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1.
ESMO Open ; 9(5): 103443, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38692082

RESUMO

BACKGROUND: The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. PATIENTS AND METHODS: Patients were classified into low or high risk according to the EPclin score, consisting of a 12-gene molecular score combined with tumor size and nodal status. Association of the EPclin score with disease-free survival (DFS) and distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier estimates. The independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics. RESULTS: EndoPredict test results were available for 768 patients: 663 patients classified as EPclin high risk (EPCH) and 105 patients as EPclin low risk (EPCL). Median follow-up was 70 months (range 1-172 months). For the 429 EPCH randomized patients, there was no significant difference in DFS between treatment arms. The 60-month relapse rate for patients in the EPCL and EPCH groups was 0% and 7%, respectively. Hazard ratio (HR) supposing continuous EPclin score was 1.87 [95% confidence interval (CI) 1.4-2.5, P < 0.0001]. This prognostic effect remained significant when assessed in a Cox model adjusting on tumor size, number of positive nodes and tumor grade (HR 1.52, 95% CI 1.09-2.13, P = 0.0141). The 60-month DMFS for patients in the EPCL and EPCH groups was 100% and 94%, respectively (adjusted HR 8.10, 95% CI 1.1-59.1, P < 0.0001). CONCLUSIONS: The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.


Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Método Duplo-Cego , Idoso , Adulto , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Everolimo/uso terapêutico , Everolimo/farmacologia , Intervalo Livre de Doença , Biomarcadores Tumorais/metabolismo
2.
J Hum Genet ; 67(6): 339-345, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35017683

RESUMO

Pathogenic Variants (PV) in major cancer predisposition genes are only identified in approximately 10% of patients with Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Next Generation Sequencing (NGS) leads to the characterization of incidental variants in genes other than those known to be associated with HBOC syndrome. The aim of this study was to determine if such incidental PV were specific to a phenotype. The detection rates of HBOC-associated and incidental PV in 1812 patients who underwent genetic testing were compared with rates in control groups FLOSSIES and ExAC. The rates of incidental PV in the PALB2, ATM and CHEK2 genes were significantly increased in the HBOC group compared to controls with, respective odds ratios of 15.2 (95% CI = 5.6-47.6), 9.6 (95% CI = 4.8-19.6) and 2.7 (95% CI = 1.3-5.5). Unsupervised Hierarchical Clustering on Principle Components characterized 3 clusters: by HBOC (P = 0.01); by ExAC and FLOSSIES (P = 0.01 and 0.02 respectively); and by HBOC, ExAC and FLOSSIES (P = 0.01, 0.04 and 0.04 respectively). Interestingly, PALB2 and ATM were grouped in the same statistical cluster defined by the HBOC group, whereas CHEK2 was in a different cluster. We identified co-occurrences of PV in ATM and BRCA genes and confirmed the Manchester Scoring System as a reliable PV predictor tool for BRCA genes but not for ATM or PALB2. This study demonstrates that ATM PV, and to a lesser extent CHEK2 PV, are associated with HBOC syndrome. The co-occurrence of ATM PV with BRCA PV suggests that such ATM variants are not sufficient alone to induce cancer, supporting a multigenism hypothesis.


Assuntos
Neoplasias da Mama , Síndrome Hereditária de Câncer de Mama e Ovário , Neoplasias Ovarianas , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína BRCA2/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Feminino , Predisposição Genética para Doença , Testes Genéticos , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Síndrome Hereditária de Câncer de Mama e Ovário/epidemiologia , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Humanos , Incidência , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética
3.
Gynecol Oncol ; 158(3): 666-672, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32624235

RESUMO

BACKGROUND: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. PATIENTS AND METHODS: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. RESULTS: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. CONCLUSION: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.


