We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in ...locoregionally advanced NPC.
The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA < 1500 copies) and high-risk group (pre-EBV DNA ≥ 1500 copies). Progression free survival (PFS), overall survival (OS), locoregional relapse free survival (LRFS), distant metastasis free survival (DMFS) and grade 3-4 toxicities were compared among different IC regimens. The survival rates were compared using log-rank test and a Cox proportional hazards model was used to perform multivariate analyses.
A multivariate analysis revealed TPF to be more effective than TP. Among stage III patients, no significant difference in clinical outcome between the different IC regimens was showed, while TPF was associated with significantly better survival conditions in the stage IV patients. A further subgroup analysis revealed that only patients with pre-EBV DNA ≥ 1500 copies could benefit from the application of TPF among stage IV NPC. In terms of acute toxicities, PF was associated with fewer grade 3/4 acute toxicities.
In low-risk NPC patients, PF-based IC showed similar efficacy as TPF and TP but was associated with fewer grade 3/4 acute toxicities. In high-risk patients, however, the TPF regimen was superior to PF and TP, although grade 3/4 toxicities were more common with the TPF regimen.
Metastasis is the primary cause of treatment failure in nasopharyngeal carcinoma (NPC); however, the current tumour-node-metastasis staging system has limitations in predicting distant metastasis and ...guiding induction chemotherapy (IC) application. Here, we established a transcriptomics-based gene signature to assess the risk of distant metastasis and guide IC in locoregionally advanced NPC.
Transcriptome sequencing was performed on NPC biopsy samples from 12 pairs of patients with different metastasis risks. Bioinformatics and qPCR were used to identify differentially expressed genes (DEGs), while univariate and multivariate analyses were used to select prognostic indicators for the gene signature. A signature-based nomogram was established in a training cohort (n = 191) and validated in an external cohort (n = 263).
Eleven DEGs were identified between metastatic and non-metastatic NPC. Four of these (AK4, CPAMD8, DDAH1 and CRTR1) were used to create a gene signature that effectively categorised patients into low- and high-risk metastasis groups (training: 91.1 versus 70.4%, p < 0.0001, C-index = 0.752; validation: 88.4 versus 73.9%, p = 0.00057, C-index = 0.741). IC with concurrent chemoradiotherapy (CCRT) improved distant metastasis-free survival in low-risk patients (94.4 versus 85.0%, p = 0.043), whereas patients in the high-risk group did not benefit from IC (72.6 versus 74.9%, p = 0.946).
Our transcriptomics-based gene signature was able to reliably predict metastasis in locoregionally advanced NPC and could be used to identify candidates that could benefit from IC + CCRT.
•Transcriptomics identified 11 DEGs between metastatic and non-metastatic NPC.•A four-DEG signature categorised patients into low and high-risk metastasis groups.•IC improved distant metastasis-free survival in patients in the low-risk group.•The signature can reliably predict metastasis in locoregionally advanced NPC.•The signature could be used to identify candidates that could benefit from IC + CCRT.
•Re-induction therapy could not improve tumor control of subsequent radiotherapy.•Re-induction therapy impaired locoregional relapse-free survival of nasopharyngeal carcinoma.•Re-induction therapy ...impaired progression-free survival of nasopharyngeal carcinoma.•Re-induction therapy increased grade 3–4 hematological toxicities.
Unsatisfactory tumor response to induction chemotherapy (IC) is an adverse prognostic factor of locoregionally advanced nasopharyngeal carcinoma (LANPC). A re-induction strategy which applies additional cycles of an alternative IC regimen prior to radiotherapy (RT) has been adopted.
A total of 419 LANPC patients who attained suboptimal response (stable disease or disease progression) according to the Response Evaluation in Solid Tumors (RECIST) guideline after initial IC were retrospectively included. They were divided into those who received additional cycles of re-induction regimen prior to RT (re-induction group, n = 87) and those who had no additional chemotherapy (direct to RT group, n = 332). Propensity score matching (PSM) was used to adjust for potential confounders. Tumor response and long-term survival were compared between two groups.
