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BACKGROUND: Peri-implantitis is an inflammatory process affecting soft and hard tissues surrounding dental implants, causing progressive marginal bone loss. Peri-implant surgery is the treatment of choice. However, evidence about its impact on patients' quality of life (QoL) is limited. This study aimed to assess pain and QoL in the first seven post-operative days and measure patient satisfaction at the end of this period. MATERIAL AND METHODS: A prospective cohort study was conducted in patients with peri-implantitis. Patients reported pain on a visual analogue scale (VAS) ranging from 0 to 100mm every day during the first week after surgery. They then completed the OHIP-14sp questionnaire. A descriptive and inferential data analysis was used to assess the effect of surgical approach (resective, regenerative or combined), gender and working status on pain, satisfaction and QoL. RESULTS: Forty-one patients (93,2%) completed the daily pain VAS; scores ranged from 0 to 95 mm. Gender, occupation, or type of surgery had no significant effect upon its evolution. The mean total OHIP-14sp score was 16.7 (range = 5 to 33), indicating low to moderate deterioration in perceived oral health. Postoperative OHRQoL was significantly higher in working patients (mean difference (MD): 3.94; P = 0.042), and with the regenerative (MD: 6.34; P = 0.044) or the combined approach (MD: 5.41; P = 0.027). CONCLUSIONS: Considering the limitations of this study, postoperative pain was mild to moderate and decreased after the third day. Surgical treatment of peri-implantitis has an impact on QoL, especially when augmentation procedures are involved. This impact is higher in working patients.
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Implantes Dentários , Peri-Implantite , Humanos , Peri-Implantite/cirurgia , Estudos Prospectivos , Qualidade de Vida , Dor Pós-Operatória , Assistência Centrada no PacienteRESUMO
BACKGROUND: To assess the effect of implantoplasty and implant-abutment design on the fracture resistance and macroscopic morphology of narrow-diameter (3.5 mm) dental implants. MATERIAL AND METHODS: Screw-shaped titanium dental implants (n = 48) were studied in vitro. Three groups (n = 16) were established, based on implant-abutment connection type: external hexagon, internal hexagon and conical. Eight implants from each group were subjected to an implantoplasty procedure; the remaining 8 implants served as controls. Implant wall thickness was recorded. All samples were subjected to a static strength test. RESULTS: The mean wall thickness reductions varied between 106.46 and 153.75 µm. The mean fracture strengths for the control and test groups were, respectively, 1211.90±89.95 N and 873.11±92.37 N in the external hexagon implants; 918.41±97.19 N and 661.29±58.03 N in the internal hexagon implants; and 1058.67±114.05 N and 747.32±90.05 N in the conical connection implants. Implant wall thickness and fracture resistance (P < 0.001) showed a positive correlation. Fracture strength was influenced by both implantoplasty (P < 0.001) and connection type (P < 0.001). CONCLUSIONS: Implantoplasty in diameter-reduced implants decreases implant wall thickness and fracture resistance, and varies depending on the implant-abutment connection. Internal hexagon and conical connection implants seem to be more prone to fracture after implantoplasty.
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Dente Suporte , Implantes Dentários , Coroas , Análise do Estresse Dentário , Teste de Materiais , TitânioRESUMO
BACKGROUND: Bone metastasis (BM) is the most common site of disease in metastatic breast cancer (MBC) patients. BM impacts health-related quality of life (HRQoL). We tested prospectively the psychometric properties of the Bone Metastasis Quality of Life (BOMET-QoL-10) measure on MBC patients with BM. METHODS: Patients completed the BOMET-QoL-10 questionnaire, the Visual Analogue Scale (VAS) for pain, and a self-perceived health status item at baseline and at follow-up visits. We performed psychometric tests and calculated the effect size of specific BM treatment on patients´ HRQoL. RESULTS: Almost 70% of the 172 patients reported symptoms, 23.3% experienced irruptive pain, and over half were receiving chemotherapy. BOMET-QoL-10 proved to be a quick assessment tool performing well in readability and completion time (about 10 min) with 0-1.2% of missing/invalid data. Although BOMET-QoL-10 scores remained fairly stable during study visits, differences were observed for patient subgroups (e.g., with or without skeletal-related events or adverse effects). Scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. BOMET-QoL-10 scores also varied prospectively according to changes in pain intensity. CONCLUSIONS: BOMET-QoL-10 performed well as a brief, easy-to-administer, useful, and sensitive HRQoL measure for potential use for clinical practice with MBC patients. TRIAL REGISTRATION: NCT03847220. Retrospectively registered on clinicaltrials.gov (February the 20th 2019).
