Assessing the optimal duration of chemotherapy in patients with colorectal liver metastases

White, Rebekah R.; Schwartz, Lawrence H.; Muñoz, J; Raggio, Greer A.; Jarnagin, William R.; Fong, Yuman; D’Angelica, Michael I.; Kemeny, Nancy E.

doi:10.1002/jso.21042

Cited by 29 publications

(21 citation statements)

References 19 publications

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“…According to a recent report, chemotherapeutic effect disappears after 4 months or more 21, supporting the present results. The tumor shrinkage rate also showed first-line chemotherapy to be the most effective and to be un-expectable though second to third line objectively.…”

Section: Discussionsupporting

confidence: 93%

Determining Timing of Hepatectomy for Colorectal Cancer with Distant Metastasis According to Imaging-Based Tumor Shrinkage Ratio

Sasaki¹,

Osada²,

Mori³

et al. 2013

Int. J. Med. Sci.

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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.

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Section: Discussionsupporting

confidence: 93%

Determining Timing of Hepatectomy for Colorectal Cancer with Distant Metastasis According to Imaging-Based Tumor Shrinkage Ratio

Sasaki¹,

Osada²,

Mori³

et al. 2013

Int. J. Med. Sci.

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“…In our case liver fibrosis with splenomegaly developed after 12 cycles of FOLFOX regimen. In the case of preoperative chemotherapy, the optimal duration is about 4 month at most to maximize therapeutic benefit, while avoiding hepatotoxicity (13). …”

Section: Discussionmentioning

confidence: 99%

A Case of Liver Fibrosis with Splenomegaly after Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer

Moon

Lee

et al. 2013

J Korean Med Sci

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Previous studies reported that oxaliplatin is associated with sinusoidal obstruction syndrome. However few reports on oxaliplatin induced liver fibrosis are found in the literature. Furthermore pathogenesis of liver fibrosis is not well known. We report a case of 45-yr-old Korean man in whom liver fibrosis with splenomegaly developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for colon cancer (T4N2M0). Thorough history taking and serological examination revealed no evidence of chronic liver disease. Restaging CT scans demonstrated a good response to chemotherapy. Five month after chemotherapy, he underwent right hepatectomy due to isolated metastatic lesion. The liver parenchyma showed diffuse sinusoidal dilatation and centrilobular vein fibrosis with necrosis without steatosis. We could conclude that splenomegaly was due to perisinusoidal liver fibrosis and liver cell necrosis induced portal hypertension by oxaliplatin. In addition, to investigate the pathogenesis of liver fibrosis, immunohistochemical stains such as CD31 and α-smooth muscle actin (α-SMA) were conducted with control group. The immunohistochemical stains for CD31 and α-SMA were positive along the sinusoidal space in the patient, while negative in the control group. Chemotherapy with oxaliplatin induces liver fibrosis which should be kept in mind as a serious complication.

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“…Probably the optimum duration of preoperative chemotherapy, to maximise therapeutic benefi t while avoiding hepatotoxicity, is likely to be 4 months. White and colleagues [51] reported that patients experienced tumour reduction after 2-4 months of chemotherapy and little reduction thereafter, indicating that chemotherapy continued beyond 4 months has little therapeutic effect.…”

Section: How Can We Prevent Liver Injury?mentioning

confidence: 97%

Multidisciplinary approach of colorectal liver metastases

2011

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Colorectal cancer (CRC) is the second most common cause of cancer death in Spain. Fifty percent of patients will develop colorectal liver metastases (CLM) during the course of the disease. Less than 20% of patients with CLM are initially resectable and for them 5-year disease-free survival (DFS) is about 20-25%, with a high recurrence rate. CLM is a heterogeneous disease. From a clinical point of view, four main groups can be differentiated: initially resectable, not optimally resectable, unresectable that could be resectable and unresectable that never will be likely to be resected. Treatment of CLM must be established, always, in a multidisciplinary team discussion with an analysis of prognostic factors and resectability. For patients with resectable CLM, the EORTC trial 364 demonstrated that chemotherapy plus surgery is better than surgery alone. Consequently most patients should be treated with perioperative chemotherapy based on oxaliplatin, and if resection has been done without chemotherapy, they should receive adjuvant chemotherapy after R0 resection. Based on oncological factors, the 5-year survival rate after resection of CLM ranges from 60% to only 14% with a poor score. If a patient has more than one of the poor prognostic factors he should probably be referred for preoperative (induction) chemotherapy. Only a minority of patients with CLM are amenable to surgery; therefore, efforts have been made to increase the percentage of patients who could be candidates for resection. Studies, mostly retrospective, have confirmed the ability of neoadjuvant chemotherapy (conversion chemotherapy) to render some metastases resectable. The regimens we must use depend on the KRAS mutational status and the toxicity profiles of drugs in the context of each patient. In k-ras mutated tumours we can use bevacizumab combined with standard chemotherapy or concomitant administration of the three active agents (FOLFOXIRI) in suitable patients. In k-ras wild-type patients, the combination of cetuximab and FOLFIRI-FOLFOX improved response rates and resection rate in phase III-II trials. With a lower level of evidence, panitumumab is an alternative combined with FOLFOX. Bevacizumab is also an alternative as it does not depend on KRAS status. Radiotherapy is becoming an alternative in selected patients, where surgery is not an alternative. For the majority of patients, who will never be resectable, the continuum of care with chemotherapy will be the paradigm for their management.

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Assessing the optimal duration of chemotherapy in patients with colorectal liver metastases

Abstract: In responders to preoperative therapy, surgical resection should be considered after 2-4 months, when most patients have achieved maximal response.

Cited by 29 publications

References 19 publications

Determining Timing of Hepatectomy for Colorectal Cancer with Distant Metastasis According to Imaging-Based Tumor Shrinkage Ratio

Determining Timing of Hepatectomy for Colorectal Cancer with Distant Metastasis According to Imaging-Based Tumor Shrinkage Ratio

A Case of Liver Fibrosis with Splenomegaly after Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer

Multidisciplinary approach of colorectal liver metastases

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