Endovascular treatment of a ruptured pseudoaneurysm of the internal carotid artery in a patient with nasopharyngeal cancer:A case report

BACKGROUND Radiation therapy(RT)for nasopharyngeal cancer can cause several complications.In rare cases,an internal carotid artery pseudoaneurysm can occur,which can be fatal.We report the experience of a nasopharyngeal cancer patient who underwent radiation therapy and subsequently developed a fatal pseudoaneurysm of the petrous internal carotid artery.CASE SUMMARY A 39-year-old man was diagnosed with nasopharyngeal cancer 2 years ago(American Joint Committee on Cancer Stage T3N2M0)and received concurrent chemoradiation therapy.He subsequently relapsed and received chemotherapy.One week after the 4th cycle of chemotherapy,he was admitted to the emergency room of our hospital because of massive epistaxis accompanied by a headache.A pseudoaneurysm of the petrous internal carotid artery was confirmed by digital subtraction angiography(DSA).Stent-assisted endovascular coil embolization was performed and complete occlusion was achieved.No pseudoaneurysm was observed on DSA after coil embolization;however,intermittent epistaxis was maintained even after coil embolization.After seven days,a diagnostic laryngoscopy was performed.Massive bleeding occurred after aspiration of the blood clot during the laryngoscopy and the patient died of hypovolemic shock.In this case,epistaxis may have been a sign of pseudoaneurysm;therefore,treatment such as embolization should be performed promptly,and careful management should be undertaken after treatment.CONCLUSION This case highlights a rare,serious complication of RT in nasopharyngeal cancer and how it should be recognized and treated.

The Current Status of the Delineation and Determination of the Targets and the Radiation Protocols for Nasopharyngeal Cancer with Intensity-Modulated Radiotherapy

IMRT has increased the local-regional control and decreased the complications from treating nasopharyngeal cancer （NPC）. Therefore studying IMRT is important. CT and MRI are complementary, and their joint use is currently considered to be the optimal modality to delineate the extent of the primary spread of NPC. The key problem in delineation of the neck nodes is how to translate anatomic node regions into the CT boundaries. The consensus guideline which narrowed the gap among different cancer centers is recommended in delineating the boundary of the cervical lymph node regions. The definition of the NPC GTV is clear and almost the same among the main cancer centers in their IMRT planning protocols. The suggested biological dose to the GTV is close to or more than 80 Gy; the main differences are the definitions of the CTVs and their schemes for the prescribed dose, and also the dosage to the high cervical region is different among those centers. According to their long-term follow-up results, it is suggested that, besides adding 5-10 mm margins to the primary lesions, the immediate high-risk structures （including the entire nasopharyngeal cavity, retropharyngeal space, clivus, base of the skull, pterygoid plates and muscles, parapharyngeal space, the sphenoid and partial ethmoid sinuses, the posterior third of the maxillary sinuses and the nasal cavity） should also be included with a prescription of more than 60 Gy, and the bilateral Ib, II and Va node levels should be ranked as high-risk regions and differentially prescribed for treatment with no less than 60 Gy.

Prognosis and Survival of Nasopharyngeal Cancer in Cameroon

Background: Nasopharyngeal carcinoma (NPC) is an entity belonging to up-per aerodigestive tract Cancers. NPC is more widespread in Southern China and South East Asia. In our country, it is the leading cause of head and neck cancers. Its prognosis remains bleak because of the late stage at diagnostic. Objectives: The objectives of this study were to determine the prognostic fac-tors and survival rate of patients with nasopharyngeal cancer in six reference hospitals in Cameroon. Material and Methods: It was a retrospective analytic study, conducted from January 2009 to December 2018. It was conducted in oncology, surgery and Ear Nose and Throat (ENT) units of six reference hos-pitals. Data from 114 files meeting the inclusion were collected. We have drawn survival curves and determined the different survival probabilities with the help of Kaplan-Meier Method. The different survival curves were compared using the Log-Rank Test (P < 0.05), variables that were statistically associated with the 5% cut off were introduced into the Cox regression model for multivariate analysis, thus allowing us to bring out the prognostic factors significantly associated with survival. Results: The mean age at the time of diagnosis of the 114 patients recruited was 45.30 ± 17.14 years. The predominant histological type was the UCNT (Undifferentiated Carcinoma of the NasoPharynx) representing 84.2%. According to the WHO classification, 2 patients were classified as stage I (1.8%), 33 as stage II (28.9%), 42 as stage III (36.8%), 25 as stage IV A (21.9%) and 12 as stage IV B (10.5%). At the end of the survival assessment period, 34 patients were dead and 73 patients (64%) were still alive. The median overall survival was 44 months. The overall survival rates at one, two, three, and four years were 80%;74%;68%;44%, respectively. The prognostic factors associated with poor survival were: late consultation time of more than 12 months, N3 lymph node involvement, 3 and 4 advanced clinical stages. Conclusion: The study showed a low survival, with a median overall survival of 44 months. The overall survival rates at one, two, three, and four years were 80%;74%;68%;44% respectively. The prognostic factors associated with poor survival were late consultation time of more than 12 months, N3 lymph Node involvement, 3 and 4 advanced clinical stages. In order to improve this survival, it is recommended that special emphasis be placed on early detection.

