Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck

Brian J. Park; Austin K. Mattox; Daniel Clayburgh; Mihir Patel; R. Bryan Bell; Bevan Yueh; Rom Leidner; Hong Xiao; Marcus Couey; Shiting Li; Tingting Qin; Maureen A. Sartor; Belinda Cairns; Tracy MacDonough; Kyle Halliwill; Daniel Deschler; Derrick T. Lin; William C. Faquin; Peter M. Sadow; Sara I. Pai

doi:10.1016/j.oraloncology.2022.106183

Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck

Brian J. Park, Austin K. Mattox, Daniel Clayburgh, Mihir Patel, R. Bryan Bell, Bevan Yueh, Rom Leidner, Hong Xiao, Marcus Couey, Shiting Li, Tingting Qin, Maureen A. Sartor, Belinda Cairns, Tracy MacDonough, Kyle Halliwill, Daniel Deschler, Derrick T. Lin, William C. Faquin, Peter M. Sadow, Sara I. Pai

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4 Scopus citations

Abstract

PD-L1 testing guides therapeutic decision-making for head and neck squamous cell carcinoma (HNSCC). We sought to understand whether chemoradiation therapy (CRT) influences the PD-L1 combined positive score (CPS) and other biomarkers of response to immunotherapy. PD-L1 expression was assessed using immunohistochemistry, and bulk RNA sequencing was performed on 146 HNSCC patients (65 primary sites, 50 paired local recurrences, and 31 paired regional recurrences). PD-L1 was scored using the CPS of ≥1, ≥20, and ≥50. Overall, 98 %, 54 %, and 17 % of HNSCCs had a CPS ≥1, ≥20, and ≥50, respectively. When using a cut-off of ≥1, CRT did not significantly change CPS at the locoregional recurrent site. However, there were significant changes when using CPS ≥20 or ≥50. The CPS changed for 32 % of patients when using a CPS ≥20 (p < 0.001). When using a CPS ≥50, there was a 20–23 % (p = 0.0058–0.00067) discordance rate at the site of locoregional recurrence. Oral cavity cancers had a significantly higher discordant rate than other primary sites for CPS ≥50, 44 % (8/18, p = 0.0058) and 58 % (7/12, p = 0.00067) discordance at the site of local and regional recurrence, respectively. When evaluating the 18 gene IFN-ɣ signature predictive of response to anti-PD-1 blockade, there was a statistically significant increase in the IFN-ɣ signature in recurrent larynx cancer (p = 0.02). Our study demonstrates that when using a higher cut-off of CPS ≥20 and ≥50, a repeat biopsy may be warranted after CRT for local and regional recurrent HNSCCs.

Original language	English (US)
Article number	106183
Journal	Oral Oncology
Volume	135
DOIs	https://doi.org/10.1016/j.oraloncology.2022.106183
State	Published - Dec 2022

Bibliographical note

Funding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.I.P. has received consultancy payments from Abbvie, Astrazeneca/MedImmune, Cue Biopharma, Fusion Pharmaceuticals, MSD/Merck, Newlink Genetics, Oncolys Biopharma, Replimmune, Scopus Biopharma, and Sensei Bio. S.I.P. has received grants/research support from Abbvie, Astrazeneca/MedImmune, Cue Biopharma, Merck, and Tesaro. R.B.B. has received consultancy payments from Merck, Regeneron, Macrogenics, and Bristol Myers Squibb. R.B.B. has received institutional research grants from Bristol Myers Squibb. All other authors declare no potential conflicts of interest.

Funding Information:
This work was supported by the National Institutes of Health/National Cancer Institute (NIH/NCI P01 240239 (DTL, WCF, PMS, SIP), R01 CA 257623 (WCF, SIP), and Abbvie.

Funding Information:
We thank Raina Tamakawa for her assistance as the Clinical Research Coordinator at the Earle A. Chiles Research Institute, Providence Cancer Institute. We also thank Dr. Zohara Cohen for her assistance as the Research Manager in the Department of Otolaryngology—Head and Neck Surgery at the University of Minnesota School of Medicine. Funding. This work was supported by the National Institutes of Health/National Cancer Institute (NIH/NCI P01 240239 (DTL, WCF, PMS, SIP), R01 CA 257623 (WCF, SIP), and Abbvie.

