Nasopharyngeal Carcinoma Survivors Research Articles

Hypothalamic pituitary dysfunction after nasopharyngeal carcinoma irradiation

PurposeRadiotherapy (RT) is the corner stone of nasopharyngeal carcinoma (NPC) treatment but it exposes to late effects especially hypothalamic pituitary deficiency (HPD). In this article,we aimed to assess the impact of RT on pituitary function in NPC survivors. MethodsWe included 55 patients treated in the radiation oncology department, of Farhat Hached Hospital in Sousse, Tunisia. ResultsAll patients received facio-cervical RT with a mean dose of 73.3 Gy to the nasopharynx. After a mean follow up of 9.56 years, 34 patients (61.8%) presented HPD. Associated peripheral involvement was seen in 18.2%. The most prevalent deficiency was of the GH axis in 50.9% followed by secondary adrenal insufficiency in 20%. Panhypopituitarism was noted in 8.8%. The development of HPD wasn’t related to RT dose (OR: 0.41(0.05–2.92), p = 0.36) but was significantly associated with male gender (OR: 1.67 (1.21–2.37), p = 0.01). ConclusionHPD post RT is a common phenomenon. Therefore, we recommend regular assessment of pituitary function amongst patients treated with RT for NPC because identification of deficits is crucial to allow early and appropriate hormone replacement therapy in order to improve patients quality of life.

Psychosocial Adjustment Experiences Among Nasopharyngeal Carcinoma Survivors: A Qualitative Study.

Nasopharyngeal carcinoma (NPC) has serious effects on the daily lives and psychosocial adjustment of survivors. In particular, psychosocial problems are a prominent concern. The aim of this study was to understand the lived experiences of NPC survivors regarding psychosocial adjustment. A qualitative design using individual semistructured interviews was conducted with 20 NPC survivors. Each participant was asked open-ended questions about their lived experience with psychosocial adjustment. The data were then subjected to thematic analysis. The following 4 themes, which had subthemes, were identified from the data: (1) grappling with discomforts (symptoms distress of late toxicities, impaired body image, and returning-to-work restrictions), (2) struggling with uncertainty (disease attribution with self-blame, contradictory rehabilitation information, fear of cancer recurrence, and distance from medical staff), (3) changing social patterns (special favors, social isolation, and social discrimination), and (4) cultivating positive change (healthy lifestyle and positive mindset). Nasopharyngeal carcinoma survivors experience many obstacles, as well as positive changes, during psychosocial adjustment. This study highlights the pressing need to consider NPC survivors' concerns about their psychosocial adjustment. Medical staff should provide NPC survivors with sufficient rehabilitation information to help them deal with possible late toxicities and mitigate their uncertainty and misunderstanding. Effective public education measures are needed to address misunderstandings about cancer in Chinese cultural settings.

Progression of cognitive dysfunction in NPC survivors with radiation-induced brain necrosis: A prospective cohort

Background and purposeThe evidence of longitudinal changes in cognition in nasopharyngeal carcinoma (NPC) survivors with radiation-induced brain necrosis (RIBN) after radiotherapy (RT) remained insufficient. We aimed to estimate the clinical progression rate of cognitive decline and identify patients with differential decline rates. Materials and methodsBased on an ongoing prospective cohort study, NPC patients aged ≥18 years old and diagnosed with RIBN were included in this current analysis if they finished the time frame of 3-year follow-up and had at least twice cognition assessments. The Chinese version of the Montreal Cognitive Assessment (MoCA) was used to assess the cognitive state. Linear mixed-effect models were used to analyze the annual progression rates of MoCA total and seven sub-items scores. ResultsAmong 134 patients in this study, the transition probability from normal to mild/moderate cognitive dysfunction were 14.2 % (19/134) and 1.49 % (2/134) respectively during the median follow-up time of 2.35 years. The total MoCA score declined by −0.569 (SE 0.208) points annually (p = 0.008). Patients with ≤6 years of duration from RT to RIBN have higher annual progression rate of total scores [−0.851 (SE 0.321), p = 0.013; p for interaction = 0.041]. ConclusionOur findings of the annual decline rate of cognition in NPC patients with RIBN from a 3-year longitudinal data, particularly for those who developed RIBN rapidly after RT, have important implications for the upcoming clinical trials designed to prevent or decrease cognitive decline in NPC patients with RIBN, regarding the selection of study patients and the calculation of sample size.

