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1.
JAMA Oncol ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030515

RESUMO

Importance: To our knowledge, this is the first randomized trial in sex cord-stromal tumors, and it establishes weekly paclitaxel as standard-of-care therapy after platinum-based therapy in this setting. Objective: To determine the efficacy of weekly paclitaxel with or without bevacizumab as treatment for relapsed sex cord-stromal tumors and evaluate whether the addition of bevacizumab to weekly paclitaxel improves 6-month progression-free rate. Design, Setting, and Participants: This open-label, academic, international, randomized phase 2 trial (ALIENOR) was conducted at 28 referral centers in France, Germany, Italy, Japan, and Belgium in collaboration with the Rare Tumor committee of the Gynecologic Cancer InterGroup and used an adaptive bayesian design. It included 60 women with sex cord-stromal tumors that had relapsed after at least 1 platinum-based chemotherapy. Enrollment occurred from 2013 to 2016, and the final analysis database lock was on March 27, 2020 (median follow-up, 38.9 months). Interventions: Participants were randomized to receive either paclitaxel (80 mg/m2, days 1, 8, and 15 every 4 weeks) alone or paclitaxel with bevacizumab (10 mg/kg, every 2 weeks) for 6 cycles followed by maintenance bevacizumab (15 mg/kg, every 3 weeks) for up to 1 year or until progression or unacceptable toxicity. Crossover to bevacizumab was permitted after progression during or following paclitaxel alone. Main Outcomes and Measures: Six-month progression-free rate. Results: Sixty patients (predominantly with granulosa cell tumors) were randomized, 32 to receive single-agent paclitaxel (median [interquartile range] age at inclusion, 60 [53-64] years) and 28 to receive paclitaxel-bevacizumab (median [interquartile range] age at inclusion, 55 [47-61] years; 1 did not receive treatment). The estimated 6-month progression-free rate was 71% (95% credible interval, 55%-84%) with paclitaxel alone and 72% (95% credible interval, 55%-87%) with paclitaxel-bevacizumab. The bayesian estimate for the probability that the 6-month progression-free rate distribution was higher with the combination than with paclitaxel alone was 57%, less than the predefined superiority threshold. The objective response rate increased from 25% (95% CI, 12%-43%) to 44% (95% CI, 26%-65%) with the addition of bevacizumab. One patient discontinued combination therapy within 6 months because of toxicity. Conclusions and Relevance: Weekly paclitaxel is a new option for relapsed sex cord-stromal tumors. In this international randomized clinical trial of patients with relapsed sex cord-stromal tumors unsuitable for surgery, adding bevacizumab to weekly paclitaxel does not improve clinical benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT01770301.

4.
Am J Surg Pathol ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32910017

RESUMO

FOXL2 somatic mutation occurs in a high percentage of ovarian adult granulosa cell tumors and DICER1 mutations in a high proportion of Sertoli-Leydig cell tumors. These mutations have only been studied in a limited number of juvenile granulosa cell tumors (JGCTs), and their occurrence and frequency in these neoplasms is controversial. We aimed to determine the frequency of FOXL2 and DICER1 mutations in a large cohort of 50 JGCTs, and to evaluate the prognostic impact of these mutations. A FOXL2 hotspot mutation was found in 2/50 JGCTs. Review of these 2 cases reclassified them as adult granulosa cell tumors. Thus, FOXL2 mutation was absent from our large cohort of JGCTs. DICER1 mutations in the RNase IIIb domain were found in 4 cases. After review of the mutated cases, 1 was reclassified as a gynandroblastoma with a prominent JGCT component. Thus, DICER1 mutations were detected in 3/47 (6%) of pathologically confirmed JGCTs. Our results show that FOXL2 mutations are not present in JGCT, whereas a small percentage of these neoplasms exhibit DICER1 mutations.