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PURPOSE: To evaluate the efficacy and safety of oral weekly vinorelbine 60 mg/m2 for metastatic breast cancer (MBC) in patients previously treated with anthracyclines or taxanes in routine clinical practice. MATERIALS AND METHODS: Fifty-five patients were enrolled in a prospective multicentre study conducted in Spain. Women ≥ 18 years of age with locally advanced breast cancer who were not candidates for surgical treatment with a radical intention or patients with stage IV disease, and who had received a prior taxane or anthracycline regimen were eligible for participation. RESULTS: Median age was 67 years. Median progression-free survival was 3.7 months (95% CI 2.5-4.9), median overall survival 10 months (95% CI 6.6-13.5), and overall response rate and clinical benefit rate were 29.1% and 49.1%, respectively. Main grade 3 and 4 toxicities were neutropenia 9.1%, febrile neutropenia 3.6% and constipation 3.6%. In total, 86% of the patients received complete treatment without delays or dose reduction. Moreover, HER2-positive patients who received oral vinorelbine concomitantly with trastuzumab showed better response (complete response: HER2-positive 14.3% vs. HER2-negative 0%; partial response: HER2-positive 42.9% vs. HER2-negative 25.6%; p = 0.008), better disease control rate (HER2-positive 100% vs. HER2-negative 46.2%; p = 0.011), and better values for the remaining analysed variables than HER2-negative patients. CONCLUSION: Our study provides real-world data on the use of oral weekly vinorelbine, which proves an effective and well-tolerated regimen for MBC patients previously treated with taxanes or anthracyclines. Patients with HER2-positive disease could also benefit from this treatment in combination with trastuzumab.
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Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Vinorelbina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/administração & dosagem , Antraciclinas/farmacologia , Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias da Mama/metabolismo , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Espanha , Análise de Sobrevida , Taxoides/administração & dosagem , Taxoides/farmacologia , Trastuzumab/administração & dosagem , Resultado do Tratamento , Vinorelbina/efeitos adversosRESUMO
BACKGROUND: To compare the accuracy of implant placement using the conventional freehand method and a dynamic navigation system; to assess the role of the surgeon's experience in implant placement using these two methods. MATERIAL AND METHODS: A randomized in-vitro study was conducted. Six resin mandible models and 36 implants were used. Two researchers with differing clinical experience (novice and experienced) placed implants using either the Navident dynamic navigation system (navigation group) or the conventional freehand method (freehand group). Accuracy was measured by overlaying the real position in the postoperative CBCT on the virtual presurgical placement of the implant in a CBCT image. Descriptive and bivariate analyses of the data were performed. RESULTS: The navigation group showed significantly higher accuracy for all the variables studied except 3D entry and depth deviation. This system significantly enhanced the accuracy of the novice professional in several outcome variables in comparison with the freehand implant placement method. However, when the implants were placed by the experienced clinician the dynamic navigation system only improved angulation deviation. Significant differences were found between the 2 professionals when the freehand method was employed. Similar deviations were observed for the implants placed with the navigation system. CONCLUSIONS: Dynamic computer assisted surgery systems allow more accurate implant placement in comparison with the conventional freehand method, regardless of the surgeon's experience. However, this system seems to offer more advantages to novice professionals, since it allows them to reduce their deviations significantly and achieve similar results to those of experienced clinicians.
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Implantação Dentária/métodos , Cirurgia Assistida por Computador , Competência Clínica , Humanos , Técnicas In Vitro , Distribuição AleatóriaRESUMO
Correction to: Clin Transl Oncol https://doi.org/10.1007/s12094-017-1801-4.
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The increased incidence and decreased mortality of breast cancer have produced an increased number of breast cancer survivors. The type of sequelae and comorbidities that these patients present call for a collaborative follow-up by hospital-based specialized care and primary care. In this document, we present a guideline drafted and agreed among scientific societies whose members care for breast cancer survivors. The purpose of this guideline is to achieve the shared and coordinated follow-up of these patients by specialized care and primary care professionals. In it, we review the health issues derived from the treatments performed, with recommendations about the therapeutic approach to each of them, as well as a proposal for joint follow-up by primary and specialized care.
