The use of adjuvant chemotherapy combined with concurrent chemoradiotherapy enhances survival rates in cases of locally advanced nasopharyngeal carcinoma.

This study aimed to evaluate the impact of adjuvant chemotherapy on survival rates, adverse events, and quality of life (QOL) in patients with locally advanced nasopharyngeal carcinoma (NPC). A retrospective cohort study was conducted, including patients with firstly histologically confirmed non-metastatic stage III-IVB NPC between February 2018 and February 2020, and with continuous follow-up data available, were chosen from the medical records of the affiliated hospital of Qingdao University and Zibo Central Hospital. There were 395 patients receiving concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (adjuvant chemotherapy group) and 428 patients receiving CCRT alone (control group). The two groups were compared for treatment response, adverse events, and QOL scores. Besides, Kaplan-Meier plots, and multivariate COX analysis were conducted. The adjuvant chemotherapy group demonstrated a significantly higher overall survival and disease-free survival compared to the control group. The use of adjuvant chemotherapy was significantly correlated with improved overall survival and disease-free survival. Adjuvant chemotherapy was associated with reduced local recurrence and distant metastasis rates. However, higher rates of adverse events were observed in the adjuvant chemotherapy group. QOL scores for physical functioning, emotional functioning, and overall quality of life were higher in the adjuvant chemotherapy group. The findings of this study indicate that adjuvant chemotherapy in locally advanced NPC is associated with improved treatment response, extended overall and disease-free survivals, and better QOL, despite higher rates of adverse events.

Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study.

BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

Prediction of severe radiation-induced oral mucositis in locally advanced nasopharyngeal carcinoma using the combined systemic immune-inflammatory index and prognostic nutritional index.

OBJECTIVE: Severe radiation-induced oral mucositis (sRIOM) can seriously affect patients' quality of life and treatment compliance. This study was to investigate the utility of the systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) in predicting sRIOM in patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: 295 patients with LANPC were retrospectively screened. The pre-radiotherapy SII and PNI were calculated based on peripheral blood samples. A receiver operating characteristic (ROC) curve was used to determine the cut-off value. Logistic regression was used for univariate and multivariate analyses. Patients were classified into three groups based on the SII-PNI score: score of 2, high SII (> cut-off value) and low PNI (≤ cut-off value); score of 1, either high SII or low PNI; score of 0, neither high SII nor low PNI. RESULTS: The SII-PNI demonstrated significant predictive ability for sRIOM occurrence, as evidenced by an area under the curve (AUC) of 0.738. The incidence rates of sRIOM with SII-PNI score of 2, 1, and 0 were 73.86%, 44.35%, and 18.07%, respectively. Multivariate analysis confirmed that the SII-PNI score was an independent risk factor for sRIOM. CONCLUSION: The SII-PNI score is a reliable and convenient indicator for predicting sRIOM in patients with LANPC.

Meta-analysis of efficacy of Chinese medicine compound combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma is a prevalent malignant tumor in clinical practice, with the highest incidence rate among otorhinolaryngological malignant tumors. OBJECTIVES: This study aims to comprehensively evaluate the clinical efficacy and safety of traditional Chinese medicine compound (CMC) combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: Relevant essays published before November 20, 2021, were retrieved from China National Knowledge Internet (CNKI), China Science and Technology Journal Database (CQVIP), Wanfang database, PubMed, and Web of Science databases. Randomized controlled trials regarding the clinical efficacy of CMC combined with concurrent radiotherapy and chemotherapy in the treatment of LA-NPC were included. RESULTS: A total of 15 publications involving 1324 patients were included in this study, including 665 in the experimental group and 659 in the control group. Meta-analyses revealed that compared with radiotherapy or chemotherapy only, CMC combined with concurrent radiotherapy and chemotherapy for LA-NPC significantly improved the efficacy [risk ratio (RR)=1.15, 95% confidence interval (95% CI) (1.09, 1.20), P<0.00001], the quality of life [RR=1.35, 95% CI (1.13, 1.62), P=0.0009], immune function indices CD4+ levels [RR=6.2, 95% CI (3.64, 8.76), P<0.00001], CD4+/CD8+ [RR=0.33, 95% CI (0.14, 0.53), P=0.0009], and alleviated the decrease in white blood cell counts [RR=0.67, 95% CI (0.52, 0.86), P=0.002]. CONCLUSION: CMC combined with concurrent radiotherapy and chemotherapy for the treatment of LA-NPC can significantly improve the efficacy and reduce severe adverse reactions caused by conventional radiotherapy and chemotherapy. However, due to limitations in the quantity and quality of the included studies, more high-quality, multi-center, and large sample-size studies are needed to provide high-level and high-quality medical evidence for systematic evaluation.

