Absolute Neutrophil Count after the First Chemotherapy Cycle as a Surrogate Marker for Treatment Outcomes in Patients with Neuroblastoma
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Purpose: We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma. Materials and methods: The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed. Results: An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC. Conclusion: In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual's susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.
Abstract
Purpose: We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma. Materials and methods: The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed. Results: An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC. Conclusion: In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual's susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.
참고문헌 (22)
- Maris JM, "Neuroblastoma", Lancet, 369, pp.2106~2120 (2007)
- Brodeur GM, "Neuroblastoma : biological insights into a clinical enigma", Nat Rev Cancer, 3, pp.203~216 (2003)
- Hero B, "Localized infant neuroblastomas often show spontaneous regression : results of the prospective trials NB95-S and NB97", J Clin Oncol, 26, pp.1504~1510 (2008)
- Moen EL, "Pharmacogenomics of chemotherapeutic susceptibility and toxicity", Genome Med, 4, pp.90~ (2012)
- Roden DM, "Pharmacogenomics", Lancet, 394, pp.521~532 (2019)
- Lennard L, "Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia", Lancet, 336, pp.225~229 (1990)
- Yang JJ, "Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia", J Clin Oncol, 33, pp.1235~1242 (2015)
- Bagatell R, "Assessment of primary site response in children with high-risk neuroblastoma : an international multicenter study", J Clin Oncol, 34, pp.740~746 (2016)
- Lee JW, "Incorporation of high-dose(131)I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma : results of the SMC NB-2009 study", J Hematol Oncol, 10, pp.108~ (2017)
- Sung KW, "Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma : results of SMC NB-2004 study", Bone Marrow Transplant, 48, pp.68~73 (2013)
- Laska E, "A maximally selected test of symmetry about zero", Stat Med, 31, pp.3178~3191 (2012)
- Kim HT, "Cumulative incidence in competing risks data and competing risks regression analysis", Clin Cancer Res, 13, pp.559~565 (2007)
- Pruim RJ, "LocusZoom : regional visualization of genome-wide association scan results", Bioinformatics, 26, pp.2336~2337 (2010)
- Kishida Y, "Chemotherapy-induced neutropenia as a prognostic factor in advanced non-small-cell lung cancer : results from Japan Multinational Trial Organization LC00-03", Br J Cancer, 101, pp.1537~1542 (2009)
- Ma RM, "Prognostic value of chemotherapy-induced neutropenia at the first cycle in invasive breast cancer", Medicine(Baltimore), 95, pp.e3240~ (2016)
- Kasi PM, "Chemotherapy induced neutropenia at 1-month mark is a predictor of overall survival in patients receiving TAS-102 for refractory metastatic colorectal cancer : a cohort study", BMC Cancer, 16, pp.467~ (2016)
- Chen Y, "Timing of chemotherapy-induced neutropenia predicts prognosis in metastatic colon cancer patients : a retrospective study in mFOLFOX6-treated patients", BMC Cancer, 17, pp.242~ (2017)
- Sung L, "Association between prolonged neutropenia and reduced relapse risk in pediatric AML : a report from the children’s oncology group", Int J Cancer, 139, pp.1930~1935 (2016)
- Alexander S, "Classification of treatment-related mortality in children with cancer : a systematic assessment", Lancet Oncol, 16, pp.e604~e610 (2015)
- White GR, "Genomic structure and expression profile of LPHH1, a 7TM gene variably expressed in breast cancer cell lines", Biochim Biophys Acta, 1491, pp.75~92 (2000)
- Eng L, "Bioinformatic analyses identifies novel protein-coding pharmacogenomic markers associated with paclitaxel sensitivity in NCI60 cancer cell lines", BMC Med Genomics, 4, pp.18~ (2011)
- Perez-Ortiz AC, "Pharmacogenetics of response to neoadjuvant paclitaxel treatment for locally advanced breast cancer", Oncotarget, 8, pp.106454~106467 (2017)