Concurrent nimotuzumab and intensity-modulated radiotherapy for elderly patients with locally advanced nasopharyngeal carcinoma.

Because of the common physical condition, reduced organ function, and comorbidities, elderly patients with nasopharyngeal carcinoma (NPC) are often underrepresented in clinical trials. The optimal treatment of elderly patients with locally advanced NPC remains unclear. The purpose of this study was to evaluate the efficacy of concurrent nimotuzumab combined with intensity-modulated radiotherapy (IMRT) in elderly patients with locally advanced NPC. We conducted a single-arm, phase II trial for elderly patients with stage III-IVA NPC (according to UICC-American Joint Committee on Cancer TNM classification, 8th edition). All patients received concurrent nimotuzumab (200 mg/week, 1 week prior to IMRT) combined with IMRT. The primary end-point was complete response (CR) rate. The secondary end-points were survival, safety, and geriatric assessment. Between March 13, 2017 and November 12, 2018, 30 patients were enrolled. In total, 20 (66.7%) patients achieved CR, and objective response was observed in 30 (100.0%) patients 1 month after radiotherapy. The median follow-up time was 56.05 months (25th-75th percentile, 53.45-64.56 months). The 5-year locoregional relapse-free survival, distant metastasis-free survival, cancer-specific survival, disease-free survival, and overall survival were 89.4%, 86.4%, 85.9%, 76.5%, and 78.8%, respectively. Grade 3 mucositis occurred in 10 (33%) patients and grade 3 pneumonia in 3 (10%) patients. Concurrent nimotuzumab combined with IMRT is effective and well-tolerated for elderly patients with locally advanced NPC.

Detection and staging of recurrent or metastatic nasopharyngeal carcinoma in the era of FDG PET/MR.

PURPOSE: The aim of this pilot study was to evaluate the accuracy of 18 fluorodeoxyglucose (FDG) PET/MR imaging in detection and staging of recurrent or metastatic NPC. PATIENTS AND METHODS: The PET/MR scans of 60 patients with clinically diagnosed recurrent or metastatic NPC between April 2017 and November 2019 were included in this study. Findings were evaluated according to the eighth edition of the American Joint Committee on Cancer staging system. Final diagnosis was confirmed at biopsy or imaging follow-up for at least 6 months. RESULTS: Of the 60 patients, 25, 26 and 42 had developed local lesions, regional nodal metastases and distant metastases, respectively. The overall accuracy of PET/MR imaging for staging of recurrent or metastatic NPC was 88.3%. CONCLUSIONS: For recurrent or metastatic NPC, 18 FDG PET/MRI might serve as a single-step staging modality.

[Prognostic significance of the number of positive lymph nodes, number of involved regions and metastatic lymph node ratio in hypopharyngeal cancer].

OBJECTIVE: To explore the relationship between positive lymph node number, involved region, positive lymph node ratio and the prognosis of patients with hypopharyngeal cancer. METHODS: Clinicopatological data of 81 patients with hypopharyngeal squamous cell carcinoma who underwent hypopharyngectomy and cervical lymph node dissection from January 2000 to December 2005 in our hospital were analyzed retrospectively. The relationship between positive lymph node number, involved region, positive lymph node ratio and the prognosis was analyzed. RESULTS: The rate of lymph node metastasis was 79.0% (64/81) in the 81 patients with hypopharyngeal cancer. Of which, the rates of unilateral metastasis and bilateral metastasis were 82.9% (53/64) and 17.1% (11/64), respectively. The rate of lymph node metastasis was increasing with advancing tumor stage. The median survival times were 81, 51 and 26 months in the patients with 0, 1-3 and ≥ 4 positive lymph nodes, respectively (P < 0.001), 84, 45 and 23 months in patients with 0, 1-2 and ≥ 3 involved regions, respectively (P < 0.001), and 84, 51 and 17 months in patients with positive lymph node ratio of 0, <10% and ≥ 10%, respectively (P < 0.001). Multivariable analysis showed that positive lymph node ratio, extracapsular infiltration, T classification and treatment modality were independent prognostic factors (P = 0.002). CONCLUSIONS: Positive lymph node ratio is an independent prognostic factor for hypopharyngeal cancer.

Zwitterionic Injectable Hydrogel-Combined Chemo- and Immunotherapy Medicated by Monomolecular Micelles to Effectively Prevent the Recurrence of Tumor Post Operation.

