[18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches.
OBJECTIVE
Nitroglycerin (NTG) is a vasodilating drug, which increases tumor blood flow and consequently decreases hypoxia. Therefore, changes in [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG PET) uptake pattern may occur. In this analysis, we investigated the feasibility of [18F]FDG PET for response assessment to paclitaxel-carboplatin-bevacizumab (PCB) treatment with and without NTG patches. And we compared the [18F]FDG PET response assessment to RECIST response assessment and survival.


METHODS
A total of 223 stage IV non-small cell lung cancer (NSCLC) patients were included in a phase II study (NCT01171170) randomizing between PCB treatment with or without NTG patches. For 60 participating patients, a baseline and a second [18F]FDG PET/computed tomography (CT) scan, performed between day 22 and 24 after the start of treatment, were available. Tumor response was defined as a 30 % decrease in CT and PET parameters, and was compared to RECIST response at week 6. The predictive value of these assessments for progression free survival (PFS) and overall survival (OS) was assessed with and without NTG.


RESULTS
A 30 % decrease in SUVpeak assessment identified more patients as responders compared to a 30 % decrease in CT diameter assessment (73 % vs. 18 %), however, this was not correlated to OS (SUVpeak30 p = 0.833; CTdiameter30 p = 0.557). Changes in PET parameters between the baseline and the second scan were not significantly different for the NTG group compared to the control group (p value range 0.159-0.634). The CT-based (part of the [18F]FDG PET/CT) parameters showed a significant difference between the baseline and the second scan for the NTG group compared to the control group (CT diameter decrease of 7 ± 23 % vs. 19 ± 14 %, p = 0.016, respectively).


CONCLUSIONS
The decrease in tumoral FDG uptake in advanced NSCLC patients treated with chemotherapy with and without NTG did not differ between both treatment arms. Early PET-based response assessment showed more tumor responders than CT-based response assessment (part of the [18F]FDG PET/CT); this was not correlated to survival. This might be due to timing of the [18F]FDG PET shortly after the bevacizumab infusion.
Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands. evelyn.dejong@maastro.nl.
Evelyn E C
EE
de Jong
Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands.
Wouter
W
van Elmpt
Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands.
Ralph T H
RT
Leijenaar
Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, Netherlands.
Otto S
OS
Hoekstra
Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Harry J M
HJ
Groen
Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, Netherlands.|Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands.
Egbert F
EF
Smit
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, Netherlands.
Ronald
R
Boellaard
Department of Biometrics, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands.
Vincent
V
van der Noort
Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands.|Institute of Radiooncology, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.|Department of Radiotherapy and Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus of Technische Universität Dresden, Dresden, Germany.
Esther G C
EG
Troost
Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands.
Philippe
P
Lambin
Department of Pulmonology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands.
Anne-Marie C
AC
Dingemans
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009426:Netherlands; D005996:Nitroglycerin / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage
D019275:Radiopharmaceuticals; D014665:Vasodilator Agents; D019788:Fluorodeoxyglucose F18; D000068258:Bevacizumab; D016190:Carboplatin; D005996:Nitroglycerin; D017239:Paclitaxel
Bevacizumab; Nitroglycerin; Response assessment; Stage IV NSCLC; [18F]FDG PET/CT