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Assistência ao Convalescente , Neoplasias da Mama/terapia , Sobreviventes de Câncer , Guias de Prática Clínica como Assunto/normas , Sociedades Médicas , Feminino , Humanos , EspanhaRESUMO
PURPOSE: Several angiogenic prognostic markers are under investigation because of their potential clinical utility, aiming to improve patient outcomes. We hypothesized that genetic variant in the VEGF pathway could be used as prognostic markers of survival in non-small cell lung cancer (NSCLC) patients undergoing pulmonary resection. METHODS: We evaluated the relationship between genetic variants in the VEGF pathway and relapse-free survival (RFS, main endpoint) and overall survival (OS, secondary endpoint) among 131 patients with stage I-III NSCLC treated with surgical resection from 2009 to 2013. Clinical, pathological and surgical data were prospectively collected. Twenty-five variants in sixteen relevant genes were selected and genotyped in tumor samples by real time PCR. The Kaplan-Meier method with the log-rank test and Cox's regression models were used for RFS and OS analyses. RESULTS: With a median follow-up of 36 (min = 2.8; max = 67.4) months, there were 31 (24%) relapses and 31 (24%) deaths. Overall, median RFS was not reached and median OS was 65 [95% confidence interval (CI) 56-75] months. The KRAS rs1137282 and PIK3C2A rs4356203 variants were significantly associated with RFS. For KRAS rs1137282, the 3-year RFS was 76% [95% CI 64-84%] in patients harboring an A/A genotype compared to 53% [95% CI 37-69%] in patients harboring an A/G or G/G genotype (p = 0.02). For PIK3C2A rs4356203, patients with an A/A or an A/G genotype had a 3-year RFS of 72% [95% CI 58-76%], whereas in patients with a G/G genotype was 49% [95% CI 28-70%] (p = 0.02). These associations remained statistically significant after adjusting for all the relevant clinical parameters in the multivariable analysis. CONCLUSION: Genetic variants in VEGF pathway may be associated with recurrence in stage I-III NSCLC. Specifically, the KRAS rs1137282 could be considered as a prognostic factor for recurrence in resectable NSCLC patients. Although PIK3C2A rs4356203 was associated with RFS, further analyses are necessary to confirm these data.
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Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Neoplasias/tratamento farmacológico , Fosfatidilinositol 3-Quinases/genética , Polimorfismo Genético , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology. METHODS: A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement. RESULTS: Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12-24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival. CONCLUSIONS: High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches.
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Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Oncologia/normas , Consenso , Técnica Delphi , Feminino , Humanos , Receptor ErbB-2 , Sociedades MédicasRESUMO
Angiogenesis is a significant biological mechanism in the progression and metastasis of solid tumors. Vascular endothelial growth factor (VEGF), its receptors and signaling effectors have a central role in tumor-induced angiogenesis. Genetic variation in the VEGF pathway may impact on tumor angiogenesis and, hence, on clinical cancer outcomes. This study evaluates the influence of common genetic variations within the VEGF pathway in the clinical outcomes of 172 metastatic colorectal cancer (mCRC) patients treated with first-line oxaliplatin/5-fluorouracil chemotherapy. A total of 27 single-nucleotide polymorphisms (SNPs) in 16 genes in the VEGF-dependent angionenesis process were genotyped using a dynamic array on the BioMark™ system. After assessing the KRAS mutational status, we found that four SNPs located in three genes (KISS1, KRAS and VEGFR2) were associated with progression-free survival. Five SNPs in three genes (ITGAV, KRAS and VEGFR2) correlated with overall survival. The gene-gene interactions identified in the survival tree analysis support the importance of VEGFR2 rs2071559 and KISS1 rs71745629 in modulating these outcomes. This study provides evidence that functional germline polymorphisms in the VEGF pathway may help to predict outcome in mCRC patients who undergo oxaliplatin/5-fluorouracil chemotherapy.
