Cervical lymphadenopathy: can the histogram analysis of apparent diffusion coefficient help to differentiate between lymphoma and squamous cell carcinoma in patients with unknown clinical primary tumor?

PURPOSE: To retrospectively evaluate the value of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating between lymphoma and metastatic squamous cell carcinoma (SCC) of unknown clinical primary in neck nodes. METHODS: A total of 39 patients, 20 affected by lymphoma and 19 affected by metastatic non-nasopharyngeal SCC, were included in this retrospective study. All patients underwent MR imaging with a 1.5 T scanner system, including diffusion-weighted imaging (DWI) with three different b values (b = 0, 500 and 800 s/mm2). The entire tumor volume was manually delineated on the ADC maps, using the T2-weighted images and DWIs with b = 800 s/mm2 as a guide to the lesion location. The Mann-Whitney rank-sum test for independent samples was performed to compare the histogram parameters of patients with lymphoma and SCC. RESULTS: The SCCs showed significantly higher median ADC (ADCmedian) and mean ADC (ADCmean) values, compared to lymphomas (p < 0.001), while they exhibited lower kurtosis and skewness without reaching significance (p = 0.066 and 0.148, respectively). The ADCmean and ADCmedian had the best discriminative powers for differentiating lymphoma and SCC, with an area under the curve of 87% and 85%, respectively. The optimal cutoff values for ADCmean and ADCmedian as predictors for lymphoma were ≤ 0.83 × 10-3 mm2/s and ≤ 0.73 × 10-3 mm2/s, respectively. CONCLUSIONS: The whole-lesion ADC histogram analysis of cervical lymphadenopathy may help to discriminate lymphomas from non-nasopharyngeal SCC in patients with unknown clinical primary tumor.

Feasibility study of reduced field of view diffusion-weighted magnetic resonance imaging in head and neck tumors.

Background Reduced field of view (rFOV) imaging may be used to improve the quality of diffusion-weighted imaging (DWI) in the head and neck (HN) region. Purpose To evaluate the feasibility of rFOV-DWI in patients affected by HN tumors, through a comparison with conventional full FOV (fFOV) DWI. Material and Methods Twenty-two patients with histologically-proven malignant or benign tumors of the head and neck were included in a retrospective study. All patients underwent pre-treatment magnetic resonance imaging (MRI) studies including rFOV-DWI and fFOV-DWI. The apparent diffusion coefficient (ADC) value distributions inside tumor and muscle were derived and the mean, standard deviation (SD), and kurtosis were calculated. Image distortion was quantitatively and qualitatively evaluated, as well as the capability of lesion identification. The Wilcoxon test was used to compare all variables. Agreements between the ADC estimations were assessed by Bland-Altman plots. Results Image distortion and lesion identification scores were both higher for rFOV-DWI compared to fFOV-DWI. A reduction in ADC values with rFOV-DWI emerged for both lesion and muscle, with a mean percentage difference in ADC of 6.2% in the lesions and 24.9% in the muscle. The difference in SD of ADC was statistically significant in the lesions, indicating a higher ADC homogeneity for rFOV DWI ( P = 0.005). Conclusion The application of rFOV DWI in patients affected by HN tumors is feasible and promising, based on both qualitative and quantitative analyses. This technique has potential for improving the diagnostic accuracy of fFOV-DWI for the study of specific tumoral areas.

Relationship between diffusion parameters derived from intravoxel incoherent motion MRI and perfusion measured by dynamic contrast-enhanced MRI of soft tissue tumors.

