RESUMO
BACKGROUND: Early-phase clinical trials (EPCT) represent an important part of innovations in medical oncology and a valuable therapeutic option for patients with metastatic cancers, particularly in the era of precision medicine. Nevertheless, adult patients' participation in oncology clinical trials is low, ranging from 2% to 8% worldwide, with unequal access, and up to 40% risk of early discontinuation in EPCT, mostly due to cancer-related complications. DESIGN: We review the tools and initiatives to increase patients' orientation and access to early phase cancer clinical trials, and to limit early discontinuation. RESULTS: New approaches to optimize the early-phase clinical trial referring process in oncology include automatic trial matching, tools to facilitate the estimation of patients' prognostic and/or to better predict patients' eligibility to clinical trials. Classical and innovative approaches should be associated to double patient recruitment, improve clinical trial enrollment experience and reduce early discontinuation rates. CONCLUSIONS: Whereas EPCT are essential for patients to access the latest medical innovations in oncology, offering the appropriate trial when it is relevant for patients should increase by organizational and technological innovations. The oncologic community will need to closely monitor their performance, portability and simplicity for implementation in daily clinical practice.
Assuntos
Segunda Neoplasia Primária , Neoplasias , Adulto , Humanos , Oncologia , Neoplasias/terapia , Seleção de Pacientes , Medicina de Precisão , Ensaios Clínicos como AssuntoRESUMO
BACKGROUND: Notch signaling plays an integral role in development and tissue homeostasis. Inhibition of Notch signaling has been identified as a reasonable target for oncotherapy. Crenigacestat (LY3039478) is a potent Notch inhibitor that decreases Notch signaling and its downstream biologic effects. METHODS: I6F-MC-JJCD was a multicenter, nonrandomized, open-label, phase 1b study with 5 separate, parallel dose escalations in patients with advanced or metastatic cancer from a variety of solid tumors followed by a dose-confirmation phase in pre-specified tumor types. This manuscript reports on 2 of 5 groups. The primary objective was to determine the recommended phase 2 dose of crenigacestat combined with other anticancer agents (gemcitabine/cisplatin or gemcitabine/carboplatin). Secondary objectives included evaluation of safety, tolerability, preliminary efficacy, and pharmacokinetics. RESULTS: Patients (N = 31) received treatment between November 2016 and July 2019. Dose-limiting toxicities occurred in 6 patients. The recommended phase 2 dose for crenigacestat was 50 mg TIW in Part 1 (combined with gemcitabine/cisplatin) and not established in Part 2 (combined with gemcitabine/carboplatin) due to poor tolerability. Patients had at least one treatment-emergent adverse event (TEAE), and most had Grade ≥ 3 TEAEs. Over 50% of the patients experienced gastrointestinal disorders (Grade ≥ 3). No patient had complete response; 5 patients had a partial response. Disease control rates were 62.5% (Part 1) and 60.0% (Part 2). CONCLUSION: This study demonstrated that the Notch inhibitor, crenigacestat, combined with different anticancer agents (gemcitabine, cisplatin, and carboplatin) was poorly tolerated and resulted in disappointing clinical activity in patients with advanced or metastatic solid tumors. CLINICALTRIALS: gov Identification Number: NCT02784795.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Segunda Neoplasia Primária , Neoplasias , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Benzazepinas , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Segunda Neoplasia Primária/tratamento farmacológico , GencitabinaRESUMO
OBJECTIVE: Pembrolizumab demonstrated a clinically meaningful objective response rate in patients with previously treated, advanced MSI-H/dMMR endometrial cancer in the multicohort phase 2 KEYNOTE-158 study (ClinicalTrials.gov, NCT02628067). We present health-related quality of life (HRQoL) results for these patients. METHODS: This analysis included patients from cohorts D (endometrial cancer with any MSI status) and K (any MSI-H/dMMR solid tumor except colorectal) who had previously treated, advanced MSI-H/dMMR endometrial cancer. Patients received pembrolizumab 200â¯mg Q3W for 35â¯cycles. EORTC QLQ-C30 and EQ-5D-3L questionnaires were administered at baseline, at regular intervals during treatment, and 30â¯days after treatment discontinuation. Pre-specified exploratory analyses included changes from baseline to week 9 in QLQ-C30 global health status (GHS)/QoL and EQ-5D-3L visual analog scale (VAS) score for all patients and by best overall response. RESULTS: 84 of 90 enrolled patients completed ≥1 HRQoL questionnaire and were included in the analysis. QLQ-C30 and EQ-5D-3L compliance rates were 90% and 94%, respectively, at baseline, and 92% and 93% at week 9. Mean (95% CI) QLQ-C30 GHS/QoL scores improved from baseline to week 9 by 6.08 (0.71-11.46) points in the overall population, with greater improvement in patients who achieved complete or partial response (11.67 [5.33-18.00]-point increase). Mean (95% CI) EQ-5D-3L VAS scores improved by 6.00 (2.25-9.75) points in the overall population and 9.11 (5.24-12.98) points in patients with CR/PR. CONCLUSIONS: Pembrolizumab maintained or improved HRQoL in patients with previously treated, advanced MSI-H/dMMR endometrial cancer, further supporting efficacy and safety results from KEYNOTE-158 and pembrolizumab use in this setting.
