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1.
J Nutr Health Aging ; 28(5): 100215, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518539

RESUMO

OBJECTIVE: To assess the prognostic value of neurocognitive disorder (NCD) for 12 month-overall mortality in patients aged 70 or more with a solid cancer. DESIGN: prospective, observational, multicenter cohort. SETTING AND PARTICIPANTS: We analyzed data from the ELCAPA longitudinal multicenter observational cohort of patients aged 70 or over, referred for a geriatric assessment (GA) before a new cancer treatment modality between January 31st, 2007, and December 29th, 2017. We defined the baseline NCD in four classes: no NCD, mild NCD, moderate NCD, and major NCD, based on the Mini-Mental State Examination (MMSE) score, memory complaint, and the Instrumental Activities of Daily Living (IADL) score. STATISTICAL METHODS: We compared the baseline characteristics of patients according to NCD classes, globally and by pairs (with Bonferroni' correction). Prognosis value of NCD classes were analysed by using univariable and then multivariable 12 month survival analysis with age as time-variable and with and without adjustement for the treatment strategy (curative, palliative or exclusive supportive care). RESULTS: 2784 patients with solid-cancer were included, with a median [interquartile range] age of 82 [78;86]. 36% of the patients were free of NCD, 34% had a mild NCD, 17% had a moderate NCD, and 13% had a major NCD. We identified the following independent prognostic factors for 12 month-overall mortality: NCD (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for a major NCD = 1.54 [1.19-1.98] (p < 0.001), type of cancer, metastatic status, inpatient consultation, poor general health (assessed as the level of fatigue and Eastern Cooperative Oncology Group performance status [ECOG-PS]), greater weight loss, palliative treatment, and exclusive supportive care. Additional adjustment for the treatment strategy did not greatly change the strength of the association of a major NCD with 12 month-overall mortality (HR [95%CI] = 1.78 [1.39-2.29] (p < 0.001). CONCLUSION: Our results suggest that the presence of a major NCD has direct prognostic value (independently of other geriatric factors, the type of cancer and the treatment strategy) in older patients with a solid cancer.


Assuntos
Avaliação Geriátrica , Neoplasias , Transtornos Neurocognitivos , Humanos , Neoplasias/mortalidade , Neoplasias/complicações , Feminino , Masculino , Estudos Prospectivos , Idoso , Prognóstico , Idoso de 80 Anos ou mais , Avaliação Geriátrica/métodos , Estudos Longitudinais , Atividades Cotidianas
2.
Crit Rev Oncol Hematol ; 193: 104212, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38007063

RESUMO

More than half of cancer cases occur in patients aged 65 years or older. The efficacy and safety of antibody drug conjugates (ADCs) in older patients remains an unclear subject as available evidence is limited. Geriatric population is underrepresented in clinical trials. Consequently, most of our knowledge regarding innovative therapeutics was studied on a younger population. In this review of published literature, we report the available information on efficacy, safety and pharmacokinetics of FDA approved ADCs for hematologic malignancies and solid tumors in the geriatric population. We explore the results of clinical trials dedicated for older individuals as well as subgroup analyses of the geriatric population in major trials evaluating these drugs. Available data suggest a similar efficacy in older adults as compared to general population. However, older patients might be prone to a higher rate of adverse events in incidence with a potential impact on quality of life. We lack data to support primary dose reductions or schedule modifications in this category of patients. No pharmacokinetic differences were reported between age groups. It is crucial to encourage the development of clinical trials dedicated to older patients with geriatric parameters (G8 score, G-CODE…) so that results can be more representative of this population outside of clinical trials.


Assuntos
Imunoconjugados , Humanos , Idoso , Imunoconjugados/efeitos adversos , Qualidade de Vida
3.
Cancer Med ; 12(22): 20940-20952, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37937731

RESUMO

BACKGROUND: In older patients with cancer, comorbidities compete with cancer for cause of death. The objectives were to evaluate cancer mortality and factors associated, according to metastatic status. METHODS: Between 2007 and 2014, patients with cancer aged ≥70 referred for pre-therapeutic geriatric assessment (GA) were included through the ELCAPA prospective cohort study. The underlying cause of death was defined according to the International Classification of Diseases, 10th Revision. The World Health Organisation definition was used to categorise the cause of death as cancer versus another disease (e.g. cardiovascular disease, infectious disease, etc.) Competing risk models were used. RESULTS: Mean (SD) age of the 1445 included patients was 80.2 (5.8) and 48% were women. Most common tumour sites were colorectal (19%), breast (17%) and urinary (15%); 773 patients (49%) had metastases. After a 34-month median follow-up, 706 cancer deaths were observed among 843 deaths. The 6-month and 3-year cancer mortality rates (95% CI) were 12% (9-15) and 34% (29-38) for non-metastatic patients and 43% (39-47) and 79% (75-82) for metastatic patients, respectively. Dependency in activities of daily living and comorbidities were associated with 6-month and 3-year cancer mortality in non-metastatic (adjusted subhazard ratio [aSHR] = 1.68 [0.99-2.85] and 1.69 [1.16-2.45]; and 1.98 [1.08-3.63] and 3.38 [1.47-7.76], respectively) and metastatic patients (aSHR = 2.81 [2.01-3.93] and 2.95 [2.14-4.07]; and 1.63 [1.18-2.25] and 2.06 [1.39-3.05], respectively). Impaired Timed-Get-Up-and-Go test was associated with 6-month and 3-year cancer mortality in metastatic patients (aSHR = 1.5 [1.06-2.12] and 1.38 [1.06-1.81], respectively). Obesity was negatively associated with 3-year cancer death in non-metastatic (aSHR = 0.53 [0.29-0.97]) and metastatic patients (aSHR = 0.71 [0.51-1.00]). CONCLUSIONS: The majority of older adults with cancer referred for pre-therapeutic GA die from cancer. Geriatric parameters are independently associated with cancer mortality and should be considered for prognosis assessment, decision-making and care.


Assuntos
Atividades Cotidianas , Neoplasias , Idoso , Humanos , Feminino , Masculino , Estudos Prospectivos , Causas de Morte , Avaliação Geriátrica
4.
J Geriatr Oncol ; : 101506, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37211514

RESUMO

INTRODUCTION: Predictors for mortality and toxicity in older patients with cancer are mainly studied in cohorts with various cancers at different stages. This study aims to identify predictive geriatric factors (PGFs) for early death and severe chemotherapy related adverse events (CRAEs) in patients aged ≥70 years with metastatic non-small-cell lung cancer (mNSCLC). MATERIAL AND METHODS: This is a secondary analysis of the multicenter, randomized, phase 3 ESOGIA trial that compared, for patients ≥70 years with mNSCLC, a treatment algorithm based on performance status and age to another algorithm based on geriatric assessment. To identify PGFs of three-month mortality and grade 3, 4, or 5 CRAEs, multivariate Cox models and logistic models, adjusted for treatment group and center, and stratified by randomization arm, were constructed. RESULTS: Among 494 included patients, 145 (29.4%) had died at three months and 344 (69.6%) had severe chemotherapy toxicity. For three-month mortality, multivariate analyses retained mobility (Test Get up and Go), instrumental activity of daily living (IADL) dependence and weight loss as PGFs. The combined effect of IADL ≤2/4 and weight loss ≥3 kg was strongly associated with three-month mortality (adjusted hazard ratio: 5.71 [95% confidence interval [CI]: 2.64-12.32]). For chemotherapy toxicity, Charlson Comorbidity Index ≥2 was independently associated with grade3, 4, or 5 CRAEs (adjusted odds ratio [95% CI]: 1.94 [1.06-3.56]). DISCUSSION: Mobility, IADL dependence, and weight loss were predictive of three-month mortality in a population aged ≥70 years treated for mNSCLC, while comorbidities were independently associated with severe chemotherapy toxicity.

