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Sample records for head-and-neck squamous cell

  1. Genetics Home Reference: head and neck squamous cell carcinoma

    Science.gov (United States)

    ... and neck squamous cell carcinoma Head and neck squamous cell carcinoma Printable PDF Open All Close All Enable Javascript ... Consumer Version: Overview of Mouth, Nose, and Throat Cancers Orphanet: Squamous cell carcinoma of head and neck University of Michigan ...

  2. Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: Metastasis or second primary?

    NARCIS (Netherlands)

    Geurts, Tom W.; Nederlof, Petra M.; van den Brekel, Michiel W. M.; van't Veer, Laura J.; de Jong, Daphne; Hart, August A. M.; van Zandwijk, Nico; Klomp, Houke; Balm, Alfons J. M.; van Velthuysen, Marie-Louise F.

    2005-01-01

    Purpose: To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma. Experimental Design: For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a

  3. Cetuximab And The Head And Neck Squamous Cell Cancer.

    Science.gov (United States)

    Concu, Riccardo; Cordeiro, Maria Natalia Dias Soeiro

    2018-01-12

    The head and neck squamous cell cancer (HNSCC) is the most common type of head and neck cancer (more than 90%), and all over the world more than a half million people have been developing this cancer in the last years. This type of cancer is usually marked by a poor prognosis with a really significant morbidity and mortality. Cetuximab received early favor as an exciting and promising new therapy with relatively mild side effect, and due to this received authorization in the 2004 from the European Medicines Agency (EMA) and in the 2006 from the Food and Drug Association (FDA) for the treatment of patients with squamous cell cancer of the head and neck in combination with radiation therapy for locally advanced disease. In this work we will review the application and the efficacy of the Cetuximab in the treatment of the HNSCC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Genetic alterations in head and neck squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Nagai M.A.

    1999-01-01

    Full Text Available The genetic alterations observed in head and neck cancer are mainly due to oncogene activation (gain of function mutations and tumor suppressor gene inactivation (loss of function mutations, leading to deregulation of cell proliferation and death. These genetic alterations include gene amplification and overexpression of oncogenes such as myc, erbB-2, EGFR and cyclinD1 and mutations, deletions and hypermethylation leading to p16 and TP53 tumor suppressor gene inactivation. In addition, loss of heterozygosity in several chromosomal regions is frequently observed, suggesting that other tumor suppressor genes not yet identified could be involved in the tumorigenic process of head and neck cancers. The exact temporal sequence of the genetic alterations during head and neck squamous cell carcinoma (HNSCC development and progression has not yet been defined and their diagnostic or prognostic significance is controversial. Advances in the understanding of the molecular basis of head and neck cancer should help in the identification of new markers that could be used for the diagnosis, prognosis and treatment of the disease.

  5. Multiple squamous cell carcinomas within the head and neck region

    International Nuclear Information System (INIS)

    Sato, Katsuro; Hanazawa, Hideyuki; Sato, Yuichiro; Takahashi, Sugata

    2004-01-01

    Clinical features of multiple squamous cell carcinoma (SCC) cases within the head and neck that were treated in our department during the recent 10 years are discussed. Multiple SCCs arose in 6.6% of the cases with primary SCC; 67% of the cases had two carcinomas, and 33% had more than three carcinomas. The most common site of the multiple SCCs was the oral cavity (54%). The most frequent interval between treatment of previous carcinoma and diagnosis of subsequent carcinoma was simultaneous, but more than 5 years' interval was observed in 36% of the patients. The most common initial treatment of the carcinoma was irradiation, but the ratio of surgery increased for subsequent carcinomas. Prognosis of the patients with more than three carcinomas was not worse than that of patients with two carcinomas. Therefore, early diagnosis of the subsequent carcinomas based on careful long-term observation in the head and neck is necessary for follow-up of the patients with SCC of the head and neck. Treatment strategies considering the treatment of subsequent carcinomas are needed for the patients with primary head and neck SCC. (author)

  6. Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lacko, Martin [Department of Otorhinolaryngology—Head and Neck Surgery, Maastricht University Medical Center, Maastricht (Netherlands); Braakhuis, Boudewijn J.M. [Department of Otolaryngology—Head and Neck Surgery, VU University Medical Center, Amsterdam (Netherlands); Sturgis, Erich M. [Department of Head and Neck Surgery and Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Boedeker, Carsten C. [Department of Otorhinolaryngology—Head and Neck Surgery, Albert-Ludwigs-University, Freiburg, Germany and Department of Otorhinolaryngology - Head and Neck Surgery, HELIOS Hanseklinikum Stralsund, Stralsund (Germany); Suárez, Carlos [Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo (Spain); Instituto Universitario de Oncología del Principado de Asturias, Oviedo (Spain); Rinaldo, Alessandra; Ferlito, Alfio [ENT Clinic, University of Udine, Udine (Italy); Takes, Robert P., E-mail: robert.takes@radboudumc.nl [Department of Otolaryngology—Head and Neck Surgery, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands)

    2014-05-01

    Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all individuals exposed to these carcinogens experience the disease. This review highlights some aspects of genetic susceptibility to HNSCC: among others, genetic polymorphisms in biotransformation enzymes, DNA repair pathway, apoptotic pathway, human papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations, familial forms of HNSCC, functional assays for HNSCC risk assessment, and the implications and perspectives of research on genetic susceptibility in HNSCC are discussed.

  7. Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Lacko, Martin; Braakhuis, Boudewijn J.M.; Sturgis, Erich M.; Boedeker, Carsten C.; Suárez, Carlos; Rinaldo, Alessandra; Ferlito, Alfio; Takes, Robert P.

    2014-01-01

    Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all individuals exposed to these carcinogens experience the disease. This review highlights some aspects of genetic susceptibility to HNSCC: among others, genetic polymorphisms in biotransformation enzymes, DNA repair pathway, apoptotic pathway, human papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations, familial forms of HNSCC, functional assays for HNSCC risk assessment, and the implications and perspectives of research on genetic susceptibility in HNSCC are discussed

  8. Human Papilloma Virus in Head and Neck Squamous Cell Cancer

    Science.gov (United States)

    Asvadi Kermani, I; Seifi, SH; Dolatkhah, R; Sakhinia, E; Dastgiri, S; Ebrahimi, A; Lotfy, A; Esmaeili, HA; G, Mohammadi; M, Naderpour; SH, Hajalipour; Haggi A, Asghari; M, Nadri

    2012-01-01

    Background Epidemiologic and molecular evidences have established a strong link between high risk types of Human Papilloma Virus and a subgroup of Head and Neck Squamous Cell Carcinomas (HNSCC). We evaluated the frequency of HPV positivity in HNSCC and its relationship to demographic and some risk factor variables in an open case- control study. Methods Fourteen recently diagnosed patients with squamous cell cancer of oropharynx, hypopharynx and larynx aged 18-50 years were examined from 2008-2010 in Tabriz, Iran. HPV DNA was extracted from paraffin-embedded blocks of each patient's sample for PCR evaluation. Saliva samples of 94 control cancer-free subjects were collected for DNA analysis. Multivariable logistic regression method was used to calculate odds ratio for case-control comparisons. Results High risk HPV was detected in 6(42.8%) patients, and 6(5.3%) control subjects which was statistically significant (p<0.0001). HPV-18 was the most frequent type both in the cases and controls. HPV-16 DNA was detected in two patients of the case group, but it was not detected in any of the controls. The relation between demographic and risk factor variables was not statistically significant. Conclusion HPV infection has a significant impact on HNSCC. Despite HPV-16 stronger impact, HPV-18 is more likely to cause malignant degeneration in such cancers amongst some communities. It is vital to introduce and conduct immunization schedules in health care systems to protect communities to some extent. PMID:25780535

  9. Novel Immunotherapeutic Approaches for Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Darrin V. Bann

    2016-09-01

    Full Text Available The immune system plays a key role in preventing tumor formation by recognizing and destroying malignant cells. For over a century, researchers have attempted to harness the immune response as a cancer treatment, although this approach has only recently achieved clinical success. Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer worldwide and is associated with cigarette smoking, alcohol consumption, betel nut use, and human papillomavirus infection. Unfortunately, worldwide mortality from HNSCC remains high, partially due to limits on therapy secondary to the significant morbidity associated with current treatments. Therefore, immunotherapeutic approaches to HNSCC treatment are attractive for their potential to reduce morbidity while improving survival. However, the application of immunotherapies to this disease has been challenging because HNSCC is profoundly immunosuppressive, resulting in decreased absolute lymphocyte counts, impaired natural killer cell function, reduced antigen-presenting cell function, and a tumor-permissive cytokine profile. Despite these challenges, numerous clinical trials testing the safety and efficacy of immunotherapeutic approaches to HNSCC treatment are currently underway, many of which have produced promising results. This review will summarize immunotherapeutic approaches to HNSCC that are currently undergoing clinical trials.

  10. Immunotherapy for Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Moskovitz, Jessica; Moy, Jennifer; Ferris, Robert L

    2018-03-03

    Discussion of current strategies targeting the immune system related to solid tumors with emphasis on head and neck squamous cell carcinoma (HNSCC).This review will outline the current challenges with immunotherapy and future goals for treatment using these agents. Agents targeting immune checkpoint receptors (IR) such as program death 1 (PD1) have been used in the clinical realm for melanoma and non-small cell lung cancer (NSCLC), and the use of these agents for these malignancies has provided crucial information about how and why patients respond or not to inhibitory checkpoint receptor blockade therapy (ICR). The anti PD1 agent, nivolumab, was recently approved by the FDA as a standard of care regimen for patients with platinum refractory recurrent/metastatic (R/M) HNSCC. Molecular pathways leading to resistance are starting to be identified, and work is underway to understand the most optimal treatment regimen with incorporation of immunotherapy. ICR has renewed interest in the immunology of cancer, but resistance is not uncommon, and thus understanding of these mechanisms will allow the clinician to appropriately select patients that will benefit from this therapy.

  11. Incidence of Etiologic Factors in Squamous Cell Carcinoma of Head and Neck in Ahvaz

    Directory of Open Access Journals (Sweden)

    Soheila Nikakhlagh

    2011-01-01

     Conclusion: According to this study, tobacco smoking was the most important etiologic factor and had a strong effect on risk of head and neck squamous cell carcinoma. Other factors are also important and need more research study.

  12. Radiotherapy plus cetuximab for the squamous cells carcinoma of head and neck

    International Nuclear Information System (INIS)

    Bonner, James A.; Harari, Paul M.; Giralt, Jordi; Azarnia, Nozar; Shin, Dong M.; Cohen, Roger B.; Jones, Cristopher U.; Sur, Ranjan; Raben, David; Jassem, Jacek; Ove, Roger; Kies, Merrill S.; Baselga, Jose; Youssoufian, Hagop; Amellal, Nadia; Rowinsky, Eric K.; Ang, K. Kian

    2006-01-01

    A multinational randomized study was realized, to compare radiotherapy alone with radiotherapy combined with cetuximab, a monoclonal antibody against the receiver epidermal growth factor in the treatment of squamous cell carcinoma of head and neck locally advanced [es

  13. Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck

    OpenAIRE

    Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

    2015-01-01

    Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and...

  14. Topographic Pattern Distribution of Head And Neck Squamous Cell ...

    African Journals Online (AJOL)

    FINEPRINT

    value of 71% of SCC in Turkey. Nevertheless a similar report documented a relatively lower value especially in. Yemen where head and neck SCC constituted only 8% of all head and neck cancers. Reports from Yemen revealed that oral cavity SCC was the most common topographic site of all head and. 3 neck cancers.

  15. General principles for treatment planning for squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Million, R.R.; Bova, F.J.

    1987-01-01

    Although squamous cell carcinoma of the head and neck represents only 5% of all malignancies, the head and neck area is one of the few anatomical areas remaining where radiotherapy is often used as the only modality for cure and often with substantial doses. There are at least 35 separate anatomical sites for origin of squamous cell carcinoma in the upper respiratory tract, and each site has its own distinctive pattern of spread, incidence of regional and distant metastases, and varying stages of presentation. It would be impossible in this short chapter to cover every contingency for treatment planning, and only general principles are outlined

  16. Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck

    DEFF Research Database (Denmark)

    Hald, Jeppe; Rasmussen, N; Claesson, Mogens Helweg

    1995-01-01

    Tumour-infiltrating lymphocytes (TIL) and tumours from six patients with squamous cell carcinomas of the head and neck (SCCHN) were investigated. The six tumours all expressed major histocompatibility complex (MHC) class I antigens both in vivo and as tumor cell lines grown in vitro. In addition...

  17. Marijuana use and increased risk of squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Zhang, Z F; Morgenstern, H; Spitz, M R; Tashkin, D P; Yu, G P; Marshall, J R; Hsu, T C; Schantz, S P

    1999-12-01

    Marijuana is the most commonly used illegal drug in the United States. In some subcultures, it is widely perceived to be harmless. Although the carcinogenic properties of marijuana smoke are similar to those of tobacco, no epidemiological studies of the relationship between marijuana use and head and neck cancer have been published. The relationship between marijuana use and head and neck cancer was investigated by a case-control study of 173 previously untreated cases with pathologically confirmed diagnoses of squamous cell carcinoma of the head and neck and 176 cancer-free controls at Memorial Sloan-Kettering Cancer Center between 1992 and 1994. Epidemiological data were collected by using a structured questionnaire, which included history of tobacco smoking, alcohol use, and marijuana use. The associations between marijuana use and head and neck cancer were analyzed by Mantel-Haenszel methods and logistic regression models. Controlling for age, sex, race, education, alcohol consumption, pack-years of cigarette smoking, and passive smoking, the risk of squamous cell carcinoma of the head and neck was increased with marijuana use [odds ratio (OR) comparing ever with never users, 2.6; 95% confidence interval (CI), 1.1-6.6]. Dose-response relationships were observed for frequency of marijuana use/day (P for trend marijuana use (P for trend marijuana use were observed with cigarette smoking, mutagen sensitivity, and to a lesser extent, alcohol use. Our results suggest that marijuana use may increase the risk of head and neck cancer with a strong dose-response pattern. Our analysis indicated that marijuana use may interact with mutagen sensitivity and other risk factors to increase the risk of head and neck cancer. The results need to be interpreted with some caution in drawing causal inferences because of certain methodological limitations, especially with regard to interactions.

  18. Radiolabeled cetuximab: dose optimization for epidermal growth factor receptor imaging in a head-and-neck squamous cell carcinoma model

    NARCIS (Netherlands)

    Hoeben, B.A.W.; Molkenboer-Kuenen, J.D.M.; Oyen, W.J.G.; Peeters, W.J.M.; Kaanders, J.H.A.M.; Bussink, J.; Boerman, O.C.

    2011-01-01

    Noninvasive imaging of the epidermal growth factor receptor (EGFR) in head-and-neck squamous cell carcinoma could be of value to select patients for EGFR-targeted therapy. We assessed dose optimization of (111) Indium-DTPA-cetuximab ((111) In-cetuximab) for EGFR imaging in a head-and-neck squamous

  19. Immunohistochemical biomarkers and FDG uptake on PET/CT in head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Rasmussen, Gregers Brünnich; Vogelius, Ivan R.; Rasmussen, Jacob H

    2015-01-01

    on the other. A number of previous studies have shown a relationship between glucose transport protein expression and 18F-Fludeoxyglucose (FDG) PET uptake. Here, FDG uptake is analyzed in relation to expression of a selected panel of IHC cancer biomarkers in head and neck squamous cell carcinomas (HNSCC...

  20. Post-therapeutic surveillance strategies in head and neck squamous cell carcinoma

    NARCIS (Netherlands)

    Digonnet, Antoine; Hamoir, Marc; Andry, Guy; Haigentz, Missak; Takes, Robert P.; Silver, Carl E.; Hartl, Dana M.; Strojan, Primoz; Rinaldo, Alessandra; de Bree, Remco; Dietz, Andreas; Gregoire, Vincent; Paleri, Vinidh; Langendijk, Johannes A.; Vander Poorten, Vincent; Hinni, Michael L.; Rodrigo, Juan P.; Suarez, Carlos; Mendenhall, William M.; Werner, Jochen A.; Genden, Eric M.; Ferlito, Alfio

    The management of head and neck squamous cell carcinomas does not end with the completion of ablative therapy. The oncologic objectives of post-treatment follow-up are to detect recurrences and second primary tumors; beyond that, follow-up should evaluate acute and chronic treatment-related side

  1. Review: Head and neck squamous cell carcinoma in sub-Saharan ...

    African Journals Online (AJOL)

    Aim Review the literature from 1990 to 2013 to determine known anatomic sites, risk factors, treatments, and outcomes of head and neck squamous cell carcinoma (HNSCC) in sub-Saharan Africa. Methods Using a systematic search strategy, literature pertaining to HNSCC in sub-Saharan Africa was reviewed and patient ...

  2. Use of next generation sequencing in head and neck squamous cell carcinomas

    DEFF Research Database (Denmark)

    Tabatabaeifar, Siavosh; Kruse, Torben A; Thomassen, Mads

    2014-01-01

    Head and neck squamous cell carcinoma (HNSCC) can primarily be attributed to alcohol consumption, tobacco use and infection with human papilloma virus. The heterogeneous nature of HNSCC has exposed a lack of tools for clinicians to provide more accurate prognosis. There is a need for biomarkers...

  3. Immunocompromised and immunocompetent mouse models for head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Lei ZG

    2016-01-01

    Full Text Available Zhen-ge Lei,1,* Xiao-hua Ren,2,* Sha-sha Wang,3 Xin-hua Liang,3,4 Ya-ling Tang3,5 1Department of Oral and Maxillofacial Surgery, Stomatological Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, 2Department of Stomatology, Sichuan Medical Science Academy and Sichuan Provincial People’s Hospital, 3State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 4Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, 5Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Abstract: Mouse models can closely mimic human oral squamous epithelial carcinogenesis, greatly expand the in vivo research possibilities, and play a critical role in the development of diagnosis, monitoring, and treatment of head and neck squamous cell carcinoma. With the development of the recent research on the contribution of immunity/inflammation to cancer initiation and progression, mouse models have been divided into two categories, namely, immunocompromised and immunocompetent mouse models. And thus, this paper will review these two kinds of models applied in head and neck squamous cell carcinoma to provide a platform to understand the complicated histological, molecular, and genetic changes of oral squamous epithelial tumorigenesis. Keywords: head and neck squamous cell carcinoma, HNSCC, mouse models, immunocompromised models, immunocompetent models, transgenic models

  4. Environmental tobacco smoking, mutagen sensitivity, and head and neck squamous cell carcinoma.

    Science.gov (United States)

    Zhang, Z F; Morgenstern, H; Spitz, M R; Tashkin, D P; Yu, G P; Hsu, T C; Schantz, S P

    2000-10-01

    Although active tobacco smoking has been considered a major risk factor for head and neck cancer, few studies have evaluated environmental tobacco smoke (ETS) and its interaction with mutagen sensitivity on the risk of head and neck cancer. We investigated the relationship between ETS and head and neck cancer in a case-control study of 173 previously untreated cases with pathologically confirmed diagnoses of squamous cell carcinoma of the head and neck and 176 cancer-free controls at Memorial Sloan-Kettering Cancer Center between 1992 and 1994. A structured questionnaire was used to collect ETS exposure and other covariates including a history of active tobacco smoking and alcohol use. ETS measures include a history of ETS exposure at home and at workplace. The associations between passive smoking and head and neck cancer were analyzed by Mantel-Haenszel methods and logistic regression models. Additive and multiplicative models were used to evaluate effect modifications between ETS and mutagen sensitivity. The crude odds ratio (OR) for ETS exposure was 2.8 [95% confidence intervals (CI), 1.3-6.0]. Controlling for age, sex, race, education, alcohol consumption, pack-years of cigarette smoking, and marijuana use, the risk of squamous cell carcinoma of the head and neck was increased with ETS (adjusted OR, 2.4; 95% CI, 0.9-6.8). Dose-response relationships were observed for the degree of ETS exposure; the adjusted ORs were 2.1 (95% CI, 0.7-6.1) for those with moderate exposure and 3.6 (95% CI, 1.1-11.5) for individuals with heavy exposure (P for trend = 0.025), in comparison with those who never had ETS exposures. These associations and the dose-response relationships were still present when the analysis was restricted to nonactive smoking cases and controls (crude OR, 2.2; 95% CI, 0.6-8.4). Crude odds ratios were 1.8 for those with moderate ETS exposure and 4.3 for individuals with heavy ETS exposure among nonsmoking cases and controls (P for trend = 0.008). More

  5. Squamous cell carcinoma antigen in serum for monitoring of head and neck and uterine cervical squamous cell carcinomas after radiotherapy

    International Nuclear Information System (INIS)

    Shirato, Hiroki; Ichimura, Wataru; Wakushima, Hiroshi; Nishioka, Takashi; Suzuki, Keishiro

    1993-01-01

    Squamous cell carcinoma antigen (SCC-A) in serum was serially measured during follow-up of 96 squamous cell carcinoma patients (75 head and neck cancers and 21 uterine cervical cancers), treated with radiotherapy. In 27 of the patients with head and neck cancer and in 12 of those with cervical cancer SCC-A had also been measured before radiotherapy. In this head and neck carcinoma group, the median level of SCC-A was 1.3 (95% CI: 1.2-1.9) ng/ml before radiotherapy and 1.4 (CI: 1.1-1.5) ng/ml after radiotherapy. In the cervical carcinoma group, the median SCC-A decreased significantly (p<0.001) from a pretreatment value of 7.5 (CI: 3.8-26.3) ng/ml to a posttreatment value of 0.9 (CI:<0.5-1.8) ng/ml. In the total group of 75 head and neck cancers 21 relapses occurred and in 4 of these the relapse was detected at a clinically silent stage by an elevation of serum SCC-A. The same was true for 4 of the 9 relapses that occurred in the total group of uterine cervical cancer. The study suggests that serum SCC-A may be useful for posttreatment monitoring of patients with uterine cervix cancer while its value in head and neck cancer probably is more marginal. (orig.)

  6. Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck

    Science.gov (United States)

    Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

    2015-01-01

    Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management. PMID:26483987

  7. Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck.

    Science.gov (United States)

    Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

    2015-01-01

    Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management.

  8. Prognostic significance of surgical extranodal extension in head and neck squamous cell carcinoma patients.

    Science.gov (United States)

    Matsumoto, Fumihiko; Mori, Taisuke; Matsumura, Satoko; Matsumoto, Yoshifumi; Fukasawa, Masahiko; Teshima, Masanori; Kobayashi, Kenya; Yoshimoto, Seiichi

    2017-08-01

    Lymph node metastasis with extranodal extension represents one of the most important adverse prognostic factors for survival in patients with head and neck squamous cell carcinoma. We propose that extranodal extension occurs to differing extents. The aim of this study was to determine the prognostic significance of extranodal extension in patients with head and neck squamous cell carcinoma. Two hundred and ninety-eight patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection were included. Cervical lymph nodes were classified into four categories: (i) pathological N negative, (ii) extranodal extension negative, (iii) non-surgical extranodal extension and (iv) surgical extranodal extension. Lymph node metastases were detected in 67.1% of laryngeal/hypopharyngeal cancer patients and 52.7% of oral cancer patients. The 3-year disease-specific survival rates for patients in the pathological N negative, extranodal extension negative, non-surgical extranodal extension and surgical extranodal extension groups were 90.9%, 79.6%, 63.8% and 48.3%, respectively. In laryngeal/hypopharyngeal cancer patients, surgical extranodal extension was associated with a significantly poorer disease-specific survival than a pathological N negative, extranodal extension negative or non-surgical extranodal extension status. In oral cancer patients, no significant differences were observed between the non-surgical and surgical extranodal extension groups. However, non-surgical extranodal extension was associated with a poorer disease-specific survival than a pathological N negative or extranodal extension negative status. Surgical extranodal extension was a poor prognostic factor in patients with head and neck squamous cell carcinoma. The prognostic significance of surgical extranodal extension differed between laryngeal/hypopharyngeal and oral cancer patients. The clinical significance of surgical extranodal extension was much greater for

  9. Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: Normal tissue complication probability modeling with latent time correction

    DEFF Research Database (Denmark)

    Rønjom, Marianne Feen; Brink, Carsten; Bentzen, Søren

    2013-01-01

    To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors.......To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors....

  10. Gastroesophageal reflux disease and odds of head and neck squamous cell carcinoma in North Carolina.

    Science.gov (United States)

    Busch, Evan L; Zevallos, Jose P; Olshan, Andrew F

    2016-05-01

    Exposure to excess gastric acid resulting from gastroesophageal reflux disease, also known as acid reflux or heartburn, might contribute to initiation of head and neck squamous cell carcinoma, particularly laryngeal cancer. Prior epidemiologic studies have reported inconsistent results. We sought to clarify this relationship using an observational study with a larger available sample size and better-characterized exposure information than most prior studies. A population-based case-control study of head and neck cancer in North Carolina with 1,340 newly diagnosed cases and 1,378 controls matched on age, race, and sex. We used unconditional logistic regression to examine associations between self-reported heartburn and development of overall head and neck cancer as well as development of cancer at specific tumor sites. Subgroup analysis by smoking and alcoholic drinking status was used to make comparisons with a previous study that used a similar study design. Overall, an increased odds of head and neck cancer was not associated with either self-reported history of heartburn symptoms (odds ratio = 0.85; 95% confidence interval 0.68, 1.06) or self-reported medical diagnosis of GERD (OR = 0.89; 95% CI 0.71, 1.11). These patterns held for specific tumor sites. For laryngopharyngeal cancer, we did not detect any associations regardless of joint smoking and alcoholic drinking status. Gastroesophageal reflux does not appear to play a role in development of head and neck cancer. 3b. Laryngoscope, 126:1091-1096, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  11. Quad shot - hypofractionated radiotherapy for palliation in advanced squamous cell carcinoma of head and neck

    International Nuclear Information System (INIS)

    Maqsood, T.; Ali, U.; Arif, S.

    2017-01-01

    The objective of this study was to determine the efficacy of quad-shot radiation therapy for palliation in locally advanced and metastatic inoperable squamous cell carcinomas of head and neck. Study Design: A quasi-experimental study. Place and Duration of Study: Oncology department, Combined Military Hospital Rawalpindi, from Sep 2012 to Sep 2013. Material and Methods: Thirty five patients were included with histologically confirmed advanced inoperable squamous cell carcinoma in head and neck region, performance status 2 or 3 and survival =3 months. Patients were treated with radiation therapy 14 Gy in four fractions, megavoltage beam, twice daily fractions (at least 6 hours apart), for 2 consecutive days. Symptoms due to cancer (pain and dysphagia) were assessed as per common toxicity criteria adverse event version 4.0 on day 0 before treatment and day 21 after start of treatment. Results: Grades of pain and dysphagia showed significant improvement after treatment with a p-value <0.001. A total of 91.4% patients showed an improvement in grade of pain (32 out of 35 patients) and 45.7% of patients showed improvement in grade of dysphagia (16 out of 35 patients). There was a statistically significant decrease in grades of pain and dysphagia after treatment. Conclusion: The short duration of hypofractionated radiotherapy with Quad Shot was effective with respect to symptom palliation in locally advanced and metastatic inoperable head and neck cancers.

  12. MRI with DWI for the Detection of Posttreatment Head and Neck Squamous Cell Carcinoma: Why Morphologic MRI Criteria Matter.

    Science.gov (United States)

    Ailianou, A; Mundada, P; De Perrot, T; Pusztaszieri, M; Poletti, P-A; Becker, M

    2018-04-01

    Although diffusion-weighted imaging combined with morphologic MRI (DWIMRI) is used to detect posttreatment recurrent and second primary head and neck squamous cell carcinoma, the diagnostic criteria used so far have not been clarified. We hypothesized that precise MRI criteria based on signal intensity patterns on T2 and contrast-enhanced T1 complement DWI and therefore improve the diagnostic performance of DWIMRI. We analyzed 1.5T MRI examinations of 100 consecutive patients treated with radiation therapy with or without additional surgery for head and neck squamous cell carcinoma. MRI examinations included morphologic sequences and DWI ( b =0 and b =1000 s/mm 2 ). Histology and follow-up served as the standard of reference. Two experienced readers, blinded to clinical/histologic/follow-up data, evaluated images according to clearly defined criteria for the diagnosis of recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment, post-radiation therapy inflammatory edema, and late fibrosis. DWI analysis included qualitative (visual) and quantitative evaluation with an ADC threshold. Recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment was present in 36 patients, whereas 64 patients had post-radiation therapy lesions only. The Cohen κ for differentiating tumor from post-radiation therapy lesions with MRI and qualitative DWIMRI was 0.822 and 0.881, respectively. Mean ADCmean in recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment (1.097 ± 0.295 × 10 -3 mm 2 /s) was significantly lower ( P .05). Although ADCs were similar in tumors and late fibrosis, morphologic MRI criteria facilitated distinction between the 2 conditions. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (95% CI) of

  13. Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines

    International Nuclear Information System (INIS)

    Kotowski, Ulana; Heiduschka, Gregor; Eckl-Dorna, Julia; Kranebitter, Veronika; Stanisz, Isabella; Brunner, Markus; Lill, Claudia; Thurnher, Dietmar; Seemann, Rudolf; Schmid, Rainer

    2015-01-01

    Cafestol is a diterpene molecule found in coffee beans and has anticarcinogenic properties. The aim of the study was to examine the effects of cafestol in head and neck squamous cell carcinoma (HNSCC) cells. Three HNSCC cell lines (SCC25, CAL27 and FaDu) were treated with increasing doses of cafestol. Then combination experiments with cisplatin and irradiation were carried out. Drug interactions and possible synergy were calculated using the combination index analysis. Clonogenic assays were performed after irradiation with 2, 4, 6 and 8 Gy, respectively, and the rate of apoptosis was measured with flow cytometry. Treatment of HNSCC cells with cafestol leads to a dose-dependent reduction of cell viability and to induction of apoptosis. Combination with irradiation shows a reduction of clonogenic survival compared to each treatment method alone. In two of the cell lines a significant additive effect was observed. Cafestol is a naturally occurring effective compound with growth-inhibiting properties in head and neck cancer cells. Moreover, it leads to a significant inhibition of colony formation. (orig.) [de

  14. SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK: NEW AVENUES OF TREATMENT?

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    T. Braunschweig

    2013-01-01

    Full Text Available Squamous cell carcinoma of the head and neck counts for 3 % of all cancers in men and half of this number less in women with a 5-year survival of 61 %. While the number of laryngeal carcinoma is decreasing, carcinoma of the oral cavity related to an infection by the human papilloma virus (HPV, high-risk subtypes is increasing, especially in younger patients. HPV related squamous cell carcinomas show better survival data, especially in regard to recurrence free rates or secondary carcinoma of adjacent locations. Squamous cell carcinomas related to the presence of HPV DNA material is almost exclusively found in carcinoma of the oral cavity and oropharyngeal mucosa. Much less frequently HPV is present in hypopharyngeal carcinomas and even less number of cases of squamous cell carcinoma with proof for HPV in the nasopharynx and larynx. In case of evidence for HPV DNA; most cases are positively tested for subtype 16, followed by subtype 18. As a surrogate immunhistochemical marker, p16 INK4A is stained positive, cytoplasmic and nuclear. In a small study by ourselves, we found a positive correlation in 100 % of p16 INK4A positivity and positive HPV testing. Oral squamous cell carcinoma is more frequently related to HPV in patients below 50 years of age with a prevalence of ca. 20 %. Whilst HPV high-risk positive carcinomas show very few mutations in single signalling molecules of the downstream receptor tyrosin kinase pathways, HPV negative carcinomas show in many cases a chaotic DNA mutation type with typical mutations in tumor suppressor genes, as p53 and CDKN2A. This pattern is often seen in carcinoma types develop from a summation of accidental mutations often caused by toxins (e.g. inhaled cigarette smoke. However, it is discussed and under investigation whether a subset of head and neck squamous cell carcinomasdevelop from so called driver mutations, as are called mutations in critical members of signalling pathways and receptor tyrosin kinases

  15. Chemoradiotherapy in head and neck squamous cell carcinoma: focus on targeted therapies

    International Nuclear Information System (INIS)

    Bozec, A.; Thariat, J.; Bensadoun, R.J.; Milano, G.

    2008-01-01

    Radiotherapy is an essential treatment for many patients with head and neck squamous cell carcinoma. Its association with molecular targeted therapies represents a real progress. Among the recent advances in the molecular targeted therapy of cancer, the applications centred on E.G.F.R. are currently the most promising and the most advanced at clinical level. Considering the set of therapeutic tools targeting E.G.F.R., there are at present two well-identified emerging categories of drugs with monoclonal antibodies, on the one hand, and tyrosine kinase inhibitors, on the other. In many preclinical studies, the combination of anti-E.G.F.R. drugs with irradiation has led to additive or supra-additive cytotoxic effects. Furthermore, anti-angiogenic agents have shown promising results in association with anti-E.G.F.R. drugs and radiotherapy. This research effort has recently produced encouraging clinical results in advanced head and neck cancer with combination of cetuximab (an anti-E.G.F.R. monoclonal antibody) with irradiation with a significant impact on patient survival. Active and efficient clinical research is currently ongoing to determine the place of molecular targeted therapies in the treatment of head and neck cancer, particularly in association with radiotherapy. (authors)

  16. Definitive chemoradiotherapy with carboplatin for squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Nagasaka, Misako; Zaki, Mark; Issa, Majd; Kim, Harold; Abrams, Judith; Sukari, Ammar

    2017-10-01

    Definitive concurrent chemoradiotherapy (CRT) is considered the standard of care for organ preservation and is the only potentially curative therapy for surgically unresectable patients with stage III to IVb locally advanced squamous cell carcinoma of the head and neck. In patients with high risks for adverse events utilizing cisplatin, carboplatin has been empirically substituted. The objective of this study was to estimate the locoregional control rate, progression-free survival, overall survival, and adverse events in locally advanced squamous cell carcinoma of the head and neck patients treated with CRT utilizing carboplatin. A retrospective single-arm analysis. Data on consecutive patients who fit the eligibility criteria were collected. Eligible patients were treated with 70 Gy of radiation therapy and at least two cycles of carboplatin (area of curve [AUC] of 5 between January 2007 to December 2013. Fifty-four patients were identified. Overall locoregional control rate was 50% (95% confidence interval [CI] 37%-63%). Median progression-free and overall survival were 21 (CI 11-33) and 40 (CI 33-NA) months, respectively. One-, 3-, and 5-year overall survival were 81% (CI 67%-89%), 59% (CI 41%-73%), and 42% (CI 22%-61%), respectively. Stage III/IVa patients (n = 45) had a median survival of 62 (CI 37-NA months) and 3 years of 71% (CI 53%-84%), whereas stage IVb (n = 9) had a median survival of 31 (CI 4-NA) months and none survived to 3 years. Definitive CRT with carboplatin for locally advanced squamous cell carcinoma of the head and neck was well tolerated and demonstrated comparable results to CRT with cisplatin. 4. Laryngoscope, 127:2260-2264, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  17. Docetaxel in the treatment of squamous cell carcinoma of the head and neck

    Directory of Open Access Journals (Sweden)

    Alexander Rapidis

    2008-11-01

    Full Text Available Alexander Rapidis1, Nicholas Sarlis2, Jean-Louis Lefebvre3, Merrill Kies41Department of Maxillofacial Surgery, Greek Anticancer Institute, Saint Savvas Hospital, Athens, Greece; 2Department of Medical Affairs, Oncology – US Sanofi-Aventis, Bridgewater, NJ, USA; 3Head and Neck Department, Centre Régional de Lutte Contre le Cancer de Lille, Lille, France; 4Department of Thoracic/Head and Neck Medical Oncology, The University of Texas – M.D. Anderson Cancer Center, Houston, TX, USAAbstract: Squamous cell carcinoma of the head and neck (SCCHN presents at a locally advanced (LA stage in many patients. Chemotherapy has been successfully integrated into first-line treatment programs, either during or prior to radiotherapy (RT – the cornerstone modality for local disease control of inoperable disease or when organ preservation is desired. Concomitant chemoradiotherapy (CCRT provides an absolute survival benefit when compared with other types of locoregional therapy that exclude chemotherapy. Nonetheless, distant metastases still represent the most common cause of treatment failure. Consequently, adding induction chemotherapy (ICT to definitive non-surgical local therapies with a curative intent has been vigorously explored in LA SCCHN. Recently, it has been shown that ICT using the combination of the taxane docetaxel with cisplatin–5-fluorouracil provides significant survival benefit over cisplatin–5-FU, when used before either definitive RT (TAX323 trial or carboplatin-based CCRT (TAX324 trial. Docetaxel is also being investigated in metastatic or recurrent (M/R disease, with promising initial results. It is very likely that the future management strategies of SCCHN will incorporate biologic agents as an add-on to docetaxel-containing schemas, administered either as ICT prior to CCRT in the LA setting or for the management of M/R disease.Keywords: chemoradiotherapy, chemotherapy, docetaxel, head and neck carcinoma, induction, locally

  18. Prognostic value of FDG PET/CT in head and neck squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Dequanter D

    2015-08-01

    Full Text Available D Dequanter,1,2 M Shahla,2 C Aubert,2 Y Deniz,2 P Lothaire2 1Department of Oncology, Laboratory of Experimental Radiotherapy, KU Leuven, Leuven, Belgium; 2Head and Neck Department, Hôpital André Vésale, CHU de Charleroi, Montigny le Tilleul, Belgium Introduction: The purpose of this study was to evaluate the use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT to identify the presence of cervical lymph nodes metastases and extracapsular spread with histologic correlations in head and neck squamous cell carcinoma.Methods: The medical records of 54 patients who underwent 18F-FDG PET/CT for head and neck squamous cell carcinoma before surgery were reviewed. Receiver operating characteristic (ROC analysis was performed to differentiate patients with cervical lymph node metastasis from those without lymph node metastasis. The same statistical analysis was done to differentiate cervical lymph nodes with extracapsular spread from those without extracapsular spread.Results: Metastatic disease was diagnosed histologically in 49% (26 of 54 of the patients. Extracapsular spread was present in ten of the 54 patients (19%. When ROC curve analysis and maximum standardized uptake (SUVmax values were used to detect cervical lymph node metastasis, the area under the ROC curve was 0.96 and the optimal cutoff value for SUVmax was 4.05 based on ROC curve analysis. The sensitivity and specificity of SUVmax for the detection of cervical lymph node metastasis using this cutoff point were 92% and 88%, respectively. When ROC curve analysis and SUVmax values were used in order to detect extracapsular spread, the area under the ROC curve was 0.86, and the optimal cutoff value for SUVmax was 4.15 based on ROC curve analysis. Using this cutoff value, the sensitivity and specificity of SUVmax for the detection of extracapsular spread were 83% and 88%, respectively.Conclusion: In our study, a median 18F-FDG PET/CT SUVmax cutoff

  19. Lymph node metastases from squamous cell carcinomas of the head and neck region

    International Nuclear Information System (INIS)

    Bartelink, H.

    1980-01-01

    A retrospective and a prospective study are described concerning the results of treatment for neck node metastases. The metastases came from squamous cell carcinomas of the head and neck region. The possibility of cure by radiotherapy is considered in detail. It appeared that the results of radiotherapy depend on the site of the primary tumour and on its occasional recurrence. From a dose-effect curve and a dose-complication curve it could be estimated that the optimal dose of irradiation was 2000 rets (72 Gray in 7 weeks). (Auth.)

  20. Severe anemia is associated with poor tumor oxygenation in head and neck squamous cell carcinomas

    International Nuclear Information System (INIS)

    Becker, Axel; Stadler, Peter; Lavey, Robert S.; Haensgen, Gabriele; Kuhnt, Thomas; Lautenschlaeger, Christine; Feldmann, Horst Juergen; Molls, Michael; Dunst, Juergen

    2000-01-01

    Purpose: To investigate the relationship between tumor oxygenation and the blood hemoglobin (Hb) concentration in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods and Materials: A total of 133 patients with SCCHN underwent pretreatment polarographic pO 2 measurements of their tumors. In 66 patients measurements were also made in sternocleidomastoid muscles. The patients were divided into three groups according to their Hb concentration--severe anemia (Hb 2 . Conclusion: Our data suggest that a low Hb concentration and cigarette smoking contribute to inadequate oxygenation of SCCHN and thus for increased radioresistance. Consequently, Hb correction and abstinence from smoking may significantly improve tumor oxygenation

  1. Squamous cell carcinomas of the lung and of the head and neck: new insights on molecular characterization

    Science.gov (United States)

    Polo, Valentina; Pasello, Giulia; Frega, Stefano; Favaretto, Adolfo; Koussis, Haralabos; Conte, Pierfranco; Bonanno, Laura

    2016-01-01

    Squamous cell carcinomas of the lung and of the head and neck district share strong association with smoking habits and are characterized by smoke-related genetic alterations. Driver mutations have been identified in small percentage of lung squamous cell carcinoma. In parallel, squamous head and neck tumors are classified according to the HPV positivity, thus identifying two different clinical and molecular subgroups of disease. This review depicts different molecular portraits and potential clinical application in the field of targeted therapy, immunotherapy and chemotherapy personalization. PMID:26933818

  2. Treatment of head and neck squamous cell carcinoma in elderly patients

    International Nuclear Information System (INIS)

    Honda, Keigo; Asato, Ryo; Tsuji, Jun; Kanda, Tomoko; Ushiro, Kohji; Watanabe, Yoshiki; Mori, Yusuke

    2010-01-01

    The object of this study was to clarify the characteristics of treatment for elderly head and neck squamous cell cancer patients. We conducted a chart review of 177 head and neck squamous cell cancer patients who had been treated at Kyoto Medical Center, from 2005 through 2009. All the collected data were analyzed to compare the clinical features and the treatment outcomes between the younger group ( or =75, EG, n=46). Male to female ratio was lower in EG (5.6:1 vs. 1.7:1, p<0.01). C urative treatment was performed in most of the patients with early disease (stage I-II) in both groups (96.7% vs. 90.5%), while the ratio of curative treatment was significantly lower in EG patients with advanced stage disease (stage III-IV) (92.3% vs. 52.0%, p<0.01). There was no significant difference in the frequency of adopted treatment modality (surgery or radiotherapy) between YG and EG. Adjuvant chemotherapy or postoperative radiotherapy was avoided in most of EG patients. Local complication rates after major surgery for advanced cases were similar in both groups (30.8% vs. 27.3%), while a higher systemic complication rate was observed in EG (0% vs. 27.3%). After curative treatment, there was no difference in disease specific three-year survival rates between YG and EG (100% vs. 100% in early stage disease, 65.2% vs. 60.6% in advanced disease, Kaplan-Meier curve). Although treatment of elderly patients with head and neck cancer can be inhibited by poor performance status and/or concomitant diseases, clinical results after curative treatment are comparable to those of younger patients. (author)

  3. Parotid metastasis--an independent prognostic factor for head and neck cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Ch'ng, S; Maitra, A; Lea, R; Brasch, H; Tan, S T

    2006-01-01

    Metastatic parotid cutaneous squamous cell carcinoma (SCC) is the most common parotid gland malignancy in New Zealand and Australia. The current AJCC TNM staging system does not account for the extent of nodal metastasis. A staging system that separates parotid (P stage) from neck disease (N stage) has been proposed recently. To review the outcome of patients with metastatic head and neck cutaneous SCC treated at our multidisciplinary Head and Neck Service using the proposed staging system. Consecutive patients were culled from our Head and Neck/Skull Base Database, 1990-2004. These patients were restaged according to the proposed staging system: P stage: P0 = no disease in the parotid (i.e., neck disease only); P1 = metastatic node P2=metastatic node > 3 cm and 6 cm, or disease involving the facial nerve or skull base. N stage: N0=no disease in the neck (i.e., parotid disease only); N1 = single ipsilateral metastatic node 3 cm, or contralateral neck involvement. Loco-regional recurrence and disease-specific survival were calculated using the Kaplan-Meier method and comparison of graphs made with the log-rank test. Multivariate analysis using the Cox regression model was carried out to assess the impact of various parameters. Sixty-seven patients with metastatic head and neck cutaneous SCC were identified. Thirty-seven patients had parotid metastasis (of whom 13 also had neck disease) while 21 had neck metastasis alone. Nine patients had dermal or soft tissue metastasis. These nine patients were excluded from this series, and data analysis was carried out on the remaining 58 (46 men, 12 women, mean age 71 years) patients. Sixty-seven percent of the patients underwent post-operative adjuvant radiotherapy. The five-year disease-specific survival rate was 54%. Among 56 patients followed up to disease recurrence or for a minimum period of 18 months, the loco-regional recurrence rate was 52%. The presence of parotid disease was an independent prognostic factor on

  4. Effect of bleomycin-radiotherapy combination in management of head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Shah, P.M.; Shukla, S.N.; Patel, K.M.; Patel, N.L.; Baboo, H.A.; Patel, D.D.

    1981-01-01

    Twenty-five patients with head and neck squamous cell carcinoma were treated with bleomycin-radiotherapy protocol, 15 mg bleomycin I.V. on alternate days followed by radiation within half an hour. The average total dose of bleomycin was 150 mg. Radiotherapy was given daily. Two patients were lost to follow-up very early in the course of the treatment and were removed from the study for statistical purposes. Thirty-six patients with head and neck squamous cell carcinoma who were treated with radiotherapy alone during the same period were used as controls. The patients were followed for two years. The incidence of response rate did not differ significantly between regimens; however, the incidence of side effects with bleomycin-radiotherapy, 82.61%, is significantly more than that of radiotherapy alone (52.78%). Median survial time (MST) of those responding to bleomycin-radiotherapy protocol was seven months and 12 days and for radiotherapy responders was six months. Neither the response rate nor the MST improve significantly after pretreatment with bleomycin. On the contrary, the incidence of side effects increased significantly

  5. MR imaging in squamous cell carcinoma of the head and neck with no palpable lymph nodes

    International Nuclear Information System (INIS)

    Yucel, T.; Sennaroglu, L.; Kaya, S.; Saatci, I.; Cekirge, S.; Aydingoz, U.

    1997-01-01

    Purpose: To assess the efficacy of MR imaging in the detection of lymph node metastasis in patients with no palpable lymph nodes ('N 0 neck') who have squamous cell carcinoma of the head and neck region. Material and Methods: MR neck imagings in 18 patients who underwent neck dissection (bilaterally in 2) for squamous cell carcinoma of the head and neck region were examined preoperatively for the purpose of detecting lymph node metastases. The imaging features taken into consideration were: size (cutoff point 10 mm), grouping, presence of central necrosis, and appearance of extracapsular spread. The MR examinations comprised spin-echo T1- and T2-weighted sequences. The MR findings were compared with those of surgery and histopathological examination. Results: MR suggested metastatic lymph node involvement in 5 necks. In 2 of these, central necrosis was seen in the enlarged lymph nodes. In a third, a grouping of the lymph nodes was noted. Extracapsular spread was not present. Histopathological examination revealed metastatic lymph nodes in 7 of 20 necks, the rate of clinically occult disease being 35%, and 4 of then had been accurately graded by MR. There was one false-positive MR examination. The MR sensitivity was 57.1% and specificity 92.3%. Conclusion: MR may reveal metastatic lymph nodes in patients with no clinical evidence of metastasis. However, conventional MR techniques are not always sufficient for decision-making on surgery in cases of 'N 0 neck'. (orig.)

  6. Regulatory T cells and their prognostic value for patients with squamous cell carcinoma of the head and neck

    Czech Academy of Sciences Publication Activity Database

    Bouček, Jan; Mrkvan, Tomáš; Chovanec, M.; Kuchař, M.; Betka, Jaroslav; Bouček, V.; Hladíková, M.; Betka, J.; Eckschlager, T.; Říhová, Blanka

    2010-01-01

    Roč. 14, 1-2 (2010), s. 426-433 ISSN 1582-1838 R&D Projects: GA MZd NR8883; GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z50200510 Keywords : regulatory T cell s * head and neck squamous cell carcinoma * tumour markers Subject RIV: EC - Immunology Impact factor: 4.608, year: 2010

  7. Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Misawa, Yuki; Misawa, Kiyoshi; Kawasaki, Hideya; Imai, Atsushi; Mochizuki, Daiki; Ishikawa, Ryuji; Endo, Shiori; Mima, Masato; Kanazawa, Takeharu; Iwashita, Toshihide; Mineta, Hiroyuki

    2017-07-01

    The aim of this study was to determine the methylation status of the genes encoding the vascular endothelial growth factor receptors and to evaluate the usefulness of VEGFR methylation as a prognostic indicator in head and neck squamous cell carcinoma. VEGFR messenger RNA expression and promoter methylation were examined in a panel of cell lines via quantitative reverse transcription and methylation-specific polymerase chain reaction, respectively. Promoter methylation was compared with clinical characteristics in 128 head and neck squamous cell carcinoma samples. The normalized methylation values for the VEGFR1, VEGFR2 and VEGFR3 promoters tended to be higher in the tumour cell lines than in normal tonsil samples, whereas amounts of VEGFR1, VEGFR2 and VEGFR3 messenger RNA were significantly higher. Methylation of the VEGFR1 promoter (p = 0.003; 66/128 head and neck squamous cell carcinoma samples, 52%) and VEGFR3 promoter (p = 0.043; 53/128 head and neck squamous cell carcinoma samples, 41%) significantly correlated with recurrence, whereas methylation of the VEGFR2 promoter significantly correlated with lymph node metastasis (p = 0.046; 47/128 head and neck squamous cell carcinoma samples, 37%). Concurrent methylation of the VEGFR1 and VEGFR3 promoters significantly correlated with reduced disease-free survival (log-rank test, p = 0.009). In a multivariate logistic regression analysis, methylation of the VEGFR1, VEGFR3 and both the VEGFR1 and VEGFR3 promoters independently predicted recurrence (odds ratios and 95% confidence intervals: 3.19, 1.51-6.75 (p = 0.002); 2.24, 1.06-4.76 (p = 0.035); and 2.56, 1.09-6.05 (p = 0.032), respectively). Methylation of the VEGFR promoters predicts poor prognosis in head and neck squamous cell carcinoma patients.

  8. Tumor and Stromal-Based Contributions to Head and Neck Squamous Cell Carcinoma Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Markwell, Steven M.; Weed, Scott A., E-mail: scweed@hsc.wvu.edu [Department of Neurobiology and Anatomy, Program in Cancer Cell Biology, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506 (United States)

    2015-02-27

    Head and neck squamous cell carcinoma (HNSCC) is typically diagnosed at advanced stages with evident loco-regional and/or distal metastases. The prevalence of metastatic lesions directly correlates with poor patient outcome, resulting in high patient mortality rates following metastatic development. The progression to metastatic disease requires changes not only in the carcinoma cells, but also in the surrounding stromal cells and tumor microenvironment. Within the microenvironment, acellular contributions from the surrounding extracellular matrix, along with contributions from various infiltrating immune cells, tumor associated fibroblasts, and endothelial cells facilitate the spread of tumor cells from the primary site to the rest of the body. Thus far, most attempts to limit metastatic spread through therapeutic intervention have failed to show patient benefit in clinic trails. The goal of this review is highlight the complexity of invasion-promoting interactions in the HNSCC tumor microenvironment, focusing on contributions from tumor and stromal cells in order to assist future therapeutic development and patient treatment.

  9. NEW OPPORTUNITIES FOR IMMUNE THERAPY IN PATIENTS WITH DISSEMINATED RECURRENT SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

    Directory of Open Access Journals (Sweden)

    A. M. Mudunov

    2017-01-01

    Full Text Available Patients with head and neck squamous cell carcinoma diagnosed with recurrent tumor or distant metastases usually have the worst prognosis. Chemotherapeutic options are very limited in these patients; there is a probability of drug resistance development. The researchers continue to search more effective and less toxic drugs. In the current article, we analyze the results of the latest randomized clinical trials devoted the assessment of novel antitumor immunotherapeutic drugs – PD-1 inhibitors – in patients with head and neck squamous cell carcinoma. This studies reveal new possibilities for the treatment of these patients.

  10. Reolysin and Histone Deacetylase Inhibition in the Treatment of Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Alena C. Jaime-Ramirez

    2017-06-01

    Full Text Available Oncolytic viruses (OVs are emerging as powerful anti-cancer agents and are currently being tested for their safety and efficacy in patients. Reovirus (Reolysin, a naturally occurring non-pathogenic, double-stranded RNA virus, has natural oncolytic activity and is being tested in phase I–III clinical trials in a variety of tumor types. With its recent US Food and Drug Administration (FDA orphan drug designation for several tumor types, Reolysin is a potential therapeutic agent for various cancers, including head and neck squamous cell carcinomas (HNSCCs, which have a 5-year survival of ∼55%. Histone deacetylase inhibitors (HDACis comprise a structurally diverse class of compounds with targeted anti-cancer effects. The first FDA-approved HDACi, vorinostat (suberoylanilide hydroxamic acid [SAHA], is currently being tested in patients with head and neck cancer. Recent findings indicate that HDAC inhibition in myeloma cells results in the upregulation of the Reolysin entry receptor, junctional adhesion molecule 1 (JAM-1, facilitating reovirus infection and tumor cell killing both in vitro and in vivo. In this study, we tested the anti-tumor efficacy of HDAC inhibitors AR-42 or SAHA in conjunction with Reolysin in HNSCCs. While HDAC inhibition increased JAM-1 and reovirus entry, the impact of this combination therapy was tested on the development of anti-tumor immune responses.

  11. Definitive radiation therapy - alone or combined with drug treatment for head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Katsarov, D.; Mihajlova, I.; Georgiev, D; Lyubomirov, V.; Gesheva, N.; Balabanova, A.; Klenova, A.; Pyrvanova, V.; Atanasov, T.

    2017-01-01

    Goal: To assess the effectiveness of three treatment methods in patients with squamous cell carcinoma of head and neck-ultimate radiotherapy (RT) up to 60 Gy, definitive radiation therapy simultaneously with chemotherapy (RT-CT) up to 60 Gy and definitive RT-CT greater than 60 Gy. Material and method: 154 patients with locally advanced head and neck carcinomas, at clinical stage T3-T4 N + M0 are included in the analysis for the period 2009-2016. Radical RT is carried out with a daily dose of 2-2.33 Gy on MV therapy equipment. There were treated as follows: in Group I - 37 patients with RT up to 60 Gy, in Group II - 58 patients with RT-CT up to 60 Gy and simultaneous radiosensitizing CT, weekly Cisplatin 50 mg i.v. or Cetuximab regimen, and Group III - 59 patients with RT-CT and a total dose over 60 Gy. The early dermatological and mucosal toxicity is assessed by the CTCAE v.3 scale. Results: RT in all patients was conducted without interruption. The mean total survival rate in the three groups with RT up to 60 Gy / RT-CT to 60 Gy / RT-CT over 60 Gy is 11 months, 21 months and 27 months respectively, with a statistically significant difference between I and III groups in favor of the latter (p = 0.049). The use of RT-CT with a dose increase above 60 Gy shows an advantage of III g over Group II, which is an extension of the mean overall survival by 61 months (p = 0.21). II-III degree toxicity was observed in II and III - dermatitis and mucositis - at the simultaneous RT-CT (Grade 3> 16%). Conclusions: The application of doses greater than 60 Gy with concurrent radiosensitizing drug treatment in advanced head and neck carcinoma is an effective method for more pronounced but reversible dermatological and mucosal toxicity. [bg

  12. Sialic acids in squamous cell carcinoma of the head and neck

    Directory of Open Access Journals (Sweden)

    Izabela Bronikowska

    2016-12-01

    Full Text Available Altered glycosylation is a universal characteristic of cancer cells, and various types of glycan structures are well‑known markers of tumor progression and invasion. The present article discusses this aspect of the role of sialic acid, biosynthesis of sialylglycoconjugates and the genetic basis of its disorder, as well as the effects and the correlation between altered sialylation and clinical prognosis in head and neck squamous cell carcinoma (HNSCC.Only a few studies concerning the level of sialic acid in head and neck tumors have been conducted so far. The conclusions of the published reports dedicated to that problem confirm the presence of elevated levels of total sialic acid in these tumors. The authors do not always agree with the level of free or associated form of sialic acid correlated with tumor size, severity of the condition, and lymph nodes. Comparing the progress that has been made in the diagnosis and treatment of other cancers thanks to extensive work on the role of sialic acids, we come to the conclusion that only further detailed studies of this subject in relation to HNSCC are able to answer the question whether the extent of glycoforms of sialic acid may act as a tumor marker or target of immunotherapy.

  13. [Planned neck dissection in the treatment of locally advanced head and neck squamous cell carcinoma].

    Science.gov (United States)

    Jiang, L; Lou, J L; Wang, K J; Fang, M Y; Fu, Z F

    2018-02-07

    Objective: To investigate the value of planned neck dissection combined with induction chemotherapy and concurrent chemoradiotherapy in regional control and the outcome of locally advanced head and neck squamous cell carcinoma. Methods: A prospective randomized controlled study totally enrolled sixty-four patients of head and neck squamous cell carcinomas(include oropharynx, hypopharynx, and larynx) in stages Ⅳa-Ⅳb with lymph node metastase was were N2-N3. All patients firstly received 2-3 cycles of induction chemotherapy(ICT), then divided into two groups randomly, according to the efficacy of ICT. Group A(the study group) received planned neck dissection(PND) and concurrent chemoradiotherapy(CCRT). Group B(the control group) received concurrent chemoradiotherapy(CCRT). The differences in clinicopathologic features, local recurrence(LR), regional recurrence(RR), disease-free survival(DFS), and overall survival(OS) between the two groups were estimated. SPSS 19.0 software was used to analyze the data. Results: Group A enrolled twenty-one patients, and group B enrolled forty-three patients.The follow-up of all patients were 4-55 months, median follow-up time was 22 months. In study group, two-year OS and DFS were 80.9% and 68.3%, respectively. In control group, two-year OS and DFS were 90.7% and 67.1%, respectively. There was no significant difference in gender( P =0.215), age( P =0.828), primary tumor site( P =0.927), LR( P =0.126), DFS( P =0.710), and OS( P =0.402) between the two groups, while the RR(χ(2)=5.640, P squamous cell carcinoma.

  14. Association between tumour volume and recurrence of squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Kazmi, F.N.; Adil, A.; Ghaffar, S.; Ahmed, F.

    2012-01-01

    Objective: To evaluate the prognostic significance of computerized tomography derived tumour volume for squamous cell cancers of the head and neck, treated primarily by surgery. Methods: The retrospective review study comprised 72 patients with head and neck malignancies who were treated primarily by surgery at Aga Khan University Hospital, Karachi, with/without adjuvant. It was done from May 2007 to November 2008. Each patient was followed up for a minimum of one year to check for recurrence. For statistical analysis SPSS 17 was used. Frequencies, cross-tabulations with chi square tests to find associations, binary logistic regression analysis, Cox regression analysis and receiver operating characteristic curve tests were run on the data. Results: Overall, the median tumour volume for patients with recurrent disease was 52 cm/sup 3/ compared to 22 cm/sup 3/ for those who did not have a recurrence. It was found that large tumour volume was associated with a significantly higher chance of recurrence (p = 0.009). Laryngeal cancers with volumes greater than 46 cm/sup 3/ and oral cancers with volumes greater than 23.1 cm/sup 3/ were associated with poor prognosis. Conclusions: The primary tumour volume can represent an important prognostic factor for treatment outcome. Patients with larger primary tumour volumes should be treated more aggressively. (author)

  15. Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review

    International Nuclear Information System (INIS)

    Swartz, Justin E; Pothen, Ajit J; Stegeman, Inge; Willems, Stefan M; Grolman, Wilko

    2015-01-01

    Awareness increases that the tumor biology influences treatment outcome and prognosis in cancer. Tumor hypoxia is thought to decrease sensitivity to radiotherapy and some forms of chemotherapy. Presence of hypoxia may be assessed by investigating expression of endogenous markers of hypoxia (EMH) using immunohistochemistry (IHC). In this systematic review we investigated the effect of EMH expression on local control and survival according to treatment modality in head and neck cancer (head and neck squamous cell carcinoma [HNSCC]). A search was performed in MEDLINE and EMBASE. Studies were eligible for inclusion that described EMH expression in relation to outcome in HNSCC patients. Quality was assessed using the Quality in Prognosis Studies (QUIPS) tool. Hazard ratios for locoregional control and survival were extracted. Forty studies of adequate quality were included. HIF-1a, HIF-2a, CA-IX, GLUT-1, and OPN were identified as the best described EMHs. With exception of HIF-2a, all EMHs were significantly related to adverse outcome in multiple studies, especially in studies where patients underwent single-modality treatment. Positive expression was often correlated with adverse clinical characteristics, including disease stage and differentiation grade. In summary, EMH expression was common in HNSCC patients and negatively influenced their prognosis. Future studies should investigate the effect of hypoxia-modified treatment schedules in patients with high In summary, EMH expression. These may include ARCON, treatment with nimorazole, or novel targeted therapies directed at hypoxic tissue. Also, the feasibility of surgical removal of the hypoxic tumor volume prior to radiotherapy should be investigated

  16. High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck

    Directory of Open Access Journals (Sweden)

    Michael J. Veness

    2007-01-01

    Full Text Available Nonmelanoma skin cancers (squamous cell and basal cell carcinomas occur at an epidemic rate in many countries with the worldwide incidence increasing. The sun-exposed head and neck are the most frequent sites for these cancers to arise and in most patients diagnosed with a cutaneous squamous cell carcinoma, local treatment is usually curative. However, a subset is diagnosed with a high-risk cutaneous squamous cell carcinoma. High-risk factors include size (> 2 cm, thickness/depth of invasion (> 4 mm, recurrent lesions, the presence of perineural invasion, location near the parotid gland, and immunosuppression. These patients have a higher risk (> 10–20% of developing metastases to regional lymph nodes (often parotid nodes, and in some cases also of experiencing local morbidity (perineural invasion, based on unfavourable primary lesion and patient factors. Despite treatment, many patients developing metastatic cutaneous squamous cell carcinoma experience mortality and morbidity usually as a consequence of uncontrolled metastatic nodal disease. It is therefore important that clinicians treating nonmelanoma skin cancers have an understanding and awareness of these high-risk patients. The aim of this article is to discuss the factors that define a high-risk patient and to present some of the issues pertinent to their management.

  17. Current state and future of photodynamic therapy for the treatment of head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Christina Mimikos

    2016-06-01

    Full Text Available Photodynamic therapy has shown promise in the treatment of early head and neck squamous cell carcinoma (SCC. In photodynamic therapy (PDT, a light sensitive drug (photosensitizer and visible light cause cancer cell death by the creation of singlet oxygen and free radicals, inciting an immune response, and vascular collapse. In this paper, we review several studies that demonstrate the effectiveness of PDT in the treatment of early stage SCC of the head and neck, with some showing a similar response rate to surgery. Two cases are presented to illustrate the effectiveness of PDT. Then, new advances are discussed including the discovery of STAT3 crosslinking as a potential biomarker for PDT response and interstitial PDT for locally advanced cancers. Keywords: Photodynamic therapy, PDT, Squamous cell carcinoma, Head and neck cancer

  18. Inhibition of STAT-3 results in greater cetuximab sensitivity in head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Bonner, James A.; Yang, Eddy S.; Trummell, Hoa Q.; Nowsheen, Somaira; Willey, Christopher D.; Raisch, Kevin P.

    2011-01-01

    Objective: The inhibition of epidermal growth factor receptor (EGFr) with the monoclonal antibody cetuximab reduces cell proliferation and survival which correlates with increased DNA damage. Since the signal transducer and activator of transcription-3 (STAT-3) is involved in the EGFr-induced signaling pathway, we hypothesized that depletion of STAT-3 may augment cetuximab-induced processes in human head and neck cancer cells. Materials and methods: Human head and neck squamous carcinoma cells (UM-SCC-5) were transfected with short hairpin RNA (shRNA) against STAT-3 (STAT3-2.4 and 2.9 cells). A mutated form of this shRNA was transfected for a control (NEG4.17 cells). Radiosensitivity was assessed by a standard colony formation assay. Proliferation was assessed by daily cell counts following treatment and apoptosis was assessed by an annexin V-FITC assay. The alkaline comet assay was used to assess DNA damage. Results: The STAT-3 knockdown cells (STAT3-2.4 and STAT3-2.9 cells) demonstrated enhanced radiosensitivity compared to control NEG4.17 cells, which correlated with increased apoptosis. Also, the STAT-3 knockdown cells demonstrated decreased proliferation with cetuximab treatments compared to control cells (NEG4.17). The increased cetuximab sensitivity of the STAT-3 knockdown cells correlated with increased apoptosis and DNA damage compared to control cells (NEG4.17). Conclusion: These studies revealed that the greater anti-proliferative effects and increased cytotoxicity of cetuximab in the STAT3-2.4 and STAT3-2.9 cells compared to control NEG4.17 cells, may be a result of STAT3-mediated effects on cellular apoptosis and DNA damage.

  19. Secondary oesophageal or gastric cancer in patients treated for head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Rosenlund Andersen, Anja; Bjerring, Ole Steen; Godballe, Christian

    2016-01-01

    SPM. CONCLUSION: In this study, we confirm that there is an elevated risk of developing oesophageal and gastric cancer in the Danish population of patients with a cancer in the supraglottic or hypopharyngeal region. Therefore, we recommend close follow-up of these patients and a low threshold......INTRODUCTION: Patients with head and neck squamous cell carcinoma (HNSCC) are at an elevated risk of developing second primary malignancies (SPM). Our objectives were to estimate the excess risk of oesophageal and gastric SPMs in patients with malignancies of the pharynx or larynx and, additionally.......004) and hypopharyngeal (OR = 3.9; p cancer compared with 3.4 years (95% CI: 3.1-4.3; range: 0.04-13.7) for patients without...

  20. Effect of ionizing radiation on the physical biology of head and neck squamous cell carcinoma cells.

    Science.gov (United States)

    Baker-Groberg, Sandra M; Bornstein, Sophia; Zilberman-Rudenko, Jevgenia; Schmidt, Mark; Tormoen, Garth W; Kernan, Casey; Thomas, Charles R; Wong, Melissa H; Phillips, Kevin G; McCarty, Owen J T

    2015-09-01

    Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide. Although there are numerous treatment options for HNSCC, such as surgery, cytotoxic chemotherapy, molecularly targeted systemic therapeutics, and radiotherapy, overall survival has not significantly improved in the last 50 years. This suggests a need for a better understanding of how these cancer cells respond to current treatments in order to improve treatment paradigms. Ionizing radiation (IR) promotes cancer cell death through the creation of cytotoxic DNA lesions, including single strand breaks, base damage, crosslinks, and double strand breaks (DSBs). As unrepaired DSBs are the most cytotoxic DNA lesion, defining the downstream cellular responses to DSBs are critical for understanding the mechanisms of tumor cell responses to IR. The effects of experimental IR on HNSCC cells beyond DNA damage in vitro are ill-defined. Here we combined label-free, quantitative phase and fluorescent microscopy to define the effects of IR on the dry mass and volume of the HNSCC cell line, UM-SCC-22A. We quantified nuclear and cytoplasmic subcellular density alterations resulting from 8 Gy X-ray IR and correlated these signatures with DNA and γ-H2AX expression patterns. This study utilizes a synergistic imaging approach to study both biophysical and biochemical alterations in cells following radiation damage and will aid in future understanding of cellular responses to radiation therapy.

  1. [Lectin-binding patterns and cell kinetics of head and neck squamous cell carcinomas].

    Science.gov (United States)

    Gotoh, T

    1991-01-01

    In order to elucidate the cell characteristics of head and neck squamous cell carcinomas, the cell kinetics and lectin binding patterns were compared with the histological classification and staging of the tumors, using surgically resected materials (maxillary sinus 10, oral cavity 21, pharynx 8, larynx 11). Eight biotinylated lectins (WGA, 1-PHA, ConA, UEA1, RCA1, SBA, DBA, PNA) were applied to the paraffin-embedded sections, and were visualized histochemically by the streptavidin-alkaline phosphatase method. The DNA contents of the isolated carcinoma cells obtained from the adjacent thick sections were evaluated using an epi-illumination cytofluorometer after propidium iodide staining. On lectin histochemistry, the binding pattern of WGA lectin was similar between carcinoma tissues and normal tissues, but the binding was more intense in well differentiated than less differentiated carcinomas. Lymph node metastasis was found to be related to the presence of cells with poor WGA-binding. In the binding patterns of the other lectins, RCA1, SBA and ConA were related to the differentiation of carcinomas, but they were not related to the TNM-classification. DNA cytofluorometry exhibited marked polyploidization, which progressed with the advancement of the clinical and pathological staging of carcinomas. However, the DNA ploidy pattern was not associated with the cell characteristics such as the degree of histological differentiation and the lectin-binding pattern, except that the appearance of aneuploidy had some relationship with the binding-patterns of UEA1 and 1-PHA.

  2. Complex p63 mRNA isoform expression patterns in squamous cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Thurfjell, N.; Coates, P.J.; Uusitalo, T.

    2004-01-01

    on the role of p63 expression in human tumours, we used quantitative real-time RT-PCR to study individual p63 isoforms in squamous cell carcinomas of the head and neck (SCCHN). In keeping with previous reports, expression of the deltaN- and p63alpha-isoforms predominated and deltaNp63 mRNA was expressed...

  3. Phase II study of 3-AP Triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma.

    NARCIS (Netherlands)

    Nutting, C.M.; Herpen, C.M.L. van; Miah, A.B.; Bhide, S.A.; Machiels, J.P.; Buter, J.; Kelly, C.; Raucourt, D. de; Harrington, K.J.

