Stage III-IVA Nasopharyngeal Carcinoma Research Articles

Efficacy of nimotuzumab added to concurrent chemoradiotherapy after induction chemotherapy for patients with locally advanced nasopharyngeal carcinoma.

6024 Background: To investigate the efficacy and toxicities associated with adding nimotuzumab to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LANPC) patients who received induction chemotherapy (IC). Methods: Patients with stage III-IVA nasopharyngeal carcinoma who received IC (TPF/TP/GP) and platinum-based CCRT between January 2017 and October 2021 were retrospectively included. We performed propensity score matching (PSM) to balance and control confounding factors, and the matching variables included gender, age, T stage, N stage, and Epstein-Barr virus (EBV) status. Patients were divided into two treatment groups: CCRT+nimotuzumab (200mg iv, weekly for 7 courses) and CCRT alone. Primary endpoints were overall survival (OS) and disease-free survival (DFS), the secondary endpoints were locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). Results: We screened 242 patients in the analysis. After PSM, 121 (50.0%) and 121 (50.0%) had CCRT+nimotuzumab and CCRT alone, respectively. The 3-year OS was 95.4% and 88.0% in those with and without nimotuzumab treatment (P=0.041), and the 3-year DFS of the CCRT+nimotuzumab group was significantly better than that in the CCRT alone group (90.3% vs. 77.5%, P=0.003). Similar LRFS was found between those with and without nimotuzumab treatment (96.5% vs. 93.7%, P=0.297). The 3-year DMFS for CCRT+nimotuzumab versus CCRT alone was 92.9% versus 82.5% (P=0.008). No significant differences in major toxicities were found between the two treatment arms including hematologic toxicities, hepatoxicity, nephrotoxicity, gastrointestinal reactions, and mucositis (P>0.05). Conclusions: The addition of nimotuzumab to CCRT after IC in LANPC has shown promising results in treatment outcomes and acceptable toxicities.

Concurrent nimotuzumab and intensity-modulated radiotherapy for elderly patients with locally advanced nasopharyngeal carcinoma.

Because of the common physical condition, reduced organ function, and comorbidities, elderly patients with nasopharyngeal carcinoma (NPC) are often underrepresented in clinical trials. The optimal treatment of elderly patients with locally advanced NPC remains unclear. The purpose of this study was to evaluate the efficacy of concurrent nimotuzumab combined with intensity-modulated radiotherapy (IMRT) in elderly patients with locally advanced NPC. We conducted a single-arm, phase II trial for elderly patients with stage III-IVA NPC (according to UICC-American Joint Committee on Cancer TNM classification, 8th edition). All patients received concurrent nimotuzumab (200 mg/week, 1 week prior to IMRT) combined with IMRT. The primary end-point was complete response (CR) rate. The secondary end-points were survival, safety, and geriatric assessment. Between March 13, 2017 and November 12, 2018, 30 patients were enrolled. In total, 20 (66.7%) patients achieved CR, and objective response was observed in 30 (100.0%) patients 1 month after radiotherapy. The median follow-up time was 56.05 months (25th-75th percentile, 53.45-64.56 months). The 5-year locoregional relapse-free survival, distant metastasis-free survival, cancer-specific survival, disease-free survival, and overall survival were 89.4%, 86.4%, 85.9%, 76.5%, and 78.8%, respectively. Grade 3 mucositis occurred in 10 (33%) patients and grade 3 pneumonia in 3 (10%) patients. Concurrent nimotuzumab combined with IMRT is effective and well-tolerated for elderly patients with locally advanced NPC.

Addition of nimotuzumab to concurrent chemoradiotherapy after induction chemotherapy improves outcomes of patients with locally advanced nasopharyngeal carcinoma.

To investigate the survival outcomes and toxicities associated with the addition of nimotuzumab to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LANPC) patients who received induction chemotherapy (IC). Patients with stage III-IVA nasopharyngeal carcinoma who received IC and CCRT between January 2017 and October 2021 were retrospectively included. We aimed to compare the locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) between patients treated with CCRT+nimotuzumab and CCRT alone. We included 411 patients in the analysis. Of these patients, 267 (65.0%) and 144 (35.0%) had CCRT+nimotuzumab and CCRT alone, respectively. Similar LRFS was found between those with and without nimotuzumab (92.9% vs. 92.6%, p = 0.855). The 3-year DMFS was 88.2% and 76.2% in those with and without nimotuzumab (p = 0.002). The 3-year DFS was 83.4% and 70.6% in those with and without nimotuzumab treatment (p = 0.003). The 3-year OS was 92.1% and 81.1% in those with and without nimotuzumab (p = 0.003). The multivariate Cox regression analysis indicated that the addition of nimotuzumab was independently associated with better DMFS (hazard ratio [HR] 0.606, p = 0.049), DFS (HR 0.613, p = 0.028), and OS (HR 0.497, p = 0.019). No significant differences in major toxicities were found between the two treatment arms, including hematologic toxicities, hepatoxicity, nephrotoxicity, gastrointestinal reactions, and mucositis (all p > 0.05). The addition of nimotuzumab to CCRT after IC in LANPC has shown promising results in improving treatment outcomes and acceptable toxicities.

Neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in elderly patients with stage III-IVa nasopharyngeal carcinoma: A real-world study based on medical comorbidities.

To evaluate the outcomes and toxicities of adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) in elderly (≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (LANPC, stage III-IVa). Using an NPC-specific database, 245 elderly patients with stage III-IVa NPC, receiving CCRT +/- NAC, and an Adult Co-morbidity Evaluation 27 (ACE-27) score <2 were included. Recursive partitioning analysis (RPA) based on TNM stage and Epstein-Barr virus (EBV) DNA were applied for risk stratification. The primary end point was disease-free survival (DFS). Two risk groups were generated by the RPA model. In the high-risk group (EBV DNA < 4000 copy/ml with stage IVa & EBV DNA ≥4000 copy/ml with stage III-IVa), patients treated with NAC plus CCRT achieved improved 5-year DFS rates compared to those who received CCRT alone (56.9% vs. 29.4%; p = 0.003). But we failed to observe the survival benefit of additional NAC in the low-risk group (EBV DNA <4000 copy/ml with stage III). The most common severe acute toxic effects were leucopenia (46.8% vs. 24.4%) and neutropenia (43.7% vs. 20.2%) in the NAC plus CCRT group versus CCRT group with statistically significant differences. The addition of NAC to CCRT was associated with better DFS for the high-risk group of elderly LANPC patients with ACE-27 score <2. However, the survival benefit of additional NAC was not observed in low-risk patients.

Dose Painting Radiotherapy Guided by Diffusion-Weighted Magnetic Resonance vs. 18F-FDG-PET/CT in Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized, Controlled Clinical Trial

This phase II randomized controlled trial aimed at comparing the efficacy and toxicity of diffusion-weighted magnetic resonance imaging (DWI)-guided dose painting radiotherapy (DP-RT), FDG-PET/CT-guided DP-RT, and conventional MRI-based radiotherapy (RT) in locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 330 patients with stage III-IVa NPC disease were randomly assigned in a 1:1:1 ratio to receive induction chemotherapy followed by concurrent chemoradiotherapy by DWI-guided DP-RT (group A, n = 110), FDG-PET/CT-guided DP-RT (group B, n = 110), or conventional MRI-based RT (group C, n = 110). All patients received volumetric modulated arc therapy (VMAT). In group A, subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC < mean). In group B, subvolume GTVnx-PET (gross tumor volume of nasopharynx in PET images) was defined within GTVnx as the SUV50%max isocontour. The doses to GTVnx-DWI in group A and GTVnx-PET in group B were escalated to 75.2 Gy/32 fx in patients with T1-2 disease and to 77.55 Gy/33 fx in those with T3-4 disease in 2.35 Gy per fraction. In group C, planning gross tumor volume of nasopharynx (PGTVnx) was irradiated at 70.4 to 72.6 Gy/32 to 33 fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn (ChiCTR2200057476). Group A and B showed significant higher complete response (CR) rates than group C (100%, 100%, and 96.4% for group A, B and C, respectively, p = 0.036). In groups A, B and C, the 1-year local recurrence-free survival (LRFS) rates were 100%, 100%, and 94.5%, respectively (p = 0.002). The 1-year disease-free survival (DFS) rates were 100%, 99.1%, and 92.7%, respectively (p = 0.001). The 1-year distant metastasis-free survival (DMFS) rates were 100%, 99.1%, and 93.6%, respectively (p = 0.004). The 1-year overall survival (OS) rates were 100%, 100%, and 95.4%, respectively (p = 0.006). Group A and B had significantly higher 1-year LRFS, DFS, DMFS, and OS than those in group C. No significant differences were observed in LRFS, DFS, DMFS and OS between group A and B. Group B (PET/CT group) had a higher incidence of grade 3-4 acute ototoxicity (3.6%) than group A (0%) and group C (0%, p = 0.036). No significant differences in other grade 3-4 acute adverse events and late toxic effects were observed among the three groups, and no patient had grade 5 toxicities. Multivariate analysis showed that dose painting (DWI-guided DP-RT and PET/CT-guided DP-RT vs conventional MRI-based RT) was associated with improved LRFS, DFS, DMFS and OS. Both DWI-guided DP-RT and PET/CT-guided DP-RT plus chemotherapy are associated with improved LRFS, DFS, DMFS and OS compared with conventional MRI-based RT among patients with locoregionally advanced NPC. DWI-guided DP-RT does not increase toxicities, but PET/CT-guided DP-RT has higher incidence of acute ototoxicity.

