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Simple Summary: Radiotherapy is the main local treatment for head and neck cancer. Radiation oncologists and patients should be alert to late carotid artery stenosis and brain necrosis after treatment. Objective: This study aims to examine whether radiation therapy doses are related to incidences of carotid artery stenosis and brain necrosis in a large-scale real-world database. Methods: We identified a cohort of HNC patients from the catastrophic illness patient dataset using ICD-9 or ICD-10 to compare the incidence and risks of carotid artery stenosis (CAS) and brain necrosis (RIBN) in patients who received a radiation therapy dose of ≥5400 cGy/30 fractions (group A) with those who received a radiation therapy dose of <5400 cGy/30 fractions (group B). The incidence and hazard ratios were quantified using Cox proportional hazards models. Results: A total of 19,964 patients were identified in group A and group B. Among them, 965 and 863 cases of CAS and 435 and 359 cases of RIBN were identified in group A and group B, respectively. There was no statistically significant association between the two groups for CAS risk, whereas there was a statistically significant association between the two groups for RIBN risk. The most common primary site of head and neck cancers was the nasopharynx (1144 of 19,964, 5.73%). Conclusions: Our study suggests that RT may increase the risk of carotid stenosis and brain necrosis in patients with NPC. To ensure patient safety during treatment, the optimal balance between tumor control and toxicity prevention in individual patients through minimization of the radiation dose to all relevant OARs must be properly understood. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)‐related cervical and nasopharyngeal cancers differ in molecular mechanisms underlying the oncogenic processes. The disparity may be attributed to differential expression of oncoproteins. The current study investigated the host oncogenes expression pattern in HPV‐associated cervical and nasopharyngeal cancer. Formalin‐fixed paraffin‐embedded tissues originating from the nasopharyngeal and cervical regions were screened using Hematoxylin and Eosin staining. Genomic DNA and total RNA were extracted from confirmed cancer biopsies and non‐cancer tissues (NC). HPV was detected by PCR using MY09/GP5+/6+ primers. Protein expression levels of AKT, IQGAP1, and MMP16 in HPV‐infected cancers and controls were determined by immunohistochemistry. RT‐qPCR was used to profile mRNAs of the oncogenes. AKT and IQGAP1 proteins were highly expressed in the epithelial cancers compared with the non‐cancer tissues (p < 0.05). IQGAP1 and MMP16 mRNAs level was significantly higher in the cancers than in the NC (p < 0.05), but not AKT mRNA levels. MMP16 protein was ubiquitously expressed in all tissues. AKT mRNA level was significantly elevated in CC compared with NPC (p < 0.001). However, the difference in AKT, IQGAP1 and MMP16 proteins level between CC and NPC was not significant (p > 0.05). The oncoproteins expression level between the HPV‐positive and HPV‐negative cancer biopsies showed no significant difference (p < 0.05). Current study reports AKT but not IQGAP1 and MMP16 mRNAs differentially expression in cervical and nasopharyngeal cancers, independent of HPV infection status. [ABSTRACT FROM AUTHOR]

Background: Epstein–Barr virus (EBV) IgA serology for viral capsid antigen (VCA) and early antigen (EA) aids early detection of nasopharyngeal cancer (NPC), resulting in improved survival. We evaluated the diagnostic performance of a prefabricated immunofluorescent assay (IFA) for NPC screening in high‐risk individuals. Methods: Sera from 96 biopsy‐proven patients with NPC diagnosed at the outpatient clinic and 96 healthy family members were tested for EBV‐VCA IgA and EBV‐EA IgA using the prefabricated IFA from EUROIMMUN (EI) and the traditional immunofluorescence method. Results: The AUC of EI EBV‐VCA IgA and EBV‐EA IgA was 0.907 (95% confidence interval [CI]: 0.894–0.965) and 0.898 (95% CI: 0.848–0.947), respectively. Combined testing with the prefabricated assay at a threshold of VCA ≥1:320 or EA ≥1:10 showed 92.7% sensitivity and 81.2% specificity. Overall, the traditional EBV‐EA IgA assay demonstrated the best accuracy (sensitivity 91.7% and specificity 96.9%) at a threshold of ≥1:5. Conclusion: While the traditional IFA method was more accurate, the prefabricated IFA test kit can be a useful tool for NPC screening in high‐risk populations. [ABSTRACT FROM AUTHOR]

Background: This study evaluated health‐related quality of life (HRQoL) in the RATIONALE‐309 (NCT03924986) intent‐to‐treat (ITT) population and in a subgroup of patients with liver metastases. Methods: Patients were randomized 1:1 to tislelizumab + chemotherapy or placebo + chemotherapy. As the secondary endpoint, HRQoL was evaluated using seven selected scores from the EORTC QLQ‐C30 and QLQ Head and Neck Cancer module (QLQ‐H&N35). Results: Of 263 randomized patients in the ITT population (tislelizumab + chemotherapy n = 131, placebo + chemotherapy n = 132), 43% had liver metastases (tislelizumab + chemotherapy n = 56; placebo + chemotherapy n = 57). No differences in change in selected scores on the QLQ‐C30 from baseline to cycle 4 or cycle 8 were observed for the ITT or liver metastases subgroup. No differences in selected QLQ‐H&N35 scores were observed between the arms from baseline to cycle 4. In the ITT population and the liver metastases subgroup, a greater reduction from baseline to cycle 8 was observed in the tislelizumab + chemotherapy arm than the placebo + chemotherapy arm in QLQ‐H&N35 pain score. At cycle 8 in the liver metastases subgroup, the tislelizumab + chemotherapy arm experienced greater improvement in the QLQ‐H&N35 senses problems score than the placebo + chemotherapy arm. Differences in time to deterioration between arms were not observed. Conclusions: The current findings, along with improved survival and favorable safety, suggests that tislelizumab + chemotherapy represents a potential first‐line treatment for recurrent or metastatic nasopharyngeal cancer. [ABSTRACT FROM AUTHOR]

