A dynamic nomogram combining tumor stage and magnetic resonance imaging features to predict the response to induction chemotherapy in locally advanced nasopharyngeal carcinoma.

OBJECTIVES: To establish an effective dynamic nomogram combining magnetic resonance imaging (MRI) findings of primary tumor and regional lymph nodes with tumor stage for the pretreatment prediction of induction chemotherapy (IC) response in locoregionally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 498 LANPC patients (372 in the training and 126 in the validation cohort) with MRI information were enrolled. All patients were classified as "favorable responders" and "unfavorable responders" according to tumor response to IC. A nomogram for IC response was built based on the results of the logistic regression model. Also, the Cox regression analysis was used to identify the independent prognostic factors of disease-free survival (DFS). RESULTS: After two cycles of IC, 340 patients were classified as "favorable responders" and 158 patients as "unfavorable responders." Calibration curves revealed satisfactory agreement between the predicted and the observed probabilities. The nomogram achieved an AUC of 0.855 (95% CI, 0.781-0.930) for predicting IC response, which outperformed TNM staging (AUC, 0.661; 95% CI 0.565-0.758) and the MRI feature-based model alone (AUC, 0.744; 95% CI 0.650-0.839) in the validation cohort. The nomogram was used to categorize patients into high- and low-response groups. An online dynamic model was built ( https://nomogram-for-icresponse-prediction.shinyapps.io/DynNomapp/ ) to facilitate the application of the nomogram. In the Cox multivariate analysis, clinical stage, tumor necrosis, EBV DNA levels, and cervical lymph node numbers were independently associated with DFS. CONCLUSIONS: The comprehensive nomogram incorporating MRI features and tumor stage could assist physicians in predicting IC response and formulating personalized treatment strategies for LANPC patients. KEY POINTS: • The nomogram can predict IC response in endemic LANPC. • The nomogram combining tumor stage with MRI-based tumor features showed very good predictive performance. • The nomogram was transformed into a web-based dynamic model to optimize clinical application.

Long-term outcomes of chemoradiotherapy versus radiotherapy alone in patients with intermediate-risk nasopharyngeal carcinoma: a population-based analysis.

PURPOSE: To investigate the efficacy of chemotherapy among intermediate-risk (stage II/T3N0) nasopharyngeal carcinoma (NPC) patients receiving radiotherapy (RT). METHODS: We identified stage II/T3N0 NPC patients who received radiotherapy with or without chemotherapy from the Surveillance, Epidemiology and End Results database (2004-2019). Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method with log-rank test and Cox proportional hazards models to evaluate the efficacy of chemotherapy. Subgroup analysis was also conducted based on the baseline characteristics. Propensity score matching (PSM) was performed to balance the intergroup covariates. RESULTS: A total of 1623 patients were enrolled in the study, 1444 received chemoradiotherapy (CRT) and 179 received RT alone. CRT, compared to RT alone, was independently associated with a better OS (HR 0.57, 95% CI 0.45-0.71) and CSS (HR 0.55, 95% CI 0.39-0.79). After PSM, similar results were obtained, and CRT was superior to RT alone in terms of OS (HR 0.60, 95% CI 0.39-0.92) and CSS (HR 0.60, 95% CI 0.40-0.91). Subgroup analysis revealed that OS benefits from CRT were mainly observed in T0-2N1(HR 0.51, 95% CI 0.38-0.70) and T3N0 (HR 0.64, 95% CI 0.42-0.98) rather than T2N0 (HR 1.00, 95% CI 0.51-1.94). Interestingly, after PSM, OS benefits were still seen in T0-2N1 (HR 0.44, 95% CI 0.24-0.82), while not seen in T2N0 (HR 1.83, 95% CI 0.56-5.97) and T3N0 (HR 0.56, 95% CI 0.28-1.12). CONCLUSION: For T0-2N1 NPC patients, CRT was superior to RT alone with better survival, whereas, for T2-3N0 patients, CRT was comparable to RT alone. Prospective large studies should be encouraged to verify the results.