357MO Comparison of long-term quality of life between survivors of adolescent and adult nasopharyngeal carcinoma

357MO Comparison of long-term quality of life between survivors of adolescent and adult nasopharyngeal carcinoma

The use of Qigong and Tai Chi in the management of temporomandibular joint dysfunction: A systematic review.

Qigong and Tai Chi (QTC) are mind-body exercises involving a sequence of graceful movements, which promote self-healing, meditation, and self-cultivation. There is growing evidence that Qigong and/or Tai Chi therapy may improve the physical and psychological health among adults with multiple health conditions including joint movement. This systematic review aims to synthesize the available evidence on the type and effectiveness of QTCtherapies used in the management of temporomandibular joint (TMJ) dysfunction. This systematic review followed the AMSTAR-2 guideline, and it was reported based on guidelines in the PRISMA checklist. The review involved a systematic search of nineelectronic databases. After deduplication and screening of the literature retrieved from the search, only onearticle was included based on the review's inclusion criteria. Data was extracted from this article and synthesized. The only included article was on a non-randomized control trial which investigated the role of Tai Chi Qigong (a form of Qigong) therapy in improving joint mobility and alleviating trismus among 52 survivors of nasopharyngeal carcinoma who had TMJ disorders. The study reported, at different time intervals (at pretest; at mid-intervention; at posttest; and at follow-up posttest), that no significant difference (p > 0.05) was observed concerning mouth opening capacity between the intervention group and the control group. However, over time, less severe deterioration in mouth-opening was noted among the participants in the intervention group (p = 0.181) as compared to the control group (p < 0.001). The role of QTC therapies in improving joint mobility and alleviating trismus is not yet fully understood, but it seems promising. The available evidence is inadequate to categorically conclude on the efficacy of these therapies. Further studies will be required to fully assess the effectiveness of QTC therapies in the management of TMJ dysfunction.

Improvement in Swallowing Function in Patients with Previous Irradiation for Nasopharyngeal Carcinoma by Expiratory Muscle Strength Training.

Dysphagia and chronic aspiration are common post-irradiation complications in nasopharyngeal carcinoma (NPC) survivors. Expiratory Muscle Strength Training (EMST) is a simple device-driven exercise therapy for swallowing training. This study investigates the effectiveness of EMST in a group of post-irradiated NPC patients. This prospective cohort, including twelve patients with previous irradiation for NPC and with swallowing disturbance, was performed between 2019 and 2021 in a single institution. Patients were trained with EMST for 8weeks. Non-parametric analyses examined effects of EMST on primary outcome, maximum expiratory pressure. Secondary outcomes were measured with Penetration-aspiration scale, Yale pharyngeal residue severity rating scale (YPRSRS) by flexible endoscopic evaluation of swallowing, and Eating Assessment Tool (EAT-10) and M.D. Anderson Dysphagia Inventory questionnaire. Twelve patients, with a mean (SD) age of 64.3 (8.2) were recruited. There was no patient dropout with 88.9% overall compliance of training. Maximum expiratory pressure improved by 41% (median 94.5 to 133.5 cmH2O, p = 0.003). There was reduction in Penetration-aspiration scale with thin liquid (median 4 to 3, p = 0.026), and in YPRSRS at pyriform fossa with mildly thick liquid (p = 0.021) and at vallecula with thin liquid (p = 0.034), mildly thick liquid (p = 0.014) and pureed meat congee (p = 0.016). Questionnaire scores did not significantly change statistically. EMST is an easy-to-use and effective exercise therapy to improve airway safety and swallowing function in post-irradiated NPC survivors.