    2009-01-01

    BACKGROUND: Treatment options for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are limited with response rates to cytotoxic chemotherapy of approximately 30% and median survival of 6 months. PATIENTS AND METHODS: In a multicentre phase II study, 32 patients with recurrent or

  4. Intratumoral injection of radioactive holmium-166 microspheres in recurrent head and neck squamous cell carcinoma : preliminary results of first use

    NARCIS (Netherlands)

    Bakker, Robbert C; van Es, Robert J J; Rosenberg, Antoine J W P; van Nimwegen, Sebastiaan A; Bastiaannet, Remco; de Jong, Hugo W A M; Nijsen, Johannes F W; Lam, Marnix G E H

    BACKGROUND: Limited treatment options exist for patients with locoregional recurrences of head and neck squamous cell carcinoma (HNSCC). In the palliative setting, a single session, minimally invasive, and relatively safe therapy is desirable. This case series illustrates the feasibility of a direct

  5. Follow-up strategies in head and neck cancer other than upper aerodigestive tract squamous cell carcinoma

    NARCIS (Netherlands)

    Digonnet, Antoine; Hamoir, Marc; Andry, Guy; Vander Poorten, Vincent; Haigentz, Missak; Langendijk, Johannes A.; de Bree, Remco; Hinni, Michael L.; Mendenhall, William M.; Paleri, Vinidh; Rinaldo, Alessandra; Werner, Jochen A.; Takes, Robert P.; Ferlito, Alfio

    Post-therapy follow-up for patients with head and neck cancer other than upper aerodigestive tract squamous cell carcinoma should meet several objectives: to detect both local, regional or distant recurrences, to evaluate acute and long-term treatment-related side effects, to guide the

  6. Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma

    NARCIS (Netherlands)

    Hanemaaijer, Saskia H; van Gijn, Stephanie E; Oosting, Sjoukje F; Plaat, Boudewijn E C; Moek, Kirsten L; Schuuring, Ed M; van der Laan, Bernard F A M; Roodenburg, Jan L N; van Vugt, Marcel A T M; van der Vegt, Bert; Fehrmann, Rudolf S N

    BACKGROUND: For patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) palliative treatment options that improve overall survival are limited. The prognosis in this group remains poor and there is an unmet need for new therapeutic options. An emerging class of

  7. Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial

    DEFF Research Database (Denmark)

    Alkureishi, Lee W T; Ross, Gary L; Shoaib, Taimur

    2010-01-01

    Sentinel node biopsy (SNB) may represent an alternative to elective neck dissection for the staging of patients with early head and neck squamous cell carcinoma (HNSCC). To date, the technique has been successfully described in a number of small single-institution studies. This report describes...

  8. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected].

    NARCIS (Netherlands)

    Stewart, J.S.; Cohen, E.E.; Licitra, L.; Herpen, C.M.L. van; Khorprasert, C.; Soulieres, D.; Vodvarka, P.; Rischin, D.; Garin, A.M.; Hirsch, F.R.; Varella-Garcia, M.; Ghiorghiu, S.; Hargreaves, L.; Armour, A.; Speake, G.; Swaisland, A.; Vokes, E.E.

    2009-01-01

    PURPOSE: To compare survival in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with gefitinib 250 or 500 mg/day or standard methotrexate. PATIENTS AND METHODS: Four hundred eighty-six patients with recurrent SCCHN were randomly assigned to oral

  9. Non-smoking and non-drinking patients with head and neck squamous cell carcinoma: a distinct population.

    NARCIS (Netherlands)

    Farshadpour, F.; Hordijk, G.J.; Koole, R.A.; Slootweg, P.J.

    2007-01-01

    OBJECTIVE: To recognize specific clinicopathological characteristics of non-smoking and non-drinking (NSND) head and neck squamous cell carcinoma (HNSCC) patients. This can increase our knowledge regarding a potentially different carcinogenesis in these patients. STUDY DESIGN/METHODS: Retrospective

  10. Lycopene inhibits the cell proliferation and invasion of human head and neck squamous cell carcinoma.

    Science.gov (United States)

    Ye, Min; Wu, Qundan; Zhang, Min; Huang, Jinbei

    2016-10-01

    Lycopene has been shown to be associated with anticancer effects in numerous tumor types. However, the underlying mechanisms of lycopene in human head and neck squamous cell carcinoma (HNSCC) remain to be determined. The present study aimed to investigate the involvement of lycopene overload and the cytotoxic effects of lycopene on HNSCC cells, and to determine the possible mechanisms involved. Treatment with lycopene at a dose of >10 µM for >24 h inhibited the growth of FaDu and Cal27 cells in a time‑ and dose‑dependent manner. The clearest increase in growth inhibition was due to the apoptotic population being significantly increased. The invasion abilities decreased with 25 µM lycopene exerting significant inhibitory effects (Plycopene induced the upregulation of the pro‑apoptotic protein, B‑cell lymphoma‑associated X protein, and therefore, resulted in the inhibition of the protein kinase B and mitogen‑activated protein kinase signaling pathway. These data provided insights into the antitumor activity of lycopene in HNSCC cells.

  11. MicroRNAs in Head and Neck Squamous Cell Carcinoma (HNSCC) and Oral Squamous Cell Carcinoma (OSCC)

    International Nuclear Information System (INIS)

    Shiiba, Masashi; Uzawa, Katsuhiro; Tanzawa, Hideki

    2010-01-01

    MicroRNAs (miRNAs) are small, noncoding RNAs which regulate cell differentiation, proliferation, development, cell cycle, and apoptosis. Expression profiling of miRNAs has been performed and the data show that some miRNAs are upregulated or downregulated in cancer. Several studies suggest that the expression profiles of miRNAs are associated with clinical outcomes. However, the set of miRNAs with altered expressing differs depending on the type of cancer, suggesting that it is important to understand which miRNAs are related to which cancers. Therefore, this review aimed to discuss potentially crucial miRNAs in head and neck squamous cell carcinoma (HNSCC) and oral squamous cell carcinoma (OSCC)

  12. Identification and characterization of cancer stem cells in human head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Han, Jing; Fujisawa, Toshio; Husain, Syed R; Puri, Raj K

    2014-01-01

    Current evidence suggests that initiation, growth, and invasion of cancer are driven by a small population of cancer stem cells (CSC). Previous studies have identified CD44+ cells as cancer stem cells in head and neck squamous cell carcinoma (HNSCC). However, CD44 is widely expressed in most cells in HNSCC tumor samples and several cell lines tested. We previously identified a small population of CD24+/CD44+ cells in HNSCC. In this study, we examined whether this population of cells may represent CSC in HNSCC. CD24+/CD44+ cells from HNSCC cell lines were sorted by flow cytometry, and their phenotype was confirmed by qRT-PCR. Their self-renewal and differentiation properties, clonogenicity in collagen gels, and response to anticancer drugs were tested in vitro. The tumorigenicity potential of CD24+/CD44+ cells was tested in athymic nude mice in vivo. Our results show that CD24+/CD44+ cells possessed stemness characteristics of self-renewal and differentiation. CD24+/CD44+ cells showed higher cell invasion in vitro and made higher number of colonies in collagen gels compared to CD24-/CD44+ HNSCC cells. In addition, the CD24+/CD44+ cells were more chemo-resistant to gemcitabine and cisplatin compared to CD24-/CD44+ cells. In vivo, CD24+/CD44+ cells showed a tendency to generate larger tumors in nude mice compared to CD24-/CD44+ cell population. Our study clearly demonstrates that a distinct small population of CD24+/CD44+ cells is present in HNSCC that shows stem cell-like properties. This distinct small population of cells should be further characterized and may provide an opportunity to target HNSCC CSC for therapy

  13. Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Kotowski, Ulana; Heiduschka, Gregor; Eckl-Dorna, Julia; Kranebitter, Veronika; Stanisz, Isabella; Brunner, Markus; Lill, Claudia; Thurnher, Dietmar [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Vienna (Austria); Seemann, Rudolf [Medical University of Vienna, Departement of Cranio-, Maxillofacial- and Oral Surgery, Vienna (Austria); Schmid, Rainer [Medical University of Vienna, Department of Radiotherapy, Vienna (Austria)

    2015-01-10

    Cafestol is a diterpene molecule found in coffee beans and has anticarcinogenic properties. The aim of the study was to examine the effects of cafestol in head and neck squamous cell carcinoma (HNSCC) cells. Three HNSCC cell lines (SCC25, CAL27 and FaDu) were treated with increasing doses of cafestol. Then combination experiments with cisplatin and irradiation were carried out. Drug interactions and possible synergy were calculated using the combination index analysis. Clonogenic assays were performed after irradiation with 2, 4, 6 and 8 Gy, respectively, and the rate of apoptosis was measured with flow cytometry. Treatment of HNSCC cells with cafestol leads to a dose-dependent reduction of cell viability and to induction of apoptosis. Combination with irradiation shows a reduction of clonogenic survival compared to each treatment method alone. In two of the cell lines a significant additive effect was observed. Cafestol is a naturally occurring effective compound with growth-inhibiting properties in head and neck cancer cells. Moreover, it leads to a significant inhibition of colony formation. (orig.) [German] Cafestol ist ein Diterpen, das in der Kaffeebohne vorkommt und antikanzerogene Eigenschaften besitzt. Ziel der Studie war, die Wirkung von Cafestol auf Kopf-Hals-Tumorzelllinien zu untersuchen. Drei Kopf-Hals-Tumorzelllinien (SCC25, CAL27 und FaDu) wurden mit steigenden Cafestol-Dosen behandelt. Anschliessend fanden Kombinationsexperimente mit Cisplatin und Bestrahlung statt. Die Wechselwirkung zwischen den Substanzen und moegliche synergistische Wirkungen wurden mit dem Combination-Index analysiert. Koloniebildungstests wurden nach Bestrahlung mit 2, 4, 6 und 8 Gy durchgefuehrt. Apoptose wurde mittels Durchflusszytometrie gemessen. Die Behandlung der Kopf-Hals-Tumorzelllinien mit Cafestol fuehrt zu einer dosisabhaengigen Abnahme des Zellueberlebens und zur Induktion von Apoptose. Die Kombination von Cafestol mit Bestrahlung zeigt eine geringere

  14. Pretreatment oral hygiene habits and survival of head and neck squamous cell carcinoma (HNSCC) patients.

    Science.gov (United States)

    Friemel, Juliane; Foraita, Ronja; Günther, Kathrin; Heibeck, Mathias; Günther, Frauke; Pflueger, Maren; Pohlabeln, Hermann; Behrens, Thomas; Bullerdiek, Jörn; Nimzyk, Rolf; Ahrens, Wolfgang

    2016-03-11

    The survival time of patients with head and neck squamous cell carcinoma (HNSCC) is related to health behavior, such as tobacco smoking and alcohol consumption. Poor oral health (OH), dental care (DC) and the frequent use of mouthwash have been shown to represent independent risk factors for head and neck cancerogenesis, but their impact on the survival of HNSCC patients has not been systematically investigated. Two hundred seventy-six incident HNSCC cases recruited for the ARCAGE study were followed through a period of 6-10 years. Interview-based information on wearing of dentures, gum bleeding, teeth brushing, use of floss and dentist visits were grouped into weighted composite scores, i.e. oral health (OH) and dental care (DH). Use of mouthwash was assessed as frequency per day. Also obtained were other types of health behavior, such as smoking, alcohol drinking and diet, appreciated as both confounding and study variables. Endpoints were progression-free survival, overall survival and tumor-specific survival. Prognostic values were estimated using Kaplan-Meier analysis and Cox proportional hazards regression models. A good dental care score, summarizing annual dental visits, daily teeth cleaning and use of floss was associated with longer overall survival time (p = .001). The results of the Cox regression models similarly suggested a higher risk of tumor progression and shortened overall survival in patients with poor dental care, but the results lost their statistical significance after other types of health behavior had been controlled for. Frequent use of mouthwash (≥ 2 times/day) significantly increased the risk of tumor-specific death (HR = 2.26; CI = 1.19-4.32). Alcohol consumption and tobacco smoking were dose-dependently associated with tumor progression and shorter overall survival. Frequent mouthwash use of ≥ 2 times/day seems to elevate the risk of tumor-specific death in HNSCC patients. Good dental care scores are associated with longer overall

  15. Efficacy of weekly docetaxel and concomitant radiotherapy for squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Fujii, Masato; Tsukuda, Mamoru; Kubota, Akira; Kida, Akinori; Okami, Kenji

    2004-01-01

    Docetaxel (DOC) is one of the most promising drugs for head and neck cancer (HNSCC). A phase II trial of concurrent DOC and radiation for HNSCC was conducted to evaluate the therapeutic benefit based on the response and toxicity of the recommended dose schedule. We also studied the prognosis of patients. Patients with squamous cell carcinoma of the head and neck were entered. All of the patients received radiation with 2.0 Gy single daily fractions up to 60 Gy. DOC was administered weekly for six consecutive weeks during radiotherapy. The recommended dose was decided to be 10 mg/m 2 in a previously reported phase I study. Thirty-nine patients with stage II, III or IV were registered; 35 patients were eligible; 32 patients were evaluable for response, and 34 were evaluable for toxicity. The overall response rate was 96.9%. The prognoses of the complete response (CR) patients were statistically better compared with the partial response (PR) patients. Grade 3 or 4 adverse events consisted of lymphopenia in 64.7%, stomatitis, in 41.2% and anorexia in 20.6% of the patients. Thirty-two of the 35 eligible patients showed high compliance of over 90%, and their toxicities were manageable. Even low-dose DOC shows a strong effect on HNSCC in combination with radiation. The CR patients showed a high survival rate, though the prognosis of non-CR patients was poor. Further treatment for non-CR patients with advanced HNSCC will be needed. (author)

  16. Autophagy induction contributes to GDC-0349 resistance in head and neck squamous cell carcinoma (HNSCC) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yajuan; Peng, Yi [Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan (China); Tang, Hao [Department of Pathology, Hubei Cancer Hospital, Wuhan 430071 (China); He, Xiaojun; Wang, Zhaohua [Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan (China); Hu, Desheng, E-mail: hudeshengvvip@sina.com [Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan (China); Zhou, Xiaoyi, E-mail: zhouxy1218@126.com [Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan (China)

    2016-08-19

    Dysregulation of mammalian target of rapamycin (mTOR) signaling contributes to head and neck squamous cell carcinoma (HNSCC) tumorigenesis and progression. In the current study, we tested the anti-HNSCC cell activity by GDC-0349, a selective ATP-competitive inhibitor of mTOR. We showed that GDC-0349 inhibited proliferation of established and primary human HNSCC cells bearing high-level of p-AKT/p-S6K. Further, it induced caspase-dependent apoptosis in the HNSCC cells. GDC-0349 blocked mTORC1 and mTORC2 activation, yet it simultaneously induced autophagy activation in HNSCC cells. The latter was evidenced by induction of LC3B-II, Beclin-1 and Autophagy-related (ATG)-7, as well as downregulation of p62. Autophagy inhibitors (3-methyladenine and bafilomycin A1) or ATG-7 siRNA dramatically potentiated GDC-0349’s cytotoxicity against HNSCC cells. Intriguingly, we showed that ceramide (C14), a pro-apoptotic sphingolipid, also induced ATG-7 degradation, and sensitized HNSCC cells to GDC-0349. Collectively, the preclinical study provided evidences to support GDC-0349 as a promising anti-HNSCC agent. GDC-0349 sensitization may be achieved via autophagy inhibition. - Highlights: • GDC-0349 inhibits proliferation of HNSCC cells bearing high-level of p-AKT/p-S6K. • GDC-0349 activates caspase-dependent apoptosis in HNSCC cells. • Simultaneous blockage of mTORC1/2 by GDC-0349 induces autophagy activation. • Autophagy inhibitor or ATG-7 siRNA potentiates GDC-0349’s cytotoxicity. • C14 ceramide downregulates ATG-7 and sensitizes HNSCC cells to GDC-0349.

  17. Down-regulation of survivin by oxaliplatin diminishes radioresistance of head and neck squamous carcinoma cells

    International Nuclear Information System (INIS)

    Khan, Zakir; Khan, Noor; Tiwari, Ram P.; Patro, Ishan K.; Prasad, G.B.K.S.; Bisen, Prakash S.

    2010-01-01

    Background: Oxaliplatin is integrated in treatment strategies against a variety of cancers including radiation protocols. Herein, as a new strategy we tested feasibility and rationale of oxaliplatin in combination with radiation to control proliferation of head and neck squamous cell carcinoma (HNSCC) cells and discussed survivin-related signaling and apoptosis induction. Methods: Cytotoxicity and apoptosis induced by radiation and/or oxaliplatin were examined in relation to survivin status using two HNSCC cell lines viz., Cal27 and NT8e, and one normal 293-cell line. Survivin gene knockdown by siRNA was also tested in relevance to oxaliplatin-mediated radiosensitization effects. Results: Survivin plays a critical role in mediating radiation-resistance in part through suppression of apoptosis via a caspase-dependent mechanism. Oxaliplatin treatment significantly decreased expression of survivin in cancer cells within 24-72 h. Apoptotic cells and caspase-3 activity were increased parallely with decrease in cell viability, if irradiated during this sensitive period. The cytotoxicity of oxaliplatin and radiation combination was greater than additive. Survivin gene knockdown experiments have demonstrated the role of survivin in radiosensitization of cancer cells mediated by oxaliplatin. Conclusions: Higher expression of survivin is a critical factor for radioresistance in HNSCC cell lines. Pre-treatment of cancer cells with oxaliplatin significantly increased the radiosensitivity through induction of apoptosis by potently inhibiting survivin.

  18. Multicenter validation of recursive partitioning analysis classification for patients with squamous cell head and neck carcinoma treated with surgery and postoperative radiotherapy.

    NARCIS (Netherlands)

    Jonkman, A.; Kaanders, J.H.A.M.; Terhaard, C.H.J.; Hoebers, F.J.; Ende, P.L. van den; Wijers, O.B.; Verhoef, C.G.; Jong, M. de; Leemans, C.R.; Langendijk, J.A.

    2007-01-01

    PURPOSE: To validate the recursive partitioning analysis (RPA) classification system for squamous cell head and neck cancer as recently reported by the VU University Medical Center. METHODS AND MATERIALS: In eight Dutch head and neck cancer centers, data necessary to classify patients according to

  19. Erythropoietin receptor is not a surrogate marker for tumor hypoxia and does not correlate with survival in head and neck squamous cell carcinomas.

    NARCIS (Netherlands)

    Hoogsteen, I.J.; Peeters, W.J.M.; Marres, H.A.M.; Rijken, P.F.J.W.; Hoogen, F.J.A. van den; Kogel, A.J. van der; Kaanders, J.H.A.M.

    2005-01-01

    BACKGROUND AND PURPOSE: To evaluate erythropoietin receptor (EPOR) expression in human head and neck squamous cell carcinomas and correlate this to the presence of tumor hypoxia and treatment outcome. PATIENTS AND METHODS: Eighty-five patients with locally advanced tumors of the head and neck were

  20. Assessment of occult cervical lymph node metastasis in primary squamous cell carcinoma of the head and neck by computed tomography

    International Nuclear Information System (INIS)

    Shakil, U.

    2015-01-01

    To determine the frequency of occult (node negative) cervical lymph node metastasis in primary head and neck squamous cell carcinoma, using contrast enhanced computed tomography (CT). Study Design: Cross sectional descriptive study. Place and Duration of Study: Study was conducted in Department of Radiology, Combined Military Hospital Rawalpindi. Duration of the study was 06 months i.e. from 19th February 2011 to 19th August 2011. Patients and Methods: A total of 141 cases, fulfilling the inclusion criteria, reporting to the radiology department, were included in the study after seeking written informed consent. All patients underwent contrast enhanced CT scan of the neck from base of skull to root of neck using Asteion Whole Body X-ray CT Scanner (Model TSX-021A). Images were evaluated for the presence or absence of cervical lymph node metastasis according to the cervical lymph node metastatic criteria at each level of the neck. Results: Of the 141 patients with clinically no head and neck squamous cell carcinoma, 45.4% were found to have lymph node metastases. Frequency of occult metastases in squamous cell carcinoma of oral cavity was 47.6%, oropharynx 23.5%, larynx 33.3% and hypopharynx 78.6%. Conclusion: In clinically node negative neck, the risk of lymph node metastases is significantly high in patients of head and neck squamous cell carcinoma in our population. All patients presenting with node negative neck should undergo CT scans for early detection of occult metastasis. (author)

  1. The small molecule inhibitor QLT0267 Radiosensitizes squamous cell carcinoma cells of the head and neck.

    Directory of Open Access Journals (Sweden)

    Iris Eke

    Full Text Available BACKGROUND: The constant increase of cancer cell resistance to radio- and chemotherapy hampers improvement of patient survival and requires novel targeting approaches. Integrin-Linked Kinase (ILK has been postulated as potent druggable cancer target. On the basis of our previous findings clearly showing that ILK transduces antisurvival signals in cells exposed to ionizing radiation, this study evaluated the impact of the small molecule inhibitor QLT0267, reported as putative ILK inhibitor, on the cellular radiation survival response of human head and neck squamous cell carcinoma cells (hHNSCC. METHODOLOGY/PRINCIPAL FINDINGS: Parental FaDu cells and FaDu cells stably transfected with a constitutively active ILK mutant (FaDu-IH or empty vectors, UTSCC45 cells, ILK(floxed/floxed(fl/fl and ILK(-/- mouse fibroblasts were used. Cells grew either two-dimensionally (2D on or three-dimensionally (3D in laminin-rich extracellular matrix. Cells were treated with QLT0267 alone or in combination with irradiation (X-rays, 0-6 Gy single dose. ILK knockdown was achieved by small interfering RNA transfection. ILK kinase activity, clonogenic survival, number of residual DNA double strand breaks (rDSB; gammaH2AX/53BP1 foci assay, cell cycle distribution, protein expression and phosphorylation (e.g. Akt, p44/42 mitogen-activated protein kinase (MAPK were measured. Data on ILK kinase activity and phosphorylation of Akt and p44/42 MAPK revealed a broad inhibitory spectrum of QLT0267 without specificity for ILK. QLT0267 significantly reduced basal cell survival and enhanced the radiosensitivity of FaDu and UTSCC45 cells in a time- and concentration-dependent manner. QLT0267 exerted differential, cell culture model-dependent effects with regard to radiogenic rDSB and accumulation of cells in the G2 cell cycle phase. Relative to corresponding controls, FaDu-IH and ILK(fl/fl fibroblasts showed enhanced radiosensitivity, which failed to be antagonized by QLT0267. A

  2. Toward the use of precision medicine for the treatment of head and neck squamous cell carcinoma.

    Science.gov (United States)

    Gong, Wang; Xiao, Yandi; Wei, Zihao; Yuan, Yao; Qiu, Min; Sun, Chongkui; Zeng, Xin; Liang, Xinhua; Feng, Mingye; Chen, Qianming

    2017-01-10

    Precision medicine is a new strategy that aims at preventing and treating human diseases by focusing on individual variations in people's genes, environment and lifestyle. Precision medicine has been used for cancer diagnosis and treatment and shows evident clinical efficacy. Rapid developments in molecular biology, genetics and sequencing technologies, as well as computational technology, has enabled the establishment of "big data", such as the Human Genome Project, which provides a basis for precision medicine. Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a high incidence rate and low survival rate. Current therapies are often aggressive and carry considerable side effects. Much research now indicates that precision medicine can be used for HNSCC and may achieve improved results. From this perspective, we present an overview of the current status, potential strategies, and challenges of precision medicine in HNSCC. We focus on targeted therapy based on cell the surface signaling receptors epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor-2 (HER2), and on the PI3K/AKT/mTOR, JAK/STAT3 and RAS/RAF/MEK/ERK cellular signaling pathways. Gene therapy for the treatment of HNSCC is also discussed.

  3. Genomics and advances towards precision medicine for head and neck squamous cell carcinoma.

    Science.gov (United States)

    Van Waes, Carter; Musbahi, Omar

    2017-10-01

    To provide a review of emerging knowledge from genomics and related basic science, preclinical, and clinical precision medicine studies in head and neck squamous cell carcinoma (HNSCC). The Cancer Genome Atlas Network (TCGA) publications, PubMed-based literature review, and ClinicalTrials.gov. TCGA publications, PubMed, and ClinicalTrials.gov were queried for genomics and related basic science, preclinical, and developmental clinical precision medicine studies in HNSCC. TCGA reported comprehensive genomic analyses of 279 HNSCC, defining the landscape and frequency of chromosomal copy number alterations, mutations, and expressed genes that contribute to pathogenesis, prognosis, and resistance to therapy. This provides a road map for basic science and preclinical studies to identify key pathways in cancer and cells of the tumor microenvironment affected by these alterations, and candidate targets for new small molecule and biologic therapies. Recurrent chromosomal abnormalities, mutations, and expression of genes affecting HNSCC subsets are associated with differences in prognosis, and define molecules, pathways, and deregulated immune responses as candidates for therapy. Activity of molecularly targeted agents appears to be enhanced by rational combinations of these agents and standard therapies targeting the complex alterations that affect multiple pathways and mechanisms in HNSCC. NA.

  4. Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level.

    Directory of Open Access Journals (Sweden)

    Deli Liu

    2015-06-01

    Full Text Available Spontaneous canine head and neck squamous cell carcinoma (HNSCC represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling, and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial-mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.

  5. Highly efficient destruction of squamous carcinoma cells of the head and neck by photochemical internalization of Ranpirnase.

    Science.gov (United States)

    Liebers, Nora; Holland-Letz, Tim; Welschof, Mona; Høgset, Anders; Jäger, Dirk; Arndt, Michaela A E; Krauss, Jürgen

    2017-11-01

    Photochemical Internalization is a novel drug delivery technology for cancer treatment based on the principle of Photodynamic Treatment. Using a photosensitizer that locates in endocytic vesicles membranes of tumor cells, Photochemical internalization enables cytosolic release of endocytosed antitumor agents in a site-specific manner. The purpose of the present in-vitro study was to explore whether Photochemical Internalization is able to enhance the efficacy of Ranpirnase, a cytotoxic amphibian ribonuclease, for eradication of squamous cell carcinoma of the head and neck. Cell viability was measured in 8 primary human cell lines of squamous cell carcinoma of the head and neck after treatment with Ranpirnase and Photochemical Internalization. For Photochemical Internalization the photosensitizer disulfonated tetraphenyl porphine was incubated with tumor cells followed by exposure to blue light (435 nm). Our study demonstrates significant enhancement of antitumor activity of Ranpirnase by Photochemical Internalization. Treatment responses were heterogeneous between the primary cancer cell lines. Combining Photochemical Internalization with Ranpirnase resulted in 4.6 to 1,940-fold increased cytotoxicity when compared with the ribonuclease alone (P Internalization in squamous cell carcinoma of the head and neck.

  6. Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.

    Science.gov (United States)

    Arosarena, Oneida A; Barr, Eric W; Thorpe, Ryan; Yankey, Hilary; Tarr, Joseph T; Safadi, Fayez F

    2018-01-01

    Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p = 0.0001), and MMP-3 (p = 0.0005) and -9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p = 0.0408) and MMP-9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP-2 (p = 0.0023) and -9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion. © 2017 Wiley Periodicals, Inc.

  7. Stimulated monocyte IL-6 secretion predicts survival of patients with head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Olofsson Jan

    2008-01-01

    Full Text Available Abstract Background This study was performed in order to determine whether monocyte in vitro function is associated with presence, stage and prognosis of head and neck squamous cell carcinoma (HNSCC disease. Methods Prospective study describing outcome, after at least five years observation, of patients treated for HNSCC disease in relation to their monocyte function. Sixty-five patients with newly diagnosed HNSCC and eighteen control patients were studied. Monocyte responsiveness was assessed by measuring levels of monocyte in vitro interleukin (IL-6 and monocyte chemotactic peptide (MCP-1 secretion after 24 hours of endotoxin stimulation in cultures supplied either with 20% autologous serum (AS or serum free medium (SFM. Survival, and if relevant, cause of death, was determined at least 5 years following primary diagnosis. Results All patients, as a group, had higher in vitro monocyte responsiveness in terms of IL-6 (AS (t = 2.03; p t = 2.49; p in vitro monocyte IL-6 endotoxin responsiveness under the SFM condition was associated with decreased survival rate (Hazard ratio (HR = 2.27; Confidence interval (CI = 1.05–4.88; p p p Conclusion In HNSCC patients, changed monocyte in vitro response to endotoxin, as measured by increased IL-6 (SFM and decreased MCP-1 (AS responsiveness, are negative prognostic factors.

  8. New candidate markers of head and neck squamous cell carcinoma progression

    Science.gov (United States)

    Kakurina, G. V.; Kolegova, E. S.; Cheremisina, O. V.; Kulbakin, D. E.; Choinzonov, E. L.

    2017-09-01

    The tumor progression in head and neck squamous cell carcinoma (HNSCC) is one of the main causes of high mortality of the patients with HNSCC. The tumor progression, particularly the metastasis, is characterized by the changes in the composition, functions and structure of different proteins. We have previously shown that serum of HNSCC patients contains the proteins which regulate various cellular processes—adenylyl cyclase associated protein 1 (CAP1), protein phosphatase 1 B (PPM1B), etc. The levels of CAP1 and PPM1B were determined using the enzyme immunoassay. The results of this study show that CAP1 and PPM1B take a part in the progression of HNSCC. The levels of CAP1 and PPM1B in the tumor and in morphologically normal tissue depended on the prevalence of the tumor process. The CAP1 and PPM1B levels were significantly higher in tumor tissue of the patients with regional metastasis. Our data allow assuming the potential possibility for predicting the outcome of the HNSCC measuring the level of tissue CAP1.

  9. Incompletely resected advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Huang, D.; Johnson, C.R.; Schmidt-Ullrich, R.K.; Sismanis, A.; Neifeld, J.P.; Weber, J.

    1992-01-01

    From 1982-1988, 441 patients were treated at Virginia Medical College for AJC Stage III and IV squamous cell carcinoma of head and neck. On 84 patients is reported, whose tumors were incompletely resected based on histopathological margins of 1mm or less. Of the 84 patients, 49 were treated with surgery alone and 35 received immediate postoperative irradiation to doses of 50-70 Gy. The 2 groups are comparable with respects to stage of disease, age, male/female and racial ratios. This retrospective analysis, based on follow-up of 24- 110 months, gives actuarial locoregional tumor control and survival data. The local control and disease-free survival rates in the combined modality group are significantly superior at the p=0.0006 and p=0.0003 levels, respectively, related to the surgery-alone-group. Patients in the first group also experienced a significantly improved adjusted and overall survival, p=0.005 and p=0.001, respectively. The administration of postoperative irradiation was not associated with an increased rate of complications. The benefit of radiotherapy on survival was only seen when given as postoperative treatment but was lost in patients treated for salvage tumor after tumor recurrence. (author). 17 refs.; 5 figs.; 6 tabs

  10. Head and Neck Squamous Cell Carcinomas Do Not Express EGFRvIII

    Energy Technology Data Exchange (ETDEWEB)

    Melchers, Lieuwe J., E-mail: l.j.melchers@umcg.nl [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Clausen, Martijn J.A.M. [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Mastik, Mirjam F. [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Slagter-Menkema, Lorian [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Laan, Bernard F.A.M. van der [Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Wal, Jacqueline E. van der; Vegt, Bert van der [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Roodenburg, Jan L.N. [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Schuuring, Ed [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

    2014-10-01

    Purpose: To assess the prevalence of EGFRvIII, a specific variant of EGFR (epidermal growth factor receptor), in 3 well-defined cohorts of head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Immunohistochemistry for the specific detection of EGFRvIII using the L8A4 antibody was optimized on formalin-fixed, paraffin-embedded tissue using glioblastoma tissue. It was compared with EGFR and EGFRvIII RNA expression using a specific reverse transcription–polymerase chain reaction also optimized for formalin-fixed, paraffin-embedded tissue. Tissue microarrays including 531 HNSCCs of various stages with complete clinicopathologic and follow-up data were tested for the presence of EGFRvIII. Results: None of the 531 cases showed EGFRvIII protein expression. Using an immunohistochemistry protocol reported by others revealed cytoplasmic staining in 8% of cases. Reverse transcription–polymerase chain reaction for the EGFRvIII transcript of the 28 highest cytoplasmic staining cases, as well as 69 negative cases, did not show expression in any of the tested cases, suggesting aspecific staining by a nonoptimal protocol. Conclusions: The EGFRvIII mutation is not present in HNSCC. Therefore, EGFRvIII does not influence treatment response in HNSCC and is not a usable clinical prognostic marker.

  11. Head and Neck Squamous Cell Carcinomas Do Not Express EGFRvIII

    International Nuclear Information System (INIS)

    Melchers, Lieuwe J.; Clausen, Martijn J.A.M.; Mastik, Mirjam F.; Slagter-Menkema, Lorian; Langendijk, Johannes A.; Laan, Bernard F.A.M. van der; Wal, Jacqueline E. van der; Vegt, Bert van der; Roodenburg, Jan L.N.; Schuuring, Ed

    2014-01-01

    Purpose: To assess the prevalence of EGFRvIII, a specific variant of EGFR (epidermal growth factor receptor), in 3 well-defined cohorts of head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Immunohistochemistry for the specific detection of EGFRvIII using the L8A4 antibody was optimized on formalin-fixed, paraffin-embedded tissue using glioblastoma tissue. It was compared with EGFR and EGFRvIII RNA expression using a specific reverse transcription–polymerase chain reaction also optimized for formalin-fixed, paraffin-embedded tissue. Tissue microarrays including 531 HNSCCs of various stages with complete clinicopathologic and follow-up data were tested for the presence of EGFRvIII. Results: None of the 531 cases showed EGFRvIII protein expression. Using an immunohistochemistry protocol reported by others revealed cytoplasmic staining in 8% of cases. Reverse transcription–polymerase chain reaction for the EGFRvIII transcript of the 28 highest cytoplasmic staining cases, as well as 69 negative cases, did not show expression in any of the tested cases, suggesting aspecific staining by a nonoptimal protocol. Conclusions: The EGFRvIII mutation is not present in HNSCC. Therefore, EGFRvIII does not influence treatment response in HNSCC and is not a usable clinical prognostic marker

  12. Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review.

    Science.gov (United States)

    Hernandes, Camila; Pereira, Ana Maria Soares; Severino, Patricia

    2017-02-01

    Squamous cell carcinoma of the head and neck is one of the most common cancer types worldwide. It initiates on the epithelial lining of the upper aerodigestive tract, at most instances as a consequence of tobacco and alcohol consumption. Treatment options based on conventional therapies or targeted therapies under development have limited efficacy due to multiple genetic alterations typically found in this cancer type. Natural products derived from plants often possess biological activities that may be valuable in the development of new therapeutic agents for cancer treatment. Several genera from the family Celastraceae have been studied in this context. This review reports studies on chemical constituents isolated from species from the Celastraceae family targeting cancer mechanisms studied to date. These results are then correlated with molecular characteristics of head and neck squamous cell carcinoma in an attempt to identify constituents with potential application in the treatment of this complex disease at the molecular level.

  13. Head and neck squamous cell carcinoma and its correlation with human papillomavirus in people living with HIV: a systematic review.

    Science.gov (United States)

    Ceccarelli, Manuela; Rullo, Emmanuele Venanzi; Facciolà, Alessio; Madeddu, Giordano; Cacopardo, Bruno; Taibi, Rosaria; D'Aleo, Francesco; Pinzone, Marilia Rita; Picerno, Isa; di Rosa, Michele; Visalli, Giuseppa; Condorelli, Fabrizio; Nunnari, Giuseppe; Pellicanò, Giovanni Francesco

    2018-03-30

    Over the last 20 years we assisted to an increase in the mean age of People Living with HIV and their comorbidities. Especially, there was an increase in Human Papillomavirus-related head and neck squamous cell carcinomas. Despite their increasing incidence in HIV-positive people, mechanisms that lead to their development and progression are only partially understood. The aim of this review is to identify key data and factors about HPV-related head and neck squamous cell carcinoma in HIV-seropositive patients. Systematic search and review of the relevant literature-peer-reviewed and grey-was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. We included in our review only the 35 full-text articles we considered the most substantial. It is mandatory to improve our knowledge about the interactions existing between HPV and HIV, and about their actions on oral mucosa immune system.

  14. Accelerated superfractionated radiotherapy with concomitant boost for locally advanced head-and-neck squamous cell carcinomas

    International Nuclear Information System (INIS)

    Morris, Monica M.; Schmidt-Ullrich, Rupert K.; DiNardo, L.; Manning, Matthew A.; Silverman, L.; Clay, L.; Johnson, Christopher R.; Amir, Cyrus

    2002-01-01

    Purpose: A growing body of evidence supports the efficacy of accelerated superfractionated radiotherapy with concomitant boost for advanced head-and-neck carcinomas. This study represents a single-institution experience, performed to identify the factors influencing tumor control, survival, and toxicity. Methods and Materials: Between 1988 and 1999, 133 patients with primary squamous cell head-and-neck carcinoma underwent accelerated superfractionated radiotherapy using a concomitant boost. The concomitant boost in this regimen was delivered using reduced fields delivered 3 times weekly in a twice-daily schedule during the final phase. The total radiation dose ranged from 64.8 Gy to 76.5 Gy (mean 71.1). Patients were evaluated in follow-up for local control and late toxicity. Multivariate analysis of treatment and patient parameters was performed to evaluate their influence on toxicity, local control, and overall survival. Results: With a mean follow-up of 37 months, the actuarial overall survival rate for the entire group at 5 years was 24% and the local control rate was 57%. The tumor volume was the most significant predictor of local control, such that each 1-cm 3 increase in volume was associated with a 1% decrease in local control. For patients with tumor volumes ≤30 cm 3 vs. >30 cm 3 , the 5-year disease-specific survival rate was 52% and 27% (p = 0.004) and locoregional control rate was 76% and 26% (p<0.001), respectively. Seventy-six patients with a minimum of 12 months and median of 39 months toxicity follow-up were studied for late effects. None of these patients experienced Grade 4 or 5 toxicity. The actuarial rate of significant toxicity (Grade III or greater) was 32% at 5 years. Of the toxicities observed, xerostomia (19%) was the most common. Multivariate analysis revealed N stage and dose as independent predictors of Grade 3 effects. Conclusion: The locoregional control and survival for patients in this institutional experience compare favorably to

  15. Correlation between egfr expression and accelerated proliferation during radiotherapy of head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Pedicini Piernicola

    2012-08-01

    Full Text Available Abstract Purpose To investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr and the reduction of the effective doubling time (TD during radiotherapy treatment and also to determine the dose per fraction to be taken into account when the overall treatment time (OTT is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC. Methods A survey of the published papers comparing 3-years of local regional control rate (LCR for a total of 2162 patients treated with conventional and accelerated radiotherapy and with a pretreatment assessment of EGFr expression, was made. Different values of TD were obtained by a model incorporating the overall time corrected biologically effective dose (BED and a 3-year clinical LCR for high and low EGFr groups of patients (HEGFr and LEGFr, respectively. By obtaining the TD from the above analysis and the sub-sites’ potential doubling time (Tpot from flow cytometry and immunohistochemical methods, we were able to estimate the average TD for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (Dprolif, was estimated. Results The averages of TD were 77 (27-9095% days in LEGFr and 8.8 (7.3-11.095% days in HEGFr, if an onset of accelerated proliferation TK at day 21 was assumed. The correspondent HEGFr sub-sites’ TD were 5.9 (6.6, 5.9 (6.6, 4.6 (6.1, 14.3 (12.9 days, with respect to literature immunohistochemical (flow cytometry data of Tpot for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The Dprolif for the HEGFr groups were 0.33 (0.29, 0.33 (0.29, 0.42 (0.31, 0.14 (0.15 Gy/day if α = 0.3 Gy-1 and α/β = 10 Gy were assumed. Conclusions A higher expression of the EGFr leads to enhanced proliferation. This study allowed to quantify the extent of the effect which EGFr expression has in terms of reduced TD and Dprolif for each head and neck

  16. Correlation between egfr expression and accelerated proliferation during radiotherapy of head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Pedicini, Piernicola; Fiorentino, Alba; Improta, Giuseppina; Storto, Giovanni; Benassi, Marcello; Orecchia, Roberto; Salvatore, Marco; Nappi, Antonio; Strigari, Lidia; Alicia Jereczek-Fossa, Barbara; Alterio, Daniela; Cremonesi, Marta; Botta, Francesca; Vischioni, Barbara; Caivano, Rocchina

    2012-01-01

    To investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr) and the reduction of the effective doubling time (T D ) during radiotherapy treatment and also to determine the dose per fraction to be taken into account when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC). A survey of the published papers comparing 3-years of local regional control rate (LCR) for a total of 2162 patients treated with conventional and accelerated radiotherapy and with a pretreatment assessment of EGFr expression, was made. Different values of T D were obtained by a model incorporating the overall time corrected biologically effective dose (BED) and a 3-year clinical LCR for high and low EGFr groups of patients (H EGFr and L EGFr ), respectively. By obtaining the T D from the above analysis and the sub-sites’ potential doubling time (T pot ) from flow cytometry and immunohistochemical methods, we were able to estimate the average T D for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (D prolif ), was estimated. The averages of T D were 77 (27-90) 95% days in L EGFr and 8.8 (7.3-11.0) 95% days in H EGFr , if an onset of accelerated proliferation T K at day 21 was assumed. The correspondent H EGFr sub-sites’ T D were 5.9 (6.6), 5.9 (6.6), 4.6 (6.1), 14.3 (12.9) days, with respect to literature immunohistochemical (flow cytometry) data of T pot for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The D prolif for the H EGFr groups were 0.33 (0.29), 0.33 (0.29), 0.42 (0.31), 0.14 (0.15) Gy/day if α = 0.3 Gy -1 and α/β = 10 Gy were assumed. A higher expression of the EGFr leads to enhanced proliferation. This study allowed to quantify the extent of the effect which EGFr expression has in terms of reduced T D and D prolif for each head and neck sub-site

  17. Clinical values for abnormal {sup 18}F-FDG uptake in the head and neck region of patients with head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hwan Seo [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jae Seung [Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Roh, Jong-Lyel, E-mail: rohjl@amc.seoul.kr [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Seung-Ho; Nam, Soon Yuhl [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Sang Yoon [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Biomedical Research Institute, Korea Institute of Science and Technology, Seoul (Korea, Republic of)

    2014-08-15

    Highlights: • Abnormal {sup 18}F-FDG uptakes in the head and neck (HN) region can be carefully interpreted as being index primary, second primary cancer (SP) or benign. • {sup 18}F-FDG PET/CT identified 91.9% primary HN squamous cell carcinomas (HNSCC). • The specificity and negative predictive value of {sup 18}F-FDG PET/CT for identification of SP were as high as 98.7% and 99.3%, respectively. • Proper detection of primary tumors and SP in the HN region may promote appropriate therapeutic planning of HNSCC patients. - Abstract: Purpose: Fluorine 18-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/computed tomography (CT) is used to identify index or second primary cancer (SP) of the head and neck (HN) through changes in {sup 18}F-FDG uptake. However, both physiologic and abnormal lesions increase {sup 18}F-FDG uptake. Therefore, we evaluated {sup 18}F-FDG uptake in the HN region to determine clinical values of abnormal tracer uptake. Methods: A prospective study approved by the institutional review board was conducted in 314 patients with newly diagnosed HN squamous cell carcinoma (HNSCC) and informed consent was obtained from all enrolled patients. The patients received initial staging workups including {sup 18}F-FDG PET/CT and biopsies. All lesions with abnormal HN {sup 18}F-FDG uptake were recorded and most of those were confirmed by biopsies. Diagnostic values for abnormal {sup 18}F-FDG uptake were calculated. Results: Abnormal {sup 18}F-FDG uptake was identified in primary tumors from 285 (91.9%) patients. False-negative results were obtained for 22.3% (23/103) T1 tumors and 2.2% (2/93) T2 tumors (P < 0.001). Thirty-eight regions of abnormal {sup 18}F-FDG uptake were identified in 36 (11.5%) patients: the thyroid (n = 13), maxillary sinus (n = 7), palatine tonsil (n = 6), nasopharynx (n = 5), parotid gland (n = 2) and others (n = 5). Synchronous SP of the HN was identified in eight (2.5%) patients: the thyroid (n = 5), palatine

  18. Clinical values for abnormal 18F-FDG uptake in the head and neck region of patients with head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Lee, Hwan Seo; Kim, Jae Seung; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

    2014-01-01

    Highlights: • Abnormal 18 F-FDG uptakes in the head and neck (HN) region can be carefully interpreted as being index primary, second primary cancer (SP) or benign. • 18 F-FDG PET/CT identified 91.9% primary HN squamous cell carcinomas (HNSCC). • The specificity and negative predictive value of 18 F-FDG PET/CT for identification of SP were as high as 98.7% and 99.3%, respectively. • Proper detection of primary tumors and SP in the HN region may promote appropriate therapeutic planning of HNSCC patients. - Abstract: Purpose: Fluorine 18-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) is used to identify index or second primary cancer (SP) of the head and neck (HN) through changes in 18 F-FDG uptake. However, both physiologic and abnormal lesions increase 18 F-FDG uptake. Therefore, we evaluated 18 F-FDG uptake in the HN region to determine clinical values of abnormal tracer uptake. Methods: A prospective study approved by the institutional review board was conducted in 314 patients with newly diagnosed HN squamous cell carcinoma (HNSCC) and informed consent was obtained from all enrolled patients. The patients received initial staging workups including 18 F-FDG PET/CT and biopsies. All lesions with abnormal HN 18 F-FDG uptake were recorded and most of those were confirmed by biopsies. Diagnostic values for abnormal 18 F-FDG uptake were calculated. Results: Abnormal 18 F-FDG uptake was identified in primary tumors from 285 (91.9%) patients. False-negative results were obtained for 22.3% (23/103) T1 tumors and 2.2% (2/93) T2 tumors (P < 0.001). Thirty-eight regions of abnormal 18 F-FDG uptake were identified in 36 (11.5%) patients: the thyroid (n = 13), maxillary sinus (n = 7), palatine tonsil (n = 6), nasopharynx (n = 5), parotid gland (n = 2) and others (n = 5). Synchronous SP of the HN was identified in eight (2.5%) patients: the thyroid (n = 5), palatine tonsil (n = 2), and epiglottis (n = 1). The sensitivity and

  19. Microarray analysis of serum mRNA in patients with head and neck squamous cell carcinoma at whole-genome scale

    Czech Academy of Sciences Publication Activity Database

    Čapková, M.; Šáchová, Jana; Strnad, Hynek; Kolář, Michal; Hroudová, Miluše; Chovanec, M.; Čada, Z.; Štefl, M.; Valach, J.; Kastner, J.; Smetana, K. Jr.; Plzák, J.

    -, April 23 (2014) ISSN 2314-6141 R&D Projects: GA MZd(CZ) NT13488 Institutional support: RVO:68378050 Keywords : Microarray Analysis * Head and Neck Squamous Cell Carcinoma * whole-genome scale Subject RIV: EB - Genetics ; Molecular Biology

  20. The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck

    DEFF Research Database (Denmark)

    Nylander, K.; Dabelsteen, Erik; Hall, P.A.

    2000-01-01

    and poor patient outcome was found when looking only at patients with laryngeal squamous cell carcinomas. Also, in oral premalignant lesions, expression of p53-positive cells in the suprabasal layers of the epithelium has been seen as an indication of impending malignant development. Concerning......Despite intense research, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (SCCHN) is still low. Several different factors have been studied in the search for one or more factors that give important prognostic information at the time of diagnosis. Many recent...

  1. Human papilloma virus prevalence in HIV patients with head and neck squamous cell carcinoma.

    Science.gov (United States)

    Picard, Annabelle; Badoual, Cécile; Hourseau, Muriel; Halimi, Caroline; Pere, Hélène; Dib, Fadia; Barry, Béatrix; Albert, Sébastien

    2016-05-15

    The implication of human papilloma virus (HPV) in head and neck squamous cell carcinoma (HNSCC) is well established, especially in oropharyngeal SCC. HIV patients have a higher risk of persistent HPV infection. We investigated the role of HPV in HNSCC carcinogenesis in HIV population. Retrospective monocentric study. We studied HIV patients who presented with HNSCC between 1994 and 2014. For each patient, tumor characteristics, HIV disease, and survival information were collected. Tumor HPV testing was performed using p16 immunohistochemistry (IHC), in-situ hybridization and PCR. We assessed the percentage of HPV in this population of HIV patients with HNSCC and compared HIV disease characteristics based on HPV status. Forty-seven patients were included: 11 women/36 men, the median age was 50 years. Tumor HPV testing was performed in 40 patients. Tumors were located in oropharynx (32%), oral cavity (32%), larynx (21%), and hypopharynx (11%). At the time of diagnosis, median CD4 level was 385 cells/μl, 31% of the patients were stage (Centers for Disease Control, stage C). The percentage of HPV linked to HNSCC for all locations in HIV patients was 30% (n = 12). HPV16 accounted for 50% of all HPV genotypes. HPV positive status was associated with a CD4 nadir of less than 200 (P = 0.026), but not with CD4 level at time of diagnosis (P = 0.414). HPV-negative tumors tend to be associated with poorer 5-year overall survival (hazard ratio = 2.9, P = 0.0711). HPV plays a critical role in HNSCC development in HIV population. HIV immunodeficiency may increase HPV persistence and progression of HNSCC.

  2. Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer.

    Science.gov (United States)

    Hayes, Richard B; Ahn, Jiyoung; Fan, Xiaozhou; Peters, Brandilyn A; Ma, Yingfei; Yang, Liying; Agalliu, Ilir; Burk, Robert D; Ganly, Ian; Purdue, Mark P; Freedman, Neal D; Gapstur, Susan M; Pei, Zhiheng

    2018-03-01

    Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC. To prospectively examine associations between the oral microbiome and incident HNSCC. This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline. Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P-value (q-value) <.10 were considered significant. Incident HNSCC. The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco

  3. Stimulated monocyte IL-6 secretion predicts survival of patients with head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Heimdal, John-Helge; Kross, Kenneth; Klementsen, Beate; Olofsson, Jan; Aarstad, Hans Jørgen

    2008-01-01

    This study was performed in order to determine whether monocyte in vitro function is associated with presence, stage and prognosis of head and neck squamous cell carcinoma (HNSCC) disease. Prospective study describing outcome, after at least five years observation, of patients treated for HNSCC disease in relation to their monocyte function. Sixty-five patients with newly diagnosed HNSCC and eighteen control patients were studied. Monocyte responsiveness was assessed by measuring levels of monocyte in vitro interleukin (IL)-6 and monocyte chemotactic peptide (MCP)-1 secretion after 24 hours of endotoxin stimulation in cultures supplied either with 20% autologous serum (AS) or serum free medium (SFM). Survival, and if relevant, cause of death, was determined at least 5 years following primary diagnosis. All patients, as a group, had higher in vitro monocyte responsiveness in terms of IL-6 (AS) (t = 2.03; p < 0.05) and MCP-1 (SFM) (t = 2.49; p < 0.05) compared to controls. Increased in vitro monocyte IL-6 endotoxin responsiveness under the SFM condition was associated with decreased survival rate (Hazard ratio (HR) = 2.27; Confidence interval (CI) = 1.05–4.88; p < 0.05). The predictive value of monocyte responsiveness, as measured by IL-6, was also retained when adjusted for age, gender and disease stage of patients (HR = 2.67; CI = 1.03–6.92; p < 0.05). With respect to MCP-1, low endotoxin-stimulated responsiveness (AS), analysed by Kaplan-Meier method, predicted decreased survival (χ = 4.0; p < 0.05). In HNSCC patients, changed monocyte in vitro response to endotoxin, as measured by increased IL-6 (SFM) and decreased MCP-1 (AS) responsiveness, are negative prognostic factors

  4. Incremental Prognostic Value of Apparent Diffusion Coefficient Histogram Analysis in Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Li, Xiaoxia; Yuan, Ying; Ren, Jiliang; Shi, Yiqian; Tao, Xiaofeng

    2018-03-26

    We aimed to investigate the incremental prognostic value of apparent diffusion coefficient (ADC) histogram analysis in patients with head and neck squamous cell carcinoma (HNSCC) and integrate it into a multivariate prognostic model. A retrospective review of magnetic resonance imaging findings was conducted in patients with pathologically confirmed HNSCC between June 2012 and December 2015. For each tumor, six histogram parameters were derived: the 10th, 50th, and 90th percentiles of ADC (ADC 10 , ADC 50 , and ADC 90 ); mean ADC values (ADC mean ); kurtosis; and skewness. The clinical variables included age, sex, smoking status, tumor volume, and tumor node metastasis stage. The association of these histogram and clinical variables with overall survival (OS) was determined. Further validation of the histogram parameters as independent biomarkers was performed using multivariate Cox proportional hazard models combined with clinical variables, which was compared to the clinical model. Models were assessed with C index and receiver operating characteristic curve analyses for the 12- and 36-month OS. Ninety-six patients were eligible for analysis. Median follow-up was 877 days (range, 54-1516 days). A total of 29 patients died during follow-up (30%). Patients with higher ADC values (ADC 10  > 0.958 × 10 -3 mm 2 /s, ADC 50  > 1.089 × 10 -3 mm 2 /s, ADC 90  > 1.152 × 10 -3 mm 2 /s, ADC mean  > 1.047 × 10 -3 mm 2 /s) and lower kurtosis (≤0.967) were significant predictors of poor OS (P histogram analysis has incremental prognostic value in patients with HNSCC and increases the performance of a multivariable prognostic model in addition to clinical variables. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  5. A phase II study of primary reirradiation in squamous cell carcinoma of head and neck

    International Nuclear Information System (INIS)

    Langendijk, Johannes A.; Kasperts, Nicolien; Leemans, Charles R.; Doornaert, Patricia; Slotman, Ben J.

    2006-01-01

    Background and purpose: In this prospective study, the effect of a second course of primary radiotherapy on locoregional control, survival and toxicity was investigated, in patients who underwent a second course of high dose irradiation for second primary or locoregional recurrent squamous cell head and neck carcinoma (HNSCC) in a previously irradiated area. Patients and methods: A total of 34 patients with second primary (n=26) or locoregional recurrent (n=8) tumours were treated with a second course of high dose radiotherapy. Patients were selected for re-irradiation in case of inoperable and/or unresectable tumours. In most cases, the target volume for re-irradiation was confined to the gross tumour volume (GTV). No elective radiotherapy was applied in the former high-dose area. A total dose of 46 Gy was applied to elective areas with a boost up to 60 Gy with conventional fractionation. The median follow-up period was 32 months. Results: The locoregional control rate after 2 years was 27%. The 3-year overall survival was 22%. The most frequently reported acute side-effect was acute mucositis resulting in swallowing complaints. Pharyngeal and oesophageal late morbidity was also the most important late side-effect. In general, acute and late radiation-induced morbidity remained within acceptable limits. Conclusions: In conclusion, primary re-irradiation appears to be feasible in terms of acute and late radiation-induced toxicity. To improve outcome in terms locoregional control and survival, future studies should be focussed on optimising radiation schedules and the addition of concomitant chemotherapy

  6. Association between GSTM1 and GSTT1 allelic variants and head and neck squamous cell cancinoma.

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    Full Text Available BACKGROUNDS: GSTM1 and GSTT1 are involved in the detoxification of carcinogens such as smoking by-products, and polymorphisms in these two genes with a result of loss of enzyme activity may increase risk of carcinogenesis. Although many epidemiological studies have investigated the association between GSTM1 or GSTT1 null genotype and head and neck squamous cell carcinoma (HNSCC, the results remain conflicting. To elucidate the overall association of GSTM1, GSTT1 and HNSCC, we included all available studies and performed this meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: A dataset including 42 articles for GSTM1, 32 articles for GSTT1, and 15 articles for GSTM1 and GSTT1 in combination were identified by a search in PubMed. Associations beween HNSCC and polymorphisms of GSTM1 and GSTT1 alone and in combination were analysed by software RevMan 5.1. Stratification analysis on ethnicity and smoking status, sensitivity analysis, heterogeneity among studies and their publication bias were also tested. Association was found in overall analysis between HNSCC and GSTM1 and GSTT1 null genotype. Stratified by ethnicity, we found increased risks of HNSCC in carriers with GSTM1 null genotype in Asian, GSTT1 null genotype in South American, and dual null genotype in European and Asian. When stratified by smoking, a more significant association of GSTM1 null genotype with HNSCC risk was observed in smokers. CONCLUSIONS/SIGNIFICANCE: This meta-analysis presented additional evidence of the association between GSTM1 and GSTT1 polymorphisms and HNSCC risk.

  7. Patient Choice of Nonsurgical Treatment Contributes to Disparities in Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Parhar, Harman S; Anderson, Donald W; Janjua, Arif S; Durham, J Scott; Prisman, Eitan

    2018-06-01

    Objectives There are well-established outcome disparities among different demographic groups with head and neck squamous cell carcinoma (HNSCC). We aimed to investigate the potential contribution of patient choice of nonsurgical treatment to these disparities by estimating the rate of this phenomenon, identifying its predictors, and estimating the effect on cancer-specific survival. Study Design Retrospective nationwide analysis. Settings Surveillance, Epidemiology, and End Results Database (2004-2014). Subjects and Methods Patients with HNSCC, who were recommended for primary surgery, were included. Multivariable logistic regression was used to identify demographic and clinical factors associated with patient choice of nonsurgical treatment, and Kaplan Meier/Cox regression was used to analyze survival. Results Of 114,506 patients with HNSCC, 58,816 (51.4%) were recommended for primary surgery, and of those, 1550 (2.7%) chose nonsurgical treatment. Those who chose nonsurgical treatment were more likely to be older (67.1 ± 12.6 vs 63.6 ± 13.1, P unmarried (OR married, 0.50; 95% CI, 0.44-0.58), had an advanced tumor, and had a hypopharyngeal or laryngeal primary. Choice of nonsurgical treatment imparted a 2.16-fold (95% CI, 2.02-2.30) increased risk of cancer-specific death. Conclusion Of the patients, 2.7% chose nonsurgical treatment despite a provider recommendation that impairs survival. Choice of nonsurgical treatment is associated with older age, having Black or Asian ethnicity, being unmarried, having an advanced stage tumor, and having a primary site in the hypopharynx or larynx. Knowledge of these disparities may help providers counsel patients and help patients make informed decisions.

  8. Quality of life assessment in patients treated for metastatic cutaneous squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Wang, A Y; Palme, C E; Wang, J T; Morgan, G J; Gebski, V; Gilchrist, J; Veness, M J

    2013-07-01

    Treatment for metastatic cutaneous head and neck squamous cell carcinoma is usually multimodal and associated with morbidity. This study aimed to evaluate the impact of treatment on patients' quality of life. Cross-sectional survey of 42 patients (35 men, 7 women) at least 6 months after metastatic cutaneous head and neck squamous cell carcinoma treatment, using two standardised quality of life questionnaires: the Functional Assessment of Cancer Therapy - Head and Neck questionnaire and the Facial Disability Index, with statistical analysis to identify potential predictors of outcome. Female gender correlated with significantly lower Facial Disability Index physical function scores (p = 0.017). Alcohol consumption correlated with significantly better scores for Functional Assessment social well-being (p = 0.016), general total score (p = 0.041) and overall total score (p = 0.033), and for Facial Disability Index physical function (p = 0.034). Marital status, education, employment, chemotherapy, time from last treatment, parotidectomy and facial nerve sacrifice did not affect quality of life. The commonest patient complaints were dry mouth (76 per cent), altered voice quality and strength (55 per cent), and physical appearance (45 per cent). Female gender predicts worse quality of life, while alcohol consumption (versus none) predicted for better quality of life.

  9. SKLB188 inhibits the growth of head and neck squamous cell carcinoma by suppressing EGFR signalling.

    Science.gov (United States)

    Barzegar, Mansoureh; Ma, Shuang; Zhang, Chao; Chen, Xin; Gu, Ying; Shang, Chaowei; Jiang, Xiaojuan; Yang, Jiao; Nathan, Cherie-Ann; Yang, Shengyong; Huang, Shile

    2017-10-10

    Overexpression of epidermal growth factor receptor (EGFR) occurs in approximately 90% of head and neck squamous cell carcinoma (HNSCC), and is correlated with poor prognosis. Thus, targeting EGFR is a promising strategy for treatment of HNSCC. Several small molecule EGFR inhibitors have been tested in clinical trials for treatment of HNSCC, but none of them are more effective than the current chemotherapeutic drugs. Thus, it is urgently needed to develop novel EGFR inhibitors for HNSCC treatment. By screening an in-house focused library containing approximately 650 000 known kinase inhibitors and kinase inhibitor-like compounds containing common kinase inhibitor core scaffolds, we identified SKLB188 as a lead compound for inhibition of EGFR. The anticancer effects of SKLB188 on HNSCC cells were investigated by in vitro cell growth, cell cycle and apoptosis assays, as well as in vivo FaDu xenograft mouse model. Molecular docking, in vitro kinase profiling and western blotting were performed to characterise EGFR as the molecular target. SKLB188 inhibited HNSCC cell proliferation by inducing G 1 cell cycle arrest, which was associated with downregulating the expression of Cdc25A, cyclins D1/A and cyclin-dependent kinases (CDK2/4), and upregulating the expression of cyclin-dependent kinase (CDK) inhibitors (p21 Cip1 and p27 Kip1 ), leading to decreased phosphorylation of Rb. SKLB188 also induced caspase-dependent apoptosis of HNSCC cells by downregulating the expression of Mcl-1 and survivin. Molecular docking revealed that SKLB188 could bind to the kinase domain of EGFR through hydrogen bonds and hydrophobic interactions. In vitro kinase assay showed that SKLB188 inhibited the activity of a recombinant human EGFR very potently (IC 50 =5 nM). Western blot analysis demonstrated that SKLB188 inhibited the phosphorylation of EGFR and its downstream targets, extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) and Akt in the cells. In addition, SKLB188 dose

  10. Stereotactic Body Radiotherapy for Head and Neck Tumors

    Science.gov (United States)

    2016-04-18

    Squamous Cell Carcinoma of the Head and Neck; Nasopharyngeal Carcinoma; Salivary Gland Cancer; Head and Neck Sarcoma; Paraganglioma of Head and Neck; Chordoma of Head and Neck; Chondrosarcoma of Head and Neck; Angiofibroma of Head and Neck

  11. Identification of a Novel Proto-oncogenic Network in Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Georgy, Smitha R; Cangkrama, Michael; Srivastava, Seema; Partridge, Darren; Auden, Alana; Dworkin, Sebastian; McLean, Catriona A; Jane, Stephen M; Darido, Charbel

    2015-09-01

    The developmental transcription factor Grainyhead-like 3 (GRHL3) plays a critical tumor suppressor role in the mammalian epidermis through direct regulation of PTEN and the PI3K/AKT/mTOR signaling pathway. GRHL3 is highly expressed in all tissues derived from the surface ectoderm, including the oral cavity, raising a question about its potential role in suppression of head and neck squamous cell carcinoma (HNSCC). We explored the tumor suppressor role of Grhl3 in HNSCC using a conditional knockout (Grhl3 (∆/-) /K14Cre (+) ) mouse line (n = 26) exposed to an oral chemical carcinogen. We defined the proto-oncogenic pathway activated in the HNSCC derived from these mice and assessed it in primary human HNSCC samples, normal oral epithelial cell lines carrying shRNA to GRHL3, and human HNSCC cell lines. Data were analyzed with two-sided chi square and Student's t tests. Deletion of Grhl3 in oral epithelium in mice did not perturb PTEN/PI3K/AKT/mTOR signaling, but instead evoked loss of GSK3B expression, resulting in stabilization and accumulation of c-MYC and aggressive HNSCC. This molecular signature was also evident in a subset of primary human HNSCC and HNSCC cell lines. Loss of Gsk3b in mice, independent of Grhl3, predisposed to chemical-induced HNSCC. Restoration of GSK3B expression blocked proliferation of normal oral epithelial cell lines carrying shRNA to GRHL3 (cell no., Day 8: Scramble ctl, 616±21.8 x 10(3) vs GRHL3-kd, 1194±44 X 10(3), P < .001; GRHL3-kd vs GRHL3-kd + GSK3B, 800±98.84 X 10(3), P = .003) and human HNSCC cells. We defined a novel molecular signature in mammalian HNSCC, suggesting new treatment strategies targeting the GRHL3/GSK3B/c-MYC proto-oncogenic network. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Elevated expression of MMP-13 and TIMP-1 in head and neck squamous cell carcinomas may reflect increased tumor invasiveness

    International Nuclear Information System (INIS)

    Culhaci, Nil; Metin, Kubilay; Copcu, Eray; Dikicioglu, Emel

    2004-01-01

    Matrix metalloproteinases [MMPs], which degrade the extracellular matrix, play an important role in the invasion and metastasis of squamous cell carcinomas. One MMP, MMP-13, is thought to play a central role in MMP activation. The purpose of this study was to investigate MMP-13 and TIMP-1 expression in squamous cell carcinomas of the head and neck and to relate these levels of expression to histologic patterns of invasion. This study included T1 lesions obtained via biopsy from the larynx, tongue, and skin/mucosa of 78 patients with head and neck squamous cell carcinomas. The relationship between expression of MMP-13 and TIMP-1 and the mode of tumor invasion [MI] was evaluated immunohistochemically, using breast carcinoma tissue as a positive control. Increased expression was observed in highly invasive tumors, as reflected by the significant correlation between the degree of staining for MMP-13 or TIMP-1 and MI grade [p < 0.05]. There was no significant relationship between the degree of staining for MMP-13 or TIMP-1 and patient age, sex, tumor site, or tumor histologic grade. In addition, levels of staining for MMP-13 did not correlate with levels of staining for TIMP-1. The expression of MMP-13 and TIMP-1 appears to play an important role in determining the invasive capacity of squamous cell carcinomas of the head and neck. Whereas additional studies are needed to confirm these findings, evaluating expression of these MMPs in small biopsy samples may be useful in determining the invasive capacity of these tumors at an earlier stage

  13. Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Besic Gyenge Emina

    2011-08-01

    Full Text Available Abstract Background Head and neck squamous cell carcinoma (HNSCC is currently the eighth leading cause of cancer death worldwide. The often severe side effects, functional impairments and unfavorable cosmetic outcome of conventional therapies for HNSCC have prompted the quest for novel treatment strategies, including the evaluation of nanotechnology to improve e.g. drug delivery and cancer imaging. Although silica nanoparticles hold great promise for biomedical applications, they have not yet been investigated in the context of HNSCC. In the present in-vitro study we thus analyzed the cytotoxicity, uptake and intracellular fate of 200-300 nm core-shell silica nanoparticles encapsulating fluorescent dye tris(bipyridineruthenium(II dichloride with hydroxyl-, aminopropyl- or PEGylated surface modifications (Ru@SiO2-OH, Ru@SiO2-NH2, Ru@SiO2-PEG in the human HNSCC cell line UMB-SCC 745. Results We found that at concentrations of 0.125 mg/ml, none of the nanoparticles used had a statistically significant effect on proliferation rates of UMB-SCC 745. Confocal and transmission electron microscopy showed an intracellular appearance of Ru@SiO2-OH and Ru@SiO2-NH2 within 30 min. They were internalized both as single nanoparticles (presumably via clathrin-coated pits or in clusters and always localized to cytoplasmic membrane-bounded vesicles. Immunocytochemical co-localization studies indicated that only a fraction of these nanoparticles were transferred to early endosomes, while the majority accumulated in large organelles. Ru@SiO2-OH and Ru@SiO2-NH2 nanoparticles had never been observed to traffic to the lysosomal compartment and were rather propagated at cell division. Intracellular persistence of Ru@SiO2-OH and Ru@SiO2-NH2 was thus traceable over 5 cell passages, but did not result in apparent changes in cell morphology and vitality. In contrast to Ru@SiO2-OH and Ru@SiO2-NH2 uptake of Ru@SiO2-PEG was minimal even after 24 h. Conclusions Our study is the

  14. CD147 and AGR2 expression promote cellular proliferation and metastasis of head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sweeny, Larissa, E-mail: larissasweeny@gmail.com [Department of Surgery, University of Alabama, Division of Otolaryngology-Head and Neck Surgery, 1670 University Boulevard, Volker Hall G082, Birmingham, Alabama (United States); Liu, Zhiyong; Bush, Benjamin D.; Hartman, Yolanda [Department of Surgery, University of Alabama, Division of Otolaryngology-Head and Neck Surgery, 1670 University Boulevard, Volker Hall G082, Birmingham, Alabama (United States); Zhou, Tong [Department of Medicine, Division of Immunology and Rheumatology, 1825 University Boulevard, Shelby Biomedical Research Building 302, Birmingham, Alabama (United States); Rosenthal, Eben L., E-mail: oto@uab.edu [Department of Surgery, University of Alabama, Division of Otolaryngology-Head and Neck Surgery, 1670 University Boulevard, Volker Hall G082, Birmingham, Alabama (United States)

    2012-08-15

    The signaling pathways facilitating metastasis of head and neck squamous cell carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane glycoprotein known to induce cell migration and invasion. AGR2 is a secreted peptide also known to promote cell metastasis. Here we describe their importance in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation, migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased primary tumor growth as well as regional and distant metastasis. -- Highlights: Black-Right-Pointing-Pointer We investigated AGR2 in head and neck squamous cell carcinoma for the first time. Black-Right-Pointing-Pointer We explored the relationship between AGR2 and CD147 for the first time. Black-Right-Pointing-Pointer AGR2 and CD147 appear to co-localize in head and squamous cell carcinoma samples. Black-Right-Pointing-Pointer Knockdown of both AGR2 and CD147 reduced migration and invasion in vitro. Black-Right-Pointing-Pointer Knockdown of both AGR2 and CD147 decreased metastasis in vivo.

  15. CD147 and AGR2 expression promote cellular proliferation and metastasis of head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Sweeny, Larissa; Liu, Zhiyong; Bush, Benjamin D.; Hartman, Yolanda; Zhou, Tong; Rosenthal, Eben L.

    2012-01-01

    The signaling pathways facilitating metastasis of head and neck squamous cell carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane glycoprotein known to induce cell migration and invasion. AGR2 is a secreted peptide also known to promote cell metastasis. Here we describe their importance in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation, migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased primary tumor growth as well as regional and distant metastasis. -- Highlights: ► We investigated AGR2 in head and neck squamous cell carcinoma for the first time. ► We explored the relationship between AGR2 and CD147 for the first time. ► AGR2 and CD147 appear to co-localize in head and squamous cell carcinoma samples. ► Knockdown of both AGR2 and CD147 reduced migration and invasion in vitro. ► Knockdown of both AGR2 and CD147 decreased metastasis in vivo.

