Induction Chemotherapy In Nasopharyngeal Carcinoma Research Articles

Clinicopathologic Features and Efficacy of Induction Chemotherapy in Nasopharyngeal Carcinoma: Real-World Experience.

Nasopharyngeal carcinoma (NPC) accounts for 0.01% of all carcinomas, and 70% of patients have locally advanced disease with a poor prognosis. The mainstay therapy is chemoradiotherapy (CRT), and concurrent administration of platinum-based agents and irradiation provides high local control rates. However, induction (neoadjuvant) chemotherapy (ICT) prior to CRT is recommended for large tumors with a high tumor burden at the category 1 level. For ICT, platinum-based doublet or triplet combination regimens are recommended. Selected patients with a high tumor burden at the time of diagnosis who did not receive ICT before CRT were given adjuvant (consolidation) therapy after CRT. This multicenter study aimed to share our experience in treatment of NPC and evaluate the factors associated with survival. The study included patients diagnosed with NPC who were followed and treated between 2008 and 2022. Hundred and forty-two patients from 6 centers were evaluated. The factors associated with disease-free survival (DFS) and overall survival (OS) were evaluated. The median age of our patients was 51 years (IQR: 16-81 years), and the male:female ratio was 2.5:1. A majority of patients (71%) had stage 3-4 disease. They had locally advanced disease, and 48 patients (34%) received ICT. Twenty patients (14%) received adjuvant therapy. The median follow-up was 41 months (range, 2.7-175.1 months). The median DFS in NPC was 92.6 months (range, 71.9-113.3 months), with a 40th month DFS of 70.9%. The median OS was 113 months (range, 91-135 months), with a 40th month OS of 84.7%. Median DFS was 95.3 months (range, 64.2-126.4 months) in patients who received ICT before CRT, which was longer than in the CRT-only group (p = 0.6). DFS at the 40th month was 75.1% in patients treated with ICT compared to 65.1% in the CRT-only group. Median OS was 117 months (range, 92-142 months) in patients receiving ICT, which was longer than in the CRT-only group (p = 0.4). OS at the 40th month was 86.7% in patients receiving ICT but 83.6% in the CRT-only group. Both the objective response rate and survival were longer in patients who radiologically responded to CRT following ICT. Nonresponse to ICT is a negative predictive indicator. The role of ICT in locally advanced NPC is increasing.

Nomograms based on multiparametric MRI radiomics integrated with clinical-radiological features for predicting the response to induction chemotherapy in nasopharyngeal carcinoma

ObjectiveTo establish nomograms integrating multiparametric MRI radiomics with clinical-radiological features to identify the responders and non-responders to induction chemotherapy (ICT) in nasopharyngeal carcinoma (NPC). MethodsWe retrospectively analyzed the clinical and MRI data of 168 NPC patients between December 2015 and April 2022. We used 3D-Slicer to segment the regions of interest (ROIs) and the “Pyradiomic” package to extract radiomics features. We applied the least absolute shrinkage and selection operator regression to select radiomics features. We developed clinical-only, radiomics-only, and the combined clinical-radiomics nomograms using logistic regression analysis. The receiver operating characteristic curves, DeLong test, calibration, and decision curves were used to assess the discriminative performance of the models. The model was internally validated using 10-fold cross-validation. ResultsA total of 14 optimal features were finally selected to develop a radiomic signature, with an AUC of 0.891 (95 % CI, 0.825–0.946) in the training cohort and 0.837 (95 % CI, 0.723–0.932) in the testing cohort. The nomogram based on the Rad-Score and clinical-radiological factors for evaluating tumor response to ICT yielded an AUC of 0.926 (95 % CI, 0.875–0.965) and 0.901 (95 % CI, 0.815–0.979) in the two cohorts, respectively. Decision curves demonstrated that the combined clinical-radiomics nomograms were clinically useful. ConclusionNomograms integrating multiparametric MRI-based radiomics and clinical-radiological features could non-invasively discriminate ICT responders from non-responders in NPC patients.