Cofilin-2 Acts as a Marker for Predicting Radiotherapy Response and Is a Potential Therapeutic Target in Nasopharyngeal Carcinoma.

BACKGROUND The purpose of this study was to determine whether cofilin-2 could serve as a protein marker for predicting radiotherapy response and as a potential therapeutic target in nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS Cofilin-2 protein levels in serum and tissue samples from patients with NPC were assessed by sandwich ELISA and IHC. In vitro, cofilin-2 levels in CNE-2R cells were significantly higher than those of CNE-2 cells. Meanwhile, CNE-2R cells were silenced for cofilin-2 to obtain a stable cofilin-2-RNAi-LV3 cell line. Then, cell proliferation, radiosensitivity, invasion and migration abilities, cell cycle, and apoptosis were evaluated by Cell Counting Kit 8 assay (CCK-8), flow cytometry (FCM), clone formation assay, and in vitro. RESULTS The secreted levels of the cofilin-2 protein in radioresistant NPC patients were significantly higher than those of radiosensitive cases. After cofilin-2 knockdown in nasopharyngeal carcinoma CNE-2R cells, proliferation was decreased, while apoptosis and radiosensitivity were enhanced; cell cycle distribution was altered, and the transplanted tumors in nude mice grew significantly less. CONCLUSIONS Overall, our findings suggest that cofilin-2 acts as a marker for predicting radiotherapy response and is a potential therapeutic target in nasopharyngeal carcinoma.

Adiponectin is associated with poor prognosis in carcinoma patients: evidence from a meta-analysis.

BACKGROUND: Studies have come to conflicting conclusions about whether adiponectin (APN) expression is associated with cancer prognosis. To help resolve this question, we meta-analyzed the available evidence. METHODS: PubMed, EMBASE, the Cochrane Library, the Chinese Biological Medical Database and the Chinese National Knowledge Infrastructure Database were systematically searched to identify all eligible studies examining APN expression and prognosis for patients with any type of cancer. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) related to overall survival (OS) or disease-free survival (DFS) were calculated. RESULTS: Ten studies involving 999 patients were meta-analyzed. Analysis across all patients revealed no significant association between high/positive APN expression and DFS, but they did show a significant association between high/positive APN expression and OS (HR 1.51, 95 %CI 1.21 to 1.89). Subgroup analysis showed that high/positive APN expression in non-Asians was significantly associated with both DFS (HR 1.36, 95% CI 1.03 to 1.80) and OS (HR 1.53, 95 %CI 1.20 to 1.96), but no such associations were observed in Asians. In addition, high/positive APN expression was significantly associated with OS across all patients with hepatocellular carcinoma (HR 1.89, 95 %CI 1.20 to 2.98). CONCLUSIONS: The available evidence suggests that high/positive APN expression is associated with poor prognosis for patients with various carcinomas, especially for non-Asian cancer patients and for all patients with hepatocellular carcinoma. These findings should be confirmed and extended in large, well-designed studies.

A Review: Proteomics in Nasopharyngeal Carcinoma.

Although radiotherapy is generally effective in the treatment of major nasopharyngeal carcinoma (NPC), this treatment still makes approximately 20% of patients radioresistant. Therefore, the identification of blood or biopsy biomarkers that can predict the treatment response to radioresistance and that can diagnosis early stages of NPC would be highly useful to improve this situation. Proteomics is widely used in NPC for searching biomarkers and comparing differentially expressed proteins. In this review, an overview of proteomics with different samples related to NPC and common proteomics methods was made. In conclusion, identical proteins are sorted as follows: Keratin is ranked the highest followed by such proteins as annexin, heat shock protein, 14-3-3σ, nm-23 protein, cathepsin, heterogeneous nuclear ribonucleoproteins, enolase, triosephosphate isomerase, stathmin, prohibitin, and vimentin. This ranking indicates that these proteins may be NPC-related proteins and have potential value for further studies.