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Neoplasias Colorretais/genética , Kisspeptinas/genética , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Prognóstico , Transdução de SinaisRESUMO
Epidermal growth factor receptor (EGFR) activation by radiation leads to increased cell proliferation and acts as a radioresistance mechanism. Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer, and to date, no biomarkers of response have been found. We analyzed polymorphisms in the EGFR and its ligands, DNA repair genes and the thymidylate synthase in 84 stages II and III rectal cancer patients treated with neoadjuvant capecitabine plus radiotherapy. The rs11942466 polymorphism in the amphiregulin (AREG) gene region was associated with a pathological complete response (ypCR) (odds ratio: 0.26; 95% confidence interval: 0.06-0.79; P=0.014). The rs11615 C>T polymorphism in the ERCC1 gene also correlated with the ypCR as no patients with a C/C genotype achieved ypCR; P=0.023. This is the first work to propose variants within the AREG and the ERCC1 genes as promising predictive biomarkers of ypCR in rectal cancer.
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Quimiorradioterapia/métodos , Reparo do DNA/genética , Desoxicitidina/análogos & derivados , Receptores ErbB/genética , Fluoruracila/análogos & derivados , Neoplasias Retais/genética , Neoplasias Retais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Capecitabina , Estudos de Coortes , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Seguimentos , Testes Genéticos/métodos , Genômica/métodos , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/diagnóstico , Resultado do TratamentoRESUMO
Breast cancer is a burden for western societies, and an increasing one in emerging economies, because of its high incidence and enormous psychological, social, sanitary and economic costs. However, breast cancer is a preventable disease in a significant proportion. Recent developments in the armamentarium of effective drugs for breast cancer prevention (namely exemestane and anastrozole), the new recommendation from the National Institute for Health and Care Excellence to use preventative drugs in women at high risk as well as updated Guidelines from the US Preventive Services Task Force and the American Society of Clinical Oncology should give renewed momentum to the pharmacological prevention of breast cancer. In this article we review recent major developments in the field and examine their ongoing repercussion for breast cancer prevention. As a practical example, the potential impact of preventive measures in Spain is evaluated and a course of practical actions is delineated.
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Neoplasias da Mama/prevenção & controle , Antineoplásicos Hormonais/uso terapêutico , Proteína BRCA1/genética , Neoplasias da Mama/genética , Feminino , Humanos , Tamoxifeno/uso terapêuticoRESUMO
BACKGROUND: Src is a non-receptor tyrosine kinase involved in signalling and crosstalk between growth-promoting pathways. We aim to investigate the relationship of active Src in response to trastuzumab of HER2-positive breast carcinomas. METHODS: We selected 278 HER2-positive breast cancer patients with (n=154) and without (n=124) trastuzumab treatment. We performed immunohistochemistry on paraffin-embedded tissue microarrays of active Src and several proteins involved in the PI3K/Akt/mTOR pathway, PIK3CA mutational analysis and in vitro studies (SKBR3 and BT474 cancer cells). The results were correlated with clinicopathological factors and patients' outcome. RESULTS: Increased pSrc-Y416 was demonstrated in trastuzumab-resistant cells and in 37.8% of tumours that correlated positively with tumour size, necrosis, mitosis, metastasis to the central nervous system, p53 overexpression and MAPK activation but inversely with EGFR and p27. Univariate analyses showed an association of increased active Src with shorter survival in patients at early stage with HER2/hormone receptor-negative tumours treated with trastuzumab. CONCLUSIONS: Src activation participates in trastuzumab mechanisms of resistance and indicates poor prognosis, mainly in HER2/hormone receptor-negative breast cancer. Therefore, blocking this axis may be beneficial in those patients.
