Judith G Villablanca1, Lingyun Ji2, Adi Shapira-Lewinson3, Araz Marachelian1, Hiroyuki Shimada4, Randall A Hawkins5, Miguel Pampaloni5, Hollie Lai6, Fariba Goodarzian7, Richard Sposto2, Julie R Park8, Katherine K Matthay9. 1. Department of Pediatrics, Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California, Los Angeles, California. 2. Department of Preventative Medicine Statistics, Keck School of Medicine of the University of Southern California, Los Angeles, California. 3. Department of Pediatric Hematology-Oncology, The Ruth Rappaport Children's Hospital, Haifa, Israel. 4. Department of Pathology, Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California, Los Angeles, California. 5. Department of Radiology, University of California San Francisco, San Francisco, California. 6. Department of Pediatric Radiology, Children's Hospital Orange County, Orange, California. 7. Department of Radiology, Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA. 8. Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington. 9. Department of Pediatrics, University of California San Francisco, San Francisco, California.
Abstract
PURPOSE: The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed. METHODS: A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology). RESULTS: Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five-year progression-free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS (P < 0.001). In multivariable analysis, MYCN amplification (P = 0.037) was associated with worse PFS; measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior progressive disease (PD; P < 0.001/P < 0.001), Curie score ≥ 1 (P < 0.001; P = 0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P = < 0.001/0.003) were associated with worse PFS and OS. CONCLUSIONS: NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial design to select novel agents for further testing.
PURPOSE: The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed. METHODS: A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology). RESULTS: Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five-year progression-free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS (P < 0.001). In multivariable analysis, MYCN amplification (P = 0.037) was associated with worse PFS; measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior progressive disease (PD; P < 0.001/P < 0.001), Curie score ≥ 1 (P < 0.001; P = 0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P = < 0.001/0.003) were associated with worse PFS and OS. CONCLUSIONS: NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial design to select novel agents for further testing.
Authors: Mark A Applebaum; Erin K Barr; Jason Karpus; Diana C West-Szymanski; Meritxell Oliva; Elizabeth A Sokol; Sheng Zhang; Zhou Zhang; Wei Zhang; Alexandre Chlenski; Helen R Salwen; Emma Wilkinson; Marija Dobratic; Robert L Grossman; Lucy A Godley; Barbara E Stranger; Chuan He; Susan L Cohn Journal: Clin Cancer Res Date: 2019-12-18 Impact factor: 12.531
Authors: Steven G DuBois; Yael P Mosse; Elizabeth Fox; Rachel A Kudgus; Joel M Reid; Renee McGovern; Susan Groshen; Rochelle Bagatell; John M Maris; Clare J Twist; Kelly Goldsmith; M Meaghan Granger; Brian Weiss; Julie R Park; Margaret E Macy; Susan L Cohn; Greg Yanik; Lars M Wagner; Randall Hawkins; Jesse Courtier; Hollie Lai; Fariba Goodarzian; Hiroyuki Shimada; Najee Boucher; Scarlett Czarnecki; Chunqiao Luo; Denice Tsao-Wei; Katherine K Matthay; Araz Marachelian Journal: Clin Cancer Res Date: 2018-08-09 Impact factor: 12.531
Authors: Kiana Kreitz; Angela Ernst; René Schmidt; Thorsten Simon; Matthias Fischer; Ruth Volland; Barbara Hero; Frank Berthold Journal: Cancer Med Date: 2019-10-20 Impact factor: 4.452
Authors: Steven G DuBois; M Meaghan Granger; Susan Groshen; Denice Tsao-Wei; Lingyun Ji; Anasheh Shamirian; Scarlett Czarnecki; Fariba Goodarzian; Rachel Berkovich; Hiroyuki Shimada; Judith G Villablanca; Kieuhoa T Vo; Navin Pinto; Yael P Mosse; John M Maris; Suzanne Shusterman; Susan L Cohn; Kelly C Goldsmith; Brian Weiss; Gregory A Yanik; Clare J Twist; Meredith S Irwin; Daphne A Haas-Kogan; Julie R Park; Araz Marachelian; Katherine K Matthay Journal: J Clin Oncol Date: 2021-07-16 Impact factor: 44.544