An Individualized Prognostic Model in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma Based on Serum Metabolomic Profiling.

PURPOSE: This study aims to evaluate the value of a serum metabolomics-based metabolic signature for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, thereby assisting clinical decisions. METHODS: In this retrospective study, a total of 320 LA-NPC patients were randomly divided into a training set (ca. 70%; n = 224) and a validation set (ca. 30%; n = 96). Serum samples were analyzed using widely targeted metabolomics. Univariate and multivariate Cox regression analyses were used to identify candidate metabolites related to progression-free survival (PFS). Patients were categorized into high-risk and low-risk groups based on the median metabolic risk score (Met score), and the PFS difference between the two groups was compared using Kaplan-Meier curves. The predictive performance of the metabolic signature was evaluated using the concordance index (C-index) and the time-dependent receiver operating characteristic (ROC), and a comprehensive nomogram was constructed using the Met score and other clinical factors. RESULTS: Nine metabolites were screened to build the metabolic signature and generate the Met score, which effectively separated patients into low- and high-risk groups. The C-index in the training and validation sets was 0.71 and 0.73, respectively. The 5-year PFS was 53.7% (95% CI, 45.12-63.86) in the high-risk group and 83.0% (95%CI, 76.31-90.26) in the low-risk group. During the construction of the nomogram, Met score, clinical stage, pre-treatment EBV DNA level, and gender were identified as independent prognostic factors for PFS. The predictive performance of the comprehensive model was better than that of the traditional model. CONCLUSION: The metabolic signature developed through serum metabolomics is a reliable prognostic indicator of PFS in LA-NPC patients and has important clinical significance.

MRI-based clinical radiomics nomogram may predict the early response after concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma.

Objective: Tumor residue after concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients often predicts poor prognosis. Thus, the objective of this retrospective study is to develop a nomogram that combines magnetic resonance (MRI) radiomics features and clinical features to predict the early response of locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: A total of 91 patients with LA-NPC were included in this study. Patients were randomly divided into training and validation cohorts at a ratio of 3:1. Univariate and multivariate analyses were performed on the clinical parameters of the patients to select clinical features to build a clinical model. In the training cohort, the Least Absolute Shrinkage and Selection Operator (LASSO) regression model was used to select radiomics features for construction of a radiomics model. The logistic regression algorithm was then used to combine the clinical features with the radiomics features to construct the clinical radiomics nomogram. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were drawn to compare and verify the predictive performances of the clinical model, radiomics model, and clinical radiomics nomogram. Results: Platelet lymphocyte ratio (PLR) and nasopharyngeal tumor volume were identified as independent predictors of early response in patients with locally advanced nasopharyngeal carcinoma. A total of 5502 radiomics features were extracted, from which 25 radiomics features were selected to construct the radiomics model. The clinical radiomics nomogram demonstrated the highest AUC in both the training and validation cohorts (training cohort 0.975 vs 0.973 vs 0.713; validation cohort 0.968 vs 0.952 vs 0.706). The calibration curve and DCA indicated good predictive performance for the nomogram. Conclusion: A clinical radiomics nomogram, which combines clinical features with radiomics features based on MRI, can predict early tumor regression in patients with LA-NPC. The performance of the nomogram is superior to that of either the clinical model or radiomics model alone. Therefore, it can be used to identify patients without CR at an early stage and provide guidance for personalized therapy.

Recombinant human endostatin injection (Endostar) combined with PF chemotherapy and sequential intensity-modulated radiotherapy is tolerable and improves prognosis of locally advanced nasopharyngeal carcinoma: a randomized, open, multicenter phase II clinical study.

