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1.
Nat Commun ; 14(1): 2973, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37221181

RESUMO

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.


Assuntos
Tumor Carcinoide , Tumores Neuroendócrinos , Humanos , Antígeno B7-H1 , Pulmão
2.
Clin Transl Oncol ; 22(12): 2350-2356, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32488803

RESUMO

PURPOSE: We analysed our initial experience with SBRT in liver metastasis from colorectal cancer at our institution. MATERIALS AND METHODS: Between January/2014 and December/2017, 22 patients with 31 LMCCR were treated. Local control (LC) was assessed using the Kaplan-Meier and log-rank tests. We analysed potential prognostic factors for LC: sex, PTV size, number of LM and the radiation scheme. RESULTS: Median age: 69 years. Prior chemotherapy or local liver treatments: 81.8% and 63.6% of patients, respectively. SBRT consisted of 3 × 20 Gy (42.9%) and 3 × 15 Gy (31.4%). There were 88.5% responses (57.1% CR and 31.4% PR). Median follow-up was 30 months. LC per lesion at 12 and 24 months was 85.3% and 61.8%, respectively. Tumour volumes > 30 cc correlated with worsened 2-year-control rates (90% vs 34.5%) (p = 0.005). There was only a patient with CTC-grade 3 toxicity. CONCLUSIONS: Liver SBRT is a safe and effective treatment that achieves high local control rates. We found a significant correlation between larger LMCRC and worse local control.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
3.
Clin Transl Oncol ; 22(2): 223-235, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32006340

RESUMO

Thyroid carcinoma is the most frequent endocrine malignancy and accounts for around 3% of global cancer incidence. Different histologies and clinical scenarios make necessary a multidisciplinary approach that includes new diagnostic methods and surgical, radiopharmaceutical and systemic therapies. This guideline updates several aspects of management of thyroid cancer.


Assuntos
Ensaios Clínicos como Assunto/normas , Guias de Prática Clínica como Assunto/normas , Neoplasias da Glândula Tireoide/terapia , Humanos , Oncologia , Sociedades Médicas
4.
Clin Transl Oncol ; 22(5): 734-750, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31385226

RESUMO

BACKGROUND: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression. METHOD: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted. RESULTS: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%). CONCLUSION: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema de Registros , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Platina/administração & dosagem , Platina/efeitos adversos , Intervalo Livre de Progressão , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
5.
Clin Transl Oncol ; 21(9): 1231-1239, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30712234

RESUMO

PURPOSE: In this paper we study the quality of life (QoL) of elderly breast cancer patients receiving endocrine treatment (ET). More QoL data on elderly patients treated with ET are needed. Our aims are to study QoL in early-stage breast cancer patients throughout the treatment period and compare the QoL of ET groups. METHODS: 148 patients > 65 years who began ET with either tamoxifen or aromatase inhibitor (AI) completed the EORTC QLQ-C30 and QLQ-BR23 and the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) questionnaires three times over 3 years of ET. Linear mixed-effect models were used to evaluate longitudinal QoL changes. ET group comparisons were conducted after 3 years of treatment via ANCOVA adjusted by basal QoL. RESULTS: QoL scores were high (> 80/100 points) in most QoL areas, with moderate limitations (> 30) in sexual functioning and enjoyment and in future perspective. After 3 years of ET, four QoL areas improved (< 6 points) compared to baseline and 3-month assessments. Hot flushes worsened (8 points) at the 3-month assessment but by 3 years had recovered. AI patients showed more hot flushes, pain and diarrhea and less sexual enjoyment than tamoxifen patients after 3 years of ET (differences 3-12 points). CONCLUSIONS: Results indicate that elderly early-stage breast cancer patients adapted well to their disease and ET treatment over the 3 years. Few QoL differences were observed between ET groups.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Qualidade de Vida , Tamoxifeno/uso terapêutico , Idoso , Feminino , Seguimentos , Humanos , Prognóstico , Estudos Prospectivos , Inquéritos e Questionários
6.
Clin. transl. oncol. (Print) ; 21(1): 55-63, ene. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-183344