Conditional survival nomogram for monitoring real-time survival of young non-metastatic nasopharyngeal cancer survivors.

The aim of this study was to clarify the improvement of the overall survival (OS) over time in young non-metastatic nasopharyngeal carcinoma (NPC) survivors by conditional survival (CS) analysis and to construct a CS-nomogram for updating individualized real-time prognosis. The study included 3409 young non-metastatic NPC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2019). OS was estimated using the Kaplan-Meier method. CS was calculated based on CS(y|x) = OS(y + x)/OS(x), defined as the probability that a patient would survive for another y years after surviving for x years since diagnosis. We identified predictors using the least absolute shrinkage and selection operator (LASSO) regression and developed the CS-nomogram using multivariate Cox regression and the CS formula. CS analysis showed a continuous increase in 10-year OS for young non-metastatic NPC from the initial 60.4% to 65.0%, 70.2%, 74.2%, 78.2%, 82.6%, 86.9%, 91.1%, 96.2% and 97.0% (surviving 1-9years after diagnosis, respectively). After screening by LASSO regression, age, race, marital status, histological type, T- and N-status were used as predictors to construct the CS-nomogram. The model accurately estimated the real-time prognosis of survivors during follow-up with a stable time-dependent area under the curve (AUC). CS analysis based on SEER database calibrated the real-time prognosis of young non-metastatic NPC survivors, revealing a dynamic improvement during follow-up time. We developed a novel CS-nomogram to update survival data for real-time optimization of monitoring strategies, medical resource allocation, and patient counseling. However, it was important to note that the model still needed external data validation and continuous improvement.

Vertebral artery sparing volumetric modulated arc therapy in nasopharyngeal carcinoma.

Vascular stenosis is a late radiation complication that develops in long-term survivors of nasopharyngeal carcinoma. Vertebral arteries (VAs) are major vessels responsible for posterior circulation. In this study, we evaluated the feasibility of VA-sparing volumetric modulated arc therapy (VMAT) techniques. A total of 20 patients with nasopharyngeal carcinoma treated by a TrueBeam linear accelerator were enrolled in this study. The original VMAT plan was designed without the contouring of VAs as organs at risk (OARs). The same image set of the original VMAT plan was used to contour the VAs for each patient. A new VA-sparing VMAT plan was developed by avoiding VAs as OARs. Finally, a paired t-test was used to compare the dosimetric differences. The VA-sparing VMAT plan had similar target coverage and dose to those of other OARs. The VA-sparing plan yielded a significantly low VA dose from 53 to 40 Gy, with V35Gy changing from 97% to 56%, V50Gy changing from 67% to 35%, and V63Gy changing from 15% to approximately 7%-10% (p < 0.001 for all comparisons). VAs should be correctly identified as OARs. Photon VMAT with VA sparing can help substantially decrease the VA dose.

Prevalence of Neurocognitive Impairment for NPC Survivors after Definitive Intensity-Modulated Radiotherapy: A Cross-Sectional Study

