Selectively sparing of the supraclavicular area during intensity-modulated radiotherapy in nasopharyngeal carcinoma: A double-center observation study.

BACKGROUND AND PURPOSE: This study was aimed at evaluating the feasibility of sparing the supraclavicular area, namely levels IVb and Vc, during intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC) patients with N1-2 disease[except N1 disease with purely restropharyngeal lymph nodes(RPN) involvement], and providing a basis for the revision of International Guideline for the delineation of the clinical target volume (CTV). PATIENTS AND MATERIALS: Patients with NPC (stage TanyN1-2M0) diagnosed pathologically in Fujian Cancer Hospital (Center 1, Only Lin SJ's attending group) from January 2014 to March 2018 and Jiangxi Cancer Hospital(Center 2) from January 2014 to December 2015 were included. According to our principle, the supraclavicular area (levels IVb and Vc) were excluded from the CTVnd. Survival outcomes focused on regional recurrence-free survival (RRFS) and recurrence rates of levels IVb and Vc were analysed. RESULTS: A total of 672 eligible patients were recruited (Center 1, n = 362; Center 2, n = 310). There was no significant difference in 5-year RRFS (97.33 % vs. 97.24 %, p = 0.980), overall survival (OS) (89.14 % vs. 88.56 %, p = 0.327), local recurrence-free survival (LRFS) (94.90 % vs. 95.30 %, p = 0.593) and distant metastasis-free survival (DMFS) (89.38 % vs. 86.60 %, p = 0.130) between Center 1 and Center 2. Twenty patients developed regional failure (median: 36 months), among them, only one case (0.15 %) was recorded as levels IVb and Vc recurrence. CONCLUSION: Omitting the supraclavicular area (levels IVb and Vc) during IMRT should be safe and feasible for N1-2 disease (except N1 disease with purely RPN involvement). Well-designed multicenter prospective trials should be conducted to confirm our findings.

Anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To identify anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma (M1-NPC). MATERIALS AND METHODS: All M1-NPC treated with chemotherapy and/or radiotherapy between 2010 and 2019 from two centers (training and validation cohort) were included. The prognostic value of metastatic disease extent and involved organs for overall survival (OS) were assessed by several multivariable analyses (MVA) models. A new M1 classification was proposed and validated in a separate cohort who received immuno-chemotherapy. RESULTS: A total of 197 M1-NPC in the training and 307 in the validation cohorts were included for M1 subdivision study with median follow-up of 46 and 57 months. MVA model with "≤2 organs/≤5 lesions" as the definition of oligometastasis had the highest C-index (0.623) versus others (0.606-0.621). Patients with oligometastasis had better OS versus polymetastasis (hazard ratio [HR] 0.47/0.63) while liver metastases carried worse OS (HR 1.57/1.45) in MVA in the training/validation cohorts, respectively. We proposed to divide M1-NPC into M1a (oligometastasis without liver metastases) and M1b (liver metastases or polymetastasis) with 3-year OS of 66.5%/31.7% and 64.9%/35.0% in the training/validation cohorts, respectively. M1a subset had a better median progress-free survival (not reach vs. 17 months, p < 0.001) in the immuno-chemotherapy cohort (n = 163). CONCLUSION: Oligometastasis (≤2 organs/≤5 lesions) and liver metastasis are prognostic for M1-NPC. Subdivision of M1-NPC into M1a (oligometastasis without liver metastasis) and M1b (liver metastasis or polymetastasis) depicts the prognosis well in M1-NPC patients who received immuno-chemotherapy.

Thyroid V40 is a good predictor for subclinical hypothyroidism in patients with nasopharyngeal carcinoma after intensity modulated radiation therapy: a randomized clinical trial.

