Table 3.
Reasons why biopsies were not performed in the EGFR TKI‐treated group and best supportive care group
| Patient | Age/sex | Smoking status | Reasons | ctDNA detection method | ctDNA results (VAF%) | Gene detection after pathological acquisitiona |
|---|---|---|---|---|---|---|
| 1 | 63/F | No | Paraplegia due to bone metastases. Lesion not amenable to transthoracic biopsy and lung puncture given anatomic location. Patient unable to tolerate bronchoscopy. | NGS |
EGFR21 L858R (15.499%) (ddPCR EGFR L858R) |
Adenocarcinoma NO detection of gene due to financial condition |
| 2 | 71/F | Yes |
The lesion not amenable to safe biopsy because of proximity to descending aorta. ECOG = 3, unacceptable thoracotomy |
NGS | EGFR 19del (8.75%) |
Adenocarcinoma NGS:EGFR 19del |
| 3 | 54/F | No | Two prior nondiagnostic bronchoscopes and lesion not amenable to transthoracic needle biopsy. Patient unable to tolerate biopsy of lumbar metastasis. Lesions not amenable to lung puncture given anatomic location. | NGS |
EGFR 19 del (33.25%) (ddPCR EGFR 19 746‐750 del) |
Adenocarcinoma NO detection of gene due to financial condition |
| 4 | 51/M | Yes | Poor performance status precluded safe bronchoscopy and thoracotomy. | NGS |
EGFR 21 L858R (0.475%) (ddPCR EGFR L858R) |
Adenocarcinoma NO detection of gene due to financial condition |
| 5 | 70/M | Yes |
Respiratory failure, multiple brain metastases, accompanied by intracranial hypertension, and intolerance to bronchoscopy. Lesions not amenable to lung puncture given anatomic location. |
NGS |
EGFR 19 del (0.323333%) (ddPCR EGFR 19 746‐750 del) |
Adenocarcinoma NO detection of gene due to financial condition |
| 6 | 83/M | Yes | Lesions not amenable to lung puncture because of anatomic location. The patient was 83 y old with multiple brain metastases, accompanied by intracranial hypertension and intolerance to bronchoscopy. | ARMS | EGFR 21 L858R | Unable to obtain pathology |
| 7 | 37/F | No | Patient with acute pericardial tamponade, and intolerance to bronchoscopy and not suitable for lung puncture. Pericardial effusion cytology was negative. |
NGS ARMS |
EGFR 21 L858R (1.617%) EGFR 21 L858R |
Adenocarcinoma NGS:EGFR 21L858R |
| 8 | 85/F | Yes | Small intrapulmonary lesions those were not successfully amenable to transthoracic needle biopsy. Pleural fluid cytology was negative. | ARMS | EGFR 21 L858R | Unable to obtain pathology |
| 9 | 66/F | No | Very poor performance status limited tolerance to invasive biopsy. | ARMS | EGFR 21 L858R | Unable to obtain pathology |
| 10 | 82/M | Unknown | Very poor performance status limited tolerance to invasive biopsy. | ARMS | EGFR 19 del | Unable to obtain pathology |
| 11 | 68/F | Unknown | ECOG = 3. Lesions not amenable to lung puncture given anatomic location, and intolerance to bronchoscopy. | ARMS | EGFR 19 del | Unable to obtain pathology |
| 12 | 70/M | Yes | ECOG = 3. The clotting time is obviously prolonged and there is a risk of bleeding during the invasive operation. | ARMS | EGFR 21 L858R | Unable to obtain pathology |
| 13 | 73/M | Yes | Patient has multiple brain metastases and accompanied by intracranial hypertension and intolerance to bronchoscopy. Lesions not amenable to lung puncture given anatomic location. | ARMS | EGFR 19del | Unable to obtain pathology |
| 14 | 58/F | No | ECOG = 4, Patient has multiple brain metastases and accompanied by intracranial hypertension and intolerance to bronchoscopy. Lesions not amenable to lung puncture given anatomic location. | NGS | EGFR p.T790M (0.438%), EGFR p.G719A (9.927%), EGFR p.L861 (9.792%), EGFR 19 747_752 del (0.5%) |
Poorly differentiated carcinoma Tissue specimen ARMS: EGFR 18 G719X, EGFR 21 L861Q |
| 15 | 71/M | Yes | No malignant cells were found by bronchoscopy in other hospital. Pneumothorax, ECOG = 3, intolerance to bronchoscopy again. Lesions not amenable to lung puncture given anatomic location. | ARMS | EGFR 21 L858R | Unable to obtain pathology |