<h3>Purpose/Objective(s)</h3> High-dose intensity-modulated radiotherapy (IMRT) has led to excellent prognosis in patients with localized nasopharyngeal carcinoma (NPC). Given the relatively young age of onset and the close anatomic relationship between the nasopharynx and the central nervous system, post-radiation neurocognitive impairment among long-term survivors represents an under-recognized late complication. This study aims to determine the prevalence and the affected cognitive domains in post-IMRT NPC survivors. <h3>Materials/Methods</h3> We undertook a cross-sectional study in a high-volume tertiary oncology center in Hong Kong. NPC survivors who underwent IMRT with a minimal post-radiotherapy interval of 1 year were eligible. All patients underwent an initial screening using the Montreal Cognitive Assessment-Hong Kong (MoCA-HK) test, followed by a 2-hour comprehensive battery of neurocognitive assessments covering 8 distinct domains: intellectual capacity (WAIS-IV), attention span (WAIS-IV digit span, WMS-III Visual Spatial Span), visual memory (WMS-III Visual reproduction span), verbal memory (Auditory Verbal Learning Test), processing speed (Color Trail Test), executive function (Stroop Test), motor dexterity (Grooved Pegboard Test) and language ability (Verbal Fluency Test). Mean percentiles and Z-scores of all neurocognitive assessments were compared with age- and/or education-matched population normative data using one-sample t-tests. Correlation of cognitive outcomes with clinical factors were analyzed using multivariable linear regression. <h3>Results</h3> A total of 182 NPC survivors were enrolled. The median post-radiotherapy interval was 6.9 years, 129 (70.9%) were long-term survivors at least 5 years beyond radiotherapy. The median age was 56 years old, 89% of the enrolled patients had stage III-IVA NPC by AJCC/UICC 8^th Edition, and 87% of patients received chemotherapy. The mean MoCA score was 23.6, 25.8% of patients were considered cognitively impaired. NPC survivors demonstrated significant cognitive impairment in verbal memory (p<0.001), processing speed (p<0.001), executive function (p<0.001), motor dexterity (p<0.001) and language ability (p=0.001). Most significant impairment was observed in executive function, mean z-scores of which were -1.76 to -1.38 below normative data. Post-IMRT interval, disease stage and chemotherapy usage showed no significant association with the degree of neurocognitive impairment. <h3>Conclusion</h3> Post-IMRT neurocognitive impairment was prevalent in NPC survivors. Neurocognitive function was not impaired globally but occurred predominantly in selected domains, particularly executive function. Cognitive assessment and training should be considered a part of survivorship care for NPC patients. Future research on the correlation between neurocognitive function and radiation dosimetry of various brain subsites would be informative.

Post-irradiation endolymphatic hydrops vs. post-irradiation sudden deafness

BackgroundIncreasing numbers of acute sensorineural hearing loss (SNHL) are recently experienced in irradiated nasopharyngeal carcinoma (NPC) survivors. AimThis study adopted MR imaging to differentiate between post-irradiation sudden deafness (PISD) and post-irradiation endolymphatic hydrops (PIEH) in long-term NPC survivors with acute SNHL. MethodsFrom 2012 to 2021, consecutive 10 irradiated NPC survivors with acute SNHL were enrolled. All patients underwent an inner ear test battery and MR imaging using HYDROPS-Mi2 technique. Six patients (11 ears) with positive cochlear hydrops on MR images were diagnosed as PIEH, while another 4 patients (4 ears) without cochlear hydrops on MR images were referred to PISD. ResultsThe interval from the onset of NPC to acute SNHL did not significantly differ between the PIEH (10 ± 6 years) and PISD (8 ± 2 years). No significant difference was found between the two disorders from any of the symptomatic, radiotherapeutic, audiological, or vestibular perspective. Interestingly, most (5/6) patients with PIEH had bilateral involvement, while all (4/4) patients with PISD showed unilateral affliction. A significantly declining sequence of abnormality rates in the inner ear test battery was noted in the PIEH patients, running from the audiometry (100%), cervical vestibular-evoked myogenic potential (VEMP) test (100%), ocular VEMP test (73%), to the caloric test (36%). However, such declining trend was not observed in patients with PISD. ConclusionWhen facing an NPC survivor who had acute SNHL over a prolonged period after irradiation, MR imaging using HYDROPS-Mi2 technique should be performed to differentiate the PIEH from the PISD, since both disorders have various treatment modalities and hearing outcome.

Causes of Death in Long-Term Nasopharyngeal Carcinoma Survivors.

