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1.
Ann Oncol ; 35(4): 392-401, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38244927

RESUMO

BACKGROUND: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate containing cytotoxic SN-38, the active metabolite of irinotecan. SG received accelerated US Food and Drug Administration approval for locally advanced (LA) or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and a checkpoint inhibitor, based on cohort 1 of the TROPHY-U-01 study. Mutations in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene are associated with increased adverse events (AEs) with irinotecan-based therapies. Whether UGT1A1 status could impact SG toxicity and efficacy remains unclear. PATIENTS AND METHODS: TROPHY-U-01 (NCT03547973) is a multicohort, open-label, phase II registrational study. Cohort 1 includes patients with LA or mUC who progressed after platinum- and checkpoint inhibitor-based therapies. SG was administered at 10 mg/kg intravenously on days 1 and 8 of 21-day cycles. The primary endpoint was objective response rate (ORR) per central review; secondary endpoints included progression-free survival, overall survival, and safety. Post hoc safety analyses were exploratory with descriptive statistics. Updated analyses include longer follow-up. RESULTS: Cohort 1 included 113 patients. At a median follow-up of 10.5 months, ORR was 28% (95% CI 20.2% to 37.6%). Median progression-free survival and overall survival were 5.4 months (95% CI 3.5-6.9 months) and 10.9 months (95% CI 8.9-13.8 months), respectively. Occurrence of grade ≥3 treatment-related AEs and treatment-related discontinuation were consistent with prior reports. UGT1A1 status was wildtype (∗1|∗1) in 40%, heterozygous (∗1|∗28) in 42%, homozygous (∗28|∗28) in 12%, and missing in 6% of patients. In patients with ∗1|∗1, ∗1|∗28, and ∗28|∗28 genotypes, any grade treatment-related AEs occurred in 93%, 94%, and 100% of patients, respectively, and were managed similarly regardless of UGT1A1 status. CONCLUSIONS: With longer follow-up, the ORR remains high in patients with heavily pretreated LA or mUC. Safety data were consistent with the known SG toxicity profile. AE incidence varied across UGT1A1 subgroups; however, discontinuation rates remained relatively low for all groups.


Assuntos
Anticorpos Monoclonais Humanizados , Camptotecina/análogos & derivados , Carcinoma de Células de Transição , Imunoconjugados , Neoplasias da Bexiga Urinária , Humanos , Irinotecano , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Platina/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Imunoconjugados/efeitos adversos
2.
Ann Oncol ; 35(2): 200-210, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37956738

RESUMO

BACKGROUND: Fibroblast growth factor receptor 3 (FGFR3) alterations are oncogenic drivers of urothelial carcinoma (UC). Pemigatinib is a selective, oral inhibitor of FGFR1-3 with antitumor activity. We report the efficacy and safety of pemigatinib in the open-label, single-arm, phase II study of previously treated, unresectable or metastatic UC with FGFR3 alterations (FIGHT-201; NCT02872714). PATIENTS AND METHODS: Patients ≥18 years old with FGFR3 mutations or fusions/rearrangements (cohort A) and other FGF/FGFR alterations (cohort B) were included. Patients received pemigatinib 13.5 mg once daily continuously (CD) or intermittently (ID) until disease progression or unacceptable toxicity. The primary endpoint was centrally confirmed objective response rate (ORR) as per RECIST v1.1 in cohort A-CD. Secondary endpoints included ORR in cohorts A-ID and B, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Overall, 260 patients were enrolled and treated (A-CD, n = 101; A-ID, n = 103; B, n = 44; unconfirmed FGF/FGFR status, n = 12). All discontinued treatment, most commonly due to progressive disease (68.5%). ORR [95% confidence interval (CI)] in cohorts A-CD and A-ID was 17.8% (10.9% to 26.7%) and 23.3% (15.5% to 32.7%), respectively. Among patients with the most common FGFR3 mutation (S249C; n = 107), ORR was similar between cohorts (A-CD, 23.9%; A-ID, 24.6%). In cohorts A-CD/A-ID, median (95% CI) DOR was 6.2 (4.1-8.3)/6.2 (4.6-8.0) months, PFS was 4.0 (3.5-4.2)/4.3 (3.9-6.1) months, and OS was 6.8 (5.3-9.1)/8.9 (7.5-15.2) months. Pemigatinib had limited clinical activity among patients in cohort B. Of 36 patients with samples available at progression, 6 patients had 8 acquired FGFR3 secondary resistance mutations (V555M/L, n = 3; V553M, n = 1; N540K/S, n = 2; M528I, n = 2). The most common treatment-emergent adverse events overall were diarrhea (44.6%) and alopecia, stomatitis, and hyperphosphatemia (42.7% each). CONCLUSIONS: Pemigatinib was generally well tolerated and demonstrated clinical activity in previously treated, unresectable or metastatic UC with FGFR3 mutations or fusions/rearrangements.


