Park Ji Hyun, Chun Sang Hoon, Lee Yun-Gyoo, Chang Hyun, Lee Keun-Wook, Kim Hye Ryun, Shin Seong Hoon, An Ho Jung, Lee Kyoung Eun, Hwang In Gyu, Ahn Myung-Ju, Kim Sung-Bae, Keam Bhumsuk
Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of Korea.
J Cancer Res Clin Oncol. 2020 Dec;146(12):3359-3369. doi: 10.1007/s00432-020-03316-5. Epub 2020 Jul 15.
Although immune-checkpoint inhibitors (ICIs) have emerged as therapeutic options for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M-HNSCC), concerns have been raised on exceptional acceleration of tumor growth during treatment with ICIs, a condition described as hyperprogressive disease (HPD). This study examined the incidence, potential predictors, and clinical impact of HPD in R/M-HNSCC.
We retrospectively collected data of patients with R/M-HNSCC treated with ICIs between January 2013 and June 2018 from 11 medical centers in Korea. HPD was defined as tumor growth kinetics ratio (TGKr) > 2, which was calculated by comparing TGK on ICIs with that before treatment with ICIs.
Of 125 patients, 68 (54.4%) obtained progressive disease as their best responses (progressors). HPD was identified in 18 (26.5% of progressors, 14.4% of total) patients. Relatively younger age, primary tumor of oral cavity, and previous locoregional irradiation were significant predictors of HPD according to multivariable analysis (p = 0.040, 0.027, and 0.015, respectively). Compared to patients without HPD, patients with HPD had significantly shorter median progression-free survival (PFS) (1.2 vs. 3.4 months, p < 0.001) and overall survival (OS) (3.4 vs. 10.7 months, p = 0.047). However, interestingly, HPD did not significantly affect the therapeutic benefit of post-ICIs chemotherapy.
Younger patients with oral cavity cancer or prior treatment with locoregional radiotherapy could be regarded potential risk groups for HPD in patients with R/M-HNSCC treated with ICIs. Although HPD could consistently predict poorer survival outcomes, patients who experienced HPD with ICIs should not be excluded from the subsequent salvage chemotherapy treatments.
尽管免疫检查点抑制剂（ICIs）已成为复发和/或转移性头颈部鳞状细胞癌（R/M-HNSCC）的治疗选择，但人们对ICIs治疗期间肿瘤生长异常加速（一种被称为超进展性疾病（HPD）的情况）表示担忧。本研究调查了R/M-HNSCC中HPD的发生率、潜在预测因素及临床影响。
我们回顾性收集了2013年1月至2018年6月期间韩国11个医疗中心接受ICIs治疗的R/M-HNSCC患者的数据。HPD定义为肿瘤生长动力学比率（TGKr）>2，该比率通过比较ICIs治疗时的TGK与ICIs治疗前的TGK来计算。
125例患者中，68例（54.4%）的最佳反应为疾病进展（进展者）。18例（进展者中的26.5%，总数的14.4%）患者被确定为HPD。多变量分析显示，相对年轻的年龄、口腔原发性肿瘤和先前的局部区域放疗是HPD的显著预测因素（p分别为0.040、0.027和0.015）。与无HPD的患者相比，HPD患者的中位无进展生存期（PFS）显著缩短（1.2个月对3.4个月，p<0.001），总生存期（OS）也显著缩短（3.4个月对10.7个月，p=0.047）。然而，有趣的是，HPD对ICIs后化疗的治疗获益没有显著影响。
患有口腔癌的年轻患者或先前接受过局部区域放疗的患者可被视为接受ICIs治疗的R/M-HNSCC患者中HPD的潜在风险群体。尽管HPD可始终预测较差的生存结果，但经历ICIs治疗后出现HPD的患者不应被排除在后续的挽救性化疗治疗之外。