PurposeTo assess the causes of death (COD) and long-term survival after nasopharyngeal carcinoma (NPC) diagnosis.MethodsUsing linked data from the Surveillance, Epidemiology, and End Results program, patients with NPC diagnosed from 1990 to 2010 and followed up >5 years were identified. Chi-squared test, the Kaplan–Meier method, and the Cox proportional hazard model were used for analyses.ResultsAmong the 3,036 long-term NPC survivors, 1,432 survived for >5–10 years and 1,604 survived for >10 years. The most common COD was primary NPC (36.9%), followed by other causes (28.7%), other cancers (15.3%), cardiac disease (12.9%), and non-malignant pulmonary disease (6.2%). With a median follow-up of 125 months, deaths from NPC decreased with increasing time from diagnosis, while death because of cardiac disease and other causes increased. In those aged <50 years, death due to NPC remained the main COD over time, while cardiopulmonary disease-related death was the leading COD in patients aged ≥50 years. In White patients, death due to NPC decreased, and death due to cardiac disease increased over time. Death from NPC remained significant in Black and Asian patients even 15 years after the diagnosis of NPC, while death due to cardiac disease significantly increased after 9 years of diagnosis in Black patients. Multivariate analyses showed that the independent factors associated with inferior NPC-specific survival were older age, Asians, American Indian/Alaska Native, regional stage, distant stage, and diagnosis in the early years.ConclusionsThe probability of death from primary NPC remains significant even 15 years after the NPC diagnosis. Our study advocates continued surveillance for NPC survivors beyond the traditional 5 years. Individualized follow-up strategies are required for patients with NPC of different ages and races.

Predictors of radiation-induced hypothyroidism in nasopharyngeal carcinoma survivors after intensity-modulated radiotherapy

BackgroundThe aim of the study is to identify clinical and dosimetric factors that could predict the risk of hypothyroidism in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT).MethodsA total of 404 non-metastatic NPC patients were included in our study. All patients were treated with IMRT. The thyroid function were performed for all patients before and after radiation at regular intervals. The time onset for developing hypothyroidism was defined as the time interval between the completion of RT and the first recorded abnormal thyroid hormone test. The cumulative incidence rates of hypothyroidism were estimated using Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to detect the most promising factors that were associated with hypothyroidism.ResultsMedian follow up was 60.6 months. The 3-, 5- and 7- year cumulative incidence rate of hypothyroidism was 39.4%, 49.1% and 54.7%, respectively. The median time to primary hypothyroidism and central hypothyroidism were 15.4 months (range 2.9–83.8 months) and 29.9 months (range 19.8–93.6 months), respectively. Univariate and multivariate analyses revealed that younger age, female gender and small thyroid volume were the most important factors in predicting the risk of hypothyroidism. Dtmean (mean dose of thyroid), V30-V50 (percentage of thyroid volume receiving a certain dose level) and VS45-VS60 (the absolute volumes of thyroid spared from various dose levels) remained statistically significant in multivariate analyses. Cutoff points of 45 Gy (Dtmean), 80% (Vt40) and 5 cm3 (VS45Gy) were identified to classify patients as high-risk or low-risk group.ConclusionThyroid Vt40 highly predicted the risk of hypothyroidism after IMRT for NPC patients. We recommended plan optimization objectives to reduce thyroid Vt40 to 80%.Trial registration: Retrospectively registered.

The mediating role of self-efficacy in the association between perceived stigma and psychosocial adjustment: a cross-sectional study among nasopharyngeal cancer survivors.