RESUMO

NENs are a heterogeneous family of tumors of challenging diagnosis and clinical management. Their incidence and prevalence continue to rise across all sites, stages and grades. Although improved diagnostic techniques have led to earlier detection and stage migration, the improved prognosis documented over time for advanced gastrointestinal and pancreatic neuroendocrine tumors also reflect improvements in therapy. The aim of this guideline is to update practical recommendations for the diagnosis and treatment of gastroenteropancreatic and lung NENs. Diagnostic procedures, histological classification and therapeutic options are briefly discussed, including surgery, liver-directed therapy, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, and treatment algorithms are provided


No disponible


Assuntos
Humanos , Neoplasias Gastrointestinais/terapia , Neoplasias Pancreáticas/terapia , Neoplasias Brônquicas/terapia , Tumores Neuroendócrinos/terapia , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Brônquicas/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Padrões de Prática Médica
7.
Clin Transl Oncol ; 21(1): 55-63, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30535553

RESUMO

NENs are a heterogeneous family of tumors of challenging diagnosis and clinical management. Their incidence and prevalence continue to rise across all sites, stages and grades. Although improved diagnostic techniques have led to earlier detection and stage migration, the improved prognosis documented over time for advanced gastrointestinal and pancreatic neuroendocrine tumors also reflect improvements in therapy. The aim of this guideline is to update practical recommendations for the diagnosis and treatment of gastroenteropancreatic and lung NENs. Diagnostic procedures, histological classification and therapeutic options are briefly discussed, including surgery, liver-directed therapy, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, and treatment algorithms are provided.


Assuntos
Neoplasias Brônquicas/terapia , Neoplasias Gastrointestinais/terapia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/terapia , Guias de Prática Clínica como Assunto/normas , Neoplasias Brônquicas/diagnóstico , Ensaios Clínicos como Assunto , Terapia Combinada , Gerenciamento Clínico , Neoplasias Gastrointestinais/diagnóstico , Humanos , Tumores Neuroendócrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Prognóstico , Sociedades Médicas
8.
Eur J Cancer ; 101: 263-272, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30054049

RESUMO

BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab/administração & dosagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Exantema/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Proteínas Proto-Oncogênicas p21(ras)/genética
9.
Gastric Cancer ; 21(1): 96-105, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28393278

RESUMO

BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sistema de Registros
10.
Clin. transl. oncol. (Print) ; 19(8): 969-975, ago. 2017. tab, ilus, graf
Artigo em Inglês | IBECS | ID: ibc-164675

RESUMO

Background. The objective of the study is to determine the correlations among the variables of dose and the sphincter function (SF) in patients with locally advanced rectal cancer treated with preoperative capecitabine/radiotherapy followed by low anterior resection (LAR) + TME. Methods. We retrospectively reviewed 92 consecutive patients with LARC treated at our center with LAR from 2006 and more than 2 years free from disease. We re-contoured the anal sphincters (AS) of patients with the help of the radiologist. SF was assessed with the Wexner scale (0-20 points, being punctuation inversely proportional to annal sphincter functionality). All questionnaires were filled out between January 2010 and December 2012. Dosimetric parameters that have been studied include V20, V30, V40, V50, mean dose (Dmean), minimum dose (Dmin), D90 (dose received by 90% of the sphincter) and D98. Statistical analysis. The correlations among the variables of dose and SF were studied by the Spearman correlation coefficient. Differences in SF relating to maximum doses to the sphincter were assessed by the Mann-Whitney test. Results. Mean Wexner score was 5.5 points higher in those patients with V20 > 0 compared to those for which V20 = 0 (p = 0.008). In a multivariate regression model, results suggest that the effect of V20 on poor anal sphincter control is independent of the effect of distance, with an adjusted OR of 3.42. Conclusions. In order to improve the SF in rectal cancer treated with preoperative radiotherapy/capecitabine followed by conservative surgery, the maximum radiation dose to the AS should be limited, when possible, to <20 Gy (AU)


