RESUMO
Breast cancer is the most common malignancy in females. Despite its well-established prognostic factors, our prognostic ability at an individual patient level remains limited. In this study, the immunohistochemical expression of B-Myb and DNA topoisomerase 2-alpha (Topo2a) was analyzed in primary tumors to identify patients with a higher risk of disease recurrence after adjuvant chemotherapy for early invasive breast cancer. We analyzed a cohort of 215 early invasive breast cancer patients having undergone surgery from 2002 to 2003 at the Zagreb University Hospital Centre, including 153 patients treated with adjuvant chemotherapy. All of them were followed-up prospectively for at least ten years according to routine institutional practice. Statistically significant correlations were found between B-Myb and Topo2a expression levels and particular well-established prognostic factors. B-Myb expression was lower in estrogen receptor (ER)-positive tumors (p=0.0773), whereas larger tumors and those with positive lymphovascular invasion displayed a statistically significantly higher B-Myb expression (p=0.0409 and p=0.0196). Higher tumor grade indicated higher Topo2a values (p=0.0102 and p=0.0069). The subgroup with the expression of both proteins above the median value had an almost statistically significantly (p=0.0613) inferior prognosis compared to the rest of the cohort. Study results showed the B-Myb and Topo2a expression to have a prognostic value in breast cancer patients after adjuvant chemotherapy, which should be additionally explored in future studies in a larger patient cohort.
Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , DNA Topoisomerases Tipo II/uso terapêutico , Feminino , Humanos , Recidiva Local de Neoplasia , Prognóstico , Receptor ErbB-2RESUMO
Triple-negative breast cancer (TNBC) occurs in around one-sixth of all breast cancer (BC) patients, with the most aggressive behavior and worst prognosis of all BC subtypes. It is a heterogeneous disease, with specific molecular characteristics and natural dynamics of early recurrence and fast progression. Due to the lack of biomarkers or any valid treatment targets, it can only be treated with classic cytotoxic chemotherapy. We analyzed a cohort of 152 patients, median age 58 years, diagnosed with and treated for early stage TNBC at the University Hospital for Tumors, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia, during the 2009-2012 period. Patients were treated with primary surgical approach, adjuvant chemotherapy and adjuvant irradiation. We observed a relatively large proportion of locally advanced TNBC at diagnosis, with large tumor size and nodal involvement, with high grade and high proliferation index Ki67. Patient age, tumor size and lymph node involvement, as expected, were significant and clinically most important prognostic factors for 5-year disease-free survival (67%; 95% CI 60%-75%) and overall absolute survival rate (74%; 95% CI 66%-81%).
Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Croácia/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
BACKGROUND: Unexpected differences in Ki-67 values among HER2 & ER/PgR defined subgroups were found. This study aims to detect possible subdivisions beyond the conventional breast cancer types. METHODS: One thousand one hundred eighty consecutive patients with invasive ductal breast carcinoma were included and distributed in 16 subgroups (four HER2 phenotypes (0+, 1+, 2+ and 3+) times four ER/PgR phenotypes). Complex distributions of Ki-67 values were tested by expectation maximization (EM) clustering. RESULTS: Pooled Ki67 values of all patients showed the presence of three EM clusters (defined as LMA-low mitotic activity, IMA-intermediate mitotic activity and HMA-high mitotic activity) with expected mean Ki-67 values of 1.17%, 40.45% and 77.79%, respectively. Only ER-PgR- tumors significantly dispersed in three clusters (29.75% tumors in LMA, 46.95% in IMA and 23.30% in the HMA cluster), while almost no detected HMA tumors were of ER + PgR+ or ER + PgR- phenotypes. Among 799 ER + PgR+ patients distribution in clusters was HER2 dependent (p = 0.000243), due to increased number of IMA HER2 3+ tumors on the expense of LMA HER2 3+ tumors (52 IMA out of 162 HER2 3+ patients versus113 IMA out of 637 HER2 < 3+ patients). This was not found among ER + PgR- patients (p = 0.186968). Among ER-PgR- patients, HER2 overexpression also increased number of IMA tumor, but by reducing the number of HMA tumors (p < 0.000001). Here, difference between HER2 absent (0+) and HER2 3+ patients was evident (10 HMA out of 125 HER2 3+ patients versus 42 HMA out of 103 HER2 0+ patients). CONCLUSIONS: Results suggest that distributions of breast cancers in three clusters of mitotic activity depend on different mechanisms for ER + PgR+ and ER negative tumors. Although HER2 overexpression increases number of IMA tumors in both settings, in the former it is done by reducing number of LMA tumors, while in the latter it reduces the number of HMA tumors. Mitotic activity of ER + PgR- tumors seems unrelated to the HER2 status, possibly as an indicator that ER dysfunctionality in cancers that lack PgR expression. Among ER negative tumors, the absence of HER2 (0+) might be as important as the HER2 overexpression.