Assuntos
Antineoplásicos , Carcinoma de Células de Transição , Morfolinas , Pirimidinas , Pirróis , Neoplasias da Bexiga Urinária , Humanos , Adolescente , Carcinoma de Células de Transição/tratamento farmacológico , Antineoplásicos/efeitos adversos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Genômica
3.
ESMO Open ; 8(6): 102038, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37922690

RESUMO

BACKGROUND: BRAF inhibitors are approved in BRAFV600-mutated metastatic melanoma, non-small-cell lung cancer (NSCLC), Erdheim-Chester disease (ECD), and thyroid cancer. We report here the efficacy, safety, and long-term results of single-agent vemurafenib given in the AcSé vemurafenib basket study to patients with various BRAF-mutated advanced tumours other than BRAFV600-mutated melanoma and NSCLC. PATIENTS AND METHODS: Patients with advanced tumours other than BRAFV600E melanoma and progressing after standard treatment were eligible for inclusion in nine cohorts (including a miscellaneous cohort) and received oral vemurafenib 960 mg two times daily. The primary endpoint was the objective response rate (ORR) estimated with a Bayesian design. The secondary outcomes were disease control rate, duration of response, progression-free survival (PFS), overall survival (OS), and vemurafenib safety. RESULTS: A total of 98 advanced patients with various solid or haematological cancers, 88 with BRAFV600 mutations and 10 with BRAFnonV600 mutations, were included. The median follow-up duration was 47.7 months. The Bayesian estimate of ORR was 89.7% in hairy cell leukaemias (HCLs), 33.3% in the glioblastomas cohort, 18.2% in cholangiocarcinomas, 80.0% in ECD, 50.0% in ovarian cancers, 50.0% in xanthoastrocytomas, 66.7% in gangliogliomas, and 60.0% in sarcomas. The median PFS of the whole series was 8.8 months. The 12-, 24-, and 36-month PFS rates were 42.2%, 23.8%, and 17.9%, respectively. Overall, 54 patients died with a median OS of 25.9 months, with a projected 4-year OS of 40%. Adverse events were similar to those previously reported with vemurafenib. CONCLUSION: Responses and prolonged PFS were observed in many tumours with BRAF mutations, including HCL, ECD, ovarian carcinoma, gliomas, ganglioglioma, and sarcomas. Although not all cancer types responded, vemurafenib is an agnostic oncogene therapy of cancers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Melanoma , Sarcoma , Humanos , Vemurafenib/farmacologia , Vemurafenib/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Teorema de Bayes , Resultado do Tratamento , Sulfonamidas/efeitos adversos , Intervalo Livre de Doença , Mutação
4.
Front Oncol ; 13: 1110003, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36741023

RESUMO

Introduction: Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC. Material and Methods: data has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020. Results: The median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment. Conclusion: UrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed.

