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1.
Lancet Oncol ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39127063

RESUMO

BACKGROUND: The long-term impact of tyrosine kinase inhibitor (TKI) discontinuation on resistance and survival in patients with advanced gastrointestinal stromal tumours (GIST) is unclear. We report the exploratory long-term outcomes of patients with advanced GIST stopping imatinib in the BFR14 trial. METHODS: BFR14, an open-label, randomised, phase 3 trial, was done in 17 comprehensive cancer centres or hospitals across France. Patients with advanced GIST aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-3, no previous treatment with imatinib, and no previous malignancy were eligible. Patients were treated with oral imatinib 400 mg daily. Patients with a complete or partial response, or stable disease, according to Response Evaluation Criteria in Solid Tumours (1.0) at 1 year, 3 years, and 5 years from the start of treatment were randomly assigned (1:1) to treatment discontinuation until progression (interruption group) or treatment continuation until progression (continuation group). Randomisation was done centrally with computer-generated permuted blocks of two and six patients stratified by participating centre and presence or absence of residual disease on CT scan. The primary endpoint was progression-free survival. Secondary endpoints included time to imatinib resistance and overall survival. Analyses were conducted on an intention-to-treat basis in all randomly assigned patients who were not lost to follow-up. This trial is registered with ClinicalTrial.gov, NCT00367861. FINDINGS: Between May 12, 2003, and March 16, 2004, after 1 year of imatinib, 32 patients were randomly assigned to the interruption group and 26 to the continuation group. Between June 13, 2005, and May 30, 2007, after 3 years of imatinib, 25 patients were randomly assigned to the interruption group and 25 to the continuation group. Between Nov 9, 2007, and July 12, 2010, after 5 years of imatinib, 14 patients were randomly assigned to the interruption group and 13 to the continuation group. Median follow-up was 235·2 months (IQR 128·8-236·6) after the 1-year randomisation, 200·9 months (190·2-208·4) after the 3-year randomisation, and 164·5 months (134·4-176·4) after the 5-year randomisation. Median progression-free survival in the interruption group versus the continuation group after 1 year of imatinib was 6·1 months (95% CI 2·5-10·1) versus 27·8 months (19·5-37·9; hazard ratio [HR] 0·36 [95% CI 0·20-0·64], log-rank p=0·0003), after 3 years of imatinib was 7·0 months (3·5-11·7) versus 67·0 months (48·8-85·6; 0·15 [0·07-0·32], log-rank p<0·0001), and after 5 years of imatinib was 12·0 months (9·0-16·6) versus not reached (NR; NR-NR; 0·13 [0·03-0·58], log-rank p=0·0016). The median time to imatinib resistance after 1 year of imatinib was 28·7 months (95% CI 18·1-39·1) versus 90·6 months (25·3-156·1; HR 0·93 [95% CI 0·51-1·71], log-rank p=0·82), after 3 years was 66·2 months (43·0-89·6) versus 127·3 months (15·0-239·7; 0·35 [0·17-0·72, log-rank p=0·0028), and after 5 years was 58·6 months (0·0-167·4) versus NR (NR-NR; 0·24 [0·05-1·12], log-rank p=0·049). Median overall survival after 1 year of imatinib was 56·0 months (95% CI 30·3-82·9) versus 105·0 months (20·6-189·6; HR 0·84 [95% CI 0·46-1·54], log-rank p=0·57), after 3 years was 104·0 months (90·7-118·7) versus 134·0 months (89·7-178·3; 0·40 [0·20-0·82], log-rank p=0·0096), and after 5 years was NR (NR-NR) versus 110·4 months (82·7-154·1; 1·28 [0·41-3·99]; log-rank p=0·67), INTERPRETATION: Imatinib interruption in patients with GIST without progressive disease is not recommended. Imatinib interruption in non-progressing patients with GIST was associated with rapid progression, faster resistance to imatinib, and shorter overall survival in the long-term follow-up when compared with imatinib continuation in patients after 3 years and 5 years of imatinib. FUNDING: Centre Léon Bérard, INCa, CONTICANET, Ligue Contre le Cancer, and Novartis.

