Lymphocyte Kinetics and Outcomes After Comprehensive Involved-Site Radiotherapy for Oligometastases
Purpose/Objective(s):
Lymphopenia is a common adverse event following radiotherapy but its prognostic relevance following comprehensive involved-site radiation (ISRT) for oligometastatic disease is unknown. We evaluated lymphocyte kinetics after ISRT for oligometastases and tested whether treatment-related lymphopenia was associated with modified progression-free survival (mPFS) and overall survival (OS).
Materials/Methods:
We performed a single-institution registry study of consecutive patients with oligometastases (defined as 1 to 5 distant metastases) treated with comprehensive ISRT by a single radiation oncologist from 2014 to 2023. Systemic therapy was administered at clinician discretion. Absolute lymphocyte count (ALC) was collected at baseline, during radiation and at 1, 3 and 12 months post-radiation. Lymphopenia was graded using CTCAE v5.0 (grade 1, ALC<1000 cells/µl; grade =3, ALC <500 cells/µl). OS and mPFS (defined as death or metastatic progression not salvageable with further local therapy) were estimated by the Kaplan-Meier method and multivariable associations were evaluated using Cox proportional-hazards models.
Results:
Among 177 patients, median follow-up for surviving patients was 44.0 months. Five-year OS was 39.6% with a median OS of 42.8 months. Median ALC declined from 1400 cells/µl at baseline (IQR, 952-1900) to 800 cells/µl during radiotherapy (IQR, 490-1190; p<0.001) and 700 cells/µl at a median of 22 days after radiation (IQR, 426-1112; p<0.01). There was partial recovery to 1000 cells/µl at 3 months (IQR, 581-1310; p<0.001) and 1000 cells/µl at 1 year (IQR 790-1400; p=0.002). The proportion with ALC <500 cells/µl was 4% at baseline and 4% at 1 year. Baseline ALC <1000 cells/µl was associated with OS on univariable analysis (p=0.04), whereas development of any lymphopenia (p=0.82) or grade ³3 lymphopenia (p=0.64) was not associated with OS. On multivariable analysis, albumin (HR 1.8; p=0.01), liver metastases (HR 2.1; p=0.02) and ECOG performance status (HR 1.6; p=0.04) independently predicted OS, but baseline ALC did not reach statistical significance (HR 1.5; p=0.10).
Conclusion:
Comprehensive ISRT for oligometastatic disease was associated with a sustained decrease in median ALC. In this heterogenous cohort, treatment-related lymphopenia was not independently associated with mPFS or OS after adjustment for established prognostic factors.
