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1.
PLoS One ; 16(4): e0249099, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33826649

RESUMO

BACKGROUND: Epidemiological studies demonstrate associations between obstructive sleep apnea (OSA) and cancer incidence and mortality. The aim of this study was to measure OSA in women with breast (BC) or endometrial cancer (EC) and associations with clinico-pathological tumor variables. METHODS AND FINDINGS: In a cross sectional study, women with BC (12 months) or EC (3 months) post-diagnosis were recruited from cancer clinics. We collected demographic, anthropometric data, cancer stage, grade, histopathology and history of cancer treatment and all subjects had in-laboratory polysomnography. Sleepiness was assessed with the Epworth Sleepiness Scale (ESS). We compared anthropometric and polysomnographic data between cancer groups (unpaired t-tests), and assessed relationships between cancer characteristics and OSA variables (Fishers exact test). There were no significant differences between average age (BC:59.6±8.7 years(n = 50); EC:60.3±7.7 years(n = 37)), or ESS score (BC:6.4±4.4; EC 6.8±4.7; mean±SD; all p>0.2), however, BMI was higher in EC (BC: 29.7±7.9kgm-2; EC: 34.2±8.0 kgm-2; p<0.05). BC had longer sleep latency (BC:31.8±32minutes; EC:19.3±17.9 minutes), less Stage 3 sleep (BC:20.0±5.2%; EC:23.6±8.2%) and more REM sleep (BC:21.1±6.9%; EC: 16.6±5.7%), all p<0.05. EC had lower average awake and asleep oxygen saturation levels (BC: 95.6±1.3%; EC: 94.6±1.9% [awake]: BC: 94.8±2.1%; EC: 93.3±2.4% [asleep]; both p<0.05). Apnea-Hypopnea Index (AHI) (BC: 21.2(7.3-36.9) events/hr; EC: 15.7 (10-33.5) events/hour (median (interquartile range)) was not different p = 0.7), however, 58% and 57% of women with BC and EC respectively, had an AHI>15 events/hour. In this small sample size group, no significant associations (all p>0.1) were detected between OSA metrics and clinico-pathological tumor variables. CONCLUSION: In postmenopausal women with breast or endometrial cancer there is high prevalence of OSA, with no association with specific tumor characteristics detected. Recognition of the high prevalence of OSA in women with cancer is important to recognise as it may impact on surgical risk and quality of life.


Assuntos
Neoplasias da Mama/complicações , Neoplasias do Endométrio/complicações , Apneia Obstrutiva do Sono/epidemiologia , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias do Endométrio/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência
2.
JCO Precis Oncol ; 2: 1-14, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35135122

RESUMO

PURPOSE: Low-grade serous ovarian carcinoma (LGSC) responds poorly to chemotherapy and is characterized by activating mutations in the Ras sarcoma-mitogen-activated protein kinase (RAS-MAPK) pathway, including oncogenic BRAF. However, response to BRAF inhibitors is tumor-type specific. Significant improvement in survival is seen in patients with BRAF-mutant melanoma, but other cancer types, such as colorectal cancers, are generally less sensitive. We examined the frequency and characteristics of BRAF-mutated LGSC and described the response to treatment with BRAF inhibitors. PATIENTS AND METHODS: Mutations were assessed in LGSC (N = 65) by using targeted, exome, and whole-genome sequencing. Patient characteristics, treatment, and clinical outcome were assessed, and the median follow-up time was more than 5 years. BRAF inhibitors were trialed in two patients with a somatic BRAF V600E mutation: one patient received dabrafenib monotherapy and was monitored clinically, biochemically (cancer antigen [CA]-125 levels), and with positron emission tomography (PET) imaging. Expression of the BRAF V600E protein in this patient was assessed by immunohistochemistry. RESULTS: Among patients with LGSC, nine (13.8%) of 65 had a somatic BRAF mutation. Of the nine patients with BRAF mutation-positive LGSC, four experienced progressive disease that did not respond to conventional chemotherapy. Two of the patients experienced progression quickly and died as a result of disease progression, and two received targeted treatment. Two patients with BRAF V600E mutation received BRAF inhibitors at relapse and both achieved durable responses. CONCLUSION: BRAF mutations are not uncommon in patients with LGSC and should be routinely tested, because BRAF inhibitors can be an effective treatment for these patients. The results highlight the need for targeted treatment in this rare tumor type, and a prospective study is needed to formally assess the response rate and clinical benefit.

