Fractional Change in Apparent Diffusion Coefficient as an Imaging Biomarker for Predicting Treatment Response in Head and Neck Cancer Treated with Chemoradiotherapy

BACKGROUND AND PURPOSE:ADC provides a measure of water molecule diffusion in tissue. The aim of this study was to evaluate whether the fractional change in ADC during therapy can be used as a valid predictive indicator of treatment response in head and neck squamous cell carcinoma treated with chemoradiotherapy.MATERIALS AND METHODS:Forty patients underwent DWI at pretreatment and 3 weeks after the start of treatment. The pretreatment ADC, fractional change in ADC, tumor regression rate, and other clinical variables were compared with locoregional control and locoregional failure and were analyzed by using logistic regression analysis and receiver operating characteristic analysis. Furthermore, progression-free survival curves divided by the corresponding threshold value were compared by means of the log-rank test.RESULTS:The fractional change in ADC_primary, the fractional change in ADC_node, primary tumor volume, nodal volume, tumor regression rate_node, N stage, and tumor location revealed significant differences between locoregional failure and locoregional control (P < .05). In univariate analysis, the fractional change in ADC_primary, fractional change in ADC_node, tumor regression rate_node, N stage, and tumor location showed significant association with locoregional control (P < .05). In multivariate analysis, however, only the fractional change in ADC_primary was identified as a significant and independent predictor of locoregional control (P = .04). A threshold fractional change in ADC_primary of 0.24 revealed a sensitivity of 100%, specificity of 78.7%, and overall accuracy of 84.8% for the prediction of locoregional control. Progression-free survival of the 2 groups divided by the fractional change in ADC_primary at 0.24 showed a significant difference (P < .05).CONCLUSIONS:The results suggest that the fractional change in ADC_primary is a valid imaging biomarker for predicting treatment response in head and neck squamous cell carcinoma treated with chemoradiotherapy.

Approximately two-thirds of patients with head and neck squamous cell carcinoma (HNSCC) present with advanced-stage disease, and regional lymph node involvement is common.¹ Surgery with or without adjuvant chemotherapy and/or radiation therapy remains a mainstay of treatment in advanced HNSCC, but radical radiation therapy alone or concurrent chemoradiotherapy as a definitive treatment has become a standard management option for many patients with HNSCC to improve the patient''s quality of life via organ preservation. Despite these rigorous treatment methods, however, locoregional disease failure occurs in as many as 30%–40% of cases.^2,3 Therefore, if a reliable indicator of response to radiation therapy or chemoradiotherapy before or at an early stage of treatment could be found, patients whose prognoses are likely to be unfavorable with current approaches might be selected for alternative strategies, improving their chances of success and sparing them from ineffective treatment with unnecessary toxicity. It has been impossible, however, to reliably predict early individual treatment response despite careful evaluation by using traditional clinical predictors such as tumor size, clinical stage, tumor location, and lymph node involvement.⁴DWI extracts information from the diffusion of water molecules in tissue. Water molecule diffusion motion can be quantified by using the ADC. In general, highly cellular cancers have more restricted diffusion, resulting in lower ADC values, while cancer treatments causing cell death increase water diffusion and lead to a rise in ADC.⁵In HNSCC, recent clinical studies have applied DWI to the prediction of treatment response to neoadjuvant chemotherapy, radiation therapy, or chemoradiotherapy before or at an early stage of treatment, revealing that pretreatment ADC correlates with treatment response and that ADC changes at 1, 2, and 4 weeks after the start of treatment can predict treatment response.^6–9 In addition, it has been reported that ADC changes at 3 weeks posttreatment can predict treatment response with higher accuracy than morphologic imaging assessment.¹⁰ Studies evaluating the predictive value of DWI for treatment response post-radiation therapy and/or chemotherapy are limited, however, and the optimal timing of the evaluation of the DWI and ADC analysis method for predicting the treatment response has not been established, to our knowledge.The aim of this study was to evaluate the usefulness of the fractional change in ADC (ΔADC) during therapy for prediction of treatment response in patients with HNSCC treated with chemoradiotherapy compared with the other clinical variables and to identify whether the ΔADC during therapy can be used as a valid imaging biomarker for prediction of treatment response.     

Selection of first-line i.v. antibiotics for acute pyelonephritis in patients requiring emergency hospital admission

Febrile urinary tract infections (UTIs) often require the intravenous infusion of antibiotics and/or hospitalization. Acute pyelonephritis (AP) is one of the most severe forms of UTI, and the antibiotics we should use as the first line and the risk factors for treatment failure remain controversial. The objective of this study was to investigate the efficacy of i.v. antibiotics selected for the treatment of febrile AP and to examine the risk factors for antibiotic resistance. We set risk factors for antibiotic treatment failure such as age, sex, and the presence of underlying urinary tract disease. We classified all cases into 49 cases of complicated AP and 24 cases of uncomplicated AP according to the presence of underlying urinary tract diseases, and examined the characteristics of the patients and the efficacy of the antibiotics used in this study. We investigated risk factors which relate to initial treatment failure and the duration of antibiotic treatment. Initial antibiotic treatment failure was significantly correlated to C-reactive protein in complicated AP and to positive blood culture in uncomplicated AP. We revealed a significant correlation between the duration of the given antibiotics and diabetes mellitus or positive blood culture in uncomplicated AP, and tazobactam/piperacillin was significantly related to prolongation of antibiotic treatment in complicated AP. In conclusion, in this study, a positive blood culture was the representative risk factor that related to both initial treatment failure and longer duration of the given antibiotics in uncomplicated AP.     