Nasopharyngeal carcinoma (NPC) is not only a common malignant disease of the head and neck, but also presented as locoregionally advanced NPC at diagnosis with poor prognosis. The efficacy of current chemoradiotherapy is unsatisfactory; therefore, in this study, we evaluated the safety and efficacy of treating locally advanced NPC using recombinant human endostatin injection (Endostar), combined with a cisplatin plus 5-fluorouracil (PF) regimen and sequential intensity-modulated radiotherapy (IMRT), and compared it with PF plus IMRT regimen. This phase II study included 83 eligible patients with stages III-IVa NPC (8th AJCC/UICC) who were randomized 1:1 into control (n = 42) and experimental (n = 41) groups. The control group received PF chemotherapy and IMRT for locally advanced NPC; One cycle of induction chemotherapy (IC) was administered before IMRT, and three cycles of adjuvant chemotherapy (AC) were administered four weeks post-radiotherapy. The experimental group received additional Endostar therapy. All patients were followed up for at least 5 years. The primary endpoints were progression-free survival (PFS) and the objective response rate. The secondary endpoints included overall survival and treatment-related toxicities. The short-term efficacy was evaluated at the end of the fourth chemotherapy cycle. Our results showed that the complete response rate of nasopharyngeal lesions was not significantly different between the experimental and control groups (80.5 vs. 71.4%, P = 0.335); however, there were significant differences in the complete response rates of cervical metastatic lymph nodes (75.6 vs. 40.5%, P = 0.001), especially for cervical N3 lymph nodes in the experimental group (55.6 vs. 9.5%, P = 0.004). The overall median follow-up time was 69.7 months. Patients in the experimental group showed significantly prolonged PFS by about four months (hazard ratio [HR] = 0.64, 95% CI: 0.41-0.99, P = 0.045). There was no significant difference in the median overall survival (P = 0.374). Furthermore, subgroup analysis indicated that the risk of death in patients with cervical N3 lymph nodes in the experimental group was reduced by 52% (HR = 0.48, 95% CI: 0.23-0.99, P = 0.046). Moreover, the incidence of radiation-induced grades 3-4 oral mucositis was significantly lower in the experimental group (29.3% vs. 54.8%, P = 0.019), while no significant differences in other severe adverse reactions were observed between the two groups (P>0.05). Taken together, our study indicated that, in patients with locally advanced NPC, Endostar in combination with PF chemotherapy and sequential IMRT significantly improved PFS, had tolerable treatment-related toxicities, improved the prognoses of patients with cervical N3 lymph nodes, and reduced the incidence of radiation-related oral mucositis.

Improvement and prognosis analysis of nimotuzumab combined with TP regimen induction chemotherapy and sequential concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma.

OBJECTIVE: To explore the effect of nimotuzumab combined with Taxol + Cisplatin (TP) regimen induction chemotherapy and sequential concurrent chemoradiotherapy on the improvement of curative effect and prognosis of patients with locally advanced nasopharyngeal carcinoma. METHOD: A retrospective analysis was performed on 91 patients with locally advanced nasopharyngeal carcinoma who were admitted to our hospital from February 2017 to February 2019, of which 41 patients received TP induction chemotherapy were assigned to control group (CG), and the remaining 50 patients received nimotuzumab on the basis of control group were assigned to observation group (OG). Both groups of patients received cisplatin chemotherapy concurrently with intensity-modulated radiotherapy (IMRT). Comparisons were made between the two group in terms of clinical efficacy, serum markers squamous cell carcinoma-associated antigen (SCCAg), cytokeratin 19 fragment 21-1 (CYFRA21-1), adverse reactions, and 3-year survival of the patients. RESULTS: Remission rate of cervical lymph nodes in OG was better than that in CG (P<0.05). After treatment, SCC-Ag and CYFRA21-1 decreased significantly in both groups, while indexes in OG were markedly lower compared to CG (P<0.05). During induction therapy and concurrent chemoradiotherapy, no notable difference was observed in short-term or long-term adverse reactions between the two groups (P>0.05). And Cox regression analysis found that clinical stage and treatment were independent factors affecting the prognosis of patients with disease-free survival (PFS). CONCLUSION: Nimotuzumab combined with TP regimen induction chemotherapy and sequential concurrent chemoradiotherapy can improve the curative effect of patients with locally advanced nasopharyngeal carcinoma.

