Locoregionally Advanced Nasopharyngeal Carcinoma Patients Research Articles

Incorporation of PD-1 blockade into induction chemotherapy improved tumor response in patients with locoregionally advanced nasopharyngeal carcinoma in a retrospective patient cohort

ObjectiveTo investigate the short-term efficacy and safety of induction chemotherapy (IC) combined with anti-PD-1 immunotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). MethodsA total of 217 patients diagnosed with LA-NPC at the First Affiliated Hospital of Nanchang University, including 67 who received IC combined with anti-PD-1 and 150 who received IC, were retrospectively enrolled. Efficacy was evaluated at the end of the IC cycles and one month after radiotherapy based on RECIST v1.1 criteria. Acute toxicities were graded based on the CTCAE v5.0 criteria. Quantitative variables were compared by unpaired t-tests, and categorical variables were evaluated by Fisher Freeman-Halton test or Pearson Chi-square test. ResultsAt the end of all induction therapy cycles, the objective response rate (ORR) of the IC + anti-PD-1 group was 88.1 % (59/67) as opposed to 70.0 % (105/150) in the IC group. Subgroup analysis showed that patients in both stage Ⅲ and ⅣA achieved a significant improvement in ORR with the inclusion of anti-PD-1 therapy. Patients with T3-4 or N2-3 category appeared to benefit more from anti-PD-1 compared to patients with T1-2 or N0-1 category. However, neither ORR nor the complete response (CR) rate was significantly different between the two treatment groups one month after the end of radiotherapy. In addition, the frequency of Grade 3–4 adverse events were also similar in both groups. ConclusionsIC combined with anti-PD-1 immunotherapy significantly improved the ORR of LA-NPC patients after induction therapy compared to IC alone.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis

BackgroundDespite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC <induction chemotherapy> plus cisplatin CCRT <concurrent chemoradiotherapy>) for LANPC patients.MethodsFrom January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors.ResultsAfter PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3–4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064).ConclusionAdditiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Impact of magnetic resonance imaging-derived skeletal muscle index in locoregionally advanced nasopharyngeal carcinoma.

To evaluate the clinical implication of magnetic resonance imaging (MRI)-derived skeletal muscle index (SMI) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients undergoing induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) and further to develop a nomogram for predicting survival prognosis. SMI was determined through baseline MRI at the third cervical level. The nomogram was based on a training cohort involving 409 LANPC patients. We validated the prognostic accuracy of this prognostic model in an internal validation cohort (n = 204) and an external independent cohort (n = 272). SMI was an independent risk factor for OS. A prognostic model comprising age, TNM stage and SMI for individual survival prediction was developed and graphically represented as a nomogram. The model showed favorable discrimination (C-index: 0.686), predictive accuracy [time dependent area under the curve (tAUC) at 5years: 0.70], and calibration, and was further validated in the internal and external validation datasets. A risk stratification derived from the model stratified these patients into three prognostic subgroups with significantly different survival. Low SMI accessed by MRI was significantly associated with poor overall survival in LANPC patients undergoing IC + CCRT. Moreover, we established and validated a novel nomogram involving age, TNM stage and SMI that could provide accurate prognostic stratification among this population.

Radiomics-based nomogram guides adaptive de-intensification in locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy.

This study aimed to construct a radiomics-based model for prognosis and benefit prediction of concurrent chemoradiotherapy (CCRT) versus intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (LANPC) following induction chemotherapy (IC). A cohort of 718 LANPC patients treated with IC + IMRT or IC + CCRT were retrospectively enrolled and assigned to a training set (n = 503) and a validation set (n = 215). Radiomic features were extracted from pre-IC and post-IC MRI. After feature selection, a delta-radiomics signature was built with LASSO-Cox regression. A nomogram incorporating independent clinical indicators and the delta-radiomics signature was then developed and evaluated for calibration and discrimination. Risk stratification by the nomogram was evaluated with Kaplan-Meier methods. The delta-radiomics signature, which comprised 19 selected features, was independently associated with prognosis. The nomogram, composed of the delta-radiomics signature, age, T category, N category, treatment, and pre-treatment EBV DNA, showed great calibration and discrimination with an area under the receiver operator characteristic curve of 0.80 (95% CI 0.75-0.85) and 0.75 (95% CI 0.64-0.85) in the training and validation sets. Risk stratification by the nomogram, excluding the treatment factor, resulted in two groups with distinct overall survival. Significantly better outcomes were observed in the high-risk patients with IC + CCRT compared to those with IC + IMRT, while comparable outcomes between IC + IMRT and IC + CCRT were shown for low-risk patients. The radiomics-based nomogram can predict prognosis and survival benefits from concurrent chemotherapy for LANPC following IC. Low-risk patients determined by the nomogram may be potential candidates for omitting concurrent chemotherapy during IMRT. The radiomics-based nomogram was constructed for risk stratification and patient selection. It can help guide clinical decision-making for patients with locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy, and avoid unnecessary toxicity caused by overtreatment. • The benefits from concurrent chemotherapy remained controversial for locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy. • Radiomics-based nomogram achieved prognosis and benefits prediction of concurrent chemotherapy. • Low-risk patients defined by the nomogram were candidates for de-intensification.