5.
Prog Urol ; 32(15): 1010-1039, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36400476

RESUMO

OBJECTIVE: To update French oncology guidelines concerning penile cancer. METHODS: Comprehensive Medline search between 2020 and 2022 upon diagnosis, treatment and follow-up of testicular germ cell cancer to update previous guidelines. Level of evidence was evaluated according to AGREE-II. RESULTS: Epidermoid carcinoma is the most common penile cancer histology. Physical examination is mandatory to define local and inguinal nodal cancer stage. MRI with artificial erection can help to assess deep infiltration in cases of organsparing intention. Node negative patients (defined by palpation and imaging) will present micro nodal metastases in up to 25% of cases. Invasive lymph node assessment is thus advocated except for low risk patients. Sentinel node dynamic biopsy is the first line technique. Modified bilateral inguinal lymphadenectomy is an option with higher morbidity. 18-FDG-PET is recommended in patients with palpable nodes. Chest, abdominal and pelvis computerized tomography is an option. Fine needle aspiration (when positive) is an easy way to assess inguinal palpable node pathological involvement. Its results determine the type of lymphadenectomy to be performed (for diagnostic or curative purposes). Treatment is mostly surgical. Free margins status is essential, but it also has to be organ-sparing when possible. Brachytherapy and topic agents can cure in selected cases. Lymph node assessment should be synchronous to the removal of the tumour when possible. Limited inguinal lymph node involvement (pN1 stage) can be cured with the only lymphadenectomy. In case of larger lymph node stage, one should consider multidisciplinary treatment including chemotherapy and inclusion in a trial. CONCLUSIONS: Penile cancer needs demanding surgery to be cured, surrounded by chemotherapy in node positive patients. Lymph nodes involvement is a major prognostic factor. Thus, inguinal node assessment cannot be neglected.


Assuntos
Neoplasias Penianas , Humanos , Masculino , Neoplasias Penianas/diagnóstico , Neoplasias Penianas/terapia , Neoplasias Penianas/patologia , Biópsia de Linfonodo Sentinela , Oncologia , Excisão de Linfonodo/métodos , Estadiamento de Neoplasias
6.
Prog Urol ; 32(15): 1040-1065, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36400477

RESUMO

INTRODUCTION: The objective of this publication is to recall the initial work-up when faced with an adrenal incidentaloma and, if necessary, to establish the oncological management of an adrenal malignant tumor. MATERIAL AND METHODS: The multidisciplinary working group updated French urological guidelines about oncological assessment of the adrenal incidentaloma, established by the CCAFU in 2020, based on an exhaustive literature review carried out on PubMed. RESULTS: Although the majority of the adrenal masses are benign and non-functional, it is important to investigate them, as a percentage of these can cause serious endocrine diseases or be cancers. Malignant adrenal tumors are mainly represented by adrenocortical carcinomas (ACC), malignant pheochromocytomas (MPC) and adrenal metastases (AM). The malignancy assessment of an adrenal incident includes a complete history, a physical examination, a biochemical/hormonal assessment to look for subclinical hormonal secretion. Diagnostic hypotheses are sometimes available at this stage, but it is the morphological and functional imaging and the histological analysis, which will make it possible to close the malignancy assessment and make the oncological diagnosis. CONCLUSIONS: ACC and MPC are mainly sporadic but a hereditary origin is always possible. ACC is suspected preoperatively but the diagnosis of certainty is histological. The diagnosis of MPC is more delicate and is based on clinic, biology and imagery. The diagnosis of certainty of AM requires a percutaneous biopsy. At the end, the files must be discussed within the COMETE - adrenal cancer network (Appendix 1).


Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Humanos , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/terapia , Feocromocitoma/diagnóstico , Oncologia
7.
Prog Urol ; 32(15): 1066-1101, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36400478

RESUMO

OBJECTIVE: Updated Recommendations for the management of testicular germ cell cancer. MATERIALS AND METHODS: Comprehensive review of the literature on PubMed since 2020 concerning the diagnosis, treatment and follow-up of testicular germ cell cancer (TGCT), and the safety of treatments. The level of evidence of the references was evaluated. RESULTS: The initial work-up for patients with testicular germ cell cancer is based on a clinical examination, biochemical (AFP, total hCG and LDH serum markers) and radiological assessment (scrotal ultrasound and thoracic-abdominal-pelvic [TAP] CT). Inguinal orchiectomy is the first therapeutic step whereby the histological diagnosis can be made, and the local stage and risk factors for stage I non-seminomatous germ cell tumours (NSGCT) can be determined. For patients with pure stage-I seminoma, the risk of progression is 15 to 20%. Therefore, surveillance in compliant patients is preferable; adjuvant chemotherapy with carboplatin AUC 7 is an option; and indications for para-aortic radiotherapy are limited. For patients with stage I NSGCT, there are various options between surveillance and a risk-adapted strategy (surveillance or 1 cycle of BEP [Bleomycin Etoposide Cisplatin] depending on the absence or presence of vascular emboli within the tumour). Retroperitoneal lymph node dissection for staging has a very limited role. The treatment for metastatic TGCT is BEP chemotherapy in the absence of any contraindication to bleomycin, for which the number of cycles is determined according to the prognostic risk group of the International Germ Cell Cancer Consortium Group (IGCCCG). Para-aortic radiotherapy is still a standard in stage IIA seminomatous germ cell tumours (SGCT). After chemotherapy, the size of residual masses should be assessed by TAP scan for NSGCT: retroperitoneal lymph node dissection is recommended for any residual mass of more than 1 cm, and all other metastatic sites should be excised. For SGCT, reassessment by 18F-FDG PET is required to specify the surgical indication for residual masses>3cm. Surgery is still rare in these situations. CONCLUSION: By adhering to TGCT management recommendations, excellent disease-specific survival rates are achieved; 99% for stage I and over 85% for metastatic stages.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Orquiectomia , Bleomicina/uso terapêutico
8.
ESMO Open ; 6(1): 100044, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33516148