5.
Oncologist ; 28(6): e341-e349, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37027521

RESUMO

BACKGROUND: Severe chemotherapy-related toxicities are frequent among older patients. The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) and the Cancer and Aging Research Group Study (CARG) score were both developed to predict these events. PATIENTS AND METHODS: The objective of this study was to evaluate the scores' predictive performance in a prospective cohort, which included patients aged 70 years and older referred for a geriatric assessment prior to chemotherapy for a solid tumor. The main endpoints were grades 3/4/5 toxicities for the CARG score and grades 4/5 hematologic toxicities and grades 3/4/5 non-hematologic toxicities for the CRASH score. RESULTS: A total of 248 patients were included, of which 150 (61%) and 126 (51%) experienced at least one severe adverse event as defined respectively in CARG and CRASH studies. The incidence of adverse events was not significantly greater in the intermediate and high-risk CARG groups than in the low-risk group (odds ratio (OR) [95% CI] = 0.3 [0.1-1.4] (P = .1) and 0.4 [0.1-1.7], respectively). The area under curve (AUC) was 0.55. Similarly, the incidence of severe toxicities was no greater in the intermediate-low, intermediate-high, and high-risk CRASH groups than in the low-risk CRASH group (OR [95%CI] = 1 [0.3-3.6], 1 [0.3-3.4], and 1.5 [0.3-8.1], respectively). The AUC was 0.52. The type of cancer, performance status, comorbidities, body mass index, and MAX2 index were independently associated with grades 3/4/5 toxicities. CONCLUSION: In an external cohort of older patients referred for a pretherapeutic GA, the CARG and CRASH scores were poor predictors of the risk of chemotherapy severe toxicities.


Assuntos
Antineoplásicos , Neoplasias , Idoso , Humanos , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Estudos Prospectivos , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Avaliação Geriátrica , Fatores de Risco
6.
Nutrients ; 15(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36904192

RESUMO

This study will address the prevalence of pre-therapeutic sarcopenia (PS) and its clinical impact during cancer treatment among adult cancer patients ≥ 18 years of age. A meta-analysis (MA) with random-effect models was performed via a MEDLINE systematic review, according to the PRISMA statement, focusing on articles published before February 2022 that reported observational studies and clinical trials on the prevalence of PS and the following outcomes: overall survival (OS), progression-free survival (PFS), post-operative complications (POC), toxicities (TOX), and nosocomial infections (NI). A total of 65,936 patients (mean age: 45.7-85 y) with various cancer sites and extensions and various treatment modes were included. Mainly defined by CT scan-based loss of muscle mass only, the pooled prevalence of PS was 38.0%. The pooled relative risks were 1.97, 1.76, 2.70, 1.47, and 1.76 for OS, PFS, POC, TOX, and NI, respectively (moderate-to-high heterogeneity, I2: 58-85%). Consensus-based algorithm definitions of sarcopenia, integrating low muscle mass and low levels of muscular strength and/or physical performance, lowered the prevalence (22%) and heterogeneity (I2 < 50%). They also increased the predictive values with RRs ranging from 2.31 (OS) to 3.52 (POC). PS among cancer patients is prevalent and strongly associated with poor outcomes during cancer treatment, especially when considering a consensus-based algorithm approach.


Assuntos
Neoplasias , Sarcopenia , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Sarcopenia/etiologia , Prevalência , Neoplasias/complicações , Força Muscular , Intervalo Livre de Progressão
7.
Eur J Cancer ; 182: 107-114, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36758475

RESUMO

BACKGROUND: We aimed to determine whether immune checkpoint inhibitors (ICI) time-of-day infusion might influence the survival of patients with advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively analysed patients who received single-agent anti-PD-(L)1 therapy in any line between 2016 and 2021. We calculated by Cox regression models the association between the proportion of ICI infusions received after 16:30h and overall survival (OS) and progression-free survival (PFS). RESULTS: 180 patients were included, 77% received ICI as second- or further-line (median of 12 infusions/patient). The median age was 65 years (IQR 57-70), 112 patients (62%) were male, 165 (92%) were current or former tobacco smokers, 140 (78%) had performance status (PS) 0 or 1, 26 (14%) were on steroid therapy at ICI initiation. Histology was non-squamous for 139 (77%), the median number of metastatic sites was 3, and 33% had brain metastases. Patients who received at least 20% of ICI infusions after 16:30h (65 out of 180, 36%) had a statistically significant shorter median PFS as compared with patients receiving less than 20% of infusions in the evening (4.9 vs 9.4 months, log-rank p = 0.020), while numerical but not statistical shorter OS was observed (14.0 vs 26.2 months, log-rank p = 0.090). In the multivariate analysis, receiving at least 20% of evening infusions did not significantly increase the risk of death, while PS and line of treatment were significantly correlated with the OS. On the contrary, a proportion of ICI administration after 16:30h ≥20% conferred an HR for the PFS of 1.44 (95% CI: 1.01-2.05, p = 0.043), but this prognostic effect was not found when including in the model the total number of ICI infusions received (HR 1.20, 95% CI: 0.83-1.75, p = 0.329). CONCLUSION: Time-of-day infusion of ICI may impact the survival of patients with advanced NSCLC. Underlying prognostic characteristics and the number of infusions received could represent conceivable confounding factors, linked to increased variance related to ICI infusion timing. Nonetheless, further studies may unravel chronobiological mechanisms modulating ICI efficacy.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Masculino , Idoso , Feminino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos
8.
Soins Gerontol ; 27(157): 21-29, 2022.
Artigo em Francês | MEDLINE | ID: mdl-36280368