CT-based peritumoral radiomics nomogram on prediction of response and survival to induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma

PurposeThe study aims to harness the value of radiomics models combining intratumoral and peritumoral features obtained from pretreatment CT to predict treatment response as well as the survival of LA-NPC(locoregionally advanced nasopharyngeal carcinoma) patients receiving multiple types of induction chemotherapies, including immunotherapy and targeted therapy.Methods276 LA-NPC patients (221 in the training and 55 in the testing cohort) were retrospectively enrolled. Various statistical analyses and feature selection techniques were applied to identify the most relevant radiomics features. Multiple machine learning models were trained and compared to build signatures for the intratumoral and each peritumoral region, along with a clinical signature. The performance of each model was evaluated using different metrics. Subsequently, a nomogram model was constructed by combining the best-performing radiomics and clinical models.ResultsIn the testing cohort, the nomogram model exhibited an AUC of 0.816, outperforming the other models. The nomogram model’s calibration curve showed good agreement between predicted and observed outcomes in both the training and testing sets. When predicting survival, the model’s concordance index (C-index) was 0.888 in the training cohort and 0.899 in the testing cohort, indicating its robust predictive ability.ConclusionIn conclusion, the combined nomogram model, incorporating radiomics and clinical features, outperformed other models in predicting treatment response and survival outcomes for LA-NPC patients receiving induction chemotherapies. These findings highlight the potential clinical utility of the model, suggesting its value in individualized treatment planning and decision-making.

Multi-task deep learning-based radiomic nomogram for prognostic prediction in locoregionally advanced nasopharyngeal carcinoma

PurposePrognostic prediction is crucial to guide individual treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients. Recently, multi-task deep learning was explored for joint prognostic prediction and tumor segmentation in various cancers, resulting in promising performance. This study aims to evaluate the clinical value of multi-task deep learning for prognostic prediction in LA-NPC patients.MethodsA total of 886 LA-NPC patients acquired from two medical centers were enrolled including clinical data, [18F]FDG PET/CT images, and follow-up of progression-free survival (PFS). We adopted a deep multi-task survival model (DeepMTS) to jointly perform prognostic prediction (DeepMTS-Score) and tumor segmentation from FDG-PET/CT images. The DeepMTS-derived segmentation masks were leveraged to extract handcrafted radiomics features, which were also used for prognostic prediction (AutoRadio-Score). Finally, we developed a multi-task deep learning-based radiomic (MTDLR) nomogram by integrating DeepMTS-Score, AutoRadio-Score, and clinical data. Harrell's concordance indices (C-index) and time-independent receiver operating characteristic (ROC) analysis were used to evaluate the discriminative ability of the proposed MTDLR nomogram. For patient stratification, the PFS rates of high- and low-risk patients were calculated using Kaplan–Meier method and compared with the observed PFS probability.ResultsOur MTDLR nomogram achieved C-index of 0.818 (95% confidence interval (CI): 0.785–0.851), 0.752 (95% CI: 0.638–0.865), and 0.717 (95% CI: 0.641–0.793) and area under curve (AUC) of 0.859 (95% CI: 0.822–0.895), 0.769 (95% CI: 0.642–0.896), and 0.730 (95% CI: 0.634–0.826) in the training, internal validation, and external validation cohorts, which showed a statistically significant improvement over conventional radiomic nomograms. Our nomogram also divided patients into significantly different high- and low-risk groups.ConclusionOur study demonstrated that MTDLR nomogram can perform reliable and accurate prognostic prediction in LA-NPC patients, and also enabled better patient stratification, which could facilitate personalized treatment planning.