Identification of patients with nasopharyngeal carcinoma by serum protein profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND: As diagnosis of nasopharyngeal carcinoma at an early disease stage is important, we attempted to distinguish between patients with nasopharyngeal carcinoma and noncancer controls by using serum protein profiles. METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and CM10 protein chip were used to detect the serum proteomic patterns of 65 patients with nasopharyngeal carcinoma before radiotherapy and 93 noncancer controls. Proteomic spectra of serum samples from 50 nasopharyngeal carcinoma patients and 60 noncancer controls were used as a training set. The validity of the classification tree was then challenged with a blind test set which included another 15 patients with nasopharyngeal carcinoma and 33 noncancer controls. Biomarker Wizard 3.01 and Biomarker Pattern 5.01 were used in combination to analyze the data and to develop diagnostic models. RESULTS: 21 protein peaks were significantly different between nasopharyngeal carcinoma and controls. 4 mass peaks (M4182, M5343, M5913 and M8702 mass/charge ratio) were chosen automatically to construct a classification tree. The classification tree correctly determined 93.8 % (45/48) of the test samples with 93.3 % (14/15) of the nasopharyngeal carcinoma samples and 93.9 % (31/33) of the noncancer samples. Using a combination of serum protein profiles and Epstein-Barr viral capsid antigen immunoglobulin A antibody tests, the diagnostic sensitivity and specificity were increased to 100 and 97 %, respectively. CONCLUSIONS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry could correctly distinguish nasopharyngeal carcinoma from noncancer individuals and showed great potential for the development of a screening test for the detection of nasopharyngeal carcinoma.

Serum ferritin predicted prognosis in patients with nasopharyngeal carcinoma.

Elevated serum ferritin (SF) levels have been associated with poor prognosis in various cancer types, but its impact on nasopharyngeal carcinoma (NPC) remains unclear. This retrospective study analyzed clinical data from 252 non-metastatic NPC patients admitted to Hainan General Hospital between January 2014 and May 2016. SF levels were measured using the chemiluminescence method. Patients were categorized into low, medium, and high-level SF groups based on tertile median SF levels. Survival outcomes were assessed using Kaplan-Meier analysis and Cox regression models. The overall survival rates of the entire patient cohort at 1, 3, 5, and 8 years were 95.2%, 85.7%, 76.2%, and 68.9% respectively. The high-level SF group (SF > 164.00 ng/mL) had significantly worse overall survival (83.1 vs 96.3 months, P = 0.023) and progression-free survival (77.8 vs 93.3 months, P = 0.019) compared to the low-level SF group. Univariate and multivariate analyses confirmed that high SF levels, along with T3/T4 staging and N3 staging, were independent risk factors for poor prognosis. In conclusion, high SF levels are associated with shorter overall survival and progression-free survival in NPC patients.

The Prognostic Value of Serum Sialic Acid in Patients with Nasopharyngeal Carcinoma: A Propensity Score Matching Study.

Purpose: Elevated serum sialic acid (SA) is one of the indicators of poor prognosis in various malignant tumors. This study intends to determine the relationship between serum SA levels and survival prognosis in nasopharyngeal carcinoma (NPC). Patients and Methods: From 2014 to 2016, NPC patients with no distance metastasis undergoing intensity-modulated radiotherapy (IMRT) were retrospectively analyzed. The serum SA levels before initial treatment were measured, and an optimal cut-off level was determined by X-tile software. A propensity score matching (PSM) technique was applied to reduce intergroup differences between the low serum SA level group and the high serum SA level group. Chi-square tests were utilized for comparing intergroup differences, Kaplan-Meier approach was utilized for plotting survival curves, and univariate and multivariate Cox proportional hazards regression models were employed for analyzing prognostic factors. Results: Overall, 293 NPC patients with no distance metastasis were included. The optimal cut-off level of serum SA was 65.10 mg/dl. The baseline levels after PSM were more balanced compared to those before PSM. Survival analysis showed that the locoregional relapse-free survival (LRRFS, p=0.010), distant metastasis-free survival (DMFS, p=0.014), progression-free survival (PFS, p=0.009), and overall survival (OS, p=0.015) survival curves of the low serum SA level group and high serum SA level group were statistically significant differences. Univariate analysis showed that American Joint Committee on Cancer (AJCC) stage, T stage, N stage, neoadjuvant chemotherapy (NC), and serum SA expression level were factors influencing the prognosis of NPC patients. Multivariate analysis showed that high serum SA expression level was related to worse PFS and OS in NPC patients with no distance metastasis. Conclusion: High serum SA level (SA > 65.10 mg/dl) before treatment is associated to poor survival outcomes in NPC and is an independent adverse prognostic factor in NPC patients with no distance metastasis.

