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1.
Int J Cancer ; 154(7): 1158-1163, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38059815

RESUMO

The identification and therapeutic targeting of actionable gene mutations across many cancer types has resulted in improved response rates in a minority of patients. The identification of actionable mutations is usually not sufficient to ensure complete nor durable responses, and in rare cancers, where no therapeutic standard of care exists, precision medicine indications are often based on pan-cancer data. The inclusion of functional data, however, can provide evidence of oncogene dependence and guide treatment selection based on tumour genetic data. We applied an ex vivo cancer explant modelling approach, that can be embedded in routine clinical care and allows for pathological review within 10 days of tissue collection. We now report that ex vivo tissue modelling provided accurate longitudinal response data in a patient with BRAFV600E -mutant papillary thyroid tumour with squamous differentiation. The ex vivo model guided treatment selection for this patient and confirmed treatment resistance when the patient's disease progressed after 8 months of treatment.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Mutação , Proteínas Proto-Oncogênicas B-raf/genética
2.
Mod Pathol ; 36(8): 100190, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37080394

RESUMO

Squamous cell carcinoma is the most common head and neck malignancy arising from the oral mucosa and the skin. The histologic and immunohistochemical features of oral squamous cell carcinoma (OSCC) and head and neck cutaneous squamous cell carcinoma (HNcSCC) are similar, making it difficult to identify the primary site in cases of metastases. With the advent of immunotherapy, reliable distinction of OSCC and HNcSCC at metastatic sites has important treatment and prognostic implications. Here, we investigate and compare the genomic landscape of OSCC and HNcSCC to identify diagnostically useful biomarkers. Whole-genome sequencing data from 57 OSCC and 41 HNcSCC patients were obtained for tumor and matched normal samples. Tumor mutation burden (TMB), Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, frequent chromosomal alterations, somatic single nucleotide, and copy number variations were analyzed. The median TMB of 3.75 in primary OSCC was significantly lower (P < .001) than that of 147.51 mutations/Mb in primary HNcSCC. The COSMIC mutation signatures were significantly different (P < .001) between OSCC and HNcSCC. OSCC showed COSMIC single-base substitution (SBS) mutation signature 1 and AID/APOBEC activity-associated signature 2 and/or 13. All except 1 HNcSCC from hair-bearing scalp showed UV damage-associated COSMIC SBS mutation signature 7. Both OSCC and HNcSCC demonstrated a predominance of tumor suppressor gene mutations, predominantly TP53. The most frequently mutated oncogenes were PIK3CA and MUC4 in OSCC and HNcSCC, respectively. The metastases of OSCC and HNcSCC demonstrated TMB and COSMIC SBS mutation signatures similar to their primary counterparts. The combination of high TMB and UV signature in a metastatic keratinizing squamous cell carcinoma suggests HNcSCC as the primary site and may also facilitate decisions regarding immunotherapy. HNcSCC and OSCC show distinct genomic profiles despite histologic and immunohistochemical similarities. Their genomic characteristics may underlie differences in behavior and guide treatment decisions in recurrent and metastatic settings.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Variações do Número de Cópias de DNA , Neoplasias Bucais/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias de Cabeça e Pescoço/genética , Mutação , Genômica , Biomarcadores Tumorais/genética
3.
Genes Chromosomes Cancer ; 61(9): 561-571, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35670448

RESUMO

INTRODUCTION: Oral squamous cell carcinoma (OSCC) in the young (<50 years), without known carcinogenic risk factors, is on the rise globally. Whole genome duplication (WGD) has been shown to occur at higher rates in cancers without an identifiable carcinogenic agent. We aimed to evaluate the prevalence of WGD in a cohort of OSCC patients under the age of 50 years. METHODS: Whole genome sequencing (WGS) was performed on 28 OSCC patients from the Sydney Head and Neck Cancer Institute (SHNCI) biobank. An additional nine cases were obtained from The Cancer Genome Atlas (TCGA). RESULTS: WGD was seen in 27 of 37 (73%) cases. Non-synonymous, somatic TP53 mutations occurred in 25 of 27 (93%) cases of WGD and were predicted to precede WGD in 21 (77%). WGD was significantly associated with larger tumor size (p = 0.01) and was frequent in patients with recurrences (87%, p = 0.36). Overall survival was significantly worse in those with WGD (p = 0.05). CONCLUSIONS: Our data, based on one of the largest WGS datasets of young patients with OSCC, demonstrates a high frequency of WGD and its association with adverse pathologic characteristics and clinical outcomes. TP53 mutations also preceded WGD, as has been described in other tumors without a clear mutagenic driver.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/genética , Duplicação Gênica , Neoplasias de Cabeça e Pescoço/genética , Humanos , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
4.
Clin Otolaryngol ; 48(2): 175-181, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36321439