Purpose: Radiation encephalopathy (REP) is one of the most common complications of radiotherapy for malignant tumors of the head and neck. Symptoms usually appear months to years following radiotherapy, with headache, insomnia, and memory loss as the main clinical features. We report a patient who was admitted to the hospital with anxiety and depressive disorder and was eventually diagnosed with REP. Patients and methods: A 48-year-old patient who had undergone over 2 years of radiotherapy for nasopharyngeal carcinoma was admitted to the Department of Psychosomatic Medicine of our hospital because of recurrent fear, low mood, and waking up from dreams. Magnetic resonance imaging (MRI) revealed a mass in the left temporal lobe with a large peripheral edema. After multidisciplinary consultation, the possibility of tumor recurrence could not be excluded. Results: Resection of the lesioned brain tissue to obtain pathological tissue showed glial cell proliferation and small focal areas of degeneration and necrosis, which indicated that the lesions were inflammatory. Postoperative MRI showed no abnormal signal, and the patient's condition improved. Conclusion: Nasopharyngeal carcinoma patients with a history of radiotherapy and symptoms of increased intracranial pressure and neurological damage should be examined for REP. Furthermore, patients may experience anxiety and depressive disorders as a result of temporal lobe damage caused by REP. [ABSTRACT FROM AUTHOR]

Background Epstein–Barr virus (EBV) is a major cause of nasopharyngeal carcinoma (NPC) and measurement of different EBV antibodies in blood may improve early detection of NPC. Prospective studies can help assess the roles of different EBV antibodies in predicting NPC risk over time. Methods A case-cohort study within the prospective China Kadoorie Biobank of 512 715 adults from 10 (including two NPC endemic) areas included 295 incident NPC cases and 745 subcohort participants. A multiplex serology assay was used to quantify IgA and IgG antibodies against 16 EBV antigens in stored baseline plasma samples. Cox regression was used to estimate adjusted hazard ratios (HRs) for NPC and C-statistics to assess the discriminatory ability of EBV-markers, including two previously identified EBV-marker combinations, for predicting NPC. Results Sero-positivity for 15 out of 16 EBV-markers was significantly associated with higher NPC risk. Both IgA and IgG antibodies against the same three EBV-markers showed the most extreme HRs, i.e. BGLF2 (IgA: 124.2 (95% CI: 63.3–243.9); IgG: 8.6 (5.5–13.5); LF2: [67.8 (30.0–153.1), 10.9 (7.2–16.4)]); and BFRF1: 26.1 (10.1–67.5), 6.1 (2.7–13.6). Use of a two-marker (i.e. LF2/BGLF2 IgG) and a four-marker (i.e. LF2/BGLF2 IgG and LF2/EA-D IgA) combinations yielded C-statistics of 0.85 and 0.84, respectively, which persisted for at least 5 years after sample collection in both endemic and non-endemic areas. Conclusions In Chinese adults, plasma EBV markers strongly predict NPC occurrence many years before clinical diagnosis. LF2 and BGLF2 IgG could identify NPC high-risk individuals to improve NPC early detection in community and clinical settings. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) constitute a class of endogenous non-coding RNAs (ncRNAs) that lack a 5'-ended cap and 3'-ended poly (A) tail and form a closed ring structure with covalent bonds. Due to its special structure, circRNA is resistant to Exonuclease R (RNaseR), making its distribution in the cytoplasm quite rich. Advanced high-throughput sequencing and bioinformatics methods have revealed that circRNA is highly conserved, stable, and disease- and tissue-specific. Furthermore, increasing research has confirmed that circRNA, as a driver or suppressor, regulates cancer onset and progression by modulating a series of pathophysiological mechanisms. As a result, circRNA has emerged as a clinical biomarker and therapeutic intervention target. This article reviews the biological functions and regulatory mechanisms of circRNA in the context of respiratory cancer onset and progression. [ABSTRACT FROM AUTHOR]

