[Oxalis inhibits prostate tumor in the mouse model of castration-resistant prostate cancer: Effect and mechanism].

OBJECTIVE: To investigate the inhibitory effect of oxalis on prostate tumor in the mouse model of castration-resistant prostate cancer (CRPC) and its action mechanism. METHODS: We established a CRPC model in 40 male C57/BL mice aged 6－8 weeks, divided them randomly into four groups of an equal number, and treated them intragastrically with normal saline (control), low-dose oxalis (5 mg/kg/d), medium-dose oxalis (10 mg/kg/d), and high-dose oxalis (15 mg/kg/d), respectively. After 28 days of treatment, we measured the tumor volume and body weight of the mice in different groups, calculated the tumor-inhibition rate, examined the histomorphological changes of the prostate tumors by HE staining, and detected the expressions of the nuclear factor-κB (NF-κB) signaling pathway and its downstream proteins in the tumor tissue by immunofluorescence assay. RESULTS: In comparison with the controls, the mice in the low-, medium- and high-dose oxalis groups showed a gradual decrease in tumor cell concentration and cell degeneration, and a gradually increased number of necrotic tumor cells. The volume and mean weight of prostate tumors were significantly reduced (P < 0.05), the expressions of NF-κB p65 and Ki67 proteins remarkably down-regulated (P < 0.05), and that of the Bax protein markedly up-regulated (P < 0.05) in the oxalis groups compared with the controls. CONCLUSION: Oxalis can inhibit the growth of prostate tumor in CRPC mice possibly by down-regulating the NF-κB signaling pathway and the expressions of p65 and Ki67 and up-regulating the expression of Bax, and thereby promoting the degeneration and necrosis of tumor cells.

MRI-based deep learning model predicts distant metastasis and chemotherapy benefit in stage II nasopharyngeal carcinoma.

Chemotherapy remains controversial for stage II nasopharyngeal carcinoma because of its considerable prognostic heterogeneity. We aimed to develop an MRI-based deep learning model for predicting distant metastasis and assessing chemotherapy efficacy in stage II nasopharyngeal carcinoma. This multicenter retrospective study enrolled 1072 patients from three Chinese centers for training (Center 1, n = 575) and external validation (Centers 2 and 3, n = 497). The deep learning model significantly predicted the risk of distant metastases for stage II nasopharyngeal carcinoma and was validated in the external validation cohort. In addition, the deep learning model outperformed the clinical and radiomics models in terms of predictive performance. Furthermore, the deep learning model facilitates the identification of high-risk patients who could benefit from chemotherapy, providing useful additional information for individualized treatment decisions.

Constructing an individualized surveillance framework for nasopharyngeal carcinoma based on a dynamic risk-adapted approach.

BACKGROUND AND PURPOSE: This study aims to evaluate the dynamic survival and recurrence hazard of nasopharyngeal carcinoma(NPC) patients after definitive chemoradiotherapy utilizing conditional survival(CS) analysis, and to propose a personalized surveillance strategy at different clinical stages. MATERIALS AND METHODS: Non-metastatic NPC patients who received curative chemotherapy between June 2005 and December 2011 were included. The Kaplan-Meier method was used to calculate the CS rate. RESULTS: A total of 1616 patients were analyzed. With the prolongation of survival time, both conditional locoregional recurrence free survival and distant metastatic free survival increased gradually. Changing pattern of annual recurrence risk over time varied among different clinical stages. The annual locoregional recurrence(LRR) risk in stage I-II was always less than 2%, while in stage III-IVa, it was greater than 2% for the first three years and decreased to below 2% only after the third year. The annual distant metastases (DM) risk was always less than 2% in stage I, but higher than 2% in stage II for the first 3 years (2.5-3.8%). For those with stage III-IVa, the annual DM risk retained at a high level(>5%), and only decreased to < 5% after the third year. Based on the dynamic changes in survival probability over time, we established a surveillance plan with different follow-up intensities and frequencies for different clinical stages. CONCLUSION: The annual risk of LRR and DM decrease over time. Our individual surveillance model will provide critical prognostic information to optimize clinical decision-making, and promote to formulate surveillance counseling and help with resources allocation.

