Purpose: The management of head and neck squamous cell carcinoma (HNSCC) is complex and often involves multimodality treatment. Currently, most management decisions are based on clinical parameters with little appreciation of patient differences in underlying tumour biology. The identification of biomarkers that predict response to radiotherapy would be clinically useful in determining optimal management. The purpose of the thesis was to investigate potential biomarkers that might predict radiotherapy outcome in patients with HNSCC. Aims: 1) To investigate the hypoxia-associated biomarkers carbonic anhydrase 9 (CA9) and hypoxia-inducible factor -1α (HIF-1α) in patients with early glottis cancer who underwent radiotherapy as their primary mode of treatment, furthermore to investigate the role of accelerated hypofractionated radiotherapy in the management of T2 glottic cancer. 2) To investigate markers of hypoxia (CA9 and HIF-1α) and viral infection in oropharyngeal cancer, and in particular to test for an association between hypoxia markers and viral infection. 3) To investigate HIF-1 and CA9 in a series of patients undergoing surgery as their primary mode of treatment to explore whether they are associated specifically with radioresponsiveness or a general poor prognosis. Results: 1) Adverse prognostic factors for locoregional control were low pre-treatment haemoglobin (Hb; p = 0.010), advancing T stage (p = 0.001) and high CA9 expression (p = 0.032). Low Hb and high CA9 expression were independent factors on multivariate analysis; and combined predicted locoregional recurrence with an odds ratio of 8.0 (95% CI: 2.7-23.9), or either/or with an odds ratio of 3.3 (95% CI 1.5-7.1). In the subset of T2 patients, five-year locoregional control following radiotherapy was 82% and cancer specific survival was 90%. Serious morbidity occurred in 1.8% of patients. T stage subdivided by vocal cord movement was significant for local control. 2) Features associated with a poor locoregional control were older age (p=0.002), tongue base subsite (p=0.002), heavy alcohol use (p=0.004), heavy smoker (p=0.0002), low Hb level (p=0.001), advancing T (p=<0.0001), N (p=0.001) and AJC (p=0.001) stage, high CA9 expression (p=0.020) and high HIF-1α expression (p<0.0001). In multivariate analysis T stage (p=0.003) and high HIF-1α expression (p=0.001) remained significant. 3) Extracapsular spread was significantly associated with poor cancer specific survival (p=0.022). No other patient variables were associated with outcome. HIF-1α expression was significantly associated with poorly differentiated tumour (p=0.019) and the tumour having a cohesive front (p=0.026). Conclusion: 1) Hb and CA9 have potential to be used together as a biomarker to identify glottis cancer patients with a high probability of a poor outcome following radiotherapy, furthermore, vocal cord movement should be taken into consideration when managing glottis cancer. 2) As it does not appear to be influenced by HPV status, HIF-1α warrants further investigation as a biomarker in oropharyngeal patients treated with primary radiotherapy. 3) As HIF-1α and CA9 had no prognostic significance in patients undergoing surgery, they should be explored further as markers to help guide management decisions in patients with HNSCC.

published_or_final_version / Pathology / Master / Master of Medical Sciences

BACKGROUND:To evaluate the feasibility of image-guided radiotherapy based on helical Tomotherapy to spare the contralateral parotid gland in head and neck cancer patients with unilateral or no neck node metastases.METHODS:A retrospective review of 52 patients undergoing radiotherapy for head and neck cancers with image guidance based on daily megavoltage CT imaging with helical tomotherapy was performed.RESULTS:Mean contralateral parotid dose and the volume of the contralateral parotid receiving 40Gy or more were compared between radiotherapy plans with significant constraint (SC) of less than 20Gy on parotid dose (23 patients) and the conventional constraint (CC) of 26Gy (29 patients). All patients had PTV coverage of at least 95% to the contralateral elective neck nodes. Mean contralateral parotid dose was, respectively, 14.1Gy and 24.7Gy for the SC and CC plans (p<0.0001). The volume of contralateral parotid receiving 40Gy or more was respectively 5.3% and 18.2% (p<0.0001)CONCLUSION:Tomotherapy for head and neck cancer minimized radiotherapy dose to the contralateral parotid gland in patients undergoing elective node irradiation without sacrificing target coverage.

