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1.
Artigo em Inglês | MEDLINE | ID: mdl-34602349

RESUMO

BACKGROUND: Cisplatin-based combination chemotherapy before surgery is the standard of care for muscle-invasive bladder cancer. However, the optimal chemotherapy modalities have not been precisely defined to date. PATIENTS AND METHODS: In the VESPER trial, patients received after randomization either gemcitabine and cisplatin (GC, 4 cycles) or methotrexate, vinblastine, doxorubicin and cisplatin (dose dense [dd]-MVAC, 6 cycles). Creatinine clearance (CrCl) was calculated before each cycle according to the Cockroft and Gault formula. Definition criteria for local control after neoadjuvant chemotherapy included pathological complete response (ypT0N0), pathological downstaging (

3.
Bull Cancer ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34452700

RESUMO

INTRODUCTION: People living with HIV (PLWHIV) are at a higher risk of cancer compared to the general population. With improved cancer treatments and the increased life expectancy of PLWHIV, the incidence of second cancers is also expected to increase. METHODS: We reviewed the cases of PLWHIV with cancer that have been presented to the CANCERVIH national multidisciplinary board since 2014. We included all cases with a history of cancer, and studied the incidence and types of second cancers. RESULTS: In total, 719 cases were reviewed, out of which 94 (13%) had a history of at least one cancer. For the first primary cancers, 46 (49%) were AIDS-defining cancers (ADCs) and 48 (51%) were non-AIDS-defining cancers (NADCs). Kaposi sarcoma (33%) and NHL (15%) occurred most frequently as first cancers. Among the first cancers that were ADCs, 15% of the second cancers were NHL, 11% anal canal cancers, 9% bladder and 9% Hodgkin lymphomas. Among the first cancers that were NADCs, 38% of the second cancers were lung cancers, 8% bladder, 8% head and neck and 8% NHL. DISCUSSION: With the aging of PLWHIV, the incidence of second and subsequent cancers is expected to increase in this population. Immuno-virological control should be maintained. Increased surveillance, early prevention and screening programs should be offered to all PLWHIV, including those with an undetectable HIV viral load and/or immune restoration.

4.
Lung Cancer ; 158: 146-150, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34217967

RESUMO

IMPORTANCE: Therapies targeting immune checkpoints, such as the programmed cell death 1 (PD-1) receptor, have become the standard-of-care for patients with non-small cell lung cancer (NSCLC), but people living with HIV (PLWH) were excluded from these studies. OBJECTIVE: To evaluate the efficacy and tolerability of nivolumab in PLWH with advanced NSCLC. DESIGN: The CHIVA2 study was a nonrandomized, open-label, phase 2 clinical trial in PLWH with previously treated advanced NSCLC. SETTING: National multicenter prospective study. PARTICIPANTS: patients had viral load of <200 copies/mL, regardless of their CD4+ T-cell count. INTERVENTION: Nivolumab was administered in second or third line, as monotherapy intravenously at 3 mg/kg every 2 weeks, until disease progression or limiting toxicity. MAIN OUTCOMES AND MEASURES: The primary endpoint was disease control rate, evaluated using the Response Evaluation Criteria in Solid Tumors, version 1.1. Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Sixteen patients with advanced NSCLC were enrolled: 14 (88 %) were men, median age was 58 years (range: 44-71), and all were smokers. The median duration of nivolumab treatment was 3.5 months (range: 0.5-26.5). The median follow-up was 23.6 months. Disease control rate was 62.5 % for 15 evaluable patients at 8 weeks (2 with partial response, 8 with stable disease, and 5 with disease progression). Twelve (75 %) patients had treatment-related adverse events, which were mild or moderate, except for one patient experiencing severe pruritus, onycholysis, and pemphigoid. There were no opportunistic infections or unexpected immune-related events. HIV viral load was stable during treatment. An increase in proliferating CD8+ and CD4+ T-cells was observed after 3 nivolumab cycles in a subgroup of 9 patients. CONCLUSIONS AND RELEVANCE: Second/third-line nivolumab treatment was well-tolerated and beneficial in PLWH with NSCLC. Future trials should investigate immune checkpoint inhibitors in first-line settings. TRIAL REGISTRATION: EudraCT.ema.europa.eu registration number: 2016-003796-22.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Infecções por HIV , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Estudos Prospectivos
6.
Lung Cancer ; 157: 124-130, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34016488

RESUMO

INTRODUCTION: HIV is an exclusion criterion for most lung cancer (LC) trials, however LC is the most common non-AIDS-defined malignancy in people living with HIV (PLHIV), poorer prognosis than the general population. Circulating tumor DNA (ctDNA) was a prognostic marker in LC patients from the general population. This study assessed ctDNA's prognostic value in PLHIV from a dedicated phase II trial. METHODS: Overall, 61 PLHIV with advanced non-squamous non-small-cell lung cancer (NSCLC) participated in the IFCT Phase II trial evaluating first-line four-cycle carboplatin (Ca) AUC5 pemetrexed (P) 500 mg/m2 induction therapy every 3 weeks, followed by P maintenance therapy. Blood samples collected before treatment were analyzed to detect ctDNA using ultra-deep targeted next-generation-sequencing (NGS). RESULTS: Appropriate samples were available from 55 PLVIH and analyzed for ctDNA detection. Including 42 males (76.4 %), 52.9 years median age, 51 smokers (92.7 %), five with non-squamous NSCLC Stage III (9%), 50 Stage IV (91 %), and performance status (PS) 0-2. ctDNA was detected in 35 patients (64 %), 22 with high and 13 with low ctDNA levels. Overall, 77 % were positive for TP53, 29 % for KRAS, and 11 % for STK11 mutations, more than one alteration was detected in 43 % of samples. Multivariate analysis showed that positive ctDNA was significantly associated with shorter PFS (HR, 4.31, 95 %CI: 2.06-8.99, p < 0.0001), and shorter OS (HR, 3.52, 95 %CI: 1.72-7.19, p < 0.001). Moreover, OS was significantly longer for patients with low ctDNA levels at diagnosis as compared to high (p = 0.01). CONCLUSION: We show that ctDNA detection using ultra-deep NGS is an independent prognostic factor in PLHIV with advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Infecções por HIV , Neoplasias Pulmonares , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação
7.
Cancers (Basel) ; 13(5)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801285

RESUMO

Anti-PD-1 antibodies prolong survival of performance status (PS) 0-1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3-4 patients is unknown. Conse- cutive PS 3-4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3-4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1-7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41-63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1-3.2). Median OS was 4.4 months (95%CI, 0.5-8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9-14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7-13.8, p = 0.003) predicted worse survival. PS improvement from 3-4 to 0-1 (n = 9) led to a median 43-month (95%CI, 0-102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.

8.
Clin Genitourin Cancer ; 19(4): e216-e222, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33753043

RESUMO

This study looked at whether epidermal growth factor receptor inhibition by the monoclonal antibody panitumumab could increase the efficacy of standard chemotherapy in advanced urothelial cancer. Results were disappointing, with higher toxicity and no improvement in efficacy in the combination arm. BACKGROUND: Epidermal growth factor receptor (EGFR) overexpression is frequent and associated with poor outcome in urothelial carcinoma. EGFR inhibition could improve the antitumor activity of chemotherapy. PATIENTS AND METHODS: Patients with advanced, treatment-naïve, histologically confirmed advanced urothelial carcinoma and no HRAS or KRAS mutation in the primary tumor received dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) without or with the anti-EGFR monoclonal antibody panitumumab (Pmab). A randomized (1:2) phase II design was used with progression-free survival (PFS) as the primary endpoint. RESULTS: Ninety-seven eligible patients were randomized; 96 patients were evaluable for toxicity and 87 for efficacy. The median PFS were 6.8 months (95% confidence interval [CI], 6.3-9.2) for dd-MVAC and 5.7 months (95% CI, 4.6-6.4 months) for dd-MVAC+Pmab. For both immunohistochemical and molecular definition of basal/squamous-like (BASQ) tumors, no difference was observed in objective response rates or PFS between the two arms in BASQ and non-BASQ tumors. CONCLUSION: dd-MVAC+Pmab was associated with more serious adverse events and no improvement in efficacy outcomes.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Cisplatino/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Panitumumabe/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Vimblastina/uso terapêutico
9.
Bull Cancer ; 108(4): 369-376, 2021 Apr.
Artigo em Francês | MEDLINE | ID: mdl-33714539