  16. Tyrosine kinase domain mutations of EGFR gene in head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Vatte C

    2017-03-01

    Full Text Available Chittibabu Vatte,1 Ali M Al Amri,2 Cyril Cyrus,1 Shahanas Chathoth,1 Sadananda Acharya,3 Tariq Mohammad Hashim,4 Zhara Al Ali,2 Saleh Tawfeeq Alshreadah,2 Ahmed Alsayyah,4 Amein K Al-Ali5 1Department of Genetic Research, Institute for Research and Medical Consultation, University of Dammam, Dammam, 2Department of Internal Medicine, King Fahd Hospital of the University, University of Dammam, Al-Khobar, 3Department of Stemcell Research, Institute for Research and Medical Consultation, 4Department of Pathology, King Fahd Hospital of the University, University of Dammam, Al-Khobar, 5Department of Biochemistry, College of Medicine, University of Dammam, Dammam, Kingdom of Saudi Arabia Background: Epidermal growth factor receptor (EGFR is a commonly altered gene that is identified in various cancers, including head and neck squamous cell carcinoma (HNSCC. Therefore, EGFR is a promising molecular marker targeted by monoclonal antibodies and small molecule inhibitors targeting the tyrosine kinase (TK domain. Objective: The objective of this study was to investigate the spectrum of mutations in exons 18, 19, 20, and 21 of the EGFR gene in HNSCC patients. Materials and methods: This retrospective study included 47 confirmed HNSCC cases. Mutations in the TK domain, exons 18, 19, 20, and 21 of the EGFR gene, were detected by Scorpion® chemistry and ARMS® technologies on Rotor-Gene Q real-time polymerase chain reaction.Results: The tumors exhibited EGFR-TK domain mutations in 57% of cases. Four cases of T790M mutations were reported for the first time among HNSCC patients. Out of the total mutations, L861Q (exon 21, exon 20 insertions and deletions of exon 19 accounted for the majority of mutations (21%, 19%, and 17%, respectively. EGFR mutation status was correlated with the higher grade (P=0.026 and advanced stage (P=0.034 of HNSCC tumors.Conclusion: Higher frequency of EGFR-TK domain mutations together with the presence of the T790M mutation suggests

  17. Distant Metastases in Head-and-Neck Squamous Cell Carcinoma Treated With Intensity-Modulated Radiotherapy

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    Yao Min, E-mail: min.yao@uhhospitals.org [Department of Radiation Oncology, University Hospitals Case Medical Center, Cleveland, OH (United States); Lu Minggen [School of Public Health, University of Nevada at Reno, Reno, NV (United States); Savvides, Panayiotis S. [Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH (United States); Rezaee, Rod; Zender, Chad A.; Lavertu, Pierre [Department of Otolaryngology-Head and Neck Surgery, University Hospitals Case Medical Center, Cleveland, OH (United States); Buatti, John M. [Department of Radiation Oncology, University of Iowa, Iowa City, IA (United States); Machtay, Mitchell [Department of Radiation Oncology, University Hospitals Case Medical Center, Cleveland, OH (United States)

    2012-06-01

    Purpose: To determine the pattern and risk factors for distant metastases in head-and-neck squamous cell carcinoma (HNSCC) after curative treatment with intensity-modulated radiotherapy (IMRT). Methods and Materials: This was a retrospective study of 284 HNSCC patients treated in a single institution with IMRT. Sites included were oropharynx (125), oral cavity (70), larynx (55), hypopharynx (17), and unknown primary (17). American Joint Committee on Cancer stage distribution includes I (3), II (19), III (42), and IV (203). There were 224 males and 60 females with a median age of 57. One hundred eighty-six patients were treated with definitive IMRT and 98 postoperative IMRT. One hundred forty-nine patients also received concurrent cisplatin-based chemotherapy. Results: The median follow-up for all patients was 22.8 months (range, 0.07-77.3 months) and 29.5 months (4.23-77.3 months) for living patients. The 3-year local recurrence-free survival, regional recurrence-free survival, locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 94.6%, 96.4%, 92.5%, 84.1%, and 68.95%, respectively. There were 45 patients with distant metastasis. In multivariate analysis, distant metastasis was strongly associated with N stage (p = 0.046), T stage (p < 0.0001), and pretreatment maximum standardized uptake value of the lymph node (p = 0.006), but not associated with age, gender, disease sites, pretreatment standardized uptake value of the primary tumor, or locoregional control. The freedom from distant metastasis at 3 years was 98.1% for no factors, 88.6% for one factor, 68.3% for two factors, and 41.7% for three factors (p < 0.0001 by log-rank test). Conclusion: With advanced radiation techniques and concurrent chemotherapy, the failure pattern has changed with more patients failing distantly. The majority of patients with distant metastases had no local or regional failures, indicating that these patients might have microscopic distant

  18. Dosimetric Factors Associated With Long-Term Dysphagia After Definitive Radiotherapy for Squamous Cell Carcinoma of the Head and Neck

    International Nuclear Information System (INIS)

    Caudell, Jimmy J.; Schaner, Philip E.; Desmond, Renee A.; Meredith, Ruby F.; Spencer, Sharon A.; Bonner, James A.

    2010-01-01

    Purpose: Intensification of radiotherapy and chemotherapy for head-and-neck cancer may lead to increased rates of dysphagia. Dosimetric predictors of objective findings of long-term dysphagia were sought. Methods and Materials: From an institutional database, 83 patients were identified who underwent definitive intensity-modulated radiotherapy for squamous cell carcinoma of the head and neck, after exclusion of those who were treated for a second or recurrent head-and-neck primary lesion, had locoregional recurrence at any time, had less than 12 months of follow-up, or had postoperative radiotherapy. Dosimetric parameters were analyzed relative to three objective endpoints as a surrogate for severe long-term dysphagia: percutaneous endoscopic gastrostomy (PEG) tube dependence at 12 months, aspiration on modified barium swallow, or pharyngoesophageal stricture requiring dilation. Results: Mean dose greater than 41 Gy and volume receiving 60 Gy (V 60 ) greater than 24% to the larynx were significantly associated with PEG tube dependence and aspiration. V 60 greater than 12% to the inferior pharyngeal constrictor was also significantly associated with increased PEG tube dependence and aspiration. V 65 greater than 33% to the superior pharyngeal constrictor or greater than 75% to the middle pharyngeal constrictor was associated with pharyngoesophageal stricture requiring dilation. Conclusions: Doses to the larynx and pharyngeal constrictors predicted long-term swallowing complications, even when controlled for other clinical factors. The addition of these structures to intensity-modulated radiotherapy optimization may reduce the incidence of dysphagia, although cautious clinical validation is necessary.

  19. Correlation of NF-κB signal pathway with tumor metastasis of human head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Yan, Ming; Xu, Qin; Zhang, Ping; Zhou, Xiao-jian; Zhang, Zhi-yuan; Chen, Wan-tao

    2010-01-01

    Nuclear factor-kappa B (NF-κB) signaling constitutes a key event in the multistep process of carcinogenesis, progression and treatment in many cancer types. However, the significance of NF-κB pathway for complex and tissue-specific aspects of head and neck cancer progression, such as invasion and metastasis, is less understood. The expression of NF-κB p65 in squamous cell carcinoma of the head and neck (SCCHN) clinical specimens by immunohistochemistry. The role of NF-κB activity in head and neck squamous cell carcinoma was determined by western blot, reporter assay and EMSA analysis in vitro and metastasis assays in vivo in different metastatic potential tumor cells. Furthermore, the apoptosis rate and expression of metastasis-related protein such as MMP9 and VEGF were examined by Annexin V/PI staining and Western blot, respectively. A higher level of active nuclear-localized NF-κB was observed in the metastatic SCCHN specimens group (p < 0.01). The NF-κB activities of SCCHN cell lines with different metastatic potentials were then determined and in excellent agreement with results found in SCCHN specimens, highly metastatic SCCHN cell lines expressed high level of NF-κB activity. The treatment of highly metastatic SCCHN cells with NF-κB inhibitors reduced the in vitro cell invasion capacity of the cells without affecting the apoptotic rate. Additionally, the NF-κB inhibitors significantly inhibited the experimental lung metastasis of Tb cells and lymph node metastasis of TL cells in nude mice. Furthermore, the expression of metastasis-related proteins, such as matrix metalloproteinase 9 and vascular endothelial growth factor, was inhibited by pyrrolidine dithiocarbonate. This study suggests that NF-κB activity significantly contributes to tumor hematologic and lymphatic metastases and may aid in the development of early detection methods or therapies targeting non-conventional molecular targets

  20. Ectopic expression of protein kinase C-β sensitizes head and neck squamous cell carcinoma to diterpene esters.

    Science.gov (United States)

    Adams, Ryan A; D'Souza, Marjorie M A; Pierce, Carly J; Korica, Natasa; Wallwork, Ben; Parsons, Peter G; Panizza, Benedict; Boyle, Glen M

    2015-03-01

    The objective of this study was to examine the effect of specific Protein kinase C (PKC) isoform re-expression in solid malignancies, particularly head and neck squamous cell carcinoma cell lines, and the impact this may have on treatment with known activators of PKC. The constitutive expression of PKC isoforms were determined in six head and neck squamous cell carcinoma (SCC) cell lines. Cytotoxicity of the prototypic phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the novel diterpene ester PEP005 was established. Viral transduction to re-express PKCβ isoforms in two of these cell lines was performed, and its effect on the sensitivity to the compounds was quantified. Tongue and hypopharyngeal SCC cell lines were resistant to both TPA and PEP005, with the concentration required to inhibit growth by 50% (IC50) being >1,000 ng/ml. CAL-27 (tongue SCC) and FaDu (hypopharyngeal SCC) cell lines re-expressing PKCβI and -βII isoforms demonstrated IC50 of 1-5 ng/ml with TPA or PEP005. Re-expression of PKCβ in head and neck SCC cell lines leads to cells one thousand-times more sensitive to the cytotoxic effects of phorbol or diterpene esters in culture. This highlights the importance of the isoform in tumor progression and presents the potential benefit of these compounds in malignancies expressing the protein, and in combination therapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. A PET/CT-based strategy is a stronger predictor of survival than a standard imaging strategy in patients with head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Rohde, Max; Nielsen, Anne L; Pareek, Manan

    2018-01-01

    Purpose: To examine whether tumor staging by upfront (18)F-fluoro-deoxy-glucose-positron emission tomography/computed tomography (PET/CT) leads to improved discrimination of survival, when compared with traditionally used imaging strategies based on chest X-ray + head and neck magnetic resonance...... imaging (CXR/MRI) or chest computed tomography + head and neck MRI (CCT/MRI) in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Blinded prospective cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were recruited at Odense University...

  2. The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines

    International Nuclear Information System (INIS)

    Heiduschka, G.; Lill, C.; Schneider, S.; Kotowski, U.; Thurnher, D.; Seemann, R.; Kornek, G.; Schmid, R.

    2014-01-01

    Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity. (orig.) [de

  3. Recurrent copy number gains of ACVR1 and corresponding transcript overexpression are associated with survival in head and neck squamous cell carcinomas

    DEFF Research Database (Denmark)

    Ambrosio, Eliane P; Drigo, Sandra A; Bérgamo, Nádia A

    2011-01-01

    AIMS: This study aimed to evaluate the copy number alteration on 2q24, its association with ACVR1 transcript expression and the prognostic value of these data in head and neck squamous cell carcinomas. METHODS AND RESULTS: Twenty-eight samples of squamous cell carcinoma were evaluated by fluoresc...

  4. E-cadherin expression and prognosis of head and neck squamous cell carcinoma: evidence from 19 published investigations

    Directory of Open Access Journals (Sweden)

    Ren X

    2016-04-01

    Full Text Available Xusheng Ren,1,2 Jianning Wang,2 Xuefen Lin,1,3 Xuxia Wang1,3 1Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Shandong University, 2Department of Oral and Maxillofacial Surgery, Jinan Stomatological Hospital, 3Shandong Province Key Laboratory of Oral Tissue Regeneration, Stomatological Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China Objective: The objective of this study was to review the published literature and investigate whether E-cadherin gene is a prognostic factor in head and neck squamous cell carcinoma by conducting a meta-analysis.Methods: Studies were identified from the databases Embase, Medline, and Cochrane Library by using the keywords “E-cadherin gene” and “head and neck cancer”. Overall survival (OS and disease-free survival (DFS were the primary outcome measurements.Results: Our literature review identified 1,458 articles; 19 studies with a total number of 2,012 cases were eligible for inclusion in the meta-analysis. The hazard ratio (HR for OS of patients with decreased expression of E-cadherin gene was 0.57 (95% CI =0.37, 0.89; P=0.000. However, statistical heterogeneity was unacceptably high (I2=74.5%, P=0.000. After sensitivity analysis, heterogeneity became acceptable, and the effect measure was still significant (I2=7.0%; HR =0.52; 95% CI =0.40, 0.66; P=0.000. The HR for DFS was 0.53 (95% CI =0.42, 0.67; P=0.000.Conclusion: This meta-analysis showed clear evidence that high E-cadherin gene expression is a positive prognostic factor of head and neck squamous cell carcinoma, resulting in better OS and DFS. However, this conclusion must be interpreted with caution due to a few limitations. Keywords: E-cadherin gene, prognosis, head and neck squamous cell carcinoma, immunohistochemistry 

  5. Evidence-based radiation oncology in head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Corvo, Renzo

    2007-01-01

    Background and purpose: Historically, radiation therapy (RT) has been an available treatment option for patients with early resectable head and neck squamous cell carcinoma (HNSCC) and the sole therapy for those with unresectable or inoperable disease. Recently, four noteworthy strategies have emerged for the improvement of therapeutic outcome in the curative treatment of HNSCC: they include the development of altered fractionation radiotherapy, integration of chemotherapy with radiotherapy, incorporation of intensity-modulated radiotherapy and the introduction of targeted biological therapy. These strategies are briefly reviewed in an effort to help interpret evidence-based data and to facilitate clinical-decision making in a clinical context. Materials and methods: For patients with early stage HNSCC no level 1 study exists in which radiation therapy is compared with conservative surgery for the evaluation of local control or survival. Only evidence from prospective and retrospective cohort studies is available to evaluate the role external radiotherapy and/or brachytherapy currently play in limited disease. For patients with locally advanced HNSCC the recommendations to address the questions about better treatment in resectable and unresectable tumors are based on more than 100 randomized Phase III trials included in six meta-analyses on chemo-radiotherapy and/or altered fractionation. Data from phase II trials and cohort studies help interpret the advances in intensity-modulated radiotherapy. Results: External radiotherapy and/or brachytherapy are crucial treatment options in patients with early stage HNSCC. For patients with locally advanced HNSCC, where outcome with conventional radiotherapy is poor, meta-analyses and collective data showed that loco-regional control may be improved at high level of evidence by altered fractionation radiotherapy, chemo-radiotherapy with concomitant approach or association of selected hypoxic cell radiosensitizer with

  6. Synchronous gastric and duodenal metastases from head and neck squamous cell carcinoma: a unique presentation of upper gastrointestinal bleeding.

    Science.gov (United States)

    Tarangelo, Nicholas P; Kistler, C Andrew; Daitch, Zachary; Jiang, Wei; Quirk, Daniel M

    2018-01-01

    Metastatic disease to the stomach or duodenum is an infrequent diagnosis, and head and neck squamous cell carcinoma (HNSCC) is one of the least common primary malignancies that lead to gastric or duodenal metastases. We report the case of a 65-year-old man with human immunodeficiency virus infection and previously diagnosed HNSCC who presented with melena. The patient had a percutaneous endoscopic gastrostomy tube placed 3 months prior to his presentation. Laboratory testing was significant for normocytic anemia and a digital rectal examination was positive for melena. Esophagogastroduodenoscopy revealed numerous cratered nodules with contact bleeding in the stomach as well as the duodenum that appeared malignant. Biopsies of the gastric and duodenal nodules were positive for p40 and CK 5/6, consistent with metastatic squamous cell carcinoma.

  7. ING Genes Work as Tumor Suppressor Genes in the Carcinogenesis of Head and Neck Squamous Cell Carcinoma

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    Xiaohan Li

    2011-01-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer in the world. The evolution and progression of HNSCC are considered to result from multiple stepwise alterations of cellular and molecular pathways in squamous epithelium. Recently, inhibitor of growth gene (ING family consisting of five genes, ING1 to ING5, was identified as a new tumor suppressor gene family that was implicated in the downregulation of cell cycle and chromatin remodeling. In contrast, it has been shown that ING1 and ING2 play an oncogenic role in some cancers, this situation being similar to TGF-β. In HNSCC, the ING family has been reported to be downregulated, and ING translocation from the nucleus to the cytoplasm may be a critical event for carcinogenesis. In this paper, we describe our recent results and briefly summarize current knowledge regarding the biologic functions of ING in HNSCC.

  8. Initial Experience of 3-Tesla Apparent Diffusion Coefficient Values in Characterizing Squamous Cell Carcinomas of the Head and Neck

    International Nuclear Information System (INIS)

    Srinivasan, A.; Dvorak, R.; Rohrer, S.; Mukherji, S.K.

    2008-01-01

    Background: With the increased clinical use of 3-Tesla (3T) magnets, it becomes important to identify the potential applications of advanced magnetic resonance (MR) imaging techniques such as diffusion-weighted imaging in head and neck pathologies. Purpose: To establish the 3T apparent diffusion coefficient (ADC) values for normal neck structures, and to examine the utility of ADC values in distinguishing head and neck squamous cell carcinomas (HNSCC) from normal neck anatomy. Material and Methods: 3T diffusion-weighted imaging was performed on 10 normal volunteers and 10 patients with known HNSCC. In the volunteers, mean ADC was calculated in the parotid gland, submandibular gland, base of the tongue, pterygoid muscle, masseter muscle, paraspinal muscles, true vocal cord, thyroid gland, thyroid cartilage, cricoid cartilage, and lymph nodes. The mean tumor ADC value was calculated from the 10 patients with HNSCC and compared with the normal ADC values from various neck structures. Results: The mean ADC value measured in the HNSCC was 1.101 (±0.214)x10 -3 mm 2 /s. This was significantly lower than ADC values of paraspinal muscles, pterygoid muscle, masseter muscle, thyroid gland, and base of the tongue (P=0.0006, 0.0002, 0.0001, 0.001, and 0.002, respectively). The tumor ADC values were not significantly different from ADC values of parotid and submandibular glands (P=0.057 and 0.14, respectively). Conclusion: 3T ADC values show potential for distinguishing HNSCC from normal extracranial head and neck structures

  9. Initial Experience of 3-Tesla Apparent Diffusion Coefficient Values in Characterizing Squamous Cell Carcinomas of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Srinivasan, A.; Dvorak, R.; Rohrer, S.; Mukherji, S.K. (Dept. of Radiology, Division of Neuroradiology, Univ. of Michigan Health System, Ann Arbor, MI (United States))

    2008-11-15

    Background: With the increased clinical use of 3-Tesla (3T) magnets, it becomes important to identify the potential applications of advanced magnetic resonance (MR) imaging techniques such as diffusion-weighted imaging in head and neck pathologies. Purpose: To establish the 3T apparent diffusion coefficient (ADC) values for normal neck structures, and to examine the utility of ADC values in distinguishing head and neck squamous cell carcinomas (HNSCC) from normal neck anatomy. Material and Methods: 3T diffusion-weighted imaging was performed on 10 normal volunteers and 10 patients with known HNSCC. In the volunteers, mean ADC was calculated in the parotid gland, submandibular gland, base of the tongue, pterygoid muscle, masseter muscle, paraspinal muscles, true vocal cord, thyroid gland, thyroid cartilage, cricoid cartilage, and lymph nodes. The mean tumor ADC value was calculated from the 10 patients with HNSCC and compared with the normal ADC values from various neck structures. Results: The mean ADC value measured in the HNSCC was 1.101 (+-0.214)x10-3mm2/s. This was significantly lower than ADC values of paraspinal muscles, pterygoid muscle, masseter muscle, thyroid gland, and base of the tongue (P=0.0006, 0.0002, 0.0001, 0.001, and 0.002, respectively). The tumor ADC values were not significantly different from ADC values of parotid and submandibular glands (P=0.057 and 0.14, respectively). Conclusion: 3T ADC values show potential for distinguishing HNSCC from normal extracranial head and neck structures

  10. Tumor microenvironment in head and neck squamous cell carcinomas: predictive value and clinical relevance of hypoxic markers. A review.

    Science.gov (United States)

    Hoogsteen, Ilse J; Marres, Henri A M; Bussink, Johan; van der Kogel, Albert J; Kaanders, Johannes H A M

    2007-06-01

    Hypoxia and tumor cell proliferation are important factors determining the treatment response of squamous cell carcinomas of the head and neck. Successful approaches have been developed to counteract these resistance mechanisms although usually at the cost of increased short- and long-term side effects. To provide the best attainable quality of life for individual patients and the head and neck cancer patient population as a whole, it is of increasing importance that tools be developed that allow a better selection of patients for these intensified treatments. A literature review was performed with special focus on the predictive value and clinical relevance of endogenous hypoxia-related markers. New methods for qualitative and quantitative assessment of functional microenvironmental parameters such as hypoxia, proliferation, and vasculature have identified several candidate markers for future use in predictive assays. Hypoxia-related markers include hypoxia inducible factor (HIF)-1alpha, carbonic anhydrase IX, glucose transporters, erythropoietin receptor, osteopontin, and others. Although several of these markers and combinations of markers are associated with treatment outcome, their clinical value as predictive factors remains to be established. A number of markers and marker profiles have emerged that may have potential as a predictive assay. Validation of these candidate assays requires testing in prospective trials comparing standard treatment against experimental treatments targeting the related microregional constituent. (c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.

  11. Value of PET/CT 3D visualization of head and neck squamous cell carcinoma extended to mandible.

    Science.gov (United States)

    Lopez, R; Gantet, P; Julian, A; Hitzel, A; Herbault-Barres, B; Alshehri, S; Payoux, P

    2018-05-01

    To study an original 3D visualization of head and neck squamous cell carcinoma extending to the mandible by using [18F]-NaF PET/CT and [18F]-FDG PET/CT imaging along with a new innovative FDG and NaF image analysis using dedicated software. The main interest of the 3D evaluation is to have a better visualization of bone extension in such cancers and that could also avoid unsatisfying surgical treatment later on. A prospective study was carried out from November 2016 to September 2017. Twenty patients with head and neck squamous cell carcinoma extending to the mandible (stage 4 in the UICC classification) underwent [18F]-NaF and [18F]-FDG PET/CT. We compared the delineation of 3D quantification obtained with [18F]-NaF and [18F]-FDG PET/CT. In order to carry out this comparison, a method of visualisation and quantification of PET images was developed. This new approach was based on a process of quantification of radioactive activity within the mandibular bone that objectively defined the significant limits of this activity on PET images and on a 3D visualization. Furthermore, the spatial limits obtained by analysis of the PET/CT 3D images were compared to those obtained by histopathological examination of mandibular resection which confirmed intraosseous extension to the mandible. The [18F]-NaF PET/CT imaging confirmed the mandibular extension in 85% of cases and was not shown in [18F]-FDG PET/CT imaging. The [18F]-NaF PET/CT was significantly more accurate than [18F]-FDG PET/CT in 3D assessment of intraosseous extension of head and neck squamous cell carcinoma. This new 3D information shows the importance in the imaging approach of cancers. All cases of mandibular extension suspected on [18F]-NaF PET/CT imaging were confirmed based on histopathological results as a reference. The [18F]-NaF PET/CT 3D visualization should be included in the pre-treatment workups of head and neck cancers. With the use of a dedicated software which enables objective delineation of

  12. C2-Ceramide Induces Cell Death and Protective Autophagy in Head and Neck Squamous Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Wenyuan Zhu

    2014-02-01

    Full Text Available Ceramides are second messengers involved in several intracellular processes in cancer cells, amongst others. The aim of this study was to evaluate the anti-tumor efficacy of C2-ceramide (C2-Cer; N-acetyl-D-sphingosine by investigating cell death and autophagy in head and neck squamous cell carcinoma (HNSCC cells. C2-Cer showed concentration-dependent cytotoxicity in HN4 and HN30 cell lines. It simultaneously induced caspase-3-independent apoptosis and programmed necrosis. C2-Cer markedly increased the expression level of microtubule-associated protein 1 light chain 3B (LC3B type II associated with protective autophagy. An autophagy inhibitor enhanced C2-Cer-mediated cytotoxicity, while a programmed-necrosis inhibitor produced the opposite effect. Furthermore, C2-Cer up-regulated the phosphorylation of extracellular signal-regulated kinase 1/2, but down-regulated its downstream substrate phospho-mammalian target of rapamycin (p-mTOR during the autophagy process. These results suggested that C2-Cer exerts anti-tumor effects by inducing programmed apoptosis and necrosis in HNSCC, and these cytotoxic effects are enhanced by an autophagy inhibitor.

  13. Cannabinoid receptor-2 immunoreactivity is associated with survival in squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Klein Nulent, Thomas J W; Van Diest, Paul J; van der Groep, Petra; Leusink, Frank K J; Kruitwagen, Cas L J J; Koole, Ronald; Van Cann, Ellen M

    2013-10-01

    The prediction of progression of individual tumours, prognosis, and survival in squamous cell carcinoma (SCC) of the head and neck is difficult. Cannabinoid-1 (CB1) and cannabinoid-2 (CB2) receptor expression is related to survival in several types of cancer, and the aim of this study was to find out whether the expression of CB1 and CB2 receptors is associated with survival in primary SCC of the head and neck. We made immunohistochemical analyses of the cannabinoid receptors on tissue arrays from 240 patients with the disease. Receptor immunoreactivity was classified as none, weak, moderate, or strong staining. Overall survival and disease-specific survival were plotted using Kaplan-Meier survival curves. A multivariate Cox proportional hazard model was created with all the relevant clinical and pathological features. Strong immunoreactivity of the CB2 receptor was significantly associated with reduced disease-specific survival (p=0.007). Cox-proportional hazard ratio (HR) showed that CB2 receptor immunoreactivity contributed to the prediction of survival (HR 3.6, 95% CI 1.5-8.7, p=0.004). Depth of invasion (HR 2.2, 95% CI 1.2-4.2, p=0.01) and vascular invasion (HR 2.5, 95% CI 1.4-4.5, p=0.001) were also associated with survival. Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  14. Profile of pembrolizumab in the treatment of head and neck squamous cell carcinoma: design development and place in therapy

    Directory of Open Access Journals (Sweden)

    Haque S

    2017-08-01

    Full Text Available Sulsal Haque,1,2 Mahender Yellu,1,2 Jaskirat Randhawa,1,2 Nooshin Hashemi-Sadraei1,2 1Division of Hematology/Oncology, Department of Medicine, University of Cincinnati, 2University of Cincinnati Cancer Institute, Cincinnati, OH, USA Abstract: Head and neck squamous cell cancer (HNSCC is the sixth most common malignancy worldwide, and despite advances in cytotoxic, surgical and radiation techniques, outcomes are still poor in those with both locally advanced and metastatic diseases. The need for development of better therapeutics along with a greater understanding of the relationship between the immune system and malignancies has led to a new therapeutic modality, immune modulators, particularly checkpoint inhibitors in HNSCC. It is now well recognized that HNSCC circumvents crucial pathways utilized by the immune system to escape surveillance. These hijacked pathways include impairing tumor antigen presentation machinery and co-opting checkpoint receptors. This understanding has led to the development of monoclonal antibodies targeting checkpoint receptors and has resulted in promising outcomes in HNSCC. This article describes the mechanisms that HNSCC utilizes to escape immune surveillance, clinical impact of checkpoint inhibitors (with a focus on pembrolizumab, ongoing studies, and future directions. Keywords: pembrolizumab, head and neck cancer, MK-3475, immunotherapy

  15. Anti EGFR therapy in the treatment of non-metastatic head and neck squamous cell carcinoma: The current evidence

    Directory of Open Access Journals (Sweden)

    Rony Benson

    2016-09-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC accounts for a large oncologic burden in the developing countries. In patients with locally advanced head and neck cancer multimodality treatment is warranted. Radiation therapy with concurrent chemotherapy has long been considered the standard for patients with disease involving the oropharynx, larynx and hypopharynx. However, addition of chemotherapy to radiotherapy increases treatment related toxicity by many folds and compliance rates decrease. In this context a systemic therapy, which when used concurrent with radiation with favorable toxicity profile is of great importance for improving disease control in locally advanced HNSCC. Anti-epithelial growth factor receptor targeted therapy emerged as a potential treatment option. In recent years many trials were conducted to find the optimum treatment option with the combination of these targeted agents. The initial trials showed excellent results with minimal morbidity and led to great enthusiasm across the globe to incorporate these regimens as a standard of care. However, subsequently many trials failed to maintain such results and now there is little agreement to the initial results achieved with these drugs. Based on the current evidence we cannot recommend the replacement of cisplatin with targeted therapy in concurrent setting. It may be considered in patients with altered renal parameters, hypersensitivity or intolerance to cisplatin. The addition of targeted therapy in addition to chemotherapy in the concurrent setting can’t also be recommended as the benefit is doubtful and is associated with a significant increase in toxicity.

  16. Oral sex and human papilloma virus-related head and neck squamous cell cancer: a review of the literature.

    Science.gov (United States)

    Shah, Ankit; Malik, Akshat; Garg, Apurva; Mair, Manish; Nair, Sudhir; Chaturvedi, Pankaj

    2017-11-01

    Head neck squamous cell carcinomas (HNSCCs) are a significant cause of morbidity and mortality all around the world. Just like tobacco and alcohol, Human papilloma virus (HPV) infection is now recognized to play a role in the pathogenesis of a subset of HNSCCs. Unprotected sexual behaviours with the HPV carrier plays an important role in transmission of this virus. The global incidence of head and neck cancers is declining, but the incidence of HPV related head and neck cancers is rapidly increasing over the last few decades. However, most institutions do not mandate documentation of sexual history or counselling of patients regarding sexual practices like they do for tobacco and alcohol addictions in HNSCC patients. The aim of this review of literature is to analyse if there is a strong evidence to correlate oral sex with HPV related HNSCC and counsel the patient's regarding sexual behaviours. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C

    2018-03-02

    The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies.

  18. Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma

    Science.gov (United States)

    Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M.; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C.

    2018-01-01

    The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies. PMID:29568372

  19. Concurrent cetuximab, cisplatin, and radiation for squamous cell carcinoma of the head and neck in vitro

    International Nuclear Information System (INIS)

    Zhang Na; Erjala, Kaisa; Kulmala, Jarmo; Qiu Xueshan; Sundvall, Maria; Elenius, Klaus; Grenman, Reidar

    2009-01-01

    Background and purpose: For locoregionally advanced HNSCC, chemoradiotherapy with cisplatin or another platinum compound is considered as one of the standard treatment regimes. Cisplatin has improved the loco-regional control, but also increased especially the acute side effects. Cetuximab blocks ligand binding and receptor activation by binding to the extracellular domain of the EGFR. The blockade of EGFR signaling in combination with cytotoxic drugs or with radiotherapy could be a novel effective management with a relatively favourable toxicity for HNSCC. In the present study we have examined in vitro a potentially novel effective management for HNSCC, cetuximab combined with cisplatin and radiotherapy. Materials and methods: Seven head and neck SCC cell lines were studied. Cetuximab concentrations of 0.22-8.20 nM and cisplatin concentrations of 0.038-0.220 μg/ml were used. In order to test the concurrent use of cetuximab, cisplatin and radiation, the cells were treated with the desired drug concentrations immediately after irradiation, plated into 96-well culture plates, and incubated for 4 weeks. The number of positive wells was counted. The PE was calculated and fraction survival data were fitted to the LQ model. AUC value was obtained with numerical integration. The types of interaction were analyzed. Results: Cetuximab and cisplatin constantly induced an additive or supra-additive effect when combined with irradiation in the seven HNSCC cell lines tested. Conclusions: We evaluated concurrent cetuximab, cisplatin, and radiation for HNSCC cell lines. Preliminary efficacy results are encouraging, and further development of this targeted combined modality paradigm is warranted.

  20. Pain as sign of recurrent disease in head and neck squamous cell carcinoma

    NARCIS (Netherlands)

    Smit, M.; Balm, A. J.; Hilgers, F. J.; Tan, I. B.

    2001-01-01

    The role of pain in head and neck cancer is seldom addressed. This retrospective study examined in a group of 190 curatively treated patients to what extent pain complaints should be considered to be the first sign of recurrent disease. The research population exists of 95 patients with a recurrent

  1. Peroxiredoxin IV Protects Cells From Radiation-Induced Apoptosis in Head-and-Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Park, Jung Je; Chang, Hyo Won; Jeong, Eun-Jeong; Roh, Jong-Lyel; Choi, Seung-Ho; Jeon, Sea-Yuong; Ko, Gyung Hyuck; Kim, Sang Yoon

    2009-01-01

    Purpose: Human peroxiredoxins (Prxs) are known as a family of thiol-specific antioxidant enzymes, among which Prx-I and -II play an important role in protecting cells from irradiation-induced cell death. It is not known whether Prx-IV also protects cells from ionizing radiation (IR). Methods and Materials: To evaluate the protective role of Prx-IV in IR, we transfected full-length Prx-IV cDNA into AMC-HN3 cells, which weakly express endogenous Prx-IV, and knocked down the expression of Prx-IV with siRNA methods using AMC-HN7 cells, which express high levels of endogenous Prx-IV. Radiosensitivity profiles in these cells were evaluated using clonogenic assay, FACS analysis, cell viability, and TUNEL assay. Results: Three Prx-IV expressing clones were isolated. Prx-IV regulated intracellular reactive oxygen species (ROS) levels and made cells more resistant to IR-induced apoptosis. Furthermore, the knockdown of Prx-IV with siRNA made cells more sensitive to IR-induced apoptosis. Conclusion: The results of these studies suggest that Prx-IV may play an important role in protecting cells from IR-induced apoptosis in head-and-neck squamous cell carcinoma

  2. Decreased Risk of Squamous Cell Carcinoma of the Head and Neck in Users of Nonsteroidal Anti-Inflammatory Drugs

    Directory of Open Access Journals (Sweden)

    Neda Ahmadi

    2010-01-01

    Full Text Available We evaluated the chemopreventive effect of nonsteroidal anti-inflammatory drug (NSAID use in head and neck squamous cell carcinomas (HNSCC by conducting a case-control study based on the administration of a standardized questionnaire to 71 incident HNSCC cases and same number of healthy controls. NSAID use was associated with a 75% reduction in risk of developing HNSCC. A significant risk reduction was noted in association with frequency of NSAID use. Restricting the analysis to aspirin users revealed a significant 90% reduction in risk of developing HNSCC. This study provides evidence for a significant reduction in the risk of developing HNSCC in users of NSAIDs, and specifically aspirin users.

  3. Developing a risk stratification tool for audit of outcome after surgery for head and neck squamous cell carcinoma.

    Science.gov (United States)

    Tighe, David F; Thomas, Alan J; Sassoon, Isabel; Kinsman, Robin; McGurk, Mark

    2017-07-01

    Patients treated surgically for head and neck squamous cell carcinoma (HNSCC) represent a heterogeneous group. Adjusting for patient case mix and complexity of surgery is essential if reporting outcomes represent surgical performance and quality of care. A case note audit totaling 1075 patients receiving 1218 operations done for HNSCC in 4 cancer networks was completed. Logistic regression, decision tree analysis, an artificial neural network, and Naïve Bayes Classifier were used to adjust for patient case-mix using pertinent preoperative variables. Thirty-day complication rates varied widely (34%-51%; P risk stratification. The artificial neural network demonstrated the best predictive performance (area under the curve [AUC] 0.85). Early postoperative complications are a measurable outcome that can be used to benchmark surgical performance and quality of care. Surgical outcome reporting in national clinical audits should be taking account of the patient case mix. © 2017 Wiley Periodicals, Inc.

  4. Function and importance of p63 in normal oral mucosa and squamous cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Thurfjell, Niklas; Coates, Philip J; Boldrup, Linda

    2005-01-01

    BACKGROUND/AIMS: Squamous cell carcinoma of the head and neck (HNSCC) is the 6th most common malignancy worldwide with a 5-year survival that has not improved over the last 20-25 years. Factors of prognostic significance for this tumour type include the presence of regional lymph node metastasis...... and amplification of chromosome 3q21-29, where the p63 gene is located. This gene encodes 6 proteins and is crucial for formation of the oral mucosa, teeth, salivary glands and skin. Each of the 6 different p63 proteins has different characteristics and functions, where some resemble the tumour suppressor protein p......53, whilst others have functions that oppose p53. METHODS: To understand the function and importance of p63 in oral mucosa and tumour development we have studied protein as well as mRNA expression in normal oral mucosa and tumours. RESULTS/CONCLUSION: Expression of p63 proteins differs between...

  5. Enhanced skin toxicity with concomitant cetuximab and radiotherapy in patients with locally advanced head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bujor, L.; Grillo, I.M.; Pimentel, N. [Hospital Santa Maria, Radioterapia, Lisboa (Portugal); Macor, C.; Catarina, M. [Hospital Santa Maria, ORL, Lisboa (Portugal); Ribeiro, L. [Hospital Santa Maria, Oncologia, Lisboa (Portugal)

    2009-10-15

    Purpose: When associated with radiotherapy the monoclonal antibodies such as cetuximab might be exacerbate skin toxicity. The aim of this study was to retrospectively analyze acute dermatological toxicity in ten consecutive patients with locally advanced head and neck squamous cell carcinoma treated from march 2008 to May 2009 according to Bonner protocol. Patients and methods: We have treated with radiotherapy and cetuximab ten patients with locally advanced head and neck squamous cell carcinoma of the oropharynx, hypopharynx, larynx or oral cavity, stage 3-4B and non metastatic. All our patients were 3D planned and scheduled for conventional fractionation 70 Gy/35 fractions over 47 days, five days weekly. Uninvolved neck received 50 Gy and gross nodal disease received 70 Gy as the primary tumor. Cetuximab was administered one week before radiotherapy at a loading dose of 400 mg per square meter of body surface area over 120 minutes, followed by weekly 60 minutes infusions at 250 mg per square meter for the duration of radiotherapy. Results: In eight patients (80%) grade 3 radiation dermatitis occurred as early as with 28 Gy at a median dose of 42 Gy (range 28-60 Gy). the median radiotherapy dose was 6 Gy with an overall treatment time of 57.7 days (range 41-70 days). were administered 78 cycles of cetuximab, one patient discontinued after five cycles due to infusion reactions. There was no correlation between toxicity and acne-like rash due to cetuximab. Conclusion: Our results albeit in disagreement with the original study are rather similar with the experience of other European centers that encounter grade 3-4 radiation dermatitis in 49% of their patients or Australian centers that reported 79% of same degree of toxicity. (authors)

  6. Enhanced skin toxicity with concomitant cetuximab and radiotherapy in patients with locally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Bujor, L.; Grillo, I.M.; Pimentel, N.; Macor, C.; Catarina, M.; Ribeiro, L.

    2009-01-01

    Purpose: When associated with radiotherapy the monoclonal antibodies such as cetuximab might be exacerbate skin toxicity. The aim of this study was to retrospectively analyze acute dermatological toxicity in ten consecutive patients with locally advanced head and neck squamous cell carcinoma treated from march 2008 to May 2009 according to Bonner protocol. Patients and methods: We have treated with radiotherapy and cetuximab ten patients with locally advanced head and neck squamous cell carcinoma of the oropharynx, hypopharynx, larynx or oral cavity, stage 3-4B and non metastatic. All our patients were 3D planned and scheduled for conventional fractionation 70 Gy/35 fractions over 47 days, five days weekly. Uninvolved neck received 50 Gy and gross nodal disease received 70 Gy as the primary tumor. Cetuximab was administered one week before radiotherapy at a loading dose of 400 mg per square meter of body surface area over 120 minutes, followed by weekly 60 minutes infusions at 250 mg per square meter for the duration of radiotherapy. Results: In eight patients (80%) grade 3 radiation dermatitis occurred as early as with 28 Gy at a median dose of 42 Gy (range 28-60 Gy). the median radiotherapy dose was 6 Gy with an overall treatment time of 57.7 days (range 41-70 days). were administered 78 cycles of cetuximab, one patient discontinued after five cycles due to infusion reactions. There was no correlation between toxicity and acne-like rash due to cetuximab. Conclusion: Our results albeit in disagreement with the original study are rather similar with the experience of other European centers that encounter grade 3-4 radiation dermatitis in 49% of their patients or Australian centers that reported 79% of same degree of toxicity. (authors)

  7. Patterns of recurrence after selective postoperative radiation therapy for patients with head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Murakami, Naoya; Matsumoto, Fumihiko; Yoshimoto, Seiichi; Ito, Yoshinori; Mori, Taisuke; Ueno, Takao; Tuchida, Keisuke; Kashihara, Tairo; Kobayashi, Kazuma; Harada, Ken; Kitaguchi, Mayuka; Sekii, Shuhei; Umezawa, Rei; Takahashi, Kana; Inaba, Koji; Igaki, Hiroshi; Itami, Jun

    2016-01-01

    The radiation field for patients with postoperative head and neck squamous cell carcinoma is narrower in our institution than in Western countries to reduce late radiation related toxicities. This strategy is at a risk of loco-regional or distant metastasis. However, because patients are more closely checked than in Western countries by every 1 to 2 months intervals and it is supposed that regional recurrences are identified and salvage surgeries are performed more quickly. Therefore, it is considered that patient survival would not be compromised with this strategy. The aim of this study was to investigate the feasibility of this strategy retrospectively. Patients who underwent neck dissection with close or positive margin, extra-capsular spread (ECS), multiple regional lymph node metastasis, pT4, with or without primary tumor resection were treated with postoperative radiation therapy. The volume of radiation field, especially the coverage of prophylactic regional lymph node area, was discussed among head and neck surgeons and radiation oncologists taking into account the clinical factors including patient’s age, performance status, number of positive lymph nodes, size of metastatic lymph nodes, extension of primary tumor beyond the midline, and existence of ECS. Seventy-two patients were identified who were treated with postoperative radiation therapy for head and neck squamous cell carcinoma between November 2005 and December 2014. There were 20 patients with oropharynx, 19 with hypopharynx, 7 with larynx, 23 with oral cavity, and 3 with other sites. Thirty eight patients had their neck irradiated bilaterally and 34 unilaterally. Median follow-up period for patients without relapse was 20.7 months (5.1–100.7). Thirty two patients had disease relapse after treatment including 22 loco-regional recurrence and 14 distant metastases. Among 22 loco-regional recurrence, seven patients underwent salvage surgery and one of them was no relapse at the time of the

  8. Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck

    NARCIS (Netherlands)

    Michalides, R.; van Veelen, N.; Hart, A.; Loftus, B.; Wientjens, E.; Balm, A.

    1995-01-01

    We evaluated the prognostic significance of overexpression of cyclin D1 in 47 patients with surgically resected squamous cell carcinomas of the head and neck. Overexpression of cyclin D1 was detected immunohistochemically using an affinity-purified polyclonal antibody directed against the

  9. Risk-group definition by recursive partitioning analysis of patients with squamous cell head and neck carcinoma treated with surgery and postoperative radiotherapy

    NARCIS (Netherlands)

    Langendijk, JA; Slotman, BJ; van der Waal, [No Value; Doornaert, P; Berkof, J; Leemans, CR

    2005-01-01

    BACKGROUND. The objective of this study was to define different prognostic groups with regard to locoregional control (LRC) derived from recursive partitioning analysis (RPA). METHODS. Eight hundred one patients with squamous cell head and neck carcinoma underwent with primary surgery and received

  10. FAZA PET/CT hypoxia imaging in patients with squamous cell carcinoma of the head and neck treated with radiotherapy: Results from the DAHANCA 24 trial

    DEFF Research Database (Denmark)

    Mortensen, Lise Saksø; Johansen, Jørgen; Kallehauge, Jesper Folsted

    2012-01-01

    Hypoxia is a cause of resistance to radiotherapy, especially in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate (18)F-fluoroazomycin arabinoside (FAZA) positron emission tomography (PET)/computed tomography (CT) hypoxia imaging as a prognostic...

  11. PET of EGFR with (64) Cu-cetuximab-F(ab')2 in mice with head and neck squamous cell carcinoma xenografts

    NARCIS (Netherlands)

    Dijk, L.K. van; Yim, C.B.; Franssen, G.M.; Kaanders, J.H.; Rajander, J.; Solin, O.; Gronroos, T.J.; Boerman, O.C.; Bussink, J.

    2016-01-01

    Overexpression of the epidermal growth factor receptor (EGFR) is linked to an adverse outcome in various solid tumors. Cetuximab is an EGFR inhibitor, which in combination with radiotherapy improves locoregional control and survival in a subgroup of patients with head and neck squamous cell

  12. Anti-Epidermal Growth Factor Receptor Therapy in Head and Neck Squamous Cell Carcinoma: Focus on Potential Molecular Mechanisms of Drug Resistance

    OpenAIRE

    Boeckx, Carolien; Baay, Marc; Wouters, An; Specenier, Pol; Vermorken, Jan B.; Peeters, Marc; Lardon, Filip

    2013-01-01

    Targeted therapy against epidermal growth factor receptor (EGFR) is one of the most promising therapeutics for head and neck squamous cell carcinoma, and EGFR is overexpressed in a wide range of malignancies. An improved understanding of the resistance to EGFR inhibitors may provide new treatment options. This review summarizes some mechanisms and decribes strategies to overcome this resistance.

  13. IAEA-HypoX. A randomized multicenter study of the hypoxic radiosensitizer nimorazole concomitant with accelerated radiotherapy in head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Metwally, Mohamed Ahmed Hassan; Ali, Rubina; Kuddu, Maire

    2015-01-01

    PURPOSE: To test the hypothesis that radiotherapy (RT) of head and neck squamous cell carcinoma (HNSCC) can be improved by hypoxic modification using nimorazole (NIM) in association with accelerated fractionation. MATERIALS AND METHODS: The protocol was activated in March 2012 as an international...

  14. Toxicities of systemic agents in squamous cell carcinoma of the head and neck (SCCHN); A new perspective in the era of immunotherapy

    NARCIS (Netherlands)

    Saba, N.F.; Mody, M.D.; Tan, E.S.; Gill, H.S.; Rinaldo, A.; Takes, R.P.; Strojan, P.; Hartl, D.M.; Vermorken, J.B.; Haigentz, M., Jr.; Ferlito, A.

    2017-01-01

    Squamous cell carcinoma of the head and neck (SCCHN) is a difficult to treat malignancy and represents the seventh most common cancer worldwide. Systemic therapy has a critical role in the treatment of locally advanced and recurrent/metastatic disease. Cytotoxic chemotherapy has been primarily used

  15. Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial

    DEFF Research Database (Denmark)

    Overgaard, Jens; Hansen, Hanne Sand; Specht, Lena

    2003-01-01

    Although head and neck cancer can be cured by radiotherapy, the optimum treatment time for locoregional control is unclear. We aimed to find out whether shortening of treatment time by use of six instead of five radiotherapy fractions per week improves the tumour response in squamous-cell carcinoma....

  16. Phase II study of cetuximab plus concomitant boost radiotherapy in Japanese patients with locally advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Okano, Susumu; Yoshino, Takayuki; Fujii, Masato

    2013-01-01

    We investigated the tolerability of cetuximab plus radiotherapy in Japanese patients with untreated locally advanced squamous cell carcinoma of the head and neck. Patients with epidermal growth factor receptor-expressing locally advanced squamous cell carcinoma of the head and neck received cetuximab (400 mg/m 2 initial dose then 250 mg/m 2 weekly) for 7 weeks plus concomitant boost radiotherapy (weeks 2-7: once daily [1.8 Gy] for 3.6 weeks, then twice daily [1.8 Gy morning and 1.5 Gy afternoon] for 2.4 weeks). The primary endpoint was treatment completion rate (the rate of treated patients completing ≥70% of the planned cetuximab dose and the full dose of radiotherapy within 2 weeks over the planned schedule). Twenty-two patients were evaluable. The treatment completion rate was 100% (95% confidence interval 85-100). The response rate 8 weeks post-radiotherapy was 82% (95% confidence interval 60-95). The most common grade 3/4 treatment-emergent adverse events were mucosal inflammation (73%); dermatitis (27%); and infection, radiation skin injury and stomatitis (23% each). Cetuximab plus concomitant boost radiotherapy can be safely administered to Japanese patients with locally advanced squamous cell carcinoma of the head and neck. Tolerability and efficacy were in line with those reported in the Phase III Bonner trial in a Western population of patients with locally advanced squamous cell carcinoma of the head and neck. (author)

  17. Multivariate analysis of potential risk factors for lymph node metastasis in patients with cutaneous squamous cell carcinoma of the head and neck

    NARCIS (Netherlands)

    Haisma, Marjolijn S.; Plaat, Boudewijn E. C.; Bijl, Hendrik P.; Roodenburg, Jan L. N.; Diercks, Gilles F. H.; Romeijn, Tonnis R.; Terra, Jorrit B.

    2016-01-01

    Background: The current knowledge about potential risk factors for lymph node (LN) metastasis in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) is primarily based on studies that lack adjustment for confounding variables. Objectives: We sought to identify independent risk

  18. Establishment and characterization of a novel head and neck squamous cell carcinoma cell line USC-HN1.

    Science.gov (United States)

    Liebertz, Daniel J; Lechner, Melissa G; Masood, Rizwan; Sinha, Uttam K; Han, Jing; Puri, Raj K; Correa, Adrian J; Epstein, Alan L

    2010-02-22

    Head and neck squamous cell carcinoma (HNSCC) is an aggressive and lethal malignancy. Publically available cell lines are mostly of lingual origin, or have not been carefully characterized. Detailed characterization of novel HNSCC cell lines is needed in order to provide researchers a concrete keystone on which to build their investigations. The USC-HN1 cell line was established from a primary maxillary HNSCC biopsy explant in tissue culture. The immortalized cells were then further characterized by heterotransplantation in Nude mice; immunohistochemical staining for relevant HNSCC biomarkers; flow cytometry for surface markers; cytogenetic karyotypic analysis; human papillomavirus and Epstein-Barr virus screening; qRT-PCR for oncogene and cytokine analysis; investigation of activated, cleaved Notch1 levels; and detailed 35,000 gene microarray analysis. Characterization experiments confirmed the human HNSCC origin of USC-HN1, including a phenotype similar to the original tumor. Viral screening revealed no HPV or EBV infection, while western blotting displayed significant upregulation of activated, cleaved Notch1. USC-HN1, a novel immortalized cell line has been derived from a maxillary HNSCC. Characterization studies have shown that the cell line is of HNSCC origin and displays many of the same markers previously reported in the literature. USC-HN1 is available for public research and will further the investigation of HNSCC and the development of new therapeutic modalities.

  19. Identification, expansion and characterization of cancer cells with stem cell properties from head and neck squamous cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kaseb, Hatem O. [Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261 (United States); Department of Clinical Pathology, National Cancer Institute (NCI), Cairo University, Cairo (Egypt); Fohrer-Ting, Helene [Department of Pathology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219 (United States); Lewis, Dale W. [Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261 (United States); Lagasse, Eric [Department of Pathology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219 (United States); Gollin, Susanne M., E-mail: gollin@pitt.edu [Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261 (United States); University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232 (United States)

    2016-10-15

    Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. Recent data indicate the presence of cancer stem cells (CSC) in many solid tumors, including HNSCC. Here, we assessed the stem cell (SC) characteristics, including cell surface markers, radioresistance, chromosomal instability, and in vivo tumorigenic capacity of CSC isolated from HNSCC patient specimens. We show that spheroid enrichment of CSC from early and short-term HNSCC cell cultures was associated with increased expression of CD44, CD133, SOX2 and BMI1 compared with normal oral epithelial cells. On immunophenotyping, five of 12 SC/CSC markers were homogenously expressed in all tumor cultures, while one of 12 was negative, four of 12 showed variable expression, and two of the 12 were expressed heterogeneously. We showed that irradiated CSCs survived and retained their self-renewal capacity across different ionizing radiation (IR) regimens. Fluorescence in situ hybridization (FISH) analyses of parental and clonally-derived tumor cells revealed different chromosome copy numbers from cell to cell, suggesting the presence of chromosomal instability in HNSCC CSC. Further, our in vitro and in vivo mouse engraftment studies suggest that CD44+/CD66− is a promising, consistent biomarker combination for HNSCC CSC. Overall, our findings add further evidence to the proposed role of HNSCC CSCs in therapeutic resistance. - Highlights: • Spheroid enrichment selects cancer stem cells (CSC) from head & neck tumors (HNSCC). • Compared to normal epithelial cells, isolated CSC express increased SC/CSC markers. • Isolated CSC display enhanced radioresistance, clonogenicity and tumorigenicity. • HNSCC CSC express chromosomal instability. • CD44+/CD66− is a promising, consistent biomarker for HNSCC CSC.

  20. Identification, expansion and characterization of cancer cells with stem cell properties from head and neck squamous cell carcinomas

    International Nuclear Information System (INIS)

    Kaseb, Hatem O.; Fohrer-Ting, Helene; Lewis, Dale W.; Lagasse, Eric; Gollin, Susanne M.

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. Recent data indicate the presence of cancer stem cells (CSC) in many solid tumors, including HNSCC. Here, we assessed the stem cell (SC) characteristics, including cell surface markers, radioresistance, chromosomal instability, and in vivo tumorigenic capacity of CSC isolated from HNSCC patient specimens. We show that spheroid enrichment of CSC from early and short-term HNSCC cell cultures was associated with increased expression of CD44, CD133, SOX2 and BMI1 compared with normal oral epithelial cells. On immunophenotyping, five of 12 SC/CSC markers were homogenously expressed in all tumor cultures, while one of 12 was negative, four of 12 showed variable expression, and two of the 12 were expressed heterogeneously. We showed that irradiated CSCs survived and retained their self-renewal capacity across different ionizing radiation (IR) regimens. Fluorescence in situ hybridization (FISH) analyses of parental and clonally-derived tumor cells revealed different chromosome copy numbers from cell to cell, suggesting the presence of chromosomal instability in HNSCC CSC. Further, our in vitro and in vivo mouse engraftment studies suggest that CD44+/CD66− is a promising, consistent biomarker combination for HNSCC CSC. Overall, our findings add further evidence to the proposed role of HNSCC CSCs in therapeutic resistance. - Highlights: • Spheroid enrichment selects cancer stem cells (CSC) from head & neck tumors (HNSCC). • Compared to normal epithelial cells, isolated CSC express increased SC/CSC markers. • Isolated CSC display enhanced radioresistance, clonogenicity and tumorigenicity. • HNSCC CSC express chromosomal instability. • CD44+/CD66− is a promising, consistent biomarker for HNSCC CSC.

  1. The Relationship Between Human Papillomavirus Status and Other Molecular Prognostic Markers in Head and Neck Squamous Cell Carcinomas

    International Nuclear Information System (INIS)

    Kong, Christina S.; Narasimhan, Balasubramanian; Cao Hongbin; Kwok, Shirley; Erickson, Julianna P.; Koong, Albert; Pourmand, Nader; Le, Quynh-Thu

    2009-01-01

    Purpose: To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status. Methods and Materials: HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16 INK4a staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO 2 and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining). Results: Forty-four percent of evaluable tumors had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16 INK4a staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16 INK4a staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO 2 or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(-) tumors. Conclusion: HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(-) tumors.

  2. Opposing function of MYBBP1A in proliferation and migration of head and neck squamous cell carcinoma cells

    International Nuclear Information System (INIS)

    Acuña Sanhueza, Gustavo A; Simon, Christian; Hess, Jochen; Faller, Leonie; George, Babitha; Koffler, Jennifer; Misetic, Vinko; Flechtenmacher, Christa; Dyckhoff, Gerhard; Plinkert, Peter P; Angel, Peter

    2012-01-01

    Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent and lethal cancers worldwide and mortality mostly results from loco-regional recurrence and metastasis. Despite its significance, our knowledge on molecular, cellular and environmental mechanisms that drive disease pathogenesis remains largely elusive, and there are limited therapeutic options, with only negligible clinical benefit. We applied global gene expression profiling with samples derived from a recently established mouse model for oral cancer recurrence and identified a list of genes with differential expression between primary and recurrent tumors. One differentially expressed gene codes for Myb-binding protein 1a (MYBBP1A), which is known as a transcriptional co-regulator that physically interacts with nuclear transcription factors, such as NFκB and p53. We confirmed significantly reduced MYBBP1A protein levels on tissue sections of recurrent mouse tumors compared to primary tumors by immunohistochemistry, and found aberrant MYBBP1A protein levels also in tumor samples of HNSCC patients. Interestingly, silencing of MYBBP1A expression in murine SCC7 and in human HNSCC cell lines elicited increased migration but decreased cell growth. We provide experimental evidence that MYBBP1A is an important molecular switch in the regulation of tumor cell proliferation versus migration in HNSCC and it will be a major challenge for the future to proof the concept whether regulation MYBBP1A expression and/or function could serve as a novel option for anti-cancer therapy

  3. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma

    Science.gov (United States)

    2011-01-01

    Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer activities via its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumorigenesis and metastasis. Curcumin has shown anti-proliferative effect in multiple cancers, and is an inhibitor of the transcription factor NF-κB and downstream gene products (including c-myc, Bcl-2, COX-2, NOS, Cyclin D1, TNF-α, interleukins and MMP-9). In addition, curcumin affects a variety of growth factor receptors and cell adhesion molecules involved in tumor growth, angiogenesis and metastasis. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and treatment protocols include disfiguring surgery, platinum-based chemotherapy and radiation, all of which may result in tremendous patient morbidity. As a result, there is significant interest in developing adjuvant chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo data supporting its therapeutic activity in head and neck cancer as well as some of the challenges concerning its development as an adjuvant chemotherapeutic agent. PMID:21299897

  4. Compliance and toxicity of the hypoxic radiosensitizer nimorazole in the treatment of patients with head and neck squamous cell carcinoma (HNSCC)

    DEFF Research Database (Denmark)

    Metwally, Mohamed Ahmed Hassan; Frederiksen, Katrine Diemer; Overgaard, Jens

    2014-01-01

    Abstract Purpose. To evaluate the compliance and toxicity of the hypoxic radiosensitizer nimorazole in head and neck cancer patients. Methods. A retrospective study of patients with head and neck squamous cell carcinoma (HNSCC), treated in Denmark between 1990 and 2013. All patients treated...... with radical radiotherapy (± chemotherapy) [66-70 Gy; 33-35 fractions; 2 Gy/fraction; 5-6 fractions/week] concomitant with the hypoxic radiosensitizer nimorazole. Nimorazole was administered as oral tablets in doses of approximately 1.2 g/m(2) body surface area in connection with the first of each daily...

  5. Does Tumor Depth Affect Nodal Upstaging in Squamous Cell Carcinoma of the Head and Neck?

    DEFF Research Database (Denmark)

    Alkureishi, Lee; Ross, Gary; Shoaib, Taimur

    2007-01-01

    AND METHODS:: One hundred seventy-two patients with cT1/2 N0 squamous cell carcinoma (SCC) of the oral cavity/oropharynx undergoing primary resection and either sentinel node biopsy (SNB) or SNB-assisted neck dissection as a staging tool for the cN0 neck. Harvested nodes were examined with hematoxylin...

  6. The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Heiduschka, G. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Comprehensive Cancer Center, Vienna (Austria); Medical University of Vienna, Clinical Pharmacology, Vienna (Austria); Lill, C.; Schneider, S.; Kotowski, U.; Thurnher, D. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Comprehensive Cancer Center, Vienna (Austria); Seemann, R. [Medical University of Vienna, Craniomaxillofacial and Oral Surgery, Vienna (Austria); Kornek, G. [Medical University of Vienna, Internal Medicine, Vienna (Austria); Schmid, R. [Medical University of Vienna, Radiotherapy and Radiobiology, Vienna (Austria)

    2014-05-15

    Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity. (orig.) [German] Durch ihre Rolle bei der Angiogenese sind Integrine ein attraktives Ziel in der onkologischen Forschung. Der derzeit vielversprechendste Inhibitor dieser Molekuele ist Cilengitide, welches bereits in klinischen Studien getestet wird. Dennoch ist erst wenig ueber die zellulaeren Vorgaenge bekannt, welche durch Cilengitide in Kopf-Hals-Karzinomen (HNSCC) insbesondere in Kombination mit Strahlentherapie und

  7. Inhibition of radiation induced migration of human head and neck squamous cell carcinoma cells by blocking of EGF receptor pathways

    International Nuclear Information System (INIS)

    Pickhard, Anja C; Schlegel, Jürgen; Arnold, Wolfgang; Reiter, Rudolf; Margraf, Johanna; Knopf, Andreas; Stark, Thomas; Piontek, Guido; Beck, Carolin; Boulesteix, Anne-Laure; Scherer, Elias Q; Pigorsch, Steffi

    2011-01-01

    Recently it has been shown that radiation induces migration of glioma cells and facilitates a further spread of tumor cells locally and systemically. The aim of this study was to evaluate whether radiotherapy induces migration in head and neck squamous cell carcinoma (HNSCC). A further aim was to investigate the effects of blocking the epidermal growth factor receptor (EGFR) and its downstream pathways (Raf/MEK/ERK, PI3K/Akt) on tumor cell migration in vitro. Migration of tumor cells was assessed via a wound healing assay and proliferation by a MTT colorimeritric assay using 3 HNSCC cell lines (BHY, CAL-27, HN). The cells were treated with increasing doses of irradiation (2 Gy, 5 Gy, 8 Gy) in the presence or absence of EGF, EGFR-antagonist (AG1478) or inhibitors of the downstream pathways PI3K (LY294002), mTOR (rapamycin) and MEK1 (PD98059). Biochemical activation of EGFR and the downstream markers Akt and ERK were examined by Western blot analysis. In absence of stimulation or inhibition, increasing doses of irradiation induced a dose-dependent enhancement of migrating cells (p < 0.05 for the 3 HNSCC cell lines) and a decrease of cell proliferation (p < 0.05 for the 3 HNSCC cell lines). The inhibition of EGFR or the downstream pathways reduced cell migration significantly (almost all p < 0.05 for the 3 HNSCC cell lines). Stimulation of HNSCC cells with EGF caused a significant increase in migration (p < 0.05 for the 3 HNSCC cell lines). After irradiation alone a pronounced activation of EGFR was observed by Western blot analysis. Our results demonstrate that the EGFR is involved in radiation induced migration of HNSCC cells. Therefore EGFR or the downstream pathways might be a target for the treatment of HNSCC to improve the efficacy of radiotherapy

  8. [Radiotherapy for head and neck squamous cell carcinoma: State of the art and future directions].

    Science.gov (United States)

    Schick, U; Huguet, F; Pointreau, Y; Pradier, O

    2017-10-01

    Therapeutic principles of radiation therapy in head and neck carcinomas will be discussed in this review. Intensity-modulated radiotherapy with concomitant cisplatin should be standard. In case of contraindication to chemotherapy, cetuximab is an option, while hyperfractionation should be considered in patients unfit for concomitant treatment. Concomitant chemotherapy should be administered in the presence of extracapsular extensions and positive margins in the postoperative setting. Current research areas such as desescalation in human papillomavirus-positive tumours, adaptive radiotherapy, radiomics and immunotherapy will also be addressed. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  9. Phase I/II trial of weekly docetaxel and concomitant radiotherapy for squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Fujii, Masato; Tsukuda, Mamoru; Kubota, Akira; Kida, Akinori; Okami, Kenji

    2003-01-01

    Docetaxel (DOC) is one of the most promising drugs for head and neck cancer (HNSCC). A phase I/II trial of concurrent DOC and radiation for HNSCC was conducted to estimate the recommended dose schedule of DOC, and then to evaluate the therapeutic benefit based on the response and toxicity of the recommended dose schedule. Patients with squamous cell carcinomas of the head and neck were entered. All the patients received radiation with 2.0 Gy single daily fractions up to 60 Gy. DOC was administered weekly for 6 consecutive weeks during radiotherapy. Dose-limiting toxicities, grade 3/4 mucositis and grade 3 pain, manifested in four patients in level 2, and that dose of DOC, 15 mg/m 2 , was considered the maximum tolerated dose (MTD). The recommended dose was decided as 10 mg/m 2 . The phase II study was conducted using DOC at 10 mg/m 2 . Thirty-nine patients with stage II, III or IV were registered, and 35 patients were eligible, 32 patients were evaluable for the response and 34 patients for the toxicity. The overall response rate was 96.9%. The prognoses of the complete response (CR) patients were statistically better than for the partial response (PR) patients. Grade 3 or 4 adverse events consisted of lymphopenia in 64.7%, mucositis in 41.2% and anorexia in 20.6% of the patients. Thirty-two of the 35 eligible patients showed high compliance of over 90%, and their toxicities were manageable. Even low-dose DOC shows a strong effect on HNSCC in combination with radiation, with high survival rates in CR patients. The effect on survival will be assessed by further follow-up. (author)

  10. Impact of comorbidity on treatment outcome in head and neck squamous cell carcinoma – A systematic review

    International Nuclear Information System (INIS)

    Bøje, Charlotte Rotbøl

    2014-01-01

    The significant association with tobacco and alcohol combined with advanced age at time of diagnosis predispose head and neck squamous cell carcinoma (HNSCC) patients to increased risk of comorbidities. The presence of comorbidity affects treatment, treatment selection and subsequent outcome. Multiple studies have demonstrated comorbidity to be a strong prognostic factor for survival, and therefore comorbidity can be a major confounder in clinical trials. This review provides a summary of the current literature on comorbidity in head and neck cancer, measurements of comorbidity, the impact of comorbidity on treatment, treatment selection, and survival. A systematic search was performed in six electronic databases. In all, 31 papers were selected for this review. A meta-analysis on the prognostic impact of comorbidity was performed including 10 studies. Furthermore, 21 studies concerning comorbidity were reviewed. Several valid indices to classify comorbidity were described in the literature, none proven to be superior over the other. The prevalence of comorbidity increased with age and the presence of comorbidity influenced treatment and treatment selection. Furthermore, comorbidity was associated with lower socio economic status and increased the risk of early retirement after treatment. The meta-analysis on comorbidity as a prognostic factor, including 22,932 patients, showed that overall survival was significantly worsened among patients with comorbidity (HR = 1.38 (1.32–1.43)). Increasing comorbidity-score was associated with increased risk of death. Comorbidity is important in HNSCC and significantly impacts on overall survival. Trials concerning HNSCC should always include information on comorbidity and randomized trials should stratify patients according to comorbidity in order to avoid bias in the study

  11. Up-front PET/CT changes treatment intent in patients with head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Rohde, Max; Godballe, Christian; Nielsen, Anne L.; Thomassen, Anders; Johansen, Joergen; Gyldenkerne, Niels; Soerensen, Jens A.; Diaz, Anabel; Asmussen, Jon T.; Gerke, Oke; Doessing, Helle; Bjoerndal, Kristine; Hoeilund-Carlsen, Poul Flemming

    2018-01-01

    In patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), we wanted to examine the differences in overall treatment decisions, i.e. curative versus palliative treatment intent, reached by a multidisciplinary team conference (MDTC) based on 18F-fluoro-deoxy-glucose-positron emission tomography/computed tomography (PET/CT) or chest X-ray + MRI of the head and neck (CXR/MRI). This was a prospective blinded cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were invited to participate. All included patients underwent CXR/MRI and PET/CT before diagnostic biopsy. An ordinary MDTC using all available imaging was conducted as per standard practice. After at least 3 months (to eliminate recall bias in the team), the first project MDTC was conducted, based on either CXR/MRI or PET/CT, and the tumor board drew conclusions regarding treatment. After an additional 3 months, a second project MDTC was conducted using the complementary imaging modality. A total of 307 patients were included. Based on CXR/MRI, 303 patients (99%) were recommended for curative treatment and only four patients (1%) for palliative treatment. Based on PET/CT, the MDTC concluded that 278 (91%) patients were suitable for curative treatment and 29 (9%) patients for palliative treatment. The absolute difference of 8% was statistically significant (95% CI: 4.8%-11.5%, p < 0.001). A PET/CT-based imaging strategy significantly changed the decisions regarding treatment intent made by a MDTC for patients diagnosed with HNSCC, when compared with the standard imaging strategy of CXR/MRI. (orig.)

  12. Up-front PET/CT changes treatment intent in patients with head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Rohde, Max; Godballe, Christian [Odense University Hospital, Department of ORL - Head and Neck Surgery, Odense (Denmark); University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Nielsen, Anne L.; Thomassen, Anders [Odense University Hospital, Department of Nuclear Medicine, Odense (Denmark); Johansen, Joergen; Gyldenkerne, Niels [Odense University Hospital, Department of Oncology, Odense (Denmark); Soerensen, Jens A. [University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Odense University Hospital, Department of Plastic Surgery, Odense (Denmark); Diaz, Anabel; Asmussen, Jon T. [Odense University Hospital, Department of Radiology, Odense (Denmark); Gerke, Oke [Odense University Hospital, Department of Nuclear Medicine, Odense (Denmark); University of Southern Denmark, Centre of Health Economics Research, Odense (Denmark); Doessing, Helle; Bjoerndal, Kristine [Odense University Hospital, Department of ORL - Head and Neck Surgery, Odense (Denmark); Hoeilund-Carlsen, Poul Flemming [University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Odense University Hospital, Department of Nuclear Medicine, Odense (Denmark)

    2018-04-15

    In patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), we wanted to examine the differences in overall treatment decisions, i.e. curative versus palliative treatment intent, reached by a multidisciplinary team conference (MDTC) based on 18F-fluoro-deoxy-glucose-positron emission tomography/computed tomography (PET/CT) or chest X-ray + MRI of the head and neck (CXR/MRI). This was a prospective blinded cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were invited to participate. All included patients underwent CXR/MRI and PET/CT before diagnostic biopsy. An ordinary MDTC using all available imaging was conducted as per standard practice. After at least 3 months (to eliminate recall bias in the team), the first project MDTC was conducted, based on either CXR/MRI or PET/CT, and the tumor board drew conclusions regarding treatment. After an additional 3 months, a second project MDTC was conducted using the complementary imaging modality. A total of 307 patients were included. Based on CXR/MRI, 303 patients (99%) were recommended for curative treatment and only four patients (1%) for palliative treatment. Based on PET/CT, the MDTC concluded that 278 (91%) patients were suitable for curative treatment and 29 (9%) patients for palliative treatment. The absolute difference of 8% was statistically significant (95% CI: 4.8%-11.5%, p < 0.001). A PET/CT-based imaging strategy significantly changed the decisions regarding treatment intent made by a MDTC for patients diagnosed with HNSCC, when compared with the standard imaging strategy of CXR/MRI. (orig.)

