Youping Xiao

Impact of intensity-modulated radiotherapy on nasopharyngeal carcinoma: Validation of the 7th edition AJCC staging system

BACKGROUND AND PURPOSE The purpose of this study was to evaluate the 7th edition UICC/AJCC staging system for nasopharyngeal carcinoma (NPC) patients who were treated with intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS The clinical data of 1241 NPC patients with initial magnetic resonance imaging (MRI) scans were studied retrospectively. All MRIs were independently reevaluated and restaged according to the 7th edition by two radiologists specializing in head and neck cancers. Analysis of prognostic factors in local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were performed. RESULTS The proportion of patients in Stage I, II, III, IVA and IVB were 4.8%, 26.2%, 45.4%, 18.4%, and 5.2%, respectively. The differences of LRFS between T1 and T2, and between T2 and T3 were not significant (P=0.055 and 0.605, respectively). Hazard ratios (HRs) for DSS and OS between T2 and T3 or between T3 and T4 differed significantly, but not between T1 and T2. The differences of DMFS between N0 and N1, between N1 and N2 were significant. However no significant difference was found in DMFS between N2 and N3a, or between N2 and N3b. For patients with T1-T3 disease, although skull base infiltration did not impact local failure, it was an independent prognostic factor for both distant failure and cancer death. CONCLUSION When treated with IMRT, the difference in the LRFS, DSS, and OS between T1 and T2 patients diminished, indicating that it is rational to merge T2 into T1. The prognostic value of the N classification of the current staging system had not changed much compared to the 6th edition.

Intravoxel Incoherent Motion-Magnetic Resonance Imaging as an Early Predictor of Treatment Response to Neoadjuvant Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma

AbstractThe aim of the study was to prospectively evaluate the clinical value of intravoxel incoherent motion (IVIM)-magnetic resonance imaging (MRI) in early predicting the treatment response to neoadjuvant chemotherapy (NAC) for nasopharyngeal carcinoma (NPC).Forty-eight patients with locoregionally advanced NPC were imaged with IVIM-MRI (14 b-factors, 0 – 1000 s/mm2) on a 3.0-T Magnetic resonance system, at the baseline, and repeatedly at the third and 21st day after NAC started. The IVIM-derived parameters (D, pure diffusion coefficient; f, perfusion fraction; and D*, pseudodiffusion coefficient) were calculated with the Interactive Data Language version 6.3 software. The baseline parameters and their corresponding changes (&Dgr;parameter(day)) during NAC were compared using the Student t test or Mann-Whitney U test. Variation analyses of IVIM-derived parameters were tested with intraclass correlation coefficient. Receiver-operating characteristic (ROC) curve analysis was conducted to estimate the best diagnostic accuracy. Statistical analyses were performed on the SPSS 18.0 software, with a 2-tailed probability value, P < 0.05 was considered significant.Among recruited patients, 37 cases were categorized as responders and 11 cases as nonresponders after NAC completed. The intra- and interobserver intraclass correlation coefficient of IVIM-derived parameters were excellent, which ranged from 0.858 to 0.971. Compared with the baseline value, at the third and 21st day, the D value was significantly higher and the D* value significantly lower (P < 0.05, P < 0.001, respectively). In contrast, f parameter only changed slightly (P > 0.05). Compared with nonresponders, responders presented a notably lower baseline D value and higher &Dgr;D3, &Dgr;D21, &Dgr;D3*, &Dgr;D21*, and &Dgr;f21 (P < 0.05), but no significant change in &Dgr;f3 was observed (P > 0.1). The receiver-operating characteristic curve analyses indicated that the threshold of baseline D values that best predicted the responders for primary nasopharynx tumors and metastatic lymph nodes were 0.911 × 10−3 mm2/s versus 0.951 × 10−3 mm2/s, and their corresponding area under curve, sensitivity, and specificity were 0.714 versus 0.774, 0.658 versus 0.538, and 0.818 versus 0.944, respectively.IVIM-MRI can potentially early predict the treatment response of NAC for NPC patients. The baseline D value, and early changes in D and D* value are better predictors of the chemotherapeutic responsiveness.

Suggestions for lymph node classification of UICC/AJCC staging system: a retrospective study based on 1197 nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy.

AbstractThis article provides suggestions for N classification of Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system of nasopharyngeal carcinoma (NPC), purely based on magnetic resonance imaging (MRI) in intensity-modulated radiation therapy (IMRT) era.A total of 1197 nonmetastatic NPC patients treated with IMRT were enrolled, and all were scanned by MRI at nasopharynx and neck before treatment. MRI-based nodal variables including level, laterality, maximal axial diameter (MAD), extracapsular spread (ECS), and necrosis were analyzed as potential prognostic factors. Modifications of N classification were then proposed and verified.Only nodal level and laterality were considered to be significant variables affecting the treatment outcome. N classification was thus proposed accordingly: N0, no regional lymph node (LN) metastasis; N1, retropharyngeal LNs involvement (regardless of laterality), and/or unilateral levels I, II, III, and/or Va involvement; N2, bilateral levels I, II, III, and/or Va involvement; and N3, levels IV, Vb, and Vc involvement. This proposal showed significant predicting value in multivariate analysis. N3 patients indicated relatively inferior overall survival (OS) and distant metastasis-free survival (DMFS) than N2 patients; however, the difference showed no statistical significance (P = 0.673 and 0.265 for OS and DMFS, respectively), and this was considered to be correlated with the small sample sizes of N3 patients (79 patients, 6.6%).Nodal level and laterality, but not MAD, ECS, and necrosis, were considered to be significant predicting factors for NPC. The proposed N classification was proved to be powerfully predictive in our cohort; however, treatment outcome of the proposed N2 and N3 patients could not differ significantly from each other. This insignificance may be because of the small sample sizes of N3 patients. Our results are based on a single-center data, to develop a new N classification that is universally acceptable; further verification by data from multicenter is warranted.

The prognosis of nasopharyngeal carcinoma involving masticatory muscles: a retrospective analysis for revising T subclassifications.

AbstractThis work is a retrospective study of magnetic resonance imaging (MRI) and T-stage subclassifications of nasopharyngeal carcinoma (NPC) involving the masticatory muscles (MMs). We examined how involvement of MMs influences the clinical T-stage classifications and the survival outcomes of NPC patients.MRI data as well as the medical records from 816 NPC patients were analyzed retrospectively. All cases were restaged according to the seventh edition of American Joint Committee on Cancer staging system criteria. The overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed by the Kaplan–Meier method, and their survival outcomes between different degrees of MM involvement and different T classifications were compared by using the log-rank test. All statistical analyses were conducted on SPSS 18.0 software. P > 0.05 was considered significant.Of the 816 NPC patients analyzed, 283 (34.68%) had tumors that involved MMs. All of those 283 patients involved the medial pterygoid muscle, and 125 cases (15.32%) involved the lateral pterygoid muscle. Multivariate analysis identified MM involvement as an independent prognostic factor for patients OS (P = 0.007) and LRFS (P = 0.024). MM involvement significantly correlated with a lower OS and LRFS (P < 0.01). In addition, compared with concurrent involvement of the medial and lateral pterygoid muscle, the medial pterygoid muscle involvement correlated with a higher OS and LRFS (P < 0.05). Among NPC patients, T-classifications 1 to 4 usually predicted the ultimate OS, LRFS, and DMFS (P > 0.1), unless the cancer involved the lateral pterygoid muscle.NPC involving the lateral pterygoid muscle presents a worse survival outcome than that involving the medial pterygoid muscle. Any cancer involving the lateral pterygoid muscle should be classified in a higher T-stage subclassification.

Parotid area lymph node metastases from preliminarily diagnosed patients with nasopharyngeal carcinoma: report on tumor characteristics and oncologic outcomes

The parotid area lymph node (PLN) is an uncommon site of metastasis originating from nasopharyngeal carcinoma (NPC). The study aimed to investigate clinical characteristics and outcomes of patients with preliminarily diagnosed NPC with PLN metastases. Here we retrospectively reviewed Magnetic resonance imaging (MRI) scans of 2221 patients with untreated nonmetastatic NPC who received intensity-modulated radiation therapy (IMRT). Finally, 64 (2.9%) patients were identified with PLN metastases, of which, 34 received PLN-sparing IMRT and 30 received PLN-radical IMRT. We also found that 42.2% had N3 disease and 95.3% had stages III-IVb. PLN metastases on MRI were characterized by ipsilateral retropharyngeal lymph node (RLN) or level II nodal extracapsular spread (ECS), ipsilateral giant cervical nodes, ipsilateral parapharyngeal extension, or solitary parotid metastasis. The 5-year overall survival, distant metastasis-free survival, regional relapse-free survival, and parotid relapse-free survival rates were 70.4%, 64.3%, 76.7%, and 87.9%, respectively. Distant metastases were the main cause of treatment failure and death. Using PLN-sparing IMRT, sparing PLN with minimal axial diameter of <10 mm, could increase the risk of parotid recurrence. However, it was not an independent prognostic factor. N classification and concurrent-based chemotherapy were almost statistically significant for distant failure and death. Overall, we demonstrated that the PLN metastases might be derived from RLN or level II nodal ECS, giant cervical nodes in a retrograde fashion, or parapharyngeal extension. Sparing PLN of <10 mm by IMRT should consider the risk of parotid recurrence. Distant metastases remained the dominant treatment failure. Further effective systemic chemotherapy should be explored.

Does MRI-detected cranial nerve involvement affect the prognosis of locally advanced nasopharyngeal carcinoma treated with intensity modulated radiotherapy?

Nasopharyngeal carcinoma (NPC) is one of the common cancers in South China. It can easily invade into cranial nerves, especially in patients with local advanced disease. Despite the fact that the magnetic resonance imaging (MRI) findings are not always consistent with the symptoms of CN palsy, MRI is recommended for the detection of CN involvement (CNI). However, the prognostic impact of MRI-detected CNI in NPC patients is still controversial. To investigate the prognostic value of MRI detected CNI, we performed a retrospective analysis on the clinical data of 375 patients with NPC who were initially diagnosed by MRI. All patients had T3-4 disease and received radical intensity modulated radiation therapy (IMRT) as their primary treatment. The incidence of MRI-detected CNI was 60.8%. A higher incidence of MRI-detected CNI was observed in T4 disease compared with T3 disease (96.8% vs. 42.8%, P<0.001), and a higher incidence was also found in patients with Stage IV disease compared with those with Stage III disease (91.5% vs. 42.3%; P<0.001). The local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) of patients with T3 disease, with or without MRI-detected CNI, was superior to that of patients with T4 disease (P<0.05). No significant differences in LRFS, DMFS or OS were observed between T3 patients with or without MRI-detected CNI. The survival of Stage III patients with or without MRI-detected CNI was significantly superior to that of Stage IV patients (P<0.01), but there was no significant difference between Stage III patients with or without MRI-detected CNI for all endpoints. Therefore, when treated with IMRT, MRI-detected CNI in patients with NPC does not appear to affect the prognosis. In patients with clinical T3 disease, the presence of MRI-detected CNI is not sufficient evidence for defining T4 disease.

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.

Unidimensional Measurement May Evaluate Target Lymph Nodal Response After Induction Chemotherapy for Nasopharyngeal Carcinoma.

AbstractThe aim of the study was to evaluate whether short axis and long axis on axial and coronal magnetic resonance imaging planes would reflect the tumor burden or alteration in size after induction chemotherapy in nasopharyngeal carcinoma.Patients with pathologically confirmed nasopharyngeal carcinoma (n = 37) with at least 1 positive cervical lymph node (axial short axis ≥15 mm) were consecutively enrolled in this prospective study. Lymph nodal measurements were performed along its short axis and long axis in both axial and coronal magnetic resonance imaging planes at diagnosis and after 2 cycles of induction chemotherapy. In addition, lymph nodal volumes were automatically calculated in 3D treatment-planning system, which were used as reference standard. Students t test or nonparametric Mann–Whitney U test was used to compare the continuous quantitative variables. Meanwhile, the &kgr; statistic and McNemars test were used to evaluate the degree of agreement and discordance in response categorization among different measurements.Axial short axis was significantly associated with volumes at diagnosis (P < 0.001). A good agreement (&kgr;=0.583) was found between axial short axis and volumetric criteria. However, the inconsistent lymph nodal shrinkage in 4 directions was observed. Axial short-axis shrinking was more rapid than the other 3 parameters. Interestingly, when utilizing the alternative planes for unidimensional measurements to assess tumor response, coronal short-axis showed the best concordance (&kgr;=0.792) to the volumes.Axial short axis may effectively reflect tumor burden or change in tumor size in the assessment of target lymph nodal response after induction chemotherapy for nasopharyngeal carcinoma. However, it should be noted that axial short axis may amplify the therapeutic response. In addition, the role of coronal short axis in the assessment of tumor response needs further evaluation.

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.

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*25 were 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.