No disponible


Assuntos
Humanos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Incontinência Fecal/complicações , Canal Anal/efeitos da radiação , Quimiorradioterapia/métodos , Capecitabina/uso terapêutico , Qualidade de Vida , Neoplasias Retais/complicações , Neoplasias Retais/cirurgia , Incontinência Fecal/radioterapia , Canal Anal/patologia , Estudos Retrospectivos , Análise Multivariada
11.
Br J Cancer ; 116(12): 1526-1535, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28463962

RESUMO

BACKGROUND: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. METHODS: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. RESULTS: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). CONCLUSIONS: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica , Nomogramas , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/química , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Neoplasias Esofágicas/química , Neoplasias Esofágicas/patologia , Nível de Saúde , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Gradação de Tumores , Neutrófilos , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Trastuzumab/administração & dosagem , Carga Tumoral , População Branca , Adulto Jovem
12.
Clin Transl Oncol ; 19(8): 969-975, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28194687

RESUMO

BACKGROUND: The objective of the study is to determine the correlations among the variables of dose and the sphincter function (SF) in patients with locally advanced rectal cancer treated with preoperative capecitabine/radiotherapy followed by low anterior resection (LAR) + TME. METHODS: We retrospectively reviewed 92 consecutive patients with LARC treated at our center with LAR from 2006 and more than 2 years free from disease. We re-contoured the anal sphincters (AS) of patients with the help of the radiologist. SF was assessed with the Wexner scale (0-20 points, being punctuation inversely proportional to annal sphincter functionality). All questionnaires were filled out between January 2010 and December 2012. Dosimetric parameters that have been studied include V 20, V 30, V 40, V 50, mean dose (D mean), minimum dose (D min), D 90 (dose received by 90% of the sphincter) and D 98. STATISTICAL ANALYSIS: The correlations among the variables of dose and SF were studied by the Spearman correlation coefficient. Differences in SF relating to maximum doses to the sphincter were assessed by the Mann-Whitney test. RESULTS: Mean Wexner score was 5.5 points higher in those patients with V 20 > 0 compared to those for which V 20 = 0 (p = 0.008). In a multivariate regression model, results suggest that the effect of V 20 on poor anal sphincter control is independent of the effect of distance, with an adjusted OR of 3.42. CONCLUSIONS: In order to improve the SF in rectal cancer treated with preoperative radiotherapy/capecitabine followed by conservative surgery, the maximum radiation dose to the AS should be limited, when possible, to <20 Gy.


Assuntos
Adenocarcinoma/terapia , Canal Anal/patologia , Quimiorradioterapia/efeitos adversos , Incontinência Fecal/etiologia , Neoplasias Retais/terapia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal/efeitos da radiação , Incontinência Fecal/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Prognóstico , Doses de Radiação , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de Sobrevida
14.
Ann Oncol ; 27(7): 1304-11, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27059553

RESUMO

BACKGROUND: Emerging agents blocking the programmed cell death 1 (PD-1) pathway show activity in metastatic clear cell renal cell carcinoma (mRCC). The aim of this study was to evaluate the efficacy and safety of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy after PD-1 inhibition. PATIENTS AND METHODS: Patients with mRCC treated with anti-PD-1 antibody (aPD-1) monotherapy or in combination (with VEGFR-TKI or ipilimumab) that subsequently received VEGFR-TKI were retrospectively reviewed. The efficacy end points were objective response rate (ORR) and progression-free survival (PFS) stratified by the type of prior PD-1 regimen. Safety by the type and PD-1 exposure was also evaluated. RESULTS: Seventy patients were included. Forty-nine patients received prior therapy with immune checkpoint inhibitors (CPIs) alone and 21 had combination therapy of aPD-1 and VEGFR-TKI. Overall, ORR to VEGFR-TKI after PD-1 inhibition was 28% (19/68) and the median PFS was 6.4 months (mo) (4.3-9.5). ORR to VEGFR-TKI after aPD-1 in combination with VEGFR-TKI was lower than that in patients treated with VEGFR-TKI after CPI alone (ORR 10% versus 36%, P = 0.039). In the multivariable analysis, patients treated with prior CPI alone were more likely to achieve an objective response than those treated with aPD-1 in combination with VEGFR-TKI (OR = 5.38; 95% CI 1.12-26.0, P = 0.03). There was a trend toward numerically longer median PFS in the VEGFR-TKI after the CPI alone group, 8.4 mo (3.2-12.4) compared with 5.5 mo (2.9-8.3) for those who had VEGFR-TKI after aPD-1 in combination with VEGFR-TKI (P = 0.15). The most common adverse events (AEs) were asthenia, hypertension, and diarrhea. CONCLUSIONS: The efficacy and safety of VEGFR-TKIs after PD-1 inhibition were demonstrated in this retrospective study. The response rate was lower and the median progression-free survival was shorter in those patients who received prior PD-1 in combination with VEGFR-TKI. PD-1 exposure does not seem to significantly influence the safety of subsequent VEGFR-TKI treatment.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Receptor de Morte Celular Programada 1/genética , Inibidores de Proteínas Quinases/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Everolimo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Sirolimo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
15.
Crit Rev Oncol Hematol ; 101: 193-206, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27021395