After receiving a second IC regimen, 39.1% of the patients in re-induction group attained partial response; however, the tumor control of subsequent RT was not significantly improved when compared with direct to RT group (patients attaining complete response after RT 55.2% vs. 52.5%, P = 0.757). Patients who received re-induction therapy showed worse locoregional relapse-free survival (LRFS) and progression-free survival (PFS) than those proceeded directly to RT (3-year LRFS 75.7% vs. 83.1%, P = 0.005; 3-year PFS 62.4% vs. 68.3%, P = 0.037). The increased hematological toxicities were observed in re-induction group that included grade 3–4 anemia, thrombocytopenia and liver enzyme increase.
Re-induction therapy decreased LRFS and PFS and increased toxicities among patients who attain suboptimal response to initial IC regimen, as compared with direct to RT strategy.
Background:
Despite the development of such multiple therapeutic approaches, approximately 20% patients experience recurrence. Identification of molecular markers for stratifying the different risks ...of tumour recurrence and progression is considered imperative.
Methods:
We used a RayBio Human Cytokine Antibody Array that simultaneously detected the levels of 297 proteins and profiled the conditioned medium of HONE1 cells and the radioresistant NPC cells HONE1-IR. We found Angiogenin(ANG) expression to be significantly increased in HONE1-IR and HONE1-IR cells exposed to 4-Gy X-ray radiation.
Results:
We investigated the expression of ANG in NPC tissues and explored its prognostic significance in patients with NPC. We found that ANG expression was increased in recurrent NPC tissues. Elevated expression of ANG induced radio-resistance in NPC cells, in addition to being significantly associated with shorter PFS, OS, and LRFS in patients with NPC. Multivariate analysis results revealed that ANG was an independent prognostic factor that predicted PFS, OS, and LRFS. Furthermore, a nomogram model was generated to predict OS in terms of ANG expression.
Conclusion:
Our results found the radioresistant function of ANG and proved the clinical prognostic significance of ANG, and the results could help predict radio-sensitivity and stratify high-risk patients or tumour recurrence.
•Three hundreds and three patients with lrNPC were retrospectively reviewed.•Four independent prognostic factors were included in nomogram.•The C-index of the nomogram was 0.687.•Local treatment ...benefited patients in the low- and intermediate-risk groups.•High-risk patients could not benefit from local treatment.
Thus far, there is no final conclusion on the treatment of local recurrent nasopharyngeal carcinoma (lrNPC) patients. Herein, we developed a nomogram which combined prognostic biomarkers to predict clinical outcome and guide individual treatment.
From 2006 to 2016, 303 patients with lrNPC were retrospectively reviewed. Overall survival (OS) was the primary endpoint. The nomogram was established with the significant prognostic factors (P < 0.05) selected by multivariate analysis using Cox regression model. Harrell Concordance Index (C-index), calibration curves, and decision curve analysis (DCA) were applied to evaluate this model.
Four independent prognostic factors (age, hypertension, relapsed T (rT) stage, and Epstein-Barr virus DNA) identified from multivariable analysis were included into the nomogram. The C-index of the nomogram was 0.687. The calibration curves for 1-, 3-, and 5-year OS rate showed satisfactory agreements between the predicted and actual values. The decision curve analysis also exhibited a preferable net benefit of this model. All patients were subdivided into three risk groups based on the nomogram. Local treatment was associated with higher OS than palliative chemotherapy alone in the low (P < 0.001) and intermediate-risk groups (P = 0.001). However, no significant difference was observed between different treatment methods in the high-risk group (P = 0.176).
We established the nomogram for patients with lrNPC to predict OS and guide individual treatment, which showed satisfactory performance in accuracy, discrimination capability, and clinical utility.
This study aimed to establish a nomogram to predict the risk of post-radiation necrosis in nasopharyngeal carcinoma (NPC) patients.
This study was performed to identify influencing factors for ...developing post-radiation necrosis, and to establish an effective nomogram model to predict individual risks in NPC patients.
