together, our findings suggest that high baseline levels of urinary PGE-M indicate a poor prognosis in HNSCC patients. Possibly, HNSCC patients with high COX-2 activity manifested by elevated urinary PGE-M will benefit from treatment with a COX-2 inhibitor.

Purpose: This study was carried out to investigate whether c-Jun NH2-terminal kinases (JNK) are potential targets for treating head and neck squamous cell carcinoma (HNSCC)., Experimental Design: JNK activity was first evaluated in 20 paired samples of human HNSCC. The antitumor activity of SP600125, a reversible nonselective ATP-competitive inhibitor of JNKs, was then investigated both in an HNSCC xenograft model and in vitro using immunohistochemistry, immunoblotting, enzyme immunoassay, flow cytometry, and a Matrigel assay of capillary tube formation. Complementary studies were carried out using small interfering RNA to JNK1/2., Results: JNK activity was increased in human HNSCC compared with normal-appearing epithelium. Treatment of mice bearing HNSCC xenografts with SP600125 resulted in >60% inhibition of tumor growth relative to vehicle-treated animals. Inhibition of tumor growth was associated with significant reductions in both cell proliferation and microvessel density. SP600125 inhibited tumor cell proliferation by causing delays in both the S and G2-M phases of the cell cycle. Inhibition of angiogenesis seemed to reflect effects on both tumor and endothelial cells. The JNK inhibitor suppressed the production of vascular endothelial growth factor and interleukin-8 by tumor cells and also inhibited endothelial cell proliferation and capillary tube formation. Reduced amounts and phosphorylation of epidermal growth factor receptor were found in tumor cells after treatment with SP600125. Small interfering RNA-mediated suppression of JNK1/2 led to reduced tumor cell proliferation and decreased levels of epidermal growth factor receptor, vascular endothelial growth factor, and interleukin-8., Conclusions: JNK activity is commonly increased in HNSCC. Our preclinical results provide a rationale for evaluating JNK inhibition as an approach to treating HNSCC.

Background: We aimed to identify patterns and predictors of second primary malignancy (SPM) of the aerodigestive tract (SPMADT) in patients with squamous cell carcinoma of the oral cavity (SCCOC) and larynx (SCCL)., Methods: One thousand two hundred fifty-seven patients from two existing databases were studied: 595 with SCCOC (1986-1995) and 662 with SCCL (1984-1998). The primary endpoint of interest was development of SPMADT, defined as a second primary neoplasm of the head and neck, esophagus, or lung., Results: The 5-year SPMADT rate was 8% in the SCCL versus 10% in the SCCOC subgroup. Lung SPM was more common in the SCCL group; head and neck SPM was more common in the SCCOC group. Smokers had a fivefold increased risk, whereas alcohol use was associated with a twofold increased risk of SPMADT., Conclusions: The rates of SPMADT after treatment of SCCOC and SCCL are comparable, but the patterns are different. Smoking and alcohol use are independent predictors of SPMADT development., ((c) 2005 Wiley Periodicals, Inc.)

Elevated levels of prostaglandin E(2) (PGE(2)) occur in head and neck squamous cell carcinoma (HNSCC) and have been associated with a poor prognosis. Recently, an inducible microsomal prostaglandin E synthase-1 (mPGES) was identified. This enzyme converts the cyclooxygenase product prostaglandin H(2) (PGH(2)) to PGE(2). Given the apparent significance of PGE(2) in carcinogenesis, it is important to elucidate the mechanisms that account for increased amounts of PGE(2) in HNSCC. By immunoblot analysis, mPGES was overexpressed in 11 of 14 (79%) cases of HNSCC compared with adjacent normal tissue. Immunohistochemistry localized mPGES expression to neoplastic epithelial cells. Cell culture was used to determine whether cellular transformation was associated with increased amounts of mPGES. Levels of mPGES protein and mRNA were markedly elevated in HNSCC cell lines (1483 and Ca9-22) versus a nontumorigenic oral epithelial cell line (MSK-Leuk1). Interestingly, treatment of MSK-Leuk1 cells with PGE(2) caused both dose- and time-dependent stimulation of cell growth. Each of the four known receptors for PGE(2) (E-prostanoid receptor subtypes 1-4) was detected in head and neck squamous mucosa. Taken together, these results suggest that overexpression of mPGES contributes to the increased levels of PGE(2) found in HNSCC. Additional studies will be needed to determine whether this enzyme is a bona fide target for anticancer therapy.

