[Show abstract][Hide abstract] ABSTRACT: Epithelioid hemangioendothelioma is a rare connective tissue tumor of vascular origin. It is most commonly found in young to middle aged women, and its clinical behavior is remakably variable from an indolent metastatic tumor to an aggressive rapidly growing neoplasm. Most tumors are diagnosed in an advanced unresectable phase and when clinically aggressive, require systemic cytotoxic treatment of sarcoma. Then, the 5-year survival rate after chemotherapy does not exceed 30%. Antiangiogenics are active in selected sarcoma subtypes: pazopanib, the only anti angiogenic registered agent for sarcoma provides a median PFS of 4.5 months only in the pivotal study. Their activity in EHE has been reported but long term outcome of these patients remain unreported. We report a case of a female patient with HEH who was treated with pazopanib for almost 8 years. Pazopanib therapy resulted in clinical improvement of symptoms and durable stabilization of liver tumors and lung lesions.
Conclusion: Pazopanib is a promising therapeutic option in patients with HEH.
[Show abstract][Hide abstract] ABSTRACT: Angiogenesis, among other signaling pathways, plays a key-role in sarcoma biology. Regorafenib (RE) has recently been shown to be effective in imatinib and sunitinib-refractory GIST in a phase III trial.
We are conducting an international trial (France, Austria and Germany) consisting in 4 parallel double-blind placebo-controlled randomized (1/1) phase II trials to assess the activity and safety of RE in doxorubicin-refractory STS (ClinicalTrials.gov: NCT01900743). Each phase II trial is dedicated to one of the 4 following histological subgroups: liposarcoma, leiomyosarcoma, synovial sarcoma and other sarcoma. Within each randomized trial the following stratification factors will be applied: countries and prior exposure to pazopanib. Key-eligibility criteria are: measurable disease, age ≥18, not > 3 previous systemic treatment lines for metastatic disease, metastatic disease not amenable to surgical resection. The primary endpoint is progression-free survival (PFS) according to central radiological review. Secondary endpoints are: Toxicity (NCI-CTC AE V4.0); time to progression; Growth modulation index in pts receiving RE after randomization; 3 and 6 months PFS-Rates, best response rate and overall survival. Each phase II trial will be separately analyzed. In 3 trials, statistical assumptions are: PFS0 = 1.6 & PFS1 = 4.6 months; 1-sided α = 0.1; β = 0.05 with a total sample size of 192 pts. To take into account the rarity of synovial sarcoma, the statistical assumptions are: PFS0 = 1.6 & PFS1 = 4.6 months; 1-sided α = 0.1; β = 0.2 Tumor assessment is done monthly during the 4 first months, and every 3 months thereafter. After central radiological confirmation of tumor progression, an optional open-label option is offered to eligible patients.
The design of this trial allows an assessment of regorafenib activity over placebo in four sarcoma strata and might provide evidence for launching a phase III trial. This study includes both integrative and exploratory translational research program. The study is enrolling since June 2013 (TRIAL REGISTRATION NUMBER: EudraCT N°: 2012-005743-24, on the 15(th) February 2012).
BMC Cancer 12/2015; 15(1):1143. DOI:10.1186/s12885-015-1143-y · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 "basket" study of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers.
We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival.
In the cohort with non-small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma.
BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600-mutated cancers. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT01524978.).
New England Journal of Medicine 08/2015; 373(8):726-36. DOI:10.1056/NEJMoa1502309 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although gastrointestinal stromal tumors (GISTs) are a rare type of cancer, they are the commonest sarcoma in the gastrointestinal tract. Molecularly targeted therapy, such as imatinib therapy, has revolutionized the treatment of advanced GIST and facilitates scientific research on GIST. Nevertheless, surgery remains a mainstay of treatment to obtain a permanent cure for GIST even in the era of targeted therapy. Many GIST guidelines have been published to guide the diagnosis and treatment of the disease. We review current versions of GIST guidelines published by the National Comprehensive Cancer Network, by the European Society for Medical Oncology, and in Japan. All clinical practice guidelines for GIST include recommendations based on evidence as well as on expert consensus. Most of the content is very similar, as represented by the following examples: GIST is a heterogeneous disease that may have mutations in KIT, PDGFRA, HRAS, NRAS, BRAF, NF1, or the succinate dehydrogenase complex, and these subsets of tumors have several distinctive features. Although there are some minor differences among the guidelines-for example, in the dose of imatinib recommended for exon 9-mutated GIST or the efficacy of antigen retrieval via immunohistochemistry-their common objectives regarding diagnosis and treatment are not only to improve the diagnosis of GIST and the prognosis of patients but also to control medical costs. This review describes the current standard diagnosis, treatment, and follow-up of GISTs based on the recommendations of several guidelines and expert consensus.