A contrast-enhanced CT radiomics-based model to identify candidates for deintensified chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma patients.

To develop a contrast-enhanced CT (CECT) radiomics-based model to identify locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients who would benefit from deintensified chemoradiotherapy. LA-NPC patients who received low-dose concurrent cisplatin therapy (cumulative: 150mg/m2), were randomly divided into training and validation groups. 107 radiomics features based on the primary nasopharyngeal tumor were extracted from each pre-treatment CECT scan. Through Cox regression analysis, a radiomics model and patients' corresponding radiomics scores were created with predictive independent radiomics features. T stage (T) and radiomics score (R) were compared as predictive factors. Combining the N stage (N), a clinical model (T + N), and a substitution model (R + N) were constructed. Training and validation groups consisted of 66 and 33 patients, respectively. Three significant independent radiomics features (flatness, mean, and gray level non-uniformity in gray level dependence matrix (GLDM-GLN)) were found. The radiomics score showed better predictive ability than the T stage (concordance index (C-index): 0.67 vs. 0.61, AUC: 0.75 vs. 0.60). The R + N model had better predictive performance and more effective risk stratification than the T + N model (C-index: 0.77 vs. 0.68, AUC: 0.80 vs. 0.70). The R + N model identified a low-risk group as deintensified chemoradiotherapy candidates in which no patient developed progression within 3years, with 5-year progression-free survival (PFS) and overall survival (OS) both 90.7% (hazard ratio (HR) = 4.132, p = 0.018). Our radiomics-based model combining radiomics score and N stage can identify specific LA-NPC candidates for whom de-escalation therapy can be performed without compromising therapeutic efficacy. Our study shows that the radiomics-based model (R + N) can accurately stratify patients into different risk groups, with satisfactory prognosis in the low-risk group when treated with low-dose concurrent chemotherapy, providing new options for individualized de-escalation strategies. • A radiomics score, consisting of 3 predictive radiomics features (flatness, mean, and GLDM-GLN) integrated with the N stage, can identify specific LA-NPC populations for deintensified treatment. • In the selection of LA-NPC candidates for de-intensified treatment, radiomics score extracted from primary nasopharyngeal tumors based on CECT can be superior to traditional T stage classification as a predictor.

Widely targeted quantitative lipidomics and prognostic model reveal plasma lipid predictors for nasopharyngeal carcinoma

BackgroundDysregulation of lipid metabolism is closely associated with cancer progression. The study aimed to establish a prognostic model to predict distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC), based on lipidomics.MethodsThe plasma lipid profiles of 179 patients with locoregionally advanced NPC (LANPC) were measured and quantified using widely targeted quantitative lipidomics. Then, patients were randomly split into the training (125 patients, 69.8%) and validation (54 patients, 30.2%) sets. To identify distant metastasis-associated lipids, univariate Cox regression was applied to the training set (P < 0.05). A deep survival method called DeepSurv was employed to develop a proposed model based on significant lipid species (P < 0.01) and clinical biomarkers to predict DMFS. Concordance index and receiver operating curve analyses were performed to assess model effectiveness. The study also explored the potential role of lipid alterations in the prognosis of NPC.ResultsForty lipids were recognized as distant metastasis-associated (P < 0.05) by univariate Cox regression. The concordance indices of the proposed model were 0.764 (95% confidence interval (CI), 0.682–0.846) and 0.760 (95% CI, 0.649–0.871) in the training and validation sets, respectively. High-risk patients had poorer 5-year DMFS compared with low-risk patients (Hazard ratio, 26.18; 95% CI, 3.52–194.80; P < 0.0001). Moreover, the six lipids were significantly correlated with immunity- and inflammation-associated biomarkers and were mainly enriched in metabolic pathways. ConclusionsWidely targeted quantitative lipidomics reveals plasma lipid predictors for LANPC, the prognostic model based on that demonstrated superior performance in predicting metastasis in LANPC patients.

Explainable machine learning via intra-tumoral radiomics feature mapping for patient stratification in adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma.

