RESUMO
Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre-treatment sera from 460 patients with stage IIB-IIIC melanoma were analyzed for MMP-8. The patients were randomized after surgery to adjuvant IFN-α for 12 or 24 months (n = 313) or observation only (n = 147). The median serum MMP-8 level was used to classify the patients into a low MMP-8 (n = 232) and a high MMP-8 (n = 228) group. In the high MMP-8 subgroup, IFN-α therapy significantly improved relapse-free survival (RFS). RFS was 36.8 months in patients with high MMP-8 levels receiving IFN-α therapy, whereas RFS for those with high MMP-8 levels with observation only was 10.6 months (P = 0.027). Median overall survival for patients with high MMP-8 and observation only was 36.7 versus 71.7 months in those receiving IFN-α (P = 0.13). In a multivariate model, IFN-α therapy was a significant predictor of favorable RFS (HR 0.74; 95 % CI 0.55-0.99; P = 0.048), after adjustment for pre-treatment MMP-8 (HR 1.17; 95 % CI 0.88-1.55; P = 0.28), gender (HR 1.16; 95 % CI 0.86-1.56; P = 0.32), age (HR 1.00; 95 % CI 1.00-1.02; P = 0.12), ulceration (HR 1.09; 95 % CI 0.81-1.46; P = 0.58), and the presence of node metastases (HR 1.36; 95 % CI 1.17-1.58; P < 0.0001). In conclusion, patients with high serum MMP-8 levels may benefit from adjuvant IFN-α therapy, but this observation should be further investigated.
Assuntos
Antineoplásicos/uso terapêutico , Interferon-alfa/uso terapêutico , Metaloproteinase 8 da Matriz/sangue , Melanoma/sangue , Melanoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Interferon alfa-2 , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: This study aims to test the effectiveness on psychosocial outcomes of electronic feedback knowledge of radiotherapy intervention (e-Re-Know) for breast cancer patients. METHOD: Randomized controlled trial in one university hospital in Finland was carried out. Breast cancer patients (n = 126) in the radiotherapy (RT) department were randomly assigned into two groups: intervention (the e-Re-Know and standard education) and control group (standard education). The e-Re-Know intervention consisted of e-feedback after response to the knowledge test delivered by e-mail. Instruments were completed before commencing first RT (M1), after concluding last RT (M2) and 3 months after last RT (M3). The main outcomes were anxiety and QOL. RESULTS: Compared with the control group, the patients in the intervention group reported a marginally significant improvement in anxiety and significant improvement in QOL over time. CONCLUSION: The e-Re-Know seems to have positive effects on psychosocial outcomes for breast cancer patients. They might gain additional value from the e-Re-Know over a longer time period. Further research needs to focus more on development of e-feedback in patient education.
Assuntos
Ansiedade/psicologia , Neoplasias da Mama/radioterapia , Correio Eletrônico , Conhecimento Psicológico de Resultados , Educação de Pacientes como Assunto/métodos , Adolescente , Adulto , Idoso , Neoplasias da Mama/psicologia , Feminino , Finlândia , Humanos , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Método Simples-Cego , Inquéritos e Questionários , Adulto JovemRESUMO
The growing number of women with breast cancer and their unmet knowledge expectations of radiotherapy pose a challenge to develop effective electronic patient education. Development efforts should be focused on e-feedback on knowledge because of its positive effects. In this study, we evaluated how an e-feedback knowledge intervention (e-Re-Know) before first radiotherapy improves breast cancer patients' knowledge of radiotherapy and identified the associations with patients' characteristics. Women with breast cancer (n = 128) were randomized prior to the radiotherapy period either to the intervention group or control group. The outcome measured three months after the radiotherapy period was knowledge level of radiotherapy. The increase in knowledge level was higher in the intervention group after adjustment for baseline knowledge level, and a significantly higher increase in knowledge level was seen in one subdomain, side-effect self-care, compared to the control group. The results of this study indicate that the e-Re-Know can be used in patient education to support empowerment. Future research should target new applications of e-Re-Know available on the Internet for those interested in the subject.