Our aim was to evaluate the link between diffusion parameters measured by intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and the perfusion metrics obtained with dynamic contrast-enhanced (DCE) MRI in soft tissue tumors (STTs). Twenty-eight patients affected by histopathologically confirmed STT were included in a prospective study. All patients underwent both DCE MRI and IVIM DWI. The perfusion fraction f, diffusion coefficient D and perfusion-related diffusion coefficient D* were estimated using a bi-exponential function to fit the DWI data. DCE MRI was acquired with a temporal resolution of 3-5 s. Maps of the initial area under the gadolinium concentration curve (IAUGC), time to peak (TTP) and maximum slope of increase (MSI) were derived using commercial software. The relationships between the DCE MRI and IVIM DWI measurements were assessed by Spearman's test. To exclude false positive results under multiple testing, the false discovery rate (FDR) procedure was applied. The Mann-Whitney test was used to evaluate the differences between all variables in patients with non-myxoid and myxoid STT. No significant relationship was found between IVIM parameters and any DCE MRI parameters. Higher f and D*f values were found in non-myxoid tumors compared with myxoid tumors (p = 0.004 and p = 0.003, respectively). MSI was significantly higher in non-myxoid tumors than in myxoid tumors (p = 0.029). From the visual assessments of single clinical cases, both f and D*f maps were in satisfactory agreement with DCE maps in the extreme cases of an avascular mass and a highly vascularized mass, whereas, for tumors with slight vascularity or with a highly heterogeneous perfusion pattern, this association was not straightforward. Although IVIM DWI was demonstrated to be feasible in STT, our data did not support evident relationships between perfusion-related IVIM parameters and perfusion measured by DCE MRI.

Early radiation-induced changes evaluated by intravoxel incoherent motion in the major salivary glands.

PURPOSE: To investigate the potential of intravoxel incoherent motion (IVIM) MRI for early evaluation of irradiated major salivary glands. MATERIALS AND METHODS: Thirty-four patients with head-neck cancer were included in a prospective study. All patients underwent three serial IVIM-MRI: before, half-way through, and at the end of radiotherapy (RT). Apparent diffusion coefficient (ADC), ADClow derived in the low b-value range, perfusion fraction f, and pure diffusion coefficient D were estimated. Pretreatment values and early changes of diffusion parameters were correlated with parotid mean dose (Dmean ) and volume reduction after RT. RESULTS: Changes in diffusion parameters over time were all significant (P < 0.001 for ADC, ADClow , and D, P = 0.003 for f). Variations of ADC, ADClow , and f were not correlated with Dmean (P = 0.089, P = 0.252 and P = 0.884, respectively), whereas a significant relationship was found between changes in D and Dmean (r = 0.197 with CI95% = 0.004-0.375, P = 0.046). Pretreatment f and Dmean were the best independent predictors for the percentage shrinkage (P = 0.0003 and 0.0597 respectively; R(2) = 0.391). CONCLUSION: Early changes of irradiated major salivary glands can be noninvasively evaluated by IVIM-MRI. Perfusion-related coefficients in conjunction with dosimetric information increase our capability to predict the change in parotid volume and hence, if further validated, guide treatment strategy in RT.

Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas.

INTRODUCTION: The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas. METHODS: Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V(tot)), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V(CE-T1) and V(NON-CE-T1), respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K(trans) maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease. RESULTS: Responding patients showed a larger reduction in V(NON-CE-T1) after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K(trans), after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V(tot) was predictive of overall survival (OS), while V(CE-T1) showed a tendency of correlation with OS. CONCLUSION: Tumor subvolumes with increased nIAUGC and K(trans) showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation.

Circulating tumor HPV DNA in the management of HPV+ oropharyngeal cancer and its correlation with MRI.

BACKGROUND: First aim was to compare ddPCR assays of ctHPVDNA with p16 IHC and qualitative HPV PCR. Second aim was to carry out longitudinal blood sampling to test for association of ctHPVDNA with histological confirmed recurrence. Third aim was to perform a multidimensional assessment which included: (1) clinical features; (2) ctHPVDNA; (3) MRI-based tumor size measurements of primary tumor (PT) and cervical lymph node metastases (CLNM). METHODS: Plasma samples were collected before treatment and during follow-up, and ddPCR assay comprising E6 of HPV16 and HPV 33 and HPV 35 was used. RESULTS: Present study was conducted at diagnosis in 117 patients and revealed a ctHPVDNA sensitivity of 100% (95% CI 95.5-100) and a specificity of 94.4 (95% CI 81.3-99.3), positive predictive value (PPV) of 94.4 (95% CI 81.3-99.3), and negative predictive value (NPP) of 100% (95% CI 89.7-100). During follow-up ctHPVDNA had a sensitivity of 100% (95% CI 72.1-100)% and specificity of 98.4% (95% CI 91.7-100)%, PPV% of 90.9% (95% CI 62.3-98.4) and NPV% of 100% (95% CI 94.3-100) for ability to detect recurrence. Correlation between both the CLNM volume and the sum of PT and CLNM volume was observed. CONCLUSIONS: ctHPVDNA was superior to p16 in identification of HPV-OPSCC at diagnosis. Introduction of ctHPVDNA, beyond diagnostic setting, represents a great opportunity to improve follow-up protocol of OPSCC patients.

