Non-metastatic Nasopharyngeal Carcinoma Research Articles

Cutoff point of neutrophil-to-lymphocyte ratio for predicting survival in nasopharyngeal carcinoma.

Neutrophil-to-lymphocyte ratio (NLR) was reported as an independent prognostic factor in many studies, but its cutoff point was not yet concluded. We set forth to prove and validate cutoff point of NLR as a poor prognostic factor for overall survival (OS) in nonmetastatic nasopharyngeal carcinoma (NPC) patients.Retrospective cohort of nonmetastatic NPC adult patients treated with intensity-modulated radiotherapy with curative aim at Siriraj hospital during 2007 to 2014 was enrolled. NLR was defined as absolute neutrophil count divided by absolute lymphocyte count. OS was the primary outcome. We explored our cutoff value by maximum concordance index (C-index) method, and we validated our cutoff and previously reported cutoff values by categorizing patients as NLR ≤ 3 or >3. Internal validation was done by bootstrapping method.Four hundred sixty-three patients were included. The median follow-up time was 70.8 months. By the end of June 2019, 211 patients had died. In univariable analysis of OS by Cox model, an NLR value of 3 showed the highest C-index (0.548) with an HR of 1.43 (95% CI: 1.08–1.89). After adjustment for body mass index, overall staging, age, gender, and histology in multivariable analysis, an NLR >3 was still an independent prognostic factor of poor OS (HR = 1.34, 95% CI = 1.01–1.79). After internal validation, the resampling method shows no overfitting condition and corrected C-index was 0.547 for univariable analysis.A cutoff point of NLR of 3 from routine blood test was found to be an independent poor prognostic factor among patients with nonmetastatic NPC. This prognostic factor could be included in clinical prediction model of NPC and this further prediction model would select high risk patients for intensive treatment.

Liquid biopsy posttreatment surveillance in endemic nasopharyngeal carcinoma: a cost-effective strategy to integrate circulating cell-free Epstein-Barr virus DNA

BackgroundThe optimal posttreatment surveillance strategy for nasopharyngeal carcinoma (NPC) remains unclear. Circulating cell-free Epstein-Barr virus (cfEBV) DNA has been recognized as a promising biomarker to facilitate early detection of NPC recurrence. Therefore, we aim to determine whether integrating circulating cfEBV DNA into NPC follow-up is cost-effective.MethodsFor each stage of asymptomatic nonmetastatic NPC patients after complete remission to primary NPC treatment, we developed a Markov model to compare the cost-effectiveness of the following surveillance strategies: routine follow-up strategy, i.e., (1) routine clinical physical examination; routine imaging strategies, including (2) routine magnetic resonance imaging plus computed tomography plus bone scintigraphy (MRI + CT + BS); and (3) routine 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT); cfEBV DNA-guided imaging strategies, including (4) cfEBV DNA-guided MRI + CT + BS and (5) cfEBV DNA-guided PET/CT. Clinical probabilities, utilities, and costs were derived from published studies or databases. Sensitivity analyses were performed.ResultsFor all disease stages, cfEBV DNA-guided imaging strategies demonstrated similar survival benefits but were considerably more economical than routine imaging strategies. They only required approximately one quarter of the number of imaging studies compared with routine imaging strategies to detect one recurrence. Specifically, cfEBV DNA-guided MRI + CT + BS was most cost-effective for stage II (incremental cost-effectiveness ratio [ICER] $57,308/quality-adjusted life-year [QALY]) and stage III ($46,860/QALY) patients, while cfEBV DNA-guided PET/CT was most cost-effective for stage IV patients ($62,269/QALY). However, routine follow-up was adequate for stage I patients due to their low recurrence risk.ConclusionsThe cfEBV DNA-guided imaging strategies are effective and cost-effective follow-up methods in NPC. These liquid biopsy-based strategies offer evidence-based, stage-specific surveillance modalities for clinicians and reduce disease burden for patients.

Long-term Therapeutic Outcome and Prognostic Factors of Patients with Nasopharyngeal Carcinoma Receiving Intensity-modulated Radiotherapy: An Analysis of 608 Patients from Low-endemic Regions of China.