Using an existing data set comprised of 368 individuals newly diagnosed with cancers of the head and neck, we investigated the predictive validity of the Head and Neck Patient Symptom Checklist (HNSC) by comparing scores on the HNSC to scores on the Patient-Generated Symptom Global Assessment (PG-SGA), and by examining the ability of HNSC scores and four demographic variables to predict dietary intake, weight loss, and functional capacity. HNSC sensitivity (0.79 0.98), specificity (0.99 1.00), positive predictive value (92% 100%), and negative predictive value (94% - 100%) were excellent. Pain, loss of appetite and difficulty swallowing predicted 82% of reduced dietary intake. Advanced tumor stage, loss of appetite and difficulty swallowing predicted 79% of weight loss. Loss of appetite, difficulty swallowing, feeling full and lack of energy predicted 78% of reduced functional capacity. The HNSC appears to be valid and could aid with early symptom identification, intervention and improved outcomes.

The purpose of this study is to evaluate the health related quality of life (QoL) of head and neck cancer (HNC) patients with cancer-free survival after treatment and to investigate the factors correlated with their health-related QoL. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) questionnaire and the EORTC head and neck cancer-specific questionnaire (QLQ H&N-35) were self-administered by all participating patients. Sociodemographic data were collected using a questionnaire specifically designed for the study and through the medical chart reviewed. The patients who have been treated radiotherapy in our department of radiation oncology were invited to participate Health-related quality of life was assessed 3 months or later after completion of radiotherapy. Data relating to sociodemographic factors, disease characteristics and treatment factors of HNC survivors were analyzed. A total of 141 head and neck cancer patients completed the questionnaires. After data analysis, the results are described as follows: In the results of EORTC QLQ-C30 questionnaire, the score of ¡§global health status¡¨ is 69.34. Most of the patient could maintain good functional quality of life. ¡§Fatigue¡¨ is the most impaired symptom score in the patient. In the results of EORTC QLQ-H&N35, the three head and neck specific symptom scores indicating the most impaired in QOL were ¡§Weight loss¡¨, ¡§Nutrition supplements¡¨ and ¡§dry mouth¡¨. After analysis through the multiple regression model, we found sex, age, tumor subsite, radiotherapy technique and surgery were the independent factors significantly correlated with the QoL scales This study is helpful for us to understand the QoL status and the factors affecting the QoL for patients with head and neck cancer after radiotherapy.

Introduction: Current treatment recommendations for advanced SCCHN include the use of combined modality therapy (e.g., radiation plus chemotherapy/biologic therapy). The new biologic agent, cetuximab, is considered a primary cost driver for SCCHN management. Cetuximab’s impact, however, has not been factored into SCCHN cost estimates; furthermore, costs have not been delineated for diagnostic, treatment, and end-of-life segments of advanced SCCHN management. We aim to characterize SCCHN segmented and overall costs, before and after cetuximab’s approval. Methods: This was a retrospective analysis of the PharMetrics Choice database. Patients >20 years of age with ICD-9-CM codes suggestive of advanced SCCHN diagnosed between 3/1/2003 and 3/1/2008 were included. Patients were divided into cohorts by diagnosis date: “pre-biologic” and “post-biologic.” Descriptive statistics were used to summarize patient characteristics, monthly and total medical costs, and cost drivers. The Mann-Whitney U test was used to compare costs between segments and cohorts; whereas, least squares regression was used to ascertain the impact of covariates. Results: A total of 365 patients met study criteria. Patients were predominately male (78%), with a median age of 57 years. Median monthly costs were: diagnosis ($2,199), treatment ($4,161), end-of-life ($6,614), and total ($4,167). Total direct medical costs were primarily driven by outpatient costs (23%). Patient age and length of follow-up had a significant impact on total costs, with older age associated with lower costs. When treatment segment was isolated, median monthly costs were lower in the “pre-biologic” as compared to the “post-biologic” era ($3,301 vs. $4,381, p=0.0024); biologic therapy accounted for 4.2% of total cost in the study period. In those patients experiencing all segments of care (“benchmark group”), median monthly costs were: diagnosis ($1,733), treatment ($8,265), end-of-life ($6,614), and total ($7,817). There were no significant differences in monthly medical costs between cohorts for the benchmark group. Conclusions: Median total cost exceeded $4,000/month for SCCHN patients; treatment and end-of-life segments incurred higher costs. Outpatient costs were the biggest cost-driver. Median monthly cost for the treatment segment increased by approximately $1,000 following cetuximab’s approval; however, this difference dissipated when the analysis was limited to those patients who experienced all segments of care. / text

published_or_final_version / Surgery / Master / Master of Philosophy

published_or_final_version / Surgery / Master / Master of Philosophy

No description available.

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.