Chemotherapy For Nasopharyngeal Carcinoma Research Articles

Clinicopathologic Features and Efficacy of Induction Chemotherapy in Nasopharyngeal Carcinoma: Real-World Experience.

Nasopharyngeal carcinoma (NPC) accounts for 0.01% of all carcinomas, and 70% of patients have locally advanced disease with a poor prognosis. The mainstay therapy is chemoradiotherapy (CRT), and concurrent administration of platinum-based agents and irradiation provides high local control rates. However, induction (neoadjuvant) chemotherapy (ICT) prior to CRT is recommended for large tumors with a high tumor burden at the category 1 level. For ICT, platinum-based doublet or triplet combination regimens are recommended. Selected patients with a high tumor burden at the time of diagnosis who did not receive ICT before CRT were given adjuvant (consolidation) therapy after CRT. This multicenter study aimed to share our experience in treatment of NPC and evaluate the factors associated with survival. The study included patients diagnosed with NPC who were followed and treated between 2008 and 2022. Hundred and forty-two patients from 6 centers were evaluated. The factors associated with disease-free survival (DFS) and overall survival (OS) were evaluated. The median age of our patients was 51 years (IQR: 16-81 years), and the male:female ratio was 2.5:1. A majority of patients (71%) had stage 3-4 disease. They had locally advanced disease, and 48 patients (34%) received ICT. Twenty patients (14%) received adjuvant therapy. The median follow-up was 41 months (range, 2.7-175.1 months). The median DFS in NPC was 92.6 months (range, 71.9-113.3 months), with a 40th month DFS of 70.9%. The median OS was 113 months (range, 91-135 months), with a 40th month OS of 84.7%. Median DFS was 95.3 months (range, 64.2-126.4 months) in patients who received ICT before CRT, which was longer than in the CRT-only group (p = 0.6). DFS at the 40th month was 75.1% in patients treated with ICT compared to 65.1% in the CRT-only group. Median OS was 117 months (range, 92-142 months) in patients receiving ICT, which was longer than in the CRT-only group (p = 0.4). OS at the 40th month was 86.7% in patients receiving ICT but 83.6% in the CRT-only group. Both the objective response rate and survival were longer in patients who radiologically responded to CRT following ICT. Nonresponse to ICT is a negative predictive indicator. The role of ICT in locally advanced NPC is increasing.

PQR309, a dual PI3K/mTOR inhibitor, synergizes with gemcitabine by impairing the GSK-3β and STAT3/HSP60 signaling pathways to treat nasopharyngeal carcinoma

End-stage nasopharyngeal carcinoma (NPC) has unsatisfactory survival. The limited benefit of chemotherapy and the scarcity of targeted drugs are major challenges in NPC. New approaches to treat late-stage NPC are urgently required. In this study, we explored whether the dual PI3K/mTOR inhibitor, PQR309, exerted a favorable antineoplastic effect and sensitized the response to gemcitabine in NPC. We observed that PI3K expression was positive and elevated in 14 NPC cell lines compared with that in normal nasopharygeal cell lines. Patients with NPC with higher PI3K levels displayed poorer prognosis. We subsequently showed that PQR309 alone effectively decreased the viability, invasiveness, and migratory capability of NPC cells and neoplasm development in mice xenograft models, and dose-dependently induced apoptosis. More importantly, PQR309 remarkably strengthened the anti-NPC function of gemcitabine both in vivo and in vitro. Mechanistically, PQR309 sensitized NPC to gemcitabine by increasing caspase pathway-dependent apoptosis, blocking GSK-3β and STAT3/HSP60 signaling, and ablating epithelial-mesenchyme transition. Thus, targeting PI3K/mTOR using PQR309 might represent a treatment option to promote the response to gemcitabine in NPC, and provides a theoretical foundation for the study of targeted drugs combined with chemotherapy for NPC.

