Magnetic Arctic Circle in a Square Ice Qubit Lattice.

Under certain boundary conditions, the square ice model exhibits a phase separation in which the core of the system is disordered while its outer region remains ordered. This phenomenon, known as the "arctic circle," has been studied theoretically in combinatorial mathematics and statistical mechanics. Here, we realize the physics of the arctic circle experimentally for the first time, using a programmable lattice of superconducting qubits, and investigate its properties under the prism of a highly frustrated magnet. Our work reveals two unexpected properties. First, the disordered spin manifold confined within the arctic curve is a spin liquid whose average spin texture resembles that of an antivortex, i.e., it is a topologically charged Coulomb phase. Second, monopole quasiparticle excitations, which are totally absent in theoretical works, can be isolated in a phase-separated system. Remarkably, a monopole segregation mechanism is observed, in which the monopoles are sorted according to the magnetic charge and magnetic moment they carry, without the application of an external driving force.

Imaging considerations for salvage surgery in nasopharyngeal carcinoma: what surgeons need to know.

Nasopharyngeal carcinoma is frequently an undifferentiated squamous cell carcinoma, which is primarily treated with radiotherapy with or without chemotherapy; however, for residual or recurrent cancer, salvage surgery is the treatment of choice for resectable disease because it reduces the significant morbidity associated with re-irradiation. This review highlights the current surgical approach, mapping the extent of disease with an emphasis on magnetic resonance imaging (MRI) and integrated positron-emission tomography (PET)/computed tomography (CT), imaging features that determine operability for nasopharyngectomy and neck dissection, and need for a succinct radiological report and multidisciplinary team discussion, which are of paramount importance for successful surgical planning.

Improved risk stratification of nasopharyngeal cancer by targeted sequencing of Epstein-Barr virus DNA in post-treatment plasma.

BACKGROUND: Quantitative measurement of plasma Epstein-Barr virus (EBV) DNA by real-time PCR at the end of primary treatment is a robust prognostic marker for nasopharyngeal carcinoma (NPC) patients. However, up to 40% of patients who would later develop disease recurrence had undetectable post-treatment plasma EBV DNA. Targeted sequencing for the entire EBV genome potentially allows a more comprehensive and unbiased detection of plasma EBV DNA and enables the use of other parameters such as fragment size as biomarkers. Hence, we explored if plasma EBV DNA sequencing might allow more accurate prognostication of NPC patients. PATIENTS AND METHODS: Plasma samples collected from 769 patients with stage IIB-IVB NPC at 6-8 weeks after radiotherapy were analysed using targeted sequencing for EBV DNA. RESULTS: The sensitivities of the PCR-based analysis, at a cut-off of any detectable levels of plasma EBV DNA, for prediction of local and distant recurrences were 42.3% and 85.3%, respectively. The sequencing-based analysis (involving quantitation and size profiling) achieved better performance for both local and distant recurrences than PCR. Using a cut-off of the proportion of plasma EBV DNA deduced by sequencing at 0.01%, the sensitivities of the sequencing-based analysis for local and distant recurrences were 88.5% and 97.1%, with the resultant negative predictive values of 99.1% and 99.4%, respectively. Among patients with undetectable EBV DNA on quantitative PCR, sequencing could further define a subgroup that enjoyed superior survival outcomes based on the proportion of plasma EBV DNA, with a 5-year progression-free survival (PFS) approaching 90%. On multivariate analysis, sequencing-based quantitative level of plasma EBV DNA was the independent prognostic factor with the highest hazard ratio for prediction of overall survival and PFS. CONCLUSION: NPC prognostication using post-treatment plasma EBV DNA could be enhanced through sequencing.

Quantitative T1ρ MRI of the Head and Neck Discriminates Carcinoma and Benign Hyperplasia in the Nasopharynx.

BACKGROUND AND PURPOSE: T1ρ imaging is a new quantitative MR imaging pulse sequence with the potential to discriminate between malignant and benign tissue. In this study, we evaluated the capability of T1ρ imaging to characterize tissue by applying T1ρ imaging to malignant and benign tissue in the nasopharynx and to normal tissue in the head and neck. MATERIALS AND METHODS: Participants with undifferentiated nasopharyngeal carcinoma and benign hyperplasia of the nasopharynx prospectively underwent T1ρ imaging. T1ρ measurements obtained from the histogram analysis for nasopharyngeal carcinoma in 43 participants were compared with those for benign hyperplasia and for normal tissue (brain, muscle, and parotid glands) in 41 participants using the Mann-Whitney U test. The area under the curve of significant T1ρ measurements was calculated and compared using receiver operating characteristic analysis and the Delong test, respectively. A P < . 05 indicated statistical significance. RESULTS: There were significant differences in T1ρ measurements between nasopharyngeal carcinoma and benign hyperplasia and between nasopharyngeal carcinoma and normal tissue (all, P < . 05). Compared with benign hyperplasia, nasopharyngeal carcinoma showed a lower T1ρ mean (62.14 versus 65.45 × ms), SD (12.60 versus 17.73 × ms), and skewness (0.61 versus 0.76) (all P < .05), but no difference in kurtosis (P = . 18). The T1ρ SD showed the highest area under the curve of 0.95 compared with the T1ρ mean (area under the curve = 0.72) and T1ρ skewness (area under the curve = 0.72) for discriminating nasopharyngeal carcinoma and benign hyperplasia (all, P < .05). CONCLUSIONS: Quantitative T1ρ imaging has the potential to discriminate malignant from benign and normal tissue in the head and neck.

MRI of benign hyperplasia in the nasopharynx: is there an association with Epstein-Barr virus?

AIM: To evaluate whether there is an association between persistently positive plasma Epstein-Barr virus (EBV) DNA and the presence and the change in benign hyperplasia. MATERIALS AND METHODS: One hundred and seventeen participants with positive-plasma EBV-DNA, but without NPC from previous nasopharyngeal carcinoma (NPC) screening, underwent follow-up magnetic resonance imaging (MRI) and plasma EBV-DNA after 2 years. Logistic regression was used to analyse associations between MRI (benign hyperplasia on the follow-up MRI and change from 2 years earlier), and plasma EBV-DNA, smoking, and age. RESULTS: At follow-up, EBV-DNA positivity and smoking were independent parameters for the presence of benign hyperplasia (p=0.027 and 0.023 respectively). Compared with participants in whom EBV-DNA became negative (n=44/117 37.6%), those in whom EBV-DNA remained positive (n=73/117 62.4%) had a greater risk of benign hyperplasia developing (previous MRI normal), being stable or processing (52/73 71.2% versus 18/44 40.9%; p=0.001). CONCLUSION: These results suggest a potential link between benign hyperplasia on MRI and the EBV. As EBV contributes to NPC oncogenesis, future MRI research is warranted to determine if persistent benign hyperplasia is a risk marker for development of NPC.

Integrating postradiotherapy plasma Epstein-Barr virus DNA and TNM stage for risk stratification of nasopharyngeal carcinoma to adjuvant therapy.

