Additional file 3: Figure S2. Comparison of Kaplan-Meier curves for progression-free survival according to GNAS mutational status in both the prospective (metronomic capecitabine and bevacizumab) and the retrospective cohort (FOLFOX-4)

Adele Busico (3422972)

Alessia Mennitto (3422978)

Annunziata Gloghini (32268)

Claudia Maggi (545430)

Dario Baratti (3422990)

Elena Tamborini (3422993)

Federica Perrone (545433)

Filippo de Braud (545440)

Filippo Pietrantonio (545429)

Giulio Settanni (3422996)

Ilaria Bossi (545437)

Luigi Mariani (3399464)

Marcello Deraco (3422999)

Maria Di Bartolomeo (545431)

Marta Caporale (3422984)

Massimo Milione (545439)

Monica Niger (3422975)

Pietro Bagnoli (3422987)

Rosa Berenato (3423002)

Shigeki Kusamura (3422981)

Additional file 1. Methods S1. MET assessment

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

MOESM3 of 
                     GNAS mutations as prognostic biomarker in patients with relapsed peritoneal pseudomyxoma receiving metronomic capecitabine and bevacizumab: a clinical and translational study

Filippo Pietrantonio

Rosa Berenato

Claudia Maggi

Marta Caporale

Massimo Milione

Federica Perrone

Elena Tamborini

Dario Baratti

Shigeki Kusamura

Luigi Mariani

Monica Niger

Alessia Mennitto

Annunziata Gloghini

Ilaria Bossi

Giulio Settanni

Adele Busico

Pietro Francesco Bagnoli

Maria Di Bartolomeo

Marcello Deraco

Filippo de Braud

Springer - Publisher Connector

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

Background: There 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. Methods: Fifteen 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\uae next generation sequencing technology (Hot-spot Cancer Panel) was used to characterize molecular features. Results: At 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. Conclusions: Metronomic 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

F. Pietrantonio

R. Berenato

C. Maggi

M. Caporale

M. Milione

F. Perrone

E. Tamborini

D. Baratti

S. Kusamura

L. Mariani

M. Niger

A. Mennitto

A. Gloghini

I. Bossi

G. Settanni

A. Busico

P.F. Bagnoli

M. Di Bartolomeo

M. Deraco

F. de Braud

AIR Universita degli studi di Milano

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

file:///data/remote/core/dit/data/Springer-OA/pdf/881/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjExODYvczEyOTY3LTAxNi0wODc3LXgucGRm.pdf

MOESM3 of GNAS mutations as prognostic biomarker in patients with relapsed peritoneal pseudomyxoma receiving metronomic capecitabine and bevacizumab: a clinical and translational study

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AIR Universita degli studi di Milano