Efficacy and safety of a treatment in patients with locoregionally advanced nasopharyngeal carcinoma (LANC) involving carotid artery invasion.

PURPOSE: Locally advanced nasopharyngeal carcinoma (LANC) often invades the parapharyngeal space and internal carotid artery. Are patients with LANC invading carotid artery are at risk of massive neck hemorrhage after radiotherapy? METHODS: This retrospective study included 130 LANC patients with carotid artery invasion admitted to our hospital between January 2012 and September 2019. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) ± epidermal growth factor receptor (EGFR) inhibitor. Univariate and multivariate analysis of risk factors were conducted for the prognosis and the occurrence of massive neck hemorrhage of LANC patients with carotid artery invasion. OUTCOMES: The 5-year progression-free survival (PFS), distant metastasis-free survival (DMFS), local nodal recurrence-free survival (LNRFS), local recurrence-free survival (LRFS), nodal recurrence-free survival (NRFS) and overall survival (OS) of the 130 patients were 75.2%, 76.8%, 90.0%, 93.9%, 95.8% and 87.2%, respectively. The incidence of fatal bleeding after radiotherapy was 2.3% (3/130). The primary site of the three cases were all the pharyngeal recess, with more than 270° carotid artery invasion, suffering nasopharyngeal necrosis after radiotherapy (2 of which were diabetics and 1 received re-radiation after recurrence). Univariate analysis showed that clinical stage was negatively correlated with DMFS and PFS (P < 0.05). The induction chemotherapy TP regimen, platinum-based concurrent chemotherapy and EGFR inhibitors (Nituzumab/Cetuximab) significantly improved PFS and DMFS (P < 0.05). Patients with hemoglobin levels > 110 g/L had significantly inferior PFS, DMFS and OS than those with hemoglobin levels ≤ 110 g/L (P < 0.05). Multivariate analysis showed that the EGFR inhibitor was an independent risk factor for PFS and DMFS, while the lowest hemoglobin level was an independent risk factor for OS. CONCLUSIONS: In LANC patients whose carotid artery invasion was < 270°, induction chemotherapy (IC) followed by helical tomotherapy (HT) and concurrent chemoradiotherapy (CCRT) with EGFR (epidermal growth factor receptor) inhibitor had mild and tolerable side effects, better PFS and DMFS, with no massive hemorrhage. In patients whose primary tumor was pharyngeal recess with carotid artery invasion ≥ 270°, poorly controlled diabetes or re-radiotherapy led to a higher risk of massive hemorrhage after radiotherapy.

The best choice of induction chemotherapy for patients with locally advanced nasopharyngeal carcinoma: Bayesian network meta-analysis.

The determination of the optimal induction chemotherapy (IC) regimen for patients with locally advanced nasopharyngeal carcinoma (NPC) remains controversial. Eligible trials included in this Bayesian network meta-analysis were judged by synthetically evaluating survival and safety outcomes. The analysis revealed that the combined IC regimen of gemcitabine plus cisplatin (GP) gained not only the most favorable overall survival (OS) benefit but also longer distant metastasis-free survival and manageable adverse events (AEs). Additionally, combination IC regimen of mitomycin, epirubicin, cisplatin, fluorouracil, and leucovorin had insufficient significant efficacy on complete response. Docetaxel combined with cisplatin and fluorouracil induction regimen provided the first exact probability of efficacy in term of local recurrence-free survival, ranking second in OS, but accompanied by the highest rates of grade 3 or above AEs. GP regimen appears to be currently the best choice of IC regimen for combined benefit of patients with locally advanced NPC.

The effect of combined TPF and intensity modulated radiotherapy after TPF induction chemotherapy on locally advanced nasopharyngeal carcinoma: a retrospective analysis.