RESUMO

BACKGROUND: Second primary cancers (SPCs) are diagnosed in over 5% of patients after a first primary cancer (FPC). We explore here the impact of immune checkpoint inhibitors (ICIs) given for an FPC on the risk of SPC in different age groups, cancer types and treatments. PATIENTS AND METHODS: The files of the 46 829 patients diagnosed with an FPC in the Centre Léon Bérard from 2013 to 2018 were analyzed. Structured data were extracted and electronic patient records were screened using a natural language processing tool, with validation using manual screening of 2818 files of patients. Univariate and multivariate analyses of the incidence of SPC according to patient characteristics and treatment were conducted. RESULTS: Among the 46 829 patients, 1830 (3.9%) had a diagnosis of SPC with a median interval of 11.1 months (range 0-78 months); 18 128 (38.7%) received cytotoxic chemotherapy (CC) and 1163 (2.5%) received ICIs for the treatment of the FPC in this period. SPCs were observed in 7/1163 (0.6%) patients who had received ICIs for their FPC versus 437/16 997 (2.6%) patients receiving CC and no ICIs for the FPC versus 1386/28 669 (4.8%) for patients receiving neither CC nor ICIs for the FPC. This reduction was observed at all ages and for all histotypes analyzed. Treatment with ICIs and/or CC for the FPC are associated with a reduced risk of SPC in multivariate analysis. CONCLUSION: Immunotherapy with ICIs alone and in combination with CC was found to be associated with a reduced incidence of SPC for all ages and cancer types.


Assuntos
Inibidores de Checkpoint Imunológico , Segunda Neoplasia Primária , Humanos , Incidência , Segunda Neoplasia Primária/epidemiologia
9.
Prog Urol ; 30(12S): S252-S279, 2020 Nov.
Artigo em Francês | MEDLINE | ID: mdl-33349426

RESUMO

OBJECTIVE: - To update French oncology guidelines concerning penile cancer. METHODS: - Comprehensive Medline search between 2018 and 2020 upon diagnosis, treatment and follow-up of testicular germ cell cancer to update previous guidelines. Level of evidence was evaluated according to AGREE-II. RESULTS: - Epidermoid carcinoma is the most common penile cancer histology. Physical examination is mandatory to define local and inguinal nodal cancer stage. MRI with artificial erection can help to assess deep infiltration in cases of organ-sparing intention. Node negative patients (defined by palpation and imaging) will present micro nodal metastases in up to 25% of cases. Invasive lymph node assessment is thus advocated except for low risk patients. Sentinel node dynamic biopsy is the first line technique. Modified bilateral inguinal lymphadenectomy is an option with higher morbidity. 18-FDG-PET is recommended in patients with palpable nodes. Chest, abdominal and pelvis computerized tomography is an option. Fine needle aspiration (when positive) is an easy way to assess inguinal palpable node pathological involvement. Its results determine the type of lymphadenectomy to be performed (for diagnostic or curative purposes). Treatment is mostly surgical. Free margins status is essential, but it also has to be organ-sparing when possible. Brachytherapy and topic agents can cure in selected cases. Lymph node assessment should be synchronous to the removal of the tumour when possible. Limited inguinal lymph node involvement (pN1 stage) can be cured with the only lymphadenectomy. In case of larger lymph node stage, one should consider multidisciplinary treatment including chemotherapy and inclusion in a trial. CONCLUSIONS: - Penile cancer needs demanding surgery to be cured, surrounded by chemotherapy in node positive patients. Lymph nodes involvement is a major prognostic factor. Thus, inguinal node assessment cannot be neglected.


