Charu Aggarwal1, Xingmei Wang2, Anjana Ranganathan3, Drew Torigian4, Andrea Troxel5, Tracey Evans3, Roger B Cohen3, Bhavesh Vaidya6, Chandra Rao7, Mark Connelly7, Anil Vachani8, Corey Langer3, Steven Albelda9. 1. Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: charu.aggarwal@uphs.upenn.edu. 2. Division of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, United States. 3. Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, United States. 4. Division of Radiology, University of Pennsylvania, Philadelphia, PA, United States. 5. Division of Biostatistics, Department of Population Health, New York University School of Medicine, NY, United States. 6. Janssen Diagnostics, LLC, Huntingdon Valley, PA, United States. 7. Division of Biostatistics, Department of Population Health, New York University School of Medicine, NY, United States; Janssen Diagnostics, LLC, Huntingdon Valley, PA, United States. 8. Division of Pulmonary and Critical Care, Thoracic Oncology Group, University of Pennsylvania, Philadelphia, PA, United States. 9. Janssen Diagnostics, LLC, Huntingdon Valley, PA, United States; Division of Pulmonary and Critical Care, Thoracic Oncology Group, University of Pennsylvania, Philadelphia, PA, United States.
Abstract
BACKGROUND: There are no biomarkers for assessment of disease burden or activity of therapy in SCLC. PATIENTS AND METHODS: We conducted a prospective study enumerating serial CTCs in patients with newly diagnosed limited disease (LD) and extensive stage (ED) SCLC. CTCs demonstrating DNA damage and apoptosis based on γH2AX and M30 staining were also assessed. We correlated CTC number with disease stage, survival outcomes and tumor burden by RECIST. RESULTS: Between 03/2011-10/2013, 50 evaluable patients were enrolled (20 LD). Baseline CTC number was higher for ED (median CTC 71 vs. 1.5 for LD; p 0.0004). Patients with <5 CTC had longer PFS but not OS (11 vs. 6.7 months, p 0.0259 and 15.5 vs. 12.9 months, p 0.4357). A higher cutoff (CTC<50 or CTC≥50) was significantly correlated with both OS (20.2 vs. 11.8 months, p 0.0116) and PFS (10 vs. 4.8 months, p 0.0002). Patients with <5 CTC on day 1 of cycle 2 had longer PFS (10 vs. 3.17 months, p<0.001) and OS (18 vs. 9 months, p 0.0001). Patients with an increase in γ2HAX-positive CTCs after chemotherapy had longer OS compared to patients without an increase (25.3 vs. 9 months, p 0.15). CONCLUSIONS: This study demonstrates that CTCs at baseline and Cycle 2 of chemotherapy correlate with disease stage and survival in patients with SCLC, suggesting that CTCs may be used as a surrogate biomarker for clinical response. Confirmatory prospective clinical trials are needed before we can incorporate routine evaluation of CTCs into clinical practice.
BACKGROUND: There are no biomarkers for assessment of disease burden or activity of therapy in SCLC. PATIENTS AND METHODS: We conducted a prospective study enumerating serial CTCs in patients with newly diagnosed limited disease (LD) and extensive stage (ED) SCLC. CTCs demonstrating DNA damage and apoptosis based on γH2AX and M30 staining were also assessed. We correlated CTC number with disease stage, survival outcomes and tumor burden by RECIST. RESULTS: Between 03/2011-10/2013, 50 evaluable patients were enrolled (20 LD). Baseline CTC number was higher for ED (median CTC 71 vs. 1.5 for LD; p 0.0004). Patients with <5 CTC had longer PFS but not OS (11 vs. 6.7 months, p 0.0259 and 15.5 vs. 12.9 months, p 0.4357). A higher cutoff (CTC<50 or CTC≥50) was significantly correlated with both OS (20.2 vs. 11.8 months, p 0.0116) and PFS (10 vs. 4.8 months, p 0.0002). Patients with <5 CTC on day 1 of cycle 2 had longer PFS (10 vs. 3.17 months, p<0.001) and OS (18 vs. 9 months, p 0.0001). Patients with an increase in γ2HAX-positive CTCs after chemotherapy had longer OS compared to patients without an increase (25.3 vs. 9 months, p 0.15). CONCLUSIONS: This study demonstrates that CTCs at baseline and Cycle 2 of chemotherapy correlate with disease stage and survival in patients with SCLC, suggesting that CTCs may be used as a surrogate biomarker for clinical response. Confirmatory prospective clinical trials are needed before we can incorporate routine evaluation of CTCs into clinical practice.
Authors: C Allison Stewart; Carl M Gay; Yuanxin Xi; Santhosh Sivajothi; V Sivakamasundari; Junya Fujimoto; Mohan Bolisetty; Patrice M Hartsfield; Veerakumar Balasubramaniyan; Milind D Chalishazar; Cesar Moran; Neda Kalhor; John Stewart; Hai Tran; Stephen G Swisher; Jack A Roth; Jianjun Zhang; John de Groot; Bonnie Glisson; Trudy G Oliver; John V Heymach; Ignacio Wistuba; Paul Robson; Jing Wang; Lauren Averett Byers Journal: Nat Cancer Date: 2020-02-17
Authors: Victoria Foy; Colin R Lindsay; Alexandra Carmel; Fabiola Fernandez-Gutierrez; Matthew G Krebs; Lynsey Priest; Mathew Carter; Harry J M Groen; T Jeroen N Hiltermann; Antonella de Luca; Francoise Farace; Benjamin Besse; Leon Terstappen; Elisabetta Rossi; Alessandro Morabito; Francesco Perrone; Andrew Renehan; Corinne Faivre-Finn; Nicola Normanno; Caroline Dive; Fiona Blackhall; Stefan Michiels Journal: Transl Lung Cancer Res Date: 2021-04