RESUMO

HIV testing is recommended at time of cancer diagnosis, HBV and HCV screening because of the risk of reactivation with certain anticancer drugs.This is a cross-sectional study. The objectives were to assess the screening practices in cancer patients and the satisfaction of professionals in the event of use of the CancerHIV network. A questionnaire drafted by the CancerHIV expert and the OncoPaca-Corse Regional Cancer Network (RCN) was distributed in the region at the end of 2018 (part 1: V1) before being extended to the national level via the CancerHIV network (part 2: V2). Participation reached 160 and 130 respondents (V1 and V2, respectively). At the initial cancer assessment, 23% of respondents declared that they systematically screened for HIV at V1 (V2: 17%), 25% for HBV (V2: 20%) and 24% for HCV (V2: 19%). Before immunotherapy, the rates were 54% for HIV in V1 (V2: 52%), 57% for HBV (V2: 60%) and 55% for HCV (V2: 57%). Among the respondents, satisfaction when requesting a regional or national remedy was high (almost 100%). Screening for HIV, HBV and HCV allows supervised prescription of immunosuppressive or cytotoxic treatment to a potentially immunosuppressed patient. This study, resulting of an original collaboration between a RCN and a national expert network, underlines the lack of screening at the 2 examined stages of patient care, and the need for raising practitioners' awareness to recommendations.


Assuntos
Infecções por HIV/diagnóstico , Hepatite B/diagnóstico , Hepatite C/diagnóstico , Programas de Rastreamento/métodos , Neoplasias/complicações , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Estudos Transversais , Feminino , França/epidemiologia , HIV/fisiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepacivirus/fisiologia , Hepatite B/complicações , Hepatite B/epidemiologia , Vírus da Hepatite B/fisiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Imunoterapia/efeitos adversos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Neoplasias/terapia , Inquéritos e Questionários , Ativação Viral/efeitos dos fármacos , Ativação Viral/imunologia
10.
Bull Cancer ; 108(4): 377-384, 2021 Apr.
Artigo em Francês | MEDLINE | ID: mdl-33745736

RESUMO

The reform of medical residency introduced in 2017 established the position of Junior Doctor, for its last phase, called the consolidation phase. Its goal is the increasing and supervised autonomy of the resident, in order to better support the transition toward senior practitioner. It appears necessary to define proper guidelines on the status and the specific role of Junior Doctor in medical oncology, in order to help the implementation of the reform of the 3rd cycle. This document is the result of a collaboration between AERIO and CNEC, that respectively represent medical oncology residents and university teachers. It aims to advise and guide local practices, without being compulsory, before the arrival of the first Junior Doctors in November 2021. It explains the Junior Doctors' principal jobs: consultation, multidisciplinary meeting, day clinic, hospitalization, clinical research, quality policy and teaching.


Assuntos
Internato e Residência , Oncologia/educação , Corpo Clínico Hospitalar/educação , França , Humanos , Internato e Residência/organização & administração , Descrição de Cargo , Papel do Médico , Guias de Prática Clínica como Assunto , Encaminhamento e Consulta , Pesquisa , Ensino
12.
Eur J Cancer ; 146: 30-47, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33578357

RESUMO

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/diagnóstico , Testes Genéticos/métodos , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/diagnóstico , Guias de Prática Clínica como Assunto/normas , Neoplasias da Mama/genética , Feminino , Humanos , Neoplasias Ovarianas/genética
13.
Genome Biol ; 22(1): 7, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397444

RESUMO

BACKGROUND: Crosstalk between genetic, epigenetic, and immune alterations in upper tract urothelial carcinomas and their role in shaping muscle invasiveness and patient outcome are poorly understood. RESULTS: We perform an integrative genome- and methylome-wide profiling of diverse non-muscle-invasive and muscle-invasive upper tract urothelial carcinomas. In addition to mutations of FGFR3 and KDM6A, we identify ZFP36L1 as a novel, significantly mutated tumor suppressor gene. Overall, mutations of ZFP36 family genes (ZFP36, ZFP36L1, and ZFP36L2) are identified in 26.7% of cases, which display a high mutational load. Unsupervised DNA methylation subtype classification identifies two epi-clusters associated with distinct muscle-invasive status and patient outcome, namely, EpiC-low and EpiC-high. While the former is hypomethylated, immune-depleted, and enriched for FGFR3-mutated, the latter is hypermethylated, immune-infiltrated, and tightly associated with somatic mutations of SWI/SNF genes. CONCLUSIONS: Our study delineates for the first time the key role for convergence between genetic and epigenetic alterations in shaping clinicopathological and immune upper tract urothelial carcinoma features.