Assuntos
Neoplasias Penianas/diagnóstico , Neoplasias Penianas/terapia , Algoritmos , Árvores de Decisões , Humanos , Masculino
10.
Prog Urol ; 30(12S): S280-S313, 2020 Nov.
Artigo em Francês | MEDLINE | ID: mdl-33349427

RESUMO

OBJECTIVE: - To update French guidelines concerning testicular germ cell cancer. MATERIALS AND METHODS: - Comprehensive Medline search between 2018 and 2020 upon diagnosis, treatment and follow-up of testicular germ cell cancer and treatments toxicities. Level of evidence was evaluated. RESULTS: - Testicular Germ cell tumor diagnosis is based on physical examination, biology tests (serum tumor markers AFP, hCGt, LDH) and radiological assessment (scrotal ultrasound and chest, abdomen and pelvis computerized tomography). Total inguinal orchiectomy is the first-line treatment allowing characterization of the histological type, local staging and identification of risk factors for micrometastases. In case of several therapeutic options, one must inform his patient balancing risks and benefits. Surveillance is usually chosen in stage I seminoma compliant patients as the evolution rate is low between 15 to 20%. Carboplatin AUC7 is an alternative option. Radiotherapy indication should be avoided. In stage I non seminomatous patients, either surveillance or risk-adapted strategy can be applied. Staging retroperitoneal lymphadenectomy has restricted indications. Metastatic germ cell tumors are usually treated by PEB chemotherapy according to IGCCCG prognostic classification. Lombo-aortic radiotherapy is still a standard treatment for stage IIA. Residual masses should be evaluated by biological and radiological assessment 3 to 4 weeks after the end of chemotherapy. Retroperitoneal lymphadenectomy is advocated for every non seminomatous residual mass more than one cm. 18FDG uptake should be evaluated for each seminoma residual mass more than 3 cm. CONCLUSIONS: - A rigorous use of classifications is mandatory to define staging since initial diagnosis. Applying treatments based on these classifications leads to excellent survival rates (99% in CSI, 85% in CSII+).


Assuntos
Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Humanos , Masculino
11.
Prog Urol ; 30(12S): S314-S330, 2020 Nov.
Artigo em Francês | MEDLINE | ID: mdl-33349428

RESUMO

OBJECTIVE: - To update French urological guidelines on retroperitoneal sarcoma. MATERIALS AND METHODS: - Comprehensive Medline search between 2018 and 2020 upon diagnosis, treatment and follow-up of retroperitoneal sarcoma. Level of evidence was evaluated. RESULTS: - Chest, abdomen and pelvis CT is mandatory to evaluate any suspected retroperitoneal sarcoma. MRI sometimes helps surgical planning. Before histological confirmation through biopsy, the patient must be registered in the French sarcoma pathology reference network. The biopsy standard should be an extraperitoneal coaxial percutaneous sampling before any retroperitoneal mass therapeutic decision. Surgery is retroperitoneal sarcoma cornerstone. The main objective is grossly negative margins and can be technically challenging. Multimodal treatment risks and benefits must be discussed in multidisciplinary teams. The relapse rate is related to tumor grade and surgical margins. Reported Negative margins rate thus encourage surgery in high-volume centers. CONCLUSION: - Retroperitoneal sarcoma prognosis is poor and closely related to the quality of initial management. Centralization through dedicated sarcoma pathology network in a high-volume center is mandatory.


Assuntos
Neoplasias Retroperitoneais/diagnóstico , Neoplasias Retroperitoneais/terapia , Sarcoma/diagnóstico , Sarcoma/terapia , Árvores de Decisões , Humanos
12.
Prog Urol ; 30(12S): S331-S352, 2020 Nov.
Artigo em Francês | MEDLINE | ID: mdl-33349429

