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1.
Mod Pathol ; 37(10): 100558, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38969270

RESUMO

Adjuvant immunotherapy has been recently recommended for patients with metastatic clear cell renal cell carcinoma (ccRCC), but there are no tissue biomarkers to predict treatment response in ccRCC. Potential predictive biomarkers are mainly assessed in primary tumor tissue, whereas metastases (METs) remain understudied. To explore potential differences between genomic alterations and immune phenotypes in primary tumors and their matched METs, we analyzed primary tumors (PTs) of 47 ccRCC patients and their matched distant METs by comprehensive targeted parallel sequencing, whole-genome copy number variation analysis, determination of microsatellite instability, and tumor mutational burden. We quantified the spatial distribution of tumor-infiltrating CD8+ T cells and coexpression of the T-cell-exhaustion marker thymocyte selection-associated high mobility group box (TOX) by digital immunoprofiling and quantified tertiary lymphoid structures. Most METs were pathologically "cold." Inflamed, pathologically "hot" PTs were associated with decreased disease-free survival, worst for patients with high levels of CD8+TOX+ T cells. Interestingly, inflamed METs showed a relative increase in exhausted CD8+TOX+ T cells and increased accumulative size of tertiary lymphoid structures compared with PTs. Integrative analysis of molecular and immune phenotypes revealed BAP1 and CDKN2A/B deficiency to be associated with an inflamed immune phenotype. Our results highlight the distinct spatial distribution and differentiation of CD8+ T cells at metastatic sites, and the association of an inflamed microenvironment with specific genomic alterations.


Assuntos
Linfócitos T CD8-Positivos , Carcinoma de Células Renais , Neoplasias Renais , Linfócitos do Interstício Tumoral , Fenótipo , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/imunologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Linfócitos T CD8-Positivos/imunologia , Biomarcadores Tumorais/genética , Adulto , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Variações do Número de Cópias de DNA , Ubiquitina Tiolesterase/genética , Proteínas Supressoras de Tumor/genética , Idoso de 80 Anos ou mais , Instabilidade de Microssatélites , Genótipo
2.
Rev Med Suisse ; 20(856-7): 80-87, 2024 Jan 17.
Artigo em Francês | MEDLINE | ID: mdl-38231107

RESUMO

The oncology field continues its remarkable evolution over the years, with promising advances leading to innovative and individualized treatments. The development of new molecules, the identification of new therapeutic targets and the search for new sequences or combinations promise to revolutionize cancer treatments and contribute to improving survival rates, patients' quality of life and to open new perspective in oncology research. In this article, the newest data released in 2023 are reviewed.


Le domaine de l'oncologie poursuit son évolution remarquable au fil des années, avec des avancées prometteuses ouvrant la voie à des traitements novateurs et individualisés. L'élaboration de nouvelles molécules, l'identification de nouvelles cibles thérapeutiques et la recherche de nouvelles séquences ou combinaisons de traitements promettent de révolutionner la prise en charge du cancer et de contribuer à améliorer les taux de survie, la qualité de vie des patients et à ouvrir de nouvelles perspectives dans la recherche en oncologie. Dans cet article, les nouveautés parues en 2023 sont passées en revue.


Assuntos
Oncologia , Qualidade de Vida , Humanos
3.
Lancet ; 399(10336): 1695-1707, 2022 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-35405085

RESUMO

BACKGROUND: Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care. METHODS: We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m2 once every 3 weeks), standard of care plus radiotherapy, standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients were masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was first assessed in the overall population and then in the population who received androgen deprivation therapy with docetaxel as standard of care (population of interest). This study is ongoing and is registered with ClinicalTrials.gov, NCT01957436. FINDINGS: Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8-4·6) for radiographic progression-free survival and 4·4 years (3·5-5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41-0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69-0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34-0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59-0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone. INTERPRETATION: Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients. FUNDING: Janssen-Cilag, Ipsen, Sanofi, and the French Government.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Próstata , Antagonistas de Androgênios , Androgênios , Androstenos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Castração , Docetaxel/uso terapêutico , Feminino , Humanos , Hipertensão/etiologia , Masculino , Prednisona/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia
4.
Rev Med Suisse ; 19(827): 950-956, 2023 May 17.
Artigo em Francês | MEDLINE | ID: mdl-37195108

RESUMO

Precision medicine is playing an increasingly crucial role in the treatment of prostate cancer. By tailoring treatments to the unique characteristics of patients and their tumors, this approach enables more targeted and personalized care, ultimately improving patient survival. In this article, we discuss the targeted therapies that have recently changed the management of this cancer.