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Neoplasias do Endométrio , Qualidade de Vida , Anticorpos Monoclonais Humanizados , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Feminino , Humanos , Instabilidade de MicrossatélitesRESUMO
BACKGROUND: Pembrolizumab demonstrated durable antitumor activity in 233 patients with previously treated advanced microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) advanced solid tumors in the phase II multicohort KEYNOTE-158 (NCT02628067) study. Herein, we report safety and efficacy outcomes with longer follow-up for more patients with previously treated advanced MSI-H/dMMR noncolorectal cancers who were included in cohort K of the KEYNOTE-158 (NCT02628067) study. PATIENTS AND METHODS: Eligible patients with previously treated advanced noncolorectal MSI-H/dMMR solid tumors, measurable disease as per RECIST v1.1, and Eastern Cooperative Oncology Group performance status of 0 or 1 received pembrolizumab 200 mg Q3W for 35 cycles or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) as per RECIST v1.1 by independent central radiologic review. RESULTS: Three hundred and fifty-one patients with various tumor types were enrolled in KEYNOTE-158 cohort K. The most common tumor types were endometrial (22.5%), gastric (14.5%), and small intestine (7.4%). Median time from first dose to database cut-off (5 October 2020) was 37.5 months (range, 0.2-55.6 months). ORR among 321 patients in the efficacy population (patients who received ≥1 dose of pembrolizumab enrolled ≥6 months before the data cut-off date) was 30.8% [95% confidence interval (CI) 25.8% to 36.2%]. Median duration of response was 47.5 months (range, 2.1+ to 51.1+ months; '+' indicates no progressive disease by the time of last disease assessment). Median progression-free survival was 3.5 months (95% CI 2.3-4.2 months) and median overall survival was 20.1 months (95% CI 14.1-27.1 months). Treatment-related adverse events (AEs) occurred in 227 patients (64.7%). Grade 3-4 treatment-related AEs occurred in 39 patients (11.1%); 3 (0.9%) had grade 5 treatment-related AEs (myocarditis, pneumonia, and Guillain-Barre syndrome, n = 1 each). CONCLUSIONS: Pembrolizumab demonstrated clinically meaningful and durable benefit, with a high ORR of 30.8%, long median duration of response of 47.5 months, and manageable safety across a range of heavily pretreated, advanced MSI-H/dMMR noncolorectal cancers, providing support for use of pembrolizumab in this setting.
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Antineoplásicos Imunológicos , Neoplasias , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/efeitos adversos , Reparo de Erro de Pareamento de DNA/genética , Humanos , Instabilidade de Microssatélites , Neoplasias/induzido quimicamente , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
Tenosynovial giant cell tumors (TGCT), are rare colony stimulating factor-1(CSF-1)-driven proliferative disorders affecting joints. Diffuse-type TGCT often causes significant morbidity due to local recurrences necessitating multiple surgeries. Imatinib mesylate (IM) blocks the CSF-1 receptor. This study investigated the long term effects of IM in TGCT. We conducted an international multi-institutional retrospective study to assess the activity of IM: data was collected anonymously from individual patients with locally advanced, recurrent or metastatic TGCT. Sixty-two patients from 12 institutions across Europe, Australia and the United States were identified. Four patients with metastatic TGCT progressed rapidly on IM and were excluded for further analyses. Seventeen of 58 evaluable patients achieved complete response (CR) or partial response (PR). One- and five-year progression-free survival rates were 71% and 48%, respectively. Thirty-eight (66%) patients discontinued IM after a median of 7 (range 1-80) months. Reported adverse events in 45 (78%) patients were among other edema (48%) and fatigue (50%), mostly grade 1-2 (89%). Five patients experienced grade 3-4 toxicities. This study confirms, with additional follow-up, the efficacy of IM in TGCT. In responding cases we confirmed prolonged IM activity on TGCT symptoms even after discontinuation, but with high rates of treatment interruption and additional treatments.