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Antígeno Ki-67/análise , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Neoplasias da Mama/classificação , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/classificação , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Receptor ErbB-2/análise , Receptores de Estrogênio/análiseRESUMO
We have previously demonstrated the nucleic acid binding capacity of phenanthridine derivatives (PHTs). Because nucleic acids are potent inducers of innate immune response through Toll-like receptors (TLRs), and because PTHs bear a structural resemblance to commonly used synthetic ligands for TLR7/8, we hypothesized that PHTs could modulate/activate immune response. We found that compound M199 induces secretion of IL-6, IL-8 and TNFα in human PBMCs and inhibits TLR3/9 activation in different cellular systems (PBMCs, HEK293 and THP-1 cell lines).
Assuntos
Fatores Imunológicos/farmacologia , Fenantridinas/farmacologia , Receptor 3 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Ureia/análogos & derivados , Ureia/farmacologia , Linhagem Celular , Regulação para Baixo , Humanos , Substâncias Intercalantes/farmacologia , Interferon-alfa/genética , Interferon-alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Oligodesoxirribonucleotídeos/farmacologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not being based on prospective studies, yet on the expert's opinion of a precise oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures' algorithm in followup of oncological patients after primary treatment, in patients with planocellular head and neck cancer, oesophageal cancer, gastric cancer and colorectal cancer.
Assuntos
Neoplasias Colorretais , Neoplasias Esofágicas , Neoplasias de Cabeça e Pescoço , Neoplasias Gástricas , Neoplasias Colorretais/terapia , Neoplasias Esofágicas/terapia , Seguimentos , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Oncologia , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Neoplasias Gástricas/terapiaRESUMO
BACKGROUND: Correlations between development of hand-foot syndrome (HFS) and efficacy in patients receiving capecitabine (CAP)-containing therapy are reported in the literature. We explored the relationship between HFS and efficacy in patients receiving CAP plus bevacizumab (BEV) in the TURANDOT randomised phase III trial. METHODS: Patients with HER2-negative locally recurrent/metastatic breast cancer (LR/mBC) who had received no prior chemotherapy for LR/mBC were randomised to BEV plus paclitaxel or BEV-CAP until disease progression or unacceptable toxicity. This analysis included patients randomised to BEV-CAP who received ⩾1 CAP dose. Potential associations between HFS and both overall survival (OS; primary end point) and progression-free survival (PFS; secondary end point) were explored using Cox proportional hazards analyses with HFS as a time-dependent covariate (to avoid overestimating the effect of HFS on efficacy). Landmark analyses were also performed. RESULTS: Among 277 patients treated with BEV-CAP, 154 (56%) developed HFS. In multivariate analyses, risk of progression or death was reduced by 44% after the occurrence of HFS; risk of death was reduced by 56%. The magnitude of effect on OS increased with increasing HFS grade. In patients developing HFS within the first 3 months, median PFS from the 3-month landmark was 10.0 months vs 6.2 months in patients without HFS. Two-year OS rates were 63% and 44%, respectively. CONCLUSIONS: This exploratory analysis indicates that HFS occurrence is a strong predictor of prolonged PFS and OS in patients receiving BEV-CAP for LR/mBC. Early appearance of HFS may help motivate patients to continue therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Síndrome Mão-Pé/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/metabolismo , Resultado do TratamentoRESUMO
Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not based on prospective studies, but on the experts opinion of a particular oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardise and rationalise the diagnostic procedures algorithm in the follow-up of oncological patients after primary treatment.