La médecine de précision joue un rôle de plus en plus crucial dans le traitement du cancer de la prostate. En adaptant les traitements aux caractéristiques individuelles des patients et de leurs tumeurs, cette approche permet une prise en charge plus ciblée et personnalisée, contribuant ainsi à améliorer la survie des patients. Dans cet article, nous abordons les traitements ciblés qui ont récemment transformé la prise en charge de ce cancer.


Assuntos
Medicina de Precisão , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Terapia de Alvo Molecular , Cuidados Paliativos
5.
Rev Med Suisse ; 19(N° 809-10): 52-57, 2023 Jan 18.
Artigo em Francês | MEDLINE | ID: mdl-36660838

RESUMO

The past year has brought several innovations in medical oncology, opening up promising new options for many solid tumors, both localized and metastatic. Immunotherapy, a real spearhead of emerging therapies in metastatic diseases, is seeing its use extend to adjuvant and neoadjuvant modalities, particularly in colon and lung cancers. 2022 also sees a great deal of focus on targeted therapies, as well as on antibody-drug conjugates, which creates new standards in both breast and lung cancers. Here we present the major advances in solid tumors.


L'année écoulée a apporté son lot d'innovations en oncologie médicale, ouvrant de nouvelles options prometteuses pour bon nombre de tumeurs solides, qu'elles soient localisées ou métastatiques. L'immunothérapie, véritable fer de lance des thérapies émergentes dans les maladies métastatiques, voit son usage s'étendre à des modalités adjuvantes et néoadjuvantes, notamment dans les cancers du côlon et du poumon. 2022 donne également la part belle aux thérapies ciblées mais aussi aux conjuguées anticorps-médicaments qui apportent de nouveaux standards tant pour les cancers du sein que du poumon. Nous vous présentons ici les avancées majeures concernant les tumeurs solides.


Assuntos
Neoplasias Pulmonares , Oncologia , Humanos , Imunoterapia , Terapia Neoadjuvante , Neoplasias Pulmonares/terapia
6.
Lancet Oncol ; 23(11): 1441-1450, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36228644

RESUMO

BACKGROUND: Standard treatment options for patients with stage IIA or stage IIB seminoma include either para-aortic and pelvic radiotherapy or three to four cycles of cisplatin-based combination chemotherapy. These options result in 3-year progression free survival rates of at least 90%, but bear risks for acute and late toxic effects, including secondary malignancies. We tested a novel approach combining de-escalated chemotherapy with de-escalated involved node radiotherapy, with the aim of reducing toxicity while preserving efficacy. METHODS: In the single-arm, multicentre, phase 2 SAKK 01/10 trial, patients with stage IIA or IIB classic seminoma (either at primary diagnosis or at relapse during active surveillance for stage I) were enrolled at ten centres of the Swiss Group for Clinical Cancer Research and ten centres of the German Testicular Cancer Study Group. WHO performance status 0-2, age 18 years or older, and adequate bone marrow and kidney function were required for eligibility. Treatment comprised one cycle of carboplatin (area under the curve 7) followed by involved-node radiotherapy (30 Gy in 15 fractions for stage IIA disease and 36 Gy in 18 fractions for stage IIB disease). The primary endpoint was 3-year progression-free survival. Efficacy analyses were done on the full analysis set, which comprised all patients who signed the informed consent, were registered in the trial, initiated trial treatment, and met all medically relevant inclusion or exclusion criteria. Safety was assessed in all patients who were treated at least once with one of the trial treatments. The study is ongoing but no longer recruiting, and is registered with Clinicaltrials.gov, NCT01593241. FINDINGS: Between Oct 18, 2012, and June 22, 2018, 120 patients were registered in the study. 116 patients were eligible and started treatment according to the study protocol (46 patients with stage IIA disease and 70 with stage IIB disease). After a median follow-up of 4·5 years (IQR 3·9-6·0), 3-year progression-free survival was 93·7% (90% CI 88·5-96·6). With a target progression-free survival of 95% at 3 years, the primary endpoint was not met. Acute treatment-related adverse events of any grade were noted in 58 (48%) of 116 patients, and grade 3 or 4 treatment-related adverse events occurred in the form of neutropenia in five (4%) patients, thrombocytopenia in three (3%) patients, and vomiting in one (1%) patient. No treatment-related deaths and no late treatment-related adverse events were reported. Serious adverse events were reported in five (4%) of 116 patients (one transient creatinine increase and four second primary tumours). INTERPRETATION: Despite the fact that the primary endpoint was not met, we observed favourable 3-year progression-free survival with single-dose carboplatin area under the curve 7 and involved-node radiotherapy, with minimal toxic effects. Our findings might warrant discussion with patients about the SAKK 01/10 regimen as an alternative to standard-of-care treatment, but more research on this strategy is needed. FUNDING: Swiss State Secretariat for Education, Research and Innovation and Rising Tide Foundation for Clinical Cancer Research.