Concurrent chemoradiotherapy with or without neoadjuvant chemotherapy in pediatric patients with stage III-IVa nasopharyngeal carcinoma: a real-world propensity score-matched cohort study.

To compare neoadjuvant chemotherapy (NAC) plus concurrent chemoradiotherapy (CCRT) to CCRT alone in children and adolescents (age ≤ 18years) with locoregionally advanced nasopharyngeal carcinoma (CA-LANPC, stage III-IVA). 195 CA-LANPC patients who were treated through CCRT with or without NAC between 2008 and 2018 were enrolled in this study. A matched cohort composed of CCRT patients and NAC-CCRT patients was generated by propensity score matching (PSM) at a 1:2 ratio. Survival outcomes and toxicities were compared between the CCRT group and NAC-CCRT group. Of the 195 patients, 158 (81%) received NAC plus CCRT, and 37 (19%) received CCRT alone. The NAC-CCRT group had higher EBV DNA levels (≥ 4000 copy/mL), more advanced TNM stage (stage IV disease), and lower incidence of a high radiation dose (> 6600cGy) than the CCRT group. To avoid bias in treatment selection within retrospectively analysis, 34 patients from the CCRT group were matched with 68 patients from the NAC-CCRT group. In the matched cohort, the 5-year DMFS rate was 94.0% in the NAC-CCRT group versus 82.4% in the CCRT group, with marginal statistical significance (HR = 0.31; 95%CI 0.09-1.10; P = 0.055). During treatment, the accumulate incidence of severe acute toxicities (65.8% vs 45.9%; P = 0.037) in the NAC-CCRT group was higher than the CCRT group. However, the CCRT group had significantly higher accumulate incidence of severe late toxicities (30.3% vs 16.8%; P = 0.041) than the NAC-CCRT group. Addition of NAC to CCRT tended to improve long-term DMFS in CA-LANPC patients with acceptable toxicity. However, relative randomized clinical trial is still needed in the future.

Individualized Concurrent Chemotherapy for Patients with Stage III-IVa Nasopharyngeal Carcinoma Receiving Neoadjuvant Chemotherapy Combined with Definitive Intensity-Modulated Radiotherapy.

This retrospective study aimed to re-evaluate the effect of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). A total of 498 patients who received neoadjuvant chemotherapy (NCT) combined with concurrent chemoradiotherapy (CCRT) or IMRT were retrospectively reviewed. The distribution of baseline characteristics was balanced using propensity score matching. Additionally, the results of NCT+IMRT and NCT+CCRT were compared using Kaplan-Meier survival analysis, and differences in survival rates were analyzed using the log rank test. There were no significant differences in overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LRFS) between the two groups. Patients were further categorized into risk subgroups based on pretreatment Epstein-Barr virus (EBV) DNA cutoff values using receiver operating characteristic curve analysis. There were no statistically significant differences in OS, PFS, DMFS, and LRFS between patients who received NCT+CCRT and NCT+IMRT in the high-risk group. In the low-risk group, although there were no differences between NCT+CCRT and NCT+IMRT in OS, PFS, and LRFS, patients who received NCT+CCRT had better DMFS than those who received NCT+IMRT. Pretreatment EBV DNA level can be used to individualize concurrent chemotherapy for patients with locally advanced NPC. Patients with low pretreatment EBV DNA levels may benefit from concurrent chemotherapy, whereas those with high levels may not. Other treatment modalities need to be explored for high-risk patients to improve their prognosis.

A Randomized Controlled Trial of Cognitive Behavior Therapy to Reduce Oral Mucositis in Patients with Locoregional Advanced Nasopharyngeal Carcinoma Undergoing Chemoradiotherapy