Establishing subdivisions of M1 stage nasopharyngeal carcinoma based on decision tree classification: A multicenter retrospective study.

OBJECTIVES: To meet the demand for personalized treatment, effective stratification of patients with metastatic nasopharyngeal carcinoma (mNPC) is essential. Hence, our study aimed to establish an M1 subdivision for prognostic prediction and treatment planning in patients with mNPC. MATERIALS AND METHODS: This study included 1239 patients with mNPC from three medical centers divided into the synchronous mNPC cohort (smNPC, n = 556) to establish an M1 stage subdivision and the metachronous mNPC cohort (mmNPC, n = 683) to validate this subdivision. The primary endpoint was overall survival. Univariate and multivariate Cox analyses identified covariates for the decision-tree model, proposing an M1 subdivision. Model performance was evaluated using time-dependent receiver operating characteristic curves, Harrell's concordance index, calibration plots, and decision curve analyses. RESULTS: The proposed M1 subdivisions were M1a (≤5 metastatic lesions), M1b (>5 metastatic lesions + absent liver metastases), and M1c (>5 metastatic lesions + existing liver metastases) with median OS of 34, 22, and 13 months, respectively (p < 0.001). This M1 subdivision demonstrated superior discrimination (C-index = 0.698; 3-year AUC = 0.707) and clinical utility over those of existing staging systems. Calibration curves exhibited satisfactory agreement between predictions and actual observations. Internal and mmNPC cohort validation confirmed the robustness. Survival benefits from local metastatic treatment were observed in M1a, while immunotherapy improved survival in patients with M1b and M1c disease. CONCLUSION: This novel M1 staging strategy provides a refined approach for prognostic prediction and treatment planning in patients with mNPC, emphasizing the potential benefits of local and immunotherapeutic interventions based on individualized risk stratification.

Efficacy of metastatic lesion radiotherapy in patients with metastatic nasopharyngeal carcinoma: A multicenter retrospective study.

OBJECTIVE: We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). MATERIALS AND METHODS: Patients with mNPC from three institutions were included in this study. Propensity score matching (PSM) was employed to ensure comparability between patient groups. Overall survival (OS) rates were assessed using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using univariate and multivariate Cox hazard analyses. Subgroup analyses were conducted to assess the effects of MLRT on specific patient populations. RESULTS: We analyzed data from 1157 patients with mNPC. Patients who received MLRT had significantly better OS than those who did not, both in the original (28 vs. 21 months) and PSM cohorts (26 vs. 23 months). MLRT was identified as an independent favorable predictor of OS in multivariate analyses, with hazard ratios of 0.67. The subgroup analysis results indicated that radiotherapy effectively treated liver, lung, and bone metastatic lesions, particularly in patients with a limited tumor burden. Higher total radiation doses of MLRT (biologically effective dose (BED) ≥ 56 Gy) were associated with improved OS, while neither radiation technique nor dose fractionation independently influenced prognosis. CONCLUSIONS: MLRT offers survival advantages to patients diagnosed with mNPC. Patients with limited metastatic burden derive the most benefit from MLRT, and the recommended regimen for MLRT is a minimum BED of 56 Gy for optimal outcomes.

Nomogram Based on Hemoglobin, Albumin, Lymphocyte and Platelet Score to Predict Overall Survival in Patients with T3-4N0-1 Nasopharyngeal Carcinoma.

Purpose: There is still uncertainty regarding the prognosis of nasopharyngeal carcinoma (NPC) based on hemoglobin, albumin, lymphocytes, and platelets (HALP) score. The aim of this study was to build and verify a nomogram using HALP score to investigate the prognostic value of NPC and identify low-risk patients in T3-4N0-1 NPC to guide treatment options. Patients and methods: A total of 568 NPC patients with stage T3-4N0-1M0 were recruited in the study, who were given either concurrent chemoradiotherapy (CCRT) or induction chemotherapy (IC) plus CCRT. The prognostic factors of overall survival (OS) were picked by Cox proportional hazards regression analysis to generate a nomogram, which appraised by discrimination, calibration and clinical utility. Patients were stratified according to risk scores calculated by the nomogram, and compared to the 8th TNM staging system using the Kaplan-Meier methods. Results: Multivariate analysis showed that TNM stage, Epstein-Barr virus DNA (EBV DNA), HALP score, lactate dehydrogenase-to-albumin ratio (LAR) and systemic inflammatory response index (SIRI) were independent prognostic indicators for OS, and these factors contained in the nomogram. The nomogram demonstrated a significant enhancement over the 8th TNM staging system in terms of assessing OS (C-index, 0.744 vs 0.615 in the training cohort, P < 0.001; 0.757 vs 0.646 in the validation cohort, P = 0.002). Calibration curves displayed good agreement and the stratification in high-risk and low-risk groups resulted in a significant divergence of Kaplan-Meier curves for OS (P < 0.001). In addition, the decision analysis (DCA) curves confirmed satisfactory discriminability and clinical utility. Conclusion: The HALP score was an independent prognostic factor for NPC. The prognostic function of the nomogram for T3-4N0-1 NPC patients was more accurate compared to the 8th TNM system, facilitating personalized treatment planning.

Efficacy of induction chemotherapy in lymph node-positive stage III nasopharyngeal carcinoma and identification of beneficiaries based on clinical features: A propensity score matching analysis.

PURPOSE: To investigate the role of induction chemotherapy (IC) in lymph node-positive (LN-positive) stage III nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). METHODS: In total, 627 patients with newly diagnosed LN-positive stage III NPC receiving CCRT or IC plus CCRT were included. The primary endpoint was progression-free survival (PFS). Propensity-score matching (PSM) was conducted to balance the intergroup covariates. Kaplan-Meier method with log-rank test was employed to compare survival curves. Subgroup analyses were conducted based on baseline characteristics. RESULTS: After 1:1 PSM, 414 patients were identified (207 patients per group). Compared with CCRT, IC plus CCRT provided better survival (5-year PFS 88.4% vs. 78.6%, P = 0.01; overall survival [OS] 94.8% vs. 85.3%, P = 0.003; and distant metastasis-free survival [DMFS] 93.1% vs. 85.6%, P = 0.03). The IC beneficial effects on PFS were mainly present in patients with grade 2-3 ENE, elevated serum lactate dehydrogenase (LDH > 170U/L), and N2 disease. Patients with grade 2 CNN had comparable PFS benefits to those with grade 0-1 CNN. For patients with grade 0-1 ENE combined with LDH ≤ 170U/L, survival between the two groups was similar with 5-year PFS 93.6% vs. 90.4% (P = 0.50), OS 94.2% vs. 93.0% (P = 0.72), and DMFS 98.6% vs. 97.7% (P = 0.98). CONCLUSION: Adding IC before CCRT improved survival in LN-positive stage III NPC patients. Additional IC did not provide better survival for patients with grade 0-1 ENE combined with LDH ≤ 170U/L and could be avoided in this population. CNN may not be a good risk factor for tailoring a personalized treatment plan.

Individualized number of induction chemotherapy cycles for locoregionally advanced nasopharyngeal carcinoma patients based on early tumor response.

