18f-faza and Squamous-Cell-Carcinoma-of-Head-and-Neck

Despite the large variety of treatment methods available for the management of advanced head and neck carcinomas, these tumours remain highly challenging due to their aggressiveness and complex anatomical location. Among the treatment challenges associated with head and neck cancers, hypoxia and tumour repopulation during treatment are, most likely, the main reason for locoregional treatment failure. Whilst the number of techniques and predictive assays designed to assess the oxygenation status or the proliferative ability of tumours is rather large, they all come with drawbacks which limit their implementation as routine clinical procedures. Latest developments in the field of nuclear medicine have opened the road to new possibilities in functional imaging, thus overcoming some of the confines imposed by the more conventional techniques.. The current paper presents the role of PET imaging as a quantitative evaluation tool for hypoxia status and proliferative ability of advanced head and neck tumours. Traditional as well as novel radioisotopes with high affinity towards hypoxia and proliferative tumour activity are presented and their pre-clinical/clinical results analysed.. While the number of clinical studies which aimed to validate novel radiotracers for head and neck cancer is limited, a number of results show promising correlation between uptake/marker activity and treatment outcome.. There is need for further studies and well designed clinical trials to obtain more conclusive results.

Topics: Carcinoma, Squamous Cell; Cell Hypoxia; Cell Proliferation; Fluorine Radioisotopes; Head and Neck Neoplasms; Humans; Nitroimidazoles; Positron-Emission Tomography; Radioisotopes; Radiotherapy, Image-Guided; Squamous Cell Carcinoma of Head and Neck

The prognostic value of positron emission tomography/computed tomography (PET/CT) with (18)F-fluoroazomycin arabinoside (FAZA) was evaluated in patients with head and neck squamous cell carcinoma (HNSCC) who underwent chemoradiotherapy (CRT).. Twenty-nine patients with head and neck cancer underwent FAZA PET/CT before treatment. Data acquisition started 2 h after FAZA administration. In 26 patients with squamous cell carcinoma, FAZA uptakes by the primary lesions (tumor-muscle ratio in primary lesion: Pr T/M) and by the lymph node metastases (tumor-muscle ratio in lymph node metastasis) were compared with various clinical parameters. For the HNSCC patients who completed CRT protocol (n = 23), those who experienced disease progression were compared with those who did not experience disease progression with respect to the clinical and PET parameters. The prognostic values of the clinical and PET parameters were then evaluated with regard to progression-free survival (PFS).. Pr T/M positively correlated with the lesion's maximum diameter, and it was significantly higher in stage IV lesions compared with stage I-III lesions. No significant differences were observed between the patients who experienced disease progression and those who did not, with respect to the clinical parameters. The average Pr T/M tended to be higher in patients with disease progression, although the differences were not statistically significant (p = 0.086). Kaplan-Meier analysis with log-rank tests indicated that Pr T/M was an only significant predictor of PFS among PET and clinical parameters evaluated (p = 0.010).. FAZA uptake by the primary lesion was a significant prognostic indicator in HNSCC patients undergoing CRT. Hence, FAZA PET/CT may provide useful information in the management of HNSCC patients treated with CRT. Registration number of clinical trial's registry: UMIN000003440.

Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Nitroimidazoles; Positron Emission Tomography Computed Tomography; Prognosis; Squamous Cell Carcinoma of Head and Neck