RESUMO

Supportive care, in the context of breast cancer in the elderly, is part of standard oncogeriatric care. Nevertheless, the multidisciplinary reinforcement of the different transversal teams can support the global approach, that is essential to the quality of care and the life course. Evaluation is the basis of this management. As a result of this evaluation, the approach to sexual health is a novelty that is often insufficiently considered with elderly patients suffering from breast malignancy.


Assuntos
Neoplasias da Mama , Qualidade da Assistência à Saúde , Idoso , Humanos , Neoplasias da Mama/terapia
9.
Cancer Treat Rev ; 106: 102394, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35472632

RESUMO

Immune checkpoint blockers (ICBs) have a pivotal role in the management of non-small cell lung cancer (NSCLC), both as single agent and in combination strategies, providing a meaningful clinical and survival benefit. Older patients are underrepresented in clinical trials, including those involving immunotherapy, even though almost half of the patients with newly diagnosed NSCLC are aged 70 years or older. Moreover, due to selection biases, usually "fit" patients are preferably enrolled. This results in a lack of evidence regarding the use of ICBs in the older population, particularly when referring to chemo-immunotherapy regimens. Since ICBs are indeed of paramount importance in the treatment of patients with NSCLC, efforts are needed to optimize their use also in the older population. This entails furthermore taking into account additional features including the degree of fitness of the patient and the different health domains that can be affected by aging. This review aims to delve into the current evidences about the efficacy and toxicity of ICBs in monotherapy and in combination in older patients with advanced NSCLC, the role of the comprehensive geriatric assessment in supporting the selection of patients receiving immunotherapy, as well as the value of immunosenescence in modulating the activity of these drugs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fatores Etários , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Avaliação Geriátrica , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico
10.
Bull Cancer ; 108(5): 513-520, 2021 May.
Artigo em Francês | MEDLINE | ID: mdl-33836861

RESUMO

The older population accounts for almost 60% of new cancers. Their management is a public health problem and is complex. It raises different questions: Is the patient's prognosis linked to cancer or another pathology? The heterogeneity of this population emphasises the importance of the overall condition assessment, in particular to avoid over-treatment (or under-treatment), and to be able to identify frail or vulnerable elderly patients who are at risk of having more treatment toxicities. Through this article, we will recall the importance of geriatric in-depth evaluation (EGA) by detailing the different factors that impact the therapeutic decision, tolerance to treatments… This EGA is however time-consuming and not all patients can be evaluated. In order to identify the subjects covered by this EGA, screening scales have been developed. Finally, we will develop the place of research in oncogeriatric management.


Assuntos
Avaliação Geriátrica/métodos , Neoplasias/diagnóstico , Acidentes por Quedas , Atividades Cotidianas , Idoso , Transtornos Cognitivos , Idoso Fragilizado , Humanos , Estado Nutricional , Desempenho Físico Funcional , Polimedicação , Prognóstico , Fatores Socioeconômicos
11.
Bull Cancer ; 108(6): 571-580, 2021 Jun.
Artigo em Francês | MEDLINE | ID: mdl-33896587

RESUMO

The emergence of the Coronavirus Disease 2019 (COVID-19) has caused profound upset in health systems around the world. As cancer patients seem to be at greater risk, the organization of oncological care had to be adapted. We first report the progress of the "first wave" of COVID-19 at the Institut Curie, a French comprehensive cancer center, by describing the measures implemented to limit the risk of transmission of COVID-19 while ensuring as much as possible the continuation of anticancer treatments. Then, we present the results of a prospective institutional database in which the characteristics and outcome of our patients with cancer and suffering from COVID-19 were collected. From March 13 to April 25, 2020, 141 patients followed at Institut Curie for cancer developed COVID-19, of which 26 (18%) died from it. The minimum incidence of COVID-19 in Institut Curie is estimated at 1.4% over this period. No risk factors for developing a severe form of COVID-19 related to cancer have been identified. Cancer patients do not appear to be at greater risk of developing COVID-19, nor of having a more severe form than the general population. With the current increase of COVID-19 cases, it seems essential to share the experience already acquired to minimize the impact of this crisis on the long-term outcome of patients followed for cancer.