BACKGROUND: Hypothyroidism (HT) and subclinical HT after radiotherapy is frequent in nasopharyngeal carcinoma (NPC) patients, results in negative impact on patients' quality of life. The percentage of thyroid volume receiving more than 40 Gy (V40) ≤ 85% was reported to be a useful dose constraint to adopt during intensity-modulated radiation therapy (IMRT) planning. This study aims to verify whether V40 ≤ 85% can be used as an effective dose constraint in IMRT planning in a randomized clinical trial. METHODS: This single-center 1:1 randomized clinical trial was conducted in Fujian province hospital between March 2018 and September 2022. All patients were treated with IMRT and randomized to induction chemo followed by concurrent chemo-IMRT or concurrent chemo-IMRT alone. Ninety-two clinically NPC patients were included in this study. The thyroid function tests were performed for all patients before and after radiation at regular intervals. Thyroid dose-constraint was defined as V40 ≤ 85%. The primary outcome in this study was subclinical HT. RESULTS: Median follow up was 34 months. Significant difference in the incidence of subclinical HT between the thyroid dose-constraint group and unrestricted group was observed (P = 0.023). The risk of subclinical HT in the thyroid dose-constraint group was lower than that in the unrestricted group (P = 0.022). Univariate and multivariate cox regression analysis indicated that thyroid dose-constraint was a protective effect of subclinical HT (HR = 0.408, 95% CI 0.184-0.904; HRadjusted = 0.361, 95% CI 0.155-0.841). CONCLUSION: V40 ≤ 85% can be used as an effective dose constraint in IMRT planning to prevent radiation-induced subclinical HT.

MRI-based deep learning model predicts distant metastasis and chemotherapy benefit in stage II nasopharyngeal carcinoma.

Chemotherapy remains controversial for stage II nasopharyngeal carcinoma because of its considerable prognostic heterogeneity. We aimed to develop an MRI-based deep learning model for predicting distant metastasis and assessing chemotherapy efficacy in stage II nasopharyngeal carcinoma. This multicenter retrospective study enrolled 1072 patients from three Chinese centers for training (Center 1, n = 575) and external validation (Centers 2 and 3, n = 497). The deep learning model significantly predicted the risk of distant metastases for stage II nasopharyngeal carcinoma and was validated in the external validation cohort. In addition, the deep learning model outperformed the clinical and radiomics models in terms of predictive performance. Furthermore, the deep learning model facilitates the identification of high-risk patients who could benefit from chemotherapy, providing useful additional information for individualized treatment decisions.

Comparison the acute toxicity of two different induction chemotherapy schedules with cisplatin and fluorouracil in nasopharyngeal carcinoma patients.

PURPOSE: To compare the acute toxicity of two different induction chemotherapy (IndCT) regimen followed by the same IMRT in patients with advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From July 2015 to December 2016, 110 NPC patients with stage III-IV diseases were prospectively randomized to receive either a conventional triweekly cisplatin + 5-fluorouracil (PF) for 3 cycles or weekly P-F for 10 doses, followed by the same IMRT to both arms. The primary endpoints of this study were grade 3/4 and any grade acute toxicities during IndCT period. The secondary endpoints included tumor response and various survivals. RESULTS: Baseline patient characteristics were comparable in both groups. Patients who received weekly P-F experienced significant reduction of grade 3/4 acute toxicities, including neutropenia (12.7% vs. 40.0%, P = 0.0012), anorexia (0% vs. 14.6%, P = 0.0059), mucositis (0% vs. 14.6%, P = 0.0059), and hyponatremia (0% vs. 16.4%, P = 0.0027), compared with the triweekly PF group, resulting in fewer IndCT interruptions (1.8% vs. 16.4%, P = 0.0203), emergency room visits (0% vs. 12.7%, P = 0.0128), and additional hospitalizations (0% vs. 9.1%, P = 0.0568). The acute toxicities during IMRT period were similar. Weekly P-F arm had higher complete response rates (83.6% vs. 61.8%, P = 0.0152) and lower relapse rates (16.4% vs. 33.3%, P = 0.0402) after a median follow-up of 67 months. Kaplan-Meier survival analyses revealed a better trend of locoregional failure-free (P = 0.0892), distant metastasis failure-free (P = 0.0775), and progression-free (P = 0.0709) survivals, favoring the weekly P-F arm. CONCLUSION: IndCT of weekly schedule does reduce acute toxicities without compromised tumor response and survivals.