RESUMO
We studied the association of the immunohistochemical bcl-2 expression in Libyan breast cancer with clinicopathological variables and patient outcome. Histological samples from 170 previously untreated primary Libyan breast carcinoma patients were examined. In immunohistochemistry, the NCL-L-bcl-2-486 monoclonal antibody was used. Positive expression of bcl-2 was found in 106 patients (62.4 %). The bcl-2 expression was significantly associated with estrogen receptor (p<0.0001) and progesterone receptor positive tumors (p=0.002), small tumor size (p<0.0001), low tumor grade (p<0.0001), negative axillary lymph nodes (p<0.0001), early stages (p=0.001), and low risk of metastasis (p<0.0001). Positive expression was also associated with older patients (>50 years; p=0.04). Histological subtypes and family history of breast cancer did not have significant relationship with bcl-2. Patients with positive expression of bcl-2 had lower recurrence rate than bcl-2-negative patients and better survival after median follow-up of 47 months. Patients with high bcl-2 staining were associated with the best survival. The role of bcl-2 as an independent predictor of disease-specific survival was assessed in a multivariate survival (Cox) analysis, including age, hormonal status, recurrence, histological grade, and clinical stage variables. Bcl-2 (p<0.0001) and clinical stage (p=0.016) were independent predicators of disease-specific survival. For analysis of disease-free survival, the same variables were entered to the model and only bcl-2 proved to be an independent predictor (p=0.002). Patients with positive expression of bcl-2 were associated with low grade of malignancy, with lower recurrence rate, with lower rate of death, and with longer survival time. Bcl-2 is an independent predictor of breast cancer outcome, and it provides useful prognostic information in Libyan breast cancer. Thus, it could be used with classical clinicopathological factors to improve patient selection for therapy.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Recidiva Local de Neoplasia/mortalidade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundário , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Líbia , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Adulto JovemRESUMO
Clinical staging and histological grading after surgery have been the "gold standard" for predicting prognosis and planning for adjuvant therapy of colorectal cancer (CRC). With the recent development of molecular markers, it has become possible to characterize tumors at the molecular level. This is important for stage II and III CRCs, in which clinicopathological features do not accurately predict heterogeneity, e.g., in their tumor response to adjuvant therapy. In the present study, archival samples from 141 patients with stage I, II, III, or IV CRC treated during 1981-1990 at Turku University Hospital (Finland) were used (as microarray blocks) to analyze MUC2 expression by immunohistochemistry. Altogether, 49.7 % of all tumors were positive for MUC2. There was no significant correlation between MUC2 expression and age (P < 0.499), tumor invasion (P < 0.127), tumor staging (P < 0.470), histological grade (P < 0.706), lymph node involvement (P < 0.854), or tumor metastasis (P < 0.586). However, loss of MUC2 expression was significantly associated with disease recurrence (P < 0.031), tumor localization (P < 0.048), and with borderline significance with gender (P < 0.085). In univariate (Kaplan-Meier) survival analysis, positive MUC2 significantly predicted longer disease-free survival (DFS) and disease-specific survival (DSS) as well. However, in multivariate (Cox) survival analysis, MUC2 lost its power as an independent predictor of DFS and DSS. Our results implicate the value of MUC2 expression in predicting disease recurrence and long-term survival in CRC.