Objective: To analyze the efficacy and adverse effects of anti‐PD‐1 immune checkpoint inhibitors aimed at nasopharyngeal carcinoma (NPC). Methods: During the first stage of the study, using 40 patients with stage III/IVa NPC treated with anti‐PD‐1 immune checkpoint inhibitors in combination with chemoradiotherapy as a first‐line treatment (observation group) and 70 patients with NPC treated with chemoradiotherapy alone (control group). In the second stage of the study, 88 patients with NPC treated with immune checkpoint inhibitors were grouped according to the number of lines of immunotherapy, the number of times, and the types of application. Results: Observation of the short‐term effects in the first stage indicated that the objective response rate (ORR) of the observation group and the control group against primary foci of NPC was 75.0% versus 40.0%; the mortality rate of the observation group was much lower than that of the control group. The overall first‐line treatment evaluation of the observation vs. control groups were as follows: ORR (67.5% vs. 38.6%); median PFS (17.52 vs. 17.21 months); and median OS (18.68 vs. 18.14 months), respectively (p < 0.05). The second stage of the study had an ORR of 53.4%, and the efficacy of immunotherapy was related to staging, timing, and frequency. Conclusion: Anti‐PD‐1 immune checkpoint inhibitors combined with chemoradiotherapy as the first‐line treatment for nasopharyngeal carcinoma may improve patient outcomes significantly. Timing, frequency, and the type of immunotherapy exerted an effect on the efficacy of immunotherapy. Adverse effects that occurred during treatment were tolerable and controllable. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to analyze patterns of failure and disease volume-treatment outcomes in patients with Nasopharyngeal carcinoma (NPC) treated with definitive radiation with or without concurrent chemotherapy at a tertiary cancer centre in northeast India. Methods: From February 2018 to February 2022, 99 histopathologically proved non-metastatic NPC patients treated with curative-intent RT with or without chemotherapy were retrospectively analyzed. Locally advanced patients received neoadjuvant or adjuvant chemotherapy. The Cox proportional hazards model was used to investigate the impact of various prognostic factors on locoregional free survival (LRFS), distant metastasis free survival (DMFS), progression free survival (PFS) and overall survival (OS). The log-rank test and Kaplan–Meir curves compared outcome variables based on ROC analysis-classified tumor volume. Results: During a median follow up of 25.4 months (17.3–39.2), 35(35.4%) patients developed recurrence. Twenty-three patients developed locoregional failures, of which 11 were in-field; 12 patient showed an out-field failure. The 3-year LRFS, DMFS, PFS and OS was 71.10%, 70.90%, 64.10% and 74.10% respectively. There was statistically significant difference in LRFS according to T staging (p < 0.0001). Gross tumor volume (GTVp) and gross nodal volume (GTVn) were an independent prognostic factor for OS, PFS, LRFS and DMFS. The cut-off volumes for GTVp and GTVn for distant metastases and locoregional failure, respectively, were found to be 13 and 22.7 mL and 3.7 and 39.2 mL, respectively, by ROC curve analysis. Based on this, 99 patients were divided into three subgroups. OS demonstrated significant differences among patients in different volume subgroups for GTVp (p = 0.03) and GTVn (p = 0.00024). Conclusions: For NPC patients who undergo curative IMRT, primary tumour and nodal volumes are independent prognostic indicators. GTVp and GTVn are highly predictive of local control, distant metastases, disease-free survival, and overall survival. This justifies their use as quantitative prognostic indicator for NPC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nasopharyngeal carcinoma (NC) is one of the prevalent malignancies of the head and neck region with poor prognosis. OBJECTIVE: The aim of this study is to establish a predictive model for assessing NC prognosis based on clinical and MR radiomics data, subsequently to develop a nomogram for practical application. METHODS: Retrospective analysis was conducted on clinical and imaging data collected between May 2010 and August 2018, involving 211 patients diagnosed with histologically confirmed NC who received concurrent chemoradiotherapy or radical surgery in Xiangyang No. 1 People's Hospital. According to 5–10 years of follow-up results, the patients were divided into two groups: the study group (n = 76), which experienced recurrence, metastasis, or death, and the control group (n = 135), characterized by normal survival. Training and testing subsets were established at a 7:3 ratio, with a predefined time cutoff. In the training set, three prediction models were established: a clinical data model, an imaging model, and a combined model using the integrated variation in clinical characteristics along with MR radiomics parameters (Delta-Radscore) observed before and after concurrent chemoradiotherapy. Model performance was compared using Delong's test, and net clinical benefit was assessed via decision curve analysis (DCA). Then, external validation was conducted on the test set, and finally a nomogram predicting NC prognosis was created. RESULTS: Univariate analysis identified that the risk factors impacting the prognosis of NC included gender, pathological type, neutrophil to lymphocyte ratio (NLR), degree of tumor differentiation, MR enhancement pattern, and Delta-Radscore (P < 0.05). The combined model established based on the abovementioned factors exhibited significantly higher predictive performance [AUC: 0.874, 95% CI (0.810–0.923)] than that of the clinical data model [AUC: 0.650, 95% CI (0.568–0.727)] and imaging model [AUC: 0.824, 95% CI (0.753–0.882)]. DCA also demonstrated superior clinical net benefit in the combined model, a finding further verified by results from the test set. The developed nomogram, based on the combined model, exhibited promising performance in clinical applications. CONCLUSION: The Delta-Radscore derived from MR radiomics data before and after concurrent chemoradiotherapy helps enhance the performance of the NC prognostic model. The combined model and resultant nomogram provide valuable support for clinical decision-making in NC treatment, ultimately contributing to an improved survival rate. [ABSTRACT FROM AUTHOR]

Background: The prevalence of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in post‐irradiated patients with nasopharyngeal carcinoma (NPC) is unknown. Materials and methods: In a cross‐sectional study, 31 NPC and 12 control patients completed questionnaires for GERD/LPR before esophageal manometry and 24‐h pH monitoring. The DeMeester score and reflux finding score (RFS) were used to define GERD and LPR, respectively. Risk factors were identified. Results: 51.6% of NPC and 8.3% of control patients, and 77.4% of NPC and 33% of control patients, were GERD‐positive and LPR‐positive, respectively. The GERD/LPR questionnaire failed to identify either condition in patients with NPC. No parameter differences in esophageal manometry or pneumonia incidence were noted between GERD/LPR‐positive and GERD/LPR‐negative patients. Post radiotherapy duration, high BMI, lack of chemotherapy, and dysphagia were positive risk factors for GERD/LPR. Conclusions: A high prevalence of GERD/LPR in patients with post‐irradiated NPC exists, but reflux symptoms are inadequate for diagnosis. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal cancer is a rare tumor with significant diversity. Head and neck cancer are common in male whereas nasopharyngeal cancer still is uncommon. There is very less data available on survival and characteristics of nasopharyngeal cancer in North India. Study design: Retrospective study. Materials and methods: The HBCR data on all nasopharyngeal cancer patients who were treated were retrieved for a period of 5 years from 2017 to 2022. Statistical analysis used: SPSS software version 20. Results: A total of 29 patients were analysed. Total male to female ratio is 1.4:1 i.e. 58.4% male and 41.4% are female. Most common age group affected is between 40 years to 60 years. Most common symptom was nasal blockade followed by neck swelling. Patient common stage of disease presentation was stage IV i.e. 45%, stage III was 34.4% and stage II was 21%. Metastasis was common in bone followed by lung and liver. In our study 59% of the patients were treated with radiation and concomitant chemotherapy. The overall survival by Kaplan meire curve at 2 years in our study population was 64.3% and 5 years survival analysis was 46.93%. Conclusion: Nasopharyngeal Carcinoma (NPC) is an infrequent head and neck malignancy in Northern India, often diagnosed at an advanced stage with a higher likelihood of distant metastasis. Concurrent chemo-radiation therapy, particularly utilizing a weekly cisplatin regimen, has demonstrated favorable outcomes and tolerability. There is a pressing need for additional prospective research to evaluate this treatment schedule further and explore the potential benefits of novel agents in managing this potentially curable malignancy. [ABSTRACT FROM AUTHOR]

Abstract Human papillomavirus (HPV)‐related cervical and nasopharyngeal cancers differ in molecular mechanisms underlying the oncogenic processes. The disparity may be attributed to differential expression of oncoproteins. The current study investigated the host oncogenes expression pattern in HPV‐associated cervical and nasopharyngeal cancer. Formalin‐fixed paraffin‐embedded tissues originating from the nasopharyngeal and cervical regions were screened using Hematoxylin and Eosin staining. Genomic DNA and total RNA were extracted from confirmed cancer biopsies and non‐cancer tissues (NC). HPV was detected by PCR using MY09/GP5+/6+ primers. Protein expression levels of AKT, IQGAP1, and MMP16 in HPV‐infected cancers and controls were determined by immunohistochemistry. RT‐qPCR was used to profile mRNAs of the oncogenes. AKT and IQGAP1 proteins were highly expressed in the epithelial cancers compared with the non‐cancer tissues (p 0.05). The oncoproteins expression level between the HPV‐positive and HPV‐negative cancer biopsies showed no significant difference (p

Purpose: With the treatment of nasopharyngeal carcinoma (NPC) by PD-1/PD-L1 inhibitors used widely in clinic, it becomes very necessary to anticipate whether patients would benefit from it. We aimed to develop a nomogram to evaluate the efficacy of anti-PD-1/PD-L1 in NPC patients. Methods: Totally 160 NPC patients were enrolled in the study. Patients were measured before the first PD-1/PD-L1 inhibitors treatment and after 8–12 weeks of immunotherapy by radiological examinations to estimate the effect. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to screen hematological markers and establish a predictive model. The nomogram was internally validated by bootstrap resampling and externally validated. Performance of the model was evaluated using concordance index, calibration curve, decision curve analysis and receiver operation characteristic curve. Results: Patients involved were randomly split into training cohort ang validation cohort. Based on Lasso logistic regression, systemic immune-inflammation index (SII) and ALT to AST ratio (LSR) were selected to establish a predictive model. The C-index of training cohort and validating cohort was 0.745 and 0.760. The calibration curves and decision curves showed the precise predictive ability of this nomogram. The benefit of the model showed in decision curve was better than TNM stage. The area under the curve (AUC) value of training cohort and validation cohort was 0.745 and 0.878, respectively. Conclusion: The predictive model helped evaluating efficacy with high accuracy in NPC patients treated with PD-1/PD-L1 inhibitors. [ABSTRACT FROM AUTHOR]

Abstract Introduction Metronomic capecitabine used as an adjuvant therapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This therapeutic approach may also contribute to improving immune function, consequently enhancing overall therapeutic efficacy. Aim We aimed to evaluate the effect of metronomic capecitabine as adjuvant therapy on immune function and survival in cases of LA-NPC. Subjects and methods 28 patients with LA-NPC were enrolled in the study and equally assigned to two groups of 14 each: experimental and control group. The experimental group received induction chemotherapy + concurrent chemotherapy + adjuvant chemotherapy as well as oral capecitabine at a dose of 650 mg/m² of body surface area twice daily for 1 year, with the option to discontinue in case of intolerance. The control group did not receive additional chemotherapy or targeted drugs after the induction chemotherapy + concurrent chemoradiotherapy; however, they were followed up regularly. Changes in immune function and survival were compared between the two groups. Results The median follow-up time was 43.5 months. One year after adjuvant chemotherapy, the experimental group showed higher levels of CD8 + cells, CD28 + CD8 + cells, and activated CD8 + cells compared to the control group (P 0 0.05 ). Conclusion Metronomic capecitabine chemotherapy was observed to induce an immunomodulatory effect in LA-NPC. Trial registration NCT02958111, date of registration 04-11-2016.

PEG (Percutaneous Endoscopic Gastrostomy) procedure is a method used in patients with head and neck cancers whose oral intake is impaired. Although very rare, metastasis may occur due to the possible implantation of tumor cells compatible with primary malignancy at the PEG site. In our case report, we aimed to present a patient who was treated for nasopharyngeal cancer and was found to have a lesion compatible with metastasis at the old PEG site 7 years later. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy allows for more effective organs at risk avoidance than photon radiotherapy, thus reducing both radiation-induced toxicity and second cancer risk. The aim of the present paper is to compare protons and photons outcomes in the context of oropharyngeal and nasopharyngeal cancer and provide an updated comprehensive overview of the most promising new approaches and methodologies for treating head and neck cancer with protons. The growing interest in proton therapy (PT) in recent decades is justified by the evidence that protons dose distribution allows maximal dose release at the tumor depth followed by sharp distal dose fall-off. But, in the holistic management of head and neck cancer (HNC), limiting the potential of PT to a mere dosimetric advantage appears reductive. Indeed, the precise targeting of PT may help evaluate the effectiveness of de-escalation strategies, especially for patients with human papillomavirus associated-oropharyngeal cancer (OPC) and nasopharyngeal cancer (NPC). Furthermore, PT could have potentially greater immunogenic effects than conventional photon therapy, possibly enhancing both the radiotherapy (RT) capability to activate anti-tumor immune response and the effectiveness of immunotherapy drugs. Based on these premises, the aim of the present paper is to conduct a narrative review reporting the safety and efficacy of PT compared to photon RT focusing on NPC and OPC. We also provide a snapshot of ongoing clinical trials comparing PT with photon RT for these two clinical scenarios. Finally, we discuss new insights that may further develop clinical research on PT for HNC. [ABSTRACT FROM AUTHOR]

Introduction: Metronomic capecitabine used as an adjuvant therapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This therapeutic approach may also contribute to improving immune function, consequently enhancing overall therapeutic efficacy. Aim: We aimed to evaluate the effect of metronomic capecitabine as adjuvant therapy on immune function and survival in cases of LA-NPC. Subjects and methods: 28 patients with LA-NPC were enrolled in the study and equally assigned to two groups of 14 each: experimental and control group. The experimental group received induction chemotherapy + concurrent chemotherapy + adjuvant chemotherapy as well as oral capecitabine at a dose of 650 mg/m² of body surface area twice daily for 1 year, with the option to discontinue in case of intolerance. The control group did not receive additional chemotherapy or targeted drugs after the induction chemotherapy + concurrent chemoradiotherapy; however, they were followed up regularly. Changes in immune function and survival were compared between the two groups. Results: The median follow-up time was 43.5 months. One year after adjuvant chemotherapy, the experimental group showed higher levels of CD8 + cells, CD28 + CD8 + cells, and activated CD8 + cells compared to the control group (P < 0.05). The CD4/CD8 ratio and proportion of monocyte-derived dendritic cells were also higher in the experimental group than in the control group, but the difference was not statistically significant (P ≥ 0.05). Comparisons of 3-year overall survival, local-regional recurrence-free survival, progression-free survival, and distant metastasis-free survival between the two groups showed percentages of 92.9% vs. 78.6%, 92.9% vs. 92.9%, 78.6% vs. 71.4%, and 85.7% vs. 0.78 0.6% respectively, but these differences were not significant (P > 0 0.05). Conclusion: Metronomic capecitabine chemotherapy was observed to induce an immunomodulatory effect in LA-NPC. Trial registration: NCT02958111, date of registration 04-11-2016. [ABSTRACT FROM AUTHOR]

Introduction: Alongside the improved survival of nasopharyngeal cancer (NPC), late radiation toxicities are alarmingly hampering survivors' quality of life. A patient-reported symptom burden survey is lacking to address the unmet need for symptom management among local NPC survivors. Methods: A single-center cross-sectional survey was conducted on 211 NPC survivors who had completed radiation therapy for three to 120 months. We employed the Chinese version M. D. Anderson Symptom Inventory - Head & Neck Module (MDASI-HN-C), Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN-C), and a question extracted from the Cancer Survivors' Unmet Needs Measure (CaSUN). Results: Two hundred valid responses were collected. Participants suffered from at least four moderate to severe symptoms (mean = 4.84, SD = 4.99). The top five severe symptoms were dry mouth, mucus problems, difficulty swallowing or chewing, teeth or gum problems, and memory problems. MDASI-HN-C subscales were negatively correlated with the physical, emotional, functional, and HN-specific domains of the FACT-HN-C. The unmet need for symptom management was positively associated with symptom burden, either general symptoms (Adjusted odds ratio [ORadj] = 1.566, 95% CI = 1.282 - 1.914, p < 0.001) or top-5 symptoms (ORadj = 1.379, 95% CI = 1.185 - 1.604, p < 0.001), while negatively associated with post-RT time (ORadj = 0.981, 95% CI [0.972, 0.991], p < 0.001). Conclusion: Virtually all NPC survivors suffer from late toxicities, which interplay with survivors' perceptions intricately to affect their unmet needs for symptom management. Personalized supportive care strategies with regular assessments and stratifications are warranted. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the predictive significance of hemoglobin (Hb) values in the incidence of radiation‐induced trismus (RIT) in locally advanced nasopharyngeal carcinoma (LA‐NPC) patients who received concurrent chemoradiotherapy (C‐CRT). Methods: Data of LA‐NPC patients were examined before and after C‐CRT and to confirm the presence of RIT, maximum mouth openings (MMO) were measured; RIT is defined as an MMO of ≤35 mm. All Hb values were derived from complete blood count tests obtained on the first day of C‐CRT. The receiver operating characteristic (ROC) curve analysis was used to scrutinize a possible connection between pre‐treatment Hb values and RIT status. Results: Two hundred and twenty three patients were included in the study and RIT was diagnosed in 46 (20.6%) patients. The Hb cutoff in ROC curve analysis that separated the patients into two groups was 12.05 g/dL [Area under the curve (AUC): 82.7%; sensitivity: 72.9%; and specificity: 71.3%]. RIT was significantly more prevalent in the Hb ≤ 12 g/dL group than in its counterpart (41.9% vs. 7.3%; p < 0.001). In multivariate analysis, Hb ≤ 12, anemia, pre‐C‐CRT MMO < 41.4 mm, and masticatory apparatus doseV58 Gy < 32% groups were found to be independently associated with significantly increased rates of RIT. Conclusion: Low pre‐C‐CRT Hb and anemia status are novel biological markers that independently predict higher RIT rates in LA‐NPC undergoing C‐CRT. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the epidemiological, clinical, and therapeutic aspects and prognosis of juvenile nasopharyngeal carcinoma in Tunis country. Materials and Methods: This study included 68 patients, younger than 18 years of age. All the patients had a clinical and para-clinical tumoral assessment. The study of survival and prognostic factors was done after a descriptive analysis. These prognostic factors were studied through uni and multivariate analysis. Results: The median age was 14.7 years and the sex ratio was 2 male to 1 female. The average time to first consultation was 4 months. Rhinological signs were the most frequent symptom for consultation (n= 41). The T3-T4 tumors accounted for 78% of patients and there was a lymph node invasion stage N2-N3 in 63% of cases. Non-metastatic patients had radiotherapy associated with chemotherapy in 97% of cases. Metastatic patients received hypofractionated radiotherapy on bone metastasis, and first-line chemotherapy followed by radiotherapy on the primitive tumor and lymph node areas in case of good response to chemotherapy (n= 2). The mean follow-up was 94 months; 78% of these patients were alive and in complete remission, 19% were in therapeutic failure, and 16% of them had metachronous metastases. The five-year-overall survival was 95%. Hyposialia and skin dystrophy were the most frequent late complications. In univariate analyses, significant prognostic factors were cranial nerve invasion, intracranial invasion, and infra-temporal fossa invasion. In multivariate analysis, the most parsimonious model associated extension to the infratemporal fossa, endo-cranial extension, and initial therapeutic modality (treatment failures were less frequent with neoadjuvant chemotherapy (p= 0.22)). Conclusion: Treatment of nasopharyngeal carcinoma in children consists of chemotherapy and radiotherapy. Synchronous or metachronous metastases are common in this patient population. Modern radiotherapy techniques, including conformal radiotherapy with intensity modulation, are promising and could overcome toxicities in long-term survivors. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim The German NPC‐GPOH trials introduced treatment including neoadjuvant chemotherapy, radiochemotherapy (RCT) and antiviral treatment in patients aged 25 years or younger with nasopharyngeal cancer (NPC). We conducted a retrospective study on outcomes of patients at the age of ≥26 years treated accordingly at our institution. Methods Consecutive patients who received primary RCT for NPC were included. The Kaplan–Meier method was used to calculate survival probabilities, and the Cox regression analysis was used to test for an influence of the variables on outcomes. Acute and late toxicity were evaluated via CTCAE criteria and LENT/SOMA criteria, respectively. Results In total, 30 patients were included. Diagnosis was made from 09/1994 to 11/2016. The median 5 year overall survival (OS), disease‐free survival (DFS), cancer‐specific survival (CSS) and locoregional recurrence‐free survival (LRC) were 75%, 56%, 83%, and 85%, respectively. We found a negative impact on outcomes (p

