Eur J Nucl Med Mol Imaging DOI 10.1007/s00259-014-2772-0
ORIGINAL ARTICLE
18
F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma
Pierre-Yves Salaun & Loïc Campion & Catherine Ansquer & Eric Frampas & Cédric Mathieu & Philippe Robin & Claire Bournaud & Jean-Philippe Vuillez & David Taieb & Caroline Rousseau & Delphine Drui & Eric Mirallié & Françoise Borson-Chazot & David M. Goldenberg & Jean-François Chatal & Jacques Barbet & Françoise Kraeber-Bodéré
Received: 16 December 2013 / Accepted: 28 March 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose PET is a powerful tool for assessing targeted therapy. Since 18F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated 18F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with
pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. Methods Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic
P.50 % decrease to a PR and a >50 % increase to PD. SD corresponded to an increase not sufficient for PD or a decrease not sufficient for PR. For biomarker DT evaluation, a significant impact after pRAIT corresponded to at least a 100 % increase in Ct or CEA DT or a prolonged decrease in the biomarker serum concentration after pRAIT [13, 14]. Integrating these different criteria, a combined response was defined as follows: a patient was considered as combined responder if a PR, CR or SD according to RECIST, PET and biomarker concentration was observed 3 months after pRAIT and a ≥100 % CEA or Ct DT increase or a prolonged decrease in the biomarker concentration was found during the post-pRAIT follow-up. Statistical considerations All data were analysed in terms of OS from pRAIT and from MTC diagnosis. OS was calculated from the date of diagnosis or pRAIT to death from all causes or last visit alive. Patients alive at the date of analyses were censored. Follow-up was calculated by means of the inverse Kaplan-Meier method. OS was summarized using the Kaplan-Meier method. OS in each
Eur J Nucl Med Mol Imaging
group were compared using the log-rank test. Finally, the Cox proportional hazards model was used to determine independent prognostic effects on OS. Proportionality of hazards was verified. Multivariate analysis was done in the 32 patients with available data for each kind of response. The different predictive models were compared using the Akaike information criterion (AIC). The prognostic value of 18F-FDG PET response in predicting OS from pRAIT and OS from diagnosis was assessed and compared with different demographic parameters at inclusion including age, sex, time from initial diagnosis of MTC, Ct and CEA concentrations, biomarker DT value before pRAIT corresponding to minimal value between CEA and Ct DT, location of disease, presence of bone marrow involvement (BMI) and SUVmax (≥5 vs.
ORIGINAL ARTICLE
18
F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma
Pierre-Yves Salaun & Loïc Campion & Catherine Ansquer & Eric Frampas & Cédric Mathieu & Philippe Robin & Claire Bournaud & Jean-Philippe Vuillez & David Taieb & Caroline Rousseau & Delphine Drui & Eric Mirallié & Françoise Borson-Chazot & David M. Goldenberg & Jean-François Chatal & Jacques Barbet & Françoise Kraeber-Bodéré
Received: 16 December 2013 / Accepted: 28 March 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose PET is a powerful tool for assessing targeted therapy. Since 18F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated 18F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with
pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. Methods Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic
P.50 % decrease to a PR and a >50 % increase to PD. SD corresponded to an increase not sufficient for PD or a decrease not sufficient for PR. For biomarker DT evaluation, a significant impact after pRAIT corresponded to at least a 100 % increase in Ct or CEA DT or a prolonged decrease in the biomarker serum concentration after pRAIT [13, 14]. Integrating these different criteria, a combined response was defined as follows: a patient was considered as combined responder if a PR, CR or SD according to RECIST, PET and biomarker concentration was observed 3 months after pRAIT and a ≥100 % CEA or Ct DT increase or a prolonged decrease in the biomarker concentration was found during the post-pRAIT follow-up. Statistical considerations All data were analysed in terms of OS from pRAIT and from MTC diagnosis. OS was calculated from the date of diagnosis or pRAIT to death from all causes or last visit alive. Patients alive at the date of analyses were censored. Follow-up was calculated by means of the inverse Kaplan-Meier method. OS was summarized using the Kaplan-Meier method. OS in each
Eur J Nucl Med Mol Imaging
group were compared using the log-rank test. Finally, the Cox proportional hazards model was used to determine independent prognostic effects on OS. Proportionality of hazards was verified. Multivariate analysis was done in the 32 patients with available data for each kind of response. The different predictive models were compared using the Akaike information criterion (AIC). The prognostic value of 18F-FDG PET response in predicting OS from pRAIT and OS from diagnosis was assessed and compared with different demographic parameters at inclusion including age, sex, time from initial diagnosis of MTC, Ct and CEA concentrations, biomarker DT value before pRAIT corresponding to minimal value between CEA and Ct DT, location of disease, presence of bone marrow involvement (BMI) and SUVmax (≥5 vs.