PhaseⅠ/Ⅱtrial evaluating concurrent carbon-ion radiotherapy plus chemotherapy for salvage treatment of locally recurrent nasopharyngeal carcinoma

Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can beneit from these treatments. Re-irradiation with X-ray—based intensity-modulated radiotherapy(IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radioresistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy(CIRT). In addition, CIRT is a high linear energy transfer(LET) radiation and provides an increased relative biological efectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 Gy E(gray equivalent), at 2.5 Gy E per daily fraction, was well tolerated in patients who were previously treated for NPC with a deinitive dose of IMXT. The short-term response rates at 3–6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can beneit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneits of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results.Methods and design: The maximal tolerated dose(MTD) of re-treatment using raster-scanning CIRT plus concurrent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 Gy E(2.5 Gy E × 21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Eicacy in terms of overall survival(OS) and local progression-free survival of patients after concurrent chemotherapy plus CIRT at the determined MTD will then be studied in the phase II stage of the trial. We hypothesize that CIRT plus chemotherapy can improve the 2-year OS rate from the historical 50% to at least 70%.Conclusions: Re-treatment of locally recurrent NPC using photon radiation techniques, including IMXT, provides moderate eicacy but causes potentially severe toxicities. Improved outcomes in terms of eicacy and toxicity proile are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemotherapy for locally recurrent NPC remains to be determined. In addition, whether the addition of chemotherapy to CIRT is needed remains unknown. These questions will be evaluated in the dose-escalating phase I and randomized phase II trials.

Clinical characteristics and changes in living quality of patients with radiation encephalopathy induced by radiation therapy for treating nasopharyngeal carcinoma

