Lymph Nodes Can Be Used to Plan Treatment for Head and Neck Cancer

In planning adjuvant chemoradiotherapy (CRT) in some patients with locally advanced head and neck cancer (LAHNC), the number of positive lymph nodes can be used as a deciding factor, according to the result of a recent retrospective analysis evaluating CRT versus radiotherapy (RT) alone in patients with LAHNC with negative surgical margins (SM negative) and no extracapsular extension (ECE).

In the analysis, the use of CRT was associated with a statistically significant improvement in overall survival (OS) compared with RT alone. Additionally, “Survival benefits of CRT versus RT alone increased in patients with multiple positive lymph nodes,” lead author Daniel Trifiletti, M.D., University of Virginia School of Medicine, and colleagues wrote.

“Findings from this study highlight the importance of further research to refine criteria for adjuvant CRT, novel approaches in the therapeutic index of CRT, as well as an insight regarding provider uncertainty in assigning treatment,” the authors added.

The National Cancer Database was used to identify a subset of 10,870 patients with SM-negative LAHNC and no ECE. Patients diagnosed from 2004 to 2012 with AJCC stage 3 to 4B squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx treated with definitive surgery and adjuvant RT or CRT were evaluated for this retrospective observational cohort study.

Among the evaluated population, 47.3 percent of patients received adjuvant CRT and 52.7 percent received RT alone; additionally, 65.1 percent of patients with pN2c-N3 disease received CRT. The study endpoints were receipt of adjuvant CRT and OS after CRT versus RT alone.

The usage of CRT increased in coordination with the increasing number of nodes involved (28.5 percent, 43.5 percent, 56.3 percent and 74.5 percent for 0, one, two to four and more than five nodes involved, respectively), and 71.0 percent of patients with positive level 4 to 5 nodes received CRT.

Median follow-up was 38.4 months. Clinical factors that were associated with difference in OS were patient age, year of diagnosis, comorbidity index, median income, and insurance status. Among patients with nonoropharyngeal primaries, survival analysis showed a consistent statistically significant OS benefit associate with CRT. CRT OS was also improved among patients with one node positive, two to four nodes, and five or more nodes, respectively, but not in patients with 0 nodes involved.

CRT proved statistically significant in OS as compared to RT alone. And survival benefits in CRT increased in patients with multiple positive lymph nodes compared with RT alone. “This observed association of CRT with improved OS remained statistically significant when using propensity score—based methods adjusting for a large number of prognostic factors and was robust to sensitivity analysis simulating the effects of unmeasured confounding,” the authors noted. “These results provide insight regarding real-world practice patterns in a clinical situation where there is conflicting level 1 evidence and provider uncertainty regarding optimal treatment.”

Survival differed among patients depending on number of positive lymph nodes, which, according to the authors, may be used as a selection factor for future studies.

Currently, adjuvant CRT is the recommended treatment for patients with LAHNC with ECE or that are SM positive. This treatment was determined from 2 randomized controlled trials, RTOG 95-01 and EORTC 22931.

Results of RTOG 95-01 showed that after two years, CRT significantly improved locoregional control and disease-free survival, but not OS. Results showed that after 10 years, CRT only benefited patients with ECE or SM positive. This study involved patients with resected LAHNC and were SM positive, ECE or had two or more lymph nodes involved.

The results of the EORTC 22931 trial reported improved progression-free survival and OS at five years in patients randomly assigned to adjuvant CRT. This evidence conflicted with RTOG 95-01, which has made it difficult for practitioners to select patients for adjuvant CRT based on these trials.