6.
Semin Cancer Biol ; 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32931951

RESUMO

Platinum resistant ovarian cancer, usually defined as progression occurring within 6 months after completing platinum-based therapy, is a heterogeneous disease with poor prognosis and short survival (less than 18 months). It is typically considered as a "cold tumor", characterized by reduced infiltration by immune cells, particularly CD8+ T cells. Response rate to anti-PD1/PD-L1 monotherapy is low, not exceeding 8%. Multiple therapeutic strategies are currently investigated in order to increase response rates to anti-PD1/PD-L1 through adding chemotherapy, anti-angiogenic agents, DNA damage (PARP inhibitors, cyclophosphamide and/or radiotherapy) or other immune checkpoint inhibitors (CTLA-4, etc.). Ovarian clear cell carcinoma, a rare histotype characterized by primary platinum-resistance, recently showed anecdotal but promising response rates to immune checkpoint blockade. Other immunotherapeutic approaches such as adoptive T cell therapy, vaccines and targeting myeloid immune checkpoints like "don't eat me" signal CD47 are currently investigated. Each approach faces distinct challenges that will be reviewed here. Robust immunogenomics studies conducted in parallel of the ongoing trials will help into refining optimal immunotherapy combination for this lethal disease and identify predictive biomarkers.

7.
Eur J Cancer Care (Engl) ; : e13313, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894629

RESUMO

OBJECTIVE: Epithelial ovarian cancer (EOC) is a poor prognosis disease partly linked to diagnosis at an advanced stage. The quality of care management is a factor that needs to be explored, more specifically optimal organisation of first-line treatment. METHODS: A retrospective study, dealing with all patients diagnosed within the Rhone-Alpes region with initial diagnosis EOC in 2012, was performed. The aim was to describe the impact of multidisciplinary tumour boards (MTB) in the organisation of care and the consequence on the patient's outcomes. RESULTS: 271 EOC were analysed. 206 patients had an advanced EOC. Median progression-free survival (PFS) is 17.8 months (CI95%, 14.6-21.2) for AOC. 157 patients (57.9%) had a front-line surgery versus 114 patients (42.1%) interval debulking surgery. PFS for AOC patients with no residual disease is 24.3 months compared with 15.3 months for patients with residual disease (p = .01). No macroscopic residual disease is more frequent in the patients discussed before surgery in MTB compared with patients not submitted before surgery (73% vs. 56.2%, p < .001). CONCLUSION: These results highlight the heterogeneity of medical practices in terms of front-line surgery versus interval surgery, in the administration of neoadjuvant chemotherapy and in the setting of MTB discussion.

8.
Oncologist ; 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32949182

RESUMO

Successful pregnancy in women with metastatic cancer is rare in the published literature. We report here on four women with sarcoma who started and conducted their first pregnancies while in metastatic disease. All four pregnancies were first pregnancies, and all four women are long-term survivors from 20 to 248 months after pregnancy. One patient had three pregnancies. All four women stopped systemic cancer treatment during their pregnancies, and two had RECIST progression during treatment interruption. Three patients still have unresectable metastatic disease, whereas one is in complete remission. In selected metastatic sarcomas with indolent courses, successful pregnancies are possible with no or minor impact on cancer progression and with prolonged life duration after pregnancy. As metastatic cancer becomes more often a chronic disease, this possibility opens important practical and ethical questions on how to best to advise women of childbearing age with metastatic cancers who are long-term survivors.