BACKGROUND： Radiation encephalopathy （RE） caused by radiation therapy of nasopharyngeal carcinoma severely influences patients＇ quality of life （QOL）. The factors, which influence such patients＇ QOL, have not been confirmed. OBJECTIVE： To observe the clinical and imageological characteristics of patients with radiation therapy of nasopharyngeal carcinoma-induced RE and the changes in QOL, and analyze QOL influencing factors. DESIGN： Retrospective case analysis. SETTING： Department of Neurology, the Second Affiliated Hospital of Sun Yat-sen University. PARTICIPANTS： Eighty-nine inpatients or outpatients with RE induced by radiation therapy of nasopharyngeal carcinoma admitted to Sun Yat-sen University Cancer Center and Department of Neurology, the Second Affiliated Hospital of Sun Yat-sen University from March 1994 to August 2004 were involved in this experiment. They all met the diagnosis criteria of RE from MERRITT＇S neurology （10th edition）. Thirty-three involved patients were randomly chosen as RE group. Another 34 concurrent inpatients or outpatients with nasopharyngeal carcinoma who received radiation therapy but without RE were chosen as control group. Informed consents of detected items were obtained from all the involved subjects. METHODS： （1） Patients were evaluated when they were followed up. The World Health Organization Quality of Life Questionnaire abbreviated version （WHOQOL-BREF） was used for on-the-spot evaluation. High points of WHOQOL-BREF indicated better QOL. The Late Effects on Normal Tissues - Subjective, Objective, Management and Analytic （LENT-SOMA） scale for evaluating radiation injury was used to evaluate headache and neurologic disorder of patients with RE induced by radiation therapy of nasopharyngeal carcinoma. The evaluation was graded into 5 degrees. High degrees indicted severer clinical symptoms. （2） Disease latency （i.e. time interval from symptoms and body signs appearing or radiation therapy ending to onset）, initial symptoms, common symptoms, imageological characteristics, QOL and other related factors of patients were recorded. （3） Statistical management was carried out with SPSS 10.0 software. MAIN OUTCOME MEASURES： QOL and clinical characteristics of patients with RE induced by radiation therapy of nasopharyngeal carcinoma as well as QOL influencing factors. RESULTS： All the involved subjects participated in the final analysis. （1） Disease latency of patients with RE ranged from 0 to 24 years, and 95% confidence interval was 0 to 15 years. There were significant differences in amount of invaded cases between 6 months after one radiation therapy and 6 months after two or more radiation therapies （ x^2=36.76, P 〈 0.01）. （2） The common initial symptom of patients with RE was glossopharyngeal paralysis （33 cases, 37%）. （3） The first 3 common symptoms of patients with RE were glossopharyngeal paralysis （52 cases, 58%）, limb inertia and sensory disorder （25 cases, 28%） and headache （25 cases, 28%）.（4）Imageology of patients with RE was characterized by long TI and T2 signal shadow on magnetic resonance. （5）Total scores of health, of daily life and of social relationship, measured with WHOQOL-BREF, of patients in RE group were significantly lower than those in the control group, respectively [ （2.06 ± 0.86） points vs. （2.59 ± 0.66） points; （2.45 ± 0.75 ） points vs. （2.91 ± 0.75 ） points; （51.67±15.24） points vs. （59.22±13.03） points, P 〈 0.05]. Patients undergoing two or more radiation therapies were inferior to those undergoing one radiation therapy in total scores of health, and of daily life, scores of physiology, and of psychology （P 〈 0.05）. （6）Glossopharyngeal paralysis was negatively correlated with scores of psychology, total scores of daily life and of health in WHOQOL-BREF （P 〈 0.05）; Head was negatively correlated with scores of psychology in WHOQOL-BREF （P 〈 0.05）; Neurologic deficit was negatively correlated with scores of psychology, and total scores of health in WHOQOL-BREF （P 〈 0.05）. CONCLUSION： （1）The latency of RE of patients undergoing two or more radiation therapies is remarkably shortened, and QOL is decreased, but there is no difference in QOL between two genders. （2） Brain edema is common in imageology of RE after radiation therapy. The first 3 ones of initial symptoms and common symptoms both are glossopharyngeal paralysis, neurologic deficit and headache, which greatly negatively influence QOL of patients.

Effect of WNT5A on epithelial-mesenchymal transition and its correlation with tumor invasion and metastasis in nasopharyngeal carcinoma

Objective:To investigate the correlation between nasopharyngeal carcinoma cell WNT5A and epithelial-mesenchytnal transition(emt)/metastasis,and investigate its possible mechanisms.Methods:RT-PCR and gene transfection were used to detect the expression of nasopharyngeal carcinoma cell strains WNT5A and EMT related factor 5-8F.Transient transfcction of NPC cell line 5-8F was determined by liposome of plasmid with WNT5A gene.The differential expressions of WNTSA and EMT-related factors in cells before and after transfection were detected by RTPCR.Cell scratch assay and Transwell assay were used to detect the motility abilities of cells before and after 5-8F transfection.Results:The expressions of WNT5A and EMT related factors matrix metalloproleinasc-2 of the WNTSA transferred group in the nasopharyngeal carcinoma cell line 5-8F were higher than the blank control group and the empty vector transferred group,and the transfer ability of the WNTSA transferred group was higher than that in the blank control group and the empty vector transferred group,while the expressions of EMT related factors E-cadherin were lower than that in the blank control group and the empty vector transferred group,and the transfer ability of the WNT5A transferred group was higher than that in the blank control group and the empty vector transferred group.Conclusions:In nasopharyngeal carcinoma cells,WNT5A can regulate the epithelial-mesenchymal transition and affect the ability of tumor invasion and metastasis of nasopharyngeal carcinoma.