2.
Int J Cancer ; 153(2): 407-416, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-36883417

RESUMO

The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected patients from the ALTITUDES cohort (NCT02867033), managed by surgery, active surveillance or systemic treatments, with pain assessment at diagnosis. Patients were invited to fill QLQ-C30 questionnaire and Hospital Anxiety Depression Scale. Determinants were identified using logistic models. Prognostic value on event-free survival (EFS) was evaluated using the Cox model. Overall, 382 patients were included in the current study (median age: 40.2 years; 117 men). The prevalence of pain was 36%, without significant difference according to first-line treatment (P = .18). In the multivariate analysis, pain was significantly associated with tumor size >50 mm (P = .013) and tumor site (P < .001); pain was more frequent in the neck and shoulder locations (odds ratio: 3.05 [1.27-7.29]). Pain at baseline was significantly associated with poor quality of life (P < .001), depression (P = .02), lower performance status (P = .03) and functional impairment (P = .001); we also observed a nonsignificant association with anxiety (P = .10). In the univariate analysis, baseline pain was associated with poor EFS; the 3-year EFS was 54% in patients with pain compared to 72% in those without pain. After adjustment for sex, age, size and line of treatment, pain was still associated with poor EFS (hazard ratio: 1.82 [1.23-2.68], P = .003). One third of recently diagnosed patients with DF experienced pain, especially those with larger tumors and neck/shoulder locations. Pain was associated with unfavorable EFS after adjustment for the confounders.


Assuntos
Fibromatose Agressiva , Adulto , Humanos , Masculino , Fibromatose Agressiva/complicações , Fibromatose Agressiva/epidemiologia , Dor/epidemiologia , Dor/etiologia , Prevalência , Prognóstico , Qualidade de Vida
3.
Oncologist ; 28(7): 633-639, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-36971503

RESUMO

INTRODUCTION: The objective of this study was to evaluate the efficacy and safety of adjuvant radiotherapy (aRT) in patients with soft-tissue sarcoma (STS) re-excised after unplanned tumor resection (UPR). MATERIALS AND METHODS: From 2000 to 2015, we retrospectively evaluated patients with STS of limb or trunk who underwent post-UPR re-excision in our expert center and received or not aRT. RESULTS: Median follow-up was 121 months (IQR 94-165). Among the 145 patients, 37 were not treated with aRT (no-RT) and 108 received aRT with a median radiation dose of 50 Gy (IQR 50-60). At 10 years, patients in the aRT and no-RT groups showed a cumulative incidence of local failure (10y-LF) of 14.7% and 37.7%, and a local recurrence-free survival (10y-LRFS) of 61.3% and 45.8%, respectively. Multivariate analysis identified aRT and age ≥70 years as independent predictors of both LF and LRFS, while grade 3 and deep-seated tumor were independent predictors of LRFS. In overall population, 10-year distant metastasis-free survival (10y-DMFS) and overall survival (10y-OS) were 63.7% and 69.4%. In multivariate analyses, age ≥70 years, grade 3, and deep-seated lesion were associated with shorter DMFS and OS. Acute severe adverse events were not significantly increased in aRT group (14.8% vs. 18.1%, P = .85) but dramatically increased if radiation dose exceeded 50 Gy (risk ratio 2.96 compared to ≤50 Gy, P = .04). CONCLUSION: In STS patients re-excised after UPR, 50 Gy aRT was safe and associated with reduced LF and longer LRFS. It seems to be beneficial even in absence of residual disease or in absence of initial adverse prognostic factors.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Idoso , Radioterapia Adjuvante/efeitos adversos , Estudos Retrospectivos , Sarcoma/radioterapia , Sarcoma/cirurgia , Sarcoma/tratamento farmacológico , Extremidades/patologia , Reoperação , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias de Tecidos Moles/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/epidemiologia
4.
Curr Opin Oncol ; 35(4): 296-300, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37222197

RESUMO

PURPOSE OF REVIEW: Radiation-associated angiosarcoma is a cutaneous aggressive tumor that is very rare and it represents a specific entity poorly studied in literature. It requires new therapeutic opportunity. RECENT FINDINGS: The complete surgical resection with negative margins is the mainstay treatment of localized treatment, even though it is difficult to reach in case of diffuse cutaneous infiltration. Adjuvant re-irradiation may improve local control with no benefit demonstrated on survival. Many systemic treatments can be efficient not only in metastatic setting but also in neoadjuvant setting in case of diffuse presentation. These treatments have never been compared to each other; the most efficient regimen remains to be determined, and a high heterogeneity of treatment is observed, even between sarcoma reference centers. SUMMARY: Immune therapy represents the most promising treatment under development. At the time of building clinical trial to assess the efficacy of immune therapy, the lack of randomized studies prevents the identification of a strong and consensual reference arm treatment. Given the rarity of the disease, only international collaborative clinical trials may have a chance to include enough patients to draw any conclusion and so will have to counteract the heterogeneity of management.