  13. Serum midkine as a biomarker for malignancy, prognosis, and chemosensitivity in head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Yamashita, Taku; Shimada, Hideaki; Tanaka, Shingo; Araki, Koji; Tomifuji, Masayuki; Mizokami, Daisuke; Tanaka, Nobuaki; Kamide, Daisuke; Miyagawa, Yoshihiro; Suzuki, Hiroshi; Tanaka, Yuya; Shiotani, Akihiro

    2016-01-01

    Improved therapies for individuals with head and neck squamous cell carcinoma (HNSCC) may be developed by identification of appropriate biomarkers. The aim of this study was to evaluate the usefulness of serum midkine measurement as a biomarker for HNSCC. Pretreatment serum midkine concentrations were measured in 103 patients with HNSCC and 116 control individuals by enzyme-linked immunosorbent assay. Midkine expression in tumor tissues from 33 patients with HNSCC who underwent definitive surgical resection without preoperative treatment was examined by immunohistochemistry. The cut-off serum midkine concentrations for predicting the presence of head and neck malignancy and chemosensitivity to induction chemotherapy, as determined using receiver operating characteristic curves, were 482 and 626 pg/mL, respectively. Spearman bivariate correlations showed positive correlations between serum midkine levels and immunohistochemistry staining score (r = 0.612, P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of serum midkine concentration for detection of HNSCC were 57.3, 85.3, 77.6, 69.2, and 72.1%, respectively. However, for predicting the response to induction chemotherapy, the values were 84.6, 60.9, 71.0, 77.8, and 73.5%, respectively. Serum midkine concentration was identified as an independent prognostic factor by multivariate analysis, using Cox's proportional hazards model (P = 0.027). Overexpression of serum midkine yielded a relative risk of death of 3.77, with 95% confidence limits ranging from 1.15 to 17.0. Serum midkine levels in patients with HNSCC were associated with malignancy, chemosensitivity, and prognosis. Serum midkine may be a useful, minimally invasive biomarker for early detection, therapeutic decision-making, and predicting prognosis

  14. Photodynamic mechanisms induced by a combination of hypericin and a chlorin based-photosensitizer in head and neck squamous cell carcinoma cells.

    OpenAIRE

    Gyenge Emina Besic; Lüscher Daniel; Forny Patrick; Antoniol Martina; Geisberger Georg; Walt Heinrich; Patzke Greta; Maake Caroline

    2013-01-01

    The aim of this study was to elucidate photodynamic therapy (PDT) effects mediated by hypericin and a liposomal meso tetrahydroxyphenyl chlorin (mTHPC) derivative with focus on their 1:1 mixture on head and neck squamous cell carcinoma cell lines. Absorption excitation and photobleaching were monitored using fluorescence spectrometry showing the same spectral patterns for the mixture as measured for single photosensitizers. In the mixture mTHPC showed a prolonged photo stability. Singlet oxyg...

  15. New Concepts for Translational Head and Neck Oncology: Lessons from HPV-Related Oropharyngeal Squamous Cell Carcinomas

    International Nuclear Information System (INIS)

    Kostareli, Efterpi; Holzinger, Dana; Hess, Jochen

    2012-01-01

    Human papillomavirus (HPV) infection is well established as an etiological agent responsible for a number of pathologies affecting the stratified epithelia of skin and anogenital sites. More recently, the infection by (mucosal) high-risk HPV types has also been found to be causally associated with squamous cell carcinoma in the head and neck region (HNSCC), especially in the oropharynx. Intriguingly, HPV-related oropharyngeal squamous cell carcinomas (OPSCC) represent a distinct clinical entity compared to HPV-negative tumors with particular regard to treatment–response and survival outcome. The association between HPV infection and OPSCC may therefore have important implications for the prevention and/or treatment of OPSCC. The improved survival of patients with HPV-related tumors also raises the question, as to whether a better understanding of the underlying differences may help to identify new therapeutic concepts that could be used in targeted therapy for HPV-negative and improved therapy for HPV-positive cancers. This review summarizes the most recent advances in our understanding of the molecular principles of HPV-related OPSCC, mainly based on functional genomic approaches, but also emphasizes the significant role played by the tumor microenvironment, especially the immune system, for improved clinical outcome and differential sensitivity of HPV-related tumors to current treatment options.

  16. Head and neck squamous cell carcinoma in chronic areca nut chewing Indian women: Case series and review of literature.

    Science.gov (United States)

    Muttagi, Sidramesh Shivanand; Chaturvedi, Pankaj; Gaikwad, Rohith; Singh, Bikramjit; Pawar, Prashant

    2012-01-01

    Head and neck squamous cell carcinoma (HNSCC) is an important public health problem in India. Several risk factors such as tobacco, human papilloma virus, alcohol, areca nut usage have been extensively studied as causative agents. Though Areca nut chewing is known cause of oral cancer, its association with hypopharynx cancer has not been previously reported. Since areca nut is mostly consumed along with tobacco, it is uncommon to find patients who consume the areca nut alone. This is a prospective case series of ten women who presented to us with HNSCC with history of chewing of areca nut alone for several years. We have excluded all those cases where areca nut was consumed along with tobacco in any form. The data were prospectively collected with regard to clinical parameters, duration and frequency of areca nut usage, the socio-economic status and education level. All ten females had varying degree of submucous fibrosis and coexisting squamous cell carcinoma either in the oral cavity or hypopharynx. Submucous fibrosis was characterized by burning mouth, unhealthy oral mucosa, buried third molars, trismus, poor oral hygiene, etc. The disease presented in an advanced stage in majority of the cases. All patients were unaware of areca nut's deleterious effects. Areca nut chewing is an important risk factor for HNSCC in females. Despite plethora of information, little importance is given to areca nut control in cancer prevention campaigns in India.

  17. The effect of red-allotrope selenium nanoparticles on head and neck squamous cell viability and growth

    Directory of Open Access Journals (Sweden)

    Hassan CE

    2016-08-01

    Full Text Available Christopher E Hassan,1 Thomas J Webster1,2 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Given their low toxicity and natural presence in the human diet, selenium nanoparticles have been established as potential candidates for the treatment of numerous cancers. Red-allotrope selenium nanoparticles (rSeNPs were synthesized and characterized in this study. Head and neck squamous cell carcinoma (HNSCC and human dermal fibroblast (HDF cells were cultured and exposed to rSeNPs at concentrations ranging from 0.01 to 100 µg rSeNP/mL media for 1–3 days. The toxicity of rSeNP toward HNSCC and HDFs was analyzed. Results indicated that the particles were approximately four times as cytotoxic toward HNSCC compared to HDFs, with their respective IC50 values at 19.22 and 59.61 µg rSeNP/mL media. Using statistical analysis, an effective dosage range for killing HNSCC cells while simultaneously minimizing damage to HDFs over a 3-day incubation period was established at 20–55 µg rSeNP/mL media. Observations showed that doses of rSeNP <5 µg rSeNP/mL media resulted in cell proliferation. Transmission electron microscopy images of HNSCC and HDF cells, both treated with rSeNPs, revealed that the rSeNPs became localized in the cytoplasm near the lysosomes and mitochondria. Analysis of cell morphology showed that the rSeNPs primarily induced HNSCC apoptosis. Collectively, these results indicated that rSeNPs are a promising option for treating HNSCC without adversely affecting healthy cells and without resorting to the use of harmful chemotherapeutics. Keywords: selenium, nanotechnology, biomaterials, head and neck squamous cell carcinoma, human dermal fibroblasts, cancer 

  18. Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yi; Cui, Jiang-Tao, E-mail: cuijingtaopaper@126.com

    2016-09-02

    Mammalian target of rapamycin (mTOR) is a therapeutic target for head and neck squamous cell carcinoma (HNSCC). Here, we evaluated the activity of AZD-2014, a potent mTOR complex 1/2 (mTORC1/2) dual inhibitor, against HNSCC cells. We showed that AZD-2014 blocked mTORC1/2 activation in established and primary human HNSCC cells, where it was anti-proliferative and pro-apoptotic. Yet, AZD-2014 was non-cytotoxic to the human oral epithelial cells with low basal mTORC1/2 activation. In an effect to identify possible AZD-2014 resistance factors, we showed that the anti-apoptosis protein Bcl-2 was upregulated in AZD-2014-resistant SQ20B HNSCC cells. Inhibition of Bcl-2 by ABT-737 (a known Bcl-2 inhibitor) or Bcl-2 shRNA dramatically potentiated AZD-2014 lethality against HNSCC cells. On the other hand, exogenous overexpression of Bcl-2 largely attenuated AZD-2014’s activity against HNSCC cells. For the in vivo studies, we showed that oral gavage of AZD-2014 suppressed SQ20B xenograft growth in severe combined immunodeficient (SCID) mice. It also significantly improved mice survival. Importantly, AZD-2014’s anti-HNSCC activity in vivo was potentiated with co-administration of ABT-737. The preclinical results of this study suggest that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. - Highlights: • AZD-2014 blocks mTORC1/2 activation in HNSCC cells. • AZD-2014 suppresses HNSCC cell proliferation. • AZD-2014 activates caspase-3 and apoptosis in HNSCC cells. • Bcl-2 is the key resistance factor of AZD-2014 in HNSCC cells. • ABT-737 sensitizes AZD-2014-induced anti-HNSCC activity in vivo.

  19. Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

    International Nuclear Information System (INIS)

    Li, Yi; Cui, Jiang-Tao

    2016-01-01

    Mammalian target of rapamycin (mTOR) is a therapeutic target for head and neck squamous cell carcinoma (HNSCC). Here, we evaluated the activity of AZD-2014, a potent mTOR complex 1/2 (mTORC1/2) dual inhibitor, against HNSCC cells. We showed that AZD-2014 blocked mTORC1/2 activation in established and primary human HNSCC cells, where it was anti-proliferative and pro-apoptotic. Yet, AZD-2014 was non-cytotoxic to the human oral epithelial cells with low basal mTORC1/2 activation. In an effect to identify possible AZD-2014 resistance factors, we showed that the anti-apoptosis protein Bcl-2 was upregulated in AZD-2014-resistant SQ20B HNSCC cells. Inhibition of Bcl-2 by ABT-737 (a known Bcl-2 inhibitor) or Bcl-2 shRNA dramatically potentiated AZD-2014 lethality against HNSCC cells. On the other hand, exogenous overexpression of Bcl-2 largely attenuated AZD-2014’s activity against HNSCC cells. For the in vivo studies, we showed that oral gavage of AZD-2014 suppressed SQ20B xenograft growth in severe combined immunodeficient (SCID) mice. It also significantly improved mice survival. Importantly, AZD-2014’s anti-HNSCC activity in vivo was potentiated with co-administration of ABT-737. The preclinical results of this study suggest that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. - Highlights: • AZD-2014 blocks mTORC1/2 activation in HNSCC cells. • AZD-2014 suppresses HNSCC cell proliferation. • AZD-2014 activates caspase-3 and apoptosis in HNSCC cells. • Bcl-2 is the key resistance factor of AZD-2014 in HNSCC cells. • ABT-737 sensitizes AZD-2014-induced anti-HNSCC activity in vivo.

  20. Detection and Typing of Human Papilloma Virus DNA by PCR in Head and Neck Squamous Cell Carcinoma in E.N.T. Ward of Ahwaz Imam Hospital

    Directory of Open Access Journals (Sweden)

    S. Nikakhlagh

    2008-07-01

    Full Text Available Introduction & Objective: Nowadays, epidemiological and experimental evidences in western countries consistently support an etiological role for human papillomavirus (HPV in head and neck squamous cell carcinoma (SCC. The role of HPV in the etiology of head and neck SCC in developing countries such as Iran has not been investigated. The purpose of the present study was to investigate HPV DNA in the head and neck cancer by polymerase chain reaction (PCR in patients referred to Imam Khomeini Hospital Ahwaz.Materials & Methods: In this prospective cross sectional study 176 patients with SCC of head and neck who admitted in Ahwaz Imam Khomeini Hospital were evaluated with PCR for HPV DNA and compared to 176 control samples with benign pathology. Results: In this study 7 specimens (3.97% of the case group were positive for HPV DNA that include HPV 16(3 cases ,18(2 cases ,57(1 case, 33 (1case and only 1 specimen (0.57% of the control group was positive that include HPV 6 ( P value<0.001Conclusion: This study demonstrates the presence of HPVs in the SCC of head and neck. Further studies are needed to evaluate larger population in Ahwaz for the presence and types of HPV.

  1. Architectural patterns of p16 immunohistochemical expression associated with cancer immunity and prognosis of head and neck squamous cell carcinoma.

    Science.gov (United States)

    Ryu, Hyang Joo; Kim, Eun Kyung; Heo, Su Jin; Cho, Byoung Chul; Kim, Hye Ryun; Yoon, Sun Och

    2017-11-01

    We evaluated the expression patterns of p16, which is used as a surrogate marker of HPV infection in head and neck squamous cell carcinoma (HNSCC), in regard to their biological and prognostic implications. p16 expression patterns and infiltrated immune cells were analyzed through immunohistochemistry of p16, CD3, CD8, PD-1, FOXP3, and CD163 on surgically resected HNSCCs (n = 393). Patterns of p16 immunoexpression were defined as STRONG (strong, diffuse expression in cytoplasm, and nucleus in >70% of tumor cells), MARGINAL (expression restricted to tumor margins), MOSAIC (ragged, discontinued expression), NUCLEAR (expression in nuclei only), and ABSENT (no expression). The STRONG pattern was more frequent in the oropharynx, and the MARGINAL pattern was noted only in the oral cavity. MOSAIC and NUCLEAR patterns were noted at variable sites. No two patterns of p16 expression showed the same immune cell composition of CD3+ T cells, CD8+ cytotoxic T cells, PD-1+ T cells, FOXP3+ regulatory T cells, and CD163+ macrophages. In overall and disease-free survival analyses, the STRONG pattern showed the most favorable prognosis, while the NUCLEAR pattern had the worst prognosis. HNSCC anatomical sites, tumor-related immune cell components, and patient outcomes were associated with p16 expression patterns. Each architectural pattern of p16 expression may be related to different biological and prognostic phenotypes. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  2. Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Yu-Chin Lin

    2012-06-01

    Full Text Available Epidermal growth factor receptor (EGFR is an important oncoprotein that promotes cell growth and proliferation. Dasatinib, a bcr-abl inhibitor, has been approved clinically for the treatment of chronic myeloid leukemia and demonstrated to be effective against solid tumors in vitro through Src inhibition. Here, we disclose that EGFR degradation mediated dasatinib-induced apoptosis in head and neck squamous cell carcinoma (HNSCC cells. HNSCC cells, including Ca9-22, FaDu, HSC3, SAS, SCC-25, and UMSCC1, were treated with dasatinib, and cell viability, apoptosis, and underlying signal transduction were evaluated. Dasatinib exhibited differential sensitivities against HNSCC cells. Growth inhibition and apoptosis were correlated with its inhibition on Akt, Erk, and Bcl-2, irrespective of Src inhibition. Accordingly, we found that down-regulation of EGFR was a determinant of dasatinib sensitivity. Lysosome inhibitor reversed dasatinib-induced EGFR down-regulation, and c-cbl activity was increased by dasatinib, indicating that dasatinib-induced EGFR down-regulation might be through c-cbl-mediated lysosome degradation. Increased EGFR activation by ligand administration rescued cells from dasatinib-induced apoptosis, whereas inhibition of EGFR enhanced its apoptotic effect. Estrogen receptor α (ERα was demonstrated to play a role in Bcl-2 expression, and dasatinib inhibited ERα at the pretranslational level. ERα was associated with EGFR in dasatinib-treated HNSCC cells. Furthermore, the xenograft model showed that dasatinib inhibited HSC3 tumor growth through in vivo down-regulation of EGFR and ERα. In conclusion, degradation of EGFR is a novel mechanism responsible for dasatinib-induced apoptosis in HNSCC cells.

  3. Prognostic value of CXCL12 and CXCR4 in inoperable head and neck squamous cell carcinoma

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    Rave-Fraenk, Margret; Tehrany, Narges; Leu, Martin; Weber, Hanne Elisabeth; Wolff, Hendrik Andreas [University Medical Center Goettingen, Department of Radiotherapy and Radiation Oncology, Goettingen (Germany); Kitz, Julia [University Medical Center Goettingen, Department of Pathology, Goettingen (Germany); Burfeind, Peter [University Medical Center Goettingen, Department of Human Genetics, Goettingen (Germany); Schliephake, Henning [University Medical Center Goettingen, Department of Oral and Maxillofacial Surgery, Goettingen (Germany); Canis, Martin [University Medical Center Goettingen, Department of Otorhinolaryngology, Head and Neck Surgery, Goettingen (Germany); Beissbarth, Tim [University Medical Center Goettingen, Institute of Medical Statistics, Goettingen (Germany); Reichardt, Holger Michael [University Medical Center Goettingen, Institute for Cellular and Molecular Immunology, Goettingen (Germany)

    2016-01-15

    The chemokine CXCL12 and its receptor CXCR4 can affect tumor growth, recurrence, and metastasis. We tested the hypothesis that the CXCL12 and CXCR4 expression influences the prognosis of patients with inoperable head and neck cancer treated with definite radiotherapy or chemoradiotherapy. Formalin-fixed paraffin-embedded pretreatment tumor tissue from 233 patients with known HPV/p16{sup INK4A} status was analyzed. CXCL12 and CXCR4 expressions were correlated with pretreatment parameters and survival data by univariate and multivariate Cox regression. CXCL12 was expressed in 43.3 % and CXCR4 in 66.1 % of the samples and both were correlated with HPV/p16{sup INK4A} positivity. A high CXCL12 expression was associated with increased overall survival (p = 0.036), while a high CXCR4 expression was associated with decreased metastasis-free survival (p = 0.034). A high CXCR4 expression could be regarded as a negative prognostic factor in head and neck cancer because it may foster metastatic spread. This may recommend CXCR4 as therapeutic target for combating head and neck cancer metastasis. (orig.) [German] Das Chemokin CXCL12 und sein Rezeptor CXCR4 beeinflussen Tumorwachstum, Auftreten von Rezidiven und Metastasierung. Es wurde die Hypothese geprueft, dass ein Zusammenhang der CXCL12- und CXCR4-Expression mit der Prognose von Patienten bestehe, die wegen eines inoperablen Kopf-Hals-Tumors eine primaere Radio- oder Radiochemotherapie erhielten. Dabei wurde auch der HPV-Status der Patienten beruecksichtigt. Formalinfixierte Proben aus unbehandelten Tumoren von 233 Patienten mit bekanntem HPV/p16{sup INK4A}-Status wurden ausgewertet. Die CXCL12- und CXCR4-Expression wurde mit klinischen Parametern und Ueberlebensdaten mittels uni- und multivariater Cox Regression analysiert. CXCL12 wurde von 43,3 %, CXCR4 von 66,1 % der Tumoren exprimiert, und beide Marker korrelierten mit einer HPV/p16{sup INK4A}-Expression. Eine hohe CXCL12-Expression war mit einem verbesserten

  4. Medical marijuana use in head and neck squamous cell carcinoma patients treated with radiotherapy.

    Science.gov (United States)

    Elliott, David A; Nabavizadeh, Nima; Romer, Jeanna L; Chen, Yiyi; Holland, John M

    2016-08-01

    The purpose of the study was to better understand why patients with history of head and neck cancer (HNC) treated with radiotherapy are using medical marijuana (MM). Established HNC quality of life questionnaires and our own MM quality of life questionnaire were sent to 15 HNC patients treated at our institution who reported using MM. Patients are clinically disease free and currently using MM to manage long-term side effects after curative HNC treatment. There was a 100 % response rate. Median time from treatment was 45 months (21-136 months). Most patients smoked marijuana (12 patients), while others reported ingestion (4 patients), vaporizing (3 patients), and use of homemade concentrated oil (1 patient). Six patients reported prior recreational marijuana use before diagnosis. MM provided benefit in altered sense, weight maintenance, depression, pain, appetite, dysphagia, xerostomia, muscle spasm, and sticky saliva. HNC patients report MM use to help with long-term side effects of radiotherapy.

  5. Receptor-type Protein Tyrosine Phosphatase β Regulates Met Phosphorylation and Function in Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yiru Xu

    2012-11-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer and has a high rate of mortality. Emerging evidence indicates that hepatocyte growth factor receptor (or Met pathway plays a pivotal role in HNSCC metastasis and resistance to chemotherapy. Met function is dependent on tyrosine phosphorylation that is under direct control by receptor-type protein tyrosine phosphatase β (RPTP-β. We report here that RPTP-β expression is significantly downregulated in HNSCC cells derived from metastatic tumors compared to subject-matched cells from primary tumors. Knockdown of endogenous RPTP-β in HNSCC cells from primary tumor potentiated Met tyrosine phosphorylation, downstream mitogen-activated protein (MAP kinase pathway activation, cell migration, and invasion. Conversely, restoration of RPTP-β expression in cells from matched metastatic tumor decreased Met tyrosine phosphorylation and downstream functions. Furthermore, we observed that six of eight HNSCC tumors had reduced levels of RPTP-β protein in comparison with normal oral tissues. Collectively, the results demonstrate the importance of RPTP-β in tumor biology of HNSCC through direct dephosphorylation of Met and regulation of downstream signal transduction pathways. Reduced RPTP-β levels, with or without Met overexpression, could promote Met activation in HNSCC tumors.

  6. Profiling EGFR activity in head and neck squamous cell carcinoma by using a novel layered membrane Western blot technology.

    Science.gov (United States)

    Patel, Vyomesh; Ramesh, Arun; Traicoff, June L; Baibakov, Galina; Emmert-Buck, Michael R; Gutkind, J Silvio; Knezevic, Vladimir

    2005-05-01

    Given the role of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC), several rational approaches have now been utilized to abrogate tyrosine kinase activity and its disengagement from downstream signal transducers. Monitoring the activity of these molecules could potentially be useful to determine not only drug efficacy but also to identify HNSCC patients most likely to benefit from this type of therapy. In this study we have used a novel high throughput multi-layered Western blotting (MLWestern) method that allows the detection of multiple proteins from a single experiment in order to characterize key components in the EGFR signaling pathway in HNSCC cells. Total and activated forms of EGFR and the downstream effectors, Erk and Akt were readily detected in HNSCC cells, where in the control cells (HaCaT) these proteins could only be detected in EGF stimulated cells. Results from conventional Western blot and MLWestern were comparable. Clustering analysis of protein expression revealed similarities in cellular response between some of the cell lines indicative of similarities in their biological response. The data indicate that MLWestern can be potentially applied to identify molecular targets that could be used for rational therapeutic intervention strategies.

  7. Phosphoinositide Kinase-3 Status Associated With Presence or Absence of Human Papillomavirus in Head and Neck Squamous Cell Carcinomas

    International Nuclear Information System (INIS)

    Yarbrough, Wendell G.; Whigham, Amy; Brown, Brandee; Roach, Michael; Slebos, Robbert

    2007-01-01

    Purpose: To investigate phosphoinositide kinase-3 (PI3K) activation in relation to human papillomavirus (HPV) status in head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Gene expression microarray data were analyzed to determine differentially expressed genes between HPV(+) and HPV(-) HNSCC. PIK3CA gene expression was confirmed by quantitative reverse transcriptase-polymerase chain reaction in seven HPV(+) and seven HPV(-) primary HNSCCs. PIK3CA mutation status in three HPV(+) and nine HPV(-) cell lines was determined by polymerase chain reaction amplification of hot spot exons (1, 9, 20) followed by direct sequencing. Results: PIK3CA was overexpressed in HPV(+)-associated HNSCC compared with the expression in HPV(-) HNSCC. Activation of PIK3CA by mutation was found in 1 of the 12 tested HNSCC cell lines. Conclusion: Activation of PI3K by mutation of PIK3CA is rare in HNSCC cell lines and was not found in three HPV(+) cell lines. One mechanism by which HPV-associated HNSCC might activate PI3K is increased expression of PIK3CA

  8. How to optimize therapeutic ratio in brachytherapy of head and neck squamous cell carcinoma?

    International Nuclear Information System (INIS)

    Mazeron, J.J.; Simon, J.M.; Hardiman, C.; Gerbaulet, A.

    1998-01-01

    Considerable experience has been accumulated with low dose rate (LDR) brachytherapy in the treatment of squamous cell carcinoma of the oral cavity and oropharynx, 4 cm or less in diameter. Recent analysis of large clinical series provided data indicating that modalities of LDR brachytherapy should be optimized in treating these tumours for increasing therapeutic ratio. LDR brachytherapy is now challenged by high dose rate (HDR) brachytherapy and pulsed dose rate (PDR) brachytherapy. Preliminary results obtained with the last two modalities are discussed in comparison with those achieved with LDR brachytherapy. (orig.)

  9. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Montejo, Michael E.; Shrieve, Dennis C. [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O. [Division of Otolaryngology-Head Neck Surgery, Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Agarwal, Neeraj [Department of Internal Medicine, Oncology Division, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Hitchcock, Ying J., E-mail: ying.hitchcock@hci.utah.edu [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States)

    2011-12-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  10. Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck.

    Science.gov (United States)

    Trieu, Vanessa; Pinto, Harlan; Riess, Jonathan W; Lira, Ruth; Luciano, Richard; Coty, Jessie; Boothroyd, Derek; Colevas, A Dimitrios

    2018-03-14

    Chemotherapy for recurrent, metastatic squamous cell carcinoma of the head and neck need not be known for extreme toxicity.The weekly regimen studied here has been demonstrated to be tolerable and effective. The objective of this study was to establish the response rate, progression-free survival (PFS) and overall survival (OS), and safety profile of weekly docetaxel, platinum, and cetuximab (TPC) in patients with relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-nine patients with metastatic or recurrent SCCHN with an Eastern Cooperative Oncology Group (ECOG) performance status <3 were enrolled in an institutional review board-approved phase II trial. This study permitted prior chemoradiation, radiation, and/or surgery, provided that 3 months had elapsed since the end of the potentially curative treatment. Patients received cisplatin 30 mg/m 2 or carboplatin area under the curve (AUC) 2, docetaxel 30 mg/m 2 , and cetuximab 250 mg/m 2 weekly for 3 weeks, followed by a break during the fourth week, for a 28-day cycle. Planned intrapatient dose modifications were based on individual toxicity. Twenty-seven patients received TPC and were evaluable for response and toxicity. Rates of complete response (CR), partial response (PR), and confirmed PR were 3%, 52%, and 30%, respectively. The overall objective response rate was 56%. Estimated median PFS and OS were 4.8 and 14.7 months, respectively. The rates of grade 3 and 4 worst-grade adverse events (AEs) per patient were 85% and 7%, respectively. Dose density through cycle 4 was preserved for all patients; however, treatment beyond cycle 6 with the TPC regimen proved unfeasible. Weekly docetaxel, cisplatin, and cetuximab is an effective regimen for patients with metastatic or recurrent SCCHN. Response rates, PFS, and OS compare favorably with other combination chemotherapy treatments. Grade 4 toxicity rates observed in this study were substantially lower than those described with regimens

  11. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    International Nuclear Information System (INIS)

    Montejo, Michael E.; Shrieve, Dennis C.; Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O.; Agarwal, Neeraj; Hitchcock, Ying J.

    2011-01-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38–55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8–78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  12. Optimising intratumoral treatment of head and neck squamous cell carcinoma models with the diterpene ester Tigilanol tiglate.

    Science.gov (United States)

    Barnett, Catherine M E; Broit, Natasa; Yap, Pei-Yi; Cullen, Jason K; Parsons, Peter G; Panizza, Benedict J; Boyle, Glen M

    2018-04-18

    The five-year survival rate for patients with head and neck squamous cell carcinoma (HNSCC) has remained at ~50% for the past 30 years despite advances in treatment. Tigilanol tiglate (TT, also known as EBC-46) is a novel diterpene ester that induces cell death in HNSCC in vitro and in mouse models, and has recently completed Phase I human clinical trials. The aim of this study was to optimise efficacy of TT treatment by altering different administration parameters. The tongue SCC cell line (SCC-15) was identified as the line with the lowest efficacy to treatment. Subcutaneous xenografts of SCC-15 cells were grown in BALB/c Foxn1 nu and NOD/SCID mice and treated with intratumoral injection of 30 μg TT or a vehicle only control (40% propylene glycol (PG)). Greater efficacy of TT treatment was found in the BALB/c Foxn1 nu mice compared to NOD/SCID mice. Immunohistochemical analysis indicated a potential role of the host's innate immune system in this difference, specifically neutrophil infiltration. Neither fractionated doses of TT nor the use of a different excipiant led to significantly increased efficacy. This study confirmed that TT in 40% PG given intratumorally as a single bolus dose was the most efficacious treatment for a tongue SCC mouse model.

  13. Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Winter, Stuart C; Stephenson, Sally-Anne; Subramaniam, Selva K; Paleri, Vinidh; Ha, Kien; Marnane, Conor; Krishnan, Suren; Rees, Guy

    2009-01-01

    Techniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment. Reconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas. Seven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival. For the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further

  14. Chemovirotherapy for head and neck squamous cell carcinoma with EGFR-targeted and CD/UPRT-armed oncolytic measles virus.

    Science.gov (United States)

    Zaoui, K; Bossow, S; Grossardt, C; Leber, M F; Springfeld, C; Plinkert, P K; Kalle, C von; Ungerechts, G

    2012-03-01

    First-line treatment of recurrent and/or refractory head and neck squamous cell carcinoma (HNSCC) is based on platinum, 5-fluorouracil (5-FU) and the monoclonal antiEGFR antibody cetuximab. However, in most cases this chemoimmunotherapy does not cure the disease, and more than 50% of HNSCC patients are dying because of local recurrence of the tumors. In the majority of cases, HNSCC overexpress the epidermal growth factor receptor (EGFR), and its presence is associated with a poor outcome. In this study, we engineered an EGFR-targeted oncolytic measles virus (MV), armed with the bifunctional enzyme cytosine deaminase/uracil phosphoribosyltransferase (CD/UPRT). CD/UPRT converts 5-fluorocytosine (5-FC) into the chemotherapeutic 5-FU, a mainstay of HNSCC chemotherapy. This virus efficiently replicates in and lyses primary HNSCC cells in vitro. Arming with CD/UPRT mediates efficient prodrug activation with high bystander killing of non-infected tumor cells. In mice bearing primary HNSCC xenografts, intratumoral administration of MV-antiEGFR resulted in statistically significant tumor growth delay and prolongation of survival. Importantly, combination with 5-FC is superior to virus-only treatment leading to significant tumor growth inhibition. Thus, chemovirotherapy with EGFR-targeted and CD/UPRT-armed MV is highly efficacious in preclinical settings with direct translational implications for a planned Phase I clinical trial of MV for locoregional treatment of HNSCC.

  15. Histogram analysis parameters of apparent diffusion coefficient reflect tumor cellularity and proliferation activity in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Surov, Alexey; Meyer, Hans Jonas; Winter, Karsten; Richter, Cindy; Hoehn, Anna-Kathrin

    2018-05-04

    Our purpose was to analyze associations between apparent diffusion coefficient (ADC) histogram analysis parameters and histopathologicalfeatures in head and neck squamous cell carcinoma (HNSCC). The study involved 32 patients with primary HNSCC. For every tumor, the following histogram analysis parameters were calculated: ADCmean, ADCmax, ADC min , ADC median , ADC mode , P10, P25, P75, P90, kurtosis, skewness, and entropy. Furthermore, proliferation index KI 67, cell count, total and average nucleic areas were estimated. Spearman's correlation coefficient (p) was used to analyze associations between investigated parameters. In overall sample, all ADC values showed moderate inverse correlations with KI 67. All ADC values except ADCmax correlated inversely with tumor cellularity. Slightly correlations were identified between total/average nucleic area and ADC mean , ADC min , ADC median , and P25. In G1/2 tumors, only ADCmode correlated well with Ki67. No statistically significant correlations between ADC parameters and cellularity were found. In G3 tumors, Ki 67 correlated with all ADC parameters except ADCmode. Cell count correlated well with all ADC parameters except ADCmax. Total nucleic area correlated inversely with ADC mean , ADC min , ADC median , P25, and P90. ADC histogram parameters reflect proliferation potential and cellularity in HNSCC. The associations between histopathology and imaging depend on tumor grading.

  16. (−-Gossypol Inhibits Growth and Promotes Apoptosis of Human Head and Neck Squamous Cell Carcinoma In Vivo

    Directory of Open Access Journals (Sweden)

    Keith G. Wolter

    2006-03-01

    Full Text Available Resistance to chemotherapy is a common problem encountered in the treatment of head and neck squamous cell carcinoma (HNSCC. Chemoresistant HNSCC tumors frequently overexpress antiapoptotic proteins, such as BCI-xL. (−-Gossypol, the negative enantiomer of a cottonseed polyphenol, binds to BCI-xL and was recently been shown to inhibit HNSCC proliferation in vitro. In this study, we assessed the in vivo efficacy of (−-gossypol in an orthotopic xenograff model of HNSCC, using two human HNSCC cell lines with high BCI-xL expression levels. Both produced tumors in a murine floor-of-mouth model that mimics human HNSCC, exhibiting growth and invasion into adjacent tissues. Mice were randomized into three groups: vehicle control and two daily intraperitoneal (−-gossypol treatment groups (5 and 15 mg/kg. Tumors were measured twice weekly. In the control group, tumors grew progressively, whereas in (−-gossypol treatment groups, tumor growth was significantly suppressed. The mitotic rate in tumors from (−-gossypol-treated animals was significantly lower than that in controls, and an increase in the percentage of apoptotic cells was observed in treated tumors versus controls. Residual tumors remained growth-suppressed for 2 weeks after cessation of (−-gossypol treatment. Our results demonstrate that (−-gossypol can inhibit tumor growth in an orthotopic model of aggressive HNSCC.

  17. PAI-1 levels predict response to fractionated irradiation in 10 human squamous cell carcinoma lines of the head and neck

    International Nuclear Information System (INIS)

    Bayer, Christine; Schilling, Daniela; Hoetzel, Joerg; Egermann, Hannes Peter; Zips, Daniel; Yaromina, Ala; Geurts-Moespot, Anneke; Sprague, Lisa Deborah; Sweep, Fred; Baumann, Michael; Molls, Michael; Adam, Markus

    2008-01-01

    Background and purpose: To investigate the relationships between hypoxia, VEGF and components of the plasminogen activation system (PAS) and to determine their influence on local tumour control after fractionated radiotherapy. Material and methods: Ten cell lines derived from human squamous cell carcinomas of the head and neck (SCCHN) were investigated in vitro and used to generate xenograft tumours. The pimonidazole hypoxic fraction in the total tumour area (pHF tot ) was used to measure hypoxia in pre-treatment tumours and the local tumour control (TCD 50 ) was used as the functional endpoint in vivo. For in vitro experiments, cells were cultured for 24 h under either normoxic or mild hypoxic (∼0.66% O 2 ) conditions. VEGF, PAI-1 and uPA antigen levels were determined by ELISA and uPA activity by an activity assay kit. Results: Of all the factors investigated, only PAI-1 expression correlated with TCD 50 (r = 0.80, p 0.010) and was significantly higher (p = 0.001) in more hypoxic than in less hypoxic tumours. Accordingly, PAI-1 secretion was significantly induced (2.4x) by in vitro hypoxia. Conclusions: These results suggest that pre-treatment PAI-1 levels are higher in more hypoxic tumours and can predict the response to fractionated irradiation in SCCHN

  18. ATN-224 enhances antitumor efficacy of oncolytic herpes virus against both local and metastatic head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ji Young Yoo

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is the sixth most frequent cancer worldwide, and the 5-year survival rates are among the worst of the major cancers. Oncolytic herpes simplex viruses (oHSV have the potential to make a significant impact in the targeted treatment of these patients. Here, we tested antitumor efficacy of RAMBO, an oHSV armed with the antiangiogenic Vstat120, alone and in conjunction with ATN-224, a copper chelator against HNSCC in vitro and in vivo animal models. We found that all tested HNSCC cells responded well to virus treatment and were sensitive to RAMBO-mediated oncolytic destruction. In vivo, RAMBO had a significant antiangiogenic and antitumorigenic effect. Physiologic levels of copper inhibited viral replication and HNSCC cell killing. Chelation of copper using ATN-224 treatment significantly improved serum stability of RAMBO and permitted systemic delivery in HNSCC tumor xenografts models. Furthermore, our results show that the combination of ATN-224 and RAMBO strongly inhibits lung metastases in a mouse model of HNSCC. These findings suggest that combining ATN-224 with RAMBO has potential for clinical trials in both early and advanced HNSCC patients.

  19. Intensity-modulated radiation treatment for head-and-neck squamous cell carcinoma-the University of Iowa experience

    International Nuclear Information System (INIS)

    Yao Min; Dornfeld, Kenneth J.; Buatti, John M.; Skwarchuk, Mark; Tan Huaming; Nguyen, Thanh; Wacha, Judith C.; Bayouth, John E.; Funk, Gerry F.; Smith, Russell B.; Graham, Scott M.; Chang, Kristi; Hoffman, Henry T.

    2005-01-01

    Purpose: To review the University of Iowa experience with intensity-modulated radiotherapy (IMRT) in the treatment of head-and-neck squamous cell carcinoma. Methods and Materials: From October 1999 to April 2004, 151 patients with head-and-neck squamous cell carcinoma were treated with IMRT for curative intent. One patient was lost to follow-up 2 months after treatment and therefore excluded from analysis. Of the remaining 150 patients, 99 were treated with definitive IMRT, and 51 received postoperative IMRT. Sites included were nasopharynx, 5; oropharynx, 56; larynx, 33; oral cavity, 29; hypopharynx, 8; nasal cavity/paranasal sinus, 8; and unknown primary, 11. None of the patients treated with postoperative IMRT received chemotherapy. Of 99 patients who had definitive IMRT, 68 patients received concurrent cisplatin-based chemotherapy. One patient received induction cisplatin-based chemotherapy, but no concurrent chemotherapy was given. Three clinical target volumes (CTV1, CTV2, and CTV3) were defined. The prescribed doses to CTV1, CTV2, and CTV3 in the definitive cohort were 70-74 Gy, 60 Gy, and 54 Gy, respectively. For high-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 64-66 Gy, 60 Gy, and 54 Gy, respectively. For intermediate-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 60 Gy, 60 Gy, and 54 Gy. Results: The median follow-up was 18 months (range, 2-60 months). All living patients were followed for at least 6 months. There were 11 local-regional failures: 7 local failures, 3 regional failures, and 1 failure both in the primary tumor and regional lymph node. There were 16 patients who failed distantly, either with distant metastasis or new lung primaries. The 2-year overall survival, local progression-free survival, locoregional progression-free survival, and distant disease-free survival rates were 85%, 94%, 92%, and 87%, respectively. The median time from treatment completion to local-regional recurrence

  20. Expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer.

    Science.gov (United States)

    Kikuchi, Ryoko; Kikuchi, Yoshihiro; Tsuda, Hitoshi; Maekawa, Hitoshi; Kozaki, Ken-Ichi; Imoto, Issei; Tamai, Seiichi; Shiotani, Akihiro; Iwaya, Keiichi; Sakamoto, Masaru; Sekiya, Takao; Matsubara, Osamu

    2014-07-01

    Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

  1. Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas

    International Nuclear Information System (INIS)

    Levy, Antonin; Blanchard, Pierre; Bellefqih, Sara; Brahimi, Nacera; Deutsch, Eric; Daly-Schveitzer, Nicolas; Tao, Yungan; Guigay, Joel; Janot, Francois; Temam, Stephane; Bourhis, Jean

    2014-01-01

    The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC). Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73 %) with three cycles of cisplatin (100 mg/m 2 , every 3 weeks) or BRT (n = 71; 27 %) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005). Median follow-up was 29 months. In all, 56 % of patients treated with CRT received the planned three cycles (92 % at least two cycles) and 79 % patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72 % and 61 %, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79 %, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76 % for CRT vs. 61 % for BRT) and DC (2-year LRC: 81 % for CRT vs. 68 % for BRT) in comparison with BRT (p [de

  2. The optimal use of granulocyte macrophage colony stimulating factor in radiation induced mucositis in head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Patni Nidhi

    2005-01-01

    Full Text Available Objective: Evaluation of response of granulocyte macrophage colony stimulating factor (GM-CSF on acute radiation toxicity profile in head and neck squamous cell carcinoma. Methods and Materials: Thirty three patients with proven stage I or II head & neck carcinoma received conventional external beam radiation therapy. Out of these, six patients received postoperative adjuvant therapy while remaining 27 received definitive RT. Patients were given 100 mcg GM-CSF subcutaneously per day along with radiation after they developed grade 2 mucositis and /or grade 2 dysphagia and / or complained of moderate pain. GM-CSF was administered till there was a subjective relief or objective response. Patients were evaluated for oral ulceration, swallowing status, pain and weight loss. Response to the treatment and patient outcome was assessed. Results: There was a decreased severity of mucositis and dysphagia in the evaluated patients. None of the patients suffered severe pain or required opioids. The mean weight loss was only 1.94%. Minimal side effects were experienced with GM-CSF. Conclusions: GM-CSF reduces the severity of acute side effects of radiation therapy thereby allowing completion of the treatment without interruption. Its remarkable response needs to be evaluated further in large randomized trials. The time of initiation and cessation of GM-CSF during radiation therapy and the required dose needs to be established.

  3. LASSO NTCP predictors for the incidence of xerostomia in patients with head and neck squamous cell carcinoma and nasopharyngeal carcinoma

    Science.gov (United States)

    Lee, Tsair-Fwu; Liou, Ming-Hsiang; Huang, Yu-Jie; Chao, Pei-Ju; Ting, Hui-Min; Lee, Hsiao-Yi

    2014-01-01

    To predict the incidence of moderate-to-severe patient-reported xerostomia among head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). Multivariable normal tissue complication probability (NTCP) models were developed by using quality of life questionnaire datasets from 152 patients with HNSCC and 84 patients with NPC. The primary endpoint was defined as moderate-to-severe xerostomia after IMRT. The numbers of predictive factors for a multivariable logistic regression model were determined using the least absolute shrinkage and selection operator (LASSO) with bootstrapping technique. Four predictive models were achieved by LASSO with the smallest number of factors while preserving predictive value with higher AUC performance. For all models, the dosimetric factors for the mean dose given to the contralateral and ipsilateral parotid gland were selected as the most significant predictors. Followed by the different clinical and socio-economic factors being selected, namely age, financial status, T stage, and education for different models were chosen. The predicted incidence of xerostomia for HNSCC and NPC patients can be improved by using multivariable logistic regression models with LASSO technique. The predictive model developed in HNSCC cannot be generalized to NPC cohort treated with IMRT without validation and vice versa. PMID:25163814

  4. Review of the Clinical and Biologic Aspects of Human Papillomavirus-Positive Squamous Cell Carcinomas of the Head and Neck

    International Nuclear Information System (INIS)

    Blitzer, Grace C.; Smith, Molly A.; Harris, Stephen L.; Kimple, Randall J.

    2014-01-01

    Human papillomavirus (HPV), a known etiology of a subset of head-and-neck squamous cell carcinomas (HNCs), causes numerous alterations in normal cellular functions. This article reviews the biology, detection, and treatment of HPV-positive HNC. The role of HPV oncoproteins in tumor development, the natural history of HPV infection, and risk factors for and prevention of transmission of oral HPV are considered. Commonly used methods for detecting HPV infection, including limitations of these methods, are discussed to aid the practicing clinician in using these tests in their clinical practice. Clinical characteristics of HPV-positive HNC, including potential explanations for the improved outcomes seen in patients with HPV-positive HNC, are assessed. Ongoing clinical trials specific for patients with HPV-positive HNC are described, and areas in need of additional research are summarized. Until the results of ongoing trials are known, treatment of HPV-positive HNC should not differ in clinical practice from treatment of similar non-HPV related cancers

  5. Review of the Clinical and Biologic Aspects of Human Papillomavirus-Positive Squamous Cell Carcinomas of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Blitzer, Grace C.; Smith, Molly A. [Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Harris, Stephen L. [Radiation Oncology Associates, Manchester, New Hampshire (United States); Kimple, Randall J., E-mail: rkimple@humonc.wisc.edu [Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States)

    2014-03-15

    Human papillomavirus (HPV), a known etiology of a subset of head-and-neck squamous cell carcinomas (HNCs), causes numerous alterations in normal cellular functions. This article reviews the biology, detection, and treatment of HPV-positive HNC. The role of HPV oncoproteins in tumor development, the natural history of HPV infection, and risk factors for and prevention of transmission of oral HPV are considered. Commonly used methods for detecting HPV infection, including limitations of these methods, are discussed to aid the practicing clinician in using these tests in their clinical practice. Clinical characteristics of HPV-positive HNC, including potential explanations for the improved outcomes seen in patients with HPV-positive HNC, are assessed. Ongoing clinical trials specific for patients with HPV-positive HNC are described, and areas in need of additional research are summarized. Until the results of ongoing trials are known, treatment of HPV-positive HNC should not differ in clinical practice from treatment of similar non-HPV related cancers.

  6. Spatial relationship of phosphorylated epidermal growth factor receptor and activated AKT in head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Nijkamp, Monique M.; Hoogsteen, Ilse J.; Span, Paul N.; Takes, Robert P.; Lok, Jasper; Rijken, Paul F.; Kogel, Albert J. van der; Bussink, Johan; Kaanders, Johannes H.A.M.

    2011-01-01

    Background: Overexpression of EGFR correlates with decreased survival after radiotherapy in head and neck squamous cell carcinoma (HNSCC). However, the contribution of the activated form, pEGFR, and its downstream signaling (PI3-K/AKT) pathway is not clear yet. Methods: Fifty-eight patients with HNSCC were included in the study. pEGFR, pAKT, hypoxia, and vessels were visualized using immunohistochemistry. Fractions (defined as the tumor area positive for the respective markers relative to the total tumor area) were calculated by automated image analysis and related to clinical outcome. Results: Both pEGFR (median 0.6%, range 0–34%) and pAKT (median 1.8%, range 0–16%) expression differed between tumors. Also, a large variation in hypoxia was found (median pimonidazole fraction 3.9% 0–20%). A significant correlation between pEGFR and pAKT (r s 0.44, p = 0.004) was seen, however, analysis revealed that this was not always based on spatial coexpression. Low pAKT expression was associated with increased risk of regional recurrence (p < 0.05, log-rank) and distant metastasis (p = 0.04). Conclusion: The correlation between expression of pEGFR and pAKT is indicative of activation of the PI3-K/AKT pathway through phosphorylation of EGFR. Since not all tumors show coexpression to the same extent, other factors must be involved in the activation of this pathway as well.

  7. Outcomes after surgery and postoperative radiotherapy for perineural spread of head and neck cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Warren, Timothy A; Panizza, Benedict; Porceddu, Sandro V; Gandhi, Mitesh; Patel, Parag; Wood, Martin; Nagle, Christina M; Redmond, Michael

    2016-06-01

    Queensland, Australia, has the highest rates of cutaneous squamous cell carcinoma (SCC). Perineural invasion (PNI) is associated with reduced local control and survival. A retrospective review of a prospective database of patients with clinical PNI from cutaneous SCC of the head and neck (SCCHN) treated with surgery and postoperative radiotherapy (PORT) between 2000 and 2011 and a minimum of 24 months follow-up. Patients were excluded if immunosuppressed, had non-SCC histology, or were treated palliatively. Fifty patients (mean age, 60 years) with median follow-up of 50 months were included in this study. A total of 54.8% of known primary tumors had incidental PNI. Ten percent had nodal disease at presentation. MRI neurogram was positive in 95.8%. Recurrence-free survival (RFS) at 5-years was 62%. Five-year disease-specific survival (DSS) and overall survival (OS) were 75% and 64%, respectively. There were no perioperative deaths. This report demonstrates that long-term survival is achievable in patients with clinical PNI from cutaneous SCCHN after surgery and PORT. © 2015 Wiley Periodicals, Inc. Head Neck 38: 824-831, 2016. © 2015 Wiley Periodicals, Inc.

  8. An Update on Cellular MicroRNA Expression in Human Papillomavirus-Associated Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Emmett, Sarah; Whiteman, David C; Panizza, Benedict J; Antonsson, Annika

    2018-06-19

    Squamous cell carcinoma of mucosal sites in the head and neck (HNSCC) is the sixth most common cause of cancer worldwide, and despite advances in conventional management, it still has significant morbidity and mortality associated with both diagnosis and treatment. Advances in our understanding of the biological mechanisms underlying this disease have demonstrated a significant difference between human papillomavirus (HPV)-associated, HPV and tobacco associated, and HPV-negative disease. It remains important to further elucidate the biologic and genetic differences between HPV-associated and tobacco-associated disease, with the aim of earlier diagnosis through screening, and advances in management including the development of novel therapeutic agents. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression, and have effects on almost every cellular function, and have potentially important applications to diagnosis, management and prognosis in HNSCC. Establishing a cellular miRNA expression profile for HPV-associated disease may therefore have important implications for the screening and treatment of this disease. This review summarises the current findings regarding miRNA expression in mucosal HNSCC, and focuses particularly on miRNA expression in HPV-associated tumours. © 2018 S. Karger AG, Basel.

  9. Dysphagia After Chemoradiotherapy for Head-and-Neck Squamous Cell Carcinoma: Dose-Effect Relationships for the Swallowing Structures

    International Nuclear Information System (INIS)

    Dirix, Piet; Abbeel, Sarah; Vanstraelen, Bianca; Hermans, Robert; Nuyts, Sandra

    2009-01-01

    Purpose: To evaluate late dysphagia after chemoradiotherapy for locally advanced head-and-neck squamous cell carcinoma, and to examine its correlation with clinical and dosimetric parameters. Methods and Materials: Consecutive patients, treated with radiotherapy (70-72 Gy) and concomitant chemotherapy (cisplatinum 100 mg/m 2 every 3 weeks) between 2004 and 2007, were examined. Swallowing was evaluated by four quality-of-life questionnaires: EORTC C30 and H and N35, the Performance Status Scale of List, and the MD Anderson Dysphagia Inventory. Clinical and dosimetric parameters were correlated with late dysphagia. Results: A total of 53 disease-free patients were evaluated; mean follow-up was 20.4 months (range, 6-45 months). The volume of the middle pharyngeal constrictor muscle receiving ≥50 Gy (p = 0.04), the mean dose to this structure (p = 0.02) and to the supraglottic larynx (p = 0.04) were significantly associated with late swallowing problems at univariate analysis, along with tumor localization (p = 0.008), T-classification (p = 0.02), and pretreatment swallowing problems (p = 0.01). Only this last factor significantly correlated with late dysphagia at multivariate analysis. Conclusion: These findings motivate further efforts to reduce the dose to the swallowing structures, especially to the pharyngeal constrictor muscles and the larynx. However, clinical parameters are also important and should be included in future prospective trials.

  10. Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: Normal tissue complication probability modeling with latent time correction

    International Nuclear Information System (INIS)

    Rønjom, Marianne Feen; Brink, Carsten; Bentzen, Søren M.; Hegedüs, Laszlo; Overgaard, Jens; Johansen, Jørgen

    2013-01-01

    Background and purpose: To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors. Patients and methods: Patients with HNSCC receiving definitive radiotherapy with 66–68 Gy without surgery were followed up with serial post-treatment thyrotropin (TSH) assessment. HT was defined as TSH >4.0 mU/l. Data were analyzed with both a logistic and a mixture model (correcting for latency) to determine risk factors for HT and develop an NTCP model based on mean thyroid dose (MTD) and thyroid volume. Results: 203 patients were included. Median follow-up: 25.1 months. Five-year estimated risk of HT was 25.6%. In the mixture model, the only independent risk factors for HT were thyroid volume (cm 3 ) (OR = 0.75 [95% CI: 0.64–0.85], p 3 , respectively. Conclusions: Comparing the logistic and mixture models demonstrates the importance of latent-time correction in NTCP-modeling. Thyroid dose constraints in treatment planning should be individualized based on thyroid volume

  11. Clinical implications of nonspecific pulmonary nodules identified during the initial evaluation of patients with head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Minsu [Eulji University School of Medicine, Department of Otorhinolaryngology, Eulji Medical Center, Seoul (Korea, Republic of); Lee, Sang Hoon; Lee, Yoon Se; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon [Asan Medical Center, University of Ulsan College of Medicine, Department of Otolaryngology, Songpa-gu, Seoul (Korea, Republic of); Lee, Choong Wook [Asan Medical Center, University of Ulsan College of Medicine, Department of Radiology, Seoul (Korea, Republic of)

    2017-09-15

    We aimed to identify the clinical implications of nonspecific pulmonary nodules (NPNs) detected in the initial staging workup for patients with head and neck squamous cell carcinoma (HNSCC). Medical records of patients who had been diagnosed and treated in our hospital were retrospectively analysed. After definite treatment, changes of NPNs detected on initial evaluation were monitored via serial chest computed tomography. The associations between NPNs and the clinicopathological characteristics of primary HNSCC were evaluated. Survival analyses were performed according to the presence of NPNs. The study consisted of 158 (49.4%) patients without NPNs and 162 (50.6%) patients with NPNs. The cumulative incidence of probabilities of pulmonary malignancy (PM) development at 2 years after treatment were 9.0% and 6.2% in NPN-negative and NPN-positive patients, respectively. Overall and PM-free survival rates were not significantly different according to NPN status. Cervical lymph node (LN) involvement and a platelet-lymphocyte ratio (PLR) ≥126 increased the risk of PMs (both P <0.05). NPNs detected in the initial evaluation of patients with HNSCC did not predict the risk of pulmonary malignancies. Cervical LN involvement and PLR ≥126 may be independent prognostic factors affecting PM-free survival regardless of NPN status. (orig.)

  12. Fast neutron therapy for squamous cell carcinoma in the head and neck region: results of a randomized trial

    International Nuclear Information System (INIS)

    Duncan, W.; Orr, J.A.; Arnott, S.J.; Jack, W.J.; Kerr, G.R.; Williams, J.R.

    1987-01-01

    A randomized trial of fast neuron therapy compared with 4MV photons for patients with head and neck cancer is reported. One hundred and sixty-eight patients were recruited between 1977 and 1984. The minimum follow-up is 2 years. Three patients were withdrawn before treatment began. Eighty-five were allocated to neutron therapy and 80 to receive photon therapy. All patients had squamous cell cancers in one of four primary sites: oral cavity, oropharynx, larynx, and hypopharynx. Local tumor control was similar in both groups: 44.7% after neutrons and 45.0% after photons. Salvage surgery was performed on 18 patients in each treatment group for residual or recurrent cancer. Acute radiation reactions of the mucous membranes were significantly more severe after photons. The number of patients with serious late reactions was greater after neutron therapy but the difference was not statistically significant. There were six deaths related to late morbidity after neutron therapy but none after photon therapy. Survival was better after photon therapy but the difference compared with the neutron group failed to reach statistical significance. When intercurrent deaths are excluded, the difference is less marked. Photon therapy was clearly better in terms of disease-free survival giving a 2-year local disease-free rate of 41.3% (s.e. 5.5%) compared with 29.4% (s.e. 4.9%) after neutrons

  13. Immunohistochemical and molecular imaging biomarker signature for the prediction of failure site after chemoradiation for head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Rasmussen, Gregers Brünnich; Håkansson, Katrin E; Vogelius, Ivan R

    2017-01-01

    .23; p: .025), Bcl-2 (HR: 2.6; p: .08), SUVmax (HR: 3.5; p: .095) and GTV (HR: 1.7; p: .063). CONCLUSIONS: The models successfully distinguished between risk of locoregional failure and risk of distant metastasis, which is important information for clinical decision-making. High p53 expression has......OBJECTIVE: To identify a failure site-specific prognostic model by combining immunohistochemistry (IHC) and molecular imaging information to predict long-term failure type in squamous cell carcinoma of the head and neck. PATIENT AND METHODS: Tissue microarray blocks of 196 head and neck squamous...... cell carcinoma cases were stained for a panel of biomarkers using IHC. Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional...

  14. MART-10, a newly synthesized vitamin D analog, represses metastatic potential of head and neck squamous carcinoma cells

    Directory of Open Access Journals (Sweden)

    Yang SW

    2016-06-01

    Full Text Available Shih-Wei Yang,1,* Chi-Ying Tsai,2,* Yi-Chun Pan,3 Chun-Nan Yeh,4 Jong-Hwei S Pang,5 Masashi Takano,6 Atsushi Kittaka,6 Horng-Heng Juang,7 Tai C Chen,8 Kun-Chun Chiang4,9 1Department of Otolaryngology – Head and Neck Surgery, Chang Gung Memorial Hospital, Keelung, 2Department of Oral and Maxillofacial Surgery, Chang Gung Memorial Hospital, Taoyuan, 3Department of General Dentistry, Chang Gung Memorial Hospital, Chang Gung University, Keelung, 4General Surgery Department, Chang Gung Memorial Hospital, Keelung, 5Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; 6Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, Japan; 7Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; 8Endocrine Core Laboratory, Boston University School of Medicine, Boston, MA, USA; 9Zebrafish Center, Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China *These authors contributed equally to this work Abstract: Even with multidisciplinary treatment, the prognosis and quality of life of patients diagnosed with head and neck squamous cell carcinoma (HNSCC are still not satisfactory. Previously, 19-Nor-2α-(3-hydroxypropyl-1α,25(OH2D3 (MART-10, the new brand 1α,25(OH2D3 analog, has been demonstrated to be an effective drug to inhibit HNSCC growth in vitro. Since most cancer patients die of metastasis, in this study, the antimetastatic effect of MART-10 on HNSCC was investigated. Our results reveal that both 1α,25(OH2D3 and MART-10 effectively repressed the migration and invasion of HNSCC cells, with MART-10 being much more potent than 1α,25(OH2D3. The antimetastatic effect of 1α,25(OH2D3 and MART-10 was mediated by attenuation of epithelial–mesenchymal transition (EMT, which was supported by the finding that the expression of EMT-inducing transcriptional factors, Sail and Twist, was inhibited by 1α,25(OH2D3 and MART

  15. MicroRNA expression profiles of cancer stem cells in head and neck squamous cell carcinoma

    OpenAIRE

    YATA, KAZUYA; BEDER, LEVENT BEKIR; TAMAGAWA, SHUNJI; HOTOMI, MUNEKI; HIROHASHI, YOSHIHIKO; GRENMAN, REIDAR; YAMANAKA, NOBORU

    2015-01-01

    Increasing evidence indicates that cancer stem cells have essential roles in tumor initiation, progression, metastasis and resistance to chemo-radiation. Recent research has pointed out biological importance of microRNAs in cancer stem cell dysregulation. Total number of mature microRNAs in human genome increased to more than 2,500 with the recent up-date of the database. However, currently no information is available regarding microRNA expression profiles of cancer stem cells in head and nec...

  16. Methods for estimating the site of origin of locoregional recurrence in head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Due, A.K.; Vogelius, I.R.; Berthelsen, A.K.; Kristensen, C.A.; Specht, L. [Copenhagen Univ. (Denmark). Dept. of Radiation Oncology Section 3994; Aznar, M.C. [Copenhagen Univ. (Denmark). Dept. of Radiation Oncology Section 3994; Copenhagen Univ. (Denmark). Niels Bohr Institute; Bentzen, S.M. [Copenhagen Univ. (Denmark). Dept. of Radiation Oncology Section 3994; Wisconsin Univ., MD (United States). Depts. of Human Oncology and Medical Physics; Korreman, S.S. [Copenhagen Univ. (Denmark). Niels Bohr Institute; Roskilde Univ. (Denmark). Dept. of Science, Systems, and Models

    2012-08-15

    Purpose: Methods to estimate the likely origin of recurrences after radiation therapy for head and neck squamous cell carcinoma are compared. Methods and materials: A total of 25 patients meeting the following inclusion criteria were randomly selected: curatively intended intensity-modulated radiotherapy planned on a positron emission tomography-computed tomography (PET/CT) scan during the period 2005-2009; squamous cell carcinoma in the oral cavity, pharynx or larynx; complete clinical response followed by locoregional recurrence; and a CT scan at recurrence before any salvage therapy. Exclusion criteria were previous cancer in the area, surgery prior to radiotherapy, or a synchronous cancer. Three methods of estimating focal points of recurrence origin and two volume overlap methods assigning the recurrences to the most central target volumes encompassing at least 50% or 95% of the recurrence volumes were tested. Treatment planning and recurrence scans were rigid and deformable co-registered in order to transfer focal points to the treatment planning scan. Double determinations of all volumes, points, and co-registrations were made. Results: The volume overlap methods assigned the recurrences to significantly more peripheral target volumes than focal methods (p < 0.0001 for all comparisons of 95% overlap vs. focal methods, p < 0.028 for all comparisons of 50% overlap vs. focal methods). Repeated registrations of the same point had higher reproducibility with deformable registration than with rigid registration (median distance 0.31 vs. 0.35 cm, p = 0.015). No significant differences were observed among the focal methods. Conclusion: Significant differences between methods were found which may affect strategies to improve radiotherapy based on pattern of failure analyses. (orig.)

  17. Incidence trends in head and neck squamous cell carcinoma in Slovenia, 1983-2009: role of human papillomavirus infection.

    Science.gov (United States)

    Strojan, Primož; Zadnik, Vesna; Šifrer, Robert; Lanišnik, Boštjan; Didanović, Vojislav; Jereb, Sara; Poljak, Mario; Kocjan, Boštjan J; Gale, Nina

    2015-12-01

    An increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) was observed in several population-based registries and has been attributed to human papillomavirus (HPV) infection. In the present study, we aimed to assess the contribution of HPV infection to the burden of mucosal head and neck squamous cell carcinoma (HNSCC) in Slovenia. For this purpose, data from the nationwide Cancer Registry of Slovenia for cases diagnosed between 1983 and 2009 were analyzed to determine time trends of age-adjusted incidence rates and survival in terms of annual percentage change (APC) for HNSCC in potentially HPV-related and HPV-unrelated sites. In addition, determination of p16 protein, HPV DNA and E6/E7 mRNA was performed in a cohort of OPSCC patients identified from the prospective database for the years 2007-2008. In total, 2,862 cases of HNSCC in potentially HPV-related sites and 7,006 cases in potentially HPV-unrelated sites were identified with decreased incidence observed over the time period in both groups (-0.58; 95 % CI -1.28 to -0.13 and -0.90; 95 % CI -1.23 to -0.57). Regardless of the group, incidence trends for both genders showed a significant decrease in men and increase in women. In a cohort of 99 OPSCC patients diagnosed between 2007 and 2008, 20 (20.2 %) patients had HPV positive tumors and exhibited a superior outcome compared to HPV-negative patients. In conclusion, results of the epidemiologic and histopathologic study confirmed that HPV infection had no major impact on the incidence trends in the Slovenian patients with HNSCC and, specifically, OPSCC during the studied period.

  18. S-1 monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck after progression on platinum-based chemotherapy

    International Nuclear Information System (INIS)

    Yokota, Tomoya; Onozawa, Yusuke; Boku, Narikazu

    2011-01-01

    Platinum compounds play pivotal roles in treatment for squamous cell carcinoma of the head and neck. The objective was to evaluate the efficacy of S-1 monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy. We retrospectively analyzed 39 consecutive patients with recurrent or metastatic squamous cell carcinoma of the head and neck who received S-1 monotherapy after failure of platinum-based chemotherapy or chemoradiotherapy at the Shizuoka Cancer Center between August 2003 and October 2010. S-1 was given orally twice daily (80 mg/m 2 /day) for 28 days followed by a 14-day rest. The median follow-up period in survivors was 31.5 months. Among 38 patients with measurable lesions, 9 (24%) showed partial response and 15 (39%) showed stable disease. The median progression-free survival was 4.9 months and the median overall survival was 13.2 months. The median progression-free survival for oropharyngeal cancer (n=7) was significantly longer than for other cancers (n=32) (14.9 vs. 4.7 months, P=0.035). The response rate in patients with a recurrence-free interval since the last platinum administration >6.0 months was significantly better than with a recurrence-free interval 6.0 months also showed a significantly better progression-free survival (6.0 vs. 2.6 months, P=0.045). The frequency of Grade 3/4 toxicities was less than 10%. S-1 monotherapy shows promising signs of efficacy and tolerability in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy in this retrospective cohort and warrants further investigation in this population. (author)

  19. Atypical fractionation in advanced squamous cell carcinomas of the head and neck

    International Nuclear Information System (INIS)

    Dobrowsky, W.; Naude, J.; Toth, M.; Millesi, W.; Grasl, M.; Koehler, W.; Kautzky, M.; Pavelka, R.; Dobrowsky, E.

    1992-01-01

    From May 1990 to May 1991, 23 patients with advanced, inoperable squamous cell cancers, clinically staged as III or IV, were treated by unconventional fractionation radiotherapy. Treatment consisted of a continuous hyper-fractionated accelerated radiotherapy, delivering a total dose of 55.3 Gy within 17 consecutive days. In ten patients radiation therapy was combined with chemotherapy: 20 mg mitomycin C/m 2 , administered by intravenous bolus injection on day 5 of treatment. Apart from a confluent mucositis, treatment tolerance was good. Haematological toxicity from mitomycin C was minor and did not require any specific therapy. The mucosal reaction lasted six weeks (median duration) and was not thought to be increased by additional chemotherapy. In twelve of 23 patients a complete remission of the primary tumour was seen, in patients with lymph node metastases there was a complete response in 14 out of 20 patients. After a median follow-up of 18 months, ten of 23 patients have survived (8/23 without evidence of disease). Eleven patients have died due to local tumour progression and one patient died with distant metastases, being without evidence of local tumour. The advantage of this unconventional fractionation, which takes the described short potential tumour doubling time for heat and neck cancers into account, is discussed. (orig.) [de

  20. Bimodal ex vivo expansion of T cells from patients with head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Junker, Niels; Andersen, Mads Hald; Wenandy, Lynn

    2011-01-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has proven effective in metastatic melanoma and should therefore be explored in other types of cancer. The aim of this study was to examine the feasibility of potentially expanding clinically relevant quantities of tumor-specific T-cell cu...

  1. Anti-lymphangiogenic properties of mTOR inhibitors in head and neck squamous cell carcinoma experimental models

    International Nuclear Information System (INIS)

    Ekshyyan, Oleksandr; Moore-Medlin, Tara N; Raley, Matthew C; Sonavane, Kunal; Rong, Xiaohua; Brodt, Michael A; Abreo, Fleurette; Alexander, Jonathan Steven; Nathan, Cherie-Ann O

    2013-01-01

    Tumor dissemination to cervical lymph nodes via lymphatics represents the first step in the metastasis of head and neck squamous cell carcinoma (HNSCC) and is the most significant predictor of tumor recurrence decreasing survival by 50%. The lymphatic suppressing properties of mTOR inhibitors are not yet well understood. Lymphatic inhibiting effects of rapamycin were evaluated in vitro using two lymphatic endothelial cell (LEC) lines. An orthotopic mouse model of HNSCC (OSC-19 cells) was used to evaluate anti-lymphangiogenic effects of rapamycin in vivo. The incidence of cervical lymph node metastases, numbers of tumor-free lymphatic vessels and those invaded by tumor cells in mouse lingual tissue, and expression of pro-lymphangiogenic markers were assessed. Rapamycin significantly decreased lymphatic vascular density (p = 0.027), reduced the fraction of lymphatic vessels invaded by tumor cells in tongue tissue (p = 0.013) and decreased metastasis-positive lymph nodes (p = 0.04). Rapamycin also significantly attenuated the extent of metastatic tumor cell spread within lymph nodes (p < 0.0001). We found that rapamycin significantly reduced LEC proliferation and was correlated with decreased VEGFR-3 expression in both LEC, and in some HNSCC cell lines. The results of this study demonstrate anti-lymphangiogenic properties of mTOR inhibitors in HNSCC. mTOR inhibitors suppress autocrine and paracrine growth stimulation of tumor and lymphatic endothelial cells by impairing VEGF-C/VEGFR-3 axis and release of soluble VEGFR-2. In a murine HNSCC orthotopic model rapamycin significantly suppressed lymphovascular invasion, decreased cervical lymph node metastasis and delayed the spread of metastatic tumor cells within the lymph nodes

  2. Lactoferricin B reverses cisplatin resistance in head and neck squamous cell carcinoma cells through targeting PD-L1.

    Science.gov (United States)

    Zhang, Pei; Liu, Jinzhong; Li, Wenlu; Li, Shanshan; Han, Xinguang

    2018-05-15

    Head and neck squamous cell carcinoma (HNSCC) ranks among the top most common cancers with a poor prognosis. The mechanism of chemoresistance is still not well known. This study is to investigate the programmed death-ligand 1 (PD-L1) expression in HNSCC, and test the effect of lactoferricin B (LfcinB) on chemoresistance and its mechanism. We analyzed 510 HNSCC patients in TCGA database and investigated how CD274 expression was related to patient prognosis. PD-L1 was verified from HNSCC samples at local hospital with immunohistochemistry. PD-L1 expression in the acquired cisplatin-resistant HNSCC cells was examined by PCR and WB in order to test PD-L1-induced chemoresistance. LfcinB inoculation in cisplatin-resistant HNSCC cells and in the nude mice was introduced to test the effect of LfcinB on targeting cisplatin resistance and its mechanism. High CD274 mRNA (>125 FPKM) from TCGA database had a significantly reduced 5-year survival rate, and a lower 5-year survival rate in the chemotherapy and radiotherapy-treated patients (P < .05). PD-L1 overexpression was further supported from analysis of 40 HNSCC specimens. PD-L1 and IL-6 in the established cisplatin-resistant HNSCC cells were shown significantly higher (P < .05). IL-6 and PD-L1 expression were partially inhibited by the anti-IL-6/STAT3 antibody. LfcinB displayed a direct cytotoxic effect on cisplatin-resistant HNSCC cells and HNSCC xenografts of cisplatin-resistant cells in the nude mice displayed significant reduction in tumor volume after LfcinB injection (P < .05). Besides, the increase of IL-6 and PD-L1 in cisplatin-resistant HNSCC cells was abolished in vitro by LfcinB (P < .05). PD-L1 expression in HNSCC cells correlates with poor prognosis and chemoresistance, and LfcinB might provide therapeutic potential in HNSCC patients through modulating IL-6 and PD-L1. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  3. Head and neck squamous cell carcinoma: usefulness of diffusion-weighted MR imaging in the prediction of a neoadjuvant therapeutic effect

    International Nuclear Information System (INIS)

    Kato, Hiroki; Tanaka, Osamu; Hoshi, Hiroaki; Kanematsu, Masayuki; Mizuta, Keisuke; Aoki, Mitsuhiro; Shibata, Toshiyuki; Yamashita, Tomomi; Hirose, Yoshinobu

    2009-01-01

    The purpose of our study was to evaluate the usefulness of diffusion-weighted imaging in predicting the responses to neoadjuvant therapy for head and neck squamous cell carcinomas. Diffusion-weighted, T2-weighted, and gadolinium-enhanced T1-weighted images were obtained from 28 patients with untreated head and neck squamous cell carcinomas with histological proof. A blinded radiologist evaluated the quantitative and qualitative signal intensities and apparent diffusion coefficients (ADCs) in the lesions on each sequence. All patients were treated by neoadjuvant therapies, and the post-therapeutic tumor regression rate was determined. Both the quantitative and qualitative signal intensities on diffusion-weighted images showed positive correlations (r=0.367 and 0.412, p<.05), and the ADCs showed a weak, inversed correlation (r=-0.384, p<.05) with the tumor regression rates. Diffusion-weighted imaging including an assessment by ADCs may be able to predict tumor response to neoadjuvant therapy for head and neck squamous cell carcinomas. (orig.)

