(P 199) A STUDY OF PRE- AND POST-TREATMENT NEUTROPHIL COUNTS, LYMPHOCYTE COUNTS, AND NEUTROPHIL-TO-LYMPHOCYTE RATIOS IN PATIENTS WITH SOFT TISSUE SARCOMA UNDERGOING RADIOTHERAPY

Author(s)

Eric C. Ku, MD

Resident Physician
Department of Radiation Oncology, University of California Irvine
Orange, California, United States

Co-Author(s)

GH

Garrett Harada, MD

Department of Radiation Oncology, University of California Irvine
Orange, California, United States
EC

Elaine J. Chiao, BS

Medical Student
School of Medicine, University of California Irvine
Chino Hills, California, United States
PR

Pranathi Rao, BS

School of Medicine, University of California Irvine
Irvine, California, United States
SS

Steven Seyedin, MD

Department of Radiation Oncology, University of California Irvine
Orange, California, United States
EH

Erin Healy, MD

Department of Radiation Oncology, University of California Irvine
orange, California, United States
PM

Peter Maxim, PhD

Department of Radiation Oncology, University of California Irvine
Orange, California, United States
Warren Chow, MD (he/him/his)

HS Clinical Professor
Department of Hematology/Oncology, University of California Irvine
Orange, California, United States
RS

Russell Stitzlein, MD

Assistant Clinical Professor
Department of Orthopedic Surgery, University of California Irvine
Orange, California, United States
JH

Jeremy Harris, MD

Assistant Professor
Department of Radiation Oncology, University of California Irvine
Orange, California, United States

Objective: Elevated neutrophil counts and lower lymphocyte counts are established markers of worse radiotherapy (RT) outcomes in numerous cancers, but their incidence and effects are unknown in soft-tissue sarcomas (STS). Radiation-induced depletion of lymphocytes is thought to negatively impact outcomes by impairing host immune response and treatment efficacy. High neutrophil count prior to and during radiation is thought to modulate both T cell-dependent and independent pathways promoting radioresistance.

The goals of this study were to determine the association between oncologic outcomes and routinely collected hematologic specimens, including neutrophil and lymphocyte counts, for patients undergoing radiotherapy for STS.

Methods: This study was a retrospective review of 60 patients who had undergone either preoperative, postoperative, or definitive RT for STS at a single academic institution between September 2009 and March 2022. Absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and neutrophil-to-lymphocyte ratio (NLR) were measured pre-treatment as well as at 3 months, 6 months, and 12 months post-RT. Kaplan-Meier methods were used to estimate PFS and OS. Univariate and multivariate Cox proportional hazard models and log-rank tests were used to determine factors associated with overall survival (OS) and disease-free survival (DFS).

Results: Median age was 59 years old with median follow-up of 23 months (Table 1). Stage I cancer was present in 20% (n = 12), Stage II in 8% (n = 5), Stage III in 68% (n = 41), and Stage IV in 3% (n = 2, all due to N1 disease). Grade 2 disease was found in 7% (n = 4), Grade 3 in 73% (n = 44), and unknown grade in 12% (n = 7). Chemotherapy was delivered to 45% (n = 27) and surgery performed on 68% (n = 41). Median RT dose was 50 Gy (range 45-78 Gy), and IMRT was used for 68% (n = 41).

Pre-treatment ANC median was 4700 cells/µL (range 1600-12,000), pre-treatment ALC median was 1700 cells/µL (range 600-3400), and pre-treatment NLR median was 2.78 (range 1.95 to 14.33). Post-RT ALC nadir median was 1000 cells/µL (range 40-2400).

For the entire cohort, median DFS was 16 months and median OS was 23 months. Median DFS was 7 months versus 20 months for patients with pre-treatment ANC greater or less than median (p = 0.01). Median DFS was 7 months versus 20 months for patients with pre-treatment NLR greater or less than median (p = 0.007). Median DFS was 21 months versus 8 months with ALC nadir greater or less than 500 cells/µL (p < 0.001).

Advanced T-stage, receipt of chemotherapy, lack of surgery, larger PTV volume, higher pre-treatment ANC, lower pre-treatment ALC, higher pre-treatment NLR, and lower ALC nadir were all associated with worse DFS (Table 2; Figure 1,2). On multivariate regression controlling for receipt of chemotherapy and surgery, pre-treatment ANC (HR 1.02 CI 1.00-1.04), pre-treatment NLR (HR 1.36 CI 1.15-1.60) remained associated with DFS but pre-treatment ALC and ALC nadir did not. When also controlling for ALC nadir, the associations with pre-treatment ANC and pre-treatment NLR remained significant.

Receipt of chemotherapy, lack of surgery, pre-treatment NLR, and lower ALC nadir were associated with worse OS. On multivariate regression, pre-treatment NLR (HR 1.22 CI 1.00-1.50) and lower ALC nadir (HR 0.88 CI 0.78-0.99) remained associated with worse OS.

Conclusion: Higher pre-treatment ANC and NLR were associated with worse DFS while pre-treatment NLR and lower ALC nadir were associated with worse OS in STS. These findings support the growing literature from other cancers and suggest that routinely collected blood samples may be used for prognostic biomarkers in STS. Future work should focus on large, multi-center analyses to better characterize cutoff values and incorporate ANC, NLR, and ALC nadir into prognostic models.

Table 1 Patient Characteristics.xlsx

Table 2. Univariate Cox Proportional Hazards Regression of Clinical Factors associated with OS and DFS.xlsx