Prognostic and Therapeutic Implications of Tumor Biology in Colorectal Liver Metastases
A special issue of Cancers (ISSN 2072-6694).
Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 19520
Special Issue Editors
2. Department of General and Visceral Surgery, Charité Campus Benjamin Franklin, 12203 Berlin, Germany
Interests: surgical oncology; hepatobiliary tumors; colorectal liver metastases; tumor biology
Special Issues, Collections and Topics in MDPI journals
Interests: surgical oncology; hepatobiliary tumors; gastric cancer; esophageal cancer
Special Issue Information
Dear Colleagues,
There has been a recent revolution in the availability and analysis of genetic data in resectable colorectal cancer liver metastases (CRLMs). During the past decade, somatic mutations such as RAS or BRAF have been repeatedly associated with worse overall and recurrence-free survival. More recently, less-common somatic mutations, alone or in combination with RAS mutations (e.g., “triple mutation” in RAS, TP53, and SMAD4) have been demonstrated to predict prognosis. However, the association of somatic mutations with cure (defined as 10-year survival) is unknown, as previous studies restricted analyses to 5-year outcomes. Similarly, little is known about the prognostic value of somatic mutations specifically in rectal cancer liver metastases.
Interestingly, some studies suggest that the interaction of somatic mutations and other prognostic factors are far from linear. In turn, some somatic mutations gain or lose significance due to the absence or presence of other variables. For example, our group has demonstrated that KRAS status has a variable prognostic impact after hepatic resection for CRLMs depending on the site of the primary CRC, while others have shown that the prognostic value of RAS mutations depends on the presence or absence of other somatic mutations such as TP53 and SMAD4. Further studies that will elucidate the interaction of somatic mutations and other prognostic factors (including other somatic mutations) are warranted.
In addition to their prognostic value, somatic gene alterations can potentially impact the surgical management of CRLMs by informing: I) patient selection for surgery (i.e., there is a need to define “biological contraindications”), II) patient selection and surgical strategy in those with bilobar CLM that is not resectable in one operation and who are candidates for 2-stage hepatectomy or ALPPS (KRAS mutation has been demonstrated to be an independent predictor of poor survival after ALPPS, although the study was very small), III) patient selection for liver transplantation (unexplored topic), IV) selection of optimal margin width (a long-lasting debate), V) post-hepatectomy surveillance (only one study has addressed this to date), and VI) selection of patients for repeat hepatectomy for recurrent disease (similarly, only a few studies have addressed the role of RAS mutations in this context). Further studies to address these aims are needed.
Dr. Georgios Antonios Margonis
Prof. Dr. Katharina Beyer
Dr. Carsten Kamphues
Guest Editors
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Keywords
- colorectal liver metastases
- somatic mutations
- tumor biology
- prognosis
- surgery
- gene alterations
- two-stage hepatectomy
- ALPPS
- RAS mutations
- margin
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