Constructing an individualized surveillance framework for nasopharyngeal carcinoma based on a dynamic risk-adapted approach.

BACKGROUND AND PURPOSE: This study aims to evaluate the dynamic survival and recurrence hazard of nasopharyngeal carcinoma(NPC) patients after definitive chemoradiotherapy utilizing conditional survival(CS) analysis, and to propose a personalized surveillance strategy at different clinical stages. MATERIALS AND METHODS: Non-metastatic NPC patients who received curative chemotherapy between June 2005 and December 2011 were included. The Kaplan-Meier method was used to calculate the CS rate. RESULTS: A total of 1616 patients were analyzed. With the prolongation of survival time, both conditional locoregional recurrence free survival and distant metastatic free survival increased gradually. Changing pattern of annual recurrence risk over time varied among different clinical stages. The annual locoregional recurrence(LRR) risk in stage I-II was always less than 2%, while in stage III-IVa, it was greater than 2% for the first three years and decreased to below 2% only after the third year. The annual distant metastases (DM) risk was always less than 2% in stage I, but higher than 2% in stage II for the first 3 years (2.5-3.8%). For those with stage III-IVa, the annual DM risk retained at a high level(>5%), and only decreased to < 5% after the third year. Based on the dynamic changes in survival probability over time, we established a surveillance plan with different follow-up intensities and frequencies for different clinical stages. CONCLUSION: The annual risk of LRR and DM decrease over time. Our individual surveillance model will provide critical prognostic information to optimize clinical decision-making, and promote to formulate surveillance counseling and help with resources allocation.

Identification of immune-related genes contributing to head and neck squamous cell carcinoma development using weighted gene co-expression network analysis.

BACKGROUND: This study aimed to identify genes related to the degree of immune cell infiltration in head and neck squamous cell carcinoma (HNSCC), explore their new biological functions, and evaluate their diagnostic and prognostic value in HNSCC. METHODS: Transcriptomic data from The Cancer Genome Atlas (TCGA) HNSCC dataset was used to screen differentially expressed genes between tumors and normal tissues, followed by weighted correlation network analysis (WGCNA) to identify immune-related modules. Differential gene expression, immune cell infiltration, and survival analyses were performed to screen key genes. The expression of these key genes was validated in Oncomine and gene expression omnibus (GEO) datasets and by immunohistochemistry (IHC). RESULTS: 1869 and 1578 genes were significantly upregulated and downregulated in HNSCC. WGCNA showed that the brown module was associated with the most significant number of immune-related genes. PPI network analysis demonstrated that PPL, SCEL, KRT4, KRT24, KRT78, KRT13, SPRR3, TGM3, CRCT1, and CRNN were key components in the brown module. Furthermore, the expression levels of KRT4, KRT78, KRT13, and SPRR3 in HNSCC correlated with infiltration levels of CD8+ T cells and macrophages. Survival analyses revealed that the expression of KRT78, KRT13, and SPRR3 in HNSCC correlated with overall survival (OS). The IHC assay indicated that KRT13 (p = .042), KRT78 (p < .001), and SPRR3 (p = .022) protein expression levels in HNSCC were significantly lower than in normal tissues. Analysis of GSE65858 and GSE41613 datasets showed that a worse OS was associated with low expression of KRT78 (p = .0086, and p = .005) and SPRR3 (p = .017, and p = .02). CONCLUSIONS: Our findings suggest that KRT4, KRT78, KRT13, and SPRR3 are related to the occurrence and development of HNSCC. Importantly, KRT78 and SPRR3 might serve as diagnostic and prognostic biomarkers of HNSCC.

Prioritizing sufficient dose to gross tumor volume over normal tissue sparing in intensity-modulated radiotherapy treatment of T4 nasopharyngeal carcinoma.