Assuntos
Assistência ao Convalescente/organização & administração , Neoplasias da Mama/terapia , Neoplasias dos Genitais Femininos/terapia , Oncologia/organização & administração , Assistência ao Convalescente/normas , Neoplasias da Mama/diagnóstico , Croácia , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Humanos , Oncologia/normas , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapiaRESUMO
The treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not based on prospective studies, but on the experts opinion of individual oncological centers or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures algorithm in the followup of oncological patients after primary treatment, in patients with renal cell cancer, urinary bladder cancer, prostate cancer and testicular cancer.
Assuntos
Assistência ao Convalescente/organização & administração , Oncologia/organização & administração , Neoplasias da Próstata/terapia , Neoplasias Testiculares/terapia , Neoplasias da Bexiga Urinária/terapia , Assistência ao Convalescente/normas , Croácia , Feminino , Humanos , Masculino , Oncologia/normas , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Neoplasias Testiculares/diagnóstico , Neoplasias da Bexiga Urinária/diagnósticoRESUMO
The treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not based on prospective studies, but on the experts opinion of individual oncological centers or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures algorithm in the follow-up of oncological patients after primary treatment, in patients with neuroendocrine neoplasms, hepatocellular carcinoma, pancreatic cancer and cancer of the bile ducts.
Assuntos
Assistência ao Convalescente/organização & administração , Neoplasias dos Ductos Biliares/terapia , Neoplasias Hepáticas/terapia , Oncologia/organização & administração , Neoplasias Pancreáticas/terapia , Assistência ao Convalescente/normas , Neoplasias dos Ductos Biliares/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/terapia , Croácia , Humanos , Neoplasias Hepáticas/diagnóstico , Oncologia/normas , Neoplasias Pancreáticas/diagnóstico , Guias de Prática Clínica como Assunto , Estudos ProspectivosRESUMO
Melanoma in the Western world has an increasing incidence. One of the most important factor for the increase in incidence is sporadic, uncontrolled exposure to the sun. The basis for the treatment of primary melanoma is surgical treatment. Treatment of metastatic disease of melanoma in recent years experienced significant changes. BRAF and MEK inhibitors, immunotherapy with programmed cell-death immune checkpoint inhibitors (anti-PD-1-antibodies) are new options for the treatment of metastatic disease. A mulitidisiplinary team of Croatian Society for Medical Oncology provides recommendations for diagnosis, treatment and follow-up of melanoma primarily driven to the discovery of new drugs and therapeutic options, that change the prognosis of patients with metastatic melanoma.
Assuntos
Antineoplásicos/uso terapêutico , Imunoterapia/métodos , Melanoma , Procedimentos Cirúrgicos Operatórios/métodos , Croácia , Gerenciamento Clínico , Humanos , Melanoma/diagnóstico , Melanoma/patologia , Melanoma/terapia , Metástase Neoplásica , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidoresRESUMO
Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a speciï¬ c oncological treatment further follow-up is managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely deï¬ ned. Nowadays, most of the existing follow-up guidelines are not based on prospective studies, but on the experts opinion of a particular oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardise and rationalise the diagnostic procedures algorithm in the follow-up of oncological patients after primary treatment.
