Muhammad M. Qureshi

Prediction of Locoregional Control in Head and Neck Squamous Cell Carcinoma with Serial CT Perfusion during Radiotherapy

BACKGROUND AND PURPOSE: Tumor hypoxia is a known factor of radioresistance in HNSCC. CTP is a noninvasive method of measuring tumor perfusion in vivo. The purpose of our study was to determine serial changes in tumor perfusion in HNSCC during a course of RT by using CTP and to correlate tumor perfusion measurements to LRC. MATERIALS AND METHODS: A prospective study was performed in 15 patients with HNSCC receiving definitive RT who underwent serial CTP before RT; at weeks 2, 4, and 6 of RT; and 6 weeks after RT. The median follow-up was 28 months (range, 6–44 months). Thirteen patients achieved LRC, and 2 patients had LRF. Tumor perfusion parameters, including BF, BV, MTT, and CP, were obtained by using a deconvolution-based analysis. RESULTS: Pretreatment tumor BF was significantly higher in patients who achieved LRC, 118.0 mL/100 g/min, compared with those with LRF, 53.4 mL/100 g/min (P = .004). Similarly, pretreatment CP was higher in patients with LRC, 16.6 mL/100 g/min, compared with those with LRF, 7.7 mL/100 g/min (P = .02). At week 2 of RT, tumor BF parameters showed a 27.5% increase versus an 18.1% decrease from pretreatment BF values (P = .046) in patients with LRC and LRF, respectively. A decrease in BF and BV was observed in both groups 6 weeks after RT compared with these values at baseline scanning. CONCLUSIONS: An increase in tumor BF and CP by using CTP early during a course of RT predicts LRC in patients with HNSCC treated with RT.

Using texture analyses of contrast enhanced CT to assess hepatic fibrosis.

PURPOSE To determine the ability of texture analyses of contrast-enhanced CT images for distinguishing between varying degrees of hepatic fibrosis in patients with chronic liver disease using histopathology as the reference standard. MATERIALS AND METHODS Following IRB approval, 83 patients who underwent contrast enhanced 64-MDCT of the abdomen and pelvis in the portal venous phase between 12/2005 and 01/2013 and who had a liver biopsy within 6 months of the CT were included. An in-house developed, MATLAB-based texture analysis program was employed to extract 41 texture features from each of 5 axial segmented volumes of liver. Using the Ishak fibrosis staging scale, histopathologic grades of hepatic fibrosis were correlated with texture parameters after stratifying patients into three analysis groups, comparing Ishak scales 0-2 with 3-6, 0-3 with 4-6, and 0-4 with 5-6. To assess the utility of texture features, receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was used to determine the performance of each feature in distinguishing between normal/low and higher grades of hepatic fibrosis. RESULTS A total of 19 different texture features with 7 histogram features, one grey level co-occurrence matrix, 6 gray level run length, 1 Laws feature, and 4 gray level gradient matrix demonstrated statistically significant differences for discriminating between fibrosis groupings. The highest AUC values fell in the range of fair performance for distinguishing between different fibrosis groupings. CONCLUSION These findings suggest that texture-based analyses of contrast-enhanced CT images offer a potential avenue toward the non-invasive assessment of liver fibrosis.

Using Texture Analysis to Determine Human Papillomavirus Status of Oropharyngeal Squamous Cell Carcinomas on CT

BACKGROUND AND PURPOSE: Human papillomavirus–associated oropharyngeal squamous cell carcinoma is increasing in prevalence and typically occurs in younger patients than human papillomavirus–negative squamous cell carcinoma. While imaging features of human papillomavirus–positive versus human papillomavirus–negative squamous cell carcinoma nodal metastases have been described, characteristics distinguishing human papillomavirus–positive from human papillomavirus–negative primary squamous cell carcinomas have not been well established. The purpose of this project was to evaluate the use of texture features to distinguish human papillomavirus–positive and human papillomavirus–negative primary oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS: Following institutional review board approval, 40 patients with primary oropharyngeal squamous cell carcinoma and known human papillomavirus status who underwent contrast-enhanced CT between December 2009 and October 2013 were included in this study. Segmentation of the primary lesion was manually performed with a semiautomated graphical-user interface. Following segmentation, an in-house-developed texture analysis program extracted 42 texture features from each segmented volume. A t test was used to evaluate differences in texture parameters between human papillomavirus–positive and human papillomavirus–negative squamous cell carcinomas. RESULTS: Of the 40 included patients, 29 had human papillomavirus–positive oropharyngeal squamous cell carcinoma and 11 had human papillomavirus–negative oropharyngeal squamous cell carcinoma. Significant differences were seen in the histogram parameters median (P = .006) and entropy (P = .016) and squamous cell carcinoma entropy (P = .043). CONCLUSIONS: There are statistically significant differences in some texture features between human papillomavirus–positive and human papillomavirus–negative oropharyngeal tumors. Texture analysis may be considered an adjunct to the evaluation of human papillomavirus status and characterization of squamous cell carcinoma.