RESUMO

OBJECTIVE: To evaluate whether prolonged operative time is negatively associated with post-operative complications and length of stay in patients undergoing microvascular free flap reconstruction for complex head and neck defects. METHODS: 342 consecutive patients undergoing microvascular reconstruction for head and neck defects between 2017-2019 at a single institution were evaluated. Operative outcomes and operative time were compared whilst controlling for patient and treatment related factors. RESULTS: Mean operative time was 551 min and length of stay was 16.2 days. An 11% increase in the risk of a post-operative complication was observed for every additional hour of operative time (OR 1.11, 95% CI 1.03-1.21, p = 0.011) after adjusting for patient and treatment factors. A cut-off of 9 h yielded a 92% increase in complications on either side of this (OR 1.92, 95% CI 1.18-3.13, p = 0.009). Increased operative time was also associated with increased length of stay and return to theatres, but not medical complications. CONCLUSION: Prolonged operative time is significantly associated with increased surgical complications, length of stay and return to theatres when performing microvascular reconstructive surgery for head and neck defects.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Humanos , Retalhos de Tecido Biológico/irrigação sanguínea , Duração da Cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Estudos Retrospectivos , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Tempo de Internação , Resultado do Tratamento
5.
Aust J Rural Health ; 31(5): 932-943, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37501345

RESUMO

INTRODUCTION: Centralisation of head and neck surgical services means that patients in regional and remote Australia need to travel long distances for treatment and follow-up, imparting a significant financial burden on patients and the health system. OBJECTIVE: To estimate costs of travel to local outreach clinics and determine potential cost savings to patients and the health system by avoiding patient travel to major cities for head and neck surgical care. DESIGN: Retrospective audit of three head and neck surgery outreach clinics in New South Wales, Australia over 4 years (2017-2020). Direct costs of travel from a patient's residence to their local outreach clinic were estimated. Costs of travel and accommodation to Sydney for an appointment were calculated for different travel modes. Estimated reimbursements for travel through government support schemes were calculated based on published rates. FINDINGS: Some 657 patients attended the three clinics, accounting for 1981 appointments. Depending on mode of travel, the estimated median cost of return travel (including accommodation) to Sydney was $379 to $739 per patient per trip and the median government reimbursement ranged from $182 to $279 per trip. In comparison, the cost of return travel by car to local outreach clinics ranged from $28 to $163 per appointment. Outreach clinics were estimated to save patients a median of $285 per trip and avoided government reimbursements of $215 per trip. DISCUSSION: Despite uptake in telehealth, outreach medical services remain an important asset for people living in regional areas to address inequities in access. However, the cost benefits are likely to be underestimated as our approach did not account for indirect costs associated with travel. CONCLUSION: Outreach head and neck surgical services located in regional areas can reduce the financial burden on both patients and the healthcare system. Greater investment in outreach clinics could ensure sustainability of services to promote equitable access to specialised surgical services.


Assuntos
Acessibilidade aos Serviços de Saúde , Viagem , Humanos , New South Wales , Redução de Custos , Estudos Retrospectivos , Austrália
6.
Ann Surg Oncol ; 29(11): 6991-6999, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35569073

RESUMO

BACKGROUND: The order of significance of clinicopathologic characteristics for the prognosis of patients with regional metastases from head and neck cutaneous squamous cell carcinoma (HNcSCC) is not well characterized. This study aimed to understand the impact of the known characteristics, including the presence of immunosuppression, number of deposits, largest deposit size, location and laterality of deposits, and presence of extranodal extension (ENE) on overall survival (OS) and disease-specific survival (DSS). METHODS: A retrospective study of 366 patients treated with curative intent for HNcSCC with regional metastatic disease was undertaken using recursive partitioning analysis (RPA). RESULTS: Using RPA modeling, the study determined that number of metastatic deposits carried the highest impact for both OS and DSS, followed by largest deposit size. The presence of ENE and immunosuppression was less significant. CONCLUSIONS: The results from this study provide new evidence for identifying and stratifying high-risk patients with metastatic HNcSCC. This information will be valuable in determining future HNcSCC staging systems.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Cutâneas , Carcinoma de Células Escamosas/patologia , Extensão Extranodal , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Metástase Linfática , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço
7.
Eur J Cancer Care (Engl) ; 31(6): e13718, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36178016

