Table 2.
Treatment-related adverse events (TRAEs) in the 21 patients
| Neoadjuvant TRAEs: Common Terminology Criteria for Adverse Events version 4.03 | |||||||||||
| Cohort | N= | Treatment | |||||||||
| 1 | 5 | Nivo/8Gy x5 | |||||||||
| 2 | 5 | Nivo/8Gy x3 | |||||||||
| 3 | 6 | 8Gy x3 | |||||||||
| 4 | 5 | Nivo/8Gy x3 | |||||||||
| Total=21 | |||||||||||
| No. (%) | |||||||||||
| Adverse event |
All pts. Any grade |
All Pts. Grade 3–4 |
Any grade | Grades 3–4 | |||||||
| Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | ||||
| Pain, head and neck | 9 (43) | – | 3 (60) | 1 (20) | 3 (50) | 2 (40) | – | – | – | – | |
| Pain, generalized/arthralgia | 3 (14) | – | 1 (20) | 1 (20) | – | 1 (20) | – | – | – | – | |
| Mucositis | 20 (95) | 1 (5) | 5 (100) | 5 (100) | 5 (83) | 5 (100) | 1 (20) | – | – | – | |
| Thrush dysgeusia/xerostomia | 15 (71) | – | 3 (60) | 4 (80) | 6 (100) | 2 (40) | – | – | – | – | |
| Rash/pruritus | 11 (52) | – | 4 (80) | 2 (40) | 2 (33) | 3 (60) | – | – | – | – | |
| Anorexia, weight loss | 3 (14) | - | 3 (60) | – | – | – | – | – | – | – | |
| Hypothyroidism | 1 (5) | – | – | – | – | 1 (20) | – | – | – | – | |
| Anemia | 4 (19) | 1 (5) | 2 (40) | – | – | 2 (40) | – | – | – | 1 (20) | |
| Leukopenia | 3 (14) | – | 2 (40) | 1 (20) | – | – | – | – | – | – | |
| Nausea/vomiting | 4 (19) | – | 2 (40) | 1 (20) | 1 (17) | – | – | – | – | – | |
| Hypotension | 6 (29) | 1 (5) | 1 (20) | 3 (60) | – | 2 (40) | – | – | – | 1 (20) | |
| Fatigue | 8 (38) | – | 2 (40) | 2 (40) | 1 (17) | 3 (60) | – | – | – | – | |
| Hypokalemia | 3 (14) | – | 2 (40) | 1 (20) | – | – | – | – | – | – | |
| Hyponatremia | 3 (14) | 1 (5) | 1 (20) | 1 (20) | – | 1 (20) | – | – | – | 1 (20) | |
| Transaminitis | 1 (5) | – | 1 (20) | – | – | – | – | – | – | – | |
| DVT | 1 (5) | – | – | 1 (20) | – | – | – | – | – | – | |
| Thrombosis (SVT) | 1 (5) | – | – | 1 (20) | – | – | – | – | – | – | |
| Infusion reaction (nivolumab) |
1 (5) | – | 1 (20) | – | – | – | – | – | – | – | |
| Fever | 2 (10) | – | – | – | 2 (33) | – | – | – | – | – | |
| Aspiration pneumonia | 1 (5) | – | – | – | – | 1 (20) | – | – | – | – | |
| Surgical/postoperative TRAEs: Clavien-Dindo Classification | |||||||||||
|
All pts. Any grade |
All pts. Grades 3–4 |
Any grade | Grades 3–4 | ||||||||
| Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | ||||
| Pain, head and neck | 9 (43) | 1 (5) | 1 (20) | 3 (60) | 2 (33) | 3 (60) | 1 (20) | – | – | – | |
| Swelling, head and neck | 4 (19) | 1 (5) | 1 (20) | 1 (20) | 1 (17) | 1 (20) | 1 (20) | – | – | – | |
| Hematoma, seroma, chyloma, cellulitis | 5 (24) | 3 (14) | 1 (20) | 2 (40) | – | 2 (40) | – | 2 (40) | – | 1 (20) | |
| Delayed healing/dehiscence | 7 (33) | 2 (10) | – | 3 (60) | – | 4 (80) | – | 1 (20) | – | 1 (20) | |
| Hypotension/syncope | 5 (24) | – | 1 (20) | 2 (40) | 1 (17) | 1 (20) | – | – | – | – | |
| Adrenal insufficiency | 1 (5) | – | – | 1 (20) | – | – | – | – | – | – | |
| Cardiac arrhythmia | 2 (10) | – | – | – | – | 2 (20) | – | – | – | – | |
| Anxiety/disorientation | 5 (24) | – | – | 2 (40) | 1 (17) | 2 (40) | – | – | – | – | |
| Nausea/vomiting | 8 (38) | – | 1 (20) | 3 (60) | 2 (33) | 2 (40) | – | – | – | – | |