Risk stratification for 1- to 2-cm gastric gastrointestinal stromal tumors: visual assessment of CT and EUS high-risk features versus CT radiomics analysis.

OBJECTIVES: To investigate the ability of CT and endoscopic sonography (EUS) in predicting the malignant risk of 1-2-cm gastric gastrointestinal stromal tumors (gGISTs) and to clarify whether radiomics could be applied for risk stratification. METHODS: A total of 151 pathologically confirmed 1-2-cm gGISTs from seven institutions were identified by contrast-enhanced CT scans between January 2010 and March 2021. A detailed description of EUS morphological features was available for 73 gGISTs. The association between EUS or CT high-risk features and pathological malignant potential was evaluated. gGISTs were randomly divided into three groups to build the radiomics model, including 74 in the training cohort, 37 in validation cohort, and 40 in testing cohort. The ROIs covering the whole tumor volume were delineated on the CT images of the portal venous phase. The Pearson test and least absolute shrinkage and selection operator (LASSO) algorithm were used for feature selection, and the ROC curves were used to evaluate the model performance. RESULTS: The presence of EUS- and CT-based morphological high-risk features, including calcification, necrosis, intratumoral heterogeneity, irregular border, or surface ulceration, did not differ between very-low and intermediate risk 1-2-cm gGISTs (p > 0.05). The radiomics model consisting of five radiomics features showed favorable performance in discrimination of malignant 1-2-cm gGISTs, with the AUC of the training, validation, and testing cohort as 0.866, 0.812, and 0.766, respectively. CONCLUSIONS: Instead of CT- and EUS-based morphological high-risk features, the CT radiomics model could potentially be applied for preoperative risk stratification of 1-2-cm gGISTs. KEY POINTS: • The presence of EUS- and CT-based morphological high-risk factors, including calcification, necrosis, intratumoral heterogeneity, irregular border, or surface ulceration, did not correlate with the pathological malignant potential of 1-2-cm gGISTs. • The CT radiomics model could potentially be applied for preoperative risk stratification of 1-2-cm gGISTs.

The role of radiologic extranodal extension in predicting prognosis and chemotherapy benefit for T1-2 N1 nasopharyngeal carcinoma: A multicenter retrospective study.

BACKGROUND AND PURPOSE: This multicenter retrospective study aimed to investigated the prognostic value of unequivocal radiologic extranodal extension (rENE) and the efficacy of chemotherapy for stage T1-2 N1 nasopharyngeal carcinoma (NPC) in the IMRT era. MATERIALS AND METHODS: We included 1,082 patients treated in 2005-2017 from three centers. rENE was recorded as G1 (coalescent nodal mass comprising ≥ 2 inseparable nodes) or G2 (invading beyond perinodal fat to frankly infiltrate adjacent structures). Multivariable analysis (MVA) evaluated the prognostic value of rENE. The value of chemotherapy was assessed in rENE-positive (rENE + ) and rENE-negative (rENE - ) subset separately. RESULTS: Centers 1, 2, and 3 had 139/515 (27.0 %), 100/365 (27.4 %), and 43/202 (21.3 %) cN + patients with rENE, respectively. Compared to rENE-, rENE + patients had a worse distant metastasis-free survival (DMFS) and overall survival (OS) (all p < 0.001). MVA confirmed the prognostic of both G1-rENE and G2-rENE for distant metastasis [G1: hazard ratio (HR): 2.933, G2: HR: 6.942, all p < 0.001] and death (G1: HR: 1.587, p = 0.040; G2: HR: 6.162, p < 0.001). There was no significant difference for DMFS and OS between chemo-radiotherapy and radiotherapy alone in rENE + and rENE - groups (all p > 0.1). However, rENE + patients with a cumulative cisplatin/nedaplatin dose (CCND) of > 160 mg/m2 had an improved DMFS (p = 0.033) but no OS (p = 0.197). CONCLUSION: Unequivocal rENE is prognostic in patients with T1-2 N1 NPC. Addition of chemotherapy to radiotherapy did not affect DMFS and OS in rENE - patients. Chemotherapy with a CCND of > 160 mg/m2 improved DMFS in rENE + patients.