BACKGROUND: To evaluate the efficacy and toxicity of docetaxel, cisplatin, and fluorouracil (TPF) regimen followed by intensity modulated radiotherapy (IMRT) on locally advanced nasopharyngeal carcinoma (NPC). METHODS: A total of 150 patients with locally advanced NPC [American Joint Committee on Cancer (AJCC) 2009 stage IIIa-IVb] received 2 or 3 cycles of a TPF regimen as induction chemotherapy. A group of 67 participants (TPF group) continued to receive TPF chemotherapy and radiotherapy, and the remaining 83 participants (P group) received cisplatin chemotherapy and radiotherapy. RESULTS: A median follow-up of 35 months (4-66 months) showed that there was no significant difference between P group and TPF group in progression-free survival (PFS) and overall survival (OS). The incidence rate of myelosuppression at 3-4 degrees was 16.9% and 34.3% in the P group and TPF group (P=0.029), respectively, and the oral mucosa reaction at 3-4 degrees was 18.1% and 37.3% in the P group and TPF group, respectively (P=0.007). The 3-4-degree skin reaction in the P group and TPF group was 15.7% and 29.9% (P=0.030), respectively. The rate of liver function injury in the P group was significantly lower than that in TPF group (P<0.05). CONCLUSIONS: Compared with concurrent cisplatin chemotherapy and radiotherapy, the concurrent TPF regimen and IMRT showed no significant improvement in OS and PFS in patients with advanced NPC, but exhibited more severe hematologic toxicity, oral mucosal responses, skin reactions, and liver functional impairment.

Comparison of TPF and TP Induction Chemotherapy for Locally Advanced Nasopharyngeal Carcinoma Based on TNM Stage and Pretreatment Systemic Immune-Inflammation Index.

PURPOSE: To evaluate the efficacy and toxicity of the two IC (induction chemotherapy) regimens, TPF (taxanes, cisplatin, and 5-fluorouracil) and TP (taxanes and cisplatin) combined with concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients. METHODS: Ultimately, we enrolled 213 patients at stage III-IVA in this retrospective study. The prognosis of TPF and TP was compared by Kaplan-Meier and Cox proportional hazard regression. The toxicities were evaluated according to CTCAE v4.0 and RTOG criteria. RESULTS: TPF was found to have a higher 5-year DMFS in stage IVA and N2-3 patients. The optimal value of pretreatment SII was 432.48. A further subgroup analysis revealed that patients in stage IVA combined with SII ≥432.48 showed superior OS (P=0.038) and DMFS (P=0.028) from TPF. Also, SII was proved to be a prognostic element for PFS (HR 2.801, P=0.018) and DMFS (HR 3.735, P=0.032) in multivariate analysis, and IC regimen (HR 2.182, P=0.049) for predicting DMFS. The rate of grade 3-4 leukopenia (P=0.038), neutropenia (P=0.021), radiation oral mucositis (P=0.048), diarrhea (P=0.036), and ear damage (P=0.046) were more common in TPF group. CONCLUSION: Our study revealed that TPF regimen showed a higher 5-year DMFS for stage IVA and N2-3 patients, while for stage III and N0-1, TP might be ample. In high-risk LA-NPC patients (stage IVA combined with pretreatment SII ≥432.48), TPF had a higher 5-year OS and DMFS, with more grade 3-4 toxicities, but most of them were endurable.

Prognostic value of pretreatment prognostic nutritional index and lactated dehydrogenase in locally advanced nasopharyngeal carcinoma patients.