Assuntos
Assistência ao Convalescente , Neoplasias da Mama/terapia , Neoplasias Ovarianas/terapia , Neoplasias do Colo do Útero/terapia , Neoplasias Uterinas/terapia , Assistência ao Convalescente/métodos , Assistência ao Convalescente/normas , Algoritmos , Croácia , Feminino , Seguimentos , Humanos , Oncologia/métodosRESUMO
Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not being based on prospective studies, yet on the expert's opinion of a precise oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures' algorithm in followup of oncological patients after primary treatment, in patients with melanoma, sarcomas, central nerve system tumors and lung cancer.
Assuntos
Assistência ao Convalescente , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias Pulmonares/terapia , Melanoma/terapia , Sarcoma/terapia , Assistência ao Convalescente/métodos , Assistência ao Convalescente/normas , Croácia , Humanos , Oncologia/métodosRESUMO
BACKGROUND: Reducing treatment delay improves outcomes in breast cancer. The aim of this study was to determine factors influencing patient- and system-related delays in commencing breast cancer treatment in different countries. METHODS: A total of 6588 female breast cancer patients from 12 countries were surveyed. Total delay time was determined as the sum of the patient-related delay time (time between onset of the first symptoms and the first medical visit) and system-related delay time (time between the first medical visit and the start of therapy). RESULTS: The average patient-related delay time and total delay time were 4.7 (range: 3.4-6.2) weeks and 14.4 (range: 11.5-29.4) weeks, respectively. Longer patient-related delay times were associated with distrust and disregard, and shorter patient-related delay times were associated with fear of breast cancer, practicing self-examination, higher education level, being employed, having support from friends and family and living in big cities. The average system-related delay time was 11.1 (range: 8.3-24.7) weeks. Cancer diagnosis made by an oncologist versus another physician, higher education level, older age, family history of female cancers and having a breast lump as the first cancer sign were associated with shorter system-related delay times. Longer patient-related delay times and higher levels of distrust and disregard were predictors of longer system-related delay times. CONCLUSIONS: The delay in diagnosis and treatment of breast cancer remains a serious problem. Several psychological and behavioural patient attributes strongly determine both patient-related delay time and system-related delay time, but their strength is different in particular countries.
Assuntos
Atitude Frente a Saúde , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/psicologia , Comportamentos Relacionados com a Saúde , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Ásia , Europa (Continente) , Medo/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Autoexame/psicologia , Autoexame/estatística & dados numéricos , Fatores Socioeconômicos , Inquéritos e Questionários , Fatores de Tempo , Confiança/psicologiaRESUMO
Toll-like receptors (TLR) are employed by the innate immune system to detect microbial pathogens based on conserved microbial pathogen molecules. For example, TLR9 is a receptor for CpG-containing microbial DNA, and its activation results in the production of cytokines and type I interferons from human B cells and plasmacytoid dendritic cells, respectively. Both are required for mounting an efficient antibacterial or antiviral immune response. These effects are mimicked by synthetic CpG oligodeoxynucleotides (ODN). Although several hyporesponsive TLR9 variants have been reported, their functional relevance in human primary cells has not been addressed. Here we report a novel TLR9 allele, R892W, which is hyporesponsive to CpG ODN and acts as a dominant-negative in a cellular model system. The R892W variant is characterized by increased MyD88 binding and defective co-localization with CpG ODN. Whereas primary plasmacytoid dendritic cells isolated from a heterozygous R892W carrier responded normally to CpG by interferon-α production, carrier B cells showed impaired IL-6 and IL-10 production. This suggests that heterozygous carriage of a hyporesponsive TLR9 allele is not associated with complete loss of TLR9 function but that TLR9 signals elicited in different cell types are regulated differently in human primary cells.
