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HNSCC
Terms modified by HNSCC Selected AbstractsHigh-Risk Cutaneous Squamous Cell Carcinoma without Palpable Lymphadenopathy: Is There a Therapeutic Role for Elective Neck Dissection?DERMATOLOGIC SURGERY, Issue 4 2007JUAN-CARLOS MARTINEZ MD PURPOSE The beneficial role of elective neck dissection (END) in the management of high-risk cutaneous squamous cell carcinoma (CSCC) of the head and neck remains unproven. Some surgical specialists suggest that END may be beneficial for patients with clinically node-negative (N0) high-risk CSCC, but there are few data to support this claim. We reviewed the available literature regarding the use of END in the management of both CSCC and head and neck SCC (HNSCC). METHODOLOGY The available medical literature pertaining to END in both CSCC and HNSCC was reviewed using PubMed and Ovid Medline searches. RESULTS Many surgical specialists recommend that END be routinely performed in patients with N0 HNSCC when the risk of occult metastases is estimated to exceed 20%; however, patients who undergo END have no proven survival benefit over those who are initially staged as N0 and undergo therapeutic neck dissection (TND) after the development of apparent regional disease. There is a lack of data regarding the proper management of regional nodal basins in patients with N0 CSCC. In the absence of evidence-based data, the cutaneous surgeon must rely on clinical judgment to guide the management of patients with N0 high-risk CSCC of the head and neck. CONCLUSIONS Appropriate work-up for occult nodal disease may occasionally be warranted in patients with high-risk CSCC. END may play a role in only a very limited number of patients with high-risk CSCC. [source] Altered fractionation and adjuvant chemotherapy for head and neck squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2010William M. Mendenhall MD Abstract Background The aim of this review was to discuss the role of altered fractionation and adjuvant chemotherapy for patients treated with definitive radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC). Methods This review explores the pertinent literature and discusses the optimal management of previously untreated patients with stage III,stage IVA and/or -B HNSCCs. Results Depending on the schedule, altered fractionation improves locoregional control and survival. Both hyperfractionation and concomitant boost RT improve locoregional control and are associated with improved overall survival (OS). Adjuvant chemotherapy improves OS; the greatest impact is observed after concomitant versus induction or maintenance chemotherapy. Monochemotherapy appears to be equivalent to polychemotherapy. Drugs associated with the greatest survival benefit include fluorouracil and cisplatin. Intraarterial chemotherapy offers no advantage over intravenous chemotherapy. Concomitant cetuximab and RT results in improved outcomes similar to those observed after concomitant cisplatin-based chemotherapy and RT. Conclusions Altered fractionation and/or concomitant chemotherapy result in improved outcomes compared with conventionally fractionated definitive RT alone for stage III,stage IV HNSCC. The optimal combination of RT fractionation and chemotherapy remains unclear. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] Detection of metachronous esophageal squamous carcinoma in patients with head and neck cancer with use of transnasal esophagoscopyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2010Yan-Ye Su MD Abstract Background The use of transnasal esophagoscopy was examined for detecting metachronous esophageal squamous carcinoma in patients with head and neck squamous cell carcinoma (HNSCC). Methods In all, 398 transnasal esophagoscopies were performed in 293 previously treated patients with HNSCC between December 2007 and January 2009. Results Metachronous esophageal squamous carcinoma was detected in 15 (5.1%) patients. The prevalence rate was 15.9% (7/44) in patients with hypopharyngeal cancer, significantly higher than the 8.3% (2/24) with laryngeal, 7.1% (3/42) with oropharyngeal, and 1.6% (3/183) with oral cancer (p = .001). The stage distributions of esophageal squamous carcinoma were I,II in 12 (80%) and III,IV in 3 (20%) patients. Subsequently, curative strategies were performed in 13 (87%) patients. Conclusions Transnasal esophagoscopy can be used as a routine survey technique in patients with HNSCC to detect metachronous esophageal squamous carcinoma, especially in those with hypopharyngeal cancer. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source] Mechanisms of resistance to EGFR inhibitors in head and neck cancer,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2009Jonathan B. Cooper BS Abstract Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that activates multiple signaling pathways, including phosphatidylinositol-3-kinase/v-AKT murine thymoma viral oncogene homolog protein (Akt), has long been a target of novel therapies. Despite universal EGFR expression in head and neck squamous cell carcinoma (HNSCC), the majority of patients do not respond to EGFR inhibitors. This review focuses on mechanisms of resistance to these agents in HNSCC, and how these may be unique when compared with other malignancies such as non-small cell lung and colorectal cancers. Published studies and abstracts reveal that there are likely several mechanisms underlying resistance, suggesting that different strategies will be required to improve efficacy of EGFR inhibitors in HNSCC. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] Positron emission tomography in surveillance of head and neck squamous cell carcinoma after definitive chemoradiotherapyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2009Yi-Fen Wang MD Abstract Background. We assessed the role of 18F-fluoro-deoxy-glucose positron emission tomography (PET) in detecting head and neck squamous cell carcinoma (HNSCC) after definitive chemoradiotherapy (CRT). Methods. A prospective study presented 80 PET before and after CRT for 44 patients, including 44 first-time post-CRT scans performed between 12 and 17 weeks after radiotherapy completion, as well as 10 repeated scans in the subsequent follow-up. PET interpretations were compared with clinicopathologic outcomes. Results. PET demonstrated better performance than CT in post-CRT surveillance. Considering all 54 post-CRT PET scans, sensitivity for detecting primary tumors was 100%, specificity 93%, positive predictive value (PPV) 80%, and negative predictive value (NPV) 100%. For cervical diseases, sensitivity was 100%, specificity 98%, PPV 92%, and NPV 100%. For distant metastases, sensitivity was 100%, specificity 98%, PPV 86%, and NPV 100%. Conclusions. Negative PET readings were reliable for predicting free of HNSCC and helpful for selected patients in post-CRT surveillance. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] Pathology reporting in head and neck cancer,Snapshot of current statusHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2009Bronwyn King MBBS Abstract Background Currently there is no standardized head and neck pathology reporting system in Victoria, Australia. The aim of this study was to document deficiencies in head and neck pathology reports at our institution. Methods The pathology reports of all patients with head and neck squamous cell carcinoma (HNSCC) who presented to Peter MacCallum Cancer Centre for postoperative radiotherapy (PORT) between January 1, 2004, and March 31, 2006, were critically assessed for 16 key pathological items. Results Only 37% reports contained all the 16 items. The most commonly missing items were "diameter of the largest involved lymph node" (38%), "presence/absence of lymphovascular space invasion" (30%), "presence/absence of peri-neural invasion" (28%), "clearance of margins in millimeters" (27%), and "presence/absence of extracapsular extension" (27%). The most variable item was the clearance in millimeters used to determine "clear margins". Conclusions Several of the most important pathological factors predicting locoregional relapse in HNSCC are currently the least reliably reported items in head and neck pathology reports. © 2008 Wiley Periodicals, Inc. Head Neck, 2009 [source] DNA copy number variation and loss of heterozygosity in relation to recurrence of and survival from head and neck squamous cell carcinoma: A reviewHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2008Yu Chen PhD Abstract Genetic aberrations, such as DNA copy number variation (CNV) and loss of heterozygosity (LOH), have been implicated in head and neck squamous cell carcinoma (HNSCC) initiation and progression. This review examines CNV and LOH as predictors of HNSCC recurrence and mortality. We searched PubMed for relevant publications and compared and discussed results from the articles. Certain CNV and LOH events have consistently been associated with HNSCC recurrence and survival. The recent high-resolution single nucleotide polymorphism (SNP) arrays have the potential to identify many more genetic changes and concurrent genome-wide CNV, copy-neutral and/or allelic imbalance LOH in HNSCC that may bear on prognosis. Our review confrms that outcome in HNSCC can be predicted to a considerable extent by the presence of tumor cell genetic aberrations. It points out the limitations of some methodologies that were used in the past and discusses the advantages and challenges of using genome-wide SNP arrays. © 2008 Wiley Periodicals, Inc. Head Neck 2008 [source] Deletion of the PDZ motif of HPV16 E6 preventing immortalization and anchorage-independent growth in human tonsil epithelial cellsHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2008William C. Spanos MD Abstract Background Human papillomavirus 16 (HPV16) has been associated with head and neck squamous cell carcinoma (HNSCC) in up to 60% of sampled specimens. Methods To understand better the viral genes required to transform human tonsil epithelial cells (HTEC), we isolated HTEC's and transduced them with retroviral vectors containing HPV16 E6 and E7. Results Immortalization and anchorage-independent growth of HTEC's only occurred with expression of E6 and E7 with resultant degradation of p53. However, cells expressing E6 lacking the PSD-95/disc-large/Zo-1 (PDZ) motif did not immortalize or grow anchorage independent. Telomerase activity and degradation of p53 were similar for wild-type and mutant E6. Conclusion The mechanism of oncogenic transformation by E6 in HTEC's is dependent on the PDZ binding motif. Identification of pathways affected by the interaction of E6 and PDZ domain containing proteins will further our understanding of how HPV causes HNSCC and will provide potential therapeutic targets. © 2007 Wiley Periodicals, Inc. Head Neck, 2008 [source] Role of metalloproteins in the clinical management of head and neck squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2007W. Cooper Scurry Jr. MD Abstract Metalloproteins are a group of catalytic proteins, which play significant roles in cell cycle and death. Matrix metalloproteinases (MMPs) are a family of endopeptidases that are capable of digesting extracellular matrix components. They have been implicated in carcinogenesis and recent developments have been made to use MMPs clinically to predict outcomes. In the future, selective inhibition of these proteins and their regulatory pathways may prove useful in anticancer therapeutics. We present a review article on the clinical applications of metalloproteins in head and neck squamous cell carcinoma (HNSCC). Metalopanstimulin is highlighted as a putative metalloprotein of interest for those treating HNSCC. Expression of particular metalloproteins has correlation with lymph node metastasis, tumor