BACKGROUND: In intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), priority is often given minimize dose to the critical organs at risk (OARs) to avoid potential morbid sequelae. However, in T4 NPC, dosimetric inadequacy enforced by dose constraints on OARs may significantly impact tumor control. METHODS: This was a single-institute cohort that patients diagnosed between July 2005 and December 2010 with T4 NPC treated with IMRT. All patients were re-classification according to the 7th-AJCC stage. RESULTS: Overall, the average doses such as Dmax , D1% , D2% and D1cc for various Central nervous system (CNS) OARs including brainstem, optic nerve, chiasm, temporal lobes and spinal cord were found to exceed published guidelines as RTOG0225. However, no clinical toxicities were seen during the follow-up period except for 13% patients with temporal lobe necrosis. CONCLUSION: Our retrospective review showed that its feasible to maximize gross tumor volume dose coverage while exceeding most CNS OAR constraint standards, with ideal local control and no obvious increase of craniocerebral toxicity.

Effect of Percutaneous Endoscopic Gastrostomy on Quality of Life after Chemoradiation for Locally Advanced Nasopharyngeal Carcinoma: A Cross-Sectional Study.

(1) Background: Prophylactic percutaneous endoscopic gastrostomy (PEG) maintained nutritional status and improved survival of patients with locally advanced nasopharyngeal carcinoma (LA-NPC). However, the role of PEG in patients' quality of life (QoL) is still controversial. We aimed to investigate the effect of PEG on the QoL of patients with LA-NPC without progression. (2) Methods: Patients with LA-NPC between 1 June 2010 and 30 June 2014 in Fujian Cancer Hospital were divided into PEG and non-PEG groups. The QoL Questionnaire core 30 (QLQ-C30), incidence of adverse effects, weight, and xerostomia recovery were compared between the two groups of patients without progression as of 30 June 2020. (3) Results: No statistically significant difference in the scores of each QLQ-C30 scale between the two groups (p > 0.05). The incidence of xerostomia was higher in the PEG group than in the non-PEG group (p = 0.044), but the association was not seen after adjusting for gender, age, T, and N stage (OR: 0.902, 95%CI: 0.485−1.680). No significant difference in the incidence of other adverse effects as well as in weight and dry mouth recovery (p > 0.05). (4) Conclusion: PEG seems not to have a detrimental effect on long-term Qol, including the self-reported swallowing function of NPC patients without progressive disease.

The role of radiologic extranodal extension in predicting prognosis and chemotherapy benefit for T1-2 N1 nasopharyngeal carcinoma: A multicenter retrospective study.

BACKGROUND AND PURPOSE: This multicenter retrospective study aimed to investigated the prognostic value of unequivocal radiologic extranodal extension (rENE) and the efficacy of chemotherapy for stage T1-2 N1 nasopharyngeal carcinoma (NPC) in the IMRT era. MATERIALS AND METHODS: We included 1,082 patients treated in 2005-2017 from three centers. rENE was recorded as G1 (coalescent nodal mass comprising ≥ 2 inseparable nodes) or G2 (invading beyond perinodal fat to frankly infiltrate adjacent structures). Multivariable analysis (MVA) evaluated the prognostic value of rENE. The value of chemotherapy was assessed in rENE-positive (rENE + ) and rENE-negative (rENE - ) subset separately. RESULTS: Centers 1, 2, and 3 had 139/515 (27.0 %), 100/365 (27.4 %), and 43/202 (21.3 %) cN + patients with rENE, respectively. Compared to rENE-, rENE + patients had a worse distant metastasis-free survival (DMFS) and overall survival (OS) (all p < 0.001). MVA confirmed the prognostic of both G1-rENE and G2-rENE for distant metastasis [G1: hazard ratio (HR): 2.933, G2: HR: 6.942, all p < 0.001] and death (G1: HR: 1.587, p = 0.040; G2: HR: 6.162, p < 0.001). There was no significant difference for DMFS and OS between chemo-radiotherapy and radiotherapy alone in rENE + and rENE - groups (all p > 0.1). However, rENE + patients with a cumulative cisplatin/nedaplatin dose (CCND) of > 160 mg/m2 had an improved DMFS (p = 0.033) but no OS (p = 0.197). CONCLUSION: Unequivocal rENE is prognostic in patients with T1-2 N1 NPC. Addition of chemotherapy to radiotherapy did not affect DMFS and OS in rENE - patients. Chemotherapy with a CCND of > 160 mg/m2 improved DMFS in rENE + patients.