9.
AJR Am J Roentgenol ; : 1-10, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991215

RESUMO

OBJECTIVE. The response of desmoid tumors (DTs) to chemotherapy is evaluated with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in daily practice and clinical trials. MRI shows early change in heterogeneity in responding tumors due to a decrease in cellular area and an increase in fibronecrotic content before dimensional response. Heterogeneity can be quantified with radiomics. Our aim was to develop radiomics-based response criteria and to compare their performances with clinical and radiologic response criteria. MATERIALS AND METHODS. Forty-two patients (median age, 38.2 years) were included in this retrospective multicenter study because they presented with progressive DT and had an MRI examination at baseline, which we refer to as "MRI-0," and an early MRI evaluation performed after the first chemotherapy cycle (mean time after first chemotherapy cycle, 3 months [SD, 28 days]), which we refer to as "MRI-1." After signal intensity normalization, voxel size standardization, discretization, and segmentation of DT volume on fat-suppressed contrast-enhanced T1-weighted imaging, 90 baseline and delta 3D radiomics features were extracted. Using cross-validation and least absolute shrinkage and selection operator-penalized Cox regression, a radiomics score was generated. The performances of models based on the radiomics score, modified Response Evaluation Criteria in Solid Tumors, European Association for the Study of the Liver criteria, Cheson criteria, Choi criteria, and revised Choi criteria from MRI-0 to MRI-1 to predict progression-free survival (PFS, as defined by RECIST 1.1) were assessed with the concordance index. The results were adjusted for performance status, tumor volume, prior chemotherapy, current chemotherapy, and ß-catenin mutation. RESULTS. There were 10 cases of progression. The radiomics score included four variables. A high score indicated a poor prognosis. The radiomics score independently correlated with PFS (adjusted hazard ratio = 5.60, p = 0.003), and none of the usual response criteria independently correlated with PFS. The prognostic model based on the radiomics score had the highest concordance index (0.84; 95% CI, 0.71-0.96). CONCLUSION. Quantifying early changes in heterogeneity through a dedicated radiomics score could improve response evaluation for patients with DT undergoing chemotherapy.

10.
J Clin Oncol ; : JCO2001164, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32822286

RESUMO

PURPOSE: Low-grade serous ovarian carcinomas (LGSOCs) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30%-60% of LGSOCs. The purpose of this study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multiple cancers, in LGSOC. METHODS: This was a 2:1 randomized study of binimetinib (45 mg twice daily) versus physician's choice chemotherapy (PCC). Eligible patients had recurrent measurable LGSOC after ≥ 1 prior platinum-based chemotherapy but ≤ 3 prior chemotherapy lines. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); additional assessments included overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety. RESULTS: A total of 303 patients were randomly assigned to an arm of the study at the time of interim analysis (January 20, 2016). Median PFS by BICR was 9.1 months (95% CI, 7.3 to 11.3) for binimetinib and 10.6 months (95% CI, 9.2 to 14.5) for PCC (hazard ratio,1.21; 95%CI, 0.79 to 1.86), resulting in early study closure according to a prespecified futility boundary after 341 patients had enrolled. Secondary efficacy end points were similar in the two groups: ORR 16% (complete response [CR]/partial responses[PRs], 32) versus 13% (CR/PRs, 13); median DOR, 8.1 months (range, 0.03 to ≥ 12.0 months) versus 6.7 months (0.03 to ≥ 9.7 months); and median OS, 25.3 versus 20.8 months for binimetinib and PCC, respectively. Safety results were consistent with the known safety profile of binimetinib; the most common grade ≥ 3 event was increased blood creatine kinase level (26%). Post hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Results from an updated analysis (n = 341; January 2019) were consistent. CONCLUSION: Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not meet its primary end point, binimetinib showed activity in LGSOC across the efficacy end points evaluated. A higher response to chemotherapy than expected was observed and KRAS mutation might predict response to binimetinib.