invasiveness, and overall prognosis in HNSCC. © 2007 Wiley Periodicals, Inc. Head Neck 2007 [source] External validation of a risk group defined by recursive partitioning analysis in patients with head and neck carcinoma treated with surgery and postoperative radiotherapyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2007Xavier León MD Abstract Background: Several clinical trials have proved that concurrent chemoradiotherapy is more efficacious than radiotherapy alone among high-risk patients with head and neck squamous cell carcinoma (HNSCC) who undergo surgery. A risk-group classification defined according to a recursive partitioning analysis (RPA) for these patients has been recently proposed. The objective of the present study was to carry out an external validation of this RPA-derived classification system. Methods: A retrospective study of 442 HNSCC patients treated with surgery and postoperative radiotherapy was conducted. The external validity of the RPA-derived classification system was assessed, and its ability to stage patients and to predict locoregional control of the disease was compared with the TNM system. Results: The RPA-derived classification system succeeded in obtaining a monotonic prognosis gradient in locoregional control of the disease with increasing stage, and achieved greater differences in survival between stages than the TNM and pTNM classifications. Besides, the RPA method had a better homogeneity of the categories included in each stage, and in the heterogeneity between stages. Conclusions: The RPA-derived classification system allowed for the clear definition of prognostic groups in surgically treated HNSCC patients, improving the prognostic capacity of the TNM and pTNM classifications. The RPA-derived classification system is a useful tool in the definition of patients who, given a poor prognosis, should be considered candidates to adjuvant chemoradiotherapy. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source] Evaluation of patterns of failure and subjective salivary function in patients treated with intensity modulated radiotherapy for head and neck squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2007Megan E. Daly BS Abstract Background. Our aim was to correlate patterns of failure with target volume delineations in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiation therapy (IMRT) and to report subjective xerostomia outcomes after IMRT as compared with conventional radiation therapy (CRT). Methods. Between January 2000 and April 2005, 69 patients with newly diagnosed nonmetastatic HNSCC underwent curative parotid-sparing IMRT at Stanford University. Sites included were oropharynx (n = 39), oral cavity (n = 8), larynx (n = 8), hypopharynx (n = 8), and unknown primary (n = 6). Forty-six patients received definitive IMRT (66 Gy, 2.2 Gy/fraction), and 23 patients received postoperative IMRT (60.2 Gy, 2.15 Gy/fraction). Fifty-one patients also received concomitant chemotherapy. Posttreatment salivary gland function was evaluated by a validated xerostomia questionnaire in 29 IMRT and 75 matched CRT patients >6 months after completing radiation treatment. Results. At a median follow-up of 25 months for living patients (range, 10,60), 7 locoregional failures were observed, 5 in the gross target or high-risk postoperative volume, 1 in the clinical target volume, and 1 at the junction of the IMRT and supraclavicular fields. The 2-year Kaplan,Meier estimates for locoregional control and overall survival were 92% and 74% for definitive IMRT and 87% and 87% for postoperative IMRT patients, respectively. The mean total xerostomia questionnaire score was significantly better for IMRT than for CRT patients (p = .006). Conclusions. The predominant pattern of failure in IMRT-treated patients is in the gross tumor volume. Parotid sparing with IMRT resulted in less subjective xerostomia and may improve quality of life in irradiated HNSCC patients. © 2006 Wiley Periodicals, Inc. Head Neck, 2007 [source] Sentinel node in head and neck cancer: Use of size criterion to upstage the no neck in head and neck squamous cell carcinoma,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2007Lee W. T. Alkureishi MBChB Abstract Background. Anatomical imaging tools demonstrate poor sensitivity in head and neck squamous cell carcinoma (HNSCC) patients with clinically node-negative necks (cN0). This study evaluates nodal size as a staging criterion for detection of cervical metastases, utilizing sentinel node biopsy (SNB) and additional pathology (step-serial sectioning, SSS; and immunohistochemistry, IHC). Methods. Sixty-five patients with clinically N0 disease underwent SNB, with a mean of 2.4 nodes excised per patient. Nodes were fixed in formalin, bisected, and measured in 3 axes before hematoxylin-eosin staining. Negative nodes were subjected to SSS and IHC. SNB-positive patients underwent modified radical neck dissection. Results. Maximum diameter was larger in levels II and III (13.1 and 13.2 mm) when compared with level I (10.5 mm; p = .004, p = .018), while minimum diameter was constant. Positive nodes were larger than negative nodes (p = .007), but nodes found positive by SSS/IHC were not significantly larger than negative nodes for either measurement (p = .433). Sensitivity and specificity were poor for all measurements. Conclusions. Nodal size is an inaccurate predictor of nodal metastases and should not be regarded as an accurate means of staging the clinically N0 neck. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] Head and neck squamous cell carcinoma cell lines: Established models and rationale for selectionHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2007Charles J. Lin BA Abstract Background. Head and neck squamous cell carcinoma (HNSCC) cell lines are important preclinical models in the search for novel and targeted therapies to treat head and neck cancer. Unlike many other cancer types, a wide variety of primary and metastatic HNSCC cell lines are available. An easily accessible guide that organizes important characteristics of HNSCC cell lines would be valuable for the selection of appropriate HNSCC cell lines for in vitro or in vivo studies. Methods. A literature search was performed. Results. Cell growth and culture parameters from HNSCC cell lines were catalogued into tables or lists of selected characteristics. Methods for establishing cancer cell lines and basic cell culture maintenance techniques were reviewed. Conclusions. A compendium of HNSCC cell line characteristics is useful for organizing the accumulating information regarding cell line characteristics to assist investigators with the development of appropriate preclinical models. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] Mouse models for human head and neck squamous cell carcinomasHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2006Shi-Long Lu MD Abstract Mouse models of human cancer play an important role in understanding the mechanisms of carcinogenesis and have accelerated the search for finding new molecular targets for cancer therapy. However, genetically engineered mouse models for head and neck squamous cell carcinoma (HNSCC) have only recently overcome major technical obstacles and begun to be explored. Here we review the current progress in the development of mouse models for human HNSCC, with emphasis on conditional transgenic and knockout mouse models. These new models faithfully recapitulate human HNSCC at both the pathologic and molecular levels. These animal models will not only be useful to define the roles of specific genes in HNSCC development and progression but will also provide a unique tool for developing and testing new therapeutic approaches. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] Complete hypopharyngeal obstruction by mucosal adhesions: A complication of intensive chemoradiation for advanced head and neck cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2006Elizabeth J. Franzmann MD Abstract Background. Severe swallowing dysfunction is the dominant long-term complication observed in patients treated for head and neck squamous cell carcinoma (HNSCC) with treatment protocols using intensive concurrent chemotherapy with radiation therapy (chemo/XRT). We identified a subset of these patients, who were seen with complete obstruction of the hypopharynx distal to the site of the primary cancer, and in whom we postulate that the obstruction was caused by separable mucosal adhesions rather than obliteration by a mature fibrous stricture. Methods. Seven patients were referred to the senior author with a diagnosis of complete hypopharyngeal obstruction between 1992 and 2001. The diagnosis was confirmed by barium swallow imaging and/or endoscopy before referral in all patients. Patients underwent recanalization by passing a Jesberg esophagoscope under general anesthesia, followed by serial dilations and intensive swallowing therapy. Patient charts were reviewed retrospectively after institutional review board approval. Results. All seven patients were successfully recanalized. No patient had a perforation or other significant complication related to the recanalization procedure or subsequent dilations. Five of the seven patients showed improvement in swallowing at some point after the initial procedure, but just two patients recovered sufficiently to have their gastrostomy tube removed permanently. Conclusions. We conclude that complete hypopharyngeal obstruction secondary to mucosal adhesions is one cause of gastrostomy tube dependence in patients who have been treated with chemo/XRT for HNSCC. It is a difficult problem to treat, but most patients can recover useful swallowing function without undergoing laryngectomy or major surgical reconstruction. The postulated pathophysiology has implications for prevention as well as treatment. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] Impact of nutrition support on treatment outcome in patients with locally advanced head and neck squamous cell cancer treated with definitive radiotherapy: A secondary analysis of RTOG trial 90-03,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2006Rachel Rabinovitch MD Abstract Background. The aim was to evaluate the relationship between nutrition support (NS) on host toxicity and cancer outcome in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) undergoing definitive radiotherapy (XRT). Methods. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 90-03, a prospective randomized trial evaluating four definitive XRT fractionation schedules in patients with locally advanced HNSCC, which prospectively collected data on NS delivered before treatment (BNS), during treatment (TNS), and after definitive XRT. NS data and pretreatment characteristics of the 1073 evaluable patients were analyzed against therapy toxicity and outcome. Results. Patients receiving BNS experienced significantly less weight loss by the end of treatment and less grade 3 to 4 mucositis than patients not receiving BNS. However, patients receiving BNS had a poorer 5-year actuarial locoregional control rate than patients receiving TNS or no NS (29%, 55%, and 57%, respectively, p < .0001) and a poorer 5-year overall survival rate (16%, 36%, and 49%, respectively, p < .0001). Patients receiving BNS were significantly more likely to have a higher T classification, N status, and overall American Joint Committee on Cancer (AJCC) stage and initial presentation with greater pretreatment weight loss, and a poorer Karnofsky Performance Status (KPS) than patients not receiving BNS. After adjusting for the impact of these prognostic factors through a recursive partition analysis, a multivariate analysis with a stratified Cox model found that BNS was still a highly significant independent