Assuntos
Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Ovarianas/terapia , Conduta Expectante , Adolescente , Adulto , Idoso , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologia , Coriocarcinoma/cirurgia , Coriocarcinoma/terapia , Disgerminoma/tratamento farmacológico , Disgerminoma/patologia , Disgerminoma/cirurgia , Disgerminoma/terapia , Tumor do Seio Endodérmico/tratamento farmacológico , Tumor do Seio Endodérmico/patologia , Tumor do Seio Endodérmico/cirurgia , Tumor do Seio Endodérmico/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos , Teratoma/tratamento farmacológico , Teratoma/patologia , Teratoma/cirurgia , Teratoma/terapia , Adulto Jovem
4.
Ann Oncol ; 29(12): 2334-2340, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30307466

RESUMO

Background: Palbociclib is a CDK4/6 inhibitor with demonstrated efficacy and safety in combination with endocrine therapy in advanced luminal breast cancer (LBC). We evaluated the respective efficacy and safety of chemotherapy and letrozole-palbociclib (LETPAL) combination as neoadjuvant treatment in patients with high-risk LBC. Patients and methods: NeoPAL (UCBG10/4, NCT02400567) is a randomised, parallel, non-comparative phase II study. Patients with ER-positive, HER2-negative, Prosigna®-defined luminal B, or luminal A and node-positive, stage II-III breast cancer, not candidate for breast-conserving surgery, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks, or to FEC100 (5FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2)×3 21-day courses followed by docetaxel 100 mg/m2×3 21-day courses. Primary end point was residual cancer burden (RCB 0-I rate). Secondary end points included clinical response, proliferation-based markers, and safety. Results: Overall, 106 patients were randomised [median Prosigna® ROR Score 71 (22-93)]. RCB 0-I was observed in four and eight patients in LETPAL [7.7% (95% CI 0.4-14.9)] and chemotherapy [15.7% (95% CI 5.7-25.7)] arms, respectively. Pathological complete response rates were 3.8% and 5.9%. Clinical response (75%) and breast-conserving surgery rates (69%) were similar in both arms. Preoperative Endocrine Prognostic Index 0 scores (breast cancer-specific survival) were observed in 17.6% and 8.0% of patients in LETPAL and chemotherapy arms, respectively. Safety profile was as expected, with 2 versus 17 serious adverse events (including 11 grade 4 serious AEs in the chemotherapy arm). Conclusion: LETPAL combination was associated with poor pathological response but encouraging clinical and biomarker responses in Prosigna®-defined high-risk LBC. Contemporary chemotherapy regimen was associated with poor pathological and biomarker responses, with a much less favourable safety profile. LETPAL combination might represent an alternative to chemotherapy in early high-risk LBC. Clinical Trial Number: NCT02400567.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/terapia , Letrozol/administração & dosagem , Piperazinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Idoso , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Letrozol/efeitos adversos , Mastectomia Segmentar , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Seleção de Pacientes , Piperazinas/efeitos adversos , Prognóstico , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos
5.
Ann Oncol ; 26(2): 325-32, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25467016

RESUMO

BACKGROUND: Neoadjuvant trials conducted using a double HER2 blockade with lapatinib and trastuzumab, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological complete response (pCR) rates, but at the cost of important toxicity. We hypothesised that this toxicity might be due to a specific interaction between paclitaxel and lapatinib. This trial assesses the toxicity and activity of the combination of docetaxel with lapatinib and trastuzumab. PATIENTS AND METHODS: Patients with stage IIA to IIIC HER2-positive breast cancer received six cycles of chemotherapy (three cycles of docetaxel followed by three cycles of fluorouracil, epirubicin, cyclophosphamide). They were randomised 1 : 1 : 1 to receive during the first three cycles either lapatinib (1000 mg orally daily), trastuzumab (4 mg/kg loading dose followed by 2 mg/kg weekly), or trastuzumab + lapatinib at the same dose. The primary end point was pCR rate defined as ypT0/is. Secondary end points included safety and toxicity. pCR rate defined as ypT0/is ypN0 was assessed as an exploratory analysis. In June 2012, arm A was closed for futility based on the results from other studies. RESULTS: From October 2010 to January 2013, 128 patients were included in 14 centres. The percentage of the 122 assessable patients with pCR in the breast, and pCR in the breast and nodes, was numerically highest in the lapatinib + trastuzumab group (60% and 56%, respectively), intermediate in the trastuzumab group (52% and 52%), and lowest in the lapatinib group (46% and 36%). Frequency (%) of the most common grade 3-4 toxicities in the lapatinib /trastuzumab/lapatinib + trastuzumab arms were: febrile neutropenia 23/15/10, diarrhoea 9/2/18, infection (other) 9/4/8, and hepatic toxicity 0/2/8. CONCLUSIONS: This study demonstrates a numerically modest pCR rate increase with double anti-HER2 blockade plus chemotherapy, but suggests that the use of docetaxel rather than paclitaxel may not reduce toxicity. CLINICALTRIALSGOV: NCT00450892.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Terapia Neoadjuvante/métodos , Adulto , Idoso , Antraciclinas/administração & dosagem , Ciclofosfamida/administração & dosagem , Docetaxel , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Lapatinib , Pessoa de Meia-Idade , Quinazolinas/administração & dosagem , Receptor ErbB-2/biossíntese , Receptor ErbB-2/genética , Taxoides/administração & dosagem , Trastuzumab/administração & dosagem
6.
Cancer Chemother Pharmacol ; 72(1): 65-73, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23636449