Assuntos
Hemangiossarcoma , Sarcoma , Neoplasias Cutâneas , Humanos , Hemangiossarcoma/etiologia , Hemangiossarcoma/radioterapia , Hemangiossarcoma/cirurgia , Terapia Combinada , Sarcoma/tratamento farmacológico , Terapia Neoadjuvante , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/radioterapia
5.
J Vasc Interv Radiol ; 34(9): 1538-1546, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37182669

RESUMO

PURPOSE: To determine the risk factors for local of adult patients treated for desmoid tumors by cryoablation. MATERIALS AND METHODS: Eighty-four patients treated for nonabdominopelvic desmoid tumors by cryoablation from July 2012 to July 2020 were included in a retrospective study. The population was composed of 64 women (76.19%) and 20 men (23.81%), aged from 16 to 75 years (median, 35 years ± 14.25). Each patient underwent preprocedural gadolinium-enhanced magnetic resonance imaging and was followed up to 36 months with the same technique. Clinical features, such as tumor size and previous treatment, epidemiological features, and the technical parameters of cryoablation, were studied. RESULTS: Local relapse was found in 19 (22.62%) of 84 patients. The 12-, 24-, and 36-month progression-free survival rates were 89% (95% confidence interval [CI], 79-94), 74% (95% CI, 60-83), and 68% (95% CI, 53-79), respectively. In univariate analysis, significant prognostic factors associated with local recurrence were non-abdominal wall location (P = .042), debulking strategy (P = .0105), risk of visceral injury (P = .034) or peripheral nerve injury during cryoablation (P = .033), previous radiation therapy (P = .043), and treatment before 2016 (P = .008). In multivariate analysis, abdominal wall tumors displayed the best outcome, whereas the neck and trunk showed a high rate of recurrence (hazard ratio, 7.307 [95% CI, 1.396-38.261]). CONCLUSIONS: The local recurrence of desmoid tumors after cryoablation depends on a number of prognostic factors, in particular, a non-abdominal wall location of the tumor and previous local treatment such as surgery or radiation therapy.


Assuntos
Criocirurgia , Fibromatose Agressiva , Adulto , Masculino , Humanos , Feminino , Fibromatose Agressiva/diagnóstico por imagem , Fibromatose Agressiva/cirurgia , Fibromatose Agressiva/patologia , Estudos Retrospectivos , Prognóstico , Criocirurgia/efeitos adversos , Criocirurgia/métodos , Recidiva Local de Neoplasia/cirurgia , Resultado do Tratamento
6.
Genes Chromosomes Cancer ; 61(6): 382-393, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35080790

RESUMO

Many neoplasms remain unclassified after histopathological examination, which requires further molecular analysis. To this regard, mesenchymal neoplasms are particularly challenging due to the combination of their rarity and the large number of subtypes, and many entities still lack robust diagnostic hallmarks. RNA transcriptomic profiles have proven to be a reliable basis for the classification of previously unclassified tumors and notably for mesenchymal neoplasms. Using exome-based RNA capture sequencing on more than 5000 samples of archival material (formalin-fixed, paraffin-embedded), the combination of expression profiles analyzes (including several clustering methods), fusion genes, and small nucleotide variations has been developed at the Centre Léon Bérard (CLB) in Lyon for the molecular diagnosis of challenging neoplasms and the discovery of new entities. The molecular basis of the technique, the protocol, and the bioinformatics algorithms used are described herein, as well as its advantages and limitations.


Assuntos
Neoplasias , Transcriptoma , Formaldeído , Perfilação da Expressão Gênica/métodos , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Inclusão em Parafina/métodos , RNA , Fixação de Tecidos/métodos , Transcriptoma/genética
7.
Curr Opin Oncol ; 34(4): 342-347, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35730520

RESUMO

PURPOSE OF REVIEW: CIC-DUX4 sarcoma (CDS) is a high-grade undifferentiated round cells sarcoma that belongs to the undifferentiated round cell sarcomas family. It represents less than one percent of sarcomas, defining a rarest among rare malignancies. It affects young adults, displaying soft tissue mass. Considered very aggressive, a high proportion of cases display an advanced disease with lung metastasis at diagnosis. Here we discuss recent progress in molecular characterization of CDS, the main tracks of CDS biology and the current and future prospects of therapeutic approaches. RECENT FINDINGS: CDS is characterized by a specific oncogenic translocation CIC::DUX4 that induce ETV4 overexpression. Patients with CDS show an aggressive clinical course and have a significantly unfavorable outcome compared to Ewing sarcoma. As of today, there is a lack of consensus on whether they should be treated with an Ewing-like approach, as currently done by most sites, or regarded as high-grade soft tissue sarcoma (STS). Anyway, when feasible, combination regimens including anthracycline and alkylating agents should be favored and patients should not benefit from a therapeutic de-escalation. Overall, registration within clinical trials and prospective registries is recommended. SUMMARY: Overall, CDS showed a poor prognosis regardless of the patterns of treatment that warrant biological studies to better understand the disease.