| 16 | 66/F | No | Poor performance status precluded invasive biopsy. | ARMS | EGFR 21 L858R | Unable to obtain pathology |
| 17 | 55/M | Yes |
ECOG = 4. Patient has multiple brain metastases and accompanied by intracranial hypertension and symptoms of pericardial tamponade, and intolerance to bronchoscopy. Pericardial effusion cytology was negative. Lesions not amenable to lung puncture given anatomic location. |
NGS |
EGFR 19del (3.3825%) (ddPCR EGFR 19 746‐750 del) |
Adenocarcinoma NGS:EGFR 19 del |
| 18 | 49/M | Yes | The patient unable to tolerance bronchoscopy due to severe vertebral metastases, and lesions not amenable to lung puncture given anatomic location. | NGS |
EGFR 19del (21.9575%) (ddPCR EGFR 19 746‐750 del) |
Adenocarcinoma NO detection of gene due to financial condition |
| 19 | 65/M | Yes | The patient intolerance to bronchoscopy and lung puncture due to severe arrhythmia and massive hemoptysis. | ARMS | EGFR 21 L858R | Unable to obtain pathology |
| 20 | 78/M | Yes | The patient unable to tolerance bronchoscopy due to severe vertebral metastases. Lesions not amenable to lung puncture given anatomic location. | ARMS | EGFR 19del | Unable to obtain pathology |
| 21 | 82/M | Yes | The patient intolerance to bronchoscopy due to respiratory failure and cerebral infarction. Lesions not amenable to lung puncture given anatomic location. | NGS | Wild type | |
| 22 | 80/F | No |
Patient has multiple brain metastases and accompanied by intracranial hypertension and intolerance to bronchoscopy. Lesions not amenable to lung puncture given anatomic location. |
NGS | Wild type | |
| 23 | 59/M | Yes | Patient has multiple brain metastases and accompanied by intracranial hypertension and massive hemoptysis, and intolerance to bronchoscopy. Lesions not amenable to lung puncture given anatomic location. | NGS | Wild type | |
| 24 | 70/M | Yes | Paraplegia due to bone metastases. Lesion not amenable to transthoracic biopsy and lung puncture given anatomic location, patient unable to tolerate bronchoscopy. | NGS | Wild type | |
| 25 | 66/M | Yes | Massive hemoptysis, not suitable for lung puncture or bronchoscopy | NGS | Wild type | |
| 26 | 67/M | Yes | Paraplegia due to bone metastases. Lesion not amenable to transthoracic biopsy and lung puncture given anatomic location, patient unable to tolerate bronchoscopy. | NGS | Wild type | |
| 27 | 78/M | Yes | Poor performance status precluded invasive biopsy. Lesions not amenable to lung puncture given anatomic location. | NGS | Wild type | |
| 28 | 55/F | Yes | Patient has multiple brain metastases and accompanied by intracranial hypertension and intolerance to bronchoscopy. Lesions not amenable to lung puncture given anatomic location. | NGS | Wild type | |
| 29 | 38/M | Yes | Paraplegia due to bone metastases. Lesion not amenable to transthoracic biopsy and lung puncture given anatomic location, patient unable to tolerate bronchoscopy. | NGS | Wild type | |
| 30 | 58/M | Yes | Patient has multiple brain metastases and accompanied by intracranial hypertension and intolerance to bronchoscopy. Lesions not amenable to lung puncture given anatomic location. | NGS | Wild type |
Abbreviations: ARMS, Amplification Refractory Mutation System; ECOG, Eastern Cooperative Oncology Group; NGS, next‐generation sequencing; VAF, variant allele frequency.
Four patients subsequently underwent gene testing on tissue specimens, and three of them were consistent with peripheral blood tests. NGS results in one case of peripheral blood: EGFR p.T790M (0.438%), EGFR p.G719A (9.927%), EGFR p.L861Q (9.792%), and EGFR 19 p747_752del (0.5%) mutation. The results of ARMS analysis of tissue samples showed G719X mutations in exon 18 and L861Q mutations in exon 21 of EGFR.