Impact of baseline and nadir neutrophil index in non-small cell lung cancer and ovarian cancer patients: Assessment of chemotherapy for resolution of unfavourable neutrophilia
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- 作者：Andreas Carus (6)
Howard Gurney (7)
Val Gebski (8)
Paul Harnett (7)
Rina Hui (7)
Richard Kefford (7)
Nicholas Wilcken (7)
Morten Ladekarl (6)
Hans von der Maase (9)
Frede Donskov (6) - 关键词：Lung cancer ; Ovarian cancer ; Neutrophils ; Tumour microenvironment ; Prognostic factor
- 刊名：Journal of Translational Medicine
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：11
- 期：1
- 全文大小：398KB
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Howard Gurney (7)
Val Gebski (8)
Paul Harnett (7)
Rina Hui (7)
Richard Kefford (7)
Nicholas Wilcken (7)
Morten Ladekarl (6)
Hans von der Maase (9)
Frede Donskov (6)
6. Department of Oncology and department of experimental clinical oncology, Aarhus University Hospital, Noerrebrogade 44, Bldg. 5, DK-8000, Aarhus, Denmark
7. Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, Australia
8. NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia
9. Department of Oncology, Copenhagen University Hospital, Copenhagen, Denmark
文摘
Background Chronic inflammation has been recognized to foster tumour development. Whether chemotherapy can be used to neutralize chronic inflammation is unclear. Methods We evaluated baseline and nadir neutrophils in 111 patients (pts.) with non-small cell lung cancer (NSCLC) and 118 pts. with ovarian cancer (OC) treated with chemotherapy administered with dose-individualization to achieve nadir neutropenia of 1.5. We used predefined baseline neutrophil cut-offs 4.5 × 109/L (NSCLC) and 3.9 × 109/L (OC). Results Absence of chemotherapy-induced nadir neutropenia (CTCAE grade 0, neutrophils?≥?LLN) was seen in 23% of OC and 25% of NSCLC pts. Absence of nadir neutropenia was associated with decreased overall survival (OS) compared with presence (>grade 0) of neutropenia (9 vs. 14?months, P--.004 for NSCLC and 23 vs. 56?months; P--.01 for OC). Obtaining grade 3/4 neutropenia did not improve survival compared with grade 1/2 neutropenia. In multivariate analyses, baseline neutrophils ?.5 × 109/L (HR: 2.0; 95% CI: 1.11-3.44;P = 0.02) and absence of nadir neutropenia (HR: 1.6; 95% CI: 1.02-2.65;P = 0.04) for NSCLC and absence of nadir neutropenia (HR: 1.7; 95% CI: 1.04;2.93;P = 0.04) for OC were independently associated with short OS. Three prognostic neutrophil index (NI) groups were defined. Favourable NI: low baseline neutrophils and presence of nadir neutropenia (>grade 0), Intermediate NI: elevated baseline neutrophils and presence of nadir neutropenia (>grade 0), and Poor NI: elevated baseline neutrophils and absence of nadir neutropenia (grade 0). For NSCLC patients, the median OS was 18.0, 13.4, and 8.8?months for favourable, intermediate and poor NI, respectively (fav vs. poor P--.002; fav vs. intermed P--.04; and intermed vs. poor P--.03). For OC patients, median OS was 69, 52 and 23?months for favourable, intermediate and poor NI, respectively (fav vs. poor P--.03; fav vs. intermed P--.3; and intermed vs. poor P--.02). Interestingly, survival rates in the intermediate NI groups indicated that individualised dose of chemotherapy to induce neutropenia may partly overcome the negative impact of elevated baseline neutrophils. Conclusions A neutrophil index comprising elevated baseline neutrophils and absence of neutropenia identified a high risk group of NSCLC and ovarian cancer patients with only modest effect of chemotherapy. New treatment options for this subset of patients are required.