Assuntos
Sarcoma de Ewing , Sarcoma de Células Pequenas , Sarcoma , Neoplasias de Tecidos Moles , Biomarcadores Tumorais , Humanos , Proteínas de Fusão Oncogênica , Estudos Prospectivos , Sarcoma/tratamento farmacológico , Sarcoma/genética , Sarcoma de Células Pequenas/patologia , Adulto Jovem
8.
Breast Cancer Res Treat ; 188(3): 601-613, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34013451

RESUMO

PURPOSE: Sarcopenia has been identified as an important prognostic factor for patients with cancer. This study aimed at exploring the potential associations between a 6-month physical activity intervention and muscle characteristics, sarcopenia, oxidative stress and toxicities in patients with metastatic breast cancer. METHODS: Women newly diagnosed with metastatic breast cancer (N = 49) participated in an unsupervised, personalized, 6-month physical activity intervention with activity tracker. Computerized tomography images at the third lumbar vertebra were analysed at baseline, three months and six months to assess sarcopenia (muscle mass index < 40 cm2/m2) and muscle quality (poor if muscle attenuation < 37.8 Hounsfield Units). Oxidative markers included plasma antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase activities), prooxidant enzymes (NADPH oxidase and myeloperoxidase activities) and oxidative stress damage markers (advanced oxidation protein products, malondialdehyde (MDA) and DNA oxidation. RESULTS: At baseline 53% (mean age 55 years (SD 10.41)) were sarcopenic and 75% had poor muscle quality. Muscle cross sectional area, skeletal muscle radiodensity, lean body mass remained constant over the six months (p = 0.75, p = 0.07 and p = 0.75 respectively), but differed significantly between sarcopenic and non-sarcopenic patients at baseline and 6-months. Sarcopenic patients at baseline were more likely to have an increase of MDA (p = 0.02) at 6 months. Being sarcopenic during at least one moment during the 6-month study was associated with a higher risk of developing severe toxicities (grade > 2) (p = 0.02). CONCLUSIONS: This study suggests potential benefits of physical activity for maintenance of muscle mass. Sarcopenia can alter many parameters and disturb the pro and antioxidant balance.


Assuntos
Neoplasias da Mama , Sarcopenia , Biomarcadores , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Exercício Físico , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Estresse Oxidativo , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Sarcopenia/patologia
9.
Cancer ; 126(1): 98-104, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31536651

RESUMO

BACKGROUND: Intimal sarcoma (InS) is an exceedingly rare neoplasm with an unfavorable prognosis, for which new potentially active treatments are under development. We report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with InS. METHODS: Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis. Patients with MDM2-positive InS who were treated with anthracycline-based regimens, gemcitabine-based regimens, or pazopanib between October 2001 and January 2018 were selected. Local pathological review was performed to confirm diagnosis. Response was assessed by RECIST1.1. Recurrence-free survival (RFS), progression-free survival (PFS) and overall survival were computed by Kaplan-Meier method. RESULTS: Seventy-two patients were included (66 anthracycline-based regimens; 26 gemcitabine-based regimens; 12 pazopanib). In the anthracycline-based group, 24 (36%) patients were treated for localized disease, and 42 (64%) patients were treated for advanced disease. The real-world overall response rate (rwORR) was 38%. For patients with localized disease, the median RFS was 14.6 months. For patients with advanced disease, the median PFS was 7.7 months. No anthracycline-related cardiac toxicity was reported in patients with cardiac InS (n = 26). For gemcitabine and pazopanib, the rwORR was 8%, and the median PFS was 3.2 and 3.7 months, respectively. CONCLUSION: This retrospective series shows the activity of anthracycline-based regimens in InS. Of note, anthracyclines were used in patients with cardiac InS with no significant cardiac toxicity. The prognosis in patients with InS remains poor, and new active drugs and treatment strategies are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Cardíacas/tratamento farmacológico , Sarcoma/tratamento farmacológico , Túnica Íntima/efeitos dos fármacos , Adulto , Idoso , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cardiotoxicidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Neoplasias Cardíacas/genética , Neoplasias Cardíacas/patologia , Humanos , Indazóis , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-mdm2/genética , Pirimidinas/administração & dosagem , Sarcoma/genética , Sarcoma/patologia , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Túnica Íntima/patologia , Gencitabina
10.
Curr Opin Oncol ; 32(4): 339-343, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32541322