Background: The current study reviews the authors' recent institutional experience in the treatment of osteosarcoma of the head and neck (OSHN)., Methods: The clinical records of 44 patients who were treated between 1981 and 1998 for OSHN were reviewed retrospectively. Archived histologic material was reviewed and data were analyzed to identify factors predictive of disease control and survival. Outcomes were compared with a previously reported historic cohort treated at the study institution., Results: Patients ranged in age from 6 to 64 years (median, 31 years). The mandible was the primary site in 18 patients (41%), the maxilla in 20 patients (45%), and the skull in 6 patients (14%). Surgery was employed in all 44 patients, neoadjuvant chemotherapy was administered in 30 patients (68%), and postoperative radiation therapy was given to 7 patients (16%). The surgical excision margins were positive in 13 patients (30%). High-grade lesions were reported in 50% patients and low-grade lesions were noted in 18% of patients (grade was not assessable in 32%). Histologic response was "unfavorable" in 22 of 30 patients (73%) who were treated with neoadjuvant chemotherapy. The 3-year overall, disease-specific, and recurrence-free survival rates were approximately 81%, 81%, and 73%, respectively (median follow-up of 41 months). Positive surgical margins were found to be the only significant predictor of worse disease-specific survival. Compared with the historical cohort, the current experience demonstrated an obvious improvement in the 5-year local control (35% vs. 78%), distant metastases (37% vs. 13%), and overall survival (23% vs. 70%)., Conclusions: Negative surgical margins were found to be the only significant predictor of overall and disease-specific survival. The results of the current study represent a considerable improvement over the authors' previously published experience and compare favorably with the results reported in the literature., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10849)

Cyclooxygenase-2 (COX-2), an enzyme that catalyzes the synthesis of prostaglandins, is overexpressed in a variety of premalignant and malignant conditions, including oral leukoplakia and squamous cell carcinoma of the head and neck. Increased levels of COX-2 may contribute to carcinogenesis by modulating xenobiotic metabolism, apoptosis, immune surveillance, and angiogenesis. In experimental models, newly developed selective COX-2 inhibitors suppress the formation of tumors, including tongue cancer. These findings provided a rationale for a number of chemoprevention trials that are underway. Selective COX-2 inhibitors also suppress the growth and metastases of established tumors and enhance the anticancer activity of both radiotherapy and chemotherapy in experimental animals. In this review, evidence is presented that inhibition of COX-2 represents a promising strategy to prevent or possibly treat human head and neck cancers., (Copyright 2002 Wiley Periodicals, Inc.)

Objective: To report the results of sentinel lymph node biopsy (SLNB) for cutaneous head and neck melanomas (CMHNs)., Design: Consecutive series followed for a median of 20 months., Setting: Tertiary cancer care center., Patients: Fifty-six individuals with clinically node-negative CMHN, median Breslow thickness, 2.6 mm (range, 0.2-20.0 mm)., Interventions: Preoperative technetium 99m sulfur colloid lymphoscintigraphy (PLSG) followed within 4 hours by intraoperative handheld gamma probe localization (IHGP). Intraoperative injection of 1% isosulfan blue dye (IBD) was used in 48 patients. Immediate completion nodal dissection was performed for metastatic SLNs on intraoperative frozen section analysis and monitoring for negative SLNs., Main Outcome Measures: Rate of SLN identification, SLN and non-SLN positivity, same-basin recurrence, and disease-specific and recurrence-free survival., Results: Combination of IHGP and IBD improved SLN identification to 96% from 93% for IHGP and 73% for IBD alone. Four patients had a positive SLN on frozen section analysis. A negative SLNB correctly predicted regional nodal control in 47 of 48 patients but missed 1 of 5 patients who had regional lymphatic disease. All 4 patients who failed SLNB remain alive and free of recurrent disease. Two-year Kaplan-Meier disease-specific and relapse-free survival was 91% and 88%, respectively. Two-year disease-specific survival was 93% for SLN-negative patients and 50% for SLN-positive patients (P=.20)., Conclusions: Combining PLSG with IHGP and IBD improves the success rate of SLNB. Although SLNB is a reliable indicator of the status of the draining lymphatic basins in CMHN, patients with negative SLNs must be observed for longer periods to understand the true implications of the procedure.