3.
Br J Cancer ; 116(9): 1218-1222, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28376081

RESUMO

BACKGROUND: Squamous cell scrotal carcinoma (SCSC) is an infrequent skin cancer associated historically with occupational carcinogens. Human papillomavirus (HPV) DNA has been associated with SCSC but there is no definitive proof of its oncogenic role. METHODS: Human papillomavirus-DNA and -E6*I mRNA were analysed in six invasive histologically typed SCSC. LCM-PCR was used to localise HPV DNA to tumour cells. P16INK4aand p53 expression were studied by immunohistochemistry. RESULTS: In three warty or basaloid SCSC HPV16-DNA and E6*I-mRNA were detected. LCM-PCR confirmed HPV16 was in p16INK4a-positive malignant cells. However, of three usual-type SCSC, all were HPV-negative and two expressed p53 protein but not p16INK4a. CONCLUSIONS: Human papillomavirus 16 was present in tumour cells and oncogenically active in basaloid and warty SCSC, whereas usual SCSC was HPV-negative and showed immunostaining, suggesting p53 mutation. The dual pathways of oncogenesis and relation between histological type of SCSC and HPV are similar to that in penile cancers.


Assuntos
Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Papillomavirus Humano 16/isolamento & purificação , Proteínas Oncogênicas Virais/biossíntese , Neoplasias Penianas/virologia , Proteínas Repressoras/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA Viral/isolamento & purificação , Regulação Neoplásica da Expressão Gênica , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Neoplasias Penianas/diagnóstico , Neoplasias Penianas/genética , Neoplasias Penianas/patologia , Proteínas Repressoras/genética , Proteína Supressora de Tumor p53/genética
4.
Br J Cancer ; 115(10): 1179-1185, 2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27764842

RESUMO

BACKGROUND: To determine the minimum survival benefits that patients, and their clinicians, judged sufficient to make adjuvant chemotherapy (ACT) worthwhile, in addition to pelvic radiotherapy, for women with high risk and advanced stage endometrial cancer. METHODS: Eighty-three participants in the PORTEC-3 trial completed a time trade-off questionnaire before and after adjuvant therapy; 44 of their clinicians completed it once only. The questionnaire used four hypothetical scenarios including baseline survival times without ACT of 5 and 8 years, and baseline survival rates at 5 years without ACT of 50 and 65%. RESULTS: Over 50% of patients judged an extra 1 year of survival time or an extra 5% in survival rate sufficient to make ACT worthwhile. Over 50% of clinicians judged an extra 1 year of survival time, or an extra 10% in survival rate, sufficient to make ACT worthwhile. Compared with patients, clinicians required similar survival time benefits (medians both 1 year, P=0.4), but larger survival rate benefits (medians 8.5% vs 5%, P=0.03), and clinicians' preferences varied less (IQR 0.5-1.5 years vs 0.4-2 years, P=0.0007; 5-10% vs 1-13%, P=0.004). Patients' preferences changed over time for the survival rate scenarios depending on whether they had ACT or not (change in median benefit - 3 months vs 2.5 months respectively, P=0.028). There were no strong predictors of patients' or clinicians' preferences. CONCLUSIONS: Patients and clinicians judged moderate survival benefits sufficient to make ACT worthwhile after pelvic radiotherapy for endometrial cancer. These benefits are larger than those judged sufficient by patients with breast or colon cancers, but similar to those judged sufficient by patients with lung or ovarian cancers.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/terapia , Pessoal de Saúde/psicologia , Preferência do Paciente/psicologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/métodos , Estudos de Coortes , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/mortalidade , Neoplasias do Colo/terapia , Terapia Combinada/métodos , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Radioterapia/métodos , Inquéritos e Questionários , Taxa de Sobrevida
5.
Clin Cancer Res ; 20(24): 6618-30, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25316818

RESUMO

PURPOSE: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies. EXPERIMENTAL DESIGN: We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling. RESULTS: We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC. CONCLUSION: Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents.


Assuntos
Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas ras/genética , Proteínas ras/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Análise por Conglomerados , Estudos de Coortes , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Variações do Número de Cópias de DNA , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Polimorfismo de Nucleotídeo Único , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Transdução de Sinais , Adulto Jovem
6.
Eur J Cancer ; 49(16): 3450-61, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23886586

RESUMO

BACKGROUND: Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. METHODS: Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). RESULTS: Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). CONCLUSION: Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide.


Assuntos
Carcinoma in Situ/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Neoplasias Vulvares/virologia , Adulto , Algoritmos , Biomarcadores Tumorais/análise , Carcinoma in Situ/química , Carcinoma in Situ/patologia , Estudos Transversais , Inibidor p16 de Quinase Dependente de Ciclina/análise , Sondas de DNA de HPV , Feminino , Genótipo , Testes de DNA para Papilomavírus Humano , Humanos , Imuno-Histoquímica , Modelos Logísticos , Pessoa de Meia-Idade , Invasividade Neoplásica , Papillomaviridae/classificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Estudos Retrospectivos , Regulação para Cima , Neoplasias Vulvares/química , Neoplasias Vulvares/patologia
7.
Sex Transm Infect ; 88(7): 517-21, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22645393

RESUMO

OBJECTIVES: To obtain health-related quality of life valuations (ie, utilities) for human papillomavirus (HPV)-related cancer health states of vulval, vaginal, penile, anal and oropharyngeal cancers for use in modelling cost-effectiveness of prophylactic HPV vaccination. METHODS: Written case descriptions of each HPV-associated cancer describing the 'average' patient surviving after the initial cancer diagnosis and treatment were developed in consultation with oncology clinicians. A general overview, standard gamble questionnaire for each health state and a quiz was conducted in 120 participants recruited from the general population. RESULTS: In the included population sample (n=99), the average age was 43 years (range = 18-70 years) with 54% men, 44% never married/43% married, 76% education beyond year 12 and 39% employed full-time. The utility values for the five health states were 0.57 (95% CI 0.52 to 0.62) for anal cancer, 0.58 (0.53 to 0.63) for oropharyngeal cancer, 0.59 (0.54 to 0.64) for vaginal cancer, 0.65 (0.60 to 0.70) for vulval cancer and 0.79 (0.74 to 0.84) for penile cancer. Participants demonstrated a very good understanding of the symptoms, diagnosis and treatment of these cancers with a mean score of 9 (SD=1.1) on a 10-item quiz. CONCLUSIONS: This study provides utility estimates for the specific HPV-related cancers of vulval, vaginal, penile, anal and oropharyngeal cancers valued by a general population sample using standard gamble. The results demonstrate considerable quality of life impact associated with surviving these cancers that will be important to incorporate into modelling cost-effectiveness of prophylactic HPV vaccination in different populations.


Assuntos
Neoplasias do Ânus/psicologia , Neoplasias Orofaríngeas/psicologia , Infecções por Papillomavirus/complicações , Neoplasias Penianas/psicologia , Qualidade de Vida , Neoplasias Vaginais/psicologia , Neoplasias Vulvares/psicologia , Adolescente , Adulto , Idoso , Neoplasias do Ânus/patologia , Neoplasias do Ânus/prevenção & controle , Neoplasias do Ânus/virologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/prevenção & controle , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Neoplasias Penianas/patologia , Neoplasias Penianas/prevenção & controle , Neoplasias Penianas/virologia , Inquéritos e Questionários , Neoplasias Vaginais/patologia , Neoplasias Vaginais/prevenção & controle , Neoplasias Vaginais/virologia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/prevenção & controle , Neoplasias Vulvares/virologia , Adulto Jovem
8.
Aust N Z J Obstet Gynaecol ; 52(1): 23-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21951130