BACKGROUND: After curative radiotherapy (RT) or chemoradiation (CRT), there is no validated tool to accurately identify patients for adjuvant therapy in nasopharyngeal carcinoma (NPC). Post-RT circulating plasma Epstein-Barr virus (EBV) DNA can detect minimal residual disease and is associated with recurrence and survival independent of TNM (tumor-lymph node-metastasis) stage. We aimed to develop and validate a risk model for stratification of NPC patients after completion of RT/CRT to observation or adjuvant therapy. PATIENTS AND METHODS: The prospective multicenter 0502 EBV DNA screening cohort (Hong Kong NPC Study Group 0502 trial) enrolled from 2006 to 2015 (n = 745) was used for model development. For internal validation, we pooled independent patient cohorts from prospective clinical studies enrolled from 1997 to 2006 (n = 340). For external validation, we used retrospective cohort of NPC patients treated at Sun Yat-sen University Cancer Center from 2009 to 2012 (n = 837). Eligible patients had histologically confirmed NPC of Union for International Cancer Control (UICC) 7th Edition stage II-IVB who completed curative RT/CRT with or without neoadjuvant chemotherapy, had post-RT EBV DNA tested within 120 days after RT and received no adjuvant therapy. The primary end point was overall survival (OS). We used recursive-partitioning analysis (RPA) to classify patients into groups of low, intermediate, and high risk of death. RESULTS: Combining post-RT EBV DNA level (0, 1-49, 50-499, and ≥500 copies/ml) and TNM stage (II, III, IVAB), RPA model classified patients into low-, intermediate-, and high-risk groups with 5-year OS of 89.4%, 78.5% and 37.2%, respectively. The RPA low-risk group had comparable OS to TNM stage II (5-year OS 88.5%) but identified more patients (64.8% versus stage II 28.1%) that could potentially be spared adjuvant therapy toxicity. The RPA model (c-index 0.712) showed better risk discrimination than either the TNM stage (0.604) or post-RT EBV DNA alone (0.675) with improved calibration and consistence. These results were validated in both internal and external cohorts. CONCLUSION: Combining post-RT EBV DNA and TNM stage improved risk stratification in NPC.

Early Detection of Cancer: Evaluation of MR Imaging Grading Systems in Patients with Suspected Nasopharyngeal Carcinoma.

BACKGROUND AND PURPOSE: We evaluated modifications to our contrast-enhanced MR imaging grading system for symptomatic patients with suspected nasopharyngeal carcinoma, aimed at improving discrimination of early-stage cancer and benign hyperplasia. We evaluated a second non-contrast-enhanced MR imaging grading system for asymptomatic patients from nasopharyngeal carcinoma plasma screening programs. MATERIALS AND METHODS: Dedicated nasopharyngeal MR imaging before (plain scan system) and after intravenous contrast administration (current and modified systems) was reviewed in patients from a nasopharyngeal carcinoma-endemic region, comprising 383 patients with suspected disease without nasopharyngeal carcinoma and 383 patients with nasopharyngeal carcinoma. The modified and plain scan systems refined primary tumor criteria, added a nodal assessment, and expanded the system from 4 to 5 grades. The overall combined sensitivity and specificity of the 3 systems were compared using the extended McNemar test (a χ2 value [Formula: see text]> 5.99 indicates significance). RESULTS: The current, modified, and plain scan MR imaging systems yielded sensitivities of 99.74%, 97.91%, and 97.65%, respectively, and specificities of 63.45%, 89.56% and 86.42%, respectively. The modified system yielded significantly better performance than the current ([Formula: see text] = 122) and plain scan ([Formula: see text] = 6.1) systems. The percentages of patients with nasopharyngeal carcinoma in grades 1-2, grade 3, and grades 4-5 for the modified and plain scan MR imaging systems were 0.42% and 0.44%; 6.31% and 6.96%; and 90.36% and 87.79%, respectively. No additional cancers were detected after contrast administration in cases of a plain scan graded 1-2. CONCLUSIONS: We propose a modified MR imaging grading system that improves diagnostic performance for nasopharyngeal carcinoma detection. Contrast was not valuable for low MR imaging grades, and the plain scan shows potential for use in screening programs.

Complementary roles of MRI and endoscopic examination in the early detection of nasopharyngeal carcinoma.

BACKGROUND: Early-stage nasopharyngeal carcinoma (NPC) evades detection when the primary tumor is hidden from view on endoscopic examination. Therefore, in a prospective study of subjects being screened for NPC using plasma Epstein-Barr virus (EBV) DNA, we conducted a study to investigate whether magnetic resonance imaging (MRI) could detect endoscopically occult NPC. PATIENTS AND METHODS: Participants with persistently positive EBV DNA underwent endoscopic examination and biopsy when suspicious for NPC, followed by MRI blinded to the endoscopic findings. Participants with a negative endoscopic examination and positive MRI were recalled for biopsy or surveillance. Diagnostic performance was assessed by calculating sensitivity, specificity and accuracy, based on the histologic confirmation of NPC in the initial study or in a follow-up period of at least two years. RESULTS: Endoscopic examination and MRI were performed on 275 participants, 34 had NPC, 2 had other cancers and 239 without cancer were followed-up for a median of 36 months (24-60 months). Sensitivity, specificity and accuracy were 76.5%, 97.5% and 94.9%, respectively, for endoscopic examination and 91.2%, 97.5% and 96.7%, respectively, for MRI. NPC was detected only by endoscopic examination in 1/34 (2.9%) participants (a participant with stage I disease), and only by MRI in 6/34 (17.6%) participants (stage I = 4, II = 1, III = 1), two of whom had stage I disease and follow-up showing slow growth on MRI but no change on endoscopic examination for 36 months. CONCLUSION: MRI has a complementary role to play in NPC detection and can enable the earlier detection of endoscopically occult NPC.

