Improved survival using specialized multidisciplinary board in sarcoma patients

Abstract:

BackgroundSarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation prior to treatment in a nationwide study over 5 years.Patients and methods:NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed.ResultsOut of the 12,528 patients aged > =15, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1/1/2010 and 31/12/2014, 5,281 (42.2%) and 7,247 (57.8%) were presented to the MDTB before and after the initiation of treatment respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, e.g. biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all p < 0.001). Local relapse-free survival and relapse-free survival were significantly better in patients presented to a MDTB before initiation of treatment, both in univariate and multivariate analysis.ConclusionThe compliance to clinical practice guidelines and relapse-free survival of sarcoma patients are significantly better when the initial treatment is guided by a pre-therapeutic specialized MDTB.

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Survivin: a novel marker and potential therapeutic target for human angiosarcoma

Summary

Human angiosarcoma is a rare malignant vascular tumor associated with extremely poor clinical outcome and generally arising in the skin of head and neck. However, little is known about the molecular pathogeneses and useful immunohistochemical markers of angiosarcoma. To investigate the mechanisms of angiosarcoma progression, we collected 85 cases of human angiosarcoma specimens with clinical records and used ISO-HAS-B patient derived angiosarcoma cells. As control subjects, 54 cases of hemangioma and 34 of pyogenic granuloma were collected. Remarkably, consistent with our recent observations regarding the involvement of Survivin expression following Hippo pathway inactivation in the neoplastic proliferation of murine hemangioendothelioma cells and human infantile hemangioma, nuclear Survivin expression was observed in all cases of angiosarcoma but not in hemangiomas and pyogenic granulomas and Hippo pathway was inactivated in 90.3% of YAP-positive angiosarcoma cases. However, Survivin expression modes and YAP localization (Hippo pathway activation modes) were not correlated with survival. In addition, we confirmed that Survivin small interference RNA (siRNA) transfection and YM155, an anti-Survivin drug, elicited decreased nuclear Survivin expression and cell proliferation in ISO-HAS-B cells which expressed Survivin consistently. Conclusively, these findings support the importance of Survivin as a good marker and critical regulator of cellular proliferation for human angiosarcoma and YM155 as a potential therapeutic agent.

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Mutational analysis using Sanger and Next Generation Sequencing in sporadic spindle cell hemangiomas: A study of 19 cases

Abstract

Spindle cell hemangioma (SCH) is a distinct vascular soft tissue lesion characterized by cavernous blood vessels and a spindle cell component mainly occurring in the distal extremities of young adults. The majority of cases harbor heterozygous mutations in IDH1/2 sporadically or rarely in association with Maffucci syndrome. However, based on mosaicism and accordingly a low percentage of lesional cells harboring a mutant allele, detection can be challenging. We tested 19 sporadic SCHs by Sanger sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), conventional Next Generation Sequencing (NGS) and NGS using a Single Molecule Molecular Inversion Probes (smMIP) based library preparation in order to compare their diagnostic value. Four out of ten cases tested by Sanger sequencing and one of the two cases analyzed using MLPA revealed a mutation in IDH1 (p.R132C). The seven remaining negative cases and additional six cases were investigated using smMIP/NGS, showing hot spot mutations in IDH1 (p.R132C) (eight cases) and IDH2 (three cases; twice p.R172S and once p.R172G, respectively). One case was negative. Due to insufficient DNA quality and insufficient coverage, two cases were excluded. In total, in 16 out of 17 cases successfully tested an IDH1/2 mutation was found. Given that IDH1/2 mutations were absent in 161 other vascular lesions tested by smMIP/NGS, the mutation can be considered as highly specific for SCH. This article is protected by copyright. All rights reserved.

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A phase II study of modified docetaxel, cisplatin, and S-1 (mDCS) chemotherapy for unresectable advanced gastric cancer

Abstract

Purpose

Triplet therapy using docetaxel, cisplatin, and S-1 (DCS) against unresectable gastric cancer as previously reported by us showed high clinical efficacy, with a 87.1% total response rate; however, it also showed a high incidence of grade 3/4 toxicity. With the aim of reducing toxicities, we conducted a phase II study of modified DCS (mDCS), using a reduced dose of docetaxel, and evaluated the clinical efficacy and adverse events of this regimen.

