Systemic therapy
FLC is not typically responsive to chemotherapy. While there is no consensus regarding the ideal chemotherapeutic regimen for FLC, platinum-based chemotherapy regimens, as well as combination regimens including interferon alpha-2b have been used with some success.54,75,76
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In a Phase II trial, Patt et al reported a complete or partial response in five out of eight patients treated with a combination therapy of fluorouracil and recombinant interferon alpha-2b.75,76
Recent case reports have described the use of gemcitabine/oxaliplatin and 5-FU/ folinic acid/oxaliplatin with some success.77–79 In addition to systemic chemotherapy, recent research has focused on taking advantage of the new understanding of the pathogenesis and molecular genetics of FLC.
For example, one current multi-institutional, randomized controlled trial is evaluating mTOR inhibition in combination with estrogen suppression in the treatment of FLC.80
In addition, FLC has been shown to express increased levels of epithelial growth factor receptor as well as transforming growth factor beta.81 Thus, these two factors are potential targets in the future treatment of FLC.
Locoregional therapy
As FLC is not typically responsive to systemic chemotherapy, locoregional therapies have been considered. While not well studied, radiation therapy has been used to treat recurrent FLC in a few small case series. In one case report, Peacock et al demonstrated an 85% decrease in tumor volume of FLC metastases using 40 Gy in ten fractions over a 13-day time period.82
External beam radiation therapy was delivered as 21 Gy to the involved field in seven fractions over 10 days for most patients.
In a separate retrospective study of ten patients with nonresectable metastatic disease who were treated with external beam radiation in addition to chemotherapy, three patients had objective partial responses by volumetric analysis, six patients had stabilization of their tumor volume, and one patient had early progression.83 While regional liverdirected therapies (eg, chemoembolization, yttrium 90, ablation) have been well described for HCC, their use in FLC remains poorly defined.
Conclusion
FLC has a distinct epidemiology, radiographic appearance, as well as pathologic characteristic than HCC. Most often, patients who present with FLC have an absence of common risk factors seen in classic HCC. While physical findings are often not helpful, cross-sectional imaging with CT or MRI will typically display features highly suggestive of FLC.
For patients with resectable disease, surgical resection with lymphadenectomy is the recommended treatment. The long-term prognosis for patients with resected FLC is good; however, many patients will experience a recurrence. A subset of patients who recur may be candidates for surgery.
For patients who present with initially unresectable disease or develop an unresectable recurrence, other therapeutic options including systemic or locoregional therapy should be considered. Unfortunately, nonsurgical options for patients with FLC remain limited, and future research is needed to identify better multimodality therapies.
Disclosure
The authors report no conflicts of interest in this work.
Kelly J Lafaro1, Timothy M Pawlik2
1Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
2Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Correspondence: Timothy M Pawlik, Division of Surgical Oncology, Department of Surgery, Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 688, Baltimore, MD 21287, USA, Email: [email protected]