This study aims to examine the levels of and associations between perceived stigma, self-efficacy, and psychosocial adjustment (PA) among nasopharyngeal carcinoma (NPC) survivors, and to identify the mediating role of self-efficacy between stigma and PA and explore the influencing factors of PA. A cross-sectional survey was conducted and 307 NPC survivors were recruited by convenience sampling method in Southern China from July 2019 to January 2020. Data analyses were performed with the SPSS WIN 25.0 program and PROCESS macro version 3.3. Stigma and self-efficacy were positively associated with PA among Chinese NPC survivors. Tumor-free survival time, late toxicities (fatigue, dizziness and headache, and hearing loss), stigma, and self-efficacy entered the final regression model and explained 55.9% of the variance of PA. The total and direct effects of stigma on PA and its subscales were significant (p<0.05). Positive indirect effects were found for stigma on PA via self-efficacy (point estimate=0.159, SE=0.032, 95% CI [0.102 to 0.229]). Stigma and self-efficacy are significantly associated with PA, and self-efficacy is also a mediating variable between stigma and PA among NPC survivors. Medical staff could improve the PA of NPC survivors by alleviating their stigma, enhancing their self-efficacy, and relieving their late toxicities (fatigue, dizziness and headache, and hearing loss).

Aberrant miR-362-3p is Associated with EBV-Infection and Prognosis in Nasopharyngeal Carcinoma and Involved in Tumor Progression by Targeting JMJD2A.

BackgroundMany microRNAs (miRNAs) are involved in the progression of nasopharyngeal carcinoma (NPC). This study aimed to examine the expression and clinical significance of microRNA (miR)-362-3p in NPC, especially in Epstein–Barr virus (EBV)-positive patients, and explore its potential mechanism in NPC progression.MethodsmiR-362-3p levels and Jumonji C domain 2A (JMJD2A) mRNA levels were detected by quantitative real-time PCR. The diagnostic value of miR-362-3p to distinguish NPC patients and EBV-positive cases was evaluated using receiver operating characteristic analysis. The association of miR-362-3p with NPC survival was assessed by Kaplan–Meier curves and Cox regression analysis. NPC cell proliferation, migration and invasion were determined using Cell Counting Kit-8 and Transwell assays, respectively. A luciferase reporter assay was used to confirm the interaction between miR-362-3p and JMJD2A.ResultsmiR-362-3p expression was decreased in the serum and tissues of NPC patients and had diagnostic value for screening NPC. According to the survival follow-up, NPC survivors had significantly higher miR-362-3p, and miR-326-3p was demonstrated as an independent prognostic indicator of NPC. Interestingly, it is found that EBV-positive NPC patients and cells had significantly lower miR-362-3p compared with EBV-negative NPC patients and cells and had certain ability to distinguish EBV-positive patients. Moreover, miR-362-3p inhibited the proliferation, migration and invasion of both EBV-positive and -negative NPC cells, and these effects might be mediated by targeting JMJD2A.ConclusionAbnormal miR-362-3p expression is related to EBV-infection and prognosis in NPC patients and may be involved in NPC progression by targeting JMJD2A.

Sensorineural Hearing Loss in Nasopharyngeal Carcinoma Survivors in the Modern Treatment Era — The Early and Late Effects of Radiation and Cisplatin

