Effect of immune-modulating metronomic capecitabine as an adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma.

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.

Cost-effectiveness of pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent or metastatic nasopharyngeal cancer.

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.

Definitive radiotherapy for nasopharyngeal carcinoma in Japan: analysis of cases in the National Head and Neck Cancer Registry from 2011 to 2014.

OBJECTIVE: This study aimed to analyze the nationwide prognosis of patients with nasopharyngeal carcinoma who underwent definitive radiotherapy in Japan, utilizing the National Head and Neck Cancer Registry data. METHODS: A total of 741 patients diagnosed with primary nasopharyngeal carcinoma were screened from 2011 to 2014. The inclusion criteria were histologically proven nasopharyngeal squamous cell carcinoma, receiving definitive radiotherapy, and no distant metastases. Patients with unclear prognoses or unknown staging were excluded. The primary endpoint was 5-year overall survival, and secondary endpoints were 5-year progression-free survival and survival by stage. RESULTS: A total of 457 patients met the inclusion criteria. The median age was 60 years, and 80% were male. The proportions of patients with performance status 0, 1, 2 and 3 were 69, 10, 1 and 1%, respectively. Chemoradiotherapy was administered to 84.7%. Radiotherapy modalities were recorded only for 29 patients (three received intensity-modulated radiotherapy and 26 received two/three-dimensional radiotherapy). Of those included, 7.4, 24.7, 35.7, 24.5 and 7.7% had Stage I, II, III, IVA and IVB disease, respectively. The 5-year overall survival was 72.5% for all patients: 82.6, 86.6, 76.0, 51.4 and 66.5% for Stage I, II, III, IVA and IVB disease, respectively. The 5-year progression-free survival was 58.6%: 75.6, 66.8, 61.5, 43.7 and 46.5% for Stage I, II, III, IVA and IVB disease, respectively. CONCLUSIONS: This nationwide survey demonstrated favorable prognoses and provided valuable foundational data for similar future surveys to monitor the penetration of appropriate treatment and changes in clinical structures based on new evidence.

Regulatory role of miRNAs in nasopharyngeal cancer involving PTEN/PI3K/AKT, TGFß/SMAD, RAS/MAPK, Wnt/ß-catenin and pRB-E2F signaling pathways: A review.

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, TGFß/SMAD, RAS/MAPK, Wnt/ß-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.

The association between chronic sinonasal inflammation and nasopharyngeal carcinoma - A systematic review and meta-analysis.

PURPOSE: There has been mounting evidence that inflammation is a key risk factor towards the development of certain cancers. Past studies have shown associations between nasopharyngeal carcinoma (NPC) and sinonasal tract inflammation. We aim to conduct a review and meta-analysis on the association between NPC and chronic sinus inflammation. MATERIALS AND METHODS: We conducted a meta-analysis, searching 4 international databases from 1 January 1973 to 28 March 2022 for studies reporting on sinonasal inflammation and NPC in adult patients (>18 years old). We included cohort, case-control or cross-sectional studies. These studies must examine the association between a prior history of sinonasal inflammation and the risk of developing NPC. The outcome is the incidence of NPC in patients who had prior sinonasal inflammation. RESULTS: 8 studies (8245 NPC; 1,036,087 non-NPC) were included. The overall odds ratio (OR) of patients having NPC after reporting sinonasal inflammation was 1.81 (95 % CI 1.73-1.89). Of note, chronic rhinosinusitis (CRS) (OR of 1.78 (95 %-CI: 1.68-1.90)) was more closely associated with an increased risk of NPC, as compared to allergic rhinitis (AR) (OR of 1.60 (95 %-CI: 1.52-1.68)). CONCLUSION: Chronic sinonasal inflammation is significantly associated with NPC in this systemic review and meta-analysis. The true cause-effect relationship and the potential effects of targeted screening need to be explored thoroughly with large scale prospective studies.

Patterns of failure in patients with nasopharyngeal cancer of Northeastern region of India: a retrospective observational study.

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.

CircLASP1 silence strengthens the therapeutic effects of MK-2206 on nasopharyngeal cancer through upregulating miR-625.

