Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer.

OBJECTIVE: To investigate the neutrophil-to-lymphocyte ratio (NLR) from peripheral blood, a general measure of inflammation, in ovarian cancer. METHODS: White cell counts and CA125 levels before treatment, tumor features, and questionnaire data on 519 women with ovarian cancer at two Boston hospitals were recorded. Counts were log-transformed and effects on these by tumor features and epidemiologic variables assessed by analysis of variance and generalized linear models. Cox proportional hazards models were used to assess effects on overall survival. RESULTS: Greater NLR was associated with higher tumor stage and grade, presence of ascites, and bilateral disease and correlated with risk factors including Jewish ethnicity, taller height, more ovulatory cycles, and family history of cancer in premenopausal women and talc use in all women. CA125 was positively correlated with neutrophil count, monocyte count, and NLR and inversely correlated with lymphocyte count. In a multivariate adjusted analysis, high NLR predicted poorer survival and high lymphocyte count better survival. CONCLUSION: An elevated NLR before treatment signals more aggressive disease and correlates with risk factors for ovarian cancer. CA125 directly correlates with neutrophils which may reflect secretion of both CA125 and neutrophilic growth factors by the tumor. CA125 inversely correlates with lymphocytes which may reflect the ability of some neutrophilic factors to induce lymphopenia and/or binding of CA125 to lymphocytes removing CA125 from the serum pool. Links between NLR, CA125, and epidemiologic factors may provide new clues about the pathogenesis and progression of ovarian cancer.

Does neoadjuvant chemotherapy decrease the risk of hospital readmission following debulking surgery?

OBJECTIVE: To compare primary debulking surgery (PDS) vs. neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) among elderly patients with ovarian/fallopian tube/primary peritoneal carcinoma. METHODS: Medical records of patients ≥70 years old with epithelial ovarian/fallopian tube/primary peritoneal carcinoma between January 2000 and December 2010 were reviewed. Patients were separated by PDS or NACT-IDS. Preoperative characteristics, surgical procedures and postoperative and oncologic outcomes were compared. Surgical procedures were given a complexity score based on a previously published method. RESULTS: Of 165 patients, 125 (75.8%) underwent PDS and 40 (24.2%) underwent NACT-IDS. Patients undergoing NACT-IDS were more likely to have a pleural effusion (without cytology) and stage 4 disease. Median CA-125 at diagnosis was greater for those undergoing NACT-IDS. The NACT-IDS group was associated with less intraoperative blood loss (250 vs. 400 mL, p=0.001), a greater chance of achieving no residual disease (40% vs. 16%, p=0.005) and a shorter hospital length of stay (LOS) (5 vs. 7 days, p<0.001). PFS (17 vs. 15 months, p=0.708) and OS (29 vs. 33 months, p=0.827) were similar between the two groups. Readmission rates within 30 days of surgery were greater in those undergoing PDS (17.6% vs. 2.5%, p=0.016). After readmission, the median hospital LOS was 6 days (range: 1-41). CONCLUSIONS: Elderly patients undergoing PDS have similar oncologic outcomes when compared to patients undergoing NACT-IDS. The risk of readmission within 30 days of surgery is significantly greater among patients undergoing PDS.

Preoperative leukocytosis imposes an increased risk of recurrence and death among patients with nonendometrioid endometrial carcinoma.

OBJECTIVE: To evaluate the impact of preoperative leukocytosis among patients with nonendometrioid endometrial carcinoma. METHODS: The medical records of all patients with nonendometrioid endometrial carcinoma who underwent surgical treatment between January 2005 and December 2010 were retrospectively reviewed. The patients were separated into 2 groups based on the presence or absence of preoperative leukocytosis (white blood cell count ≥ 10,000/µL). The groups were then compared with respect to pathologic findings, progression-free survival, and overall survival. RESULTS: A total of 222 patients were identified, and preoperative leukocytosis was observed in 33 patients (14.9%). The leukocytosis group was associated with a larger mean size of the primary tumor (6.8 vs 4.6 cm, P = 0.016) and a greater percentage of patients with cervical stromal involvement (36.4% vs 20.1%, P = 0.039), adnexal involvement (42.4% vs. 22.8%, P = 0.017), and pelvic/para-aortic lymph node involvement (50% vs 27.4%, P = 0.025). On multivariate analysis, preoperative leukocytosis was independently associated with an increased risk of recurrence (hazard ratio, 2.07; 95% confidence interval, 1.12-3.84) and an increased risk of death (hazard ratio, 3.33; 95% confidence interval, 2.01-5.53). CONCLUSIONS: Among patients with nonendometrioid endometrial carcinoma, preoperative leukocytosis is independently associated with an increased risk of recurrence and death.

Polymorphisms of MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival.

OBJECTIVE: To examine single nucleotide polymorphism (SNPs) in MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival. METHODS: We genotyped germline variants of MUC16 (rs2547065, rs1559168, rs12984471, rs2121133) and MUC1 (rs2070803, rs4072037, rs1045253) using samples collected from 758 ovarian cancer cases and 788 controls enrolled in the New England Case-Control Study between 2003 and 2008. We calculated age-adjusted odds ratios (OR) and 95% confidence intervals (CIs) for disease risk using unconditional and polytomous logistic regression and hazard ratios (HR) for survival using Cox proportional hazard ratios. In a subset of cases, we compared log-normalized CA125 values by genotype using generalized linear models. RESULTS: Cases homozygous for the variant allele of MUC16 SNP, rs12984471, had poorer overall survival (log-rank p = 0.03) and higher CA125 levels, especially cases over age 65 (p = 0.01). For MUC1 SNP, rs4072037, women homozygous for the G variant had a non-significantly decreased risk for serous invasive types but elevated risk for serous borderline tumors, mucinous borderline and invasive tumors, and endometrioid tumors. Women with the variant allele of MUC16 SNP, rs2547065, especially those who were homozygous had an elevated risk for ovarian cancer; but this association was not confirmed in an independent dataset. CONCLUSION: This targeted screen of seven polymorphisms of MUC16 and MUC1 genes failed to identify and confirm effects on ovarian cancer risk overall. However, there may be effects of MUC16 rs12984471 on survival and MUC1 rs4072037 on risk for histologic types of ovarian cancer other than invasive serous. Further study is warranted.