Assessment of diffusion parameters by intravoxel incoherent motion MRI in head and neck squamous cell carcinoma.

The objectives of this study were to assess the diffusion parameters derived from intravoxel incoherent motion (IVIM) MRI in head and neck squamous cell carcinoma (HNSCC) and to investigate the agreement between different methods of tumor delineation and two numerical methods to extract the perfusion fraction f. Thirty-seven untreated patients with histopathologically confirmed primary HNSCC were included retrospectively in the study. The entire volume of the primary tumor was outlined on diffusion-weighted images using co-registered morphological images as a guide to the tumor location. Apparent diffusion coefficient (ADC) and IVIM diffusion parameters were estimated considering the largest tumor section as well as the entire tumor volume. A bi-exponential fit was implemented to extract f, D (pure diffusion coefficient) and D* (pseudo-diffusion coefficient). A second simplified method, based on an asymptotic extrapolation, was used to determine f. The agreement between ADC and IVIM diffusion parameters derived from the delineation of single and multiple slices, and between the two f estimations, was assessed by Bland-Altman plots. The inter-slice variability of ADC and IVIM diffusion parameters was evaluated. The Kruskal-Wallis test was used to investigate whether the tumor location had a statistically significant influence on the values of the parameters. Comparing the tumor delineation methods, a better accordance was found for ADC and D, with a mean percentage difference of less than 2%. Larger discrepancies were found for f and D*, with mean differences of 4.5% and 5.5%, respectively. When comparing the two f estimation methods, small mean differences were found (<3.5%), suggesting that the two methods may be considered as equivalent for the assessment of f in our patient population. The observed ADC and IVIM diffusion parameters were dependent on the anatomic site of the lesion, carcinoma of the nasopharynx showing more homogeneous and dissimilar estimations than other HNSCCs.

Magnetic resonance imaging-based prediction models for tumor stage and cervical lymph node metastasis of tongue squamous cell carcinoma.

Purpose: To evaluate the ability of preoperative MRI-based measurements to predict the pathological T (pT) stage and cervical lymph node metastasis (CLNM) via machine learning (ML)-driven models trained in oral tongue squamous cell carcinoma (OTSCC). Materials and methods: 108 patients with a new diagnosis of OTSCC were enrolled. The preoperative MRI study included post-contrast high-resolution T1-weighted images acquired in all patients. MRI-based depth of invasion (DOI) and tumor dimension-together with shape-based and intensity-based features-were extracted from the lesion volume segmentation. The entire dataset was randomly divided into a training set and a validation set, and the performances of different types of ML algorithms were evaluated and compared. Results: MRI-based DOI and tumor dimension together with several shape-based and intensity-based signatures significantly discriminated the pT stage and LN status. The overall accuracy of the model for predicting the pT stage was 0.86 (95%CI, 0.78-0.92) and 0.81 (0.64-0.91) in the training and validation sets, respectively. There was no improvement in the model performance upon including shape-based and intensity-based features. The model for predicting CLNM based on DOI and tumor dimensions had a fair accuracy of 0.68 (0.57-0.78) and 0.69 (0.51-0.84) in the training and validation sets, respectively. The shape-based and intensity-based signatures have shown potential for improving the model sensitivity, with a comparable accuracy. Conclusion: MRI-based models driven by ML algorithms could stratify patients with OTSCC according to the pT stages. They had a moderate ability to predict cervical lymph node metastasis.

Predictors of Outcome after (Chemo)Radiotherapy for Node-Positive Oropharyngeal Cancer: The Role of Functional MRI.