To evaluate the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) from low-endemic regions of China who received definitive intensity-modulated radiation therapy (IMRT). The clinical data from 608 patients with newly-diagnosed non-metastatic NPC who have received initial treatment at our cancer center from January, 2008 to December, 2013 were retrospectively reviewed. All patients received definitive IMRT, and 87.7% received platinum-based chemotherapy. The median follow-up duration was 51 months (follow-up rate, 98.5%; range, 10-106 months) for the entire cohort. The 5-year overall survival rate was 79.7%. The 5-year local relapse-free survival rate, regional relapse-free survival rate, distant metastasis-free survival rate and progression-free survival rate were 92.4%, 93.3%, 79.2% and 74.3%, respectively. A total of 153 patients had experienced treatment failure, with distant metastasis as the primary cause in 77.1% (118/153). Patients with T4 or N3 diseases had a significantly poorer prognosis than other subcategories. Stage T4 and N3 were closely associated with distant metastasis, with the metastatic rate of 29.3% and 45.5%, respectively. IMRT provides patients with non-metastatic NPC with satisfactory long-term survival. Both T stage and N stage are important prognostic factors for NPC patients. Patients with T4 or N3 diseases have significantly increased distant metastatic rates and poor survival time.

Prognostic value of hypertension in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy.

BackgroundThe prognostic value of hypertension remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). In this study, we aimed to develop hypertension as a prognostic signature for improving the clinical outcome of non-metastatic NPC patients treated with IMRT.MethodsA clinical cohort, comprising 1,057 patients with non-metastatic, histologically proven, NPC who were treated with IMRT were retrospectively reviewed. Associations between hypertension and overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) were estimated by Cox regression. A subgroup analysis of the relationship between hypertension grade and NPC prognosis was also conducted.ResultsAmong the 1057 patients, 94 (8.9%) had hypertension. Significant differences were observed between patients with hypertension and patients without hypertension in relation to OS (66.6% vs. 85.4%; P<0.0001), PFS (60.8% vs. 76.3%; P=0.001), LRRFS (85.3% vs. 90.5%; P=0.024), and DMFS (77.4% vs. 85.1%; P=0.048), and patients without hypertension had greater treatment success rates. The Cox analysis showed that hypertension was an independent unfavorable prognostic factor for OS [hazards ratio (HR), 2.056; P=0.001], PFS (HR, 1.716; P=0.005), and DMFS (HR, 1.658; P=0.049). The patients with more severe levels of hypertension had worse OS and LRRFS. Specifically, the 5-year OS and LRRFS for grades 1, 2, and 3 were 70.6%, 64.3%, and 62.4% (P=0.712), and 89.5%, 86.4%, and 76.1% (P=0.376), respectively.ConclusionsHypertension is an independent adverse prognostic factor in NPC patients treated with IMRT. The question of whether the severity of hypertension affects prognosis needs to be further verified by large sample data.

Nomogram Based on Lactate Dehydrogenase-to-Albumin Ratio (LAR) and Platelet-to-Lymphocyte Ratio (PLR) for Predicting Survival in Nasopharyngeal Carcinoma.

PurposeThe prognosis of inflammation-related indicators like lactate dehydrogenase/albumin ratio (LAR) and the platelet/lymphocyte ratio (PLR) in nasopharyngeal carcinoma (NPC) is not yet clear. Our objective is to establish and verify the nomogram using LAR and PLR ratio for the first time to explore the prognostic value in NPC.Patients and MethodsThis was a retrospective collection of 1661 patients with non-metastatic NPC admitted to our hospital from 2010 to 2017. The final variables of overall survival (OS) and progression-free survival (PFS) were selected by Cox regression analysis to establish nomograms, and the methods to verify the prediction precision and discriminative ability of the nomograms were concordance index (C index), the receiver operating characteristic (ROC) curve and calibration curve. The risk stratification was carried out through the nomograms and compared with the current staging system by the Kaplan–Meier methods.ResultsMultivariate Cox analysis resulted that age, plasma Epstein–Barr Virus (EBV) DNA, T stage, N stage, white blood cells (WBC), PLR and LAR were independent prognostic risk factors for OS and PFS, and sex is an independent prognostic risk factor for OS. The C-indexes of OS nomogram were 0.722 (95% CI: 0.706–0.738) and 0.747 (95% CI: 0.717–0.777) in the training cohort and validation cohort, which were statistically higher than the current 8th AJCC staging system (0.646 and 0.688). The C-indexes of PFS nomogram were 0.696 (95% CI: 0.680–0.713) and 0.690 (95% CI: 0.660–0.720), which were also statistically higher than the current 8th AJCC staging system (0.632 and 0.666). Otherwise, ROC curves and the calibration curve for probability also confirmed satisfied consistency with actual observations.ConclusionLAR is a novel useful independent factor in NPC. The proposed nomogram LAR and PLR resulted in more accurate prognostic prediction than current staging system for NPC patients.