Assuntos
Seminoma , Neoplasias Testiculares , Masculino , Humanos , Adolescente , Carboplatina , Seminoma/tratamento farmacológico , Seminoma/radioterapia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico
7.
Int J Cancer ; 151(3): 422-434, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35411939

RESUMO

Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomised patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards and flexible parametric models, accounting for baseline stratification factors. One thousand and three patients were contemporaneously randomised (November 2011 to January 2014): median age 67 years; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% unassessable; median PSA 97 ng/mL. At 6.1 years median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC + AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0.60 (95% CI: 0.50-0.71; P = 0.31 × 10-9 ) favoured SOC + AAP, with 5-years survival improved from 41% SOC-alone to 60% SOC + AAP. This was similar in low-risk (HR = 0.55; 95% CI: 0.41-0.76) and high-risk (HR = 0.54; 95% CI: 0.43-0.69) patients. Median and current maximum time on SOC + AAP was 2.4 and 8.1 years. Toxicity at 4 years postrandomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Acetato de Abiraterona/uso terapêutico , Idoso , Antagonistas de Androgênios/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Seguimentos , Hormônios , Humanos , Masculino , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
8.
Rev Med Suisse ; 18(767): 182-186, 2022 Feb 02.
Artigo em Francês | MEDLINE | ID: mdl-35107893

RESUMO

Despite COVID-19 pandemic, which is still deeply affecting world economy and global health, medical oncology specialists keep pursuing their effort for the identification of new therapeutic options to improve patients' life expectancy and quality of life. 2021 confirms the immunotherapy efficacy, alone or in combination with other modalities, across several indications. This year, we are summarizing the new approaches in the following sectors: lung, breast, melanoma, gynecological, digestive, urological and ENT areas.


En dépit de la pandémie de Covid-19 qui continue à grandement impacter l'économie mondiale et la santé, l'oncologie médicale poursuit sa quête d'identification de nouvelles options thérapeutiques ayant pour buts la prolongation de l'espérance de vie et l'amélioration de la qualité de vie de ses patients, en nombre croissant. L'année 2021 confirme également l'efficacité de l'immunothérapie, seule ou en combinaison à d'autres modalités, dans de nombreuses indications. Cette année, nous vous résumons les nouvelles approches dans les domaines suivants: poumon, sein, mélanome, sphères gynécologique, digestive, urologique et ORL.


Assuntos
COVID-19 , Melanoma , Humanos , Oncologia , Pandemias , Qualidade de Vida , SARS-CoV-2
9.
Rev Med Suisse ; 17(739): 974-977, 2021 May 19.
Artigo em Francês | MEDLINE | ID: mdl-34009756

RESUMO

Intravesical immunotherapy with Calmette-Guerin bacillus (BCG) have been used since decades for the treatment of non-muscle invasive bladder cancer and is a proof of principle that immunotherapy works for this malignancy. Since 2016, immune checkpoint inhibitors (ICI) demonstrated clinical benefits in locally advanced or metastatic bladder cancer, providing potentially durable tumor control in first line therapy or upon relapse after standard treatments. Ongoing clinical trials aim to demonstrate the efficiency of ICI for the treatment of localized disease.


