Treatment Of Recurrent Nasopharyngeal Carcinoma Research Articles

Strategies for patients with recurrent nasopharyngeal carcinoma involved internal carotid artery who are intolerant to embolization.

The surgical treatment of recurrent nasopharyngeal carcinoma (rNPC) involving the internal carotid artery (ICA) is challenging, as the massive bleeding caused by intraoperative rupture of the ICA is life-threatening. We reported that ICA embolization is an effective pretreatment to avoid fatal bleeding, but some patients cannot tolerate the procedure. We used endovascular vascular protection (ICA stents), vascular sacrifice (bypass grafting) and extravascular vascular protection (transcervical external stent placement) of the ICA to provide alternative options for these patients. METHODOLOGYy: This study enrolled patients with rNPC adjacent to or invading the ICA who were unsuitable for ICA embolization from January 2015 to June 2020. ICA pretreatment combined with endoscopic nasopharyngectomy (ENPG) was performed for the 30 patients. We report the survival outcome and incidence of complications after ICA pretreatment. ICA pretreatment was performed for the 30 enrolled patients, among whom 8 underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, 6 underwent bypass grafting, and 16 underwent ICA stent implantation followed by ENPG. After pretreatment, at a median follow-up of 43 months (range, 2-80 months), the 3-year locoregional overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 62.9%, 61.3%, 70.2%, and 71.4%, respectively. ICA pretreatment combined with salvage ENPG enables the feasible and effective resection of rNPC lesions involving the ICA in patients who cannot tolerate ICA embolization. Therefore, this treatment may be an effective method for improving outcomes. Multidisciplinary therapy is needed to reduce operation-related complications.

Strategies for patients with recurrent nasopharyngeal carcinoma involved internal carotid artery who are intolerant to embolization

BACKGROUND: The surgical treatment of recurrent nasopharyngeal carcinoma (rNPC) involving the internal carotid artery (ICA) is challenging, as the massive bleeding caused by intraoperative rupture of the ICA is life-threatening. We reported that ICA embolization is an effective pretreatment to avoid fatal bleeding, but some patients cannot tolerate the procedure. We used endovascular vascular protection (ICA stents), vascular sacrifice (bypass grafting) and extravascular vascular protection (transcervical external stent placement) of the ICA to provide alternative options for these patients. METHODOLOGYy: This study enrolled patients with rNPC adjacent to or invading the ICA who were unsuitable for ICA embolization from January 2015 to June 2020. ICA pretreatment combined with endoscopic nasopharyngectomy (ENPG) was performed for the 30 patients. We report the survival outcome and incidence of complications after ICA pretreatment. RESULTS: ICA pretreatment was performed for the 30 enrolled patients, among whom 8 underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, 6 underwent bypass grafting, and 16 underwent ICA stent implantation followed by ENPG. After pretreatment, at a median follow-up of 43 months (range, 2-80 months), the 3-year locoregional overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 62.9%, 61.3%, 70.2%, and 71.4%, respectively. CONCLUSIONS: ICA pretreatment combined with salvage ENPG enables the feasible and effective resection of rNPC lesions involving the ICA in patients who cannot tolerate ICA embolization. Therefore, this treatment may be an effective method for improving outcomes. Multidisciplinary therapy is needed to reduce operation-related complications.

Prognosis Forecast of Re-Irradiation for Recurrent Nasopharyngeal Carcinoma Based on Deep Learning Multi-Modal Information Fusion.

Radiation therapy is the primary treatment for recurrent nasopharyngeal carcinoma. However, it may induce necrosis of the nasopharynx, leading to severe complications such as bleeding and headache. Therefore, forecasting necrosis of the nasopharynx and initiating timely clinical intervention has important implications for reducing complications caused by re-irradiation. This research informs clinical decision-making by making predictions on re-irradiation of recurrent nasopharyngeal carcinoma using deep learning multi-modal information fusion between multi-sequence nuclear magnetic resonance imaging and plan dose. Specifically, we assume that the hidden variables of model data can be divided into two categories: task-consistency and task-inconsistency. The task-consistency variables are characteristic variables contributing to target tasks, while the task-inconsistency variables are not apparently helpful. These modal characteristics are adaptively fused when the relevant tasks are expressed through the construction of supervised classification loss and self-supervised reconstruction loss. The cooperation of supervised classification loss and self-supervised reconstruction loss simultaneously reserves the information of characteristic space and controls potential interference simultaneously. Finally, multi-modal fusion effectively fuses information through an adaptive linking module. We evaluated this method on a multi-center dataset. and found the prediction based on multi-modal features fusion outperformed predictions based on single-modal, partial modal fusion or traditional machine learning methods.