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Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/enzimologia , Neoplasias do Sistema Nervoso Central/enzimologia , Receptor ErbB-2/metabolismo , Quinases da Família src/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/secundário , Quimioterapia Adjuvante , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais , Trastuzumab , Quinases da Família src/antagonistas & inibidoresRESUMO
BACKGROUND: The addition of trastuzumab (T) and lapatinib (L) to neoadjuvant chemotherapy increases the pathological complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We investigated the efficacy of T or L with neoadjuvant chemotherapy and specific efficacy biomarkers. METHODS: Patients with stages I-III (including inflammatory) HER2-positive breast cancer were randomised to receive epirubicin (E) plus cyclophosphamide (C) × 4 cycles followed by docetaxel (D) plus either T (EC-DT) or L (EC-DL). End points included pCR (primary), clinical response, toxicity, and pCR-predictive biomarkers. RESULTS: We randomised 102 patients to EC-DT (50) and EC-DL (52). Median age was 48, 56% were premenopausal and 58% had oestrogen receptor (ER)-positive tumours. Pathological complete response in breast was 52.1% (95% CI:38.0-66.2%) for EC-DT and 25.5% (95% CI:13.5-37.5%) for EC-DL (P=0.0065). Pathological complete response in breast and axilla was 47.9% for EC-DT and 23.5% for EC-DL (P=0.011). Grade 3-4 toxicity did not differ across treatments, except for diarrhoea (2% in EC-DT vs 13.5% in EC-DL, P=0.030). Multivariate analyses showed that treatment (P=0.036) and ER (P=0.014) were the only predictors of pCR in both groups. CONCLUSION: EC-DT exhibited higher efficacy and lower toxicity than EC-DL. Of the different biomarkers studied, only the absence of ER expression was associated with increased pCR.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/biossíntese , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Ciclofosfamida/administração & dosagem , Docetaxel , Epirubicina/administração & dosagem , Feminino , Humanos , Lapatinib , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Quinazolinas/administração & dosagem , Receptor ErbB-2/genética , Taxoides/administração & dosagem , TrastuzumabRESUMO
In the epidermal growth factor receptor (EGFR) pathway, polymorphisms in EGFR and its ligand EGF have been studied as biomarkers for anti-EGFR treatment. However, the potential pharmacogenetic role of other EGFR ligands such as amphiregulin (AREG) and epiregulin (EREG) has not been elucidated. We studied 74 KRAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan. Twenty-two genetic variants in EGFR, EGF, AREG and EREG genes were selected using HapMap database and literature resources. Three tagging single-nucleotide polymorphisms in the AREG gene region (rs11942466 C>A, rs13104811 A>G, and rs9996584 C>T) predicted disease control in the multivariate analyses. AREG rs11942466 C>A and rs9996584 C>T were also associated with overall survival (OS). The functional polymorphism, EGFR rs712829 G>T, was associated with progression-free and OS. Our findings support that intergenic polymorphisms in the AREG gene region might help to identify colorectal cancer patients that will benefit from irinotecan plus anti-EGFR therapy.
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Anfirregulina/genética , Biomarcadores/metabolismo , Camptotecina/análogos & derivados , Neoplasias Colorretais/genética , Receptores ErbB/antagonistas & inibidores , Polimorfismo Genético , Sequência de Bases , Camptotecina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Primers do DNA , Feminino , Humanos , Irinotecano , Masculino , Metástase Neoplásica , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Epidermal growth factor receptor gene (EGFR) alteration is a common feature in most of glioblastoma multiforme (GBM). Robust response of anti-EGFR treatments has been mostly associated with the EGFR deletion mutant variant III (EGFRvIII) and expression of PTEN. We have performed a prospective trial in order to confirm the efficacy of erlotinib treatment in patients with relapsed GBM who expressed EGFRvIII and PTEN. All patients included in the trial were required to be PTEN (+++), EGFR (+++) and EGFRvIII (+++) positives by immunohistochemistry. This new phase II trial enrolled 40 patients and was design to be stopped in case of fewer than two responses in the first 13 patients. Patient eligibility included histopathology criteria, radiological progression, more than 18 years old, Karnofsky performed status, KPS > 50, and adequate bone marrow and organ function. There was no limit to the number of prior treatments for relapses. No enzyme-inducing antiepileptic drugs were allowed. The primary endpoints were response and progression-free survival at 6 months (PFS6). Thirteen patients (6 men, 7 women) with recurrent GBM received erlotinib 150 mg/day. Median age was 53 years, median KPS was 80, and median prior treatments for relapses were 2. There was one partial response and three stable diseases (one at 18 months). PFS at 6 months was 20 %. Dose reduction for toxicity was not needed in any patient. Dermatitis was the main treatment-related toxicity, grade 1 in 8 patients and grade 2 in 5 patients. No grade 3 toxicity was observed. Median survival was 7 months (95 % IC 1.41-4.7). As conclusion, monotherapy with erlotinib in GBM relapses patients with high protein expression for PTEN (+++), EGFR (+++), and EGFRvlII (+++) showed low toxicity but minimal efficacy and the trial stopped.