Level Ib sparing intensity-modulated radiation therapy in selected nasopharyngeal carcinoma patients based on the International Guideline.

BACKGROUND AND PURPOSE: To investigate the feasibility of level Ib sparing in selected nasopharyngeal carcinoma (NPC) patients during intensity-modulated radiation therapy (IMRT) based on the International Guideline. PATIENTS AND MATERIALS: Patients with histologically-proven NPC who received definitive IMRT at our group were candidates for this analysis. Other eligibility criteria for analysis were designed according to the recommendation of International Guideline for selective coverage of level Ib. Survival outcomes focused on regional recurrence-free survival (RRFS) and level Ib recurrence rate were analyzed. RESULTS: A total of 450 patients were included, 60 of them received level Ib-covering IMRT due to the first three principles of the International Guideline according to our protocol. Of note, patients with level Ib involvement would receive ultrasound guided puncture, only those with positive pathological results would undergo level Ib-covering IMRT. For the remaining 390 patients who only fulfilled the last two criteria and/or level Ib involvement with negative pathological results, level Ib-sparing IMRT was delivered, with a median follow-up time of 112 months (range 6 to 194 months), reported 5- and 10-year RRFS were 95.4% and 92.9%, respectively. Twenty-two patients occurred regional recurrence at censorship (median 44.5 months), only 4(4/390, 1.03%) were recorded as level Ib recurrence. CONCLUSION: Level Ib-sparing IMRT should be safe and feasible for patients who only had level II involvement with ECE, and/or had a MAD of greater than 2 cm in level II, and/or level Ib involvement with negative pathological results. Further well-designed multi-center prospective trials should be conducted.

Re-evaluation of the prognostic significance of retropharyngeal node metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: To investigate the prognostic value of retropharyngeal lymphadenopathy in nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy. MATERIALS AND METHODS: Retrospective studies were performed in a total of 1197 patients. We evaluated the incidence of the retropharyngeal node (RPN) metastasis and the characteristics of the metastatic RPN including laterality, size, necrosis, and extranodal neoplastic spread. RESULTS: RPN metastasis occured in 86.3% of patients. The RPN and level II metastasis shared similar survival outcomes. RPN metastasis was an independent prognostic factor for distant failure (hazard ratio = 1.615; 95% confidence interval, 1.063-2.452; P = 0.025), in which the laterality of RPN metastasis significantly influences both the distant failure (P = 0.006) and disease progression (P = 0.001). In N1 disease, the occurrence of unilateral and bilateral RPN metastasis resulted in significantly different outcomes of the disease-specific survival (P = 0.045) and progression-free survival (P = 0.049). The co-occurrence of bilateral RPN and cervical lymph nodes (CLN) metastasis was an independent adverse prognostic factor (P < 0.01) for distant failure and disease progression but not for locoregional recurrence. CONCLUSION: Both the RPN and level II are the first stations of NPC lymph node metastasis. For N1-stage NPC patients, RPN metastasis, especially co-occurrence of bilateral RPN and CLN metastasis, have an adverse influence on survival outcomes.

Prognostic Factors for Overall Survival in Nasopharyngeal Cancer and Implication for TNM Staging by UICC: A Systematic Review of the Literature.

This study aims to identify prognostic factors in nasopharyngeal carcinoma (NPC) to improve the current 8th edition TNM classification. A systematic review of the literature reported between 2013 and 2019 in PubMed, Embase, and Scopus was conducted. Studies were included if (1) original clinical studies, (2) ≥50 NPC patients, and (3) analyses on the association between prognostic factors and overall survival. The data elements of eligible studies were abstracted and analyzed. A level of evidence was synthesized for each suggested change to the TNM staging and prognostic factors. Of 5,595 studies screened, 108 studies (44 studies on anatomical criteria and 64 on non-anatomical factors) were selected. Proposed changes/factors with strong evidence included the upstaging paranasal sinus to T4, defining parotid lymph node as N3, upstaging N-category based on presence of lymph node necrosis, as well as the incorporation of non-TNM factors including EBV-DNA level, primary gross tumor volume (GTV), nodal GTV, neutrophil-lymphocyte ratio, lactate dehydrogenase, C-reactive protein/albumin ratio, platelet count, SUVmax of the primary tumor, and total lesion glycolysis. This systematic review provides a useful summary of suggestions and prognostic factors that potentially improve the current staging system. Further validation studies are warranted to confirm their significance.