BACKGROUND: To evaluate the prognostic value of pretreatment prognostic nutritional index (PNI), lactated dehydrogenase (LDH) and their combination (PNI-LDH) in patients with locally advanced NPC receiving induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT). METHODS: A total of 213 patients diagnosed with locally advanced (III-IVA) NPC between January 2013 and December 2017 were retrospectively reviewed. The optimal PNI and LDH cutoff values were determined by the quartiles. The association between PNI and LDH and the clinicopathological characteristics of the patients was examined. Survival curves were analyzed using the Kaplan-Meier method and compared by the log-rank test between the different PNI and LDH subgroups. Univariate and multivariate analyses were performed by the Cox proportional hazards regression model to evaluate the prognostic impact on overall survival (OS), progression-free survival (PFS), locoregional recurrence free survival (LRFS) and distant metastasis-free survival (DMFS). Furthermore, the prognostic values of the PNI, LDH, and PNI-LDH were evaluated by comparing the AUC area. RESULTS: The optimal cut-off values of PNI and LDH were 52 and 177, respectively. Multivariate analyses revealed that patients with a higher PNI had inferior OS (P=0.027), PFS (P=0.040), LRFS (P=0.015) and DMFS (P=0.040), and patients with a higher LDH level had poorer OS (P=0.040), PFS (P=0.001), LRFS (P=0.001) and DMFS (P=0.001). Furthermore, EBV DNA positive, stage IVA were independent prognostic factors for survival outcomes in the multivariate analyses. Moreover, we further demonstrated that low PNI-high LDH in locally advanced NPC patients was significantly related to poor OS (P=0.012), PFS (P=0.001), LRFS (P=0.001) and DMFS (P=0.001). The AUC of the PNI, LDH and PNI-LDH were 0.653 (P=0.021), 0.647 (P=0.028) and 0.751 (P=0.001), respectively, indicating that PNI-LDH is superior to either score alone. CONCLUSIONS: Pretreatment PNI and LDH could be considered as valuable predictors for survival outcomes in locally advanced NPC patients. The combination of them, superior to either score alone, can be used as a supplement to the traditional TNM staging system.

Prognostic efficacy of the combination of the pretreatment systemic Immune-Inflammation Index and Epstein-Barr virus DNA status in locally advanced Nasopharyngeal Carcinoma Patients.

Background: The systemic immune-inflammation index (SII) and Epstein-Barr virus DNA (EBV DNA) levels has been used as a prognostic marker for nasopharyngeal carcinoma (NPC) patients, but there is no in-depth study in locally advanced NPC patients and no research on the predictive value of their combination. Our study aimed to evaluate the prognostic efficacy of the pretreatment SII, EBV DNA levels and their combination in locally advanced NPC patients receiving induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT). Materials and methods: 319 patients diagnosed with locally advanced NPC receiving IC followed by CCRT were retrospectively reviewed (213 in the training cohort and 106 in the validation cohort). The cut-off value for the SII was determined using receiver operating characteristic (ROC) curve. Correlations between characteristics of patients were assessed using the Pearson correlation coefficient. Survival curves for the SII, EBV DNA levels and their combination were analyzed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed by the Cox proportional hazards regression model to evaluate the prognostic impact on overall survival (OS) and progression-free survival (PFS). A prognostic nomogram was generated and its prediction ability was measured by the concordance index (C-index). Results: The optimal cutoff point for the SII was 402.10. A higher SII and EBV DNA positivity were demonstrated to be related to poorer survival outcomes (P < 0.05). Multivariate analyses showed that a higher SII, EBV DNA positivity and their combination were powerful independent risk factors for OS and PFS (P < 0.05). The SII - EBV DNA had the largest area under the curve (AUC) compared to either score alone. The incorporation of the SII - EBV DNA into established nomogram achieved higher C-index in the prediction of OS and PFS, indicating its superior for predicting survival. All results were found in the training cohort and confirmed in the validation cohort. Conclusions: The pretreatment SII and EBV DNA levels are promising factors for predicting survival in locally advanced NPC patients. The combination of them, which was superior to either score alone, was a complement to the conventional TNM staging system.

Acute Adverse Effects and Prognosis of Locally Advanced Nasopharyngeal Carcinoma Patients Treated with GP Regimen: A Meta-analysis / 肿瘤防治研究

Objective To compare the adverse effects and prognosis of locally advanced nasopharyngeal carcinoma (LANC) patients between the gemcitabine combined platinum (GP) regimen and other platinum-containing chemotherapy regimens by meta-analysis. Methods We searched relevant databases and included the studies about comparing GP and other chemotherapy regimens in the treatment of LANC. Methodological quality was assessed for each included study. Statistical analysis was carried out using RevMan5.3 and Stata15 software. Results The patients on GP regimen had a lower incidence of severe leukopenia and severe gastrointestinal reaction but a higher incidence of severe thrombocytopenia and hepatoxicity than those on other regimens (P < 0.05). The patients on GP regimen had a higher distant metastasis-free survival (P=0.004). Conclusion GP regimen can be used as a safe, alternative and economical induction chemotherapy regimen for locally advanced nasopharyngeal carcinoma.