Staging nodal metastases in nasopharyngeal carcinoma: which method should be used to measure nodal dimension on MRI?

AIM: To investigate four methods to measure the maximum dimension (MD) of metastatic neck nodes and correlate with clinical outcome in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Magnetic resonance imaging (MRI) examinations of 712 NPC patients were analysed. MD measurements using methods 1, 2, 3, and 4 were obtained from a single node in the axial plane; a single node in the axial/coronal plane; a single and/or confluent nodes in the axial/coronal plane; and a single and/or confluent and/or contiguous nodes in the axial/coronal plane, respectively. MDs obtained from the four methods were correlated with nodal volume (NV) using Pearson's correlation test. MDs obtained from the four methods, T and N stages, age, gender, and treatment were correlated with overall survival (OS), disease-specific survival (DSS), distant metastases free survival (DMFS), and regional relapse-free survival (RRFS) using cox regression. RESULTS: Method 4 (R: 0.84) had the strongest correlation with NV followed by method 3 (R: 0.77), method 2 (R: 0.70) and method 1(R: 0.69). Method 4 was the only independent nodal measurement of OS, DSS, and DMFS (p-values = 0.008, <0.001 and <0.001, respectively). None of the MD methods was an independent measurement of RRFS. CONCLUSIONS: The best method to obtain the MD for staging incorporates not only single and confluent, but also contiguous metastatic nodes measured in the plane with the MD.

MR Imaging Criteria for the Detection of Nasopharyngeal Carcinoma: Discrimination of Early-Stage Primary Tumors from Benign Hyperplasia.

BACKGROUND AND PURPOSE: MR imaging can detect nasopharyngeal carcinoma that is hidden from endoscopic view, but for accurate detection carcinoma confined within the nasopharynx (stage T1) must be distinguished from benign hyperplasia of the nasopharynx. This study aimed to document the MR imaging features of stage T1 nasopharyngeal carcinoma and to attempt to identify features distinguishing it from benign hyperplasia. MATERIALS AND METHODS: MR images of 189 patients with nasopharyngeal carcinoma confined to the nasopharynx and those of 144 patients with benign hyperplasia were reviewed and compared in this retrospective study. The center, volume, size asymmetry (maximum percentage difference in area between the right and left nasopharyngeal halves), signal intensity asymmetry, deep mucosal white line (greater contrast enhancement along the deep tumor margin), and absence/distortion of the adenoidal septa were evaluated. Differences were assessed with logistic regression and the χ2 test. RESULTS: The nasopharyngeal carcinoma center was lateral, central, or diffuse in 134/189 (70.9%), 25/189 (13.2%), and 30/189 (15.9%) cases, respectively. Nasopharyngeal carcinomas involving the walls showed that a deep mucosal white line was present in 180/183 (98.4%), with a focal loss of this line in 153/180 (85%) cases. Adenoidal septa were absent or distorted in 111/111 (100%) nasopharyngeal carcinomas involving the adenoid. Compared with benign hyperplasia, nasopharyngeal carcinoma had a significantly greater volume, size asymmetry, signal asymmetry, focal loss of the deep mucosal white line, and absence/distortion of the adenoidal septa (P < .001). Although size asymmetry was the most accurate criterion (89.5%) for nasopharyngeal carcinoma detection, use of this parameter alone would have missed 11.9% of early-stage T1 nasopharyngeal carcinomas. CONCLUSIONS: MR imaging features can help distinguish stage T1 nasopharyngeal carcinoma from benign hyperplasia in most cases.

