Evaluation of tumour hypoxia during radiotherapy using [<Superscript>18</Superscript>F]HX4 PET imaging and blood biomarkers in patients with head and neck cancer

Background and purpose

Increased tumour hypoxia is associated with a worse overall survival in patients with head and neck squamous cell carcinoma (HNSCC). The aims of this study were to evaluate treatment-associated changes in [¹⁸F]HX4-PET, hypoxia-related blood biomarkers, and their interdependence.

Material and methods

[¹⁸F]HX4-PET/CT scans of 20 patients with HNSCC were acquired at baseline and after ±20Gy of radiotherapy. Within the gross-tumour-volumes (GTV; primary and lymph nodes), mean and maximum standardized uptake values, the hypoxic fraction (HF) and volume (HV) were calculated. Also, the changes in spatial uptake pattern were evaluated using [¹⁸F]HX4-PET/CT imaging. For all patients, the plasma concentration of CAIX, osteopontin and VEGF was assessed.

Results

At baseline, tumour hypoxia was detected in 69 % (22/32) of the GTVs. During therapy, we observed a significant decrease in all image parameters. The HF decreased from 21.7?±?19.8 % (baseline) to 3.6?±?10.0 % (during treatment; P?<?0.001). Only two patients had a HV?>?1 cm³ during treatment, which was located for >98 % within the baseline HV. During treatment, no significant changes in plasma CAIX or VEGF were observed, while osteopontin was increased.

Conclusions

[¹⁸F]HX4-PET/CT imaging allows monitoring changes in hypoxia during (chemo)radiotherapy whereas the blood biomarkers were not able to detect a treatment-associated decrease in hypoxia.

     

Glucocorticoid‐Induced Proliferation in Untreated Pediatric Acute Myeloid Leukemic Blasts

We evaluated the in vitro glucocorticoid (GC) responsiveness of 117 pediatric acute myeloid leukemia cells by considering GC resistance, GC‐induced proliferation, and GC‐induced differentiation. None of the samples was highly GC sensitive, and only 15% were intermediately sensitive. GC‐induced differentiation was not observed, while GC‐induced proliferation was observed in 27% of the samples. Samples with French‐American‐British classification (FAB) type M5 or activating Fms‐like tyrosine kinase 3 (FLT3) mutations were significantly more prone to this phenomenon. Although we could not confirm this in our study, if induced proliferation in vitro is paralleled in vivo, GCs during consolidation may have adverse effects on minimal residual leukemic cells, which might increase relapse risk.     

Decline of Systolic and Diastolic 2D Strain Rate During Follow-Up of HLHS Patients After Fontan Palliation

Accurate assessment of ventricular function is particularly important in children with hypoplastic left heart syndrome (HLHS) after completion of the total cavopulmonary connection (TCPC). For this purpose, two-dimensional speckle tracking (2DST) is a promising technique as it does not depend on the angle of insonation or the geometry of the ventricle. The objective of this study was to assess changes in systolic and diastolic right ventricular (RV) function within a 5-year follow-up period of HLHS patients after TCPC using conventional and 2DST echocardiography. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), E/A, E/e′ and 2DST parameters [global longitudinal peak systolic strain (GS) and strain rate (GSRs), global strain rate in early (GSRe) and late (GSRa) diastole] of 40 HLHS patients were compared at 1.6 and at 5.1 years after TCPC. RVFAC, E/A, E/e′ and GS did not change, whereas TAPSE (13.7 ± 3.2 vs. 10.5 ± 2.4 mm/m², p < 0.001), GSRs (?1.56 ± 0.28 vs. ?1.35 ± 0.31 1/s, p < 0.001), GSRe (2.22 ± 0.49 vs. 1.96 ± 0.44 1/s, p = 0.004) and GSRa (1.19 ± 0.39 vs. 0.92 ± 0.39 1/s, p < 0.001) decreased significantly. Systolic and diastolic RV function parameters of HLHS patients decreased from 1.6 to 5.1 years after TCPC in our patients. Changes in global strain rate parameters may be signaling early RV dysfunction that is not detectable by traditional echocardiography. Further study is needed to verify this and to determine whether these changes are clinically relevant.