<h3>Purpose/Objective(s)</h3> Our previous study showed that cognitive behavioral therapy (CBT) significantly reduced the incidence of oral mucositis in patients with locoregional advanced nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy (Liu F, et al. Integr Cancer Ther. 2021;20:1-9), but it was limited by its retrospective nature. The purpose of this phase 2 randomized controlled trial was to evaluate the efficacy of cognitive behavioral therapy on reducing the occurrence and severity of oral mucositis in patients with locoregional advanced NPC undergoing chemoradiotherapy. <h3>Materials/Methods</h3> From July 2020 to June 2021, a total of 302 patients with diagnosis of stage III-IVA NPC (AJCC 8th) were randomly assigned (1:1) to receive CBT plus chemoradiotherapy (CBT group, n=151) or treatment as usual (TAU) plus chemoradiotherapy (TAU group or controlled group, n=151). Patients in both groups received induction chemotherapy (three cycles of gemcitabine/cisplatin or docetaxel/cisplatin/ 5-fluorouracil) followed by concurrent chemoradiotherapy (three cycles of 100 mg/m² cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). And all patients received education given at irregular intervals that included information about health, nutrition, and psychology. Patients in the CBT group received a series of six CBT sessions for 6 weeks during concurrent chemoradiotherapy. Weekly themes and main content of CBT sessions included introduction and establishment of a therapeutic relationship in the first week, understanding the relationships between thoughts, emotions, and behavior in the second week, cognitive restructuring from week 3 to week 5, and consolidating the experiences of dealing with emotional problems in the sixth week. The Primary end point was oral mucositis incidence. Treatment response, acute and late adverse events were evaluated. This trial is registered with chictr.org.cn, number ChiCTR2000034701. <h3>Results</h3> The incidence of oral mucositis was significantly lower in the CBT group (84.1%) compared with that in the TAU group (93.4%, P=0.011). Compared with the TAU, CBT significantly reduced oral mucositis severity scores recorded by investigators (25.0 [0.0–65.0] vs. 55.8 [0.0–88.0], <i>P</i><0.01) and patients (3.0 [0–10] vs. 6.0 [0–10], <i>P</i><0.01). Compared with the TAU group, the CBT group also showed a significantly lower incidence of Grade 3–4 fatigue (6.0% vs. 13.9% P=0.021), insomnia (5.3% vs. 14.6% P=0.007), anemia (0.0% vs. 5.3% P=0.012), and weight losing (0.0% vs. 4.0% P=0.039). The objective response rate (ORR) was 100% in both groups, and the complete response (CR) rate was similar in patients with CBT and with TAU (97.4% vs. 95.4%, P=0.539). <h3>Conclusion</h3> Cognitive behavioral therapy significantly reduced the occurrence and severity of oral mucositis in patients with locoregional advanced nasopharyngeal carcinoma during chemoradiotherapy treatment.

Prevalence of Neurocognitive Impairment for NPC Survivors after Definitive Intensity-Modulated Radiotherapy: A Cross-Sectional Study

<h3>Purpose/Objective(s)</h3> High-dose intensity-modulated radiotherapy (IMRT) has led to excellent prognosis in patients with localized nasopharyngeal carcinoma (NPC). Given the relatively young age of onset and the close anatomic relationship between the nasopharynx and the central nervous system, post-radiation neurocognitive impairment among long-term survivors represents an under-recognized late complication. This study aims to determine the prevalence and the affected cognitive domains in post-IMRT NPC survivors. <h3>Materials/Methods</h3> We undertook a cross-sectional study in a high-volume tertiary oncology center in Hong Kong. NPC survivors who underwent IMRT with a minimal post-radiotherapy interval of 1 year were eligible. All patients underwent an initial screening using the Montreal Cognitive Assessment-Hong Kong (MoCA-HK) test, followed by a 2-hour comprehensive battery of neurocognitive assessments covering 8 distinct domains: intellectual capacity (WAIS-IV), attention span (WAIS-IV digit span, WMS-III Visual Spatial Span), visual memory (WMS-III Visual reproduction span), verbal memory (Auditory Verbal Learning Test), processing speed (Color Trail Test), executive function (Stroop Test), motor dexterity (Grooved Pegboard Test) and language ability (Verbal Fluency Test). Mean percentiles and Z-scores of all neurocognitive assessments were compared with age- and/or education-matched population normative data using one-sample t-tests. Correlation of cognitive outcomes with clinical factors were analyzed using multivariable linear regression. <h3>Results</h3> A total of 182 NPC survivors were enrolled. The median post-radiotherapy interval was 6.9 years, 129 (70.9%) were long-term survivors at least 5 years beyond radiotherapy. The median age was 56 years old, 89% of the enrolled patients had stage III-IVA NPC by AJCC/UICC 8^th Edition, and 87% of patients received chemotherapy. The mean MoCA score was 23.6, 25.8% of patients were considered cognitively impaired. NPC survivors demonstrated significant cognitive impairment in verbal memory (p<0.001), processing speed (p<0.001), executive function (p<0.001), motor dexterity (p<0.001) and language ability (p=0.001). Most significant impairment was observed in executive function, mean z-scores of which were -1.76 to -1.38 below normative data. Post-IMRT interval, disease stage and chemotherapy usage showed no significant association with the degree of neurocognitive impairment. <h3>Conclusion</h3> Post-IMRT neurocognitive impairment was prevalent in NPC survivors. Neurocognitive function was not impaired globally but occurred predominantly in selected domains, particularly executive function. Cognitive assessment and training should be considered a part of survivorship care for NPC patients. Future research on the correlation between neurocognitive function and radiation dosimetry of various brain subsites would be informative.