RESUMO

Pancreatic neuroendocrine tumours (PanNETs) are considered a relatively unusual oncologic entity. Due to its relative good prognosis, surgery remains the goal standard therapy not only in localized disease but also in the setting of locally or metastatic disease. Most of the patients are diagnosed in metastatic scenario, where multidisciplinary approach based on surgery, chemotherapies, liver-directed and/or molecular targeted therapies are commonly used. Owing to a deeper molecular knowledge of this disease, these targeted therapies are nowadays widely implemented, being the likely discovery of predictive biomarkers that would allow its use in other settings. This review is focused on describing the different classifications, etiology, prognostic biomarkers and multidisciplinary approaches that are typically used in PanNET.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Biomarcadores Tumorais/sangue , Humanos , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico
16.
17.
Clin. transl. oncol. (Print) ; 17(2): 139-144, feb. 2015. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-132884

RESUMO

Objective. To determine the impact of initial FDG PET/CT staging on clinical stage and the management plan in patients with locally advanced head and neck cancer (LAHNC). Materials and methods. We retrospectively reviewed the records of 72 consecutive patients (2007–2010) staged with PET/CT and conventional CT with tumours of hypopharynx/larynx (26 patients, 36 %), oral cavity (17 patients, 24 %), oropharynx (16 patients, 22 %), nasopharynx (12 patients, 17 %), and others (2 %). The impact of PET/CT on management plans was considered high when PET/CT changed the planned treatment modality or treatment intent, and intramodality changes were considered as minor changes with low impact. Results. FDG PET/CT changed the stage in 27 patients and had high impact on the management plan in 12 % of patients (detection of distant metastases in 6 patients and stage II in 2 patients). Intramodality changes were more frequent: FDG PET/CT altered the TNM stage in 18/72 (25 %) of patients, upstaging N stage in 90 % of patients with low impact. Conclusions. Initial FDG PET/CT staging not only improves stage but also affects the management plan in LAHNC patients (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Neoplasias de Cabeça e Pescoço , Tomografia por Emissão de Pósitrons/instrumentação , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons , Estadiamento de Neoplasias/instrumentação , Estadiamento de Neoplasias/métodos , Neoplasias de Cabeça e Pescoço/fisiopatologia , Neoplasias de Cabeça e Pescoço/radioterapia , Tomografia por Emissão de Pósitrons/normas , Estudos Retrospectivos , Hipofaringe/patologia , Hipofaringe , Neoplasias Hipofaríngeas , Boca , Nasofaringe , Neoplasias Nasofaríngeas
18.
Clin Transl Oncol ; 17(2): 139-44, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25078571