The prognosis of a subset of patients with locally advanced oropharyngeal cancer (LA-OPC) is still poor despite improvements in patient selection and treatment. Identifying specific patient- and tumor-related factors can help to select those patients who need intensified treatment. We aimed to assess the role of historical risk factors and novel magnetic resonance imaging (MRI) biomarkers in predicting outcomes in these patients. Patients diagnosed with LA-OPC were studied with diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI at baseline and at the 10th radiotherapy (RT) fraction. Clinical information was collected as well. The endpoint of the study was the development of disease progression, locally or distantly. Of the 97 patients enrolled, 68 were eligible for analysis. Disease progression was recorded in 21 patients (11 had loco-regional progression, 10 developed distant metastases). We found a correlation between N diameter and disease control (p = 0.02); features such as p16 status and extranodal extension only showed a trend towards statistical significance. Among perfusion MRI features, higher median values of Kep both in primary tumor (T, p = 0.016) and lymph node (N, p = 0.003) and lower median values of ve (p = 0.018 in T, p = 0.004 in N) correlated with better disease control. Kep P90 and N diameter were identified by MRMR algorithm as the best predictors of outcome. In conclusion, the association of non-invasive MRI biomarkers and patients and tumor characteristics may help in predicting disease behavior and patient outcomes in order to ensure a more customized treatment.

Microenvironmental Factors in Oral Cavity Squamous Cell Carcinoma Undergoing Surgery: Correlation with Diffusion Kurtosis Imaging and Dynamic Contrast-Enhanced MRI.

BACKGROUND: In this prospective study, we hypothesized that magnetic resonance imaging (MRI) may represent not only the tumor but also the microenvironment, reflecting the heterogeneity and microstructural complexity of neoplasms. We investigated the correlation between both diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced (DCE)-MRI with the pathological factors in oral cavity squamous cell carcinomas (OSCCs). METHODS: A total of 37 patients with newly diagnosed OSCCs underwent an MR examination on a 3T system. The diffusion coefficient (D), the kurtosis parameter (K), the transfer constants Ktrans and Kep and the volume of extravascular extracellular space ve were quantified. A histogram-based approach was proposed to investigate the associations between the imaging and the pathological factors based on the histology and immunochemistry. RESULTS: Significant differences in the DCE-MRI and DKI parameters were found in relation to the inflammatory infiltrate, tumor grading, keratinization and desmoplastic reaction. Relevant relationships emerged between tumor-infiltrating lymphocytes (TILs) and DKI, with lower D and higher K values being associated with increased TILs. CONCLUSION: Although a further investigation is needed, these findings provide a more comprehensive biological characterization of OSCCs and may contribute to a better understanding of DKI-derived parameters, whose biophysical meaning is still not well-defined.

Response on DCE-MRI predicts outcome of salvage radiotherapy for local recurrence after radical prostatectomy.

OBJECTIVE: To assess the predictive role of response on dynamic contrast enhancement on magnetic resonance imaging (DCE-MRI) of visible local lesions in the setting of salvage radiotherapy (sRT) after radical prostatectomy. METHODS: All patients referred for sRT for biochemical failure after radical prostatectomy from February 2014 to September 2016 were considered eligible if they had been restaged with DCE-MRI and had been found to have a visible lesion in the prostatic bed, but no distant/nodal disease on choline positron emission tomography (PET)-computed tomography (CT). Eligible patients were contacted during follow-up and offered reimaging with serial DCE-MRI until lesion resolution. Complete response (CR) was defined as the disappearance of the target lesion on DCE-MRI; prostate-specific antigen (PSA) recurrence was defined as a 0.2 ng/mL PSA rise above the nadir. Median follow-up after sRT was 41.5 months (range, 12.1-61.2 months). RESULTS: Fifty-nine patients agreed to undergo repeated DCE-MRI for a total of 64 studied lesions. Overall, 57 lesions (89.1%) showed a CR after 1 (51 patients) or 2 (6 patients) scans, while 7 lesions did not show any change (no response [NR]). At 42 months, no evidence of biochemical disease (bNED) survival was 74.7±6.4% and 64.3±21.0% for patients with CR and NR lesions, respectively (hazard ratio [HR], 3.181; 95% confidence interval [CI], 0.157-64.364; p = 0.451). When only patients treated with sRT without androgen deprivation were selected (n = 41), bNED survival rates at 42 months were 72.1±8.0% and 0, respectively (HR, 52.830; 95% CI, 1.893-1474.110; p = 0.020). CONCLUSIONS: Patients whose lesions disappear during follow-up have a better outcome than those with unchanged lesions after sRT alone.

