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.

Specific-CT brain template construction and retrospective dosimetric comparison study in brain for nasopharyngeal carcinoma patients treated with IMRT or VMAT.

The current Radiotherapy (RT) technology still inevitably irradiated normal brain tissue, causing implicit radiation-induced injury. This study investigates the precise localization and the corresponding radiation dosage of brain regions susceptible to damage in nasopharyngeal carcinoma (NPC) patients following RT. Utilizing the Advanced Normalization Tools (ANTs) package, a computed tomography (CT) brain template was created in the standard Montreal Neurological Institute (MNI) space, based on 803 Chinese NPC patients (T0~T4) who underwent RT. With this template, all patients' CT and RTdose data were registered to the MNI space, and the RTdose distribution characteristics in normal brain tissues were compared for NPC patients treated with Intensity-modulated radiotherapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT), with patients' age and gender as covariates. Analysis of the average dosages indicated that certain areas within the Limbic, Temporal, and Posterior Lobes, the Brainstem, and the Cerebellum Posterior Lobe were exposed to doses exceeding 50 Gy. Inter-group analysis revealed that IMRT delivered higher doses than VMAT to brain regions anterior to the nasopharyngeal tumor, whereas VMAT affected the posterior regions more. Interestingly, VMAT showed a drawback in preserving the normal brain tissues for T4-stage patients. This revealed that the two treatment modalities have unique characteristics in preserving normal brain tissue, each with advantages. With better localization precision, the created CT brain template in MNI space may be beneficial for NPC patients' toxicity and dosimetric analyses.

Long-term efficacy analysis of radiotherapy and local management of metastases in patients with newly diagnosed oligometastatic nasopharyngeal carcinoma: A prospective, single-arm, single-center clinical study.

PURPOSE: We conducted a single-center, single-arm study (NCT03129412) to prospectively analyze the long-term outcomes of newly diagnosed patients with oligometastatic nasopharyngeal carcinoma (NPC) who received radical radiotherapy and local treatment of metastases. PATIENTS AND METHODS: Patients who reached disease controll after platinum-based palliative chemotherapy continued to receive radical radiotherapy for the nasopharyngeal region and neck. Appropriate local treatments were selected to treat the metastatic lesions. The primary endpoint of this study was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). RESULTS: Fifty-one patients were included in the final analysis. During a median follow-up of 60 months, the median OS and PFS were 53.87 and 24.23 months, respectively. The 1-year, 3-year, and 5-year PFS and OS rates were 76.5 %, 38.1 %, and 31.8 % and 98 %, 75.4 %, 45.6 %, respectively. Both single and multivariate analysis indicated that maintenance therapy after radiotherapy could significantly increase PFS (36.43 vs. 16.1 months, P = 0.005). The OS of patients with single organ metastasis was significantly better than that of patients with double organ metastasis (P = 0.001). In addition, the number of metastatic organs also significantly affected PFS in the multifactor analysis. CONCLUSION: Patients with newly diagnosed oligometastatic NPC can achieve long-term survival after receiving radical radiotherapy to the primary site and local treatment for metastases.

Radiation dose escalation for locally advanced nasopharyngeal carcinoma patients with local and/or regional residual lesions after standard chemoradiotherapy: a non-randomized, observational study.

BACKGROUND: To assess the effectiveness and toxicity of radiation dose escalation for locally advanced nasopharyngeal carcinoma (LA-NPC) in patients with local and/or regional residual lesion(s) after standard treatment. METHODS: From November 2011 to November 2020, 259 LA-NPC patients who had local and/or regional residual lesion(s) after induction chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) from our hospital were included. The total dose of primary radiotherapy (RT) was 68.1-74.25 Gy (median, 70.4 Gy). The boost doses were 4.0-18.0 Gy (median, 9 Gy), 1.8-2.0 Gy/fraction. RESULTS: For all patients, the 5-year local relapse-free survival was 90.2%, regional relapse-free survival was 89.1%, locoregional relapse-free survival (LRRFS) was 79.5%, distant metastasis-free survival (DMFS) was 87.9%, failure-free survival (FFS) was 69.0%, and overall survival (OS) was 86.3%. LRRFS, DMFS, FFS, and OS in patients with age ≤ 65 versus > 65, plasma Epstein-Barr virus-deoxyribonucleic acid ≤ 500 versus > 500, T1-2 versus T3-4, N0-1 versus N2-3, and stage III versus stage IV showed no statistically significant differences. The interval between primary RT and boost was not a prognostic factor for LRRFS, DMFS, FFS, and OS. Males had a lower 3-year FFS rate than females (72.9% vs. 83.7%, P = 0.024). LA-NPCs with locally and regionally residual lesion(s) had the worst 3-year DMFS and OS rates compared with locally or regionally residual lesion(s) (77.7% vs. 98.8% vs. 87.4%, P = 0.014; 75.9% vs. 94.5% vs. 82.4%, P = 0.002). CONCLUSION: Boost radiation was an option for LA-NPCs with locally and/or regionally residual lesions after receiving IC + CCRT. It warrants further prospective study. TRIAL REGISTRATION:  Retrospectively registered.