Methods

Patients with unresectable gastric cancer received chemotherapy with S-1 (40 mg/m² b.i.d) on days 1–14, and docetaxel (50 mg/m²) plus cisplatin (60 mg/m²) on day 8 every 3 weeks. The primary endpoint was the response rate (RR). Overall (OS) and progression-free survival (PFS), and toxicities were also evaluated.

Results

Forty-nine patients were enrolled from November 2011 to April 2014, and 43 were eligible. The overall RR was 79.1%, including two cases of a complete response (4.7%), and 32 cases of a partial response (74.4%). Nine cases had stable disease (20.9%) but none showed progressive disease. Of the 43 cases, 15 cases (34.9%) underwent curative conversion surgery. The median PFS was 350 days (95% CI 240–416 days) and median OS was 722 days (95% CI 411 days–not reached). Grade 3/4 neutropenia developed in 79.1%, and febrile neutropenia in 34.9%, of patients. Non-hematological grade 3/4 adverse events were anorexia (25.6%), nausea (4.7%), and diarrhea (9.3%).

Conclusion

Modified DCS therapy showed high clinical efficacy sufficient enough to attempt conversion therapy against unresectable gastric cancer. Modified DCS showed fewer toxicities, but careful management of these is still essential.

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The insufficient prognostic power of stenosis in patients with esophageal cancer

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Disparities in cancer incidence by area-level socioeconomic status in the French West Indies

Abstract

Purpose

Social inequalities in cancer incidence and mortality have been reported in France, but no data are available for the French overseas territories. Our objective was to explore the association between cancer incidence and the socioeconomic level of the residence area in the French West Indies.

Methods

Cancer incidence data were obtained from the cancer registries of Guadeloupe and Martinique (2009–2010). To assess socioeconomic status, we developed a specific index of social deprivation from census data at a small area level. We used Bayesian methods to evaluate the association between cancer incidence and the deprivation index, for all cancers combined and for the major cancer sites.

Results

There was no clear association between area-based deprivation and the incidence of all cancers combined. In men, higher area deprivation was associated with a higher incidence of prostate cancer (relative risk (RR) 1.25, 95% credible interval (CI) 1.04–1.49; RR 1.08, CI 0.91–1.29 in the categories of intermediate and high deprivation, respectively, compared to low deprivation), but was not associated with respiratory cancer. Women living in the most deprived areas had a higher incidence of stomach (RR 1.77, CI 1.12–2.89), breast (RR 1.15, CI 0.90–1.45), and cervical (RR 1.13, CI 0.63–2.01) cancers and a lower incidence of respiratory cancer (RR 0.65, CI 0.38–1.11).

Conclusion

These first results in the French West Indies suggest specific patterns for some cancer sites that need to be further investigated.

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Pubertal growth and adult height in relation to breast cancer risk in African American women

Abstract

Adult height has been positively associated with breast cancer risk. The timing of pubertal growth – as measured by age at menarche and age at attained height – may also influence risk. We evaluated associations of adult height, age at attained height, and age at menarche with incidence of invasive breast cancer in 55,687 African American women in the prospective Black Women's Health Study. Over 20 years, 1,826 invasive breast cancers [1,015 estrogen receptor (ER) positive; 542 ER negative] accrued. We used multivariable Cox proportional hazards regression to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for associations with breast cancer overall and by ER status, mutually adjusted for the three factors of interest. Adult height was associated with increased risk of ER+ breast cancer (HR for ≥70 inches vs. ≤63 inches: 1.44; 95% CI: 1.09, 1.89) but not ER- (corresponding HR: 1.16; 95% CI: 0.78, 1.71) (P-heterogeneity=0.34). HRs for attained height before age 13 vs. age >17 were 1.30 (95% CI: 0.96, 1.76) for ER+ and 1.25 (95% CI: 0.80, 1.96) for ER- breast cancer. Results for age at menarche (≤11 years vs. ≥14 years) were similar for ER+ and ER- breast cancer (HR for breast cancer overall: 1.30; 95%CI: 1.12, 1.50). We confirmed height as a strong risk factor for ER+ breast cancer in African American women and identified early age at attained height as a risk factor for both ER+ and ER- breast cancer, albeit without statistical significance of the latter associations. While adult height and timing of pubertal growth are inter-related, our findings suggest that they may be independent risk factors for breast cancer. This article is protected by copyright. All rights reserved.

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