The Current Role of Adjuvant Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck, and it originates from the mucous epithelium of the nasopharynx. Because it is "hidden", the symptoms of NPC can easily be missed, and more than 70% of patients present with locally advanced disease at diagnosis. Concurrent radiation therapy with chemotherapy can significantly improve regional control of NPC. At present, distant metastasis is the main cause of treatment failure. At the end of the 20th century, clinical trial No. IG0099 in the United States confirmed the effectiveness of adjuvant chemotherapy (AC) for the first time. However, in the past 20 years, various clinical trials and meta-analyses conducted globally have yielded contradictory results regarding the effect of AC on locally advanced NPC. AC has changed from category 1 to the current category 2A in the National Comprehensive Cancer Network (NCCN) guidelines, and it remains controversial whether AC can significantly improve the survival of NPC patients. Here, we comprehensively analyzed the role of AC in locally advanced NPC by comparing some treatment methods. We conclude the role of AC in treating locally advanced NPC, based on the studies presented, remains undefined but is associated with increased toxicity.

Administration of nimotuzumab combined with cisplatin plus 5-fluorouracil as induction therapy improves treatment response and tolerance in patients with locally advanced nasopharyngeal carcinoma receiving concurrent radiochemotherapy: a multicenter randomized controlled study.

BACKGROUND: Nimotuzumab (NTZ) is an anti-EGFR monoclonal antibody. However,the effect of targeted drugs combined with induction therapy in locally advanced nasopharyngeal carcinoma remains unclear. The aim of this study is to investigate the safety and efficacy of NTZ combined with cisplatin plus 5-fluorouracil (PF) as induction regimen in locally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent radiochemotherapy. METHODS: This was a multicenter randomized controlled study performed in eight Guangxi hospitals in 2015-2017. Eligible patients with NPC were randomized into nimotuzumab/PF (NPF group) and docetaxel/PF (DPF group) regimens, respectively, as induction therapy. After 2 cycles of induction therapy, all patients received cisplatin and concurrent intensity modulated radiation therapy (IMRT). Then, the two groups were compared for safety and efficacy. RESULTS: A total of 118 patients with stage III-IVa NPC were assessed, with 58 and 60 in the NPF and DPF groups, respectively. Compared with DPF treatment, NPF induction therapy showed a more pronounced effect on cervical lymph nodes (P = 0.036), with higher response rate (RR) (81% vs 60%). Compared with the DPF group, the NPF group showed significantly reduced leukopenia, neutropenia and gastrointestinal reactions (all P < 0.05); rash only appeared in the NPF group, but all cases were grade 1. During concurrent treatment with radiotherapy and chemotherapy, the NPF group showed better tolerance to radiotherapy and chemotherapy; neutropenia, anemia, gastrointestinal reactions, oral mucositis and radiation dermatitis in the NPF group were significantly reduced (P < 0.05). The expression rate of EGFR was 94.9% (112/118). Compared with the DPF group, patients with EGFR expression in the NPF group showed better response (77.8% vs 63.0%, P = 0.033). CONCLUSION: For locally advanced NPC patients receiving follow-up cisplatin and IMRT, nimotuzumab/PF for induction therapy has better lymph node response rate and milder adverse reactions than the DPF regimen. In addition, the patients have better tolerance in subsequent concurrent radiotherapy and chemotherapy; however, long-term efficacy needs further follow-up evaluation. TRIAL REGISTRATION: The registration number of the clinical trial is ChiCTR-OIC-16008201 and retrospectively registered on March 31, 2016.

Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma.

BACKGROUND: Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT. METHODS: This retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated. RESULTS: Of the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p = 0.057). CONCLUSIONS: The results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

The effects of recombinant human granulocyte colony-stimulating factor mouthwash on radiotherapy-induced oral mucositis in locally advanced nasopharyngeal carcinoma patients.