Mixed Photon and Carbon-Ion Beam Radiotherapy in the Management of Non-Metastatic Nasopharyngeal Carcinoma.

BackgroundCarbon-ion radiotherapy (CIRT) may further increase the therapeutic ratio for patients with newly diagnosed nasopharyngeal carcinoma (NPC). The purpose of the current study is to examine the effectiveness and toxicity profile of photon-based intensity-modulated radiotherapy (IMRT) plus CIRT boost in a relatively large cohort of NPC patients.MethodsIn the current study, non-metastatic NPC patients treated with IMRT plus CIRT boost at Shanghai Proton and Heavy Ion Center between June, 2015 and June, 2018 were included. Overall survival (OS), progression-free survival (PFS), local control, regional control, and distant control were calculated with Kaplan–Meier method. Acute and late toxicities were graded using CTCAE 4.03.ResultsA total of 69 patients were included in the analysis. Among those, 74% of the patients had locoregionally advanced (stage III/IV) disease, and 92.8% had cervical lymphadenopathy. With a median follow-up of 31.9 months, the 3-year OS, PFS, local control, regional control, and distant control rates were 94.9, 85.2, 96.9, 98.4, and 89.7%, respectively. Mixed treatment of IMRT with CIRT boost was well tolerated. Severe acute toxicities induced by radiation therapy were observed in only two patients (dermatitis). No severe radiation-induced late toxicity was observed at the time of analysis. Univariable analysis showed N2/3 disease was correlated with an inferior distant control (p = 0.040).ConclusionMixed treatment of IMRT plus CIRT boost provides an excellent disease control and a favorable toxicity profile for patients with non-metastatic NPC. Further follow-up is necessary to evaluate the long-term survivals and toxicities more accurately.

Early risk-assessment of patients with nasopharyngeal carcinoma: the added prognostic value of MR-based radiomics

ObjectivesTo assess the additive prognostic value of MR-based radiomics in predicting progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC) MethodsPatients newly diagnosed with non-metastatic NPC between June 2006 and October 2019 were retrospectively included and randomly grouped into training and test cohorts (7:3 ratio). Radiomic features (n=213) were extracted from T2-weighted and contrast-enhanced T1-weighted MRI. The patients were staged according to the 8th edition of American Joint Committee on Cancer Staging Manual. The least absolute shrinkage and selection operator was used to select the relevant radiomic features. Univariate and multivariate Cox proportional hazards analyses were conducted for PFS, yielding three different survival models (clinical, stage, and radiomic). The integrated time-dependent area under the curve (iAUC) for PFS was calculated and compared among different combinations of survival models, and the analysis of variance was used to compare the survival models. The prognostic performance of all models was validated using a test set with integrated Brier scores. ResultsThis study included 81 patients (training cohort=57; test cohort=24), and the mean PFS was 57.5 ± 43.6 months. In the training cohort, the prognostic performances of survival models improved significantly with the addition of radiomics to the clinical (iAUC, 0.72–0.80; p=0.04), stage (iAUC, 0.70–0.79; p=0.001), and combined models (iAUC, 0.76–0.81; p<0.001). In the test cohort, the radiomics and combined survival models were robustly validated for their ability to predict PFS. ConclusionIntegration of MR-based radiomic features with clinical and stage variables improved the prediction PFS in patients diagnosed with NPC.

Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Nasopharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy

Patients with nonmetastatic nasopharyngeal carcinoma (NPC) are primarily treated by radiotherapy with curative intent with or without chemotherapy and often experience substantial treatment-related toxic effects even with modern radiation techniques, such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) may improve the toxicity profile; however, there is a paucity of data given the limited availability of IMPT in regions with endemic NPC. To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic NPC when treated with IMPT vs IMRT with or without chemotherapy. This retrospective cohort study included 77 patients with newly diagnosed nonmetastatic NPC who received curative-intent radiotherapy with IMPT or IMRT at a tertiary academic cancer center from January 1, 2016, to December 31, 2019. Forty-eight patients with Epstein-Barr virus (EBV)-positive tumors were included in a 1:1 propensity score-matched analysis for survival outcomes. The end of the follow-up period was March 31, 2021. IMPT vs IMRT with or without chemotherapy. The main outcomes were the incidence of acute and chronic treatment-related adverse events (AEs) and oncologic outcomes, including locoregional failure-free survival (LRFS), progression-free survival (PFS), and overall survival (OS). We identified 77 patients (25 [32.5%] women; 52 [67.5%] men; median [interquartile range] age, 48.7 [42.2-60.3] years), among whom 28 (36.4%) were treated with IMPT and 49 (63.6%) were treated with IMRT. Median (interquartile range) follow-up was 30.3 (17.9-41.5) months. On multivariable logistic regression analyses, IMPT was associated with lower likelihood of developing grade 2 or higher acute AEs compared with IMRT (odds ratio [OR], 0.15; 95% CI, 0.03-0.60; P = .01). Only 1 case (3.8%) of a chronic grade 3 or higher AE occurred in the IMPT group compared with 8 cases (16.3%) in the IMRT group (OR, 0.21; 95% CI, 0.01-1.21; P = .15). Propensity score matching generated a balanced cohort of 48 patients (24 IMPT vs 24 IMRT) and found similar PFS in the IMPT and IMRT groups (2-year PFS, 95.7% [95% CI, 87.7%-100%] vs 76.7% [95% CI, 60.7%-97.0%]; hazard ratio [HR], 0.31; 95% CI, 0.07-1.47; P = .14). No locoregional recurrence or death was observed in the IMPT group from the matched cohort. Two-year LRFS was 100% (95% CI, 100%-100%) in the IMPT group and 86.2% (95% CI, 72.8%-100%) in the IMRT group (P = .08). Three-year OS was 100% (95% CI, 100%-100%) in the IMPT group and 94.1% (95% CI, 83.6%-100%) in the IMRT group (P = .42). Smoking history was the only clinical factor significantly associated with both poor LRFS (HR, 63.37; 95% CI, 3.25-1236.13; P = .006) and poor PFS (HR, 6.33; 95% CI, 1.16-34.57; P = .03) on multivariable analyses. In this study, curative-intent radiotherapy with IMPT for nonmetastatic NPC was associated with significantly reduced acute toxicity burden in comparison with IMRT, with rare late complications and excellent oncologic outcomes, including 100% locoregional control at 2 years. Prospective trials are warranted to direct the optimal patient selection for IMPT as the primary radiotherapy modality for nonmetastatic NPC.

Influence of CDK5 Regulatory Subunit-Associated Protein 1-Like 1 Expression on the Survival of Patients with Non-Metastatic Nasopharyngeal Carcinoma.

BackgroundThe aim of this study was to investigate the influence of CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1) expression on the survival of nasopharyngeal carcinoma (NPC) patients.MethodsA total of 140 non-metastatic NPC patients were retrospectively analyzed. The expression of CDKAL1 was detected by immunohistochemistry.ResultsThe CDKAL1-negative group exhibited better overall survival (OS) according to Kaplan–Meier curve analysis (p = 0.006), with 5-year OS rates for the CDKAL1-negative and -positive groups of 89.7% and 70.2%, respectively. The CDKAL1-negative group also exhibited a tendency toward a better progression-free survival (PFS) rate. Multivariate analysis showed that CDKAL1 expression was independently associated with both OS (p = 0.002) and PFS (p = 0.043).ConclusionCDKAL1 expression is an independent negative predictor of patient survival in non-metastatic NPC.

Prognostic nomogram for pediatric nasopharyngeal carcinoma in the intensity-modulated radiotherapy era.

e18036 Background: There was no prognostic nomogram model exclusive for pediatric nasopharyngeal carcinoma (NPC). This study aimed to establish a nomogram, incorporating clinical characteristics and MRI features, for predicting progression-free survival (PFS) and overall survival (OS) in pediatric NPC. Methods: Children with nonmetastatic NPC treated with intensity-modulated radiotherapy (IMRT) in Sun Yat-sen University cancer center in China between 2004 to 2018 were enrolled and separated in a 3:1 ratio into a training cohort and a validation cohort. The data of the training cohort were analyzed to identify the variables independently associated with PFS and OS, and these variables were used to construct the prognostic nomogram. The predictive accuracy and discriminative capability of the nomogram were evaluated by the calibration curve and the concordance index (C-index). The nomogram was validated in the validation cohort. Results: A total of 200 patients were enrolled: 152 in the training cohort and 48 in the validation cohort. Age, serum lactate dehydrogenase level, and invasion of the clivus were the independent prognostic factors for PFS in the training cohort. The C-index of the nomogram constructed using these variables was 0.86. The calibration curve showed consistency between the nomogram prediction and the actual observation for 5-, 6- and 7-year PFS. In the validation cohort, the C-index of the nomogram was 0.64, and the calibration curve showed good consistency between the nomogram and actual observation for 5-, 6- and 7-year PFS. For OS, no independent prognostic factors were identified. Conclusions: The prognostic nomogram could be a useful tool for predicting PFS in pediatric NPC patients treated with IMRT.

