Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, 48202, USA.
Department of Radiation Oncology, Henry Ford Cancer Institute, Detroit, MI, 48202, USA.
BMC Cancer. 2022 Jun 7;22(1):626. doi: 10.1186/s12885-022-09708-9.
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 intensifies RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, has been associated with lower rates of anemia for locally advanced head and neck squamous cell carcinoma (HNSCC). We hypothesized that concomitant cetuximab could prevent RT-induced anemia.
We queried our institutional head and neck cancers database for non-metastatic HNSCC cases that received RT with concomitant cetuximab or RT-only between 2006 and 2018. Cetuximab was administered for some high-risk cases medically unfit for platinum agents per multidisciplinary team evaluation. We only included patients who had at least one complete blood count in the 4 months preceding and after RT. We compared the prevalence of anemia (defined as hemoglobin (Hb) below 12 g/dL in females and 13 g/dL in males) and mean Hb levels at baseline and after RT. Improvement of anemia/Hb (resolution of baseline anemia and/or an increase of baseline Hb ≥1 g/dL after RT), and overall survival (OS) in relation to anemia/Hb dynamics were also compared.
A total of 171 patients were identified equally distributed between cetuximab-plus-RT and RT-only groups. The cetuximab-plus-RT group had more locally-advanced stage, oropharyngeal and high grade tumors (p < 0.001 for all). Baseline anemia/Hb were similar, however anemia after RT conclusion was higher in the cetuximab-plus-RT vs RT-only (63.5% vs. 44.2%; p = 0.017), with a mean Hb of 11.98 g/dL vs. 12.9 g/dL; p = 0.003, for both respectively. This contributed to significantly worse anemia/Hb improvement for cetuximab-plus-RT (18.8% vs. 37.2%; p = 0.007). This effect was maintained after adjusting for other factors in multivariate analysis. The prevalence of iron, vitamin-B12 and folate deficiencies; and chronic kidney disease, was non-different. Baseline anemia was associated with worse OS (p = 0.0052) for the whole study cohort. Nevertheless, improvement of anemia/Hb was only marginally associated with better OS (p = 0.068).
In contrast to previous studies, cetuximab was not associated with lower rates of anemia after RT for nonmetastatic HNSCC patients compared to RT-alone. Dedicated prospective studies are needed to elucidate the effect of cetuximab on RT-induced anemia.
表皮生长因子受体 (EGFR) 的激活与白细胞介素 6 (IL6) 的产生增加有关，而放射治疗 (RT) 引起的炎症反应会加剧这种情况。升高的 IL6 水平通过上调铁调素导致功能性缺铁，从而加剧 RT 引起的贫血。西妥昔单抗是一种 EGFR 抑制剂，与局部晚期头颈部鳞状细胞癌 (HNSCC) 的贫血发生率较低有关。我们假设同时使用西妥昔单抗可以预防 RT 引起的贫血。
我们在机构头颈部癌症数据库中查询了 2006 年至 2018 年间接受 RT 联合西妥昔单抗或单纯 RT 的非转移性 HNSCC 病例。根据多学科团队评估，对于一些不适合铂类药物的高危病例，给予西妥昔单抗进行治疗。我们仅纳入了在 RT 前后 4 个月内至少有一次完整血细胞计数的患者。我们比较了贫血（定义为女性血红蛋白 (Hb) 低于 12g/dL，男性低于 13g/dL）的发生率和 RT 前后的平均 Hb 水平。还比较了贫血/Hb 的改善（基线贫血的缓解和/或 RT 后 Hb 增加≥1g/dL）以及与贫血/Hb 动态相关的总生存期 (OS)。
共确定了 171 例患者，他们在西妥昔单抗联合 RT 组和单纯 RT 组中平均分配。西妥昔单抗联合 RT 组的局部晚期、口咽和高级别肿瘤比例更高（所有肿瘤均为 p<0.001）。RT 前后的基线贫血/Hb 相似，但 RT 后西妥昔单抗联合 RT 组的贫血发生率高于单纯 RT 组（63.5% vs. 44.2%；p=0.017），平均 Hb 分别为 11.98g/dL 和 12.9g/dL；p=0.003）。这导致西妥昔单抗联合 RT 组的贫血/Hb 改善明显更差（18.8% vs. 37.2%；p=0.007）。这一效应在多变量分析中调整其他因素后仍然存在。缺铁、维生素 B12 和叶酸缺乏症以及慢性肾病的患病率没有差异。基线贫血与整个研究队列的 OS 较差有关（p=0.0052）。然而，贫血/Hb 的改善仅与 OS 略有相关（p=0.068）。
与之前的研究相比，与单纯 RT 相比，西妥昔单抗在非转移性 HNSCC 患者中并未降低 RT 后贫血的发生率。需要专门的前瞻性研究来阐明西妥昔单抗对 RT 诱导性贫血的影响。