Nomograms based on multiparametric MRI radiomics integrated with clinical-radiological features for predicting the response to induction chemotherapy in nasopharyngeal carcinoma

ObjectiveTo establish nomograms integrating multiparametric MRI radiomics with clinical-radiological features to identify the responders and non-responders to induction chemotherapy (ICT) in nasopharyngeal carcinoma (NPC). MethodsWe retrospectively analyzed the clinical and MRI data of 168 NPC patients between December 2015 and April 2022. We used 3D-Slicer to segment the regions of interest (ROIs) and the “Pyradiomic” package to extract radiomics features. We applied the least absolute shrinkage and selection operator regression to select radiomics features. We developed clinical-only, radiomics-only, and the combined clinical-radiomics nomograms using logistic regression analysis. The receiver operating characteristic curves, DeLong test, calibration, and decision curves were used to assess the discriminative performance of the models. The model was internally validated using 10-fold cross-validation. ResultsA total of 14 optimal features were finally selected to develop a radiomic signature, with an AUC of 0.891 (95 % CI, 0.825–0.946) in the training cohort and 0.837 (95 % CI, 0.723–0.932) in the testing cohort. The nomogram based on the Rad-Score and clinical-radiological factors for evaluating tumor response to ICT yielded an AUC of 0.926 (95 % CI, 0.875–0.965) and 0.901 (95 % CI, 0.815–0.979) in the two cohorts, respectively. Decision curves demonstrated that the combined clinical-radiomics nomograms were clinically useful. ConclusionNomograms integrating multiparametric MRI-based radiomics and clinical-radiological features could non-invasively discriminate ICT responders from non-responders in NPC patients.

Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma

Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients’ survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.

Development and Internal Validation of a Prediction Model for Nasopharyngeal Carcinoma: Using BMI and Inflammatory Response for Deciding Sequence of Chemotherapy.

Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-AC) and induction chemotherapy followed by concurrent chemoradiotherapy (IC-CRT) are among the best treatments in nasopharyngeal carcinoma (NPC). This study aimed to develop a model for deciding the sequence of chemotherapy in NPC. Data were separated into two cohorts. The CRT-AC cohort had 295 patients, while the IC-CRT cohort had 112. The predictors were standard factors with BMI and neutrophil-lymphocyte ratio (NLR) to predict overall survival (OS). A flexible parametric survival model was used. A total of 132 (44.7%) and 72 patients (64.3%) died in the CRT-AC and IC-CRT cohorts, respectively. The predictors in the final models were age, sex, T, N, NLR, and BMI. The models of OS for CRT-AC and IC-CRT had concordance indices of 0.689 and 0.712, respectively, with good calibration curves. When changing the burden of disease along with NLR and BMI, we found that CRT-AC was not significantly different OS from IC-CRT when low NLR (<3) and high burden of disease (T3N3). By contrast, CRT-AC was remarkably more effective when there were high levels of NLR (≥3) and BMI (≥25) with any burden of disease (anyT anyN). With additional BMI and NLR in model, it could be easier to decide between CRT-AC and IC-CRT in countries with limited health care resources.

Circulating Tumor DNA Profiling Approach Based on In Silico Background Elimination Guides Chemotherapy in Nasopharyngeal Carcinoma.

Circulating tumor DNA (ctDNA) analysis increasingly provides a promising minimally invasive alternative to tissue biopsies in precision oncology. However, there are no ctDNA analysis approaches available in nasopharyngeal carcinoma (NPC) and current methods of ctDNA mutation profiling have limited resolution because of the high background noise and false-positive rate caused by benign variants in plasma cell-free DNA (cfDNA), majorly generated during clonal hematopoiesis. Although personalized parallel white blood cell genome sequencing suppresses the noise of clonal hematopoiesis variances, the system cost and complexity restrict its extensive application in clinical settings. We developed Matched WBC Genome sequencing Independent CtDNA profiling (MaGIC) approaches, which synergically integrated a ctDNA capturing panel for a hybrid capture cfDNA deep sequencing, in silico background elimination, and a reliable readout measurement. We profiled the ctDNAs of 80 plasma samples from 40 patients with NPC before and during chemotherapy by MaGICs. In addition, the public cfDNA sequencing data and The Cancer Genome Atlas project data were analyzed by MaGICs to evaluate their application in other scenarios of patient classification. The MaGIC version-2 has the ability to predict the chemosensitivity of patients with NPC with high accuracy by utilizing a single sample of liquid biopsy from each patient prior to a standardized treatment regimen. Moreover, both versions of MaGICs are of ideal performance in the diagnosis of patients with prostate cancer by liquid biopsy and prognosis prediction of multiple cancers by tissue biopsy. This study has the potential to enhance the sensitivity and expand the application scope of ctDNA detection, independently of other paired genome sequencing methods. As a result, it might further increase the clinical utilization of liquid biopsy based on ctDNA.