7144 NPC patients receiving radical radiotherapy from 2007 to 2012 were involved in the study, and 207 of them developed nasopharyngeal necrosis (NPN). The clinical characteristics and baseline laboratory results were collected and analyzed. Independent predictive factors were selected using the Cox proportional model and incorporated into the nomogram. The receiver operating characteristic curve and the calibration curve were used to verify discrimination and calibration.
The experience of re-irradiation contributed most to the occurrence of NPN (HR, 15.56, 95% CI 10.84-22.35,
<0.001). Clinical factors including age, pathology type, history of diabetes, and original T stage were independent predictors of NPN. Factors reflecting patients' baseline nutritional and inflammatory status such as hemoglobin, albumin, and C-reactive protein were also significantly associated with the development of NPN. With all independent predictive factors incorporated, a nomogram was generated, and it showed excellent discrimination and calibration.
This study was the first large-scale cohort study focusing on the development of NPN and established a nomogram to predict its occurrence based on the clinical and laboratory indicators. The nomogram demonstrated good discriminative capacity and satisfactory agreement, which would offer valuable clues for clinicians to distinguish the high-risk NPN population and maintain close surveillance.
•Salvage radiotherapy did not improve overall survival in advanced recurrent disease.•Sex, prior toxicities and performance status predicted effects of re-irradiation.•The proposed model could ...identify a patient subgroup to benefit from re-irradiation.
Salvage radiotherapy (RT) is a potentially curative approach for advanced locally recurrent nasopharyngeal carcinoma (NPC), but it is associated with severe toxicities. We aimed to develop a model to predict which patients would benefit from salvage RT.
A total of 809 patients who were diagnosed with advanced locally recurrent NPC and treated with salvage RT or palliative chemotherapy (CT) at a high-volume cancer center were included. Patients were randomly split into a training and validation set and matched using inverse probability of treatment weighting. The primary outcome was overall survival (OS). Candidate variables associated with heterogeneous treatment effects were identified with interaction terms in Cox model and incorporated into Salvage Radiotherapy Outcome Score (SARTOS).
The final model included five interaction terms indicating that female sex, presence of prior RT-induced grade ≥ 3 late toxicities and suboptimal performance status were associated with less benefit from salvage RT. SARTOS from the model significantly predicted treatment effects of salvage RT in matched training (Pinteration < 0.001) and validation cohorts (Pinteration = 0.027). Of patients in high SARTOS subgroup, salvage RT significantly improved survival versus palliative CT in matched training (3-year OS 67.3% vs. 42.0%, HR 0.51, 95% CI 0.32–0.82, P = 0.005) and validation cohorts (3-year OS 71.8% vs. 22.8%, HR 0.40, 95% CI 0.17–0.97, P = 0.042); in low SARTOS subgroup, salvage RT failed to induce survival benefit.
We found that the SARTOS model could identify a subgroup of patients who benefit from salvage RT versus palliative CT, which helps personalize treatment recommendations for patients with recurrent NPC.
Object
To ascertain the treatment effect of concurrent chemotherapy (CCT) in stage II‐III nasopharyngeal carcinoma (NPC) patients with different Epstein‐Barr virus (EBV) DNA level in ...intensity‐modulated radiotherapy (IMRT) era.
Methods
A total of 2742 patients diagnosed with stage II‐III NPC were involved in this study. Patients received IMRT with/without CCT. Overall survival (OS) was the primary endpoint. Receiver operating characteristics curve was used to determine the cut‐off value of pre‐DNA based on OS. After propensity score matching, the role of CCT was explored in patients with different EBV DNA level.
Results
In our cohort, the cut‐off value of pre EBV DNA was 1460 copies/mL (area under curve AUC, 0.695‐0.769; sensitivity, 0.766; specificity, 0.599). Patients with high EBV DNA level showed poor survival in OS, progression free survival (PFS), locoregional relapse‐free survival (LRFS) and distant metastasis‐free survival (DMFS). In patients with EBV DNA level >1460 copies/mL, the concurrent chemoradiotherapy (CCRT) group achieved higher 3‐year OS compared with IMRT groups. However, the CCRT and IMRT groups showed comparable OS in patients with EBV DNA ≤1460 copies/mL. In multivariate analyses, CCT was a protective factor for OS, PFS, and LRFS in high‐risk patients (EBV DNA level >1460 copies/mL), while not an independent prognostic factor among the low‐risk patients (EBV DNA level ≤1460 copies/mL).
