GNAS mutations as prognostic biomarker in patients with relapsed peritoneal pseudomyxoma receiving metronomic capecitabine and bevacizumab: a clinical and translational study

Journal of Translational Medicine

Research

Pietro Francesco Bagnoli¹  Marta Caporale²  Monica Niger²  Rosa Berenato²  Alessia Mennitto²  Ilaria Bossi²  Filippo Pietrantonio²  Claudia Maggi²  Maria Di Bartolomeo²  Filippo de Braud²  Elena Tamborini³  Adele Busico³  Giulio Settanni³  Annunziata Gloghini³  Federica Perrone³  Massimo Milione³  Dario Baratti⁴  Marcello Deraco⁴  Shigeki Kusamura⁴  Luigi Mariani⁵ 

[1] Department of Cancer Surgery, Humanitas Clinical and Research Center, Milan, Rozzano, Italy;Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133, Milan, Italy;Pathology and Molecular Biology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;Surgery Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;

关键词: Peritoneal pseudomyxoma;    Appendiceal cancer;    Metronomic capecitabine;    Bevacizumab;    Next-generation sequencing;    GNAS;   

DOI  :  10.1186/s12967-016-0877-x

 received in 2015-12-16, accepted in 2016-04-26,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThere is lack of evidence about systemic treatment of pseudomyxoma peritonei (PMP) relapsing after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. There is also lack of biomarkers able to predict outcomes beyond known clinical and pathological prognostic features.MethodsFifteen patients with relapsed PMP and progressive disease within the last 6 months were included and received metronomic capecitabine (625 mg/mq/day b.i.d.) and bevacizumab (7.5 mg/Kg three-weekly) until progressive disease/unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Ion Torrent® next generation sequencing technology (Hot-spot Cancer Panel) was used to characterize molecular features.ResultsAt a median follow up of 12 months, median PFS was 8.2 months and 1-year overall survival was 91 %. Partial responses were observed in 20 % of cases, but a significant reduction of tumor markers in up to 79 %. Treatment was very well tolerated without no new safety signals. All tumor samples except one had KRAS mutations. Patients with GNAS mutations had a significantly shorter median PFS as compared to GNAS wild-type ones (5.3 months vs. not reached; p < 0.007). The results were externally validated on our previous series of PMP patients. GNAS mutations were rare in a parallel cohort of 121 advanced colorectal cancers (2.5 %), but were associated with peculiar clinical-pathological features and aggressive course.ConclusionsMetronomic capecitabine and bevacizumab is an active and well tolerated option in patients with relapsed PMP. The negative prognostic effect of GNAS mutations in gastrointestinal cancers warrants further confirmatory studies and may prompt the development of effective targeted strategies.

【 授权许可】

CC BY   
© Pietrantonio et al. 2016