Effect of Nutritional Intervention on the Management of Radiotherapy and Chemotherapy for Nasopharyngeal Carcinoma

Objective To investigate the application of nutritional intervention in the management of radiotherapy and chemotherapy for nasopharyngeal carcinoma. Methods There were 60 patients with nasopharyngeal carcinoma who were treated with chemoradiotherapy in our department from June 2020 to August 2022, including 30 subjects from the control group and 30 cases from the intervention group. Results (1) In 2002, the 3-week and 24-week NRS scores for radiotherapy and chemotherapy in the control group were higher than those in the intervention group (2.36 ± 0.85 and 1.86 ± 0.57, p = 0.014; 2.76 ± 0.77 and 2.43 ± 0.77, p = 0.023), and the difference was statistically significant (p < 0.05) (Table 2). (2) The weight of patients in the two groups after 3 wk and 24 wk of radiotherapy and chemotherapy were compared, and we found that the weights of the control group were lower than those of the intervention group (66.13 ± 5.53 and 69.03 ± 5.22, p = 0.037; 61.03 ± 5.83 and 64.93 ± 6.85, p = 0.044), and again, the difference was statistically significant (p < 0.05) (Table 3). At week 10 of chemoradiotherapy, the control group lost ≥10% of their weight in the intervention group, and severe malnutrition occurred. The control group lost ≥5% of their weight at 24 wk of chemoradiotherapy and developed malnutrition. (3) The quality of life (measured by the SF-36 scale score) after 24 wk between the two groups was compared, and the control group was lower than the intervention group in all aspects, and this difference was statistically significant (p < 0.05) (Table 4). Conclusion Nutritional intervention is used in the whole management of radiotherapy and chemotherapy for nasopharyngeal carcinoma to improve patient nutritional status and quality of life.

Involved site radiation therapy in stage I-III nasopharyngeal carcinoma with limited lymph node burden (ISRT-NPC) or elective region irradiation: a study protocol for a multicenter non-inferiority randomized controlled phase III clinical trial

BackgroundCurrent radiotherapy guidelines and consensus statements uniformly recommend elective region irradiation (ERI) as the standard strategy for nasopharyngeal carcinoma (NPC). However, given the scarcity of skip-metastasis, the improved assessment accuracy of nodal involvement, and the striking advancements in chemotherapy for NPC, a one-fits-all delineation scheme for clinical target volumes of the nodal region (CTVn) may not be appropriate anymore, and modifications of the CTVn delineation strategy may be warranted. Involved site irradiation (ISI) covering merely the initially involved nodal site and potential extranodal extension has been confirmed to be as effective as ERI with decreased radiation-related toxicities in some malignancies, but has not yet been investigated in NPC. This study aims to compare the regional control, survival outcomes, radiation-related toxicities, and quality of life (QoL) of ISI with conventional ERI in NPC patients with a limited nodal burden.MethodsISRT-NPC is a prospective, multicenter, open-label, noninferiority, phase III randomized controlled trial. A total of 414 patients will be randomly assigned in a 1:1 ratio to receive ISI or ERI. Randomization will be stratified by institution scale and N stage. Generally, in the ISI group, the high-risk CTV1 (dose: 60 Gy) includes a 1-cm expansion of the positive LN as well as the VIIa and the retrostyloid space above the bilateral transverse process of the atlantoaxial spine (C1), regardless of N status. The low-risk CTV2 (dose: 50 Gy) covers the cervical nodal region with a 3-cm caudal expansion below the transverse process of C1 for N0 disease and a 3-cm expansion below the positive LN for positive LNs.DiscussionThe results of this trial are expected to confirm that ISI is a non-inferior strategy to ERI in stage I-III patients with low LN burden, enabling the minimization of treatment-related toxicity and improvement of long-term QoL without compromising regional control.Trial registrationClinicalTrails.gov, NCT05145660. Registered December 6, 2021.

Combination of Cefotaxime and Cisplatin Specifically and Selectively Enhances Anticancer Efficacy in Nasopharyngeal Carcinoma.