  4. Prediction of Neck Dissection Requirement After Definitive Radiotherapy for Head-and-Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Thariat, Juliette; Ang, K. Kian; Allen, Pamela K.; Ahamad, Anesa; Williams, Michelle D.; Myers, Jeffrey N.; El-Naggar, Adel K.; Ginsberg, Lawrence E.; Rosenthal, David I.; Glisson, Bonnie S.; Morrison, William H.; Weber, Randal S.; Garden, Adam S.

    2012-01-01

    Background: This analysis was undertaken to assess the need for planned neck dissection in patients with a complete response (CR) of involved nodes after irradiation and to determine the benefit of a neck dissection in those with less than CR by tumor site. Methods: Our cohort included 880 patients with T1-4, N1-3M0 squamous cell carcinoma of the oropharynx, larynx, or hypopharynx who received treatment between 1994 and 2004. Survival curves were calculated by the Kaplan-Meier Method, comparisons of rates with the log–rank test and prognostic factors by Cox's proportional hazard model. Results: Nodal CR occurred in 377 (43%) patients, of whom 365 patients did not undergo nodal dissection. The 5-year actuarial regional control rate of patients with CR was 92%. Two hundred sixty-eight of the remaining patients (53%) underwent neck dissections. The 5-year actuarial regional control rate for patients without a CR was 84%. Those who had a neck dissection fared better with 5-year actuarial regional control rates of 90% and 76% for those operated and those not operated (p < 0.001). Variables associated with poorer regional control rates included higher T and N stage, non-oropharynx cancers, non-CR, both clinical and pathological. Conclusions: With 92% 5-year neck control rate without neck dissection after CR, there is little justification for systematic neck dissection. The addition of a neck dissection resulted in higher neck control after partial response though patients with viable tumor on pathology specimens had poorer outcomes. The identification of that subgroup that benefits from additional treatment remains a challenge.

  5. Immunoexpression of EGFR and EMMPRIN in a series of cases of head and neck squamous cell carcinoma.

    Science.gov (United States)

    de Andrade, Ana Luiza Dias Leite; Ferreira, Stefânia Jeronimo; Ferreira, Sonia Maria Soares; Ribeiro, Camila Maria Beder; Freitas, Roseana de Almeida; Galvão, Hébel Cavalcanti

    2015-10-01

    The epidermal growth factor receptor (EGFR) and the extracellular matrix metalloproteinase inducer (EMMPRIN) have been identified as oncologically important targets. This study aimed to evaluate the immunoexpression of EGFR and EMMPRIN in a series of cases of head and neck squamous cell carcinoma (HNSCC). Forty-five cases of HNSCC were selected for this study and evaluated with anti-EGFR and anti-EMMPRIN antibodies. The percentage of positive cells was determined assessing to the following categories: score 1 (staining in 0-50% of cells), score 2 (staining in 51-75% of cells), and score 3 (staining in >75% of cells). Immunostaining intensity was graded according to the following parameters: score 1 (absent/weak expression) and score 2 (strong expression). For EGFR, a predominance of high median scores was observed in cases of both histological grades of malignancy and in different clinical stages (p>0.05). For EMMPRIN, a statistically significant difference was observed between the histological grades of malignancy (p=0.030). Regarding the immunostaining intensity of EMMPRIN, it was observed a predominance of score 1 in cases with stages I/II, whereas most cases with stages III/IV presented score 2 (p=0.032). Considering the anatomical location, most cases of buccal floor presented higher median score of EMMPRIN in comparison with the other sites (p=0.015). These findings suggest that both proteins are potential targets for cancer therapy and EMMPRIN can be used as a prognostic marker of a more aggressive biological behavior in patients with HNSCC. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. THE EXPRESSION OF Bcl-2 AND PRO-CASPASE 3 IN HEAD AND NECK SQUAMOUS CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Andrej Cör

    2002-12-01

    Full Text Available Background. Head and neck squamous cell carcinoma (HNSCC is the sixth most common cancer and accounts for 6% of cancers worldwide. A better understanding of its biology could lead to improved treatment options. Generally, the goal of cancer treatment is to abolish cell proliferation and to induce necrotic or aptoptotic cell death. Apoptosis has been recognized as a key mechanism of tumour cell elimination. Different apoptotic signals converge to induce caspase cascade activation. Caspase 3 is the central executioner caspase and is necessary for effective apoptotic cell death. Bcl-2 protein family regulates apoptosis. The Bcl-2 protein itself is a product of a proto-oncogene and has an antiapoptotic action.Methods. In our study, the expression of Bcl-2 and pro-caspase 3 by immunohistochemistry in 28 HNSCC graded into well, moderately and poorly differentiated cancers were investigated.Results. Our results of Bcl-2 expression confirm and extend previous reports in which Bcl-2 over-expression has been recognised as an important parameter in HNSCC biological behaviour. Three of 28 tumours (11% showed significant Bcl-2 expression. Two of them were poorly and one was moderately differentiated. Pro-caspase 3 immunoreactivity was confined mainly to the cytoplasm. Absent or low pro-caspase 3 immunoreactivity was found only in 1 of 6 well differentiated and in 1of 10 moderately differentiated tumours in contrast to 5 of 12 poorly differentiated tumours. In six of 12 poorly differentiated tumours procasapse 3 immunoreactivity was strongly positive. In two cases hyperplastic epithelium was strongly positive in contrast to adjacent HNSCC in the same slide which was completely negative for pro-caspase 3.Conclusions. Our results indicate downregulation of pro-caspase 3 expression, especially in poorly differentiated HNSCC. Further studies are needed to test whether this is related to HNSCC behaviour and predict treatment outcome.

  7. Targeting Polo-Like Kinase 1 Enhances Radiation Efficacy for Head-and-Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Gerster, Kate; Shi Wei; Ng, Benjamin; Yue Shijun; Ito, Emma; Waldron, John; Gilbert, Ralph; Liu Feifei

    2010-01-01

    Purpose: To investigate the efficacy of targeting polo-like kinase 1 (Plk1) combined with ionizing radiotherapy (RT) for head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Polo-like kinase 1 messenger ribonucleic acid (mRNA) was targeted by small interfering RNA (siRNA) transfection into the FaDu HNSCC cell line; reduction was confirmed using quantitative real-time polymerase chain reaction. The cellular effects were assessed using [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) -2-(4-sulfophenyl)-2H-tetrazolium], clonogenic, flow cytometric, and caspase assays. In vivo efficacy of siPlk1 was evaluated using mouse xenograft models. Results: Small interfering Plk1 significantly decreased Plk1 mRNA expression, while also increasing cyclin B1 and p21(Waf1/CIP1) mRNA levels after 24 h. This depletion resulted in a time-dependent increase in FaDu cytotoxicity, which was enhanced by the addition of RT. Flow cytometric and caspase assays demonstrated progressive apoptosis, DNA double-strand breaks (γ-H2AX), G2/M arrest, and activation of caspases 3 and 7. Implantation of siPlk1-treated FaDu cells in severe combined immunodeficient mice delayed tumor formation, and systemic administration of siPlk1 inhibited tumor growth enhanced by RT. Conclusions: These data demonstrate the suitability of Plk1 as a potential therapeutic target for HNSCC, because Plk1 depletion resulted in significant cytotoxicity in vitro and abrogated tumor-forming potential in vivo. The effects of Plk1 depletion were enhanced with the addition of RT, indicating that Plk1 represents an important potential radiation sensitizer for HNSCC.

  8. DAHANCA 10 – Effect of darbepoetin alfa and radiotherapy in the treatment of squamous cell carcinoma of the head and neck. A multicenter, open-label, randomized, phase 3 trial by the Danish head and neck cancer group

    DEFF Research Database (Denmark)

    Overgaard, Jens; Hoff, Camilla Molich; Hansen, Hanne Sand

    2018-01-01

    Purpose: To evaluate if correction of low hemoglobin (Hb) levels by means of darbepoetin alfa improves the outcomes of radiotherapy in patients with squamous cell carcinoma of the head and neck (HNSCC). Patients and methods: Patients eligible for primary radiotherapy and who had Hb values below 14.......0 g/dl were randomized to receive accelerated fractionated radiotherapy with or without darbepoetin alfa. Patients also received the hypoxic radiosensitizer nimorazole. Darbepoetin alfa was given weekly during radiotherapy or until the Hb value exceeded 15.5 g/dl. Results: Following a planned interim...... distributed according to the stratification parameters (gender, T and N staging, tumor site). Treatment with darbepoetin alfa increased the Hb level to the planned value in 81% of the patients. The compliance was good without excess serious adverse events. The results showed a poorer outcome with a 5-year...

  9. MAML1 and TWIST1 co-overexpression promote invasion of head and neck squamous cell carcinoma.

    Science.gov (United States)

    Ardalan Khales, Sima; Ebrahimi, Ehsan; Jahanzad, Eisa; Ardalan Khales, Sahar; Forghanifard, Mohammad Mahdi

    2018-01-15

    Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with considerable morbidity and mortality. Invasion and metastasis of HNSCC is a complex process involving multiple molecules and signaling pathways. Twist Family BHLH Transcription Factor 1 (TWIST1) and Mastermind-like 1 (MAML1) are essential in induction of epithelial-mesenchymal transition through direct regulation of implicated molecules in cellular adhesion, migration and invasion. Our aim in this study was to assess the clinical significance of MAML1 and TWIST1 expression in HNSCC, and elucidate the probable correlation between these genes to exhibit their possible associations with progression and metastasis of the disease. The gene expression profile of MAML1 and TWIST1 was assessed in fresh tumoral compared to distant tumor-free tissues of 55 HNSCC patients using quantitative real-time Polymerase chain reaction (PCR). Significant overexpression of MAML1 and TWIST1 mRNA was observed in 49.1% and 38.2% (P ˂ 0.05) of tumor specimens, respectively. Overexpression of MAML1 was associated with vascular invasion (P = 0.048). Concomitant overexpression of MAML1 and TWIST1 was significantly correlated to each other (P = 0.004). Co-overexpression of the genes was significantly correlated to the various clinicopathological indices of poor prognosis including depth of tumor invasion (P < 0.01), lymphatic invasion and grade of tumor cell differentiation (P < 0.05). Significant correlation between MAML1 and TWIST1 in HNSCC was revealed. This study was the first report elucidating MAML1 clinical relevance in HNSCC. These new findings suggest an oncogenic role for concomitant expression of MAML1 and TWIST1 genes in HNSCC invasion and metastasis. © 2018 John Wiley & Sons Australia, Ltd.

  10. Functional Genomics Uncover the Biology behind the Responsiveness of Head and Neck Squamous Cell Cancer Patients to Cetuximab.

    Science.gov (United States)

    Bossi, Paolo; Bergamini, Cristiana; Siano, Marco; Cossu Rocca, Maria; Sponghini, Andrea P; Favales, Federica; Giannoccaro, Marco; Marchesi, Edoardo; Cortelazzi, Barbara; Perrone, Federica; Pilotti, Silvana; Locati, Laura D; Licitra, Lisa; Canevari, Silvana; De Cecco, Loris

    2016-08-01

    To identify the tumor portrait of the minority of head and neck squamous cell carcinoma (HNSCC) patients with recurrent-metastatic (RM) disease who upon treatment with platinum-based chemotherapy plus cetuximab present a long-lasting response. The gene expression of pretreatment samples from 40 HNSCC-RM patients, divided in two groups [14 long-progression-free survival (PFS) and 26 short-PFS (median = 19 and 3 months, respectively)], was associated with PFS and was challenged against a dataset from metastatic colon cancer patients treated with cetuximab. For biologic analysis, we performed functional and subtype association using gene set enrichment analysis, associated biology across all currently available HNSCC signatures, and inferred drug sensitivity using data from the Cancer Genomic Project. The identified genomic profile exhibited a significant predictive value that was essentially confirmed in the single publicly available dataset of cetuximab-treated patients. The main divergence between long- and short-PFS groups was based on developmental/differentiation status. The long-PFS patients are characterized by basal subtype traits such as strong EGFR signaling phenotype and hypoxic differentiation, further validated by the significantly higher association with the hypoxia metagene. The short-PFS patients presented a strong activation of RAS signaling confirmed in an in vitro model of two isogenic HNSCC cell lines sensitive or resistant to cetuximab. The predicted drug sensitivity for all four EGFR inhibitors was higher in long- versus short-PFS patients (P range: biology behind response to platinum-based chemotherapy plus cetuximab in RM-HNSCC cancer and may have translational implications improving treatment selection. Clin Cancer Res; 22(15); 3961-70. ©2016 AACRSee related commentary by Chau and Hammerman, p. 3710. ©2016 American Association for Cancer Research.

  11. Combined cetuximab and reirradiation for locoregional recurrent and inoperable squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Balermpas, Panagiotis; Roedel, Claus; Weiss, Christian; Hambek, Markus; Seitz, Oliver

    2009-01-01

    Purpose: to investigate the feasibility, toxicity, and efficacy of external-beam reirradiation (Re-RT) combined with cetuximab for patients with inoperable and recurrent squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: seven patients with inoperable recurrence of SCCHN after adjuvant or definitive radiotherapy (RT) and simultaneous or sequential cisplatin-based chemotherapy for primary SCCHN were treated between August and December 2008 with Re-RT (1.8 Gy/fraction to 50.4 Gy) and cetuximab (400 mg/m 2 initial dose in the 1st week, and then 250 mg/m 2 once weekly). Recurrence had to be located at least ≥ 50% in the preirradiated field. Long term toxicity from previous treatment was recorded before Re-RT as a baseline value. Acute and late toxicity derived from the experimental regimen were recorded every week during RT, and then every 3 months. Efficacy was assessed with repeated imaging using response evaluation criteria in solid tumors (RECIST) and clinical examinations 8-12 weeks after end of the treatment and every 3 months thereafter (Tables 1 and 2). Results: only mild localized mucositis occurred in all patients. Two patients developed a grade 3 acneiform rash related to cetuximab. After treatment one patient developed a grade 2 trismus, another showed grade 3 abacterial salivary gland inflammation with severe pain requiring opioid medication. Two patients achieved a complete response after 7 months, one remained stable, three progressed, and one died from pneumonia without having restaging magnetic resonance imaging. Conclusion: A second course of RT combined with cetuximab in patients with inoperable, recurrent HNSCC proved to be feasible with mild or moderate toxicity and encouraging response to treatment. (orig.)

  12. Combined cetuximab and reirradiation for locoregional recurrent and inoperable squamous cell carcinoma of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Balermpas, Panagiotis; Roedel, Claus; Weiss, Christian [Dept. of Radiation Therapy and Oncology, Goethe Univ., Frankfurt/Main (Germany); Hambek, Markus [Dept. of Otorhinolaryngology, Goethe Univ., Frankfurt/Main (Germany); Seitz, Oliver [Dept. of Oral Maxillofacial and Plastic Facial Surgery, Goethe Univ., Frankfurt/Main (Germany)

    2009-12-15

    Purpose: to investigate the feasibility, toxicity, and efficacy of external-beam reirradiation (Re-RT) combined with cetuximab for patients with inoperable and recurrent squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: seven patients with inoperable recurrence of SCCHN after adjuvant or definitive radiotherapy (RT) and simultaneous or sequential cisplatin-based chemotherapy for primary SCCHN were treated between August and December 2008 with Re-RT (1.8 Gy/fraction to 50.4 Gy) and cetuximab (400 mg/m{sup 2} initial dose in the 1st week, and then 250 mg/m{sup 2} once weekly). Recurrence had to be located at least {>=} 50% in the preirradiated field. Long term toxicity from previous treatment was recorded before Re-RT as a baseline value. Acute and late toxicity derived from the experimental regimen were recorded every week during RT, and then every 3 months. Efficacy was assessed with repeated imaging using response evaluation criteria in solid tumors (RECIST) and clinical examinations 8-12 weeks after end of the treatment and every 3 months thereafter (Tables 1 and 2). Results: only mild localized mucositis occurred in all patients. Two patients developed a grade 3 acneiform rash related to cetuximab. After treatment one patient developed a grade 2 trismus, another showed grade 3 abacterial salivary gland inflammation with severe pain requiring opioid medication. Two patients achieved a complete response after 7 months, one remained stable, three progressed, and one died from pneumonia without having restaging magnetic resonance imaging. Conclusion: A second course of RT combined with cetuximab in patients with inoperable, recurrent HNSCC proved to be feasible with mild or moderate toxicity and encouraging response to treatment. (orig.)

  13. Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma.

    Science.gov (United States)

    Gleber-Netto, Frederico O; Zhao, Mei; Trivedi, Sanchit; Wang, Jiping; Jasser, Samar; McDowell, Christina; Kadara, Humam; Zhang, Jiexin; Wang, Jing; William, William N; Lee, J Jack; Nguyen, Minh Ly; Pai, Sara I; Walline, Heather M; Shin, Dong M; Ferris, Robert L; Carey, Thomas E; Myers, Jeffrey N; Pickering, Curtis R

    2018-01-01

    Human immunodeficiency virus-infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those of HNSCC patients without a human immunodeficiency virus (HIV) infection. The reasons for these differences are not clear, and molecular differences between HIV-related HNSCC and non-HIV-related HNSCC may exist. This study compared the mutational patterns of HIV-related HNSCC and non-HIV-related HNSCC. The DNA of 20 samples of HIV-related HNSCCs and 32 samples of non-HIV-related HNSCCs was sequenced. DNA libraries covering exons of 18 genes frequently mutated in HNSCC (AJUBA, CASP8, CCND1, CDKN2A, EGFR, FAT1, FBXW7, HLA-A, HRAS, KEAP1, NFE2L2, NOTCH1, NOTCH2, NSD1, PIK3CA, TGFBR2, TP53, and TP63) were prepared and sequenced on an Ion Personal Genome Machine sequencer. DNA sequencing data were analyzed with Ion Reporter software. The human papillomavirus (HPV) status of the tumor samples was assessed with in situ hybridization, the MassARRAY HPV multiplex polymerase chain reaction assay, and p16 immunostaining. Mutation calls were compared among the studied groups. HIV-related HNSCC revealed a distinct pattern of mutations in comparison with non-HIV-related HNSCC. TP53 mutation frequencies were significantly lower in HIV-related HNSCC. Mutations in HIV+ patients tended to be TpC>T nucleotide changes for all mutated genes but especially for TP53. HNSCC in HIVIIs presents a distinct pattern of genetic mutations, particularly in the TP53 gene. HIV-related HNSCC may have a distinct biology, and an effect of the HIV virus on the pathogenesis of these tumors should not be ruled out. Cancer 2018;124:84-94. © 2017 American Cancer Society. © 2017 American Cancer Society.

  14. Volumetric PET/CT parameters predict local response of head and neck squamous cell carcinoma to chemoradiotherapy

    International Nuclear Information System (INIS)

    Hanamoto, Atsushi; Tatsumi, Mitsuaki; Takenaka, Yukinori; Hamasaki, Toshimitsu; Yasui, Toshimichi; Nakahara, Susumu; Yamamoto, Yoshifumi; Seo, Yuji; Isohashi, Fumiaki; Ogawa, Kazuhiko; Hatazawa, Jun; Inohara, Hidenori

    2014-01-01

    It is not well established whether pretreatment 18 F-FDG PET/CT can predict local response of head and neck squamous cell carcinoma (HNSCC) to chemoradiotherapy (CRT). We examined 118 patients: 11 with nasopharyngeal cancer (NPC), 30 with oropharyngeal cancer (OPC), and 77 with laryngohypopharyngeal cancer (LHC) who had completed CRT. PET/CT parameters of primary tumor, including metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and mean standardized uptake value (SUV max and SUV mean ), were correlated with local response, according to primary site and human papillomavirus (HPV) status. Receiver-operating characteristic analyses were made to access predictive values of the PET/CT parameters, while logistic regression analyses were used to identify independent predictors. Area under the curve (AUC) of the PET/CT parameters ranged from 0.53 to 0.63 in NPC and from 0.50 to 0.54 in OPC. HPV-negative OPC showed AUC ranging from 0.51 to 0.58, while all of HPV-positive OPCs showed complete response. In contrast, AUC ranged from 0.71 to 0.90 in LHC. Moreover, AUCs of MTV and TLG were significantly higher than those of SUV max and SUV mean (P < 0.01). After multivariate analysis, high MTV >25.0 mL and high TLG >144.8 g remained as independent, significant predictors of incomplete response compared with low MTV (odds ratio [OR], 13.4; 95% confidence interval [CI], 2.5–72.9; P = 0.003) and low TLG (OR, 12.8; 95% CI, 2.4–67.9; P = 0.003), respectively. In conclusion, predictive efficacy of pretreatment 18 F-FDG PET/CT varies with different primary sites and chosen parameters. Local response of LHC is highly predictable by volume-based PET/CT parameters

  15. Pembrolizumab in Asia-Pacific patients with advanced head and neck squamous cell carcinoma: Analyses from KEYNOTE-012.

    Science.gov (United States)

    Tahara, Makoto; Muro, Kei; Hasegawa, Yasuhisa; Chung, Hyun Cheol; Lin, Chia-Chi; Keam, Bhumsuk; Takahashi, Kenichi; Cheng, Jonathan D; Bang, Yung-Jue

    2018-03-01

    KEYNOTE-012 was a phase Ib, multicohort study designed to investigate efficacy and safety of pembrolizumab in advanced solid tumors. Results from the subset of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) from the Asia-Pacific region are reported. Patients with recurrent/metastatic HNSCC, measurable disease (RECIST version 1.1), and ECOG performance status (PS) 0-1 were eligible for enrollment in the HNSCC expansion cohort. Patients received pembrolizumab 200 mg every 3 weeks. Response was assessed every 8 weeks. Co-primary end-points were safety and overall response rate (RECIST version 1.1, central review). Secondary end-points included overall survival and response duration. Patients enrolled at any of the five centers throughout the Asia-Pacific region were included in these analyses. Twenty-six patients with HNSCC from the Asia-Pacific region received pembrolizumab. The median age was 62 years, 65% of patients had ECOG PS 1, and 62% had received two or more prior therapies for recurrent/metastatic disease. Sixteen (62%) patients experienced a treatment-related adverse event of any grade, including two (8%) patients who experienced one or more events of grade 3 severity. No treatment-related deaths occurred. The overall response rate was 19% (95% confidence interval, 7%-39%). After a median follow-up of 12 months (range, 2-21 months), a median response duration was not reached (range, 6 to 17+ months); four of five responses lasted ≥6 months. Median overall survival was 11.6 months (95% confidence interval, 4.7-17.7 months). Pembrolizumab was well tolerated and had durable antitumor activity in patients with HNSCC from the Asia-Pacific region. (Trial registration no. NCT01848834.). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  16. Economic Analyses in Squamous Cell Carcinoma of the Head and Neck: A Review of the Literature From a Clinical Perspective

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Jonas A. de, E-mail: jdesouza@medicine.bsd.uchicago.edu [The University of Chicago Medicine, Chicago, Illinois (United States); Santana, Iuri A.; Castro, Gilberto de [Instituto do Câncer do Estado de São Paulo, São Paulo (Brazil); Lima Lopes, Gilberto de [Johns Hopkins Singapore International Medical Centre (Singapore); Tina Shih, Ya-Chen [The University of Chicago Medicine, Chicago, Illinois (United States)

    2014-08-01

    The purpose of this review was to describe cost-effectiveness and cost analysis studies across treatment modalities for squamous cell carcinoma of the head and neck (SCCHN), while placing their results in context of the current clinical practice. We performed a literature search in PubMed for English-language studies addressing economic analyses of treatment modalities for SCCHN published from January 2000 to March 2013. We also performed an additional search for related studies published by the National Institute for Health and Clinical Excellence in the United Kingdom. Identified articles were classified into 3 clinical approaches (organ preservation, radiation therapy modalities, and chemotherapy regimens) and into 2 types of economic studies (cost analysis and cost-effectiveness/cost-utility studies). All cost estimates were normalized to US dollars, year 2013 values. Our search yielded 23 articles: 13 related to organ preservation approaches, 5 to radiation therapy modalities, and 5 to chemotherapy regimens. In general, studies analyzed different questions and modalities, making it difficult to reach a conclusion. Even when restricted to comparisons of modalities within the same clinical approach, studies often yielded conflicting findings. The heterogeneity across economic studies of SCCHN should be carefully understood in light of the modeling assumptions and limitations of each study and placed in context with relevant settings of clinical practices and study perspectives. Furthermore, the scarcity of comparative effectiveness and quality-of-life data poses unique challenges for conducting economic analyses for a resource-intensive disease, such as SCCHN, that requires a multimodal care. Future research is needed to better understand how to compare the costs and cost-effectiveness of different modalities for SCCHN.

  17. High expression of nuclear survivin and Aurora B predicts poor overall survival in patients with head and neck squamous cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Erpolat, O.P.; Akmansu, M. [Medical School of Gazi Univ., Besevler-Ankara (Turkey). Dept. of Radiation Oncology; Gocun, P.U.; Karakus, E.; Akyol, G. [Medical School of Gazi Univ., Besevler-Ankara (Turkey). Dept. of Pathology

    2012-03-15

    Survivin is one of the apoptosis inhibitor proteins. Together with Aurora B, it also plays a role in regulating several aspects of mitosis. High expression of these markers is correlated with malignant behavior of various cancers and resistance to therapy. Our aim was to evaluate the prognostic role of these markers in head and neck cancers. We evaluated the expression of Aurora B and survivin in tissue specimens of 58 patients with head and neck squamous cell carcinoma using immunohistochemistry. Patients who showed high expression of cytoplasmic and nuclear survivin and Aurora B had significantly shorter overall survival (p = 0.036, p < 0.000, p = 0.032, respectively). In multivariate analysis, high expression of nuclear survivin was the only independent negative prognostic factor (p = 0.024). Moreover, it was found that high co-expression of nuclear survivin and Aurora B had a negative effect on survival in univariate (p < 0.000) and multivariate (p < 0.000) analyses. The negative prognostic values of high expression of Aurora B and high co-expression of nuclear survivin and Aurora B on survival were shown. These findings suggest that co-expression of nuclear survivin and Aurora B can be useful diagnostic markers and therapeutic targets for head and neck squamous cell carcinoma. However, further studies with a larger number of patients in a more homogeneous disease group are needed to confirm the conclusion.

  18. Mild pulmonary emphysema a risk factor for interstitial lung disease when using cetuximab for squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Okamoto, Isaku; Tsukahara, Kiyoaki; Sato, Hiroki; Motohashi, Ray; Yunaiyama, Daisuke; Shimizu, Akira

    2017-12-01

    Interstitial lung disease (ILD) is an occasionally fatal adverse event associated with cetuximab (Cmab) therapy. Our objective was to clarify to what degree pulmonary emphysema is a risk factor in the treatment of head and neck cancer with Cmab through a retrospective analysis. Subjects were 116 patients who were administered Cmab for head and neck squamous cell carcinoma. The degree of pulmonary emphysema before initiating treatment with Cmab was visually assessed retrospectively, with scoring according to the Goddard classification used in Japanese chronic obstructive pulmonary disease (COPD) guidelines for chest computed tomography (CT). Scoring was conducted by two diagnostic radiologists and mean scores were used. Cutoffs for the development and nondevelopment of ILD were examined by receiver operating characteristic (ROC) analysis and Fisher's exact test. Values of p pulmonary emphysema would represent a risk factor for ILD when using Cmab.

  19. Review of sentinel node procedure in cN0 head and neck squamous cell carcinomas. Guidelines from the French evaluation cooperative subgroup of GETTEC.

    Science.gov (United States)

    Garrel, R; Poissonnet, G; Temam, S; Dolivet, G; Fakhry, N; de Raucourt, D

    2017-04-01

    The reliability of the sentinel lymph node (SN) technique has been established for more than ten years in T1-T2 oral cavity and oropharynx squamous cell carcinoma. Although most authors stress the necessity of rigorous implementation, there are no agreed guidelines. Moreover, other indications have been described, in other anatomical areas of the upper aerodigestive tract and in case of previous surgery or radiotherapy. SN expert teams, under the GETTEC head and neck tumor study group, conducted a review of the key points for implementation in head and neck cancers through guidelines and a review of classical and extended indications. Reliability depends on respecting key points of preoperative landmarking by lymphoscintigraphy, and intraoperative SN sampling and histological analysis. The SN technique is the best means of diagnosing occult lymph node involvement, whatever the primary tumor location, T stage or patient history. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Radioresistant head and neck squamous cell carcinoma cells: Intracellular signaling, putative biomarkers for tumor recurrences and possible therapeutic targets

    International Nuclear Information System (INIS)

    Skvortsov, Sergej; Jimenez, Connie R.; Knol, Jaco C.; Eichberger, Paul; Schiestl, Bernhard; Debbage, Paul; Skvortsova, Ira; Lukas, Peter

    2011-01-01

    Purpose: Treatment of local and distant head and neck cancer recurrences after radiotherapy remains an unsolved problem. In order to identify potential targets for use in effective therapy of recurrent tumors, we have investigated protein patterns in radioresistant (FaDu-IRR and SCC25-IRR, “IRR cells”) as compared to parental (FaDu and SCC25) head and neck carcinoma cells. Methods and materials: Radiation resistant IRR cells were derived from parental cells after repeated exposure to ionizing radiation 10 times every two weeks at a single dose of 10 Gy, resulting in a total dose of 100 Gy. Protein profiling in parental and IRR cells was carried out using two-dimensional differential gel electrophoresis (2D-DIGE) followed by MALDI-TOF/TOF mass spectrometry. Cell viability, cell migration assays and Western blot analysis were used to confirm results obtained using the proteome approach. Results: Forty-five proteins that were similarly modulated in FaDu-IRR and SCC25-IRR cells compared to parental cells were selected to analyze their common targets. It was found that these either up- or down-regulated proteins are closely related to the enhancement of cell migration which is regulated by Rac1 protein. Further investigations confirmed that Rac1 is up-regulated in IRR cells, and inhibiting its action reduces the migratory abilities of these cells. Additionally, the Rac1 inhibitor exerts cytostatic effects in HNSCC cells, mostly in migratory cells. Conclusions: Based on these results, we conclude that radioresistant HNSCC cells possess enhanced metastatic abilities that are regulated by a network of migration-related proteins. Rac1 protein may be considered as a putative biomarker of HNSCC radiation resistance, and as a potential therapeutic target for treating local and distant HNSCC recurrences.

  1. Impact of apigenin and kaempferol on human head and neck squamous cell carcinoma

    Science.gov (United States)

    Swanson, Hollie I.; Choi, Eun-Young; Helton, W. Brian; Gairola, C. Gary; Valentino, Joseph

    2014-01-01

    Objective Apigenin and kaempferol are plant flavonoids with reported chemopreventive activities. This study aimed to determine the effect of apigenin and kaempferol on cell viability in cultured cells derived from the pharynx (FaDu cell line), an oral cavity carcinoma (PCI-13 cell line), and a metastatic lymph node (PCI-15B cell line) and in explanted FaDu cells. Study Design The in vitro viability of FaDu, PCI-13, and PCI-15B cells treated with apigenin and kaempferol was determined. Tumor growth of FaDu explants was evaluated in athymic mice that were gavaged with either apigenin or kaempferol. Results Although apigenin and kaempferol treatment decreased viability of cells in vitro, cell-type-dependent differences in responsiveness were observed. In vivo apigenin treatment significantly increased the tumor size of FaDu explants. Results obtained using kaempferol were similar. Conclusions The in vitro decrease in FaDu cell viability by apigenin and kaempferol was not observed in in vivo tumor explants using the conditions described in this study. PMID:24439916

  2. Nucleostemin expression in squamous cell carcinoma of the head and neck

    Czech Academy of Sciences Publication Activity Database

    Čada, Z.; Bouček, Jan; Dvoranova, B.; Chovanec, M.; Plzák, J.; Kodet, R.; Betka, J.; Pinot, G. L.; Gabius, H. J.; Smetana Jr, K.

    2007-01-01

    Roč. 27, - (2007), s. 3273-3284 ISSN 0250-7005 Grant - others:GA MZd(CZ) NR9049 Institutional research plan: CEZ:AV0Z50200510 Source of funding: V - iné verejné zdroje Keywords : basal cell carcinoma * epidermis * keratin Subject RIV: EC - Immunology Impact factor: 1.414, year: 2007

  3. Technical and clinical performance of a new assay to detect squamous cell carcinoma antigen levels for the differential diagnosis of cervical, lung, and head and neck cancer.

    Science.gov (United States)

    Holdenrieder, Stefan; Molina, Rafael; Qiu, Ling; Zhi, Xiuyi; Rutz, Sandra; Engel, Christine; Kasper-Sauer, Pia; Dayyani, Farshid; Korse, Catharina M

    2018-04-01

    In squamous cell carcinoma, squamous cell carcinoma antigen levels are often elevated. This multi-center study evaluated the technical performance of a new Elecsys ® squamous cell carcinoma assay, which measures serum squamous cell carcinoma antigen 1 and 2 levels in an equimolar manner, and investigated the potential of squamous cell carcinoma antigen for differential diagnosis of cervical, lung, and head and neck squamous cell carcinoma.Assay precision and method comparison experiments were performed across three European sites. Reference ranges for reportedly healthy individuals were determined using samples from banked European and Chinese populations. Differential diagnosis experiments determined whether cervical, lung, or head and neck cancer could be differentiated from apparently healthy, benign, or other malignant cohorts using squamous cell carcinoma antigen levels alone. Squamous cell carcinoma antigen cut-off levels were calculated based on squamous cell carcinoma antigen levels at 95% specificity. Repeatability coefficients of variation across nine analyte concentrations were ≤5.3%, and intermediate precision coefficients of variation were ≤10.3%. Method comparisons showed good correlations with Architect and Kryptor systems (slopes of 1.1 and 1.5, respectively). Reference ranges for 95th percentiles for apparently healthy individuals were 2.3 ng/mL (95% confidence interval: 1.9-3.8; European cohort, n = 153) and 2.7 ng/mL (95% confidence interval: 2.2-3.3; Chinese cohort, n = 146). Strongest differential diagnosis results were observed for cervical squamous cell carcinoma: receiver operating characteristic analysis showed that squamous cell carcinoma antigen levels (2.9 ng/mL cut-off) differentiate cervical squamous cell carcinoma (n = 127) from apparently healthy females (n = 286; area under the curve: 86.2%; 95% confidence interval: 81.8-90.6; sensitivity: 61.4%; specificity: 95.6%), benign diseases (n = 187; area

  4. Cell-free mitochondrial DNA copy number variation in head and neck squamous cell carcinoma: A study of non-invasive biomarker from Northeast India.

    Science.gov (United States)

    Kumar, Manish; Srivastava, Shilpee; Singh, Seram Anil; Das, Anup Kumar; Das, Ganesh Chandra; Dhar, Bishal; Ghosh, Sankar Kumar; Mondal, Rosy

    2017-10-01

    Head and neck squamous cell carcinoma is the most commonly diagnosed cancer worldwide. The lifestyle, food habits, and customary practices manifest the Northeast Indian population toward higher susceptibility to develop head and neck squamous cell carcinoma. Here, we have investigated the association of smoke and smokeless tobacco, and alcohol with copy number variation of cell-free mitochondrial DNA and cell-free nuclear DNA in cases and controls. Cell-free DNA from plasma was isolated from 50 head and neck squamous cell carcinoma cases and 50 controls with informed written consent using QIAamp Circulating Nucleic Acid Kit. Real-time polymerase chain reaction was done for copy number variation in cell-free mitochondrial DNA and cell-free nuclear DNA. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic application between the two study groups using clinicopathological parameters. The levels of cell-free nuclear DNA and cell-free mitochondrial DNA of cases in association with smoke and smokeless tobacco, alcohol with smoking (p squamous cell carcinoma cases and controls, we distinguished cell-free mitochondrial DNA (cutoff: 19.84 raw Ct; sensitivity: 84%; specificity: 100%; p < 0.001) and cell-free nuclear DNA (cutoff: 463,282 genomic equivalent/mL; sensitivity: 53%; specificity: 87%; p < 0.001). The copy number variation in cases (cell-free nuclear DNA: 5451.66 genomic equivalent/mL and cell-free mitochondrial DNA: 29,103,476.15 genomic equivalent/mL) and controls (cell-free nuclear DNA: 1650.9 genomic equivalent/mL and cell-free mitochondrial DNA: 9,189,312.54 genomic equivalent/mL), respectively. Our result indicates that the cell-free mitochondrial DNA content is highly associated with smoke and smokeless tobacco, betel quid chewing, and alcohol which shows greater promises, holding the key characteristics of diagnostic biomarkers, that is, minimal invasiveness, high specificity, and sensitivity.

  5. Histogram analysis parameters identify multiple associations between DWI and DCE MRI in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Meyer, Hans Jonas; Leifels, Leonard; Schob, Stefan; Garnov, Nikita; Surov, Alexey

    2018-01-01

    Nowadays, multiparametric investigations of head and neck squamous cell carcinoma (HNSCC) are established. These approaches can better characterize tumor biology and behavior. Diffusion weighted imaging (DWI) can by means of apparent diffusion coefficient (ADC) quantitatively characterize different tissue compartments. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) reflects perfusion and vascularization of tissues. Recently, a novel approach of data acquisition, namely histogram analysis of different images is a novel diagnostic approach, which can provide more information of tissue heterogeneity. The purpose of this study was to analyze possible associations between DWI, and DCE parameters derived from histogram analysis in patients with HNSCC. Overall, 34 patients, 9 women and 25 men, mean age, 56.7±10.2years, with different HNSCC were involved in the study. DWI was obtained by using of an axial echo planar imaging sequence with b-values of 0 and 800s/mm 2 . Dynamic T1w DCE sequence after intravenous application of contrast medium was performed for estimation of the following perfusion parameters: volume transfer constant (K trans ), volume of the extravascular extracellular leakage space (Ve), and diffusion of contrast medium from the extravascular extracellular leakage space back to the plasma (Kep). Both ADC and perfusion parameters maps were processed offline in DICOM format with custom-made Matlab-based application. Thereafter, polygonal ROIs were manually drawn on the transferred maps on each slice. For every parameter, mean, maximal, minimal, and median values, as well percentiles 10th, 25th, 75th, 90th, kurtosis, skewness, and entropy were estimated. Сorrelation analysis identified multiple statistically significant correlations between the investigated parameters. Ve related parameters correlated well with different ADC values. Especially, percentiles 10 and 75, mode, and median values showed stronger correlations in comparison to other

  6. Evidence-Based Treatment Options in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

    Directory of Open Access Journals (Sweden)

    Athanassios Argiris

    2017-05-01

    Full Text Available The major development of the past decade in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy (CT, followed by maintenance cetuximab (the “EXTREME” regimen. This regimen is supported by a phase 3 randomized trial and subsequent observational studies, and it confers well-documented survival benefits, with median survival ranging between approximately 10 and 14 months, overall response rates between 36 and 44%, and disease control rates of over 80%. Furthermore, as indicated by patient-reported outcome measures, the addition of cetuximab to platinum-based CT leads to a significant reduction in pain and problems with social eating and speech. Conversely, until very recently, there has been a lack of evidence-based second-line treatment options, and the therapies that have been available have shown low response rates and poor survival outcomes. Presently, a promising new treatment option in R/M SCCHN has emerged: immune checkpoint inhibitors (ICIs, which have demonstrated favorable results in second-line clinical trials. Nivolumab and pembrolizumab are the first two ICIs that were approved by the US Food and Drug Administration. We note that the trials that showed benefit with ICIs included not only patients who previously received ≥1 platinum-based regimens for R/M SCCHN but also patients who experienced recurrence within 6 months after combined modality therapy with a platinum agent for locally advanced disease. In this review, we outline the available clinical and observational evidence for the EXTREME regimen and the initial results from clinical trials for ICIs in patients with R/M SCCHN. We propose that these treatment options can be integrated into a new continuum of care paradigm, with first-line EXTREME regimen followed by second-line ICIs. A number of ongoing clinical trials

  7. Impact of the prophylactic gastrostomy for unresectable squamous cell head and neck carcinomas treated with radio-chemotherapy on quality of life: Prospective randomized trial

    International Nuclear Information System (INIS)

    Salas, Sebastien; Baumstarck-Barrau, Karine; Alfonsi, Marc; Digue, Laurence; Bagarry, Danielle; Feham, Nasreddine; Bensadoun, Rene Jean; Pignon, Thierry; Loundon, Anderson; Deville, Jean-Laurent; Zanaret, Michel; Favre, Roger; Duffaud, Florence; Auquier, Pascal

    2009-01-01

    Background and purpose: Concomitant radio-chemotherapy is the gold standard treatment for unresectable head and neck carcinomas. Placement of prophylactic gastrostomy has been proposed to provide adequate nutrition during the therapeutic sequence. The objectives of this study were to assess the impact of prophylactic gastrostomy on the 6-month quality of life, and to determine the factors related to this quality of life. Materials and methods: Design. randomized, controlled, open study ('systematic percutaneous gastrostomy' versus 'no systematic gastrostomy'). Patients. squamous cell head and neck carcinoma (stages III and IV, UICC 1997). Setting. oncological departments of French university teaching hospitals. Treatment. optimal concomitant radio-chemotherapy. Evaluations. T0 baseline evaluation, T1 during the treatment, T2 end of the treatment, and T3 6-month post-inclusion. Primary endpoint. 6-month quality of life (Qol) assessed using SF36, EORTC QLQ-C30, EORTC QLQ H and N35 questionnaires. Results: The Qol changes from baseline included a decline (T1 and T2) followed by an improvement (T3). Qol at 6 months was significantly higher in the group receiving systematic prophylactic gastrostomy (p = 10 -3 ). Higher initial BMI and lower initial Karnofsky index were significant factors related to a higher 6-month Qol. Conclusions: The study results suggest that prophylactic gastrostomy improves post-treatment quality of life for unresectable head and neck cancer patients, after adjusting for other potential predictive quality of life factors.

  8. Detection of human papillomavirus (HPV) type 6, 16 and 18 in head and neck squamous cell carcinomas by in situ hybridization

    International Nuclear Information System (INIS)

    Cerovac, Z.; Sarcevic, B.; Kralj, Z.; Ban, J.

    1996-01-01

    Seventy seven squamous cell carcinomas (10 oral cavity, 15 tongue, 26 pharynx and larynx), with different grading were analyzed for the presence of HPV DNA by in situ hybridization. Positive signals were found on the nuclei of cancer cells in 25 (32.5%), in the epithelia adjacent to squamous cell carcinomas in 2 (8.7%), and in the resected margins in 1 (4.3%) case. HPV DNA positive signals were obtained in 42% of laryngeal, 34% of pharyngeal, in 20% of oral, and 20% of tongue carcinomas. Out of 25 HPV positive carcinomas a single HPV type was detected in at least 11 (44%), and double or multiple infection in 36% cases; altogether , HPV 6 DNA was determined in 15 (60%), and HPV 16 and/or 18 DNA in 17 (68%) head and neck tumors. The detection rate of HPV was lower than of HPV 16 and/or 18 for tumors in oral cavity, tongue and larynx. Out of 25 HPV DNA positive carcinomas 21% were graded as G1, 27% as G2, and and 44% were G3. The results indicate that HPV may be involved in the pathogenesis of head and neck squamous cell carcinomas. (author)

  9. Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head and neck mucosal site treated with radiation therapy with palliative intent

    International Nuclear Information System (INIS)

    Erkal, Haldun S.; Mendenhall, William M.; Amdur, Robert J.; Villaret, Douglas B.; Stringer, Scott P.

    2001-01-01

    Minimal information has been published about the results of palliative irradiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. Forty patients with this diagnosis were treated at the University of Florida with radiation therapy with palliative intent. The nodal response rate was 65% and the symptomatic response rate was 57% at 1 year. The absolute survival rate was 25% at 1 year, as was the cause-specific survival rate. Radiotherapy successfully palliates more than half of those treated. Approximately one fourth are alive 1 year after irradiation

  10. Combined inhibition of EMMPRIN and epidermal growth factor receptor prevents the growth and migration of head and neck squamous cell carcinoma cells.

    Science.gov (United States)

    Suzuki, Shinsuke; Ishikawa, Kazuo

    2014-03-01

    It has been reported that the epidermal growth factor receptor (EGFR) expression is associated with the extracellular matrix metalloproteinase inducer (EMMPRIN) in some solid tumors; however, the relationship of EMMPRIN with EGFR in head and neck cancers is not fully understood. To determine the relationship between EMMPRIN and EGFR in head and neck squamous cell carcinoma (HNSCC), HNSCC cells were stimulated with epidermal growth factor (EGF), a ligand of EGFR. EMMPRIN expression in HNSCC cells was upregulated by EGF. In addition, EGF stimulation induced HNSCC cell invasion and MMP-9 expression. This increase in invasion and MMP-9 expression was abrogated by downmodulation of EMMPRIN. Furthermore, to determine the effects of combined EMMPRIN and EGFR targeting in HNSCC, HNSCC cells were treated with an EMMPRIN function-blocking antibody and the EGFR inhibitor AG1478. This combined treatment resulted in greater inhibition of HNSCC cell proliferation and migration compared with the individual agents alone. These results suggest that EMMPRIN mediates EGFR-induced tumorigenicity and that combined targeting of EMMPRIN and EGFR may be an efficacious treatment approach.

  11. Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Antonin; Blanchard, Pierre; Bellefqih, Sara; Brahimi, Nacera; Deutsch, Eric; Daly-Schveitzer, Nicolas; Tao, Yungan [Gustave Roussy, Department of Radiation Oncology, Villejuif (France); Guigay, Joel [Gustave Roussy, Department of Medical Oncology, Villejuif (France); Janot, Francois; Temam, Stephane [Gustave Roussy, Department of Head and Neck Surgery, Villejuif (France); Bourhis, Jean [Gustave Roussy, Department of Radiation Oncology, Villejuif (France); University Hospital Lausanne, Department of Radiation Oncology, Lausanne (Switzerland)

    2014-09-15

    The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC). Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73 %) with three cycles of cisplatin (100 mg/m{sup 2}, every 3 weeks) or BRT (n = 71; 27 %) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005). Median follow-up was 29 months. In all, 56 % of patients treated with CRT received the planned three cycles (92 % at least two cycles) and 79 % patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72 % and 61 %, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79 %, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76 % for CRT vs. 61 % for BRT) and DC (2-year LRC: 81 % for CRT vs. 68 % for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001). This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS. (orig.) [German] Die Therapieeffektivitaet mit Platin

  12. DNA methylation regulated microRNAs in HPV-16-induced head and neck squamous cell carcinoma (HNSCC).

    Science.gov (United States)

    Sannigrahi, M K; Sharma, Rajni; Singh, Varinder; Panda, Naresh K; Rattan, Vidya; Khullar, Madhu

    2018-02-17

    Epigenetic modifications have been reported to play an important role in regulating gene expression and these modifications become critical when they have a role in controlling another important layer of epigenetic regulation namely microRNAs. In the present study, we have identified the microRNAs that may be regulated by promoter DNA methylation and histone acetylation in Human papilloma virus-positive head and neck squamous cell carcinoma. HPV-negative cell line (UPCI:SCC-116) and HPV-16 +ve cell line (UPCI:SCC-090) were treated with methylation inhibitor (5-aza-2'-deoxycytidine, AZA) and acetylation inhibitor (Trichostatin-A, TSA), followed by micro-array analysis. The differentially expressed miRNAs were validated in control (n = 10), HPV-16 +ve (n = 30), and HPV -ve (n = 30) HNC, TCGA (n = 529) tissue samples, and two HPV -ve (SCC116 and Hacat) and two HPV +ve (SCC090 and SiHa) cell lines. Methylation-specific PCR (MSP) and chromatin immunoprecipitation assay (CHIP) were performed to validate their regulation. In silico and in vitro analyses of identified miRNAs were done to study putative pathways they target and their possible role in carcinogenesis. Among 10 miRNAs specifically up-regulated in microarray analysis of AZA-treated SCC090 cells, we observed significantly decreased expression of hsa-miR-181c-5p, hsa-miR-132-5p, hsa-miR-658 in HPV +ve HNC cohort, TCGA tissue samples, and cell lines as compared to their HPV -ve counterpart, and their promoter region also possesses CpG islands. MSP and analysis of TCGA data (MethHC) revealed increased frequency of methylation at the promoter of hsa-miR-132-5p that is negatively correlated with its expression. In TSA-treated SCC090 cells, out of 7 miRNAs, two namely Hsa-miR-129-2-3p and Hsa-miR-449a were found to be up-regulated as compared to HPV -ve cells. However, the levels of enrichment by anti-acetyl-H3 and anti-acetyl-H4 were significantly low in cell lines compared to respective controls

  13. An update on head and neck squamous cell carcinoma in respect to classification and systemic therapy. Extended review

    Directory of Open Access Journals (Sweden)

    A. Mudunov

    2018-01-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is among the 10 most common cancers and demonstrates high mortality rates. Well known for its relation to smoking and alcohol consumption, in within the past 10 years a high number of cases, especially of the oropharynx could  be shown to be based on an infection of human papilloma virus, high risk subtypes, mostly type 16 and 18. Often it is connected to younger age at onset, better outcome and better response to radiochemotherapy.Next to well established radiochemotherapy schemes, including targeted therapy as cetuximab, in the recent 2 years a complete new therapeutic approach manifested, called checkpoint inhibition. The drugs of this class block a binding of a membranous ligand to a surface receptor  on T-cells. Without blocking, this binding is physiological in antigen-presenting cells or many other normal tissue cells (e.g. heart muscle, trophoblast inhibiting activation of the cytotoxic T-cells. Research revealed an identical way of tumor cells escaping cell death caused  by patient’s own immune system. By blocking this inhibition, in several carcinoma entities, a very effective disease control was achieved.  So far, 2 pairs of binding are approved for treatment: CD80-CTLA4 and PD1-PDL1. In CD80-CTLA4, it is an inhibitor to CTLA4 (e. g. Ipilimumab, in PD1-PDL1, for both, the ligand an receptor are several inhibitors on the market (e. g. Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab. So far, there could not be found a highly predictive marker for the grade of efficiency of these inhibitors. Next  to very recent and complex markers, tumor mutational burden, the immunohistochemical staining for the ligand, PD-L1 could be established in a few number of carcinoma, incuding adenocarcinoma of the lung. Next to different ways of interpretation of the staining, also different staining procedures used in the trials are hindering an easy establishment of this marker in pathology laboratories

  14. Chemical Composition and antiproliferative activity of essential oil from the leaves of a medicinal herb, Levisticum officinale, against UMSCC1 head and neck squamous carcinoma cells.

    Science.gov (United States)

    Sertel, Serkan; Eichhorn, Tolga; Plinkert, Peter K; Efferth, Thomas

    2011-01-01

    Oral squamous cell carcinoma (OSCC) is a challenging disease with a high mortality rate. Natural products represent a valuable source for the development of novel anticancer drugs. We investigated the cytotoxic potential of essential oil from the leaves of a medicinal plant, Levisticum officinale (lovage) on head and neck squamous carcinoma cells (HNSCC). Cytotoxicity of lovage essential oil was investigated on the HNSCC cell line, UMSCC1. Additionally, we performed pharmacogenomics analyses. Lovage essential oil extract had an IC₅₀ value of 292.6 μg/ml. Genes involved in apoptosis, cancer, cellular growth and cell cycle regulation were the most prominently affected in microarray analyses. The three pathways to be most significantly regulated were extracellular signal-regulated kinase 5 (ERK5) signaling, integrin-linked kinase (ILK) signaling, virus entry via endocytic pathways and p53 signaling. Levisticum officinale essential oil inhibits human HNSCC cell growth.

  15. Factors associated with acute oral mucosal reaction induced by radiotherapy in head and neck squamous cell carcinoma: A retrospective single-center experience.

    Science.gov (United States)

    Tao, Zhenchao; Gao, Jin; Qian, Liting; Huang, Yifan; Zhou, Yan; Yang, Liping; He, Jian; Yang, Jing; Wang, Ru; Zhang, Yangyang

    2017-12-01

    To investigate risk factors for acute oral mucosal reaction during head and neck squamous cell carcinoma radiotherapy.A retrospective study of patients with head and neck squamous cell carcinoma who underwent radiotherapy from November 2013 to May 2016 in Anhui Provincial Cancer Hospital was conducted. Data on the occurrence and severity of acute oral mucositis were extracted from clinical records. Based on the Radiation Therapy Oncology Group (RTOG) grading of acute radiation mucosal injury, the patients were assigned into acute reaction (grades 2-4) and minimum reaction (grades 0-1) groups. Preradiotherapy characteristics and treatment factors were compared between the 2 groups. Multivariate logistic regression analysis was used to detect the independent factors associated with acute oral mucosal reactions.Eighty patients completed radiotherapy during the study period. Oral mucosal reactions were recorded as 25, 31, and 24 cases of grades 1, 2, and 3 injuries, respectively. Significant differences between acute reaction and minimum reaction groups were detected in cancer lymph node (N) staging, smoking and diabetes history, pretreatment platelet count and T-Helper/T-Suppressor lymphocyte (Th/Ts) ratio, concurrent chemotherapy, and total and single irradiation doses.Multivariate analysis showed that N stage, smoking history, single dose parapharyngeal irradiation, and pretreatment platelet count were independent risk factors for acute radiation induced oral mucosal reaction. Smoking history, higher grading of N stage, higher single dose irradiation, and lower preirradiation platelet count may increase the risk and severity of acute radiation oral mucosal reaction in radiotherapy of head and neck cancer patients. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  16. Comparing staging by positron emission tomography with contrast-enhanced computed tomography and by pathology in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Qualliotine, J R; Mydlarz, W K; Chan, J Y K; Zhou, X; Wang, H; Agrawal, N

    2015-12-01

    This study aimed to evaluate the ability of positron emission tomography with contrast-enhanced computed tomography to correctly stage head and neck squamous cell carcinomas, in comparison with pathological staging. Positron emission tomography computed tomography was used to determine the tumour-node-metastasis classification and overall cancer stage in 85 head and neck squamous cell carcinoma patients who underwent pre-operative imaging using this modality and primary surgery between July 2010 and January 2013. Staging by positron emission tomography computed tomography was retrospectively compared with staging using pathological specimens. Agreement between imaging stage and pathological stage was examined by univariate and multivariate analysis both overall and for each primary tumour site. This imaging modality was 87.5 per cent sensitive and 44.8 per cent specific in identifying regional cervical metastases, and had false positive and false negative rates of 18.8 per cent and 8.2 per cent, respectively. The positive predictive and negative predictive values were 75.4 per cent and 65.0 per cent, respectively. Univariate and multivariate analyses revealed a significant agreement between positron emission tomography computed tomography and pathological node classification in older patients and for the oral cavity primary tumour site. There was significant agreement between both methods in the overall classification only for tumours classified as T3 or greater. Positron emission tomography computed tomography should be used with caution for the pre-operative staging of head and neck cancers because of its high false positive and false negative rates.

  17. Co-Expression of Bmi-1 and Podoplanin Predicts Overall Survival in Patients With Squamous Cell Carcinoma of the Head and Neck Treated With Radio(chemo)therapy

    International Nuclear Information System (INIS)

    Vormittag, Laurenz; Thurnher, Dietmar; Geleff, Silvana; Pammer, Johannes; Heiduschka, Gregor; Brunner, Markus; Grasl, Matthaeus Ch.; Erovic, Boban M.

    2009-01-01

    Purpose: This study was conducted to determine the expression of Bmi-1 and podoplanin in healthy oral mucosa and in untreated tumor tissues samples of patients with squamous cell carcinomas of the head and neck. All patients were treated by primary radio(chemo)therapy. Methods and Materials: The expression of Bmi-1 and podoplanin was immunohistochemically evaluated in 12 normal oral mucosa and 63 tumor specimens and correlated with patients' clinical data. Results: In healthy mucosa expression of Bmi-1 and podoplanin was restricted to the basal cell layer. Expression of both proteins was found in 79% and 86% of our tumor samples, respectively. In 17 and 8 samples, Bmi-1 and podoplanin were co-expressed at the invasive border or diffuse in the bulk of the tumor, respectively. Univariate analysis showed that the co-expression of Bmi-1 and podoplanin correlated to decreased overall survival (p = 0.044). Moreover, multivariate testing identified high expression of podoplanin (p = 0.044), co-expression of Bmi-1 and podoplanin (p = 0.007) and lack of response to therapy (p < 0.0001) as predictors of shortened overall survival in patients treated with primary radio(chemo)therapy. Conclusions: Bmi-1 and podoplanin are expressed at the invasive front of squamous cell carcinomas of the head and neck. Co-expression of Bmi-1 and podoplanin predicts significantly overall survival of patients treated with primary radio(chemo)therapy

  18. Pembrolizumab and Vorinostat in Treating Patients With Recurrent Squamous Cell Head and Neck Cancer or Salivary Gland Cancer That Is Metastatic and/or Cannot Be Removed by Surgery

    Science.gov (United States)

    2017-08-23

    Head and Neck Squamous Cell Carcinoma; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharynx Carcinoma; Recurrent Salivary Gland Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage III Major Salivary Gland Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Nasopharyngeal Carcinoma; Stage IV Nasopharyngeal Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma

  19. Head and neck squamous cell carcinoma of unknown primary: Outcomes of a pre-defined institutional treatment policy in a region with a high prevalence of skin cancer.

    Science.gov (United States)

    Huo, Michael; Panizza, Benedict; Bernard, Anne; Porceddu, Sandro V

    2018-02-01

    To determine the rate of subsequent primary site failure in patients with head and neck squamous cell carcinoma of unknown primary (UKP HNSCC) in a region with a high prevalence of cutaneous squamous cell carcinoma, according to a pre-determined institutional policy. Secondary aims included regional and distant control, and overall survival. Patients presenting between April 2005 and June 2016 to the Princess Alexandra Hospital Head and Neck Multidisciplinary Meeting with UKP HNSCC from either presumed mucosal or cutaneous sites treated with curative intent were eligible. Patients with presumed mucosal origin were treated with radiation therapy (RT) with or without chemotherapy, while patients with presumed cutaneous SCC were treated with surgery and post-operative RT with or without chemotherapy. A total of 63 patients met the inclusion criteria. Median follow up duration was 3.9 years (IQR 2.07-5.14). There were no subsequent primary site failures. The rate of nodal failure among presumed mucosal patients was 11.5%, and 8.1% among presumed cutaneous patients. The rate of distant metastatic failure was 11.1% among all patients. The estimated 5 year overall survival was 71.2% (95% CI 59.2-85.7%). Treatment according to our pre-defined institutional policy for UKP HNSCC in a region with a high prevalence of cutaneous SCC appears to be safe and effective with low rates of mucosal primary emergence and nodal failure. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  20. 18F-FLT uptake kinetics in head and neck squamous cell carcinoma: A PET imaging study

    International Nuclear Information System (INIS)

    Liu, Dan; Fenwick, John D.; Chalkidou, Anastasia; Landau, David B.; Marsden, Paul K.

    2014-01-01

    Purpose: To analyze the kinetics of 3 ′ -deoxy-3 ′ -[F-18]-fluorothymidine (18F-FLT) uptake by head and neck squamous cell carcinomas and involved nodes imaged using positron emission tomography (PET). Methods: Two- and three-tissue compartment models were fitted to 12 tumor time-activity-curves (TACs) obtained for 6 structures (tumors or involved nodes) imaged in ten dynamic PET studies of 1 h duration, carried out for five patients. The ability of the models to describe the data was assessed using a runs test, the Akaike information criterion (AIC) and leave-one-out cross-validation. To generate parametric maps the models were also fitted to TACs of individual voxels. Correlations between maps of different parameters were characterized using Pearson'sr coefficient; in particular the phosphorylation rate-constants k 3-2tiss and k 5 of the two- and three-tissue models were studied alongside the flux parameters K FLT-2tiss and K FLT of these models, and standardized uptake values (SUV). A methodology based on expectation-maximization clustering and the Bayesian information criterion (“EM-BIC clustering”) was used to distil the information from noisy parametric images. Results: Fits of two-tissue models 2C3K and 2C4K and three-tissue models 3C5K and 3C6K comprising three, four, five, and six rate-constants, respectively, pass the runs test for 4, 8, 10, and 11 of 12 tumor TACs. The three-tissue models have lower AIC and cross-validation scores for nine of the 12 tumors. Overall the 3C6K model has the lowest AIC and cross-validation scores and its fitted parameter values are of the same orders of magnitude as literature estimates. Maps ofK FLT and K FLT-2tiss are strongly correlated (r = 0.85) and also correlate closely with SUV maps (r = 0.72 for K FLT-2tiss , 0.64 for K FLT ). Phosphorylation rate-constant maps are moderately correlated with flux maps (r = 0.48 for k 3-2tiss vs K FLT-2tiss and r = 0.68 for k 5 vs K FLT ); however, neither phosphorylation

  1. Combined human papillomavirus typing and TP53 mutation analysis in distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma.

    Science.gov (United States)

    Daher, Tamas; Tur, Mehmet Kemal; Brobeil, Alexander; Etschmann, Benjamin; Witte, Biruta; Engenhart-Cabillic, Rita; Krombach, Gabriele; Blau, Wolfgang; Grimminger, Friedrich; Seeger, Werner; Klussmann, Jens Peter; Bräuninger, Andreas; Gattenlöhner, Stefan

    2018-06-01

    In head and neck squamous cell carcinoma (HNSCC), the occurrence of concurrent lung malignancies poses a significant diagnostic challenge because metastatic HNSCC is difficult to discern from second primary lung squamous cell carcinoma (SCC). However, this differentiation is crucial because the recommended treatments for metastatic HNSCC and second primary lung SCC differ profoundly. We analyzed the origin of lung tumors in 32 patients with HNSCC using human papillomavirus (HPV) typing and targeted next generation sequencing of all coding exons of tumor protein 53 (TP53). Lung tumors were clearly identified as HNSCC metastases or second primary tumors in 29 patients, thus revealing that 16 patients had received incorrect diagnoses based on clinical and morphological data alone. The HPV typing and mutation analysis of all TP53 coding exons is a valuable diagnostic tool in patients with HNSCC and concurrent lung SCC, which can help to ensure that patients receive the most suitable treatment. © 2018 Wiley Periodicals, Inc.

  2. The association, clinicopathological significance, and diagnostic value of CDH1 promoter methylation in head and neck squamous cell carcinoma: a meta-analysis of 23 studies

    Directory of Open Access Journals (Sweden)

    Shen ZS

    2016-10-01

    Full Text Available Zhisen Shen,1 Chongchang Zhou,1,2 Jinyun Li,2 Hongxia Deng,1 Qun Li,1 Jian Wang3 1Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital, Ningbo University, 2Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, 3Department of Otorhinolaryngology-Head and Neck Surgery, Ningbo Yinzhou People’s Hospital, Ningbo, Zhejiang, People’s Republic of China Abstract: Epithelial cadherin (encoded by the CDH1 gene is a tumor suppressor glycoprotein that plays a role in the invasion and metastasis of human cancers. As previous studies regarding the association between CDH1 promoter methylation and head and neck squamous cell carcinoma (HNSCC have yielded inconsistent conclusions, a meta-analysis was performed. A systematic literature review was undertaken from four databases: PubMed, Embase, Google Scholar, and Web of Science. Finally, a total of 23 studies (including 1,727 cases of HNSCC and 555 normal controls were included in the present study. Our results showed that the frequency of CDH1 promoter methylation in HNSCC was statistically greater than in controls (odds ratio [OR] =5.94, 95% confidence interval [CI]: 3.36–10.51, P<0.001. In reported cases of HNSCC, CDH1 promoter methylation was statistically associated with tumor stage (OR =0.46, 95% CI: 0.27–0.78, P=0.004 and a history of alcohol consumption (OR =6.04, 95% CI: 2.41–15.14, P<0.001. Moreover, the sensitivity, specificity, and area under the curve of the summary receiver operator characteristic for the included studies were 0.50 (95% CI: 0.4–0.61, 0.89 (95% CI: 0.79–0.95, and 0.74 (95% CI: 0.70–0.78, respectively. In conclusion, our meta-analyses indicated that CDH1 promoter methylation was associated with HNSCC risk, and may be utilized as a valuable diagnostic biomarker for HNSCC. Keywords: CDH1, methylation, diagnosis, head and neck squamous cell carcinoma, HNSCC 

  3. 3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226

    International Nuclear Information System (INIS)

    Hehlgans, Stephanie; Lange, Inga; Eke, Iris; Cordes, Nils

    2009-01-01

    Background and purpose: Focal adhesion kinase (FAK), a main player in integrin signaling and survival, is frequently overexpressed in human cancers and therefore postulated as potential target in cancer therapy. The aim of this study was to evaluate the radiosensitizing potential of the FAK inhibitor TAE226 in three-dimensional (3D) tumor cell cultures. Materials and methods: Head and neck squamous cell carcinoma (HNSCC) cells (FaDu, UT-SCC15, UT-SCC45), lung cancer cells (A549), colorectal carcinoma cells (DLD-1, HCT-116) and pancreatic tumor cells (MiaPaCa2, Panc1) were treated with different concentrations of TAE226 (0-1 μm; 1 or 24 h) without or in combination with irradiation (0-6 Gy, X-ray, single dose). Subsequently, 3D clonogenic survival assays (laminin-rich extracellular matrix) and Western blotting (expression/phosphorylation, e.g. FAK, Akt, ERK1/2) were performed. Results: All investigated 3D cell cultures showed a dose-dependent reduction in clonogenic survival by TAE226. Intriguingly, TAE226 only significantly radiosensitized 3D HNSCC cell cultures accompanied by a pronounced dephosphorylation of FAK, Akt and ERK1/2. Conclusions: Our data demonstrate TAE226 as potent FAK inhibitor that enhances the cellular radiosensitivity particularly of HNSCC cells grown in a 3D cell culture model. Future in vitro and in vivo investigations will clarify, to which extent this approach might be clinically relevant for radiotherapy of HNSCC.

  4. Recent results of cetuximab use in the treatment of squamous cell carcinoma of the head and neck

    Directory of Open Access Journals (Sweden)

    Francesco Perri

    2009-08-01

    Full Text Available Francesco Perri1, Francesco Longo2, Franco Ionna2, Francesco Caponigro11Head and Neck Medical Oncology Unit, 2Head and Neck Surgery Unit, National Tumor Institute of Naples, Naples, ItalyAbstract: Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. The role of cetuximab is paramount in several subsets of head and neck cancer. In particular, the EXTREME study has indicated cetuximab as the only drug to improve survival when associated with cisplatin and 5-fluorouracil in patients with recurrent/metastatic disease. Furthermore, cetuximab, both alone and in combination with cisplatin, is active in patients with recurrent/metastatic disease who have failed prior platinum-based chemotherapy. Cetuximab, given in association with radiation therapy, is a treatment of choice in first-line therapy of patients with locally advanced inoperable disease. In the same setting, the role of induction chemotherapy has gained considerable interest over the last few years and a number of efforts are being pursued to optimally integrate induction chemotherapy with radiation therapy plus cetuximab. The combination of cetuximab and other targeted therapies is among the most promising new perspectives for patients with head and neck cancer.Keywords: cetuximab, head and neck cancer, locally advanced, recurrent/metastatic

  5. Acid sphingomyelinase activity as an indicator of the cell stress in HPV-positive and HPV-negative head and neck squamous cell carcinoma.