Difference Between HPV-Positive and HPV-Negative Non-Oropharyngeal Head and Neck Cancer: Texture Analysis Features on CT.

Objective To identify the specific texture parameter that shows significant differences between human papillomavirus (HPV)–positive (HPV+) and HPV-negative (HPV-) non-oropharyngeal carcinoma (non-OPC) using texture analysis. Methods Forty-six patients of non-OPC patients (oral cavity, larynx, and hypopharynx) with known HPV status, who underwent contrast-enhanced computed tomography for initial staging, were retrospectively reviewed. Segmentations of the primary lesion were manually performed, and an in-house developed texture analysis program extracted 42 texture features from each segmented volume. A t test was used to evaluate differences between HPV+ and HPV- non-OPCs (P < 0.05). Results Sixteen texture parameters, including 5 histogram features (P ⩽ 0.03), 3 gray-level co-occurrence matrix features (P ⩽ 0.02), 1 gray-level run-length feature (P = 0.009), 2 gray-level gradient matrix features (P ⩽ 0.02), and 5 Law features (P ⩽ 0.04), showed significant differences. Conclusions Texture analysis demonstrated significant differences between HPV+ and HPV- non-OPCs on computed tomography images, which may have a potential to prove morphologic feature differences among HPV-related tumors.

Usefulness of the blood hematocrit level to predict development of heart failure in a community.

Current data suggest that increases in hemoglobin may decrease nitric oxide and adversely affect vascular function. In the preclinical setting, these changes could precipitate the development of heart failure (HF). We hypothesized that higher hematocrit (HCT) would be associated with an increased incidence of new-onset HF in the community. We evaluated 3,523 participants (59% women) from the Framingham Heart Study who were 50 to 65 years old and free of HF. Participants were followed prospectively until an HF event, death, or the end of 20 years of follow up. HCT was subdivided into 4 gender-specific categories (women: HCT 36.0 to 40.0, 40.1 to 42.0, 42.1 to 45.0, >45.0; men: 39.0 to 44.0, 44.1 to 45.0, 45.1 to 49.0, >49.0). Gender-pooled multivariable Cox proportional hazards models were used to estimate the association of HCT with incident HF, adjusting for clinical risk factors. During the follow-up period (61,417 person-years), 217 participants developed HF (100 events in women). There was a linear increase in risk of HF across the 4 HCT categories (p for trend = 0.002). Hazards ratios for HF in the low-normal, normal, and high HCT categories were 1.27 (95% confidence interval 0.82 to 1.97), 1.47 (1.01 to 2.15), and 1.78 (1.15 to 2.75), respectively, compared to the lowest HCT category (p for trend <0.0001). Adjustment for interim development of other cardiovascular diseases and restriction of the sample to nonsmokers did not alter the results. In conclusion, higher levels of HCT, even within the normal range, were associated with an increased risk of developing HF in this long-term follow-up study.