Assuntos
COVID-19/epidemiologia , Institutos de Câncer/estatística & dados numéricos , Neoplasias/complicações , Idoso , COVID-19/mortalidade , COVID-19/prevenção & controle , COVID-19/transmissão , Institutos de Câncer/organização & administração , Causas de Morte , Bases de Dados Factuais , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/prevenção & controle , Neoplasias/terapia , Estudos Prospectivos
12.
JNCI Cancer Spectr ; 5(1): pkaa090, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33604509

RESUMO

BACKGROUND: Concerns have emerged about the higher risk of fatal coronavirus disease 2019 (COVID-19) in cancer patients. In this article, we review the experience of a comprehensive cancer center. METHODS: A prospective registry was set up at Institut Curie at the beginning of the COVID-19 pandemic. All cancer patients with suspected or proven COVID-19 were entered and actively followed for 28 days. RESULTS: Among 9842 patients treated at Institut Curie between March 13 and May 1, 2020, 141 (1.4%) were diagnosed with COVID-19, based on reverse transcription polymerase chain reaction testing and/or computerized tomography scan. In line with our case mix, breast cancer (40.4%) was the most common tumor type, followed by hematological and lung malignancies. Patients with active cancer therapy or/and advanced cancer accounted for 87.9% and 68.9% of patients, respectively. At diagnosis, 78.7% of patients had COVID-19-related symptoms, with an extent of lung parenchyma involvement inferior to 50% in 95.8% of patients. Blood count variations and C-reactive protein elevation were the most common laboratory abnormalities. Antibiotics and antiviral agents were administered in 48.2% and 6.4% of patients, respectively. At the time of analysis, 26 patients (18.4%) have died from COVID-19, and 100 (70.9%) were cured. Independent prognostic factors at the time of COVID-19 diagnosis associated with death or intensive care unit admission were extent of COVID-19 pneumonia and decreased O2 saturation. CONCLUSIONS: COVID-19 incidence and presentation in cancer patients appear to be very similar to those in the general population. The outcome of COVID-19 is primarily driven by the initial severity of infection rather than patient or cancer characteristics.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Neoplasias/terapia , Sistema de Registros/estatística & dados numéricos , SARS-CoV-2/efeitos dos fármacos , Idoso , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste para COVID-19/métodos , Comorbidade , Feminino , França/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pandemias/prevenção & controle , Fatores de Risco , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Análise de Sobrevida
13.
JCO Precis Oncol ; 5: 215-226, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34994597

RESUMO

Development of high-throughput technologies helped to decipher tumor genomic landscapes revealing actionable molecular alterations. We aimed to rank the level of evidence of recurrent actionable molecular alterations in head and neck squamous cell carcinoma (HNSCC) on the basis of the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) to help the clinicians prioritize treatment. We identified actionable alterations in 33 genes. HRAS-activating mutations were ranked in tier IB because of the efficacy of tipifarnib (farnesyltransferase inhibitor) in HRAS-mutated patients with HNSCC (nonrandomized clinical trial). Microsatellite instability (MSI), high tumor mutational burden (TMB), and NTRK fusions were ranked in tier IC because of PD-1 and TRK tyrosine kinase inhibitors tissue-agnostic approvals. CDKN2A-inactivating alterations and EGFR amplification were ranked in tier IIA because of the efficacy of palbociclib (CDK4/6 inhibitor) and afatinib (tyrosine kinase inhibitor) in these respective molecular subgroups in retrospective analyses of clinical trials. Molecular alterations in several genes, including PIK3CA gene, were ranked in tier IIIA because of clinical benefit in other tumor types, whereas molecular alterations in IGF1R and TP53 genes were ranked in tier IVA and tier V, respectively. The most compelling actionable molecular alterations in HNSCC according to ESCAT include HRAS-activating mutations, MSI, high TMB, NTRK fusions, CDKN2A-inactivating alterations, and EGFR amplification.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Ciclo Celular/genética , Reparo do DNA/genética , Humanos , Sistema de Sinalização das MAP Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo
14.
Rev Prat ; 71(10): 1051-1056, 2021 12.
Artigo em Francês | MEDLINE | ID: mdl-35147355

