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

Abstract

BackgroundChronic inflammation has been recognized to foster tumour development. Whether chemotherapy can be used to neutralize chronic inflammation is unclear.MethodsWe 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).ResultsAbsence 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 = 0.004 for NSCLC and 23 vs. 56 months; P = 0.01 for OC). Obtaining grade 3/4 neutropenia did not improve survival compared with grade 1/2 neutropenia. In multivariate analyses, baseline neutrophils ≥4.5 × 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 = 0.002; fav vs. intermed P = 0.04; and intermed vs. poor P = 0.03). For OC patients, median OS was 69, 52 and 23 months for favourable, intermediate and poor NI, respectively (fav vs. poor P = 0.03; fav vs. intermed P = 0.3; and intermed vs. poor P = 0.02). 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.ConclusionsA 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.

Chemotherapy-induced neutropenia as a prognostic factor in patients with unresectable pancreatic cancer

“…Similarly, it has been suggested that neutropenia is associated with good prognosis in first-line treatment for other types of cancers [15][16][17][18][19][20][21][22][23][24][25]. In addition, in the present study, all patients in the first-line treatment group exhibited prolonged OS for grades 1-3, with particularly good survival for grades 2 and 3.…”

“…Subsequent reports described similar outcomes for nonsmall cell lung cancer [17][18][19], gastric cancer [20], colorectal cancer [21,22], and ovarian cancer [19,23]. These reports suggest that neutropenia could be a predictive factor of treatment responsiveness.…”

“…In this study, grade of neutropenia has been using nadir during all GEM courses similar to the methodology of other studies [17][18][19][20][21][22][23]. Among the 99 subjects who experienced neutropenia in the first-line population, 71 patients (72 %) have reached the nadir in neutropenia of first course, and 89 (90 %) patients have reached the nadir until the second course.…”

Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: An exploratory study of the Gynecologic Oncology Group

“…Because an association between C-iN and improved PFS was not observed, post-progression therapy may have a greater, if as yet poorly understood, impact among neutropenic patients, but this is just conjecture. Nevertheless, these results are consistent with the observations reported by others who have noted that C-iN is positively correlated with patient outcomes in a variety of solid tumors including non-small cell lung, colorectal, gastric, breast, cervical, and ovarian cancer [11][12][13][14][15][16][17][18][19][20][21]. Shitara et al conducted a meta-analysis comprised of 9528 patients from 13 prospective and retrospective studies that evaluated neutropenia or leucopenia as a prognostic factor for survival [21].…”

Predictive value of inflammatory indexes on the chemotherapeutic response in patients with unresectable lung cancer: A retrospective study

“…Cancer may induce an inflammatory state, resulting in multiple inflammatory cells being recruited to the cancer microenvironment, and contributing to the hallmarks of cancer (16,17). Notably, indexes of inflammatory cells [including the pretreatment neutrophil count (PNC), macrophage, neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR)] in the bloodstream can reflect the scope and extent of inflammation (18,19). Previous studies have reported that elevations in the PNC, NLR or PLR indicate a poor prognosis in various human cancer types, most notably in colorectal cancer (19), hepatocellular carcinoma (20), and in gastric (21), esophageal (22), breast (23,24), ovarian (25), cervical (26) and lung cancer (27,28).…”