Global and Regional Brain Assessment with Quantitative MR Imaging in Patients with Prior Exposure to Linear Gadolinium-based Contrast Agents

Purpose To assess the association of global and regional brain relaxation times in patients with prior exposure to linear gadolinium-based contrast agents (GBCAs). Materials and Methods The institutional review board approved this cross-sectional study. Thirty-five patients (nine who had received GBCA gadopentetate dimeglumine injections previously [one to eight times] and 26 patients who did not) who underwent brain magnetic resonance (MR) imaging with a mixed fast spin-echo pulse sequence were assessed. The whole brain was segmented according to white and gray matter by using a dual-clustering algorithm. In addition, regions of interest were measured in the globus pallidus, dentate nucleus, thalamus, and pons. The Mann-Whitney U test was used to assess the difference between groups. Multiple regression analysis was performed to assess the association of T1 and T2 with prior GBCA exposure. Results T1 values of gray matter were significantly shorter for patients with than for patients without prior GBCA exposure (P = .022). T1 of the gray matter of the whole brain (P < .001), globus pallidus (P = .002), dentate nucleus (P = .046), and thalamus (P = .026) and T2 of the whole brain (P = .004), dentate nucleus (P = .023), and thalamus (P = .002) showed a significant correlation with the accumulated dose of previous GBCA administration. There was no significant correlation between T1 and the accumulated dose of previous GBCA injections in the white matter (P = .187). Conclusion Global and regional quantitative assessments of T1 and T2 demonstrated an association with prior GBCA exposure, especially for gray matter structures. The results of this study confirm previous research findings that there is gadolinium deposition in wider distribution throughout the brain.

Radiation Dose to the Brachial Plexus in Head-and-Neck Intensity-Modulated Radiation Therapy and Its Relationship to Tumor and Nodal Stage

PURPOSE The purpose of this retrospective study was to determine tumor factors contributing to brachial plexus (BP) dose in head-and-neck cancer (HNC) patients treated with intensity-modulated radiotherapy (IMRT) when the BP is routinely contoured as an organ at risk (OAR) for IMRT optimization. METHODS AND MATERIALS From 2004 to 2011, a total of 114 HNC patients underwent IMRT to a total dose of 69.96 Gy in 33 fractions, with the right and left BP prospectively contoured as separate OARs in 111 patients and the ipsilateral BP contoured in 3 patients (total, 225 BP). Staging category T4 and N2/3 disease were present in 34 (29.8%) and 74 (64.9%) patients, respectively. During IMRT optimization, the intent was to keep the maximum BP dose to ≤60 Gy, but prioritizing tumor coverage over achieving the BP constraints. BP dose parameters were compared with tumor and nodal stage. RESULTS With a median follow-up of 16.2 months, 43 (37.7%) patients had ≥24 months of follow-up with no brachial plexopathy reported. Mean BP volume was 8.2 ± 4.5 cm(3). Mean BP maximum dose was 58.1 ± 12.2 Gy, and BP mean dose was 42.2 ± 11.3 Gy. The BP maximum dose was ≤60, ≤66, and ≤70 Gy in 122 (54.2%), 185 (82.2%), and 203 (90.2%) BP, respectively. For oropharynx, hypopharynx, and larynx sites, the mean BP maximum dose was 58.4 Gy and 63.4 Gy in T0-3 and T4 disease, respectively (p = 0.002). Mean BP maximum dose with N0/1 and N2/3 disease was 52.8 Gy and 60.9 Gy, respectively (p < 0.0001). CONCLUSIONS In head-and-neck IMRT, dose constraints for the BP are difficult to achieve to ≤60 to 66 Gy with T4 disease of the larynx, hypopharynx, and oropharynx or N2/3 disease. The risk of brachial plexopathy is likely very small in HNC patients undergoing IMRT, although longer follow-up is required.

A prognostic volumetric threshold of gross tumor volume in head and neck cancer patients treated with radiotherapy

Objectives:To determine the prognostic utility of a volumetric threshold for gross tumor volume (GTV) of the primary and nodal disease when accounting for the TNM classification in head and neck cancer (HNC) patients treated with definitive radiotherapy (RT). Materials and Methods:From 2004 to 2011, 79 HNC patients were treated to a median dose of 70 Gy, using intensity-modulated RT in 78.5% and 3-dimensional conformal RT in 21.5% with 83.5% receiving concurrent chemotherapy. Primary (GTV-P) and nodal (GTV-N) GTVs were derived from computed tomography (CT)-based contours for RT planning, of which 89.7% were aided by positron emission tomography-computed tomography. Local (LC), nodal (NC), distant (DC) control, and overall survival (OS) were assessed using the Kaplan-Meier product-limit method. Results:With a median follow-up of 27.1 months GTV-P, threshold of <32.9 mL (mean value) compared with ≥32.9 mL, correlated with improved 2-year LC (96.2% vs. 63.9%, P<0.0001), NC (100% vs. 69.2%, P<0.0001), DC (87.9% vs. 64.2%, P=0.001), and OS (88.4% vs. 58.6%, P=0.001). GTV-P demonstrated its prognostic utility in multivariate analyses when adjusted for tumor category, cancer site, and chemotherapy regimen. Nodal GTV (mean, 34.0 mL) was not predictive of nodal control and survival. Conclusions:A volumetric threshold of the primary tumor may be used as an independent prognostic factor in patients with HNC undergoing definitive RT.

