RESUMO
CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65-79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10-5 by next-generation sequencing at 18 months from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10-5 were reported in 35 patients (26%, 95% confidence interval (CI) 19-34) in IsaRd versus 71 (53%, 95% CI 44-61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89-5.28, P < 0.0001). The MRD benefit was consistent across subgroups at 10-5 and 10-6, and was already observed at month 12. The proportion of patients with complete response or better at 18 months was higher with Isa-VRd (58% versus 33%; P < 0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P = 0.0003). At a median follow-up of 23.5 months, no difference was observed for survival times (immature data). The addition of weekly bortezomib did not significantly affect the relative dose intensity of IsaRd. Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10-5, the primary endpoint, compared with IsaRd. This study proposes Isa-VRd as a new SOC for patients with NDMM that are TI. ClinicalTrials.gov identifier: NCT04751877 .
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Lenalidomida , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Idoso , Masculino , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasia Residual , Resultado do TratamentoRESUMO
INTRODUCTION: General practitioners (GPs) play a central role in the management and coordination of care of patients with malignant tumors and blood diseases. Civilian GPs encounter certain difficulties during the care of such patients. The practice of unit medicine in a military environment differs from that in a civilian context through expertise in fitness to serve and to deployment and the target population. We identified the difficulties encountered by "unit" physicians during and after cancer treatment. MATERIALS AND METHODS: We conducted a multicenter cross-sectional descriptive study from July 2, 2021, to September 30, 2022, targeting all military GPs belonging to the French Armed Forces Health Service. We sent a questionnaire consisting of 1 open- and 16 closed multiple-choice questions describing the population of unit physicians and their patients (questions 1-5), the difficulties encountered by physicians in the follow-up of military personnel with cancer (Questions 6, 7, 11, 12, and 13), and the potential information networks accessible to physicians (questions 8-10, 14, and 17). RESULTS: Three hundred and ninety physicians completed the questionnaires. Among the 700 military GPs, 390 physicians responded to the questionnaire and 327 completed it exhaustively. The questionnaire response rate was 55%. Of the responding physicians, 49% and 70% reported following patients with an "active" malignant tumor and a malignant tumor pathology in remission, respectively. Thirty-one percent of the physicians encountered difficulties with these patients as follows: 26% concerning fitness for duty, 17% in medical follow-up, 14% in addressing the psychological aspect, 11% concerning specialist accessibility for advice, 10% in managing deconditioning to effort, 9% in addressing the social aspect, 7% in medical management, and 6% concerning other issues. CONCLUSIONS: Difficulties in the follow-up of patients with cancer affect military doctors. They mainly concern fitness for duty and medical follow-up.
Assuntos
Clínicos Gerais , Militares , Neoplasias , Humanos , Estudos Transversais , Seguimentos , Neoplasias/terapiaRESUMO
Relapsed/Refractory Diffuse Large B Cell Lymphoma have a dismal prognosis in need of innovative treatments. This prospective phase 2 study enrolled 32 patients between 2013 and 2017 with Relapsed/Refractory Diffuse Large B Cell Lymphoma treated with Rituximab and Lenalidomide (R2). Median age was 69 years (40-86), 90.1% had received at least 2 prior lines of treatment, 81% were defined as having High Risk disease according to our criteria and ECOG performance status was > 2 in 51.6%. Patients received a median number of 2 cycles of R2 (1-12). With a median follow up of 22.6 months, the objective response rate was 12.5%. Median progression free survival was 2.6 months (95% CI, [1.7-2.9]) and median overall survival was 9.3 months (95% CI, [5.1-Not estimable]). This study therefore did not achieve its primary endpoint and the R2 regimen cannot be recommended in Relapsed/Refractory Diffuse Large B Cell Lymphoma patients with High Risk features.
Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Idoso , Rituximab/efeitos adversos , Lenalidomida/efeitos adversos , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma não Hodgkin/tratamento farmacológico , Resultado do TratamentoAssuntos
Antineoplásicos/uso terapêutico , Carbolinas/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Carcinoma de Células Pequenas/diagnóstico por imagem , Carcinoma de Células Pequenas/secundário , Humanos , Masculino , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologiaRESUMO
INTRODUCTION: The maintenance of military surgeons' operative skills is challenging. Different and specific training strategies have been implemented in this context; however, little has been evaluated with regard to their effectiveness. Cancer surgery is a part of military surgeons' activities in their home hospitals. This study aimed to assess the role of oncological surgery in the improvement of military surgeons' operative skills. METHODS: Between January and June 2019, the surgical activities of the departments of visceral, ear, nose, and throat, urological, and thoracic surgery were retrospectively reviewed and assessed in terms of the operative time (OT). All surgeons working at the Sainte Anne Military Teaching Hospital were sent a survey to rate on a 5-point scale the current surgical practices on their usefulness in improving surgical skills required for treating war injuries during deployment (primary endpoint) and to compare on a 10-point visual analog scale the influence of cancer surgery and specific training on surgical fluency (secondary endpoint). RESULTS: Over the study period, 2,571 hours of OT was analyzed. Oncological surgery represented 52.5% of the surgical activity and almost 1,350 hours of cumulative OT. Considering the primary endpoint, the mean rating allocated to cancer surgery was 4.53 ± 0.84, which was not statistically different than that allocated to trauma surgery (4.42 ± 1.02, P = 0.98) but higher than other surgery (2.47 ± 1.00, P < 0.001). Considering the secondary endpoint, cancer surgery was rated higher than specific training by all surgeons, without statistically significant difference (positive mean score of + 2.00; 95% IC: 0.85-3.14). CONCLUSION: This study demonstrates the usefulness of cancer surgery in improving the operative skills of military surgeons.
Assuntos
Cirurgia Geral , Militares , Neoplasias , Cirurgiões , Traumatologia , Competência Clínica , Humanos , Neoplasias/cirurgia , Estudos Retrospectivos , Traumatologia/educaçãoRESUMO
FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM.
Assuntos
Corticosteroides/administração & dosagem , Eosinofilia , Neoplasias Hematológicas , Transtornos Mieloproliferativos , Proteínas de Fusão Oncogênica , Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Fatores de Poliadenilação e Clivagem de mRNA , Adulto , Intervalo Livre de Doença , Eosinofilia/sangue , Eosinofilia/tratamento farmacológico , Eosinofilia/genética , Eosinofilia/mortalidade , Feminino , França/epidemiologia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/mortalidade , Proteínas de Fusão Oncogênica/sangue , Proteínas de Fusão Oncogênica/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/sangue , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Estudos Retrospectivos , Taxa de Sobrevida , Triptases/sangue , Vitamina B 12/sangue , Fatores de Poliadenilação e Clivagem de mRNA/sangue , Fatores de Poliadenilação e Clivagem de mRNA/genéticaAssuntos
Carcinoma/secundário , Neoplasias Orbitárias/secundário , Neoplasias da Próstata/patologia , Neoplasias Cranianas/secundário , Osso Esfenoide , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico por imagem , Carcinoma/cirurgia , Exoftalmia/diagnóstico por imagem , Exoftalmia/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/cirurgia , Neoplasias da Próstata/diagnóstico , Neoplasias Cranianas/diagnóstico por imagem , Neoplasias Cranianas/cirurgia , Osso Esfenoide/diagnóstico por imagemAssuntos
Antivirais/uso terapêutico , Hepatite E/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Ribavirina/uso terapêutico , Adenina/análogos & derivados , Idoso , Alemtuzumab/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Doença Crônica , Progressão da Doença , Hepatite E/complicações , Hepatite E/diagnóstico , Hepatite E/virologia , Vírus da Hepatite E/efeitos dos fármacos , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , PiperidinasAssuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Carcinoma de Mama in situ/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Furanos/uso terapêutico , Cetonas/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Carcinoma de Mama in situ/diagnóstico por imagem , Carcinoma de Mama in situ/secundário , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/secundário , Feminino , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaAssuntos
Encefalopatias/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Adenina/análogos & derivados , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encefalopatias/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Piperidinas , Síndrome , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/diagnóstico por imagemAssuntos
Anemia Macrocítica/tratamento farmacológico , Dessensibilização Imunológica/métodos , Toxidermias/prevenção & controle , Fatores Imunológicos/uso terapêutico , Lenalidomida/uso terapêutico , Idoso , Anemia Macrocítica/imunologia , Deleção Cromossômica , Cromossomos Humanos Par 5/imunologia , Esquema de Medicação , Toxidermias/etiologia , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Lenalidomida/efeitos adversosAssuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/complicações , Carcinoma Hepatocelular/complicações , Leucocitose/complicações , Neoplasias Hepáticas/complicações , Ácido Úrico/efeitos adversos , Injúria Renal Aguda/patologia , Idoso , Carcinoma Hepatocelular/patologia , Humanos , Leucocitose/patologia , Neoplasias Hepáticas/patologia , MasculinoRESUMO
The prognosis of multiple myeloma is mainly dependent upon chromosomal changes. The 2 major abnormalities driving poor outcome are del(17p) and t(4;14). However, the outcome of these high-risk patients is not absolutely uniform, with some patients presenting long survival. We hypothesized that these better outcomes might be related to concomitant "good-risk" chromosomal changes exploring hyperdiploidy. We analyzed a large series of 965 myeloma patients, including 168 patients with t(4;14) and 126 patients with del(17p), using high-throughput single-nucleotide polymorphism arrays after plasma cell sorting. As expected, trisomic chromosomes were highly associated. Using the LASSO model, we found that only chromosome 3, when trisomic, was associated with a longer progression-free survival and that 3 trisomies modulated overall survival (OS) in myeloma patients: trisomies 3 and 5 significantly improved OS, whereas trisomy 21 worsened OS. In patients with t(4;14), trisomies 3 and/or 5 seemed to overcome the poor prognosis. For the first time, using a specific modeling approach, we show that not all trisomies display the same prognostic impact. This finding could be important for routine assessment of prognosis in myeloma, and some high-risk patients with a traditional evaluation could in fact be standard-risk patients.