This study aimed to discover intra-tumor heterogeneity signature and validate its predictive value for adjuvant chemotherapy (ACT) following concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). 397 LA-NPC patients were retrospectively enrolled. Pre-treatment contrast-enhanced T1-weighted (CET1-w) MR images, clinical variables, and follow-up were retrospectively collected. We identified single predictive radiomic feature from primary gross tumor volume (GTVnp) and defined predicted subvolume by calculating voxel-wised feature mapping and within GTVnp. We independently validate predictive value of identified feature and associated predicted subvolume. Only one radiomic feature, gldm_DependenceVariance in 3mm-sigma LoG-filtered image, was discovered as a signature. In the high-risk group determined by the signature, patients received CCRT + ACT achieved 3-year disease free survival (DFS) rate of 90% versus 57% (HR, 0.20; 95%CI, 0.05-0.94; P = 0.007) for CCRT alone. The multivariate analysis showed patients receiving CCRT + ACT had a HR of 0.21 (95%CI: 0.06-0.68, P = 0.009) for DFS compared to those receiving CCRT alone. The predictive value can also be generalized to the subvolume with multivariate HR of 0.27 (P = 0.017) for DFS. The signature with its heterogeneity mapping could be a reliable and explainable ACT decision-making tool in clinical practice.

An Individualized Prognostic Model in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma Based on Serum Metabolomic Profiling.

This study aims to evaluate the value of a serum metabolomics-based metabolic signature for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, thereby assisting clinical decisions. In this retrospective study, a total of 320 LA-NPC patients were randomly divided into a training set (ca. 70%; n = 224) and a validation set (ca. 30%; n = 96). Serum samples were analyzed using widely targeted metabolomics. Univariate and multivariate Cox regression analyses were used to identify candidate metabolites related to progression-free survival (PFS). Patients were categorized into high-risk and low-risk groups based on the median metabolic risk score (Met score), and the PFS difference between the two groups was compared using Kaplan-Meier curves. The predictive performance of the metabolic signature was evaluated using the concordance index (C-index) and the time-dependent receiver operating characteristic (ROC), and a comprehensive nomogram was constructed using the Met score and other clinical factors. Nine metabolites were screened to build the metabolic signature and generate the Met score, which effectively separated patients into low- and high-risk groups. The C-index in the training and validation sets was 0.71 and 0.73, respectively. The 5-year PFS was 53.7% (95% CI, 45.12-63.86) in the high-risk group and 83.0% (95%CI, 76.31-90.26) in the low-risk group. During the construction of the nomogram, Met score, clinical stage, pre-treatment EBV DNA level, and gender were identified as independent prognostic factors for PFS. The predictive performance of the comprehensive model was better than that of the traditional model. The metabolic signature developed through serum metabolomics is a reliable prognostic indicator of PFS in LA-NPC patients and has important clinical significance.

Efficacy of concurrent chemoradiotherapy alone for loco-regionally advanced nasopharyngeal carcinoma: long-term follow-up analysis

BackgroundTo analysis the clinical outcomes of concurrent chemoradiotherapy (CCRT) alone based on 10-year results for loco-regionally advanced nasopharyngeal carcinoma (LANPC), so as to provide evidence for individualized treatment strategy and designing appropriate clinical trial for different risk LANPC patients.MethodsConsecutive patients with stage III-IVa (AJCC/UICC 8th) were enrolled in this study. All patients received radical intensity-modulated radiotherapy (IMRT) and concurrent cisplatin chemotherapy (CDDP). The hazard ratios (HRs) of death risk in patients with T3N0 was used as baseline, relative HRs were calculated by a Cox proportional hazard model to classify different death risk patients. Survival curves for the time-to-event endpoints were analyzed by the Kaplan–Meier method and compared using the log-rank test. All statistical tests were conducted at a two-sided level of significance of 0.05.ResultsA total of 456 eligible patients were included. With 12-year median follow-up, 10-year overall survival (OS) was 76%. 10-year loco-regionally failure-free survival (LR-FFS), distant failure-free survival (D-FFS) and failure-free survival (FFS) were 72%, 73% and 70%, respectively. Based on the relative hazard ratios (HRs) of death risk, LANPC patients were classified into 3 subgroups, low-risk group (T1-2N2 and T3N0-1) contained 244 patients with HR < 2; medium-risk group (T3N2 and T4N0-1) contained 140 patients with HR of 2 – 5; high-risk group (T4N2 and T1-4N3) contained 72 patients with HR > 5. The 10-year OS for patients in low-, medium-, and high-risk group were 86%, 71% and 52%, respectively. Significantly differences of OS rates were found between each of the two groups (low-risk group vs. medium-risk group, P < 0.001; low-risk group vs. high-risk group, P < 0.001; and medium-risk group vs. high-risk group, P = 0.002, respectively). Grade 3–4 late toxicities included deafness/otitis (9%), xerostomia (4%), temporal lobe injury (5%), cranial neuropathy (4%), peripheral neuropathy (2%), soft tissue damage (2%) and trismus (1%).ConclusionsOur classification criteria demonstrated that significant heterogeneity in death risk among TN substages for LANPC patients. IMRT plus CDDP alone maybe suitable for low-risk LANPC (T1-2N2 or T3N0-1), but not for medium- and high-risk patients. These prognostic groupings provide a practicable anatomic foundation to guide individualized treatment and select optimal targeting in the future clinical trials.