State of the art MRI in head and neck cancer.

Head and neck cancer affects more than 11,000 new patients per year in the UK1 and imaging has an important role in the diagnosis, treatment planning, and assessment, and post-treatment surveillance of these patients. The anatomical detail produced by magnetic resonance imaging (MRI) is ideally suited to staging and follow-up of primary tumours and cervical nodal metastases in the head and neck; however, anatomical images have limitations in cancer imaging and so increasingly functional-based MRI techniques, which provide molecular, metabolic, and physiological information, are being incorporated into MRI protocols. This article reviews the state of the art of these functional MRI techniques with emphasis on those that are most relevant to the current management of patients with head and neck cancer.

Identifying an early indicator of drug efficacy in patients with metastatic colorectal cancer-a prospective evaluation of circulating tumor cells, 18F-fluorodeoxyglucose positron-emission tomography and the RECIST criteria.

BACKGROUND: This study investigated the predictive and prognostic significance of assessing early drug response with both positron-emission computerized tomography (PET-CT) and circulating tumor cells (CTCs) in patients receiving first-line chemotherapy for metastatic colorectal cancer. PATIENTS AND METHODS: Eligible patients had PET-CT and CTC analysis at baseline and 4-6 weeks after starting chemotherapy, and then a CT scan at 10-12 weeks to assess the Response Evaluation Criteria In Solid Tumors (RECIST) response. Early response was defined as achieving a dual-endpoint consisting of PET-CT (30% drop in the sum of maximum standard uptake values-SUVmax-of target lesions) and CTC response (CTC < 3 cells/7.5 ml blood) at 4-6 weeks after starting chemotherapy. RESULTS: About 84 patients were enrolled with a median follow-up of 32.9 months (95% confidence interval, CI, 24.5 months-not reached, NR), and 70 patients (84.3%) completed all assessments. Achieving an early response based on the dual-endpoint was independently associated with progression-free survival (hazard ratio, HR = 0.452, 95% CI 0.267-0.765). The median progression-free survival of early responders was 7.41 months (95% CI, 6.05-9.11) compared with 5.37 months (95% CI, 4.68-6.24) in non-responders (log-rank, P = 0.0167). RECIST response at 10 weeks was independently associated with overall survival (OS) (HR = 0.484, 95% CI, 0.275-0.852). Early response based on the dual-endpoint could predict the subsequent RECIST response with a sensitivity, specificity and positive predictive value of 64%, 70% and 74%, respectively. CONCLUSIONS: Early response based on both PET-CT and CTC analysis has prognostic and probably predictive significance in patients undergoing first-line chemotherapy for metastatic colorectal cancer. Its utility as a new tool for assessing early drug response should be further validated.

Diffusion-Weighted Imaging of Nasopharyngeal Carcinoma: Can Pretreatment DWI Predict Local Failure Based on Long-Term Outcome?

BACKGROUND AND PURPOSE: Pretreatment prediction of patients with nasopharyngeal carcinoma who will fail conventional treatment would potentially allow these patients to undergo more intensive treatment or closer posttreatment monitoring. The aim of the study was to determine the ability of pretreatment DWI to predict local failure in patients with nasopharyngeal carcinoma based on long-term clinical outcome. MATERIALS AND METHODS: One hundred fifty-eight patients with pretreatment DWI underwent analysis of the primary tumor to obtain the ADC mean, ADC skewness, ADC kurtosis, volume, and T-stage. Univariate and multivariate analyses using logistic regression were performed to compare the ADC parameters, volume, T-stage, and patient age in primary tumors with local failure and those with local control, by using a minimum of 5-year follow-up to confirm local control. RESULTS: Local control was achieved in 131/158 (83%) patients (range, 60.3-117.7 months) and local failure occurred in 27/158 (17%) patients (range, 5.2-79.8 months). Compared with tumors with local control, those with local failure showed a significantly lower ADC skewness (ADC values with the greatest frequencies were shifted away from the lower ADC range) (P = .006) and lower ADC kurtosis (curve peak broader) (P = .024). The ADC skewness remained significant on multivariate analysis (P = .044). There was a trend toward higher tumor volumes in local failure, but the volume, together with T-stage and ADC mean, were not significantly different between the 2 groups. CONCLUSIONS: Pretreatment DWI of primary tumors found that the skewness of the ADC distribution curve was a predictor of local failure in patients with nasopharyngeal carcinoma, based on long-term clinical outcome.