Surgical resection remains the most common method of tumor treatment; however, the high recurrence and metastasis after surgery need to be solved urgently. Herein, we report an injectable zwitterionic hydrogel based on "thiol-ene" click chemistry containing doxorubicin (DOX) and a macrophage membrane (MM)-coated 1-methyl-tryptophan (1-MT)-loaded polyamide-amine dendrimer (P-DOX/1MT) for preventing the postoperative recurrence of tumors. The results indicated that P-DOX/1MT@MM exhibited enhanced recognition and uptake of the dendrimer by tumor cells and induced the immunogenic cell death. In the mice tumor model, the P-DOX/1MT@MM-Gel exhibited high therapeutic efficiency, which could significantly reduce the recurrence of the tumor, including suppressing tumor growth, promoting dendritic cell maturation, and increasing tumor-infiltrating cytotoxic T lymphocytes. The mechanism analysis revealed that the hydrogel greatly reduces the side effects to normal tissues and significantly improves its therapeutic effect. 1MT in the hydrogel is released more rapidly, improving the tumor suppressor microenvironment and increasing the tumor cell sensitivity to DOX. Then, the DOX in the P-DOX/1MT@MM effectively eliminatedo the residual tumor cells and exerted enhanced toxicity. In conclusion, this novel injectable hydrogel that combines chemotherapy and immunotherapy has the property of sequential drug release and is a promising strategy for preventing the postoperative recurrence of tumors.

Injectable Zwitterionic Physical Hydrogel with Enhanced Chemodynamic Therapy and Tumor Microenvironment Remodeling Properties for Synergistic Anticancer Therapy.

Surgical resection is the first-line therapy for breast cancer. However, residual tumor cells and the highly immunosuppressive tumor microenvironment (TME) continue to have a serious impact on tumor recurrence and metastasis postresection. Implantation of an in situ hydrogel system postresection has shown to be an effective treatment with great clinical potential. Herein, an injectable zwitterionic hydrogel system was developed for local drug delivery with enhanced immune activation and prevention of tumor recurrence. Driven by electrostatic interactions, poly(sulfobetaine methacrylate) (PSBMA) self-assembles into a hydrogel in saline, achieving low protein adsorption and tunable biodegradability. The chemotherapy drug doxorubicin (DOX) was loaded into copper peroxide nanoparticles (CuO2/DOX), which were coated with macrophage membranes to form tumor-targeting nanoparticles (M/CuO2/DOX). Next, M/CuO2/DOX and the stimulator of interferon genes (STING) agonist 2',3'-cGAMP were coloaded into PSBMA hydrogel (Gel@M/CuO2/DOX/STING). The hydrophilic STING agonist was first released by diffusion from hydrogel to activate the STING pathway and upregulate interferon (IFN) signaling related genes, remodeling the immunosuppressive TME. Then, M/CuO2/DOX targeted the residual tumor cells, combining with DOX-induced DNA damage, immunogenic tumor cell death, and copper death. Hence, this work combines chemodynamic therapy with STING pathway activation in TME, encouraging residual tumor cell death, promoting the maturation of dendritic cells, enhancing tumor-specific CD8+ T cell infiltration, and preventing postoperative recurrence and metastasis.

Intracavity hyperthermia in nasopharyngeal cancer: a phase III clinical study.

PURPOSE: To compare the local tumour control, survival, and acute mucous toxicity of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy (RT) combined with intracavity hyperthermia versus conventional RT alone. METHODS AND MATERIALS: Previously untreated NPC patients were assigned randomly into the conventional RT group and the hyperthermia group. In addition to curative RT, hyperthermia group patients received intracavity hyperthermia before or after RT; T90 was 42.5°-43°C for 50 min twice a week for 7 weeks. RESULTS: From August 2001 to July 2006, 180 eligible patients with NPC were enrolled in this study. The complete response (CR) rate in the two arms (RT plus hyperthermia versus conventional RT) was 95.6% and 81.1%, respectively (p = 0.003, χ² test). CR rates for T2 and T3 patients in the hyperthermia group were 97.1% and 96.9%, respectively, while in the conventional RT group they were 79.5% and 76.7%, respectively. The difference between the two groups was statistically significant (p = 0.03 and p = 0.024, respectively). The 5-year local control rate was 91.1% and 78.9% for the two arms, respectively (p = 0.022). Oral mucous toxicity in both arms was comparable. The 5-year PFS and 5-year OS rate for the hyperthermia arm vs. the conventional arm were 72.7% versus 63.1% (p = 0.039) and 78.2% versus 70.3% (p = 0.14), respectively. CONCLUSIONS: Conventional RT treatment followed by intracavity hyperthermia was well tolerated by the NPC patients. The addition of hyperthermia improved the local tumour control, and our results indicated a positive impact on PFS of NPC patients.