Conclusion
Pre‐EBV DNA could be a useful tool to guide individualized treatment for stage II‐III NPC patients. Additional CCT to IMRT improved the survival for patients with high pre‐EBV DNA, while those with low pre‐EBV DNA could not.
Our study ascertained the treatment effect of concurrent chemotherapy (CCT) in stage II‐III nasopharyngeal carcinoma (NPC) patients with different Epstein–Barr virus (EBV) DNA level in intensity‐modulated radiotherapy (IMRT) era. Pre‐EBV DNA could be a useful tool guiding for individualized treatment for stage II‐III NPC patients. Additional CCT to IMRT improved the survival for patients with high pre‐EBV DNA, while those with low pre‐EBV DNA could not.
We compared the clinical characteristics and survival outcomes after radical radiotherapy between nasopharyngeal carcinoma (NPC) with early and late metastases based on a relatively large cohort, ...which provides valuable data for the planning of clinical surveillance strategies.
This was a single-center retrospective analysis of 10,566 patients who received radical radiotherapy in China from January 2000 to December 2016. Overall survival was the primary endpoint. Kaplan-Meier survival analysis and log-rank tests were applied to investigate the association between early or late metastasis and the endpoints. The prognostic value of clinicopathological features was identified using univariate and multivariate Cox proportional hazards models.
The cutoff value for time to metastasis was based on ROC analysis. A total of 559 (5.3%) patients developed distant metastases, 297 (53.1%) of which developed early metastatic disease, with the rest (46.9%) developing late metastatic disease. The K-M analysis showed that the patients with late metastatic foci had significantly better post-metastatic OS (P = 0.0056). Multivariate analysis indicated that age, liver metastasis, the number of metastatic foci and time to metastasis (P = 0.013) are independent prognostic factors for OS. After analyzing the impact of different treatment methods, we found that local treatment was an independent protective factor for LM, while local treatment was not associated with a survival benefit for EM disease.
The time to metastasis after radical radiotherapy affected the prognosis of NPC patients and local treatment was an independent protective factor that could improve the survival of late metastatic NPC patients.
To compare the survival outcomes brought by different radiation dose schedules to bone lesions and different chemotherapy regimens in bone metastatic nasopharyngeal carcinoma (NPC).
The current ...treatment strategy for bone metastatic NPC patients was empirically given and poorly studied before. It is of necessity to optimize the treatment for bone metastasis to enhance the therapeutic effect and increase the proportion of long-term survived patients.
Three hundred patients who received chemoradiotherapy from 2002 to 2018 were involved in the study. Demographics, laboratory results, and detailed treatment plans were recorded. Radiotherapy plans were classified into three categories based on the intensity, and the survival analysis was performed using log-rank test. Multivariable analysis was made by the Cox proportional regression model.
Patients who received 60-75 Gy/30-35 fractions of radiation to the metastatic bones had significantly longer bone relapse-free survival (BRFS) (HR, 0.53, 95% CI, 0.37-0.78,
= 0.003), overall survival (OS) (HR, 0.63, 95% CI, 0.46-0.84,
= 0.007), and progression-free survival (PFS) (HR, 0.80, 95% CI, 0.67-0.95,
= 0.041). The administration of paclitaxel, cisplatin and 5-fluorouracil regimen was also associated with better BRFS (HR, 0.27, 95% CI, 0.10-0.75,
= 0.007), PFS (HR, 0.60, 95% CI, 0.42-0.87,
= 0.007), and OS with borderline significance (HR, 0.54, 95% CI, 0.29-1.03,
= 0.058). In multivariable analysis, the post-treatment EBV DNA level and radical radiation dose were proved as independent prognostic factors for both BRFS and OS.
Radiotherapy to metastatic bones with palliative dose prescription should not be considered in bone metastatic NPC patients. TPF chemotherapy regimen might help to improve the survivals in NPC patients but failed to be an independent protective factor.
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