L'immunothérapie par instillation de bacille de Calmette-Guérin est utilisée depuis plusieurs décennies dans le cancer de la vessie non musculo-invasif. Cette forme d'immunothérapie locale est témoin de l'efficacité de cette approche thérapeutique. Depuis 2016, les inhibiteurs de points de contrôle immunitaire (IPCI) complètent l'arsenal thérapeutique notamment lors d'une maladie localement avancée ou métastatique. Ils permettent d'obtenir des résultats bénéfiques potentiellement durables en première ligne de traitement et après échec des traitements standards. Des efforts sont en cours afin de démontrer le bénéfice des IPCI dans la prise en charge de la maladie localisée.


Assuntos
Neoplasias da Bexiga Urinária , Administração Intravesical , Vacina BCG , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/tratamento farmacológico
10.
Rev Med Suisse ; 17(761): 2082-2085, 2021 Dec 01.
Artigo em Francês | MEDLINE | ID: mdl-34851055

RESUMO

The University Hospital of Lausanne has heavily invested in the development of interdisciplinary oncology centers to improve the quality of care, and structure research and training. By integrating specialist nurses, it follows international recommendations. These specialists' nurses rephrase the information given by the doctor and ensure patients' understanding. They assess the patient's psychosocial situation and provides guidance if necessary. They support the patient in making informed choices about treatment and coping strategies. In addition to the outpatient clinics planned in accordance with the care pathway, she can be contacted between appointments to answer questions or concerns of any kind. This article shows the added value of these nurses in the care of oncology patients.


Le CHUV s'est fortement investi dans le développement de centres interdisciplinaires en oncologie afin d'améliorer la qualité de la prise en charge, de structurer la recherche et la formation. En y intégrant des infirmières cliniciennes, il suit les recommandations internationales. Ces infirmières reprennent les informations données par le médecin et s'assurent de la compréhension du patient. Elles évaluent sa situation psychosociale et l'orientent au besoin. Elles soutiennent le patient dans ses choix de traitement ainsi que dans ses stratégies d'adaptation. Outre les entretiens planifiés en fonction du parcours de soins, elles sont joignables entre les rendez-vous pour répondre à des questions ou préoccupations de tout ordre. Cet article montre la plus-value que la présence de ces infirmières offre à la prise en charge des patients oncologiques.


Assuntos
Neoplasias da Próstata , Instituições de Assistência Ambulatorial , Humanos , Masculino , Neoplasias da Próstata/terapia
11.
Rev Med Suisse ; 17(723): 201-205, 2021 Jan 27.
Artigo em Francês | MEDLINE | ID: mdl-33507661

RESUMO

The COVID-19 pandemic that has swept around the world in early 2020 has changed our daily practice and habits. Fortunately, however, 2020 also brings its share of new approaches and therapeutic combinations as well as new therapies. These advances are improving the outcomes and quality of life of our patients across the spectrum of oncological diseases. This article summarises the latest oncological advances and novelties for 2020 in the following tumor entities : lung, breast, digestive, gynecological, urological and ENT.


La pandémie de Covid-19 survenue début 2020 dans le monde entier aura bouleversé notre pratique quotidienne et nos habitudes. Heureusement, sur le plan thérapeutique, l'année 2020 apporte également son lot de nouvelles approches et combinaisons thérapeutiques ainsi que l'introduction de nouvelles molécules, permettant d'améliorer le pronostic vital et la qualité de vie de nos patients, dans de nombreux domaines. Cet article résume les dernières avancées et nouveautés oncologiques de l'année 2020 dans les domaines suivants : poumon, sein, sphère digestive, gynécologique, urologique et ORL.