Assuntos
Antineoplásicos/uso terapêutico , Tumor de Células Gigantes de Bainha Tendinosa/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Adulto , Austrália , Progressão da Doença , Intervalo Livre de Doença , Europa (Continente) , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Receptores de Fator Estimulador de Colônias/antagonistas & inibidores , Estudos Retrospectivos , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Numerous phase I trials testing immune checkpoint inhibitors (CPI)-based combinations are currently being conducted to improve response rates observed with single agents. However, methodology varies across studies, especially regarding the use of dose escalation. MATERIALS AND METHODS: A literature search was conducted in Pubmed and major oncology meetings libraries for phase I trials reported between 2011 and 2018, containing at least one CPI [CLTA-4 blocking antibody or a PD(L)1 blocking antibody] plus at least one second agent (e.g. tyrosine kinase inhibitor, chemotherapy). Dose escalation schemes, target doses and recommended phase II doses (RP2D) were captured in our database for each study. Combination RP2D (combo-RP2D) was compared with target dose. RESULTS: We identified 113 different studies comprising a total of 120 individual cohorts. The backbone was an anti- cytotoxic T-lymphocyte antigen 4 (CTLA-4) in 40 cohorts and an anti-PD(L)1 in 80 cohorts. Dose escalation was used for the CPI in 29 (24%) cohorts [11% for anti-PD(L)1 and 50% for anti-CTLA-4] and for the second agent in 55 cohorts (46%). For 31 s agents (26%), the combo-RP2D was significantly lower than the expected target dose. Failure to reach the target dose was explained by the type of second agent form (e.g. small molecules versus monoclonal antibodies) (P < 0.001) and the choice of trial design for the second agent by investigators. CONCLUSION: Design of studies investigating new CPI-based combinations must consider the type of second agent. Dose escalation is required for combinations with small molecules but is unnecessary with vaccine/virus/dendritic therapies and monoclonal antibodies.
Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ensaios Clínicos Fase I como Assunto/normas , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Antineoplásicos Imunológicos/toxicidade , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Relação Dose-Resposta a Droga , Humanos , Dose Máxima Tolerável , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Inibidores de Proteínas Quinases/toxicidade , Projetos de Pesquisa/normas , Resultado do TratamentoRESUMO
BACKGROUND: Emactuzumab is a monoclonal antibody against the colony-stimulating factor-1 receptor and targets tumor-associated macrophages (TAMs). This study assessed the safety, clinical activity, pharmacokinetics (PK) and pharmacodynamics (PD) of emactuzumab, as monotherapy and in combination with paclitaxel, in patients with advanced solid tumors. PATIENTS AND METHODS: This open-label, phase Ia/b study comprised two parts (dose escalation and dose expansion), each containing two arms (emactuzumab, every 2 or 3 weeks, as monotherapy or in combination with paclitaxel 80 mg/m2 weekly). The dose-escalation part explored the maximum tolerated dose and optimal biological dose (OBD). The dose-expansion part extended the safety assessment and investigated the objective response rate. A PK/PD analysis of serial blood, skin and tumor biopsies was used to explore proof of mechanism and confirm the OBD. RESULTS: No maximum tolerated dose was reached in either study arm, and the safety profile of emactuzumab alone and in combination does not appear to preclude its use. No patients receiving emactuzumab monotherapy showed an objective response; the objective response rate for emactuzumab in combination with paclitaxel was 7% across all doses. Skin macrophages rather than peripheral blood monocytes or circulating colony-stimulating factor-1 were identified as an optimal surrogate PD marker to select the OBD. Emactuzumab treatment alone and in combination with paclitaxel resulted in a plateau of immunosuppressive TAM reduction at the OBD of 1000 mg administered every 2 weeks. CONCLUSIONS: Emactuzumab showed specific reduction of immunosuppressive TAMs at the OBD in both treatment arms but did not result in clinically relevant antitumor activity alone or in combination with paclitaxel. (ClinicalTrials.gov Identifier: NCT01494688).