Comparison of rigid and deformable coregistration between mpMRI and CT images in radiotherapy of prostate bed cancer recurrence.

PURPOSE: To evaluate the accuracy of rigid coregistration between multiparametric magnetic resonance (mpMR) and computed tomography (CT) images for radiotherapy of prostate bed cancer recurrence. MATERIALS AND METHOD: Fifty-three patients (59 nodules) accrued in a prospective study on salvage radiotherapy for prostatic bed recurrence were suitable for the analysis. Patients underwent a pre radiotherapy mpMR exam and a planning CT in the same treatment position and with control of organ filling. The site of recurrence was delineated on mpMR images and contours transferred on planning CT images using both rigid and deformable registrations. Coregistrations were evaluated by mathematical operators that quantify deformation (Jacobian determinant and vector curl) and similarity indices (Dice and Jaccard coefficients). Dose coverage was evaluated. RESULTS: Deformable registration did not change volumes, (p = 0.92 MW test). The Jacobian coefficient and the vector curl revealed no important image deformations. Dice and Jaccard coefficients indicated dislocation of the nodule volumes. Dislocation magnitude was d = (5.6 ± 3.1) mm. Organ filling was not correlated with deformation or dislocation. Volumes were covered by the 95% isodose in 96% of cases when rigid registration was performed versus 75% of cases when deformed. CONCLUSIONS: Rigid image coregistration is sufficiently accurate in this setting. The results indicate that the deformable registration tends to shrink the voxels and to dislocate the ROI, the adopted expansion for the recurrence volume adequately accounts for the observed deformation and dislocation, provided that organ filling is controlled.

The Role of Patient- and Treatment-Related Factors and Early Functional Imaging in Late Radiation-Induced Xerostomia in Oropharyngeal Cancer Patients.

The advent of quantitative imaging in personalized radiotherapy (RT) has offered the opportunity for a better understanding of individual variations in intrinsic radiosensitivity. We aimed to assess the role of magnetic resonance imaging (MRI) biomarkers, patient-related factors, and treatment-related factors in predicting xerostomia 12 months after RT (XER12) in patients affected by oropharyngeal squamous cell carcinoma (OSCC). Patients with locally advanced OSCC underwent diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI at baseline; DWI was repeated at the 10th fraction of RT. The Radiation Therapy Oncology Group (RTOG) toxicity scale was used to evaluate salivary gland toxicity. Xerostomia-related questionnaires (XQs) were administered weekly during and after RT. RTOG toxicity ≥ grade 2 at XER12 was considered as endpoint to build prediction models. A Decision Tree classification learner was applied to build the prediction models following a five-fold cross-validation. Of the 89 patients enrolled, 63 were eligible for analysis. Thirty-six (57.1%) and 21 (33.3%) patients developed grade 1 and grade 2 XER12, respectively. Including only baseline variables, the model based on DCE-MRI and V65 (%) (volume of both glands receiving doses ≥ 65 Gy) had a fair accuracy (77%, 95% CI: 66.5-85.4%). The model based on V65 (%) and XQ-Intmid (integral of acute XQ scores from the start to the middle of RT) reached the best accuracy (81%, 95% CI: 71-88.7%). In conclusion, non-invasive biomarkers from DCE-MRI, in combination with dosimetric variables and self-assessed acute XQ scores during treatment may help predict grade 2 XER12 with a fair to good accuracy.

Stereotactic body radiotherapy for T1 glottic cancer: dosimetric data in 27 consecutive patients.

AIM: Because the clinical feasibility of stereotactic body radiotherapy (SBRT) for early glottic cancer (T1) is controversial, we report dosimetric results in 27 consecutive patients from a prospective phase I and II study that started in 2017. METHODS: In our approach, only the parts of the true vocal cord containing cancer and those immediately adjacent are planned to be treated to 36 Gy and 30 Gy, respectively, in 3 fractions. Several dosimetric metrics for both target volumes and organs at risk were extracted from individual plans and results were compared to those achieved by other authors in a similar setting. RESULTS: Proper coverage was reached at planning in 2/3 of planning treatment volume 30 Gy, but only 4 planning treatment volume 36 Gy; conversely, the maximum dose objective was met for most of the patients on either arytenoid cartilage, but this was not the case for 51.9% and 96.3% of cricoid and thyroid cartilages, respectively. Our dosimetric results are similar to if not better than those achieved by others. CONCLUSION: SBRT in 3 fractions for T1 glottic lesions is dosimetrically challenging. Clinical validation is awaited.