RESUMO

INTRODUCTION: - The objective of this publication is to recall the initial oncological management of adrenal incidentalomas. MATERIAL & METHODS: - The multidisciplinary working group updated french urological guidelines established by the CCAFU in 2018, based on an exhaustive literature review carried out on PubMed. RESULTS: - Although the majority of the adrenal masses are benign and non-functional, it is important to investigate them, as a percentage of these can cause serious endocrine diseases or be cancers. Malignant adrenal tumors are mainly represented by Adrenocortical Carcinomas (ACC), malignant pheochromocytomas (MPC) and adrenal metastases (AM). The malignancy assessment of an adrenal incident includes a complete history, a physical examination, a biochemical / hormonal assessment to look for subclinical hormonal secretion. Diagnostic hypotheses are sometimes available at this stage, but it is the morphological and functional imaging and the histological analysis which will make it possible to close the malignancy assessment and make the oncological diagnosis. CONCLUSIONS: - AC and MPC are mainly sporadic but a hereditary origin is always possible. ACC is suspected preoperatively but the diagnosis of certainty is histological. The diagnosis of MPC is more delicate and is based on clinic, biology and imagery. The diagnosis of certainty of AM requires a percutaneous biopsy. At the end, the files must be discussed within the COMETE - adrenal cancer network (Appendix 1).


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/terapia , Algoritmos , Árvores de Decisões , Humanos
13.
Ann Oncol ; 30(5): 757-765, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30865223

RESUMO

BACKGROUND: Antitumor activity of molecular-targeted agents is guided by the presence of documented genomic alteration in specific histological subtypes. We aim to explore the feasibility, efficacy and therapeutic impact of molecular profiling in routine setting. PATIENTS AND METHODS: This multicentric prospective study enrolled adult or pediatric patients with solid or hematological advanced cancer previously treated in advanced/metastatic setting and noneligible to curative treatment. Each molecular profile was established on tumor, relapse or biopsies, and reviewed by a molecular tumor board (MTB) to identify molecular-based recommended therapies (MBRT). The main outcome was to assess the incidence rate of genomic mutations in routine setting, across specific histological types. Secondary objectives included a description of patients with actionable alterations and for whom MBRT was initiated, and overall response rate. RESULTS: Four centers included 2579 patients from February 2013 to February 2017, and the MTB reviewed the molecular profiles achieved for 1980 (76.8%) patients. The most frequently altered genes were CDKN2A (N = 181, 7%), KRAS (N = 177, 7%), PIK3CA (N = 185, 7%), and CCND1 (N = 104, 4%). An MBRT was recommended for 699/2579 patients (27%), and only 163/2579 patients (6%) received at least one MBRT. Out of the 182 lines of MBRT initiated, 23 (13%) partial responses were observed. However, only 0.9% of the whole cohort experienced an objective response. CONCLUSION: An MBRT was provided for 27% of patients in our study, but only 6% of patients actually received matched therapy with an overall response rate of 0.9%. Molecular screening should not be used at present to guide decision-making in routine clinical practice outside of clinical trials.This trial is registered with ClinicalTrials.gov, number NCT01774409.


Assuntos
Mutação , Recidiva Local de Neoplasia/diagnóstico , Neoplasias/diagnóstico , Adulto , Biomarcadores Tumorais/genética , Criança , Bases de Dados Genéticas , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Medicina de Precisão/métodos , Estudos Prospectivos
14.
Prog Urol ; 28(12S): S147-S164, 2018 11.
Artigo em Francês | MEDLINE | ID: mdl-30472999

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). Cet article est retiré de la publication à la demande des auteurs car ils ont apporté des modifications significatives sur des points scientifiques après la publication de la première version des recommandations. Le nouvel article est disponible à cette adresse: doi:10.1016/j.purol.2019.01.009. C'est cette nouvelle version qui doit être utilisée pour citer l'article. This article has been retracted at the request of the authors, as it is not based on the definitive version of the text because some scientific data has been corrected since the first issue was published. The replacement has been published at the doi:10.1016/j.purol.2019.01.009. That newer version of the text should be used when citing the article.


Assuntos
Oncologia/normas , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/terapia , França , Humanos , Masculino , Oncologia/organização & administração , Oncologia/tendências , Padrões de Prática Médica/normas , Padrões de Prática Médica/tendências , Sociedades Médicas/organização & administração , Sociedades Médicas/normas
15.
Prog Urol ; 28(12S): S165-S174, 2018 11.
Artigo em Francês | MEDLINE | ID: mdl-30473000

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). Cet article est retiré de la publication à la demande des auteurs car ils ont apporté des modifications significatives sur des points scientifiques après la publication de la première version des recommandations. Le nouvel article est disponible à cette adresse: doi:10.1016/j.purol.2019.01.010. C'est cette nouvelle version qui doit être utilisée pour citer l'article. This article has been retracted at the request of the authors, as it is not based on the definitive version of the text because some scientific data has been corrected since the first issue was published. The replacement has been published at the doi:10.1016/j.purol.2019.01.010. That newer version of the text should be used when citing the article.