    Science.gov (United States)

    Gerle, Mirko; Medina, Tuula Peñate; Gülses, Aydin; Chu, Hanwen; Naujokat, Hendrik; Wiltfang, Jörg; Açil, Yahya

    2018-03-21

    Human papillomavirus (HPV) infection, especially HPV-16 and HPV-18, has been increasingly associated with head and neck squamous cell carcinoma. The treatment of HPV-positive squamous cell carcinoma has a better response to both radiotherapy and chemotherapy and presents a better prognosis for the patient. Defining the underlying mechanism of the difference might help in developing future treatment options and could be an important factor in personal therapy planning. Endogenously secreted acid sphingomyelinase (ASMase) levels in the cellular stress caused by irradiation and cisplatin were investigated. MTT assay was performed to evaluate the viability of the treated cells. Keratinocytes were used to evaluate the effects of radiation on normal tissues. Irradiation caused a dose-dependent increase in ASMase activity in both SCC9 HPV-negative, and UDSCC2 HPV-positive cells. ASMase activity in UDSCC2 cells was significantly higher than that in SCC9 cells. UDSCC cells were more sensitive to cisplatin treatment than SCC cells, and the dose-response in the activity was observed in long-time treatments when high doses of cisplatin were used. The results of the current study have clearly showed that HPV positivity should be considered as one of the determinative factors which should be considered when tumor treatments are planned. However, further studies are needed to determine the differences in cellular responses and pathways among HPV-negative and HPV-positive cells.

  6. Irradiation-induced regulation of plasminogen activator inhibitor type-1 and vascular endothelial growth factor in six human squamous cell carcinoma lines of the head and neck

    International Nuclear Information System (INIS)

    Artman, Meri Tuuli

    2014-01-01

    Radiation therapy is frequently used to treat squamous cell carcinoma of the head and neck (SCCHN), although, it can be unsuccessful due to radiation resistance of the tumor. Currently, there are no established predictive markers for radiation resistance in SCCHN. The aim of this work was to investigate PAI-1 and VEGF secretion as markers for radiation resistance in six human SCCHN cell lines. The cell lines differed in their basal secretion levels and in their in vitro radiation sensitivity. PAI-1 and VEGF levels increased after irradiation in a dose-dependent manner. A significant correlation was detected between radiation-induced PAI-1 and VEGF secretion, which suggests that irradiation-induced secretion of PAI-1 and VEGF are partially regulated by related mechanisms. However, neither basal levels nor radiation-induced PAI-1 and VEGF secretion correlated with radiation resistance. Therefore, PAI-1 and VEGF are most likely not predictive markers for radiation resistance in SCCHN.

  7. Histogram analysis of apparent diffusion coefficient maps for the differentiation between lymphoma and metastatic lymph nodes of squamous cell carcinoma in head and neck region.

    Science.gov (United States)

    Wang, Yan-Jun; Xu, Xiao-Quan; Hu, Hao; Su, Guo-Yi; Shen, Jie; Shi, Hai-Bin; Wu, Fei-Yun

    2018-06-01

    Background To clarify the nature of cervical malignant lymphadenopathy is highly important for the diagnosis and differential diagnosis of head and neck tumors. Purpose To investigate the role of first-order apparent diffusion coefficient (ADC) histogram analysis for differentiating lymphoma from metastatic lymph nodes of squamous cell carcinoma (SCC) in the head and neck region. Material and Methods Diffusion-weighted imaging (DWI) data of 67 patients (lymphoma, n = 20; SCC, n = 47) with malignant lymphadenopathy were retrospectively analyzed. The SCC group was divided into nasopharyngeal SCC and non-nasopharyngeal SCC groups. The ADC histogram features (ADC 10 , ADC 25 , ADC mean , ADC median , ADC 75 , ADC 90 , skewness, and kurtosis) were derived and then compared by independent-samples t-test and one-way analysis of variance test, respectively. Receiver operating characteristic curve analyses were employed to investigate diagnostic performance of the significant parameters. Results Lymphoma showed significantly lower ADC mean , ADC median , ADC 75 , and ADC 90 than SCC (all P  0.05). Lymphoma showed significantly lower ADC 25 , ADC mean , ADC median , ADC 75 , and ADC 90 than non-nasopharyngeal SCC (all P histogram analysis is capable of differentiating lymphoma from metastatic lymph nodes of SCC, especially those of non-nasopharyngeal SCC.

  8. Hyperfractionated radiation in combination with local hyperthermia in the treatment of advanced squamous cell carcinoma of the head and neck: a phase I-II study

    International Nuclear Information System (INIS)

    Amichetti, Maurizio; Romano, Mario; Busana, Lucia; Bolner, Andrea; Fellin, Gianni; Pani, Giuseppe; Tomio, Luigi; Valdagni, Riccardo

    1997-01-01

    Twenty-seven patients with cervical metastases from squamous cell head and neck tumours were treated with hyperfractionated XRT (total dose 69.60-76.80 Gy, 1.2 Gy b.i.d. five times a week) combined with a total of two to six sessions of superficial external HT. Acute local toxicity was mild; as major acute side effects, only one ulceration was recorded. No severe late side effects were observed. Late toxicity was similar to that observed in our previous studies with the combination of heat and radiation. Nodal complete response was observed in 77% of patients, partial response was observed in 15% of patients and no change was observed in 8% of patients. Five-year actuarial nodal control was 64.5 ± 19% and 5-year actuarial survival was 24 ± 10%. The treatment of nodal metastases from head and neck tumours with the combination of HT and hyperfractionated XRT is feasible with an acceptable acute and late toxicity profile

  9. Locally Advanced Stage IV Squamous Cell Carcinoma of the Head and Neck: Impact of Pre-Radiotherapy Hemoglobin Level and Interruptions During Radiotherapy

    International Nuclear Information System (INIS)

    Rades, Dirk; Stoehr, Monika; Kazic, Nadja; Hakim, Samer G.; Walz, Annette; Schild, Steven E.; Dunst, Juergen

    2008-01-01

    Purpose: Stage IV head and neck cancer patients carry a poor prognosis. Clear understanding of prognostic factors can help to optimize care for the individual patient. This study investigated 11 potential prognostic factors including pre-radiotherapy hemoglobin level and interruptions during radiotherapy for overall survival (OS), metastases-free survival (MFS), and locoregional control (LC) after radiochemotherapy. Methods and Materials: Eleven factors were investigated in 153 patients receiving radiochemotherapy for Stage IV squamous cell head and neck cancer: age, gender, Karnofsky performance score (KPS), tumor site, grading, T stage, N stage, pre-radiotherapy hemoglobin level, surgery, chemotherapy type, and interruptions during radiotherapy >1 week. Results: On multivariate analysis, improved OS was associated with KPS 90-100 (relative risk [RR], 2.36; 95% confidence interval [CI], 1.20-4.93; p = .012), hemoglobin ≥12 g/dL (RR, 1.88; 95% CI, 1.01-3.53; p = .048), and no radiotherapy interruptions (RR, 2.59; 95% CI, 1.15-5.78; p = .021). Improved LC was significantly associated with lower T stage (RR, 2.17; 95% CI, 1.16-4.63; p = .013), hemoglobin ≥12 g/dL (RR, 4.12; 95% CI, 1.92-9.09; p 1 week. It appears important to avoid anemia and radiotherapy interruptions to achieve the best treatment results

  10. Re-irradiation with cetuximab or cisplatin-based chemotherapy for recurrent squamous cell carcinoma of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Dornoff, Nicolas; Weiss, Christian; Roedel, Franz [J. W. Goethe University, Department of Radiotherapy and Oncology, Frankfurt a. M. (Germany); Wagenblast, Jens [J. W. Goethe University, Department of Otorhinolaryngology, Frankfurt a. M. (Germany); Ghanaati, Shahram [J. W. Goethe University, Department of Maxillofacial Surgery, Frankfurt a. M. (Germany); Atefeh, Nateghian; Roedel, Claus; Balermpas, Panagiotis [J. W. Goethe University, Department of Radiotherapy and Oncology, Frankfurt a. M. (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); German Cancer Consortium (DKTK) partner site: Frankfurt, Frankfurt a. M. (Germany)

    2015-08-15

    Locoregional recurrence remains the main pattern of failure after primary combined modality treatment of squamous cell carcinoma of the head and neck (SCCHN). We compared the efficacy and toxicity of either cisplatin or cetuximab in combination with re-irradiation (ReRT) for recurrent unresectable SCCHN. Various clinicopathological factors were investigated to establish a prognostic score. Between 2007 and 2014, 66 patients with recurrent SCCHN originating in a previously irradiated area received cetuximab (n = 33) or cisplatin-based chemotherapy (n = 33) concomitant with ReRT. Toxicity was evaluated weekly and at every follow-up visit. Physical examination, endoscopy, CT or MRI scans were used to evaluate response and disease control. With a mean follow-up of 18.3 months, the 1-year overall survival (OS) rates for Re-RT with cetuximab and cisplatin-based chemotherapy were 44.4 and 45.5 % (p = 0.352), respectively. At 1 year, local control rates (LCR) were 46.4 and 54.2 % (p = 0.625), freedom from metastases (FFM) rates 73.6 and 81 % (p = 0.842), respectively. Haematological toxicity ≥ grade 3 occurred more often in the cisplatin group (p < 0.001), pain ≥ grade 3 was increased in the cetuximab group (p = 0.034). A physiological haemoglobin level and a longer interval between primary RT and ReRT, proved to be significant prognostic factors for OS (multivariate: p = 0.003, p = 0.002, respectively). Site of the recurrence and gross target volume (GTV) did not show a significant impact on OS in multivariate analysis (p = 0.160, p = 0.167, respectively). A prognostic-score (1-4 points) based on these four variables identified significantly different subgroups: 1-year OS for 0/1/2/3/4 prognostic points: 10, 38, 76, 80 and 100 %, respectively (p < 0.001). Both cetuximab- and cisplatin-based ReRT of SCCHN recurrences are feasible and effective treatment options with comparable results in terms of tumour control and survival. Acute adverse events may differ slightly

  11. Alpha-2 Heremans Schmid Glycoprotein (AHSG) Modulates Signaling Pathways in Head and Neck Squamous Cell Carcinoma Cell Line SQ20B

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Pamela D.; Sakwe, Amos [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Koumangoye, Rainelli [Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Yarbrough, Wendell G. [Division of Otolaryngology, Departments of Surgery and Pathology and Yale Cancer Center, Yale University, New Haven, CT 06520 (United States); Ochieng, Josiah [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Marshall, Dana R., E-mail: dmarshall@mmc.edu [Department of Pathology, Anatomy and Cell Biology, Meharry Medical College, Nashville, TN 37208 (United States)

    2014-02-15

    This study was performed to identify the potential role of Alpha-2 Heremans Schmid Glycoprotein (AHSG) in Head and Neck Squamous Cell Carcinoma (HNSCC) tumorigenesis using an HNSCC cell line model. HNSCC cell lines are unique among cancer cell lines, in that they produce endogenous AHSG and do not rely, solely, on AHSG derived from serum. To produce our model, we performed a stable transfection to down-regulate AHSG in the HNSCC cell line SQ20B, resulting in three SQ20B sublines, AH50 with 50% AHSG production, AH20 with 20% AHSG production and EV which is the empty vector control expressing wild-type levels of AHSG. Utilizing these sublines, we examined the effect of AHSG depletion on cellular adhesion, proliferation, migration and invasion in a serum-free environment. We demonstrated that sublines EV and AH50 adhered to plastic and laminin significantly faster than the AH20 cell line, supporting the previously reported role of exogenous AHSG in cell adhesion. As for proliferative potential, EV had the greatest amount of proliferation with AH50 proliferation significantly diminished. AH20 cells did not proliferate at all. Depletion of AHSG also diminished cellular migration and invasion. TGF-β was examined to determine whether levels of the TGF-β binding AHSG influenced the effect of TGF-β on cell signaling and proliferation. Whereas higher levels of AHSG blunted TGF-β influenced SMAD and ERK signaling, it did not clearly affect proliferation, suggesting that AHSG influences on adhesion, proliferation, invasion and migration are primarily due to its role in adhesion and cell spreading. The previously reported role of AHSG in potentiating metastasis via protecting MMP-9 from autolysis was also supported in this cell line based model system of endogenous AHSG production in HNSCC. Together, these data show that endogenously produced AHSG in an HNSCC cell line, promotes in vitro cellular properties identified as having a role in tumorigenesis. Highlights: • Head

  12. Alpha-2 Heremans Schmid Glycoprotein (AHSG) Modulates Signaling Pathways in Head and Neck Squamous Cell Carcinoma Cell Line SQ20B

    International Nuclear Information System (INIS)

    Thompson, Pamela D.; Sakwe, Amos; Koumangoye, Rainelli; Yarbrough, Wendell G.; Ochieng, Josiah; Marshall, Dana R.

    2014-01-01

    This study was performed to identify the potential role of Alpha-2 Heremans Schmid Glycoprotein (AHSG) in Head and Neck Squamous Cell Carcinoma (HNSCC) tumorigenesis using an HNSCC cell line model. HNSCC cell lines are unique among cancer cell lines, in that they produce endogenous AHSG and do not rely, solely, on AHSG derived from serum. To produce our model, we performed a stable transfection to down-regulate AHSG in the HNSCC cell line SQ20B, resulting in three SQ20B sublines, AH50 with 50% AHSG production, AH20 with 20% AHSG production and EV which is the empty vector control expressing wild-type levels of AHSG. Utilizing these sublines, we examined the effect of AHSG depletion on cellular adhesion, proliferation, migration and invasion in a serum-free environment. We demonstrated that sublines EV and AH50 adhered to plastic and laminin significantly faster than the AH20 cell line, supporting the previously reported role of exogenous AHSG in cell adhesion. As for proliferative potential, EV had the greatest amount of proliferation with AH50 proliferation significantly diminished. AH20 cells did not proliferate at all. Depletion of AHSG also diminished cellular migration and invasion. TGF-β was examined to determine whether levels of the TGF-β binding AHSG influenced the effect of TGF-β on cell signaling and proliferation. Whereas higher levels of AHSG blunted TGF-β influenced SMAD and ERK signaling, it did not clearly affect proliferation, suggesting that AHSG influences on adhesion, proliferation, invasion and migration are primarily due to its role in adhesion and cell spreading. The previously reported role of AHSG in potentiating metastasis via protecting MMP-9 from autolysis was also supported in this cell line based model system of endogenous AHSG production in HNSCC. Together, these data show that endogenously produced AHSG in an HNSCC cell line, promotes in vitro cellular properties identified as having a role in tumorigenesis. Highlights: • Head

  13. Chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)

    International Nuclear Information System (INIS)

    Katori, Hideaki; Tsukuda, Mamoru; Mochimatu, Izumi; Ishitoya, Junichi; Mikami, Yasukazu; Tanigaki, Yuji; Ikeda, Yoichi; Taguchi, Takahide

    2003-01-01

    This study evaluated the efficacy and toxicity of chemoradiotherapy using docetaxel (DOC), cisplatin (CDDP) and 5-fluorouracil (5-FU) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Nineteen patients with previously untreated stage III-IV SCCHN were entered onto this trial. Patients received two cycles of chemotherapy with TPF. Radiation was targeted to begin on the first day of chemotherapy, day 1. The total radiation dose was between 63.0 and 74.0 Gy. At least three patients were examined at each dose level before advancing to the next level. The maximum-tolerated dose (MTD) of this regimen was DOC 60, CDDP 60 and 5-FU 600 mg/m 2 /day. The main toxicities were mucositis, leukocytopenia, neutropenia, anemia, liver dysfunction and renal dysfunction. The overall response rate was 100%, including 84% complete responses (CR). The high complete response rate justifies further evaluation of this chemoradiotherapy modality in advanced SCCHN patients. (author)

  14. Detection of Local Tumor Recurrence After Definitive Treatment of Head and Neck Squamous Cell Carcinoma: Histogram Analysis of Dynamic Contrast-Enhanced T1-Weighted Perfusion MRI.

    Science.gov (United States)

    Choi, Sang Hyun; Lee, Jeong Hyun; Choi, Young Jun; Park, Ji Eun; Sung, Yu Sub; Kim, Namkug; Baek, Jung Hwan

    2017-01-01

    This study aimed to explore the added value of histogram analysis of the ratio of initial to final 90-second time-signal intensity AUC (AUCR) for differentiating local tumor recurrence from contrast-enhancing scar on follow-up dynamic contrast-enhanced T1-weighted perfusion MRI of patients treated for head and neck squamous cell carcinoma (HNSCC). AUCR histogram parameters were assessed among tumor recurrence (n = 19) and contrast-enhancing scar (n = 27) at primary sites and compared using the t test. ROC analysis was used to determine the best differentiating parameters. The added value of AUCR histogram parameters was assessed when they were added to inconclusive conventional MRI results. Histogram analysis showed statistically significant differences in the 50th, 75th, and 90th percentiles of the AUCR values between the two groups (p Histogram analysis of AUCR can improve the diagnostic yield for local tumor recurrence during surveillance after treatment for HNSCC.

  15. Histopathological features of clinical perineural invasion of cutaneous squamous cell carcinoma of the head and neck and the potential implications for treatment.

    Science.gov (United States)

    Panizza, Benedict; Warren, Timothy A; Solares, C Arturo; Boyle, Glen M; Lambie, Duncan; Brown, Ian

    2014-11-01

    Nonmelanoma skin cancer (NMSC) with perineural invasion (PNI) is most commonly seen in cutaneous squamous cell carcinoma of the head and neck (SCCHN). The cranial nerves are a conduit for skin cancer to reach the brainstem. The histopathological features of 51 tissue specimens from 49 patients with cutaneous SCCHN and clinical PNI were assessed with consecutive transverse and longitudinal sections. No skip lesions were identified. Tumor spread was contiguous in all specimens. No tumor spread into the perineural space from surrounding or adjacent tumor was seen. Proximal large cranial nerves showed epineural involvement in 3.9% in areas with large tumor bulk, extensive PNI, and intraneural invasion. Perineural tumor spread in cutaneous SCCHN was contiguous and no skip lesions were evident in nerve specimens assessed in this series. Spread beyond cranial nerve perineurium was uncommon, reflecting its multilayer barrier function at this level. These findings may have treatment implications. © 2013 Wiley Periodicals, Inc.

  16. Summary of major radiation fractionation and chemotherapy trials for organ preservation therapy in locally advanced head and neck squamous cell carcinoma.

    Science.gov (United States)

    Parsons, James T; Greene, Bruce D

    2015-01-01

    To review radiation fractionation and chemotherapy trials for patients undergoing organ preservation therapy for locally advanced head and neck squamous cell carcinoma. Radiation therapy fractionation and chemotherapy trial results as well as historical evidence are systematically reviewed. Trial results, which involve nearly 30,000 patients, have been interpreted, compared, and presented in a structured manner to demonstrate the changing approaches in treatment over the years from the 1960s to the present. The review includes data from the split-course radiation therapy era, meta-analyses of chemotherapy and radiation therapy fractionation trials, cetuximab trials, "triple-drug trials," and modern trials of induction chemotherapy followed by concomitant chemotherapy and radiation therapy. This summary will be useful to clinicians making treatment decisions today and to investigators designing trials in the future. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  17. Bifidobacterium breve as a delivery vector of IL-24 gene therapy for head and neck squamous cell carcinoma in vivo.

    Science.gov (United States)

    Wang, L; Vuletic, I; Deng, D; Crielaard, W; Xie, Z; Zhou, K; Zhang, J; Sun, H; Ren, Q; Guo, C

    2017-11-01

    Beneficial bacteria are becoming ever more popular gene delivery method for hypoxia-tumor targeting in vivo. In this study we investigated the therapeutic effect of new recombinant Bifidobacterium breve strain expressing interleukin (IL)-24 gene (B. breve-IL24) on head and neck tumor xenograft in mice. Briefly, B. breve transformants were obtained through electro-transformation. Bacteria-tumor-targeting ability were analyzed in vivo over different time points (1, 3 and 7 days post-bacteria injection). Furthermore, the therapeutic effect of bacteria on tumor cells in vivo were analyzed as follows: 30 Balb/c nude mice bearing subcutaneous tumor were randomly divided in three groups (Drug group, green fluorescent protein (GFP) group and Saline group). The therapy lasted for 2 weeks and included B. breve-IL24 administration via tail vein for Drug group, B. breve-GFP for GFP group and phosphate buffered saline for Saline group. The tumor growth was monitored using standard caliper technique, while the apoptosis induction in vivo was analyzed by Real-time Positron Emission Tomography/Computed Tomography (PET/CT) imaging ([18F]-ML-10 tracer). At the end of the experiment, tumor tissues were collected and analyzed by western blotting. Briefly, our results suggested that our new recombinant bacterium has the capability of targeting tumor tissue in vivo. As for the therapeutic effect, our new strain has revealed to be a promising therapeutic approach against tumor growth in vivo. Briefly, higher tumor growth inhibition and higher tumor cell apoptosis induction were observed in Drug group compared with the GFP and Saline groups. To conclude, a new recombinant strain B. breve-IL24 offers a novel, safe and clinically acceptable therapeutic approach for tumor therapy in vivo.

  18. Prospective Assessment of Patterns of Failure After High-Precision Definitive (Chemo)Radiation in Head-and-Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Gupta, Tejpal; Jain, Sandeep; Agarwal, Jai Prakash; Ghosh-Laskar, Sarbani; Phurailatpam, Reena; Pai-Shetty, Rajershi; Dinshaw, Ketayun A.

    2011-01-01

    Purpose: To prospectively analyze patterns of failure in patients with head-and-neck squamous cell carcinoma treated with definitive high-precision radiotherapy with a focus on location of failure relative to target volume coverage. Methods and Materials: Sixty patients treated with three-dimensional conformal radiotherapy or intensity-modulated radiation therapy were included. Locoregional failure volume was defined on the planning data set at relapse, and dose received was analyzed by use of dose-volume histograms. Results: Thirteen patients were deemed to have had locoregional failures, of which two did not have any viable tumor on salvage neck dissection, leaving eleven patients with proven persistent or recurrent locoregional disease. Of these, 9 patients had in-field failure, 1 marginal failure, and 1 both in-field and marginal failures. Overall, only 2 of 11 patients (18%) with relapse had any marginal failure. Of the 20 sites of locoregional failure, 15 (75%) were in-field and 5 (25%) marginal. Distant metastases were detected in 3 patients, whereas a second new primary developed in 3 others. With a median follow-up of 26 months (interquartile range, 18-31 months) for surviving patients, the 3-year local control, locoregional control, disease-free survival, and overall survival rates were 75.3%, 74%, 67.2%, and 60.5%, respectively. Conclusions: Locoregional relapse remains the predominant pattern of failure in head-and-neck squamous cell carcinoma treated with high-precision definitive radiotherapy with the majority of failures occurring 'in-field' within the high-dose volume. Marginal failures can occur, particularly in the vicinity of the spared parotid gland. The therapeutic index of high-precision conformal radiotherapy is largely dependent on adequate selection and delineation of target volumes and organs at risk.

  19. Occupational dust exposure and head and neck squamous cell carcinoma risk in a population-based case–control study conducted in the greater Boston area

    International Nuclear Information System (INIS)

    Langevin, Scott M; McClean, Michael D; Michaud, Dominique S; Eliot, Melissa; Nelson, Heather H; Kelsey, Karl T

    2013-01-01

    Head and neck cancers account for an estimated 549,000 global cancer diagnoses each year. While tobacco use, alcohol consumption, and HPV16 infection are considered to be the major risk factors for this disease, occupational risk factors, including exposure to asbestos, have also been described, although dust exposures other than asbestos have been historically understudied. We have investigated the relationship between occupational exposures to five types of dusts, including sawdust, concrete dust, leather dust, metal dust, and chimney soot, and head and neck squamous cell carcinomas (HNSCC) in the greater Boston area. We report findings from a population-based case–control study involving 951 incident HNSCC cases and 1193 controls, frequency matched on age (±3 years), sex, and town/neighborhood of residence. Multivariable logistic regression was used to assess the association between occupational exposure to each type of dust and HNSCC, overall and by primary tumor site. After adjusting for age, sex, race, smoking, alcohol consumption, education, and HPV16 serology, laryngeal carcinoma risk increased for each decade of occupational exposure to sawdust (OR = 1.2, 95% CI: 1.0, 1.3) and metal dust (OR = 1.2, 95% CI: 1.0, 1.4); and HNSCC risk increased for each decade of occupational leather dust exposure (OR = 1.5, 95% CI: 1.2, 1.9). We have provided evidence for an association between occupational sawdust and metal dust and laryngeal squamous cell carcinoma, and leather dust and HNSCC, with increasing risk with longer duration at the exposed occupation

  20. Clinical utility and prospective comparison of ultrasonography and computed tomography imaging in staging of neck metastases in head and neck squamous cell cancer in an Indian setup

    International Nuclear Information System (INIS)

    Ashraf, M.; Biswas, J.; Jha, J.; Nayak, S.; Singh, V.; Majumdar, S.; Bhowmick, A.; Dam, A.

    2011-01-01

    Preoperative lymph node screening of all neck compartments is favored by clinicians for the management of the neck. The presence of a metastatic node on one side of the neck reduces the 5-year survival rate to 50%, and the presence of a metastatic node on both sides of the neck reduces the 5-year survival rate to 25%. This study compared the evaluation of lymph node metastases by ultrasonography (USG) and computed tomography (CT) in patients with squamous cell cancer of the head and neck region. Five hundred and eighty-four patients with squamous cell cancer of the head and neck were prospectively evaluated for the presence of cervical lymph node metastases. All patients underwent clinical examination (palpation), USG and CT imaging. Neck dissection was performed in all the patients, and the results of the preoperative evaluation were correlated with the surgical and histopathological findings. Metastases in neck nodes were identified in 148 patients by histopathological examination. Doppler USG correctly identified 136 node-positive patients (n=148; sensitivity 91.8%, specificity 97%). CT imaging correctly identified 122 patients with metastatic lymph nodes (n=148; sensitivity 83%, specificity 93%). Positive predictive values of USG and CT imaging were 95.6% and 91.3%, respectively, whereas the negative predictive values of these two imaging studies were 95.4% and 89.6%, respectively. The accuracy and sensitivity of USG in detection of cervical lymph node metastases make it a potentially promising and cheap preoperative tool for staging neck node metastases and optimizing the treatment plan for surgeons, especially in countries such as India. (author)

  1. Can radiological changes in lymph node volume during treatment predict success of radiation therapy in patients with locally advanced head and neck squamous cell carcinoma?

    International Nuclear Information System (INIS)

    Mishra, Sanju; Hammond, Alexander; Read, Nancy; Venkatesan, Varagur; Warner, Andrew; Winquist, Eric; Nichols, Anthony

    2013-01-01

    Assessment of nodal response after radiotherapy (RT) for head and neck squamous cell carcinoma is difficult, as both CT and positron emission tomography scanning have limited predictive value for residual disease. We sought to measure changes in nodal volume during RT to determine whether such changes are predictive of nodal disease control. Patients with locally advanced head and neck squamous cell carcinoma treated with 70Gy of radical RT (±chemotherapy or anti-epidermal growth factor receptor (EGFR) antibodies) were eligible. Baseline pre-RT scans and cone-beam CT scans done at the outset of treatment and at weeks 3, 5 and 7 (cone-beam CTs 1, 2, 3 and 4, respectively) were deformably coregistered, and 3D nodal volumes were measured. Thirty-eight eligible patients were identified. The main primary tumour site was oropharyngeal; most patients had stage IVa disease. Twenty-seven patients received concurrent platinum-based chemotherapy, 10 received only an EGFR inhibitor with RT and one received RT alone. Twelve patients had a failure in the neck. After week 1 of treatment, a 4% mean decrease in nodal volume was observed, increasing to 40% at week 7. Platinum-based chemotherapy achieved significantly greater decreases in nodal volume than EGFR inhibitors (44 vs. 25%; P=0.026). Advanced tumour stage predicted neck failure (P=0.002), but nodal volumes did not correlate with neck control. Changes in nodal volume are minimal initially during RT but accelerate during the latter weeks of therapy. This study suggests that chemotherapy achieves a greater decrease in nodal volume than EGFR inhibitors and that nodal changes do not predict disease control in the neck.

  2. Occupational dust exposure and head and neck squamous cell carcinoma risk in a population-based case-control study conducted in the greater Boston area.

    Science.gov (United States)

    Langevin, Scott M; McClean, Michael D; Michaud, Dominique S; Eliot, Melissa; Nelson, Heather H; Kelsey, Karl T

    2013-12-01

    Head and neck cancers account for an estimated 549,000 global cancer diagnoses each year. While tobacco use, alcohol consumption, and HPV16 infection are considered to be the major risk factors for this disease, occupational risk factors, including exposure to asbestos, have also been described, although dust exposures other than asbestos have been historically understudied. We have investigated the relationship between occupational exposures to five types of dusts, including sawdust, concrete dust, leather dust, metal dust, and chimney soot, and head and neck squamous cell carcinomas (HNSCC) in the greater Boston area. We report findings from a population-based case-control study involving 951 incident HNSCC cases and 1193 controls, frequency matched on age (±3 years), sex, and town/neighborhood of residence. Multivariable logistic regression was used to assess the association between occupational exposure to each type of dust and HNSCC, overall and by primary tumor site. After adjusting for age, sex, race, smoking, alcohol consumption, education, and HPV16 serology, laryngeal carcinoma risk increased for each decade of occupational exposure to sawdust (OR = 1.2, 95% CI: 1.0, 1.3) and metal dust (OR = 1.2, 95% CI: 1.0, 1.4); and HNSCC risk increased for each decade of occupational leather dust exposure (OR = 1.5, 95% CI: 1.2, 1.9). We have provided evidence for an association between occupational sawdust and metal dust and laryngeal squamous cell carcinoma, and leather dust and HNSCC, with increasing risk with longer duration at the exposed occupation. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  3. L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Geomela Panagiota-Aikaterini

    2012-10-01

    Full Text Available Abstract Background Head and neck squamous cell carcinoma (HNSCC represents one of the most commonly diagnosed malignancies worldwide. The DDC gene encodes L-DOPA decarboxylase, an enzyme catalyzing the decarboxylation of L-DOPA to dopamine. We have recently shown that DDC mRNA is a significant predictor of patients’ prognosis in colorectal adenocarcinoma and prostate cancer. The aim of the current study was to analyze the DDC mRNA expression in HNSCC patients. Methods 53 malignant tumors were resected from the larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissues of HNSCC patients, and were homogenized. Total RNA was isolated and converted into first-strand cDNA. An ultrasensitive real-time PCR method based on the SYBR Green chemistry was used for DDC mRNA quantification in head and neck tissue specimens. Relative quantification was performed using the comparative Ct (2-ddCt method. Results DDC mRNA levels were lower in squamous cell carcinomas (SCCs of the larynx and tongue than in adjacent non-cancerous tissue specimens. Furthermore, low DDC mRNA expression was noticed in laryngeal and tongue tumors of advanced TNM stage or bigger size, compared to early-stage or smaller tumors, respectively. No statistically significant differences were observed between SCCs resected from pharynx, buccal mucosa, or nasal cavity, and their normal counterparts. Conclusion This is the first study examining the DDC mRNA expression in HNSCC. According to our results, DDC mRNA expression may constitute a potential prognostic biomarker in tongue and/or larynx SCCs, which principally represent the overwhelming majority of HNSCC cases.

  4. L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study

    International Nuclear Information System (INIS)

    Geomela, Panagiota-Aikaterini; Kontos, Christos K; Yiotakis, Ioannis; Fragoulis, Emmanuel G; Scorilas, Andreas

    2012-01-01

    Head and neck squamous cell carcinoma (HNSCC) represents one of the most commonly diagnosed malignancies worldwide. The DDC gene encodes L-DOPA decarboxylase, an enzyme catalyzing the decarboxylation of L-DOPA to dopamine. We have recently shown that DDC mRNA is a significant predictor of patients’ prognosis in colorectal adenocarcinoma and prostate cancer. The aim of the current study was to analyze the DDC mRNA expression in HNSCC patients. 53 malignant tumors were resected from the larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissues of HNSCC patients, and were homogenized. Total RNA was isolated and converted into first-strand cDNA. An ultrasensitive real-time PCR method based on the SYBR Green chemistry was used for DDC mRNA quantification in head and neck tissue specimens. Relative quantification was performed using the comparative Ct (2 -ddCt ) method. DDC mRNA levels were lower in squamous cell carcinomas (SCCs) of the larynx and tongue than in adjacent non-cancerous tissue specimens. Furthermore, low DDC mRNA expression was noticed in laryngeal and tongue tumors of advanced TNM stage or bigger size, compared to early-stage or smaller tumors, respectively. No statistically significant differences were observed between SCCs resected from pharynx, buccal mucosa, or nasal cavity, and their normal counterparts. This is the first study examining the DDC mRNA expression in HNSCC. According to our results, DDC mRNA expression may constitute a potential prognostic biomarker in tongue and/or larynx SCCs, which principally represent the overwhelming majority of HNSCC cases

  5. Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Soares Fernando A

    2011-04-01

    Full Text Available Abstract Background Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+ and recurrent head and neck squamous cell carcinoma (HNSCC may increase our understanding of the complex biology of this disease. Methods Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative or tumor recurrence (recurrent or non-recurrent tumor after treatment (surgery with neck dissection followed by radiotherapy. Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category. Results The most frequent alterations were the repression of modules in negative lymph node (N0 and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed. Conclusions The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway

  6. Early Response Monitoring with 18F-FDG PET and Cetuximab-F(ab')2-SPECT After Radiotherapy of Human Head and Neck Squamous Cell Carcinomas in a Mouse Model

    NARCIS (Netherlands)

    Dijk, L.K. van; Boerman, O.C.; Franssen, G.M.; Lok, J.; Kaanders, J.H.A.M.; Bussink, J.

    2014-01-01

    Only a subset of patients with head and neck squamous cell carcinomas (HNSCCs) benefit from radiotherapy and concurrent epidermal growth factor receptor (EGFR) inhibitor therapy with cetuximab, indicating the need for patient selection. The aim of this study was to visualize the change in

  7. Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study

    NARCIS (Netherlands)

    Psyrri, A.; Fortpied, C.; Koutsodontis, G.; Avgeris, M.; Kroupis, C.; Goutas, N.; Menis, J.; Herman, L.; Giurgea, L.; Remenar, E.; Degardin, M.; Pateras, I.S.; Langendijk, J.A.; Herpen, C.M.L. van; Awada, A.; Germa-Lluch, J.R.; Kienzer, H.R.; Licitra, L.; Vermorken, J.B.

    2017-01-01

    Background: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell

  8. Salinomycin induces cell death and differentiation in head and neck squamous cell carcinoma stem cells despite activation of epithelial-mesenchymal transition and Akt

    International Nuclear Information System (INIS)

    Kuo, Selena Z; Blair, Katherine J; Rahimy, Elham; Kiang, Alan; Abhold, Eric; Fan, Jian-Bing; Wang-Rodriguez, Jessica; Altuna, Xabier; Ongkeko, Weg M

    2012-01-01

    Cancer stem cells (CSC) are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells. MTS and TUNEL assays were used to study cell proliferation and apoptosis as a function of salinomycin exposure in JLO-1, a putative HNSCC stem cell culture. MTS and trypan blue dye exclusion assays were performed to investigate potential drug interactions between salinomycin and cisplatin or paclitaxel. Stem cell-like phenotype was measured by mRNA expression of stem cell markers, sphere-forming capacity, and matrigel invasion assays. Immunoblotting was also used to determine expression of epithelial-mesenchymal transition (EMT) markers and Akt phosphorylation. Arrays by Illumina, Inc. were used to profile microRNA expression as a function of salinomycin dose. In putative HNSCC stem cells, salinomycin was found to significantly inhibit cell viability, induce a 71.5% increase in levels of apoptosis, elevate the Bax/Bcl-2 ratio, and work synergistically with cisplatin and paclitaxel in inducing cell death. It was observed that salinomycin significantly inhibited sphere forming-capability and repressed the expression of CD44 and BMI-1 by 3.2-fold and 6.2-fold, respectively. Furthermore, salinomycin reduced invasion of HNSCC stem cells by 2.1 fold. Contrary to expectations, salinomycin induced the expression of EMT markers Snail, vimentin, and Zeb-1, decreased expression of E-cadherin, and also induced phosphorylation of Akt and its downstream targets GSK3-β and mTOR. These results demonstrate that in HNSCC cancer stem cells, salinomycin can cause cell death and decrease stem cell properties despite activation of both EMT and

  9. Cetuximab Concomitant with Second-Line Radiation Therapy in Patients with Locally Advanced Recurrent Squamous Cell Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Muge Akmansu

    2010-12-01

    Full Text Available We presented 9 recurrent head and neck carcinoma patients. Priorly all of them had received radiochemotherapy. We used cetuximab and irradiation concomitantly. Overall survival analysis of the patients was performed using the Kaplan-Meier method on SPSS version 15.0. Based on this calculation, mean follow-up duration is 12.8 months. Mean survival time is 19.8 months and annual mean survival rate is 59.3%.

  10. Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: a pilot study

    International Nuclear Information System (INIS)

    Mizushima, Takeshi; Ohnishi, Shunsuke; Shimizu, Yuichi; Hatanaka, Yutaka; Hatanaka, Kanako C.; Hosono, Hidetaka; Kubota, Yoshimasa; Natsuizaka, Mitsuteru; Kamiya, Mako; Ono, Shouko; Homma, Akihiro; Kato, Mototsugu; Sakamoto, Naoya; Urano, Yasuteru

    2016-01-01

    Detecting superficial head and neck squamous cell carcinoma (HNSCC) by endoscopy is challenging because of limited morphological hallmarks, and iodine cannot be applied to head and neck lesions due to severe mucosal irritation. γ-glutamyltranspeptidase (GGT), a cell surface enzyme, is overexpressed in several cancers, and it has been reported that γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent targeting agent which can be enzymatically activated and becomes fluorescent after cleavage of a GGT-specific sequence, can be activated within a few minutes after application to animal models. We investigated whether early HNSCC can be detected by applying gGlu-HMRG to clinical samples. gGlu-HMRG was applied to four HNSCC cell lines, and fluorescence was observed by fluorescence microscopy and flow cytometry. Immunohistological examination was performed in three recent cases of endoscopic submucosal dissection (ESD) to investigate GGT expression. Fluorescence imaging with gGlu-HMRG in eight clinical samples resected by ESD or surgery was performed, and fluorescence intensity of tumor and normal mucosa regions of interest (ROI) was prospectively measured. All four gGlu-HMRG-applied cell lines emitted green fluorescence. Immunohistological examination demonstrated that GGT was highly expressed in HNSCC of the recent three ESD cases but barely in the normal mucosa. Fluorescence imaging showed that iodine-voiding lesions became fluorescent within a few minutes after application of gGlu-HMRG in all eight resected tumors. Tumor ROI fluorescence intensity was significantly higher than in the normal mucosa five minutes after gGlu-HMRG application. Fluorescence imaging with gGlu-HMRG would be useful for early detection of HNSCC

  11. Growth inhibition of head and neck squamous cell carcinoma cells by sgRNA targeting the cyclin D1 mRNA based on TRUE gene silencing.

    Directory of Open Access Journals (Sweden)

    Satoshi Iizuka

    Full Text Available Head and neck squamous cell carcinoma (HNSCC exhibits increased expression of cyclin D1 (CCND1. Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial small guide RNA (sgRNA. In this study, we designed several sgRNAs targeting human cyclin D1 mRNA to examine growth inhibition of HNSCC cells. Transfection of certain sgRNAs decreased levels of cyclin D1 mRNA and protein in HSC-2 and HSC-3 cells, and also inhibited their proliferation. The combination of these sgRNAs and cisplatin showed more than additive inhibition of cancer cell growth. These findings demonstrate that TRUE gene silencing of cyclin D1 leads to inhibition of the growth of HNSCC cells and suggest that these sgRNAs alone or combined with cisplatin may be a useful new therapy for HNSCCs.

  12. Selective blockade of B7-H3 enhances antitumour immune activity by reducing immature myeloid cells in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Mao, Liang; Fan, Teng-Fei; Wu, Lei; Yu, Guang-Tao; Deng, Wei-Wei; Chen, Lei; Bu, Lin-Lin; Ma, Si-Rui; Liu, Bing; Bian, Yansong; Kulkarni, Ashok B; Zhang, Wen-Feng; Sun, Zhi-Jun

    2017-09-01

    Immature myeloid cells including myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) promote tumour growth and metastasis by facilitating tumour transformation and angiogenesis, as well as by suppressing antitumour effector immune responses. Therefore, strategies designed to reduce MDSCs and TAMs accumulation and their activities are potentially valuable therapeutic goals. In this study, we show that negative immune checkpoint molecule B7-H3 is significantly overexpressed in human head and neck squamous cell carcinoma (HNSCC) specimen as compared with normal oral mucosa. Using immunocompetent transgenic HNSCC models, we observed that targeting inhibition of B7-H3 reduced tumour size. Flow cytometry analysis revealed that targeting inhibition of B7-H3 increases antitumour immune response by decreasing immunosuppressive cells and promoting cytotoxic T cell activation in both tumour microenvironment and macroenvironment. Our study provides direct in vivo evidence for a rationale for B7-H3 blockade as a future therapeutic strategy to treat patients with HNSCC. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. PD-L1 expression is associated with p16INK4A expression in non-oropharyngeal head and neck squamous cell carcinoma

    Science.gov (United States)

    Chen, San-Chi; Chang, Peter Mu-Hsin; Wang, Hsiao-Jung; Tai, Shyh-Kuan; Chu, Pen-Yuan; Yang, Muh-Hwa

    2018-01-01

    PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD-L1 expression in non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non-OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin-embedded non-OPHNSCC samples obtained from patients were constructed, and PD-L1 and p16INK4A expression were determined using immunohistochemistry. Systemic inflammatory factors, including C-reactive protein, serum white blood cell, neutrophil, monocyte and lymphocyte counts were also analyzed. The current study demonstrated that PD-L1 was overexpressed in 32.1% (34/106) and p16INK4A in 20.8% (22/106) of patients. The expression of PD-L1 was associated with p16INK4A expression (P<0.01) but was not associated with levels of systemic inflammatory factors. Tumor stage was determined to be a significant prognostic value (stage I/II vs. III/IV, P=0.03), however, PD-L1, p16INK4A or other clinicopathological factors were not. The current study identified an association between PD-L1 and p16INK4A expression in non-OPHNSCC. This may facilitate the development of anti-PD1/PDL1 therapies to treat patients with head and neck cancer. PMID:29434933

  14. miR-204 inhibits angiogenesis and promotes sensitivity to cetuximab in head and neck squamous cell carcinoma cells by blocking JAK2-STAT3 signaling.

    Science.gov (United States)

    Wu, Qingwei; Zhao, Yingying; Wang, Peihua

    2018-03-01

    This study aims to investigate the roles of miR-204 in tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). Here, we found that miR-204 level was reduced in HNSCC tissues relative to that in normal adjacent tissues. Overexpression of miR-204 promoted tumor angiogenesis in HNSCC cells. Mechanistically, JAK2 was identified as a direct target of miR-204, and miR-204 overexpression blocked JAK2/STAT3 pathway. Moreover, overexpression of JAK2 attenuated the inhibition of miR-204 on tumor angiogenesis of HNSCC. Furthermore, overexpression of miR-204 enhanced sensitivity of cetuximab in HNSCC cells, this effect was attenuated by JAK2 overexpression too. Importantly, JAK2 expression was negatively correlated with miR-204 level in HNSCC tissues. Therefore, miR-204 acts as a tumor suppressor by blocking JAK2/STAT3 pathway in HNSCC cells. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  15. Variation in cisplatinum sensitivity is not associated with Fanconi Anemia/BRCA pathway inactivation in head and neck squamous cell carcinoma cell lines.

    Science.gov (United States)

    Snyder, Eric R; Ricker, Justin L; Chen, Zhong; Waes, Carter Van

    2007-01-08

    Fanconi Anemia has recently been associated with a high risk of head and neck squamous cell carcinoma (HNSCC). Inactivation of the Fanconi Anemia (FANC-BRCA) pathway via promoter methylation of the FANCF gene has been proposed to be responsible for variation in cisplatinum (CDDP) sensitivity seen in ovarian and HNSCCs. Promoter methylation of the FANCF gene has been observed in 15% of HNSCC specimens, but the relationship to FANC pathway activation and CDDP sensitivity has not been reported. In the present study, 10 HNSCC cell lines were examined for expression of nine genes involved in the FANC-BRCA pathway by RT-PCR: FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, BRCA1 and BRCA2. FANC pathway function was evaluated by western blotting for FANCD2 mono-ubiquitination. All of the cell lines were also analyzed for variation in CDDP cytotoxicity. While significant differences were found in CDDP cytotoxicity, Fanconi pathway defects are an infrequent cause, as no evidence of transcriptional down-regulation of FANCF or other FANC mRNAs, or functional FANC-BRCA pathway defects were observed. These findings suggest that the variation in CDDP sensitivity of many HNSCCs is most frequently due to factors other than FANC-BRCA pathway inactivation.

  16. Adenylyl cyclase-associated protein 1 in metastasis of squamous cell carcinoma of the head and neck and non-small cell lung cancer

    Science.gov (United States)

    Kakurina, G. V.; Kolegova, E. S.; Cheremisina, O. V.; Zavyalov, A. A.; Shishkin, D. A.; Kondakova, I. V.; Choinzonov, E. L.

    2016-08-01

    Progression of tumors and metastasis in particular is one of the main reasons of the high mortality rate among cancer patients. The primary role in developing metastases plays cell locomotion which requires remodeling of the actin cytoskeleton. Form, dynamics, localization and mechanical properties of the actin cytoskeleton are regulated by a variety of actin-binding proteins, which include the adenylyl cyclase-associated protein 1 (CAP1). The study is devoted to the investigation of CAP1 level depending on the presence or absence of metastases in patients with squamous cell carcinoma of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC). The results show the contribution of CAP1 to SCCHN and NSCLC progression. We detected the connection between the tissue protein CAP1 level and the stage of NSCLC and SCCHN disease. Also the levels of the CAP1 protein in tissues of primary tumors and metastases in lung cancer were different. Our data showed that CAP is important in the development of metastases, which suggests further perspectives in the study of this protein for projecting metastasis of NSCLC and SCCHN.

  17. Effect of smoking on oxygen delivery and outcome in patients treated with radiotherapy for head and neck squamous cell carcinoma – A prospective study

    International Nuclear Information System (INIS)

    Molich Hoff, Camilla; Grau, Cai; Overgaard, Jens

    2012-01-01

    Background: Head and neck cancer patients with high hemoglobin respond better to irradiation compared to patients with low hemoglobin possibly due to hypoxia induced radioresistance. The hemoglobin level is, however, a crude indicator of the amount of oxygen available to the tissue and may be influenced by a number of factors, smoking being of potential importance. The aim of the present study was to examine the effect of smoking on available oxygen to tumors and the effect on outcome in head and neck cancer patients treated with radiotherapy in a prospective study. Materials and methods: A total of 232 consecutive patients with squamous cell carcinoma of the larynx, pharynx and oral cavity completed questionnaires on smoking habits prior to treatment. Venous blood samples were collected before and/or during treatment to determine the hemoglobin and carboxyhemoglobin level. Patients were treated with primary curative radiotherapy 62–68 Gy, 2 Gy/fx, 5 fx/week. Results: All but 12 patients had a history of smoking, 35 were long term quitters, 23 recent quitters, 54 moderate smokers and 108 heavy smokers (>1 pack/day). There was no relationship between total hemoglobin and carboxyhemoglobin, but effective hemoglobin and carboxyhemoglobin were linearly correlated. The amount of carboxyhemoglobin increased with increasing smoking status. Actuarial 5-year univariate analysis showed that heavy smokers had a significantly reduced probability of loco-regional control (44% vs. 65%, p = 0.001), disease-specific (56% vs. 77%, p = 0.003) and overall survival (39% vs. 66%, p = 0.0004) compared to non-smoking patients. Multivariate analyses showed that patients characterized as non-smokers, with low T and N classifications and high hemoglobin level had the best outcome measurements. A rise in carboxyhemoglobin significantly decreased the probability of loco-regional control and each additional pack year increased the risk of death. Smokers and former smokers develop secondary

  18. Objective and subjective image quality of primary and recurrent squamous cell carcinoma on head and neck low-tube-voltage 80-kVp computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Scholtz, Jan-Erik; Kaup, Moritz; Kraft, Johannes; Noeske, Eva-Maria; Schulz, Boris; Burck, Iris; Kerl, J.M.; Bauer, Ralf W.; Lehnert, Thomas; Vogl, Thomas J.; Wichmann, Julian L. [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology, Frankfurt (Germany); Scheerer, Friedrich [University Hospital Frankfurt, Department of Cranio-Maxillofacial and Plastic Facial Surgery, Frankfurt (Germany); Wagenblast, Jens [University Hospital Frankfurt, Department of Otolaryngology, Head and Neck Surgery, Frankfurt (Germany)

    2015-03-26

    To investigate low-tube-voltage 80-kVp computed tomography (CT) of head and neck primary and recurrent squamous cell carcinoma (SCC) regarding objective and subjective image quality. We retrospectively evaluated 65 patients (47 male, 18 female; mean age: 62.1 years) who underwent head and neck dual-energy CT (DECT) due to biopsy-proven primary (n = 50) or recurrent (n = 15) SCC. Eighty peak kilovoltage and standard blended 120-kVp images were compared. Attenuation and noise of malignancy and various soft tissue structures were measured. Tumor signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Subjective image quality was rated by three reviewers using 5-point grading scales regarding overall image quality, lesion delineation, image sharpness, and image noise. Radiation dose was assessed as CT dose index volume (CTDI{sub vol}). Interobserver agreement was calculated using intraclass correlation coefficient (ICC). Mean tumor attenuation (153.8 Hounsfield unit (HU) vs. 97.1 HU), SNR (10.7 vs. 8.3), CNR (8.1 vs. 4.8), and subjective tumor delineation (score, 4.46 vs. 4.13) were significantly increased (all P < 0.001) with 80-kVp acquisition compared to standard blended 120-kVp images. Noise of all measured structures was increased in 80-kVp acquisition (P < 0.001). Overall interobserver agreement was good (ICC, 0.86; 95 % confidence intervals: 0.82-0.89). CTDI{sub vol} was reduced by 48.7 % with 80-kVp acquisition compared to standard DECT (4.85 ± 0.51 vs. 9.94 ± 0.81 mGy cm, P < 0.001). Head and neck CT with low-tube-voltage 80-kVp acquisition provides increased tumor delineation, SNR, and CNR for CT imaging of primary and recurrent SCC compared to standard 120-kVp acquisition with an accompanying significant reduction of radiation exposure. (orig.)

  19. Evaluation of the prognostic role of tumor cell podoplanin expression in locally advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Huttenlocher, Stefan; Seibold, Nina D.; Rades, Dirk; Gebhard, Maximilian P.; Noack, Frank; Thorns, Christoph; Hasselbacher, Katrin; Wollenberg, Barbara; Schild, Steven E.

    2014-01-01

    To investigate the potential prognostic role of tumor cell podoplanin expression in patients treated with resection followed by irradiation or chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN). Podoplanin expression (≤10 % versus > 10 %) and 12 other factors were evaluated in 160 patients for their association with locoregional control (LRC), metastases-free (MFS) and overall survival (OS). Other factors were age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, preradiotherapy (pre-RT) hemoglobin level, tumor site, histological grading, T category, N category, American Joint Committee on Cancer (AJCC) stage, human papillomavirus (HPV) status, extent of resection and concurrent chemotherapy. In multivariate analysis, ECOG performance status 0-1 (risk ratio, RR: 3.01; 95 % confidence interval, CI: 1.42-7.14; p = 0.003), pre-RT hemoglobin levels ≥ 7.45 mmol/l (12 g/dl; RR: 2.03; 95 % CI: 1.04-3.94; p = 0.038), oropharyngeal cancer (RR: 1.25; 95 % CI: 1.01-1.55; p = 0.038) and T category T1-2 (RR: 1.81; 95 % CI: 1.24-2.79; p = 0.002) were significantly associated with improved LRC. T category T1-2 (RR: 1.90; 95 % CI: 1.25-3.06; p = 0.002) and N category N0-2a (RR: 5.22; 95 % CI: 1.96-18.09; p 10 %. (orig.) [de

  20. Primary Tumor Volume Is an Important Predictor of Clinical Outcomes Among Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Treated With Definitive Chemoradiotherapy

    International Nuclear Information System (INIS)

    Strongin, Anna; Yovino, Susannah; Taylor, Rodney; Wolf, Jeffrey; Cullen, Kevin; Zimrin, Ann; Strome, Scott; Regine, William; Suntharalingam, Mohan

    2012-01-01

    Purpose: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. Methods and Materials: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. Results: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm 3 , and patients with a tumor volume 3 had a significantly better prognosis than those with a tumor volume >35 cm 3 at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume 3 had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = 3 larger than tumors without locoregional failure (p = .028) and 27.1-cm 3 larger than tumors that recurred as distant metastases (p = .020). Conclusion: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer of the head and neck undergoing definitive chemoradiotherapy and correlated with the treatment outcomes better than the T or N stage.

  1. Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck

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    Tribius, Silke; Kilic, Yasemin [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Kronemann, Stefanie [Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schroeder, Ursula [Dept. of Head and Neck Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Hakim, Samer [Dept. of Oro-Maxillo-Facial Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Rades, Dirk [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany)

    2009-10-15

    Background and purpose: the optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m{sup 2}/d1-5 + 29-33; n = 74). Results: at least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. Conclusion: two courses of fractionated cisplatin (20 mg/m{sup 2}/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity. (orig.)

  2. Macrolide Antibiotics Exhibit Cytotoxic Effect under Amino Acid-Depleted Culture Condition by Blocking Autophagy Flux in Head and Neck Squamous Cell Carcinoma Cell Lines

    Science.gov (United States)

    Hirasawa, Kazuhiro; Moriya, Shota; Miyahara, Kana; Kazama, Hiromi; Hirota, Ayako; Takemura, Jun; Abe, Akihisa; Inazu, Masato; Hiramoto, Masaki; Tsukahara, Kiyoaki

    2016-01-01

    Autophagy, a self-digestive system for cytoplasmic components, is required to maintain the amino acid pool for cellular homeostasis. We previously reported that the macrolide antibiotics azithromycin (AZM) and clarithromycin (CAM) have an inhibitory effect on autophagy flux, and they potently enhance the cytocidal effect of various anticancer reagents in vitro. This suggests that macrolide antibiotics can be used as an adjuvant for cancer chemotherapy. Since cancer cells require a larger metabolic demand than normal cells because of their exuberant growth, upregulated autophagy in tumor cells has now become the target for cancer therapy. In the present study, we examined whether macrolides exhibit cytotoxic effect under an amino acid-starving condition in head and neck squamous cancer cell lines such as CAL 27 and Detroit 562 as models of solid tumors with an upregulated autophagy in the central region owing to hypovascularity. AZM and CAM induced cell death under the amino acid-depleted (AAD) culture condition in these cell lines along with CHOP upregulation, although they showed no cytotoxicity under the complete culture medium. CHOP knockdown by siRNA in the CAL 27 cells significantly suppressed macrolide-induced cell death under the AAD culture condition. CHOP-/- murine embryonic fibroblast (MEF) cell lines also attenuated AZM-induced cell death compared with CHOP+/+ MEF cell lines. Using a tet-off atg5 MEF cell line, knockout of atg5, an essential gene for autophagy, also induced cell death and CHOP in the AAD culture medium but not in the complete culture medium. This suggest that macrolide-induced cell death via CHOP induction is dependent on autophagy inhibition. The cytotoxicity of macrolide with CHOP induction was completely cancelled by the addition of amino acids in the culture medium, indicating that the cytotoxicity is due to the insufficient amino acid pool. These data suggest the possibility of using macrolides for “tumor-starving therapy”. PMID

  3. Oculocutaneous Albinism and Squamous Cell Carcinoma of the Skin of the Head and Neck in Sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    P. T. Lekalakala

    2015-01-01

    Full Text Available Oculocutaneous albinism which is characterised by impaired melanin biosynthesis is the most common inherited pigmentary disorder of the skin and it is common among Blacks in sub-Saharan Africa. All albinos are at great risk of developing squamous cell carcinoma of sun-exposed skin, and Black albinos in sub-Saharan Africa are at about a 1000-fold higher risk of developing squamous cell carcinoma of the skin than the general population. In Black albinos, skin carcinoma tends to run an aggressive course and is likely to recur after treatment, very probably because the aetiology and predisposing factors have not changed. Prevention or reduction of occurrence of squamous cell carcinoma of the skin in Black albinos might be achieved through educating the population to increase awareness of the harmful effects of exposure to sunlight and at the same time making available effective screening programs for early detection of premalignant and malignant skin lesions in schools and communities and for early treatment.

  4. The dual mTORC1 and mTORC2 inhibitor AZD8055 inhibits head and neck squamous cell carcinoma cell growth in vivo and in vitro

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    Li, Qiang; Song, Xin-mao; Ji, Yang-yang; Jiang, Hui; Xu, Lin-gen, E-mail: drlingenxu@126.com

    2013-11-01

    Highlights: •AZD8055 induces significant cytotoxic effects in cultured HNSCC cells. •AZD8055 blocks mTORC1 and mTORC2 activation in cultured HNSCC cells. •JNK activation is required for AZD8055-induced HNSCC cell death. •AZD8055 inhibits Hep-2 cell growth in vivo, and was more efficient than rapamycin. -- Abstract: The serine/threonine kinase mammalian target of rapamycin (mTOR) promotes cell survival and proliferation, and is constitutively activated in head and neck squamous cell carcinoma (HNSCC). Thus mTOR is an important target for drug development in this disease. Here we tested the anti-tumor ability of AZD8055, the novel mTOR inhibitor, in HNSCC cells. AZD8055 induced dramatic cell death of HNSCC lines (Hep-2 and SCC-9) through autophagy. AZD8055 blocked both mTOR complex (mTORC) 1 and mTORC2 activation without affecting Erk in cultured HNSCC cells. Meanwhile, AZD8055 induced significant c-Jun N-terminal kinase (JNK) activation, which was also required for cancer cell death. JNK inhibition by its inhibitors (SP 600125 and JNK-IN-8), or by RNA interference (RNAi) alleviated AZD8055-induced cell death. Finally, AZD8055 markedly increased the survival of Hep-2 transplanted mice through a significant reduction of tumor growth, without apparent toxicity, and its anti-tumor ability was more potent than rapamycin. Meanwhile, AZD8055 administration activated JNK while blocking mTORC1/2 in Hep-2 tumor engrafts. Our current results strongly suggest that AZD8055 may be further investigated for HNSCC treatment in clinical trials.

  5. In Vivo1H Magnetic Resonance Spectroscopy of Lactate in Patients With Stage IV Head and Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Le, Quynh-Thu; Koong, Albert; Lieskovsky, Yee Yie; Narasimhan, Balasubramanian; Graves, Edward; Pinto, Harlan; Brown, J. Martin; Spielman, Daniel

    2008-01-01

    Purpose: To investigate in vivo 1 H magnetic resonance spectroscopy imaging of lactate for assessing tumor hypoxia in head and neck cancers and to determine its utility in predicting the response and outcomes. Methods and Materials: Volume-localized lactate-edited 1 H magnetic resonance spectroscopy at 1.5 T was performed in vivo on involved neck nodes and control subcutaneous tissues in 36 patients with Stage IV head and neck cancer. The signal intensities (SIs) of lactate, choline, and creatine and the choline/creatine ratio were measured. The tumor partial pressure of oxygen (pO 2 ) was obtained in the same lymph node before MRS. Patients were treated with either two cycles of induction chemotherapy (tirapazamine, cisplatin, 5-fluorouracil) followed by simultaneous chemoradiotherapy or the same regimen without tirapazamine. The lactate SI and the choline/creatine ratio correlated with the tumor pO 2 , nodal response, and locoregional control. Results: The lactate SI was greater for the involved nodes (median, 0.25) than for the subcutaneous tissue (median, 0.04; p = 0.07). No significant correlation was found between the lactate SI and tumor pO 2 (mean, 0.46 ± 0.10 for hypoxic nodes [pO 2 ≤10 mm Hg, n = 15] vs. 0.36 ± 0.07 for nonhypoxic nodes [pO 2 >10 mm Hg, n = 21], p = 0.44). A significant correlation was found between the choline/creatine ratios and tumor pO 2 (mean, 2.74 ± 0.34 for hypoxic nodes vs. 1.78 ± 0.31 for nonhypoxic nodes, p = 0.02). No correlation was found between the lactate SI and the complete nodal response (p = 0.52) or locoregional control rates. Conclusions: The lactate SI did not correlate with tumor pO 2 , treatment response, or locoregional control. Additional research is needed to refine this technique

  6. Loss of Mitochondrial Tumor Suppressor Genes Expression Is Associated with Unfavorable Clinical Outcome in Head and Neck Squamous Cell Carcinoma: Data from Retrospective Study.

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    Ishrat Mahjabeen

    Full Text Available Mitochondrial genes play important roles in cellular energy metabolism, free radical generation, and apoptosis. Dysregulation of these genes have long been suspected to contribute to the generation of reactive oxygen species (ROS, increased proliferation and progression of cancer. A family of orthologues of yeast silent information regulator 3 (SIRT3, 4 (SIRT4 and mitochondrial tumor suppressor 1 (MTUS1 are important mitochondrial tumor suppressor genes which play an important role in the progression of multiple cancers. However, their role in the development of oxidative stress, enhanced proliferation and progression of head and neck squamous cell carcinoma (HNSCC has not yet been studied. In this study we aimed to test the association between reduced mitochondrial tumor suppressor genes' activities and enhancement in tissue oxidative stress and cell proliferation in HNSCC cases. The expression of mitochondrial tumor suppressor genes (SIRT3, SIRT4 and MTUS1, mitochondrial DNA repair gene (OGG1-2a and a proliferation marker (Ki-67 was studied in a study cohort of 120 HNSCC patients and controls with reverse transcriptase polymerase chain reaction (RT-PCR and real-time PCR (qPCR in order to determine the potential prognostic significance of these genes. A statistically significant downregulation of SIRT3 (p<0.001, SIRT4 (p<0.0001, MTUS1 (p<0.002 and OGG1 (p<0.0001 was observed in HNSCC compared to control samples. Ki-67 was also overexpressed (p<0.0001 in HNSCC versus control samples. Additionally, to explore gene-gene relationship, we observed a positive spearmen correlation between SIRT3 versus SIRT4 (r = 0.523***, p<0.0001, SIRT3 versus MTUS1 (r = 0.273***, p<0.001, SIRT3 versus OGG1-2a (r = 0.213*, p<0.03, SIRT4 versus OGG1 (r = 0.338***, p<0.0001 and MTUS1 versus OGG1-2a (r = 0.215*, p<0.03 in HNSCC cases. A negative spearman correlation was observed between OGG1 versus Ki-67 (r = -0.224**, p<0.01 and OGG1-2a versus Ki-67 (r = -0.224**, p<0

  7. The hypoxic tumor microenvironment and drug resistance against EGFR inhibitors: preclinical study in cetuximab-sensitive head and neck squamous cell carcinoma cell lines.

    Science.gov (United States)

    Boeckx, Carolien; Van den Bossche, Jolien; De Pauw, Ines; Peeters, Marc; Lardon, Filip; Baay, Marc; Wouters, An

    2015-06-02

    Increased expression of the epidermal growth factor receptor (EGFR) is observed in more than 90% of all head and neck squamous cell carcinomas (HNSCC). Therefore, EGFR has emerged as a promising therapeutic target. Nevertheless, drug resistance remains a major challenge and an important potential mechanism of drug resistance involves the hypoxic tumor microenvironment. Therefore, we investigated the cytotoxic effect of the EGFR-targeting agents cetuximab and erlotinib under normoxia versus hypoxia. Three cetuximab-sensitive HNSCC cell lines (SC263, LICR-HN2 and LICR-HN5) were treated with either cetuximab or erlotinib. Cells were incubated under normal or reduced oxygen conditions (<0.1% O2) for 24 or 72 h immediately after drug addition. Cell survival was assessed with the sulforhodamine B assay. Cetuximab and erlotinib established a dose-dependent growth inhibition under both normal and prolonged reduced oxygen conditions in all three HNSCC cell lines. However, a significantly increased sensitivity to cetuximab was observed in SC263 cells exposed to hypoxia for 72 h (p = 0.05), with IC50 values of 2.38 ± 0.59 nM, 0.64 ± 0.38 nM, and 0.10 ± 0.05 nM under normoxia, hypoxia for 24 h and hypoxia for 72 h, respectively. LICR-HN5 cells showed an increased sensitivity towards erlotinib when cells were incubated under hypoxia for 24 h (p = 0.05). Our results suggest that both EGFR-inhibitors cetuximab and erlotinib maintain their growth inhibitory effect under hypoxia. These results suggest that resistance to anti-EGFR therapy in HNSCC is probably not the result of hypoxic regions within the tumor and other mechanisms are involved.

  8. 5-lipoxygenase mediates docosahexaenoyl ethanolamide and N-arachidonoyl-L-alanine-induced reactive oxygen species production and inhibition of proliferation of head and neck squamous cell carcinoma cells.

    Science.gov (United States)

    Park, Seok-Woo; Hah, J Hun; Oh, Sang-Mi; Jeong, Woo-Jin; Sung, Myung-Whun

    2016-07-13

    Endocannabinoids have recently drawn attention as promising anti-cancer agents. We previously observed that anandamide (AEA), one of the representative endocannabinoids, effectively inhibited the proliferation of head and neck squamous cell carcinoma (HNSCC) cell lines in a receptor-independent manner. In this study, using HNSCC cell lines, we examined the anti-cancer effects and the mechanisms of action of docosahexaenoyl ethanolamide (DHEA) and N-arachidonoyl-L-alanine (NALA), which are polyunsaturated fatty acid (PUFA)-based ethanolamides like AEA. DHEA and NALA were found to effectively inhibit HNSCC cell proliferation. These anti-proliferative effects seemed to be mediated in a cannabinoid receptor-independent manner, since the antagonist of cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (VR1), two endocannabinoid receptors, did not reverse the ability of DHEA and NALA to induce cell death. Instead, we observed an increase in reactive oxygen species (ROS) production and a decrease of phosphorylated Akt as a result of DHEA and NALA treatment. Antioxidants efficiently reversed the inhibition of cell proliferation and the decrease of phosphorylated Akt induced by DHEA and NALA; inhibition of 5-lipoxygenase (5-LO), which is expected to be involved in DHEA- and NALA-degradation pathway, also partially blocked the ability of DHEA and NALA to inhibit cell proliferation and phosphorylated Akt. Interestingly, ROS production as a result of DHEA and NALA treatment was decreased by inhibition of 5-LO. From these findings, we suggest that ROS production induced by the 5-LO pathway mediates the anti-cancer effects of DHEA and NALA on HNSCC cells. Finally, our findings suggest the possibility of a new cancer-specific therapeutic strategy, which utilizes 5-LO activity rather than inhibiting it.

  9. 5-lipoxygenase mediates docosahexaenoyl ethanolamide and N-arachidonoyl-L-alanine-induced reactive oxygen species production and inhibition of proliferation of head and neck squamous cell carcinoma cells

    International Nuclear Information System (INIS)

    Park, Seok-Woo; Hah, J. Hun; Oh, Sang-Mi; Jeong, Woo-Jin; Sung, Myung-Whun

    2016-01-01

    Endocannabinoids have recently drawn attention as promising anti-cancer agents. We previously observed that anandamide (AEA), one of the representative endocannabinoids, effectively inhibited the proliferation of head and neck squamous cell carcinoma (HNSCC) cell lines in a receptor-independent manner. In this study, using HNSCC cell lines, we examined the anti-cancer effects and the mechanisms of action of docosahexaenoyl ethanolamide (DHEA) and N-arachidonoyl-L-alanine (NALA), which are polyunsaturated fatty acid (PUFA)-based ethanolamides like AEA. DHEA and NALA were found to effectively inhibit HNSCC cell proliferation. These anti-proliferative effects seemed to be mediated in a cannabinoid receptor-independent manner, since the antagonist of cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (VR1), two endocannabinoid receptors, did not reverse the ability of DHEA and NALA to induce cell death. Instead, we observed an increase in reactive oxygen species (ROS) production and a decrease of phosphorylated Akt as a result of DHEA and NALA treatment. Antioxidants efficiently reversed the inhibition of cell proliferation and the decrease of phosphorylated Akt induced by DHEA and NALA; inhibition of 5-lipoxygenase (5-LO), which is expected to be involved in DHEA- and NALA-degradation pathway, also partially blocked the ability of DHEA and NALA to inhibit cell proliferation and phosphorylated Akt. Interestingly, ROS production as a result of DHEA and NALA treatment was decreased by inhibition of 5-LO. From these findings, we suggest that ROS production induced by the 5-LO pathway mediates the anti-cancer effects of DHEA and NALA on HNSCC cells. Finally, our findings suggest the possibility of a new cancer-specific therapeutic strategy, which utilizes 5-LO activity rather than inhibiting it. The online version of this article (doi:10.1186/s12885-016-2499-3) contains supplementary material, which is available to authorized users

  10. Combination of thalidomide and cisplatin in an head and neck squamous cell carcinomas model results in an enhanced antiangiogenic activity in vitro and in vivo.

    Science.gov (United States)

    Vasvari, Gergely P; Dyckhoff, Gerhard; Kashfi, Farzaneh; Lemke, Britt; Lohr, Jennifer; Helmke, Burkhard M; Schirrmacher, Volker; Plinkert, Peter K; Beckhove, Philipp; Herold-Mende, Christel C

    2007-10-15

    Thalidomide is an immunomodulatory, antiangiogenic drug. Although there is evidence that it might be more effective in combination with chemotherapy the exact mechanism of action is unclear. Therefore, we investigated its effect in combination with metronomically applied cisplatin in a xenotransplant mouse model characteristic for advanced head and neck squamous cell carcinomas, its possible synergistic action in vitro, and which tumor-derived factors might be targeted by thalidomide. Although thalidomide alone was ineffective, a combined treatment with low-dose cisplatin inhibited significant tumor growth, proliferation and angiogenesis in vivo as well as migration and tube formation of endothelial cells in vitro. Noteworthy, the latter effect was enhanced after coapplication of cisplatin in nontoxic doses. An inhibitory effect on tumor cell migration was also observed suggesting a direct antitumor effect. Although thalidomide alone did not influence cell proliferation, it augmented antiproliferative response after cisplatin application emphasizing the idea of a potentiated effect when both drugs are combined. Furthermore, we could show that antiangiogenic effects of thalidomide are related to tumor-cell derived factors including vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and Il-8 some known and with, granulocyte colony stimulating growth factor and granulocyte macrophage colony stimulating growth factor, some new target molecules of thalidomide. Altogether, our findings reveal new insights into thalidomide-mediated antitumor and antiangiogenic effects and its interaction with cytostatic drugs. (c) 2007 Wiley-Liss, Inc.