Preclinical evaluation and pilot clinical study of [^(18)F]AlF-labeled FAPI-tracer for PET imaging of cancer associated fibroblasts

In recent years,fibroblast activation protein(FAP)has emerged as an attractive target for the diagnosis and radiotherapy of cancers using FAP-specific radioligands.Herein,we aimed to design a novel^(18)Flabeled FAP tracer([^(18)F]Al F-P-FAPI)for FAP imaging and evaluated its potential for clinical application.The[^(18)F]Al F-P-FAPI novel tracer was prepared in an automated manner within 42 min with a non-decay corrected radiochemical yield of 32±6%(n=8).Among A549-FAP cells,[^(18)F]Al F-P-FAPI demonstrated specific uptake,rapid internalization,and low cellular efflux.Compared to the patent tracer[^(18)F]FAPI-42,[^(18)F]Al F-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo.Micro-PET imaging in the A549-FAP tumor model indicated higher specific tumor uptake of[^(18)F]Al F-P-FAPI(7.0±1.0%ID/g)compared to patent tracers[^(18)F]FAPI-42(3.2±0.6%ID/g)and[68 Ga]Ga-FAPI-04(2.7±0.5%ID/g).Furthermore,in an initial diagnostic application in a patient with nasopharyngeal cancer,[^(18)F]Al F-P-FAPI and[^(18)F]FDG PET/CT showed comparable results for both primary tumors and lymph node metastases.These results suggest that[^(18)F]Al F-P-FAPI can be conveniently prepared,with promising characteristics in the preclinical evaluation.The feasibility of FAP imaging was demonstrated using PET studies.

Emerging radiotherapy technologies and trends in nasopharyngeal cancer

AbTechnology has always driven advances in radiotherapy treatment.In this review,we describe the main technological advances in radiotherapy over the past decades for the treatment of nasopharyngeal cancer(NPC)and highlight some of the pressing issues and challenges that remain.We aim to identify emerging trends in radiation medicine.These include advances in personalized medicine and advanced imaging modalities,standardization of planning and delineation,assessment of treatment response and adaptive re-planning,impact of particle therapy,and role of artificial intelligence or automation in clinical care.In conclusion,we expect significant improvement in the therapeutic ratio of radiotherapy treatment for NPC over the next decade.

Nasopharyngeal cancer-derived microRNA-21 promotes mmune suppressive B cells

The prevalence of nasopharyngeal cancer （NPC） is high in the southern area of China and some other districts in the world. The pathogenesis of NPC is unclear. It is reported that some microRNAs （miR） are involved in the progression of NPC. This study aims to investigate the role of miR-21 in the induction of immune tolerance of NPC. In this study, NPC tissue was collected from patients with NPC. Assessment of miR was performed with real time quantitative RT-PCR. Western blotting was used to assess proteins of interleukin 10 and nuclear factor I-A （NFI-A）, Immune ceils were analyzed by flow cytometry. The results showed that NPC cell line C666-1 and surgically removed NPC tissue expressed miR-21, which was upregulated by the presence of the Toll-like receptor 3 ligand, Poly h C. Exposure to miR-21 increased the expression of NFI-A and interleukin （IL）-IO in naive B cells. High frequency of IL-10＋ B cells was detected in the NPC tissue. The NPC- or miR-21-primed B ceils suppressed cytotoxic CD8＋ T cell activities. We conclude that NPC-derived miR-21 induces IL-10＋ B ceils; the latter is capable of suppressing CD8＋ T-cell activities, miR-21 may be a potential target in the treatment of NPC.

Clinical outcomes for nasopharyngeal cancer with intracranial extension after taxanebased induction chemotherapy and concurrent chemo-radiotherapy in the modern era

Objective:To evaluate the survival outcomes for a cohort of nasopharyngeal cancer with intracranial extension(ICE)treated with induction chemotherapy(ICT)followed by chemo-intensity-modulated radiotherapy(CTRT)at a tertiary cancer center.Methods:We retrospectively analyzed 45 patients with histologically proven,non-metastatic NPC with ICE treated at our institute between October 2008 and October 2016.Patients were classified as minor ICE or major ICE,based on the extent of ICE.All the patients received 2-3 cycles of a taxane-based ICT regimen followed by CTRT.Radiotherapy was delivered with"riskadapted"intensity-modulated radiotherapy(IMRT)technique in all patients.Results:After a median follow up of 45 months(range:8-113 months),the estimated 5-year DFS,LRFS,DMFS,and OS of the entire cohort was 58%,82%,67%and 74%respectively.On multivariate analysis,histological subtype was an independent predictor of LRFS,and age was an independent predictor of DFS.The extent of ICE showed only a trend towards worse DFS(P=0.06).None of the factors significantly predicted for DMFS or OS.Gender,N-stage,and response to ICT did not significantly affect any of the outcomes.Grade 2 or worse subcutaneous fibrosis was seen in 22%of patients and grade 2 or worse xerostomia was seen in 24%of patients at last follow up.Thirty-three percent of the patients developed clinical hypothyroidism at last follow up.None of the patients experienced any neurological or vascular complications.Conclusions:Taxane-based induction chemotherapy followed by chemo-intensity modulated radiotherapy resulted in excellent locoregional control and survival with acceptable toxicities in patients of nasopharyngeal cancer with intracranial extension.Distant metastasis continues to be the predominant problem in these patients.

Detection and analysis of anti-latent membrane protein 2A antibodies in the sera of patients with Epstein-Barr virus associated malignancies

Background Epstein-Barr virus (EBV) associated malignancies with a Type Ⅱ latency gene expression pattern, such as Hodgkin’s disease, and nasopharyngeal carcinoma (NPC), frequently express the EBV antigen latent membrane protein 2A (LMP2A). We expected to establish a highly expressing LMP2A yeast cell strain and get the high quality LMP2A protein, which was used for detection, analysis and characterization of its antibodies in various patients’ sera of EBV associated malignancies.Methods The plasmid pPICZαA-LMP2A containing the full length of LMP2A cDNA was constructed and transformed to Pichia pastoris GS115 to express LMP2A protein. After fermentation and purification, the LMP2A protein was used as an antigen to detect anti-LMP2A antibodies (Abs) in the sera of patients with EBV-associated malignancies in enzyme linked immunosorbent assay (ELISA) or Western-blot.Results LMP2A was expressed successfully with an expected molecular weight of approximately 54 kD and Abs to LMP2A were strikingly specific to NPC. Two-thirds or more sera from NPC patients were positive for anti-LMP2A immunoglobulin G (IgG) Abs. The antibodies were absent from the sera of other EBV-associated diseases except a small fraction of the gastric carcinoma. Comparing anti-viral capsid Ags (VCA) IgA and LMP2A IgA titers in the sera from 76 NPC patients, only 55% were positive for anti-LMP2A IgA Abs while 70% were positive for anti-VCA IgA. However, we found that 3 sera negative for VCA IgA were positive for LMP2A IgA.Conclusion The results suggested the potential significance of LMP2A specific Abs for the diagnosis of EBV-associated malignancies, especially NPC.

Clinical Observation on Nasopharyngeal Carcinoma Treated with Combined Therapy of Radiotherapy and Ginseng Polysaccharide Injection

To observe the effect of radiotherapy (RT) combined with ginseng polysaccharide (GSP) injection in treating nasopharyngeal carcinoma (NPC) and its influence on immune function.Methods: One hundred and thirty-one patients of NPC were randomly divided into two groups, the RT-GSP group (n=64) treated with RT and GSP, and the control group (n=67) treated with conventional radiotherapy, to observe the local cancer remission rate, 1-year total survival rate, no tumor survival rate and no remote metastasis survival rate. Moreover, the changes of T-lymphocyte subsets, natural killer cell (NK) activity and lymphokine-activated killer cell (LAK) activity before and after treatment were determined.Results: Clinical examination conducted 3 months after treatment showed that the complete remission rate in the RT-GSP group was 96.6%, and in the control group 93.3%, the complete remission rate of cervical lymph node metastasis in the two groups was 85.7% and 78.0%, the NPC remission rate shown by CT 60.3% and 51.7%, respectively. Re-examination carried out 1 year after treatment showed that the total survival rate in the two groups was 100% and 96.5%, tumor free survival rate 84.4% and 74.6%, and no remote metastasis survival rate 93.8% and 88.1% respectively. The activity of NK cell and LAK cell as well as T3, T4 value in peripheral blood increased significantly in the RT-GSP group (all P<0.05) after treatment, while with the control group, no significant influence on NK and LAK activities were shown but significant lowering of T3, T4 was, P<0.05. No toxic-adverse reaction of GSP was found.Conclusion: GSP has certain immune function improving effect in NPC patients during RT, and it could also eliminate the occurred adverse reaction to RT and improve the general condition of patients.