Abstract Objective To analyze the efficacy and adverse effects of anti‐PD‐1 immune checkpoint inhibitors aimed at nasopharyngeal carcinoma (NPC). Methods During the first stage of the study, using 40 patients with stage III/IVa NPC treated with anti‐PD‐1 immune checkpoint inhibitors in combination with chemoradiotherapy as a first‐line treatment (observation group) and 70 patients with NPC treated with chemoradiotherapy alone (control group). In the second stage of the study, 88 patients with NPC treated with immune checkpoint inhibitors were grouped according to the number of lines of immunotherapy, the number of times, and the types of application. Results Observation of the short‐term effects in the first stage indicated that the objective response rate (ORR) of the observation group and the control group against primary foci of NPC was 75.0% versus 40.0%; the mortality rate of the observation group was much lower than that of the control group. The overall first‐line treatment evaluation of the observation vs. control groups were as follows: ORR (67.5% vs. 38.6%); median PFS (17.52 vs. 17.21 months); and median OS (18.68 vs. 18.14 months), respectively (p

Handoko,1– 3,&ast; Marlinda Adham,2,4,&ast; Lisnawati Rachmadi,2,5,&ast; Heri Wibowo,6,&ast; Soehartati A Gondhowiardjo1,2,&ast; 1Department of Radiation Oncology, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 2Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 4Department of Otorhinolaryngology - Head and Neck Surgery Department, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 5Department of Anatomical Pathology, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 6Integrated Laboratory, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia&ast;These authors contributed equally to this workCorrespondence: Soehartati A Gondhowiardjo, Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No. 6, Jakarta, 10430, Indonesia, Email handoko12@ui.ac.id; gondhow@gmail.comIntroduction: Nasopharyngeal cancer (NPC) is a complex cancer due to its unique genomic features and association with the Epstein–Barr virus (EBV). Despite therapeutic advancements, NPC prognosis remains poor, necessitating a deeper understanding of its genomics. Here, we present a comprehensive whole genome sequencing (WGS) view of NPC genomics and its correlation with the phenotype.Methods: This study involved WGS of a clinical NPC biopsy specimen. Sequencing was carried out using a long read sequencer from Oxford Nanopore. Analysis of the variants involved correlation with the phenotype of NPC.Results: A loss of genes within chromosome 6 from copy number variation (CNV) was found. The lost genes included HLA-A, HLA-B, and HLA-C, which work in the antigen presentation process. This loss of the major histocompatibility complex (MHC) apparatus resulted in the tumour’s ability to evade immune recognition. The tumour exhibited an immunologically “cold” phenotype, with mild tumour-infiltrating lymphocytes, supporting the possible etiology of loss of antigen presentation capability. Furthermore, the driver mutation PIK3CA gene was identified along with various other gene variants affecting numerous signaling pathways.Discussion: Comprehensive WGS was able to detect various mutations and genomic losses, which could explain tumour progression and immune evasion ability. Furthermore, the study identified the loss of other genes related to cancer and immune pathways, emphasizing the complexity of NPC genomics. In conclusion, this study underscores the significance of MHC class I gene loss and its probable correlation with the cold tumour phenotype observed in NPC.Keywords: nasopharyngeal cancer, genomic, MHC class I, antigen processing and presentation, copy number variation, deletion

Abstract Background Programmed cell death protein 1 (PD-1) monoclonal antibody, pembrolizumab, is a promising drug for platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (NPC). We aimed to assess the cost-effectiveness of pembrolizumab compared with chemotherapy for Chinese patients in this NPC. Methods The cost-effectiveness of pembrolizumab versus chemotherapy was evaluated using a partitioned survival model with a 5-year boundary. Efficacy and toxicity data were derived from the KEYNOTE-122 trials. Economic indicators including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and lifetime cost were used. One-way analysis and probabilistic sensitivity analysis (PSA) were performed to explore the uncertainties. Additionally, various scenario analyses, including different pembrolizumab price calculations and discount rates were performed. Results Pembrolizumab or chemotherapy alone respectively yielded 2.82 QALYs (3.96 LYs) and 2.73 QALYs (3.93 LYs) with an ICER of $422,535 per QALYs ($1,232,547 per LYs). This model was primarily influenced by the price of pembrolizumab. Furthermore, PSA indicated that pembrolizumab had none probability of being cost-effective compared with chemotherapy at a willingness-to- pay (WTP) of $38223. Scenario analyses revealed that irrespective of any potential price reduction or adjustments in the discount rate, no discernible impact on the ultimate outcome was observed. Conclusion Pembrolizumab was less cost-effective for patients with platinum-pretreated, recurrent or metastatic NPC compared with chemotherapy in China.