RESUMO

PURPOSE OF REVIEW: First clinical trials investigating immune check point (ICP) inhibitors in patients with sarcoma, regardless histological or molecular subtypes did not demonstrate any prolonged benefit. To maximize the chance of benefit from immunotherapy, recent strategies explore the combination of treatments and aim to improve identification of responsive histological subtypes. RECENT FINDINGS: Combination of several ICP inhibitors tends to increase toxicity and efficacy. Mechanisms of synergistic action remain unclear. Combination of ICP blockade with tyrosine kinase inhibitor increases efficacy in specific histological subtypes already identified as sensitive to each drug separately. The role of the combination is not established yet. Several ongoing trials assess the combination of ICP blockade with chemotherapy or radiotherapy. ICP blockade seems highly effective in some selected histological subtypes like alveolar soft part sarcoma, chordoma, malignant rhabdoid tumor, and angiosarcoma. Encouraging preliminary results need to be confirmed in larger cohorts and biological mechanisms that sustain this efficacy should be further explored. Adoptive cell therapy seems very promising in synovialosarcoma. SUMMARY: Significant efforts are underway to efficiently develop immunotherapy in patients with sarcoma and better characterize patients who would benefit the most from it.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sarcoma/tratamento farmacológico , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/imunologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Imunoterapia/métodos , Inibidores de Proteínas Quinases/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Sarcoma/imunologia
11.
Curr Opin Oncol ; 32(4): 295-300, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32541316

RESUMO

PURPOSE OF REVIEW: Alveolar soft part sarcoma (ASPS) represent 0.5% of sarcomas, defining a rarest among rare malignancies. It affects young adults, displaying slow-growing mass of the thigh, head and neck, and trunk. Although quite indolent, a majority of cases displays an advanced disease with lung bone or central nervous system metastasis. Complete surgery is the cornerstone of localized ASPS, and advanced diseases poorly respond to chemotherapy. Here discuss recent progress in molecular characterization of ASPS and future prospects of therapeutic approaches. RECENT FINDINGS: ASPS is characterized by a specific oncogenic translocation ASPSCR1-TFE3 that induce hepatocyte growth factor receptor (MET) overexpression, angiogenesis, and immunosuppression in the tumor microenvironment. These specific biological features have encouraged the successful exploration of MET inhibitors, antiangiogenic drugs, and immunotherapy. We reviewed the main tracks of ASPS biology and recent insights from targeted therapies is ASPS mainly driven tyrosine kinase inhibitors (especially antiangiogenics), immune-checkpoint inhibitors, and their combinations. SUMMARY: Overall, antiangiogenics and anti Programmed cell death 1/Programmed cell death ligand 1 therapies showed a significant activity in ASPS that warrants additional investigation through randomized trials to validate those results and through ancillary biological studies to better understand resistance mechanisms and biomarkers of response.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Sarcoma Alveolar de Partes Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Humanos , Terapia de Alvo Molecular , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Sarcoma Alveolar de Partes Moles/irrigação sanguínea , Sarcoma Alveolar de Partes Moles/genética , Sarcoma Alveolar de Partes Moles/imunologia , Neoplasias de Tecidos Moles/irrigação sanguínea , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/imunologia
12.
Eur J Cancer Care (Engl) ; 29(1): e13169, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31571315

RESUMO

OBJECTIVE: This secondary analysis of the ABLE Trial (ClinicalTrials.gov NCT03148886) aimed to assess physical activity preferences before and after a 6-month physical activity intervention for women recently diagnosed with metastatic breast cancer and to investigate demographic and clinical correlates of these preferences. METHODS: Forty-nine patients participated in the ABLE Trial, a single-arm, unsupervised 6-month physical activity intervention with activity trackers. At baseline and 6 months, physical activity preferences, physical activity level, clinical variables, demographics and social vulnerability were assessed. RESULTS: At baseline, 49 participants were included, among whom 85% were interested in receiving physical activity counselling and 89% were interested in following a physical activity programme designed for metastatic breast cancer. At the end of the study, more participants preferred practising in a community fitness centre (66%) rather than at home (19% vs. 44% at baseline, p = .03). A higher social vulnerability score and not being treated by chemotherapy at baseline were significantly associated with lower desire to receive physical activity counselling (p = .01 and p = .04 respectively). CONCLUSIONS: This study will help design future studies within patients with metastatic breast cancer in accordance with their preferences. Designing tailored physical activity interventions according to the participant's preferences may be one key to success for adherence.