Therapeutic effects of MK-2206 are largely limited due to the complexity of the pathogenesis of nasopharyngeal cancer (NPC). Here, we aimed to investigate whether and how circLASP1 is involved in the therapeutic effects of MK-2206 on NPC. We showed circLASP1 was increased while miR-625 was decreased in NPC tissues and cell lines. CircLASP1 silence strengthened the therapeutic effects of MK-2206 via suppressing NPC cell proliferation and inducing autophagy and apoptosis in vitro. In mechanism analyses, we found that circLASP1 indirectly released AKT by directly binding to miR-625 in NPC cells, and miR-625 acted as a tumor suppressor in NPC and activated cell autophagy through inhibiting the AKT/mTOR pathway. Most importantly, knockdown of circLASP1 was revealed to enhance the therapeutic effects of MK-2206 on NPC in vivo. Our results suggest that the circLASP1/miR-625 axis is involved the therapeutic effects of MK-2206 on NPC by regulating autophagy, proliferation, and apoptosis through the AKT/mTOR pathway. miR-625 is involved in NPC tumorigenesis.

Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial.

BACKGROUND: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented. PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population. RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage). CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.

Utility of pre-chemoradiotherapy Pan-Immune-Inflammation-Value for predicting the osteoradionecrosis rates in locally advanced nasopharyngeal cancers.

PURPOSE: The aim of this retrospective study was to explore whether pretreatment Pan-Immune-Inflammation-Value (PIV) measurements might predict the risk of mandibular osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal cancer (LA-NPC). METHODS: The platelet, monocyte, neutrophil, and lymphocyte counts acquired on the first day of CCRT were used to compute pretreatment PIV levels: PIV = (Plateletsâ€¯× Monocytesâ€¯× Neutrophils) ÷ Lymphocytes. Receiver operating characteristic curve analysis was used to determine the association between ORN rates and PIV levels. Spearman correlation analysis was used to examine the probable intergroup correlations. The potential link between the pretreatment PIV levels and the post-treatment ORN rates was determined as the primary objective. RESULTS: 21 (10.0%) of 210 eligible patients were diagnosed with ORN. The optimal pre-CCRT PIV cutoff was 833, which separated patients into two PIV groups with divergent ORN prevalence estimates: Group 1: PIV < 833 (N = 153), and Group 2: PIV ≥ 833 (N = 57). The comparison analysis found that the PIV ≥ 833 cohort had significantly higher ORN rates than the PIV < 833 cohort (29.8% vs. 2.6%; P < 0.001). Other characteristics linked to significantly higher ORN rates were the patient's continuing smoking, the use of the Three-dimensional conformal radiation therapy technique, the mean mandibular dose of ≥ 58.1 Gy, the number of tooth extractions before CCRT ≥ 4, and the presence of tooth extractions after CCRT. The independent importance of all factors on higher ORN occurrence rates were retained in multivariate analysis (P < 0.05). CONCLUSIONS: Our findings revealed a strong link between aggravated inflammatory response and ORN genesis, with high pretreatment PIV levels related to significantly higher ORN rates.

Classification of multiple cancer types by combination of plasma-based near-infrared spectroscopy analysis and machine learning modeling.

BACKGROUND AND AIM: Near-infrared spectroscopy (NIRS) is a non-invasive and convenient tool, which gains features related to chemical components in biological samples. Machine learning (ML) has been popularized in medical diagnosis. This study aimed at investigating a novel cancer diagnosis strategy using NIRS data based ML modeling. METHODS: Plasma samples were collected from a total of 247 participants, including lung cancer, cervical cancer, nasopharyngeal cancer, and healthy control, and were randomly split into train set and test set. After performing NIRS analysis, the train dataset was utilized to train ML models, including partial least-squares (PLS), random forest (RF), gradient boosting machine (GBM), and support-vector machine (SVM). Subsequently, these models were tested for their prediction performance by the test set. RESULTS: All ML models demonstrated high prediction performance in differentiating cancers from controls, and SVM had high prediction accuracy for different types of cancers. SVM was considered as the most suitable model for its minimal computational cost and high accuracies for both binary and quaternary classification. CONCLUSIONS: This strategy coupling NIRS with ML is insightful that may aid in clinic cancer diagnosis, while further studies should test our results in a larger cohort with better representativeness.

NLG-919 combined with cisplatin to enhance inhibitory effect on cell migration and invasion via IDO1-Kyn-AhR pathway in human nasopharyngeal carcinoma cell.

As a common aggressive head and neck cancer, nasopharyngeal carcinoma (NPC) received cisplatin treatment as a first-line chemotherapy. Platinum-induced resistance is a major limitation of current treatment strategy in the advanced NPC. Increased indoleamine 2,3-dioxygenase (IDO1) activities are found in cisplatin-resistant NPC cells versus cisplatin-sensitive NPC cells. As an IDO1 immunosuppressant, NLG-919 has entered clinical phase I to treat advanced solid tumors. To reverse cisplatin resistance, we investigated the combinatory application of cisplatin and NLG-919 in NPC treatment. In vitro biological studies on cisplatin-resistant and cisplatin-sensitive NPC cells were taken to imply that the combination of NLG-919 and cisplatin got a stronger impact on the induction of cell apoptosis and the inhibition of cell migration, exploring superior effect of antitumor over single drug. We proved that the mechanism of the combined therapy could inhibit the activity of IDO1, blocking amino acid tryptophan conversion to kynurenine through the kynurenine pathway, which further inhibited the aryl hydrocarbon receptor expression. Our study underscored the combination of cisplatin and NLG-919 as a potent therapeutic way for the reversal of cisplatin resistance.