Stage-dependent conditional survival and failure hazard of non-metastatic nasopharyngeal carcinoma after intensity-modulated radiation therapy: Clinical implications for treatment strategies and surveillance.

PurposeConditional survival (CS) and failure hazard estimations can provide important dynamic prognostic information for clinical decision‐making and surveillance counseling. The current study aimed to investigate the CS and dynamic failure hazard in non‐metastatic nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT).MethodsConditional overall survival (COS) and progression‐free survival (CPFS) estimates adjusted for age and gender against each AJCC 8th stage were calculated. Multivariable Cox regression (MCR) models were fitted in the entire population at baseline and subsequently separate MCR models were fitted in patients who have maintained event‐free time of 1 to 10 years to generate respective hazard ratio (HR). Annual hazard rates of death and progression over 10 years for each stage were also estimated.ResultsA total of 1993 patients were eligible for analysis. The estimated 5‐year OS and PFS for entire cohort were 79.0% and 70.7% at initial diagnosis. After 5 years of event‐free follow‐up, additional 5‐year COS and CPFS increased to 85.9% and 85.5%, respectively. Stage I/II maintained dramatically favorable CS and low hazard (< 5%) of death and progression over time. Relative to stage I/II, stage III manifested non‐significantly higher failure hazard for the first 3 years of survivorship and approached to similar level of stage I/II afterwards. Stage IVA presented most impressive improvement in terms of both COS (∆=9.8%) and CPFS (∆ = 16.8%) whereas still drastically inferior to that of stage I‐III across all conditional time points. After 4 years of follow‐up, progression hazard of stage IVA became relatively steady of approximate 6%.ConclusionsSurvival prospect of non‐metastatic NPC improves over years with distinct dynamic patterns across stages, providing important implications for personalized decision‐making in terms of both clinical management and surveillance counseling. Stage‐dependent and hazard‐adapted clinical management and surveillance are warranted.

Prognostic and Predictive Value of Circulating Inflammation Signature in Non-Metastatic Nasopharyngeal Carcinoma: Potential Role for Individualized Induction Chemotherapy.

PurposeWe sought to assess the prognostic and predictive value of a circulating inflammation signature (CISIG) and develop CISIG-based tools for predicting prognosis and guiding individualized induction chemotherapy (ICT) in non-metastatic nasopharyngeal carcinoma (NPC).Patients and MethodsWe retrospectively collected a candidate inflammatory biomarker panel from patients with NPC treated with definitive radiotherapy between 2012 and 2017. We developed the CISIG using candidate biomarkers identified by a least absolute shrinkage and selection operator (LASSO) Cox regression model. The Cox regression analyses were used to evaluate the CISIG prognostic value. A CISIG-based prediction model was constructed, validated, and assessed. Potential stratified ICT treatment effects were examined.ResultsA total of 1149 patients were analyzed. Nine biomarkers selected by LASSO regression in the training cohort were used to construct the CISIG, including hyaluronidase, laminin, procollagen III, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, high-density lipoprotein, lactate dehydrogenase, and C-reactive protein-to-albumin ratio. CISIG was an independent prognostic factor for disease-free survival (DFS; hazard ratio: 2.65, 95% confidence interval: 1.93–3.64; P < 0.001). High CISIG group (>−0.2) was associated with worse 3-year DFS than low CISIG group in both the training (67.5% vs 88.3%, P < 0.001) and validation cohorts (72.3% vs 85.1%, P < 0.001). We constructed and validated a CISIG-based nomogram, which showed better performance than the clinical stage and Epstein–Barr virus DNA classification methods. A significant interaction between CISIG and the ICT treatment effect was observed (P for interaction = 0.036). Patients with high CISIG values did not benefit from ICT, whereas patients with low CISIG values significantly benefited from ICT.ConclusionThe developed CISIG, based on a circulating inflammatory biomarker panel, adds prognostic information for patients with NPC. The proposed CISIG-based tools offer individualized risk estimation to facilitate suitable ICT candidate identification.

