Dynamics of tumor hypoxia assessed by 18F-FAZA PET/CT in head and neck and lung cancer patients during chemoradiation: Possible implications for radiotherapy treatment planning strategies

• Published in: Radiotherapy and oncology 2014-11, Vol.113 (2), p.198-203
• Main Authors: Bollineni, Vikram R., Koole, Michel J.B., Pruim, Jan, Brouwer, Charlotte L., Wiegman, Erwin M., Groen, Harry J.M., Vlasman, Renske, Halmos, Gyorgy B., Oosting, Sjoukje F., Langendijk, Johannes A., Widder, Joachim, Steenbakkers, Roel J.H.M.
• Format: Article
• Language: English
• Subjects: 18F-FAZA-PET/CT; Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung - diagnostic imaging; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - therapy; Carcinoma, Squamous Cell - diagnostic imaging; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - therapy; Cell Hypoxia - physiology; Chemoradiotherapy; Cohort Studies; Female; FHV; Head and Neck Neoplasms - diagnostic imaging; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - therapy; Head and neck tumors; Humans; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - metabolism; Lung Neoplasms - therapy; Male; Middle Aged; Multimodal Imaging - methods; Nitroimidazoles; Non-small-cell lung cancer; Positron-Emission Tomography - methods; Prospective Studies; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted - methods; Squamous Cell Carcinoma of Head and Neck; Tomography, X-Ray Computed - methods; Tumor hypoxia
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2014.10.010

To define the optimal time point for the integration of hypoxia 18F-FAZA-PET/CT information into radiotherapy treatment planning to benefit from hypoxia modification or dose escalation treatment. Therefore, we performed a prospective cohort study, using serial hypoxic imaging (18F-FAZA-PET/CT) prior to and at several time-points during (chemo)radiotherapy (CHRT) in six head and neck squamous cell (HNSCC) and six non-small cell lung cancer (NSCLC) patients. The spatio-temporal dynamics of tumor hypoxia and fractional hypoxic volumes (FHV) were evaluated using a voxel-by-voxel analysis based on a 18F-FAZA-T/B ratio of 1.4 at four time points in HNSCC patients, at baseline (FAZA-BL), at week one (FAZA-W1), two (FAZA-W2), and four (FAZA-W4) during CHRT and at three time points in NSCLC patients (baseline; W2, W4). Ten out of twelve patients showed a substantial pre-treatment tumor hypoxia representing a FHV⩾1.4 assessed by 18F-FAZA-PET/CT. The median FHV was 38% (FAZA-BL), 15% (FAZA-W1), 17% (FAZA-W2) and 1.5% (FAZA-W4) in HNSCC patients, and 34% (FAZA-BL), 26% (FAZA-W2) and 26% (FAZA-W4) in NSCLC patients, respectively. Stable tumor hypoxia was observed in three HNSCC patients and two NSCLC patients at FAZA-W2. In three HNSCC patients and two NSCLC patients FHVs declined to non-detectable hypoxia levels at FAZA-W4 during CHRT, while two NSCLC patients, showed increasing FHVs. Our results indicate that, instead of using the FAZA-BL scan as the basis for the dose escalation, FAZA-W2 of CHRT is most suitable and might provide a more reliable basis for the integration of 18F-FAZA-PET/CT information into radiotherapy treatment planning for hypoxia-directed dose escalation strategies.