Assuntos
Neoplasias da Mama/reabilitação , Terapia por Exercício/métodos , Exercício Físico , Preferência do Paciente , Idoso , Neoplasias Ósseas/reabilitação , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/reabilitação , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Institutos de Câncer , Aconselhamento , Feminino , Academias de Ginástica , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Oncologistas
13.
Int J Cancer ; 145(8): 2135-2143, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30924137

RESUMO

Soft tissue sarcomas (STS) are rare tumors accounting for less than 1% of human cancers. While the highest incidence of sarcomas is observed in elderly, this population is often excluded or poorly represented in clinical trials. The present study reports on clinicopathological presentation, and outcome of sarcoma patients over 90 recorded in the Netsarc.org French national database. NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor board (MDTB), funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB, second pathological review, and collection of sarcoma patient characteristics and follow-up are collected in a database Information of patients registered from January 1, 2010, to December 31, 2016, in NETSARC were collected, analyzed and compared to the younger population. Patients with sarcomas aged >90 have almost exclusively sarcomas with complex genomics (92.0% vs. 66.3%), are less frequently metastatic (5.3% vs. 14·7%) at diagnosis, have more often superficial tumors (39.8% vs. 14.7%), as well as limbs and head and neck sites (75.2% vs. 38.7%) (all p < 0.001). Optimal diagnostic procedures and surgery were less frequently performed in patients over 90 (p < 0.001). These patients were less frequently operated in NETSARC centers, as compared to those of younger age groups including aged 80-90. However, local relapse-free survival, metastatic relapse-free survival and relapse-free survival were not significantly different from those of younger patients, in the whole cohort, as well as in the subgroup of operated patients. As expected overall survival was worse in patients over 90 (p < 0.001). Patients over 90 who were not operated had worse overall survival than younger patients (9.9 vs. 27.3 months, p < 0.001). Patients with STS diagnosed after 90 have distinct clinicopathological features, but comparable relapse-free survival, unless clinical practice guidelines recommendations are not applied. Standard management should be proposed to these patients if oncogeriatric status allows.


Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Sarcoma/diagnóstico , Sarcoma/epidemiologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/epidemiologia , Adulto Jovem
14.
Curr Opin Oncol ; 31(4): 304-309, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31033565

RESUMO

PURPOSE OF REVIEW: Development of immune therapy in sarcoma faces the rarity and heterogeneity of the disease. This review analyses the data available from published clinical trials, and the new clinical strategies under assessment, developed in parallel to the exploration of biological mechanisms underlying the efficacy of immune therapy. RECENT FINDINGS: Published data of four clinical trials assessing the efficacy of immune therapy in metastatic bone and soft-tissue sarcoma and associated translational programs are available. Response rate and progression-free survival with single-agent immune check point blockade in unselected sarcoma are low. No biomarkers of efficacy have been identified so far. To increase the efficacy of such treatments, combination of immune check point blockade with chemotherapy, radiotherapy or targeted therapy is currently assessed. Signal of specific sensibility of some histological subtypes is explored. Adoptive cell therapy or vaccine seems particularly promising in translocation-associated sarcoma. SUMMARY: Characterization of immune environment, mechanism of action of combined regimen and identification of biomarkers will be key steps to build the next clinical trials to improve the efficacy of such strategy.


Assuntos
Neoplasias Ósseas/terapia , Imunoterapia/métodos , Osteossarcoma/terapia , Sarcoma/terapia , Antineoplásicos Imunológicos/administração & dosagem , Neoplasias Ósseas/imunologia , Ensaios Clínicos como Assunto , Humanos , Osteossarcoma/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Sarcoma/imunologia
15.
Cancer Sci ; 106(5): 650-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25707497

RESUMO

Desmoid tumor is a rare connective tissue tumor with locoregional aggressiveness but unpredictable behavior. The miRNA profile was ascertained for 26 patients included in the Desminib phase II trial and an independent validation cohort of 15 patients. Predictive and prognostic supervised analysis on the Desminib cohort failed to identify miRNAs differentially expressed between progressive and non-progressive patients under imatinib treatment or between progressive and non-progressive patients after discontinuation of imatinib. However, an unsupervised hierarchical clustering of the Desminib cohort identified two groups (A and B) of 13 patients each, where only the number of previous lines of treatment before inclusion in the study differed significantly between the two groups. Time to progression after discontinuation of imatinib was longer in group B than in group A. Fifteen miRNAs were highly statistically differentially expressed between groups A and B, targeting more than 3000 genes, including AGO1, BCL2, CDK6, SMAD4, PTEN, CCND1, VEGFA, and RB1. These results were confirmed in the independent validation cohort: hierarchical clustering of these 15 miRNAs identified two groups, in which time to recurrence was statistically different (28.8 months vs 68.8 months). These results provide the first indication of the prognostic value of miRNA expression profiling with a possible direct impact on patient management. A more precise miRNA signature must now be determined to select patients who would not benefit from surgical resection of their tumor and who ought to be monitored without treatment.


Assuntos
Fibromatose Agressiva/genética , Fibromatose Agressiva/patologia , Perfilação da Expressão Gênica , MicroRNAs/análise , Neoplasias Abdominais/tratamento farmacológico , Neoplasias Abdominais/genética , Neoplasias Abdominais/patologia , Adulto , Idoso , Benzamidas/uso terapêutico , Biomarcadores Tumorais/genética , Feminino , Fibromatose Agressiva/tratamento farmacológico , Fibromatose Agressiva/cirurgia , Regulação Neoplásica da Expressão Gênica , Humanos , Mesilato de Imatinib , Modelos Logísticos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Prognóstico , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
16.
BMC Cancer ; 15: 780, 2015 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-26498480

RESUMO

BACKGROUND: Tumor genotype plays a crucial role in clinical management of GIST. Whether genetic polymorphism of KIT may influence GIST patient outcome is unclear. METHODS: We investigated the biological and clinical significance of the presence of KIT exon 10 variant (c.1621 A > C), KIT (L541), in a transfected cell line (3 T3 L541) and in two retrospectively collected series of 109 GIST patients in total. The control group consisted of 60 healthy donors collected at the French department of blood transfusion. RESULTS: In the 3 T3 L541 cell line, KIT(L541) protein exhibited a spontaneous phosphorylation status comparable to that of wild-type KIT but displayed a phosphorylation pattern of AKT and ERK1/2 that was found similar to that of the classical mutated forms of the KIT receptor. Of 109 patients enrolled in this retrospective translational research study, 24 (22%) harboured KIT (L541), similarly to the control group of healthy donors (n = 10 of 60, 17%). A higher prevalence of the variant KIT (L541) was observed in patients with metastatic status at diagnosis (KIT (L541) correlated nine of 22 versus 15 of 87, p = 0.02). In addition, patients with KIT (L541) and localized GIST had a higher rate of relapse at 5 years and lower relapse free survival at 5 years in univariate, as well as in multivariate analysis. Response rate and duration of response to imatinib was similar in KIT (L541) and KIT (M541) patients. CONCLUSION: KIT (L541) genotype is associated with a higher risk of metastasis at diagnosis and a higher risk of relapse in GIST patients.


Assuntos
Tumores do Estroma Gastrointestinal/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-kit/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/farmacologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Recidiva , Estudos Retrospectivos , Adulto Jovem
17.
BMC Cancer ; 14: 632, 2014 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-25174682

RESUMO

BACKGROUND: Aggressive fibromatosis (AF) is a rare fibroblastic proliferative disease with a locally aggressive behavior and no distant metastasis, characterized by driver mutations in CTNNB1 or the APC gene. When progressive and/or symptomatic AF is not amenable to local management, a variety of medical treatments may be efficient, including imatinib mesylate. The phase II "Desminib trial" included 40 patients with AF to evaluate the toxicity and efficacy of imatinib resulting in a 65% tumor control rate at 1 year. We investigated a potential predictive value of KIT exon 10 M541L variant (KITL541) on this prospective series. METHODS: DNA was extracted in sufficient quantity from 33 patients included in the Desminib trial. The detection of KITL541 was performed by Competitive Allele-Specific Taqman® PCR technology. Chi-2 analyses were performed to search for a correlation between KIT status and tumor response. Progression free (PFS) and overall survival (OS) were compared by log-rank test after Kaplan-Meier analysis. RESULTS: In 6 out of 33 cases (18%), the technique failed to determine the mutational status; 5 patients (19%) harboured KITL541 and 22 patients (81%) were classified as KIT wild type. Compared with total cohort, KITL541 frequency did not distinguish between different clinical characteristics. In the KITL541 and the KITWT subgroups, the tumor control rate at 1 year was 100% and 68%, respectively (p = 0.316). The median PFS of patients harboring KITL541 or not is 29.9 and 24.5 months, respectively (p = 0.616), and the median OS is not reached, in any of the groups. CONCLUSION: Our results do not support a predictive effect of KITL541 on the efficacy of imatinib for patients with AF.


