Predictive value of quantitative F-18-FDG-PET radiomics analysis in patients with head and neck squamous cell carcinoma

BACKGROUND: Radiomics is aimed at image-based tumor phenotyping, enabling application within clinical-decision-support-systems to improve diagnostic accuracy and allow for personalized treatment. The purpose was to identify predictive 18-fluor-fluoro-2-deoxyglucose (18F-FDG) positron-emission tomography (PET) radiomic features to predict recurrence, distant metastasis, and overall survival in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy. METHODS: Between 2012 and 2018, 103 retrospectively (training cohort) and 71 consecutively included patients (validation cohort) underwent 18F-FDG-PET/CT imaging. The 434 extracted radiomic features were subjected, after redundancy filtering, to a projection resulting in outcome-independent meta-features (factors). Correlations between clinical, first-order 18F-FDG-PET parameters (e.g., SUVmean), and factors were assessed. Factors were combined with 18F-FDG-PET and clinical parameters in a multivariable survival regression and validated. A clinically applicable risk-stratification was constructed for patients' outcome. RESULTS: Based on 124 retained radiomic features from 103 patients, 8 factors were constructed. Recurrence prediction was significantly most accurate by combining HPV-status, SUVmean, SUVpeak, factor 3 (histogram gradient and long-run-low-grey-level-emphasis), factor 4 (volume-difference, coarseness, and grey-level-non-uniformity), and factor 6 (histogram variation coefficient) (CI = 0.645). Distant metastasis prediction was most accurate assessing metabolic-active tumor volume (MATV)(CI = 0.627). Overall survival prediction was most accurate using HPV-status, SUVmean, SUVmax, factor 1 (least-axis-length, non-uniformity, high-dependence-of-high grey-levels), and factor 5 (aspherity, major-axis-length, inversed-compactness and, inversed-flatness) (CI = 0.764). CONCLUSIONS: Combining HPV-status, first-order 18F-FDG-PET parameters, and complementary radiomic factors was most accurate for time-to-event prediction. Predictive phenotype-specific tumor characteristics and interactions might be captured and retained using radiomic factors, which allows for personalized risk stratification and optimizing personalized cancer care. TRIAL REGISTRATION: Trial NL3946 (NTR4111), local ethics commission reference: Prediction 2013.191 and 2016.498. Registered 7 August 2013, https://www.trialregister.nl/trial/3946

Predictive value of quantitative 18F-FDG-PET radiomics analysis in patients with head and neck squamous cell carcinoma

BACKGROUND: Radiomics is aimed at image-based tumor phenotyping, enabling application within clinical-decision-support-systems to improve diagnostic accuracy and allow for personalized treatment. The purpose was to identify predictive 18-fluor-fluoro-2-deoxyglucose (18F-FDG) positron-emission tomography (PET) radiomic features to predict recurrence, distant metastasis, and overall survival in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy. METHODS: Between 2012 and 2018, 103 retrospectively (training cohort) and 71 consecutively included patients (validation cohort) underwent 18F-FDG-PET/CT imaging. The 434 extracted radiomic features were subjected, after redundancy filtering, to a projection resulting in outcome-independent meta-features (factors). Correlations between clinical, first-order 18F-FDG-PET parameters (e.g., SUVmean), and factors were assessed. Factors were combined with 18F-FDG-PET and clinical parameters in a multivariable survival regression and validated. A clinically applicable risk-stratification was constructed for patients' outcome. RESULTS: Based on 124 retained radiomic features from 103 patients, 8 factors were constructed. Recurrence prediction was significantly most accurate by combining HPV-status, SUVmean, SUVpeak, factor 3 (histogram gradient and long-run-low-grey-level-emphasis), factor 4 (volume-difference, coarseness, and grey-level-non-uniformity), and factor 6 (histogram variation coefficient) (CI = 0.645). Distant metastasis prediction was most accurate assessing metabolic-active tumor volume (MATV)(CI = 0.627). Overall survival prediction was most accurate using HPV-status, SUVmean, SUVmax, factor 1 (least-axis-length, non-uniformity, high-dependence-of-high grey-levels), and factor 5 (aspherity, major-axis-length, inversed-compactness and, inversed-flatness) (CI = 0.764). CONCLUSIONS: Combining HPV-status, first-order 18F-FDG-PET parameters, and complementary radiomic factors was most accurate for time-to-event prediction. Predictive phenotype-specific tumor characteristics and interactions might be captured and retained using radiomic factors, which allows for personalized risk stratification and optimizing personalized cancer care. TRIAL REGISTRATION: Trial NL3946 (NTR4111), local ethics commission reference: Prediction 2013.191 and 2016.498. Registered 7 August 2013, https://www.trialregister.nl/trial/3946

Diagnostic value of diffusion-weighted imaging and 18F-FDG-PET/CT for the detection of unknown primary head and neck cancer in patients presenting with cervical metastasis