Radiomic analysis of MRI for prediction of response to induction chemotherapy in nasopharyngeal carcinoma patients

To establish and validate radiomic models for response prediction to induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) using the radiomic features from pretreatment MRI. This retrospective analysis included 184 consecutive NPC patients, 132 in the primary cohort and 52 in the validation cohort. Radiomic features were derived from contrast-enhanced T1-weighted imaging (CE-T1) and T2-weighted imaging (T2-WI) for each subject. The radiomic features were then selected and combined with clinical characteristics to build radiomic models. The potential of the radiomic models was evaluated based on its discrimination and calibration. To measure the performance of these radiomic models in predicting the treatment response to IC in NPC, the area under the receiver operating characteristic curve (AUC), and sensitivity, specificity, and accuracy were used. Four radiomic models were constructed in the present study including the radiomic signature of CE-T1, T2-WI, CE-T1 + T2-WI, and the radiomic nomogram of CE-T1. The radiomic signature of CE-T1 + T2-WI performed well in distinguishing response and non-response to IC in patients with NPC, which yielded an AUC of 0.940 (95% CI, 0.885-0.974), sensitivity of 83.1%, specificity of 91.8%, and accuracy of 87.1% in the primary cohort, and AUC of 0.952 (95% CI, 0.855-0.992), sensitivity of 74.2%, specificity of 95.2%, and accuracy of 82.7% in the validation cohort. MRI-based radiomic models could be helpful for personalised risk stratification and treatment in NPC patients receiving IC.

A comparative study of functional MRI in predicting response of regional nodes to induction chemotherapy in patients with nasopharyngeal carcinoma.

PurposeTo identify and compare the value of functional MRI (fMRI) in predicting the early response of metastatic cervical lymph nodes (LNs) to induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients.MethodsThis prospective study collected 94 metastatic LNs from 40 consecutive NPC patients treated with IC from January 2021 to May 2021. Conventional diffusion-weighted imaging, diffusion kurtosis imaging, intravoxel incoherent motion, and dynamic contrast-enhanced magnetic resonance imaging were performed before and after IC. The parameter maps apparent diffusion coefficient (ADC), mean diffusion coefficient (MD), mean kurtosis (MK), Dslow, Dfast, perfusion fraction (PF), Ktrans, Ve, and Kep) of the metastatic nodes were calculated by the Functool postprocessing software. All LNs were classified as the responding group (RG) and non-responding group (NRG) according to Response Evaluation Criteria in Solid Tumors 1.1. The fMRI parameters were compared before and after IC and between the RG and the NRG. The significant parameters are fitted by logistic regression analysis to produce new predictive factor (PRE)–predicted probabilities. Logistic regression analysis and receiver operating characteristic (ROC) curves were performed to further identify and compare the efficacy of the parameters.ResultsAfter IC, the mean values of ADC, MD, and Dslow significantly increased, while MK, Dfast, and Ktrans values decreased dramatically, while no significant difference was detected in Ve and Kep. Compared with NRG, PF-pre and Ktrans-pre values in the RG were higher statistically. The areas under the ROC for the pretreatment PF, Ktrans, and PRE were 0.736, 0.722, and 0.810, respectively, with the optimal cutoff value of 222 × 10-4, 934 × 10-3/min, and 0.6624, respectively.ConclusionsThe pretreatment fMRI parameters PF and Ktrans showed promising potential in predicting the response of the metastatic LNs to IC in NPC patients.Clinical Trial RegistrationThis study was approved by the ethics board of the Chinese PLA General Hospital, and registered on 30 January 2021, in the Chinese Clinical Trial Registry; http://www.chictr.org.cn/showproj.aspx?proj=121198, identifier (ChiCTR2100042863).

Survival impact of additional induction chemotherapy in nasopharyngeal carcinoma with chronic hepatitis B infection: a retrospective, bi-center study.

