Determining timing of hepatectomy for colorectal cancer with distant metastasis according to imaging-based tumor shrinkage ratio

Abstract

Background: The optimal timing of surgical resection of liver metastasis remains controversial, and guidelines regarding the upper limits of operative indications have not yet been defined. Surgical indication for metastasis from colorectal cancer (CLM) based on results of preoperative chemotherapy and RNF8 was investigated.

Methods: Differences in CLM size on CT were evaluated as shrinkage rate/day by dividing tumor shrinkage rates by the interval in days between CT. Levels of RNF8 of resected colorectal cancer and CLM frozen specimen were detected.

Results: When the cut line for shrinkage rate at 12 weeks was set at 0.35%, disease-free survival was significantly better in patients with a shrinkage rate >0.35% vs. ≤0.35% (p=0.003). RNF8 expression was significantly higher in Tis (p=0.001). In liver metastasis, RNF8 expression level was significantly lower in patients with partial response to FOLFOX than with stable disease, (p=0.017).

Conclusions: A strategy of FOLFOX administration for 12 weeks to patients with low RNF8 expression and hepatectomy planned after 4 weeks rest may be accepted as the best therapeutic option for treating CLM.

Keywords: RNF8; chemotherapy; colorectal cancer; liver metastasis; surgical resection; tumor shrinkage rate.

Fig 1

Effect of chemotherapy as evaluated by tumor shrinkage rate. The cumulative tumor shrinkage rate is shown for all patients (A). The effective chemotherapy-induced cumulative shrinkage ratio is described (B). The dotted line indicates first-line chemotherapy, the dashed line second-line therapy, and the solid line third-line therapy. Cumulative tumor shrinkage rates separated by different timings are shown (C).

Fig 1

Effect of chemotherapy as evaluated by tumor shrinkage rate. The cumulative tumor shrinkage rate is shown for all patients (A). The effective chemotherapy-induced cumulative shrinkage ratio is described (B). The dotted line indicates first-line chemotherapy, the dashed line second-line therapy, and the solid line third-line therapy. Cumulative tumor shrinkage rates separated by different timings are shown (C).

Fig 1

Effect of chemotherapy as evaluated by tumor shrinkage rate. The cumulative tumor shrinkage rate is shown for all patients (A). The effective chemotherapy-induced cumulative shrinkage ratio is described (B). The dotted line indicates first-line chemotherapy, the dashed line second-line therapy, and the solid line third-line therapy. Cumulative tumor shrinkage rates separated by different timings are shown (C).

Fig 2

Most effective chemotherapy regimens for each timing. Shrinkage rates for Bev+FOLFOX (solid line) or FOLFOX (dotted line) as first-line therapy are compared (A). Shrinkage rates for Bev+FOLFOX (solid line) or FOLFIRI (dashed line) or Bev+FOLFIRI (dotted line) or FL (one-point chain line) or Bev+FL (two-point chain line) as second-line therapy are compared (B). Shrinkage rates for FOLFIRI (dashed line) or Bev+FOLFIRI (dotted line) or FL (one-point chain line) or CET+CPT11 (long dashed line) as third-line therapy are compared (C).

Fig 2

Most effective chemotherapy regimens for each timing. Shrinkage rates for Bev+FOLFOX (solid line) or FOLFOX (dotted line) as first-line therapy are compared (A). Shrinkage rates for Bev+FOLFOX (solid line) or FOLFIRI (dashed line) or Bev+FOLFIRI (dotted line) or FL (one-point chain line) or Bev+FL (two-point chain line) as second-line therapy are compared (B). Shrinkage rates for FOLFIRI (dashed line) or Bev+FOLFIRI (dotted line) or FL (one-point chain line) or CET+CPT11 (long dashed line) as third-line therapy are compared (C).

Fig 2

Most effective chemotherapy regimens for each timing. Shrinkage rates for Bev+FOLFOX (solid line) or FOLFOX (dotted line) as first-line therapy are compared (A). Shrinkage rates for Bev+FOLFOX (solid line) or FOLFIRI (dashed line) or Bev+FOLFIRI (dotted line) or FL (one-point chain line) or Bev+FL (two-point chain line) as second-line therapy are compared (B). Shrinkage rates for FOLFIRI (dashed line) or Bev+FOLFIRI (dotted line) or FL (one-point chain line) or CET+CPT11 (long dashed line) as third-line therapy are compared (C).

Fig 3

Prediction of patient prognosis. Shrinkage rate was separated into three patterns (A) and the prognosis of each pattern was evaluated (B). The solid line indicates Regular type, the dotted line Straight type, and the dashed line Falling type. (C) Tumor shrinkage rate at the 84th day (12th week) and disease-free survival period are shown. The disease-free survival rate in patients with a shrinkage rate of >0.35% (dotted line) was significantly higher than that in patients with a shrinkage rate of ≤0.35% (p=0.003%).

Fig 3

Prediction of patient prognosis. Shrinkage rate was separated into three patterns (A) and the prognosis of each pattern was evaluated (B). The solid line indicates Regular type, the dotted line Straight type, and the dashed line Falling type. (C) Tumor shrinkage rate at the 84th day (12th week) and disease-free survival period are shown. The disease-free survival rate in patients with a shrinkage rate of >0.35% (dotted line) was significantly higher than that in patients with a shrinkage rate of ≤0.35% (p=0.003%).

Fig 3

Prediction of patient prognosis. Shrinkage rate was separated into three patterns (A) and the prognosis of each pattern was evaluated (B). The solid line indicates Regular type, the dotted line Straight type, and the dashed line Falling type. (C) Tumor shrinkage rate at the 84th day (12th week) and disease-free survival period are shown. The disease-free survival rate in patients with a shrinkage rate of >0.35% (dotted line) was significantly higher than that in patients with a shrinkage rate of ≤0.35% (p=0.003%).

Fig 4

Expression of RNF8 in colorectal cancer cell lines. The expressions of RNF8 were different for cancer cell lines evaluated by RT-PCR (A) and Western blotting (B). In the cell line with the highest expression, SW1417, blockage of RNF8 by the siRNA technique significantly decreased the IC50 of oxaliplatin (C). The solid line indicates SW1417, and the dashed line indicates SW1417 siRNA. The experimental techniques are described in “Patients and Methods”.

Fig 4

Expression of RNF8 in colorectal cancer cell lines. The expressions of RNF8 were different for cancer cell lines evaluated by RT-PCR (A) and Western blotting (B). In the cell line with the highest expression, SW1417, blockage of RNF8 by the siRNA technique significantly decreased the IC50 of oxaliplatin (C). The solid line indicates SW1417, and the dashed line indicates SW1417 siRNA. The experimental techniques are described in “Patients and Methods”.

Fig 4

Expression of RNF8 in colorectal cancer cell lines. The expressions of RNF8 were different for cancer cell lines evaluated by RT-PCR (A) and Western blotting (B). In the cell line with the highest expression, SW1417, blockage of RNF8 by the siRNA technique significantly decreased the IC50 of oxaliplatin (C). The solid line indicates SW1417, and the dashed line indicates SW1417 siRNA. The experimental techniques are described in “Patients and Methods”.