RESUMO

Immunotherapy In oncology cancer management has experienced a new paradigm with the outbreak of immunotherapy. These treatments aim to cancel the inhibition exerted by tumour cells on the immune system and thus restore an anti-tumour immune response. Main treatments of this new therapeutic Class are immune checkpoint inhibitors, targeting pd-1 or pd-l1 (or ctla-4), which indications extend to a wide variety of cancer types, localized or metastatic, in monotherapy Or in combination (with other immunotherapy, chemotherapy or targeted therapy). However, these treatments Are associated with new forms of tumor responses, such as pseudoprogressions and hyperprogressions, but also with new forms of immuno-mediated toxicities, which can take many forms, some severe. Patients treated with immunotherapy must therefore benefit from a specific clinical, biological and radiological follow-up.


L'immunothérapie en oncologie La prise en charge des cancers connaît un nouveau pa¬radigme depuis l'avènement de l'immunothérapie. Cette dernière a pour but de lever l'inhibition exercée par les cellules tumorales sur le système immunitaire et ainsi de restaurer une réponse immunitaire antitumorale. Les principaux traitements de cette nouvelle classe thérapeu¬tique sont les inhibiteurs des points de contrôle immuni¬taire ciblant les molécules pd-1 ou pd-l1 (et ctla-4 dans une moindre mesure), dont les indications s'étendent à une grande variété de cancers, localisés ou métasta¬tiques, en monothérapie ou en association (à d'autres immunothérapies, à une chimiothérapie ou à une thérapie ciblée). Cependant, ces traitements sont associés à de nouvelles formes de réponses tumorales, comme les pseudo-progressions et les hyperprogressions, et à des toxicités immunomédiées, pouvant prendre de multiples formes, dont certaines sévères. Les patients qui reçoivent une immunothérapie doivent donc bénéficier d'une sur¬veillance clinique, biologique et radiologique particulière.


Assuntos
Neoplasias , Receptor de Morte Celular Programada 1 , Humanos , Fatores Imunológicos , Imunoterapia , Neoplasias/terapia
16.
Mol Oncol ; 15(1): 104-115, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32750212

RESUMO

High-throughput molecular profiling of solid tumours using core needle biopsies (CNB) allows the identification of actionable molecular alterations, with around 70% success rate. Although several studies have demonstrated the utility of small biopsy specimens for molecular testing, there remains debate as to the sensitivity of the less invasive fine-needle aspiration (FNA) compared to CNB to detect molecular alterations. We aimed to prospectively evaluate the potential of FNA to detect such alterations in various tumour types as compared to CNB in cancer patients included in the SHIVA02 trial. An in-house amplicon-based targeted sequencing panel (Illumina TSCA 99.3 kb panel covering 87 genes) was used to identify pathogenic variants and gene copy number variations (CNV) in concomitant CNB and FNA samples obtained from 61 patients enrolled in the SHIVA02 trial (NCT03084757). The main tumour types analysed were breast (38%), colon (15%), pancreas (11%), followed by cervix and stomach (7% each). We report 123 molecular alterations (85 variants, 23 amplifications and 15 homozygous deletions) among which 98 (80%) were concordant between CNB and FNA. The remaining discordances were mainly related to deletions status, yet undetected alterations were not exclusively specific to FNA. Comparative analysis of molecular alterations in CNB and FNA showed high concordance in terms of variants as well as CNVs identified. We conclude FNA could therefore be used in routine diagnostics workflow and clinical trials for tumour molecular profiling with the advantages of being minimally invasive and preserve tissue material needed for diagnostic, prognostic or theranostic purposes.


Assuntos
Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias/genética , Neoplasias/patologia , Medicina de Precisão , Biópsia por Agulha Fina , Biópsia com Agulha de Grande Calibre , Variações do Número de Cópias de DNA/genética , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes
17.
BioDrugs ; 34(4): 463-476, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32394415