11.
Gynecol Oncol ; 159(1): 256-263, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32712155

RESUMO

OBJECTIVE: MicroRNAs (miRNAs) are promising biomarkers in ovarian cancer. Their kinetics during treatment might be useful for monitoring disease burden, and guiding treatments in patients treated with peri-operative chemotherapy and interval debulking surgery (IDS). METHODS: Serial blood samples of patients enrolled in the randomized phase II CHIVA trial, comparing first line carboplatin-paclitaxel +/- nintedanib (NCT01583322) and IDS, were investigated to assess the kinetics of 11 relevant miRNAs. Their prognostic/predictive values regarding the likelihood of complete IDS, and the patient survival, were assessed and compared to those of CA125 kinetics. The selection of the miRNAs (miR-15b-5p, miR-16-5p, miR-20a-5p, miR-21-5p, miR-93-5p, miR-122-5p, miR-150-5p, miR-195-5p, miR-200b-3p, miR-148b-5p and miR-34a-5p) was based on the expression levels found with a large explorative panel, and on the literature data. RESULTS: 756 serial blood samples from 119 patients were analyzed for a total of 8172 miRNA assays, and 1299 CA125 values. The longitudinal kinetics of the miRNA expressions were highly inconsistent, and were not related to CA125 dynamics. The miRNA changes during neoadjuvant treatment were not found associated with RECIST tumor response or IDS outcomes. Decreases of miR-34a-5p and miR-93-5p were associated with PFS benefit (p = .009) and OS benefits (p < .001), respectively, using univariate tests. CONCLUSIONS: The longitudinal kinetics of miRNA expressions during neoadjuvant treatment in ovarian cancer patients were inconsistent, and were not found to be associated with tumor burden changes. Although some prognostic value could be discussed, no predictive value regarding tumor responses or IDS quality could be identified.

12.
Gynecol Oncol ; 159(1): 129-135, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32723678

RESUMO

PURPOSE: Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is a rare and rapidly lethal disease affecting young women. Cytoreductive surgery associated with chemotherapy followed by a high dose chemotherapy regimen (HDC) demonstrated improved outcomes in a unique prospective and several retrospective studies, and this report aimed to confirm these results in an independent and larger cohort. METHODS: Between 2006 and 2018, we conducted a multicentric prospective study on 44 women diagnosed with SCCOHT. Patients were treated homogeneously with optimal cytoreductive surgery and chemotherapy protocol for four to six cycles (PAVEP). In case of complete response, patients received HDC with stem-cell support, followed by pelvic radiotherapy. The primary endpoint was the event-free survival (EFS) in the per-protocol cohort. Secondary analysis explored the effect of HDC with outcomes. RESULTS: Mean age at diagnosis was 33 years old (range 13.8-75.8). 14 patients presented with stage FIGO I, 21 with stage III and 9 with stage IV. Median follow-up was 53.4 months. 38 patients underwent optimal surgery with up to 6 cycles of PAVEP. 30 received HDC, and 21 pelvic radiotherapy. 21 relapses were reported leading to death for 18 patients. Median EFS in the per-protocol cohort was 18.2 months, and 2-year EFS rate was 40%. HDC was significantly associated with better overall survival (p < .001). Grades 3/4 adverse events were frequent but, in most cases, manageable, although one grade-5 adverse-event occurred during HDC. CONCLUSION: Intensive regimen containing multidrug chemotherapy, HDC and pelvic radiotherapy, for the management of SCCOHT, demonstrated encouraging survival and should be proposed for all patients. However, the significant toxicity cost associated is of concern and it should be restricted to expert centers.

13.
Eur J Gen Pract ; 26(1): 95-101, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32674614

RESUMO

BACKGROUND: The overall activity of general practitioners (GPs) related to cancer screening and follow-up is poorly documented. OBJECTIVES: To describe cancer screening and follow-up activities carried out in general practice and analyse them according to the socio-economic characteristics of patients. METHODS: We used data from a French nationwide, multicentre, cross-sectional study that described the distribution of health problems managed in general practice and the associated processes of care. Analyses were adjusted on age and gender when appropriate, using a multivariate, hierarchical, linear mixed-effects model. RESULTS: Among 20,613 consultations recorded, 580 involved cancer screening (2.8%) and 475 cancer follow-ups (2.3%). The most frequent cancer screening procedures concerned colorectal cancer (38.6% of screening procedures), breast cancer (32.6%), cervical cancer (17.0%), and prostate cancer (9.3%). In consultations with female patients, the most frequent types of cancer followed up were breast (44.9%) and colorectal cancer (10.5%), and with male patients, the most frequent were prostate (37.3%) and skin cancer (10.3%). After adjustment on age and gender, consultations with cancer follow-up included a mean 1.9 health problems managed in addition to cancer. Consultations with cancer screening or follow-up issue less often involved a patient on low income than other consultations (2.4% vs. 4.2%, and 1.1% vs. 4.2%, respectively). CONCLUSION: Around 5% of French general practice consultations include cancer screening or follow-up. Socio-economical inequalities demand further research.

