Early reduction in tumour [18F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone

Ioannis Trigonis; Pek Keng Koh; Ben Taylor; Mahbubunnabi Tamal; David Ryder; Mark Earl; Jose Anton-Rodriguez; Kate Haslett; Helen Young; Corinne Faivre-Finn; Fiona Blackhall; Alan Jackson; Marie Claude Asselin

doi:10.1007/s00259-013-2632-3

Early reduction in tumour [¹⁸F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone

Ioannis Trigonis^*, Pek Keng Koh, Ben Taylor, Mahbubunnabi Tamal, David Ryder, Mark Earl, Jose Anton-Rodriguez, Kate Haslett, Helen Young, Corinne Faivre-Finn, Fiona Blackhall, Alan Jackson, Marie Claude Asselin

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

Abstract

Purpose: Changes in tumour 3′-deoxy-3′-[¹⁸F] fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability. Methods: Sixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5-11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUV_mean and SUV_max) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions. Results: In all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUV_mean reproducibility in primary tumours (SD 8.9 %) was better than SUV_max reproducibility (SD 12.6 %). In nodes, SUV_mean and SUV_max reproducibilities (SD 18.0 and 17.2 %) were comparable but worse than for primary tumours. After 5-11 RT fractions, primary tumour SUV_mean decreased significantly by 25 % (p=0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31 % (p=0.020) with a larger SUV_mean decrease of 40 % (p<0.0001). Similar changes were found for SUV_max. Conclusion: Across this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously reported for concurrent chemo-RT at a similar time point. These results confirm the potential for FLT PET to report early on radiation response and to enhance the clinical development of novel drug-radiation combinations by providing an interpretable, early pharmacodynamic end point.

Original language	English
Pages (from-to)	682-693
Number of pages	12
Journal	European Journal of Nuclear Medicine
Volume	41
Issue number	4
DOIs	https://doi.org/10.1007/s00259-013-2632-3
Publication status	Published - Apr 2014
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgments This is a contribution from the Cambridge—Manchester Cancer Imaging Centre, which is funded by the EPSRC and Cancer Research UK and from the Manchester-UCL Lung Cancer Centre of Excellence, which is funded by CRUK. The authors gratefully acknowledge the financial support from AstraZeneca Pharmaceuticals, the Oglesby Charitable Trust and Cancer Research UK. We also thank Pamela Hindmarsh for her help with patient recruitment and the technical staff at the WMIC for PET scanning. We are also grateful to all participants for volunteering in the study.

Keywords

Early response monitoring
Non-small cell lung cancer
Radiotherapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s00259-013-2632-3

Cite this

Trigonis, I., Koh, P. K., Taylor, B., Tamal, M., Ryder, D., Earl, M., Anton-Rodriguez, J., Haslett, K., Young, H., Faivre-Finn, C., Blackhall, F., Jackson, A., & Asselin, M. C. (2014). Early reduction in tumour [¹⁸F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone. European Journal of Nuclear Medicine, 41(4), 682-693. https://doi.org/10.1007/s00259-013-2632-3

@article{8e4a32f2b5964d1ea38705b1679a6a7c,

title = "Early reduction in tumour [18F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone",

abstract = "Purpose: Changes in tumour 3′-deoxy-3′-[18F] fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability. Methods: Sixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5-11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUVmean and SUVmax) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions. Results: In all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUVmean reproducibility in primary tumours (SD 8.9 %) was better than SUVmax reproducibility (SD 12.6 %). In nodes, SUVmean and SUVmax reproducibilities (SD 18.0 and 17.2 %) were comparable but worse than for primary tumours. After 5-11 RT fractions, primary tumour SUVmean decreased significantly by 25 % (p=0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31 % (p=0.020) with a larger SUVmean decrease of 40 % (p<0.0001). Similar changes were found for SUVmax. Conclusion: Across this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously reported for concurrent chemo-RT at a similar time point. These results confirm the potential for FLT PET to report early on radiation response and to enhance the clinical development of novel drug-radiation combinations by providing an interpretable, early pharmacodynamic end point.",

keywords = "Early response monitoring, Non-small cell lung cancer, Radiotherapy",

author = "Ioannis Trigonis and Koh, {Pek Keng} and Ben Taylor and Mahbubunnabi Tamal and David Ryder and Mark Earl and Jose Anton-Rodriguez and Kate Haslett and Helen Young and Corinne Faivre-Finn and Fiona Blackhall and Alan Jackson and Asselin, {Marie Claude}",