15.
Eur J Cancer ; 136: 1-3, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32610172
16.
Autoimmun Rev ; 19(8): 102586, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32535094

RESUMO

BACKGROUND: In addition to restoring anti-tumor immune responses, immune checkpoint inhibitors (ICI) may also induce immune-related adverse events (irAE) that can affect any organ. We aim to determine the spectrum, timing, clinical features, and fatalities of rheumatic and musculoskeletal immune-related adverse events (RMS-irAE) associated with ICI. PATIENTS METHODS: We performed an observational, retrospective, pharmacovigilance study using the World Health Organization international pharmacovigilance database, VigiBase, from inception to January 2019. RMS-irAE reporting rate on ICI versus full database was performed using disproportionality analysis with computation of reporting-odds-ratios (ROR) and a Bayesian disproportional estimate (information component, IC). IC025 (lower end of the IC 95% credibility interval) >0 is deemed significant. RESULTS: We identified 1288 RMS-irAE significantly associated with ICI: polymyalgia rheumatica (n = 76, ROR = 14.6 [11.6-18.4], IC025 = 3.34), sarcoidosis (n = 94; ROR = 9.6 [7.9-11.9]; IC025 = 2.85), Sjogren's syndrome (n = 49; ROR = 6.9 [5.2-9.2]; IC025 = 2.24), myositis (n = 465; ROR = 4.9 [4.5-5.4]; IC025 = 2.12), arthritis (n = 606; ROR = 1.4 [1.3-1.5]; IC025 = 0.34) and scleroderma (n = 17; ROR = 2.0 [1.2-3.2]; IC025 = 0.17). Arthritis, myositis, and Sjogren's syndrome were over-reported in patients treated with ICI combination versus those treated with ICI monotherapy (ROR = 1.6-2.9, p < .05) and more frequently reported on anti-PD1/PDL1 monotherapy vs. anti-CTLA4 monotherapy (2.1-4.4, p < .05). Median time to onset occurred early for myositis (31 days [19.2-57.8]) and was the most delayed for scleroderma (395 days [323.8-457.2], p < .0001). The fatality rate for RMS-irAE ranged from 24% for myositis (n = 106/441) (up to 56.7% with concurrent myocarditis) to [0-6.7%] for other RMS-irAE (p < .0001). CONCLUSIONS: Clinicians should be aware of the spectrum of RMS-irAE. Myositis can be particularly life-threatening, particularly when associated with myocarditis.


Assuntos
Antineoplásicos Imunológicos , Miosite , Antineoplásicos Imunológicos/efeitos adversos , Teorema de Bayes , Humanos , Miosite/induzido quimicamente , Miosite/mortalidade , Miosite/patologia , Farmacovigilância , Estudos Retrospectivos
17.
Eur J Cancer ; 135: 130-146, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32580130

RESUMO

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new virus that has never been identified in humans before. COVID-19 caused at the time of writing of this article, 2.5 million cases of infections in 193 countries with 165,000 deaths, including two-third in Europe. In this context, Oncology Departments of the affected countries had to adapt quickly their health system care and establish new organizations and priorities. Thus, numerous recommendations and therapeutic options have been reported to optimize therapy delivery to patients with chronic disease and cancer. Obviously, while these cancer care recommendations are immediately applicable in Europe, they may not be applicable in certain emerging and low- and middle-income countries (LMICs). In this review, we aimed to summarize these international guidelines in accordance with cancer types, making a synthesis for daily practice to protect patients, staff and tailor anti-cancer therapy delivery taking into account patients/tumour criteria and tools availability. Thus, we will discuss their applicability in the LMICs with different organizations, limited means and different constraints.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/prevenção & controle , Controle de Infecções/organização & administração , Oncologia/organização & administração , Neoplasias/terapia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Países em Desenvolvimento/economia , Carga Global da Doença , Humanos , Controle de Infecções/economia , Controle de Infecções/normas , Oncologia/economia , Oncologia/normas , Neoplasias/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Pobreza , SARS-CoV-2
18.
J Neurointerv Surg ; 12(9): 879-885, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32354844

RESUMO

BACKGROUND: Osteolytic lesions of the atlas (C1) are challenging to treat by vertebroplasty due to the vicinity of the vertebral artery and the spinal cord. OBJECTIVE: To present our experience with transoral vertebroplasty (TOV) for osteolytic lesions of the lateral mass of the atlas. METHODS: Retrospective case series involving 15 consecutive patients (nine male, six female, mean age 63 years) who underwent TOV for the treatment of an osteolytic lesion of the lateral mass of the atlas. Among the osteolytic lesions, 10/15 (67%) were bone metastases from various cancers; 4/15 (27%) were lesions related to multiple myeloma; and one lesion (7%) was an aggressive hemangioma. All the TOVs were performed under general anesthesia and in most cases (10/15; 67%) in a hybrid angiosuite combining a C-arm flat panel and a CT scan. The remaining five patients were treated under biplane fluoroscopic guidance. RESULTS: Vertebroplasty of the lateral mass of C1 through a transoral route was feasible in all cases. Significant pain relief was obtained in most cases (1 month average decrease in Numeric Rating Scale: 4.9±4.1). No major complication was recorded. In 7/15 cases (47%), cement leakage surrounding the C1 lateral mass was seen; none of these leakages had a significant clinical consequence. No additional spine surgery was required in any of the patients. CONCLUSION: TOV of osteolytic lesions of the lateral mass of the atlas is feasible and seems safe and effective, providing pain relief and bone stabilization.


