[18F]-HX4 PET/CT hypoxia in patients with squamous cell carcinoma of the head and neck treated with chemoradiotherapy: Prognostic results from two prospective trials

Sebastian Sanduleanu; Olga Hamming-Vrieze; Frederik W. R. Wesseling; Aniek J. G. Even; Frank J. Hoebers; Ann Hoeben; Wouter V. Vogel; Margot E. T. Tesselaar; Daniel Parvin; Harry Bartelink; Philippe Lambin

doi:10.1016/j.ctro.2020.04.004

[18F]-HX4 PET/CT hypoxia in patients with squamous cell carcinoma of the head and neck treated with chemoradiotherapy: Prognostic results from two prospective trials

Sebastian Sanduleanu^*, Olga Hamming-Vrieze, Frederik W. R. Wesseling, Aniek J. G. Even, Frank J. Hoebers, Ann Hoeben, Wouter V. Vogel, Margot E. T. Tesselaar, Daniel Parvin, Harry Bartelink, Philippe Lambin

^*Corresponding author for this work

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

Abstract

Introduction: The presence of hypoxia in head-and-neck squamous cell carcinoma is a negative prognostic factor. PET imaging with [18F] HX4 can be used to visualize hypoxia, but it is currently unknown how this correlates with prognosis. We investigated the prognostic value of [18F] HX4 PET imaging in patients treated with definitive radio(chemo)therapy (RTx).

Materials and methods: We analyzed 34 patients included in two prospective clinical trials (NCT01347281, NCT01504815). Static [18F] HX4 PET-CT images were collected, both pre-treatment (median 4 days before start RTx, range 1-16), as well as during RTx (median 13 days after start RTx, range 317 days). Static uptake at both time points (n = 33 pretreatment, n = 28 during RTx) and measured changes in hypoxic fraction (HF) and hypoxic volume (HV) (n = 27 with 2 time points) were analyzed. Univariate cox analyses were done for local progression free survival (PFS) and overall survival (OS) at both timepoints. Change in uptake was analyzed by comparing outcome with Kaplan-Meier curves and log-rank test between patients with increased and decreased/stable hypoxia, similarly between patients with and without residual hypoxia (rHV = ratio week 2/baseline HV with cutoff 0.2). Voxelwise Spearman correlation coefficients were calculated between normalized [18F] HX4 PET uptake at baseline and week 2.

Results: Analyses of static images showed no prognostic value for [18F] HX4 uptake. Analysis of dynamic changes showed that both OS and local PFS were significantly shorter (log-rank P <0.05) in patients with an increase in HV during RTx and OS was significantly shorter in patients with rHV, with no correlation to HPV-status. The voxel-based correlation to evaluate spatial distribution yielded a median Spearman correlation coefficient of 0.45 (range 0.11-0.65).

Conclusion: The change of [18F] HX4 uptake measured on [18F] HX4 PET early during treatment can be considered for implementation in predictive models. With these models patients with a worse prognosis can be selected for treatment intensification. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.

Original language	English
Pages (from-to)	9-15
Number of pages	7
Journal	Clinical and Translational Radiation Oncology
Volume	23
DOIs	https://doi.org/10.1016/j.ctro.2020.04.004
Publication status	Published - Jul 2020

Keywords

Head and neck
Radiaton therapy
Hypoxia
Positron emission tomography
[F-18]-HX4
Prognosis
TUMOR HYPOXIA
HUMAN-PAPILLOMAVIRUS
POSITIVE HEAD
RADIOTHERAPY
SURVIVAL
CANCER
REPRODUCIBILITY
F-18-FLUOROMISONIDAZOLE
RADIOCHEMOTHERAPY
ANGIOGENESIS

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Sanduleanu, S., Hamming-Vrieze, O., Wesseling, F. W. R., Even, A. J. G., Hoebers, F. J., Hoeben, A., Vogel, W. V., Tesselaar, M. E. T., Parvin, D., Bartelink, H., & Lambin, P. (2020). [18F]-HX4 PET/CT hypoxia in patients with squamous cell carcinoma of the head and neck treated with chemoradiotherapy: Prognostic results from two prospective trials. Clinical and Translational Radiation Oncology, 23, 9-15. https://doi.org/10.1016/j.ctro.2020.04.004