Diffusion-Weighted Magnetic Resonance Imaging-Guided Dose Painting in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma Treated With Induction Chemotherapy Plus Concurrent Chemoradiotherapy: A Randomized, Controlled Clinical Trial

We hypothesized that diffusion-weighted magnetic resonance imaging (DWI)-guided dose-painting intensity modulated radiation therapy (DP-IMRT) is associated with improved local tumor control and survival in locoregionally advanced nasopharyngeal carcinoma (NPC). The purpose of this randomized study was to compare the efficacy and toxicity of DWI-guided DP-IMRT to conventional magnetic resonance imaging (MRI)-based IMRT in locoregional advanced NPC. A total of 260 patients with stage III-IVa NPC disease were randomly assigned in a 1:1 ratio to receive induction chemotherapy followed by chemoradiotherapy by DWI-guided DP-IMRT (group A, n=130) or conventional MRI-based IMRT (group B, n=130) in this prospective clinical trial. In group A, subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC < mean) according to MRI before induction chemotherapy. The dose to GTVnx-DWI was escalated to 75.2 Gy/32 fx in patients with T1-2 disease and to 77.55 Gy/33 fx in those with T3-4 disease in 2.35 Gy per fraction. In group B, planning gross tumor volumeof nasopharynx was irradiated at 70.4 to 72.6 Gy/32 to 33 fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn (ChiCTR1800015779). A total of 260 patients were included in the trial (130 patients in group A and 130 in group B). Complete response rates after chemoradiotherapy were 99.2% (129 of 130) and 93.8% (122 of 130) in groups A and B, respectively (P=.042). At a median follow-up of 25 months, DWI-guided DP-IMRT was associated with improved 2-year disease-free survival (DFS; 93.6% [95% confidence interval {CI}, 88.1%-99.1%] vs 87.5% [95% CI, 81.4%-93.6%], P=.015), local recurrence-free survival (100% [95% CI, not applicable {NA}] vs 91.3% [95% CI, 85.4%-97.2%]), locoregional recurrence-free survival (LRRFS; 95.8% [95% CI, NA] vs 91.3% [95% CI, 85.4%-97.2%]), distant metastasis-free survival (DMFS; 97.8% [95% CI, NA] vs 90.9% [95% CI, 85.8%-96.0%]), and overall survival (100% [95% CI, NA] vs 94.5% [95% CI, 89.2%-99.8%]). Zero and 3 patients had local-only recurrences in group A and B, respectively. The most common site of first failure in each arm was distant organ failure. No statistically significant differences in acute and late toxic effects were observed. Multivariate analyses showed that DP (DWI-guided DP-IMRT vs conventional MRI-based IMRT without DP) was associated with DFS, local recurrence-free survival, LRRFS, and distant metastasis-free survival. Epstein-Barr virus DNA level was associated with DFS and LRRFS. DWI-guided DP-IMRT plus chemotherapy is associated with a disease-free survival benefit compared with conventional MRI-based IMRT among patients with locoregionally advanced NPC without increasing acute toxic effects.

Predictive Value of Ki-67 for Neoadjuvant Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> To assess the predictive value of Ki-67 expression for adjuvant chemotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). <h3>Materials/Methods</h3> The authors retrospectively evaluated 1374 patients with stage III-IVa nasopharyngeal carcinoma in Sichuan Cancer Hospital from 2013 to 2019, of which 638 patients received induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT), and 736 patients received concurrent chemoradiotherapy (CCRT) alone. Clinical and pathological features of the patients with LA-NPC were retrieved from the hospital records. Follow-up was measured from the first day of therapy to last examination or death. The endpoints were overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS) and Metastasis-free survival (MFS). The ROC curve was carried out to analyze the Ki-67 cut off value related to OS. According to the cut off value of Ki-67, LA-NPC patients was divided into two groups. The efficacy of neoadjuvant chemotherapy was analysis in the two groups respectively. The OS, PFS, LRFS and MFS rates were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazard models were used to evaluate independent risk factors for OS, PFS, MFS and LRFS. <h3>Results</h3> The median (interquartile range) follow-up time was (42.3 months [10.3-62.4]). The level of Ki-67 expression was not significantly correlated with age, gender, T stage, N stage, or histological type. The ROC curve showed that the Ki-67 cut off value related to OS was 50%. Among the LA-NPC patients with higher Ki-67 expression (>50%), we observed a significant difference between IC+CCRT group and CCRT group, including 3-years OS (96.7% vs 75.5%, <i>P</i> = 0.011), PFS (81.7% vs 66.7%, <i>P</i> = 0.007), LRFS (88.9% vs 94.1%, <i>P</i> = 0.530), and MFS (91.9% vs 66.7%, <i>P</i> = 0.003). However, among the LA-NPC patients with lower Ki-67 expression (≤50%), there was no significant difference between IC+CCRT group and CCRT group, including 3-years OS (91.1% vs 80.4%, <i>P</i> = 0.631), PFS (80.9% vs 85.2%, <i>P</i> = 0.921), LRFS (91.6% vs 96.7%, <i>P</i> = 0.312), and MFS (84.0% vs 85.2%, <i>P</i> = 0.913). <h3>Conclusion</h3> We found that LA-NPC patients got survival benefit from neoadjuvant chemotherapy may depend on the expression of Ki-67. LA-NPC patients with higher expression of Ki-67 (> 50%) can have a better survival outcome after neoadjuvant chemotherapy. The expression level of Ki-67 was a potential marker for predicting the efficacy of neoadjuvant chemotherapy in LA-NPC.