Background and purpose: Head and neck squamous cell carcinoma (HNSCC) may present with cervical metastases without an apparent primary tumor. Detecting the primary tumor results in more targeted treatment. Acquisition of DWI is improving with less artifacts and image distortion. We assessed the diagnostic value of DWI and 18F-FDG-PET/CT for detecting primary tumors in patients presenting with nodal metastasis of an unknown primary HNSCC. Materials and methods: For this retrospective study we included 31 patients (male/female ratio = 23/8, median age = 66 years, age range = 40–80 years) who presented with a pathologically proven cervical nodal metastasis from HNSCC without overt primary tumor location between January 2013 and November 2016 and underwent both DWI and 18F-FDG-PET/CT. Both modalities were assessed qualitatively and quantitatively. With ROC analysis we determined the optimal cut-off for imaging parameters in separating occult malignancy from benign tissue. Results: Qualitative analysis of MRI including DWI resulted in a sensitivity of 81.3% (95%CI) = 53.7–95.0) and specificity of 73.3% (95%CI = 44.8–91.1). With qualitative scoring of 18F-FDG-PET/CT a sensitivity and specificity of 93.8% (95%CI = 67.8–99.7) and 73.3% (95%CI = 44.8–91.1) were found. With quantitative analysis sensitivity and specificity of SUVmax were 81.3% (95%CI = 53.6–95.0) and 93.3% (95%CI = 66.0–99.7), respectively. Combining DWI and 18F-FDG-PET/CT resulted in a sensitivity of 93.8% (95%CI = 67.7–99.7%) and specificity of 60.0% (95%CI = 32.9–82.5%). Conclusion: In this study on HNSCC patients presenting with clinically UP lesions the diagnostic accuracy of qualitative analysis with DWI and 18F-FDG-PET/CT and quantitative analysis of 18F-FDG-PET/CT using SUVmax were high. Adding DWI did not improve the accuracy of 18F-FDG-PET/CT

Detection of residual head and neck squamous cell carcinoma after (chemo)radiotherapy: a pilot study assessing the value of diffusion-weighted magnetic resonance imaging as an adjunct to PET-CT using 18F-FDG

Objective Diagnosing residual malignancy after (chemo)radiotherapy presents a diagnostic challenge because of overlapping symptoms and imaging characteristics. We assessed the added diagnostic value of diffusion-weighted imaging (DWI) to positron emission tomography combined with computed tomography (PET-CT) in patients with head and neck squamous cell carcinoma (HNSCC) with residual fluorodeoxyglucose (18F-FDG) uptake at the primary tumor site 3 months after (chemo)radiotherapy. Study Design For this retrospective study from January 2010 to June 2012, 22 cases (median patient age of 61 years; range 41-77 years) were included for analysis. Both PET-CT and magnetic resonance imaging (MRI), including DWI, were performed as part of the institutional protocol and were qualitatively assessed for the presence of residual malignancy at the primary tumor site. Results The sensitivity and specificity of PET-CT were 100% and 47%, respectively. For DWI, sensitivity and specificity were 80% and 82%, respectively. When DWI was added to PET-CT with residual 18F-FDG uptake, and only a positive read on both PET-CT and DWI was considered to be overall positive, sensitivity remained 80% (95% confidence interval [CI] 28%-99%), and specificity was 88% (95% CI 64%-99%). Conclusions In this pilot study of the selected patients with residual 18F-FDG uptake at the primary tumor site 3 months after (chemo)radiotherapy, we demonstrated that the addition of DWI to PET-CT has the potential to increase the specificity of the response evaluation with limited decrease in sensitivity

Diagnostic value of diffusion-weighted imaging and 18F-FDG-PET/CT for the detection of unknown primary head and neck cancer in patients presenting with cervical metastasis