14.
Eur J Cancer ; 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: covidwho-548776

RESUMO

BACKGROUND: Cancer patients presenting with COVID-19 have a high risk of death. In this work, predictive factors for survival in cancer patients with suspected SARS-COV-2 infection were investigated. METHODS: PRE-COVID-19 is a retrospective study of all 302 cancer patients presenting to this institute with a suspicion of COVID-19 from March 1st to April 25th 2020. Data were collected using a web-based tool within electronic patient record approved by the Institutional Review Board. Patient characteristics symptoms and survival were collected and compared in SARS-COV-2 real-time or reverse-transcriptase PCR (RT-PCR)-positive and RT-PCR-negative patients. RESULTS: Fifty-five of the 302 (18.2%) patients with suspected COVID-19 had detectable SARS-COV-2 with RT-PCR in nasopharyngeal samples. RT-PCR-positive patients were older, had more frequently haematological malignancies, respiratory symptoms and suspected COVID-19 pneumonia of computed tomography (CT) scan. However, respectively, 38% and 20% of SARS-COV-2 RT-PCR-negative patients presented similar respiratory symptoms and CT scan images. Thirty of the 302 (9.9%) patients died during the observation period, including 24 (80%) with advanced disease. At the median follow-up of 25 days after the first symptoms, the death rate in RT-PCR-positive and RT-PCR-negative patients were 21% and 10%, respectively. In both groups, independent risk factors for death were male gender, Karnofsky performance status <60, cancer in relapse and respiratory symptoms. Detection of SARS-COV-2 on RT-PCR was not associated with an increased death rate (p = 0.10). None of the treatment given in the previous month (including cytotoxics, PD1 Ab, anti-CD20, VEGFR2…) correlated with survival. The survival of RT-PCR-positive and -negative patients with respiratory symptoms and/or COVID-19 type pneumonia on CT scan was similar with a 18.4% and 19.7% death rate at day 25. Most (22/30, 73%) cancer patients dying during this period were RT-PCR negative. CONCLUSION: The 30-day death rate of cancer patients with or without documented SARS-COV-2 infection is poor, but the majority of deaths occur in RT-PCR-negative patients.

15.
Cancer Treat Rev ; 87: 102040, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32485510

RESUMO

BACKGROUND: The second decade of 2000s is witnessing a new ovarian cancer (OC) paradigm shift thanks to the results recently obtained by a new class of targeted agents: the Poly(ADP-ribose)polymerase (PARP)-Inhibitors (PARPi). Aim of this meta-analysis is to analyze available results obtained with PARPi, administered alone or in combination with chemo- and/or target-therapies in terms of efficacy and safety for the treatment of recurrent and primary advanced OC. METHODS: On December 2019, all published phase II/III randomized clinical studies were systematically searched using the terms "[Parp-Inhibitor] AND [ovar*]". Twelve phase II/III randomized controlled trials were identified, with a total number of 5171 patients included. RESULTS: Results demonstrated that PARPi account for a significant improvement of PFS in both recurrent and primary OC setting, independently from their administration schedule and independently from patients' BRCA mutational status. Moreover, patients harboring a Homologous Recombination Deficiency (HRD) positive testing primary or recurrent OC progress significantly later after PARPi administration/association. Results also reported that PARPi increase the occurrence of severe (G3-G4) anemia. Furthermore, severe fatigue occurred more frequently among patients subjected to PARPi combined with chemotherapy and to PARPi plus Bevacizumab. Finally, a significant increase in severe high blood pressure occurrence was observed when PARPi was added to antiangiogenetics, compared to PARPi alone but a significant decrease in G3-G4 hypertension occurrence was found in PARPi plus bevacizumab users compared to Bevacizumab alone. CONCLUSIONS: PARPi are a valid option for the treatment of both primary and relapsed OC patients, with a relative low incidence of severe side effects.


Assuntos
Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Int J Gynecol Cancer ; 30(10): 1633-1637, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32546554

RESUMO

BACKGROUND: Uterine sarcomas are a group of rare tumors that include different subtypes. Patients with histopathological high-grade diseases are at high-risk of recurrence or progression, and have a poor prognosis. We aim to explore the most appropriate management in patients with uterine high-grade sarcomas. PRIMARY OBJECTIVE: To assess the efficacy of maintenance treatment with cabozantinib in patients with high-grade uterine sarcomas who achieved clinical benefit after standard chemotherapy. STUDY HYPOTHESIS: Maintenance treatment with cabozantinib after standard chemotherapy given as an adjuvant treatment after curative surgery, or in locally advanced or metastatic disease, increases progression-free survival compared with placebo TRIAL DESIGN: This is a randomized double blinded phase II trial. MAJOR INCLUSION/EXCLUSION CRITERIA: The study is enrolling adult patients with high-grade undifferentiated uterine sarcomas, high-grade endometrial stromal sarcomas, high-grade leiomyosarcoma, and high-grade adenosarcoma, FIGO (Federation International gynecologue Obstétricien) stage II/III to IV in stable disease or who achieved complete or partial response with doxorubicin ± ifosfamide, who are assigned 1:1 to 60 mg daily cabozantinib (experimental arm) or placebo (control arm), as maintenance therapy. Exclusion criteria include low-grade sarcoma. PRIMARY ENDPOINT: Progression-free survival at 4 months. SAMPLE SIZE: The study plans to enroll 90 patients to allow the randomization of 54 patients to detect an improvement in 4-month progression-free survival from 50% to 80% with 15% significance level and 85% power. Estimated dates for accrual completion: recruitment for the trial started in February 2015, and has currently enrolled 83 patients, of whom 35 patients have been randomized. The end of recruitment is anticipated for December 2020. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT01979393.

17.
Curr Opin Oncol ; 32(4): 321-331, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32541320

RESUMO

PURPOSE OF REVIEW: Sarcomas are a diverse group of rare solid tumors with limited treatment options for patients with advanced, inoperable disease. Cabozantinib is a tyrosine kinase inhibitor currently approved for advanced renal cell, hepatocellular, and medullary thyroid carcinoma. Cabozantinib has potent activity against a variety of kinases, including MET, vascular endothelial growth factor receptor, and AXL, that are associated with sarcoma growth and development. Here we review the preclinical findings and clinical development of cabozantinib in the treatment of soft tissue sarcoma, gastrointestinal stromal tumors (GIST), osteosarcoma, and Ewing sarcoma. RECENT FINDINGS: In vitro, cabozantinib has shown relevant activity in inhibiting the growth and viability of soft tissue sarcoma, GIST, osteosarcoma, and Ewing sarcoma tumor cell lines. Cabozantinib also promoted the regression of GIST in various murine xenografts, including imatinib-resistant models. More than 10 prospective trials with cabozantinib that included patients with sarcomas have been completed or are currently ongoing. Clinical activity with cabozantinib has been recently reported in phase 2 clinical trials for patients with GIST and for patients with osteosarcoma or Ewing sarcoma. SUMMARY: Cabozantinib has shown promising activity for the treatment of various sarcomas, supporting further evaluation in this setting.

18.
Eur J Cancer ; 135: 251-259, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32540204

RESUMO

BACKGROUND: Cancer patients presenting with COVID-19 have a high risk of death. In this work, predictive factors for survival in cancer patients with suspected SARS-COV-2 infection were investigated. METHODS: PRE-COVID-19 is a retrospective study of all 302 cancer patients presenting to this institute with a suspicion of COVID-19 from March 1st to April 25th 2020. Data were collected using a web-based tool within electronic patient record approved by the Institutional Review Board. Patient characteristics symptoms and survival were collected and compared in SARS-COV-2 real-time or reverse-transcriptase PCR (RT-PCR)-positive and RT-PCR-negative patients. RESULTS: Fifty-five of the 302 (18.2%) patients with suspected COVID-19 had detectable SARS-COV-2 with RT-PCR in nasopharyngeal samples. RT-PCR-positive patients were older, had more frequently haematological malignancies, respiratory symptoms and suspected COVID-19 pneumonia of computed tomography (CT) scan. However, respectively, 38% and 20% of SARS-COV-2 RT-PCR-negative patients presented similar respiratory symptoms and CT scan images. Thirty of the 302 (9.9%) patients died during the observation period, including 24 (80%) with advanced disease. At the median follow-up of 25 days after the first symptoms, the death rate in RT-PCR-positive and RT-PCR-negative patients were 21% and 10%, respectively. In both groups, independent risk factors for death were male gender, Karnofsky performance status <60, cancer in relapse and respiratory symptoms. Detection of SARS-COV-2 on RT-PCR was not associated with an increased death rate (p = 0.10). None of the treatment given in the previous month (including cytotoxics, PD1 Ab, anti-CD20, VEGFR2…) correlated with survival. The survival of RT-PCR-positive and -negative patients with respiratory symptoms and/or COVID-19 type pneumonia on CT scan was similar with a 18.4% and 19.7% death rate at day 25. Most (22/30, 73%) cancer patients dying during this period were RT-PCR negative. CONCLUSION: The 30-day death rate of cancer patients with or without documented SARS-COV-2 infection is poor, but the majority of deaths occur in RT-PCR-negative patients.


Assuntos
Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias/mortalidade , Pneumonia Viral/mortalidade , Fatores Etários , Betacoronavirus/genética , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Humanos , Avaliação de Estado de Karnofsky/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Mortalidade , Recidiva Local de Neoplasia/complicações , Neoplasias/complicações , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , RNA Viral/isolamento & purificação , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Análise de Sobrevida , Fatores de Tempo
19.
Curr Opin Oncol ; 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32453033

RESUMO

PURPOSE OF REVIEW: Sarcomas are a diverse group of rare solid tumors with limited treatment options for patients with advanced, inoperable disease. Cabozantinib is a tyrosine kinase inhibitor currently approved for advanced renal cell, hepatocellular, and medullary thyroid carcinoma. Cabozantinib has potent activity against a variety of kinases, including MET, vascular endothelial growth factor receptor, and AXL, that are associated with sarcoma growth and development. Here we review the preclinical findings and clinical development of cabozantinib in the treatment of soft tissue sarcoma, gastrointestinal stromal tumors (GIST), osteosarcoma, and Ewing sarcoma. RECENT FINDINGS: In vitro, cabozantinib has shown relevant activity in inhibiting the growth and viability of soft tissue sarcoma, GIST, osteosarcoma, and Ewing sarcoma tumor cell lines. Cabozantinib also promoted the regression of GIST in various murine xenografts, including imatinib-resistant models. More than 10 prospective trials with cabozantinib that included patients with sarcomas have been completed or are currently ongoing. Clinical activity with cabozantinib has been recently reported in phase 2 clinical trials for patients with GIST and for patients with osteosarcoma or Ewing sarcoma. SUMMARY: Cabozantinib has shown promising activity for the treatment of various sarcomas, supporting further evaluation in this setting.

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