Table 1

Clinicopathological feature, treatment, and outcome of four CRLM patients harboring POLE EDM

CharacteristicsCase 1Case 2Case 3Case 4
AgeLate 30sEarly 70sLate 20sEarly 30s
Primary tumor siteRectumAscending colonSigmoidTransverse colon
Stage*cT3N1M1a, IVacT4aN1M1a, IVacT3N1M1a, IVacT4aN2M1a, IVa
Metastatic siteLiver onlyLiver onlyLiver onlyLiver only
Clinical Risk Score4443
RAS/RAF statusKRAS G13Dw.t.w.t.w.t.
POLE mutation siteP286RP286RP286RP286R
TMB (mutations/Mb)453.12255.36320.64307.20
Microsatellite statusMSI-HMSSMSSMSS
Liver metastases†
 Diameter (largest lesion, cm)8.55.914.66.7
 ResectabilityUnresectableResectablePotential resectablePotential resectable
Treatment before ICI
 Systematic (response‡)NoneFOLFOX (PD)Bev +FOLFOX (PR)None
 SurgeryNoneNoneColectomy, first liver metastasectomyNone
ICI combined treatment
 Radiological responsePRPRPRPR
Surgical treatment (after ICI)
 Primary siteDixonColectomy- §Colectomy
 Liver metastasesResection +ablationResectionResectionResection
Pathological response
 Primary tumorpCRpCR- §pCR
 Reginal lymph nodespCRpCR- §pCR
 Liver metastasespCRpCRpCRpCR
Postoperative treatmentToripalimabNoneSintilimabToripalimab
Survival statusAlive (NED)Alive (NED)Alive (NED)Alive (NED)
OS (months)¶1218714
  • *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.