MRI-Based Radiomics to Differentiate between Benign and Malignant Parotid Tumors With External Validation.

BACKGROUND: The differentiation between benign and malignant parotid lesions is crucial to defining the treatment plan, which highly depends on the tumor histology. We aimed to evaluate the role of MRI-based radiomics using both T2-weighted (T2-w) images and Apparent Diffusion Coefficient (ADC) maps in the differentiation of parotid lesions, in order to develop predictive models with an external validation cohort. MATERIALS AND METHODS: A sample of 69 untreated parotid lesions was evaluated retrospectively, including 37 benign (of which 13 were Warthin's tumors) and 32 malignant tumors. The patient population was divided into three groups: benign lesions (24 cases), Warthin's lesions (13 cases), and malignant lesions (32 cases), which were compared in pairs. First- and second-order features were derived for each lesion. Margins and contrast enhancement patterns (CE) were qualitatively assessed. The model with the final feature set was achieved using the support vector machine binary classification algorithm. RESULTS: Models for discriminating between Warthin's and malignant tumors, benign and Warthin's tumors and benign and malignant tumors had an accuracy of 86.7%, 91.9% and 80.4%, respectively. After the feature selection process, four parameters for each model were used, including histogram-based features from ADC and T2-w images, shape-based features and types of margins and/or CE. Comparable accuracies were obtained after validation with the external cohort. CONCLUSIONS: Radiomic analysis of ADC, T2-w images, and qualitative scores evaluating margins and CE allowed us to obtain good to excellent diagnostic accuracies in differentiating parotid lesions, which were confirmed with an external validation cohort.

Multiparametric MRI Evaluation of Oropharyngeal Squamous Cell Carcinoma. A Mono-Institutional Study.

The aim of this paper is to define the pre-treatment radiological characteristics of oropharyngeal squamous cell carcinoma (OPSCC) using morphological and non-morphological magnetic resonance imaging (MRI), based on HPV status, in a single-institution cohort. In total, 100 patients affected by OPSCC were prospectively enrolled in the present study. All patients underwent 1.5T MR with standard sequences, including diffusion-weighted imaging with and intravoxel incoherent motion (IVIM-DWI) technique and a dynamic contrast-enhanced (DCE) MRI. For all patients, human papillomavirus (HPV) status was available. No statistically significant differences in the volume of primary tumors (PTs) and lymph nodes (LNs) were observed based on HPV status. When comparing the two patient groups, no significant differences were found for the PT radiologic characteristics (presence of well-defined borders, exophytic growth, ulceration, and necrosis) and LN morphology (solid/cystic/necrotic). Tumor subsite, smoking status, and alcohol intake significantly differed based on HPV status, as well as ADC and Dt values of both PTs and LNs. We detected no significant difference in DCE-MRI parameters by HPV status. Based on a multivariate logistic regression model, the combination of clinical factors, such as tumor subsite and alcohol habits, with the perfusion-free diffusion coefficient Dt of LNs, may help to accurately discriminate OPSCC by HPV status.

On the dependence of quantitative diffusion-weighted imaging on scanner system characteristics and acquisition parameters: A large multicenter and multiparametric phantom study with unsupervised clustering analysis.