note = "Funding Information: Acknowledgments This is a contribution from the Cambridge—Manchester Cancer Imaging Centre, which is funded by the EPSRC and Cancer Research UK and from the Manchester-UCL Lung Cancer Centre of Excellence, which is funded by CRUK. The authors gratefully acknowledge the financial support from AstraZeneca Pharmaceuticals, the Oglesby Charitable Trust and Cancer Research UK. We also thank Pamela Hindmarsh for her help with patient recruitment and the technical staff at the WMIC for PET scanning. We are also grateful to all participants for volunteering in the study.",

year = "2014",

month = apr,

doi = "10.1007/s00259-013-2632-3",

language = "English",

volume = "41",

pages = "682--693",

journal = "European Journal of Nuclear Medicine",

issn = "1619-7070",

publisher = "Springer Verlag",

number = "4",

}

Trigonis, I, Koh, PK, Taylor, B, Tamal, M, Ryder, D, Earl, M, Anton-Rodriguez, J, Haslett, K, Young, H, Faivre-Finn, C, Blackhall, F, Jackson, A & Asselin, MC 2014, 'Early reduction in tumour [¹⁸F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone', European Journal of Nuclear Medicine, vol. 41, no. 4, pp. 682-693. https://doi.org/10.1007/s00259-013-2632-3

TY - JOUR

T1 - Early reduction in tumour [18F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone

AU - Trigonis, Ioannis

AU - Koh, Pek Keng

AU - Taylor, Ben

AU - Tamal, Mahbubunnabi

AU - Ryder, David

AU - Earl, Mark

AU - Anton-Rodriguez, Jose

AU - Haslett, Kate

AU - Young, Helen

AU - Faivre-Finn, Corinne

AU - Blackhall, Fiona

AU - Jackson, Alan

AU - Asselin, Marie Claude

N1 - Funding Information: Acknowledgments This is a contribution from the Cambridge—Manchester Cancer Imaging Centre, which is funded by the EPSRC and Cancer Research UK and from the Manchester-UCL Lung Cancer Centre of Excellence, which is funded by CRUK. The authors gratefully acknowledge the financial support from AstraZeneca Pharmaceuticals, the Oglesby Charitable Trust and Cancer Research UK. We also thank Pamela Hindmarsh for her help with patient recruitment and the technical staff at the WMIC for PET scanning. We are also grateful to all participants for volunteering in the study.

PY - 2014/4

Y1 - 2014/4

N2 - Purpose: Changes in tumour 3′-deoxy-3′-[18F] fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability. Methods: Sixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5-11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUVmean and SUVmax) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions. Results: In all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUVmean reproducibility in primary tumours (SD 8.9 %) was better than SUVmax reproducibility (SD 12.6 %). In nodes, SUVmean and SUVmax reproducibilities (SD 18.0 and 17.2 %) were comparable but worse than for primary tumours. After 5-11 RT fractions, primary tumour SUVmean decreased significantly by 25 % (p=0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31 % (p=0.020) with a larger SUVmean decrease of 40 % (p<0.0001). Similar changes were found for SUVmax. Conclusion: Across this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously reported for concurrent chemo-RT at a similar time point. These results confirm the potential for FLT PET to report early on radiation response and to enhance the clinical development of novel drug-radiation combinations by providing an interpretable, early pharmacodynamic end point.

AB - Purpose: Changes in tumour 3′-deoxy-3′-[18F] fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability. Methods: Sixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5-11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUVmean and SUVmax) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions. Results: In all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUVmean reproducibility in primary tumours (SD 8.9 %) was better than SUVmax reproducibility (SD 12.6 %). In nodes, SUVmean and SUVmax reproducibilities (SD 18.0 and 17.2 %) were comparable but worse than for primary tumours. After 5-11 RT fractions, primary tumour SUVmean decreased significantly by 25 % (p=0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31 % (p=0.020) with a larger SUVmean decrease of 40 % (p<0.0001). Similar changes were found for SUVmax. Conclusion: Across this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously reported for concurrent chemo-RT at a similar time point. These results confirm the potential for FLT PET to report early on radiation response and to enhance the clinical development of novel drug-radiation combinations by providing an interpretable, early pharmacodynamic end point.

KW - Early response monitoring

KW - Non-small cell lung cancer

KW - Radiotherapy

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