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Neoplasias Encefálicas/terapia , Hemangiopericitoma/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/etiologia , Radiocirurgia/métodosRESUMO
BACKGROUND: Cisplatin and fluoropyrimidine (CF) are standard first- line treatment in advanced gastric cancer, but no second-line treatment has yet been established. We present a phase II study in which we evaluated the efficacy and toxicity of the combination of Sorafenib (S), and Oxaliplatin as second-line therapy. METHODS: Patients with progressive gastric adenocarcinoma after CF- first-line, ECOG 0-2, and measurable disease were included. The primary objective was PFS. Treatment doses were Oxaliplatin 130 mg/m²/3 weeks and Sorafenib 800 mg/bid/d. RESULTS: We included 40 patients. CR was 2.5% and SD was 47.2%. Grade 3-4 toxic effects were neutropenia (9.8%), thrombocytopenia (7.3%), neurotoxicity (4.9%) and diarrhea (4.9%). Median PFS was 3 months (95%CI: 2.3-4.1) and median OS was 6.5 months (95% CI: 5.2-9.6). Time to progression (TTP) to first line therapy was a prognosis factor. Median OS was 9.7 months when time-to-progression during first-line chemotherapy was >6 months and 5.6 m when it was <6 months (p = 0.04). CONCLUSIONS: Time-to-progression under a CF-based first-line therapy determines subgroups of GC patients with different prognosis. The combination of Oxaliplatin-Sorafenib in advanced GC patients previously treated with CF appears safe, but our results do not support the implementation of a phase III trial.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Compostos de Fenilureia/administração & dosagem , Sorafenibe , Resultado do TratamentoRESUMO
The purpose of this article is to update our previous work on the treatment and follow-up in early breast cancer. In this new version we have classified a treatment by immunohistochemistry subtypes of breast cancer. Latest advances in the management of this disease have been compiled, either in the adjuvant and neoadjuvant setting or chemotherapy and hormonal treatment. This review is presented in an easy way for oncologist, fellows and for other specialties.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/normas , Feminino , Genes erbB-2 , Humanos , Monitorização Fisiológica/normas , Terapia Neoadjuvante/normas , Estadiamento de NeoplasiasRESUMO
AIMS: To compare different methods in order to assess adherence and persistence with oral endocrine therapy in women diagnosed with breast cancer (BC) in Catalonia. MATERIALS AND METHODS: This study covered all women newly diagnosed with stage I, II or IIIa BC and positive hormone receptors at six hospitals in Catalonia (Spain) in 2004. Adherence was assessed on the basis of physician report and patient self-report using a telephone questionnaire. Persistence was measured by refill prescriptions. We used the Kappa index to compare adherence measures and logistic regression to evaluate adherence-related risk factors. RESULTS: The study covered a total of 692 women. Adherence ranged from 92% (self-report) to 94.7% (physician report), depending on the measure used; persistence was 74.7% at 5 years of follow-up. Low concordance between measures was observed (Kappa range: 0.018-0.267). Patients aged 50-74 years showed higher adherence than those aged <50 years. Adherence was also associated with: adjuvant chemotherapy and sequential hormonal therapy. CONCLUSIONS: Concordance between the different measures was remarkably low, indicating the need for further research. Adherence is an issue in the management of BC patients taking oral drugs, and should be assessed in clinical practice.
Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Adesão à Medicação/estatística & dados numéricos , Administração Oral , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Autorrelato , EspanhaRESUMO
The purpose of this study was to identify molecular markers associated with tumor recurrence and survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). We studied the expression profile of 63 pre-treatment tumor biopsies obtained from locally advanced HNSCCs treated with standard treatments. Cluster analysis identified three tumor subtypes associated with significant differences in local recurrence-free survival (LRFS) (P<0.001), progression free-survival (PFS) (P<0.009) and overall survival (OS) (P<0.004). Tumor subtype 1, associated with short LRFS, PFS and OS, showed features of epithelial-mesenchymal transition and undifferentiation. It also overexpressed genes involved in cell adhesion, NF-κB and integrin signalling. Tumor subtype 3, associated with longer LRFS, PFS and OS, showed a high degree of differentiation and overexpressed genes located in chromosomal regions 19q13 and 1q21. Tumor subtype 2, which had an intermediate clinical outcome between subtype 1 and subtype 3, overexpressed genes involved in branching morphogenesis. Finally, we validated the association between gene cluster classification and patient survival using Gene Set Enrichment Analysis and two HNSCC data sets obtained from two independent patient cohorts. In conclusion, we generated a gene prognostic signature associated with survival in locally advanced patients using the expression profile of the pre-treatment tumor biopsy. Independent prospective studies would be necessary to assess if the proposed survival signature could help to guide clinical management of HNSCC.