RESUMO

OBJECTIVE: The objective of this study to explore experiences of patients and carers of the pathway to diagnosis and treatment of head and neck cancer (HNC), focusing on differences based on remoteness of residence. METHODS: Patients ≥6 months post-treatment completion, and their carers, were recruited. Semi-structured interviews, guided by the Model of Pathways to Treatment as the theoretical framework, were conducted to examine pathways to treatment of HNC and facilitators and barriers to early diagnosis and treatment. Thematic analysis with an iterative and data-driven approach was used to identify themes. RESULTS: A total of 39 patients and 17 carers participated in the interviews. Facilitators of timely diagnosis and treatment included a sense of urgency from health care professionals (HCPs), advocacy by the HCP or carers, and leveraging social capital. Distance to services, financial costs, and a perceived lack of emotional investment by HCPs arose as barriers to timely diagnosis and treatment. Participants were often able to rationalise that not all delays were negative, depending causes and expected impact on cancer management. CONCLUSION: The findings highlight the complex nature of factors facilitating and impeding early HNC diagnosis and treatment that may be targeted in interventions to support patients and meet important benchmarks for high-quality cancer care.


Assuntos
Cuidadores , Neoplasias de Cabeça e Pescoço , Humanos , Cuidadores/psicologia , Detecção Precoce de Câncer , Pessoal de Saúde/psicologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Pesquisa Qualitativa
8.
Aust J Rural Health ; 30(4): 501-511, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35276017

RESUMO

INTRODUCTION: General practitioners (GPs) play a crucial role in cancer care and GPs are often the first doctor that patients with symptoms suggestive of cancer will encounter. Head and neck cancer (HNC) is a relatively uncommon presentation in primary care, and evidence suggests that times to diagnosis and treatment of HNC vary based on geographical location of patients. This may be due to barriers to referral faced by regional or rural GPs as compared to those in metropolitan cities in Australia. OBJECTIVE: To investigate the effect of geographical location of GPs on management of patients with symptoms suggestive of HNC. DESIGN: This was a descriptive, analytical, cross-sectional survey. Surveys were sent to GPs at practices in two primary health care networks in New South Wales, Australia (Mid North Coast Primary Healthcare Network and the Central and Eastern Sydney Primary Healthcare Network) between February and May 2020. Main outcome measures were perceived time from referral to specialist appointment, factors affecting timeliness of patient help-seeking, and awareness and use of clinical guidelines. FINDINGS: A total of 1803 GPs were sampled, of which 196 responded (45 regional GPs and 151 metropolitan GPs). Less than half (48%) of regional GPs reported patients could expect to be seen by a specialist within 2 weeks of referral, compared to 70% of metropolitan GPs (p = 0.001). Most metropolitan GPs stated they would refer a patient with suspected HNC to a surgeon subspecialising in HNC. Regional GPs were split between ear, nose, and throat (ENT) and general surgeons. Availability of services was the most common factor influencing referral practices for regional GPs, whereas for metropolitan GPs, this was the patient's symptoms. Awareness of government resources for cancer referrals was generally low. DISCUSSION: Regional GPs report patients with HNC are less likely to be seen by a specialist within optimal time frames compared to metropolitan GPs. Respondents reported different barriers to early referral of patients with suspected HNC, with regional GPs more often citing system-level factors while metropolitan GPs more often cited patient-level factors. CONCLUSION: Evaluating service provision and uptake with respect to community need, and addressing of barriers to implementation, may minimise unwarranted clinical variation.


Assuntos
Clínicos Gerais , Neoplasias , Austrália , Estudos Transversais , Humanos , Encaminhamento e Consulta , Inquéritos e Questionários
9.
Eur Arch Otorhinolaryngol ; 278(4): 1209-1222, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32696251