AimsHearing loss is a common debilitating complication in nasopharyngeal carcinoma (NPC) survivors. The aim of the present study was to investigate the impact of inner ear/cochlear radiation dose and cisplatin use on early and late sensorineural hearing loss (SNHL) in NPC patients treated with radiotherapy alone, concurrent chemoradiation (cCRT) and induction chemotherapy followed by cCRT (iCRT) in the intensity-modulated radiotherapy era. Materials and methodsThe study included 81 NPC patients treated with intensity-modulated radiotherapy between 2014 and 2016. Pure tone audiometry was carried out at baseline and follow-up. The effects of cochlear/inner ear radiation and cisplatin doses on early (<12 months) and late (≥24 months) SNHL were analysed using multivariable regression after adjusting for important predictors. ResultsIn total, 156 ears were examined. In early SNHL (n = 136), cisplatin use predicted the incidence of early high-frequency SHNL (HF-SNHL) (odds ratio 6.4, 95% confidence interval 1.7–23.9, P = 0.005). Ninety ears were analysed for late SNHL (median follow-up 38 months). Inner ear/cochlear radiation and cisplatin doses and better pre-treatment hearing were independent predictors of threshold change at 4 kHz. Every 10 Gy increase in inner ear/cochlear Dmean resulted in 5-dB and 6-dB threshold changes, respectively (cochlear Dmean: B = 0.005, 95% confidence interval 0.0004–0.009, P = 0.031; inner ear Dmean: B = 0.006, 95% confidence interval 0.001–0.010, P = 0.014). Cisplatin use was associated with late HF-SNHL (odds ratio 3.74, 95% confidence interval 1.1–12.3, P = 0.031). In the cCRT and iCRT subgroups, no cisplatin dose-dependent ototoxicity was observed. Severe (≥30 dB) late HF-SNHL occurred in 14% and 25% of the patients when the cochlear dose constraints were 40 Gy and 44 Gy, respectively. The radiotherapy-alone group did not develop severe late HF-SNHL. ConclusionCochlear/inner ear radiation dose and cisplatin use showed differential and independent ototoxicity in early and late SNHL. As cochlear/inner ear dose-dependent ototoxicity was demonstrated, the cochlear dose constraint should be as low as reasonably achievable, especially when cisplatin is also administered.

Stigma, self-efficacy and late toxicities among Chinese nasopharyngeal carcinoma survivors.

This study explores the level of stigma among Chinese nasopharyngeal carcinoma survivors, its influencing factors and relationship with self-efficacy. In total, 281 nasopharyngeal carcinoma survivors were recruited from China, who completed the demographic, disease-related and late toxicities questionnaire, as well as the General Self-Efficacy Scale and Social Impact Scale. The mean scores for stigma and self-efficacy were 57.22 ± 9.58 and 28.06 ± 3.97, respectively, both showing a moderate level. The late toxicities with the highest incidence were xerostomia (91.8%), fatigue (78.3%) and hearing loss (63.0%). Stigma was significantly and negatively related to self-efficacy (r = -0.295, P < 0.001). Multivariable linear regression showed that self-efficacy, number of children, educational level, perceived support from spouse and other family members and some late toxicities (nasal obstruction and toothache) were influencing factors of stigma, accounting for 49.4% of the variance. Medical staff should be more aware of stigma among Chinese nasopharyngeal carcinoma survivors, especially those with more children and weaker educational backgrounds who are at a higher risk of stigma. They should take effective measures to alleviate stigma by improving patients' self-efficacy, relieving late toxicities and encouraging spouses and family members to provide more support for them.

The Relationships Between Radiation Dosage and Long-term Swallowing Kinematics and Timing in Nasopharyngeal Carcinoma Survivors.

This study aimed to investigate the relationship between intensity-modulated radiation therapy (IMRT) dosimetry and swallowing kinematic and timing measures. Thirteen kinematic and timing measures of swallowing from videofluoroscopic analysis were used as outcome measures to reflect swallowing function. IMRT dosimetry was accessed for thirteen swallowing-related structures. A cohort of 44 nasopharyngeal carcinoma (NPC) survivors at least 3 years post-IMRT were recruited. The cohort had a mean age of 53.2 ± 11.9 years, 77.3% of whom were male. There was an average of 68.24 ± 14.15 months since end of IMRT; 41 (93.2%) had undergone concurrent chemotherapy. For displacement measures, female sex and higher doses to the cricopharyngeus, glottic larynx, and base of tongue were associated with reduced hyolaryngeal excursion and pharyngeal constriction, and more residue. For timing measures, higher dose to the genioglossus was associated with reduced processing time at all stages of the swallow. The inferior pharyngeal constrictor emerged with a distinctly different pattern of association with mean radiation dosage compared to other structures. Greater changes to swallowing kinematics and timing were observed for pudding thick consistency than thin liquid. Increasing radiation dosage to swallowing-related structures is associated with reduced swallowing kinematics. However, not all structures are affected the same way, therefore organ sparing during treatment planning for IMRT needs to consider function rather than focusing on select muscles. Dose-response relationships should be investigated with a comprehensive set of swallowing structures to capture the holistic process of swallowing.