Intra- and peritumoral MRI radiomics assisted in predicting radiochemotherapy response in metastatic cervical lymph nodes of nasopharyngeal cancer.

BACKGROUND: To establish and validate radiomic models combining intratumoral (Intra) and peritumoral (Peri) features obtained from pretreatment MRI for the prediction of treatment response of lymph node metastasis from nasopharyngeal cancer (NPC). METHODS: One hundred forty-five NPC patients (102 in the training and 43 in the validation set) were retrospectively enrolled. Radiomic features were extracted from Intra and Peri regions on the metastatic cervical lymph node, and selected with the least absolute shrinkage and selection operator (LASSO). Multivariate logistic regression analysis was applied to build radiomic models. Sensitivity, specificity, accuracy, and the area under the curve (AUC) of receiver operating characteristics were employed to evaluate the predictive power of each model. RESULTS: The AUCs of the radiomic model of Intra, Peri, Intra + Peri, and Clinical-radiomic were 0.910, 0.887, 0.934, and 0.941, respectively, in the training set and 0.737, 0.794, 0.774, and 0.783, respectively, in the validation set. There were no significant differences in prediction performance among the radiomic models in the training and validation sets (all P > 0.05). The calibration curve of the radiomic model of Peri demonstrated good agreement between prediction and observation in the training and validation sets. CONCLUSIONS: The pretreatment MRI-based radiomics model may be useful in predicting the treatment response of metastatic lymph nodes of NPC. Besides, the generalization ability of the radiomic model of Peri was better than that of Intra and Intra + Peri.

Low hemoglobin levels predict increased radiation-induced trismus rates in nasopharyngeal cancer.

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.

Hemoglobin-to-platelet ratio in predicting the incidence of trismus after concurrent chemoradiotherapy.

OBJECTIVE: The significance of pre-hemoglobin-to-platelet ratio (HPR) in predicting the occurrence of radiation-induced trismus (RIT) in locally advanced nasopharyngeal carcinoma patients (LA-NPC) who received concurrent chemoradiotherapy (C-CRT). METHODS: The records of LA-NPC patients with oral examination before and after C-CRT were analyzed. Maximum mouth openings (MMO) were measured before and after C-CRT to confirm RIT status, with an MMO of ≤35 mm defined as RIT. HPR values were calculated on the first day of C-CRT. The relationship between the HPR values and RIT status was discovered using the receiver operating characteristic curve analysis. RESULTS: A total of 43 patients RIT cases among 198 individuals were diagnosed. The optimal HPR cutoff that stratified the patients into two groups was 0.54. RIT incidence was found to be significantly higher in the HPR ≤0.54 group than its HPR >0.54 counterpart(p < 0.001). Univariately T3-4 stage, mean masticator apparatus dose>57.2Gy, and pre-C-CRT MMO ≤40.7 mm were found as the other significant correlates of increased RIT rates(p < 0.05). All four variables seemed to be independently connected to greater RIT incidence in multivariate analysis (p < 0.05, for each). CONCLUSION: The risk of post-C-CRT RIT may be significantly increased when pre-treatment HPR levels are low.

Pre-chemoradiotherapy low hemoglobin levels indicate increased osteoradionecrosis risk in locally advanced nasopharyngeal cancer patients.

PURPOSE: We aimed to determine whether pretreatment hemoglobin (Hb) levels can predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: ORN cases were identified from the records of LA-NPCs who had oral exams before and after CCRT. All Hb measurements were obtained on the first day of treatment. Receiving operating characteristic curve analysis was used to determine the relationship between Hb levels and ORN rates. The relationship between pretreatment Hb levels and ORN rates served as the primary endpoint, and secondary endpoints included the discovery of additional potential ORN risk factors. RESULTS: Among the 263 eligible LA-NPCs, we identified 8.7% ORN cases. The ideal cutoff Hb before CCRT was 10.6 g/dL. It was revealed that HPR ≤ 10.6 group had a significantly higher ORN rate (32.5% vs. 1.5% for Hb > 10.6; P < 0.001). The mandibular V59.8 ≥ 36% Gy, pre-CCRT ≥ 4 tooth extractions, the presence of post-CCRT tooth extractions, and the time of post-CCRT tooth extractions > 8 months were the other factors associated with significantly increased ORN rates (P < 0.05 for each). CONCLUSION: Low pre-CCRT Hb levels appeared to be independently linked to significantly higher ORN rates. Pretreatment Hb levels may be used to establish preventive measures and predict ORN.