Cone-beam computed tomography image guided therapy to evaluate lumpectomy cavity variation before and during breast radiotherapy

The purpose of this study was to evaluate the rate of change (RoC) in the size of the lumpectomy cavity (LC) before and during breast radiotherapy (RT) using cone‐beam computed tomography (CBCT), relative to the initial LC volume at CT simulation (CTVLC) and timing from surgery. A prospective institutional review board‐approved study included 26 patients undergoing breast RT: 20 whole breast irradiation (WBI) patients and six partial breast irradiation (PBI) patients, with surgical clips outlining the LC. The patients underwent CT simulation (CTsim) followed by five CBCTs during RT, once daily for PBI and once weekly for WBI. The distance between surgical clips and their centroid (D) acted as a surrogate for LC size. The RoC of the LC size, defined as the percentage change of D between two scans divided by the time interval in days between the scans, was calculated before (CTsim to CBCT1) and during RT (CBCT1 to CBCT5). The mean RoC of D for all patients before starting RT was −0.25%/day (range, −1.3 to 1.4) and for WBI patients during RT was −0.15%/day (range, −0.45 to 0.40). Stratified by median CTVLC, the RoC before RT for large CTVLC group (≥25.7cc) was 15 times higher (−0.47%/day) than for small CTVLC group (<25.7 cc) (−0.03%/day), p=0.06. For patients undergoing CTsim < 42 days from surgery, the RoC before RT was −0.43%/day compared to −0.07%/day for patients undergoing CTsim≥42 days from surgery, p=0.12. For breast cancer RT, the rate of change of the LC is affected by the initial cavity size and the timing from surgery. Resimulation closer to the time of boost treatment should be considered in patients who are initially simulated within six weeks of surgery and/or with large CTVLC. PACS number: 87.55.de

Correlating Computed Tomography Perfusion Changes in the Pharyngeal Constrictor Muscles During Head-and-Neck Radiotherapy to Dysphagia Outcome

PURPOSE To measure changes in perfusion of the pharyngeal constrictor muscles (PCM) using CT perfusion (CTP) imaging during a course of definitive radiotherapy (RT) in head-and-neck cancer (HNC) patients and correlate with dysphagia outcome after RT. METHODS AND MATERIALS Fifteen HNC patients underwent CTP imaging of the PCM at baseline and Weeks 2, 4, and 6 during RT and 6 weeks after RT. Blood flow and blood volume were measured in the PCM, and percentage change from baseline scan was determined. A single physician-based assessment of dysphagia was performed every 3 months after RT using the Common Terminology Criteria for Adverse Events, version 3.0 grading system. RESULTS With a median follow-up of 28 months (range, 6-44 months), Grade 3 dysphagia was present in 7 of 15 patients, and 8 patients experienced Grade 0-2 dysphagia. The CTP parameters at Week 2 of RT demonstrated an increase in mean PCM blood flow of 161.9% vs. 12.3% (p = 0.007) and an increase in mean PCM blood volume of 96.6% vs. 8.7% (p = 0.039) in patients with 6-month post-RT Grade 3 dysphagia and Grade 0-2 dysphagia, respectively. On multivariate analysis, when adjusting for smoking history, tumor volume, and baseline dysphagia status, an increase in blood flow in the second week of RT was significant for 3- and 6-month Grade 3 dysphagia (p < 0.05). CONCLUSIONS Perfusion changes in the PCM during Week 2 of RT in the PCM may predict the severity of dysphagia after HNC RT.