| Weight loss | 3 (14) | 1 (5) | 1 (20) | 1 (20) | 1 (17) | – | 1 (20) | – | – | – | |
| Rash/pruritus | 3 (14) | – | – | 1 (20) | 1 (17) | 1 (20) | – | – | – | – | |
| Constipation | 4 (19) | – | 1 (20) | 1 (20) | 1 (17) | 1 (20) | – | – | – | – | |
| Diarrhea | 3 (14) | – | – | 1 (20) | – | 2 (40) | – | – | – | – | |
| Fatigue | 2 (10) | – | 1 (20) | 1 (20) | – | – | – | – | – | – | |
| Cough/increased secretions | 6 (29) | – | – | 1 (20) | 2 (33) | 3 (60) | – | – | – | – | |
| Shortness of breath | 2 (10) | – | – | 1 (20) | – | 1 (20) | – | – | – | – | |
| Pneumonia, aspiration | 1 (5) | 1 (5) | – | – | – | 1 (20) | – | – | – | 1 (20) | |
| Pneumothorax | 1 (5) | 1 (5) | – | – | – | 1 (20) | – | – | – | 1 (20) | |
| Pneumonitis | 1 (5) | 1 (5) | – | – | – | 1 (20) | – | – | – | 1 (20) | |
| Thrombocytosis | 1 (5) | – | – | – | – | 1 (20) | – | – | – | – | |
| Urinary retention | 2 (10) | 1 (5) | – | 2 (40) | – | – | – | 1 (20) | – | – | |
| Neurosensory changes, head and neck, torso | 5 (24) | – | 1 (20) | 1 (20) | 1 (17) | 1 (20) | – | – | – | – | |
| Delayed TRAEs>30 days post-op: Common Terminology Criteria for Adverse Events Version 4.03 | |||||||||||
|
All pts. Any grade |
All pts. Grades 3–4 |
Any grade | Grades 3–4 | ||||||||
| Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | ||||
| Pain, head and neck | 18 (86) | 4 (19) | 4 (80) | 5 (100) | 5 (83) | 4 (80) | 3 (60) | – | 1 (17) | – | |
| Pain, generalized/arthralgia | 3, 14% | – | 1, 20% | – | 2, 33% | – | – | – | – | – | |
| Delayed wound healing | 15 (71) | 6 (29) | 3 (60) | 4 (80) | 3 (50) | 4 (80) | 3 (60) | 2 (40) | – | 1 (20) | |
| Anorexia/cachexia | 8 (38) | 3 (14) | 3 (60) | 2 (40) | 3 (50) | – | 3 (60) | – | – | – | |
| Pneumonitis | 1 (5) | 1 (5) | – | – | – | 1 (5) | – | – | – | 1 (5) | |
| Adrenal insufficiency | 5 (24) | – | 3 (60) | 2 (40) | – | – | – | – | – | – | |
| Hyponatremia | 6 (29) | 1 (5) | 3 (60) | 2 (40) | – | 1 (20) | – | – | – | 1 (20) | |
| Nausea/vomiting | 6 (29) | – | 2 (40) | – | 2 (33) | 2 (40) | – | – | – | – | |
| Hypotension | 5 (24) | – | 1 (20) | 2 (40) | 1 (17) | 1 (20) | – | – | – | – | |
| Hypothyroidism | 3 (14) | – | 1 (20) | 1 (20) | – | 1 (20) | – | – | – | – | |
| Fatigue | 6 (29) | – | 3 (60) | – | 2 (33) | 1 (20) | – | – | – | – | |
| Congestion/respiratory | 5 (24) | – | 2 (40) | 1 (20) | 2 (33) | – | – | – | – | – | |
| Thrush dysgeusia/xerostomia | 6 (29) | – | 2 (40) | 1 (20) | 2 (33) | 1 (20) | – | – | – | – | |
| Rash/pruritus | 7 (33) | – | 1 (20) | 3 (60) | 2 (33) | 1 (20) | – | – | – | – | |
| Leukopenia | 4 (19) | – | 3 (60) | – | 1 (17) | – | – | – | – | – | |
| Anemia | 4 (19) | – | 2 (40) | – | 1 (17) | 1 (20) | – | – | – | – | |
| Hypokalemia | 9 (43) | – | 3 (60) | 2 (40) | 3 (50) | 1 (20) | – | – | – | – | |
| Transaminitis | 1 (5) | – | – | – | 1 (17) | – | – | – | – | – | |
| Constipation | 5 (24) | – | 3 (60) | – | 2 (33) | – | – | – | – | – | |
Upfront feeding tube placement was required in 4 of the 5 patients in cohort 4 (HPV-neg), which subsequently played a role in averting late/delayed anorexia, whereas no patients in cohorts 1–3 (HPV-pos) required upfront feeding tube placement.
HPV, human papilloma virus.