RESUMO

Indications of immunotherapy in oncology are continuously expanding, and unconventional types of response have been observed with these new treatments. These include transient progressive disease followed by a partial response, described as pseudoprogression, that raises the question of treatment beyond progression; and rapid disease progression associated with clinical decline, reported as hyperprogression. However, there are currently no consensual definitions of these phenomena and their impact on daily practice remains unclear. We reviewed existing data on pseudoprogression and hyperprogression with a focus on the definitions, incidence, predictive factors, potential biological mechanisms, and methods published to help distinguish pseudoprogression from progression and hyperprogression. The incidence of pseudoprogression ranged from 0 to 15%, with some authors also including disease stabilization after a first progression. For hyperprogression, incidence ranged from 4 to 29% with various definitions, and several authors reported a correlation with worse survival. Both phenomena were observed in a large panel of cancer types. Several radiological and biological methods have been reported to help distinguish pseudoprogression from progression and hyperprogression, such as analysis of radiomics, and circulating-tumor DNA or cell-free DNA, but these need to be confirmed in larger prospective cohorts. In conclusion, pseudoprogression and hyperprogression are both frequent types of responses under immunotherapy, and there is a need to better characterize these to improve the management of cancer patients. Treatment beyond progression should always be considered with caution and necessitates close clinical monitoring. In case of suspected hyperprogression, immunotherapy should be stopped early.


Assuntos
Imunoterapia , Neoplasias , Progressão da Doença , Humanos , Neoplasias/tratamento farmacológico , Estudos Prospectivos
18.
Breast Cancer Res ; 22(1): 55, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32460829

RESUMO

BACKGROUND: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France). METHODS: An IRB-approved prospective registry was set up at ICH on March 13, 2020, for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features, and outcome. Data extraction was done on April 25, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT scan abnormalities. RESULTS: Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N = 41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized, and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed, and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (> 70) were the two factors associated with a higher risk of intensive care unit admission and/or death. CONCLUSIONS: This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients.


Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Idoso , Betacoronavirus , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , COVID-19 , Causas de Morte , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Feminino , França/epidemiologia , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Prognóstico , RNA Viral/sangue , Fatores de Risco , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Cancers (Basel) ; 11(12)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817566

RESUMO

Although a quarter of cervical cancers occur after the age of 65 years, there is no treatment consensus for these patients. The aim of this work was to survey how physicians treat patients with advanced cervical cancer, focusing on treatment adjustments according to age and frailty status. Specialists were invited to an online survey. Data collected included information on respondent and treatment strategy in four cases (FIGO IIb, FIGO IVa, FIGO IVb, metastatic recurrence) with three age scenarios (45-year-old, 75-year-old and fit, 75-year-old and unfit). We received 237 responses of which 117 were fully completed. Thirty-four percent of respondents reported they had available access to a geriatric team and 25% used a frailty screening tool in routine. Therapeutic strategies did not differ between young and old fit patients. However, treatment modalities and intensity were different for old and unfit patients. Physicians answered that they would treat old fit patients as their younger counterparts but would reduce treatment intensity for old unfit patients. However, even if they were willing to adapt their treatment strategy based on frailty status, most of them do not use the tools that would allow distinguishing "fit" and "unfit" older patients, leaving room for improving accurate geriatric evaluation.

20.
Int J Mol Sci ; 20(11)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151303

RESUMO

Immunotherapy is now widely prescribed in oncology, leading to the observation of new types of responses, including rapid disease progression sometimes reported as hyperprogression. However, only a few studies have assessed the question of hyperprogression and there is no consensual definition of this phenomenon. We reviewed existing data on hyperprogression in published studies, focusing on reported definitions, predictive factors, and potential biological mechanisms. Seven studies retrospectively assessed hyperprogression incidence, using various definitions, some based on the tumoral burden variation across time with repeated computed-tomography (CT) scan, others based on an association of radiological and clinical criteria. Reported hyperprogression incidence varied between 4% and 29% of all responses, mostly in multi-tumor cohorts and with patients receiving immune checkpoint inhibitors. Hyperprogression correlated with worse chances of survival than standard progression in two studies. However, no strong predictive factors of hyperprogression were identified, and none were consistent across studies. In total, hyperprogression is a frequent pattern of response under immunotherapy, with a strong impact on patient outcome. There is a need for a consensual definition of hyperprogression. Immunotherapy should be stopped early in cases where there is suspicion of hyperprogression.


Assuntos
Imunoterapia , Neoplasias/diagnóstico , Neoplasias/terapia , Gerenciamento Clínico , Progressão da Doença , Humanos , Imunoterapia/métodos , Incidência , Neoplasias/epidemiologia , Neoplasias/imunologia , Prognóstico
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