To evaluate from a planning point of view the dose distribution of adaptive radiation dose escalation in head and neck squamous cell carcinoma (HNSCC) using (18)F-Fluoroazomycin arabinoside (FAZA) positron emission tomography/computed tomography (PET-CT).. Twelve patients with locally advanced HNSCC underwent three FAZA PET-CT before treatment, after 7 fractions and after 17 fractions of a carboplatin-5FU chemo-radiotherapy regimen (70 Gy in 2 Gy per fraction over 7 weeks). The dose constraints were that every hypoxic voxel delineated before and during treatment (newborn hypoxic voxels) should receive a total dose of 86 Gy. A median dose of 2.47 Gy per fraction was prescribed on the hypoxic PTV defined on the pre-treatment FAZA PET-CT; a median dose of 2.57 Gy per fraction was prescribed on the newborn voxels identified on the first per-treatment FAZA PET-CT; a median dose of 2.89 Gy per fraction was prescribed on the newborn voxels identified on the second per-treatment FAZA PET-CT.. Ten of 12 patients had hypoxic volumes. Six of 10 patients completed all the FAZA PET-CT during radiotherapy. For the hypoxic PTVs, the average D50% matched the prescribed dose within 2% and the homogeneity indices reached 0.10 and 0.12 for the nodal PTV 86 Gy and the primary PTV 86 Gy, respectively. Compared to a homogeneous 70 Gy mean dose to the PTVs, the dose escalation up to 86 Gy to the hypoxic volumes did not typically modify the dose metrics on the surrounding normal tissues.. From a planning point of view, FAZA-PET-guided dose adaptive escalation is feasible without substantial dose increase to normal tissues above tolerance limits. Clinical prospective studies, however, need to be performed to validate hypoxia-guided adaptive radiation dose escalation in head and neck carcinoma.

Topics: Aged; Carcinoma, Squamous Cell; Dose Fractionation, Radiation; Female; Head and Neck Neoplasms; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Multimodal Imaging; Nitroimidazoles; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Squamous Cell Carcinoma of Head and Neck; Tomography, X-Ray Computed

(18)F-fluoroazomycinarabinoside ((18)F-FAZA) is a promising hypoxia radiopharmaceutical agent with outstanding biokinetic parameters. We aimed to determine the accuracy of (18)F-FAZA-PET/CT scan in detecting hypoxic regions within the tumor using immunohistochemical markers in a pilot study.. Eleven patients with primary or recurrent laryngeal squamous cell carcinoma were indicated for total laryngectomy (TLE). Patients underwent (18)F-FAZA-PET/CT scan before TLE. Hypoxic regions inside the laryngeal tumor were determined. After TLE, regions with high uptake on (18)F-FAZA-PET scan were selected for immunohistochemical examination for exogenous (pimonidazole) and endogenous (HIF1α, CA-IX and GLUT-1) hypoxia markers. To assess the accuracy of (18)F-FAZA-PET scanning, radiopharmacon accumulation was related with immunohistochemical expression of hypoxia markers.. Inter- and intratumoral heterogeneity of tumor hypoxia was observed on (18)F-FAZA-PET scan. Nine of the eleven tumors were hypoxic with (18)F-FAZA-PET. Hypoxia could also be detected with pimonidazole, HIF1α, CA-IX and GLUT-1 expression in some tumors. No clear association was observed between (18)F-FAZA uptake and hypoxia markers.. This pilot study could not prove the accuracy of (18)F-FAZA-PET in determining hypoxic subvolumes in laryngeal cancer. Further study is required to investigate the benefit of (18)F-FAZA-PET imaging in radiotherapy planning.

Topics: Aged; Aged, 80 and over; Biomarkers; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Hypoxia; Laryngeal Neoplasms; Laryngectomy; Male; Middle Aged; Multimodal Imaging; Neoplasm Recurrence, Local; Nitroimidazoles; Pilot Projects; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Squamous Cell Carcinoma of Head and Neck; Tomography, X-Ray Computed

To define the optimal time point for the integration of hypoxia (18)F-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 ((18)F-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 (18)F-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 (18)F-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 (18)F-FAZA-PET/CT information into radiotherapy treatment planning for hypoxia-directed dose escalation strategies.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cell Hypoxia; Chemoradiotherapy; Cohort Studies; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Middle Aged; Multimodal Imaging; Nitroimidazoles; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Squamous Cell Carcinoma of Head and Neck; Tomography, X-Ray Computed