An overall survival predictive nomogram to identify high-risk patients among locoregionally advanced nasopharyngeal carcinoma: Developed based on the SEER database and validated institutionally.

Locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, even at the same stage, have different prognoses. We aim to construct a prognostic nomogram for predicting the overall survival (OS) to identify the high-risk LA-NPC patients. Histologically diagnosed WHO type II and type III LA-NPC patients in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled as the training cohort (n= 421), and LA-NPC patients from Shantou University Medical College Cancer Hospital (SUMCCH) served as the external validation cohort (n= 763). Variables were determined in the training cohort through Cox regression to form a prognostic OS nomogram, which was verified in the validation cohort, and compared with traditional clinical staging using the concordance index (C-index), Kaplan-Meier curves, calibration curves and decision curve analysis (DCA). Patients with scores higher than the specific cut-off value determined by the nomogram were defined as high-risk patients. Subgroup analyses and high-risk group determinants were explored. Our nomogram had a higher C-index than the traditional clinical staging method (0.67 vs. 0.60, p<0.001). Good agreement between the nomogram-predicted and actual survival were shown in the calibration curves and DCA, indicating a clinical benefit of the nomogram. High-risk patients identified by our nomogram had worse prognosis than the other groups, with a 5-year overall survival (OS) of 60.4%. Elderly patients at advanced stage and without chemotherapy had a tendency for high risk than the other patients. Our OS predictive nomogram for LA-NPC patients is reliable to identify high-risk patients.

Effects of induction chemotherapy on nutrition status in locally advanced nasopharyngeal carcinoma: a multicentre prospective study.

Induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) is the standard of care for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This intensive treatment regimen increases acute toxicities, which could negatively impact patients' nutritional status. We conducted this prospective, multicentre trial to investigate the effects of IC and CCRT on nutritional status in LA-NPC patients, so as to provide evidence for further study of nutritional intervention, which was registered in ClinicalTrials.gov (NCT02575547). Patients with biopsy-proven NPC and planned for IC+CCRT were recruited. IC entailed two cycles of 3-weekly docetaxel 75mg/m2 and cisplatin 75mg/m2 ; CCRT entailed two to three cycles of 3-weekly cisplatin 100mg/m2 depending on the duration of radiotherapy. Nutritional status and quality of life (QoL) were assessed pre-IC, post-cycles one and two of IC, W4 and W7 of CCRT. Primary endpoint was the cumulative proportion of ≥ 5.0% weight loss (WL5.0 ) by the end of treatment (W7-CCRT). Secondary endpoints included body mass index, NRS2002 and PG-SGA scores, QoL, hypoalbuminaemia, treatment compliance, acute and late toxicitiesand survivals. The associations between primary and secondary endpoints were also evaluated. One hundred and seventy-one patients were enrolled. Median follow-up was 67.4 (IQR: 64.1-71.2) months. 97.7% (167/171) patients completed two cycles of IC, and 87.7% (150/171) completed at least two cycles of concurrent chemotherapy; all, except one patient (0.6%), completed IMRT. WL was minimal during IC (median of 0.0%), but increased sharply at W4-CCRT (median of 4.0% [IQR: 0.0-7.0%]) and peaked at W7-CCRT (median of 8.5% [IQR: 4.1-11.7%]). 71.9% (123/171) of patients recorded a WL5.0 by W7-CCRT, which was associated with a higher malnutrition risk (NRS2002≥3 points: 87.7% [WL≥5.0%] vs 58.7% [WL<5.0%], P<0.001) and requirement of nutritional intervention (PG-SGA≥9 points: 82.0% [WL≥5.0%] vs 66.7% [WL <5.0%], P=0.038). The median %WL at W7-CCRT was higher in patients who suffered from ≥ G2 mucositis (9.0% vs 6.6%, P=0.025) and xerostomia (9.1% vs 6.3%, P=0.003). Besides, patients with cumulative WL5.0 also reported a higher detriment on QoL at W7-CCRT compared with patients without, with a difference of -8.3 points (95% CI [-15.1, -1.4], P=0.019). We observed a high prevalence of WL among LA-NPC patients who were treated with IC+CCRT, which peaked during CCRT, and had a detriment on patients' QoL. Our data support the need to monitor patient's nutritional status during the later phase of treatment with IC+CCRT and inform on nutritional intervention strategies.

