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Letters To The Editor

¹⁸F-Fluorodeoxyglucose Positron Emission Tomography for Monitoring Response to Sorafenib Treatment in Patients with Hepatocellular Carcinoma

Departments of ^aMedical Oncology and ^bNuclear Medicine and Molecular Imaging, University Medical Center Groningen, and University of Groningen, Groningen, The Netherlands

Correspondence: E. J. M. Siemerink, M.D., University Medical Center Groningen, Department of Medical Oncology, Post Box 30001, 9700 RB Groningen, The Netherlands. Telephone: 0031-50-3612821; Fax: 0031-50-3614862; e-mail: e.j.m.siemerink{at}int.umcg.nl

Received March 12, 2008; accepted for publication April 15, 2008.

Disclosure: No potential conflicts of interest were reported by the authors.

In a previous issue of The Oncologist, O'Neil and Venook [1] described the emerging evidence of clinically relevant activity of sorafenib in patients with advanced hepatocellular carcinoma (HCC) [2, 3]. They also emphasized the difficulty of adequate response assessment of treatment with conventional anatomic imaging. In the pivotal phase III study [3], several tumors demonstrated tumor necrosis in spite of an increase in size. This discrepancy might be an explanation for the significant longer overall survival time in spite of a very low rate of radiographic response.

To improve diagnosis, functional imaging with ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) has emerged in the past years. For HCC, the uptake of ¹⁸F-FDG is variable, with an inadequate sensitivity of 50%–65% [4, 5]. Therefore, it cannot replace conventional imaging modalities in primary diagnosis.

However, in HCC, in addition to differentiating between tumor grades and identifying metastatic disease, ¹⁸F-FDG-PET is useful in monitoring response to therapy [4, 6]. In another issue of The Oncologist, Boss et al. [7] hallmarked the use of ¹⁸F-FDG-PET in early response measurements to avoid ineffective therapies and unnecessary side effects.

In this context, we recently investigated the use of ¹⁸F-FDG-PET scans in patients with advanced HCC to distinguish, in an early phase, responders from nonresponders to sorafenib treatment. ¹⁸F-FDG-PET scans were performed at baseline and 3 weeks after the start of treatment, in addition to conventional imaging. Whole-body two-dimensional PET images were acquired 60–90 minutes after i.v. injection (>6-hour fasting period) of on-site produced ¹⁸F-FDG (5 MBq/kg) on a Siemens ECAT HR+ (high resolution) positron emission camera (Siemens, Knoxville, TN) with attenuation correction. Images were reconstructed via ordered subset expectation maximization (two iterations, eight subsets).

In this letter, we would like to describe two patients treated with sorafenib—a responder (Fig. 1A) and a nonresponder (Fig. 1B). In the first patient at baseline (Fig. 1A), the ¹⁸F-FDG-PET scan showed focal uptake in the liver. After 3 weeks (Fig. 1A), a partial response to sorafenib treatment was evident with less uptake in the liver. This was in accordance with the computed tomography scan (week 12), which showed a partial response. In the second patient at baseline (Fig. 1B), the ¹⁸F-FDG-PET scan showed multiple lesions (in the lungs, mediastinum, and liver). After 3 weeks, the ¹⁸F-FDG-PET scan (Fig. 1B) showed progressive disease with multiple new lesions. This was in accordance with progressive lesions on the chest x-ray and a bone scan, performed because of complaints of dyspnea and pain in the bones. This patient died of progressive disease 12 weeks after the start of treatment.

View larger version (49K): [in this window] [in a new window]   Figure 1. Assessment of response to sorafenib using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). (A): Responder. At baseline (A1), the 18F-FDG-PET scan shows a focal lesion in the liver; at week 3 (A2), a partial response can be seen, with a decrease in the size of the larger liver lesion, which now is shown to consist of two lesions near each other. (B): Nonresponder. At baseline (B1), the 18F-FDG-PET scan shows multiple lesions in the lungs, mediastinum, and liver; at week 3 (B2), progressive disease can be seen, with numerous new lesions.

	AUTHOR CONTRIBUTIONS

Top Author Contributions Acknowledgments References

 
Conception/design: Ester J. M. Siemerink, Geke A. P. Hospers

Financial support: Ester J. M. Siemerink, Nanno H. Mulder, Adrienne H. Brouwers, Geke A. P. Hospers

Collection/assembly of data: Ester J. M. Siemerink, Nanno H. Mulder, Geke A. P. Hospers

Data analysis and interpretation: Ester J. M. Siemerink, Nanno H. Mulder, Adrienne H. Brouwers, Geke A. P. Hospers

Manuscript writing: Ester J. M. Siemerink, Nanno H. Mulder, Adrienne H. Brouwers, Geke A. P. Hospers

Final approval of manuscript: Ester J. M. Siemerink, Nanno H. Mulder, Adrienne H. Brouwers, Geke A. P. Hospers

	ACKNOWLEDGMENTS

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We acknowledge the assistance of Dr. Jan Pruim, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, with the ¹⁸F-FDG-PET images.

	REFERENCES

Top Author Contributions Acknowledgments References

 

1. O'Neil BH, Venook AP. Hepatocellular carcinoma: The role of the North American GI Steering Committee Hepatobiliary Task Force and the advent of effective drug therapy. The Oncologist 2007;12:1425–1432.[Abstract/Free Full Text]
2. Abou-Alfa GK, Schwartz L, Ricci S et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006;24:4293–4300.[Abstract/Free Full Text]
3. Llovet J, Ricci S, Mazzaferro V et al. Randomized phase III trial of sorafenib versus placebo in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol 2007;25(suppl 18):1.[Free Full Text]
4. Hain SF, Fogelman I. Recent advances in imaging hepatocellular carcinoma: Diagnosis, staging and response assessment: Functional imaging. Cancer J 2004;10:121–127.[CrossRef][Medline]
5. Sun L, Wu H, Guan YS. Positron emission tomography/computer tomography: Challenge to conventional imaging modalities in evaluating primary and metastatic liver malignancies. World J Gastroenterol 2007;13:2775–2783.[Medline]
6. Larson SM, Schwartz LH. ¹⁸F-FDG-PET as a candidate for "qualified biomarker": Functional assessment of treatment response in oncology. J Nucl Med 2006;47:901–903.[Free Full Text]
7. Boss DS, Olmos RV, Sinaasappel M et al. Application of PET/CT in the development of novel anticancer drugs. The Oncologist 2008;13:25–38.[Abstract/Free Full Text]

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