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Anticorpos Monoclonais Humanizados/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Macrófagos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Paclitaxel/farmacologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Fator Estimulador de Colônias de Macrófagos/sangue , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/imunologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/imunologia , Neoplasias/patologia , Paclitaxel/uso terapêutico , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Pele/citologia , Pele/imunologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The role of adjuvant radiotherapy (RT) in the management of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WD-LPS) remains controversial. METHODS: Two hundred eighty-three patients with operable ALT/WD-LPS, no history of previous cancer, chemotherapy (CT) or RT, treated between 1984 and 2011 registered in the Conticabase database were included and described. Overall (OS), progression-free survival (PFS) and time to local relapse (TTLR) were evaluated from the time of first treatment. RESULTS: Three of 20 centers enrolled 58% of the patients. Median age at diagnosis was 61 (range 25-94) years, 147 patients (52%) were males, 222 (78%) patients had their primary tumor located in an extremity while 36 (13%) and 25 (9%) had tumors involving the girdle and the trunk wall, respectively. The median size of primary tumors was 17 cm (range 2-48 cm). Adjuvant RT was given to 132 patients (47%). Patients who received adjuvant RT had larger tumors (P = 0.005), involving more often the distal limbs (P < 0.001). Use of adjuvant RT varied across centers and along the study period. Other characteristics were balanced between the two groups. Median follow-up was 61.7 months. None of the patients developed metastasis during follow-up. The 5-year local relapse-free survival rates were 98.3% versus 80.3% with and without adjuvant RT, respectively (P < 0.001). Once stratified on time period (before/after 2003), adjuvant RT, tumor site and margin status (R0 versus other) were independently associated with TTLR. No OS difference was observed (P = 0.105). CONCLUSION: In this study, adjuvant RT following resection of ALT/WD-LPS was associated with a reduction of LR risk.
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Lipossarcoma/mortalidade , Lipossarcoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Lipossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Radioterapia AdjuvanteAssuntos
Antineoplásicos/uso terapêutico , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Indóis/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Tumores do Estroma Gonadal e dos Cordões Sexuais/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/farmacologia , Ensaios Clínicos Fase II como Assunto , Feminino , Inibidores de Histona Desacetilases/farmacologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Indóis/farmacologia , Pessoa de Meia-Idade , Panobinostat , Resultado do TratamentoRESUMO
BACKGROUND: Although sarcomas account for only 1% of all solid tumours, patients with sarcomas comprise a larger proportion of patients entering phase I trials, due to the limited number of registered or active drugs for these diseases. To help in patient selection, we evaluated the utility of the predictive Royal Marsden Score which had been derived in carcinoma patients. In addition, we analysed efficacy and toxicity regarding the sarcoma population enrolled in phase I trials. PATIENTS AND METHODS: We used data from a European Database comprising 2182 patients treated in phase I trials in 14 European institutions between 2005 and 2007. RESULTS: One hundred and seventy-eight patients diagnosed with advanced sarcoma or other mesenchymal tumours were identified and accounted for 217 phase I trial participations during the study period. Histological type, class of drug, number of metastatic sites, high serum lactate dehydrogenase activity (LDH), low albumin and high white blood cell count were independent prognostic factors. Poor performance status (PS), liver metastases and high leucocyte count were associated with increased risk of early death. The class of drug used was the strongest predictor of progression-free survival (PFS) duration, inhibitors of angiogenesis and histone deacetylase giving the best results. Poor PS, high serum LDH and low lymphocyte count correlated with shorter PFS. In this heterogeneous population, PFS with investigational agents appeared comparable with that previously published for patients receiving standard treatments beyond first line. CONCLUSION: Prognostic factors in sarcoma patients do not differ from a broader phase I population. Efficacy measures suggest that some patients with sarcoma derive benefit from therapy in this setting which could therefore be considered for patients with no remaining standard therapeutic option.