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Adenocarcinoma/mortalidade , Neoplasias Colorretais/mortalidade , Mucina-2/metabolismo , Recidiva Local de Neoplasia/mortalidade , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Idoso , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Análise Serial de TecidosRESUMO
BACKGROUND: Regorafenib inhibits VEGF receptors 1, 2, and 3 and PDGF receptors like other anti-angiogenic tyrosine-kinase inhibitors approved for treatment of advanced renal-cell cancer. Regorafenib also inhibits other potentially important angiogenic kinases like TIE2, activation of which is thought to be important in tumour escape mechanisms. This phase 2, open-label, non-randomised study assessed the safety and efficacy of the multikinase inhibitor regorafenib for treatment of renal-cell carcinoma. METHODS: Patients were recruited from 18 academic oncology centres across Europe and USA. Patients with previously untreated metastatic or unresectable clear-cell renal-cell carcinoma received oral regorafenib (160 mg per day) in repeating cycles of 3 weeks on, 1 week off until disease progression or until patients met the criteria for removal from study. The primary efficacy endpoint was the proportion of patients who achieved an objective overall response, assessed in all patients who were evaluable for response. The trial has finished. This trial is registered with ClinicalTrials.gov, number NCT00664326. FINDINGS: The study was done between April 30, 2008, and June 1, 2011. We screened 64 patients, of whom 49 received regorafenib. Median duration of treatment was 7·1 months (range 0·7-34·4, IQR 2·5-18·0) and at the time of data cutoff, six patients (12%) were still receiving treatment. 48 patients were assessable for tumour response. 19 patients (39·6%, 90% CI 27·7-52·5) had an objective response, all of which were partial responses. Drug-related adverse events occurred in 48 patients (98%) and drug-related serious adverse events in 17 (35%). Grade 3 drug-related adverse events were common, most frequently hand and foot skin reaction (16 patients, 33%), diarrhoea (five patients, 10%), renal failure (five patients, 10%), fatigue (four patients, 8%), and hypertension (three patients, 6%). Two patients had grade 4 treatment-related adverse events: two cardiac ischaemia or infarction, one hypomagnesaemia, and one pain in the chest or thorax. Four patients died during study treatment or within 30 days of last dose, of which two were deemed likely to be related to the study drug. INTERPRETATION: Regorafenib has antitumour activity as first-line treatment for metastatic or unresectable renal-cell carcinoma. The drug's safety profile requires close monitoring.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Idoso , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
BACKGROUND/AIM: Interferon-alpha (IFN-alpha) has shown survival benefits in metastatic renal cell carcinoma (mRCC), but the knowledge about long-term outcome is sparse. Additional knowledge is beneficial because IFN-alpha usage in combination therapy such as immune checkpoint inhibitor for mRCC is an area of interest. This is the longest follow-up concerning IFN-alpha treatment. PATIENTS AND METHODS: A total of 117 metastatic renal cell cancer (mRCC) patients without prior chemotherapy were enrolled between 1994-2002 and followed-up until January 2022. The median follow-up was 18 months. After progression to IFN-alpha, the patients were not treated with tyrosine kinase, mTOR inhibitors or bevacizumab as these were not standard therapies at that time or the patients' performance status was too poor. Mean treatment duration was 11 months. RESULTS: Median overall survival was 19.0 months, 5-year survival rate 16.2%, and 10-year survival rate 9.0%. There were statistically significant differences in survival in response to treatment (log-rank test, p<0.001): median overall survival was 52.0 months for objective responses, 25.0 months for stable disease and 5.0 months for progressive disease. Proportion of 5-year survivors was 29% in low, 20% in intermediate, and 7% in high-risk groups, respectively (p=0.001). CONCLUSION: With prolonged INF-alpha treatment stable and responding patients can obtain late objective responses, long-lasting complete responses, and long-term outcome with acceptable toxicity. IFN-alpha is an alternative therapy when multiple treatment lines are used for mRCC and an interesting option to study for combined therapies such as immune checkpoint inhibitor-based therapies.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Interferon-alfa/uso terapêutico , Neoplasias Renais/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Bevacizumab/efeitos adversos , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: We evaluated the relation of nuclear DNA content and clinicopathological features and prognosis in primary breast cancer of female Libyan patients with variable stage and grade and different treatment regimes. PATIENTS AND METHODS: Histological samples from 104 patients of breast carcinoma were retrospectively studied by computerized nuclear DNA cytometry. Isolated nuclei from paraffin sections were stained with Feulgen stain and DNA was measured using a computer-assisted image analysis cytometry system. In each case, 200 nuclei were measured and the DNA histograms, S phase fraction (SPF) and number of cells above 5c and 9c were determined. We applied different approaches in the analysis of DNA to compare the DNA histograms with different clinicopathological features and survival. RESULTS: The mean of DNA ploidy mode for all tumors was 3.43; 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF was 3.5% for