Purpose/Objective(s): Epidermal growth factor receptor (EGFR) activation is associated with increased production of interleukin 6 (IL6), which is intensified by radiotherapy (RT) induced inflammatory response. Elevated IL6 levels promote RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, resulted in significantly lower rates of RT induced anemia for locally advanced head and neck squamous cell carcinoma (HNSCC) patients receiving definitive RT vs RT-alone according to Bonner et al; and other studies compared to concomitant chemotherapy. However, little is known for cases receiving cetuximab with RT in the adjuvant setting.
Materials/Methods: We queried our institutional HNSCC database for surgically staged non-metastatic cases that received adjuvant RT with or without concomitant cetuximab between 2006-2018. Cetuximab was administered for some high-risk cases medically unfit for platinum agents per multidisciplinary team evaluation. All included patients need to have at least one complete blood count pre- and post-RT end. We compared RT-cetuximab vs RT-alone for prevalence of baseline and post-RT anemia, defined as Hb below 12g/dL in females and 13g/dL in males, and mean hemoglobin (Hb) levels. We also assessed the improvement in Hb level post-RT (resolution of baseline anemia or Hb increase of at least 1g/dL above baseline), in addition to overall survival (OS) in relation to anemia/Hb dynamics.
Results: We were able to identify 66 patients who fit our inclusion criteria, of which 27 (41%) received RT-cetuximab, with the remaining receiving RT-alone (n=39, 59%). Median age was 62.5 years (range, 34-88 years), males 80%, black 29%, and 85% had a smoking history. The majority of cases (73%) were locally advanced. Oral cavity and oropharynx were the most common subsites (37.5% each), with HPV+ve cases representing 52% of the later. The study groups were well-balanced, except for higher rates of positive final surgical margins, and extracapsular space invasion and median RT dose (p\u3c0.05). Baseline anemia was diagnosed in 70.4% in RT-cetuximab vs 76.9% in the RT-alone, p=0.76; with similar mean Hb level (11.7g/dL in both). Meanwhile, baseline iron, vitamin-B12 and folate deficiencies, and chronic kidney disease were non-different. After completion of RT, mean Hb was significantly higher in the RT-alone (12.9±1.4 g/dL) compared to RT-Cetuximab (11.9±2.1 g/dL), p=0.02. Nevertheless, higher anemia levels (70% vs 51%) and lower improvement of Hb post-RT (81.5% vs 92.3%) were both non-significant for RT-cetuximab vs RT-alone respectively, p\u3e0.05 for both. On multivariate analysis, baseline anemia was associated with worse OS (p=0.0052), unlike improvement of Hb post-RT (p=0.14) with a corresponding better improvement of Hb (56.4% vs. 25.9%, p=0.014), albeit lower anemia levels (70% vs. 51%), was non significant (p=0.195). On multivariate analysis, lack of baseline anemia was associated with better OS (p=0.0052), whereas improvement of Hb post-RT was only marginal (p=0.068).
Conclusion: In a homogenous cohort of HNSCC patients treated postoperatively, concomitant cetuximab was not associated with lower RT-induced anemia, in contrast to previous studies