Locoregional Extension Patterns of Nasopharyngeal Carcinoma Detected by FDG PET/MR.

PURPOSE: We sought to define the locoregional extension patterns of nasopharyngeal carcinomas (NPCs) by positron emission tomography (PET)/magnetic resonance imaging (MRI) and to improve clinical target volume (CTV) delineation. METHODS: Between May 2017 and March 2021, 331 consecutive patients with nonmetastatic NPCs who underwent pretreatment, simultaneous whole-body PET/MRI for staging were included in this study. RESULTS: The high-risk regions included the base of the sphenoid bone, the prestyloid compartment, prevertebral muscle, foramen lacerum, medial pterygoid plate, sphenoidal sinus, clivus, petrous apex, and foramen ovale. When the high-risk regions were invaded, the incidence rates of tumor invasion into the medium-risk regions increased. In contrast, when the high-risk regions were not involved, the incidence rates of tumor invasion into the medium-risk regions were mostly less than 10%, excluding the post-styloid compartment and oropharynx. According to the updated consensus guidelines of the neck node levels for head and neck tumors from 2013, level IIa (77.3%, 256/331), level IIb (75.8%, 251/331), and level VIIa (71.3%, 236/331) were the most frequently involved levels, followed by levels III (42.6%), Va (13.9%), IVa (8.8%), IVb (3.6%), Ib (3.6%), Vb (2.4%), VIIb (2.4%), VIII (1.8%), Vc (0.9%), and Xa (0.3%). Skip lymph node metastasis occurred in only 1.9% of patients. CONCLUSIONS: For NPCs, primary disease and regional lymph node spread follow an orderly pattern, and a skip pattern of lymph node metastasis was unusual. Involved level radiotherapy might be feasible for cervical lymph node levels below the caudal border of cricoid cartilage and level VIIb.

Outcome and Optimal Treatment for Esthesioneuroblastoma in the Era of Intensity-Modulated Radiation Therapy: A Single-Center Experience.

PURPOSE: Esthesioneuroblastoma (ENB) is a type of rare malignant neoplasm of the sinonasal cavity. Optimal treatment for ENB is still controversial. A retrospective study was conducted to identify the clinical outcome and optimal treatment for ENB in the era of intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: Between December 2006 and August 2018, 37 patients with ENB without distant metastasis who underwent neoadjuvant chemotherapy followed by chemoradiotherapy (C+RC) or surgery followed by radiotherapy or chemoradiotherapy (S+R/RC) were retrospectively reviewed at our center. RESULTS: The median follow-up period was 63.7 months (range, 13.2-111.5 months). Five-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were similar between treatment arms (P values > 0.05). With a multivariate analysis, a Karnofsky Performance Status (KPS) of ≤80 was a prognostic factor for poor five-year OS. A KPS of ≤80 and Kadish class C-D tumors were prognostic factors for poor PFS. A KPS of ≤80 was a prognostic factor for poor LRFS. When KPS was ≤80 and tumors were Kadish class C-D, T3-4 and N1 were prognostic factors for poor DMFS. Subgroup analyses also demonstrated that the two treatment arms exhibited similar trends for OS, PFS, LRFS, and DMFS, excluding patients with N1 or Kadish class A-B tumors (P values > 0.05). CONCLUSION: In the era of IMRT, S+R/RC failed to improve the outcomes of patients with ENB. C+RC may be a feasible treatment option for patients with ENB.

Apatinib in treating patients with recurrent or metastatic nasopharyngeal carcinoma who had failed prior platinum-based chemotherapy.

BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for recurrent/metastatic nasopharyngeal carcinoma (NPC); however, there is no standard regimen for those who failed first-line treatment. This study aimed to evaluate the efficacy and safety of apatinib in treating patients with recurrent/metastatic NPC who failed prior platinum-based chemotherapy. METHODS: Patients aged 18-65 years with recurrent/metastatic NPC were treated with apatinib at an initial dose of 500 mg once daily and continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoints were clinical benefit rate (CBR) and toxicity. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). RESULTS: Nineteen patients were enrolled in this study. At the final follow-up, the CBR was 52.6% (95% CI: 29.8-76.2%) in the intention-to-treat population. The median PFS and OS were 3.7 (95% CI: 0.6-6.8) months and 12.9 (95% CI: 9.3-16.5) months, respectively. The most common grade 3-4 adverse events (AEs) were hand-foot syndrome [3 (15.8%)], neutropenia [2 (10.5%)], proteinuria [2 (10.5%)], oral mucosal pain [2 (10.5%)], hypertension [1 (5.3%)], hyponatremia [1 (5.3%)], artery dissection [1 (5.3%)], and nasopharyngeal hemorrhage [1 (5.3%)]. A serious AEs was reported in one patient who died of nasopharyngeal hemorrhage. Treatment with apatinib did not significantly influence patient-reported quality-of-life, except for nausea/vomiting and pain (P<0.05). CONCLUSIONS: Apatinib achieved modest disease control with acceptable toxicity in recurrent/metastatic NPC patients pretreated with platinum-based chemotherapy.

A prospective randomized controlled trial on the value of prophylactic oral nutritional supplementation in locally advanced nasopharyngeal carcinoma patients receiving chemo-radiotherapy.

OBJECTIVES: We investigated the effect of prophylactic oral nutrition supplements (ONS) in locally advanced nasopharyngeal carcinoma patients receiving neoadjuvant chemotherapy and concurrent chemoradiotherapy (CCRT). METHODS: Eligible patients were randomly assigned to an intervention or control group. Patients in the intervention group were supported with prophylactic ONS from the beginning of CCRT. The control group received nutritional support only when necessary. Bodyweight, hematological indexes, nutritional status, and quality of life were measured at baseline and before, during, and after RT. RESULTS: We evaluated 114 patients from October 2016 to May 2018. More than half of patients experienced significant weight loss during CCRT, which continued for three months after radiotherapy (RT). Compared to baseline, the rate of weight loss ≥ 5% before, during, at the end of RT, and one and three months after RT were 3.5%, 28.9%, 51.8%, 61.4%, and 61.4%, respectively. Nutritional status and global health status scores progressively decreased during treatment. The rate of RT interruption was higher in the control group than in the intervention group (7.14% vs. 0%, χ2 = 4.29, P = 0.04). More patients experienced concurrent chemotherapy interruption in the control group than in the intervention group (28.57% vs 10.34%, χ2 = 6.08, P = 0.01). There were no significant differences in weight loss, nutritional status, quality of life, and global health status between two groups. CONCLUSIONS: Malnutrition and weight loss progressively increased during treatment. Prophylactic ONS can improve tolerance to CCRT, but it offers no advantage on short-term weight loss or nutritional assessment scores.

Grading of MRI-detected skull-base invasion in nasopharyngeal carcinoma with skull-base invasion after intensity-modulated radiotherapy.

BACKGROUND: The aim of this study is to evaluate the prognostic value of grading MRI-detected skull-base invasion in nasopharyngeal carcinoma (NPC) with skull-base invasion after intensity-modulated radiotherapy (IMRT). METHODS: This study is a retrospective chart review of 469 non-metastatic NPC patients with skull-base invasion. Patients were classified as extensive skull-base invasion (ESBI) group and limited skull-base invasion (LSBI) group. RESULTS: Multivariate analysis showed that the skull-base invasion (LSBI vs. ESBI) was an independent prognostic predictor of progression free survival (PFS). The estimated 5-year local failure free survival (LFFS), distant metastasis free survival (DMFS), PFS, and overall survival (OS) rates for patients in the T3-LSBI and T3-ESBI group were 92.9% versus 93.5, 89.8% versus 86.1, 81.6% versus 76.4, and 93.5% versus 86.3%, respectively (P > 0.05). CONCLUSION: Grading of MRI-detected skull-base invasion is an independent prognostic factor of NPC with skull-base invasion. It is scientific and reasonable for skull-base invasion as a single entity to be classified as T3 classification.

Prognostic Value and Staging Classification of Lymph Nodal Necrosis in Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy.