Second Primary Malignancies in Pediatric and Adolescent Nasopharyngeal Carcinoma Survivors: Experience of a Single-center

Second Primary Malignancies in Pediatric and Adolescent Nasopharyngeal Carcinoma Survivors: Experience of a Single-center

Accumulation of LOX-1+ PMN-MDSCs in nasopharyngeal carcinoma survivors with chronic hepatitis B might permit immune tolerance to epstein-barr virus and relate to tumor recurrence.

Chronic hepatitis B (CHB) has been reported to be associated with impaired prognosis for patients with nasopharyngeal carcinoma (NPC). However, the latent mechanism is unclear. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) induce immune suppression in CHB and promote the development of hepatocellular carcinoma. Lectin-type oxidized LDL receptor-1 (LOX-1) was recently identified as a specific marker for PMN-MSDC. We found NPC survivors with CHB had high levels of LOX-1+ PMN-MDSCs. LOX-1+ PMN-MDSCs significantly reduced T cell proliferation and activation. Endoplasmic reticulum stress was induced in LOX-1+ PMN-MDSCs. In addition, LOX-1+ PMN-MDSCs increased their expression of NOX2, a key reactive oxygen species (ROS)-related genes, and levels of ROS illustrated by the DCFDA test. The ROS inhibitor N-acetylcysteine abrogated the suppression of LOX-1+ PMN-MDSCs on T cell activation. The EBV DNA-positivity rate was higher in NPC survivors with CHB than in NPC patients without CHB. Those presenting with positive EBV DNA displayed higher LOX-1+ PMN-MDSC levels. LOX-1+ PMN-MDSCs suppressed the CD8+ T cell response against EBV. This study revealed LOX-1+ PMN-MDSC accumulation and activation in NPC survivors with CHB. LOX-1+ PMN-MDSCs might suppress the host immune response to EBV through ER stress/ROS pathway. These results explained the association of CHB with unfavorable NPC prognosis.

Second primary cancer after intensity-modulated radiotherapy for nasopharyngeal carcinoma: A territory-wide study by HKNPCSG.

Long-term risk of second primary cancer (SPC) after definitive intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) remains unclear. This study aims to evaluate the risk, predictive factors and survival impact of SPC in a large territory-wide cohort of NPC survivors in an endemic region. In this multicenter study, consecutive NPC patients (n = 3166) who underwent definitive IMRT in all six public oncology centers in Hong Kong between 2001 and 2010 were included. SPC risks were quantified by standardized incidence ratios (SIRs) and absolute excess risks (AERs) estimated from corresponding age-, sex-, and calendar year-specific population cancer incidence data from the Hong Kong Cancer Registry. Predictive factors and SPC-specific mortality were analyzed. Over a median follow-up period of 10.8 years, 290 cases of SPC were observed with a crude incidence of 9.2%. Cancer risk in NPC survivors was 90% higher than that in general population [SIR, 1.9; 95% confidence interval (CI), 1.7-2.2], with an AER of 52.1 (95% CI, 36.8-67.3) per 10,000 person-years at risk. Significant excess cancer risks were observed for oral cavity, sarcoma, oropharynx, paranasal sinus, salivary gland, thyroid, skin and lung. Advanced age, smoking, hepatitis B status, and re-irradiation were independent predictive factors. SPC accounted for 9.4% of all deaths among NPC survivors during the study period, and 10-year SPC-specific mortality was 3.4%. Second cancer risk after IMRT was substantial among NPC patients. SPC impairs long-term survival, and close surveillance is warranted as part of survivorship care.