RESUMO

PURPOSE: Whether an anticoagulant prophylaxis is needed for patients with cancer with a central venous catheter is a highly controversial subject. We designed a study to compare different prophylactic strategies over 3 months of treatment. METHODS: We performed a phase III prospective, open-label randomized trial. After the insertion of a central venous access device, consecutive patients with planned chemotherapy for cancer were randomized to no anticoagulant prophylaxis, low molecular weight heparin [low molecular weight heparin (LMWH); with isocoagulation doses], or warfarin 1 mg/day. Treatments were given over the first 3 months. Doppler ultrasound and venographies were performed on days 1 and 90, respectively, or sooner in case of clinical presumption of thrombosis. RESULTS: A total of 420 patients were randomized, and 407 were evaluable. Forty-two catheter-related deep vein thrombosis (DVT) occurred (10.3 %), 20 in those with no anticoagulation, 8 in those receiving warfarin, and 14 in those receiving LMWH. Nine additional non-related catheter deep vein thrombosis (CDVT) occurred. Anticoagulation significantly reduced the incidence of catheter-related DVT (p = 0.035) and catheter non-related DVT (p = 0.007), with no difference between warfarin and LMWH. Safety was good (3.4 % of attributable events) but compliance with randomized prophylaxis was lower than expected. CONCLUSIONS: Prophylaxis showed a benefit regarding catheter-related and non-catheter-related DVT with no increase in serious side effects.


Assuntos
Anticoagulantes/uso terapêutico , Antineoplásicos/administração & dosagem , Cateteres Venosos Centrais/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Neoplasias/tratamento farmacológico , Trombose Venosa Profunda de Membros Superiores/prevenção & controle , Varfarina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Feminino , França/epidemiologia , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Incidência , Análise de Intenção de Tratamento , Perda de Seguimento , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Neoplasias/complicações , Índice de Gravidade de Doença , Trombose Venosa Profunda de Membros Superiores/epidemiologia , Trombose Venosa Profunda de Membros Superiores/etiologia , Trombose Venosa Profunda de Membros Superiores/fisiopatologia , Trombose Venosa/complicações , Trombose Venosa/epidemiologia , Trombose Venosa/fisiopatologia , Trombose Venosa/prevenção & controle , Varfarina/administração & dosagem , Varfarina/efeitos adversos , Adulto Jovem
7.
Case Rep Oncol ; 3(1): 45-48, 2010 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-20740158

RESUMO

Neuroblastoma (NB) rarely occurs in adults, and less than 10% of the cases occur in patients older than 10 years. Currently, there are no standard treatment guidelines for adult NB patients. We report the case of a young man suffering from NB in adulthood with multiple recurrences. Treatment included multiple resections, chemotherapy, and radiotherapy. This patient remains free of clinical disease more than 7 years after diagnosis.