PURPOSE: The aim of the present study was to evaluate the prognostic value of magnetic resonance imaging (MRI)‒determined lymph nodal necrosis (LNN) in nasopharyngeal carcinoma (NPC) and explore the feasibility of an N-classification system based on the 8th edition of the American Joint Committee on Cancer (AJCC) system. MATERIALS AND METHODS: The MRI scans of 616 patients with newly diagnosed stage T1-4N1-3M0 NPC who were treated with definitive intensity-modulated radiotherapy (IMRT) were reviewed. RESULTS: Multivariate analysis showed that LNN was an independent negative prognostic predictor of distant metastasis free survival (hazard ratio, 1.634; 95% confidence interval, 1.023 to 2.609; p=0.040) and overall survival (hazard ratio, 2.154; 95% confidence interval, 1.282 to 3.620; p=0.004). Patients of classification N1 disease with LNN were reclassified as classification N2, and classification N2 disease with LNN as classification N3 in the proposed N-classification system. Correlation with death and distant failure was significant, and the total difference between N1 and N3 was wider with the proposed system. CONCLUSION: MRI-determined LNN is an independent negative prognostic factor for NPC. The proposed N classification system is powerfully predictive.

Feasibility of multiparametric imaging with PET/MR in nasopharyngeal carcinoma: A pilot study.

OBJECTIVE: The aim of this pilot study was to explore the integrated positron emission tomography and magnetic resonance imaging scanner (PET/MR) for biological characterization of nasopharyngeal carcinoma (NPC) and potential therapeutic applications of dose painting (DP). PATIENTS AND METHODS: Twenty-one NPC patients with PET/MR were included in this study. Overlap of tumor volumes was analyzed on T2-weighted images (volume of interest, VOIT2), diffusion-weighted magnetic resonance imaging (VOIDWI) and 18F-fluorodeoxyglucose positron emission tomography (VOIPET). The overlap percentages of low-metabolic sub-region (cluster 1) and high-metabolic sub-region (cluster 2) in VOIPET and VOIDWI were analyzed by cluster analysis. RESULTS: Both the VOIDWI and VOIPET were encompassed in the VOIT2, respectively 99.6% and 97.5%. The median tumor overlap was 94.4% (VOIDWI within VOIPET). The median overlap of cluster 2 in VOIPET and VOIDWI was 43.61% (27.67-52.66%) and 21.86%(10.47-40.89%), respectively. The median overlap of cluster 1 in VOIPET and VOIDWI was 48.03% (23.91-63.15%) and 24.40% (7.44-51.44%), respectively. Separation between clusters appeared to be defined by a SUV value. CONCLUSION: For NPC, the VOIs of DWI and FDG PET were not overlapped completely and the volume defined by cluster-analysis might be meaningful for DP.

PD-1 and PD-L1 in locoregionally advanced nasopharyngeal carcinoma: Substudy of a randomized phase III trial.

BACKGROUND: To evaluate the expression of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) by using immunohistochemistry analysis in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving cisplatin, fluorouracil, and docetaxel followed by concurrent chemoradiotherapy. METHODS: As part of a previously reported trial, 108 patients were enrolled in this study. RESULTS: We observed that Epstein-Barr Virus (EBV) antibody levels were associated with PD-1 positive staining in NPC and PD-1 positive staining was identified as an independent prognostic factor for progression-free survival (hazard ratio 0.363, 95% confidence interval 0.134-0.987, P = .047). By contrast, the correlation between the PD-L1 level and hemoglobin, lactate dehydrogenase and high-sensitivity C-reactive protein was not identified. Moreover, high levels of PD-L1 staining were not significantly associated with clinical outcomes. CONCLUSION: NPC patients with negative PD-1 staining had a significantly reduced survival outcome. Furthermore, patients with positive PD-1 staining had significantly higher EBV antibody levels.

Paranasal Sinus Invasion in Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy.

