Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect.
Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect.
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用新辅助纳武利尤单抗治疗的原发性头颈肿瘤与淋巴结转移之间的不一致反应：放射学和病理治疗效果的相关性。
DOI：
10.3389/fonc.2020.566315
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发表时间：
2020
影响因子：
4.7
通讯作者：
Luginbuhl AJ
中科院分区：
文献类型：
--
作者：
Merlino DJ;Johnson JM;Tuluc M;Gargano S;Stapp R;Harshyne L Jr;Leiby BE;Flanders A;Zinner R;Axelrod R;Curry J;Cognetti DM;Mannion K;Kim YJ;Rodeck U;Argiris A;Luginbuhl AJ
PD-1阻断剂代表了头颈部鳞状细胞癌（HNSCC）患者的一种有前景的治疗方法。我们分析了nivolumab加/减他达拉非的新辅助随机机会窗试验的结果，以研究免疫治疗介导的治疗效果是否因受累部位（原发性肿瘤，淋巴结）而异，并确定放射学肿瘤缩小与病理治疗效果的相关性。入组试验NCT 03238365的44例患者在第1天和第15天接受nivolumab 240 mg静脉给药，伴或不伴口服他达拉非（通过随机分配确定），随后在第31天接受手术。放射学体积反应（RVR）定义为治疗前至治疗后CT扫描肿瘤体积的百分比变化。应答者定义为原发肿瘤或淋巴结（LN）体积减少10%的患者。病理治疗效果（PTE）定义为显示纤维化或淋巴组织细胞炎症的面积除以肿瘤总面积。32例有病理学证据的LN患者中有16例（50%）的原发部位和LN之间的PTE不一致。在4例广泛不一致的邻近LN患者中，PTE增加与肿瘤CD 8 + T细胞和CD 163+巨噬细胞浸润增加相关，而间质调节性T细胞与淋巴结PTE降低相关。RVR与原发肿瘤（斜率= 0.55，p < 0.001）和LN（斜率= 0.62，p < 0.05）的PTE相关。89%（16/18）的T1-T3原发部位影像学无应答者无（n = 7）或极轻微（n = 9）PTE，而15/17（88%）的影像学应答者有中度（n = 12）或完全（n = 3）PTE。纳武单抗通常在受试者的原发性肿瘤部位和转移性淋巴结之间诱导不一致的治疗效果。在相邻淋巴结中也证实了这种治疗不一致性，这可能与局部免疫细胞组成相关。最后，尽管这些数据是由相对较小的人群规模产生的，但我们的数据支持使用早期放射学反应来评估HNSCC的免疫治疗效果。
PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect. Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent change in tumor volume from pretreatment to posttreatment CT scan. Responders were defined as those with a 10% reduction in the volume of the primary tumor or lymph nodes (LN). Pathologic treatment effect (PTE) was defined as the area showing fibrosis or lymphohistiocytic inflammation divided by total tumor area. Sixteen of 32 patients (50%) with pathologic evidence of LN involvement exhibited discordant PTE between primary sites and LN. In four patients with widely discordant adjacent LN, increased PTE was associated with increased infiltration of tumor CD8+ T cells and CD163+ macrophages, whereas stromal regulatory T cells were associated with low nodal PTE. RVR correlated with PTE at both primary tumor (slope = 0.55, p < 0.001) and in LN (slope = 0.62, p < 0.05). 89% (16/18) of radiographic non-responders with T1–T3 primary sites had no (n = 7) or minimal PTE (n = 9), whereas 15/17 (88%) of radiographic responders had moderate (n = 12) or complete (n = 3) PTE. Nivolumab often induces discordant treatment effects between primary tumor sites and metastatic lymph nodes within subjects. This treatment discordance was also demonstrated in adjacent lymph nodes, which may correlate with local immune cell makeup. Finally, although these data were generated by a relatively small population size, our data support the use of early radiographic response to assess immunotherapy treatment effect in HNSCC.
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影响因子：
64.5
作者：
Jiménez-Sánchez A;Memon D;Pourpe S;Veeraraghavan H;Li Y;Vargas HA;Gill MB;Park KJ;Zivanovic O;Konner J;Ricca J;Zamarin D;Walther T;Aghajanian C;Wolchok JD;Sala E;Merghoub T;Snyder A;Miller ML
通讯作者：
Miller ML
DOI：
10.1158/1078-0432.ccr-20-1695
发表时间：
2020-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Uppaluri R;Campbell KM;Egloff AM;Zolkind P;Skidmore ZL;Nussenbaum B;Paniello RC;Rich JT;Jackson R;Pipkorn P;Michel LS;Ley J;Oppelt P;Dunn GP;Barnell EK;Spies NC;Lin T;Li T;Mulder DT;Hanna Y;Cirlan I;Pugh TJ;Mudianto T;Riley R;Zhou L;Jo VY;Stachler MD;Hanna GJ;Kass J;Haddad R;Schoenfeld JD;Gjini E;Lako A;Thorstad W;Gay HA;Daly M;Rodig SJ;Hagemann IS;Kallogjeri D;Piccirillo JF;Chernock RD;Griffith M;Griffith OL;Adkins DR
通讯作者：
Adkins DR
影响因子：
50.5
作者：
Machiels, J. -P.;Bossi, P.;Licitra, L. F.
通讯作者：
Licitra, L. F.
DOI：
10.1002/hed.26022
发表时间：
2019-11-27
影响因子：
2.9
作者：
Sadeghi, Nader;Khalife, Sarah;Siegel, Robert
通讯作者：
Siegel, Robert
影响因子：
8.4
作者：
Tazdait, M.;Mezquita, L.;Caramella, C.
通讯作者：
Caramella, C.