BACKGROUND: Acute oral mucositis is a common complication of radiotherapy for nasopharyngeal carcinoma (NPC) patients. OBJECTIVES: The aim of the study was to observe the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on radiotherapy-induced oral mucositis in locally advanced NPC patients. MATERIAL AND METHODS: The study involved 64 locally advanced NPC patients that were randomly allocated to receive either rhG-CSF mouthwash (2 µg/mL rhG-CSF; group A, n = 34) or a compounded mouth rinse (10 µg/mL vitamin B12, 0.48 mg/mL gentamicin and 0.04 mg/mL dexamethasone in saline; group B, n = 30) during radiotherapy. Both mouthwashes were used 6 times daily at the onset of oral mucositis, and the treatments continued until the end of all intensity-modulated radiotherapy sessions. Oral mucositis was graded according to the Radiation Therapy Oncology Group acute radiation morbidity scoring criteria. A visual analog scale was used to assess peak mouth pain once a week, and the duration of oral mucositis was recorded. RESULTS: In comparison with group B, the patients in group A had a significantly lower incidence of oral mucositis of grade 3 or above (38.2% vs 66.7%, p < 0.05) and less peak mucosal pain in the 5th, 6th and 7th weeks of radiotherapy (p < 0.05). group A patients also had shorter durations of oral mucositis (35.1 days vs 39.4 days, p < 0.05) and lower peak swallowing function scores (p < 0.05). CONCLUSIONS: The rhG-CSF mouthwash may be more effective than the compounded mouth rinse in preventing and treating radiotherapy-induced mucositis and mucositis-related pain, and thus improving the quality of life for locally advanced NPC patients. These effects should be further investigated in a prospective controlled study.

Effects of hippocampal-sparing intensity-modulated radiotherapy on dose distribution of target volume and organs at risk in locally advanced nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To investigate the effects of hippocampal?sparing intensity?modulated radiotherapy ( IMRT) on dose distribution of target volume and organs at risk ( OARs) in locally advanced nasopharyngeal carcinoma. Methods A retrospective dosimetric analysis was performed among 11 patients with locally advanced nasopharyngeal carcinoma. The MONACO ? v5. 10 Treatment Planning System was used to design three treatment plans:routine volumetric modulated arc therapy ( VMAT ) , hippocampal?sparing VMAT, and nine fixed?fields IMRT. The D98%, D50%, D2%, Dmean , conformity index ( CI ) , and homogeneity index (HI) of planning target volume (PTV) and PTVnx as well as dose distribution of the hippocampus and OARs were evaluated. Using single factor analysis of variance,two group comparative was LSD or paired t?test. Results For the above three plans,the D2% values of PTVnx were ,7 513,and 7 462 cGy,respectively (P=0. 016);the D98% values of PTV were 5837,5812,and 5914 cGy,respectively (P=0. 029);the average D2% values of PTV were 7 399,7 380,and 7 333 cGy,respectively ( P=0. 047);the HI values of PTV were 0. 239,0. 241,and 0. 220,respectively (P=0. 016);the V10 values of the brain stem were 97. 2%,88. 1%,and 90. 3%,respectively ( P=0. 001);the V20 values of the brain stem were 74. 2%, 62. 3%,and 67. 1%,respectively ( P=0. 032);the V30 values of the brain stem were 50. 9%,35. 8%,and 45. 5%, respectively ( P= 0. 020 );the V40 values of brain stem were 24. 4%, 14. 4%, and 23. 3%, respectively ( P=0. 018);the Dmean values of hippocampus were 1 518,899,and 896 cGy,respectively ( P=0. 000);the D40% values of hippocampus were 1 379,642,and 639 cGy,respectively ( P=0. 000);the V10 values of the hippocampus were 54. 1%,25. 1%,and 3. 8%,respectively ( P=0. 000);the V20 values of the hippocampus were 26. 2%, 12. 6%, and 12. 0%, respectively ( P=0. 001 ) . Conclusions Hippocampal?sparing VMAT and nine fixed?fields IMRT can significantly reduce the dose to the hippocampus without affecting dose distribution of target volume and OARs. VMAT may be superior to IMRT because VMAT can simultaneously reduce the dose to the brain stem.