@article{a060ef899ff942cfaa8a7be93b9868ea,

title = "[18F]-HX4 PET/CT hypoxia in patients with squamous cell carcinoma of the head and neck treated with chemoradiotherapy: Prognostic results from two prospective trials",

abstract = "Introduction: The presence of hypoxia in head-and-neck squamous cell carcinoma is a negative prognostic factor. PET imaging with [18F] HX4 can be used to visualize hypoxia, but it is currently unknown how this correlates with prognosis. We investigated the prognostic value of [18F] HX4 PET imaging in patients treated with definitive radio(chemo)therapy (RTx).Materials and methods: We analyzed 34 patients included in two prospective clinical trials (NCT01347281, NCT01504815). Static [18F] HX4 PET-CT images were collected, both pre-treatment (median 4 days before start RTx, range 1-16), as well as during RTx (median 13 days after start RTx, range 317 days). Static uptake at both time points (n = 33 pretreatment, n = 28 during RTx) and measured changes in hypoxic fraction (HF) and hypoxic volume (HV) (n = 27 with 2 time points) were analyzed. Univariate cox analyses were done for local progression free survival (PFS) and overall survival (OS) at both timepoints. Change in uptake was analyzed by comparing outcome with Kaplan-Meier curves and log-rank test between patients with increased and decreased/stable hypoxia, similarly between patients with and without residual hypoxia (rHV = ratio week 2/baseline HV with cutoff 0.2). Voxelwise Spearman correlation coefficients were calculated between normalized [18F] HX4 PET uptake at baseline and week 2.Results: Analyses of static images showed no prognostic value for [18F] HX4 uptake. Analysis of dynamic changes showed that both OS and local PFS were significantly shorter (log-rank P <0.05) in patients with an increase in HV during RTx and OS was significantly shorter in patients with rHV, with no correlation to HPV-status. The voxel-based correlation to evaluate spatial distribution yielded a median Spearman correlation coefficient of 0.45 (range 0.11-0.65).Conclusion: The change of [18F] HX4 uptake measured on [18F] HX4 PET early during treatment can be considered for implementation in predictive models. With these models patients with a worse prognosis can be selected for treatment intensification. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.",

keywords = "Head and neck, Radiaton therapy, Hypoxia, Positron emission tomography, [F-18]-HX4, Prognosis, TUMOR HYPOXIA, HUMAN-PAPILLOMAVIRUS, POSITIVE HEAD, RADIOTHERAPY, SURVIVAL, CANCER, REPRODUCIBILITY, F-18-FLUOROMISONIDAZOLE, RADIOCHEMOTHERAPY, ANGIOGENESIS",

author = "Sebastian Sanduleanu and Olga Hamming-Vrieze and Wesseling, {Frederik W. R.} and Even, {Aniek J. G.} and Hoebers, {Frank J.} and Ann Hoeben and Vogel, {Wouter V.} and Tesselaar, {Margot E. T.} and Daniel Parvin and Harry Bartelink and Philippe Lambin",

note = "Funding Information: Authors acknowledge financial support from ERC advanced grant (ERC-ADG-2015, n° 694812 – Hypoximmuno) and the QuIC-ConCePT project, which is partly funded by EFPI A companies and the Innovative Medicine Initiative Joint Undertaking (IMI JU) under Grant Agreement No. 115151. This research is also supported by the Dutch Technology Foundation STW (grant n° 10696 DuCAT & n° P14-19 Radiomics STRaTegy), which is the applied science division of NWO, and the Technology Programme of the Ministry of Economic Affairs. Authors also acknowledge financial support from the EU 7th framework program (ARTFORCE – n° 257144, REQUITE – n° 601826), SME Phase 2 (RAIL – n°673780), EUROSTARS (DART, DECIDE, COMPACT), the European Program H2020-2015-17 (BD2Decide – PHC30-689715, ImmunoSABR – n° 733008 and PREDICT – ITN – n° 766276), Interreg V-A Euregio Meuse-Rhine (“Euradiomics”), Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society . Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2020",