C-Met is a chimeric antigen receptor T-cell target for treating recurrent nasopharyngeal carcinoma

Background aimsRadiation therapy is the standard treatment for patients with nasopharyngeal carcinoma (NPC), but relapse occurs in 10% to 20% of patients. The treatment of recurrent nasopharyngeal carcinoma (rNPC) remains challenging. Chimeric antigen receptors (CAR)-T-cell therapy has achieved good outcomes in the treatment of leukemia and seems to be a promising therapeutic strategy for solid tumors. c-Met has been found to be highly expressed in multiple cancer types, and the activation of c-Met leads to the proliferation and metastasis of cancer cells. However, the expression of c-Met in rNPC tissues and whether it can be used as a target for CAR-T therapy in rNPC remain to be investigated. MethodsWe detected the expression of c-Met in 24 primary human rNPC tissues and three NPC cell lines and constructed two different antibody-derived anti-c-Met CARs, namely, Ab928z and Ab1028z. To estimate the function of these two different c-Met-targeted CAR-T cells, CD69 expression, cytotoxicity and cytokine secretion of CAR-T cells were assessed after coculture with target cells. A cell line-derived xenograft mouse model also was used to evaluate these two anti-c-Met CAR-T cells. Furthermore, we determined whether combination with an anti-EGFR antibody could promote the antitumor effect of CAR-T cells in a patient-derived xenograft mouse model. ResultsHigh c-Met expression was detected in 23 of 24 primary human rNPC tissues by immunohistochemistry staining and in three NPC cell lines by flow cytometry. Ab928z-T cells and Ab1028z-T cells showed significantly upregulated expression of CD69 after coculture with targeted cells. However, Ab1028z-T cells showed superior cytokine secretion and antitumor activity. Furthermore, Ab1028z-T cells effectively suppressed tumor growth compared with control CAR-T cells, and the combination with nimotuzumab further enhanced the tumor-clearing ability of Ab1028z-T cells. ConclusionsWe found that c-Met is highly expressed in rNPC tissues and confirmed its potential as a CAR-T target for rNPC. Our study provides a new idea for the clinical treatment of rNPC.

Innovative Fudan rT staging in endoscopic surgery for recurrent nasopharyngeal carcinoma.

American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) rT staging have great clinical impracticality. The aim of the present study was to establish a new rT staging to guide endoscopic surgery for the treatment of recurrent nasopharyngeal carcinoma (rNPC). This surgical rT staging (named Fudan rT staging) was constructed using two significant risk factors: the distance from the tumor margin to the internal carotid artery, and dural invasion. Log-rank and receiver operating characteristic (ROC) curve analyses were used to evaluate its effectiveness. Fudan rT staging can effectively separate the overall survival (OS) and progression-free survival (PFS) of patients with rNPC according to the different rT stages (p < 0.05). In addition, ROC analysis showed that the Fudan rT staging exhibited enhanced prognostic value for OS and PFS compared with the AJCC/UICC rT staging. The innovative Fudan rT staging has a better predictive value for the survival of patients with rNPC than AJCC/UICC rT staging.

Gamma Knife Radiosurgery as a Salvage Treatment for Nasopharyngeal Carcinoma with Skull Base and Intracranial Invasion (T4b).

It is usually difficult to achieve good outcomes with salvage treatment for recurrent nasopharyngeal carcinoma (NPC) because of its deep-seated location, surrounding critical structures, and patient history of high-dose irradiation. Gamma Knife radiosurgery (GKS) is a treatment option for malignancies with skull base and intracranial invasion. We conducted a retrospective, observational, single-center study including 15 patients with recurrent NPC (stage T4b) involving the skull base and intracranial invasion, who underwent GKS as a salvage treatment. Patients were enrolled over 12 years. Per a previous study, the TNM classification T4b was subclassified into T4b1 and T4b2, defined as the involvement of the skull base or cavernous sinus with an intracranial extension of &lt;5 mm and &gt;5 mm, respectively. The effect of prognostic factors, including age, sex, survival period, magnetic resonance imaging (MRI) presentation, presence of other distant metastases, tumor volume, marginal dose, maximal dose, and Karnofsky Performance Status (KPS), on outcomes was analyzed. The patients with T4b1 NPC (p = 0.041), small tumor volume (p = 0.012), higher KPS (p &lt; 0.001), and no other metastasis (p = 0.007) had better outcomes after GKS treatment, suggesting that it is a viable treatment modality for NPC. We also suggest that detailed brain imaging studies may enable the early detection of intracranial invasion.

Surgical treatment of recurrent nasopharyngeal carcinoma: promise and challenge

复发性鼻咽癌（recurrent nasopharyngeal carcinoma，rNPC）的诊治具有一定的挑战性。传统上，放疗是rNPC最常用的治疗办法。随着颅底解剖研究的不断深入和内镜颅底外科技术的发展，外科手术逐渐成为rNPC的主流治疗方式。但由于rNPC疾病本身的复杂性和周围解剖结构的重要性，使得其手术治疗仍具有较大的风险。本文从rNPC的诊断、放化疗、手术治疗以及相关并发症等方面分别进行阐述。.

Benefit of [18F] FDG PET/CT in the diagnosis and salvage treatment of recurrent nasopharyngeal carcinoma.

To compare PET/CT, MRI and ultrasonography in detecting recurrence of nasopharyngeal carcinoma and identify their benefit in staging, contouring and overall survival (OS). Cohort A included 1453 patients with or without histopathology-confirmed local recurrence, while cohort B consisted of 316 patients with 606 histopathology-confirmed lymph nodes to compare the sensitivities and specificities of PET/CT, MRI and ultrasonography using McNemar test. Cohorts C and D consisted of 273 patients from cohort A and 267 patients from cohort B, respectively, to compare the distribution of PET/CT-based and MRI-based rT-stage and rN-stage and the accuracy of rN-stage using McNemar test. Cohort E included 30 random patients from cohort A to evaluate the changes in contouring with or without PET/CT by related-samples T test or Wilcoxon rank test. The OS of 61 rT3-4N0M0 patients staged by PET/CT plus MRI (cohort F) and 67 MRI-staged rT3-4N0M0 patients (cohort G) who underwent similar salvage treatment were compared by log-rank test and Cox regression. PET/CT had similar specificity to MRI but higher sensitivity (93.9% vs. 79.3%, P < 0.001) in detecting local recurrence. PET/CT, MRI and ultrasonography had comparable specificities, but PET/CT had greater sensitivity than MRI (90.9% vs. 67.6%, P < 0.001) and similar sensitivity to ultrasonography in diagnosing lymph nodes. According to PET/CT, more patients were staged rT3-4 (82.8% vs. 68.1%, P < 0.001) or rN + (89.9% vs. 69.3%, P < 0.001), and the rN-stage was more accurate (90.6% vs. 73.8%, P < 0.001). Accordingly, the contours of local recurrence were more precise (median Dice similarity coefficient 0.41 vs. 0.62, P < 0.001) when aided by PET/CT plus MRI. Patients staged by PET/CT plus MRI had a higher 3-year OS than patients staged by MRI alone (85.5% vs. 60.4%, P = 0.006; adjusted HR = 0.34, P = 0.005). PET/CT more accurately detected and staged recurrence of nasopharyngeal carcinoma and accordingly complemented MRI, providing benefit in contouring and OS.

Dosimetric comparison of intensity modulated radiotherapy and intensity modulated proton therapy in the treatment of recurrent nasopharyngeal carcinoma.