HMOX1 has a dual role in cancers, especially involving chemoresistance. We demonstrate that cephalosporin antibiotics exert strong anticancer activity in nasopharyngeal carcinoma mainly via drastic upregulation of HMOX1. Cephalosporin antibiotics are commonly used for the treatment or prophylaxis of bacterial infectious diseases in cancer patients. It is unknown whether they lead to chemoresistance in cancer patients, especially in nasopharyngeal carcinoma patients, who are being treated or required prophylaxis for an infectious syndrome with cephalosporin antibiotics. MTT and clonogenic colony formation assays assessed the viability and proliferation of cultured cancer cells. Flow cytometry was used to detect apoptosis. Tumor growth was assessed using a xenograft model. Microarray and RT-qPCR expression analyses investigated differential gene expression. Cefotaxime enhanced anticancer efficacy of cisplatin in nasopharyngeal carcinoma without enhancing the toxic side effects both in vitro and in vivo. However, cefotaxime significantly reduced the cytotoxicity of cisplatin in other cancer cell lines. Cefotaxime and cisplatin co-regulated 5 differential genes in CNE2 cells in a direction supporting the enhancement of anticancer efficacy, of which, THBS1 and LAPTM5 were further upregulated, STAG1, NCOA5, and PPP3CB were further downregulated. Out of the 18 apoptotic pathways significantly enriched in the combination group, THBS1 and HMOX1 overlapped in 14 and 12 pathways, respectively. Extrinsic apoptotic signaling pathway (GO: 2001236) was the only apoptotic pathway commonly enriched in cefotaxime group, cisplatin group and combination group, and THBS1 and HMOX1 were the overlapped genes of this pathway. THBS1 also overlapped in P53 signaling pathway and ECM-receptor interaction signaling pathway enriched by KEGG. Cephalosporin antibiotics are chemosensitizers of conventional chemotherapeutic drugs in the chemotherapy of nasopharyngeal carcinoma, but they may lead to chemoresistance by cytoprotection in other cancers. Cefotaxime and cisplatin co-regulate THBS1, LAPTM5, STAG1, NCOA5 and PPP3CB suggesting their involvement in the enhancement of anticancer efficacy in nasopharyngeal carcinoma. Targeting of P53 signaling pathway and ECM-receptor interaction signaling pathway was correlated to the enhancement. With additional benefit for treatment or prophylaxis of an infectious syndrome, cephalosporin antibiotics can benefit the therapy of nasopharyngeal carcinoma either as anticancer agents or as chemosensitizers of chemotherapeutic drugs in combination chemotherapy.

Radiomic analysis of MRI for prediction of response to induction chemotherapy in nasopharyngeal carcinoma patients

To establish and validate radiomic models for response prediction to induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) using the radiomic features from pretreatment MRI. This retrospective analysis included 184 consecutive NPC patients, 132 in the primary cohort and 52 in the validation cohort. Radiomic features were derived from contrast-enhanced T1-weighted imaging (CE-T1) and T2-weighted imaging (T2-WI) for each subject. The radiomic features were then selected and combined with clinical characteristics to build radiomic models. The potential of the radiomic models was evaluated based on its discrimination and calibration. To measure the performance of these radiomic models in predicting the treatment response to IC in NPC, the area under the receiver operating characteristic curve (AUC), and sensitivity, specificity, and accuracy were used. Four radiomic models were constructed in the present study including the radiomic signature of CE-T1, T2-WI, CE-T1 + T2-WI, and the radiomic nomogram of CE-T1. The radiomic signature of CE-T1 + T2-WI performed well in distinguishing response and non-response to IC in patients with NPC, which yielded an AUC of 0.940 (95% CI, 0.885-0.974), sensitivity of 83.1%, specificity of 91.8%, and accuracy of 87.1% in the primary cohort, and AUC of 0.952 (95% CI, 0.855-0.992), sensitivity of 74.2%, specificity of 95.2%, and accuracy of 82.7% in the validation cohort. MRI-based radiomic models could be helpful for personalised risk stratification and treatment in NPC patients receiving IC.