Assuntos
Benzamidas/administração & dosagem , Fibromatose Agressiva/tratamento farmacológico , Piperazinas/administração & dosagem , Reação em Cadeia da Polimerase/métodos , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas c-kit/genética , Pirimidinas/administração & dosagem , Adulto , Idoso , Benzamidas/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Feminino , Fibromatose Agressiva/genética , Fibromatose Agressiva/patologia , Variação Genética , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
18.
Eur J Cancer ; 207: 114188, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38954898

RESUMO

INTRODUCTION: While available systemic treatments have modest long term efficacy in advanced angiosarcoma, immunotherapy represents an interesting new therapeutic opportunity. To establish its benefit, it is required to conduct a clinical trial assessing its efficacy and toxicity compared to standard treatments. MATERIAL AND METHODS: This is a literature review from PubMed search. RESULTS: Several systemic treatments (chemotherapy and TKI) are currently used in advanced angiosarcoma with ORR ranging from 12.5 to 68 % and PFS from 2 to 7 months. However, few randomized trials, mainly phase II, has been conducted to compare these treatments. While most centers propose doxorubicin containing regimens or paclitaxel in 1st or 2nd line, a high heterogeneity of regimens administered in this setting is observed even across sarcoma specialized centers with no consensual standard treatment. Encouraging signals of immunotherapy activity have been reported in angiosarcoma from several retrospective and phase II studies assessing anti-PD1 either alone or in combination with anti CTLA4 or TKI. Although cutaneous and head and neck location seems to benefit more from immunotherapy, response may be observed in any angiosarcoma subtype. In sarcoma in general and AS in particular, no biomarker has been clearly established to predict the efficacy of immunotherapy: high tumor mutational burden and presence of tertiary lymphoid structures are under assessment. DISCUSSION: Even essential, developing a randomized clinical trial in AS struggles with the heterogeneity of the disease, the lack of consensual standard regimen, the uncertainty on optimal immunotherapy administration and the absence of established predictive biomarkers. CONCLUSION: International collaboration is essential to run randomized trial in advanced AS and asses the efficacy of immune therapy in this rare and heterogeneous disease.


Assuntos
Hemangiossarcoma , Humanos , Hemangiossarcoma/terapia , Hemangiossarcoma/tratamento farmacológico , Hemangiossarcoma/patologia , Imunoterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos como Assunto , Inibidores de Checkpoint Imunológico/uso terapêutico
19.
Cancer Med ; 13(7): e7115, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38553950

RESUMO

INTRODUCTION: The objective was to determine the added value of comprehensive molecular profile by whole-exome and RNA sequencing (WES/RNA-Seq) in advanced and refractory cancer patients who had no molecular-based treatment recommendation (MBTR) based on a more limited targeted gene panel (TGP) plus array-based comparative genomic hybridization (aCGH). MATERIALS AND METHODS: In this retrospective analysis, we selected 50 patients previously included in the PROFILER trial (NCT01774409) for which no MBT could be recommended based on a targeted 90-gene panel and aCGH. For each patient, the frozen tumor sample mirroring the FFPE sample used for TGP/aCGH analysis were processed for WES and RNA-Seq. Data from TGP/aCGH were reanalyzed, and together with WES/RNA-Seq, findings were simultaneously discussed at a new molecular tumor board (MTB). RESULTS: After exclusion of variants of unknown significance, a total of 167 somatic molecular alterations were identified in 50 patients (median: 3 [1-10]). Out of these 167 relevant molecular alterations, 51 (31%) were common to both TGP/aCGH and WES/RNA-Seq, 19 (11%) were identified by the TGP/aCGH only and 97 (58%) were identified by WES/RNA-Seq only, including two fusion transcripts in two patients. A MBTR was provided in 4/50 (8%) patients using the information from TGP/aCGH versus 9/50 (18%) patients using WES/RNA-Seq findings. Three patients had similar recommendations based on TGP/aCGH and WES/RNA-Seq. CONCLUSIONS: In advanced and refractory cancer patients in whom no MBTR was recommended from TGP/aCGH, WES/RNA-Seq allowed to identify more alterations which may in turn, in a limited fraction of patients, lead to new MBTR.


Assuntos
Exoma , Neoplasias , Humanos , Hibridização Genômica Comparativa , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Estudos Retrospectivos , RNA , Análise de Sequência de RNA , Ensaios Clínicos como Assunto
20.
Eur J Cancer ; 208: 114228, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39018632

RESUMO

RATIONALE: We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up. PATIENTS AND METHODS: This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m2 and CDDP 100 mg/m2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives. RESULTS: From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16-63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3-4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months. CONCLUSION: Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ósseas , Ifosfamida , Osteossarcoma , Humanos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Ifosfamida/uso terapêutico , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Intervalo Livre de Doença , Seguimentos
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