Table 1.
Patients’ characteristics and performance of the signatures to detect tumor sensitivity to treatment.
| Treatment arm | Nivolumab | Docetaxel | Gefitinib |
|---|---|---|---|
| Tumor characteristics | |||
| Tumor type | Squamous cell carcinoma | Squamous cell carcinoma | Bronchioloalveolar |
| Stage (AJCC) | Advanced (IIIB/IV) | Advanced (IIIB/IV) | Early-stage (resectable I/II) |
| Lesion segmented | Lung lesion | Lung lesion | Primary lung cancer |
| Original clinical trial characteristics | |||
| Biomarker | PD-L1 | PD-L1 | EGFR mutational status |
| Treatment regimen | |||
| Immunotherapy | Nivolumab | None | None |
| Chemotherapy | None | Docetaxel | None |
| Anti-EGFR mAbs | None | None | Gefitinib |
| Primary endpoint | |||
| Outcome | OS, PFS | OS, PFS | Surgery at 3 weeks |
| First CT scan assessment | Baseline/8-week | Baseline/8-week | Baseline/3-week |
| Reference standard for treatment sensitivity | Above/below median PFS | Above/below median PFS | Surgery at 3 weeks |
| Clinical trial number | NCT01642004, NCT01721759 | NCT01642004 | NCT00588445 |
| Available | |||
| n | 153 patients | 65 patients | 46 patients |
| Included | |||
| n | 92 patients | 50 patients | 46 patients |
| Randomization | |||
| Ratio | 4: 1 | 2: 1 | 2: 1 |
| Training | |||
| n | 72 patients | 32 patients | 31 patients |
| Reference standard | |||
| Sensitive | 28 patients | 5 patients | 13 patients |
| Insensitive | 44 patients | 27 patients | 18 patients |
| Signature | |||
| AUC (95 CI) | 0.80 (0.69–0.89) | 0.68 (0.38–0.98) | 0.81 (0.61–0.92) |
| Delta features | 1. Volume (burden) 2. GLCM IMC1 (heterogeneity) 3. DWT1 (heterogeneity) 4. Sigmoid slope (boundaries) |
1. Volume (burden) | 1. Shape SI4 (boundaries) 2. LoG Z Entropy (heterogeneity) 3. GTDM Contrast (heterogeneity) 4. LoG X Entropy (heterogeneity) |
| Algorithm (42) | Random Forest | Random Forest | Random Forest |
| Validation | |||
| n | 20 patients | 18 patients | 15 patients |
| Reference standard | |||
| Sensitive | 5 patients | 6 patients | 7 patients |
| Insensitive | 15 patients | 12 patients | 8 patients |
| Signature | |||
| AUC (95 CI) | 0.77 (0.55–1.00) | 0.67 (0.37–0.96) | 0.82 (0.53–0.97) |
| Sensitivity | 0.80 | 0.92 | 0.83 |
| Specificity | 0.53 | 0.45 | 0.88 |
Note: The EGFR signature was designed in a cohort of patients with metastatic colorectal cancer treated with anti-EGFR using CT scans acquired at baseline and 8 weeks (44). The signature was then transferred and validated in Gefitinib patients with NSCLC treated with gefitinib. Signature features are all delta features measuring the change in the imaging feature between baseline and first response assessment.