month = jul,

doi = "10.1016/j.ctro.2020.04.004",

language = "English",

volume = "23",

pages = "9--15",

journal = "Clinical and Translational Radiation Oncology",

issn = "2405-6308",

publisher = "Elsevier Ireland Ltd",

}

Sanduleanu, S, Hamming-Vrieze, O, Wesseling, FWR, Even, AJG , Hoebers, FJ , Hoeben, A, Vogel, WV, Tesselaar, MET, Parvin, D, Bartelink, H & Lambin, P 2020, '[18F]-HX4 PET/CT hypoxia in patients with squamous cell carcinoma of the head and neck treated with chemoradiotherapy: Prognostic results from two prospective trials', Clinical and Translational Radiation Oncology, vol. 23, pp. 9-15. https://doi.org/10.1016/j.ctro.2020.04.004

[18F]-HX4 PET/CT hypoxia in patients with squamous cell carcinoma of the head and neck treated with chemoradiotherapy: Prognostic results from two prospective trials. / Sanduleanu, Sebastian; Hamming-Vrieze, Olga; Wesseling, Frederik W. R. et al.
In: Clinical and Translational Radiation Oncology, Vol. 23, 07.2020, p. 9-15.

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

TY - JOUR

T1 - [18F]-HX4 PET/CT hypoxia in patients with squamous cell carcinoma of the head and neck treated with chemoradiotherapy: Prognostic results from two prospective trials

AU - Sanduleanu, Sebastian

AU - Hamming-Vrieze, Olga

AU - Wesseling, Frederik W. R.

AU - Even, Aniek J. G.

AU - Hoebers, Frank J.

AU - Hoeben, Ann

AU - Vogel, Wouter V.

AU - Tesselaar, Margot E. T.

AU - Parvin, Daniel

AU - Bartelink, Harry

AU - Lambin, Philippe

N1 - Funding Information: Authors acknowledge financial support from ERC advanced grant (ERC-ADG-2015, n° 694812 – Hypoximmuno) and the QuIC-ConCePT project, which is partly funded by EFPI A companies and the Innovative Medicine Initiative Joint Undertaking (IMI JU) under Grant Agreement No. 115151. This research is also supported by the Dutch Technology Foundation STW (grant n° 10696 DuCAT & n° P14-19 Radiomics STRaTegy), which is the applied science division of NWO, and the Technology Programme of the Ministry of Economic Affairs. Authors also acknowledge financial support from the EU 7th framework program (ARTFORCE – n° 257144, REQUITE – n° 601826), SME Phase 2 (RAIL – n°673780), EUROSTARS (DART, DECIDE, COMPACT), the European Program H2020-2015-17 (BD2Decide – PHC30-689715, ImmunoSABR – n° 733008 and PREDICT – ITN – n° 766276), Interreg V-A Euregio Meuse-Rhine (“Euradiomics”), Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society . Publisher Copyright: © 2020 The Author(s)

PY - 2020/7

Y1 - 2020/7

N2 - Introduction: The presence of hypoxia in head-and-neck squamous cell carcinoma is a negative prognostic factor. PET imaging with [18F] HX4 can be used to visualize hypoxia, but it is currently unknown how this correlates with prognosis. We investigated the prognostic value of [18F] HX4 PET imaging in patients treated with definitive radio(chemo)therapy (RTx).Materials and methods: We analyzed 34 patients included in two prospective clinical trials (NCT01347281, NCT01504815). Static [18F] HX4 PET-CT images were collected, both pre-treatment (median 4 days before start RTx, range 1-16), as well as during RTx (median 13 days after start RTx, range 317 days). Static uptake at both time points (n = 33 pretreatment, n = 28 during RTx) and measured changes in hypoxic fraction (HF) and hypoxic volume (HV) (n = 27 with 2 time points) were analyzed. Univariate cox analyses were done for local progression free survival (PFS) and overall survival (OS) at both timepoints. Change in uptake was analyzed by comparing outcome with Kaplan-Meier curves and log-rank test between patients with increased and decreased/stable hypoxia, similarly between patients with and without residual hypoxia (rHV = ratio week 2/baseline HV with cutoff 0.2). Voxelwise Spearman correlation coefficients were calculated between normalized [18F] HX4 PET uptake at baseline and week 2.Results: Analyses of static images showed no prognostic value for [18F] HX4 uptake. Analysis of dynamic changes showed that both OS and local PFS were significantly shorter (log-rank P <0.05) in patients with an increase in HV during RTx and OS was significantly shorter in patients with rHV, with no correlation to HPV-status. The voxel-based correlation to evaluate spatial distribution yielded a median Spearman correlation coefficient of 0.45 (range 0.11-0.65).Conclusion: The change of [18F] HX4 uptake measured on [18F] HX4 PET early during treatment can be considered for implementation in predictive models. With these models patients with a worse prognosis can be selected for treatment intensification. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.

AB - Introduction: The presence of hypoxia in head-and-neck squamous cell carcinoma is a negative prognostic factor. PET imaging with [18F] HX4 can be used to visualize hypoxia, but it is currently unknown how this correlates with prognosis. We investigated the prognostic value of [18F] HX4 PET imaging in patients treated with definitive radio(chemo)therapy (RTx).Materials and methods: We analyzed 34 patients included in two prospective clinical trials (NCT01347281, NCT01504815). Static [18F] HX4 PET-CT images were collected, both pre-treatment (median 4 days before start RTx, range 1-16), as well as during RTx (median 13 days after start RTx, range 317 days). Static uptake at both time points (n = 33 pretreatment, n = 28 during RTx) and measured changes in hypoxic fraction (HF) and hypoxic volume (HV) (n = 27 with 2 time points) were analyzed. Univariate cox analyses were done for local progression free survival (PFS) and overall survival (OS) at both timepoints. Change in uptake was analyzed by comparing outcome with Kaplan-Meier curves and log-rank test between patients with increased and decreased/stable hypoxia, similarly between patients with and without residual hypoxia (rHV = ratio week 2/baseline HV with cutoff 0.2). Voxelwise Spearman correlation coefficients were calculated between normalized [18F] HX4 PET uptake at baseline and week 2.Results: Analyses of static images showed no prognostic value for [18F] HX4 uptake. Analysis of dynamic changes showed that both OS and local PFS were significantly shorter (log-rank P <0.05) in patients with an increase in HV during RTx and OS was significantly shorter in patients with rHV, with no correlation to HPV-status. The voxel-based correlation to evaluate spatial distribution yielded a median Spearman correlation coefficient of 0.45 (range 0.11-0.65).Conclusion: The change of [18F] HX4 uptake measured on [18F] HX4 PET early during treatment can be considered for implementation in predictive models. With these models patients with a worse prognosis can be selected for treatment intensification. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.

KW - Head and neck

KW - Radiaton therapy

KW - Hypoxia

KW - Positron emission tomography

KW - [F-18]-HX4

KW - Prognosis

KW - TUMOR HYPOXIA

KW - HUMAN-PAPILLOMAVIRUS

KW - POSITIVE HEAD

KW - RADIOTHERAPY

KW - SURVIVAL

KW - CANCER

KW - REPRODUCIBILITY

KW - F-18-FLUOROMISONIDAZOLE

KW - RADIOCHEMOTHERAPY

KW - ANGIOGENESIS

U2 - 10.1016/j.ctro.2020.04.004

DO - 10.1016/j.ctro.2020.04.004

M3 - Article

C2 - 32368624

SN - 2405-6308

VL - 23

SP - 9

EP - 15

JO - Clinical and Translational Radiation Oncology

JF - Clinical and Translational Radiation Oncology

ER -