Comprehensive Genomic Profiling Reveals Clinical Associations in Response to Immune Therapy in Head and Neck Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Population on C-CAT Database
2.2. Patient Population at Tokyo Medical and Dental University (TMDU)
2.3. Comprehensive Genomic Profiling (CGP)
2.4. Molecular Tumor Board
2.5. Efficacy Assessments of ICI Therapy
2.6. Statistical Analysis
3. Results
3.1. Patient Characteristics and Clinical Utility of CGP in C-CAT Data
3.2. Patient Characteristics in TMDU
3.3. Sequencing Results
3.4. Outcomes of ICI Therapy
3.5. Association between TMB and ICI Response
3.6. Association between PD-L1 Expression and ICI response
3.7. Association between Specific Genetic Mutation and ICI Response
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | SCC | non-SCC |
---|---|---|
All patients | 34 (100) | 20 (100) |
Age | ||
Median (range, y) | 60 (42–81) | 61 (15–74) |
CorrectedGender, n (%) | ||
Male | 21 (62) | 9 (45) |
Female | 13 (38) | 11 (55) |
Primary site of disease, n (%) | ||
Oral cavity | 25 (74) | - |
Salivary glands | - | 12 (60) |
Nasal cavity and paranasal sinuses | 4 (11) | 2 (10) |
Pharynx | 2 (6) | - |
Larynx | 2 (6) | - |
Parapharyngeal space | - | 2 (10) |
Unknown primary | 1 (3) | 1 (5) |
Other | - | 3 (15) |
Histological classification, n (%) | ||
Squamous Cell Carcinoma | 34 (100) | - |
Adenoid cystic carcinoma | - | 7 (35) |
Salivary duct carcinoma | - | 3 (15) |
Carcinoma ex pleomorphic adenoma | - | 2 (10) |
Basal cell carcinoma | - | 1 (5) |
Esthesioneuroblastoma | - | 1 (5) |
Sarcoma | - | 4 (20) |
NOS | - | 2 (10) |
ECOG performance status, n (%) | ||
0 | 15 (44) | 16 (80) |
1 | 15 (44) | 3 (15) |
≥2 | 4 (12) | 1 (5) |
Smoking status, n (%) | ||
Never or <10 packs/year | 12 (35) | 10 (50) |
Current or Former (≥10 packs/year) | 22 (65) | 10 (50) |
Cancer staging, n (%) | ||
Stage I–Ⅲ | 1 (3) | 0 (0) |
Stage IV | 33 (97) | 20 (100) |
HPV, n (%) | ||
Negative | 33 (97) | 19 (95) |
Positive | 1 (3) | 1 (5) |
Characteristic | n (%) | Best Response | ORR | p-Value | DCR | p-Value | ||||
---|---|---|---|---|---|---|---|---|---|---|
CR | PR | SD | PD | NE | ||||||
All patients | 33 (100) | 0 (0) | 6 (18) | 6 (18) | 20 (60) | 1 (3) | 6 (18) | 12 (36) | ||
TMB | 33 (100) | |||||||||
Low (≤5) | 21 (64) | 0 (0) | 1 (5) | 4 (19) | 16 (76) | 0 (0) | 1/21 (5) | Ref | 5/21 (24) | Ref |
Intermediate (6–9) | 7 (21) | 0 (0) | 3 (43) | 0 (14) | 4 (43) | 0 (0) | 3/7 (43) | 0.03 | 3/7 (44) | 0.5 |
High (≥10) | 4 (12) | 0 (0) | 2 (50) | 1 (33) | 0 (0) | 1 (1) | 2/4 (50) | 0.04 | 3/4 (75) | 0.1 |
Not detected | 1 (3) | - | - | - | - | - | - | - | - | |
PD-L1 | 27 (100) | |||||||||
CPS < 1 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | 0 (0) | - |
1 ≤ CPS < 20 | 14 (52) | 0 (0) | 2 (15) | 0 (0) | 10 (77) | 1 (8) | 2/14 (14) | NA | 2/14 (14) | Ref |
CPS ≥ 20 | 13 (48) | 0 (0) | 2 (14) | 3 (21) | 8 (57) | 0 (0) | 2/13 (15) | NA | 5/13 (38) | 0.2 |
Case No. | Age (yr)/Gender | Primary Site | Tumor Mutational Burden | Immune Checkpoint Inhibitor | Best Response |
---|---|---|---|---|---|
1 | 70/F | Buccal mucosa | 13 mut/Mb | Pembrolizumab | PR |
2 | 52/M | Maxillary sinus | 34 mut/Mb | Nivolumab | PR |
3 | 61/F | Buccal mucosa | 10 mut/Mb | Pembrolizumab | SD |
4 | 76/M | Unknown primary | 14 mut/Mb | Nivolumab | NE |
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Noji, R.; Tohyama, K.; Kugimoto, T.; Kuroshima, T.; Hirai, H.; Tomioka, H.; Michi, Y.; Tasaki, A.; Ohno, K.; Ariizumi, Y.; et al. Comprehensive Genomic Profiling Reveals Clinical Associations in Response to Immune Therapy in Head and Neck Cancer. Cancers 2022, 14, 3476. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143476
Noji R, Tohyama K, Kugimoto T, Kuroshima T, Hirai H, Tomioka H, Michi Y, Tasaki A, Ohno K, Ariizumi Y, et al. Comprehensive Genomic Profiling Reveals Clinical Associations in Response to Immune Therapy in Head and Neck Cancer. Cancers. 2022; 14(14):3476. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143476
Chicago/Turabian StyleNoji, Rika, Kohki Tohyama, Takuma Kugimoto, Takeshi Kuroshima, Hideaki Hirai, Hirofumi Tomioka, Yasuyuki Michi, Akihisa Tasaki, Kazuchika Ohno, Yosuke Ariizumi, and et al. 2022. "Comprehensive Genomic Profiling Reveals Clinical Associations in Response to Immune Therapy in Head and Neck Cancer" Cancers 14, no. 14: 3476. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143476