Stereotactic body radiotherapy extends the clinical benefit of PD-1 inhibitors in refractory recurrent/metastatic nasopharyngeal carcinoma.

PURPOSE: Emerging evidence shows that immune checkpoint inhibitors lead to durable responses in a variety of cancers, including nasopharyngeal carcinoma (NPC), however, combination approaches (i.e., stereotactic body radiation therapy, SBRT) are required to extend this benefit beyond a subset of patients. This study retrospectively evaluated eight recurrent/metastatic NPC patients, to investigate how radiation could potentiate PD-1 checkpoint inhibition therapy. METHODS: Between September 2016 and July 2017, eight consecutive cases with histologically confirmed PDL1-positive status, for which prior standard therapy had been ineffective (five patients), were treated at our institution and Macao Clinics and two patients had disease progression within 6 months of completion of definitive chemoradiation, or one patient refused to receive chemoradiotherapy. All received PD-1 inhibitors first, seven of them accepted SBRT with an unmodified PD-1 inhibitors regimen after first evaluation as they were unresponsive to PD-1 inhibitors alone. Treatment was discontinued as long as patients were experiencing a clinical benefit in the opinion of the physicians and at least five cycles were given before stoppage. RESULTS: Median follow-up time was 56.7 months. The confirmed objective response rate based on RECIST-v1.1 at first evaluation was 12.5% (1/8). For the seven cases who received SBRT, six of them experience an objective response (6/7, 85.7%) after SBRT. Only one patient showed rapid progress and die within 95 days after the initiation of SBRT intervention. Three patients who did not have all lesions exposed to irradiation were available to evaluate the incidence of an abscopal effect, however, it did not occur as expected. Median PFS and OS for the seven patients were 8.0 and 30.8 months after SBRT intervention, respectively. Two-year OS as indicated was 71.0%. CONCLUSIONS: PD-1 inhibitors combined with SBRT demonstrated promising antitumor activity in patients with PD-L1 positive RM-NPC. Patients may benefit from continue immunotherapy beyond disease progression when SBRT was introduced.

Plasma Epstein-Barr Virus MicroRNA BART8-3p as a Diagnostic and Prognostic Biomarker in Nasopharyngeal Carcinoma.

BACKGROUND: Nasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-associated tumor that is highly common in southern China. Our previous sequencing data demonstrated that the EBV-encoded microRNA BART8-3p was most upregulated in nasopharyngeal carcinoma (NPC) and was closely associated with the metastasis of NPC. However, the values of plasma BART8-3p in NPC patients have not yet been well characterized. MATERIAL AND METHODS: We quantified plasma BART8-3p expression by quantitative real-time PCR in 205 newly diagnosed NPC patients. Kaplan-Meier analysis was used to compare overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) between the groups. RESULTS: Plasma pretreatment BART8-3p was highly expressed in NPC patients compared with healthy controls. Pretreatment BART8-3p yielded a 92% predictive value for detecting NPC. Importantly, BART8-3p decreased dramatically after therapy relative to pretreatment levels. High levels of pretreatment or post-treatment BART8-3p were associated with worse OS, DMFS, and LRRFS. Multivariate analysis showed that high pretreatment or post-treatment BART8-3p was an independent unfavorable prognostic marker for OS (HR 3.82, 95% CI 1.77-8.24, P = .001 or HR 2.74, 95% CI 1.27-5.91, P = .010), DMFS (HR 2.82, 95% CI 1.36-5.85, P = .005 or HR 3.27, 95% CI 1.57-6.81, P = .002), and LRRFS (HR 1.94, 95% CI 1.12-3.35, P = .018 or HR 2.03, 95% CI 1.14-3.62, P = .016) in NPC. Subgroup analysis revealed that for patients with locally advanced NPC with high levels of pretreatment BART8-3p (n = 58), more cycles of chemotherapy (≥6 cycles) tended to prolong OS (P = .070). Over 50% (6/11) patients with high levels of post-treatment BART8-3p presented distant metastasis. CONCLUSION: Plasma BART8-3p is a promising biomarker for the detection and prognosis of NPC.

