CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Tumores malignos de origem nÃo epitelial sÃo considerados raros na regiÃo de cabeÃa e pescoÃo e podem apresentar grande morbidade e mortalidade. Este estudo teve o objetivo de fazer um levantamento dos casos de sarcomas e melanomas em regiÃo de cabeÃa e pescoÃo no perÃodo de 1999 a 2008, em trÃs centros especializados no MunicÃpio de Fortaleza, CearÃ. A coleta de dados foi feita com base nos livros de registros das cirurgias de cabeÃa e pescoÃo e dos prontuÃrios dos centros avaliados. Foram observados 54 casos, sendo 36 sarcomas e 18 melanomas. Quanto à avaliaÃÃo dos sarcomas, observamos que os indivÃduos mais acometidos foram homens adultos, da raÃa parda, na faixa etÃria de 20 a 59 anos, com idade mÃdia de 39,7. A relaÃÃo homem/mulher foi de 1,76:1. O tipo histolÃgico mais prevalente foi o rabdomiossarcoma, e as localizaÃÃes mais acometidas foram face e regiÃo cervical. Em relaÃÃo aos melanomas, homens adultos tambÃm foram predominantes, na faixa etÃria de 20 a 59 anos, com idade mÃdia de 54,6. Verificou-se igual acometimento nas raÃas parda e branca, com 33,3%, cada uma. A relaÃÃo homem/mulher foi de 1,25:1. O tipo histolÃgico mais prevalente foi o melanoma de disseminaÃÃo superficial, e a pele da face foi a localizaÃÃo mais frequente. Na avaliaÃÃo da procedÃncia, houve semelhanÃa em ambas as doenÃas, sendo aproximadamente metade dos pacientes da capital e metade do interior do estado. Quanto ao acompanhamento, a maior parte da amostra foi de pacientes vivos sem evidÃncia de doenÃa na Ãltima consulta, correspondendo a 41,6% nos sarcomas e 44,5% entre os melanomas. A variaÃÃo de terapia tambÃm foi observada em ambos os grupos, sendo os tipos mais comuns de tratamento a associaÃÃo de cirurgia, radioterapia e quimioterapia e cirurgia e radioterapia para sarcomas, e cirurgia, seguida da associaÃÃo de cirurgia e radioterapia para melanomas. Apesar de os tumores malignos de origem nÃo epitelial em cabeÃa e pescoÃo serem lesÃes raras, eles apresentam grande morbidade e mortalidade e dessa forma, necessita-se de que seus aspectos clinicopatolÃgicos sejam estudados e conhecidos, sempre com o objetivo de melhorar as formas de tratamento dessas lesÃes, garantindo assim maiores chances de cura e melhor qualidade de vida para os pacientes acometidos. / Malignant tumors of non-epithelial origin are considered rare in the head and neck region and they can show great morbidity and mortality. The aim of this study was to investigate the cases of sarcomas and melanomas in the head and neck region over the period from 1999 to 2008, in specialized centers located in the Municipality of Fortaleza. The data were collected from the register books of surgery of the head and neck and patient reports at the evaluated centers. Fifty-four cases were observed, being 36 sarcomas and 18 melanomas. As per the evaluation of the sarcomas, we have observed that the most assailed individuals were men with brown skin, ranging from 20 to 59 years old, with median age of 39.7. The relation man/woman was 1.7:1. The most prevailing histological type was the rhabdomyosarcoma, and the most attacked areas were the face and the cervical region. And as per the melanomas, adult men were also prevailing, ranging from 20 to 59 years old, with median age of 54.6. It has also been verified equal assailment in the brown and white races, with 33.3% in each one. The relation man/woman was 1.25:1. The most prevailing histological type was the superficial spreading melanoma, and the face skin was the most frequent location. In the evaluation of the origin, there was similarity in both diseases, being approximately half the patients in the capital city, and half in the stateÂs hinterland. As concerning the monitoring, the greatest part of the sample came from patients alive without evidence of the disease from the last consultation, corresponding to 41.6% in sarcomas and 44.5% in melanomas. The variation of therapy has also been observed in both groups, being the most common types of treatments, the association of surgery, radiotherapy and chemotherapy and surgery and radiotherapy for sarcomas and surgery, followed by surgery and radiotherapy for melanomas. Although malignant tumors of non-epithelial origin are rare in the head and neck region, they can show great morbidity and mortality and it is necessary the better understanding of their clinicalpatological aspects, in order to establish better treatment and life quality to these patients.