Assuntos
Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cimentos Ósseos/uso terapêutico , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
19.
Eur Respir J ; 56(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32444410

RESUMO

HIV infection is an exclusion criterion in lung cancer trials. This multicentre phase II trial aimed to assess feasibility, efficacy and safety of first-line carboplatin plus pemetrexed (CaP) followed by pemetrexed (P) maintenance in people living with HIV (PLHIV) with advanced non-squamous non-small cell lung cancer (NS-NSCLC).Four cycles of CaP were followed by P-maintenance therapy in patients with Eastern Cooperative Oncology Group performance status ≤2. The primary objective was a disease control rate (DCR) ≥30% after 12 weeks.Of the 61 PLHIV enrolled, 49 (80%) had a performance status of 0-1, and 19 (31%) had brain metastases. Median CD4 lymphocyte count was 418 cells·µL-1 (range 18-1230), median CD4 lymphocyte nadir was 169.5 cells·µL-1 (1-822); 48 (80%) patients were virologically controlled. Four-cycle inductions were achieved by 38 (62%) patients, and 31 (51%) started P-maintenance (median of 4.1 cycles (range 1-19)). The 12-week DCR was 50.8% (95% CI 38.3-63.4) and partial response rate 21.3%. Median progression-free survival and overall survival were 3.5 (95% CI 2.7-4.4) and 7.6 months (5.7-12.8), respectively. Patients with a performance status of 0-1 had the longest median progression-free survival (4.3 months, 95% CI 3.1-5.2) and overall survival (11.9 months, 95% CI 6.4-14.3). During induction, CaP doublet was well tolerated apart from grade 3-4 haematological toxicities (neutropenia 53.8%; thrombocytopenia 35.0%; anaemia 30.0%). Two fatal treatment-related sepses were reported. No opportunistic infections were experienced.In PLHIV with advanced NS-NSCLC, first-line four-cycle CaP induction followed by P-maintenance was effective and reasonably well-tolerated. Further studies should evaluate combination strategies of CaP with immunotherapy in PLHIV.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Infecções por HIV , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede/uso terapêutico , Resultado do Tratamento
20.
J Infect Dis ; 222(8): 1320-1328, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32282911

RESUMO

BACKGROUND: Kaposi sarcoma (KS)-associated herpesvirus (KSHV) subtype depends mostly on patient origin. The current study aimed to assess KSHV diversity in a population of men who have sex with men (MSM) living in France. METHODS: The study included 264 patients. In 65 MSM, including 57 human immunodeficiency virus (HIV)-infected men with KS, multicentric Castleman disease, or primary effusion lymphoma and 8 HIV-uninfected men receiving HIV preexposure prophylaxis (PrEP), we performed KSHV typing with K1 open reading frame Sanger and KSHV whole-genome sequencing. In 199 other patients, we performed real-time polymerase chain reaction screening for the new variant. RESULTS: We found that 51% of KSHV-strains were subtype C (85% C3), and 33% were subtype A. Four patients with severe KSHV disease (2 with visceral KS, 1 with multicentric Castleman disease, and 1 with primary effusion lymphoma) and 1 asymptomatic PrEP user had a new variant resembling the Ugandan subtype F, but with different K1 open reading frame and KSHV whole-genome sequences and a different epidemiological context (MSM vs African population). Its prevalence was 4.5% in Caucasian MSM, and it was absent in other epidemiological groups. CONCLUSIONS: Subtype C predominated among MSM living in France. The new F variant was identified in Caucasian MSM and associated with severe KSHV disease, suggesting that subtype F could be split into F1 and F2 variants. Careful screening for this variant may be required in MSM, given the severe clinical presentation of associated diseases.


Assuntos
Herpesvirus Humano 8/genética , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/virologia , Adulto , DNA Viral/genética , França/epidemiologia , Variação Genética , Genoma Viral/genética , Herpesvirus Humano 8/classificação , Herpesvirus Humano 8/isolamento & purificação , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , Estudos Retrospectivos , Sarcoma de Kaposi/epidemiologia , Minorias Sexuais e de Gênero , Proteínas Virais/genética
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