PURPOSE: The purpose of this multicenter phantom study was to exploit an innovative approach, based on an extensive acquisition protocol and unsupervised clustering analysis, in order to assess any potential bias in apparent diffusion coefficient (ADC) estimation due to different scanner characteristics. Moreover, we aimed at assessing, for the first time, any effect of acquisition plan/phase encoding direction on ADC estimation. METHODS: Water phantom acquisitions were carried out on 39 scanners. DWI acquisitions (b-value = 0-200-400-600-800-1000 s/mm2) with different acquisition plans (axial, coronal, sagittal) and phase encoding directions (anterior/posterior and right/left, for the axial acquisition plan), for 3 orthogonal diffusion weighting gradient directions, were performed. For each acquisition setup, ADC values were measured in-center and off-center (6 different positions), resulting in an entire dataset of 84 × 39 = 3276 ADC values. Spatial uniformity of ADC maps was assessed by means of the percentage difference between off-center and in-center ADC values (Δ). RESULTS: No significant dependence of in-center ADC values on acquisition plan/phase encoding direction was found. Ward unsupervised clustering analysis showed 3 distinct clusters of scanners and an association between Δ-values and manufacturer/model, whereas no association between Δ-values and maximum gradient strength, slew rate or static magnetic field strength was revealed. Several acquisition setups showed significant differences among groups, indicating the introduction of different biases in ADC estimation. CONCLUSIONS: Unsupervised clustering analysis of DWI data, obtained from several scanners using an extensive acquisition protocol, allows to reveal an association between measured ADC values and manufacturer/model of scanner, as well as to identify suboptimal DWI acquisition setups for accurate ADC estimation.

Refinement & validation of rectal wall dose volume objectives for prostate hypofractionation in 20 fractions.

BACKGROUND AND PURPOSE: Dose-volume objectives for the rectum have been proposed to limit long term toxicity after moderately hypofractionated radiotherapy (MHRT) for localized prostate cancer. The purpose of the present study is to validate and possibly refine dose volume objective for the rectal wall after 20-fraction MHRT. MATERIALS AND METHODS: All patients treated by 20-fraction MHRT at a single Institution were identified and relative rectal wall (%RW) DVH retrieved. The endpoint of the study is the development of grade 2+ late rectal bleeding (LRB) according to a modified RTOG scale. Clinical and dosimetric predictors of LRB were investigated at both uni- and multi-variable analysis. RESULTS: 293 patients were identified and analyzed. Of them, 35 (12%) developed the endpoint. At univariable analysis, antithrombotic drug usage (yes vs no), technique (3DCRT vs IMRT/VMAT) and several %RW DVH cut-points were significantly correlated with LRB. However, within patients treated by 3DCRT (N = 106), a bi-variable model including anti-thrombotic drug usage and selected %RW dose/volume metrics failed to identify independent dosimetric predictors of LRB. Conversely, within patients treated with intensity modulation (N = 187), the same model showed a progressively higher impact of the percent of RW receiving doses above 40 Gy. Based on this model, we were able to confirm (V32), refine (V60) and identify a novel (V50) cut-point for the %RW. CONCLUSION: We recommend the following dose volume objectives for the %RW in order to minimize the risk of LRB after 20-fraction MHRT: V32 ≤ 50%; V50 ≤ 25.8% and V60 ≤ 10%.

Diffusion kurtosis imaging in head and neck cancer: A correlation study with dynamic contrast enhanced MRI.

PURPOSE: To investigate the biophysical meaning of Diffusion Kurtosis Imaging (DKI) parameters via correlations with the perfusion parameters obtained from a long Dynamic Contrast Enhanced MRI scan, in head and neck (HN) cancer. METHODS: Twenty two patients with newly diagnosed HN tumor were included in the present retrospective study. Some patients had multiple lesions, therefore a total of 26 lesions were analyzed. DKI was acquired using 5b values at 0, 500, 1000,1500 and 2000 s/mm2. DCE-MRI was obtained with 130 dynamic volumes, with a temporal resolution of 5 s, to achieve a long scan time (>10 min). The apparent diffusion coefficient Dapp and apparent diffusional kurtosis Kapp were calculated voxel-by-voxel, removing the point at b value = 0 to eliminate possible perfusion effects on the parameter estimations. The transfer constants Ktrans and Kep, ve, and the histogram-based entropy (En) and interquartile range (IQR) of each DCE-MRI parameter were quantified. Correlations between all variables were investigated by the Spearman's Rho correlation test. RESULTS: Moderate relationships emerged between Dapp and Kep (Rho =  - 0.510, p = 0.009), and between Dapp and ve (Rho = 0.418, p = 0.038). En(Kep) was significantly related to Kapp (Rho = 0.407, p = 0.043), while IQR(Kep) showed an inverse association with Dapp (Rho = -0.422, p = 0.035). CONCLUSIONS: A weak to intermediate correlation was found between DKI parameters and both Kep and ve. The kurtosis was associated to the intratumoral heterogeneity and complexity of the capillary permeability, expressed by En(Kep).