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Ensaios Clínicos Fase I como Assunto , Sarcoma/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/uso terapêutico , Bases de Dados Factuais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Preclinical findings suggest that imatinib mesylate (IM) and metronomic cyclophosphamide (MC) combination provides synergistic antiangiogenic activity on both pericytes and endothelial cells. METHODS: We have designed a 3+3 dose-escalating phase I trial with a fixed dose of MC (50 mg two times daily) plus IM (400 mg per day; 300 and 400 mg two times daily). Enrolled patients had IM- and sutininib-refractory advanced gastrointestinal stromal tumours (GIST) (n=17), chordoma (n=7) and mucosal melanoma (n=2). Dose-limiting toxicities were monitored for the first 6 weeks. Progression-free survival (PFS) and response assessment are based on RECIST 1.0 guidelines. Pharmacokinetics of IM were measured before and after exposure to MC. RESULTS: No dose-limiting toxicity was observed. Fourteen patients of the expanded cohort received 400 mg two times daily of IM with MC. Apart from a case of possibly related acute leukaemia occurring after 4 years of treatment, we did not see unexpected toxicity. No drug-drug pharmacokinetic interaction was observed. There was no objective response. We have observed long-lasting stable disease in chordoma patients (median PFS=10.2 months; range, 4.2-18+) and short-term stable disease in heavily GIST pretreated patients (median PFS=2.3 months; range, 2.1-6.6). CONCLUSION: This combination is feasible and may warrant further exploration in refractory GIST or chordoma patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzamidas/administração & dosagem , Ciclofosfamida/administração & dosagem , Neoplasias/tratamento farmacológico , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Administração Metronômica , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas/efeitos adversos , Benzamidas/farmacocinética , Cordoma/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Mesilato de Imatinib , Masculino , Dose Máxima Tolerável , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Piperazinas/efeitos adversos , Piperazinas/farmacocinética , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
BACKGROUND: Soft tissue sarcomas (STS) are rare tumours for which treatment options are limited in the advanced setting. Histone deacetylase inhibitors have shown activity in preclinical models of STS. METHODS: We conducted a single-arm, open-label, multicentre phase II study to assess the efficacy and tolerability of panobinostat given orally, 40 mg thrice weekly in patients with advanced pretreated STS. The primary endpoint was the 3-month progression-free rate. RESULTS: Forty-seven STS patients were enrolled between January 2010 and December 2010. Median age was 59 (range 21-79) years, 22 (47%) patients were males. Panobinostat dose was lowered to 20 mg thrice weekly after nine patients were enrolled, based on the recommendation of an independent safety committee. The most common grade 3/4 adverse events were thrombocytopenia, fatigue, lymphopenia and anaemia. Forty-five patients were evaluable for the primary endpoint. Among them, nine patients (20%, 95% CI (10-35%)) were progression-free at 3 months. No partial response was seen, but 17 patients (36%) had stable disease (SD) as their best response. Six patients were progression-free at 6 months. CONCLUSION: Panobinostat was poorly tolerated at 40 mg thrice a week. Efficacy in unselected advanced STS was limited, although some patients had prolonged SD.
Assuntos
Antineoplásicos/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Indóis/uso terapêutico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/patologia , Lipossarcoma/tratamento farmacológico , Lipossarcoma/patologia , Lipossarcoma Mixoide/tratamento farmacológico , Lipossarcoma Mixoide/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias de Bainha Neural/tratamento farmacológico , Neoplasias de Bainha Neural/patologia , Panobinostat , Terapia de Salvação/métodos , Sarcoma/patologia , Sarcoma Alveolar de Partes Moles/tratamento farmacológico , Sarcoma Alveolar de Partes Moles/patologia , Sarcoma do Estroma Endometrial/tratamento farmacológico , Sarcoma do Estroma Endometrial/patologia , Sarcoma Sinovial/tratamento farmacológico , Sarcoma Sinovial/patologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Preliminary data indicate that the molecular epidemiology of localised gastrointestinal stromal tumour (GIST) may be different from that of advanced GIST. We sought to investigate the molecular epidemiology of sarcomas, including GIST, in the Rhone-Alpes region in France. PATIENTS AND METHODS: A prospective and exhaustive study in the Rhone-Alpes Region in France to assess the precise incidence of primary sarcomas with systematic centralised pathological review and molecular analysis was conducted for 2 consecutive years. RESULTS: Among 760 patients with a confirmed diagnosis of sarcoma, 131 (17%) had a GIST. The majority of patients had gastric primaries (61%). Mutational analysis could be performed in 106 tumour samples (74%), and 71 (67%) had exon 11 mutations. PDGFRA mutations were found in 16% of cases, which is twice as high as previously reported for advanced GIST. CONCLUSION: Data indicate that PDGFRA mutations in localised GIST may be twice as high as what was previously reported in patients with advanced disease. This finding may have important consequences for patients offered adjuvant imatinib, although most of these tumours are in the low-risk group.