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© 2022 Elsevier Ltd

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Park, B. J., Mattox, A. K., Clayburgh, D., Patel, M., Bell, R. B., Yueh, B., Leidner, R., Xiao, H., Couey, M., Li, S., Qin, T., Sartor, M. A., Cairns, B., MacDonough, T., Halliwill, K., Deschler, D., Lin, D. T., Faquin, W. C., Sadow, P. M., & Pai, S. I. (2022). Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck. Oral Oncology, 135, Article 106183. https://doi.org/10.1016/j.oraloncology.2022.106183

Park, BJ, Mattox, AK, Clayburgh, D, Patel, M, Bell, RB, Yueh, B, Leidner, R, Xiao, H, Couey, M, Li, S, Qin, T, Sartor, MA, Cairns, B, MacDonough, T, Halliwill, K, Deschler, D, Lin, DT, Faquin, WC, Sadow, PM & Pai, SI 2022, 'Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck', Oral Oncology, vol. 135, 106183. https://doi.org/10.1016/j.oraloncology.2022.106183

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title = "Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck",

abstract = "PD-L1 testing guides therapeutic decision-making for head and neck squamous cell carcinoma (HNSCC). We sought to understand whether chemoradiation therapy (CRT) influences the PD-L1 combined positive score (CPS) and other biomarkers of response to immunotherapy. PD-L1 expression was assessed using immunohistochemistry, and bulk RNA sequencing was performed on 146 HNSCC patients (65 primary sites, 50 paired local recurrences, and 31 paired regional recurrences). PD-L1 was scored using the CPS of ≥1, ≥20, and ≥50. Overall, 98 %, 54 %, and 17 % of HNSCCs had a CPS ≥1, ≥20, and ≥50, respectively. When using a cut-off of ≥1, CRT did not significantly change CPS at the locoregional recurrent site. However, there were significant changes when using CPS ≥20 or ≥50. The CPS changed for 32 % of patients when using a CPS ≥20 (p < 0.001). When using a CPS ≥50, there was a 20–23 % (p = 0.0058–0.00067) discordance rate at the site of locoregional recurrence. Oral cavity cancers had a significantly higher discordant rate than other primary sites for CPS ≥50, 44 % (8/18, p = 0.0058) and 58 % (7/12, p = 0.00067) discordance at the site of local and regional recurrence, respectively. When evaluating the 18 gene IFN-ɣ signature predictive of response to anti-PD-1 blockade, there was a statistically significant increase in the IFN-ɣ signature in recurrent larynx cancer (p = 0.02). Our study demonstrates that when using a higher cut-off of CPS ≥20 and ≥50, a repeat biopsy may be warranted after CRT for local and regional recurrent HNSCCs.",

author = "Park, {Brian J.} and Mattox, {Austin K.} and Daniel Clayburgh and Mihir Patel and Bell, {R. Bryan} and Bevan Yueh and Rom Leidner and Hong Xiao and Marcus Couey and Shiting Li and Tingting Qin and Sartor, {Maureen A.} and Belinda Cairns and Tracy MacDonough and Kyle Halliwill and Daniel Deschler and Lin, {Derrick T.} and Faquin, {William C.} and Sadow, {Peter M.} and Pai, {Sara I.}",

note = "Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.I.P. has received consultancy payments from Abbvie, Astrazeneca/MedImmune, Cue Biopharma, Fusion Pharmaceuticals, MSD/Merck, Newlink Genetics, Oncolys Biopharma, Replimmune, Scopus Biopharma, and Sensei Bio. S.I.P. has received grants/research support from Abbvie, Astrazeneca/MedImmune, Cue Biopharma, Merck, and Tesaro. R.B.B. has received consultancy payments from Merck, Regeneron, Macrogenics, and Bristol Myers Squibb. R.B.B. has received institutional research grants from Bristol Myers Squibb. All other authors declare no potential conflicts of interest. Funding Information: This work was supported by the National Institutes of Health/National Cancer Institute (NIH/NCI P01 240239 (DTL, WCF, PMS, SIP), R01 CA 257623 (WCF, SIP), and Abbvie. Funding Information: We thank Raina Tamakawa for her assistance as the Clinical Research Coordinator at the Earle A. Chiles Research Institute, Providence Cancer Institute. We also thank Dr. Zohara Cohen for her assistance as the Research Manager in the Department of Otolaryngology—Head and Neck Surgery at the University of Minnesota School of Medicine. Funding. This work was supported by the National Institutes of Health/National Cancer Institute (NIH/NCI P01 240239 (DTL, WCF, PMS, SIP), R01 CA 257623 (WCF, SIP), and Abbvie. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",

year = "2022",

month = dec,

doi = "10.1016/j.oraloncology.2022.106183",

language = "English (US)",

volume = "135",

journal = "Oral Oncology",

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publisher = "Elsevier Limited",

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T1 - Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck

AU - Park, Brian J.

AU - Mattox, Austin K.

AU - Clayburgh, Daniel

AU - Patel, Mihir

AU - Bell, R. Bryan

AU - Yueh, Bevan

AU - Leidner, Rom

AU - Xiao, Hong

AU - Couey, Marcus

AU - Li, Shiting

AU - Qin, Tingting

AU - Sartor, Maureen A.

AU - Cairns, Belinda

AU - MacDonough, Tracy

AU - Halliwill, Kyle

AU - Deschler, Daniel

AU - Lin, Derrick T.

AU - Faquin, William C.