BACKGROUND AND PURPOSE: Head and neck squamous cell carcinoma (HNSCC) may present with cervical metastases without an apparent primary tumor. Detecting the primary tumor results in more targeted treatment. Acquisition of DWI is improving with less artifacts and image distortion. We assessed the diagnostic value of DWI and 18F-FDG-PET/CT for detecting primary tumors in patients presenting with nodal metastasis of an unknown primary HNSCC. MATERIALS AND METHODS: For this retrospective study we included 31 patients (male/female ratio = 23/8, median age = 66 years, age range = 40-80 years) who presented with a pathologically proven cervical nodal metastasis from HNSCC without overt primary tumor location between January 2013 and November 2016 and underwent both DWI and 18F-FDG-PET/CT. Both modalities were assessed qualitatively and quantitatively. With ROC analysis we determined the optimal cut-off for imaging parameters in separating occult malignancy from benign tissue. RESULTS: Qualitative analysis of MRI including DWI resulted in a sensitivity of 81.3% (95%CI) = 53.7-95.0) and specificity of 73.3% (95%CI = 44.8-91.1). With qualitative scoring of 18F-FDG-PET/CT a sensitivity and specificity of 93.8% (95%CI = 67.8-99.7) and 73.3% (95%CI = 44.8-91.1) were found. With quantitative analysis sensitivity and specificity of SUVmax were 81.3% (95%CI = 53.6-95.0) and 93.3% (95%CI = 66.0-99.7), respectively. Combining DWI and 18F-FDG-PET/CT resulted in a sensitivity of 93.8% (95%CI = 67.7-99.7%) and specificity of 60.0% (95%CI = 32.9-82.5%). CONCLUSION: In this study on HNSCC patients presenting with clinically UP lesions the diagnostic accuracy of qualitative analysis with DWI and 18F-FDG-PET/CT and quantitative analysis of 18F-FDG-PET/CT using SUVmax were high. Adding DWI did not improve the accuracy of 18F-FDG-PET/CT

Intravoxel incoherent motion magnetic resonance imaging in head and neck cancer: A systematic review of the diagnostic and prognostic value

Intravoxel incoherent motion (IVIM) imaging is increasingly applied in the assessment of head and neck cancer (HNC). Our purpose was to determine the diagnostic and prognostic performance of IVIM in HNC by performing a critical review of the literature. Pubmed and EMBASE were searched until May 2016. Study and patients characteristics, imaging protocol and diagnostic or prognostic outcomes were extracted by 2 independent reviewers. The studied IVIM parameters were diffusion coefficient (D), pseudodiffusion coefficient (D∗), and perfusion fraction (f). We included 10 diagnostic studies, 5 prognostic studies and 2 studies assessing both. Studies were very heterogeneous in terms of applied b-values, imaging protocols, outcome measurements and reference standards; therefore we did not perform a meta-analysis. The most commonly used sequence was “spin-echo planar imaging”. A median of 10.5 b-values (range, 3–17) were used. All but three studies included at least 4 b-values below b = 200 s/mm2. By combining IVIM-parameters squamous cell carcinomas, lymphomas, malignant salivary gland tumors, Warthin's tumors and pleomorphic adenomas could be differentiated with a sensitivity of 85–87% and specificity of 80–100%. Low pre-treatment D or f and an increase in D during treatment were associated with a favorable response to treatment. D∗ appeared to be the parameter with the lowest prognostic value. Future research should focus on finding the optimal IVIM protocol, using uniformly accepted study methods and larger patient populations

Intravoxel incoherent motion magnetic resonance imaging in head and neck cancer : A systematic review of the diagnostic and prognostic value

Intravoxel incoherent motion (IVIM) imaging is increasingly applied in the assessment of head and neck cancer (HNC). Our purpose was to determine the diagnostic and prognostic performance of IVIM in HNC by performing a critical review of the literature. Pubmed and EMBASE were searched until May 2016. Study and patients characteristics, imaging protocol and diagnostic or prognostic outcomes were extracted by 2 independent reviewers. The studied IVIM parameters were diffusion coefficient (D), pseudodiffusion coefficient (D∗), and perfusion fraction (f). We included 10 diagnostic studies, 5 prognostic studies and 2 studies assessing both. Studies were very heterogeneous in terms of applied b-values, imaging protocols, outcome measurements and reference standards; therefore we did not perform a meta-analysis. The most commonly used sequence was "spin-echo planar imaging". A median of 10.5 b-values (range, 3-17) were used. All but three studies included at least 4 b-values below b=200s/mm(2). By combining IVIM-parameters squamous cell carcinomas, lymphomas, malignant salivary gland tumors, Warthin's tumors and pleomorphic adenomas could be differentiated with a sensitivity of 85-87% and specificity of 80-100%. Low pre-treatment D or f and an increase in D during treatment were associated with a favorable response to treatment. D∗ appeared to be the parameter with the lowest prognostic value. Future research should focus on finding the optimal IVIM protocol, using uniformly accepted study methods and larger patient populations

Contrast-enhanced perfusion magnetic resonance imaging for head and neck squamous cell carcinoma: a systematic review