  11. Human papillomavirus (HPV) and Oropharyngeal Squamous Cell Carcinoma (OP-SCC) of the Head and Neck: a Growing Epidemic

    Science.gov (United States)

    Bauman, Jessica; Wirth, Lori

    2015-01-01

    Human papillomavirus (HPV) is now considered a major causative agent in oropharyngeal squamous cell carcinoma (OP-SCC). The incidence of HPV+ OP-SCC is increasing dramatically, is higher in men, and is now more common than cervical cancer in the United States. HPV+ OPSCCs usually present as locally advanced, stage IV cancers, requiring intensive treatment with surgery, chemotherapy, and/or radiation that can cause tremendous morbidity. HPV vaccination is predicted to prevent HPV+ OP-SCC because over 90% are caused by vaccine-type HPV. However, current vaccination rates are not yet high enough to be effective at preventing HPV-associated malignancies at a population level. PMID:27132327

  12. Expression of the T cell receptor αβ on a CD123+ BDCA2+ HLA-DR+ subpopulation in head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Annette Thiel

    Full Text Available Human Plasmacytoid Dendritic Cells (PDCs infiltrating solid tumor tissues and draining lymph nodes of Head and Neck Squamous Cell Carcinoma (HNSCC show an impaired immune response. In addition to an attenuated secretion of IFN-α little is known about other HNSCC-induced functional alterations in PDCs. Particular objectives in this project were to gain new insights regarding tumor-induced phenotypical and functional alterations in the PDC population. We showed by FACS analysis and RT-PCR that HNSCC orchestrates an as yet unknown subpopulation exhibiting functional autonomy in-vitro and in-vivo besides bearing phenotypical resemblance to PDCs and T cells. A subset, positive for the PDC markers CD123, BDCA-2, HLA-DR and the T cell receptor αβ (TCR-αβ was significantly induced subsequent to stimulation with HNSCC in-vitro (p = 0.009 and also present in metastatic lymph nodes in-vivo. This subgroup could be functionally distinguished due to an enhanced production of IL-2 (p = 0.02, IL-6 (p = 0.0007 and TGF-β (not significant. Furthermore, after exposure to HNSCC cells, mRNA levels revealed a D-J-beta rearrangement of the TCR-beta chain besides a strong enhancement of the CD3ε chain in the PDC population. Our data indicate an interface between the PDC and T cell lineage. These findings will improve our understanding of phenotypical and functional intricacies concerning the very heterogeneous PDC population in-vivo.

  13. Photodynamic mechanisms induced by a combination of hypericin and a chlorin based-photosensitizer in head and neck squamous cell carcinoma cells.

    Science.gov (United States)

    Gyenge, Emina Besic; Lüscher, Daniel; Forny, Patrick; Antoniol, Martina; Geisberger, Georg; Walt, Heinrich; Patzke, Greta; Maake, Caroline

    2013-01-01

    The aim of this study was to elucidate photodynamic therapy (PDT) effects mediated by hypericin and a liposomal meso-tetrahydroxyphenyl chlorin (mTHPC) derivative, with focus on their 1:1 mixture, on head and neck squamous cell carcinoma cell lines. Absorption, excitation and photobleaching were monitored using fluorescence spectrometry, showing the same spectral patterns for the mixture as measured for single photosensitizers. In the mixture mTHPC showed a prolonged photo-stability. Singlet oxygen yield for light-activated mTHPC was Φ(Δ) = 0.66, for hypericin Φ(Δ) = 0.25 and for the mixture Φ(Δ) = ~0.4. A linear increase of singlet oxygen yield for mTHPC and the mixture was found, whereas hypericin achieved saturation after 35 min. Reactive oxygen species fluorescence was only visible after hypericin and mixture-induced PDT. Cell viability was also more affected with these two treatment options under the selected conditions. Examination of death pathways showed that hypericin-mediated cell death was apoptotic, with mTHPC necrotic and the 1:1 mixture showed features of both. Changes in gene expression after PDT indicated strong up-regulation of selected heat-shock proteins. The application of photosensitizer mixtures with the features of reduced dark toxicity and combined apoptotic and necrotic cell death may be beneficial in clinical PDT. This will be the focus of our future investigations. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  14. Dasatinib blocks cetuximab- and radiation-induced nuclear translocation of the epidermal growth factor receptor in head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Li Chunrong; Iida, Mari; Dunn, Emily F.; Wheeler, Deric L.

    2010-01-01

    Background and purpose: The aberrant expression of epidermal growth factor receptor (EGFR) has been linked to the etiology of head and neck squamous cell carcinoma (HNSCC). The first major phase III trial combining cetuximab with radiation confirmed a strong survival advantage. However, both cetuximab and radiation can promote EGFR translocation to the nucleus where it enhances resistance to both of these modalities. In this report we sought to determine how to block cetuximab- and radiation-induced translocation of EGFR to the nucleus in HNSCC cell lines. Material and methods: We utilized three established HNSCC cell lines, SCC1, SCC6 and SCC1483 and measured nuclear translocation of EGFR after treatment with cetuximab or radiation. We then utilized dasatinib (BMS-354825), a potent, orally bioavailable inhibitor of several tyrosine kinases, including the Src family kinases, to determine if SFKs blockade could abrogate cetuximab- and radiation-induced nuclear EGFR translocation. Results: Cetuximab and radiation treatment of all three HNSCC lines lead to translocation of the EGFR to the nucleus. Blockade of SFKs abrogated cetuximab- and radiation-induced EGFR translocation to the nucleus. Conclusions: The data presented in this report suggest that both cetuximab and radiation can promote EGFR translocation to the nucleus and dasatinib can inhibit this process. Collectively these findings may suggest that dasatinib can limit EGFR translocation to the nucleus and may enhance radiotherapy plus cetuximab in HNSCC.

  15. Monitoring of Circulating Tumor Cells and Their Expression of EGFR/Phospho-EGFR During Combined Radiotherapy Regimens in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

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    Tinhofer, Ingeborg, E-mail: ingeborg.tinhofer@charite.de [Translational Radiooncology Laboratory, Department of Radiooncology and Radiotherapy, Charite Campus Mitte, Charite Universitaetsmedizin Berlin, Berlin (Germany); Hristozova, Tsvetana; Stromberger, Carmen [Translational Radiooncology Laboratory, Department of Radiooncology and Radiotherapy, Charite Campus Mitte, Charite Universitaetsmedizin Berlin, Berlin (Germany); KeilhoIz, Ulrich [Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Universitaetsmedizin Berlin, Berlin (Germany); Budach, Volker [Translational Radiooncology Laboratory, Department of Radiooncology and Radiotherapy, Charite Campus Mitte, Charite Universitaetsmedizin Berlin, Berlin (Germany)

    2012-08-01

    Purpose: The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were determined. Methods and Materials: Peripheral blood samples from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study. Using flow cytometry, the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form (pEGFR) during the course of treatment were assessed. Results: Before treatment, we detected {>=}1 CTC per 3.75 mL blood in 9 of 31 patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of the CTC+ cases. The frequency of CTC detection was not influenced by induction chemotherapy. However, the number of CTC+ samples significantly increased after radiotherapy. This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil. The former treatment regimen was also more effective in reducing pEGFR expression in CTCs. Conclusions: Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells. Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases.

  16. Serendipitous discovery of potent human head and neck squamous cell carcinoma anti-cancer molecules: A fortunate failure of a rational molecular design.

    Science.gov (United States)

    Zagni, Chiara; Pistarà, Venerando; Oliveira, Luciana A; Castilho, Rogerio M; Romeo, Giovanni; Chiacchio, Ugo; Rescifina, Antonio

    2017-12-01

    Histone deacetylase inhibitors (HDACis) play an important role as valuable drugs targeted to cancer therapy: several HDACis are currently being tested in clinical trials. Two new potential HDACis 1a and 1d, characterized by the presence of a biphenyl-4-sulfonamide group as a connection unit between the N-{4-[(E)-(2-formylhydrazinylidene)methyl]-3-hydroxyphenyl} and the 2-hydroxy-N-(trifluoroacetyl)benzamide moiety, respectively, as two zinc-binding group (ZBG), have been designed, synthesized and tested for their biological activity. Surprisingly, compounds 1a and 12, this last exclusively obtained in place of 1d, exhibited a very low HDAC inhibitory activity. A serendipitous assay of these two compounds, conducted on three chemoresistant cell lines of head and neck squamous cell carcinoma (HNSCC), showed their antiproliferative activity at low nanomolar concentrations, better than cisplatin. In vitro, biological assays indicated that compounds 1a and 12 are able to increase acetylation of histone H3 and to interfere with the PI3K/Akt/mTOR pathway by inducing the accumulation of PTEN protein. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Genetic variants of NOXA and MCL1 modify the risk of HPV16-associated squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Zhou, Ziyuan; Sturgis, Erich M; Liu, Zhensheng; Wang, Li-E; Wei, Qingyi; Li, Guojun

    2012-01-01

    The cooperation between phorbol 12-myristate 13-acetate induced protein 1 (NOXA) and myeloid cell leukemia 1 (MCL1) is critical in the intrinsic apoptotic pathway. Human papillomavirus 16 (HPV16), by inducing p53 and pRb-E2F degradation, may play an essential role in development of squamous cell carcinoma of the head and neck (SCCHN) through NOXA-MCL1 axis-mediated apoptosis. Therefore, genetic variants of NOXA and MCL1 may modify the SCCHN risk associated with HPV16 seropositivity. HPV16 serology was obtained by immunoadsorption assay. Four functional SNPs in the promoter of NOXA (rs9957673, rs4558496) and MCL1 (rs9803935, rs3738485) were genotyped for 380 cases and 335 frequency-matched cancer-free controls of non-Hispanic whites. Associations between the four polymorphisms and SCCHN risk were not significant, while we observed a significantly joint effect on SCCHN risk between the polymorphisms and HPV16 seropositivity. Notably, this effect modification was particularly pronounced for oropharyngeal cancer in subgroups including never smokers, never drinkers and younger subjects. Our results suggested that polymorphisms of NOXA and MCL1 may modify the risk of HPV16-associated oropharyngeal cancer. The further identification of population subgroups at higher risk provides evidence that HPV-targeting treatment may help benefit SCCHN. However, larger studies are needed to validate our findings

  18. Value of MR and CT Imaging for Assessment of Internal Carotid Artery Encasement in Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    W. L. Lodder

    2013-01-01

    Full Text Available Objective. This study was conducted to assess the value of CT and MR imaging in the preoperative evaluation of ICA encasement. Methods. Based upon three patient groups this study was performed. Retrospective analysis of 260 neck dissection reports from 2001 to 2010 was performed to determine unexpected peroperative-diagnosed encasement. Two experienced head and neck radiologists reviewed 12 scans for encasement. Results. In four out of 260 (1.5% patients undergoing neck dissection, preoperative imaging was false negative as there was peroperative encasement of the ICA. Of 380 patients undergoing preoperative imaging, the radiologist reported encasement of the ICA in 25 cases. In 342 cases no encasement was described, 125 of these underwent neck dissection, and 2 had encasement peroperatively. The interobserver variation kappa varied from 0.273 to 1 for the different characteristics studied. Conclusion. These retrospectively studied cohorts demonstrate that preoperative assessment of encasement of the ICA using MRI and/or CT was of value in evaluation of ICA encasement and therefore contributively in selecting operable patients (without ICA encasement, since in only 1.5% encasement was missed. However, observer variation affects the reliability of this feature.

  19. Intensity Modulated Radiation Therapy in Head and Neck Squamous Cell Carcinoma: state of the art and future challenges

    International Nuclear Information System (INIS)

    Gregoire, V.; Maingon, P.

    2005-01-01

    Intensity-modulated radiation therapy (IMRT) for head and neck (HN) tumors refers to a new approach to the whole treatment procedure from patient immobilization to beam delivery. Implementation of IMRT thus requires knowledge of setup uncertainties, adequate selection and delineation of target volumes based on clinical examination and optimal imaging modalities, appropriate specification and dose prescription regarding dose-volume constraints, and ad hoc quality control of both the clinical and physical aspects of the whole procedure. A large number of issues still need to be resolved and/or further refined, such as the optimal selection and delineation of the target volume in particular, with the introduction of functional imaging, and a better integration of improved dose distribution into the fractionation strategy. IMRT is associated with a potentially increased incidence of carcinogenesis, although in the HN area this risk is relative to the intrinsic risk of co-morbidity and secondary cancer associated with the patient's lifestyle. Currently, the implementation of IMRT into routine clinical practice for HN cancers may not be a straightforward matter, and should probably be restricted to selected patients and selected institutions with adequate resources and experience. This review emphasizes the above aspects and provides some recommendations for the future use of IMRT in patients with HN tumors. (author)

  20. A randomized trial of combined multidrug chemotherapy and radiotherapy in advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    1986-01-01

    This report concerns the design and results of a randomized prospective trial (SECOG I) in the treatment of advanced Stage III and IV head and neck cancer with radical radiotherapy combined with polychemotherapy. Synchronous administration of chemotherapy and radiotherapy was compared with sequential chemotherapy and radiotherapy and VBM (vincristine, bleomycin and methotrexate) compared with VBM plus 5-fluorouracil in a 2 x 2 standard factorial design. Two-hundred-and-seventy patients were entered and 267 were included in the analysis. Treatment did not present serious problems of toxicity. The addition of 5-fluorouracil to VBM produced a significant improvement in disease-free survival (P=0.04) though not in overall survival. Synchronous chemotherapy was similarly better than sequential chemotherapy, though not significantly so (P=0.1). A new study (SECOG II), based on this was started in February 1984, and one-third of the patients are now being allocated to treatment by radiotherapy as the sole method of treatment. (author)

  1. Postoperative radiotherapy dose requirement in standard combined-modality practice for head and neck squamous cell carcinoma: Analysis of salient surgical and radiotherapy parameters in 2 cohorts.

    Science.gov (United States)

    Mohanti, Bidhu K; Thakar, Alok; Kaur, Jaspreet; Bahadur, Sudhir; Malik, Monica; Gandhi, Ajeet K; Bhasker, Suman; Sharma, Atul

    2017-09-01

    This study compared 2 sequential cohorts to identify the postoperative radiotherapy (PORT) dose requirement for head and neck squamous cell carcinoma (HNSCC). Two distinct PORT dose regimens were prescribed over 11 years; group 1 received 56 Gy or less, and group 2 received 60 Gy or more. The 2D and 3D techniques were used. Two sequential cohorts consisted of 478 patients, with mean and median follow-up for group 1 and 2 as: 37.0 versus 28.5 months and 13.8 versus 13.1 months, respectively. Grades 3-4 mucosal toxicities (11.4% vs 28.3%), hospitalization (3.2% vs 17.4%), and nasogastric feeding (11.9% vs 29.7%) were higher in group 2. The 2-year disease-free survival (DFS) was higher with PORT >60 Gy for the following factors: age ≤ 50 years (P = .041); ≥ 4 positive nodes (P = .029); and overall treatment time (OTT) ≥ 100 days (P = .042). Except for the benefit of doses >60 Gy for limited parameters, a lower PORT dose did not compromise the results and can potentially reduce the morbidities and healthcare costs. © 2017 Wiley Periodicals, Inc.

  2. A comparative study of survival rates after treatment with induction chemotherapy or concurrent chemoradiotherapy in locoregionally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Hiraga, Yukihiro; Kou, Junichi

    2012-01-01

    Since 1989 our treatment approach for head and neck squamous cell carcinoma (HNSCC) has involved comprehensive treatment with chemotherapy, radiation followed by surgery, if needed. Between 1989 and 2005 chemotherapy using fluorouracil and carboplatin div was administered as induction chemotherapy (ICT), and concurrent chemoradiotherapy (CCRT) was administered more recently between 2006 and 2011. In this study we compared the statistical difference in 3-year survival rates between the ICT group and CCRT group. The number of target patients was 137, all of which were previously untreated and suffered from locoregionally advanced HNSCC: 52 with Stage III, 78 with Stage IVA, 7 with Stage IVB. In the ICT and CCRT groups, 3-year cause-specific survival rates were 68.2% and 76.3% respectively, both of which were statistically not recessive compared to those in the other issues. Furthermore, the rate between the two groups was identified as significant for Stage III and not significant for Stage IV. In conclusion, the addition of new modalities for the treatment of far-advanced HNSCC should be mandatory. (author)

  3. Combined high-intensity local treatment and systemic therapy in metastatic head and neck squamous cell carcinoma: An analysis of the National Cancer Data Base.

    Science.gov (United States)

    Zumsteg, Zachary S; Luu, Michael; Yoshida, Emi J; Kim, Sungjin; Tighiouart, Mourad; David, John M; Shiao, Stephen L; Mita, Alain C; Scher, Kevin S; Sherman, Eric J; Lee, Nancy Y; Ho, Allen S

    2017-12-01

    There is increasing evidence that primary tumor ablation can improve survival for some cancer patients with distant metastases. This may be particularly applicable to head and neck squamous cell carcinoma (HNSCC) because of its tropism for locoregional progression. This study included patients with metastatic HNSCC undergoing systemic therapy identified in the National Cancer Data Base. High-intensity local treatment was defined as radiation doses ≥ 60 Gy or oncologic resection of the primary tumor. Multivariate Cox regression, propensity score matching, landmark analysis, and subgroup analysis were performed to account for imbalances in covariates, including adjustments for the number and location of metastatic sites in the subset of patients with this information available. In all, 3269 patients were included (median follow-up, 51.5 months). Patients undergoing systemic therapy with local treatment had improved survival in comparison with patients receiving systemic therapy alone in propensity score-matched cohorts (2-year overall survival, 34.2% vs 20.6%; P treatment, whereas those receiving lower-intensity local treatment had survival similar to that of patients receiving systemic therapy without local treatment. The impact of high-intensity local therapy was time-dependent, with a stronger impact within the first 6 months after the diagnosis (adjusted hazard ratio [AHR], 0.255; 95% confidence interval [CI], 0.210-0.309; P treatment warrants prospective evaluation for select patients with metastatic HNSCC. Cancer 2017;123:4583-4593. © 2017 American Cancer Society. © 2017 American Cancer Society.

  4. Anti-Epidermal Growth Factor Receptor Therapy in Head and Neck Squamous Cell Carcinoma: Focus on Potential Molecular Mechanisms of Drug Resistance

    Science.gov (United States)

    Baay, Marc; Wouters, An; Specenier, Pol; Vermorken, Jan B.; Peeters, Marc; Lardon, Filip

    2013-01-01

    Targeted therapy against the epidermal growth factor receptor (EGFR) is one of the most promising molecular therapeutics for head and neck squamous cell carcinoma (HNSCC). EGFR is overexpressed in a wide range of malignancies, including HNSCC, and initiates important signal transduction pathways in HNSCC carcinogenesis. However, primary and acquired resistance are serious problems and are responsible for low single-agent response rate and tumor recurrence. Therefore, an improved understanding of the molecular mechanisms of resistance to EGFR inhibitors may provide valuable indications to identify biomarkers that can be used clinically to predict response to EGFR blockade and to establish new treatment options to overcome resistance. To date, no predictive biomarker for HNSCC is available in the clinic. Therapeutic resistance to anti-EGFR therapy may arise from mechanisms that can compensate for reduced EGFR signaling and/or mechanisms that can modulate EGFR-dependent signaling. In this review, we will summarize some of these molecular mechanisms and describe strategies to overcome that resistance. PMID:23821327

  5. COX-2 rs689466, rs5275, and rs20417 polymorphisms and risk of head and neck squamous cell carcinoma: a meta-analysis of adjusted and unadjusted data

    International Nuclear Information System (INIS)

    Leng, Wei-Dong; Wen, Xiu-Jie; Kwong, Joey S. W.; Huang, Wei; Chen, Jian-Gang; Zeng, Xian-Tao

    2016-01-01

    Numerous case–control studies have been performed to investigate the association between three cyclooxygenase-2 (COX-2) polymorphisms (rs20417 (−765G > C), rs689466 (−1195G > A), and rs5275 (8473 T > C)) and the risk of head and neck squamous cell carcinoma (HNSCC). However, the results were inconsistent. Therefore, we conducted this meta-analysis to investigate the association. We searched in PubMed, Embase, and Web of Science up to January 20, 2015 (last updated on May 12, 2016). Two independent reviewers extracted the data. Odds ratios (ORs) with their 95 % confidence intervals (CIs) were used to assess the association. All statistical analyses were performed using the Review Manager (RevMan) 5.2 software. Finally 8 case–control studies were included in this meta-analysis. For unadjusted data, an association with increased risk was observed in three genetic models in COX-2 rs689466 polymorphism; however, COX-2 rs5275 and rs20417 polymorphisms were not related to HNSCC risk in this study. The pooled results from adjusted data all revealed non-significant association between these three polymorphisms and risk of HNSCC. We also found a similar result in the subgroup analyses, based on both unadjusted data and adjusted data. Current results suggest that COX-2 rs689466, rs5275, and rs20417 polymorphisms are not associated with HNSCC. Further large and well-designed studies are necessary to validate this association

  6. Chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)

    International Nuclear Information System (INIS)

    Katori, Hideaki; Ishitoya, Junichi; Ikeda, Yoichi; Kimura, Machiko; Hirose, Shouji; Sakuma, Yasunori; Yamamoto, Kaoru; Tsukuda, Mamoru

    2004-01-01

    The aim of this study was to evaluate the efficacy and toxicity of chemoradiotherapy using docetaxel (DOC), cisplatin (CDDP) and 5-fluorouracil (5-FU) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Nineteen patients with previously untreated stage III-IV SCCHN were entered onto this trial. Patients received 2 cycles of chemotherapy with TPF. Radiation was targeted to begin on the first day of chemotherapy, day 1. The total radiation dose was between 63.0 and 74.0 Gy At least three patients were examined at each dose level before advancing to the next level. The maximum-tolerated dose (MTD) of this regimen was that DOC 60, CDDP 60 and 5-FU 600 mg/m 2 /day. The main toxicities were mucositis, leukocytopenia, neutropenia, anemia, liver dysfunction and renal dysfunction. The overall response rate was 100%, including 84% complete responses (CR). The high complete response rate justifies further evaluation of this chemoradiotherapy modality in advanced SCCHN patients. (author)

  7. Elevated ZNF703 Protein Expression Is an Independent Unfavorable Prognostic Factor for Survival of the Patients with Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Hang Yang

    2015-01-01

    Full Text Available Aim. Data from The Cancer Genome Atlas (TCGA show that the ZNF703 gene amplifies and overexpresses in head and neck squamous cell carcinomas (HNSCC. However, the clinical relevance of this observation in HNSCC is unclear. The purpose of this study was to clarify the expression of ZNF703 protein and its prognostic effect on HNSCC. Methods. Two hundred ten HNSCC patients from Sun Yat-Sen University Cancer Center with complete survival follow-up were included in this study. Tumor samples from primary sites were collected. The expression of the ZNF703 protein was tested by immunohistochemistry (IHC. Results. The high expression of ZNF703 in HNSCC tumor tissues was significantly higher than that of the matched noncancerous tissues (48.6% versus 11.6%, P<0.001. ZNF703 overexpression was correlated with tumor position (laryngeal carcinoma and recurrence (all P<0.05. Multivariate analysis revealed that ZNF703 protein overexpression was an independent prognostic factor (P=0.022, hazard ratio = 1.635, 95% CI 1.073–2.493 in HNSCC patients. Conclusion. ZNF703 overexpression is associated with adverse prognosis in HNSCC, which might be a novel biomarker of HNSCC.

  8. Outcomes after primary chemoradiotherapy for N3 (>6 cm) head and neck squamous cell carcinoma after an FDG-PET--guided neck management policy.

    Science.gov (United States)

    Adams, Gerard; Porceddu, Sandro V; Pryor, David I; Panizza, Benedict; Foote, Matthew; Rowan, Ann; Burmeister, Bryan

    2014-08-01

    The purpose of this study was to assess whether a positron emission tomography (PET)-directed policy remains appropriate for managing neck nodes (N3; >6 cm) in head and neck squamous cell carcinoma (HNSCC). All patients with N3 (>6 cm) HNSCC treated with definitive chemoradiotherapy (CRT) at our institution between 2005 and 2012 were included in the analysis. Patients underwent PET assessment before and 12 weeks after CRT. Neck dissections were performed for PET-avid residual nodal abnormalities after complete response at the primary site. Rate of isolated nodal failure (INF) was the primary outcome. Median follow-up from diagnosis for 33 patients was 30 months (range, 6-76 months). INF occurred in 2 patients (6%) with neck dissections performed in 4 cases (12%). First failure was predominantly distant metastatic (10; 30%). The rate of INF remains low when following a PET-directed neck management policy after definitive CRT for N3 (>6 cm) HNSCC. Copyright © 2013 Wiley Periodicals, Inc.

  9. Retrospective analysis of concurrent chemoradiotherapy for head and neck squamous-cell carcinoma: preliminary experience from ABC School of Medicine, Santo Andre, Sao Paulo State, Brazil

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    Borba Junior, Antonio Freitas; Giglio, Auro del; Philbert, Paula Lajolo; Kaliks, Rafael

    2005-01-01

    Background: concurrent chemoradiotherapy constitutes an option for head and neck squamous-cell carcinoma (HNSCC) treatment. Although we found a high incidence of this tumor in our population, we do not have so far results reported for the Brazilian population. Methods: medical records from HNSCC patients who ere treated with concurrent chemoradiotherapy between January 2001 to June 2004 were systematically reviewed. Results: twenty-two HNSCC patients were treated with chemoradiotherapy. The median age was 56 years. The primary tumor site was located in the oropharynx in 11, the larynx in 9 and hypopharynx in 2 patients. Most of the patients (86%) presented with stage III or IV disease. 19 (86%) patients were treated with Cisplatin 100 mg/m 2 D1-22-43, and 3 (14%) patients used Cisplatin 20 mg/m 2 weekly, concurrent with radiotherapy. Hematological and renal toxicity grade 3 or higher was seen in 58% and 10% patients, respectively. Eleven patients achieved a complete response and 8 a partial response. Median disease-free survival was 10 months and median overall survival was 25 months. (author)

  10. Prevalence and clinical significance of cancer cachexia based on time from treatment in advanced-stage head and neck squamous cell carcinoma.

    Science.gov (United States)

    Kwon, Minsu; Kim, Rock Bum; Roh, Jong-Lyel; Lee, Sang-Wook; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

    2017-04-01

    The purpose of this study was to identify the prevalence of cancer cachexia and its prognostic impact in patients with advanced head and neck squamous cell carcinoma (HNSCC). The prevalence of cancer cachexia was analyzed according to the follow-up periods during the first year after curative initial treatment. Recurrences, noncancer health events (NCHEs), and cause-specific survival outcomes were also analyzed according to the incidence of cancer cachexia during follow-up. Cancer cachexia was identified in 22 (6.1%), 148 (41%), 66 (18.4%), and 65 (18.7%) of 361 enrolled patients at pretreatment, immediately after treatment, 6-months after treatment, and 12-months after treatment, respectively. Sustained or newly developed cachexia at 6 and 12 months showed a significant association with recurrence and NCHE occurrence (p cachexia had a higher probability of cancer-specific death, noncancerous death, and overall death (p Cachexia prevalence at 6 and 12 months after treatment for HNSCC indicates a higher chance of recurrence, NCHE, and death. © 2016 Wiley Periodicals, Inc. Head Neck 39: 716-723, 2017. © 2016 Wiley Periodicals, Inc.

  11. A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck

    Directory of Open Access Journals (Sweden)

    Budach V

    2006-01-01

    Full Text Available Abstract Background Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX to radiotherapy (RT and to some extent also for the use of hyperfractionated radiation therapy (HFRT and accelerated radiation therapy (AFRT in locally advanced squamous cell carcinoma (SCC of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. Methods Randomised trials testing curatively intended RT (≥60 Gy in >4 weeks/>50 Gy in Results Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p Conclusion RT combined with simultaneous 5-FU, cisplatin, carboplatin, and mitomycin C as single drug or combinations of 5-FU with one of the other drugs results in a large survival advantage irrespective the employed radiation schedule. If radiation therapy is used as single modality, hyperfractionation leads to a significant improvement of overall survival. Accelerated radiation therapy alone, especially when given as split course radiation schedule or extremely accelerated treatments with decreased total dose, does not increase overall survival.

  12. Long-term functional and survival outcomes after induction chemotherapy and risk-based definitive therapy for locally advanced squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Hutcheson, Katherine A; Lewin, Jan S; Holsinger, F Christopher; Steinhaus, Ganene; Lisec, Asher; Barringer, Denise A; Lin, Heather Y; Villalobos, Sandra; Garden, Adam S; Papadimitrakopoulou, Vali; Kies, Merrill S

    2014-04-01

    The purpose of this study was to evaluate long-term outcomes after induction chemotherapy followed by "risk-based" local therapy for locally-advanced squamous cell carcinoma of the head and neck (SCCHN). Forty-seven patients (stage IV; ≥N2b) were enrolled in a phase II trial. Baseline and 24-month functional measures included modified barium swallow (MBS) studies, oropharyngeal swallow efficiency (OPSE), and the MD Anderson Dysphagia Inventory (MDADI). Functional status was assessed at 5 years. Five-year overall survival (OS) was 89% (95% confidence interval [CI], 81% to 99%). A nonsignificant 13% average reduction in swallowing efficiency (OPSE) was observed at 24 months relative to baseline (p = .191). MDADI scores approximated baseline at 24 months. Among 42 long-term survivors (median, 5.9 years), 3 patients (7.1%) had chronic dysphagia. The rate of final gastrostomy dependence was 4.8% (2 of 42). Sequential chemoradiotherapy achieved favorable outcomes among patients with locally advanced SCCHN, mainly of oropharyngeal origin. MBS and MDADI scores found modest swallowing deterioration at 2 years, and chronic aspiration was uncommon in long-term survivors. Copyright © 2013 Wiley Periodicals, Inc.

  13. High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

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    Chien Chih-Yen

    2011-03-01

    Full Text Available Abstract Background This study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1 expression on response to cisplatin-based induction chemotherapy (IC followed by concurrent chemoradiation (CCRT in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC patients. Methods Fifty-seven patients with locally advanced unresectable HNSCC who received cisplatin-based IC followed by CCRT from January 1, 2006 through January 1, 2008. Eligibility criteria included presence of biopsy-proven HNSCC without a prior history of chemotherapy or radiotherapy. Immunohistochemistry was used to assess ERCC1 expression in pretreatment biopsy specimens from paraffin blocks. Clinical parameters, including smoking, alcohol consumption and betel nuts chewing, were obtained from the medical records. Results The 12-month progression-free survival (PFS and 2-year overall survival (OS rates of fifty-seven patients were 61.1% and 61.0%, respectively. Among these patients, thirty-one patients had low ERCC1 expression and forty-one patients responded to IC followed by CCRT. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 12-month PFS rates (73.3% vs. 42.3%, p Conclusions Our study suggest that a high expression of ERCC1 predict a poor response and survival to cisplatin-based IC followed by CCRT in patients with locally advanced unresectable HNSCC in betel nut chewing area.

  14. Stereotactic Body Radiotherapy for Recurrent Squamous Cell Carcinoma of the Head and Neck: Results of a Phase I Dose-Escalation Trial

    International Nuclear Information System (INIS)

    Heron, Dwight E.; Ferris, Robert L.; Karamouzis, Michalis; Andrade, Regiane S.; Deeb, Erin L.; Burton, Steven; Gooding, William E.; Branstetter, Barton F.; Mountz, James M.; Johnson, Jonas T.; Argiris, Athanassios; Grandis, Jennifer R.; Lai, Stephen Y.

    2009-01-01

    Purpose: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) in previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: In this Phase I dose-escalation clinical trial, 25 patients were treated in five dose tiers up to 44 Gy, administered in 5 fractions over a 2-week course. Response was assessed according to the Response Evaluation Criteria in Solid Tumors and [ 18 F]-fluorodeoxyglucose standardized uptake value change on positron emission tomography-computed tomography (PET-CT). Results: No Grade 3/4 or dose-limiting toxicities occurred. Four patients had Grade 1/2 acute toxicities. Four objective responses were observed, for a response rate of 17% (95% confidence interval 2%-33%). The maximum duration of response was 4 months. Twelve patients had stable disease. Median time to disease progression was 4 months, and median overall survival was 6 months. Self-reported quality of life was not significantly affected by treatment. Fluorodeoxyglucose PET was a more sensitive early-measure response to treatment than CT volume changes. Conclusion: Reirradiation up to 44 Gy using SBRT is well tolerated in the acute setting and warrants further evaluation in combination with conventional and targeted therapies.

  15. Serum Levels of IGF-1 and IGFBP-3 in Relation to Clinical and Pathobiological Aspects of Head and Neck Squamous Cell Carcinomas.

    Science.gov (United States)

    Kalfert, David; Ludvikova, Marie; Topolcan, Ondrej; Celakovsky, Petr; Kucera, Radek; Windrichova, Jindra; Ludvik, Jaroslav; Skalova, Katerina; Kulda, Vlastimil; Pesta, Martin; Plzak, Jan

    2017-06-01

    Head and neck squamous cell carcinoma (HNSCC) includes tumors of various anatomical sites sharing multifactorial etiopathogenesis and generally dismal response to conventional treatment. The objective of this study was to determine the clinical significance of serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) in HNSCC. A total of 46 patients, with histologically-confirmed diagnosis of HNSCC (21 oropharyngeal, 21 laryngeal, and 4 hypopharyngeal cancers) were enrolled in this study. IGF-1 and IGFBP-3 serum levels were measured by an immunoradiometric assay using commercial kits. The adjustment of serum levels at 60 years of age was performed. Significant differences were found in IGF-1 serum concentrations between patients with p16 positive and p16 negative HNSCC (p=0.0062), with higher IGF-1 levels in p16 positive tumors, between low-grade and high-grade cancers (p=0.0323) only in larynx, with elevated IGF-1 concentrations associated with high-grade and between recurrent and non-recurrent HNSCC (p=0.0354), with lower IGF-1 levels in recurrent tumors. The conflicting results of this study may reflect some abnormality of IGF axis regulation in HNSCC, as well as the influence of other etiological factors (e.g. smoking, HPV infection). Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Re-irradiation combined with capecitabine in locally recurrent squamous cell carcinoma of the head and neck. A prospective phase II trial

    Energy Technology Data Exchange (ETDEWEB)

    Vormittag, L.; Kornek, G. [Medical Univ. Vienna (Austria). Div. of Clinical Oncology; Lemaire, C.; Radonjic, D.; Selzer, E. [Medical Univ. Vienna (Austria). Dept. for Radiotherapy and Radiobiology

    2012-03-15

    We performed a prospective phase II trial to investigate the safety and efficacy of radiotherapy combined with capecitabine in patients suffering from a recurrence of a squamous cell carcinoma of the head and neck (SCCHN) within a previously irradiated field. A total of 31 evaluable patients with recurrent SCCHN received re-irradiation with a total dose of 50 Gy (25 fractions over 5 weeks) up to a maximum of 60 Gy combined with 900 mg/m{sup 2}/day capecitabine given on the days of radiotherapy. The median time to relapse after the first course of radiotherapy was 15 months. The overall response rate in our study was 68% including 6 patients with a complete response. The median overall survival was 8.4 months. Grade 3 or 4 mucositis occurred in 4 patients and 1 patient, respectively. No grade 4 hematological toxicities were observed; 1 patient had grade 3 anemia. The cumulative median lifetime dose was 116 Gy. Capecitabine combined with re-irradiation is a well-tolerated treatment in patients with recurrent SCCHN. In light of its good tolerability, it appears to be a potential option for patients with a reduced performance status and may also serve as a basis for novel treatment concepts, such as in combination with targeted therapies.

  17. Correlation of human papillomavirus status with apparent diffusion coefficient of diffusion-weighted MRI in head and neck squamous cell carcinomas.

    Science.gov (United States)

    Driessen, Juliette P; van Bemmel, Alexander J M; van Kempen, Pauline M W; Janssen, Luuk M; Terhaard, Chris H J; Pameijer, Frank A; Willems, Stefan M; Stegeman, Inge; Grolman, Wilko; Philippens, Marielle E P

    2016-04-01

    Identification of prognostic patient characteristics in head and neck squamous cell carcinoma (HNSCC) is of great importance. Human papillomavirus (HPV)-positive HNSCCs have favorable response to (chemo)radiotherapy. Apparent diffusion coefficient, derived from diffusion-weighted MRI, has also shown to predict treatment response. The purpose of this study was to evaluate the correlation between HPV status and apparent diffusion coefficient. Seventy-three patients with histologically proven HNSCC were retrospectively analyzed. Mean pretreatment apparent diffusion coefficient was calculated by delineation of total tumor volume on diffusion-weighted MRI. HPV status was analyzed and correlated to apparent diffusion coefficient. Six HNSCCs were HPV-positive. HPV-positive HNSCC showed significantly lower apparent diffusion coefficient compared to HPV-negative. This correlation was independent of other patient characteristics. In HNSCC, positive HPV status correlates with low mean apparent diffusion coefficient. The favorable prognostic value of low pretreatment apparent diffusion coefficient might be partially attributed to patients with a positive HPV status. © 2015 Wiley Periodicals, Inc. Head Neck 38: E613-E618, 2016. © 2015 Wiley Periodicals, Inc.

  18. Cancer/testis antigens: A prospective reagent as diagnostic and immunotherapeutic targets for squamous cell carcinoma of the head and neck

    Directory of Open Access Journals (Sweden)

    Shohei Domae

    2014-11-01

    Full Text Available Numerous tumor antigens have so far been identified from various tumors using the serological identification of antigens by recombinant expression cloning (SEREX method. Among them, cancer/testis (CT antigens are considered promising target molecules for immunotherapy for patients with various cancers. We performed several SEREX analyses of various cancers to identify CT antigens, including gastric adenocarcinoma, lung adenocarcinoma, and colon cancer, and consequently identified additional CT antigens, such as XAGE-1, CCDC62-2, GKAP1, and TEKT5. However, although SEREX analysis of squamous cell carcinoma of the head and neck (HNSCC has been performed several times, only a few CT or HNSCC specific antigens have yet been isolated. Compared with other tumors, a small number of studies have been reported on the antigen proteins specific to HNSCC. We here reported the expression of selected CT antigens and their immunogenicity in patients with HNSCC. The results obtained suggested that CCDC62-2, GKAP1, and TEKT5 are immunogenic in HNSCC and also demonstrated their potencies as diagnostic markers for patients with HNSCC in combination with other CT antigens such as NY-ESO-1, MAGE-A3, and MAGE-A4.

  19. Phase I study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma.

    Science.gov (United States)

    Papadimitrakopoulou, Vasiliki A; Frank, Steven J; Cohen, Ezra W; Hirsch, Fred R; Myers, Jeffrey N; Heymach, John V; Lin, Heather; Tran, Hai T; Chen, Changhu R; Jimeno, Antonio; Nedzi, Lucien; Vasselli, Joseph R; Lowe, Elizabeth S; Raben, David

    2016-03-01

    Vandetanib, added to cisplatin and radiation therapy (RT) overcomes chemoradiation therapy (CRT) and epidermal growth factor receptor (EGFR) inhibitor resistance in head and neck squamous cell carcinoma (HNSCC) lines and models. Patients with previously untreated HNSCC received vandetanib daily for 14 days (starting dose 100 mg) and then vandetanib + RT (2.2 Gy/day, 5 days/week) for 6 weeks (regimen 1) or vandetanib + RT (2 Gy/day, 5 days/week) + cisplatin (30 mg/m(2) weekly) for 7 weeks (regimen 2). The primary objective was the maximum tolerated dose (MTD) of vandetanib with RT +/- cisplatin. Of 33 treated patients, 30 completed therapy (regimen 1, n = 12; regimen 2, n = 18). MTD in regimen 2 was 100 mg (3 dose limiting toxicities [DLTs] at 200 mg), whereas regimen 1 was stopped because of poor recruitment (1 DLT at 200 mg). Most common grade ≥3 adverse events (AEs) were dysphagia (30%), stomatitis (33%), and mucosal inflammation (27%). Five patients discontinued vandetanib because of AEs. Vandetanib with CRT was feasible. © 2015 Wiley Periodicals, Inc.

  20. Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Predictor of Outcome in Head-and-Neck Squamous Cell Carcinoma Patients With Nodal Metastases

    International Nuclear Information System (INIS)

    Shukla-Dave, Amita; Lee, Nancy Y.; Jansen, Jacobus F.A.; Thaler, Howard T.; Stambuk, Hilda E.; Fury, Matthew G.; Patel, Snehal G.; Moreira, Andre L.; Sherman, Eric; Karimi, Sasan; Wang, Ya; Kraus, Dennis; Shah, Jatin P.; Pfister, David G.

    2012-01-01

    Purpose: Dynamic contrast-enhanced MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of this study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery. Methods and Materials: Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using the Tofts model. DCE-MRI parameters were related to treatment outcome (progression-free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD), or dead of other causes (DOC). Prognostic significance was assessed using the log-rank test for single variables and Cox proportional hazards regression for combinations of variables. Results: At last clinical follow-up, for Stage III, all 12 patients were NED. For Stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. K trans is volume transfer constant. In a stepwise Cox regression, skewness of K trans (volume transfer constant) was the strongest predictor for Stage IV patients (PFS and OS: p trans was the strongest predictor of PFS and OS in Stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter K trans as a predictor of outcome in these patients.

  1. Radionuclides detected in lime samples that consumed with tobacco and betel nuts by people of Northeast India where head and neck squamous cells cancer (HNSCC) is prevalent

    International Nuclear Information System (INIS)

    Dilip Bhattacharjee; Satoru Endo; Kenichi Tanaka; Masaharu Hoshi

    2007-01-01

    Complete text of publication follows. Head and neck squamous cell cancer (HNSCC) is a very predominant type of cancer amongst the population of northeastern states of India than the rest of the world. Epidemiological and other data suggest consumption of betel nuts with/without tobacco and lime or tobacco alone with lime is a probable cause of high cancer incidence. The fundamental question arises that why this particular cancer is induced more in this region while people follow the similar habits elsewhere. Here we report the results on analysis of lime samples, collected from 12 different locations spectrophotometrically by high-purity germanium detector. The calculated activity of radionuclides showed to an average of 2.68, 0.10 and 0.83 Bq/gm for 238 U, 235 U and 232 Th series respectively for ten samples which are about 8 times higher than the normal background level of 0.37, 0.02 and 0.02 Bq/gm for 238 U, 235 U and 232 Th series found in control samples, collected from outside of northeast. The results conclusively showed for the first time that the lime samples almost throughout the northeastern India contain high proportion of radionuclides of uranium, thorium and actinides series. Further, annual effective dose of gamma radiation calculations from these results of earth's crust in northeast showed that gamma rays emitted at an average dose of up to 2.5 mSv/year/consumer approximately. This dose calculation in the oral cavity is underestimated as short range radiations by decay of alpha, beta and electron-capture etc are not considered in the present study. Continuous exposure of such low dose radiations emitting from different radionuclides to the sensitive squamous cells of the oral cavity for a long twenty years or more amounting to a total minimum dose of at least 50 mSv evidently contributes towards excessive HNSCC to the people of northeast than other parts of India.

  2. Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

    International Nuclear Information System (INIS)

    Nyflot, Matthew J.; Kruser, Tim J.; Traynor, Anne M.; Khuntia, Deepak; Yang, David T.; Hartig, Gregory K.; McCulloch, Timothy M.; Wiederholt, Peggy A.; Gentry, Lindell R.; Hoang, Tien; Jeraj, Robert

    2015-01-01

    Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m 2 and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [ 18 F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [ 61 Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging demonstrates

  3. Should PET/CT be implemented in the routine imaging work-up of locally advanced head and neck squamous cell carcinoma? A prospective analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cacicedo, Jon; Bilbao, Pedro [Cruces University Hospital, Radiation Oncology Department, Barakaldo, Bizkaia (Basque Country) (Spain); BioCruces Health Research Institute, Bizkaia, Basque Country (Spain); Fernandez, Iratxe [Cruces University Hospital, Nuclear Medicine Department, Barakaldo (Spain); Hoyo, Olga del; Hortelano, Eduardo [Cruces University Hospital, Radiation Oncology Department, Barakaldo, Bizkaia (Basque Country) (Spain); Dolado, Ainara [Cruces University Hospital, Radiodiagnostic and Medical Imaging Department, Barakaldo (Spain); Gomez-Suarez, Javier [Cruces University Hospital, Otolaryngology Department, Barakaldo (Spain); Sancho, Aintzane [Cruces University Hospital, Medical Oncology Department, Barakaldo (Spain); Pijoan, Jose I. [BioCruces Health Research Institute, Bizkaia, Basque Country (Spain); Cruces University Hospital, Clinical Epidemiology Unit, Barakaldo (Spain); CIBER de Epidemiologia y Salud Publica (CIBERESP), Madrid (Spain); Alvarez, Julio [Cruces University Hospital, Oral and Maxillofacial Surgery Department, Barakaldo (Spain); Espinosa, Jose M. [Cruces University Hospital, Medical Physics Department, Barakaldo (Spain); Gaafar, Ayman [Cruces University Hospital, Department of Pathology, Barakaldo (Spain)

    2015-08-15

    The objective of this study was to determine the incremental staging information provided by positron emission tomography/computed tomography (PET/CT) and its impact on management plans in patients with untreated stage III-IV head and neck squamous cell carcinoma (HNSCC). We prospectively studied, between September 2011 and February 2013, 84 consecutive patients [median age 63.5 years (39-84); 73 men] with histologically confirmed HNSCC. First, based on a conventional work-up (physical examination, CT imaging of the head, neck and chest), the multidisciplinary Head and Neck Tumour Board documented the TNM stage and a management plan for each patient, outlining the modalities to be used, including surgery, radiation therapy (RT), chemotherapy or a combination. After release of the PET/CT results, new TNM staging and management plans were agreed on by the multidisciplinary Tumour Board. Any changes in stage or intended management due to the PET/CT findings were then analysed. The impact on patient management was classified as: low (treatment modality, delivery and intent unchanged), moderate (change within the same treatment modality: type of surgery, radiation technique/dose) or high (change in treatment intent and/or treatment modality → curative to palliative, or surgery to chemoradiation or detection of unknown primary tumour or a synchronous second primary tumour). TNM stage was validated by histopathological analysis, additional imaging or follow-up. Accuracy of the conventional and PET/CT-based staging was compared using McNemar's test. Conventional and PET/CT stages were discordant in 32/84 (38 %) cases: the T stage in 2/32 (6.2 %), the N stage in 21/32 (65.7 %) and the M stage 9/32 (28.1 %). Patient management was altered in 22/84 (26 %) patients, with a moderate impact in 8 (9.5 %) patients and high impact in 14 (16.6 %) patients. PET/CT TNM classification was significantly more accurate (92.5 vs 73.7 %) than conventional staging with a p value < 0

  4. Should PET/CT be implemented in the routine imaging work-up of locally advanced head and neck squamous cell carcinoma? A prospective analysis

    International Nuclear Information System (INIS)

    Cacicedo, Jon; Bilbao, Pedro; Fernandez, Iratxe; Hoyo, Olga del; Hortelano, Eduardo; Dolado, Ainara; Gomez-Suarez, Javier; Sancho, Aintzane; Pijoan, Jose I.; Alvarez, Julio; Espinosa, Jose M.; Gaafar, Ayman

    2015-01-01

    The objective of this study was to determine the incremental staging information provided by positron emission tomography/computed tomography (PET/CT) and its impact on management plans in patients with untreated stage III-IV head and neck squamous cell carcinoma (HNSCC). We prospectively studied, between September 2011 and February 2013, 84 consecutive patients [median age 63.5 years (39-84); 73 men] with histologically confirmed HNSCC. First, based on a conventional work-up (physical examination, CT imaging of the head, neck and chest), the multidisciplinary Head and Neck Tumour Board documented the TNM stage and a management plan for each patient, outlining the modalities to be used, including surgery, radiation therapy (RT), chemotherapy or a combination. After release of the PET/CT results, new TNM staging and management plans were agreed on by the multidisciplinary Tumour Board. Any changes in stage or intended management due to the PET/CT findings were then analysed. The impact on patient management was classified as: low (treatment modality, delivery and intent unchanged), moderate (change within the same treatment modality: type of surgery, radiation technique/dose) or high (change in treatment intent and/or treatment modality → curative to palliative, or surgery to chemoradiation or detection of unknown primary tumour or a synchronous second primary tumour). TNM stage was validated by histopathological analysis, additional imaging or follow-up. Accuracy of the conventional and PET/CT-based staging was compared using McNemar's test. Conventional and PET/CT stages were discordant in 32/84 (38 %) cases: the T stage in 2/32 (6.2 %), the N stage in 21/32 (65.7 %) and the M stage 9/32 (28.1 %). Patient management was altered in 22/84 (26 %) patients, with a moderate impact in 8 (9.5 %) patients and high impact in 14 (16.6 %) patients. PET/CT TNM classification was significantly more accurate (92.5 vs 73.7 %) than conventional staging with a p value < 0

  5. Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Nyflot, Matthew J., E-mail: nyflot@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Kruser, Tim J. [Department of Radiation Oncology, Cadence Cancer Center at Delnor Hospital, Geneva, Illinois (United States); Traynor, Anne M. [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Khuntia, Deepak [Varian Medical Systems, Palo Alto, California (United States); Yang, David T. [Departments of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hartig, Gregory K.; McCulloch, Timothy M. [Department of Surgery-Otolaryngology, H& N Surgery Division, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Wiederholt, Peggy A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Gentry, Lindell R. [Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hoang, Tien [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Jeraj, Robert [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Medical Physics, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); and others

    2015-04-01

    Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m{sup 2} and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [{sup 18}F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [{sup 61}Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging

  6. Retrospective analysis of chronomodulated chemotherapy versus conventional chemotherapy with paclitaxel, carboplatin, and 5-fluorouracil in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Chen D

    2013-10-01

    Full Text Available Dan Chen, Jue Cheng, Kai Yang, Yue Ma, Fang Yang Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China Background: Chronomodulated chemotherapy has emerged as a new therapy as a result of recent studies focusing on the biological clock. It has been demonstrated that combination chronomodulated chemotherapy of platinum-based drugs and 5-fluorouracil (5-Fu can significantly improve efficacy and reduce the incidence of adverse events in patients with metastatic colorectal cancer, as compared with conventional chemotherapy. However, the results may be different in different tumors. Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC is very difficult to treat, with an extremely unfavorable prognosis. So far, no report is available on chronomodulated chemotherapy for HNSCC. Methods: Retrospective analyses were made on 49 patients with local recurrent and/or metastatic HNSCC who underwent palliative treatments with paclitaxel, carboplatin, and 5-Fu. The patients were divided into a chronomodulated chemotherapy group (28 patients and a conventional chemotherapy group (21 patients according to their administration times. The two groups were compared for tumor objective response rate, overall survival (OS, progression-free survival (PFS, and the incidence of adverse events. Results: The tumor objective response rate and patients' OS were significantly higher and longer in the chronomodulated chemotherapy group than in the conventional chemotherapy group (71.43% versus 42.86%, respectively, P0.05. The global incidence of adverse events in the chronomodulated chemotherapy group was significantly lower than that in the conventional chemotherapy group (46.43% versus 76.19%, P<0.05, with significantly lower incidence of grade 3–4 adverse events (7.14% versus 33.33%, P<0.05. Conclusion: Chronomodulated chemotherapy with paclitaxel, carboplatin, and

  7. A Phase I Clinical Trial of AZD1775 in Combination With Neoadjuvant Weekly Docetaxel and Cisplatin Before Definitive Therapy in Head and Neck Squamous Cell Carcinoma. | Office of Cancer Genomics

    Science.gov (United States)

    Purpose: The WEE1 tyrosine kinase regulates G2/M transition and maintains genomic stability, particularly in p53-deficient tumors which require DNA repair after genotoxic therapy. There is a need to exploit the role of WEE1 inhibition in head and neck squamous cell carcinoma (HNSCC) mostly driven by tumor-suppressor loss. This completed phase I clinical trial represents the first published clinical experience using the WEE1 inhibitor, AZD1775, with cisplatin and docetaxel.

  8. ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography in malignancies of the thyroid and in head and neck squamous cell carcinoma: a review of the literature.

    Science.gov (United States)

    Lauridsen, Jeppe Kiilerich; Rohde, Max; Thomassen, Anders

    2015-01-01

    18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is a valuable diagnostic tool in a spectrum of malignant and benign conditions, because of a high sensitivity to detect even very small lesions with increased metabolism. This review focuses on the use of FDG-PET/CT in malignancies of the thyroid gland and in head and neck squamous cell carcinoma. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1)

    DEFF Research Database (Denmark)

    Machiels, Jean-Pascal H; Haddad, Robert I; Fayette, Jérôme

    2015-01-01

    BACKGROUND: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting......%]), and neutropenia (1 [... provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC. FUNDING: Boehringer Ingelheim....

  10. Clinicopathological characteristics of head and neck Merkel cell carcinomas.

    Science.gov (United States)

    Knopf, Andreas; Bas, Murat; Hofauer, Benedikt; Mansour, Naglaa; Stark, Thomas

    2017-01-01

    There are still controversies about the therapeutic strategies and subsequent outcome in head and neck Merkel cell carcinoma. Clinicopathological data of 23 Merkel cell carcinomas, 93 cutaneous head and neck squamous cell carcinomas (HNSCCs), 126 malignant melanomas, and 91 primary parotid gland carcinomas were comprehensively analyzed. Merkel cell carcinomas were cytokeratin 20 (CK20)/neuron-specific enolase (NSE)/chromogranin A (CgA)/synaptophysin (Syn)/thyroid transcription factor-1 (TTF-1)/MIB1 immunostained. All Merkel cell carcinomas underwent wide local excision. Parotidectomy/neck dissection was performed in 40%/33% cutaneous Merkel cell carcinoma and 100%/100% in parotid gland Merkel cell carcinoma. Five-year recurrence-free interval (RFI)/overall survival (OS) was significantly higher in malignant melanoma (81/80%) than in cutaneous Merkel cell carcinoma/HNSCC. Interestingly, 5-year RFI/OS was significantly higher in Merkel cell carcinoma (61%/79%) than in HNSCC (33%/65%; p Merkel cell carcinoma and parotid gland carcinomas, nor in the immunohistochemical profile. Five-year RFI/OS was significantly better in cutaneous Merkel cell carcinoma when compared with TNM classification matched HNSCC. Five-year RFI/OS was comparable in parotid gland Merkel cell carcinoma and other primary parotid gland malignancies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 92-97, 2017. © 2016 Wiley Periodicals, Inc.

  11. The prognostic value of endogenous hypoxia-related markers for head and neck squamous cell carcinomas treated with ARCON

    International Nuclear Information System (INIS)

    Jonathan, Ruth A.; Wijffels, Karien I.E.M.; Peeters, Wenny; Wilde, Peter C.M. de; Marres, Henri A.M.; Merkx, Matthias A.W.; Oosterwijk, Egbert; Kogel, Albert van der J.; Kaanders, Johannes H.A.M.

    2006-01-01

    Background and purpose: Hypoxic radioresistance is an important cause for treatment failure in a number of tumor types including head and neck cancers. Recent studies suggest that outcome can be improved by oxygenation modifying treatments such as ARCON. A robust endogenous marker of hypoxia might be a valuable aid to select patients for such treatments. The aim of this investigation was to study associations between the putative endogenous hypoxia markers CA-IX, Glut-1 and Glut-3 and clinical tumor and patient characteristics and to evaluate the prognostic value of these markers. Patients and methods: Tumor biopsies from 58 patients treated with ARCON in a phase II trial were included. Tumor sections were immunohistochemically stained for CA-IX, Glut-1 and Glut-3. Sections were scored for relative tumor area stained by the markers (CA-IX and Glut-3) and for intensity of staining (Glut-1 and Glut-3). Further, sections were stained for CD34, an endothelial marker to assess microvascular density. Results: Staining of CA-IX and Glut-3 was observed at some distance from vessels and adjacent to necrosis. Glut-1 staining was generally very diffuse. The distribution of clinical characteristics was equal between tumors with high and low marker expression. Significant differences were found for locoregional control (P=0.04) and for freedom of distant metastases (P=0.02) in favour of patients with high CA-IX positivity (>25% of tumor area). High Glut-3 expression was associated with a better locoregional control (P=0.04). Higher Glut-1 intensity was associated with an increased rate of distant metastases (P=0.0005) and a worse overall survival (P=0.001). Conclusions: The inconsistent associations with outcome of CA-IX and the glucose transporters indicate that different factors play a role in up-regulation of these markers. Compared to studies with conventional treatment, the correlation between CA-IX expression and Glut-3 expression and outcome was reversed after treatment

  12. Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models.

    Science.gov (United States)

    Koonce, Nathan A; Griffin, Robert J; Dings, Ruud P M

    2017-12-09

    Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding. Immuno-fluorescence was used to determine vessel normalization status. Continued OTX008 treatment caused a transient reoxygenation in SQ20B tumors peaking on day 14, while a steady increase in tumor oxygenation was observed over 21 days in the HEp-2 model. A >50% decrease in immunohistochemical staining for tumor hypoxia verified the oxygenation data measured using a partial pressure of oxygen (pO₂) probe. Additionally, OTX008 induced tumor vessel normalization as tumor pericyte coverage increased by approximately 40% without inducing any toxicity. Moreover, OTX008 inhibited tumor growth as effectively as Anginex and Avastin, except in the HEp-2 model where Avastin was found to suspend tumor growth. Galectin-1 inhibitor OTX008 transiently increased overall tumor oxygenation via vessel normalization to various degrees in both HNSCC models. These findings suggest that targeting galectin-1-e.g., by OTX008-may be an effective approach to treat cancer patients as stand-alone therapy or in combination with other standards of care.

  13. In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nestor, M.; Anniko, M. [Uppsala University, Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala (Sweden); Persson, M. [Uppsala University, Unit of Urology, Department of Surgical Sciences, Uppsala (Sweden); Uppsala University, Unit of Biomedical Radiation Science, Department of Oncology, Radiology and Clinical Immunology, Uppsala (Sweden); Dongen, G.A.M.S. van [Vrije Universiteit Medical Center, Department of Otolaryngology/Head and Neck Surgery, Amsterdam (Netherlands); Jensen, H.J. [Righshospitalet, PET and Cyclotron Unit, Department of Clinical Physiology and Nuclear Medicine, Copenhagen (Denmark); Lundqvist, H.; Tolmachev, V. [Uppsala University, Unit of Biomedical Radiation Science, Department of Oncology, Radiology and Clinical Immunology, Uppsala (Sweden)

    2005-11-01

    The purpose of this study was to analyse the properties of the astatinated chimeric MAb (cMAb) U36 as a conjugate to selectively target and eradicate head and neck squamous cell carcinoma (HNSCC). cMAb U36 was labelled with {sup 211}At via the linker N-succinimidyl 4-(trimethylstannyl)benzoate (SPMB). The quality of the conjugate was extensively evaluated for binding and internalisation capacity, and compared with {sup 125}I-SPMB-cMAb U36. The cellular toxicity of the astatinated conjugate was assessed in two types of in vitro growth assay and compared with {sup 131}I-labelled cMAb U36 (directly labelled). Comparisons between {sup 211}At-cMAb U36 and {sup 125}I-cMAb U36 demonstrated an optimal functional capacity of the labelled products. Immunoreactivity and affinity assays showed high immunoreactive fractions (>93%), and an affinity in good agreement between the astatinated and iodinated antibodies. For both conjugates, specific binding to HNSCC cells could be demonstrated, as well as some internalisation. Retention of the astatinated conjugate was just slightly lower than for the iodinated conjugate and still reasonable for therapeutic use (31{+-}2% vs 42.6{+-}1.0% at 22 h), demonstrating no adverse effects from astatination of the antibody. Studies on cellular toxicity demonstrated a dose-dependent and antigen-specific cellular toxicity for {sup 211}At-cMAb U36, with about 10% cell survival at 50 decays per cell. The {sup 131}I-labelled conjugate was not as efficient, with a surviving cell fraction of about 50% at 55 decays per cell. (orig.)

  14. In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Nestor, M.; Anniko, M.; Persson, M.; Dongen, G.A.M.S. van; Jensen, H.J.; Lundqvist, H.; Tolmachev, V.

    2005-01-01

    The purpose of this study was to analyse the properties of the astatinated chimeric MAb (cMAb) U36 as a conjugate to selectively target and eradicate head and neck squamous cell carcinoma (HNSCC). cMAb U36 was labelled with 211 At via the linker N-succinimidyl 4-(trimethylstannyl)benzoate (SPMB). The quality of the conjugate was extensively evaluated for binding and internalisation capacity, and compared with 125 I-SPMB-cMAb U36. The cellular toxicity of the astatinated conjugate was assessed in two types of in vitro growth assay and compared with 131 I-labelled cMAb U36 (directly labelled). Comparisons between 211 At-cMAb U36 and 125 I-cMAb U36 demonstrated an optimal functional capacity of the labelled products. Immunoreactivity and affinity assays showed high immunoreactive fractions (>93%), and an affinity in good agreement between the astatinated and iodinated antibodies. For both conjugates, specific binding to HNSCC cells could be demonstrated, as well as some internalisation. Retention of the astatinated conjugate was just slightly lower than for the iodinated conjugate and still reasonable for therapeutic use (31±2% vs 42.6±1.0% at 22 h), demonstrating no adverse effects from astatination of the antibody. Studies on cellular toxicity demonstrated a dose-dependent and antigen-specific cellular toxicity for 211 At-cMAb U36, with about 10% cell survival at 50 decays per cell. The 131 I-labelled conjugate was not as efficient, with a surviving cell fraction of about 50% at 55 decays per cell. (orig.)

  15. miRNA array analysis determines miR-205 is overexpressed in head and neck squamous cell carcinoma and enhances cellular proliferation

    Directory of Open Access Journals (Sweden)

    Howard JD

    2013-08-01

    Full Text Available MicroRNAs (miRNAs play a critical role in cell cycle and pro-survival signal regulation. Consequently, their deregulation can enhance tumorigenesis and cancer progression. In the current investigation, we determined whether cancer- or human papillomavirus (HPV-specific miRNA deregulation could further elucidate signal transduction events unique to head and neck squamous cell carcinoma (HNSCC. Twenty-nine newly diagnosed HNSCC tumors (HPV-positive: 14, HPV-negative: 15 and four normal mucosa samples were analyzed for global miRNA expression. Differential miRNA expression analysis concluded HNSCC is characterized by a general upregulation of miRNAs compared to normal mucosa. Additionally, miR-449a and miR-129-3p were statistically significant miRNAs differentially expressed between HPV-positive and HPV-negative HNSCC. The upregulation of miR-449a was also validated within an independent dataset obtained from TCGA containing 279 HNSCCs and 39 normal adjacent mucosa samples. To gain a better understanding of miRNA-mediated cell cycle deregulation in HNSCC, we functionally evaluated miR-205, a transcript upregulated in our cancer-specific analysis and a putative regulator of E2F1. Modulation of miR-205 with a miRNA mimic and inhibitor revealed miR-205 is capable of regulating E2F1 expression in HNSCC and overexpression of this transcript enhances proliferation. This study demonstrates miRNA expression is highly deregulated in HNSCC and functional evaluations of these miRNAs may reveal novel HPV context dependent mechanisms in this disease.

  16. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Téllez-Gabriel, Marta; Arroyo-Solera, Irene; León, Xavier; Gallardo, Alberto; López, Montserrat; Céspedes, Maria V; Casanova, Isolda; López-Pousa, Antonio; Quer, Miquel; Mangues, Maria A; Barnadas, Agustí; Mangues, Ramón; Pavón, Miguel A

    2013-01-01

    Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment

  17. Dose dependent activation of retinoic acid-inducible gene-I promotes both proliferation and apoptosis signals in human head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Jingzhou Hu

    Full Text Available The retinoic-acid-inducible gene (RIG-like receptor (RLR family proteins are major pathogen reorganization receptors (PRR responsible for detection of viral RNA, which initiates antiviral response. Here, we evaluated the functional role of one RLR family member, RIG-I, in human head and neck squamous cell carcinoma (HNSCC. RIG-I is abundantly expressed both in poorly-differentiated primary cancer and lymph node metastasis, but not in normal adjacent tissues. Activation of RIG-I by transfection with low dose of 5'-triphosphate RNA (3p-RNA induces low levels of interferon and proinflammatory cytokines and promotes NF-κB- and Akt-dependent cell proliferation, migration and invasion. In contrast, activation of RIG-I by a high dose of 3p-RNA induces robust mitochondria-derived apoptosis accompanied by decreased activation of Akt, which is independent of the interferon and TNFα receptor, but can be rescued by over-expression of constitutively active Akt. Furthermore, co-immunoprecipitation experiments indicate that the CARD domain of RIG-I is essential for inducing apoptosis by interacting with caspase-9. Together, our results reveal a dual role of RIG-I in HNSCC through regulating activation of Akt, in which RIG-I activation by low-dose viral dsRNA increases host cell survival, whereas higher level of RIG-I activation leads to apoptosis. These findings highlight the therapeutic potential of dsRNA mediated RIG-I activation in the treatment of HNSCC.

  18. PET imaging of EGF receptors using [{sup 18}F]FBEM-EGF in a head and neck squamous cell carcinoma model

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weihua [Harbin Medical University, Department of Medical Imaging and Nuclear Medicine, Fourth Affiliated Hospital, Harbin (China); National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), Bethesda, MD (United States); Niu, Gang; Lang, Lixin; Guo, Ning; Ma, Ying; Kiesewetter, Dale O.; Chen, Xiaoyuan [National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), Bethesda, MD (United States); Backer, Joseph M. [SibTech Inc., Brookfield, CT (United States); Shen, Baozhong [Harbin Medical University, Department of Medical Imaging and Nuclear Medicine, Fourth Affiliated Hospital, Harbin (China)

    2012-02-15

    To prepare and evaluate a new radiotracer for molecular imaging of cell surface receptors for epidermal growth factor (EGF). Cys-tagged EGF (cEGF) was labeled with {sup 18}F by coupling the free thiol group of the Cys tag with N-[2-(4-[{sup 18}F]fluorobenzamido)ethyl]maleimide ([{sup 18}F]FBEM) to form [{sup 18}F]FBEM-cEGF. Cell uptake, internalization and efflux of [{sup 18}F]FBEM-cEGF were tested in human head and neck squamous carcinoma UM-SCC1 cells. In vivo tumor targeting and pharmacokinetics of the radiotracers were evaluated in UM-SCC1 tumor-bearing athymic nude mice by static and dynamic microPET imaging. Ex vivo biodistribution assays were performed to confirm the noninvasive imaging results. The radiolabeling yield for [{sup 18}F]FBEM-cEGF was over 60%, based on starting [{sup 18}F]FBEM. [{sup 18}F]FBEM-cEGF exhibited rapid blood clearance through both hepatobiliary and renal excretion. UM-SCC1 tumors were clearly visualized and showed modest tracer uptake of 2.60 {+-} 0.59 %ID/g at 30 min after injection. Significantly higher tumor uptake of [{sup 18}F]FBEM-cEGF (5.99 {+-} 1.61%ID/g at 30 min after injection, p < 0.01) and tumor/nontumor ratio were achieved by coinjection of 50 {mu}g of unlabeled EGF. Decreased liver uptake of [{sup 18}F]FBEM-cEGF was observed when unlabeled EGF was coadministered. With optimized liver blocking, [{sup 18}F]FBEM-cEGF has the potential to be used in a noninvasive and quantitative manner for detection of malignant lesions and evaluation of EGFR activity. (orig.)

  19. Hyperfractionated radiation in the treatment of squamous cell carcinomas of the head and neck: a comparison of two fractionation schedules

    Energy Technology Data Exchange (ETDEWEB)

    Garden, Adam S; Morrison, William H; Ang, K Kian; Peters, Lester J

    1995-02-01

    Purpose: In 1984 we began treating patients with squamous cell carcinomas of the larynx and hypopharynx with hyperfractionated radiotherapy. Patients received 76.8 Gy in 1.2 Gy fractions twice daily, with a 4 h interfraction interval. In 1988, this schedule was modified in patients treated with shrinking field techniques. The dose per fraction was slightly reduced (while not changing the total dose), and the interfraction interval was increased to 6 h. The goal was to decrease toxicity while maintaining satisfactory local-regional control. This retrospective study analyzes the results of this schedule modification. Methods and Materials: Two hundred thirty-six patients were included in the analysis. Distribution of patients by primary site and T stage was as follows: supraglottic larynx, 120 patients; hypopharynx, 70; true vocal cord, 24; and oropharynx, 22; T1, 5 patients; T2, 118; T3, 93; T4, 19; and Tx, 1. Ninety-nine patients presented with cervical nodal disease. Seventy-eight patients (group A), including 16 treated with induction chemotherapy, were treated throughout with 1.2 Gy fractions twice daily and a 4-h interfraction interval. Subsequently, 158 patients (group B), 57 of whom received chemotherapy, received 1.1 Gy fractions to 55 Gy, and then 1.2 Gy fractions to their boost volumes to 76.6 Gy. The interfraction interval was 6 h. Median follow-up was 91 and 35 months for group A and B, respectively. Results: Two-year actuarial survival, local control, and ultimate local rates were 70%, 75%, and 85%, respectively. Differences between survival rates for group A and group B were not statistically significant, with 2-year rates of 66% and 72%, respectively. Overall local control rates at 2 years were 77% and 74%, respectively, for groups A and B (p = 0.22). However, there was a trend toward inferior results in group B patients with T3 disease (67% at 2 years compared to 76% in group A, p = 0.13). Confluent mucositis and persistent mucositis developed in 52

  20. Genomic amplification of Fanconi anemia complementation group A (FancA) in head and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance and clinical relevance.