To compare the dosimetric performance of Intensity Modulated Proton Therapy (IMPT) and Intensity Modulated Radiotherapy (IMRT) in terms of target volume coverage and sparing of neurological organs-at-risk (OARs) in salvaging recurrent nasopharyngeal carcinoma (rNPC). The maximum dose to the internal carotid artery (ICA) and nasopharyngeal (NP) mucosa, which are associated with potential carotid blowout and massive epistaxis, were also evaluated. IMRT and IMPT treatment plans were created for twenty patients with locally advanced rNPC. Planning Target Volume (PTV) was used to account for the setup and spatial error/uncertainty in the IMRT planning. Robust optimization on Clinical Target Volume (CTV) coverage with consideration of range and setup uncertainty was employed to produce two IMPT plans with 3-field and 4-field arrangements. The planning objective was to deliver 60 Gy to the PTV (IMRT) and CTV (IMPT) without exceeding the maximum lifetime cumulative Biologically Effective Dose (BED) of the neurological OARs (applied to the Planning organs-at-risk volume). The target dose coverage as well as the maximum dose to the neurological OARs, ICA, and NP mucosa were compared. Compared with IMRT, 3-field IMPT achieved better coverage to GTV V100% (83.3% vs. 73.2%, P <0.01) and CTV V100% (80.5% vs. 72.4%, P <0.01), and lower maximum dose to the critical OARs including the spinal cord (19.2 Gy vs. 22.3 Gy, P <0.01), brainstem (30.0 Gy vs. 32.3 Gy, P <0.01) and optic chiasm (6.6 Gy vs. 9.8 Gy, P <0.01). The additional beam with the 4-fields IMPT plans further improved the target coverage from the 3-field IMPT (CTV V98%: 85.3% vs. 82.4%, P <0.01) with similar OAR sparing. However, the target dose was highly non-uniform with both IMPT plans, leading to a significantly higher maximum dose to the ICA (∼68 Gy vs. 62.6 Gy, P <0.01) and NP mucosa (∼72 Gy vs. 62.8 Gy, P <0.01) than IMRT. IMPT demonstrated some dosimetric advantage over IMRT in treating rNPC. However, IMPT could also result in very high dose hot spots in the target volume. Careful consideration of the ICA and NP mucosal complications is recommended when applying IMPT on rNPC patients.

Effect of triptolide and chemotherapy on carcinoembryonic and carbohydrate antigens levels and first-line treatment of recurrent nasopharyngeal carcinoma.

To investigate the first-line treatment of recurrent Nasopharyngeal Carcinoma treprimcab combined with chemotherapy. From January 2019 to January 2020, 48 patients with recurrent nasopharyngeal Carcinoma (RNPC) were treated in our hospital. According to the method of the random number, 24 patients were divided into the combined group and the Control Group. The patients in the combined group were given the Combined Treatment of triptolide and chemotherapy. While the Control Group only received chemotherapy. The therapeutic effects and adverse reactions of the two groups were compared, the levels of Carcinoembryonic Antigen (CEA) and carbohydrate Antigen 19-9 (CA19-9) were measured before and after treatment. The total effective rate of the combined group was 79.17% higher than that of the control group (62.50%). The total effective rate of the two groups was statistically significant (P & Lt; 0.05). The incidence of grade i/ii adverse reaction in the control group was lower than that in the combined group, such as nausea and vomiting, oral mucositis, Leukopenia, liver and kidney function damage, central granulocyte count reduction, anaemia adverse reaction. The incidence of grade iii/iv Adr in the control group was higher than that in the combined group. The incidence of grade i/ii Adr in the thrombocytopenia group was higher than that in the combined group, and the incidence of grade iii/iv Adr in the control group was lower than that in the combined group. The side effects of nausea and vomiting and oral mucositis in the control group and the combined group were statistically significant (P & Lt; 0.05). There was no significant difference between the control group and the combined group in the incidence of Leukopenia, liver and kidney injury, neutrophil, anaemia and Thrombocytopenia (P & GT; 0.05). The level of CD4 + / CD8 + in control group and combined group before treatment was higher than that after treatment (P & Lt; 0.05). The quality of life of the combined group was 91.67% higher than that of the control group (70.83%). The quality of life of the control group was significantly higher than that of the combined group (P & Lt; 0.05). The levels of CEA and CA19-9 in the two groups after treatment were lower than those before treatment, and the levels of CEA and CA19-9 in the combined group were lower than those in the control group (P & Lt; 0.05). The first-line treatment of recurrent nasopharyngeal Carcinoma with triprimmab combined with chemotherapy has a good clinical effect and has a broad clinical research prospect.

Preliminary Efficacy Report and Prognosis Analysis of Endoscopic Endonasal Nasopharyngectomy for Recurrent Nasopharyngeal Carcinoma.