Determination of optimum number of cycles of induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: a single-center retrospective study.

Induction chemotherapy (IC) followed by concurrent chemo-radiotherapy (CCRT) is the current standard of care for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients. However, there is still no consensus on the optimum number of IC cycles. In this study, we aimed to assess the efficacy and toxicities of two or more cycles of IC for LA-NPC patients. Data of LA-NPC patients consecutively treated with IC followed by concurrent chemo-radiotherapy (CCRT) in our institute from 2017 to 2022 were retrospectively retrieved and analyzed. Survival outcomes of patients who received two IC cycles were compared with those who received more than two IC cycles. Univariate and multivariate Cox regression analysis were then performed to determine factors that could be independent predictors of survival. Chi-square test and Fisher's exact test were used to compare treatment associated acute toxicities between the two groups. A total of 125 patients were recruited in this study. There were 89 patients who received 2 cycles (IC = 2) of IC and 36 received more than 2 cycles (IC > 2) of IC. The median follow-up time was 26months [IQR 16-38]. The 3-year overall survival rate was not statistically significant between the two groups (95.50% vs. 86.11%, P = 0.501). Similarly, loco-regional recurrence free survival and progression free survival were not significant (97.75% vs. 97.22%, P = 0.694; and 88.76% vs. 83.33%, P = 0.129), but distant metastasis free survival was significant (88.76% vs. 86.11%, P = 0.049). Multivariate Cox regression analysis showed that IC regimen was an independent prognostic factor. Two cycles of IC is effective and more than two does not add any additional benefit to the survival outcomes of LA-NPC patients.

Concurrent chemotherapy using taxane plus cisplatin versus cisplatin alone in high-risk nasopharyngeal carcinoma patients with suboptimal response to induction chemotherapy.

Detectable Epstein-Barr virus (EBV) DNA levels and unsatisfactory tumor response to induction chemotherapy (IC) could be used to guide the risk-adapted treatment strategy of locoregionally advanced nasopharyngeal carcinoma (LANPC) before concurrent chemoradiotherapy. We aim to compare the efficacy and safety of concurrent chemotherapy using taxane plus cisplatin [double-agent concurrent chemotherapy (DACC) group] with those of cisplatin alone [single-agent concurrent chemotherapy (SACC) group] in high-risk LANPC. Overall, 197 LANPC patients with detectable EBV DNA or stable disease (SD) after IC were retrospectively included. Potential confounders between the DACC and SACC groups were adjusted by propensity score matching. Short-term efficacy and long-term survival were assessed in the two groups. Although the objective response rate of the DACC group was marginally higher than that of the SACC group, the difference was not significant (92.7% versus 85.3%, p = 0.38). Concerning long-term survival, DACC did not show superiority to SACC after patient matching: 3-year progression-free survival: 87.8% versus 81.7%, p = 0.80; overall survival: 97.6% versus 97.3%, p = 0.48; distant metastasis-free survival: 87.8% versus 90.5%, p = 0.64, and; locoregional relapse-free survival: 92.3% versus 86.9%, p = 0.77. The incidence of grade 1-4 hematological toxicities was significantly higher in the DACC group. Due to the small sample size, we do not have sufficient evidence that concurrent chemotherapy using taxane plus cisplatin provides additional survival benefits in LANPC patients with an unfavorable response (detectable EBV DNA levels or SD) after IC. But concurrent taxane and cisplatin chemotherapy is associated with a higher rate of hematologic adverse events. Further clinical trials will be required to establish evidence and identify more effective treatment modalities for high-risk LANPC patients.

Integrated strategies for chemotherapy cycles in nasopharyngeal carcinoma patients: Real-world data from two epidemic centers guiding decision-making.