BackgroundPatients with nasopharyngeal carcinoma (NPC) who have hepatitis B virus (HBV) infection tend to be treated with induction chemotherapy (IC) due to a higher metastasis rate. However, additional IC may lead to immunosuppression and can negatively affect the prognosis. We evaluated whether receiving IC improved the prognosis of patients with NPC co-infected with HBV, on the basis of concurrent chemoradiotherapy (CCRT).MethodsThis large-scale retrospective cohort study included data of patients with pathologically confirmed NPC that were collected from two hospitals between January 2010 and March 2014. Patients were followed-up every 3 months during the first 2 years and once every 6 months thereafter. Univariate analysis identified confounding factors associated with prognosis. Stage-based subgroup analyses and 1:1 random-matched pair analyses were performed to compare the survival differences between patients treated with IC + CCRT and those treated with CCRT alone.ResultsAmong the 1,076 enrolled patients, 16.6% were hepatitis B surface antigen (HBsAg)-positive. Among HBsAg-positive patients with stage II/III/IV NPC, distant metastasis-free survival (DMFS) (79.3% vs. 89.9%; P=0.045) and progression-free survival (PFS) (70.6% vs. 83.7%; P=0.025) were lower in patients who received IC + CCRT than in those who received CCRT alone. After adjusting for confounding factors, IC + CCRT was validated as a negative prognosticator for DMFS and PFS, while matched-pair analysis with HBsAg-negative patients showed a better overall survival (OS) for IC + CCRT (88.4% vs. 82.6%; P=0.04).ConclusionsCompared with CCRT alone, IC + CCRT negatively affects DMFS and PFS in patients with NPC with chronic HBV infection. We advocate withholding IC but administering stronger initial treatment in NPC patients complicated with HBV infection.

A spectral CT-based nomogram for predicting the response to induction chemotherapy in nasopharyngeal carcinoma

To establish a spectral computed tomography (CT)-based nomogram for predicting the response to induction chemotherapy (ICT) in nasopharyngeal carcinoma (NPC). Fifty-four patients with NPC who underwent spectral CT examination before ICT were enrolled prospectively. Patients were assigned to response and non-response groups according to response evaluation. The predictive indicators were spectral CT parameters of venous phase, including iodine concentration (IC), normalised IC (NIC), slope of the spectral attenuation curve in Hounsfield units (λHU), effective atomic number (Eff-Z), and water concentration. Multivariate logistic regression was used to construct a predictive model. The receiver operating characteristic (ROC) and calibration curves were used to evaluate the robustness of model, while the bootstrap method was used for internal validation. The Hosmer-Lemeshow test was used to test the goodness of fit of the discriminant model. Multivariate logistic regression analysis showed that NIC, λHU, and Eff-Z were the potential predictors, and the three indicators were further used to establish a predictive model. The nomogram was evaluated to have good predictive performance, the area under the ROC curve was 0.909 (95% confidence interval [CI]: 0.799-0.970), and the model was well calibrated (χ2=8.149, p=0.419). The spectral CT nomogram has potential clinical value in predicting response to ICT in NPC and may help guide individualised treatment decisions.

De-escalating elective nodal irradiation for nasopharyngeal carcinoma.

