Clinicopathological feature, treatment, and outcome of four CRLM patients harboring POLE EDM
| Characteristics | Case 1 | Case 2 | Case 3 | Case 4 |
| Age | Late 30s | Early 70s | Late 20s | Early 30s |
| Gender | Male | Male | Male | Male |
| Primary tumor site | Rectum | Ascending colon | Sigmoid | Transverse colon |
| Stage* | cT3N1M1a, IVa | cT4aN1M1a, IVa | cT3N1M1a, IVa | cT4aN2M1a, IVa |
| Metastatic site | Liver only | Liver only | Liver only | Liver only |
| Clinical Risk Score | 4 | 4 | 4 | 3 |
| RAS/RAF status | KRAS G13D | w.t. | w.t. | w.t. |
| POLE mutation site | P286R | P286R | P286R | P286R |
| TMB (mutations/Mb) | 453.12 | 255.36 | 320.64 | 307.20 |
| Microsatellite status | MSI-H | MSS | MSS | MSS |
| Liver metastases† | ||||
| No | 8 | 7 | 1 | 5 |
| Diameter (largest lesion, cm) | 8.5 | 5.9 | 14.6 | 6.7 |
| Resectability | Unresectable | Resectable | Potential resectable | Potential resectable |
| Treatment before ICI | ||||
| Systematic (response‡) | None | FOLFOX (PD) | Bev +FOLFOX (PR) | None |
| Surgery | None | None | Colectomy, first liver metastasectomy | None |
| ICI combined treatment | ||||
| Line | First | Second | Second | First |
| Regimen | Toripalimab+FOLFOX | Sintilimab+FOLFIRI | Sintilimab+FOLFIRI | Toripalimab+Bev+XELOX |
| Cycles | 7 | 5 | 5 | 5 |
| Radiological response | PR | PR | PR | PR |
| Surgical treatment (after ICI) | ||||
| Primary site | Dixon | Colectomy | - § | Colectomy |
| Liver metastases | Resection +ablation | Resection | Resection | Resection |
| Pathological response | ||||
| Primary tumor | pCR | pCR | - § | pCR |
| Reginal lymph nodes | pCR | pCR | - § | pCR |
| Liver metastases | pCR | pCR | pCR | pCR |
| Postoperative treatment | Toripalimab | None | Sintilimab | Toripalimab |
| Survival status | Alive (NED) | Alive (NED) | Alive (NED) | Alive (NED) |
| OS (months)¶ | 12 | 18 | 7 | 14 |
*According to the American Joint Committee on Cancer (8th edition).
†At initial diagnosis.
‡Assessed by the Response Evaluation Criteria in Solid Tumors 1.1 criteria.
§Colectomy was conducted before ICI combined treatment.
¶Defined from initial ICI combined treatment to last follow-up.
Bev, bevacizumab; CRLM, colorectal cancer liver metastases; EDM, exonuclease domain mutation; FOLFIRI, fluorouracil+irinotecan+leucovorin calcium; FOLFOX, fluorouracil+oxaliplatin+leucovorin calcium; ICI, immune checkpoint inhibitor; MSI-H, microsatellite instability-high; MSS, microsatellite stable; NED, no evidence of disease; OS, overall survival; pCR, pathological complete response; PD, progressive disease; POLE, polymerase epsilon; PR, partial response; w.t., wild type; XELOX, capecitabine+oxaliplatin.