Impact of pre- and early per-treatment FDG-PET based dose-escalation on local tumour control in fractionated irradiated FaDu xenograft tumours

Christina Jentsch*, Ralf Bergmann, Kerstin Bruechner, Birgit Mosch, Ala Yaromina, Mechthild Krause, Daniel Zips, Esther G. C. Troost, Steffen Loeck, Joerg Kotzerke, Joerg Steinbach, Howard Thames, Michael Baumann, Bettina Beuthien-Baumann

*Corresponding author for this work

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Objective: To investigate local tumour control after dose-escalation based on [18F]2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) obtained before and early during fractionated irradiation. Materials and methods: 85 mice bearing FaDu xenografts underwent FDG-PET twice: first immediately prior to the first 2-Gy fraction of irradiation (PET1_0) and second after 18 degrees Gy (PET2_18). After these 9 fractions, animals were randomly allocated to: (1) continuation of 2-Gy fractions (cumulative dose of 60 degrees Gy; n = 31), (2) dose-escalation with 3-Gy fractions (cumulative EQD2-dose 86.25 degrees Gy [alpha/beta-value:10]; n = 25), or (3) with 4-Gy fractions (cumulative EQD2-dose 116 degrees Gy; n = 29). The effects of SUV(max)0 degrees Gy, SUV(max)18 degrees Gy, and dose on local tumour control were analysed in two ways. First, the Cox proportional hazards model was used with two covariates: continuous SUVmax values and dose. Second, the Kaplan-Meier method was used, with tumours classified according to SUVmax greater than or less than (1) median maximum standardized uptake value (SUVmax) at PET1_0 and PET2_18, or (2) the cut-off value 2.5. Results: The multivariate Cox analysis revealed a significant negative association between higher SUVmax determined before start of treatment and local control (HR = 1.59, [95% CI 1.04, 2.42], p = 0.031), whereas higher dose had a significant positive effect (HR = 0.95, [0.93, 0.98], p <0.001). In contrast, FDG uptake at 18 Gy did not correlate with local control (HR = 1.14, [0.53, 2.45], p = 0.73). Neither FDG uptake prior to irradiation nor at 18 Gy correlated with local control irrespective of the delivered dose (log-rank test) when using the median SUVmax values for stratification (SUV(max)0 Gy: 60 Gy: p = 0.25, 86.25 Gy: p = 0.47,116 Gy: p = 0.88 and SUVmax 18 Gy: 60 Gy: p = 0.42, 86.25 Gy: p = 0.34, 116 Gy: p = 0.99). By contrast, stratifying the animals by the cut-off 2.5 at PET1_0 reveals a significant difference in local control for the 60 Gy group (p = 0.034), but not for the other dose groups. At PET2_18, no significant effect for any dose group was detected. Conclusions: The multivariate Cox analysis revealed a significantly higher hazard of recurrence for mice with higher SUVmax determined before start of treatment. These results support the hypothesis that patients with high pre-therapeutic FDG uptake should be considered at increased risk of local failure and therefore as possible candidates for dose escalation strategies.
Original languageEnglish
Pages (from-to)447-452
JournalRadiotherapy and Oncology
Issue number3
Publication statusPublished - Dec 2016


  • FDG positron emission tomography
  • Squamous cell carcinoma
  • FaDu xenografts
  • Fractionated irradiation
  • Local tumour control
  • Dose escalation

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