Assuntos
Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Oligodesoxirribonucleotídeos/farmacologia , Receptor Toll-Like 9/metabolismo , Alelos , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Genótipo , Humanos , Immunoblotting , Imunoprecipitação , Mutagênese , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Reação em Cadeia da Polimerase , Ligação Proteica/genética , Ligação Proteica/fisiologia , Estrutura Secundária de Proteína , Análise de Sequência de DNA , Receptor Toll-Like 9/química , Receptor Toll-Like 9/genéticaRESUMO
Significant advances in early breast cancer detection and increased quality of care within developed countries resulted in longer than five years survival in almost 90% of women diagnosed and treated for breast cancer. One in twenty women diagnosed with breast cancer will develop a new primary non-breast malignancy within 10 years from initial diagnosis. Mutations in BRCA 1 i 2, RAD51C, MMR, p53, CDKN2A and 113insArg genes are linked with increased risk of breast cancer and other cancer sites. It seems that treatment modalities also play significant role in development of new primary malignancies. Tissues that receive higher doses of radiation during radiotherapy of breast cancer are under increased risk of developing new primary tumor, especially in younger women, ten years after the treatment. Chemotherapy may cause higher incidence of leukemia and myelodysplastic syndrome but lower overall risk for development of other malignancies. Connection between tamoxifen therapy and increased risk of endometrial cancer is well known and confirmed also in recent studies. The true mechanism of cancer development is still unclear. Significance of hereditary factors, possible common environmental risk factors or unwanted side effects of the specific anticancer treatments are yet to be discovered.
Assuntos
Neoplasias da Mama/diagnóstico , Segunda Neoplasia Primária/etiologia , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Humanos , Segunda Neoplasia Primária/diagnósticoRESUMO
Introduction: Interleukin 17 (IL-17) has a key role in inflammatory responses. Increased serum concentrations of IL-17 have been reported in patients with different types of cancer. Some studies suggest antitumor activity of IL-17 while others speak in favor of its association with poorer prognosis. The lack of data on IL-17 behavior in vivo hinders the efforts to clarify the exact role of IL-17 in breast cancer patients and precludes the usage of IL-17 as potential therapeutic target. Methods: The study included 118 patients with early invasive breast cancer. The serum concentration of IL-17A was measured before surgery and during adjuvant treatment and compared with healthy controls. The correlation of serum IL-17A concentration and different clinical and pathological parameters, including IL-17A expression in the corresponding tumor tissue samples, was analyzed. Results: Significantly higher serum concentrations of IL-17A were found in women with early breast cancer before surgery, but also during adjuvant treatment in comparison to healthy controls. No significant correlation to tumor tissue IL-17A expression was observed. There was a significant postoperative decrease of serum IL-17A concentrations even in patients with relatively lower preoperative values. A significant negative correlation was found between serum IL-17A concentrations and the tumor estrogen receptor expression. Conclusion: The results suggest that the immune response in early breast cancer is mediated by IL-17A, particularly in triple-negative breast cancer. IL-17A-mediated inflammatory response subsides postoperatively, but IL-17A concentrations remain elevated compared to the values in healthy controls, even after the removal of the tumor.