Comparing the 7th and 8th editions of UICC/AJCC staging system for nasopharyngeal carcinoma in the IMRT era

BackgroundTo compare the prognostic value of 7th and 8th editions of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy and simultaneous integrated boost– intensity-modulated radiation therapy (SIB-IMRT).MethodsPatients with NPC (n = 300) who received SIB-IMRT were included. Survival by T-classification, N-classification, and stage group of each staging system was assessed.ResultsFor T-classification, nonsignificant difference was observed between T1 and T3 and between T2 and T3 disease (P = 0.066 and 0.106, respectively) for overall survival (OS) in the 7th staging system, whereas all these differences were significant in the 8th staging system (all P < 0.05). The survival curves for disease-free survival (DFS) and locoregional recurrence-free survival (LRRFS) in both staging systems were similar, except for the comparison of T2 and T4 disease for LRRFS (P = 0.070 for 7th edition; P = 0.011 for 8th edition). For N-classification, significant differences were observed between N2 and N3 diseases after revision (P = 0.046 and P = 0.043 for OS and DFS, respectively). For staging system, no significant difference was observed between IVA and IVB of 7th edition.ConclusionThe 8th AJCC staging system appeared to have superior prognosis value in the SIB-IMRT era compared with the 7th edition.

Prognostic Value of the Albumin-to-Alkaline Phosphatase Ratio before Chemoradiotherapy in Patients with Nonmetastatic Nasopharyngeal Carcinoma

Introduction: The aim of this study was to evaluate the prognostic value of the albumin-to-alkaline phosphatase ratio (AAPR) in patients with nonmetastatic nasopharyngeal carcinoma (NPC). Methods: Patients with nonmetastatic NPC who underwent chemoradiotherapy (CRT) were retrospectively analyzed. The AAPR was calculated using the last value of albumin to alkaline phosphatase that was measured within 1 week before CRT. The optimal cutoff value for the AAPR value was determined by an X-tile plot. Propensity score matching (PSM) was performed to balance the differences of the baseline characteristics. The Kaplan-Meier method and log-rank test were used to calculate the survival. A Cox proportional hazards regression model was conducted for the multivariate analysis. Results: Totally, 87 patients with nonmetastatic NPC who underwent CRT were included in the analysis. The optimal cutoff level for the AAPR was 0.46. The group with an AAPR ≤0.46 was more likely to have poorer overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) (p = 0.023, p = 0.031 and p = 0.027, for OS, PFS, and DMFS, respectively). In Cox proportional hazards analysis, high AAPR was a better prognostic predictor. Conclusion: AAPR may be a reliable prognostic index for nonmetastatic NPC patients.

The effect of adjuvant chemotherapy and early tumor regression on the outcome of nasopharyngeal cancer patients treated with concurrent chemoradiotherapy.

We assessed the role of adjuvant chemotherapy (ACT) in patients with advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy (CCRT) and investigated the prognostic factors for recurrence and survival. Between January 2008 and January 2018, 88 non-metastatic nasopharyngeal carcinoma patients treated with CCRT and with or without ACT in two institutions were retrospectively reviewed. The initial tumor response evaluation was performed 1month after CCRT completion. Survival analysis was performed for factors such as initial tumor regression, ACT and other clinical factors. Subgroup analysis was performed for the four-group categorized according to tumor regression and ACT (CR with/without ACT, non-CR with/without ACT). Complete response (CR) 1month after CCRT was a favorable prognosticator for progression-free survival (PFS) (hazard ratio [HR] 3.16, 95% confidence interval [CI] 1.02-9.85, p=0.046) and overall survival (OS) (HR 3.19, 95% CI 1.14-8.93, p=0.027). Also, ACT was an independent factor for PFS (HR 0.38, 95% CI 0.15-0.98, p=0.047) and OS (HR 0.37, 95% CI 0.13-0.99, p=0.047). In subgroup analysis, the CR after CCRT followed by ACT group showed significantly higher locoregional recurrence-free survival (p=0.02), OS (p=0.003), distant-metastasis free survival (p=0.07), and PFS (p=0.01) than the other three groups. Tumor regression 1month after CCRT, and administration of ACT identified as an independent prognosticator for PFS and OS in this study. Even patients who show early tumor regression after CCRT may benefit from ACT. Further randomized trials should define the role of ACT in patients with nasopharyngeal cancer who achieved CR after CCRT.