Efficacy and Toxicity of Three Induction Chemotherapy Regimens in Locoregionally Advanced Nasopharyngeal Carcinoma: Outcomes of 10-Year Follow-Up.

Background/ObjectiveWe aimed to compare the 10-year survival outcomes of induction docetaxel plus cisplatin and 5-fluorouracil (TPF), docetaxel plus cisplatin (TP), and cisplatin plus 5-fluorouracil (PF) regimens additional to concurrent chemoradiotherapy (CRT) in locoregionally advanced nasopharyngeal carcinoma (NPC).MethodsEligible patients with newly diagnosed stage III-IVA NPC were included. Propensity score matching (PSM) was used to balance prognostic covariates. Survival outcomes and toxicities between different groups were compared.ResultsA total of 855 patients between 2009 and 2012 were included, with 395 (46.2%), 258 (30.2%), and 202 (23.6%) receiving TPF plus CRT, TP plus CRT, and PF plus CRT regimens, respectively. After a median follow-up of 111.8 months, multivariate analysis both in the whole cohort and PSM selected 202 pairs showed that TPF plus CRT and TP plus CRT achieved significantly better 10-year overall survival (OS) than PF plus CRT. Sensitivity analysis after excluding patients with T3-4N0 disease demonstrated that TPF plus CRT still achieved significantly better OS than PF plus CRT (HR, 0.580; 95% CI, 0.395-0.852; P = 0.005), while the difference between TP plus CRT and PF plus CRT was marginally significant (HR, 0.712; 95% CI, 0.503-1.008; P = 0.056). With regard to toxicity profile, PF regimen achieved the lowest grade 3–5 toxicities (27.3%).ConclusionTPF plus CRT and TP plus CRT were better than PF plus CRT in improving the 10-year OS of patients with stage III-IVA NPC.

Nomogram-aided individual induction chemotherapy regimen selection in advanced nasopharyngeal carcinoma

ObjectiveWe undertook this study to clarify how TPF, TP and PF induction chemotherapy (IC) regimens benefit for nasopharyngeal carcinoma (NPC) patients with different risk of disease progression. Materials and MethodsPatients with newly diagnosed, stage III-IVA NPC were included. A quantitative nomogram was built using the independent prognostic factors identified for disease-free survival (DFS). Patients were stratified into low-risk and high-risk groups by the nomogram. Survival outcomes and toxicities between different IC regimens were compared. ResultsIn total, 1647 (41.0%), 1123 (28.0%) and 1242 (31.0%) patients received TPF, PF and TP regimen, respectively. Consequently, 2253 (56.2%) patients were clarified as low-risk group and the other 1759 (43.8%) as high-risk group. Survival outcomes did not significantly differ between TPF, PF and TP regimens within the low-risk group. However, TPF was associated with significantly improved 3-year DFS (76.2% vs. 67.5% vs. 68.3%), overall survival (88.3% vs. 84.1% vs. 83.9%), distant metastasis-free survival (81.9% vs. 75.0% vs. 77.4%) and locoregional relapse-free survival (92.0% vs. 87.5% vs. 86.9%; all P < 0.05) compared with PF and TP within high-risk group. Multivariate analysis also confirmed these findings. Toxicity analysis showed that TP regimen has the highest percentage of grade 3–5 hematologic toxicities while PF regimen achieved the lowest percentages of overall grade 3–5 adverse events. ConclusionsPatients with high risk should receive TPF for better efficacy and PF may be a better choice for low-risk patients with regard to less grade 3–5 toxicities.

Prognostic Value of Serum Epstein-Barr Virus Antibodies and Their Correlation with TNM Classification in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

PurposeThis study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients.Materials and MethodsSerum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS).ResultsRta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis–free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3–4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05).ConclusionRta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.

Effects of Cognitive Behavioral Therapy for Depression and Anxiety, Response Rates and Adverse Events in Patients with Locoregional Advanced Nasopharyngeal Carcinoma.