Background: We sought to determine whether pretreatment total masseter muscle volume (TMMV) measures can predict radiation-induced trismus (RIT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT). Methods: We retrospectively reviewed the medical records of LA-NPC patients who received C-CRT and had pretreatment maximum mouth openings (MMO) greater than 35 mm. MMO of 35 mm or less after C-CRT were considered RIT. We employed receiver operating characteristic (ROC) curve analysis to explore the correlation between pre-treatment TMMV readings and RIT status. Results: Out of the 112 eligible patients, 22.0% of them received a diagnosis of RIT after C-CRT. The optimal TMMV cutoff that was significantly linked to post-C-CRT RIT rates was determined to be 35.0 cc [area under the curve: 79.5%; sensitivity: 75.0%; and specificity: 78.6%; Youden index: 0.536] in the ROC curve analysis. The incidence of RIT was significantly higher in patients with TMMV ≤ 5.0 cc than in those with TMMV > 35.0 cc [51.2% vs. 8.7%; Odds ratio: 6.79; p < 0.001]. A multivariate logistic regression analysis revealed that pre-C-CRT MMO ≤ 41.6 mm (p = 0.001), mean masticatory apparatus dose V56.5 ≥ 34% group (p = 0.002), and TMMV ≤ 35 cc were the independent predictors of significantly elevated rates of RIT. Conclusion: The presence of a smaller pretreatment TMMV is a reliable and independent novel biological marker that can confidently predict higher RIT rates in LA-NPC patients who receive C-CRT.

Simple Summary: Intensity-modulated proton therapy (IMPT) has proven to be more effective in minimizing radiation exposure to normal organs when compared to photon-based volumetric modulated arc therapy (VMAT) in patients diagnosed with nasopharyngeal cancer (NPC). This retrospective cohort study represents the first quantitative assessment of the longitudinal impact on the quality of life (QoL) outcomes in NPC patients undergoing treatment with IMPT (n = 41) as opposed to VMAT (n = 246). We gathered data on global QoL, functional QoL, C30 symptoms, and HN35 symptoms using the EORTC QLQ-C30 and QLQ-HN35 questionnaires at four time points: pre radiotherapy (RT), during RT, 3 months post RT, and 12 months post RT. IMPT demonstrated superior mean dose reductions in 12 of the 16 organs at risk compared to VMAT. This reduction in radiation dose, attributed to the IMPT technique, appears to be associated with positive outcomes in functional QoL, reflecting a noteworthy increase of 7.5 points and a decrease of 10.7 points in HN35 symptoms. However, this effect is time dependent and exclusively observed at the time point of during RT. Purpose: This retrospective cohort study aims to compare the quality of life (QoL) in patients with nasopharyngeal cancer (NPC) treated with intensity-modulated proton therapy (IMPT) versus volumetric modulated arc therapy (VMAT) at different time points. Materials and Methods: We conducted a longitudinal assessment of QoL on 287 newly diagnosed NPC patients (IMPT: 41 and VMAT: 246). We collected outcomes of global QoL, functional QoL, C30 symptoms, and HN35 symptoms from EORTC QLQ-C30 and QLQ-HN35 questionnaires at pre-radiotherapy, during radiotherapy (around 40 Gy), 3 months post radiotherapy, and 12-months post radiotherapy (RT). The generalized estimating equation was utilized to interpret the group effect, originating from inherent group differences; time effect, attributed to RT effects over time; and interaction of the group and time effect. Results: IMPT demonstrated superior mean dose reductions in 12 of the 16 organs at risk compared to VMAT, including a significant (>50%) reduction in the oral cavity and larynx. Both groups exhibited improved scores of global QoL, functional QoL, and C30 symptoms at 12 months post RT compared to the pre-RT status. Regarding global QoL and C30 symptoms, there was no interaction effect of group over time. In contrast, significant interaction effects were observed on functional QoL (p = 0.040) and HN35 symptoms (p = 0.004) during RT, where IMPT created an average of 7.5 points higher functional QoL and 10.7 points lower HN35 symptoms than VMAT. Conclusions: Compared to VMAT, dose reduction attributed to IMPT could translate into better functional QoL and HN35 symptoms, but the effect is time dependent and exclusively observed during the RT phase. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) is an epithelial malignancy arising from the nasopharyngeal mucosal lining. A high incidence was recorded in EBV-endemic areas (EA) such as East and Southeast Asia [1] while in Europe, a non-endemic area (NEA), is low (1/105/year); however, the estimated survival rate is much lower than that recorded in Asian EA (5-year age-standardized relative survival = 54–57% vs. 74%) [2]. Risk factors of NPC include genetic, ethnic and environmental factors [3]. Differences in incidence and survival rates between EA and NEA NPCs could involve several factors, including EBV-related factors, genetic susceptibility of the population to EBV infections, and environmental factors such as diet and pollution [4-7]. Nevertheless, all proposed models of NPC pathogenesis are based on data derived from EA in Asia. Furthermore, clinical, pathogenic, and microenvironmental characteristics may play additional roles. EBV-related NPC in EA has already been characterized using genomic and transcriptomic data analysis [8-9]. However, gene expression analysis data [10] of NEA NPC is limited. Comparing gene expression data from EA and NEA diseases allows the recognition of similarities and differences in incidence and outcome among diseases arising in different geographical areas. We investigated the transcriptomic patterns of genes involved in EA NPC to interpret these differences and verifying them to an Italian cohort with available tumor tissue and clinical data. The immune and biological/functional characterization of EA and NEA NPC could improve the identification of new therapeutic strategies. Currently, the treatment for localized NPC includes radiotherapy, which is often combined with platinum-based chemotherapy, especially for locally advanced cancer. Neoadjuvant chemotherapy with cisplatin and gemcitabine was administered in the case of high-risk disease [11 -12]. Immunotherapy with checkpoint inhibitors has shown clinical efficacy in recurrent/metastatic advanced NPC and is currently under evaluation to define its mechanism of action [13]. Our study aimed to dissect the gene expression (GE) and microenvironment of NPC, leading to the identification of the molecular subtypes of EA and NEA NPC. We also aimed to elucidate the biological and functional differences within EA NPC and between EA NPC and NEA NPC to eventually provide new insights into novel treatment strategies. Six GE datasets of NPC-EA transcriptomic repositories, including tumor and normal samples (GSE12452, GSE34573, GSE132112, GSE53819, GSE68799, GSE102349) and one validation dataset including both EA and NEA (https://doi.org/10.5281/zenodo.5347891) were retrieved. Four GE signatures associated to EBV related NPC prognosis (PMID: 24297049, 35262435, 32596151, 33096113), genes/pathways and gene sets (PMID: 35846746, 35394843, 35105963) were applied on EA and NEA NPC cohorts (Liu_NPC, Wood EBV EBNA1 Targets Down, Sengupta NPC_with LMP1 UP, REACTOME DNA Repair; Hallmarks). A bioinformatic meta-analysis approach was used to integrate the six EA datasets, and the classifier method was applied to the validation dataset in order to identify the subtype with worst prognosis. Moreover, RNA sequencing was performed on 50 Italian NEA NPC samples (study number: INT188/19; GSE208281). Biological and functional profiling of EA and NEA were performed using xCell, Gene set enrichment analyses, and treatment prediction methods (radiosensitivity index PMID: 16103067, pRRophetic R package, Immunophenoscore PMID: 28052254). Through the meta-analysis of EA-NPC datasets, four clusters (Cl) were identified. Prognostic analyses revealed that Cl3 had the worst prognosis (P=0.0476), confirmed by three of the four prognostic signatures and in the validation dataset (P=0.0368). The biological and functional characterization of these clusters disclosed the relative GE subtypes: Cl1, Immune-active; Cl2, Defense-response; Cl3, Proliferation;Cl4, Perineural-interaction/EBV-exhaustion. According to the treatment prediction methods, the sensitivity of each cluster was radiotherapy and immunotherapy for immune-active, radiochemotherapy and immunotherapy for defense-response, chemotherapy for proliferation, and cisplatin treatment for perineural-interaction/EBV-exhaustion. Only three clusters, excluding perineural-interaction/EBV-exhaustion, were expressed in our NEA cohort. Immune/biological characterization and treatment prediction analyses of NEA partially replicated the EA results. Our study provides a relevant biological overview of EBV-related NPC in both EA and NEA. The immune microenvironment plays a critical role in NPC owing to the viral etiology of this malignancy. The presence of a perineural-interaction/EBV-exhaustion cluster in EA suggests an inactive EBV infection according to the viral related "hit and run theory". Evaluation of miRNAs is ongoing along with miRNA/gene expression integration. Well characterized EA- and NEA-NPC retrospective and prospective cohorts are needed to validate the obtained results and can help designing future clinical studies. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNA) are small and conserved noncoding RNA molecules that regulate gene expression at the posttranscriptional level. These groups of RNAs are crucial in various cellular processes, especially in mediating disease pathogenesis, particularly cancer. The dysregulation of miRNAs was reported in many cancer types, including nasopharyngeal cancer (NPC), which is a malignant tumor of the nasopharynx. In this review, miRNAs involvement in crucial signaling pathways associated with NPC such as PTEN/PI3K/AKT, TGFβ/SMAD, RAS/MAPK, Wnt/β‐catenin and pRB‐E2F was investigated. miRNAs could function as tumor suppressor‐miR or onco‐miR in NPC profoundly influenced cell cycle, apoptosis, proliferation, migration, and metastasis. This comprehensive review of current literature provided a thorough profile of miRNAs and their interplay with the aforementioned signaling pathways in NPC. Understanding these molecular interactions could remarkably impact the diagnosis, prognosis, and therapeutic strategies for NPC. Significance statement: miRNAs play a pivotal role in orchestrating crucial signaling pathways in nasopharyngeal carcinoma, affecting fundamental cellular processes. The iintricate regulation of PTEN/PI3K/AKT, TGFβ/SMAD, RAS/MAPK, Wnt/β‐Catenin and pRB‐E2F pathways underscores their significance as potential therapeutic targets in combating disease progression. [ABSTRACT FROM AUTHOR]