DNA diploid and 13.5% for DNA aneuploid tumors. DNA aneuploid tumors and high SPF were associated with advanced stage, distant metastasis, high histological grade and lymph node involvement. The SPF was also associated with large tumor size and with younger patients (<50 years). In the overall population (median follow-up 51 months), patients with aneuploid DNA histograms and high SPF values had shorter survival times than those with diploid DNA histograms and low SPF values (p = 0.001, p < 0.0001, respectively). Also, short survival was associated with a multiploid DNA histogram and with DNA aneuploid cells ≥5 cells (p < 0.0001, p = 0.001, respectively). In a Cox multivariate analysis, DNA ploidy (p = 0.010), age (p = 0.038) and clinical stage (p = 0.001) were independent predictors of overall survival, and DNA ploidy (p = 0.018) and clinical stage (p = 0.001) also proved to be independent predictors of disease-specific survival. The SPF cutoff point of 11% might be applied to separate patients into good and poor prognosis groups. CONCLUSIONS: DNA image cytometry with careful analysis of the histograms may provide valuable prognostic information in Libyan breast cancer, with potential clinical implications in patient management, particularly in predicting the patients at high risk for metastasis and recurrence who should be considered as candidates for combined adjuvant therapy.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , DNA de Neoplasias/análise , Citometria por Imagem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , DNA de Neoplasias/genética , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Líbia , Pessoa de Meia-Idade , Ploidias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The influence of pregnancy on survival in melanoma has been a controversial issue. OBJECTIVE: In this retrospective study we investigated whether pregnancy (overall or temporally melanoma-related) has any effect on melanoma progression or patient outcome. METHODS: Patient data were collected from Turku University Hospital records concerning all women in fertile age (15-45 years) and diagnosed with melanoma between January 1, 1990 and December 31, 2009. We collected data on melanoma characteristics, treatment, pregnancies and patient outcomes. RESULTS: Of the 334 patients, 248 (74%) had been pregnant in some point during their life while 55 (17%) were nulliparous. The history of pregnancies could not be verified in 31 women (9%). Progression of melanoma to advanced stage was found in 58 (17%) of these women. Altogether, 35 women (14%) with at least one pregnancy had disease progression in contrast to 14 women (26%) with no pregnancies (p =0.049). Women with at least one pregnancy had a 94% probability to survive from melanoma compared to nulliparous women of whom only 83% survived (p =0.041). In Multivariate (COX) analysis pregnancy was a favourable factor for disease-specific survival (DSS) (HR 3.75; 95% CI 1.24-11.34; p =0.019) when adjusted for age (HR 1.064; 95% CI 1.00-1.13; p =0.50), localisation and stage (p =0.040), and Breslow (HR 1.32; 95% CI 1.10-1.58; p =0.002). However, when ulceration of the primary tumour was included in the multivariate model, Breslow remained as the only independent predictor of DSS (HR 1.58; 95% CI 1.34-1.86; p =0.0001) and pregnancy was dropped from the stepwise backward model in the step preceding the last one (p =0.081). CONCLUSION: Pregnancy is not a risk factor for disease recurrence or progression in melanoma patients, but instead can exert some favourable influence on prognosis.
Assuntos
Melanoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Complicações Neoplásicas na Gravidez/mortalidade , Neoplasias Cutâneas/mortalidade , Adolescente , Adulto , Progressão da Doença , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Melanoma/epidemiologia , Melanoma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Paridade , Gravidez , Complicações Neoplásicas na Gravidez/epidemiologia , Complicações Neoplásicas na Gravidez/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Adulto JovemRESUMO
Cancer-testis antigens (CTAs) are expressed mainly in various cancer tissues and in testis or placenta. Because of their restricted expression pattern, the CTAs can be potentially used for vaccine development and diagnostic applications. CTA CT16 has been found to be expressed in lung and renal cancers as well as in melanomas. Detection of CT16 protein directly from patient serum could facilitate monitoring of tumor growth and response to therapy in CT16-positive patients. A highly sensitive time-resolved fluorescence-based immunoassay measuring CTA CT16 in serum was developed. Generally, CTAs have not been measured directly from body fluids. CT16 level was detectable in 14 of 23 (61%) patients with metastatic melanoma, whereas none of the nine healthy volunteers collected by us had measurable CT16 level. For an unknown reason, 1 of 20 commercial control serum samples gave a positive result. The Wilcoxon-Mann-Whitney exact test showed statistically significant difference when patients with metastatic melanoma were compared to our control group (p = 0.006) or to the commercial set (p < 0.001). Four melanoma patients had exceptionally high serum CT16 level. CT16 did not correlate either with S100B, a recognized marker of progressing melanoma, or with unspecific serum marker lactate dehydrogenase. Elevation of CT16 titers preceded or followed the clinical diagnosis of disease progression in four patients with metastatic melanoma. As a conclusion, our results show that CT16 protein can be measured directly from patient serum, and the developed assay has a potential for clinical use.