PURPOSE: The aim of this study is to evaluate the prognostic significance of paranasal sinus invasion for nasopharyngeal carcinoma (NPC) and its suitable position in the T classification. MATERIALS AND METHODS: The magnetic resonance imaging (MRI) scans of 695 patients with previously untreated, biopsy-proven, non-metastatic NPC that was treated with intensity-modulated radiotherapy (IMRT) were reviewed retrospectively. RESULTS: The incidence of paranasal sinus invasion was 39.4% (274 of 695 patients). Multivariate analysis showed that paranasal sinus invasion was an independent negative prognostic factor for local failure-free survival (LFFS) (p < 0.05). According to the eighth American Joint Committee on Cancer (AJCC) staging system, 275 patients were classified as T3 classification. Of these, 78 patients (28.4%) developed paranasal sinus invasion (T3b) and 197 (71.6%) didn't (T3a). The estimated 5-year LFFS and overall survival (OS) rates for the patients with T3b and T3a classification were 88.6% versus 95.0% (p=0.047), and 84.5% versus 93.3% (p=0.183), respectively. The estimated 5-year LFFS and OS rates for the patientswith T4 classificationwere 89.5% and 83.2%,whichwere similarwith the outcomes of patients with T3b classification. CONCLUSION: MRI-determined paranasal sinus invasion is an independent prognostic factor of NPC treated by IMRT. Paranasal sinus invasion is recommended to classify as T4 classification in the 8th AJCC staging system for NPC.

Intensity-modulated radiotherapy for elderly patients with nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to evaluate the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for elderly patients with nasopharyngeal carcinoma (NPC). METHODS: Fifty-two patients treated with IMRT were eligible for study inclusion. Comorbidity was rated using the Adult Comorbidity Evaluation-27 (ACE-27) system. RESULTS: Twenty-six patients (50.0%) had an ACE-27 score of 1; and 6 (11.5%) had an ACE-27 score of 2. Eleven patients had died and 5 (45.5%) of them died of NPC. Two patients had developed local recurrence only, 1 had developed regional recurrence only, and 7 had developed distant metastasis only. The locoregional failure-free survival, distant failure-free survival, cancer-specific survival (CSS), and overall survival (OS) rates at 5 years were 92.6%, 83.7%, 84.9%, and 69.4%, respectively. CONCLUSION: The results of treating elderly patients with NPC by IMRT were excellent. Distant metastasis remains the most difficult treatment challenge for elderly patients with NPC.

Locoregional extension and patterns of failure for nasopharyngeal carcinoma with intracranial extension.

OBJECTIVE: To evaluate the locoregional extension and patterns of failure for nasopharyngeal carcinoma (NPC) with intracranial extension to improve clinical target volume (CTV) delineation. PATIENTS AND METHODS: A total of 205 NPC patients with intracranial extension by magnetic resonance imaging (MRI) were retrospectively reviewed. RESULTS: According to the cumulative incidence rates of tumor invasion, we initially classified anatomic sites surrounding the nasopharynx into three risk grades: high risk (≥35%), medium risk (≥10-35%), and low risk (<10%). It was concluded that the anatomic sites at high risk of tumor invasion were the middle/posterior skull base and the anatomic sites adjacent to the nasopharynx. The rate of lymph node (LN) metastasis was 90.2% (185/205). Retropharyngeal region (RP) and level IIb were the most frequently involved regions. Skip metastasis occurred in only 1.6% (3/185). At their last follow-up visit, 53 patients (25.9%) had developed treatment failure. Of the 18 local failures, 12 were considered in-field failure; the other 5 were marginal; one of the patients had outside-field failure. Among the 5 patients with marginal failures, 4 occurred mainly intracranially, and 1 occurred in the floor and the left lateral wall of the nasopharynx. Of the 11 regional failures, 10 were considered in-field failures and most of them (8/10) occurred in the unilateral upper neck. CONCLUSION: For NPC with intracranial extension, primary disease and regional LN spread follow an orderly pattern and LN skipping was unusual. Clinical target volume reduction may be feasible for selected patients.

Cytomembranic PD-L1 expression in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the expression of cytomembranic programmed death-ligand 1 (PD-L1) and its clinical significance in locoregionally advanced nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded tissue biopsies from 85 patients with histological diagnosis of locoregionally advanced NPC treated with radical intensity-modulated radiotherapy and concurrent cisplatin-based chemotherapy were studied. By using immunohistochemistry staining, expressions of cytomembranic PD-L1 on tumor cells were detected. RESULTS: After a median follow-up duration of 65.8 months, 7 (8.2%), 5 (5.9%), and 5 (5.9%) patients suffered from local failure, regional failure, and distant metastases, respectively. The 5-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival (OS) rates were 90.9%, 94.8%, 94.0%, and 92.2%, respectively. Our results revealed that a high expression of cytomembranic PD-L1 was correlated with shorter OS (5y-OS: 82.5% vs 97.6%, P=0.022). In the multivariate analysis, only the cytomembranic PD-L1 was an independent prognostic factor for OS (hazard ratio: 6.176, 95% confidence interval, 1.166-32.710, P=0.032). CONCLUSION: Cytomembranic PD-L1 expression levels correlated with OS in locoregionally advanced NPC. Agreement between different methods is needed for further application of PD-L1 biomarker assays in NPC.

