Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
Department of Biostatistics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
Oral Oncol. 2020 Dec;111:104853. doi: 10.1016/j.oraloncology.2020.104853. Epub 2020 Aug 14.
Improved prognosis for p16+ oropharyngeal squamous cell carcinoma (OPSCC) has led to efforts to mitigate long-term complications of treatment, which remains poorly defined in late survivors. Here we characterize very late dysphagia in OPSCC.
Long-term review of 93 p16+ OPSCC patients treated with chemoradiation was performed. We scored videofluoroscopic swallow studies (VFSS) according to the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale. Very late dysphagia was defined >2.5 years from end of treatment. Fine-Gray regression models were used to assess dysphagia with competing risk of death.
Median follow up was 10.5 years. 402 total VFSS were assessed (median 4 per patient, range 0-8). 15.1% of patients had a DIGEST score ≥2 very late after treatment. Very late DIGEST score ≥2 correlated with T-stage (HR 1.7, p = 0.049), second cancer (HR 6.5, p = 0.004), superior pharyngeal constrictor dose (HR 1.11, p = 0.050), total tongue dose (HR 1.07, p = 0.045), but not hypoglossal nerve dose (p > 0.2). Seven patients (7.5%) had late progressive dysphagia, defined as DIGEST score that increased by ≥2 beyond one year after treatment, and this correlated with higher ipsilateral hypoglossal nerve D1cc dose (75 vs 72 Gy, p = 0.037).
In p16+ OPSCC patients treated with definitive chemoradiation, at least 7.5% developed late progressive dysphagia, and 15.1% experienced moderate dysphagia >2.5 years from treatment. Our study suggests that dose to tongue musculature may be associated with very late dysphagia, and hypoglossal nerve dose may be associated with late progressive dysphagia. More intensive long-term dysphagia survivorship monitoring is suggested.
p16+口咽鳞状细胞癌（OPSCC）患者预后的改善促使人们努力减轻治疗的长期并发症，但在晚期幸存者中，这些并发症仍未得到明确界定。在此，我们对 OPSCC 患者的极晚期吞咽困难进行了研究。
对 93 例接受放化疗的 p16+OPSCC 患者进行了长期回顾性研究。我们根据动态吞咽毒性影像学分级（DIGEST）量表对视频荧光透视吞咽研究（VFSS）进行评分。极晚期吞咽困难定义为治疗结束后>2.5 年。采用 Fine-Gray 回归模型评估有死亡竞争风险的吞咽困难情况。
中位随访时间为 10.5 年。共评估了 402 份 VFSS（每位患者的中位数为 4 份，范围为 0-8 份）。15.1%的患者在治疗后极晚期出现 DIGEST 评分≥2。极晚期 DIGEST 评分≥2 与 T 分期（HR 1.7，p=0.049）、第二原发癌（HR 6.5，p=0.004）、上咽缩肌剂量（HR 1.11，p=0.050）、总舌剂量（HR 1.07，p=0.045）相关，但与舌下神经剂量无关（p>0.2）。7 例（7.5%）患者出现晚期进行性吞咽困难，定义为治疗后 1 年以上 DIGEST 评分增加≥2，且与同侧舌下神经 D1cc 剂量较高相关（75 与 72 Gy，p=0.037）。
在接受根治性放化疗的 p16+OPSCC 患者中，至少有 7.5%的患者出现晚期进行性吞咽困难，15.1%的患者在治疗结束后 2.5 年以上出现中度吞咽困难。我们的研究表明，舌肌的剂量可能与极晚期吞咽困难有关，而舌下神经的剂量可能与晚期进行性吞咽困难有关。建议加强对晚期吞咽困难患者的长期生存监测。