Level Ib sparing intensity-modulated radiation therapy in selected nasopharyngeal carcinoma patients based on the International Guideline.

BACKGROUND AND PURPOSE: To investigate the feasibility of level Ib sparing in selected nasopharyngeal carcinoma (NPC) patients during intensity-modulated radiation therapy (IMRT) based on the International Guideline. PATIENTS AND MATERIALS: Patients with histologically-proven NPC who received definitive IMRT at our group were candidates for this analysis. Other eligibility criteria for analysis were designed according to the recommendation of International Guideline for selective coverage of level Ib. Survival outcomes focused on regional recurrence-free survival (RRFS) and level Ib recurrence rate were analyzed. RESULTS: A total of 450 patients were included, 60 of them received level Ib-covering IMRT due to the first three principles of the International Guideline according to our protocol. Of note, patients with level Ib involvement would receive ultrasound guided puncture, only those with positive pathological results would undergo level Ib-covering IMRT. For the remaining 390 patients who only fulfilled the last two criteria and/or level Ib involvement with negative pathological results, level Ib-sparing IMRT was delivered, with a median follow-up time of 112 months (range 6 to 194 months), reported 5- and 10-year RRFS were 95.4% and 92.9%, respectively. Twenty-two patients occurred regional recurrence at censorship (median 44.5 months), only 4(4/390, 1.03%) were recorded as level Ib recurrence. CONCLUSION: Level Ib-sparing IMRT should be safe and feasible for patients who only had level II involvement with ECE, and/or had a MAD of greater than 2 cm in level II, and/or level Ib involvement with negative pathological results. Further well-designed multi-center prospective trials should be conducted.

Re-evaluation of the prognostic significance of retropharyngeal node metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: To investigate the prognostic value of retropharyngeal lymphadenopathy in nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy. MATERIALS AND METHODS: Retrospective studies were performed in a total of 1197 patients. We evaluated the incidence of the retropharyngeal node (RPN) metastasis and the characteristics of the metastatic RPN including laterality, size, necrosis, and extranodal neoplastic spread. RESULTS: RPN metastasis occured in 86.3% of patients. The RPN and level II metastasis shared similar survival outcomes. RPN metastasis was an independent prognostic factor for distant failure (hazard ratio = 1.615; 95% confidence interval, 1.063-2.452; P = 0.025), in which the laterality of RPN metastasis significantly influences both the distant failure (P = 0.006) and disease progression (P = 0.001). In N1 disease, the occurrence of unilateral and bilateral RPN metastasis resulted in significantly different outcomes of the disease-specific survival (P = 0.045) and progression-free survival (P = 0.049). The co-occurrence of bilateral RPN and cervical lymph nodes (CLN) metastasis was an independent adverse prognostic factor (P < 0.01) for distant failure and disease progression but not for locoregional recurrence. CONCLUSION: Both the RPN and level II are the first stations of NPC lymph node metastasis. For N1-stage NPC patients, RPN metastasis, especially co-occurrence of bilateral RPN and CLN metastasis, have an adverse influence on survival outcomes.

Comparison of radiotherapy combined with nimotuzumab vs. chemoradiotherapy for locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). METHODS: Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. RESULTS: A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). CONCLUSION: Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

Prognostic Factors for Overall Survival in Nasopharyngeal Cancer and Implication for TNM Staging by UICC: A Systematic Review of the Literature.