Assuntos
Mieloma Múltiplo/genética , Trissomia/genética , Intervalo Livre de Doença , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Polimorfismo de Nucleotídeo Único , Prognóstico , Modelos de Riscos Proporcionais , Translocação GenéticaAssuntos
Inibidores da Angiogênese/efeitos adversos , Colo Sigmoide/lesões , Indóis/efeitos adversos , Perfuração Intestinal/diagnóstico , Pirróis/efeitos adversos , Reto/lesões , Inibidores da Angiogênese/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Colo Sigmoide/cirurgia , Humanos , Indóis/administração & dosagem , Perfuração Intestinal/cirurgia , Neoplasias Renais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pirróis/administração & dosagem , Radiografia , Reto/cirurgia , Retropneumoperitônio/diagnóstico por imagem , SunitinibeRESUMO
The aim of this phase 2 study was to evaluate the efficacy and safety of trastuzumab, a humanized monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2), for adult patients with relapsed/refractory HER2-positive B-ALL. Fifteen patients, with a median age of 62 years, received trastuzumab according to the schedule approved for breast cancer patients (ie, 4 mg/kg intravenous loading dose followed by 2 mg/kg weekly). The overall response rate was 13% with 2 patients achieving partial response and partial remission cytolytic response, respectively. Two other patients were documented with blast clearance. Only 1 reversible grade 3 cardiac toxic event occurred. This phase 2 study showed that trastuzumab monotherapy can allow for some responses in a very high-risk refractory/relapsed HER2-positive adult B-ALL population. Combination of trastuzumab with chemotherapy or other therapeutic monoclonal antibodies should be tested in the future.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Recidiva Local de Neoplasia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Trastuzumab , Resultado do Tratamento , Adulto JovemRESUMO
FDG-PET is now an established diagnostic tool in oncology. Fluorodeoxyglucose is not a specific tracer for malignant lesions but rather for elevated glucose metabolism, present not only in cancer but also in inflammatory and infectious lesions. FDG-PET has thus been suggested for diagnosis of fevers of unknown origin, deep bone or visceral infectious foci, inflammatory vasculitis or sarcoidosis and unknown primary tumors, all frequent situation in internal medicine. The main characteristics of FDG-PET are its ability to rule out focal inflammation or infection with a high degree of certainty when the examination is negative because of its good negative predictive value and its usefulness as an early marker of therapeutic response, compared with anatomy-based or conventional scintigraphic imaging. Large-scale prospective studies are necessary, however, before FDG-PET is integrated into routine clinical use. It should be compared with different techniques already validated (biology, radiology, conventional scintigraphic imaging) and its cost-effectiveness should be evaluated.
Assuntos
Medicina Interna/métodos , Tomografia por Emissão de Pósitrons , Humanos , Infecções/diagnóstico por imagemAssuntos
Hipotireoidismo/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Benzamidas , Proteínas de Fusão bcr-abl , Humanos , Mesilato de Imatinib , Indóis/efeitos adversos , Piperazinas/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , SunitinibeRESUMO
INTRODUCTION: Diagnosis of endobronchial metastases is facilitated by immunolabeling techniques on bronchial biopsy samples. CASE: Endobronchial tumors appeared in a 70-year-old woman with an adenocarcinoma of the crypts of Lieberkuhn, diagnosed two years previously. Immunohistochemical examinations made it possible to diagnose endobronchial metastases of the rectal adenocarcinoma. COMMENTS: The endobronchial zone is a relatively rare metastatic site. Metastases associated with rectal adenocarcinoma account for 11-26% of secondary endobronchial lesions. After endoscopic biopsy, immunolabeling techniques help to differentiate between primary adenocarcinoma and endobronchial metastasis. Prognosis is poor.