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The patients with the nasopharyngeal cancer are required to breath through their mouth after performing the surgery. Hence, it is required to perform the breathing site classification and employs the classification results to indicate whether the patients breath correctly or not. Nevertheless, there is currently no such a medical aided tool in the market. To address this issue, this paper extracts both the mel frequency cepstral coefficients (MFCCs) based features and the gammatone frequency cepstral coefficients (GFCCs) based features as well as employs the random forest as the classifier for performing the breathing site classification. The data lasted for a few minutes acquired from 10 volunteers are employed to demonstrate the effectiveness of our proposed method. The computer numerical simulation results show that the average accuracy, the average specificity and the average sensitivity yielded by our proposed method are 95.30±2.00%, 93.27±3.87% and 97.15±1.87%, respectively. Although this paper proposes a method based on the fusion of two types of the acoustic features for classifying different breathing sites, the computer numerical simulation results show that our proposed method outperforms the common respiration or speech processing based methods. Besides, our proposed method is also compared to a series of relevant methods. It is found that our proposed method achieves the highest classification results at the majority signal to noise ratios among the state of the arts methods. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death protein 1 (PD-1) monoclonal antibody, pembrolizumab, is a promising drug for platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (NPC). We aimed to assess the cost-effectiveness of pembrolizumab compared with chemotherapy for Chinese patients in this NPC. Methods: The cost-effectiveness of pembrolizumab versus chemotherapy was evaluated using a partitioned survival model with a 5-year boundary. Efficacy and toxicity data were derived from the KEYNOTE-122 trials. Economic indicators including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and lifetime cost were used. One-way analysis and probabilistic sensitivity analysis (PSA) were performed to explore the uncertainties. Additionally, various scenario analyses, including different pembrolizumab price calculations and discount rates were performed. Results: Pembrolizumab or chemotherapy alone respectively yielded 2.82 QALYs (3.96 LYs) and 2.73 QALYs (3.93 LYs) with an ICER of $422,535 per QALYs ($1,232,547 per LYs). This model was primarily influenced by the price of pembrolizumab. Furthermore, PSA indicated that pembrolizumab had none probability of being cost-effective compared with chemotherapy at a willingness-to- pay (WTP) of $38223. Scenario analyses revealed that irrespective of any potential price reduction or adjustments in the discount rate, no discernible impact on the ultimate outcome was observed. Conclusion: Pembrolizumab was less cost-effective for patients with platinum-pretreated, recurrent or metastatic NPC compared with chemotherapy in China. [ABSTRACT FROM AUTHOR]