This study aims to identify prognostic factors in nasopharyngeal carcinoma (NPC) to improve the current 8th edition TNM classification. A systematic review of the literature reported between 2013 and 2019 in PubMed, Embase, and Scopus was conducted. Studies were included if (1) original clinical studies, (2) ≥50 NPC patients, and (3) analyses on the association between prognostic factors and overall survival. The data elements of eligible studies were abstracted and analyzed. A level of evidence was synthesized for each suggested change to the TNM staging and prognostic factors. Of 5,595 studies screened, 108 studies (44 studies on anatomical criteria and 64 on non-anatomical factors) were selected. Proposed changes/factors with strong evidence included the upstaging paranasal sinus to T4, defining parotid lymph node as N3, upstaging N-category based on presence of lymph node necrosis, as well as the incorporation of non-TNM factors including EBV-DNA level, primary gross tumor volume (GTV), nodal GTV, neutrophil-lymphocyte ratio, lactate dehydrogenase, C-reactive protein/albumin ratio, platelet count, SUVmax of the primary tumor, and total lesion glycolysis. This systematic review provides a useful summary of suggestions and prognostic factors that potentially improve the current staging system. Further validation studies are warranted to confirm their significance.

SEC61G overexpression and DNA amplification correlates with prognosis and immune cell infiltration in head and neck squamous cell carcinoma.

BACKGROUND: The SEC61 translocon gamma subunit (SEC61G) is a component of the SEC61 complex, which import protein into the endoplasmic reticulum. However, the correlation between SEC61G and disease prognosis in head and neck squamous cell carcinoma (HNSCC) remains unclear. METHODS: SEC61G expression was analyzed using publicly available datasets. The association between SEC61G and disease prognosis was evaluated. SEC61G methylation and copy number variation were investigated and gene set enrichment analysis and gene ontology analyses identified SEC61G-associated functions. We also investigated the correlation between SEC61G and immune cell infiltration. Finally, immunohistochemistry was used to detect SEC61G expression in oropharyngeal carcinoma. RESULTS: SEC61G was overexpressed in pan-cancers, including HNSCC, and negatively correlated with overall survival (OS) (p < 0.001 for TCGA-HNSCC and p = 0.019 for GSE65858). Moreover, SEC61G was an independent prognostic factor for OS in TCGA and GSE65858 [hazard ratio (HR) = 1.80, 95% CI: 1.35-2.39, p < 0.001; HR = 1.87, 95% CI: 1.14-3.07, p = 0.013, respectively). SEC61G DNA amplification (9.66% of patients) was significantly associated with poor OS (p = 0.034). SEC61G overexpression and DNA amplification negatively correlated with B cell (p < 0.001), CD8+ T cell (p < 0.001), CD4+ T cell (p < 0.001), macrophage (p < 0.05), neutrophil (p < 0.001), and dendritic cell infiltration (p < 0.001). Among patients with metastatic urothelial cancer received atezolizumab, patients with high SEC61G expression had an inferior OS (p = 0.006). Furthermore, SEC61G protein expression was also an independent prognostic factor of OS (HR = 2.46, 95% CI: 1.15-5.28, p = 0.021) and progression-free survival (HR = 2.82, 95% CI: 1.36-5.85, p = 0.005) for oropharyngeal cancer. CONCLUSIONS: SEC61G is overexpressed in HNSCC and is an independent prognostic factor for OS. SEC61G DNA amplification contributes to overexpression and poor outcome. Interestingly, SEC61G correlates with immune cell infiltration in HNSCC. These findings suggest that SEC61G is a potential broad-spectrum biomarker for prognosis in HNSCC.

Percutaneous endoscopic gastrostomy can improve survival outcomes in patients with N3 nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy.