Title: Inhibition of interleukin-6 trans-signaling by sgp130Fc is anti-tumorigenic in head and neck squamous cell carcinoma. Background: Head and neck squamous cell carcinoma (HNSCC) is a highly inflammatory cancer type, and interleukin-6 (IL-6) is associated with this phenotype. Elevated expression of IL-6 is linked to tumor progression, recurrence, metastasis, and resistance to therapy in HNSCC. However, targeting IL-6 or IL-6 receptor (IL-6R) has demonstrated little to no clinical efficacy. IL-6 signals through a classical signaling pathway via membrane IL-6R or a trans-signaling pathway via soluble IL-6R (sIL-6R). Recent evidence suggests that classical signaling induces acute, transient inflammation, eventually resulting in homeostasis; whereas trans-signaling may induce chronic, pro-tumorigenic inflammation. Therefore we propose that IL-6 trans-signaling is associated with the pro-inflammatory phenotype observed in HNSCC. We wanted to determine whether inhibition of IL-6 trans-signaling by sgp130Fc would better demonstrate anti-tumor efficacy and increase HNSCC tumor response to radiation, chemotherapy, and targeted therapy (cetuximab) compared to global IL-6 pathway inhibition. Method/Results: Baseline levels of IL-6, IL-6R, sIL-6R, and sgp130 proteins in HNSCC cells were determined using ELISA and flow cytometry. Cisplatin, radiation, and cetuximab treatments each induced HNSCC cell secretion of IL-6 and sIL-6R in vitro, yet adding sgp130Fc to those treatments did not further reduce clonogenic survival. Sgp130Fc treatment significantly suppressed SQ20B tumor growth in nude mice, whereas global IL-6 pathway inhibition by IL-6R antagonist tocilizumab did not; however, cetuximab reduced the efficacy of sgp130Fc in this animal model. Sgp130Fc also sensitized SQ20B xenograft tumors to radiation and chemotherapy in nude mice and suppressed SCCVII tumor growth in male but not female C3H/HeJ mice. Conclusion: Inhibition of IL-6 trans-signaling by sgp130Fc displayed significant anti-tumor effects as a single therapy and sensitized resistant HNSCC tumors to radiation and chemotherapy in vivo; however, sgp130Fc did not reduce survival of HNSCC cells in vitro. These results suggest that the efficacy of sgp130Fc relies on targeting another part of the microenvironment instead of tumor cells directly. Sgp130Fc has promise both as a single therapy and potentially as combined therapy with radiation and chemotherapy in HNSCC.

Thesis (Ph. D.)--Ohio State University, 2007. / Full text release at OhioLINK's ETD Center delayed at author's request

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (p. 125-137).

Introduction: Frailty represents a complex geriatric syndrome associated with elevated rates of postoperative complications as shown for several malignant entities, including head and neck cancer. A specific screening instrument to assess frailty in head and neck patients does not exist. Both the FRAIL Scale and the G8 questionnaire are well-established and easy to use as screening tools. The present study’s aim was to assess the potential of frailty screening to predict postoperative complications in head and neck patients prior to surgery. Patients and methods: We recorded demographic data, pre-existing medical conditions and clinical characteristics in a prospective cohort of 104 head and neck cancer patients undergoing major head and neck surgery and assessed frailty prospectively on the day of admission utilizing the G8 questionnaire and the FRAIL Scale. We analyzed the link between occurrence of postoperative complications up to the twenty-first postoperative day and age, frailty and other covariates using χ 2 tests and receiver operating characteristic (ROC) curves. Results: There was no significant correlation between patients’ pre-existing medical conditions and postoperative complications. Whereas chronological age alone did not predict the occurrence of postoperative complications, frailty posed the highest risk for complications. Frailty according to either the G8 questionnaire or the FRAIL Scale predicted occurrence of complications with an area under the curve (AUC) of 0.64 (p = 0.018) and 0.62 (p = 0.039) and severe complications with an AUC of 0.72 (p = 0.014) and 0.69 (p=0.031), respectively. Neither frailty score correlated with age or with each other. Conclusion: Prospective screening using the FRAIL Scale or the G8 questionnaire reliably detected frailty in our sample group. Frailty is linked to increased risk of postoperative complications. The correct prediction of severe postoperative complications as shown identifies vulnerable cases and triggers awareness of potential complications. Anticipating risk allows for a more comprehensive view of the patient and triggers decision making towards risk adjustment, and therefore a selective view of alternative treatment modalities.