Assuntos
COVID-19 , Pandemias , Humanos , Oncologia , Neoplasias , Qualidade de Vida , SARS-CoV-2
12.
N Engl J Med ; 377(4): 338-351, 2017 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-28578639

RESUMO

BACKGROUND: Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design. METHODS: We randomly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5 mg daily) (combination therapy). Local radiotherapy was mandated for patients with node-negative, nonmetastatic disease and encouraged for those with positive nodes. For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease, treatment continued until radiologic, clinical, or prostate-specific antigen (PSA) progression; otherwise, treatment was to continue for 2 years or until any type of progression, whichever came first. The primary outcome measure was overall survival. The intermediate primary outcome was failure-free survival (treatment failure was defined as radiologic, clinical, or PSA progression or death from prostate cancer). RESULTS: A total of 1917 patients underwent randomization from November 2011 through January 2014. The median age was 67 years, and the median PSA level was 53 ng per milliliter. A total of 52% of the patients had metastatic disease, 20% had node-positive or node-indeterminate nonmetastatic disease, and 28% had node-negative, nonmetastatic disease; 95% had newly diagnosed disease. The median follow-up was 40 months. There were 184 deaths in the combination group as compared with 262 in the ADT-alone group (hazard ratio, 0.63; 95% confidence interval [CI], 0.52 to 0.76; P<0.001); the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease. There were 248 treatment-failure events in the combination group as compared with 535 in the ADT-alone group (hazard ratio, 0.29; 95% CI, 0.25 to 0.34; P<0.001); the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease. Grade 3 to 5 adverse events occurred in 47% of the patients in the combination group (with nine grade 5 events) and in 33% of the patients in the ADT-alone group (with three grade 5 events). CONCLUSIONS: Among men with locally advanced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than ADT alone. (Funded by Cancer Research U.K. and others; STAMPEDE ClinicalTrials.gov number, NCT00268476 , and Current Controlled Trials number, ISRCTN78818544 .).


Assuntos
Acetato de Abiraterona/administração & dosagem , Antagonistas de Androgênios/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prednisolona/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Acetato de Abiraterona/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Prednisolona/efeitos adversos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores , Análise de Sobrevida
13.
Future Oncol ; 16(29): 2307-2328, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32964728

RESUMO

The therapy of advanced (clear-cell) renal cell carcinoma (RCC) has recently experienced tremendous changes. Several new treatments have been developed, with PD-1 immune-checkpoint inhibition being the backbone of therapy. Diverse immunotherapy combinations change current first-line standards. These changes also require new approaches in subsequent lines of therapy. In an expert panel, we discussed the new treatment options and how they change clinical practice. While first-line immunotherapies introduce a new level of response rates, data on second-line therapies remains poor. This scenario poses a challenge for clinicians as guideline recommendations are based on historical patient cohorts and agents may lack the appropriate label for their in guidelines recommended use. Here, we summarize relevant clinical data and consider appropriate treatment strategies.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/terapia , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Biomarcadores Tumorais , Carcinoma de Células Renais/etiologia , Tomada de Decisão Clínica , Ensaios Clínicos como Assunto , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Neoplasias Renais/etiologia , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Retratamento , Resultado do Tratamento
14.
Rev Med Suisse ; 16(676-7): 72-77, 2020 Jan 15.
Artigo em Francês | MEDLINE | ID: mdl-31961089

RESUMO

Driven by highly specialized medicine, research and the quest for personalization of treatments, oncology witnessed substantial advances in 2019. This year numerous treatments have consolidated their importance and broadened their indications. Multiple innovative treatments, currently under study, brought hope for future advances, while biomarkers, such as PD-L1, microsatellite instability (MSI), tumor mutational burden (TMB), BRCA1/2 gene mutations, and homologous recombination deficiency (HRD) allowed better selection and customization of available treatments. This article provides an overview of this year's advances in oncology.


Sous l'égide de la médecine hautement spécialisée, de la personnalisation des traitements et secondée par une recherche énergique, l'oncologie a connu en 2019 des avancées considérables. Cette année, de nombreux traitements ont consolidé leur importance et élargi leurs indications. L'annonce d'une pléthore de traitements novateurs, en étude, est source d'espoir pour l'avenir. Des biomarqueurs simples ou composites, tels que l'expression PD-L1, l'instabilité de microsatellite (MSI), la charge mutationnelle tumorale (TMB), les mutations des gènes BRCA1/2 ou un déficit du mécanisme de la recombinaison homologue des bases (HRD) permettent une meilleure sélection et personnalisation des traitements disponibles. Le but du présent article est de rassembler les avancées oncologiques de l'année.