RESUMO

PURPOSE: The purpose of this study is to assess the general course of acoustic, patient rated, and clinician-rated voice outcomes from pre- up to 12 months post total laryngectomy. METHODS: Patients admitted to a total laryngectomy in five participating hospitals in Australia and The Netherlands were included. Assessments took place at pre-, 3 months, 6 months, and 12 months post-surgery. Voice outcomes are evaluated with the Acoustic Voice Quality Index (AVQI), perceptual scales, and patient-reported outcome measures including VHI-10 and EQ-5D-5L. Statistical analyses include descriptive statistics, t tests (pre- to 6 months post-surgery), Linear Mixed Effect models. RESULTS: The study included 43 participants. A significant worsening of AVQI is seen from pre- to post-surgery evaluated with t test (p < 0.001). The Linear Mixed Effect model confirmed Time as a significant factor in predicting AVQI score (p ≤ 0.001), as well as perceptual rated voice quality by the clinician (p = 0.015) and patient-reported perceptual rated voice quality (p = 0.002). No statistical significance was found in VHI-10 scores over time. CONCLUSION: Successful TE-speech was achieved in most participants, some had to rely on augmentative alternative communication methods. Patient-reported outcomes indicate acceptance of the condition and sufficient coping in the long term. However, acoustic rated voice quality is abnormal at all post-surgery time-points. AVQI proved to be a useful instrument to evaluate TE-speech. There is a need for validation and determination of cut-off values for VHI-10 and AVQI for use in TE-speech.


Assuntos
Disfonia , Laringectomia , Austrália , Humanos , Países Baixos , Estudos Prospectivos , Acústica da Fala , Medida da Produção da Fala
10.
Eur Respir J ; 55(1)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31601716

RESUMO

BACKGROUND AND AIM: Hypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severity via genioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNS via a small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system. METHODS: This prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea-hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, number NCT03048604. RESULTS: 22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m-2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h-1, a mean change of 10.8 events·h-1 (p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h-1, a mean change of 9.3 events·h-1 (p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period. CONCLUSIONS: Bilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.


Assuntos
Nervo Hipoglosso , Apneia Obstrutiva do Sono , Adulto , Austrália , Feminino , França , Humanos , Masculino , Estudos Prospectivos , Qualidade de Vida , Apneia Obstrutiva do Sono/terapia , Resultado do Tratamento
11.
Ann Surg Oncol ; 27(8): 2840-2845, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32072378

RESUMO

BACKGROUND: Soft tissue metastases (STMs) are reported to predict worse prognosis than extra-nodal extension (ENE) in metastatic head and neck cutaneous squamous cell carcinoma. This study aimed to update the authors' previous analysis of STM in a larger series. METHODS: The study analyzed 535 cases of consecutive cSCC metastatic to the parotid and/or neck treated by primary surgical resection between 1987 and 2007. A Cox proportional hazard model was used to determine the effect of STM, with adjustment for other relevant prognostic factors. Overall survival (OS) and disease-specific survival (DSS) were the primary end points. RESULTS: Of the 535 patients, 275 (51.4%) had STM. After adjustment for the effects of age, tumor location, number of metastatic deposits, and adjuvant radiotherapy, both STM (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.08-2.22; p = 0.018) and ENE (HR, 1.56; 95% CI 1.10-2.22; p = 0.013) were shown to be independent predictors of reduced OS, with similar size of effect. CONCLUSION: In metastatic cSCC of the head and neck, STM is an independent predictor of reduced survival and has an impact on survival similar to that of ENE.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/cirurgia , Humanos , Metástase Linfática , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
12.
J Surg Oncol ; 122(8): 1755-1760, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32926758

RESUMO

BACKGROUND: The treatment of advanced cutaneous head and neck cutaneous squamous cell carcinomas (HNcSCC) results in significant morbidity. Recently, immune checkpoint inhibitor treatment has been approved for DNA mismatch repair (MMR) deficient patients in a histology-agnostic manner. This study aims to evaluate the incidence of MMR deficiency in advanced HNcSCC and its association with clinicopathologic factors. METHODS: The cohort included 176 consecutive HNcSCC cases treated with curative intent. Immunohistochemistry for MMR proteins (hMLH1, hMSH2, hMSH6, and hPMS2) was performed. Clinicopathological and survival data was collected prospectively. RESULTS: The incidence of MMR protein deficiency was 9.1%. There was no association between age, incidence of metachronous malignancies, clinicopathological factors, or survival outcomes. CONCLUSION: A higher incidence of MMR deficiency was observed in this cohort of advanced HNcSCC. The lack of association with young age at onset or increased incidence of metachronous malignancies suggests that MMR deficiency is likely to be sporadic in HNcSCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/epidemiologia , Neoplasias Colorretais/epidemiologia , Reparo de Erro de Pareamento de DNA , Enzimas Reparadoras do DNA/metabolismo , Síndromes Neoplásicas Hereditárias/epidemiologia , Neoplasias Cutâneas/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Idoso , Austrália/epidemiologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Síndromes Neoplásicas Hereditárias/metabolismo , Síndromes Neoplásicas Hereditárias/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
13.
Am J Otolaryngol ; 41(1): 102323, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31732305