Modified reduced-volume intensity-modulated radiation therapy in non-metastatic nasopharyngeal carcinoma: A prospective observation series

Background and purposeAlthough the efficacy of “reduced-volume intensity-modulated radiation therapy (IMRT)” in nasopharyngeal carcinoma (NPC) has been confirmed, two issues regarding the necessity of clinical target volume 1(CTV1) delineation and the optimal margin of CTV2 remained undetermined. The current series, utilized de-intensification technique that omitted the contouring of CTV1 and narrowed the margin of CTV2 from 10 mm to 8 mm, namely “modified reduced-volume IMRT” was initiated to evaluate the efficacy and feasibility of this renew technique in a prospective series. Patients and materialsDosimetric analysis was performed in 40 non-metastatic NPC cases to evaluate whether our modification is feasible. Then this de-intensification technique was applied in non-metastatic NPC patients treated in our attending group since late 2014. Survival outcomes focused on local recurrence-free survival (LRFS) and local failure pattern were analyzed. ResultsPreliminary dosimetric evaluation of “modified reduced-volume IMRT” showed that the 60 Gy isodose curve generated naturally by this technique could well wrap the target area of CTV1. Subsequent observation series, which included a total of 471 patients and had a median follow-up time of 46.2 months(range,3.7–70.8 months), reported that 4-year estimated LRFS, regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.6%, 97.7%, 87.7% and 92.4%, respectively. All local recurrence lesions occurred within 95% isodose lines and were considered in-field failures. ConclusionsOur de-intensification technique “modified reduced-volume IMRT” was feasible and did not compromise therapeutic efficacy, well-designed multicenter prospective trials are needed for further research.

The change in tumor volume after induction chemotherapy with docetaxel plus cisplatin in 259 nasopharyngeal carcinoma patients.

To assess the tumor volume change after induction chemotherapy with docetaxel plus cisplatin (DP) in nasopharyngeal carcinoma (NPC). A total of 259 non-metastatic NPC patients who received DP induction chemotherapy were retrospectively reviewed. Gross tumor volume of nasopharynx and lymph nodes (GTVnx and GTVnd) were contoured before and after chemotherapy. Univariate and multivariate analyses were performed to identify factors associated with tumor volume reduction. For GTVnx, the mean volume before and after chemotherapy were 43.2 cm3 vs 37.4 cm3 (p < 0.001) and the mean relative volume reduction was 12.7%. For GTVnd, the mean volume before and after chemotherapy were 24.6 cm3 vs 17.6 cm3 (p < 0.001) and the mean relative volume reduction was 13.9%. There was a positive linear correlation between the reduction of GTVnx and GTVnd (r = 0.351, p < 0.001). For GTVnx volume reduction, pretreatment GTVnx volume (≤ 20 cm3 vs > 20 cm3, OR = 4.644, p = 0.001) and chemotherapy cycle (2 cycles vs 3 cycles, OR = 2.418, p = 0.009) were independently associated factors. For GTVnd volume reduction, pretreatment GTVnd volume (≤ 8 cm3 vs > 8 cm3, OR = 7.472, p < 0.001) and chemotherapy cycle (2 cycles vs 3 cycles, OR = 2.621, p = 0.007) were independently associated factors. DP induction chemotherapy reduces tumor volumes moderately in NPC. Larger pre-treatment tumor volumes and three cycles of chemotherapy are associated with higher likelihood of tumor volume reduction.

Development of a risk classification system combining TN-categories and circulating EBV DNA for non-metastatic NPC in 10,149 endemic cases.

Background:The objective of this study was to construct a risk classification system integrating cell-free Epstein-Barr virus (cfEBV) DNA with T- and N- categories for better prognostication in nasopharyngeal carcinoma (NPC).Methods:Clinical records of 10,149 biopsy-proven, non-metastatic NPC were identified from two cancer centers; this comprised a training (N = 9,259) and two validation cohorts (N = 890; including one randomized controlled phase 3 trial cohort). Adjusted hazard ratio (AHR) method using a two-tiered stratification by cfEBV DNA and TN-categories was applied to generate the risk model. Primary clinical endpoint was overall survival (OS). Performances of the models were compared against American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 8th edition TNM-stage classification and two published recursive partitioning analysis (RPA) models, and were validated in the validation cohorts.Results:We chose a cfEBV DNA cutoff of ⩾2,000 copies for optimal risk discretization of OS, disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the training cohort. AHR modeling method divided NPC into six risk groups with significantly disparate survival (p < 0.001 for all): AHR1, T1N0; AHR2A, T1N1/T2-3N0 cfEBV DNA < 2,000 (EBVlow); AHR2B, T1N1/T2-3N0 cfEBV DNA ⩾ 2,000 (EBVhigh) and T1-2N2/T2-3N1 EBVlow; AHR3, T1-2N2/T2-3N1 EBVhigh and T3N2/T4N0 EBVlow; AHR4, T3N2/T4 N0-1 EBVhigh and T1-3N3/T4N1-3 EBVlow; AHR5, T1-3N3/T4 N2-3 EBVhigh. Our AHR model outperformed the published RPA models and TNM stage with better hazard consistency (1.35 versus 3.98–12.67), hazard discrimination (5.29 versus 6.69–13.35), explained variation (0.248 versus 0.164–0.225), balance (0.385 versus 0.438–0.749) and C-index (0.707 versus 0.662–0.700). In addition, our AHR model was superior to the TNM stage for risk stratification of OS in two validation cohorts (p < 0.001 for both).Conclusion:Herein, we developed and validated a risk classification system that combines the AJCC/UICC 8th edition TN-stage classification and cfEBV DNA for non-metastatic NPC. Our new clinicomolecular model provides improved OS prediction over the current staging system.