    Science.gov (United States)

    Hess, Julia; Unger, Kristian; Orth, Michael; Schötz, Ulrike; Schüttrumpf, Lars; Zangen, Verena; Gimenez-Aznar, Igor; Michna, Agata; Schneider, Ludmila; Stamp, Ramona; Selmansberger, Martin; Braselmann, Herbert; Hieber, Ludwig; Drexler, Guido A; Kuger, Sebastian; Klein, Diana; Jendrossek, Verena; Friedl, Anna A; Belka, Claus; Zitzelsberger, Horst; Lauber, Kirsten

    2017-02-01

    Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance. Silencing of FancA expression in HNSCC cell lines with genomic gains on 16q23-24 resulted in significantly impaired clonogenic survival upon irradiation. Conversely, overexpression of FancA in immortalized keratinocytes conferred increased survival accompanied by improved DNA repair, reduced accumulation of chromosomal translocations, but no hyperactivation of the FA/BRCA-pathway. Downregulation of interferon signaling as identified by microarray analyses, enforced irradiation-induced senescence, and elevated production of the senescence-associated secretory phenotype (SASP) appeared to be candidate mechanisms contributing to FancA-mediated radioresistance. Data of the TCGA HNSCC cohort confirmed the association of gains on 16q24.3 with FancA overexpression and impaired overall survival. Importantly, transcriptomic alterations similar to those observed upon FancA overexpression in vitro strengthened the clinical relevance. Overall, FancA amplification and overexpression appear to be crucial for radiotherapeutic failure in HNSCC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Combining standardized uptake value of FDG-PET and apparent diffusion coefficient of DW-MRI improves risk stratification in head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Preda, Lorenzo; Summers, Paul E. [European Institute of Oncology, Department of Radiology, Milan (Italy); Conte, Giorgio; Bonello, Luke; Giannitto, Caterina; Ruju, Francesca [University of Milan, Specialisation School of Radiology, Milan (Italy); Travaini, Laura L.; Grana, Chiara [European Institute of Oncology, Department of Nuclear Medicine, Milan (Italy); Raimondi, Sara [European Institute of Oncology, Department of Epidemiology and Biostatistics, Milan (Italy); Mohssen, Ansarin [European Institute of Oncology, Department of Head and Neck Surgery, Milan (Italy); Alterio, Daniela [European Institute of Oncology, Department of Radiotherapy, Milan (Italy); Cossu Rocca, Maria [European Institute of Oncology, Department of Urogenital Cancer Medical Treatment, Milan (Italy); Bellomi, Massimo [European Institute of Oncology, Department of Radiology, Milan (Italy); University of Milan, Department of Oncology and Haematology-Oncology, Milan (Italy)

    2016-12-15

    To assess the independent prognostic value of standardized uptake value (SUV) and apparent diffusion coefficient (ADC), separately and combined, in order to evaluate if the combination of these two variables allows further prognostic stratification of patients with head and neck squamous cell carcinomas (HNSCC). Pretreatment SUV and ADC were calculated in 57 patients with HNSCC. Mean follow-up was 21.3 months. Semiquantitative analysis of primary tumours was performed using SUV{sub maxT/B}, ADC{sub mean}, ADC{sub min} and ADC{sub max}. The prognostic value of SUV{sub maxT/B}, ADC{sub mean}, ADC{sub min} and ADC{sub max} in predicting disease-free survival (DFS) was evaluated with log-rank test and Cox regression models. Patients with SUV{sub maxT/B} ≥5.75 had an overall worse prognosis (p = 0.003). After adjusting for lymph node status and diameter, SUV{sub maxT/B} and ADC{sub min} were both significant predictors of DFS with hazard ratio (HR) = 10.37 (95 % CI 1.22-87.95) and 3.26 (95 % CI 1.20-8.85) for SUV{sub maxT/B} ≥5.75 and ADC{sub min} ≥0.58 x 10{sup -3} mm{sup 2}/s, respectively. When the analysis was restricted to subjects with SUV{sub maxT/B} ≥5.75, high ADC{sub min} significantly predicted a worse prognosis, with adjusted HR = 3.11 (95 % CI 1.13-8.55). The combination of SUV{sub maxT/B} and ADC{sub min} improves the prognostic role of the two separate parameters; patients with high SUV{sub maxT/B} and high ADC{sub min} are associated with a poor prognosis. (orig.)

  2. Association of drug transporter expression with mortality and progression-free survival in stage IV head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Rolf Warta

    Full Text Available Drug transporters such as P-glycoprotein (ABCB1 have been associated with chemotherapy resistance and are considered unfavorable prognostic factors for survival of cancer patients. Analyzing mRNA expression levels of a subset of drug transporters by quantitative reverse transcription polymerase chain reaction (qRT-PCR or protein expression by tissue microarray (TMA in tumor samples of therapy naïve stage IV head and neck squamous cell carcinoma (HNSCC (qRT-PCR, n = 40; TMA, n = 61, this in situ study re-examined the significance of transporter expression for progression-free survival (PFS and overall survival (OS. Data from The Cancer Genome Atlas database was used to externally validate the respective findings (n = 317. In general, HNSCC tended to lower expression of drug transporters compared to normal epithelium. High ABCB1 mRNA tumor expression was associated with both favorable progression-free survival (PFS, p = 0.0357 and overall survival (OS, p = 0.0535. Similar results were obtained for the mRNA of ABCC1 (MRP1, multidrug resistance-associated protein 1; PFS, p = 0.0183; OS, p = 0.038. In contrast, protein expression of ATP7b (copper transporter ATP7b, mRNA expression of ABCG2 (BCRP, breast cancer resistance protein, ABCC2 (MRP2, and SLC31A1 (hCTR1, human copper transporter 1 did not correlate with survival. Cluster analysis however revealed that simultaneous high expression of SLC31A1, ABCC2, and ABCG2 indicates poor survival of HNSCC patients. In conclusion, this study militates against the intuitive dogma where high expression of drug efflux transporters indicates poor survival, but demonstrates that expression of single drug transporters might indicate even improved survival. Prospectively, combined analysis of the 'transportome' should rather be performed as it likely unravels meaningful data on the impact of drug transporters on survival of patients with HNSCC.

  3. Local recurrence of squamous cell carcinoma of the head and neck after radio(chemo)therapy. Diagnostic performance of FDG-PET/MRI with diffusion-weighted sequences

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Minerva; Varoquaux, Arthur D.; Rager, Olivier; Delattre, Benedicte M.A.; Katirtzidou, Eirini; Ratib, Osman; Zaidi, Habib; Becker, Christoph D. [Geneva University Hospitals (Switzerland). Div. of Radiology and Nuclear Medicine; Combescure, Christophe [Geneva University Hospitals (Switzerland). Centre for Clinical Research; Pusztaszeri, Marc; Burkhardt, Karim [Geneva University Hospitals (Switzerland). Div. of Clinical Pathology; Dulguerov, Pavel; Dulguerov, Nicolas [Geneva University Hospitals (Switzerland). Clinic of Otorhinolaryngology Head and Neck Surgery; Caparrotti, Francesca [Geneva University Hospitals (Switzerland). Div. of Radiation Oncology

    2018-02-15

    To determine the diagnostic performance of FDG-PET/MRI with diffusion-weighted imaging (FDG-PET/DWIMRI) for detection and local staging of head and neck squamous cell carcinoma (HNSCC) after radio(chemo)therapy. This was a prospective study that included 74 consecutive patients with previous radio(chemo)therapy for HNSCC and in whom tumour recurrence or radiation-induced complications were suspected clinically. The patients underwent hybrid PET/MRI examinations with morphological MRI, DWI and FDG-PET. Experienced readers blinded to clinical/histopathological data evaluated images according to established diagnostic criteria taking into account the complementarity of multiparametric information. The standard of reference was histopathology with whole-organ sections and follow-up ≥24 months. Statistical analysis considered data clustering. The proof of diagnosis was histology in 46/74 (62.2%) patients and follow-up (mean ± SD = 34 ± 8 months) in 28/74 (37.8%). Thirty-eight patients had 43 HNSCCs and 46 patients (10 with and 36 without tumours) had 62 benign lesions/complications. Sensitivity, specificity, and positive and negative predictive value of PET/DWIMRI were 97.4%, 91.7%, 92.5% and 97.1% per patient, and 93.0%, 93.5%, 90.9%, and 95.1% per lesion, respectively. Agreement between imaging-based and pathological T-stage was excellent (kappa = 0.84, p < 0.001). FDG-PET/DWIMRI yields excellent results for detection and T-classification of HNSCC after radio(chemo)therapy. (orig.)

  4. Efficacy and Safety of Subcutaneous Amifostine in Minimizing Radiation-Induced Toxicities in Patients Receiving Combined-Modality Treatment for Squamous Cell Carcinoma of the Head and Neck

    International Nuclear Information System (INIS)

    Law, Amy; Kennedy, Thomas; Pellitteri, Phillip; Wood, Craig; Christie, Douglas; Yumen, Omar

    2007-01-01

    Purpose: To report long-term data from a prospective trial of subcutaneous (s.c.) amifostine in patients who received chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Methods and Materials: Patients ≥18 years of age with previously untreated Stage III/IV SCCHN received fractionated radiotherapy, 1.8-2.0 Gy/day, 5 days per week, to a total dose of 70-72 Gy, plus weekly paclitaxel (40 mg/m 2 ) and carboplatin (100 mg/m 2 ) administered intravenously (i.v.) for 6 weeks. All patients received 500 mg s.c. amifostine 30-60 min before radiotherapy with antihistamine and antiemetic prophylaxis. Results: Twenty patients were evaluable (median age, 55 years). The incidence of Grade 2 xerostomia was 42% and 29% at 12 and 18 months, respectively; there were no reports of Grade ≥3 xerostomia. Grade ≥3 mucositis occurred in 30% of patients, with median time to resolution of 12.5 weeks (range, 5-17 weeks). Survival estimates at 1 and 2 years were 95% and 71%, respectively. All patients experienced Grade 2 weight loss; 7 patients (35%) experienced Grade ≤2 nausea/vomiting. There were no reports of Grade ≥3 amifostine-related adverse events. Conclusions: Subcutaneous amifostine was well tolerated by patients receiving chemoradiotherapy for SCCHN, with lower rates of nausea/vomiting than reported in trials with i.v. amifostine. Xerostomia and mucositis rates were similar to those reported in trials with i.v. amifostine

  5. Feasibility study of single agent cisplatin and concurrent radiotherapy in Japanese patients with squamous cell carcinoma of the head and neck. Preliminary results

    International Nuclear Information System (INIS)

    Zenda, Sadamoto; Tahara, Makoto; Kawashima, Mitsuhiko; Onozawa, Yusuke; Boku, Narikazu; Shikama, Naoto; Sasaki, Shigeru

    2007-01-01

    Concurrent chemoradiotherapy with the single agent cisplatin (CDDP+RT) has been recognized worldwide as the standard treatment for unresectable locally advanced SCCHN. The objective of this study was to clarify the feasibility of CDDP+RT in Japanese patients. Patients with unresectable squamous cell carcinoma of the head and neck were given single daily fractionated radiation (70 Gy at 2 Gy/day) and chemotherapy consisting of a 2 h infusion of CDDP 100 mg/m 2 on days 1, 22 and 43. The primary endpoint was the rate of completion of CDDP+RT. Between November 2005 and January 2007, 20 patients were enrolled, 19 males and one female with a median age of 61.5 years (range 50-74). One patient had recurrent unresectable disease after surgery and the remaining 19 had stage IV disease. No grade 4 hematologic toxicities were observed. The incidence of grade 3 mucositis was 55% and no treatment-related death occurred. Full-dose irradiation was performed in all patients, with a median duration of radiotherapy of 50 days (range 48-54). Although all patients received the first two administrations of CDDP, the third dose was administed in 17 patients (85%). The rate of completion of CDDP+RT was 85% and the dose intensity of CDDP was 28.9 mg/m 2 /week (relative dose intensity 89%). Overall complete response rate was 50% and the rate of primary complete response was 90%. Concurrent chemoradiation therapy with the standard dose of CDDP is feasible in Japanese patients. Treatment modification based on racial differences is not necessary. (author)

  6. Evaluation and analysis of superselective intra-arterial chemotherapy for patients with head and neck squamous cell carcinoma and its complications

    Energy Technology Data Exchange (ETDEWEB)

    Shiga, Kiyoto; Tateda, Masaru; Saijo, Shigeru [Miyagi Cancer Center Hospital, Natori (Japan); Yokoyama, Junkichi

    2001-03-01

    Superselective intra-arterial (IA) chemotherapy was administered 213 times to 76 patients, from April 1995 to August 1999, in our hospital. These included 64 patients with head and neck squamous cell carcinoma, and 5 cases out of these 64 cases dropped out because of severe complications when their survival was evaluated. The five-year overall survival rate, calculated by the Kaplan-Meier method, was 49% for all patients, 78% for the patients who underwent surgery before or after IA chemotherapy (20 cases), and 48% for the patients who were treated by IA chemotherapy in combination with radiation therapy (26 cases). No renal failure was observed in these patients. The five-year overall survival rate was 53% for the patients with stage III or stage IV disease who were treated by surgery alone or surgery and radiation therapy (+chemotherapy), while it was 45% for the patients with stage III or stage IV disease who were treated by IA chemotherapy and radiation therapy. Since this study was not randomized and more advanced cases tended to be treated by IA chemotherapy, this result was assumed to be good enough to improve the prognosis of the patients with advanced disease. The prognosis of the patients treated by IA chemotherapy and radiation therapy who had recurrence, or who were cases of secondary treatment, was poor and similar to that of the patients who received palliative radiation therapy (+chemotherapy). Drop-out cases of IA chemotherapy encountered severe complications, such as 2 cerebral infarctions, one sudden death, one pneumonia with DIC, and one ARDS. There was also a sudden death, and deaths due to bleeding from local recurrent lesions after the treatment was finished. As some patients complained of dysphagia and/or dyspnea after IA chemotherapy and radiation therapy, the QOL of the patients was not very satisfactory. It is suggested that the indication of IA chemotherapy should be limited, considering the patient's condition and the location of

  7. Evaluation and analysis of superselective intra-arterial chemotherapy for patients with head and neck squamous cell carcinoma and its complications

    International Nuclear Information System (INIS)

    Shiga, Kiyoto; Tateda, Masaru; Saijo, Shigeru; Yokoyama, Junkichi

    2001-01-01

    Superselective intra-arterial (IA) chemotherapy was administered 213 times to 76 patients, from April 1995 to August 1999, in our hospital. These included 64 patients with head and neck squamous cell carcinoma, and 5 cases out of these 64 cases dropped out because of severe complications when their survival was evaluated. The five-year overall survival rate, calculated by the Kaplan-Meier method, was 49% for all patients, 78% for the patients who underwent surgery before or after IA chemotherapy (20 cases), and 48% for the patients who were treated by IA chemotherapy in combination with radiation therapy (26 cases). No renal failure was observed in these patients. The five-year overall survival rate was 53% for the patients with stage III or stage IV disease who were treated by surgery alone or surgery and radiation therapy (+chemotherapy), while it was 45% for the patients with stage III or stage IV disease who were treated by IA chemotherapy and radiation therapy. Since this study was not randomized and more advanced cases tended to be treated by IA chemotherapy, this result was assumed to be good enough to improve the prognosis of the patients with advanced disease. The prognosis of the patients treated by IA chemotherapy and radiation therapy who had recurrence, or who were cases of secondary treatment, was poor and similar to that of the patients who received palliative radiation therapy (+chemotherapy). Drop-out cases of IA chemotherapy encountered severe complications, such as 2 cerebral infarctions, one sudden death, one pneumonia with DIC, and one ARDS. There was also a sudden death, and deaths due to bleeding from local recurrent lesions after the treatment was finished. As some patients complained of dysphagia and/or dyspnea after IA chemotherapy and radiation therapy, the QOL of the patients was not very satisfactory. It is suggested that the indication of IA chemotherapy should be limited, considering the patient's condition and the location of the

  8. Integrative miRNA-Gene Expression Analysis Enables Refinement of Associated Biology and Prediction of Response to Cetuximab in Head and Neck Squamous Cell Cancer

    Directory of Open Access Journals (Sweden)

    Loris De Cecco

    2017-01-01

    Full Text Available This paper documents the process by which we, through gene and miRNA expression profiling of the same samples of head and neck squamous cell carcinomas (HNSCC and an integrative miRNA-mRNA expression analysis, were able to identify candidate biomarkers of progression-free survival (PFS in patients treated with cetuximab-based approaches. Through sparse partial least square–discriminant analysis (sPLS-DA and supervised analysis, 36 miRNAs were identified in two components that clearly separated long- and short-PFS patients. Gene set enrichment analysis identified a significant correlation between the miRNA first-component and EGFR signaling, keratinocyte differentiation, and p53. Another significant correlation was identified between the second component and RAS, NOTCH, immune/inflammatory response, epithelial–mesenchymal transition (EMT, and angiogenesis pathways. Regularized canonical correlation analysis of sPLS-DA miRNA and gene data combined with the MAGIA2 web-tool highlighted 16 miRNAs and 84 genes that were interconnected in a total of 245 interactions. After feature selection by a smoothed t-statistic support vector machine, we identified three miRNAs and five genes in the miRNA-gene network whose expression result was the most relevant in predicting PFS (Area Under the Curve, AUC = 0.992. Overall, using a well-defined clinical setting and up-to-date bioinformatics tools, we are able to give the proof of principle that an integrative miRNA-mRNA expression could greatly contribute to the refinement of the biology behind a predictive model.

  9. Outcomes of patients with loco-regionally recurrent or new primary squamous cell carcinomas of the head and neck treated with curative intent reirradiation at Mayo Clinic

    International Nuclear Information System (INIS)

    Curtis, Kelly K.; Ross, Helen J.; Garrett, Ashley L.; Jizba, Theresa A.; Patel, Ajay B.; Patel, Samir H.; Wong, William W.; Halyard, Michele Y.; Ko, Stephen J.; Kosiorek, Heidi E.; Foote, Robert L.

    2016-01-01

    We reviewed outcomes of patients with loco-regionally recurrent (LRR) or new primary (NP) squamous cell carcinoma of the head and neck (SCCHN) treated at our institution with reirradiation (RRT). Patients received definitive RRT (DRRT) or post-operative RRT following salvage surgery (PRRT) from 2003 to 2011. Measured survival outcomes included loco-regional relapse free survival (LRFS) and overall survival (OS). Among 81 patients (PRRT, 42; DRRT, 39), median PRRT and DRRT doses were 60 Gy (12–70 Gy) and 69.6 Gy (48–76.8 Gy). The majority of patients received IMRT-based RRT (n = 77, 95 %). With median follow-up of 78.1 months (95 % CI, 56–96.8 months), 2-year OS was 53 % with PRRT and 48 % with DRRT (p = 0.12); 23 % of patients were alive at last follow-up. LRFS at 2 years was 60 %, and did not differ significantly between PRRT and DRRT groups. A trend toward inferior LRFS was noted among patients receiving chemotherapy with RRT versus RRT alone (p = 0.06). Late serious toxicities were uncommon, including osteoradionecrosis (2 patients) and carotid artery bleeding (1 patient, non-fatal). OS of PRRT- and DRRT-treated patients in this series appears superior to the published literature. We used IMRT for the majority of patients, in contrast to several series and trials previously reported, which may account in part for this difference. Future studies should seek to improve outcomes among patients with LRR/NP SCCHN via alternative therapeutic modalities such as proton radiotherapy and by incorporating novel systemic agents

  10. Dynamic contrast-enhanced computed tomography to assess early activity of cetuximab in squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Schmitz, Sandra; Rommel, Denis; Michoux, Nicolas; Lhommel, Renaud; Hanin, François-Xavier; Duprez, Thierry; Machiels, Jean-Pascal

    2015-01-01

    Cetuximab, a monoclonal antibody targeting the Epidermal Growth Factor Receptor (EGFR), has demonstrated activity in various tumor types. Using dynamic contrast-enhanced computed tomography (DCE-CT), we investigated the early activity of cetuximab monotherapy in previously untreated patients with squamous cell carcinoma of the head and neck (SCCHN). Treatment-naïve patients with SCCHN received cetuximab for 2 weeks before curative surgery. Treatment activity was evaluated by DCE-CT at baseline and before surgery. Tumor vascular and interstitial characteristics were evaluated using the Brix two-compartment kinetic model. Modifications of the perfusion parameters (blood flow F p , extravascular space v e , vascular space v p , and transfer constant PS) were assessed between both time points. DCE data were compared to FDG-PET and histopathological examination obtained simultaneously. Plasmatic vascular markers were investigated at different time points. Fourteen patients had evaluable DCE-CT parameters at both time points. A significant increase in the extravascular extracellular space v e accessible to the tracer was observed but no significant differences were found for the other kinetic parameters (F p , v p or PS). Significant correlations were found between DCE parameters and the other two modalities. Plasmatic VEGF, PDGF-BB and IL-8 decreased as early as 2 hours after cetuximab infusion. Early activity of cetuximab on tumor interstitial characteristics was detected by DCE-CT. Modifications of plasmatic vascular markers are not sufficient to confirm anti-angiogenic cetuximab activity in vivo. Further investigation is warranted to determine to what extent DCE-CT parameters are modified and to evaluate whether they are able to predict treatment outcome

  11. {sup 18}F-FDG PET/CT quantification in head and neck squamous cell cancer: principles, technical issues and clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Manca, Gianpiero; Volterrani, Duccio [University Hospital of Pisa, Regional Center of Nuclear Medicine, Pisa (Italy); Vanzi, Eleonora [University Hospital of Siena, Service of Medical Physics, Siena (Italy); Rubello, Domenico; Grassetto, Gaia [Santa Maria della Misericordia Rovigo Hospital, Department of Nuclear Medicine, Rovigo (Italy); Giammarile, Francesco [Faculte Charles Merieux, Medecine Nucleaire, Centre Hospitalier and Biophysique, Lyon (France); Wong, Ka Kit [University of Michigan Hospital, Nuclear Medicine/Radiology Department, Ann Arbor, MI (United States); Nuclear Medicine Service, Department of Veterans Affairs Health System, Ann Arbor, MI (United States); Perkins, Alan C. [University of Nottingham, Department of Radiological Sciences, School of Medicine, Nottingham (United Kingdom); Colletti, Patrick M. [Southern University of California, Department of Radiology, Los Angeles, CA (United States)

    2016-07-15

    {sup 18}F-FDG PET/CT plays a crucial role in the diagnosis and management of patients with head and neck squamous cell cancer (HNSCC). The major clinical applications of this method include diagnosing an unknown primary tumour, identifying regional lymph node involvement and distant metastases, and providing prognostic information. {sup 18}F-FDG PET/CT is also used for precise delineation of the tumour volume for radiation therapy planning and dose painting, and for treatment response monitoring, by detecting residual or recurrent disease. Most of these applications would benefit from a quantitative approach to the disease, but the quantitative capability of {sup 18}F-FDG PET/CT is still underused in HNSCC. Innovations in PET/CT technology promise to overcome the issues that until now have hindered the employment of dynamic procedures in clinical practice and have limited ''quantification'' to the evaluation of standardized uptake values (SUV), de facto a semiquantitative parameter, the limits of which are well known to the nuclear medicine community. In this paper the principles of quantitative imaging and the related technical issues are reviewed so that professionals involved in HNSCC management can reflect on the advantages of ''true'' quantification. A discussion is then presented on how semiquantitative information is currently used in clinical {sup 18}F-FDG PET/CT applications in HNSCC, by discussing the improvements that could be obtained with more advanced and ''personalized'' quantification techniques. (orig.)

  12. Patterns of Recurrence in Electively Irradiated Lymph Node Regions After Definitive Accelerated Intensity Modulated Radiation Therapy for Head and Neck Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bosch, Sven van den, E-mail: sven.vandenbosch@radboudumc.nl; Dijkema, Tim; Verhoef, Lia C.G.; Zwijnenburg, Ellen M.; Janssens, Geert O.; Kaanders, Johannes H.A.M.

    2016-03-15

    Purpose: To provide a comprehensive risk assessment on the patterns of recurrence in electively irradiated lymph node regions after definitive radiation therapy for head and neck cancer. Methods and Materials: Two hundred sixty-four patients with stage cT2-4N0-2M0 squamous cell carcinoma of the oropharynx, larynx, or hypopharynx treated with accelerated intensity modulated radiation therapy between 2008 and 2012 were included. On the radiation therapy planning computed tomography (CT) scans from all patients, 1166 lymph nodes (short-axis diameter ≥5 mm) localized in the elective volume were identified and delineated. The exact sites of regional recurrences were reconstructed and projected on the initial radiation therapy planning CT scan by performing coregistration with diagnostic imaging of the recurrence. Results: The actuarial rate of recurrence in electively irradiated lymph node regions at 2 years was 5.1% (95% confidence interval 2.4%-7.8%). Volumetric analysis showed an increased risk of recurrence with increasing nodal volume. Receiver operating characteristic analysis demonstrated that the summed long- and short-axis diameter is a good alternative for laborious volume calculations, using ≥17 mm as cut-off (hazard ratio 17.8; 95% confidence interval 5.7-55.1; P<.001). Conclusions: An important risk factor was identified that can help clinicians in the pretreatment risk assessment of borderline-sized lymph nodes. Not overtly pathologic nodes with a summed diameter ≥17 mm may require a higher than elective radiation therapy dose. For low-risk elective regions (all nodes <17 mm), the safety of dose de-escalation below the traditional 45 to 50 Gy should be investigated.

  13. Postoperative Concurrent Chemoradiotherapy Versus Postoperative Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck: The Randomized Phase III TROG 05.01 Trial.

    Science.gov (United States)

    Porceddu, Sandro Virgilio; Bressel, Mathias; Poulsen, Michael Geoffrey; Stoneley, Adam; Veness, Michael John; Kenny, Lizbeth Moira; Wratten, Chris; Corry, June; Cooper, Stephen; Fogarty, Gerald Blaise; Collins, Marnie; Collins, Michael Kevin; Macann, Andrew Martin John; Milross, Christopher Gerard; Penniment, Michael Gordon; Liu, Howard Yu-Hao; King, Madeleine Trudy; Panizza, Benedict James; Rischin, Danny

    2018-05-01

    Purpose To report the results of the Trans Tasman Radiation Oncology Group randomized phase III trial designed to determine whether the addition of concurrent chemotherapy to postoperative radiotherapy (CRT) improved locoregional control in patients with high-risk cutaneous squamous cell carcinoma of the head and neck. Patients and Methods The primary objective was to determine whether there was a difference in freedom from locoregional relapse (FFLRR) between 60 or 66 Gy (6 to 6.5 weeks) with or without weekly carboplatin (area under the curve 2) after resection of gross disease. Secondary efficacy objectives were to compare disease-free survival and overall survival. Results Three hundred twenty-one patients were randomly assigned, with 310 patients commencing allocated treatment (radiotherapy [RT] alone, n = 157; CRT, n = 153). Two hundred thirty-eight patients (77%) had high-risk nodal disease, 59 (19%) had high-risk primary or in-transit disease, and 13 (4%) had both. Median follow-up was 60 months. Median RT dose was 60 Gy, with 84% of patients randomly assigned to CRT completing six cycles of carboplatin. The 2- and 5-year FFLRR rates were 88% (95% CI, 83% to 93%) and 83% (95% CI, 77% to 90%), respectively, for RT and 89% (95% CI, 84% to 94%) and 87% (95% CI, 81% to 93%; hazard ratio, 0.84; 95% CI, 0.46 to 1.55; P = .58), respectively, for CRT. There were no significant differences in disease-free or overall survival. Locoregional failure was the most common site of first treatment failure, with isolated distant metastases as the first site of failure seen in 7% of both arms. Treatment was well tolerated in both arms, with no observed enhancement of RT toxicity with carboplatin. Grade 3 or 4 late toxicities were infrequent. Conclusion Although surgery and postoperative RT provided excellent FFLRR, there was no observed benefit with the addition of weekly carboplatin.

  14. Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the head and neck: a randomized Phase III study

    International Nuclear Information System (INIS)

    Lewin, Freddi; Damber, Lena; Jonsson, Haakan; Andersson, Torsten; Berthelsen, Anne; Bioerklund, Anders; Blomqvist, Erik; Evensen, Jan F.; Hansen, Hanne S.; Hansen, Olfred; Jetlund, Olav; Mercke, Claes; Modig, Hans; Overgaard, Marie; Rosengren, Bengt; Tausjoe, Johan; Ringborg, Ulrik

    1997-01-01

    Background and purpose: In 1986 a prospective, randomized, multi-centre trial for evaluation of neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in the treatment of advanced squamous cell carcinoma of the head and neck was initiated. As survival in this group of patients is poor the purpose was to find a possible survival benefit of the chemotherapy in addition to radiotherapy compared to radiotherapy only. Methods. Four-hundred sixty-one patients from Denmark, Norway and Sweden with tumors in oral cavity, oropharynx, hypopharynx and larynx were randomized to receive either standard treatment (radiotherapy or radiotherapy followed by surgery) or neoadjuvant chemotherapy followed by standard treatment. Chemotherapy included three courses of cisplatin 100 mg/m 2 i.v. infusion on day 1 followed by 5-fluorouracil 1000 mg/m 2 per day continuous i.v. infusion for 120 hours. Radiotherapy 64-70 Gy in 2 Gy per fraction, 5 times/week, was given to patients in both treatment arms. Results: Response rate was 71% for patients randomized to chemotherapy-radiotherapy and 66% for patients randomized to standard treatment (not statistically significant). Residual tumors were excised if possible. After surgery 62% of the patients randomized to chemotherapy-radiotherapy and 60% of the patients in the standard treatment group were clinically tumor free. Conclusions: No statistically significant benefit in survival was observed for patients treated with neoadjuvant chemotherapy followed by radiotherapy. Nor was there any impact of chemotherapy on the number of patients achieving loco-regional tumor control after primary treatment

  15. Reirradiation With Cetuximab in Locoregional Recurrent and Inoperable Squamous Cell Carcinoma of the Head and Neck: Feasibility and First Efficacy Results

    Energy Technology Data Exchange (ETDEWEB)

    Balermpas, Panagiotis; Keller, Christian [Department of Radiation Therapy and Oncology, Goethe University, Frankfurt am Main (Germany); Hambek, Markus; Wagenblast, Jens [Department of Otorhinolaryngology, Goethe University, Frankfurt am Main (Germany); Seitz, Oliver [Department of Oral Maxillofacial and Plastic Facial Surgery, Goethe University, Frankfurt am Main (Germany); Roedel, Claus [Department of Radiation Therapy and Oncology, Goethe University, Frankfurt am Main (Germany); Weiss, Christian, E-mail: christian.weiss@kgu.de [Department of Radiation Therapy and Oncology, Goethe University, Frankfurt am Main (Germany)

    2012-07-01

    Purpose: To report our experience with a prospective protocol of external beam reirradiation (Re-RT) combined with cetuximab for patients with inoperable, recurrent squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: Between August 2008 and June 2010, 18 patients with inoperable recurrence of SCCHN after adjuvant or definitive radiotherapy (RT) and simultaneous or sequential cisplatin-based chemotherapy for primary SCCHN were enrolled. Acute and late toxicity from the experimental regimen were recorded every week during RT and every 3 months thereafter. Efficacy was assessed with repeated imaging using response evaluation criteria in solid tumors and clinical examinations 8-12 weeks after completion of the treatment and every 3 months thereafter. Results: Median follow-up time for all patients was 9.4 (range: 3.85-31.7) months and for patients alive 30.4 (range: 15.7-31.7) months. Acute toxicity was generally mild or moderate. Five patients developed a grade 3 acneiform rash related to cetuximab. Late toxicity occurred as grade 3 trismus in five and as grade 3 abacterial salivary gland inflammation in one patient, respectively. Overall response rate was 47%. Median overall and progression-free survival for all patients was 8.38 months and 7.33 months, respectively. The overall survival rate was 44% at 1 year, with a 1 year local control rate of 33%. Conclusion: Notwithstanding the limitations of our preliminary data Re-RT combined with cetuximab for recurrent and inoperable SCCHN is feasible and the integration of newer targeted agents seems to be less toxic compared to conventional chemotherapy with encouraging response rates at least for a subset of patients.

  16. Diffusion-Weighted Magnetic Resonance Imaging Early After Chemoradiotherapy to Monitor Treatment Response in Head-and-Neck Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Vandecaveye, Vincent, E-mail: Vincent.Vandecaveye@uzleuven.be [Department of Radiology, University Hospitals Leuven (Belgium); Dirix, Piet [Department of Radiation Oncology, Leuven Cancer Institute, University Hospitals Leuven (Belgium); De Keyzer, Frederik; Op de Beeck, Katya [Department of Radiology, University Hospitals Leuven (Belgium); Vander Poorten, Vincent [Department of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven (Belgium); Hauben, Esther [Department of Pathology, University Hospitals Leuven (Belgium); Lambrecht, Maarten; Nuyts, Sandra [Department of Radiation Oncology, Leuven Cancer Institute, University Hospitals Leuven (Belgium); Hermans, Robert [Department of Radiology, University Hospitals Leuven (Belgium)

    2012-03-01

    Purpose: To evaluate diffusion-weighted imaging (DWI) for assessment of treatment response in head and neck squamous cell carcinoma (HNSCC) three weeks after the end of chemoradiotherapy (CRT). Methods and Materials: Twenty-nine patients with HNSCC underwent magnetic resonance imaging (MRI) prior to and 3 weeks after CRT, including T{sub 2}-weighted and pre- and postcontrast T{sub 1}-weighted sequences and an echo-planar DWI sequence with six b values (0 to 1,000 s/mm{sup 2}), from which the apparent diffusion coefficient (ADC) was calculated. ADC changes 3 weeks posttreatment compared to baseline ( Increment ADC) between responding and nonresponding primary lesions and adenopathies were correlated with 2 years locoregional control and compared with a Mann-Whitney test. In a blinded manner, the Increment ADC was compared to conventional MRI 3 weeks post-CRT and the routinely implemented CT, on average 3 months post-CRT, which used size-related and morphological criteria. Positive and negative predictive values (PPV and NPV, respectively) were compared between the Increment ADC and anatomical imaging. Results: The Increment ADC of lesions with later tumor recurrence was significantly lower than lesions with complete remission for both primary lesions (-2.3% {+-} 0.3% vs. 80% {+-} 41%; p < 0.0001) and adenopathies (19.9% {+-} 32% vs. 63% {+-} 36%; p = 0.003). The Increment ADC showed a PPV of 89% and an NPV of 100% for primary lesions and a PPV of 70% and an NPV of 96% for adenopathies per neck side. DWI improved PPV and NPV compared to anatomical imaging. Conclusion: DWI with the Increment ADC 3 weeks after concluding CRT for HNSCC allows for early assessment of treatment response.

  17. Local recurrence of squamous cell carcinoma of the head and neck after radio(chemo)therapy: Diagnostic performance of FDG-PET/MRI with diffusion-weighted sequences.

    Science.gov (United States)

    Becker, Minerva; Varoquaux, Arthur D; Combescure, Christophe; Rager, Olivier; Pusztaszeri, Marc; Burkhardt, Karim; Delattre, Bénédicte M A; Dulguerov, Pavel; Dulguerov, Nicolas; Katirtzidou, Eirini; Caparrotti, Francesca; Ratib, Osman; Zaidi, Habib; Becker, Christoph D

    2018-02-01

    To determine the diagnostic performance of FDG-PET/MRI with diffusion-weighted imaging (FDG-PET/DWIMRI) for detection and local staging of head and neck squamous cell carcinoma (HNSCC) after radio(chemo)therapy. This was a prospective study that included 74 consecutive patients with previous radio(chemo)therapy for HNSCC and in whom tumour recurrence or radiation-induced complications were suspected clinically. The patients underwent hybrid PET/MRI examinations with morphological MRI, DWI and FDG-PET. Experienced readers blinded to clinical/histopathological data evaluated images according to established diagnostic criteria taking into account the complementarity of multiparametric information. The standard of reference was histopathology with whole-organ sections and follow-up ≥24 months. Statistical analysis considered data clustering. The proof of diagnosis was histology in 46/74 (62.2%) patients and follow-up (mean ± SD = 34 ± 8 months) in 28/74 (37.8%). Thirty-eight patients had 43 HNSCCs and 46 patients (10 with and 36 without tumours) had 62 benign lesions/complications. Sensitivity, specificity, and positive and negative predictive value of PET/DWIMRI were 97.4%, 91.7%, 92.5% and 97.1% per patient, and 93.0%, 93.5%, 90.9%, and 95.1% per lesion, respectively. Agreement between imaging-based and pathological T-stage was excellent (kappa = 0.84, p recurrence. • Prospective one-centre study showed excellent agreement between imaging-based and pathological T-stage. • 97.5% of positive concordant MRI, DWI and FDG-PET results correspond to recurrence. • 87% of discordant MRI, DWI and FDG-PET results correspond to benign lesions. • Multiparametric FDG-PET/DWIMRI facilitates planning of salvage surgery in the irradiated neck.

  18. Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a retrospective study in a single comprehensive European cancer institution.

    Directory of Open Access Journals (Sweden)

    Ramon Andrade de Mello

    Full Text Available BACKGROUND: The use of cetuximab in combination with platinum (P plus 5-fluorouracil (F has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN. We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS, progression-free-survival (PFS, overall response rate (ORR and the treatment toxicity profile in a retrospective cohort. PATIENTS AND METHODS: This study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first. RESULTS: The median patient age was 53 (37-78 years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684-13.316 and PFS of 8 months (CI 95%, 6.051-9.949. The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%, skin rash (3.8% and mucosistis (3.8%. CONCLUSIONS: The results of this study suggest that cetuximab plus platinum-fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.

  19. Association of cytochrome P450 2C9 polymorphism with locally advanced head and neck squamous cell carcinoma and response to concurrent cisplatin-based radical chemoradiation

    Directory of Open Access Journals (Sweden)

    Sayan Paul

    2014-01-01

    Full Text Available Aims: The aim of the present study is to investigate the association between polymorphism of cytochrome P450 2C9 (CYP2C9 enzyme with head and neck squamous cell carcinoma (HNSCC and response in patients receiving cisplatin-based radical chemoradiation (CT-RT. Materials and Methods: Four hundred and sixty patients suffering from locally advanced HNSCC and an equal number of healthy controls were genotyped for CYP2C9FNx012 and CYP2C9FNx013, leading to poor metabolizers (PMs by polymerase chain reaction (PCR-based restriction fragment length polymorphism (RFLP. Each case was assessed thoroughly for treatment response as per the World Health Organization (WHO criteria. Results and Analysis: The frequency of heterozygous genotypes of both CYP2C9FNx012 (27.8% and CYP2C9FNx013 (25% were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several folds increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9FNx012 or CYP2C9FNx013. Further, majority of the cases assessed for response (n = 436 carrying variant alleles of CYP2C9FNx012 (69.6% or CYP2C9FNx013 (65.2% were found to respond poorly to cisplatin-based radical CT-RT. Conclusion: The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment protocol.

  20. Nuclear NF-κB Expression Correlates With Outcome Among Patients With Head and Neck Squamous Cell Carcinoma Treated With Primary Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Balermpas, Panagiotis [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Michel, Yvonne [Senckenberg Institute of Pathology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Wagenblast, Jens [Department of Otorhinolaryngology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Seitz, Oliver [Department of Maxillofacial Surgery, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Sipek, Florian; Rödel, Franz; Rödel, Claus [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany)

    2013-07-15

    Background: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Methods and Materials: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. Results: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. Conclusion: NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.

  1. Association between novel PLCE1 variants identified in published esophageal cancer genome-wide association studies and risk of squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Ma, Hongxia; Wang, Li-E; Liu, Zhensheng; Sturgis, Erich M; Wei, Qingyi

    2011-01-01

    Phospholipase C epsilon 1 (PLCE1) (an effector of Ras) belonging to the phospholipase family plays crucial roles in carcinogenesis and progression of several cancers, including squamous cell carcinoma of the head and neck (SCCHN). A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus in genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) that share similar risk factors with SCCHN. Therefore, we investigated the association between potentially functional SNPs in PLCE1 and susceptibility to SCCHN. We genotyped three potentially functional SNPs (rs2274223A/G, rs3203713A/G and rs11599672T/G) of PLCE1 in 1,098 SCCHN patients and 1,090 controls matched by age and sex in a non-Hispanic white population. Although none of three SNPs was alone significantly associated with overall risk of SCCHN, their combined effects of risk alleles (rs2274223G, rs3203713G and rs11599672G) were found to be associated with risk of SCCHN in a locus-dose effect manner (P trend = 0.046), particularly for non-oropharyngeal tumors (P trend = 0.017); specifically, rs2274223 was associated with a significantly increased risk (AG vs. AA: adjusted OR = 1.29, 95% CI = 1.01-1.64; AG/GG vs. AA: adjusted OR = 1.30, 95% CI = 1.03-1.64), while rs11599672 was associated with a significantly decreased risk (GG vs. TT: adjusted OR = 0.54, 95% CI = 0.34-0.86; TG/GG vs. TT: adjusted OR = 0.76, 95% CI = 0.61-0.95). Our findings suggest that PLCE1 variants may have an effect on risk of SCCHN associated with tobacco and alcohol exposure, particularly for those tumors arising at non-oropharyngeal sites. These findings, although need to be validated by larger studies, are consistent with those in esophageal and gastric cancers

  2. Cisplatin, Intensity-Modulated Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    2018-05-18

    CDKN2A-p16 Negative; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  3. Scheduling cisplatin and radiotherapy in the treatment of squamous cell carcinomas of the head and neck: a modelling approach

    International Nuclear Information System (INIS)

    Marcu, L; Bezak, E; Olver, I

    2006-01-01

    The aim of the present work was to implement the kinetics of cisplatin into a previously developed tumour growth model and to simulate the combined cisplatin-radiotherapy treatment with the emphasis on time sequencing and scheduling of drug and radiation. An investigation into whether the effect of cisplatin-radiation is determined by independent cell kill or by cisplatin-produced radiosensitization was also undertaken. It was shown that cisplatin administered before radiation conferred similar tumour control to the post-radiation sequencing of the drug. The killing effect of the combined modality treatment on tumour increased with the increase in cell recruitment. Furthermore, the individual cell kill produced by the two cytotoxins led to an additive only tumour response when the treatments were given concurrently, suggesting that for a synergistic effect, cisplatin must potentiate the effect of radiation, through the radiosensitizing mechanisms addressed in the literature. It was concluded that the optimal timing of cisplatin should be close to radiation. The model showed that daily administration of cisplatin led to a 35% improvement of tumour control as compared to radiation alone, while weekly cisplatin has improved radiotherapy by only 6%

  4. Can Imaging Parameters Provide Information Regarding Histopathology in Head and Neck Squamous Cell Carcinoma? A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Alexey Surov

    2018-04-01

    Full Text Available OBJECT: Our purpose was to provide data regarding relationships between different imaging and histopathological parameters in HNSCC. METHODS: MEDLINE library was screened for associations between different imaging parameters and histopathological features in HNSCC up to December 2017. Only papers containing correlation coefficients between different imaging parameters and histopathological findings were acquired for the analysis. RESULTS: Associations between 18F-FDG positron emission tomography (PET and KI 67 were reported in 8 studies (236 patients. The pooled correlation coefficient was 0.20 (95% CI = [−0.04; 0.44]. Furthermore, in 4 studies (64 patients, associations between 18F-fluorothymidine PET and KI 67 were analyzed. The pooled correlation coefficient between SUVmax and KI 67 was 0.28 (95% CI = [−0.06; 0.94]. In 2 studies (23 patients, relationships between KI 67 and dynamic contrast-enhanced magnetic resonance imaging were reported. The pooled correlation coefficient between Ktrans and KI 67 was −0.68 (95% CI = [−0.91; −0.44]. Two studies (31 patients investigated correlation between apparent diffusion coefficient (ADC and KI 67. The pooled correlation coefficient was −0.61 (95% CI = [−0.84; −0.38]. In 2 studies (117 patients, relationships between 18F-FDG PET and p53 were analyzed. The pooled correlation coefficient was 0.0 (95% CI = [−0.87; 0.88]. There were 3 studies (48 patients that investigated associations between ADC and tumor cell count in HNSCC. The pooled correlation coefficient was −0.53 (95% CI = [−0.74; −0.32]. Associations between 18F-FDG PET and HIF-1α were investigated in 3 studies (72 patients. The pooled correlation coefficient was 0.44 (95% CI = [−0.20; 1.08]. CONCLUSIONS: ADC may predict cell count and proliferation activity, and SUVmax may predict expression of HIF-1α in HNSCC. SUVmax cannot be used as surrogate marker for expression of KI 67 and p53.

  5. Curcumin as therapeutics for the treatment of head and neck squamous cell carcinoma by activating SIRT1

    Science.gov (United States)

    Hu, An; Huang, Jing-Juan; Li, Rui-Lin; Lu, Zhao-Yang; Duan, Jun-Li; Xu, Wei-Hua; Chen, Xiao-Ping; Fan, Jing-Ping

    2015-01-01

    SIRT1 is one of seven mammalian homologs of Sir2 that catalyzes NAD+-dependent protein deacetylation. The aim of the present study is to explore the effect of SIRT1 small molecule activator on the anticancer activity and the underlying mechanism. We examined the anticancer activity of a novel oral agent, curcumin, which is the principal active ingredient of the traditional Chinese herb Curcuma Longa. Treatment of FaDu and Cal27 cells with curcumin inhibited growth and induced apoptosis. Mechanistic studies showed that anticancer activity of curcumin is associated with decrease in migration of HNSCC and associated angiogenesis through activating of intrinsic apoptotic pathway (caspase-9) and extrinsic apoptotic pathway (caspase-8). Our data demonstrating that anticancer activity of curcumin is linked to the activation of the ATM/CHK2 pathway and the inhibition of nuclear factor-κB. Finally, increasing SIRT1 through small molecule activator curcumin has shown beneficial effects in xenograft mouse model, indicating that SIRT1 may represent an attractive therapeutic target. Our studies provide the preclinical rationale for novel therapeutics targeting SIRT1 in HNSCC. PMID:26299580

  6. Merkel cell carcinoma of the head and neck: poorer prognosis than non-head and neck sites.

    Science.gov (United States)

    Morand, G B; Madana, J; Da Silva, S D; Hier, M P; Mlynarek, A M; Black, M J

    2016-04-01

    Merkel cell carcinoma is a rare, aggressive neurocutaneous malignancy. This study investigated whether patients with Merkel cell carcinoma in the head and neck had poorer outcomes than patients with Merkel cell carcinoma located elsewhere. A retrospective study was performed of patients with Merkel cell carcinoma treated at the Jewish General Hospital in Montréal, Canada, from 1993 to 2013. Associations between clinicopathological characteristics and disease-free and disease-specific survival rates were examined according to the Kaplan-Meier method. Twenty-seven patients were identified. Although basic clinicopathological characteristics and treatments were similar between head and neck and non-head and neck Merkel cell carcinoma groups, disease-free and disease-specific survival rates were significantly lower in the head and neck Merkel cell carcinoma group (log-rank test; p = 0.043 and p = 0.001, respectively). Mortality was mainly due to distant metastasis. Patients with head and neck Merkel cell carcinoma had poorer survival rates than patients with non-head and neck Merkel cell carcinoma in our study. The tendency to obtain close margins, a less predictable metastatic pattern, and/or intrinsic tumour factors related to the head and neck may explain this discrepancy.

  7. Gene-expression signature regulated by the KEAP1-NRF2-CUL3 axis is associated with a poor prognosis in head and neck squamous cell cancer.

    Science.gov (United States)

    Namani, Akhileshwar; Matiur Rahaman, Md; Chen, Ming; Tang, Xiuwen

    2018-01-06

    NRF2 is the key regulator of oxidative stress in normal cells and aberrant expression of the NRF2 pathway due to genetic alterations in the KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2 like 2)-CUL3 (cullin 3) axis leads to tumorigenesis and drug resistance in many cancers including head and neck squamous cell cancer (HNSCC). The main goal of this study was to identify specific genes regulated by the KEAP1-NRF2-CUL3 axis in HNSCC patients, to assess the prognostic value of this gene signature in different cohorts, and to reveal potential biomarkers. RNA-Seq V2 level 3 data from 279 tumor samples along with 37 adjacent normal samples from patients enrolled in the The Cancer Genome Atlas (TCGA)-HNSCC study were used to identify upregulated genes using two methods (altered KEAP1-NRF2-CUL3 versus normal, and altered KEAP1-NRF2-CUL3 versus wild-type). We then used a new approach to identify the combined gene signature by integrating both datasets and subsequently tested this signature in 4 independent HNSCC datasets to assess its prognostic value. In addition, functional annotation using the DAVID v6.8 database and protein-protein interaction (PPI) analysis using the STRING v10 database were performed on the signature. A signature composed of a subset of 17 genes regulated by the KEAP1-NRF2-CUL3 axis was identified by overlapping both the upregulated genes of altered versus normal (251 genes) and altered versus wild-type (25 genes) datasets. We showed that increased expression was significantly associated with poor survival in 4 independent HNSCC datasets, including the TCGA-HNSCC dataset. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and PPI analysis revealed that most of the genes in this signature are associated with drug metabolism and glutathione metabolic pathways. Altogether, our study emphasizes the discovery of a gene signature regulated by the KEAP1-NRF2-CUL3 axis which is strongly associated with

  8. Continuous-Course Reirradiation With Concurrent Carboplatin and Paclitaxel for Locally Recurrent, Nonmetastatic Squamous Cell Carcinoma of the Head-and-Neck

    Energy Technology Data Exchange (ETDEWEB)

    Kharofa, Jordan [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Choong, Nicholas [Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Wang, Dian; Firat, Selim; Schultz, Christopher [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Sadasiwan, Chitra [Medical College of Wisconsin, Milwaukee, WI (United States); Wong, Stuart, E-mail: Swong@mcw.edu [Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

    2012-06-01

    Purpose: To examine the efficacy and toxicity of continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin for the treatment of locally recurrent, nonmetastatic squamous cell carcinoma of the head and neck (SCCHN) in a previously irradiated field. Methods and Materials: Patients treated with continuous course-reirradiation with concurrent carboplatin and paclitaxel at the Medical College of Wisconsin and the Clement J. Zablocki VA from 2001 through 2009 were retrospectively reviewed. Patients included in the analysis had prior radiation at the site of recurrence of at least 45 Gy. The analysis included patients who received either intensity-modulated radiotherapy (RT) or three-dimensional conformal RT techniques. All patients received weekly concurrent carboplatin (AUC2) and paclitaxel (30-50 mg/m{sup 2}). Results: Thirty-eight patients with nonmetastatic SCCHN met the entry criteria for analysis. The primary sites at initial diagnosis were oropharyngeal or laryngeal in most patients (66%). Median reirradiation dose was 60 Gy (range, 54-70 Gy). Acute toxicity included Grade 2 neutropenia (5%), Grade 3 neutropenia (15%), and Grade 1/2 thrombocytopenia (8%). No deaths occurred from hematologic toxicity. Chemotherapy doses held (50%) was more prevalent than radiation treatment break (8%). Sixty-eight percent of patients required a gastrostomy tube in follow-up. Significant late toxicity was experienced in 6 patients (16%): 1 tracheoesophageal fistula, 1 pharyngocutaneous fistula, 3 with osteoradionecrosis, and 1 patient with a lingual artery bleed. Patients treated with three-dimensional conformal RT had more frequent significant late toxicites than patients treated with intensity-modulated RT (44% and 7% respectively, p < 0.05). The median time to progression was 7 months and progression-free rates at 1, 2, and 5 years was 44%, 34%, and 29% respectively. The median overall survival was 16 months. Overall survival at 1, 3, and 5 years was 54

  9. GTSP1 expression in non-smoker and non-drinker patients with squamous cell carcinoma of the head and neck

    Science.gov (United States)

    Soares, Pamela de Oliveira; Maluf Cury, Patrícia; Mendoza López, Rossana Verónica; Cernea, Cláudio Roberto; Fukuyama, Erika Erina; Livingstone Alves Figueiredo, David; Gorgonio da Nobrega, Francisco; Curioni, Otavio Alberto; Nunes, Fabio Daumas; Bueno Garcia, Maria Lúcia

    2017-01-01

    Introduction The main risk factors for head and neck squamous cell carcinoma (HNSCC) are tobacco and alcohol consumption and human papillomavirus (HPV) infection. However, in a subset of patients, no risk factors can be identified. Glutathione S-transferase π (GTSP1) is a carcinogen-detoxifying enzyme that is activated by exposure to carcinogens, and it is associated with a reduction in response to toxic therapies. We studied the expression of GTSP1 in tumor and non-tumor tissue samples from patients with and without these risks to identify whether GTSP1 expression differs according to exposure to carcinogens. Materials and methods Non-smoker/non-drinker (NSND) and smoker/drinker (SD) patients were matched according to age, gender, tumor site, TNM stage, grade and histological variants to establish 47 pairs of patients who have been previously tested for HPV. GTSP1 immunostaining was analyzed using a semi-quantitative method with scores ranging from 0 to 3 according to the area of immunostaining. Results GTSP1 expression was detected in the tumors of both groups. GTSP1 expression was higher in the non-tumor margins of SD patients (p = 0.004). There was no association between GTSP1 expression and positivity for HPV. No differences in survival were observed according to GTSP1 staining in tumors and non-tumor margins. Conclusion This study showed that GTSP1 was expressed in tumors of HNSCC patients regardless of smoking, drinking or HPV infection status. The difference in GTSP1 expression in non-tumor margins between the two groups may have been due to two possible reasons. First, elevated GTSP1 expression in SD patients might be the result of activation of GTSP1 in response to exposure to carcinogens. Second, alternatively, impairment in the detoxifying system of GTSP1, as observed by the reduced expression of GTSP1, might make patients susceptible to carcinogens other than tobacco and alcohol, which may be the underlying mechanism of carcinogenesis in the absence

  10. Pulsed Radiation Therapy With Concurrent Cisplatin Results in Superior Tumor Growth Delay in a Head and Neck Squamous Cell Carcinoma Murine Model

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    Meyer, Kurt; Krueger, Sarah A.; Kane, Jonathan L.; Wilson, Thomas G.; Hanna, Alaa; Dabjan, Mohamad; Hege, Katie M.; Wilson, George D.; Grills, Inga; Marples, Brian, E-mail: brian.marples@beaumont.edu

    2016-09-01

    Purpose: To assess the efficacy of 3-week schedules of low-dose pulsed radiation treatment (PRT) and standard radiation therapy (SRT), with concurrent cisplatin (CDDP) in a head and neck squamous cell carcinoma xenograft model. Methods and Materials: Subcutaneous UT-SCC-14 tumors were established in athymic NIH III HO female mice. A total of 30 Gy was administered as 2 Gy/d, 5 d/wk for 3 weeks, either by PRT (10 × 0.2 Gy/d, with a 3-minute break between each 0.2-Gy dose) or SRT (2 Gy/d, uninterrupted delivery) in combination with concurrent 2 mg/kg CDDP 3 times per week in the final 2 weeks of radiation therapy. Treatment-induced growth delays were defined from twice-weekly tumor volume measurements. Tumor hypoxia was assessed by {sup 18}F-fluoromisonidazole positron emission tomography imaging, and calculated maximum standardized uptake values compared with tumor histology. Tumor vessel density and hypoxia were measured by quantitative immunohistochemistry. Normal tissues effects were evaluated in gut and skin. Results: Untreated tumors grew to 1000 mm{sup 3} in 25.4 days (±1.2), compared with delays of 62.3 days (±3.5) for SRT + CDDP and 80.2 days (±5.0) for PRT + CDDP. Time to reach 2× pretreatment volume ranged from 8.2 days (±1.8) for untreated tumors to 67.1 days (±4.7) after PRT + CDDP. Significant differences in tumor growth delay were observed for SRT versus SRT + CDDP (P=.04), PRT versus PRT + CDDP (P=.035), and SRT + CDDP versus PRT + CDDP (P=.033), and for survival between PRT versus PRT + CDDP (P=.017) and SRT + CDDP versus PRT + CDDP (P=.008). Differences in tumor hypoxia were evident by {sup 18}F-fluoromisonidazole positron emission tomography imaging between SRT and PRT (P=.025), although not with concurrent CDDP. Tumor vessel density differed between SRT + CDDP and PRT + CDDP (P=.011). No differences in normal tissue parameters were seen. Conclusions: Concurrent CDDP was more effective in combination PRT than SRT at

  11. Concurrent weekly docetaxel and concomitant boost radiation therapy in the treatment of locally advanced squamous cell cancer of the head and neck

    International Nuclear Information System (INIS)

    Tishler, Roy B.; Posner, Marshall R.; Norris, Charles M.; Mahadevan, Anand; Sullivan, Christopher; Goguen, Laura; Wirth, Lori J.; Costello, Rosemary; Case, MaryAnn; Stowell, Sara; Sammartino, Dan; Busse, Paul M.; Haddad, Robert I.

    2006-01-01

    Purpose: In a Phase I/II trial, we investigated concurrent weekly docetaxel and concomitant boost radiation in patients with locally advanced squamous cell cancer of the head and neck (SCCHN) after induction chemotherapy. Patients and Methods: Patients presented with American Joint Committee on Cancer Stage III/IV and were treated initially with induction chemotherapy using cisplatinum/5-fluorouracil (PF), carboplatinum-5-FU, or docetaxel-PF. Patients then received docetaxel four times weekly with concomitant boost (CB) radiation (1.8 Gy once-daily X20, 1.8/1.5 Gy twice a day). Fifteen patients each received 20 mg/M 2 and 25 mg/M 2 . Results: Thirty-one patients were enrolled and 30 were evaluable for response and toxicity. Median follow-up was 42 months (range, 27-63 months). Primary sites were: oropharynx 19, oral cavity 2, larynx/hypopharynx 5, and unknown primary 4. Eighty-seven percent of patients had N2/N3 disease; 60% had T3/T4 disease. Twenty percent of patients had a complete response (CR) to induction chemotherapy. After chemoradiotherapy, 21 of 30 patients had a CR, 2 had progressive disease, and 7 had partial response (PR). Nineteen of 26 patients presenting with neck disease had neck dissections, and 7 of 19 were positive. Ninety-three percent of all patients were rendered disease-free after all planned therapy. Treatment failed in 8 patients, and 7 have died of disease. An additional patient died with no evidence of disease. Twenty-one patients (70%) are currently alive with no evidence of disease. No acute dose-limiting toxicity was observed at either dose level. Conclusions: This intensive treatment regimen of concurrent docetaxel/concomitant boost radiation and surgery after induction chemotherapy in poor prognosis patients yields good local regional control and survival. Docetaxel/CB chemoradiotherapy represents an aggressive alternative regimen to platinum-based chemoradiotherapy or surgery in patients who have a poor response to induction

  12. RTOG 96-10: reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck

    International Nuclear Information System (INIS)

    Spencer, S.A.; Harris, J.; Wheeler, R.H.; Machtay, M.; Schultz, C.; Spanos, W.; Rotman, M.; Meredith, R.

    2001-01-01

    Purpose: Patients with recurrent squamous cell cancer of the head and neck (SCH and N) are generally treated with systemic chemotherapy. Improvement in survival has not occurred, despite an increased objective response rate. This study was undertaken to explore the feasibility and toxicity, and estimate the therapeutic impact of, reirradiation (RRT) with concurrent hydroxyurea and 5-fluorouracil. Methods and Materials: The eligibility requirements included SCH and N presenting as a second primary or recurrence ≥6 months after definitive RT to ≥45 Gy, with ≥75% of the tumor volume within the previous field. The cumulative spinal cord dose was limited to 50 Gy, and measurable disease was required. Four weekly cycles were given, each separated by 1 week of rest. A cycle consisted of 5 days, Monday through Friday, of 1.5-Gy twice-daily repeated RT, with the fractions separated by ≥6 h, with 1.5 g of hydroxyurea given 2 h and 300 mg/m 2 of a 5-fluorouracil IV bolus given 30 min before each second daily fraction. Results: Eighty-six patients were entered; 81 patients were assessable. The median prior radiation dose was 61.2 Gy. The 4 planned cycles were delivered in 79% of patients. Grade 3 mucositis occurred in 14% of patients, and Grade 4 in 5%. Grade 3 acute pharyngeal toxicity was seen in 17%. Grade 3 neutropenia occurred in 9%, Grade 4 in 10%, and Grade 5 in 7%. Six patients died of treatment-related toxicity. Two died of hemorrhage from the tumor site without thrombocytopenia. With a median follow-up of 16.3 months for living patients, the estimated median overall survival was 8.2 months and the estimated 1-year survival rate 41.7%. Patients treated >3 years after the previous RT had a 1-year survival rate of 48% compared with 35% for patients treated within 3 years (p=0.017). The 1-year survival rate for patients with a second primary was 54% compared with 38% for patients with recurrence (p=0.083). Conclusion: Repeated RT with concurrent chemotherapy as

  13. Phase 2 Study of Docetaxel, Cisplatin, and Concurrent Radiation for Technically Resectable Stage III-IV Squamous Cell Carcinoma of the Head and Neck

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    Inohara, Hidenori, E-mail: hinohara@ent.med.osaka-u.ac.jp [Department of Otorhinolaryngology—Head and Neck Surgery, Osaka University Faculty of Medicine, Suita, Osaka (Japan); Takenaka, Yukinori; Yoshii, Tadashi; Nakahara, Susumu; Yamamoto, Yoshifumi; Tomiyama, Yoichiro [Department of Otorhinolaryngology—Head and Neck Surgery, Osaka University Faculty of Medicine, Suita, Osaka (Japan); Seo, Yuji; Isohashi, Fumiaki; Suzuki, Osamu; Yoshioka, Yasuo; Sumida, Iori; Ogawa, Kazuhiko [Department of Radiation Oncology, Osaka University Faculty of Medicine, Suita, Osaka (Japan)

    2015-04-01

    Purpose: We investigated the efficacy and safety of weekly low-dose docetaxel and cisplatin therapy concurrent with conventionally fractionated radiation in patients with technically resectable stage III-IV squamous cell carcinoma of the head and neck. Methods and Materials: Between March 2004 and October 2011, we enrolled 117 patients, of whom 116 were analyzable (43 had oropharyngeal cancer, 54 had hypopharyngeal cancer, and 19 had laryngeal cancer), and 85 (73%) had stage IV disease. Radiation consisted of 66 Gy in 33 fractions. Docetaxel, 10 mg/m{sup 2}, followed by cisplatin, 20 mg/m{sup 2}, administered on the same day were given once a week for 6 cycles. The primary endpoint was overall complete response (CR) rate after chemoradiation therapy. Human papillomavirus (HPV) DNA in oropharyngeal cancer was examined by PCR. Results: Of 116 patients, 82 (71%) completed treatment per protocol; 102 (88%) received the full radiation therapy dose; and 90 (78%) and 12 (10%) patients received 6 and 5 chemotherapy cycles, respectively. Overall CR rate was 71%. After median follow-up of 50.9 months (range: 15.6-113.9 months for surviving patients), 2-year and 4-year overall survival rates were 82% and 68%, respectively. Cumulative 2-year and 4-year local failure rates were 27% and 28%, respectively, whereas distant metastasis rates were 15% and 22%, respectively. HPV status in oropharyngeal cancer was not associated with treatment efficacy. Acute toxicity included grade 3 and 4 in-field mucositis in 73% and 5% of patients, respectively, whereas myelosuppression and renal injury were minimal. No patients died of toxicity. Feeding tube dependence in 8% and tracheostomy in 1% of patients were evident at 2 years postchemoradiation therapy in patients who survived without local treatment failure. Conclusions: Local control and survival with this regimen were satisfactory. Although acute toxicity, such as mucositis, was common, late toxicity, such as laryngoesophageal

  14. Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-and-neck mucosal site treated with radiation therapy alone or in combination with neck dissection

    International Nuclear Information System (INIS)

    Erkal, Haldun S.; Mendenhall, William M.; Amdur, Robert J.; Villaret, Douglas B.; Stringer, Scott P.

    2001-01-01

    Purpose: The present study presents the experience at the University of Florida with treatment of patients with squamous cell carcinomas (SCC) metastatic to cervical lymph nodes from an unknown head-and-neck mucosal (H and NM) site with radiotherapy (RT) alone or in combination with neck dissection (ND). Methods and Materials: The study included 126 patients treated with curative intent from 1964 to 1997. All patients had follow-up for at least 2 years. No patients were lost to follow-up. Results: Twelve patients (10%) developed SCC in H and NM sites at 0.5 to 10.9 years (median, 1.8 years). The rate of developing carcinomas in H and NM sites at 5 years was 13%. Histologic differentiation significantly affected the rate of developing carcinomas in H and NM sites in multivariate analysis. Sixteen patients (13%) had persistent nodal disease and 12 patients (10%) developed recurrent nodal disease at 0.5 to 10.9 years (median, 1.1 years). The nodal control rate at 5 years was 78%. Nodal size, N stage, and planned ND significantly affected the rate of nodal control in multivariate analysis. Nineteen patients (15%) developed distant metastasis at 0.2-5.1 years (median, 0.9 years). The distant metastases rate at 5 years was 14%. Extracapsular extension and RT dose significantly affected the risk of distant metastases in multivariate analysis. The overall absolute survival rate at 5 years was 47%. Extracapsular extension, N stage, RT dose for H and NM sites, and planned ND significantly affected absolute survival in multivariate analysis. The rate of cause-specific survival at 5 years was 67%. Extracapsular extension, nodal size, N stage, overall treatment time, and planned ND significantly affected cause-specific survival in multivariate analysis. Eight patients (6%) had severe postoperative complications and 6 patients (5%) had severe late complications. Conclusion: The present study supports the effectiveness of RT in lowering the rate of developing carcinomas in the H

  15. A prospective trial comparing FDG-PET/CT and CT to assess tumor response to cetuximab in patients with incurable squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Adkins, Douglas; Ley, Jessica; Dehdashti, Farrokh; Siegel, Marilyn J; Wildes, Tanya M; Michel, Loren; Trinkaus, Kathryn; Siegel, Barry A

    2014-01-01

    Computed tomography (CT), the standard method to assess tumor response to cetuximab in incurable squamous cell carcinoma of the head and neck (SCCHN), performs poorly as judged by the disparity between high disease control rate (46%) and short time to progression (TTP) (70 days). F-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/CT is an alternative method to assess tumor response. The primary objective of this prospective trial was to evaluate the metabolic response of target lesions, assessed as the change in maximum standardized uptake value (SUV max ) on FDG-PET/CT before and after 8 weeks (cycle 1) of cetuximab. Secondary objectives were to compare tumor response by CT (RECIST 1.0) and FDG-PET/CT (EORTC criteria) following cycle 1, and determine TTP with continued cetuximab administration in patients with disease control by CT after cycle 1 but stratified for disease control or progression by FDG-PET/CT. Among 27 patients, the mean percent change of SUV max of target lesions after cycle 1 was −21% (range: +72% to −81%); by FDG-PET/CT, partial response (PR)/stable disease (SD) occurred in 15 patients (56%) and progression in 12 (44%), whereas by CT, PR/SD occurred in 20 (74%) and progression in 7 (26%). FDG-PET/CT and CT assessments were discordant in 14 patients (P = 0.0029) and had low agreement (κ = 0.30; 95% confidence interval [CI]: 0.12, 0.48). With disease control by CT after cycle 1, median TTP was 166 days (CI: 86, 217) if the FDG-PET/CT showed disease control and 105 days (CI: 66, 159) if the FDG-PET/CT showed progression (P < 0.0001). Median TTP of the seven patients whose post cycle 1 CT showed progression compared to the 12 whose FDG-PET/CT showed progression were similar (53 [CI: 49, 56] vs. 61 [CI: 50, 105] days, respectively). FDG-PET/CT may be better than CT in assessing benefit of cetuximab in incurable SCCHN

  16. A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Budach, W; Hehr, T; Budach, V; Belka, C; Dietz, K

    2006-01-01

    Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX) to radiotherapy (RT) and to some extent also for the use of hyperfractionated radiation therapy (HFRT) and accelerated radiation therapy (AFRT) in locally advanced squamous cell carcinoma (SCC) of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. Randomised trials testing curatively intended RT (≥60 Gy in >4 weeks/>50 Gy in <4 weeks) on SCC of the oral cavity, oropharynx, hypopharynx, and larynx published as full paper or in abstract form between 1975 and 2003 were eligible. Trials comparing RT alone with concurrent or alternating chemoradiation (5-fluorouracil (5-FU), cisplatin, carboplatin, mitomycin C) were analyzed according to the employed radiation schedule and the used CHX regimen. Studies comparing conventionally fractionated radiotherapy (CFRT) with either HFRT or AFRT without CHX were separately examined. End point of the meta-analysis was overall survival. Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p < 0.001). Separate analyses by cytostatic drug indicate a prolongation of survival of 24.0 months, 16.8 months, 6.7 months, and 4.0 months, respectively, for the simultaneous administration of 5-FU, cisplatin-based, carboplatin-based, and mitomycin C-based CHX to RT (each p < 0.01). Whereas no significant gain in overall survival was observed for AFRT in comparison to CFRT, a substantial prolongation of median survival (14.2 months, p < 0.001) was seen for HFRT compared to CFRT (both without CHX). RT combined with simultaneous 5-FU, cisplatin, carboplatin, and mitomycin C as

  17. A Prospective Phase 2 Trial of Reirradiation With Stereotactic Body Radiation Therapy Plus Cetuximab in Patients With Previously Irradiated Recurrent Squamous Cell Carcinoma of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Vargo, John A. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Ferris, Robert L. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Ohr, James [Division Medical Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Clump, David A. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Davis, Kara S.; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T. [Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Bauman, Julie E.; Gibson, Michael K. [Division Medical Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Branstetter, Barton F. [Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Heron, Dwight E., E-mail: herond2@umpc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States)

    2015-03-01

    Purpose: Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. Methods and Materials: From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normal hepatic and renal function were enrolled. Patie