BACKGROUND: The optimal number of cycles of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) is unclear. We aimed to combine the tumor response during IC and tumor stage to individualize the number of IC cycles. METHODS: Totally, 498 LANPC patients who received IC plus CCRT between 2014 and 2018 were reviewed. Tumor response during IC was used to stratify patients with different risks. All patients were classified into those who received two cycles of IC and those who were treated with three cycles. Propensity score matching methods were performed to compare the treatment efficiency. RESULTS: After two cycles of IC, 340/498 (68.3%) cases showed complete tumor response (CR)/partial response (PR) and 158 (31.7%) achieved stable disease (SD)/disease progression (PD). Unfavorable responders (SD/PD) exhibited poor survival outcomes. The three-cycle IC regimen was correlated with better OS and PFS than the two-cycle regimen for N2-3 patients in the CR/PR group. However, the use of different IC cycle strategies achieved similar survival outcomes for SD/PD or N0-1 patients. The incidences of acute toxicities were higher in the IC = 3 group. CONCLUSIONS: Tumor response during IC could be a powerful predictor of LANPC and could be used to guide the individualized number of IC cycles. A three-cycle IC regimen seemed to be preferable for N2-3 patients who received CR/PR during IC. However, an additional cycle of IC could not benefit N0-1 or SD/PD patients, and the optimal treatment strategies for these patients require further consideration.

Nomogram Based on Inflammatory Biomarkers and Nutritional Indicators for Predicting Overall Survival in Locoregionally Advanced Nasopharyngeal Carcinoma.

Purpose: To establish and validate a nomogram to predict overall survival in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) based on inflammatory biomarkers and nutritional indicators. Patients and Methods: A total of 1304 patients who underwent concurrent chemoradiotherapy (CCRT) with or without induction chemotherapy (IC) or adjuvant chemotherapy (AC) were included in the study. The prognosis factors of overall survival (OS) were selected by Cox regression analysis to establish the nomogram. Concordance index (C-index), calibration curves, decision curve analysis (DCA) and Kaplan-Meier curves were used to evaluate the nomogram. Results: Using multivariate Cox analysis of clinically important variables, the following variables were incorporated in the prediction of OS: age, gender, T stage, N stage, pre-treatment plasma Epstein-Barr virus (EBV) DNA, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), lactic dehydrogenase-to-albumin ratio (LAR) and prognostic nutritional index (PNI). The discriminative ability, clinical usefulness and calibration of the nomogram revealed good predictive ability as indicated by the C-index (0.717 in nomogram and 0.602 in the 8th AJCC staging system), decision curves, calibration curves and K-M curves. Conclusion: Inflammatory biomarkers and nutritional indicators of survival for LA-NPC were selected to create a nomogram predicting OS. The proposed nomogram resulted in more accurate prognostic prediction than 8th AJCC staging system.

Optimize the number of cycles of induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: a propensity score matching analysis.

Background: There is no conclusive on the optimal number of cycles of induction chemotherapy (IC) with the greatest benefit to patient survival. This study aimed to assess the efficiency and acute toxicities of different cycles of IC for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Methods: We reviewed data from patients with LA-NPC treated with IC plus concurrent chemoradiation (CCRT). Propensity score matching (PSM) was applied to match paired patients. After PSM, survival outcomes of matched patients were compared between two and three cycles of IC groups. Univariate and multivariate Cox regression analysis were carried out to identify potentially independent predictors. Treatment-related acute toxicities between the two groups were compared by Pearson X2 test or Fisher's exact test. Results: In total, 189 pairs were selected. The median follow-up time was 60 months (range 5 to 126 months). There was no difference between two and three cycles of IC in terms of 5-year overall survival (87.0% vs. 89.7%, p = 0.991), distant metastasis-free survival (90.1% vs. 86.8%, p = 0.587), locoregional recurrence-free survival (97.0% vs. 93.8%, p = 0.488), or progression-free survival (79.4% vs. 79.3%, p = 0.896). Multivariate Cox analysis showed that T stage, N stage, and clinical stage were independent prognostic factors. Three cycles of IC were associated with a higher incidence of Grade 1-2 acute toxicity than two cycles during IC period. Conclusion: The efficacy of two cycles of IC achieved similar survival outcomes as three cycles and has a lower incidence of treatment-related acute toxicity.

