Elevated Levels of BRAF V600 Mutant Circulating Tumor DNA and Circulating Hepatocyte Growth Factor Are Associated With Poor Prognosis in Patients With Metastatic Melanoma.

Autor:	Lu W; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Burton L; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Larkin J; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Chapman PB; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Ascierto PA; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Ribas A; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Robert C; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Sosman JA; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., McArthur GA; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Chang I; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Caro I; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Penuel E; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Yan Y; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia., Wongchenko MJ; William Lu, Luciana Burton, Ilsung Chang, Ivor Caro, Elicia Penuel, Yibing Yan, and Matthew J. Wongchenko, Genentech, South San Francisco; Antoni Ribas, The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA; James Larkin, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Caroline Robert, Institut Gustave Roussy and Paris Sud University, Paris, France; Jeffrey A. Sosman, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, and University of Melbourne, Parkville, Australia.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2018 Nov; Vol. 2, pp. 1-17.
DOI:	10.1200/PO.17.00168
Abstrakt:	Purpose: We performed a retrospective exploratory analysis to evaluate the prognostic and predictive effect of two circulating biomarkers, BRAF V600 mutant circulating tumor DNA (ctDNA) and circulating hepatocyte growth factor (cHGF), in metastatic melanoma. Materials and Methods: This study evaluated patients from BRIM-3, a phase III trial comparing vemurafenib and dacarbazine in 675 patients with BRAF V600 mutated advanced melanoma. ctDNA was measured using droplet digital polymerase chain reaction, and cHGF was measured by enzyme-linked immunosorbent assay. Overall survival (OS) was estimated using the Kaplan-Meier method, and hazard ratios (HRs) were estimated using Cox proportional hazards modeling. Partitioning analysis was used to group patients into risk categories. Results: Patients with elevated levels of baseline BRAF V600 ctDNA had significantly shorter median OS than those with undetectable levels of ctDNA (vemurafenib arm, 9.9 v 21.4 months, respectively, and dacarbazine arm: 6.1 v 21.0 months, respectively). Median OS was also shorter in patients with high levels of cHGF compared with those with low cHGF (vemurafenib arm, 11.9 v 17.3 months, respectively, and dacarbazine arm, 6.1 v 14.4 months, respectively). In a multivariable proportional hazards model with adjustment for lactate dehydrogenase, Eastern Cooperative Oncology Group status, disease stage, and treatment, ctDNA and cHGF were both independent prognostic factors for OS, (HR, 1.75; 95% CI, 1.35 to 2.28 for high v undetectable ctDNA; HR, 1.24; 95% CI, 1.00 to 1.53 for high v low cHGF). Using partitioning analysis, we found that patients with elevated ctDNA combined with elevated cHGF constituted the highest risk group with significantly shorter OS. Conclusion: Here, we report that BRIM-3 patients with high levels of ctDNA and cHGF have worse OS regardless of treatment and that these factors are independent prognostic markers for metastatic melanoma.
Databáze:	MEDLINE
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