Detection of Nasopharyngeal Carcinoma by MR Imaging: Diagnostic Accuracy of MRI Compared with Endoscopy and Endoscopic Biopsy Based on Long-Term Follow-Up.

BACKGROUND AND PURPOSE: Our previous nasopharyngeal carcinoma detection study, comparing MR imaging, endoscopy, and endoscopic biopsy, showed that MR imaging is a highly sensitive test that identifies nasopharyngeal carcinomas missed by endoscopy. However, at the close of that study, patients without biopsy-proved nasopharyngeal carcinoma nevertheless had shown suspicious abnormalities on endoscopy and/or MR imaging. The aim of this study was to determine whether there were any patients with undiagnosed nasopharyngeal carcinoma by obtaining long-term follow-up and to use these data to re-evaluate the diagnostic performance of MR imaging. MATERIALS AND METHODS: In the previous study, 246 patients referred to a hospital ear, nose, and throat clinic with suspected nasopharyngeal carcinoma, based on a wide range of clinical indications, had undergone MR imaging, endoscopy, and endoscopic biopsy, and 77 had biopsy-proved nasopharyngeal carcinoma. One hundred twenty-six of 169 patients without biopsy-proved nasopharyngeal carcinoma underwent re-examination of the nasopharynx after a minimum of 3 years, including 17 patients in whom a previous examination (MR imaging = 11; endoscopy = 7) had been positive for nasopharyngeal carcinoma, but the biopsy had been negative for it. Patients with nasopharyngeal carcinoma were identified by biopsy obtained in the previous and this follow-up study; patients without nasopharyngeal carcinoma were identified by the absence of a tumor on re-examination of the nasopharynx. The sensitivity and specificity of the previous investigations were updated and compared by using the Fisher exact test. RESULTS: One patient with a previous positive MR imaging finding was subsequently proved to have nasopharyngeal carcinoma. Nasopharyngeal carcinomas were not found in the remaining 125 patients at follow-up, and the previous positive findings for nasopharyngeal carcinoma on MR imaging and endoscopy were attributed to benign lymphoid hyperplasia. The diagnostic performances for the previous MR imaging, endoscopy, and endoscopic biopsy were 100%, 88%, and 94%, respectively, for sensitivity, and 92%, 94%, and 100%, respectively, for specificity; the differences between MR imaging and endoscopy were significant for sensitivity (P = .003) but not specificity (P = .617). CONCLUSIONS: MR imaging detected the 12% of nasopharyngeal carcinomas that were endoscopically invisible, including 1 cancer that remained endoscopically occult for several years. Lymphoid hyperplasia reduced the specificity of MR imaging.

Multicenter phase II study of the AKT inhibitor MK-2206 in recurrent or metastatic nasopharyngeal carcinoma from patients in the mayo phase II consortium and the cancer therapeutics research group (MC1079).