An evaluation of nutrition intervention during radiation therapy in patients with locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the effectiveness of nutrition intervention during radiation for patients with locoregionally advanced (III-IVa) nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We retrospectively reviewed 117 patients with locoregionally advanced (III-IVa) NPC treated between December 2015 and March 2016 in Zhejiang Cancer Hospital. All the patients underwent radical chemo-radiotherapy. First, all the patients were divided into the nutrition intervention group and the control group, depending on whether they accepted nutrition intervention. Repeated measures were used to analyze the change of nutritional indicators before, during, and after radiation therapy and to simultaneously compare the difference in nutritional status between the two groups at the same time point. Subsequently, the 117 patients were divided into the malnourished group (weight loss > 5%) and the non-malnourished group (weight loss ≤ 5%) according to whether their weight loss was over 5% of their body weight during radiotherapy. Chi-square tests and logistic regression analysis were used to explore the influence factors for the weight loss. RESULTS: The repeated measures showed that all indicators including weight, body mass index (BMI), albumin, pre-albumin(PA), and prognostic nutritional index (PNI) dramatically declined in both groups compared with their levels before radiation therapy (All p < 0.001). However, there was no significant difference between the intervention and non-intervention groups regarding the mean values of nutritional indicators at the same time point, that before, during, and after radiation therapy, except BMI (All p > 0.05). Logistic regression analysis revealed grade ≥ 3 radiation-induced oral mucositis as the prognostic factor for a poor nutrition status (odds ratio, OR = 3.232, p = 0.021, confidence interval, CI [1.198, 8.820]). Besides this, patients with a decrease of >15% in pre-albumin level were more likely to be malnourished (OR = 2.442, p = 0.041, CI [1.036, 5.757]). Similar to that observed in our former analysis, we did not find that existing nutrition intervention can significantly improve nutritional status (OR = 1.217, p = 0.704, CI [0.042, 3.348]). CONCLUSIONS: Our study shows that the nutritional status of the patients gradually declined during treatment. We concluded that grade ≥ 3 radiation-induced oral mucositis would aggravate the extent of malnutrition during radiation therapy in patients with locoregionally advanced NPC. Pre-albumin level was a predictive marker for weight loss in patients with NPC. However, current nutrition intervention during radiation therapy can't significantly reverse nutritional status.

Correlation between pretreatment serum LDL-cholesterol levels and prognosis in nasopharyngeal carcinoma patients.

PURPOSE: To investigate the correlations between long-term survival outcomes in patients with nasopharyngeal carcinoma (NPC) and pretreatment serum low-density lipoprotein cholesterol (LDL-C) levels. PATIENTS AND METHODS: Between January 2008 and December 2011, 935 patients with newly diagnosed NPC who were treated with intensity-modulated radiation therapy were included in this retrospective clinical analysis. Patients were divided into two groups based on pretreatment LDL-C levels: normal LDL-C (≤3.64 mmol/L; n=816) and elevated LDL-C (>3.64 mmol/L; n=119). Associations between pretreatment LDL-C levels and treatment outcome were analyzed by univariate and multivariate analyses. RESULTS: The overall patient follow-up rate was 95.1%, and 726 patients received more than 5 years of follow-up. Five-year overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) rates of the entire patient population were 87.1%, 91.1%, and 87.2%, respectively. Rates of 5-year OS, LC, and DMFS for the elevated versus normal LDL-C groups were 77.0% vs 89.1% (P<0.001), 85.8% vs 91.9% (P=0.041), and 81.1% vs 88.1% (P=0.038), respectively. Compared with normal LDL-C levels, elevated LDL-C levels were identified as an independent prognostic factor of a poorer OS (hazard ratio [HR] =2.171; 95% confidence interval [CI] =1.424-3.309), LC rate (HR =1.762; 95% CI =1.021-3.942), and DMFS (HR =1.594; 95% CI =1.003-2.532). CONCLUSION: This study found that elevated pretreatment LDL-C levels are negative prognostic indicators of NPC. Elevated LDL-C levels may be useful indicators of locoregional control and distant metastasis in NPC patients.