Prognostic value of serum uric acid and tumor response to induction chemotherapy in locally advanced nasopharyngeal carcinoma.

BACKGROUND: To explore the combined predictive value of serum uric acid (SUA) and tumor response to induction chemotherapy (IC) in locally advanced nasopharyngeal carcinoma (LANPC) patients receiving IC followed by concurrent chemoradiation therapy (CCRT). METHODS: A total of 341 LANPC patients treated with IC + CCRT were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared by the Kaplan-Meier analysis and the log-rank test, and multivariable survival analysis was carried out to investigate the independent prognostic factors. RESULTS: Univariate analysis showed that a low SUA level and unsatisfactory tumor response to two cycles of IC both were negative predictors for OS, PFS, and DMFS in patients with LANPC. multivariable analysis demonstrated that the SUA level after two cycles of IC was an independent prognostic factor for OS (P = 0.012) but of borderline significance for PFS and DMFS (P = 0.055 and P = 0.067, respectively). Furthermore, tumor response to IC was of independent significance for predicting OS, PFS, and DMFS, respectively. Finally, LANPC patients with satisfactory tumor response and a high SUA level after two cycles of IC had a better OS, PFS, and DMFS than those with unsatisfactory tumor response and a low SUA level. CONCLUSION: The SUA level and the tumor response to two cycles of IC had predictive value for LANPC patients treated with IC plus CCRT. However, more aggressive therapeutic strategies are recommended for those with a low SUA level and unsatisfactory tumor response to two cycles of IC.

Modified reduced-volume intensity-modulated radiation therapy in non-metastatic nasopharyngeal carcinoma: A prospective observation series.

BACKGROUND AND PURPOSE: Although the efficacy of "reduced-volume intensity-modulated radiation therapy (IMRT)" in nasopharyngeal carcinoma (NPC) has been confirmed, two issues regarding the necessity of clinical target volume 1(CTV1) delineation and the optimal margin of CTV2 remained undetermined. The current series, utilized de-intensification technique that omitted the contouring of CTV1 and narrowed the margin of CTV2 from 10 mm to 8 mm, namely "modified reduced-volume IMRT" was initiated to evaluate the efficacy and feasibility of this renew technique in a prospective series. PATIENTS AND MATERIALS: Dosimetric analysis was performed in 40 non-metastatic NPC cases to evaluate whether our modification is feasible. Then this de-intensification technique was applied in non-metastatic NPC patients treated in our attending group since late 2014. Survival outcomes focused on local recurrence-free survival (LRFS) and local failure pattern were analyzed. RESULTS: Preliminary dosimetric evaluation of "modified reduced-volume IMRT" showed that the 60 Gy isodose curve generated naturally by this technique could well wrap the target area of CTV1. Subsequent observation series, which included a total of 471 patients and had a median follow-up time of 46.2 months(range,3.7-70.8 months), reported that 4-year estimated LRFS, regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.6%, 97.7%, 87.7% and 92.4%, respectively. All local recurrence lesions occurred within 95% isodose lines and were considered in-field failures. CONCLUSIONS: Our de-intensification technique "modified reduced-volume IMRT" was feasible and did not compromise therapeutic efficacy, well-designed multicenter prospective trials are needed for further research.

Key Technologies of New Type of Intravascular Ultrasound Image Processing.

Since entering the 21st century, the application of ultrasound technology has developed rapidly. Intravascular ultrasound technology has been widely used in the diagnosis and treatment of cardiovascular diseases. With the help of computer image processing technology, it can provide clinicians with more accurate diagnosis. Based on the information to improve the success rate of clinical treatment. Based on this, this article combines the development history of intravascular ultrasound technology, explores the principles of new intravascular ultrasound technology, and analyzes the application of new intravascular ultrasound technology. On this basis, the preprocessing of intravascular ultrasound image data is discussed, involving the acquisition of intravascular ultrasound image data and image analysis. On this basis, explore the combined application of new intravascular ultrasound technology and other imaging examination methods, such as X-rays to use three-dimensional image technology to reconstruct new intravascular ultrasound image sequences, and provide doctors with clearer morphology and properties of tube wall lesions. In order to make a more accurate diagnosis of the lesion, a more detailed and accurate treatment plan can be given, which has extremely high clinical application value.

Diffusion kurtosis imaging and tumour microstructure for monitoring response to radiotherapy in human nasopharyngeal carcinoma xenografts.

OBJECTIVE: To investigate the correlations and feasibility of diffusion kurtosis imaging (DKI) parameters and tumour histopathology after radiotherapy in human nasopharyngeal carcinoma (NPC) xenografts on nude mice. MATERIALS AND METHODS: Seventy-two nude mice were used for the construction of CNE-1 (radio-insensitive) and CNE-2 (radio-sensitive) NPC xenograft models, followed by fraction irradiation at different doses of X-ray. The nude mice were randomly divided into six groups in each cell line models according to the dose of X-ray they have received and with six mice in each group. DKI scan was performed after radiation. DKI parameters, tumour histopathology and AQP-1 biomarkers were detected. One-way ANOVA and Pearson's correlation analysis were used in statistical analysis. RESULTS: In CNE-1 and CNE-2 NPC xenografts, D values were increased (P < 0.01 and P < 0.001), while K values (P < 0.01 and P < 0.001) and tumour size (P < 0.001 and P < 0.001) were reduced during fraction irradiation. Additionally, cell density (CD) and AQP-1 expressions were decreased, and necrosis ratio (NR) was increased in CNE-2 xenografts after fraction irradiation (P < 0.001). The changes in D values were negatively correlated with tumour size (r = -0.856, P < 0.001), CD (r = -0.918, P < 0.001), AQP-1 mRNA (r = -0.856, P < 0.001) and protein (r = -0.381, P = 0.022) expressions while positively correlated with NR (r = 0.908, P < 0.001) in CNE-2 xenografts. The changes in K values were positively correlated with tumour size (r = 0.964, P < 0.001), CD (r = 0.888, P < 0.001), AQP-1 mRNA (r = 0.955, P < 0.001) and protein (r = 0.330, P = 0.049) expression levels while negatively correlated with NR (r = -0.930, P < 0.001). However, in CNE-1 xenografts, there were no correlation between DKI parameters and the expression of AQP-1. CONCLUSION: Changes in D and K parameters after fractional irradiation are closely related with NPC cellular and pathological characteristics, especially size reduction and necrosis induction. These parameters exhibit potential abilities of monitoring the response to fractional irradiation in radio-sensitive NPC xenografts.

Prognostic value of radiologic extranodal extension and its potential role in future N classification for nasopharyngeal carcinoma.

PURPOSE: We evaluated the prognostic value of various grades of radiologic extranodal extension (rENE) and their potential roles in N-classification refinement for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All NPC patients treated with IMRT in our institution between 2005 and 2011 were included. Pre-treatment MR of cN+ cases were reviewed and rENE was recorded asG0: lymph nodes (LNs) without rENE; G1: tumor infiltrating beyond individual nodal capsule(s) into the surrounding fat plane; G2: coalescent nodal mass with unequivocal evidence of rENE; G3: tumor infiltrating beyond nodal capsule into adjacent structures. Multivariable analysis (MVA) assessed prognostic value of rENE for distant metastasis (DM) and death adjusted for age, gender, LDH, T-classification, N-classification, and chemotherapy cycles. RESULTS: A total of 1390 of 1616 (86%) NPC were cN+, and rENE was detected in 826/1390 (59%) patients: 256 (18.4%) G1-rENE, 487 (35%) G2-rENE, and 83 (6%) G3-rENE. MVA confirmed that G2-/G3-rENE had increased risk of DM (HR: 2.05/3.18, both p < 0.001) and death (HR: 1.62/2.39, p = 0.002/p < 0.001), while G1-rENE was non-prognostic (DM: p = 0.172; death: p = 0.320). We propose a refined N: New-N1: N1/N2 without G2-/G3-rENE; New-N2: N1_G2-rENE; New-N3: N2_G2-rENE, N1/N2_G3-rENE, or N3. The New-N classification had a lower AIC and higher c-index for DM (AIC: 3809.6 vs 3830.9; c-index: 0.700 vs. 0.677) and death (AIC: 3693.8 vs. 3705.9; c-index: 0.735 vs. 0.725) versus TNM-8 N. CONCLUSIONS: G2- and G3-rENE are independently prognostic for DM and death in NPC. Compared to the TNM8 N-classification, a refined N-classification incorporating G2- and G3-rENE improves prognostication of DM and mortality risk.