Anti-PD-1 Monoclonal Antibody Combined With Anti-VEGF Agent Is Safe and Effective in Patients With Recurrent/Metastatic Head and Neck Squamous Cancer as Second-Line or Beyond Treatment.

Background: Numerous preclinical studies have revealed the complex regulatory mechanisms between anti-angiogenesis and immune inhibition in the tumor immune microenvironment and have proposed the efficacy of combined immunotherapy and anti-angiogenic treatment. Moreover, the combination strategy had been confirmed in a number of clinical trials. In this study, we aimed to evaluate the safety and efficacy of this combination strategy in recurrent/metastatic head and neck squamous cell carcinoma. Methods: In this real-world study, 43 patients who received the combination of programmed cell death protein 1 (PD-1) inhibitors and anti-vascular endothelial growth factor (VEGF) agents in Zhejiang cancer hospitals between March 2019 and December 2020 were reviewed. Clinical characteristics and follow-up data were collected, and the preliminary efficacy and safety of the combination therapy were assessed. Results: The median follow-up time was 12.4 months (range, 3.7-25.3 months), and the follow-up rate was 100%. The median duration of exposure was 9.5 months. Thirty-seven patients (86.0%) reported treatment-related adverse events (TRAEs) of any grade. The most frequently reported events were fatigue, decreased appetite, and hypertension. Grade 3 TRAEs occurred in 8 patients (18.6%), and no grade 4 or 5 TRAEs occurred. Twenty-four patients (55.9%) had an overall response to treatment: 6 (14.0%) had a complete response and 18 (41.9%) had a partial response. In addition, 5 (11.6%) patients had stable disease, and the disease control rate 12 was 67.4%. The median time to response was 1.6 months (range, 1.1-2.8 months). The median progression-free survival (PFS) was not reached, and the 1-year PFS rate was 69.1%. The 1-year overall survival (OS) rate was 87.7%. Patients with primary tumors located in the nasopharynx had better OS than those with tumors outside the nasopharynx. ECOG PS were related to PFS; patients with an ECOG PS of 0 had a slight survival advantage. Conclusion: The combination strategy of anti-PD-1 monoclonal antibodies and anti-VEGF agents was tolerable in patients with recurrent/metastatic head and neck cancer. This treatment exhibited antitumor potential despite the heavily pretreated population.

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.

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.

Explore the Value of Adding Induction Chemotherapy to Concurrent Chemoradiotherapy in T3-4N0M0 Nasopharyngeal Carcinoma Patients: A Retrospective Study.

PURPOSE: Patients with T3-4N0M0 nasopharyngeal carcinoma (NPC) are a unique subgroup of locoregional advanced NPC, which generally have a better prognosis than others and are often excluded in most randomized controlled clinical trials focusing on locoregional advanced NPC. The management of this population is still controversial. This study aims to evaluate the outcomes of T3-4N0M0 NPC patients treated with sequential induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT) or chemoradiotherapy (CCRT) alone. PATIENTS AND METHODS: We included 362 patients diagnosed with T3-4N0M0 NPC from two hospitals between December 2005 and December 2014. All patients were received IC + CCRT (n=146) or CCRT (n=216). Locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were retrospectively estimated. RESULTS: The median follow-up was 95 (range: 11-168) months. Univariable analyses have shown that 5-year LRFFS, DFS and OS in the IC+CCRT group and the CCRT group were 87.4% vs 93.4% (P = 0.035), 80.4% vs 87.0% (P = 0.047) and 86.3% vs 93.0% (P = 0.040). Multivariate analyses demonstrated that only the T stage was the independent prognostic factor for LRFFS, DFS, and OS in the entire group analysis. Subgroup analysis revealed that patients with T3 tumors who received IC+CCRT had significantly lower LRFFS, DFS, and OS than those treated with CCRT. For T4 patients, the outcomes had no significant difference between the two groups. CONCLUSION: This retrospective study showed that T3N0M0 patients who received CCRT had better prognosis than those treated with IC+CCRT. In terms of T4N0M0 disease, treatment outcomes are similar in both treatment groups. However, these results require further confirmation of large sample size, prospectively, randomized controlled trials.

