Change in total lesion glycolysis and clinical outcome after 90Y radioembolization in intrahepatic cholangiocarcinoma,☆☆

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Abstract

Introduction

Our aim was to assess the prognostic value of post-treatment decrease in total lesion glycolysis (ΔTLG) assessed by 2-[18 F]-fluorodeoxyglucose ([18 F] FDG) PET-CT performed 6 weeks after 90Y radioembolization (90Y RE) in patients affected by intrahepatic cholangiocarcinoma (ICC).

Methods

A total of 18 patients were accepted into our department for 90Y RE. Before the procedure, all patients underwent [18 F] FDG PET-CT, and total lesion glycolysis was calculated. Six weeks after 90Y administration, PET scan was performed, and ΔTLG was determined. Patients underwent follow up by imaging and laboratory at quarterly intervals until death or for at least 24 months from 90Y RE. Furthermore, subjects were divided in 2 groups (group 1: 6 weeks ΔTLG > 50%, group 2: ΔTLG < 50%). Kaplan–Meier method was used to achieve time to progression (TTP) and overall survival (OS) curves for each group. TTP and OS curves were compared to demonstrate eventual relevant differences between the 2 groups.

Results

Seventeen patients underwent 90Y RE, and one subject was considered ineligible. According to PET Response Criteria in Solid Tumors, partial response was found in 14 patients (82.4%), stable disease in 3 (17.6%). No patient showed complete metabolic response. The mean OS for all patients was 64.5 ± 5.0 weeks. Subjects with a ΔTLG > 50% and ΔTLG < 50% had a mean OS of 79.6 ± 3.6 and 43.1 ± 2.0 weeks, respectively (p < 0.001). TTP resulted of 28.9 ± 3.8 weeks for the whole cohort. Patients with ΔTLG > 50% had a significantly longer TTP (mean 36.9 ± 3.6 weeks) than those with ΔTLG < 50% (mean 13.7 ± 1.7 weeks, p = 0.001).

Conclusion

Our results indicate that 90Y RE can be an effective and safe therapy for ICC. ΔTLG calculated on post-treatment [18 F] FDG PET-CT agrees with patients' final outcome.

Introduction

Intrahepatic cholangiocarcinoma (ICC) is a relatively rare neoplasm originating from the intrahepatic bile ducts [1], [2]. It can be rapidly fatal, associated with median survival between 3.1 and 7.7 months in case of unresectable tumor. Surgery is the only curative approach; nevertheless, it is not always practicable. This is because, at the moment of diagnosis, most patients' disease has already reached an advanced state. Systemic chemotherapy has been used with modest survival benefit (i.e. overall survival time shorter than 1 year) [3]. Minimally invasive loco-regional therapies, such as trans-arterial chemoembolization (TACE), have been widely demonstrated to be effective in the treatment of primitive hepatic tumors such us hepatocellular carcinoma (HCC). However, these techniques are still far from representing the standard of care in locally advanced ICC [4], [5].

90Y Radioembolization (RE) is a well standardized procedure used for the treatment of primary or secondary hepatic lesions. 90Y embedded in resin or glass microspheres is infused directly into the circulation trough angiographic catheters placed in the hepatic arteries [6], [7]. 90Y is a beta-emitter that decays to stable zirconium-90 with an average energy of 0.94 MeV (half-life 2.67 days), with a mean tissue penetration of 2.5 mm and a maximum range of 11 mm. 90Y spheres, once implanted in liver, can release a significant amount of radiation to the neoplastic cells and a relatively low dose to the normal parenchyma due to different vascularisation pattern.

90Y RE is an effective treatment in hepatocellular cancer and in liver metastases from colon and breast cancer [8], [9], [10]. Previously published papers suggest that 90Y RE can be effective and safe to treat locally advanced ICC [11], [12], [13].

2-[18 F]-fluorodeoxyglucose ([18 F] FDG) PET-CT proved to be useful in many oncological scenarios; it can be for example applied to detect metabolic response to 90Y RE [14]. Functional tumor volume (FTV) and total lesion glycolysis (TLG) are measures of tumor metabolic activity determined by [18 F] FDG PET. Gulec et al. have recently demonstrated that these values can be useful quantitative criteria for patient selection and disease prognostication in patients affected by cancer colon liver metastases treated with 90Y RE [15]. It is worthy of note that the authors demonstrated that metabolic response in liver tumors can be detected as early as 4 weeks post 90RE. The FTV and TLG changes thus represent predictors of anatomic tumor volume changes.

The aim of this study was to investigate the relationship between the clinical outcome of patients affected by ICC having undergone 90Y RE and the decrease in TLG (ΔTLG) assessed 6 weeks post procedure by [18 F] FDG PET-CT.

Section snippets

Patients

A total of 18 patients affected by unresectable and chemotherapy-refractory ICC were accepted into our department for 90Y RE. The enrolment criteria were: histological proof of ICC; liver-only or liver-predominant disease; age  18 years; ability and willingness to provide written informed consent; life expectancy > 3 months; Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; bilirubin < 2.0 mg/dl, albumin > 2.0 g/dl, international normalized ratio (INR) < 1.5; creatinine < 2.0 mg/dl;

Patients and tumor characteristics

Seventeen patients (6 males, 11 female; mean age 59.4 ± 10.4 years) underwent 90Y RE. One patient was considered ineligible due to the detection of peri-hepatic fluid at the preprocedure imaging.

Patients' clinical features and their final outcome after 90Y RE are summarized in Table 1.

Previous treatments included systemic chemotherapy in 11 patients, chemotherapy plus surgery in 4 patients, and no previous therapy in 2 subjects. On the pre-treatment [18 F] FDG PET-CT scan, fourteen out of 17

Discussion

In this study 90Y RE was found to provide an effective rate of tumor control in patients affected by ICC. Furthermore, our results indicate that ΔTLG, determined on the [18 F] FDG PET-CT performed after 90Y RE, agrees with patients' final outcome both in terms of OS and TTP. To our knowledge, the present study is the first correlating survival in ICC after 90Y RE and the changes in TLG assessed by [18 F] FDG PET.

There are relatively few data addressing the utility of 90Y RE in unresectable and

Conclusion

Our results indicate that 90Y RE can be an effective and safe therapy for ICC. ΔTLG calculated 6 weeks after treatment by [18 F] FDG PET-CT agrees with patients' final outcome.

References (24)

  • R. Cianni et al.

    Radioembolisation with (90)Y-labelled resin microspheres in the treatment of liver metastasis from breast cancer

    Eur Radiol

    (2013)
  • S.A. Padia et al.

    Superselective Yttrium-90 radioembolization for hepatocellular carcinoma yields high response rates with minimal toxicity

    J Vasc Interv Radiol

    (2014)
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    Acknowledgements: None.

    ☆☆

    Conflict of Interest: All authors declare no potential conflicts of interest.

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