Assuntos
Oncologia/normas , Neoplasias Retroperitoneais/terapia , Sarcoma/terapia , França , Humanos , Oncologia/organização & administração , Oncologia/tendências , Padrões de Prática Médica/normas , Padrões de Prática Médica/tendências , Sociedades Médicas/organização & administração , Sociedades Médicas/normas
16.
Prog Urol ; 28(12S): S175-S193, 2018 11.
Artigo em Francês | MEDLINE | ID: mdl-30473001

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). Cet article est retiré de la publication à la demande des auteurs car ils ont apporté des modifications significatives sur des points scientifiques après la publication de la première version des recommandations. Le nouvel article est disponible à cette adresse: doi:10.1016/j.purol.2019.01.011. C'est cette nouvelle version qui doit être utilisée pour citer l'article. This article has been retracted at the request of the authors, as it is not based on the definitive version of the text because some scientific data has been corrected since the first issue was published. The replacement has been published at the doi:10.1016/j.purol.2019.01.011. That newer version of the text should be used when citing the article.


Assuntos
Neoplasias das Glândulas Suprarrenais/terapia , Oncologia/normas , França , Humanos , Oncologia/organização & administração , Oncologia/tendências , Padrões de Prática Médica/normas , Padrões de Prática Médica/tendências , Sociedades Médicas/organização & administração , Sociedades Médicas/normas
17.
Prog Urol ; 28(12S): S131-S146, 2018 11.
Artigo em Francês | MEDLINE | ID: mdl-30361138

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). Cet article est retiré de la publication à la demande des auteurs car ils ont apporté des modifications significatives sur des points scientifiques après la publication de la première version des recommandations. Le nouvel article est disponible à cette adresse: doi:10.1016/j.purol.2019.01.008. C'est cette nouvelle version qui doit être utilisée pour citer l'article. This article has been retracted at the request of the authors, as it is not based on the definitive version of the text because some scientific data has been corrected since the first issue was published. The replacement has been published at the doi:10.1016/j.purol.2019.01.008. That newer version of the text should be used when citing the article.


Assuntos
Oncologia/normas , Neoplasias Penianas/terapia , França , Humanos , Masculino , Oncologia/organização & administração , Oncologia/tendências , Padrões de Prática Médica/normas , Padrões de Prática Médica/tendências , Sociedades Médicas/organização & administração , Sociedades Médicas/normas
18.
Prog Urol ; 28(8-9): 407-415, 2018 Jun.
Artigo em Francês | MEDLINE | ID: mdl-29650457

RESUMO

BACKGROUND: Help in management of non-palpable testicular tumors. French Urologic Association Genital cancer committee's Edit. OBJECTIVES: To review their characterization at imaging findings of non-palpable testicular tumors. DOCUMENTARY SOURCES: Literature review (PubMed, Medline) of urological and radiological studies dealing with testicular tumors using keywords: non-palpable/incidental testicular tumors; color Doppler ultrasound; US elastography; magnetic resonance imaging; contrast enhanced sonography; partial surgery. RESULTS: Color Doppler is the basic exam. The size, the presence of microlithts/microlithiasis/macrocalcifications, the vascular architecture are major semiological findings to suggest the benign or the malignant nature of the lesion. Other techniques like multiparametric MRI, contrast-enhanced sonography, sonographic elastography are still in evaluation. The frequency of benign tumors such as Leydig cell tumors lead to preservation management, through improved characterization, monitoring or tumorectomy. LIMITS: Non-randomized study - a very few prospective studies. CONCLUSION: The era of total orchiectomy for any uncertain testicular lesion is over. We try the challenge of characterization, and define management's algorithms based on the suspected nature of the tumors.


Assuntos
Técnicas de Diagnóstico Urológico , Cirurgia Assistida por Computador , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Adulto , Diagnóstico por Imagem/normas , Diagnóstico por Imagem/tendências , Técnicas de Diagnóstico Urológico/normas , Técnicas de Diagnóstico Urológico/tendências , França , Humanos , Masculino , Orquiectomia/métodos , Orquiectomia/normas , Orquiectomia/tendências , Exame Físico , Sociedades Médicas/normas , Cirurgia Assistida por Computador/métodos , Cirurgia Assistida por Computador/normas , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/cirurgia , Tato , Carga Tumoral/fisiologia , Urologia/métodos , Urologia/organização & administração , Urologia/normas
19.
Prog Urol ; 28 Suppl 1: R133-R148, 2018 11.
Artigo em Francês | MEDLINE | ID: mdl-31610869

RESUMO

OBJECTIVE: To update French oncology guidelines concerning penile cancer. METHODS: Comprehensive Medline search between 2016 and 2018 upon diagnosis, treatment and follow-up of testicular germ cell cancer to update 2016-2018 guidelines. Level of evidence was evaluated according to AGREE-II. RESULTS: Epidermoid carcinoma is the most common penile cancer histology. Physical examination is mandatory to define local and inguinal nodal cancer stage. MRI with artificial erection can help to assess deep infiltration in cases of organ-sparing intention. Node negative patients (defined by palpation and imaging) will present micro nodal metastases in up to 25% of cases. Invasive lymph node assessment is thus advocated except for low risk patients. Sentinel node dynamic biopsy is the first line technique. Modified bilateral inguinal lymphadenectomy is an option with higher morbidity. 18-FDG-PET is recommended in patients with palpable nodes. Chest, abdominal and pelvis computerized tomography is an option. Fine needle aspiration (when positive) is an easy way to assess inguinal palpable node pathological involvement. Treatment is mostly surgical. Free margins status is essential, but it also has to be organ-sparing when possible. Brachytherapy and topic agents can cure in selected cases. Lymph node assessment should be synchronous to the removal of the tumour when possible. Limited inguinal lymph node involvement (pN1 stage) can be cured with the only lymphadenectomy. In case of larger lymph node stage, one should consider multidisciplinary treatment including chemotherapy and inclusion in a trial. CONCLUSIONS: Penile cancer needs demanding surgery to be cured, surrounded by chemotherapy in node positive patients. Lymph nodes involvement is a major prognostic factor. Thus, inguinal node assessment cannot be neglected.

20.
Prog Urol ; 28 Suppl 1: R149-R166, 2018 11.
Artigo em Francês | MEDLINE | ID: mdl-31610870

RESUMO

OBJECTIVE: To update French guidelines concerning testicular germ cell cancer. METHODS: Comprehensive Medline search between 2016 and 2018 upon diagnosis, treatment and follow-up of testicular germ cell cancer and treatments toxicities. Level of evidence was evaluated. RESULTS: Testicular Germ cell tumor diagnosis is based on physical examination, biology tests (serum tumor markers AFP, hCGt, LDH) and radiological assessment (scrotal ultrasound and chest, abdomen and pelvis computerized tomography). Total inguinal orchiectomy is the first- line treatment allowing characterization of the histological type, local staging and identification of risk factors for micrometastases. In case of several therapeutic options, one must inform his patient balancing risks and benefits. Surveillance is usually chosen in stage I seminoma compliant patients as the evolution rate is low between 15 to 20 %. Carboplatin AUC7 is an alternative option. Radiotherapy indication should be avoided. In stage I non-seminomatous patients, either surveillance or risk-adapted strategy can be applied. Staging retroperitoneal lymphadenectomy has restricted indications. Metastatic germ cell tumors are usually treated by PEB chemotherapy according to IGCCCG prognostic classification. Lombo-aortic radiotherapy is still a standard treatment for stage IIA. Residual masses should be evaluated by biological and radiological assessment 3 to 4 weeks after the end of chemotherapy. Retroperitoneal lymphadenectomy is advocated for every non-seminomatous residual mass more than one cm. 18FDG uptake should be evaluated for each seminoma residual mass more than 3cm. CONCLUSIONS: A rigorous use of classifications is mandatory to define staging since initial diagnosis. Applying treatments based on these classifications leads to excellent survival rates (99 % in CSI, 85 % in CSII+).

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