BACKGROUND: This study investigated the activity of MK-2206, an AKT inhibitor, in metastatic or recurrent nasopharyngeal carcinoma (NPC). METHOD: Oral MK-2206 at a dose of 200 mg was administered on days 1, 8, 15 and 22 of a 28-day cycle until progression. Plasma EBV DNA clearance during the first month of treatment was measured, and archived tumors were analyzed for the expression of AKT and PIK3CA mutation and PIK3CA amplification. The dual primary endpoint was objective response rate and 6-month progression-free survival (PFS) rate. RESULTS: 21 patients were enrolled and one patient achieved a partial response (5 %) and 11 had stable disease (52 %), with a median PFS of 3.5 months (95 % confidence interval, CI: 0.9-7.3). The 6-month PFS rate was 43 % (95 % CI: 22-66 %) and the median OS was 10 months (95 % CI: 5.9 months-not reached). Seven patients (33 %) experienced grade 3 toxicities which could be related to MK-2206. Macular-papular rash was the most common (n = 6), followed by hyperglycemia (n = 2) and fatigue (n = 1). In the 12 tumor samples analyzed, PIK3CA amplification was detected in one patient's primary NPC, who had SD lasting over 12 months. Patients with decreasing EBV DNA values over time were more likely to be alive and progression-free for at least 6 months than those without a decrease (p = 0.001). CONCLUSION: The study was terminated due to the limited activity observed in this heavily pre-treated group of patients. Further studies are needed to elucidate the optimal way of selecting patients for AKT inhibitors.

T2-weighted MR imaging early after chemoradiotherapy to evaluate treatment response in head and neck squamous cell carcinoma.

BACKGROUND AND PURPOSE: T2-weighted MRI shows potential in early posttreatment assessment of the primary tumor. Residual masses composed entirely of low T2-signal scar tissue suggest local control and those ≥1 cm of similar signal to untreated tumor suggest local failure. The purpose of this study was to investigate the diagnostic accuracy of T2-weighted MR imaging early after chemoradiotherapy for identifying primary tumor treatment failure in squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: At 6 weeks after treatment, T2-weighted MR images of 37 primary tumors in 37 patients were assessed. Residual masses were divided into 3 patterns: pattern 1 = scar tissue only (flat-edged/retracted mass of low T2 signal intensity); pattern 2 = mass without features described in pattern 1 or 3; and pattern 3 = any pattern that included an expansile mass ≥1 cm of intermediate T2 signal intensity (similar grade of signal intensity to the untreated tumor). T2 patterns were analyzed for local outcome (Fisher exact test) and time to local failure (univariate and multivariate analysis of T2 pattern, age, T stage, and tumor size by use of the Cox regression model). RESULTS: Residual masses after treatment were present in 34 (92%) of 37 patients. Local failures occurred in residual masses with pattern 1 in 0 (0%) of 14 patients; pattern 2 in 6 (55%) of 11 patients; and pattern 3 in 9 (100%) of 9 patients. Significant associations were found between local control and pattern 1 (P = <.0001; sensitivity, 74%; specificity, 100%; PPV, 100%; NPV, 75%; accuracy, 85%), and between local failure and pattern 3 (P = <.0001; sensitivity, 60%; specificity, 100%; PPV, 100%; NPV, 76%; accuracy, 82%). Pattern 2 showed no significant associations with local outcome. Univariate analysis of time to local failure showed that the T2 pattern was significant (P < .0001) and remained significant on multivariate analysis. CONCLUSIONS: T2-weighted MR imaging is a potential tool for early posttreatment assessment of primary HNSCC treatment response. Awareness of correlation of the T2 pattern of any residual mass with treatment outcome at the primary site may contribute to patient treatment.

A five-colour colour-coded mapping method for DCE-MRI analysis of head and neck tumours.

AIM: To devise a method to convert the time-intensity curves (TICs) of head and neck dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) data into a pixel-by-pixel colour-coded map for identifying normal tissues and tumours. MATERIALS AND METHODS: Twenty-three patients with head and neck squamous cell carcinoma (HNSCC) underwent DCE-MRI. TIC patterns of primary tumours, metastatic nodes, and normal tissues were assessed and a program was devised to convert the patterns into a classified colour-coded map. The enhancement patterns of tumours and normal tissue structures were evaluated and categorized into nine grades (0-8) based on the predominance of coloured pixels on maps. RESULTS: Five identified TIC patterns were converted into a colour-coded map consisting of red (maximum enhancement), brown (continuous slow rise-up), yellow (rapid wash-in and wash-out), green (rapid wash-in and plateau), and blue (rapid wash-in and rise-up). The colour-coded map distinguished all 21 primary tumours and 15 metastatic nodes from normal structures. Primary tumours and metastatic nodes were colour coded as predominantly yellow (grades 1-2) in 17/21 and 6/15, green (grades 3-5) in 3/21 and 5/15, and blue (grades 6-7) in 1/21 and 4/15, respectively. Vessels were coded red in 46/46 (grade 0) and muscles were coded brown in 23/23 (grade 8). Salivary glands, thyroid glands, and palatine tonsils were coded into predominantly yellow (grade 1) in 46/46 and 10/10 and 18/22, respectively. CONCLUSION: DCE-MRI derived five-colour-coded mapping provides an objective easy-to-interpret method to assess the dynamic enhancement pattern of head and neck cancers.

