Prognostic impact of lymphopenia and neutrophil-lymphocyte ratio for patients with anal squamous cell carcinoma

Brian De, Ethan B. Ludmir, Craig A. Messick, Matthew C. Cagley, Van K. Morris, Prajnan Das, Bruce D. Minsky, Cullen M. Taniguchi, Grace L. Smith, Eugene J. Koay, Albert C. Koong, Radhe Mohan, Emma B. Holliday

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: Outcomes after definitive chemoradiation for squamous cell carcinoma are generally favorable. However, biomarkers to further yield prognostic information are desired. Treatment-related lymphopenia as well as an elevated baseline neutrophil-lymphocyte ratio have been associated with worse survival in several cancer types. We evaluated absolute lymphocyte count and neutrophil-lymphocyte ratio at baseline and at treatment-related nadir in patients with anal cancer for associations with oncologic endpoints. Methods: We conducted a retrospective analysis of 428 consecutive patients with non-metastatic anal cancer treated with definitive, intensity-modulated radiation therapy-based chemoradiation. We analyzed absolute neutrophil and lymphocyte counts at several timepoints: pretreatment, weekly during treatment, and in the six weeks following treatment completion. Neutrophil-lymphocyte ratio was calculated at baseline and treatment-related nadir. We estimated oncologic endpoints using life tables and compared them using the log-rank test. We conducted univariate and multivariable time-to-event analyses using Cox proportional hazards. Results: Median absolute lymphocyte count at baseline and nadir were 1.80 [interquartile range (IQR), 1.45–2.32] k/µL and 0.26 (IQR, 0.18–0.36) k/µL, respectively, and 31% developed treatment-related grade 4 lymphopenia. Median neutrophil-lymphocyte ratio at baseline and nadir were 2.34 (IQR, 1.68–3.30) and 8.80 (IQR, 5.86–12.68), respectively. Estimates of overall survival, local failure-free survival, distant metastasis-free survival (DMFS), and freedom from colostomy at 5 years were 87%, 86%, 82%, and 88%, respectively. Baseline and nadir absolute lymphocyte count were not associated with selected outcomes on univariate analysis. On multivariable analysis, factors independently associated with death included T3-T4 disease, HIV-positive status, treatment break, and baseline neutrophil-lymphocyte ratio >3. Baseline neutrophil-lymphocyte ratio showed a trend toward association with distant progression or death (P=0.07). The 5-year overall survival estimates for patients with baseline neutrophil-lymphocyte ratios ≤3 and >3 were 92.3% and 80.6%, respectively. Conclusions: Lymphopenia during and after chemoradiation for anal cancer is common but does not appear to be associated with worse survival, recurrence, or metastases. However, elevated baseline neutrophil-lymphocyte ratio was independently associated with overall survival, local recurrence-free survival, and DMFS. Further studies are needed to determine the clinical utility of baseline neutrophil-lymphocyte ratio to guide treatment and follow-up.

Original languageEnglish (US)
Pages (from-to)2412-2422
Number of pages11
JournalJournal of Gastrointestinal Oncology
Issue number5
StatePublished - Oct 2021


  • Anal cancer
  • Lymphopenia
  • Neutrophil
  • Neutrophil-to-lymphocyte ratio (NLR)
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology


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