OBJECTIVES: Our previous study revealed that percutaneous endoscopic gastrostomy (PEG) and intensive nutritional support may minimize body weight loss, maintain nutritional status, and offer better treatment tolerance for patients with locally advanced nasopharyngeal carcinoma (LA-NPC) during concurrent chemoradiotherapy (CCRT). This study aimed to further explore the potential long-term survival benefits of PEG in LA-NPC. METHODS: Between June 1, 2010 and June 30, 2014, a total of 133 consecutive LA-NPC patients who received prophylactic PEG (pPEG) feeding before the initiation of CCRT were included. Meanwhile, an additional 133 non-PEG patients, who were matched for age; sex; and tumor, node, and metastases stage, were selected as control cohort. The log-rank test was used to compare survival distributions between groups. Multivariate prognosis analysis was conducted using a Cox's proportional hazards regression model. RESULTS: After a median follow-up time of 81 months (range: 4-119 months), pPEG was not associated with significant survival benefits in the whole cohort. However, the N3 NPC patients who underwent PEG had significantly higher 5-year overall survival (OS) and progression-free survival (PFS) (84.0 and 76.0%, respectively) than those who did not undergo PEG (56.7 and 45.6%, respectively; p < 0.05). Univariate and multivariate analyses demonstrated that PEG was an independent factor for N3 survival. CONCLUSION: PEG can maintain the nutritional status and improve the rate of treatment completion for LA-NPC patients who underwent CCRT, and these advantages can transfer into survival benefits in N3 NPC. Further multicenter prospective clinical trials are warranted.

Administration of oral maintenance chemotherapy for 1 year following definitive chemoradiotherapy may improve the survival of patients with stage N3 nasopharyngeal carcinoma.

OBJECTIVES: This study aims to evaluate the effectiveness and the optimal maintenance period of oral chemotherapy using S1 following definitive chemoradiotherapy in patients with stage N3 nasopharyngeal carcinoma (N3-NPC). MATERIALS AND METHODS: A retrospective review was performed for N3-NPC treatment with maintenance chemotherapy (MC) [chemoradiotherapy (CRT)-MC] or without MC (CRT-non-MC) following definitive CRT between May 2014 and December 2017. Toxicities during MC were recorded. Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were compared between CRT-MC and CRT-non-MC cohorts. The optimal duration of using maintenance S1 (MC-S1) was also analyzed. RESULTS: A total of 304 patients with stage N3-NPC were identified, of whom 56 were treated with CRT-MC and 248 with CRT-non-MC. After a median follow-up of 48 months, significant differences in OS (74.9 vs. 91.7%; P = 0.003), PFS (60.7 vs. 83.7%; P = 0.001) and DMFS (68.8 vs. 85.5%; P = 0.015) were observed between the CRT-non-MC and CRT-MC groups. Skin hyperpigmentation, leukopenia and fatigue were common but not severe (grade 1-2) side effects of MC. The OS, DMFS and PFS were significantly higher for patients who received S1 administration over a period of ≥12 cycles compared with those who received <12 cycles (3-year OS, 100 vs. 87.5%, P = 0.018; 3-year PFS, 93.9 vs. 67.9%, P = 0.006; 3-year DMFS, 97.1 vs. 67.9%, P = 0.002). CONCLUSIONS: Using MC-S1 in patients with N3-NPC following definitive chemoradiotherapy achieved superior survival rate compared with the patients with non-MC. The side effects of MC-S1 were mild and tolerable. S1 should be maintained for ≥12 cycles.

Identifying the optimal candidates for locoregional radiation therapy in patients with de novo metastatic nasopharyngeal carcinoma.

BACKGROUND: To evaluate the value of locoregional radiation therapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (mNPC) and identify suitable candidates for additional LRRT after palliative chemotherapy (PCT). METHODS: Patients with de novo mNPC received platinum-based chemotherapy for a minimum of four cycles with or without definitive LRRT via intensity-modulated radiation therapy (IMRT) were all candidates for this study. RESULTS: A total of 168 patients were included for this analysis. Additional LRRT was associated with significantly longer median OS (69.5 vs. 17.8 months, p < 0.001) when compared with PCT alone. However, this survival benefit of LRRT was only reflected in patients with oligometastatic diseases (90.8 vs. 17 months, p < 0.001), but not for those with polymetastatic disease (p = 0.86). CONCLUSIONS: Additional LRRT after PCT may only improve OS for oligometastatic patients. For patients with polymetastatic disease, intensive systemic treatment such as the combination of immunotherapy and adequate PCT might be necessary.