High-grade radiologic extra-nodal extension predicts distant metastasis in stage II nasopharyngeal carcinoma.

BACKGROUND: To investigate the prognostic value of radiologic extra-nodal extension (rENE) in stage II nasopharyngeal carcinoma (NPC). METHODS: Stage II NPC patients with N1 category (n = 365) were enrolled and divided into three groups according to the situation of rENE: without rENE, suspected rENE, and confirmed rENE (grades: A, infiltration into surrounding fat; B, matted nodes; C, infiltration into adjacent structures). RESULTS: Only high-grade rENE (including matted nodes and infiltration into adjacent structures) could significantly influence the survival outcomes, patients with high-grade rENE had significantly poorer survival than those without, with the 7-year distant metastasis-free survival and overall survival demonstrated to be 78.5% vs 93.0% (P < .001) and 81.9% vs 89.9% (P = .05), respectively. High-grade rENE, as defined in our study, is a stable criterion, with high intra-rater and inter-rater consistency. CONCLUSION: High-grade rENE was an evaluable predictor that could help with the selection of stage II patients with high risk of distant metastasis.

Depicting distant metastatic risk by refined subgroups derived from the 8th edition nasopharyngeal carcinoma TNM.

BACKGROUND: Tumor-nodal-metastasis (TNM) is the most important survival predictor in nasopharyngeal carcinoma (NPC). Distant metastasis (DM) is the predominant failure pattern of NPC in the intensity-modulated radiotherapy (IMRT) era. The DM risk appears to be different for T-N subsets within the same clinical stage. Appropriately depicting DM risk has emerged as an important issue in tailoring individualized treatment and underpins the reason for this study. METHODS: A total of 1616 non-metastatic (M0) NPC patients treated with IMRT were included. All were re-staged according to the 8th edition AJCC/UICC TNM (TNM-8). DM-free survival (DMFS) was calculated and compared among T-N subsets within each stage and DM risk groups were derived by Recursive-partitioning analysis (RPA) based on ordinal T and N categories. RESULTS: Significant heterogeneity in DM risk was evident among T-N subsets within cTNM-8 stages II-IV. The RPA algorithm classified patients into four DM risk groups: RPA-I (T1N0-1 and T2-3N0), RPA-II (T2-3N1), RPA-III (T4N0-1 and T1-3N2) and RPA-IV (T4N2 and T1-4N3), with 5-year DMFS of 93.4% (95% CI: 91.3-96.1), 84.3% (80.8-87.8), 78.9% (75.4-82.4) and 63.6% (56.3-70.9), respectively (p < 0.001). Compared to cTNM-8 stage grouping, RPA grouping had a lower Akaike information criterion (AIC) and higher Harrell's concordance index (c-index) for DMFS. CONCLUSIONS: Significant heterogeneity in DM risk exists among T-N subsets within cTNM-8 stages. The RPA groups demonstrated improved intra-group hazard consistency compared to cTNM-8 stage groups. While further validation is warranted, these RPA prognostic groupings provide a strong anatomic foundation to augment DM prediction for optimal targeting in future clinical trials.

Longitudinal Assessment of Intravoxel Incoherent Motion Diffusion Weighted Imaging in Evaluating the Radio-sensitivity of Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiation Therapy.