Background: Compared with radiotherapy, endoscopic endonasal nasopharyngectomy (EEN) is increasingly used to treat recurrent nasopharyngeal carcinoma (NPC) because of its good prognosis and mild complications. This study aims to investigate the efficacy of EEN in the treatment of recurrent NPC and factors affecting prognosis.Methods: This study included all patients who received EEN for recurrent nasopharyngeal carcinoma from April 2016 to April 2020. All operations were performed in Xiangya Hospital Central South University. The patient's 2-year overall survival (OS) rate, disease-free survival (DFS) rate and significant prognostic factors are reported.Results: There were 38 (67.9%) males and 28 (32.1%) females, with a median age of 43 (range, 24–69 years).43 (76.8%) of the patients in our study were in advanced rT3-rT4 stage and 32 (74.4%) of the patients in the advanced stage had tumor growth closely related to the internal carotid artery (ICA). During a mean follow up period of 44 month (range 1–65 months) post-surgery. The 2-year OS rate was 48.6%, 2-year DFS rate was 42.6%. The 2-year OS rates of rT1-2 and rT3-4 recurrent NPC were 83.9 and 35.6%, respectively. The 2-year DFS rates of rT1-2 and rT3-4 recurrent NPC 76.2 and 56.3%. The advanced T stage were associated with a poor prognosis in terms of OS and DFS.Conclusions: Data indicate that T staging may be an independent prognostic factor for OS and DFS. Through proper preoperative evaluation, EEN is an alternative treatment option for advanced recurrent NPC that ensures a certain level of efficacy and is relatively safe with few complications. However, additional studies with long-term follow-up and a larger sample size are required.

Stereotactic radiation therapy for recurrent nasopharyngeal carcinoma

: Radiation therapy is the mainstay treatment modality for nasopharyngeal carcinoma. Recurrent disease affects about 10% of patients, and reirradiation is the most common treatment for recurrent nasopharyngeal carcinoma. Serious complications are not uncommon during the second course of radiation therapy because of the full-tolerance radiation dose applied to normal tissue. Catastrophic toxicity may be induced by treatment for recurrent nasopharyngeal tumor. Salvage surgery has a 3-year overall survival of 85.8% with a 5% incidence of late fatal toxicity. However, the surgical approach is still relatively new with limited information and experience regarding its optimal implementation. Another technique used for recurrent nasopharyngeal carcinoma is stereotactic radiation therapy (SRT), which delivers radiation to a specific target with a rapid dose fall-off to adjacent normal tissue that can reduce the risk of complications. Single-shot radiation therapy for nasopharyngeal carcinoma has a local control rate of up to 72% for 2 years, although there is a 10% chance of cranial neuropathy and temporal lobe necrosis. Conventional fractionated SRT has shown a 3-year control rate of 56% with complications of 11% nasopharyngeal necrosis and 8.3% nasal bleeding. Hypofractionation SRT with a large fraction dose has demonstrated a 5-year control rate of 78% with a 12.5% to 16% incidence of fatal complications. Local recurrent nasopharyngeal carcinoma with a limited volume should be treated with SRT. For reirradiation, the dose constraints in organs at risk (OARs) of recurrent nasopharyngeal carcinoma are critical. Despite the lack of data regarding SRT, the radiation doses of OARs in SRT may be converted to a biologically equivalent dose and summed with doses of primary radiation therapy for evaluation. Hypofractionation may have an optimal treatment response rate with acceptable complications. For recurrent nasopharyngeal carcinoma, SRT has shown certain therapeutic advantages, but conventional fractionation radiation therapy may still be the appropriate setting for reirradiation. Patients undergoing SRT should be counseled carefully before initiation of therapy, especially if the targets are close to a critical organ that may cause serious side effects. The treatment decision of recurrent nasopharyngeal carcinoma should be based on the patient’s overall condition and disease status.