Nasopharyngeal cancer: the impact of guidelines and teaching on radiation target volume delineation.

Target volume delineation in the radiation treatment of nasopharyngeal cancer is challenging due to several reasons such as the complex anatomy of the site, the need for the elective coverage of definite anatomical regions, the curative intent of treatment and the rarity of the disease, especially in non-endemic areas. We aimed to analyze the impact of educational interactive teaching courses on target volume delineation accuracy between Italian radiation oncology centers. Only one contour dataset per center was admitted. The educational course consisted in three parts: (1) The completely anonymized image dataset of a T4N1 nasopharyngeal cancer patient was shared between centers before the course with the request of target volume and organs at risk delineation; (2) the course was held online with dedicated multidisciplinary sessions on nasopharyngeal anatomy, nasopharyngeal cancer pattern of diffusion and on the description and explanation of international contouring guidelines. At the end of the course, the participating centers were asked to resubmit the contours with appropriate corrections; (3) the pre- and post-course contours were analyzed and quantitatively and qualitatively compared with the benchmark contours delineated by the panel of experts. The analysis of the 19 pre- and post-contours submitted by the participating centers revealed a significant improvement in the Dice similarity index in all the clinical target volumes (CTV1, CTV2 and CTV3) passing from 0.67, 0.51 and 0.48 to 0.69, 0.65 and 0.52, respectively. The organs at risk delineation was also improved. The qualitative analysis consisted in the evaluation of the inclusion of the proper anatomical regions in the target volumes; it was conducted following internationally validated guidelines of contouring for nasopharyngeal radiation treatment. All the sites were properly included in target volume delineation by >50% of the centers after correction. A significant improvement was registered for the skull base, the sphenoid sinus and the nodal levels. These results demonstrated the important role that educational courses with interactive sessions could have in such a challenging task as target volume delineation in modern radiation oncology.

The predictive value of pretreatment hemoglobin-to-platelet ratio on osteoradionecrosis incidence rates of locally advanced nasopharyngeal cancer patients managed with concurrent chemoradiotherapy.

BACKGROUND: This retrospective study aimed to investigate whether the pretreatment hemoglobin-to-platelet ratio (HPR) could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (C-CRT) for locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: ORN cases were reported from the records of LA-NPC patients who had oral examinations before and after C-CRT. The pretreatment HPR values were calculated on the first day of C-CRT. The connection between HPR values and ORN occurrences was determined using receiver operating characteristic curve analysis. The primary endpoint was the relationship between the pretreatment HPR values and post-C-CRT ORN incidence rates, while secondary endpoints included the identification of other putative ORN risk factors. RESULTS: We distinguished 10.9% incidences of ORN during the post-C-CRT follow-up period among 193 LA-NPC patients. The optimal cutoff for pre-C-CRT HPR was 0.48 that grouped the patients into two HPR groups with fundamentally different post-C-CRT ORN incidence rates: Group 1: HPR ≤ 0.48 (N = 60), and Group 2: HPR > 0.48 (N = 133). The comparative analysis indicated a significantly higher ORN incidence in HPR ≤ 0.48 group (30%; P < 0.001). The other factors associated with meaningfully increased ORN rates included the presence of pre-C-CRT ≥ 5 teeth extractions, mandibular volume receiving ≥ 64 Gy, post-C-CRT tooth extractions, mean mandibular dose ≥ 50.6 Gy, and C-CRT to tooth extraction interval > 5.5 months. CONCLUSION: Low pretreatment HPR levels were independently and unequivocally linked to significantly increased incidence of ORN post-C-CRT. Pre-C-CRT HPR levels may be used to estimate the incidence of ORN and be useful for taking preventive and therapeutic measures in these patients such as monitoring oral hygiene with strict follow-up, avoidance of unnecessary tooth extractions, particularly after C-CRT, and use of more rigorous mandibular RT dose limits.

CXCL8, MMP1, MMP2, and FN1 Gene Expression and Tumor Extension in Nasopharyngeal Cancer Patients: A Cross-sectional Study.

BACKGROUND: There are correlations between tumor staging, lymph node involvement, and patient survival in Nasopharyngeal cancer (NPC) which is one of the most common types of cancer in Indonesia.  The inflammation process plays a role in tumor progression over the long term and this marked by increased proinflammatory cytokine and gene overexpression. This study aims to identify differentially expressed genes (DEGs) in NPC using T and N staging. METHODS: This is a cross-sectional study of NPC patients in Cipto Mangunkusumo, Jakarta, between 2018 and 2022. DEGs were identified based on the amount of mRNA detected on paraffin blocks with a 1.5- to -1.5-fold change and an adjusted p-value of <0.05. RESULTS: We included 48 subjects. The mean age of subjects was 47.75 (10.48) years, and most were male (77.1%). Non-keratinized squamous cell carcinoma was the most common histopathology type. Differences in the tumor size of the T4 and non-T4 in metastatic (33.3%) group when compared to the non-metastatic (37.5%) group were insignificant (p = 0.763). The proportion of N3 subjects in the metastatic vs non-metastatic group was different significantly (83.3% vs. 50%, p = 0.030). Gene expression analysis showed that C-X-C motif ligand 8 (CXCL8), matrix metalloproteinase-1 (MMP1), matrix metalloproteinase-1 (MMP2), and fibronectin-1 (FN1) genes of the T4 and non-T4 group to be different significantly. CONCLUSION: There was significant finding in the N3 subjects of the metastatic and non-metastatic groups. The DEGs of CXCL8, MMP1, MMP2, and FN1 were statistically significant in the T4 when compared to the non-T4 group.

Racial and ethnic disparities in nasopharyngeal cancer with an emphasis among Asian Americans.

Despite the overall decreasing incidence, nasopharyngeal cancer (NPC) continues to cause a significant health burden among Asian Americans (AAs), who are a fast-growing but understudied heterogeneous racial group in the United States. We aimed to examine the racial/ethnic disparities in NPC incidence, treatment, and mortality with a specific focus on AA subgroups. NPC patients aged ≥15 years were obtained from the Surveillance, Epidemiology, and End Results (SEER) 18 (1975-2018). AAs were divided into Chinese, Filipino, Vietnamese, Hawaiian, Japanese, Laotian, Korean, Cambodian, Indian/Pakistani and other Asian/Pacific Islanders (APIs). Age-adjusted incidence was calculated using the SEER*Stat software. Cox proportional and Fine-Gray subdistribution hazard models were used to calculate overall and cause-specific mortalities after adjusting for confounders. Among the total 11 964 NPC cases, 18.4% were Chinese, 7.7% Filipino, 5.0% Vietnamese, 1.2% Hawaiian, 1.0% Japanese, 0.8% Laotian, 0.8% Korean, 0.6% Cambodian, 0.5% Indian/Pakistani and 4.4% other APIs. Laotians had the highest age-adjusted NPC incidence (9.21 per 100 000), which was 18.04 times higher than it in non-Hispanic Whites (NHWs). Chinese and Filipinos observed lower overall mortalities, however, Chinese saw increased NPC-specific mortality than NHWs. Disparities in mortality were also found across different histology subtypes. This is the first and largest study examining the NPC incidence and outcomes in AA subgroups. The significant disparities of NPC within AAs underline the importance of adequate AA-subgroup sample size in future studies to understand the prognostic role of ethnicity in NPC and advocate more ethnically and culturally tailored cancer prevention and care delivery.

Occupational risk variation of nasopharyngeal cancer in the Nordic countries.

BACKGROUND: The aim of this study was to estimate occupational risk variation in the incidence of nasopharyngeal cancer (NPC) in a large population-based cohort of the Nordic Occupational Cancer (NOCCA) study. METHODS: This study is based on a cohort of almost 15 million persons from Denmark, Finland, Iceland, Norway and Sweden, with 2898 nasopharyngeal cancer cases diagnosed in 1961-2005. The data on occupations were gathered from population censuses and cancer data from the national cancer registries. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were estimated using the national NPC incidence rates as the reference. RESULTS: There were 1980 male and 918 female NPC patients. The highest SIRs of NPC were observed among male waiters (SIR 3.69, 95% CI 1.91-6.45) and cooks and stewards (SIR 2.24, 95% CI 1.16-3.91). Among women, launderers had the highest SIR of NPC (2.04, 95% CI 1.02-3.65). Significantly decreased SIRs were found among male farmers (SIR 0.79, 95% CI 0.68-0.92) and male textile workers (SIR 0.49, 95% CI 0.22-0.93). CONCLUSIONS: This study suggests that NPC may be associated with several work-related exposure agents such as smoking, kitchen air pollution and solvents. In future, occupational exposure-risk relations should be studied to understand more about causality and to assess effective prevention strategies.