Assuntos
Biomarcadores Tumorais , Neoplasias , Humanos , Mutação , Neoplasias/diagnóstico , Neoplasias/terapia
15.
Rev Med Suisse ; 15(N° 632-633): 78-81, 2019 Jan 09.
Artigo em Francês | MEDLINE | ID: mdl-30629376

RESUMO

The year 2018 has been incredibly prolific regarding novelties. Several studies have given impressive results and offer new anticancer perspectives. Immunotherapy is gaining more and more place defining a new standard of care for different types of cancer. In parallel with a new approach combining immunotherapy and chemotherapy that is emerging, new forms of adoptive immunotherapy are on the path of approval by regulatory authorities. At the decision-making level, a large somatic genetic analysis is becoming dominant, whereas the addition of more specific biomarkers is still needed regarding immunotherapy. This article aims to summarize the significant new developments in oncology for 2018 concerning the five most common cancers and adoptive cellular immunotherapy.


L'année 2018 a été extrêmement prolifique en termes de nouveautés. Plusieurs études ont amené des résultats intéressants et offrent de nouvelles perspectives anticancéreuses. L'immunothérapie prend de plus en plus de place définissant un nouveau standard pour le traitement des différents types de cancer. En parallèle d'une nouvelle approche combinant l'immunothérapie et la chimiothérapie qui voit le jour, des nouvelles formes d'immunothérapie adoptive se situent sur la voie d'approbation par les autorités réglementaires. Sur le plan décisionnel, l'analyse génétique somatique large des tumeurs devient prépondérante, alors que l'addition de biomarqueurs plus spécifiques est encore nécessaire concernant l'immunothérapie. Cet article a pour but de résumer les nouveautés majeures survenues en oncologie pour 2018 concernant les cinq cancers les plus fréquents et l'immunothérapie cellulaire adoptive.


Assuntos
Imunoterapia , Oncologia , Neoplasias , Terapia Combinada , Humanos , Imunoterapia Adotiva , Oncologia/tendências , Neoplasias/terapia
16.
J Urol ; 200(6): 1207-1214, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30012366

RESUMO

PURPOSE: We evaluated the impact of the number of cycles of platinum based, first line chemotherapy (fewer than 6 cycles vs the conventional 6 cycles or more) on the survival of patients with metastatic urothelial carcinoma. MATERIALS AND METHODS: We used the RISC (Retrospective International Study of Invasive/Advanced Cancer of the Urothelium) database. The association of the number of cycles of chemotherapy with overall survival was investigated by Cox multiple regression analysis after controlling for recognized prognostic factors. We excluded patients who received fewer than 3 or more than 9 platinum chemotherapy cycles to reduce confounding factors. The primary analysis was a comparison of overall survival for 3 to 5 vs 6 to 9 cycles using 6-month landmark analysis when 281 death events were observed. RESULTS: Of the 1,020 patients in the RISC 472 received cisplatin or carboplatin, of whom 338 and 134, respectively, were evaluable. A total of 157 patients received 3 to 5 cycles (median 4) and 315 received 6 to 9 cycles (median 6). There was no significant difference in overall survival between 3 to 5 and 6 to 9 cycles (HR 1.02, 95% CI 0.78-1.33, p = 0.91). No significant interactions were observed for the type of platinum (p = 0.09) and completed planned chemotherapy (p = 0.56). The limitations of a hypothesis generating, retrospective analysis applied. CONCLUSIONS: Four cycles of platinum based, first line chemotherapy appeared adequate and did not significantly compromise the survival of patients with advanced urothelial carcinoma. The omission of excessive cycles may avoid unnecessary cumulative toxicity and facilitate a better transition to second line therapy and investigational switch maintenance therapy strategies. These results require prospective validation but they may impact practice in select patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Compostos de Platina/administração & dosagem , Neoplasias Urológicas/tratamento farmacológico , Idoso , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia
17.
Rev Med Suisse ; 13(585): 2083-2086, 2017 Nov 29.
Artigo em Francês | MEDLINE | ID: mdl-29185632

RESUMO

In the past, it was generally considered that the window of curability had been missed in metastatic solid cancers. At present, novel evidence suggests that oligometastatic cancer might be amenable to a multimodal curative treatment, including ablation of the primary tumour. In this article, we summarise the indications, the controversies and future perspectives of local treatment in oligometastatic urological malignancies.