Treatment outcomes for endemic nasopharyngeal carcinoma have steadily improved over the past two decades with routine use of intensity-modulated radiotherapy (IMRT), concurrent chemotherapy, and MRI staging. 1 Peng G Wang T Yang KY et al. A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma. Radiother Oncol. 2012; 104: 286-293 Summary Full Text Full Text PDF PubMed Scopus (420) Google Scholar , 2 Blanchard P Lee A Marguet S et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015; 16: 645-655 Summary Full Text Full Text PDF PubMed Scopus (459) Google Scholar In the past decade, trials have primarily focused on treatment escalation with induction and consolidative chemotherapy. 3 Zhang Y Chen L Hu GQ et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med. 2019; 381: 1124-1135 Crossref PubMed Scopus (312) Google Scholar , 4 Pan JJ Ng WT Zong JF et al. Proposal for the 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy. Cancer. 2016; 122: 546-558 Crossref PubMed Scopus (164) Google Scholar , 5 Chen YP Liu X Zhou Q et al. Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. Lancet. 2021; 398: 303-313 Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar However, with modern treatment, fewer than 20% of patients with non-metastatic nasopharyngeal carcinoma develop disease recurrence. In this population with few competing risks, these excellent outcomes have promoted renewed interest in individualised treatment de-intensification. Elective upper-neck versus whole-neck irradiation of the uninvolved neck in patients with nasopharyngeal carcinoma: an open-label, non-inferiority, multicentre, randomised phase 3 trialElective UNI of the uninvolved neck provides similar regional control and results in less radiation toxicity compared with standard WNI in patients with N0–N1 nasopharyngeal carcinoma. Full-Text PDF

Baseline Amide Proton Transfer Imaging at 3T Fails to Predict Early Response to Induction Chemotherapy in Nasopharyngeal Carcinoma.

BackgroundEarly identification of nasopharyngeal carcinoma (NPC) patients with high risk of failure to induction chemotherapy (IC) would facilitate prompt individualized treatment decisions and thus reduce toxicity and improve overall survival rate. This study aims to investigate the value of amide proton transfer (APT) imaging in predicting short-term response of NPC to IC and its potential correlation with well-established prognosis-related clinical characteristics.Methods and MaterialsA total of 80 pathologically confirmed NPC patients receiving pre-treatment APT imaging at 3T were retrospectively enrolled. Using asymmetry analysis, APT maps were calculated with mean (APTmean), 90th percentile (APT90) of APT signals in manually segmented NPC measured. APT values were compared among groups with different histopathological subtypes, clinical stages (namely, T, M, N, and overall stages), EBV-related indices (EBV-DNA), or responses to induction chemotherapy, using Mann–Whitney U test or Kruskal–Wallis H test.ResultsNPC showed significantly higher APTmean than normal nasopharyngeal tissues (1.81 ± 0.62% vs.1.32 ± 0.56%, P <0.001). APT signals showed no significant difference between undifferentiated and differentiated NPC subtypes groups, different EBV-DNA groups, or among T, N, M stages and overall clinical stages of II, III, IVA and IVB (all P >0.05). Similarly, baseline APT-related parameters did not differ significantly among different treatment response groups after IC, no matter if evaluated with RECIST criteria or sum volumetric regression ratio (SVRR) (all P >0.05).ConclusionNPC showed significantly stronger APT effect than normal nasopharyngeal tissue, facilitating NPC lesion detection and early identification. However, stationary baseline APT values exhibited no significant correlation with histologic subtypes, clinical stages and EBV-related indices, and showed limited value to predict short-term treatment response to IC.

Differential benefit of induction chemotherapy according to body mass index in nasopharyngeal carcinoma – Pooled analysis of two randomized trials

ObjectiveInduction chemotherapy followed by concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, survival benefits from additional induction chemotherapy varied significantly among patients. This study aimed to determine the predictive value of body mass index (BMI) in induction chemotherapy in NPC. Materials and methodsThis post-hoc analysis included patients from two multicenter, randomized, phase 3 trials (NCT01245959 and NCT01872962), in which patients were randomized to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone. ResultsAmong 960 patients participated, 957 were included in this analysis. 82 (8.6%) patients had baseline BMI < 18.5 kg/m2 (underweight) and 875 (91.4%) had BMI ≥ 18.5 kg/m2 (normal /overweight). Higher proportion of normal/overweight patients completed ≥2 cycles of induction chemotherapy than underweight patients (96.5% vs. 88.4%, p = 0.042). A strong trend for interaction was observed between BMI and induction chemotherapy regarding failure-free survival (FFS) and overall survival (OS, both pinteraction < 0.001). Normal/overweight patients benefited from induction chemotherapy regarding FFS (83.8% vs. 72.9%, p < 0.001) or OS (93.1% vs. 86.9%, p < 0.001), while underweight patients did not (p = 0.24 and p = 0.65, respectively). These results were confirmed in multivariate analysis and multiple sensitivity analyses. ConclusionUsing pooled data from two landmark phase III trials, we found that underweight patients might not benefit from additional induction chemotherapy in locoregionally advanced NPC. If confirmed in prospective studies, this could help guide individual treatment in the clinic.

Survival impact of increasing time to IMRT initiation following induction chemotherapy in nasopharyngeal carcinoma: A propensity score-matched analysis

PurposeTo explore the prognostic impact of waiting time for radiotherapy (RT) after induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC). Methods and materialsA total of 648 NPC patients receiving IC between 2009 and 2011 were included. Propensity score matching (PSM) was performed to balance the variables. Survival outcomes were compared in subgroups based on time to RT (TTR) after IC. ResultsThe optimal cutoff point for TTR was 28 days. A total of 330 patients were selected by 1:2 PSM. Stratified and dichotomized TTRs were both strongly correlated with prognosis. Patients with TTR > 28 days had significantly worse 5-year LRFS, DMFS, DFS and OS than those with TTR ≤ 28 days (P < 0.05). In multivariate analysis, TTR > 28 days was an independent predictor of worse LRFS [HR=2.08; 95% CI, 1.18-3.66; P = 0.011), DMFS (HR=1.65; 95% CI, 1.04-2.62; P = 0.033), DFS (HR=1.86; 95% CI, 1.35-2.62; P < 0.001) and OS (HR=1.90; 95% CI, 1.26-2.85; P < 0.001). High-risk patients with T4 or N2-3 disease were highly susceptible to RT delay with impaired DFS and OS. In high-risk patients with TTR > 28 days, concurrent chemotherapy yielded better DMFS (70.9% vs. 52.0%, P = 0.041), DFS (52.5% vs. 34.3%, P = 0.039) and OS (70.3% vs. 53.2%, P = 0.048). ConclusionsProlonged waiting is detrimental to survival in NPC, and it is strongly recommended to start RT within 28 days after IC. T4/N2-3 NPC has a higher risk of treatment failure with delayed RT. With potential protection against RT delay, concurrent chemotherapy should be performed in high-risk patients as salvage therapy.

Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1

BackgroundCircular RNAs (circRNAs), a new type of noncoding RNA (ncRNA), have been identified as significant gene expression regulators and are involved in cancer progression. However, the roles of circRNAs in nasopharyngeal carcinoma (NPC) remain largely unknown.MethodsHere, the expression profile of circRNAs in a pair of NPC cell lines with different metastatic abilities (S18 and S26 cells) was analyzed by RNA-sequencing. Quantitative reverse transcription PCR was used to detect the expression level of circCRIM1 in NPC cells and tissues. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circCRIM1 on NPC metastasis and EMT. Mechanistically, RNA immunoprecipitation, luciferase reporter assay, pull-down assay with biotinylated miRNA, fluorescent in situ hybridization were performed to confirm the interaction between circCRIM1 and miR-422a in NPC. The clinical value of circCRIM1 was evaluated in NPC metastasis and chemosensitivity.ResultsWe identified that circCRIM1 was upregulated in highly metastatic NPC cells. CircCRIM1 was also overexpressed in NPC tissues with distant metastasis, and its overexpression promoted NPC cell metastasis and EMT. Mechanistically, circCRIM1 competitively bound to miR-422a and prevented the suppressive effects of miR-422a on its target gene FOXQ1, which finally led to NPC metastasis, EMT and docetaxel chemoresistance. Furthermore, high circCRIM1 expression was associated with unfavorable survival in NPC patients. We established a prognostic model based on circCRIM1 expression and N stage that effectively predicted the risk of distant metastasis and treatment response to docetaxel-containing induction chemotherapy in NPC patients.ConclusionsOur findings reveal the critical role of circCRIM1 specifically in promoting NPC metastasis and chemoresistance via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for prognosis and treatment resistance in NPC patients.