A phase II study of concurrent cetuximab-cisplatin and intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: Based on our previous work on the clinical activity of cetuximab in recurrent nasopharyngeal carcinoma (NPC), we evaluated the feasibility of adding cetuximab to concurrent cisplatin and intensity-modulated radiotherapy (IMRT) in locoregionally advanced NPC. PATIENTS AND METHODS: Patients with American Joint Committee on Cancer stage III-IVB NPC were given an initial dose of cetuximab (400 mg/m(2)) 7-10 days before receiving concurrent IMRT, weekly cisplatin (30 mg/m(2)/week) and cetuximab (250 mg/m(2)/week). RESULTS: Thirty patients (median age of 45 years) with stage III (67%), IVA (30%) and IVB (3%) nonkeratinizing NPC were enrolled. Grade 3-4 oropharyngeal mucositis occurred in 26 (87%) patients and 10 (33%) patients required short-term nasogastric feeding. Grade 3 radiotherapy-related dermatitis occurred in six patients (20%) and three patients (10%) had grade 3 cetuximab-related acneiform rash. These grade 3-4 skin and mucosal toxic effects were manageable and reversible. At a median follow-up of 31.8 months [95% confidence interval (CI) 26.2-32.1 months], the 2-year progression-free survival was 86.5% (95% CI 74.3% to 98.8%). CONCLUSIONS: Concurrent administration of cetuximab, weekly cisplatin and IMRT is a feasible strategy against locoregionally advanced NPC. Preliminary survival data compare favorably with historic data and further follow-up is warranted.

Cystic change in thyroid nodules: a confounding factor for real-time qualitative thyroid ultrasound elastography.

OBJECTIVE: To evaluate real-time qualitative ultrasound elastography for focal thyroid masses undergoing fine-needle aspiration in a routine thyroid ultrasound clinic. MATERIALS AND METHODS: Ninety-four thyroid nodules scheduled for fine-needle aspiration cytology in a thyroid ultrasound clinic also underwent real-time freehand elastography. Colour-scaled elastograms were graded visually on the stiffness of the solid component of nodules relative to thyroid parenchyma using an elastography score (ES) scale from 1 (soft) to 4 (stiff). The ES for benign and malignant nodules and the influence of cystic change on ES were analysed using Chi-square with trend and Fishers exact tests, with a p<0.05 used to indicate statistical significance. RESULTS: There were 19 papillary carcinomas, five metastases, 57 hyperplastic nodules, and four follicular adenomas based on definitive cytology (n=54) or histology (n=31). Nine nodules were excluded due to indeterminate cytology and no histology. Of malignancies (all solid), two were ES=1, four were ES=2, eight were ES=3, and 10 were ES=4. Of benign nodules, 17 were ES=1, 17 were ES=2, 16 were ES=3, and 11 were ES=4. An ES>2 was more common in benign nodules with predominant cystic components (17/18) than mildly cystic (3/12) or completely solid (7/31) benign nodules (p=0.0004, p<0.0001). The ES was not significantly different between benign and malignant nodules (p=0.09) unless partially cystic nodules were excluded (p=0.005). For solid nodules, an ES>2 optimally predicted malignancy, achieving 74% sensitivity, 77% specificity, and 76% accuracy. CONCLUSION: Qualitative real-time thyroid elastography predicts malignancy only if predominantly cystic nodules are excluded, which may limit its utility in routine clinical practice.