Integrating pre- and post-treatment Plasma Epstein-Barr Virus DNA levels for better prognostic prediction of Nasopharyngeal Carcinoma.

Background: Pre- and post-treatment plasma Epstein‐Barr virus (EBV) DNA are important biomarkers for the prognosis of nasopharyngeal carcinoma (NPC). This study was performed to determine the prognostic potential of integrating EBV DNA levels in plasma measured pre-treatment (pre-EBV) and 3 months post-treatment (3 m-EBV).Materials and methods: A total of 543 incident non-metastatic NPC patients treated with intensity-modulated radiotherapy, with or without chemotherapy, were reviewed. Patients were divided into four subgroups based on pre-EBV and 3 m-EBV status. The data for pre-EBV and 3 m-EBV samples were integrated, and the predictability of the survival of patients with NPC was analyzed.Results: There were significant differences in the 5-year progression-free survival, distant metastasis-free survival, locoregional relapse-free survival, and overall survival among the four patient subgroups (P<0.001). Patients who tested negative for both pre-EBV and 3 m-EBV had the best prognosis, followed by patients who tested positive for pre-EBV and negative for 3 m-EBV, and those who tested negative for pre-EBV and positive for 3 m-EBV; however, patients who tested positive for both pre-EBV and 3 m-EBV had the poorest chances of survival. Multivariate analyses demonstrated that integration of pre-EBV and 3 m-EBV data was an independent predictor of NPC progression in patients. Receiver operating characteristic curve analysis further confirmed that the combination of pre-EBV and 3 m-EBV had a greater prognostic value than pre-EBV or 3 m-EBV alone.Conclusions: Integrating pre-EBV and 3 m-EBV data could provide more accurate risk stratification and better prognostic prediction in NPC.

Long‐term monitoring of dynamic changes in plasma EBV DNA for improved prognosis prediction of nasopharyngeal carcinoma

BackgroundThis study was performed to investigate whether long‐term monitoring of dynamic changes in plasma Epstein‐Barr virus (EBV) DNA could improve prognosis prediction of nasopharyngeal carcinoma (NPC).Materials and methodsAbout 1077 nonmetastatic NPC patients were recruited to retrospectively analyze the prognostic value of plasma EBV DNA load pretreatment and 3, 12, 24, and 36 months posttreatment. We also examined the prognostic value of dynamic changes in plasma EBV DNA at various time points.ResultsPatients with plasma EBV DNA load above optimal pre‐ and posttreatment cut‐offs had significantly worse five‐year progression‐free survival, distant metastasis‐free survival, locoregional relapse‐free survival, and overall survival (OS) at all‐time points, excluding only OS at 36 months posttreatment due to limited mortalities. Patients with persistently undetectable plasma EBV DNA at the first four time points had the best prognosis, followed by those with positive detection pretreatment and consistently negative detection posttreatment, those with negative detection pretreatment and positive detection at one time point posttreatment, and those with positive detection pretreatment and at one time point posttreatment, whereas patients with positive detection at ≥2 time points posttreatment had the worst prognosis. Cox proportional hazard models identified the dynamic change pattern as an independent prognostic factor, and receiver operating characteristic curve analysis demonstrated that the dynamic change at four time point was more valuable than any single time point for predicting disease progression, distant metastasis, locoregional relapse, and mortality.ConclusionsDynamic changes in plasma EBV DNA pre‐ and posttreatment could predict the long‐term survival outcome and provide accurate risk stratification in NPC.