RESUMO

OBJECTIVE: To determine the impact of initial FDG PET/CT staging on clinical stage and the management plan in patients with locally advanced head and neck cancer (LAHNC). MATERIALS AND METHODS: We retrospectively reviewed the records of 72 consecutive patients (2007-2010) staged with PET/CT and conventional CT with tumours of hypopharynx/larynx (26 patients, 36 %), oral cavity (17 patients, 24 %), oropharynx (16 patients, 22 %), nasopharynx (12 patients, 17 %), and others (2 %). The impact of PET/CT on management plans was considered high when PET/CT changed the planned treatment modality or treatment intent, and intramodality changes were considered as minor changes with low impact. RESULTS: FDG PET/CT changed the stage in 27 patients and had high impact on the management plan in 12 % of patients (detection of distant metastases in 6 patients and stage II in 2 patients). Intramodality changes were more frequent: FDG PET/CT altered the TNM stage in 18/72 (25 %) of patients, upstaging N stage in 90 % of patients with low impact. CONCLUSIONS: Initial FDG PET/CT staging not only improves stage but also affects the management plan in LAHNC patients.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/secundário , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Estadiamento de Neoplasias , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos
19.
Clin. transl. oncol. (Print) ; 16(8): 739-745, ago. 2014. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-126562

RESUMO

AIMS: Pathological response has been shown to be a predictor for survival after preoperative chemotherapy and surgical resection of colorectal cancer liver metastases. This retrospective analysis evaluated the effect on pathological response of adding bevacizumab to standard neoadjuvant chemotherapy in patients with metastatic colorectal cancer (mCRC) and liver metastases. METHODS: Patient records from two Spanish centres were retrospectively examined for this analysis. Patients were included if they had stage IV mCRC with liver metastases, were unresectable or marginally resectable tumour before chemotherapy, and had oxaliplatin- or irinotecan-based chemotherapy, with or without bevacizumab, before resection. Tumour response was evaluated using response evaluation criteria in solid tumours (RECIST). Pathological response was assessed by pathologists blinded to treatment. RESULTS: Ninety-five patients were included. Good pathological responses (PR0/PR1) were observed in 37 patients (39 %). The RECIST response rate was 51 %. Only 42 % of patients with a good pathological response had a complete or partial response according to RECIST, while 57 % of those with a poor pathological response had a complete or partial response according to RECIST. RECIST response rates were similar with and without bevacizumab, although 49 % of bevacizumab-treated patients had a good pathological response versus 27 % of those receiving chemotherapy alone (χ (2) P = 0.0302). CONCLUSION: Pathological response may be a better indicator of treatment efficacy than RECIST for patients with mCRC receiving bevacizumab in the neoadjuvant setting. Adding bevacizumab to chemotherapy has the potential to increase pathological response rates. Well-designed prospective clinical studies are required to establish the efficacy and tolerability of this approach (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Metástase Neoplásica/tratamento farmacológico , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante , Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais Humanizados/metabolismo , Estudos Retrospectivos , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico
20.
Crit Rev Oncol Hematol ; 92(3): 166-80, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25048167

RESUMO

The application of nanotechnology in oncology has increased the efficacy and efficiency of some cytotoxic agents. The paradigm in this field is nab-paclitaxel, a soluble form of paclitaxel that is linked to albumin nanoparticles. The development of nanotechnology as a delivery system for paclitaxel has provided better pharmacokinetic and pharmacodynamic characteristics, neutralizing its hydrophobicity. This procedure significantly improves the treatment of metastatic breast cancer compared to conventional paclitaxel-based therapies, including other type of cancers such as metastatic pancreatic cancer, stage IIIB-IV non-small cell lung cancer (NSCLC) and metastatic melanoma. In these last cases, significant differences were found in primary end-points for patients treated with nab-paclitaxel-based chemotherapy compared to those treated with conventional treatments. The application of nanotechnology in cancer treatment may also improve the efficacy of other known drugs, as a result of improved pharmacokinetic and pharmacodynamic profiles, similarly to paclitaxel.


Assuntos
Albuminas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Paclitaxel/uso terapêutico , Albuminas/farmacologia , Animais , Antineoplásicos/farmacologia , Transporte Biológico , Biomarcadores , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Nanomedicina , Paclitaxel/farmacologia , Resultado do Tratamento
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