prognostic factor for increased locoregional failure (hazards ratio [HR], 1.47; 95% confidence interval [CI], 1.21,1.79; p < .0001) and death (HR, 1.41; 95% CI, 1.19,1.67; p < .0001). Conclusion. In this study, the largest prospective evaluation of nutrition data in treated patients with cancer, BNS was associated with inferior treatment outcome in the patients with HNSCC undergoing XRT. These results should be considered hypothesis generating and encourage prospective clinical research and identification of the mechanisms underlying this finding. © 2005 Wiley Periodicals, Inc. Head Neck28: 287,296, 2006 [source] CT of the chest and abdomen in patients with newly diagnosed head and neck squamous cell carcinoma,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2005Harri T. Keski-Säntti MD Abstract Background. The benefits of CT scanning of the chest and abdomen as a routine screening method for patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC) remain unclear. Methods. Consecutive patients with a primary HNSCC (T classification, T2,T4) and or regionally metastatic disease (ie, N+) were eligible for inclusion. Patients who were considered incurable and patients with recurrent disease were excluded. CT scans of the chest and abdomen were performed. Results. We examined 100 patients. Two patients had pulmonary metastases at presentation. An occult aortic aneurysm required surgical repair before anticancer therapy in one patient. In many patients, nonspecific CT findings warranted further examinations or close follow-up. The abdominal CT was negative for metastatic HNSCC in all patients. Conclusions. Routine CT screening of the chest and abdomen resulted in upstaging of disease in two patients (2%) and altered the treatment approach in three patients (3%). Abdominal CT does not seem beneficial in patients with previously untreated HNSCC. Chest CT is not indicated routinely. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Treatment of the N0 neck during salvage surgery after radiotherapy of head and neck squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2005Stephane Temam MD Abstract Background. The morbidity and mortality rates of salvage surgery in patients with local recurrence of head and neck squamous cell carcinoma (HNSCC) after radiotherapy are high. The aim of this study was to determine the rate of occult neck node metastasis and the surgical morbidity of patients after salvage surgery for local relapse after definitive radiotherapy. Methods. Thirty patients who underwent salvage surgery with a simultaneous neck node dissection for a local relapse after definitive radiotherapy for HNSCC between 1992 and 2000 were included in this study. The primary tumor sites were oral cavity in six patients, oropharynx in 17, supraglottic larynx in three, and hypopharynx in four. Initially, seven patients had T2 disease, eight had T3, and 15 had T4. Results. Twelve patients (40%) experienced postoperative complications, including two deaths. There was no cervical lymph node metastasis (pN0) in 29 of the 30 patients. Fifteen patients (50%) had a recurrence after salvage surgery, including 11 new local recurrences and four patients with distant metastasis. Conclusions. The risk of neck node metastasis during salvage surgery for local recurrence in patients treated initially with radiation for N0 HNSCC is low. Neck dissection should be performed in only limited area, depending on the surgical procedure used for tumor resection. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Molecular mediators of metastasis in head and neck squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2005Gina M. S. Howell BA Abstract Background. The presence of regional metastasis in patients with head and neck squamous cell carcinoma (HNSCC) is a common and adverse event associated with poor prognosis and high mortality. Although significant improvements in standard therapies have increased the efficacy of local tumor management, the high incidence of tumor recurrence has resulted in limited improvements in overall survival rates. Understanding the molecular mechanisms that mediate HNSCC invasion and metastasis may enable identification of novel therapeutic targets for the prevention and management of tumor dissemination. Methods. A literature review was performed. Results. Several biologic mediators and mechanisms that have been implicated in HNSCC metastasis, such as cell adhesion molecules, proteolytic enzymes, growth factor signaling, metastasis suppressor genes, and chemokine receptors were reviewed. Conclusions. Prevention of HNSCC metastasis is an important clinical objective that requires an increased understanding of the molecular mechanisms of tumor invasion and dissemination. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with a residual structural abnormality after definitive treatment for squamous cell carcinoma of the head and neckHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2004Robert E. Ware MB Abstract Background. Residual structural abnormalities after definitive treatment of head and neck squamous cell carcinoma (HNSCC) are common and pose difficult management problems. The usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) to supplement conventional evaluation with clinical and standard radiologic examination (CE) in such patients was assessed. Methods. Fifty-three eligible patients were identified with residual structural abnormalities on CE. True disease extent could be validated in 46 patients. Patients had a median potential follow-up of 55 months (range, 41,75 months) from the date of PET scan to the analysis closeout date. Results. PET had better diagnostic accuracy than CE (p = .0002) and induced management change in 21 patients (40%; 95% confidence interval [CI], 26%,54%), including avoidance of unnecessary planned surgery in 14 patients with negative PET. Appropriate management change was confirmed in 19 (95%) of 20 evaluable cases. Disease presence and extent assessment by PET were significant predictors of survival (p < .0001), whereas the extent of disease determined by CE was not. Conclusion. PET added significantly to the value of CE in restaging disease in patients with structural abnormalities after definitive treatment of HNSCC. Management decisions based on PET were appropriate in most patients. © 2004 Wiley Periodicals, Inc. Head Neck26: 1008,1017, 2004 [source] High frequency of HPV16-associated head and neck squamous cell carcinoma in the Puerto Rican populationHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2004Adriana Báez PhD Abstract Background. Recent evidence has accumulated suggesting that human papillomavirus (HPV) plays a role in the development of head and neck squamous cell carcinoma (HNSCC). HPV16 is the most common of the HPV subtypes associated with oral and laryngeal malignancies. This study estimated the prevalence of HPV16 DNA in Puerto Rican patients with HNSCC. Methods. DNA was extracted from frozen tissue of 118 HNSCCs. Genomic DNA was screened for the presence of HPV16 DNA with E6-specific and E7-specific primers. Results. HPV16 was detected in tumor tissue of 52 patients (44%) with HNSCC. The oropharynx had a slightly higher incidence of HPV16 DNA. Fifteen of 66 patients with HPV16-negative HNSCC later had recurrences. Positivity for HPV16 was independent of the tumor grade, tumor stage, nodal status, and tobacco or alcohol use. The 3-year survival rate was higher in HPV16-positive patients than in HPV16-negative patients (36% vs 21%). Conclusions. Our findings suggest that HPV16 may play a role in the etiology of a subgroup of HNSCC in Puerto Ricans. Overall survival times of the HPV16-positive patients were not significantly different from those of HPV16-negative patients. Increasing our understanding of the role of HPV16 in the etiology of HNSCC might facilitate the development of new treatment modalities for this subgroup of HNSCC. © 2004 Wiley Periodicals, Inc. Head Neck26: 778,784, 2004 [source] Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: A multicenter, randomized, double-blind, phase III study in North America,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2003Dan J. Castro MD Abstract Background. The objective was to evaluate the efficacy and safety of a novel intratumoral cisplatin/epinephrine injectable gel (CDDP/epi gel) for local control and palliation of tumor-related symptoms in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Patients and Methods. Eighty-seven patients were randomly assigned to either CDDP/epi or placebo gel in this phase III, double-blind study. Tumors were ,20 cm3; most recurrences (88%) were in a previously irradiated field. The most symptomatic or threatening tumor was designated as the target tumor. Dose: 0.25 mL CDDP/epi gel/cm3 tumor volume. Treatments: ,6 weekly intratumoral injections in an 8-week period. Primary outcomes: target tumor response and symptom relief. Results. During the blinded phase, 34% (21 of 62) of patients achieved an objective response (CR or PR) in the target tumor treated with CDDP/epi gel vs 0% (0 of 24) treated with placebo gel (p < .001). Responses occurred within a median of four treatments (range, 2,6) and were durable (median, 95 days; range, 34,168+ days). More patients treated with CDDP/epi gel achieved palliative benefit than did those treated with placebo gel (37% vs 12%, p = .036). Most frequent side effects were local pain and local cutaneous reactions, which resolved over 3,12 weeks. Renal and hematologic toxicities were rare. Conclusions. This phase III trial showed that CDDP/epi gel significantly reduces tumor burden, palliates tumor-related symptoms, and is an effective local treatment for recurrent tumors. © 2003 Wiley Periodicals, Inc. Head Neck 25: 717,731, 2003 [source] Differentially expressed genes associated with CIS -diamminedichloroplatinum (II) resistance in head and neck cancer using differential display and CDNA microarrayHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2003Eisaku Higuchi MD Abstract Background. The mechanism by which cancer cells become resistant to cis -Diamminedichloroplatinum (II) (cDDP) is not completely understood. To investigate the molecular markers involved in the cDDP resistance, we compared the gene expression profiles between a head and neck squamous cell carcinoma (HNSCC) line sensitive to cDDP and its cDDP-resistant variant. Methods. Both a fluorescent differential display and a cDNA microarray analysis were applied to distinguish the gene profiles between KB, a human HNSCC line, and its cDDP-resistant variant (KB/cDDP). These results were confirmed by Northern blot analysis. Results. One up-regulated gene, glycoprotein hormone ,-subunit, and two down-regulated genes coding membrane proteins, human folate receptor and tumor-associated antigen L6, were identified in KB/cDDP cells. Conclusions. Our findings suggest that development of the cDDP-resistant phenotype is accompanied by alternations of gene expression including a glycoprotein hormone and membrane proteins. These gene products could be new molecular markers for resistance to cDDP. © 2003 Wiley Periodicals, Inc. Head Neck 25: 187,193, 2003 [source] FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2002Eva Brun MD Background Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2-[18 F] fluoro-2-deoxy- D -glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC. Methods Between 1993 and 1999 47 patients underwent PET before (PET1) and after (PET2) 1 to 3 weeks of radical treatment with evaluation of metabolic rate (MR) and standardized uptake value (SUV) of FDG. All patients received radiotherapy, and 10 also received neoadjuvant chemotherapy. Median follow-up time was 3.3 years. Results Low and high MR FDG at PET2, with median