Treatment effects of cumulative cisplatin dose during radiotherapy following induction chemotherapy in nasopharyngeal carcinoma: propensity score analyses.

Background:The treatment effects of cumulative cisplatin dose (CCD) during radiotherapy (RT) following induction chemotherapy (IC) have not been determined for patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Methods:A total of 3460 patients with locoregionally advanced NPC who were treated with IC plus cisplatin-based concurrent chemoradiotherapy or RT alone were included in this retrospective study. Three CCD groups (0 mg/m2 ⩽ CCD <100 mg/m2, 100 mg/m2 ⩽ CCD <200 mg/m2, CCD ⩾200 mg/m2) were balanced through the inverse probability of treatment weighting based on propensity scores estimated by a general boosted model. The primary endpoint was overall survival (OS); the secondary endpoints were distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRFS).Results:CCD ⩾200 mg/m2 and <200 mg/m2 exhibited similar treatment effects for OS and DMFS, and were both superior to CCD <100 mg/m2 for OS and DMFS in patients with stage IVa NPC. The three CCD groups achieved similar treatment effects for patients with stage II–III NPC. After IC, CCD during RT appeared to exert little treatment effect on LRFS.Conclusion:The CCD during RT exerts treatment effects and improves OS by reducing the risk of distant metastasis for patients with stage IVa NPC following IC, and CCD <200 mg/m2 (mainly 160 mg/m2 in this group) is recommended. However, RT alone may be sufficient after IC in patients with stage II–III NPC.

A Pairwise Meta-Analysis of Induction Chemotherapy in Nasopharyngeal Carcinoma.

Locoregionally advanced nasopharyngeal carcinoma has high risk of distant metastasis and mortality. Induction chemotherapy is commonly administrated in clinical practice, but the efficacy was quite controversial in and out of randomized controlled trials. We thus conducted this pairwise meta-analysis. Trials that randomized patients to receive radiotherapy or concurrent chemoradiotherapy with or without induction chemotherapy were identified via searches of PubMed, MEDLINE, and ClinicalTrials.gov. A total of ten trials (2,627 patients) were included. The pooled hazard ratios (HRs) based on fixed effect model were 0.68 (95% confidence interval [CI] 0.56-0.80, p < .001) for overall survival (OS) and 0.70 (95% CI 0.61-0.79, p < .001) for progression-free survival (PFS), which strongly favored the addition of induction chemotherapy. The absolute 5-year survival benefits were 8.47% in OS and 10.27% in PFS, respectively. In addition, based on the available data of eight trials, induction chemotherapy showed significant efficacy in reducing locoregional failure rate (risk ratio [RR] = 0.81, 95% CI 0.68-0.96, p = .017) and distant metastasis rate (RR = 0.69, 95% CI 0.58-0.82, p < .001). This pairwise meta-analysis confirms the benefit in OS, PFS, and locoregional and distant controls associated with the addition of induction chemotherapy in nasopharyngeal carcinoma. According to the results of this meta-analysis of ten trials, induction chemotherapy can prolong overall survival and progression-free survival and improve locoregional and distant controls for nasopharyngeal carcinoma.

Liposomal paclitaxel versus docetaxel in induction chemotherapy using Taxanes, cisplatin and 5-fluorouracil for locally advanced nasopharyngeal carcinoma