Kinetics and pathogenicity of oral infection by equine herpesvirus-9 in mice and suckling hamsters

The pathogenesis and kinetics of oral infection by equine herpesvirus (EHV)-9 were studied in mice and hamsters. After oral inoculation of 10(5) plaque-forming units (PFU) of virus, 1-week-old suckling hamsters showed varying severity of neurological disease from 72 hours post inoculation (hpi) and all of these animals had died by 96 hpi. Four-week-old ICR mice inoculated orally with 4 × 10(4)PFU of virus showed no clinical signs, but they developed erosive and ulcerative gastritis from 36 hpi. Varying degrees of encephalitis were seen in infected mice and hamsters, and the hamsters also developed myelitis by 96 hpi. Immunohistochemistry performed on whole body sections of suckling hamsters revealed the kinetics of spread of the virus to the central nervous system. EHV-9 antigen was detected initially in macrophages of the oral and lingual submucosa. At 36 hpi virus antigen was detected in the nerve fibres and pseudounipolar neurons of the trigeminal ganglion and at 96 hpi antigen was present in the myenteric plexuses of the intestine. Virus antigen was also detected in the liver, lungs and heart of affected animals. EHV-9 DNA was detected by polymerase chain reaction in the brain, blood and spinal cord of suckling hamsters at 36, 48 and 96 hpi. These findings show that EHV-9 may spread via the trigeminal nerve when mice and hamsters are inoculated orally with virus.     

Arterial-phase contrast-enhanced ultrasonography for evaluating anti-angiogenesis treatment: a pilot study

AIM:To verify whether arterial-phase contrast-enhanced ultrasonography(CEUS) of tumor parenchymal tissue is useful for evaluation of anti-angiogenesis agents.METHODS:Rabbits with liver tumor were subjected to CEUS,and images of the nodular maximal diameter in vascular phase were recorded.Image analysis was performed to plot the time intensity curve(TIC) at the tumor parenchyma,which set the diameter of the region of interest of intensity measurement.The TIC was calculated to obtain the time to peak intensit...     

Variants of the myocilin gene in Japanese patients with normal-tension glaucoma

Myocilin (MYOC) mutations are associated with juvenile- and adult-onset primary open-angle glaucoma (POAG). The purpose of this study was to determine whether MYOC gene mutations are associated with normal-tension glaucoma (NTG). The prevalence of MYOC mutations was determined in 80 Japanese NTG patients and 100 control subjects. In addition, the expression of mutant MYOC was determined by transforming COS-1 cells with five myocilin variants (R158Q, D208E, I360N, A363T, and I477S) and examining whether myocilin was present in the cultured cells and/or the culture medium by western blotting. Six different nucleotide sequence variants, R46Stop, R76K, R158Q, D208E, A488A, and one in the 3' non-coding region, were identified in 80 NTG patients. Variants in codon 46 (R46Stop), codon 158 (R158Q), and codon 488 (A488A) were not found in the 100 normal controls. The frequency of other sequence changes (R76K, D208E, and 3' non-coding) in NTG patients did not differ significantly from the frequencies in the control subjects. COS-1 cells transfected with the wild type, R158Q, or D208E variants secreted myocilin into the culture medium. On the other hand, the detected myocilin was significantly reduced in the medium of cells transfected with the I360N, A363T, or I477S variants that were previously identified as mutations for POAG. Definitive evidence of MYOC variants associated with NTG was not found.     

Anatomical relation between nasal septum deviation and oropharynx volume in different facial patterns evaluated through cone beam computed tomography

Introduction

The objective of this study was to establish the anatomical relation between nasal septum deviation (NSD) and oropharynx volume in different facial patterns using cone beam computed tomography (CBCT).

Methods

Ninety CBCT examinations were analyzed. InVivoDental software was used to evaluate cephalometric image reconstructions in terms of facial type, determined from cephalometric measurements indicative of growth direction; the presence of NSD was also evaluated. ITK-SNAP software was employed for delimitation of the oropharynx. Intra-examiner error methods were recorded. The results were subjected to parametric and non-parametric tests using Bioestat 5.0.

Results

A comparison of facial types revealed a significantly lower prevalence of NSD in the dolichofacial group compared with the brachyfacial and mesofacial groups (P = 0.0101 and 0.0149, respectively). In the total sample, there was a very strong positive relation between the presence of NSD and oropharynx space volume (P = 0.0162). The oropharynx volume was larger in all facial patterns in the presence of NSD.

Conclusion

The presence of NSD was not associated with facial type, although the oropharynx volume in patients with NSD increased. Therefore, deviation of the septum influences oropharynx volume.