Purpose:This retrospective study investigated the effects of cognitive behavioral therapy (CBT) on depression, anxiety, response rates, and adverse events in patients with locoregional advanced nasopharyngeal carcinoma (NPC).Methods:A total of 269 patients with diagnosis of stage III-IVA NPC received either CBT plus chemoradiotherapy (CBT group, n = 136) or treatment as usual (TAU) plus chemoradiotherapy (TAU group, n = 133). Patients in the CBT group received a series of 6 CBT sessions for 6 weeks during concurrent chemoradiotherapy. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS) score at baseline, the completion of radiotherapy, and 6, 12, and 24 months after radiotherapy. Response rates and adverse events were also evaluated.Results:Patients in the CBT group showed significantly less depression and anxiety than patients in the TAU group after the completion of radiotherapy (P < .05). Complete response rates were 99.3% (135/136) and 92.5% (123/133) in the CBT group and TAU group with a small effect size (Phi coefficient = .171), respectively (P = .005). Compared with the TAU group, the CBT group showed a significantly lower incidence of acute adverse events and late toxic effects.Conclusions:The addition of CBT to chemoradiotherapy significantly reduced depressive and anxiety symptoms. CBT combined with chemoradiotherapy is associated with improved response rates, with reduced incidence of toxic effects in patients with locoregional advanced NPC. Based on this study, we registered a randomized controlled clinical trials to better define the role of CBT in patients with locoregional advanced NPC (Registration number: ChiCTR2000034701).

Real-World Cost-Effectiveness Analysis of Gemcitabine and Cisplatin Compared to Docetaxel and Cisplatin Plus Fluorouracil Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma.

BackgroundAddition of gemcitabine and cisplatin (GP) or docetaxel and cisplatin plus fluorouracil (TPF) to concurrent chemoradiotherapy (CCRT) significantly improved survival in locoregionally advanced nasopharyngeal carcinoma (NPC). However, an economic evaluation of these regimens remains unknown. The purpose of this study is to compare the cost-effectiveness of GP versus TPF regimen in the treatment of locoregionally advanced NPC in China.Materials and methodsA comprehensive Markov model was developed to evaluate the health and economic outcomes of GP versus TPF regimen for patients with locoregionally advanced NPC. Baseline and clinical outcome were derived from 158 patients with newly diagnosed stage III-IVA NPC between 2010 and 2015. We evaluated the quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) from the perspective of the Chinese healthcare system. One-way sensitive analysis explored the impact of uncertainty in key model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis.ResultsGP regimen provided an additional 0.42 QALYs with incremental cost of $3,821.99, resulting in an ICER of $9,099.98 per QALY versus TPF regimen at the real-world setting. One-way sensitivity analysis found that the results were most sensitive to the cost and proportion of receiving subsequent treatment in two groups. The probability that GP regimen being cost-effective compared with TPF regimen was 86.9% at a willingness-to-pay (WTP) of $31,008.16 per QALY.ConclusionUsing real-world data, GP regimen was demonstrated a cost-effective alternative to TFP regimen for patients with locoregionally advanced NPC in China. It provides valuable evidence for clinicians when making treatment decisions to improve the cost-effectiveness of treatment.

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

BackgroundNimotuzumab (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.MethodsThis 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.ResultsA 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).ConclusionFor 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 registrationThe registration number of the clinical trial is ChiCTR-OIC-16008201 and retrospectively registered on March 31, 2016.

Induction Therapy of Nituzumab Combined PF Regimen to Improve the Treatment Response and Tolerance of Locally Advanced Nasopharyngeal Carcinoma Undergoing the Concurrent Chemoradiotherapy: A Multi-Center Controlled Randomized Clinical Study

The role of targeted combined with chemotherapy-based induction therapy in locally advanced nasopharyngeal carcinoma with concurrent intensity-modulated radiotherapy(IMRT) is unclear. Through a multi-center randomized controlled study to investigate the safety and efficacy of the induction therapy of nimotuzumab combined with PF regimen (cisplatin + 5-fluorouracil) in the follow-up treatment of locally advanced nasopharyngeal carcinoma patients received concurrent chemoradiotherapy. From January 2015 to November 2017，We included 118 patients with stage III-IVa nasopharyngeal carcinoma from 8 tumor centers, 58 cases in NPF group (induction therapy of nimotuzumab combined with PF regimen) and 60 cases in TPF group (induction chemotherapy of docetaxel, cisplatin and fluorouracil regimen). After two cycles of induction therapy, all patients received cisplatin concurrent intensity-modulated radiotherapy (IMRT), and the safety and short-term efficacy of the two groups were compared. To analyze the correlation between the curative effect of induction therapy and EGFR expression. Until May 2018, all patients were treated and evaluated immediately after treatment. Compared with the TPF regimen , the nimotuzumab combined PF scheme was more effective for the cervical lymph node (p=0.036), and the response rate (CR+PR) was higher (60% vs 81%) , but there was no statistically significant difference in the curative effect of nasopharyngeal lesion and induction therapy (p=0.446,p=0.143); there was no statistically significant difference in immediate curative effect (p=0.449). Compared with the TPF group, although the incidence of 1 grade rash was significantly increased (p=0.012), the neutropenia and gastrointestinal reaction of NPF group was significantly reduced, the difference was statistically significant (p=0.028;p=0.049).The treatment tolerance of cisplatin during the IMRT stage is better in the NPF group, the gastrointestinal reaction, oral mucositis and radiation dermatitis were significantly reduced, and the difference was statistically significant (p=0.038,p=0.041,p=0.035).The expression rate of EGFR in the whole group was 94.9%. Compared with chemotherapy, patients with EGFR high expression can get a better treatment response (P=0.033) from the induction treatment of nituzumab monoclonal combined chemotherapy. For the locally advanced nasopharyngeal carcinoma patients received treated with cisplatin concurrent IMRT, the induction therapy of nimotuzumab combined with PF regimen has a better lymph node remission rate and mild adverse reactions. Patients had better tolerance in subsequent concurrent chemoradiochemotherapy , but the long-term efficacy requires further follow-up observation. Patients with EGFR high expression may gain more benefits from the induction treatment of EGFR combined chemotherapy.

