Dataset Information

[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 3-17 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.

SUBMITTER: Sanduleanu S

PROVIDER: S-EPMC7184102 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

[<sup>18</sup>F]-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 S Hamming-Vrieze Olga O Wesseling Frederik W R FWR Even Aniek J G AJG Hoebers Frank J FJ Hoeben Ann A Vogel Wouter V WV Tesselaar Margot E T MET Parvin Daniel D Bartelink Harry H Lambin Philippe P

Clinical and translational radiation oncology 20200418

<h4>Introduction</h4>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).<h4>Materials and methods</h4>We analyzed 34 patients included in two prospective clinical trials (NCT01347281, NCT01504815). Static ...[more]

PMID: 32368624

Similar Datasets

Project description:PurposeThere is growing recognition that biologic features of the tumor microenvironment affect the response to cancer therapies and the outcome of cancer patients. In head and neck cancer (HNC) one such feature is hypoxia. We investigated the utility of 18F-fluoromisonidazole (FMISO) dynamic positron emission tomography (dPET) for monitoring the early microenvironmental response to chemoradiotherapy in HNC.Experimental designSeventy-two HNC patients underwent FMISO dPET scans in a customized immobilization mask (0-30 min dynamic acquisition, followed by 10 min static acquisitions starting at ∼95 min and ∼160 min post-injection) at baseline and early into treatment where patients have already received one cycle of chemotherapy and anywhere from five to ten fractions of 2 Gy per fraction radiation therapy. Voxelwise pharmacokinetic modeling was conducted using an irreversible one-plasma two-tissue compartment model to calculate surrogate biomarkers of tumor hypoxia (k 3 and Tumor-to-Blood Ratio (TBR)), perfusion (K 1 ) and FMISO distribution volume (DV). Additionally, Tumor-to-Muscle Ratios (TMR) were derived by visual inspection by an experienced nuclear medicine physician, with TMR > 1.2 defining hypoxia.ResultsOne hundred and thirty-five lesions in total were analyzed. TBR, k 3 and DV decreased on early response scans, while no significant change was observed for K 1 . The k 3 -TBR correlation decreased substantially from baseline scans (Pearson's r = 0.72 and 0.76 for mean intratumor and pooled voxelwise values, respectively) to early response scans (Pearson's r = 0.39 and 0.40, respectively). Both concordant and discordant examples of changes in intratumor k 3 and TBR were identified; the latter partially mediated by the change in DV. In 13 normoxic patients according to visual analysis (all having lesions with TMR = 1.2), subvolumes were identified where k 3 indicated the presence of hypoxia.ConclusionPharmacokinetic modeling of FMISO dynamic PET reveals a more detailed characterization of the tumor microenvironment and assessment of response to chemoradiotherapy in HNC patients than a single static image does. In a clinical trial where absence of hypoxia in primary tumor and lymph nodes would lead to de-escalation of therapy, the observed disagreement between visual analysis and pharmacokinetic modeling results would have affected patient management in <20% cases. While simple static PET imaging is easily implemented for clinical trials, the clinical applicability of pharmacokinetic modeling remains to be investigated.

Project description:The aim of this phase II clinical trial (NCT02965001) was to evaluate the prognostic value of urokinase-type plasminogen activator receptor (uPAR) PET/CT with the novel ligand 68Ga-NOTA-AE105 in head and neck cancer and compare it with 18F-FDG. Methods: Patients with head and neck squamous cell carcinoma referred for curatively intended radiotherapy were eligible and prospectively included in this study. 68Ga-uPAR and 18F-FDG PET/CT were performed before initiation of curatively intended radiotherapy, and the SUVmax of the primary tumor was measured on both PET/CT studies by 2 independent readers. Relapse-free survival (RFS) and overall survival (OS) were calculated, and optimal cutoffs were established for 68Ga-uPAR and 18F-FDG PET independently and compared using log rank and Kaplan-Meier statistics, as well as univariate and multivariate analysis in a Cox proportional-hazards model. Results: In total, 57 patients were included and followed for a median of 33.8 mo (range, 2.30-47.2, mo). The median SUVmax of the primary tumors was 2.98 (range, 1.94-5.24) for 68Ga-uPAR and 15.7 (range, 4.24-45.5) for 18F-FDG. The optimal cutoffs for 68Ga-NOTA-AE105 SUVmax in the primary tumor were 2.63 for RFS and 2.66 for OS. A high uptake of 68Ga-NOTA-AE105 (SUVmax above cutoff) was significantly associated with poor RFS and OS (log-rank P = 0.012 and P = 0.022). 68Ga-NOTA-AE105 uptake in the primary tumor was significantly associated with poor RFS in univariate analysis (hazard ratio [HR], 8.53 [95% CI, 1.12-64.7]; P = 0.038), and borderline-associated with OS (HR, 7.44 [95% CI, 0.98-56.4]; P = 0.052). For 18F-FDG PET, the optimal cutoffs were 22.7 for RFS and 22.9 for OS. An 18F-FDG SUVmax above the cutoff was significantly associated with reduced RFS (log-rank P = 0.012) and OS (log-rank P = 0.000). 18F-FDG uptake was significantly associated with reduced RFS (HR, 3.27 [95% CI, 1.237-8.66]; P = 0.017) and OS (HR, 7.10 [95% CI, 2.60-19.4]; P < 0.001) in univariate analysis. In a multivariate analysis including 68Ga-uPAR SUVmax, 18F-FDG SUVmax, TNM stage, and p16 status, only 68Ga-uPAR SUVmax remained significant (HR, 8.51 [95% CI, 1.08-66.9]; P = 0.042) for RFS. For OS, only TNM stage and 18F-FDG remained significant. Conclusion: The current trial showed promising results for the use of 68Ga-uPAR PET SUVmax in the primary tumor to predict RFS in head and neck squamous cell carcinoma patients referred for curatively intended radiotherapy when compared with 18F-FDG PET, TNM stage, and p16 status. 68Ga-uPAR PET could potentially become valuable for identification of patients suited for deescalation of treatment and risk-stratified follow-up schemes.

Dataset Information

[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.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets