Table 6.
Clinical outcome: other treatment strategies
| Study | Treatment | Stage | EMH | Pos/n | Cutoff | Correlations | LRC | OS | DFS | DSS |
|---|---|---|---|---|---|---|---|---|---|---|
| Oral cavity cancer | ||||||||||
| Pérez-Sayáns et al. 55 | Any | Any | CA-IX | 23/501 | 50% M | Disease stage | 0.34 (0.1–1.2)2 | |||
| Oropharyngeal cancer | ||||||||||
| Hong et al. 56 | Any | Any | HIF-1a | 137/233 | 10% N | T-stage, tumor grade | 0.72 (0.48–1.03) | 0.75 (0.46–1.22) | ||
| Rahimi et al. 60 | XRT/CRT3 | Any | HIF-1a | 26/58 | 1% N | 0.76 (0.55–1.01) | 0.81 (0.67–0.99) | |||
| HIF-1a | NS/58 | 1% C | 1.10 (0.72–1.67) | 1.06 (0.83–1.35) | ||||||
| Any | CA-IX | NS/57 | 1% C | 1.52 (0.71–3.23) | 1.03 (0.81–1.32) | |||||
| CA-IX | NS/57 | 1% M | 0.93 (0.77–1.12) | 1.01 (0.88–1.15) | ||||||
| Wan et al. 59 | nC+R/nC+CRT4 | Any | HIF-1a | 66/1441 | 5/16 C/N5 | 0.53 (0.31–1.01) | ||||
| Multiple subsites | ||||||||||
| Choi et al. 57 | Any | Any | HIF-1a | 25/76 | 1% C | None | LR P = 0.237 | 0.55 (0.33–1.15) | ||
| Eriksen et al. 61 | 6 | Any | CA-IX | 370 | M7 | None | LR P = 0.8 | |||
| Le et al. 58 | Any | Any | CA-IX | 29/948 | Int C9 | LR P = 0.011 | LR P = 0.030 | |||
| Any | OPN | 70/84 | Int D | NS | ||||||
The outcomes locoregional control (LRC), overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) are shown as hazard ratio (95% confidence interval). Hazard ratios <1 indicate beneficial prognosis for nonhypoxic tumors. Significant values are shown in bold. Cutoff: EMHs were scored according to nuclear (N), membranous (M), cytoplasmic (C) or diffuse (D) staining patterns. Pos: number of patients with staining above the mentioned cutoff. LR: Logrank test. ns: not specified. Multiple subsites: patients were not analyzed per subsite. EMH, endogenous markers of hypoxia; HIF-1, hypoxia-inducible factor 1.
Twenty-three patients had intense staining, 18 patients had moderate staining and 9 patients had no staining.
Strong vs. no CA-IX staining.
Chemotherapy was added in the case of T4 or N3 disease.
Patients participated in a RCT between neoadjuvant chemotherapy followed by either radiotherapy or chemoradiation
A score was calculated from 0–16, based on staining proportion and intensity. Both cytoplasmic and nuclear patterns were scored.
Patients were randomized between radiotherapy or radiotherapy and the radiosensitizer nimorazole
Patients were analyzed in groups: <1%, 1–10%, 10–30%, and above 30%. None of these subgroups showed significantly better improvement compared to the other groups
Results for CA-IX and OPN were available for 94 and 84 patients, respectively, because of TMA core availability.
Expression was scored as negative, weak or strong by a single pathologist.