This systematic review gives an extensive overview of the current state of perfusion-weighted magnetic resonance imaging (MRI) for head and neck squamous cell carcinoma (HNSCC). Pubmed and Embase were searched for literature until July 2014 assessing the diagnostic and prognostic performance of perfusion-weighted MRI in HNSCC. Twenty-one diagnostic and 12 prognostic studies were included for qualitative analysis. Four studies used a T2(∗) sequence for dynamic susceptibility (DSC)-MRI, 29 studies used T1-based sequences for dynamic contrast enhanced (DCE)-MRI. Included studies suffered from a great deal of heterogeneity in study methods showing a wide range of diagnostic and prognostic performance. Therefore we could not perform any useful meta-analysis. Perfusion-weighted MRI shows potential in some aspects of diagnosing HNSCC and predicting prognosis. Three studies reported significant correlations between hypoxia and tumor heterogeneity in perfusion parameters (absolute correlation coefficient |ρ|>0.6, P <0.05). Two studies reported synergy between perfusion-weighted MRI and positron emission tomography (PET) parameters. Four studies showed a promising role for response prediction early after the start of chemoradiotherapy. In two studies perfusion-weighted MRI was useful in the detection of residual disease. However more research with uniform study and analysis protocols with larger sample sizes is needed before perfusion-weighted MRI can be used in clinical practic

Adherence to pretreatment and intratreatment imaging of head and neck squamous cell carcinoma patients undergoing (chemo) radiotherapy in a research setting

PURPOSE: The emerge of improved personalized treatment adaptations and outcome prediction is accompanied with increasing non-invasive assessments in early treatment phase, leading to increased patient burden. This study assessed the adherence of patients with head and neck squamous cell carcinoma (HNSCC) to undergo pretreatment and research-related intratreatment imaging, and assessed which factors caused drop-out. METHOD: Between 2013 and 2019, advanced-staged HNSCC patients were prospectively included, underwent (chemo) radiotherapy with curative intent and planned for both pre-treatment and intratreatment sequential 18F-FDG-PET/CT, 18F-FDG-PET/MRI and thereafter MRI (including DWI/DCE). Drop-out-factors were described as healthcare-related (logistics and imaging-system defects) and patient-related (psychological, physical, not-specified). Common Toxicity Criteria (CTC) were routinely scored by radiation/medical oncologists throughout the first 3 weeks, and compared between patient drop-outs and who complete imaging. RESULTS: Ninety-seven patients (mean age 61 ± 6.8 years) were included; 95 patients (97.9%) underwent pretreatment imaging and 63 (64.9%) intratreatment imaging. For 18F-FDG-PET/CT, 18F-FDG-PET/MRI and MRI pretreatment drop-outs were 2, 10 and 3 patients and for intratreatment drop-outs were 34, 39 and 35 patients, respectively. Patient-related drop-out-factors were physical (n = 16, e.g. dysphagia), psychological (n = 6, e.g. claustrophobia) and non-specified (n = 12). Healthcare-related drop-out-factors were logistics (n = 6) and 18F-FDG-PET/CT-/MRI-system defects (n = 2). The CTC mucosal toxicity was significantly higher (p = 0.023) at week 2 of (chemo)radiotherapy in patient drop-outs than with complete imaging. CONCLUSIONS: The drop-out frequency of advanced-staged HNSCC patients for imaging during (chemo)radiotherapy in a research-setting was high and mainly patient-related. Treatment of patient-related inconveniences, communication of rationale and healthcare-related imaging protocol efficiency improvements may contribute to improved adherence

The Additional Value of Ultrafast DCE-MRI to DWI-MRI and 18F-FDG-PET to Detect Occult Primary Head and Neck Squamous Cell Carcinoma

To evaluate diagnostic accuracy of qualitative analysis and interobserver agreement of single ultrafast-DCE, DWI or 18F-FDG-PET and the combination of modalities for the detection of unknown primary tumor (UPT) in patients presenting with cervical lymph node metastasis from squamous cell carcinoma (SCC). Between 2014-2019, patients with histologically proven cervical lymph node metastasis of UPT SCC were prospectively included and underwent DWI, ultrafast-DCE, and 18F-FDG-PET/CT. Qualitative assessment was performed by two observers per modality. Interobserver agreement was calculated using the proportion specific agreement. Diagnostic accuracy of combined use of DWI, ultrafast-DCE and 18F-FDG-PET/CT was assessed. Twenty-nine patients were included (20 males. [68%], median age 60 years). Nine (31%) primary tumors remained occult. Ultrafast-DCE added reader confidence for suspicious locations (one additional true positive (5%), 2 decisive true malignant (10%). The per-location analysis showed highest specific positive agreement for ultrafast-DCE (77.6%). The per-location rating showed highest sensitivity (95%, 95%CI = 75.1-99.9, YI = 0.814) when either one of all modalities was scored positive, and 97.4% (95%CI = 93.5-99.3, YI = 0.774) specificity when co-detected on all. The per-patient analysis showed highest sensitivity (100%) for 18F-FDG-PET/CT (YI = 0.222) and either DWI or PET (YI = 0.111). Despite highest trends, no significant differences were found. The per-patient analysis showed highest specific positive agreement when co-detected on all modalities (55.6%, 95%CI = 21.2-86.3, YI = 0.456). Ultrafast-DCE showed potential to improve detection of unknown primary tumors in addition to DWI and 18F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and 18F-FDG-PET/CT yielded highest sensitivity