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FDG and FLT-PET for Early measurement of response to 37.5 mg daily sunitinib therapy in metastatic renal cell carcinoma.

Horn KP, Yap JT, Agarwal N, Morton KA, Kadrmas DJ, Beardmore B, Butterfield RI, Boucher K, Hoffman JM - Cancer Imaging (2015)

Bottom Line: Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients.Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036).Conversely, baseline (18) F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1-2 weeks after initiating therapy.

View Article: PubMed Central - PubMed

Affiliation: Center for Quantitative Cancer Imaging, Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Dr, Suite 6810, Salt Lake City, UT, 84112-5560, USA. kevin.horn@hsc.utah.edu.

ABSTRACT

Background: Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. Sunitinib is an oral receptor tyrosine kinase inhibitor that has been used as a first-line targeted therapy in metastatic renal cell carcinoma. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy.

Methods: Twenty patients underwent dynamic acquisition positron emission tomography (PET) imaging using (18) F-fluorodeoxyglucose (FDG) and (18) F-fluorothymidine (FLT) at baseline and early in treatment (after 1, 2, 3 or 4 weeks) with 37.5 mg continuous daily dosing of sunitinib. Semi-quantitative analyses were performed to characterize the tumor metabolic (FDG) and proliferative (FLT) responses to treatment.

Results: Proliferative responses were observed in 9/19 patients and occurred in 2 patients at one week (the earliest interval evaluated) after the initiation of therapy. A metabolic response was observed in 5/19 patients, however this was not observed until after two weeks of therapy were completed. Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients. Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036). Conversely, baseline (18) F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1-2 weeks after initiating therapy.

Conclusions: While preliminary in nature, these results show an immediate and sustained proliferative response followed by a delayed metabolic response beginning after two weeks in metastatic renal cell carcinoma treated with a continuous daily dose of 37.5 mg sunitinib. The results provide evidence of tumor response to lower-dose sunitinib while also supporting the inclusion of PET imaging as a tool for early assessment in oncological clinical trials.

Trial registration: ID: NCT00694096.

No MeSH data available.


Related in: MedlinePlus

Proliferative tumor response to 37.5 mg daily sunitinib over time measured with FLT-PET. Graphs illustrating the percent change in FLT SUVmax from pre-treatment baseline to after 1 (a), 2 (b), 3 (c), or 4 (d) weeks of sunitinib therapy in individual patients. There was an immediate proliferative response to continuous lower-dose sunitinib that was maintained throughout the duration of this study. Green bars represent proliferative response (≥25 % decrease in FLTSUVmax), red bars represent proliferative progression (≥25 % increase in FLT SUVmax), and blue bars represent stable disease (<25 % change in SUVmax). The bars are labeled with the corresponding patient study identification number
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Fig4: Proliferative tumor response to 37.5 mg daily sunitinib over time measured with FLT-PET. Graphs illustrating the percent change in FLT SUVmax from pre-treatment baseline to after 1 (a), 2 (b), 3 (c), or 4 (d) weeks of sunitinib therapy in individual patients. There was an immediate proliferative response to continuous lower-dose sunitinib that was maintained throughout the duration of this study. Green bars represent proliferative response (≥25 % decrease in FLTSUVmax), red bars represent proliferative progression (≥25 % increase in FLT SUVmax), and blue bars represent stable disease (<25 % change in SUVmax). The bars are labeled with the corresponding patient study identification number

Mentions: Similarly to FDG, the target lesions identified on previous clinical imaging were associated with FLT uptake on both baseline and follow-up PET imaging in all patients (Fig. 3). A partial proliferative response (reduction in tumor proliferation of ≥ 25 % as measured with FLT-PET) was observed in 9/19 (47 %) of patients; with 2, 3, 2, and 2 patients at 1, 2, 3, and 4 weeks, respectively (Fig. 4, Table 3). Proliferative disease progression (increase in tumor proliferation of ≥ 25 % as measured with FLT-PET) was observed in 1/19 (5 %) of patients; with 0, 0, 1, and 0 patients at 1, 2, 3, and 4 weeks, respectively. Unlike metabolic responses measured with FDG-PET, tumor proliferative response to continuous lower-dose sunitinib was not delayed as it was observed at the earliest interval of follow-up (1 week) and appeared to remain stable throughout the entire period of observation for this study with similar response rates for each cohort. In contrast to FDG-PET, there is no trend in proliferative response with FLT-PET across cohorts with increasing weeks of treatment (likelihood ratio chi-square = 0.01, p = 0.93).Fig. 3


FDG and FLT-PET for Early measurement of response to 37.5 mg daily sunitinib therapy in metastatic renal cell carcinoma.

Horn KP, Yap JT, Agarwal N, Morton KA, Kadrmas DJ, Beardmore B, Butterfield RI, Boucher K, Hoffman JM - Cancer Imaging (2015)

Proliferative tumor response to 37.5 mg daily sunitinib over time measured with FLT-PET. Graphs illustrating the percent change in FLT SUVmax from pre-treatment baseline to after 1 (a), 2 (b), 3 (c), or 4 (d) weeks of sunitinib therapy in individual patients. There was an immediate proliferative response to continuous lower-dose sunitinib that was maintained throughout the duration of this study. Green bars represent proliferative response (≥25 % decrease in FLTSUVmax), red bars represent proliferative progression (≥25 % increase in FLT SUVmax), and blue bars represent stable disease (<25 % change in SUVmax). The bars are labeled with the corresponding patient study identification number
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig4: Proliferative tumor response to 37.5 mg daily sunitinib over time measured with FLT-PET. Graphs illustrating the percent change in FLT SUVmax from pre-treatment baseline to after 1 (a), 2 (b), 3 (c), or 4 (d) weeks of sunitinib therapy in individual patients. There was an immediate proliferative response to continuous lower-dose sunitinib that was maintained throughout the duration of this study. Green bars represent proliferative response (≥25 % decrease in FLTSUVmax), red bars represent proliferative progression (≥25 % increase in FLT SUVmax), and blue bars represent stable disease (<25 % change in SUVmax). The bars are labeled with the corresponding patient study identification number
Mentions: Similarly to FDG, the target lesions identified on previous clinical imaging were associated with FLT uptake on both baseline and follow-up PET imaging in all patients (Fig. 3). A partial proliferative response (reduction in tumor proliferation of ≥ 25 % as measured with FLT-PET) was observed in 9/19 (47 %) of patients; with 2, 3, 2, and 2 patients at 1, 2, 3, and 4 weeks, respectively (Fig. 4, Table 3). Proliferative disease progression (increase in tumor proliferation of ≥ 25 % as measured with FLT-PET) was observed in 1/19 (5 %) of patients; with 0, 0, 1, and 0 patients at 1, 2, 3, and 4 weeks, respectively. Unlike metabolic responses measured with FDG-PET, tumor proliferative response to continuous lower-dose sunitinib was not delayed as it was observed at the earliest interval of follow-up (1 week) and appeared to remain stable throughout the entire period of observation for this study with similar response rates for each cohort. In contrast to FDG-PET, there is no trend in proliferative response with FLT-PET across cohorts with increasing weeks of treatment (likelihood ratio chi-square = 0.01, p = 0.93).Fig. 3

Bottom Line: Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients.Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036).Conversely, baseline (18) F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1-2 weeks after initiating therapy.

View Article: PubMed Central - PubMed

Affiliation: Center for Quantitative Cancer Imaging, Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Dr, Suite 6810, Salt Lake City, UT, 84112-5560, USA. kevin.horn@hsc.utah.edu.

ABSTRACT

Background: Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. Sunitinib is an oral receptor tyrosine kinase inhibitor that has been used as a first-line targeted therapy in metastatic renal cell carcinoma. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy.

Methods: Twenty patients underwent dynamic acquisition positron emission tomography (PET) imaging using (18) F-fluorodeoxyglucose (FDG) and (18) F-fluorothymidine (FLT) at baseline and early in treatment (after 1, 2, 3 or 4 weeks) with 37.5 mg continuous daily dosing of sunitinib. Semi-quantitative analyses were performed to characterize the tumor metabolic (FDG) and proliferative (FLT) responses to treatment.

Results: Proliferative responses were observed in 9/19 patients and occurred in 2 patients at one week (the earliest interval evaluated) after the initiation of therapy. A metabolic response was observed in 5/19 patients, however this was not observed until after two weeks of therapy were completed. Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients. Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036). Conversely, baseline (18) F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1-2 weeks after initiating therapy.

Conclusions: While preliminary in nature, these results show an immediate and sustained proliferative response followed by a delayed metabolic response beginning after two weeks in metastatic renal cell carcinoma treated with a continuous daily dose of 37.5 mg sunitinib. The results provide evidence of tumor response to lower-dose sunitinib while also supporting the inclusion of PET imaging as a tool for early assessment in oncological clinical trials.

Trial registration: ID: NCT00694096.

No MeSH data available.


Related in: MedlinePlus