Assuntos
Biomarcadores Tumorais/sangue , Imunoensaio/métodos , Antígenos Específicos de Melanoma/sangue , Melanoma/sangue , Sequência de Bases , Linhagem Celular Tumoral , Primers do DNA , Humanos , Soros Imunes , Melanoma/patologia , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
BACKGROUND: Securin is an oncogene with functions in cell proliferation, tumour initiation and progression. Its prognostic value in rectal cancer is somewhat unknown. Accordingly, we studied securin expression together with Ki-67 in rectal cancer in relation to preoperative (chemo)radiotherapy (RT) and disease outcome. MATERIAL AND METHODS: Biopsies (n = 65 for securin; n = 57 for Ki-67) and operative specimens (n = 207) from 211 patients treated with short-course RT (n = 87), long-course RT (n = 54) or surgery only (n = 70) were studied with immunohistochemistry (IHC) for securin and Ki-67 expression. In the long-course RT group, 45 patients received chemotherapy (5-fluorouracil or capecitabine) concomitantly with RT. The results of IHC were related to clinicopathological variables, disease outcome and tumour regression grade (TRG) after long-course RT. RESULTS: Both markers showed significant reduction after RT (p < 0.001). No differences in expression was seen in the long-course RT group between the patients with or without concomitant chemotherapy (p = 0.23 for securin; p = 0.31 for Ki-67). Low Ki-67 expression, but not that of securin, in operative specimens was significantly related to excellent TRG (p = 0.02 for Ki-67; p = 0.21 for securin). In univariate survival analysis, excellent TRG predicted longer disease-specific survival (DSS; p = 0.03). In multivariate Cox analysis, high securin expression after long-course (chemo)RT was an independent predictor of shorter DSS (p = 0.036) together with patient age (p = 0.043) and disease recurrence (local or distant; p = 0.009), whereas no similar appearance was seen in other treatment groups. CONCLUSION: Securin expression in rectal cancer is significantly reduced after RT. High securin expression and poor TRG after long-course (chemo)RT are indicators of unfavourable disease outcome.
Assuntos
Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Proteínas de Neoplasias/biossíntese , Neoplasias Retais/metabolismo , Neoplasias Retais/terapia , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Biópsia , Capecitabina , Quimioterapia Adjuvante , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Radioterapia Adjuvante , Neoplasias Retais/patologia , Securina , Resultado do TratamentoRESUMO
Extracellular matrix degradation is required for invasion and metastasis formation in colorectal carcinoma (CRC), therefore, we have examined matrix metalloproteinases MMP-9 expression in tumors from patients with CRC. The study comprises of 360 patients who underwent bowel resection for stage II, III, IV tumors. Paraffin-embedded CRC tissue samples were used for immunohistochemical staining. Negative MMP-9 expression levels correlated with longer survival time as evaluated by disease-free survival and disease-specific survival (p =.023, p =.006). In multivariate survival (Cox) analysis, MMP9 was a significant independent predictor of DFS (p =.014), but not of DSS, which was independently predicted by disease recurrence, stage and localization. The detection of MMP-9 expression may be valuable in finding patients who are at high risk of developing disease recurrence.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma/enzimologia , Carcinoma/mortalidade , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/mortalidade , Metaloproteinase 9 da Matriz/análise , Idoso , Carcinoma/secundário , Carcinoma/cirurgia , Colectomia , Neoplasias Colorretais/secundário , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Razão de Chances , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Tempo , Análise Serial de Tecidos , Resultado do TratamentoRESUMO
UNLABELLED: Information on detailed treatment costs and the economic burden of renal cell carcinoma (RCC) is rare. The current study provides treatment costs and outcomes of patients with metastatic RCC (mRCC), as well as estimates of the future burden from the perspective of Finnish health care. These results offer a baseline against which the impact of emerging treatments may be evaluated. MATERIALS AND METHODS: Information on treatment modalities, survival, and the cost of treatment was retrospectively gathered from mRCC patients (n = 83) receiving first-line interferon-alpha (IFN). Predictions of the number of new cases, premature deaths, and productivity losses were made using local epidemiological data, which were projected to the future using population