BackgroundWe wished to evaluate the efficacy and safety of liposomal paclitaxel and docetaxel for induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC).MethodsA total of 1498 patients with newly-diagnosed NPC between 2009 and 2017 treated with IC plus concurrent chemotherapy were included in our observational study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and grade-3–4 toxicities were compared between groups using propensity score matching (PSM).ResultsIn total, 767 patients were eligible for this study, with 104 (13.6%) and 663 (86.4%) receiving a liposomal paclitaxel-based and docetaxel-based taxanes, cisplatin and 5-fluorouracil (TPF) regimen, respectively. PSM identified 103 patients in the liposomal-paclitaxel group and 287 patients in the docetaxel group. There was no significant difference at 3 years for OS (92.2% vs. 93.9%, P = 0.942), PFS (82.6% vs. 81.7%, P = 0.394), LRFS (94.7% vs. 93.3%, P = 0.981) or DMFS (84.6% vs. 87.4%, P = 0.371) between the two groups after PSM. Significant interactions were not observed between the effect of chemotherapy regimen and sex, age, T stage, N stage, overall stage, or Epstein–Barr virus DNA level in the subgroup multivariate analysis. The prevalence of grade-3–4 leukopenia and neutropenia in the liposomal-paclitaxel group was significantly lower than that of the docetaxel group (P < 0.05 for all).ConclusionsCompared with docetaxel, liposomal paclitaxel has identical anti-tumor efficacy, but causes fewer and milder adverse reactions in IC for NPC.

Induction chemotherapy in the treatment of nasopharyngeal carcinoma: Clinical outcomes and patterns of care.

The role of induction chemotherapy in nasopharyngeal carcinoma (NPC) remains controversial. The primary aim of this study was to use the National Cancer Database to evaluate the patterns of care of induction chemotherapy in NPC and its impact on overall survival (OS). Patients with NPC from 2004 to 2014 were obtained from the NCDB. Patients were considered to have received induction chemotherapy if it was started ≥43 days before the start of RT and concurrent CRT if chemotherapy started within 21 days after the start of RT. Propensity score matching was used to control for selection bias. Cox proportional hazards model was used to determine significant predictors of OS. Logistic regression model was used to determine predictors of the use of induction chemotherapy. Significance was defined as a P value <.05. A total of 4857 patients were identified: 4041 patients (87.2%) received concurrent CRT and 816 patients (16.8%) received induction chemotherapy. The use of induction therapy remained stable between 2004 and 2014. Younger patients and those with higher T‐ and N‐stage had a higher likelihood of being treated with induction chemotherapy. The 5‐year OS in patients treated with induction chemotherapy and CRT was 66.3% vs 69.1%, respectively (P = .25). There was no difference in OS when these two groups were analyzed after propensity score matching. No differences in OS existed between these treatment groups in patients with T3‐T4N1 or TanyN2‐3 disease (P = .76). Propensity score matching also did not reveal any difference in OS in patients with T3‐T4N1 or TanyN2‐3 disease. The use of induction chemotherapy has remained stable in the last decade. In this study of patients with NPC, induction chemotherapy was not associated with improved OS compared to CRT alone.

Validation of published nomograms and accordingly individualized induction chemotherapy in nasopharyngeal carcinoma

ObjectivesWe have attempted to validate two published nomograms in nasopharyngeal carcinoma (NPC) and individualize induction chemotherapy (IC) accordingly. Materials and methodsFrom 2007 to 2011, 920 patients were included in the study. The validity of the nomograms was assessed by Harrell’s concordance index (C-index), areas under the curve (AUC), and calibration curves. Disease-free survival (DFS) and overall survival (OS) by IC were evaluated in and out of risk stratified patients with and without propensity score matching analysis. ResultsCompared with the 7th edition of the Union for International Cancer Control (UICC) staging system, Tang’s nomogram better discriminated DFS (C-index 0.629 versus 0.569, P=0.002; AUC 0.635 versus 0.576, P=0.018), whereas Yang’s nomogram had no advantage in predicting OS (C-index 0.648 versus 0.606, P=0.184; AUC 0.643 versus 0.604, P=0.157). Calibration curves indicated good agreement between predicted and observed DFS or OS probability. Without risk stratification, patients achieved no benefit from IC in DFS (P⩾0.101) or OS (P⩾0.370). However, among 580 high-risk patients stratified by Tang’s nomogram, IC improved five-year DFS from 68.8 to 74.8% (P=0.072), and OS from 82.6 to 87.9% (P=0.065), and the improvement of DFS and OS increased to 9.3% (P=0.019) and 7.3% (P=0.036), respectively, in 426 propensity-matched patients. ConclusionsTang’s nomogram helps to stratify stage III-IVa-b NPC, and IC is beneficial to high-risk patients in clinical practice.