PH-0169: Dosimetric comparison of IMRT and IMPT in the treatment of recurrent nasopharyngeal carcinoma

PH-0169: Dosimetric comparison of IMRT and IMPT in the treatment of recurrent nasopharyngeal carcinoma

Efficacy and Prognosis of CT-Guided Implantation of 125I Seeds As Salvage Treatment for Recurrent Nasopharyngeal Carcinoma after External Beam Radiotherapy--a Long-Term Experience at a Single Institution

To assess the safety and efficacy of computed tomography (CT)-guided 125I seeds implantation for recurrent nasopharyngeal carcinoma (NPC) after external beam radiotherapy (EBRT). Twenty-nine patients with recurrent NPC (thirty-nine lesions) after EBRT from February 2003 to December 2017 were enrolled. All the patients experienced preoperative assessment, patient immobilization, and CT scan, preoperative planning, 125I seeds implantation, postoperative dosimetry assessment, and postoperative care. Median radioactivity of 125I seeds was 0.61 (range, 0.22-0.79) mCi. Median number of implanted seeds was 34 (3-83). Median value of D90 was 136 (62.4-246) Gy. The adverse event was evaluated by the Radiation Therapy Oncology Group (RTOG) classification criteria. Overall survival (OS), local control (LC), local progression-free survival (LPFS), were investigated for their relationship with the prognosis. Median duration of follow-up was 13.7 (4.4-71.2) months. Median duration of LC was 31.6 (2.1-60.2) months. LC at 1, 3, and 5 years was 69.0%, 46.7% and 18.7%, respectively. Median duration of OS was 33.4 (4.4∼71.2) months. OS at 1-, 3- and 5-years was 73.8%, 40.8% and 40.8%, respectively. Median duration of LPFS was 22.6 (3.0-60.2) months. LPFS at1-, 3- and 5-years was 72.0%, 38.7% and 38.7%, respectively. Univariate analysis suggested that sex(P=0.048) and frequency of previous external beam radiotherapy (P=0.018) were prognostic factors influencing survival without local recurrence. Moreover, sex (P=0.023), frequency of previous EBRT (P=0.001), time from the first EBRT to seeds implantation (P=0.007), and D90 (P=0.049) were prognostic factors influencing LC. Multivariate retrospective analysis indicated that sex (P=0.03) was an independent prognostic factor for survival without local recurrence. Prevalence of side effects (≥grade 3) was 20.7%. 125I seeds implantation was a safe and feasible salvage treatment for recurrent NPC after EBRT.

Clinical efficacy and safety of hypofractionated three-dimensional conformal radiotherapy in the treatment of recurrent nasopharyngeal carcinoma

Objective To evaluate the clinical efficacy and safety of the hypofractionated three-dimensional conformal radiotherapy in the treatment of recurrent nasopharyngeal carcinoma. Methods Clinical data of 153 patients with recurrent nasopharyngeal carcinoma admitted to our hospital from 2008 to 2013 undergoing hypofractionated three-dimensional conformal radiotherapy (3 Gy for each time, 5 times a week, a total dose of 51-60 Gy, 17-20 times/4 weeks) were retrospectively analyzed. The short-and long-term radiation-induced injury, Karnofsky performance score (KPS), short-and long-term clinical efficacy were evaluated. Results For the short-term radiation-induced injury, the incidence of oral mucosa and fatigue significantly differed before and after treatment (both P<0.05). Regarding the long-term radiation-induced injury, the incidence of dry mouth (95.4%) and deafness (51.0%), difficulty in opening mouth (79.1%), maxillofacial fibrosis (33.3%) and radiation-induced encephalopathy (15.0%) significantly differed before and following treatment (all P<0.05). The actual long-term radiation-induced injury included dry mouth (91.5%), deafness (50.9%), difficulty in opening mouth (76.5%), maxillofacial fibrosis (32.0%) and radiation-induced encephalopathy (14.4%). The number of patients with changes in the KPS scores significantly differed between the end of treatment and 3 months after treatment (P<0.05). The local control rates were 29.4%, 68.6%, 79.1%, 83.7% and 86.9% at 1-, 3-, 6-, 9-and 12-month after corresponding treatment, respectively. The local control rate significantly differed between 1 and 3 months, and between 3 and 6 months after treatment (both P<0.05). The 1-, 2-, 3-, 4-and 5-year survival rates were calculated as 96.1%, 80.4%, 68.5%, 57.9% and 51.1%, respectively. Conclusions Hypofractionated three-dimensional conformal radiotherapy is an efficacious and safe treatment of recurrent nasopharyngeal nasopharyngeal carcinoma, which yields relatively high short-and long-term clinical efficacy, high local control rate and well tolerance by the patients. Key words: Nasopharyngeal neoplasm recurrence/three-dimensional conformal radiotherapy; Radiotherapy, hypofractionated; Radiation-induced injury; Treatment outcome