Two cycles of induction chemotherapy (IC) followed by 2 cycles of platinum-based concurrent chemoradiotherapy (CCRT) (2IC+2CCRT) for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is widely adopted but not evidence-confirmed. This study aimed to determine the clinical value of 2IC+2CCRT regarding efficacy, toxicity and cost-effectiveness. This real-world study from two epidemic centers used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses. The enrolled patients were divided into three groups based on treatment modality: Group A (2IC+2CCRT), Group B (3IC+2CCRT or 2IC+3CCRT) and Group C (3IC+3CCRT). Long-term survival, acute toxicities and cost-effectiveness were compared among the groups. We developed a prognostic model dividing the population into high- and low-risk cohorts, and survivals including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were compared among the three groups according to certain risk stratifications. Of 4,042 patients, 1,175 were enrolled, with 660, 419, and 96 included in Groups A, B and C, respectively. Five-year survivals were similar among the three groups after PSM and confirmed by IPTW. Grade 3-4 neutropenia and leukocytopenia were significantly higher in Groups C and B than in Group A (52.1% vs. 41.5% vs. 25.2%; 41.7% vs. 32.7% vs. 25.0%) as were grade 3-4 nausea/vomiting and oral mucositis (29.2% vs. 15.0% vs. 6.1%; 32.3% vs. 25.3% vs. 18.0%). Cost-effective analysis suggested that 2IC+2CCRT was the least expensive, while the health benefits were similar to those of the other groups. Further exploration showed that 2IC+2CCRT tended to be associated with a shorter PFS in high-risk patients, while 3IC+3CCRT potentially contributed to poor PFS in low-risk individuals, mainly reflected by LRRFS. In LA-NPC patients, 2IC+2CCRT was the optimal choice regarding efficacy, toxicity and cost-effectiveness; however, 2IC+2CCRT and 3IC+3CCRT probably shortened LRRFS in high- and low-risk populations, respectively.

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

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). 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). After two cycles of IC, 340 patients were classified as "favorableresponders" and 158 patients as "unfavorableresponders." 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. The comprehensive nomogram incorporating MRI features and tumor stage could assist physicians in predicting IC response and formulating personalized treatment strategies for LANPC patients. • 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.

247TiP Addition of induction, concurrent and maintenance durvalumab to induction and concurrent chemoradiation vs induction and concurrent chemoradiation for previously untreated locoregionally advanced nasopharyngeal carcinoma: A phase II randomised-controlled trial

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Despite the most aggressive and devastating treatment with induction chemotherapy followed by concurrent chemoradiation, about 20-30% of patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) suffer from relapse at 5 years. Addition of anti-PD(L)1 immune checkpoint inhibitor to this intensive radical treatment may help improve treatment outcomes and survival. We are conducting a phase II randomised-controlled trial on adding durvalumab as induction, concurrent and maintenance therapy to induction and concurrent chemoradiation compared to the same regimen without durvalumab for previously untreated LANPC patients.

A Radiomics-Based Model to Identify Candidates for De-Intensified Treatment in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> To develop an optimal radiomics-based model to identify locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients who can benefit from the de-intensified treatment. <h3>Materials/Methods</h3> LA-NPC patients treated between 2013 and 2018 in Shantou University Medical College Cancer Hospital receiving low dose concurrent cisplatin were divided into training and validation cohort in a 2:1 ratio. For each patient, 107 radiomics features extracted from the primary nasopharyngeal tumor in pre-treatment contrast-enhanced CT scan were analyzed. Clinical model, radiomics model, and combined model were built and validated by Cox proportional hazard analysis. <h3>Results</h3> Training and validation cohort consisted of 66 and 33 patients, respectively. Three predictive independent factors (Flatness representing the sphere-like shape, Mean calculating the average gray level, Gray Level Non-Uniformity (GLDM-GLN) measuring the heterogeneity of gray-level intensity) were remained significantly. The c-index of the clinical model, radiomics model, combined model in the validation cohort was 0.74 (0.64-0.84), 0.73 (0.55-0.91), 0.81 (0.70-0.92), respectively. Combined model, as the optimal model, has a high accuracy with area under curve (AUC) of 0.86 (p=0.01), stratifying patients into low-risk and high-risk group with the 5-year PFS rate 93.5% and 50.8%, respectively (hazard ratio [HR]: 7.37 (1.5-37.3), p=0.006), 5-year OS rate 93.5% and 54.5%, respectively (HR: 7.37 (1.5-37.3), p=0.01). <h3>Conclusion</h3> A radiomics-based combined model can select specific LA-NPC populations for de-intensified treatment without compromising efficacy.

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

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. 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. 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. 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.