A Systematic Review and Meta-Analysis of Studies Comparing Concurrent Chemoradiotherapy With Radiotherapy Alone in the Treatment of Stage II Nasopharyngeal Carcinoma.

Purpose: The role of concurrent chemoradiotherapy (CCRT) in stage II nasopharyngeal carcinoma (NPC) is still controversial. Our objective is to evaluate the value of concurrent chemotherapy in stage II NPC receiving radiotherapy (RT). Methods: We searched the PubMed, Embase, and Scopus databases for studies comparing CCRT versus RT alone in stage II NPC with survival outcomes and toxicities, including locoregional recurrence-free survival (LRFS), metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and grade 3-4 acute toxicities. The hazard ratios (HRs) of survival outcomes and risk ratios (RRs) of toxicities were extracted for meta-analysis. Subgroup analysis for stage N1 patients was performed to further explore whether these populations can earn benefits from concurrent chemotherapy. Results: Nine eligible studies with a total of 4,092 patients were included. CCRT was associated with a better OS (HR = 0.61, 95% CI 0.44-0.82), LRFS (HR = 0.62, 95% CI 0.50-0.78), and PFS (HR = 0.65, 95% CI 0.54-0.79), but with similar DMFS (HR = 0.81, 95% CI = 0.46-1.45) compared with two-dimensional RT (2DRT) alone. However, CCRT showed no survival benefit in terms of OS (HR = 0.84, 95% CI 0.62-1.15), LRFS (HR = 0.85, 95% CI 0.54-1.34), DMFS (HR = 0.96, 95% CI 0.60-1.54), and PFS (HR = 0.96, 95% CI 0.66-1.37) compared with intensity-modulated RT (IMRT) alone. Subgroup analyses indicated that CCRT had similar OS (HR = 1.04, 95% CI 0.37-2.96), LRFS (HR = 0.70, 95% CI 0.34-1.45), DMFS (HR = 1.03, 95% CI 0.53-2.00), and PFS (HR = 1.04, 95% CI 0.58-1.88) in the stage N1 populations. Meanwhile, compared to RT alone, CCRT significantly increased the incidence of grade 3-4 leukopenia (RR = 4.00, 95% CI 2.29-6.97), mucositis (RR = 1.43, 95% CI 1.16-1.77), and gastrointestinal reactions (RR = 8.76, 95% CI 2.63-29.12). No significant differences of grade 3-4 toxicity in thrombocytopenia (RR = 3.45, 95% CI 0.85-13.94) was found between the two groups. Conclusion: For unselected patients with stage II NPC, CCRT was superior to 2DRT alone with better LRFS, PFS, and OS, while adding concurrent chemotherapy to IMRT did not significantly improve survival but exacerbated acute toxicities. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022318253.

A nomogram based on tumor response to induction chemotherapy may predict survival in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: To evaluate the clinical significance of tumor response to induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients and further to develop a nomogram for predicting survival prognosis. METHODS: A total of 498 patients with stage III-IVA NPC applying IC and concurrent chemotherapy were reviewed (training cohort, n = 376; validation cohort, n = 122). RESULTS: Tumor response was an independent predictor for clinical outcomes. The nomogram included age, N stage, pretreatment Epstein-Barr virus DNA, lymphocyte-to-monocyte ratio, and tumor response achieved an ideal C-index of 0.703 (95% CI 0.655-0.751) in the validation cohort for predicting overall survival (OS), which outperformed than that of the TNM system alone (C-index, 0.670, 95% CI: 0.622-0.718). In addition, the nomogram could successfully classified patients into different risk groups. CONCLUSIONS: We established and validated a precise and convenient nomogram based on tumor response for predicting the OS of LANPC patients.