AU - Sadow, Peter M.

AU - Pai, Sara I.

N1 - Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.I.P. has received consultancy payments from Abbvie, Astrazeneca/MedImmune, Cue Biopharma, Fusion Pharmaceuticals, MSD/Merck, Newlink Genetics, Oncolys Biopharma, Replimmune, Scopus Biopharma, and Sensei Bio. S.I.P. has received grants/research support from Abbvie, Astrazeneca/MedImmune, Cue Biopharma, Merck, and Tesaro. R.B.B. has received consultancy payments from Merck, Regeneron, Macrogenics, and Bristol Myers Squibb. R.B.B. has received institutional research grants from Bristol Myers Squibb. All other authors declare no potential conflicts of interest. Funding Information: This work was supported by the National Institutes of Health/National Cancer Institute (NIH/NCI P01 240239 (DTL, WCF, PMS, SIP), R01 CA 257623 (WCF, SIP), and Abbvie. Funding Information: We thank Raina Tamakawa for her assistance as the Clinical Research Coordinator at the Earle A. Chiles Research Institute, Providence Cancer Institute. We also thank Dr. Zohara Cohen for her assistance as the Research Manager in the Department of Otolaryngology—Head and Neck Surgery at the University of Minnesota School of Medicine. Funding. This work was supported by the National Institutes of Health/National Cancer Institute (NIH/NCI P01 240239 (DTL, WCF, PMS, SIP), R01 CA 257623 (WCF, SIP), and Abbvie. Publisher Copyright: © 2022 Elsevier Ltd

PY - 2022/12

Y1 - 2022/12

N2 - PD-L1 testing guides therapeutic decision-making for head and neck squamous cell carcinoma (HNSCC). We sought to understand whether chemoradiation therapy (CRT) influences the PD-L1 combined positive score (CPS) and other biomarkers of response to immunotherapy. PD-L1 expression was assessed using immunohistochemistry, and bulk RNA sequencing was performed on 146 HNSCC patients (65 primary sites, 50 paired local recurrences, and 31 paired regional recurrences). PD-L1 was scored using the CPS of ≥1, ≥20, and ≥50. Overall, 98 %, 54 %, and 17 % of HNSCCs had a CPS ≥1, ≥20, and ≥50, respectively. When using a cut-off of ≥1, CRT did not significantly change CPS at the locoregional recurrent site. However, there were significant changes when using CPS ≥20 or ≥50. The CPS changed for 32 % of patients when using a CPS ≥20 (p < 0.001). When using a CPS ≥50, there was a 20–23 % (p = 0.0058–0.00067) discordance rate at the site of locoregional recurrence. Oral cavity cancers had a significantly higher discordant rate than other primary sites for CPS ≥50, 44 % (8/18, p = 0.0058) and 58 % (7/12, p = 0.00067) discordance at the site of local and regional recurrence, respectively. When evaluating the 18 gene IFN-ɣ signature predictive of response to anti-PD-1 blockade, there was a statistically significant increase in the IFN-ɣ signature in recurrent larynx cancer (p = 0.02). Our study demonstrates that when using a higher cut-off of CPS ≥20 and ≥50, a repeat biopsy may be warranted after CRT for local and regional recurrent HNSCCs.

AB - PD-L1 testing guides therapeutic decision-making for head and neck squamous cell carcinoma (HNSCC). We sought to understand whether chemoradiation therapy (CRT) influences the PD-L1 combined positive score (CPS) and other biomarkers of response to immunotherapy. PD-L1 expression was assessed using immunohistochemistry, and bulk RNA sequencing was performed on 146 HNSCC patients (65 primary sites, 50 paired local recurrences, and 31 paired regional recurrences). PD-L1 was scored using the CPS of ≥1, ≥20, and ≥50. Overall, 98 %, 54 %, and 17 % of HNSCCs had a CPS ≥1, ≥20, and ≥50, respectively. When using a cut-off of ≥1, CRT did not significantly change CPS at the locoregional recurrent site. However, there were significant changes when using CPS ≥20 or ≥50. The CPS changed for 32 % of patients when using a CPS ≥20 (p < 0.001). When using a CPS ≥50, there was a 20–23 % (p = 0.0058–0.00067) discordance rate at the site of locoregional recurrence. Oral cavity cancers had a significantly higher discordant rate than other primary sites for CPS ≥50, 44 % (8/18, p = 0.0058) and 58 % (7/12, p = 0.00067) discordance at the site of local and regional recurrence, respectively. When evaluating the 18 gene IFN-ɣ signature predictive of response to anti-PD-1 blockade, there was a statistically significant increase in the IFN-ɣ signature in recurrent larynx cancer (p = 0.02). Our study demonstrates that when using a higher cut-off of CPS ≥20 and ≥50, a repeat biopsy may be warranted after CRT for local and regional recurrent HNSCCs.

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Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck

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