growth forecasts. The future costs of mRCC treatment and the budget impact of sunitinib were estimated through modeling. RESULTS: Patients survived 11.9 months (median; 95% CI 9.2-14.7) after initiation of active IFN treatment, accruing an average total treatment cost of 951 euros. Most of the treatment costs were due to hospitalization and active IFN treatment. The aging of the population leads to nearly a 2% increase in the absolute number of new diagnoses annually, while at the same time it results in declining productivity losses. The estimated five-year population cost of IFN-based treatment was 16M euros-26M euros. Adding sunitinib to the first-line treatment protocol increased this cost by 13M eruos-41M euros. CONCLUSIONS: Despite the limited number of patients, metastatic renal cell carcinoma places a considerable economic burden on Finnish society. Treatment costs are likely to increase substantially due to the adoption of new and more expensive medications, the aging population, and enhanced survival times.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/economia , Custos de Cuidados de Saúde , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Intervalos de Confiança , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Custos de Medicamentos , Feminino , Finlândia , Humanos , Indóis/administração & dosagem , Indóis/economia , Interferon-alfa/administração & dosagem , Interferon-alfa/economia , Interleucina-2/administração & dosagem , Interleucina-2/economia , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pirróis/administração & dosagem , Pirróis/economia , Sunitinibe , Resultado do TratamentoRESUMO
Treatment results of metastatic malignant melanoma of the skin have failed to exhibit significant improvement for 30 years. Owing to the poor efficiency of cytotoxic therapies, attention has focused on the patient's own immune system and its strengthening or "teaching" to counteract the melanoma tissue. The most significant forms of immunotherapy currently include the interferons, interleukin-2 and antibody therapy directed against a specific T-lymphocyte associated antigen (CTLA-4). So far, therapeutic vaccines for melanoma have not ended up into routine clinical use.
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Imunoterapia/métodos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Antígenos CD , Antígeno CTLA-4 , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Humanos , Interferons/imunologia , Interferons/uso terapêutico , Interleucina-2/imunologia , Interleucina-2/uso terapêutico , Melanoma/imunologia , Neoplasias Cutâneas/imunologia , Linfócitos T/imunologiaRESUMO
BACKGROUND: The prognostic value of vascular endothelial growth factor-A (VEGFA) and epithelial cadherin (E-cadherin) expression in patients with metastatic colorectal cancer (mCRC) is controversial. MATERIALS AND METHODS: In this prospective study, patients diagnosed with mCRC between August 1, 1998, and August 30, 2003, at the Turku University Hospital, Finland were included. Expression of E-cadherin (membranous and cytoplasmic pattern) and VEGFA in tumour samples was assessed by immunohistochemistry. Tumours were classified as E-cadherin expressers if they demonstrated moderate or strong cytoplasmic or membranous staining, while those positive for VEGFA expression showed a moderate or strong cytoplasmic staining. Of particular interest was the association between membranous or cytoplasmic expression of E-cadherin and VEGFA. The value of strong VEGF-A staining and membranous or cytoplasmic expression of E-cadherin as a predictor of disease outcome over a 6-year period was another point of interest in this study. RESULTS: Of the 67 patients with mCRC, 43 (64%) had tumours positive for cytoplasmic E-cadherin, while in 24 cases (36%), E-cadherin expression was membranous. Strong VEGFA staining was present in half of the cases (n=36, 54% of all 67 mCRC cases). VEGFA expression was significantly correlated with cytoplasmic E-cadherin expression in that 28/36 cases of VEGFA-positive tumours were also positive for cytoplasmic E-cadherin (p=0.012). In addition, among the patients with intense VEGFA expression (n=36), those who had positive cytoplasmic E-cadherin in their tumours had a lower response-rate to first-line therapy with irinotecan, fluorouracil and leucovorin regimen: 5 out of 36 (14%) were chemosensitive. This is in contrast to the patients with VEGFA-positive tumours and membranous E-cadherin (8/36, 22% chemosensitive (p=0.004). The former group also had more ominous prognosis (p<0.001). CONCLUSION: Reduced membranous expression of E-cadherin and increased cytoplasmic E-cadherin expression predict poor survival in mCRC.