BACKGROUND:The aim of the study is to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) for the prevention of retropharyngeal nodal recurrences in locally advanced head and neck cancer.METHODS:A retrospective review of 76 patients with head and neck cancer undergoing concurrent chemoradiation or postoperative radiotherapy with IMRT or IGRT who were at risk for retropharyngeal nodal recurrences because of anatomic site (hypopharynx, nasopharynx, oropharynx) and/or the presence of nodal metastases was undertaken.The prevalence of retropharyngeal nodal recurrences was assessed on follow-up positron emission tomography (PET)-CT scans.RESULTS:At a median follow-up of 22months (4-53months), no patient developed retropharyngeal nodal recurrences.CONCLUSION:Prophylactic irradiation of retropharyngeal lymph nodes with IMRT or IGRT provides effective regional control for individuals at risk for recurrence in these nodes.

Bei dieser Arbeit handelt es sich um eine retrospektive Studie bezüglich Inzidenz und Therapie von Mundhöhlen- und Oropharynxkarzinomen, welche in dem Zeitraum von 1993 bis 2009 in der HNO-Klinik der Universität Leipzig als „High Volume Center“ behandelt wurden, mit besonderem Augenmerk auf die Stadien III-IV nach UICC/AJCC. In unserer Studie konnten wir eine Zunahme der an der Universität in Leipzig registrierten Patienten mit Mundhöhlen- und Oropharynxkarzinomen über die Jahre 1993 bis 2009 verzeichnen. Männer waren mehr als fünfmal so häufig betroffen wie Frauen. Diese Verteilung hielt sich über den Beobachtungszeitraum konstant. Bei den weiblichen Patientinnen wurden im Durchschnitt niedrigere Tumorstadien bei Erstdiagnose festgestellt. Frauen hatten insgesamt eine höhere 5-Jahresüberlebensrate. Die Stadienverteilung nach UICC/AJCC bei Erstdiagnose eines Mundhöhlen- und Oropharynxkarzinoms blieb über die Jahre hinweg annähernd gleich. Es wurden meist hohe Stadien festgestellt (62,7% Stadium IV). Das mittlere Erkrankungsalter von Mundhöhlen- und Oropharynxkarzinomen sank über den Beobachtungszeitraum. Das Alter bei Rezidivmanifestation blieb allerdings über die Jahre gleich und lag unter dem durchschnittlichen Alter bei Erstdiagnosestellung. In diesem Zeitraum wird in der Literatur eine zunehmende Infektionsrate mit HPV beschrieben, welche gemäß der Literaturdaten mit einem jüngeren Erkrankungsalter einhergeht. Über die Jahre fanden wir in dem von uns untersuchten Patientenkollektiv der Universitätsklinik Leipzig eine stetige Verbesserung der mittleren Überlebensraten. In zeitlicher Assoziation zu dieser Entwicklung fand eine Änderung der Therapiemodalitäten insbesondere mit Einführung der systemischen Chemotherapie ab ca. 2004 in Richtung einer zunehmenden multimodalen Therapie statt. Es konnte ein Vorteil im Gesamtüberleben nach einer kombiniert-operativen Therapie mit adjuvanter Radiochemotherapie gegenüber allen anderen Therapieformen gezeigt werden. Insbesondere im Stadium IV nach UICC/AJCC zeigte sich ebenfalls ein Vorteil der kombinierten Radiochemotherapie gegenüber einer alleinigen Radiotherapie.

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