Prognostic significance of wait time for radical radiotherapy in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: The prognostic significance of wait time between definite diagnosis and initial radical radiotherapy is not well established in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) receiving both induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT). METHODS: From 2010 to 2018, 648 patients with LA-NPC treated with IC followed by CCRT were included. RESULTS: A total of 172 pairs of patients with LA-NPC were selected by propensity score matching (PSM). Compared to patients with an acceptable wait time (≤75 days), patients with a prolonged wait time (>75 days) had a significant lower 5-year DMFS rate (86.6% vs. 74.1%, p = 0.006). Subgroup analyses indicated that the unfavorable effects of longer waiting times were mainly seen among stage IVa patients. CONCLUSIONS: A prolonged wait time (>75 days) between definite diagnosis and initial radical radiotherapy has negative prognostic effects on patients with LA-NPC receiving IC plus CCRT, particularly those with IVa stage.

Efficiency of high cumulative cisplatin dose in high- and low-risk patients with locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: The optimal cumulative cisplatin dose (CCD) during radiation therapy for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients receiving induction chemotherapy (IC) plus CCRT remains controversial. This study aimed to explore the treatment efficiency of CCD for high-and low-risk patients with LA-NPC. METHODS: Data from 472 LA-NPC patients diagnosed from 2014 to 2018 and treated with IC plus CCRT were reviewed. After propensity score matching, the therapeutic effects of a CCD > 200 and CCD ≤ 200 mg/m2 were evaluated comparatively. Five factors selected by multivariate analysis were incorporated to develop a nomogram. Subgroup analysis was conducted to explore the role of different CCDs in nomogram-defined high- and low-risk groups. Additionally, acute toxicities were evaluated comparatively between the high- and low-CCD groups. RESULTS: After matching, there was no difference between different CCD groups for all patients in terms of 3-year overall survival (OS), distant metastasis-free survival (DMFS), locoregional recurrence-free survival (LRRFS), or progression-free survival (PFS). A nomogram was built by integrating pretreatment EBV DNA, clinical stage, and post-IC EBV DNA, post-IC primary gross tumor and lymph node volumes obtained a C-index of 0.674. The high-risk group determined by the nomogram had poorer 3-year PFS, OS, DMFS, and LRRFS than the low-risk group. A total of CCD > 200 mg/m2 increased the survival rates of 3-year PFS and DMFS (PFS: 72.5% vs. 54.4%, p = 0.012; DMFS: 81.9% vs. 61.5%, p = 0.014) in the high-risk group but not in the low-risk group. Moreover, the high CCD increased treatment-related acute toxicities. CONCLUSIONS: A high CCD was associated with better 3-year PFS and DMFS rates than a low dose for high-risk patients but could not produce a survival benefit for low-risk patients.

A nomogram to predict survival and guide individualized induction chemotherapy in T3-4N1M0 nasopharyngeal carcinoma.

Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) and CCRT alone were the optional treatment regimens for T3-4N1M0 nasopharyngeal carcinoma (NPC) patients. Therefore, we established a nomogram to predict clinical prognosis and guide individualized IC in T3-4N1M0 NPC. Overall, 699 T3-4N1M0 NPC patients treated with CCRT with or without IC between January 2010 and December 2018 were examined. Overall survival (OS) was the main endpoint. A nomogram was developed that included prognostic variables selected by multivariable analysis. The risk score, which was calculated according to the nomogram, was used for risk stratification. The survival difference of patients undergoing CCRT with or without IC was then compared in risk-stratified subgroups. The nomogram yielded C-indexes of 0.708 (95% confidence interval [CI]: 0.682-0.734) in the training cohort and 0.670 (95% CI: 0.625-0.715) in the validation cohort. Calibration curves for 1-, 3- and 5-year OS suggested a good association between the nomogram predicted and observed probabilities. High-risk patients stratified by nomogram benefited from IC (IC + CCRT vs CCRT: 5-year OS: 77.8% vs 58.8%; P = 0.040; 5-year disease-free survival: 75.0% vs 58.2%; P = 0.017), whereas in the low-risk group, the application of IC was associated with worse locoregional recurrence-free survival and distant metastasis-free survival. This nomogram can serve as a reliable model for prognostic prediction and can be used to guide individualized treatment of T3-4N1M0 NPC. High-risk patients are candidates for IC before CCRT, while the use of IC for low-risk patients should be considered carefully.