Assuntos
Antígenos CD/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Caderinas/análise , Neoplasias Colorretais/tratamento farmacológico , Irinotecano/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Celular/química , Neoplasias Colorretais/química , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Citoplasma/química , Feminino , Finlândia , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Colorectal cancer (CRC) cell lines displaying microsatellite instability (MSI) are resistant to 5-fluorouracil in vitro, which can be overcome by restoring DNA mismatch repair (MMR) competence. Furthermore, elevated levels of Bcl-2 protein confers cytotoxic drug resistance to tumour cell lines. We examined the expression of Bcl-2 and two MMR proteins (hMLH1 and hMSH2) in advanced CRC patients, to determine their mutual relationship, association to therapeutic response and impact on disease outcome. Tumour samples from 73 CRC patients who were treated in advanced stage with either irinotecan alone or in combination with 5-FU/leucovorin, were analysed for expression of Bcl-2, hMLH1 and hMSH2 using immunohistochemistry. Bcl-2 expression was closely correlated with hMLH1 and hMSH2 expression (negative-weak/moderate-strong) (p=0.01). Bcl-2/MMR expression was significantly (p=0.030 for whole series; p=0.018 for the 5-FU-treated cases) related to the response to treatment; tumours with low levels of both Bcl-2 and MMR responded better (n=18/31, 58%) than those with high Bcl-2 and MMR (n=3/16, 18%). Patients with high Bcl-2/MMR expression had a significantly longer DFS (47 vs. 11 months, n=26) than those with low Bcl-2/MMR index (p=0.005). Bcl-2/MMR index was not significantly related to disease-specific survival or survival with metastases. The present data suggest that MSI patients with low Bcl-2/MMR demonstrate a significantly shorter DFS, whereas patients with high expression of the two markers obtain the greatest benefit from 5-FU-based chemotherapy.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Instabilidade de Microssatélites , Proteína 2 Homóloga a MutS/biossíntese , Proteínas Nucleares/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/metabolismo , Intervalo Livre de Doença , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , PrognósticoRESUMO
BACKGROUND: Angiogenesis plays an important role in progression of colorectal carcinoma (CRC). Evidence from preclinical and clinical studies indicates that vascular endothelial growth factor (VEGF) is the predominant angiogenic factor in CRC. Indeed, VEGF is expressed in approximately 50% of CRCs, with minimal to no expression in normal colonic mucosa and adenomas. In this study, the expression of VEGF-1 was examined in stage I-IV CRCs to determine its clinicopathological correlates, and association with the response to treatment and disease outcome. PATIENTS AND METHODS: The present series consisted of tissue samples obtained from 360 patients with stage I, II, III, or IV CRC who had undergone large bowel resection during 1981-1990 at Turku University Hospital. Archival paraffin-embedded CRC tissue samples were used to build up tissue microarray (TMA) blocks and VEGF-1 expression was assessed immunohistochemically using an automated staining system. Three different grading systems were applied to evaluate the expression of VEGF-1. RESULTS: Seventy percent of patients with stage IV CRC had positive VEGF-1 expression, while 50% and 47%, respectively of patients with stage II and III CRC had positive VEGF-1 expression (p = 0.005). VEGF-1 expression in the left colon and rectum was significantly higher than that in the right colon (61% vs. 45%, respectively) (p = 0.006). Significant statistical correlation (p = 0.04) was found between VEGF-1 and 10-year disease-specific survival: patients who died of the disease more frequently had a VEGF-1-expressing tumour than did those who survived for 10 years. CONCLUSION: Quantification of VEGF-1 expression seems to provide valuable prognostic information in CRC, particularly in selecting those patients at high risk for disease progression who are likely to benefit from adjuvant therapy.
Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Idoso , Neoplasias Colorretais/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do TratamentoRESUMO
AIM: To examine the expression of thymidylate synthase (TS) and oncoprotein Bcl-2 in advanced colorectal cancer (CRC) patients, and to determine their mutual relationship, association to therapeutic response and impact on disease outcome. METHODS: Tumor samples from 67 patients with CRC, who were treated at advanced stage with either irinotecan alone or in combination with 5-fluorouracil/leucovorin, were analyzed for expression of TS and Bcl-2 using immunohistochemistry. RESULTS: A significant linear correlation between lower expression levels of Bcl-2 and lower levels of TS expression was found (P = 0.033). Patients with high levels of both TS and Bcl-2 expression had a significantly longer disease-free survival (DFS) (42.6 mo vs 5.4 mo, n = 25) than those with low TS/Bcl-2 index (P = 0.001). Tumors with low levels of both TS and Bcl-2 were associated with a longer survival with metastasis (WMS) interval in the whole patients group (n = 67, P = 0.035). TS/Bcl-2 index was not significantly related to disease-specific survival. CONCLUSION: The present data suggest that CRC patients with low TS/Bcl-2 demonstrate a significantly shorter DFS and longer WMS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias Colorretais/química , Proteínas Proto-Oncogênicas c-bcl-2/análise , Timidilato Sintase/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To investigate the changing pattern of beta-catenin expression and its prognostic value in advanced colorectal cancer (CRC). METHODS: Archival tumor samples were analyzed for beta-catenin using immunohistochemistry (IHC) in 95 patients with advanced CRC. RESULTS: Membranous beta-catenin expression was found in the normal colorectal epithelium. Almost 100% of CRC cases showed membranous and cytoplasmic expression, and 55 (58%) cases showed nuclear expression. In univariate (Kaplan-Meier) survival analysis, only the nuclear index (NI) was a significant predictor of disease free survival (DFS) (P = 0.023; n = 35), with a NI above the median associated with longer DFS (34.2 mo) than those with a NI below the median (15.5 mo) (P = 0.045, ANOVA). The other indices were not significant predictors of DFS, and none of the three tested indices (for membranous, cytoplasmic, or nuclear expression) predicted disease-specific survival (DSS). However, when dichotomized as positive or negative nuclear expression, the former was a significant predictor of more favorable DFS (P = 0.041) and DSS (P = 0.046). CONCLUSION: Nuclear beta-catenin expression provides additional information in predicting patient outcome in advanced CRC.
Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Núcleo Celular/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , beta Catenina/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos ProspectivosRESUMO
AIM: To investigate the changing pattern of alpha-catenin expression and its relationship to clinical and pathological features of colorectal cancer (CRC) patients. METHODS: Archival tumor samples were analyzed using immunohistochemistry (IHC) for alpha-catenin in 91 patients with advanced CRC. RESULTS: The values of alpha-catenin membrane index (MI) and cytoplasmic index (CI) were significantly related to the depth of tumor invasion (P = 0.027, P = 0.020, respectively), high indices being associated with increased depth of the primary tumor invasion (T3 and T4). Similarly, patients with high alpha-catenin expression had a significantly increased risk of lymph node metastasis (32/39 vs 37/52 for MI and 37/45 vs 32/46 for CI) (P = 0.001, P = 0.0001, respectively, for LNN status). An altered expression (i.e., cytoplasmic pattern) was also related (P = 0.047) to the response to chemotherapy; patients with low CI were more responsive (CR: 7/46) than patients with high CI values (CR: 0/45). There was a marginal effect on survival in patients time with metastases (SWM) (P = 0.087); patients with low CI showing slightly longer SWM, but no such effect on disease free survival (DFS) or disease specific survival (DSS). As to co-expression with another member of the adhesion complex (beta-catenin), high alpha-catenin/beta-catenin MI index was of marginal significance in predicting longer DSS (P = 0.063, log-rank). CONCLUSION: The results implicate that high alpha-catenin expression is intimately involved in the key regulatory mechanisms leading to invasive phenotype, lymph node metastases, and progressive disease in CRC.