Anti-PD1 checkpoint inhibitor with or without chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma.

PURPOSE: To compare the efficacy and safety of anti-PD1 checkpoint inhibitor plus chemotherapy with anti-PD1 checkpoint inhibitor alone in recurrent and metastatic nasopharyngeal carcinoma (R/M NPC) progressing after first or subsequent-line therapy. METHODS AND MATERIALS: A total of 67 patients with recurrent and metastatic nasopharyngeal carcinoma from our hospital were included. All patients were sorted into two arms: anti-PD1 checkpoint inhibitor+ chemotherapy arm and anti-PD1 checkpoint inhibitor arm. We retrospectively estimated objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in patients of both arms. Chi-square test and Kaplan-Meier methodology were used to analyze. RESULTS: From September 2018 to March 2020, this research included 67 patients. For anti-PD1 checkpoint inhibitor+ chemotherapy arm, partial response and stable disease were observed in fourteen and 11 patients, respectively, for an ORR of 53.8%. For anti-PD1 checkpoint inhibitor arm, complete response and partial response were observed in one and 5 patients, respectively, for an ORR of 14.6%. The incidence of hyperprogressive disease was higher in the anti-PD1 checkpoint inhibitor group compared with anti-PD1 checkpoint inhibitor+ chemotherapy group (39.0% vs 3.8%, p<0.05). Univariable analyses discovered that 6-month PFS and OS benefits were observed for anti-PD1 checkpoint inhibitor+ chemotherapy arm compared to anti-PD1 checkpoint inhibitor arm (65.4% vs. 28.6%, P = 0.001; 100.0% vs. 73.5%, P = 0.014). CONCLUSION: In present study, we revealed that adding chemotherapy to anti-PD1 checkpoint inhibitor significantly improved 6-month PFS and OS for patients with R/M NPC progressing after first-line therapy. It warrants further study.

Nutritional Status and Its Association With Radiation-Induced Oral Mucositis in Patients With Nasopharyngeal Carcinoma During Radiotherapy: A Prospective Study.

BACKGROUND AND AIMS: Malnutrition is a concern in patients with nasopharyngeal carcinoma (NPC) during chemoradiotherapy (CRT)/radiotherapy (RT), which is considered to be related with radiation-induced oral mucositis (ROM). The study aimed to evaluate the nutritional status of NPC patients during RT and investigate its association with ROM. METHODS: A prospective study was conducted in NPC patients. Patients were divided into three subgroups (mild, moderate, and severe groups) based on the duration of severe ROM (≥ grade 3). Body weight, body mass index (BMI), albumin, prealbumin, NRS2002, and ROM grade were assessed on a weekly basis before and during CRT/RT. The statistical analysis was performed in the overall group and between three subgroups. RESULTS: A total of 176 patients were included. In the overall group, body weight and BMI kept decreasing since week 1 of RT, and NRS2002 score and ROM grade increased (p < 0.001). NRS2002 score and prealbumin levels were significantly different between each subgroup (p ≤ 0.046). Significant differences were observed in the proportion of patients receiving enteral nutrition, duration of parenteral nutrition, and total calories provided by nutritional support among three subgroups (p = 0.045-0.001). CONCLUSIONS: Malnutrition occurred early in NPC patients and worsened continuously during RT. ROM was strongly associated with nutritional status. Nutritional support should be provided at the start of RT, especially in patients at high-risk of severe ROM.

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.

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.

[Surgical treatment and prognosis of Borrmann type IIII( gastric cancer involving the whole stomach].

OBJECTIVE: To explore the surgical treatment and prognosis of Borrmann type IIII( gastric cancer involving the whole stomach. METHODS: Clinicopathological characteristics and survival data of 223 patients with Borrmann type IIII( gastric cancer involving the whole stomach (defined as the tumor infiltrating 3 regions of the stomach) receiving surgical treatment at the Department of Abdominal Surgery of Zhejiang Cancer Hospital between January 2002 and December 2015 were analyzed retrospectively. The survival time of patients with different clinicopathological features and different treatment methods was compared. Cox regression was used to analyze the independent prognostic factors. RESULTS: Two hundred and twenty-three patients with Borrmann type IIII( gastric cancer involving the whole stomach accounted for 24.0% (223/930) of all Borrmann type IIII( gastric cancer cases undergoing surgical resection at the same period. There were 147 males and 76 females with an average age of 57.8 years. All the patients underwent total gastrectomy. Of these patients, radical resection was performed in 149 cases(66.8%) and palliative resection in 74 cases (33.2%). Combined organ resection was performed in 43 patients (19.3%), including 25 splenectomies, 6 pancreatic body and tail plus spleen and transverse colon resections, 2 transverse colon plus spleen resections, 2 right colon resections, 2 transverse colon resections, 2 ovariectomies, 1 partial jejunal resection, 1 pancreatoduodenectomy, 1 pancreatic tail plus transverse colon resection, and 1 partial pancreatectomy. Postoperative complications occurred in 28 patients(12.6%), including 10 patients with combined organ resection. Esophagojejunal fistula was the most frequent complication, accounting for 39.3%(11/28). Perioperative mortality occurred in 3 patients (1.3%). Thirty-nine patients underwent preoperative adjuvant chemotherapy (clinical stage: cT4aN0M0 in 1 patient, cT4bN1-2M0 in 12 patients, cT4aN1-2M0 in 20 patients, and cT4aN3M0 in 6 patients). Among these 39 patients, post-chemotherapeutic degenerative response was detected in 25 postoperative pathological specimens (64.1%), radical resection was performed in 21 patients (53.8%), distant metastasis was observed in 7 patients (17.9%) and peritoneal metastasis was found in 17 patients (43.6%) during operation. The average maximal tumor diameter was 13.2 cm (range from 6 to 22). Histological types included 23 moderate-poorly differentiated adenocarcinomas (10.3%), 146 poorly differentiated adenocarcinomas (65.5%), 41 signet ring cell carcinomas (18.4%), 11 mucinous adenocarcinomas(4.9%), 1 squamous cell carcinoma (0.4%) and 1 undifferentiated carcinoma (0.4%). Tumor-infiltrating duodenum was found in 57 patients (25.6%) and tumor-infiltrating esophagus in 132 patients (59.2%). The positive margin was found in 66 patients (29.6%): upper margin in 35 patients (15.7%), lower margin in 22 patients (9.9%), and both margins in 9 patients(4.0%). Immunohistochemical positive HER2(3+) was detected in 4 patients (1.8%). Tumor infiltrating into serosa(T4a) was found in 197 patients (88.3%) and infiltrating into adjacent organ (T4b) in 26 patients(11.7%). One hundred and forty-three cases (64.1%) had lymphatic or venous invasion, 187 (83.9%) had neural invasion, and 35 (15.7%) had cancer nodules. Of 149 patients undergoing radical resection, 5 patients were stage II(b, 9 patients were III(a, 20 patients were III(b and 115 patients were III(c. Of 145 patients(65.0%) undergoing postoperative chemotherapy, the average cycles of chemotherapy was 3.6 (median 3 cycles) and only 69 patients (47.6%) completed 4 cycles or more. Patients were followed up for 1-102 months (average 17.3 months). The median overall survival time was 13.8 months and the 1-, 3-, and 5-year survival rate was 57.9%, 14.1% and 6.8% respectively. The median survival time of the 149 cases with radical resection was 16.7 months and the 1-, 3- and 5-year survival rate was 67.5%, 16.5% and 8.4% respectively; the median survival time of the 74 cases with palliative resection was 10.3 months and the 1-, 3- and 5-year survival rate was 42.6%, 8.5% and 1.7% respectively, whose differences were statistically significant (all P=0.000). Multivariate analysis showed that tumor staging (P=0.005), radical resection (P=0.009), lymphatic or venous invasion (P=0.017) and postoperative chemotherapy (P=0.001) were independent prognostic factors. CONCLUSIONS: Surgical treatment for Borrmann type IIII( gastric cancer involving the whole stomach is safe. Radical resection can improve the prognosis though the overall survival is poor.

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.

Polyphyllin I inhibits gastric cancer cell proliferation by downregulating the expression of fibroblast activation protein alpha (FAP) and hepatocyte growth factor (HGF) in cancer-associated fibroblasts.

The aim of this study was to identify the anti-cancer mechanism of Polyphyllin I (PPI) on gastric cancer cells via its activity on cancer-associated fibroblasts (CAFs). We cultured purified gastric CAFs obtained from fresh human gastric cancer tissue and examined the effect of Polyphyllin I on CAF proliferation using a colorimetric viability assay. In addition, we established a nude mouse xenograft model to examine the effect of Polyphyllin I administration on tumorigenesis. Using Western analysis, we quantified protein expression of the CAF-derived cytokines fibroblast activation protein alpha (FAP), secreted protein acidic and cysteine rich (SPARC), stromal cell-derived factor 1 (SDF-1), hepatocyte growth factor tenascin-C (TNC), and hepatocyte growth factor (HGF) in both in vitro and in vivo models. We found that Polyphyllin I inhibits the proliferation of CAFs in a concentration-dependent manner. Following treatment with 2 µg/ml PPI for 24 h in vitro, the expression of FAP, SDF-1 and HGF protein in CAFs was significantly lower than that in the control group, but there was no significant difference in SPARC and TNC protein expression between the two groups. In the nude mouse xenograft model, the tumor inhibition rate was 45.5% when PPI was administered early and 29.4% with administration in the third week. The expression of FAP and HGF in the xenografts was significantly decreased, while the expression of SPARC, SDF-1, and TNC was largely unaltered. Altogether, these data suggest that Polyphyllin I can inhibit the proliferation of gastric cancer cells by downregulating the expression of FAP and HGF in CAFs in vivo.

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.

Effect of capilliposide for induction apoptosis in human nasopharyngeal cancer CNE-2 cells through up-regulating PUMA expression.

OBJECTIVE: To observe the apoptosis of capilliposide against human nasopharyngeal cancer CNE-2 cells and to study its primary mechanisms. MATERIALS AND METHODS: Vectors pSilencer-PUMA-small interfering RNA (siRNA) were constructed to transcribe functional siRNA specially targeting PUMA. The interfering plasmids were used to transfect CNE-2 cells with lipofectamine 2000 transfection reagent. PUMA messenger RNA (mRNA) expression levels were analyzed by polymerase chain reaction. The proliferation of CNE-2 cells was detected using MTT colorimetry. Annexin V/propidium iodide double staining was applied to detect the apoptosis rate of CNE-2 cells. The protein levels of p53, PUMA, and Bax were detected using Western blot analysis. RESULTS: Recombinant siRNA expression vector targeting PUMA was constructed. MTT assays showed capilliposide inhibited the proliferation of CNE-2 cells in a concentration-dependent manner. The inhibition was strengthened along with increased concentrations. Apoptosis detected by flow cytometry in control group, drug group, siRNA group, and drug combined siRNA group was 9.3 ± 2.3%, 31.4 ± 5.6%, 12.3 ± 4.1%, and 13.2 ± 3.7%, respectively. After pretreated by capilliposide, PUMA protein was upregulated, and BAX was distributed to mitochondria in CNE-2 cells using Western blot analysis, but this effect can be interrupted by PUMA-siRNA. CONCLUSIONS: Capilliposide could induce the apoptosis of CNE-2 cells, which might be related with the increasing in PUMA-Bax pathway.

Effect of number and ratio of positive lymph nodes in hypopharyngeal cancer.

BACKGROUND: The number and ratio of positive lymph nodes are important prognostic factors in gastric cancer, but there is little data reported in hypopharyngeal cancer. METHODS: Medical data from 81 patients with hypopharyngeal cancer undergoing radical hypopharyngectomy and cervical lymph node dissection were reviewed. RESULTS: The median survival time was 84, 54, 30, and 13 months in patients with N0, N1, N2, and N3, respectively, and 84, 51, and 17 months with positive lymph node ratios (N ratio) 0, <10%, and >10%, respectively. Of the 24 N1 patients, the 20 patients that had an N ratio <10% had a better prognosis than the 4 patients with an N ratio >10%. Similar data was seen for the N2 patients. Tumor (T) classification, adjuvant therapy, and N ratio were independent prognostic factors in multivariate analysis. CONCLUSION: The positive lymph node ratio is complementary to the current N classification system.

[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.

[Clinicopathological and prognostic analysis of 178 patients with hypopharyngeal cancer].

OBJECTIVE: To study the clinicopathological characteristics and the prognostic factors in patients with hypopharyngeal cancer. METHODS: Clinical and pathological data of 178 cases with hypopharyngeal cancer from January 2000 to December 2006 were studied. RESULTS: Of the 178 hypopharyngeal cancer, the median survival time was 42.8 months (1 - 127 months). Total 3- and 5-year survival rates were 47% and 35%, respectively. The 5-year survival rates of stage I + II, stage III and stage IV were 76.2%, 46.7% and 29.6%, respectively. The second primary carcinoma occurred in 14.0% patients (25/178), of them 18 patients with synchronous carcinoma and 7 patients with metachronous carcinoma. The independent risk factors associated with the prognosis of these patients were T staging, N staging, clinical staging, performance status (PS), smoking index and treatment model (all P < 0.01). Multivariate Cox analysis showed that smoking index, staging of tumor and treatment were independent risk factors of prognosis. The rate of larynx function preservation was increasing with years from 2000 to 2006. CONCLUSIONS: Surgery plus radiotherapy is the most important treatment for the patients with hypopharyngeal cancer. Tumor stage and treatment model are important predictors of survival in patients with hypopharyngeal cancer.