Comparison of GP and TPF induction chemotherapy for locally advanced nasopharyngeal carcinoma

ObjectivesThis study aims to compare two induction chemotherapy regimens, TPF and GP, for patients with locally advanced nasopharyngeal carcinoma (NPC). Materials and methodsWe analyzed patients with newly diagnosed stage III-IVA NPC (excluding T3/T4N0, AJCC) between December 2010 and May 2015 who were treated with TPF or GP induction chemotherapy (IC) followed with concurrent chemoradiotherapy (CCRT) and those treated with CCRT alone. Treatment compliance, survival outcomes and grade 3–4 side effects were compared among these three groups. ResultsA total of 189 patients were eligible for this study, with 87 (46.0%), 71 (37.6%) and 31 (16.4%) in the TPF, GP and CCRT alone groups. All patients were followed for 3 years. There was no difference in the 3-year survival rate between GP- and TPF-treated patients. Disease-free survival (DFS) and overall survival (OS) were significantly improved in both IC groups compared with those in the CCRT alone group. Multivariable analysis suggested that patients with N3 had a higher risk of distant metastasis than those with N1-2. GP is not inferior to TPF regardless of different N categories. There were significant more grade 3–4 treatment-related toxicity in TPF group than in GP group. ConclusionOur study found that in locally advanced NPC, the GP induction chemotherapy regimen is equivalent to TPF in treatment outcomes, but with significant less grade 3–4 acute toxicity. Further studies are needed to validate our findings.

Intensity-modulated radiotherapy combined with endostar has similar efficacy but weaker acute adverse reactions than IMRT combined with chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma.

The present study is to compare the efficacy and adverse effects of intensity-modulated radiotherapy (IMRT) combined with endostar and IMRT combined with concurrent chemotherapy on locally advanced nasopharyngeal carcinoma (NPC).A total of 23 patients with stage III-IVa NPC were included in the present study, and randomly divided into experimental group (10 cases treated with IMRT + endostar) and control group (13 cases treated with IMRT + chemotherapy of cis-dichlorodiamineplatinum). Endostar was intravenously administered from the first day of IMRT. The patients received a total of 2 cycles (14 days each) separating by a 7-day interval.IMRT combined with endostar did not have significantly different recent efficacy compared with IMRT combined with chemotherapy. IMRT combined with endostar and IMRT combined with chemotherapy had 2-year overall survival (OS) rates of 100.0% and 69.6%, respectively, without significant difference between each other (χ2 = 1.446, P = .299). The 2-year local relapse-free survival (LRFS) of the 2 groups were 100.0% and 81.3%, respectively, without significant difference between each other (χ2 = 1.000, P = .317). The 2-year distant metastasis-free survival (DMFS) of the 2 groups were 100.0% and 73.5% (χ2 = 1.591, P = .207), respectively. The 2-year progression-free survival (PFS) of the 2 groups were 100.0% and 67.3% (χ2 = 2.164, P = .141), respectively. However, the cumulative survival curves of OS, LRFS, DMFS, and PFS were separated between the 2 groups. The result that IMRT combined with endostar did not have significantly different long-term efficacy than IMRT combined with chemotherapy probably due to limited case number and short follow-up time. IMRT combined with endostar resulted in significantly lower grades of leucopenia, nausea/vomiting, weight loss, and oral mucositis compared with IMRT combined with chemotherapy. The grades of late adverse reactions of IMRT combined with endostar were not different from those of IMRT combined with chemotherapy.The present study demonstrates that, compared with IMRT combined with chemotherapy, IMRT combined with endostar has similar efficacy in the treatment of locally advanced NPC, but significantly weaker acute adverse reactions, which improve the life quality of NPC patients.