The immunologic advantage of recurrent nasopharyngeal carcinoma from the viewpoint of Galectin-9/Tim-3-related changes in the tumour microenvironment

Given salvage treatment for recurrent nasopharyngeal carcinoma (NPC) remains a clinical dilemma, immunotherapy targeting NPC-specific immunosuppression may bring new hope. We analyzed the expression of CD8, CD4, Foxp3 and Tim-3 in lymphocytes, and of Galectin-9 in tumour cells between paired primary and recurrent NPC from 95 patients and we noted that there was significant increase in the expression of Galectin-9+ tumour cells (p < 0.001) and Foxp3+ lymphocytes (p < 0.001) but a significant decrease in the expression of CD8+ lymphocytes (p = 0.01) between paired primary and recurrent NPC. Of all patients, 53 patients (55.79%) and 57 patients (60%) had increased percentages of Galectin-9+ tumour cells and of Foxp3+ lymphocytes, respectively. Conversely, 42 patients (44.21%) had decreased percentages of CD8+ lymphocytes. The patients with high Galectin-9 expression in recurrent NPC frequently also had high Tim-3 (p = 0.04) and Foxp3 (p = 0.01), and low CD8 (p = 0.04) expression in lymphocytes. After multivariate analyses, low CD8 expression in lymphocytes was an independent risk factor for relapse-free survival (p = 0.002) and overall survival (p = 0.02). Our data suggests that recurrent NPC may had more immunologic advantage than primary NPC, especially the Galectin-9/Tim-3 pathway. The immunotherapies targeting Galectin-9/Tim-3/Foxp3 interaction may serve as a potential salvage treatment for recurrent NPC.

Efficacy and safety of recombinant human adenovirus p53 combined with chemoradiotherapy in the treatment of recurrent nasopharyngeal carcinoma.

This study aims to explore the efficacy and safety of recombinant human adenovirus p53 (rAd-p53) combined with chemoradiotherapy (CRT) in the treatment of recurrent nasopharyngeal carcinoma (NPC). A total of 162 recurrent NPC patients were selected and divided randomly into the rAd-p53+CRT, CRT, and rAd-p53 groups. An electrochemical luminescence immune analyzer was used to detect serum levels of tumor markers (carcinoembryonic antigen, cancer antigen 199, and cancer antigen 153). Efficacy evaluation was in accordance with Response Evaluation Criteria in Solid Tumor. Toxicity evaluation was performed according to the WHO grading standard. A 3-year follow-up was performed. A Kaplan-Meier curve was drawn to calculate progression-free survival and the 3-year survival rate. The complete response rate and effective rate (complete response+partial response) of recurrent NPC patients in the rAd-p53+CRT group were higher than those in the CRT and rAd-p53groups. After treatment, compared with the CRT and rAd-p53 groups, the rAd-p53+CRT group had lower serum levels of carcinoembryonic antigen, cancer antigen 199, and cancer antigen 153. The incidences of leukopenia and oral mucositis in the rAd-p53+CRT group were lower than those in the CRT group, but no differences were found between the rAd-p53+CRT and rAd-p53 groups. The progression-free survival and 3-year survival rate of recurrent NPC patients in the rAd-p53+CRT group were higher than the than those in the CRT and rAd-p53 groups. Our study supports that rAd-p53 combined with CRT may provide better efficacy and lower toxicity than rAd-p53 or CRT alone for the treatment of recurrent NPC patients.

Endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma: a review of 71 patients and analysis of the prognostic factors

To evaluate the efficacy of endoscopic nasopharyngectomy in the management of recurrent nasopharyngeal cancers (NPC) and to identify the prognostic factors. Between January 2006 and March 2014, 71 patients who received endoscopic nasopharyngectomy for recurrent NPC were retrospectively reviewed. The sex and the age of the patients, T stage, and tumor necrosis were recorded. Correlation between clinicopathological features and survival time was analyzed. Kaplan-Meier analysis was used to calculate the disease overall survival, disease-specific survival, and disease-free survival rates. Cox multivariate regression analysis and ROC curve analysis were used to determine the predictive value of the parameters. The median age of 71 patients with recurrent nasopharyngeal carcinoma was 51.0 years old. Male to female ratio was 2.9:1 (male: 53, female: 18). The lesions were staged as follows (AJCC, 2010, seventh edition): rT1, 27; rT2, 10; rT3, 19 and rT4, 15. All patients underwent successful endoscopic nasopharyngectomy. No patient was transferred to open approach. The mean operative time was 155 minutes. The average blood loss was 450 ml. Three patients needed intraoperative blood transfusion. No serious postoperative complications occurred. Postoperative follow-up time was 5-96 months. During follow-up, 48 cases survived, including that 7 patients survived with disease, 1 patient had pulmonary metastases, and 1 case had cervical lymph node metastasis. Two-year overall survival and disease-free survival rates were 74.0% and 60.5%, respectively. Five-year overall survival and disease-free survival rates were 39.0% and 31.9%, respectively. Multivariate analysis showed that tumor necrosis was an independent prognostic factor for survival in recurrent nasopharyngeal carcinoma patients (P=0.001). Endoscopic nasopharyngectomy is a safe and effective procedure for the treatment of recurrent nasopharyngeal carcinoma.

Efficacy analysis of IMRT on 22 cases with recurrent nasopharyngeal carcinoma

Objective To analyze the efficacy of IMRT in the treatment of recurrentnasopharyngeal carcinoma. Methods Clinical data of 22 patients with recurrent nasopharyngeal carcinoma （NPC）were retrospectively analyzed,We have recurrent NPC tune the amount of synchronization push radiation therapy in patients with clinical data,treatment efficacy and acute toxicity were analyzed.Results All patients were hospitalized on average 50 days, between median follow-up period of 12 months.At the end of 22 patients with no treatment deaths,three deaths （both metastasis） during follow-up,overall survival 86.3%（19/22）,local recurrence in 2 cases,2 cases of bone metasta-sis,1 case of throat and neck lymph node metastasis.The local control rate was 63.6%（14/22）.Acute toxicity main-ly acute skin,oropharyngeal mucosa （12 cases） and bone marrow suppression （4 cases）.1 patient had symptoms of hearing loss and auditory nerve damage,1 case of necrosis of the mandible,all symptoms of dry mouth in patients with radiotherapy were heavier than that of the first drive.Conclusion With the growing popularity of IMRT,NPC patients had significantly improved overall survival, but distant metastasis and recurrence of the tumor, radiotherapy again cause adverse reactions in clinical practice still needs further development and improvement,IMRT treatoffing with re-current nasopharyngeal has broad prospects. Key words: Nasopharyngeal neoplasms/recurrence; Intensity modulated radiation therapy

Reirradiation with robotic stereotactic body radiotherapy for recurrent nasopharyngeal carcinoma.

Recurrent nasopharyngeal carcinoma (NPC) after previous radiotherapy is challenging. There is no standard approach for salvage treatment. Here we present toxicity and treatment results for recurrent NFC patients who underwent fractionated stereotactic radiotherapy (FSRT) as second line radiotherapy (RT). Between April 2009 and July 2012, 24 patients, with a male to female ratio of 3:1, were treated with CykerKnife® FSRT for recurrent NFC in our institution. Seven out of 24 patients had metastatic recurrent disease. Median age was 53 years (range, 20-70 years). Initial RT dose was 70Gy. The time period between initial RT and FSRT was a median of 33.2 months. The median prescription dose for FSRT was 30Gy (range, 24-30 Gy) in a median of 5 fractions (range, 4-6). The median follow-up for all patients was 19.5 months (IQR: 12.2. -29.2 months). The locoregional control; progression free survival and overall survival (OS) rates for 1-, 2- and 3-year were 64%, 38%, 21%; 60%, 30%, 17% and 83%, 43%, 31%, respectively. Median OS for the entire cohort was 22 months (95% CI: 16.5-27.5). On multivariate analysis recurrent tumor stage was the only prognostic factor for OS (p=0.004). One patient exhibited grade III temporal lobe necrosis. One died because of grade IV mucositis and overlapping infection. The treatment of recurrent NPC is controversial. Fractionated stereotactic radiotherapy is promising. However, the published trials are heterogeneous with respect to the selection criteria and treatment details. Prospective studies with long term follow-up data are warranted.