Gastric Cancer 08/2015; DOI:10.1007/s10120-015-0526-8 · 3.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a highly aggressive neoplasm occurring in young females. Paraneoplastic hypercalcaemia is associated in two-third of cases. Recent studies demonstrated that this rare tumor harbors molecular features of a malignant rhabdoid tumor secondary to SMARCA4/BRG1 mutations. We illustrate herein a typical bilateral case of SCCOHT in a 14 year-old girl comprehensively molecularly characterized . We also discuss the invaluable input of SMARCA4 immunostaining in the diagnostic approach of undifferentiated ovarian and pelvic malignancies in routine practice.
Pediatric and Developmental Pathology 07/2015; DOI:10.2350/15-04-1624-CR.1 · 0.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Validated predictive biomarkers for multi-tyrosine kinase inhibitors (MTKI) efficacy are lacking. We hypothesized that interindividual response variability is partially dependent on somatic DNA copy number alterations (SCNAs), particularly those of genes encoding the protein tyrosines targeted by MTKI (called target genes). Genomic alterations were investigated in MTKI responsive and non responsive patients with different histological subtypes included in the ProfiLER protocol (NCT 01774409). From March 2013 to August 2014, 58 patients with advanced cancer treated with one of 7 MTKIs were included in the ProfiLER trial and split into one discovery cohort (n = 13), and 2 validation cohorts (n = 12 and 33). An analysis of the copy number alterations of kinase-coding genes for each of 7 MTKIs was conducted. A prediction algorithm (SUMSCAN) based on the presence of specific gene gains (Tumor Target Charge, TTC) and losses (Tumor Target Losses, TTL) was conceived and validated in 2 independent validation cohorts. MTKI sensitive tumors present a characteristic SCNA profile including a global gain profile, and specific gains for target genes while MTKI resistant tumors present the opposite. SUMSCAN favorable patients achieved longer progression-free and overall survival. This work shows that the copy number sum of kinase-coding genes enables the prediction of response of cancer patients to MTKI, opening a novel paradigm for the treatment selection of these patients.
[Show abstract][Hide abstract] ABSTRACT: One of the current goals of the French national cancer plan is to reduce healthcare inequalities. This study investigated the potential links between vulnerable social status, exposure to lung cancer risk factors and access to healthcare to highlight ways to improve lung cancer control in this population. The nationwide observational study EDIFICE 3 was carried out through phone interviews of a representative sample of 1603 individuals (age 40-75 years). The EPICES validated questionnaire was used to assess and classify vulnerable respondents. The vulnerable population identified represented 33% of the sample. Compared with nonvulnerable individuals, they had more risk factors for cancer: a higher BMI (26.0 vs. 24.8, P≤0.01), 38% were active smokers (vs. 23%, P≤0.01) with a heavier and longer-lasting tobacco consumption (16.0 cigarettes/day vs. 10.1, P≤0.01 and 29.4 vs. 26.3 years of smoking, P≤0.01) and they were less likely to undertake any physical activities (42 vs. 77%, P≤0.01). They also presented more comorbidities (on average 2.2 vs. 1.8, P≤0.01). Access to healthcare, however, was not discriminatory: vulnerable individuals declared consulting a general practitioner or an oncologist more often than the nonvulnerable subgroup (5.4 vs. 3.7 and 6.7 vs. 2.5 consultations in the previous 12 months, respectively, P≤0.01). Because access to healthcare and screening attendance show no signs of discrimination against vulnerable populations, efforts to reduce inequities in lung cancer control should focus on prevention.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2015; 24 Suppl:S82-6. DOI:10.1097/CEJ.0000000000000143 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This analysis aimed to assess the extent to which exposure to cancer risk factors and attendance of screening programmes are influenced by social characteristics. The validated Evaluation of deprivation and health inequalities in public health centres (EPICES) index was used to measure social deprivation. A sample of the general population (N=1603) was assessed to search for potential correlations between screening attendance, risk factors and any components of the EPICES score. In 2011, 33% of the population studied was classified as 'vulnerable'. Sex had no significant impact on this rating (32% men, 35% women), whereas occupational status did. Vulnerable individuals were more likely already to have cancer (10 vs. 7%; nonsignificant difference; odds ratio 1.43 [0.98-2.10]). The mean BMI was 26.0 kg/m (SD 4.9) for the vulnerable population versus 24.8 kg/m (SD 3.9) in the nonvulnerable population (P<0.01). The prevalence of current smoking was higher in the vulnerable group (38 vs. 23%, odds ratio 2.03 [1.61-2.56]). In contrast, no statistically significant difference was observed between attendance rates for nationwide organized cancer screening programmes (breast and colorectal; target age group 50-74 years) by the vulnerable and nonvulnerable groups. Social indicators of vulnerable populations are associated with increased rates of risk factors for cancer, but not with screening attendance. Our data support the previously reported marked impact of organized programmes that reduce or even remove inequalities in access to cancer screening. However, although the organized programmes have indeed enabled population-wide, nonselective access to screening, primary prevention as it stands today remains inadequate in the underserved population and further improvements are warranted.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2015; 24 Suppl:S77-81. DOI:10.1097/CEJ.0000000000000144 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Cochrane analysis exploring the risk/benefit ratio of breast cancer screening resulted in a controversy worldwide spread by the mass media. Our survey sought to assess the impact of this controversy in terms of breast cancer screening awareness and attendance. A nationwide observational study, recorded in the EDIFICE iterative surveys, with a representative sample of 451 women aged 40-75 years, living in France, was carried out in the 3 months after the start of the controversy in January 2013. Of the 405 women with no personal history of cancer, 69 (17%) declared having heard of the controversy (aware group). Women remembering the controversy were more likely to belong to higher socioprofessional categories and to have a higher level of education. The most frequently remembered issues were overdiagnosis (38%), unreliability (16%) and radiation risk (9%). Compared with women who were unaware of the controversy, the aware group knew more about the limits of breast cancer screening (undiagnosed cancers, 20 vs. 7%, P<0.05 and risk of false positives, 20 vs. 2%, P<0. 05) and were more likely to change their opinion for the worse over the mass media debate (8.7 vs. 1.2%, P<0.05). Nevertheless, only 1% of the aware-group declared their intention to subsequently undergo screening less frequently. The low impact of the controversy on the behaviour of women with respect to screening suggests that it should not be seen as a threat to screening attendance rates, but more as an opportunity to improve awareness.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2015; 24 Suppl:S73-6. DOI:10.1097/CEJ.0000000000000145 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The EDIFICE programme began in 2005 and set out to provide a clearer insight over time into the participation of the French population in cancer screening. EDIFICE 3 was conducted in 2011 by phone interviews among a representative sample of 1603 individuals aged between 40 and 75 years using the quota method. The analysis focused on the target populations (50-74 years) of the national screening programmes for breast and colorectal cancer. The same populations were also assessed with respect to prostate cancer screening. In 2005, 93% of the sample population had undergone at least one mammogram in their lifetime; this figure reached 94% in 2008 and 95% in 2011. Compliance with recommended intervals improved between 2005 and 2011, and significantly so for women aged 65-74 years. In 2005, 25% of respondents reported having undergone at least one colorectal cancer screening test; this figure reached 38% in 2008 and 59% in 2011. Recommended intervals were respected by 30 and 51% in 2008 and 2011, respectively. In 2005, 2008 and 2011, a total of 36, 49 and 50% of men reported having undergone at least one prostate cancer screening test. This rate decreased significantly in men aged 50-59 years between 2008 and 2011 (44 vs. 37%, P≤0.05). Attendance rates in national screening programmes are high and stable for breast cancer, and although currently improving for colorectal cancer, the European guideline target has not yet been reached. Despite the absence of recommendations for prostate cancer screening, participation remains constant.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2015; 24 Suppl:S68-72. DOI:10.1097/CEJ.0000000000000146 · 3.03 Impact Factor