Abstract
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.Patients and MethodsForty-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.ResultsSixteen 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.ConclusionNivolumab 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.
Highlights
Immunotherapy with the use of checkpoint inhibitors targeting PD-1 has demonstrated survival benefit in the first-line and second-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) [1,2,3]
Our study investigated HNSCC patients treated with a brief course of neoadjuvant nivolumab prior to surgical resection and evaluated treatment effect by CT imaging as well as by pathology
Because most patients included in this study had multiple sites of malignancy [primary and lymph node(s)], we had the opportunity to compare treatment effect of nivolumab within individual patients
Summary
Immunotherapy with the use of checkpoint inhibitors targeting PD-1 has demonstrated survival benefit in the first-line and second-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) [1,2,3]. The rapidly-growing interest in PD-1/PD-L1 inhibition for HNSCC and the use of neoadjuvant therapy underscores the unmet need for validated methods to accurately assess treatment response. The gold standard method to evaluate treatment efficacy remains surgical resection and pathologic examination of tumor. An ideal surrogate measure would correlate with pathologic treatment effect, be minimally invasive, permit rapid and inexpensive tumor evaluation, and be compatible with longitudinal tracking of tumor response. The Response Evaluation Criteria in Solid Tumors (RECIST) have been developed to provide a uniform methodology to assess tumor response to therapy relying primarily on imaging modalities [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