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a serious complication following gynaecological surgery, with malignancy placing patients at an even greater risk. AIMS: To review the incidence of VTE following gynaecological surgery for suspected or confirmed malignancy with respect to prophylactic modalities and to assess the incidence and associated risk factors for bleeding complications. METHODS: A retrospective cohort study was undertaken between 2001 to 2006 on 1363 women undergoing surgery for suspected or confirmed gynaecological malignancy. Data on demographic details, diagnosis, radiotherapy/chemotherapy treatment, operative details, and hospital length of stay (LOS), thromboprophylaxis, in-hospital and 3-month readmission rates for deep vein thrombosis (DVT) and/or pulmonary embolism (PE) were collected. RESULTS: Median age was 54 years (IQR 44-66) and hospital LOS 7 days (IQR 5-9). 51.6% had a new malignancy and 33.0% benign disease. All in-hospital VTE events (0.4%; 95% CI 0.2-1.0%) occurred in women with advanced malignancy. VTE rate was 1.5% (95% CI 1.0-2.3%) at 3 months. In-hospital and 3-month non fatal PE occurred in 0.4% (95% CI 0.2-0.9%) and 1.1% (95% CI 0.7-1.8%) respectively, with a fatal PE rate of 0.1% (95% CI 0.04-0.5%). Malignancy (OR 10.3; 95% CI 1.3-80.6; P = 0.026) and duration of surgery (OR 2.1; 95% CI 1.4-3.2; P = 0.001) significantly increased bleeding risk. CONCLUSIONS: In-hospital VTE risk is higher following gynaecological surgery for malignancy than for benign disease, despite the use of thromboprophylaxis. Given the higher non fatal PE rate after discharge and increasing trend towards shorter hospital LOS, extended prophylaxis in these patients should be considered.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos em Ginecologia , Heparina de Baixo Peso Molecular/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Adulto , Estudos de Coortes , Feminino , Neoplasias dos Genitais Femininos/complicações , Humanos , Incidência , Pessoa de Meia-Idade , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/etiologia , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle
9.
PLoS One ; 6(3): e17617, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21423607

RESUMO

Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute to the development of ovarian cancer.


Assuntos
Epitélio/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos/genética , Estudos de Associação Genética , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Animais , Estudos de Coortes , Epitélio/patologia , Ciclo Estral/genética , Feminino , Dosagem de Genes/genética , Humanos , Imuno-Histoquímica , Camundongos , Pessoa de Meia-Idade , Mutação/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias Ovarianas/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Reprodutibilidade dos Testes
11.
Maturitas ; 65(3): 205-9, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20036786

RESUMO

Prophylactic HPV vaccines have demonstrated high efficacy against a range of HPV related diseases. They have been widely adopted as population health interventions in many jurisdictions and their routine use has been endorsed by the WHO. The development of these vaccines comes after an increased understanding of the natural history and epidemiology of HPV infection and disease in both males and females. Persistent HPV infection with oncogenic types induces malignant transformation in a range of epithelia including the cervix, anogenital regions, the penis and a number of head and neck sites. In relation to HPV disease prevention in the post-reproductive years, most infections occur soon after commencement of sexual activity but new infections do occur throughout the age spectrum. This reduces the likely impact of prophylactic vaccines in this population. The major impact on HPV related disease in this age group will come from advances in screening and early detection of HPV and neoplastic precursors. The most appropriate prevention for any individual man or women in this age group will be an individualised combination of vaccination, screening and early detection depending on the individual's own circumstances.


Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero/prevenção & controle , Diagnóstico Precoce , Feminino , Humanos , Masculino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Comportamento Sexual , Neoplasias Urogenitais/diagnóstico , Neoplasias Urogenitais/etiologia , Neoplasias Urogenitais/prevenção & controle , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/etiologia
12.
Aust N Z J Obstet Gynaecol ; 49(4): 419-25, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19694700

RESUMO

OBJECTIVE: To evaluate the outcome in patients with uterine papillary serous carcinoma (UPSC). METHODS: A retrospective review of women treated for UPSC between 1995 and 2006 in Westmead Hospital, Sydney. The patients were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy and surgical staging. The majority of the patients had platinum-based adjuvant chemotherapy and radiotherapy. Sites of initial recurrence were documented. Overall survival (OS) and progression free survival (PFS) were estimated using Kaplan-Meier method. Univariate and multivariate analysis was performed using Cox regression analysis to test the effects of multiple prognostic factors on survival. RESULTS: Two-year and five-year OS was 65% and 43%. The median OS was 39 months. Two-year and five-year PFS was 60% and 35%. Macroscopic residual disease at the completion of surgery was the only significant prognostic factor associated with worse OS on both univariate and multivariate analysis (P < 0.001). The median OS was only 11 months if patients had macroscopic residual disease, and all patients died within 18 months despite adjuvant therapies. Twenty-one patients relapsed. The site(s) of initial recurrence were: vagina (five patients), pelvic lymph nodes (four patients), abdomen (11 patients), para-aortic lymph nodes (six patients), inguinal lymph nodes (two patients) and distant metastases in seven patients. Only one of 16 patients who received vaginal brachytherapy failed in the vagina, but three of seven patients who received external beam pelvic radiotherapy failed in the vagina. CONCLUSION: We recommend optimal cytoreduction surgery with the aim of leaving no macroscopic disease at the end of the operation. Vaginal brachytherapy should be considered as a component of adjuvant radiotherapy. Abdominal failure was the commonest mode of failure in our cohort of patients.


Assuntos
Cistadenocarcinoma Papilar/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Recidiva Local de Neoplasia/patologia , Neoplasias Uterinas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Austrália , Quimioterapia Adjuvante , Terapia Combinada/métodos , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Papilar/terapia , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Radioterapia Adjuvante , Estudos Retrospectivos , Falha de Tratamento , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia
13.
Clin Cancer Res ; 14(21): 6924-32, 2008 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-18980987

RESUMO

PURPOSE: The standard of care for ovarian cancer includes platinum-based chemotherapy. It is not possible, however, to predict clinical platinum sensitivity or to design rational strategies to overcome resistance. We used a novel approach to identify altered gene expression associated with high sensitivity to cisplatin, to define novel targets to sensitize tumor cells to platins and ultimately improve the effectiveness of this widely used class of chemotherapeutics. EXPERIMENTAL DESIGN: Using differential display PCR, we identified genes differentially expressed in a mutagenized cell line with unusual sensitivity to cisplatin. The most highly differentially expressed gene was selected, and its role in determining cisplatin sensitivity was validated by gene transfection and small interfering RNA (siRNA) approaches, by association of expression levels with cisplatin sensitivity in cell lines, and by association of tumor expression levels with survival in a retrospective cohort of 71 patients with serous ovarian adenocarcinoma. RESULTS: The most highly differently expressed gene identified was ANKRD1, ankyrin repeat domain 1 (cardiac muscle). ANKRD1 mRNA levels were correlated with platinum sensitivity in cell lines, and most significantly, decreasing ANKRD1 using siRNA increased cisplatin sensitivity >2-fold. ANKRD1 was expressed in the majority of ovarian adenocarcinomas tested (62/71, 87%), and higher tumor levels of ANKRD1 were found in patients with worse outcome (overall survival, P=0.013). CONCLUSIONS: These findings suggest that ANKRD1, a gene not previously associated with ovarian cancer or with response to chemotherapy, is associated with treatment outcome, and decreasing ANKRD1 expression, or function, is a potential strategy to sensitize tumors to platinum-based drugs.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Cisplatino/uso terapêutico , Proteínas Musculares/genética , Proteínas Nucleares/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Proteínas Repressoras/genética , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Animais , Antineoplásicos/uso terapêutico , Células CHO , Linhagem Celular Tumoral , Cricetinae , Cricetulus , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Neoplasias Ovarianas/mortalidade , Análise de Sequência de Proteína , Análise de Sobrevida
15.
J Psychosoc Oncol ; 25(4): 89-104, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18032267

