Radiation Biology

PV QA 1 - Poster Viewing Q&A 1

SU_40_2403 - NLR as a Prognostic Factor in Solid Tumors and in a transplantable solid tumor mouse model

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

NLR as a Prognostic Factor in Solid Tumors and in a transplantable solid tumor mouse model
R. Kabarriti1, Y. Zhang2, T. Savage3, S. Baliga2, P. Brodin1, S. Kalnicki1, M. K. Garg1, and C. Guha4; 1Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, 2Montefiore Medical Center, Bronx, NY, 3Albert Einstein College of Medicine, Riverdale, NY, 4Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY

Purpose/Objective(s): Elevated serum neutrophil-lymphocyte ratio (NLR) has been reported as a poor prognostic biomarker of overall survival (OS) in certain cancers. However, the mechanism associated with the poor outcome remains to be elucidated. Here we investigate the association between elevated NLR at diagnosis and OS in a large database of patients with solid tumors. In pilot studies, we model NLR in a transplantable solid tumor mouse model.

Materials/Methods: We retrospectively reviewed patients diagnosed with solid tumors in our institution between 2005-2016. Elevated NLR was defined as >4.0 and the association with OS was determined using multivariable Cox regression, adjusting for age, gender, ethnicity, socio-economic status, smoking status, Charlson co-morbidity score, stage, and distant metastasis at diagnosis. Hazard ratios (HRs) were calculated for the cohort overall and stratified for either disease site or stage. For the mouse model, we utilized a 4T1 triple negative breast carcinoma. 4T1 cells were injected in the mammary fat pad of female Balb/C mice. We monitored peripheral blood NLR, primary tumor growth, and survival after inoculation without treatment. Initial NLR was measured when a palpable tumor formed and weekly thereafter, with high and low NLR designations being determined based on the median of the animal cohort.

Results: 27,373 patients were included in the analysis. Elevated NLR was an independent predictor of OS with HR of 1.87 (95% CI: 1.76-2.00; p< .001), and also an independent predictor for OS in most individual disease sites (table 1). The association was strongest in anal cancer and mesothelioma. HRs were 1.6, 2.0, 1.6, 1.8 for stage I, II, III, IV respectively (all p<.001). The differences in HRs were significant between disease sites (p=0.01), but not between stages (p=0.14). In the mouse model, NLR did not correlate with tumor size and we found no difference in rate of tumor growth between high and low NLR animals. However, mice with low NLR demonstrated improved OS with increasing log-rank significance (p=0.081, p=0.0561, p=0.027) as tumors progressed. Day 41 OS survival was 43% in the initial low NLR group as compared with 0% in the initial high NLR group (p=0.11). Maintaining a low NLR across all blood draws was associated with a significant improvement in OS (p=0.006). Table 1 (top 9 sites by HR)
Site (n) HR (95% CI)
Anal (304) 4.9 (1.5-15.6)
Mesothelioma (67) 4.5 (1.1-19.0)
Nasopharyngeal (116) 2.6 (0.8-8.2)
Urothelial (883) 2.4 (1.5-3.9)
Prostate (5,439) 2.2 (1.9-2.7)
Breast (8,909) 2.0 (1.7-2.4)
Liver (1,586) 2.0 (1.6-2.4)
NSCLC (645) 1.9 (1.5-2.4)
Gastroesophageal (1,583) 1.8 (1.5-2.2)

Conclusion: An elevated NLR is an independent poor prognostic marker for OS in most solid tumors. In the mouse model, high NLR was also associated with worse OS. Strategies looking at modifying NLR and its impact on survival are ongoing.

Author Disclosure: R. Kabarriti: None. Y. Zhang: None. T. Savage: None. S. Kalnicki: Travel Expenses; Varian Oncology Systems. Committee Member; American College of Radiology. M.K. Garg: Speaker's Bureau; Varian, Covidien. C. Guha: Translational Research Program, Gastrointestinal O; RTOG.

Rafi Kabarriti, MD

Montefiore Medical Center

Presentation(s):

Send Email for Rafi Kabarriti


Assets

SU_40_2403 - NLR as a Prognostic Factor in Solid Tumors and in a transplantable solid tumor mouse model



Attendees who have favorited this

Please enter your access key

The asset you are trying to access is locked. Please enter your access key to unlock.

Send Email for NLR as a Prognostic Factor in Solid Tumors and in a transplantable solid tumor mouse model