8.
Anticancer Res ; 29(7): 2563-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19596929

RESUMO

BACKGROUND: [18F]-fluorodeoxyglucose with positron-emission tomography (PET) and computed tomography (CT) scans were used to assess morphological and metabolic tumour response after chemotherapy in metastatic colorectal cancer. PATIENTS AND METHODS: Twenty-five patients were evaluated after 4 courses of chemotherapy (+/-target therapy), and among them 20 patients after 2 courses. Response Evaluation Criteria In Solid Tumors (RECIST) and European Organisazion for Research and Treatment of Cancer (EORTC) criteria were used to evaluate CT and PET respectively. RESULTS: Discrepancies between the two procedures were noted after 4 courses of chemotherapy in patient-based analysis. Two morphologically complete responses (CR) were correlated with metabolic response. Seven morphological partial responses (PR) were evaluated as 3 metabolic PR, 2 CR and 1 progressive disease (PD). Seventeen cases of morphologically stable disease (SD) were evaluated as 3 metabolic CR, 13 PR and 1 PD. These discrepancies were confirmed in lesion-based analysis. Perfect concordance was noted between metabolic responses obtained after 2 and 4 cycles. CONCLUSION: Morphological and metabolic imaging does not permit concordant therapeutic assessment in metastatic colorectal cancer.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Metástase Neoplásica , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X
9.
Br J Cancer ; 97(7): 883-7, 2007 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-17876327

RESUMO

The aim of this study was to evaluate with a long follow-up the efficacy of concomitant chemoradiotherapy in non-metastatic inflammatory breast cancer (IBC) and to evaluate the breast conservation rate. Between 1990 and 2000, 66 non-metastatic patients with IBC were treated with chemotherapy and concomitant irradiation. The induction chemotherapy consisted of epirubicine, cyclophosphamide and vindesine, in association with split-course bi-fractionated irradiation to a total dose of 65 Gy with concomitant cisplatin and 5-fluorouracil. Maintenance chemotherapy consisted of high-dose methotrexate and six cycles of epirubicine, cyclophosphamide and fluorouracil. Hormonal treatment was given if indicated. Mastectomy was not systemic. Among 65 evaluable patients, 57 (87.6%) achieved a complete clinical response and had a breast conservation. Only six loco regional relapses were noted in six patients with a delay of 20 months and with concomitant metastatic dissemination in four cases. Median disease-free survival (DFS) was 28 months. Median overall survival (OS) was 63 months and median follow-up was 55.5 months. Induction chemotherapy and concomitant irradiation is feasible in patients with IBC, permitting a breast conservation with a high rate of local control with an OS comparable to that of the best recent series.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/patologia , Carcinoma Lobular/radioterapia , Cisplatino/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Menopausa , Pessoa de Meia-Idade , Indução de Remissão , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
10.
Anticancer Drugs ; 14(10): 829-32, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14597878

RESUMO

We report one new case of hemolytic-uremic syndrome (HUS) and one case of digital necrosis after treatment with gemcitabine (Gemzar). Case 1, a 34-year-old man, was given first-line metastatic treatment with gemcitabine for a adenocarcinoma of the pancreas. After a cumulative dose of 10 000 mg/m2 gemcitabine, the onset of subacute renal failure associated with hemolytic anemia of mechanical origin was observed. A diagnosis of probable gemcitabine-induced thrombotic microangiopathy was arrived at. Symptoms resolved after stopping the chemotherapy, in spite of the progression of the disease. Case 2, a 61-year-old man, was administered a combination of gemcitabine and a platinum salt as first-line metastatic treatment for carcinoma of the bladder urothelium. Following a cumulative dose of 10 000 mg/m2 of gemcitabine, the patient suffered from bilateral peripheral vascular disease of somewhat acute onset with hemorrhagic lesions of the finger pads that became necrotic. The work-up was negative and a causal relationship was attributed to gemcitabine. The patient made good progress when given an i.v. infusion of Ilomedine (iloprost trometamol) and chemotherapy was withdrawn. We conclude that gemcitabine must be added to the list of drugs that cause HUS and necrotizing vasculitis.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/efeitos adversos , Dedos/patologia , Síndrome Hemolítico-Urêmica/induzido quimicamente , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/secundário , Desoxicitidina/uso terapêutico , Gangrena/induzido quimicamente , Gangrena/tratamento farmacológico , Síndrome Hemolítico-Urêmica/patologia , Humanos , Iloprosta/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vasodilatadores/uso terapêutico , Gencitabina
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