Unidimensional Measurement May Evaluate Target Lymph Nodal Response After Induction Chemotherapy for Nasopharyngeal Carcinoma.

The aim of the study was to evaluate whether short axis and long axis on axial and coronal magnetic resonance imaging planes would reflect the tumor burden or alteration in size after induction chemotherapy in nasopharyngeal carcinoma.Patients with pathologically confirmed nasopharyngeal carcinoma (n = 37) with at least 1 positive cervical lymph node (axial short axis ≥15 mm) were consecutively enrolled in this prospective study. Lymph nodal measurements were performed along its short axis and long axis in both axial and coronal magnetic resonance imaging planes at diagnosis and after 2 cycles of induction chemotherapy. In addition, lymph nodal volumes were automatically calculated in 3D treatment-planning system, which were used as reference standard. Student's t test or nonparametric Mann–Whitney U test was used to compare the continuous quantitative variables. Meanwhile, the κ statistic and McNemar's test were used to evaluate the degree of agreement and discordance in response categorization among different measurements.Axial short axis was significantly associated with volumes at diagnosis (P < 0.001). A good agreement (κ=0.583) was found between axial short axis and volumetric criteria. However, the inconsistent lymph nodal shrinkage in 4 directions was observed. Axial short-axis shrinking was more rapid than the other 3 parameters. Interestingly, when utilizing the alternative planes for unidimensional measurements to assess tumor response, coronal short-axis showed the best concordance (κ=0.792) to the volumes.Axial short axis may effectively reflect tumor burden or change in tumor size in the assessment of target lymph nodal response after induction chemotherapy for nasopharyngeal carcinoma. However, it should be noted that axial short axis may amplify the therapeutic response. In addition, the role of coronal short axis in the assessment of tumor response needs further evaluation.

Comparison of two induction chemotherapy regimens in combination with radiotherapy in patients with advanced nasopharyngeal carcinoma

5535 Background: Prospective randomized trials failed to show any survival benefits associated with the use of induction chemotherapy in nasopharyngeal carcinoma (NPC). Although cisplatin-based regimens were commonly used in these trials, the impact of cisplatin dose was not clear. Methods: Individual patient data of two published phase III trials using different cisplatin-based induction chemotherapy regimens were pooled together for analysis. A total of 365 patients with stage II-IV NPC received either cisplatin &amp; epirubicin (EP, n = 144) or cisplatin, bleomycin &amp; fluorouracil (PBF, n = 221) followed by radiotherapy between September 1989 and July 1994. The mean total cisplatin dose received by patients ranged from 162 mg/m2 in EP group to 232 mg/m2 in PBF group. Median follow-up time was 59 months. Results: The response rates at the end of induction chemotherapy were 86% in PBF group and 84% in EP group. No significant differences in tumor control and survival were observed between the two groups. Five-year overall survival rates were 63% in PBF group and 62.5% in EP group. Five-year loco-regional failure-free rates were 74% in PBF group and 65% in EP group, the difference being not significant after adjusting for stage grouping. Conclusions: No significant difference in treatment outcome was observed in patients using different cisplatin-based induction chemotherapy. The absence of survival benefits in chemotherapy arms was probably not related to the dose-intensity of cisplatin used, and escalating the total cisplatin dose alone in induction chemotherapy is not likely to improve survival. No significant financial relationships to disclose.

Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials

Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage. Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months. No significant differences in overall survival, locoregional failure-free, or distant metastasis-free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis-free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis-free rates were 86% and 74% (p = 0.0053). Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation.