Genomic analysis of exceptional responder to regorafenib in treatment-refractory metastatic rectal cancer: a case report and review of the literature.

We present the case of a 53-year-old male with metastatic rectal cancer who was treatment resistant to FOLFOX and FOLFOXIRI. Due to a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, regorafenib was given in the third line setting. Surprisingly, the patient had a prolonged partial response that lasted 27 months. Mutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for this unusual event. A poorly characterized but nontransforming mutation in Fms-like tyrosine kinase 4 (FLT4) was present in the tumor. Prior to and at the time of clinical progression, we found amplification of fibroblast growth factor receptor 1 (FGFR1) and epidermal growth factor receptor (EGFR), loss of the FLT4 mutation, and gain of KIT proto-oncogene receptor tyrosine kinase (KIT) G961S suggesting potential roles in acquired resistance.

Portal hypertension associated with oxaliplatin administration: clinical manifestations of hepatic sinusoidal injury.

Oxaliplatin-based chemotherapy regimens are currently a standard of care for the treatment of colorectal cancer (CRC) in both the adjuvant treatment and metastatic disease settings. Significant improvements in outcomes have been achieved with oxaliplatin-based combinations in these settings when compared with administration of 5-fluorouracil alone. Pathologic evaluation of normal liver from patients undergoing neoadjuvant oxaliplatin treatment has identified histologic evidence of sinusoidal injury, although the effect of this finding on patient outcomes after hepatic resection appears to be minimal. This article describes the use of oxaliplatin-based chemotherapy in 6 patients with stage III or IV CRC who developed evidence of noncirrhotic portal hypertension. These patients developed complications of portal hypertension including esophageal or hemorrhoidal varices with bleeding, splenomegaly with associated thrombocytopenia, and ascites. In each case, oxaliplatin-induced hepatic sinusoidal injury was identified as the most likely factor contributing to the development of noncirrhotic portal hypertension. The literature on hepatic sinusoidal injury after oxaliplatin is reviewed and the proposed pathophysiology is discussed.