RESUMO

Cancer patients and their partners experience elevated distress and unmet supportive care needs at the time of treatment, however, their ongoing needs have not been adequately described. This qualitative study explores the needs of disease-free cancer survivors and their partners using semi-structured telephone interviews. A convenience sample of 25 key informants' identified needs in the domains of information, health care, physical functioning, relationships, emotions, socio-economic issues, expectations and life perspective; and the positive outcomes are widely reported. The identification of unique needs of survivors and partners supports the development of supportive care measures to specifically assess ongoing care need in these populations.


Assuntos
Depressão/etiologia , Depressão/psicologia , Neoplasias/diagnóstico , Neoplasias/psicologia , Apoio Social , Sobreviventes/psicologia , Adulto , Idoso , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
16.
Sex Health ; 4(3): 165-75, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17931529

RESUMO

BACKGROUND: The cost-effectiveness of adding a human papillomavirus (HPV) vaccine to the Australian National Cervical Screening Program compared to screening alone was examined. METHODS: A Markov model of the natural history of HPV infection that incorporates screening and vaccination was developed. A vaccine that prevents 100% of HPV 16/18-associated disease, with a lifetime duration of efficacy and 80% coverage offered through a school program to girls aged 12 years, in conjunction with current screening was compared with screening alone using cost (in Australian dollars) per life-year (LY) saved and quality-adjusted life-year (QALY) saved. Sensitivity analyses included determining the cost-effectiveness of offering a catch-up vaccination program to 14-26-year-olds and accounting for the benefits of herd immunity. RESULTS: Vaccination with screening compared with screening alone was associated with an incremental cost-effectiveness ratio (ICER) of $51 103 per LY and $18 735 per QALY, assuming a cost per vaccine dose of $115. Results were sensitive to assumptions about the duration of vaccine efficacy, including the need for a booster ($68 158 per LY and $24 988 per QALY) to produce lifetime immunity. Accounting for herd immunity resulted in a more attractive ICER ($36 343 per LY and $13 316 per QALY) for girls only. The cost per LY of vaccinating boys and girls was $92 052 and the cost per QALY was $33 644. The cost per LY of implementing a catch-up vaccination program ranged from $45 652 ($16 727 per QALY) for extending vaccination to 14-year-olds to $78 702 ($34 536 per QALY) for 26-year-olds. CONCLUSIONS: These results suggest that adding an HPV vaccine to Australia's current screening regimen is a potentially cost-effective way to reduce cervical cancer and the clinical interventions that are currently associated with its prevention via screening alone.


Assuntos
Técnicas de Apoio para a Decisão , Papillomavirus Humano 16 , Vacinação em Massa/economia , Infecções por Papillomavirus/economia , Vacinas contra Papillomavirus/economia , Neoplasias do Colo do Útero/economia , Adolescente , Austrália/epidemiologia , Análise Custo-Benefício , Feminino , Humanos , Cadeias de Markov , Vacinação em Massa/estatística & dados numéricos , Programas Nacionais de Saúde/economia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle
17.
Psychooncology ; 16(11): 1039-45, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17352005

RESUMO

AIMS: To explore views on the ideal structure and process of support groups for cancer patients. PATIENTS AND METHODS: From 184 cancer support groups identified in NSW, Australia, 50 were randomly selected within strata of five variations in group structure: homogenous versus heterogenous participants; urban versus rural; community versus hospital setting, leader with cancer experience or not; and with professional training or not. Four hundred and seventy-six group members completed a questionnaire. RESULTS: Participants valued being with others like them, gaining information about cancer and having an effective leader. Groups were seen to be currently failing people from culturally and linguistically diverse backgrounds, and links with oncology health professionals were inadequate. Few clear preferences for structure were expressed, except for the non-exclusion of those with a poor prognosis. Patients tended to prefer the structure of their own group, but patients longer since diagnosis, those with better informal support and carers preferred to meet in the community setting, while men with prostate cancer preferred a medical setting. CONCLUSIONS: Some suggestions for group structure and process can be made on the basis of these findings; however, individual variation suggests that a needs analysis should be made by individual groups.