value as cutoff, was associated with complete remission in 96% and 62% (p = .007), with 5-year overall survival in 72% and 35% (p = .0042) and with local control in 96% and 55% (p = .002), respectively. Conclusions FDG PET in the early phase of treatment of HNSCC is associated with tumor response, survival, and local control. © 2002 John Wiley & Sons, Inc. [source] Prediction of survival in patients with head and neck cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2001Robert Jan Baatenburg de Jong PhD Abstract Background In patients with head and neck squamous cell carcinoma (HNSCC) the estimated prognosis is usually based on the TNM classification. The relative weight of the three contributing parameters is often not completely clear. Moreover, the impact of other important clinical variables such as age, gender, prior malignancies, etc is very difficult to substantiate in daily clinical practice. The Cox-regression model allows us to estimate the effect of different variables simultaneously. The purpose of this study was to design a model for application in new HNSCC patients. In our historical data-base of patients with HNSCC, patient, treatment, and follow-up data are stored by trained oncological data managers. With these hospital-based data, we developed a statistical model for risk assessment and prediction of overall survival. This model serves in clinical decision making and appropriate counseling of patients with HNSCC. Patients and Methods All patients with HNSCC of the oral cavity, the pharynx, and the larynx diagnosed in our hospital between 1981 and 1998 were included. In these 1396 patients, the prognostic value of site of the primary tumor, age at diagnosis, gender, T-, N-, and M-stage, and prior malignancies were studied univariately by Kaplan-Meier curves and the log-rank test. The Cox-regression model was used to investigate the effect of these variables simultaneously on overall survival and to develop a prediction model for individual patients. Results In the univariate analyses, all variables except gender contributed significantly to overall survival. Their contribution remained significant in the multivariate Cox model. Based on the relative risks and the baseline survival curve, the expected survival for a new HNSCC patient can be calculated. Conclusions It is possible to predict survival probabilities in a new patient with HNSCC based on historical results from a data-set analyzed with the Cox-regression model. The model is supplied with hospital-based data. Our model can be extended by other prognostic factors such as co-morbidity, histological data, molecular biology markers, etc. The results of the Cox-regression may be used in patient counseling, clinical decision making, and quality maintenance. © 2001 John Wiley & Sons, Inc. Head Neck 23: 718,724, 2001. [source] Prognostic significance of serum p53 protein and p53 antibody in patients with surgical treatment for head and neck squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2001Vivian Chow M. Phil Abstract Objectives This study aims at investigating the prognostic values of serum p53 protein and anti-p53 antibody in patients undergoing surgical treatment for head and neck squamous cell carcinoma (HNSCC). Methods Serum p53 protein and anti-p53 antibody concentrations were determined by an enzyme-linked immunosorbent assay (ELISA) in 75 patients with HNSCC and 28 healthy controls. In 28 patients, formalin-fixed tumor tissues were also available for immunohistochemical staining by an anti-p53 DO7 monoclonal antibody. The results were correlated with the clinicopathologic parameters. Results The mean preoperative serum concentration of p53 protein in patients with HNSCC was significantly higher than healthy controls (59.45 pg/mL vs 16.4 pg/mL, p = .007). Preoperative serum p53 antibody was present in 23 (31%) patients and was present in one healthy control. Eighteen (62%) tumor tissues showed p53 overexpression by immunohistochemistry. The presence of serum anti-p53 antibody before operation was associated with a significantly higher incidence (65%) of nodal metastasis compared with 27% nodal metastasis in patients with absence of serum anti-p53 antibody (p = .002). Conclusion Preoperative serum p53 antibody was a significant prognostic factor for nodal metastasis of HNSCC. © 2001 John Wiley & Sons, Inc. Head Neck 23: 286,291, 2001. [source] Altered patterns of the interferon-inducible gene IFI16 expression in head and neck squamous cell carcinoma: immunohistochemical study including correlation with retinoblastoma protein, human papillomavirus infection and proliferation indexHISTOPATHOLOGY, Issue 6 2004B Azzimonti Aims:, To investigate whether the expression of interferon (IFN)-inducible gene IFI16 is inversely related to proliferative activity in vivo, we compared immunohistochemical reactivity of IFI16 in a series of head and neck squamous cell carcinomas (HNSCCs) with their proliferation index and the cell cycle regulator pRb. As human papillomavirus (HPV) infection is manifested by changes in the function or expression level of host genes such as IFN-inducible genes, we also investigated the presence of HPV DNA to determine whether head and neck cancers associated with HPV DNA can be distinguished from tumours that are presumably transformed by other mechanisms. Methods:, Thirty-six HNSCCs were evaluated for IFI16, pRb and Ki67 expression by immunohistochemistry. The presence of HPV was also detected by polymerase chain reaction. Nine tumours were located in the oropharynx (tonsillar area) and 27 in the larynx. Results:, HPV DNA was found in 14 of 25 (56%) laryngeal SCCs and in five of nine (56%) tonsillar SCC specimens examined; 17 out of the 19 HPV-DNA-positive cases showed high-grade IFI16 expression. Overall, proliferative activity was significantly related to tumour differentiation and histological grading. IFI16 protein expression was significantly inversely correlated with Ki67 (P = 0.039). Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. Conclusions:, To our knowledge, this is the first expression analysis of the IFN-inducible IFI16 gene in HNSCC. Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. [source] High serum levels of YKL-40 in patients with squamous cell carcinoma of the head and neck are associated with short survivalINTERNATIONAL JOURNAL OF CANCER, Issue 4 2008Anne Roslind Abstract YKL-40 is a glycoprotein secreted by macrophages, neutrophils and malignant tumor cells. Elevated serum levels of YKL-40 are associated with poor prognosis in several malignancies. In this study, we examined the prognostic value of serum YKL-40 before treatment and during follow-up in patients with squamous cell carcinoma of the head and neck (HNSCC). YKL-40 was determined by ELISA retrospectively in serum from 173 patients with primary HNSCC before treatment and up to 2 years after treatment. Median follow-up time was 7.9 years. YKL-40 protein expression in tumor biopsies was assessed by immunohistochemistry in 50 patients. Pretreatment serum YKL-40 was elevated in 53%. Patients with high serum YKL-40 had shorter survival than patients with normal serum YKL-40 (33 vs. 84 months; p = 0.008). Multivariate Cox analysis including pretreatment serum YKL-40, age, sex, primary tumor site, TNM classification and treatment demonstrated that TNM classification (HR = 2.61, p = 0.02) and serum YKL-40 (log-transformed continuous variable: HR = 1.55, p < 0.0001) were independent prognostic variables of overall survival (OS). Multivariate Cox analysis demonstrated that TNM classification (HR = 5.77, p = 0.001) and serum YKL-40 (dichotomous variable: HR = 2.75, p = 0.01) were independent predictors of recurrence-free survival. During follow-up after radiotherapy, a high serum YKL-40 (log-transformed continuous variable) in patients with TNM Stage III and IV disease predicted poorer OS within 6 months (HR = 1.95, p < 0.0001). Immunohistochemical analysis showed YKL-40 expression in the malignant tumor cells. In conclusion, serum YKL-40 was demonstrated to be an independent prognostic biomarker of recurrence-free and overall survival in patients with HNSCC. © 2007 Wiley-Liss, Inc. [source] The effect of nitric oxide on cyclooxygenase-2 (COX-2) overexpression in head and neck cancer cell linesINTERNATIONAL JOURNAL OF CANCER, Issue 5 2003Seok-Woo Park Abstract The overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) has been previously reported in head and neck squamous cell carcinoma (HNSCC), as well as in many cancers. We hypothesized that endogenous nitric oxide (NO) might increase the expression of COX-2 in cancer cells. Therefore, we investigated the cross-talk between NO and the prostaglandin (PG) pathways in HNSCC cell lines. We found that COX-2 and iNOS expressions were elevated simultaneously. On adding the NO donor, SNAP, the PGE2 level was increased 2,20 times due to increased COX-2 expression. This increase of COX-2 expression by SNAP or PMA (potent inducer of both iNOS and COX-2) was blocked to various degrees by NO scavengers and NOS inhibitors (L-NAME and 1400W). Also, the expression of COX-2 in resting cells was inhibited by NOS inhibitors. Moreover, COX-2 expression, induced by SNAP, was inhibited by ODQ, a soluble guanylate cyclase (sGC) inhibitor. The effect of dibutyryl-cGMP on COX-2 expression was similar to that of SNAP. These results imply that endogenous or exogenous NO activates sGC and that the resulting increase of cGMP induces a signaling that upregulates the expression of COX-2 in HNSCC cell lines. We also observed that NO increased COX-2 expression in different cancer cell lines, including cervic and gastric cancer cell lines. These findings further support the notion that NO can be associated with carcinogenesis through the upregulation of COX-2, and that NOS inhibitor may be also useful for cancer prevention. © 2003 Wiley-Liss, Inc. [source] Overexpression of Fos-related antigen-1 in head and neck squamous cell carcinomaINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2005Flavia R. R. Mangone Summary The activating protein-1 (AP-1) family of transcription factors has been implicated in the control of proliferation and differentiation of keratinocytes, but its role in malignant transformation is not clear. The aim of this study is to assess the pattern of mRNA expression of jun-fos AP-1 family members in 45 samples of head and neck squamous cell carcinomas (HNSCC) and matched adjacent mucosa by means of Northern blot analysis. Transcripts of all family members were identified, except for JunB that was detected only by means of reverse transcription polymerase chain reaction. Neither c-Fos nor JunD or FosB mRNA differed between tumours and normal tissues. We observed a strong Fos-related antigen-1 (Fra-1) and Fra-2 expression, but only Fra-1 mRNA densitometric values were higher in tumour, compared to normal adjacent mucosa (t -test, P = 0.006). A direct relationship between the positive expression of Fra-1 mRNA, above tumour median, was associated with the presence of compromised lymph nodes (Fischer exact test, P = 0.006). In addition, Fra-1 protein staining was assessed in a collection of 180 tumours and 29 histologically normal samples adjacent to tumours in a tissue array. Weak reactivity, restricted to the basal cell layer, was detected in 79% of tumour adjacent normal tissues, opposed to the intense reactivity of cancer tissues. In the subgroup of oral cancers, we have observed a shift in Fra-1 immunoreactivity, as long as the number of patients in each category, cytoplasmic or nuclear/cytoplasmic staining, was analysed (Fischer exact test, P = 0.0005). Thus, Fra-1 gene induction and accumulation of Fra-1 protein may contribute to the neoplastic phenotype in HNSCC. [source] |