RESUMO

OBJECTIVE: Cadaveric experiments and more recently clinical data have demonstrated that patients with vertical height discrepancy between their arytenoids experience poorer voice outcomes in patients with unilateral vocal cord palsy (UVP) after medialisation laryngoplasty. However, the presence or severity of height discrepancy in normal patients without UVP has not yet been clearly defined. STUDY DESIGN: Case-control study. SETTING: Tertiary Australian hospitals. SUBJECTS AND METHODS: A retrospective review was performed on patients who underwent high computed tomography imaging of the neck. Scans were assessed for discrepancy in arytenoid vertical height discrepancy and compared to a cohort with known UVP. RESULTS: 44 normal patients (50% female, mean age 57.6 ±â€¯14.8 years) were compared to 23 patients with UVP (43.4% female, mean age 52.3 ±â€¯14.9 years.) Normal patients were found to have a smaller height discrepancy compared to UVP patients (student's t-test,2.00 mm ±â€¯0.00 vs 2.39 mm ±â€¯0.72, p < .001.) CONCLUSION: This study suggests that discrepancy is pathologic, and it is plausible that this results in acoustic consequences.


Assuntos
Cartilagem Aritenoide/anatomia & histologia , Cartilagem Aritenoide/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Paralisia das Pregas Vocais/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales , Estudos Retrospectivos
14.
Ann Surg Oncol ; 26(13): 4481-4488, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31583542

RESUMO

BACKGROUND: Regional nodal metastases from cutaneous squamous cell carcinoma (cSCC) is strongly associated with a poor prognosis, but these metastases are difficult to predict clinically. Sentinel node biopsy (SNB) has been used for a wide range of malignancies to assess for regional nodal metastasis, but is not widely used for cSCC. METHODS: Patients presenting with high-risk cSCC of the head and neck with clinically N0 necks were offered SNB at the time of primary cSCC excision or secondary wide local excision. Patients with positive sentinel nodes were offered completion lymph node dissection, and all the patients were followed up at regular intervals for up to 5 years. RESULTS: In this study, 105 lesions underwent SNB, and 10 sentinel nodes (9.5%) were positive. In an additional five patients, regional recurrence developed after a negative sentinel node, with a total subclinical nodal metastasis rate of 14.3%. Nodal metastases were significantly associated with reduced disease-specific survival. The significant predictors of metastasis were four or more high-risk features or tumors with a concurrent invasion deeper than 5 mm and PNI. CONCLUSION: For high-risk cSCC, SNB is a safe and feasible staging technique. The total number of high risk features and certain combinations of high-risk features predicted metastasis better than individual high-risk features.


Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
15.
Mod Pathol ; 31(2): 275-287, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28984303

RESUMO

Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalin-fixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (<45 years). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Mutação , Neoplasias Cutâneas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Proteína Supressora de Tumor p53/genética , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Feminino , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-kit/genética , Receptor ErbB-4/genética , Proteínas de Ligação a Retinoblastoma/genética , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Ubiquitina-Proteína Ligases/genética
16.
Ann Surg Oncol ; 25(6): 1730-1736, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29352431

RESUMO

BACKGROUND: The American Joint Committee on Cancer (AJCC) uses the same nodal staging system for cutaneous and mucosal squamous cell carcinoma of the head and neck in its 8th edition (AJCC 8) despite differences in the etiology, risk factors, and clinical behavior of the two diseases. This study aims to evaluate the performance of the AJCC 8 nodal staging system by direct comparison of cutaneous (cSCC) versus oral squamous cell carcinoma (oSCC) patients. METHODS: Patients with metastatic cSCC (N = 382) and oSCC (N = 325) were identified from a prospective database (years 1987-2016). Multivariable analysis was performed using Cox proportional hazards competing risk model. To assess staging system performance, an explained variation measure (proportion of variation explained, PVE) as well as a discrimination measure (Harrell's concordance index, C-index) were used. RESULTS: Inclusion of extranodal extension (ENE) in AJCC 8 increased the proportion of patients in N3b category (48.7% in cSCC, 40.3% in oSCC). AJCC 8 stratified poorly with regards to risk of death from cSCC and oSCC and showed limited monotonicity of the nodal categories. Estimates of model performance revealed modest predictive capacity for overall survival (OS) and disease-specific survival (DSS) in oSCC (Harrell's C of 0.66 in both) and weak predictive capacity in cSCC (Harrell's C of 0.58 and 0.61, respectively). CONCLUSIONS: The AJCC 8 nodal staging system performs poorly in terms of stratifying survival by N category, especially in cSCC. The data indicate that cSCC merits an independent nodal staging system from that for mucosal SCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Linfonodos/patologia , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/secundário , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Carga Tumoral , Adulto Jovem
17.
J Surg Oncol ; 117(4): 765-772, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29049841