Assuntos
Cuidadores/psicologia , Avaliação das Necessidades , Neoplasias/psicologia , Satisfação do Paciente , Grupos de Autoajuda/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Feminino , Processos Grupais , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , New South Wales
18.
Gynecol Oncol ; 104(2): 381-9, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17027072

RESUMO

OBJECTIVES: To assess the long-term psychosocial outcomes and supportive care needs of gynecologic cancer survivors. METHODS: Women who had received care in a tertiary-based gynecologic cancer center 1-8 years earlier and who were disease-free were invited to complete a mailed self-report questionnaire to assess psychosocial outcomes and supportive care needs. RESULTS: In total, 199 survivors participated in the study. Survivors reported normal quality of life and relationship adjustment although functioning was at the lower end of the range; over two-thirds (68%) reported positive outcomes. However, nearly one-third (29%) reported clinical levels of anxiety and the most frequently endorsed need concerned fear of disease recurrence (24%). About one-fifth (19%) reported symptoms that indicated posttraumatic stress disorder (PTSD) and this rose to close to one-third (29%) for survivors of advanced stage disease. Nearly 90% of survivors reported supportive care needs and the diagnosis of anxiety or PTSD resulted in a four-fold increase in unmet needs. Needs most frequently concerned "existential survivorship" (e.g., spiritual beliefs, decision making, the meaning of life) and "comprehensive cancer care" (e.g., team care, communication, local health care services). Years since diagnosis was not related to distress or need levels. CONCLUSIONS: All members of the care team need to be aware that significant psychosocial morbidity may occur many years after the successful treatment of a gynecologic malignancy and may be associated with elevated supportive care needs. Comprehensive and extended supportive care services are required to address anxiety and trauma responses and investigate strategies to meet ongoing needs in order to improve long-term psychosocial outcomes.


Assuntos
Neoplasias dos Genitais Femininos/psicologia , Cuidados Paliativos , Apoio Social , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Intervalo Livre de Doença , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Pessoa de Meia-Idade , Psicologia
19.
Support Care Cancer ; 15(5): 515-23, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17120068

RESUMO

GOALS OF THE WORK: A significant proportion of breast cancer patients experience psychosocial morbidity after treatment, although their longer-term outcomes and supportive care service needs have not been comprehensively documented. The aim of this study was to identify longer-term outcomes and supportive care needs in disease-free breast cancer survivors. MATERIALS AND METHODS: One hundred seventeen patients who had been diagnosed with breast cancer 2-10 years earlier completed questionnaires to assess psychosocial outcomes including supportive care needs, psychological distress, and quality of life (QoL). MAIN RESULTS: QoL and depression scores were consistent with community rates although anxiety scores were higher. Approximately two thirds of survivors reported at least one unmet need, most frequently concerning existential survivorship issues, thereby highlighting the unique needs of survivors. Years since diagnosis was not correlated with need levels. Survivors classified as clinically anxious reported over three times as many unmet needs and survivors classified as depressed reported over two and a half times as many unmet needs. Positive outcomes were frequently reported. CONCLUSIONS: The findings have direct clinical relevance: irrespective of years since diagnosis, comprehensive and extended supportive care services are required to identify breast cancer survivors in need of supportive care interventions and remediate high levels of anxiety.


Assuntos
Neoplasias da Mama , Apoio Social , Sobreviventes/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , New South Wales , Inquéritos e Questionários
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