RESUMO
KRAS p.G13D mutant metastatic colorectal cancer (mCRC) has been identified as representing a cetuximab-sensitive subtype of KRAS mutant mCRC. This analysis aims to answer the question of whether first-line treatment of p.G13D mCRCs should include cetuximab or bevacizumab. Fifty-four patients with p.G13D mutant mCRC were pooled in this analysis. All patients underwent systemic first-line treatment with a fluoropyrimidine and oxaliplatin/irinotecan that was combined with either cetuximab or bevacizumab. The analysis of cetuximab-based and bevacizumab-based regimens in mCRC patients with p.G13D-mutated tumours indicated comparable data for the overall response rate (58 vs. 57%) and progression-free survival (8.0 vs. 8.7 months; hazard ratio: 0.96, P=0.9). Overall survival (OS) was 20.1 months in patients treated with cetuximab-based first-line therapy compared with 14.9 months in patients receiving bevacizumab-containing regimens (hazard ratio: 0.70, P=0.29). Logistic regressions modelling OS revealed oxaliplatin-based first-line treatment to correlate with a poor outcome (P=0.03). Moreover, a strong trend in favour of capecitabine compared with infusional 5-FU (P=0.06) was observed. Response to treatment correlated with OS in patients receiving cetuximab-based, but not bevacizumab-based regimens. This retrospective pooled analysis suggests comparable efficacy of cetuximab-based and bevacizumab-based first-line therapy in patients with p.G13D mutant mCRC. The combination with capecitabine and irinotecan was associated with a more favourable outcome compared with infusional 5-FU and oxaliplatin.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina , Cetuximab , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Irinotecano , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mutação , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Proteínas Proto-Oncogênicas p21(ras) , Estudos RetrospectivosRESUMO
Summary. Breast cancer has a high potential for metastasis, usually to the lungs, bones, liver and lymph nodes. Metastases in the holow organs of the digestive system are rare and mainly affectes the stomach and colon. They are characterized by very different clinical and radiological manifestations. We have warned that the initial unrecognized breast cancer can appear as a primary tumor of the stomach and colon, and onlya histopathological analysis reveales that it is a metastatic breast cancer. Metastases to the stomach or intestine involve deep layer of the mucosa and pathohistological findings of standard biopsy sample can be falsely negative, despite positive imaging technique (abdominal ultrasound and MSCT, endoscopic ultrasound) that indicate the tumor process. That's,why we emphasize the importance of endoscopic mucosal resection in the detection of malignant process of deeper layers of the gastric mucosa and deep intestinal mucosal biopsies with postoperative analysis of its walls.
Assuntos
Neoplasias da Mama/patologia , Neoplasias do Colo/secundário , Neoplasias Gástricas/secundário , Idoso , Neoplasias do Colo/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Gástricas/diagnósticoRESUMO
BACKGROUND: Gastric cancer (GC) is the eighth most common cause of cancer deaths in Croatia and one of the most common causes of cancer deaths worldwide. A reliable diagnostic tool for the early detection of GC is essential. OBJECTIVE: We previously suggested a pepsinogen test method to reduce the mortality from GC by allowing early detection. Here, we report an updated analysis from a prospective single-center clinical study to evaluate the sensitivity and specificity of the pepsinogen test method and to determine whether this test can be used as a part of routine laboratory assessment of high-risk patients. METHODS: We present mature data of the pepsinogen test method in the Croatian population after a median follow-up of 36 months. Statistical analyses were performed using a Mann-Whitney U test, multiple logistic regression, and receiver operating characteristics (ROC) to evaluate the predictive power of the assayed biomarkers. RESULTS: Of the 116 patients, 25 patients had GC and 91 demonstrated a nonmalignant pathology based on tissue biopsy. Cutoff values were pepsinogen I ⩽70 and pepsinogen I/II ratio ⩽3.0. Using ROC curve analysis, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were determined to be 87.22%, 78.12%, 90.10%, 71.43%, and 92.86%, respectively, for the diagnosis of GC. The area under the curve was 0.700 (95% confidence interval 0.57-0.83). CONCLUSION: Pepsinogen tests are valuable for screening a population in need of further diagnosis and could help to avoid unnecessary invasive endoscopic procedures.
Assuntos
Pepsinogênio A , Pepsinogênio C , Neoplasias Gástricas , Humanos , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologiaRESUMO
Gastrointestinal stromal tumors are the most common mesenchymal tumors in gastrointestinal tract. They are often asymptomatic and discovered incidentally during endoscopic or barium studies. About 80% GISTs have a KIT (CD 117 antigen) gene mutation. Most affect exon 11, less commonly exon 9,13 or 17, that results in uncontrolled KIT signaling. This led to effective systemic therapies in the form of small molecule inhibitors of the receptor tyrosine kinase such as imatinib mesylat. With the purpose of providing standardized approach to rational and effective diagnostic and treatment algorithm in Croatia, a multidisciplinary session was organized. Results of the session are given in the form of Consensus guidelines.