Yuanji Xu

A Comparison Between the Chinese 2008 and the 7th Edition Ajcc Staging Systems for Nasopharyngeal Carcinoma

Objectives:The Chinese 1992 staging system for nasopharyngeal carcinoma (NPC) was revised in 2008 and was renamed as the Chinese 2008 staging system. The seventh edition of the American Joint Committee on Cancer (AJCC) staging manual also defined new rules for classifying NPC in 2010. The purpose of the current study is to compare the 2 in terms of patient distribution and efficacy in predicting prognosis. Methods:A total of 816 patients with untreated nondisseminated NPC who underwent magnetic resonance imaging scan of the nasopharynx and neck were studied retrospectively. All magnetic resonance imaging scans were reevaluated independently by 2 radiologists specialized in head and neck cancers. All patients were restaged according to the Chinese 2008 staging system and the AJCC staging system of NPC. Results:Using the 2 staging systems, the consistency for patient distributions in T, N, and overall stages was found to be moderate, with the &kgr; value of 0.65, 0.54, and 0.46, respectively. According to the Chinese 2008 and the AJCC staging systems, the proportion of patients in stages I, II, III, and IV accounted for 2.3% versus 2.3%, 11.0% versus 23.7%, 39.4% versus 49.1%, and 47.3% versus 24.9%, respectively. The AJCC T classification was better in predicting the 5-year local relapse-free survival, whereas the Chinese 2008 N classification was superior in predicting the 5-year distant metastasis-free survival. However, survival curves for the 5-year overall survival were comparable in both systems. Conclusions:We revealed a slightly better patient distribution of overall stage with AJCC comparing with the Chinese 2008 staging system. The prognostic value of AJCC T classification was considered to be better, whereas that of Chinese 2008 N classification was superior.

Surface-enhanced Raman spectroscopy of saliva proteins for the noninvasive differentiation of benign and malignant breast tumors

The capability of saliva protein analysis, based on membrane protein purification and surface-enhanced Raman spectroscopy (SERS), for detecting benign and malignant breast tumors is presented in this paper. A total of 97 SERS spectra from purified saliva proteins were acquired from samples obtained from three groups: 33 healthy subjects; 33 patients with benign breast tumors; and 31 patients with malignant breast tumors. Subtle but discernible changes in the mean SERS spectra of the three groups were observed. Tentative assignments of the saliva protein SERS spectra demonstrated that benign and malignant breast tumors led to several specific biomolecular changes of the saliva proteins. Multiclass partial least squares–discriminant analysis was utilized to analyze and classify the saliva protein SERS spectra from healthy subjects, benign breast tumor patients, and malignant breast tumor patients, yielding diagnostic sensitivities of 75.75%, 72.73%, and 74.19%, as well as specificities of 93.75%, 81.25%, and 86.36%, respectively. The results from this exploratory work demonstrate that saliva protein SERS analysis combined with partial least squares–discriminant analysis diagnostic algorithms has great potential for the noninvasive and label-free detection of breast cancer.

A noninvasive cancer detection strategy based on gold nanoparticle surface-enhanced raman spectroscopy of urinary modified nucleosides isolated by affinity chromatography.

The search for tumor biomarkers in the urine for cancer diagnosis is currently a hot topic in clinical oncology, with potential for cancer screening and diagnosis. Modified nucleosides excreted through the urine are considered to be a general tumor marker for various cancer types. Herein, we explore a new method that utilizes surface-enhanced Raman scattering (SERS) spectroscopy to obtain a complete biochemical profile of urinary modified nucleosides. In our method, modified nucleosides are first isolated from urine sample utilizing the excellent separation ability of affinity chromatography; then supplemented with gold (Au) nanoparticles as substrate for SERS spectroscopy analysis. The obtained SERS spectra present rich diagnostic and fingerprinting type signatures of urinary modified nucleosides. The utility of this new method in cancer detection was evaluated by analyzing urine samples from three groups of subjects: nasopharyngeal cancer patients (n=62), esophageal cancer patients (n=55), and healthy volunteers (n=52). Partial least squares and linear discriminant analysis (PLS-DA) were used to analyze and classify the SERS spectra of urinary modified nucleosides from nasopharyngeal cancer, esophageal cancer, and the normal group, achieving diagnostic sensitivities of 95.2%, 90.9% and 98.1% and specificities of 97.2%, 98.2% and 95.7%, respectively. These results demonstrated great potential of this novel method for non-invasive and label-free cancer detection and screening.

Decreased expression of the NKG2D ligand ULBP4 may be an indicator of poor prognosis in patients with nasopharyngeal carcinoma

U16-binding protein 4 (ULBP4), a human ligand for natural killer group 2, member D (NKG2D) receptor on NK cells and subsets of T cells, is thought to activate anticancer immune responses. However, the expression pattern and prognostic effect of ULBP4 in nasopharyngeal carcinoma (NPC) has not been investigated. We first compared ULBP4 expression between archival 15 NPC tissues and 8 normal nasopharynx (NP) tissues using qPCR. Then ULBP4 expression among 111 NPC specimens was validated on immunohistochemical examination. In addition, the association of ULBP4 expression with clinical characteristics and survival outcomes was analyzed. Furthermore, the impact of ULBP4 expression in NPC cells on the cytotoxic activity of NK cells was investigated. Both mRNA and protein ULBP4 expressions of NPC tissues were significantly lower than those in normal NP tissues. However, no association of ULBP4 expression with clinical characteristics was observed. Patients with NPC having decreased expression of UBLP4 had significantly poorer overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) than those with preserved levels of ULBP4. On multivariate analyses, low expression of ULBP4 was of borderline significance for OS, PFS, and DMFS (P = 0.060, 0.053, and 0.076, respectively). Further, LDH analysis demonstrated that the cytotoxic activitity of NK cells against C666-1 or 5-8F NPC cells with lenti-ULBP4 was considerably increased as compared to those with lenti-vector at various E/T ratios. Hence, restoration of ULBP4 expression may be a novel therapeutic strategy for treatment of NPC. However, further study is required to confirm these findings.

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.

Changes in Tumor Volumes and Spatial Locations Relative to Normal Tissues During Cervical Cancer Radiotherapy Assessed by Cone Beam Computed Tomography

Purpose: To assess changes in the volumes and spatial locations of tumors and surrounding organs by cone beam computed tomography during treatment for cervical cancer. Materials and Methods: Sixteen patients with cervical cancer had intensity-modulated radiotherapy and off-line cone beam computed tomography during chemotherapy and/or radiation therapy. The gross tumor volume (GTV-T) and clinical target volumes (CTVs) were contoured on the planning computed tomography and weekly cone beam computed tomography image, and changes in volumes and spatial locations were evaluated using the volume difference method and Dice similarity coefficients. Results: The GTV-T was 79.62 cm3 at prior treatment (0f) and then 20.86 cm3 at the end of external-beam chemoradiation. The clinical target volume changed slightly from 672.59 cm3 to 608.26 cm3, and the uterine volume (CTV-T) changed slightly from 83.72 cm3 to 80.23 cm3. There were significant differences in GTV-T and CTV-T among the different groups (P < .001), but the clinical target volume was not significantly different in volume (P > .05). The mean percent volume changes ranged from 23.05% to 70.85% for GTV-T, 4.71% to 6.78% for CTV-T, and 5.84% to 9.59% for clinical target volume, and the groups were significantly different (P < .05). The Dice similarity coefficient of GTV-T decreased during the course of radiation therapy (P < .001). In addition, there were significant differences in GTV-T among different groups (P < .001), and changes in GTV-T correlated with the radiotherapy (P < .001). There was a negative correlation between volume change rate (DV) and Dice similarity coefficient in the GTV-T and organs at risk (r < 0; P < .05). Conclusion: The volume, volume change rate, and Dice similarity coefficient of GTV-T were all correlated with increase in radiation treatment. Significant variations in tumor regression and spatial location occurred during radiotherapy for cervical cancer. Adaptive radiotherapy approaches are needed to improve the treatment accuracy for cervical cancer.

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.

Early discrimination of nasopharyngeal carcinoma based on tissue deoxyribose nucleic acid surface-enhanced Raman spectroscopy analysis

Abstract. Surface-enhanced Raman spectroscopy (SERS) was employed to detect deoxyribose nucleic acid (DNA) variations associated with the development of nasopharyngeal carcinoma (NPC). Significant SERS spectral differences between the DNA extracted from early NPC, advanced NPC, and normal nasopharyngeal tissue specimens were observed at 678, 729, 788, 1337, 1421, 1506, and 1573  cm−1, which reflects the genetic variations in NPC. Principal component analysis combined with discriminant function analysis for early NPC discrimination yielded a diagnostic accuracy of 86.8%, 92.3%, and 87.9% for early NPC, advanced NPC, and normal nasopharyngeal tissue DNA, respectively. In this exploratory study, we demonstrated the potential of SERS for early detection of NPC based on the DNA molecular study of biopsy tissues.

Analysis of rare periparotid recurrence after parotid gland-sparing intensity-modulated radiotherapy for nasopharyngeal carcinoma

PURPOSE Periparotid recurrence is an uncommon phenomenon after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma. This study aimed to discuss the clinical characteristics, reasonable causes and feasible therapeutic modalities of patients with nasopharyngeal carcinoma and periparotid recurrence. PATIENTS AND METHODS The medical records of 1852 patients with non-metastatic nasopharyngeal carcinoma treated with initial IMRT between January 2008 and December 2012 were retrospectively reviewed, and nine patients were finally found to have developed periparotid recurrence after IMRT. After periparotid failure, four received radiotherapy and chemotherapy, two had surgery, two had surgery and adjuvant radiotherapy or chemotherapy, and one received radiotherapy alone. RESULT The incidence rate of periparotid recurrence was 4.9‰. According to pretreatment magnetic resonance imaging (MRI) scans, all patients had both ipsilateral retropharyngeal lymph nodes metastasis with 66.7% of extracapsular spread and level II lymphadenopathy with all extracapsular spread. The median time interval to periparotid failure was 14.8 months, and six patients were found to have a relapse in the primary sites of unsuspicious parotid nodules. After a median follow-up of 46.4 months, five patients developed distant metastasis, three of them developed local failure. In addition, one developed regional failure, one developed locoregional recurrence, and only one was alive without evidence of disease at the last follow-up. CONCLUSION Periparotid recurrences are rare after definitive IMRT for nasopharyngeal carcinoma. However, patients with ipsilateral retropharyngeal lymph nodes or level II nodal extracapsular spread on pretreatment MRI could be suspicious of metastatic periparotid nodules. Distant metastases were the main treatment failure despite a combination of several salvage treatment of periparotid recurrence. More effective chemotherapy should be explored.