PURPOSE: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI)was evaluated regarding its ability to preliminarily predict the short-term treatment response of nasopharyngeal carcinoma (NPC) following intensity-modulated radiation therapy. MATERIALS AND METHODS: IVIM-DWI with 14 b-factors (0-1,000 sec/mm2 ) was performed with a 3T MR system on 47 consecutive NPCs before, during (end of the 5th, 10th, 15th, 20th, and 25th fractions), and after fractional radiotherapy. IVIM parametrics (D, f, and D*) were calculated and compared to the baseline and xth fraction. Patients were categorized into responders and non-responders after radiotherapy. IVIM parametrics were also compared between subgroups. RESULTS: After fractional radiations, the D (except D5 and D at the end of the 5th fraction) after radiations were larger than the baseline D0 (p < 0.05), and the post-radiation D* (except D*5 and D*10) were smaller than D*0 (p < 0.05). f0 was smaller than f5 and f10 (p < 0.001) but larger than fend (p < 0.05). Furthermore, greater D5, D10, D15, and f10 coupled with smaller f0, D*20, and D*25were observed in responders than non-responders (all p < 0.01). Responders also presented larger ΔD10, Δf10, ΔD*20, and δD*20 than non-responders (p < 0.05). Receiver operating characteristic curve analysis indicated that the D5, D*20, and f10 could better differentiate responders from non-responders. CONCLUSION: IVIM-DWI could efficiently assess tumor treatment response to fractional radiotherapy and predict the radio-sensitivity for NPCs.

Early diagnosis of radio-insensitive human nasopharyngeal carcinoma xenograft models by diffusion kurtosis imaging.

OBJECTIVE: To investigate the feasibility of DKI in early detection of radio-insensitive nasopharyngeal carcinoma (NPC) xenografts in nude mice. MATERIALS AND METHODS: Seventy-two nude mice were implanted with CNE-1 (low radio-sensitive) and CNE-2 (high radio-sensitive) NPC cell lines, and their respective xenografts were obtained. Then, the NPC-bearing nude mice were exposed to different doses of fraction irradiation, which are divided into non-irradiated group (G0), 10Gy group (G1), 20Gy group (G2), 30Gy group (G3), 3rd (G4) and 5th (G5) days after the entire dose (30y) of irradiation. Subsequently, DKI was performed on each group. Tumor volumes, shrink rates, D and K parameters were measured by two experienced radiologists. Student's t-test and receiver operating characteristic (ROC) curve analysis were conducted in this study. RESULTS: The differences of volume shrinkage rate between CNE-1 and -2 were observed in G2 (P = 0.032), with the shrink rates of 5.954% and 27.716%, respectively. The D values were reduced at G1 (DG1, P = 0.001) and then increased gradually after irradiation. The K values were increased at G1 (KG1, P = 0.001) and then declined sharply in CNE-2 (P < 0.01), but not in CNE-1 xenografts (P > 0.05). The respective AUC values for DG1 and KG1 were 0.875 and 0.917, with 66.7% and 83.3% sensitivity and 100% specificity, at the cutoff values of 1.27 × 10-3 mm2/s for parameter D and 0.88 for parameter K. CONCLUSION: DKI can be used for early detection of radio-insensitive NPC xenografts prior to morphological change, where DG1 and KG1 may be the most valuable indicators.

Role of diffusion-weighted imaging in the discrimination of benign and metastatic parotid area lymph nodes in patients with nasopharyngeal carcinoma.

To assess the utility of apparent diffusion coefficient (ADC) determined on diffusion-weighted MR imaging (DWI) to differentiate between benign and malignant parotid area lymph nodes (PLN) in nasopharyngeal carcinoma (NPC) patients. Thirty-nine consecutive NPC patients with a total of 40 enlarged, biopsied PLNs underwent DWI examination. ADC values for benign and malignant PLNs were measured and compared. Receiver operating characteristic (ROC) curve analysis was to evaluate the optimal threshold level of ADC values for metastatic PLNs. The kappa was to assess the degree of agreement between histopathological diagnoses and ADC values, or imaging features of PLNs on MRI. We found the mean ADC value for benign PLNs was markedly higher than malignant PLNs. A threshold ADC of 1.01 × 10-3 mm2/s was associated with a sensitivity of 85.7% and a specificity of 72.7% (area under the curve: 0.84). A moderate agreement was observed between the histopathological diagnosis and the threshold of ADC value (k value: 0.483). However, short axis diameter, necrosis, extranodal extension, and regional grouping of PLNs on MRI showed only a fair agreement with the histopathological diagnosis (k value: 0.257, 0.305, 0.276, and 0.205, respectively). Therefore, DWI may be a promising technique to differentiate metastatic from benign PLNs.

Diffusion kurtosis imaging of a human nasopharyngeal carcinoma xenograft model: Initial experience with pathological correlation.

PURPOSE: The aim of this study was to investigate the relationship between diffusion kurtosis imaging (DKI)-related parameters and pathological measures using human nasopharyngeal carcinoma (NPC) xenografts in a nude mouse model. MATERIALS AND METHODS: Twenty-six BALB/c-nu nude mice were divided into two groups that were injected with two different nasopharyngeal squamous cell carcinoma cell lines (CNE1 and CNE2). DK magnetic resonance (MR) imaging was performed on a 3.0 Tesla MR scanner. DWI and DKI-related parameters, including apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis (MK) were measured. Mice were euthanatized when the maximum diameter of the primary tumor reached 1.5cm after MR scanning. Tumor tissues were then processed for hematoxylin and eosin staining. The pathological images were analyzed using a computer-aided pixel-wise clustering method to evaluate tumor cellular density, nuclei portion, cytoplasm portion, extracellular space portion, the ratio of nuclei to cytoplasm and the ratio of nuclei to extracellular space. The relationships between DWI and DKI-related parameters and pathological features were analyzed statistically. RESULTS: The ADC and MD values of the CNE1 group (1.16±0.24×10-3mm2/s, 2.28±0.29×10-3mm2/s) was higher than that of the CNE2 group (0.82±0.14×10-3mm2/s, 1.53±0.24×10-3mm2/s, P<0.001), but the MK values between the two groups were not significantly different (CNE1: 0.55±0.14; CNE2: 0.47±0.23; P>0.05). A Pearson test showed that the ADC and MD values were significantly correlated with cellular density, nuclei portion, extracellular space portion and the ratio of nuclei to extracellular space (r=-0.861; -0.909, P<0.001; r=-0.487; 0.591, P<0.05; r=0.567; 0.625, P<0.05; r=-0.645; -0.745, P<0.001, respectively). The MK values were significantly correlated with nuclei portion, cytoplasm portion and the ratio of nuclei to cytoplasm (r=-0.475, P<0.05; r=0.665, P<0.001; r=-0.494, P<0.05, respectively). CONCLUSION: The preliminary animal results suggest that DKI findings can provide valuable bio-information for NPC tissue characterization. DKI imaging might be utilized as a surrogate biomarker for the non-invasive assessment of tumor microstructures.

Prognostic effect of parotid area lymph node metastases after preliminary diagnosis of nasopharyngeal carcinoma: a propensity score matching study.

Parotid area lymph node (PLN) metastasis in nasopharyngeal carcinoma (NPC) is rare, and its prognosis remains largely unknown. Our study aimed to investigate the prognostic value and staging categories of PLN metastasis in patients with NPC and treated with intensity-modulated radiation therapy (IMRT), to provide a reference for clinical treatment for NPC with PLN metastasis. Records for 1616 untreated NPC patients without distant metastasis was retrospectively reviewed. All patients underwent magnetic resonance imaging (MRI) examination prior to treatment and then received IMRT as their primary treatment. Forty-five NPC patients (2.8%) showed initial PLN metastasis on follow-up MRI. PLN metastasis was significantly associated with the N classification and clinical stage. Univariate analysis showed that PLN metastasis had an unfavorable influence on overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and regional relapse-free survival (RRFS) in NPC patients. Using propensity score matching (PSM) to calibrate selection bias and confounding bias, it was observed that PLN metastasis remained an adverse prognostic factor for OS, PFS, DMFS, and RRFS. Furthermore, the 5-year DMFS and RRFS curves for PLN metastasis were significantly separated from that for N2 disease but crossed that for N3 disease. Therefore, PLN metastasis was found to be an adverse prognostic factor for NPC and to be associated with the same DMFS as N3 disease. Therefore, more aggressive therapeutic strategies consistent with those for N3 disease are recommended for NPC with PLN metastasis to reduce distant metastasis.