Dans le passé, on considérait le plus souvent que la fenêtre de curabilité dans les cancers solides à un stade métastatique avait été manquée. De nouvelles évidences suggèrent à présent que la maladie à un stade oligométastatique est accessible, dans certains cas, à un traitement multimodal curatif, incluant l'ablation de la tumeur primaire. Dans cet article, nous résumons les indications, les controverses ainsi que les perspectives futures du traitement local dans les cancers oligométastatiques urologiques.


Assuntos
Metástase Neoplásica , Neoplasias Urológicas , Terapia Combinada , Humanos , Metástase Neoplásica/terapia , Neoplasias Urológicas/patologia , Neoplasias Urológicas/terapia
18.
Rev Med Suisse ; 12(519): 994-8, 2016 May 18.
Artigo em Francês | MEDLINE | ID: mdl-27424427

RESUMO

Renal cell carcinoma (RCC) is composed of several histopathological entities. There are more than 1,000 new cases in Switzerland every year, one third of which are diagnosed at an advanced stage. The development of chemotherapy had no impact on its overall prognosis. Since the mid-2000s, treatment of metastatic RCC was transformed by the arrival of targeted therapies. In the early 90s, high dose interleukine-2 (IL-2) allowed first cases of complete response, demonstrating the immunogenicity of RCC. More than twenty years after its first steps, immunotherapy progressed due to the recently approved nivolumab (an anti-PD1 monoclonal antibody) in second line of treatment. This review outlines the progress that has been made in the understanding and treatment of this pathology.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Humanos , Imunoterapia/métodos , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Nivolumabe , Prognóstico , Suíça
19.
Rev Med Suisse ; 12(541): 2068-2071, 2016 Nov 30.
Artigo em Francês | MEDLINE | ID: mdl-28700151

RESUMO

A possible association between prostate cancer and metabolic syndrome has recently been observed. Further, multiple experimental and epidemiologic studies have recently reported a probable association between common medications and prostate cancer. In this article, we summarize the results of those studies that explore the role of aspirin, oral antidiabetic medication and statins.


Une possible association entre le cancer de la prostate et le syndrome métabolique a récemment été mise en évidence. Plusieurs récentes études expérimentales et épidémiologiques ont suggéré un rôle protecteur de plusieurs médicaments largement utilisés en médecine de premier recours dans le cancer de la prostate. Nous résumons ici les résultats de ces études, en particulier pour l'aspirine, les antidiabétiques oraux et les statines.


Assuntos
Aspirina/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipoglicemiantes/efeitos adversos , Neoplasias da Próstata/etiologia , Aspirina/administração & dosagem , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipoglicemiantes/administração & dosagem , Masculino , Síndrome Metabólica/epidemiologia , Neoplasias da Próstata/epidemiologia
20.
Cancer ; 121(15): 2586-93, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25872978

RESUMO

BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC versus GC given their baseline characteristics. These propensity scores were then included in a new logistic regression model to estimate an adjusted odds ratio comparing the odds of attaining a pathologic complete response (pCR) between patients who received MVAC and those who received GC. RESULTS: In total, 212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort) met criteria for inclusion in the analysis. The majority of patients in the MVAC cohort (77%) received dose-dense MVAC. The median age of patients was 63 years, they were predominantly men (74%), and they received a median of 3 cycles of neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the GC cohort. There was no significant difference in the pCR rate when adjusted for propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence interval, 0.48-1.72; P = .77). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P = .48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has become routine practice.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Neoplasias Musculares/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Cisplatino/uso terapêutico , Desoxicitidina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Neoplasias Musculares/mortalidade , Neoplasias Musculares/secundário , Terapia Neoadjuvante , Invasividade Neoplásica , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Vimblastina/uso terapêutico , Gencitabina
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