RESUMO

BACKGROUND: The 8th edition American Joint Committee on Cancer (AJCC8) provides the same nodal staging system for mucosal and cutaneous squamous cell carcinoma of the head and neck (HNcSCC) and includes extranodal extension (ENE) as an adverse prognostic criterion. This study evaluates the prognostic efficacy of the AJCC8 pathologic nodal staging system (pN) for HNcSCC. METHODS: Univariate analysis of 382 patients with metastatic HNcSCC staged according to both the 7th (AJCC7) and the 8th edition staging systems. RESULTS: The AJCC7 pN3 category was associated with reduced disease specific survival (DSS HR 5.49; 95% CI: 1.83-16.53; P = 0.002) and overall survival (OS HR 3.42; 95% CI: 1.54-7.58; P = 0.002) as compared with pN1. However, no difference was observed between pN1, pN2, and pN3 categories as defined by the AJCC8. Also, when comparing Stages III and IV as defined by AJCC8, there was no difference in DSS (HR 0.75; 95% CI: 0.34-1.67; P = 0.478) or OS (HR 0.88; 95% CI: 0.51-1.51; P = 0.648). CONCLUSION: The AJCC8 performed poorly as a prognostic indicator for patients with metastatic HNcSCC in this cohort. HNcSCC would benefit from a staging system that accounts for its unique biologic characteristics distinct from mucosal SCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Linfonodos/patologia , Neoplasias Cutâneas/patologia , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Carcinoma de Células Escamosas de Cabeça e Pescoço
19.
Cancer ; 123(11): 1949-1957, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28081302

RESUMO

BACKGROUND: Head and neck cancer (HNC) encompasses a diverse group of tumors, and thus providing appropriate and tailored information to patients before, during, and after treatment is a challenge. The objective of the current study was to characterize the experience and unmet needs of patients with HNC with regard to information and support provision. METHODS: A 28-question, cross-sectional survey was completed by patients treated for HNC at 1 of 4 institutions in New South Wales, Australia (Chris O'Brien Lifehouse and Liverpool, Westmead, and Wollongong hospitals). It consisted of the adapted Kessler Psychological Distress Scale and questions assessing information quality, quantity, and format. RESULTS: A total of 597 patients responded. The mean age of the patients was 58 years (range, 21-94 years) with 284 men and 313 women (1:1.1). The majority of patients reported information concerning the disease process (76%), prognosis (67%), and treatment (77%) was sufficient, and approximately 50% reporting having received little or no information regarding coping with stress and anxiety. A substantial percentage of patients reported receiving minimal information concerning psychosexual health (56%) or the availability of patient support groups (56%). The majority of patients preferred access to multiple modes of information delivery (72%), with the preferred modality being one-on-one meetings with a health educator (37%) followed by internet-based written information (19%). CONCLUSIONS: Patients with HNC are a diverse group, with complex educational and support needs. Patients appear to be given information regarding survivorship topics such as psychological well-being, patient support groups, and psychosexual health less frequently than information concerning disease and treatment. Verbal communication needs to be reinforced by accessible, well-constructed, written and multimedia resources appropriate to the patient's educational level. Cancer 2017;123:1949-1957. © 2017 American Cancer Society.


Assuntos
Adaptação Psicológica , Neoplasias de Cabeça e Pescoço/psicologia , Educadores em Saúde , Internet , Avaliação das Necessidades , Educação de Pacientes como Assunto , Grupos de Autoajuda , Apoio Social , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/psicologia , Estudos Transversais , Progressão da Doença , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales , Prognóstico , Saúde Reprodutiva , Estresse Psicológico/psicologia , Inquéritos e Questionários , Adulto Jovem
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