The effect of neutrophil-lymphocyte ratio on neck nodule size in nasopharyngeal carcinoma chemotherapy

ABSTRACTBackground: Nasopharyngeal carcinoma (NPC) is a cancer of the head and neck, that ranks as the 4th most malignant cancer in Indonesia. The prognosis of NPC patients is determined from the clinical stage based on the Tumor, Nodule, Metastatic (TNM) classification system. These prognosis factors are not entirely reliable for predicting treatment outcomes. The Neutrophil Lymphocyte Ratio (NLR) represents an index of pro-tumor and anti-tumor activity, that can be used to predict the outcome of neoadjuvant chemotherapy and the patient’s well-being as assessed by Karnofsky status, Body Mass Index (BMI), and neck nodule size (NNS). Purpose: To study the effect of NLR on Karnofsky status, BMI, and NNS in WHO type III NPC patients who underwent 3 cycles of neoadjuvant chemotherapy. Method: Analytical observational research with a cohort-retrospective approach on WHO type III NPC subjects who underwent platinum-based regimen neoadjuvant chemotherapy. NLR pre-chemotherapy was analyzed for its effect on Karnofsky status, BMI, and NNS. Result: NLR had no significant effect on Karnofsky status pre- and post-chemotherapy, BMI pre- and post-chemotherapy, NNS pre-chemotherapy, changes in Karnofsky status and BMI pre-and post-chemotherapy, but had significant effect on the size of neck nodules post-chemotherapy, and changes in the size of neck nodules. Conclusion: NLR has no significant effect on Karnofsky status, on BMI pre- and post-chemotherapy, and neck nodule size pre-chemotherapy. However, NLR had a significant effect on neck nodule size post-chemotherapy and neck nodule size changes. ABSTRAKLatar belakang: Karsinoma Nasofaring (KNF) merupakan keganasan dalam bidang THT yang menempati urutan ke-4 keganasan di Indonesia. Prognosis pasien KNF terutama ditentukan dari stadium klinis berdasarkan sistem klasifikasi Tumor, Nodul, Metastasis (TNM) yang tidak sepenuhnya dapat diandalkan untuk memprediksi hasil pengobatan. Sedangkan Ratio Netrofil-Limfosit (RNL) mempresentasikan indeks aktivitas protumor dan antitumor sehingga dapat digunakan sebagai pelengkap stadium klinis untuk memprediksi hasil kemoterapi neoadjuvan dan kesejahteraan subjek melalui status Karnofsky, Index Massa Tubuh (IMT) dan ukuran nodul leher. Tujuan: Mempelajari efek Rasio Netrofil-Limfosit (RNL), Index Massa Tubuh (IMT), dan ukuran nodul leher pada subjek dengan KNF WHO tipe III yang telah menjalani 3 siklus kemoterapi neoadjuvan. Metode: Penelitian observasional analitik dengan pendekatan kohort-retrospektif menggunakan data rekam medis penderita KNF tipe III WHO yang menjalani kemoterapi neoadjuvan menggunakan regimen berbasis platinum. RNL sebelum kemoterapi dianalisis pengaruhnya terhadap status Karnofsky, IMT dan ukuran nodul leher. Hasil: RNL berpengaruh tidak signifikan terhadap status Karnofsky sebelum dan sesudah kemoterapi, IMT sebelum dan sesudah kemoterapi, ukuran nodul leher sebelum kemoterapi, perubahan status Karnofsky, perubahan IMT, namun berpengaruh signifikan terhadap ukuran nodul leher sesudah kemoterapi dan perubahan ukuran nodul leher. Kesimpulan: RNL berpengaruh tidak signifikan terhadap status Karnofsky, IMT sebelum dan sesudah kemoterapi, ukuran nodul leher sebelum kemoterapi, namun berpengaruh signifikan terhadap ukuran nodul leher sesudah kemoterapi dan perubahan ukuran nodul leher sebelum kemoterapi, namun berpengaruh signifikan terhadap ukuran nodul leher sesudah kemoterapi dan perubahan ukuran nodul leher.

Role of neo-adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a rare type of tumor which arises from the surface and lining epithelium of nasopharynx. Management of nasopharyngeal carcinoma is one of the greatest clinical challenges but it is radiosensitive and chemosensitive; excellent tumor control can be attained with radiotherapy with or without adjuvant therapies concurrent chemoradiation therapy. This review will focus on role of neoadjuvant chemotherapy in nasopharyngeal carcinoma on disease free survival (DFS), distant metastases free survival and overall survival (OS) and systemic toxicities, indications and choice and number of cycles of regimen for neoadjuvant chemotherapy.

Survival impact of additional induction chemotherapy in nasopharyngeal carcinoma with chronic hepatitis B infection: a retrospective, bi-center study.

BackgroundPatients with nasopharyngeal carcinoma (NPC) who have hepatitis B virus (HBV) infection tend to be treated with induction chemotherapy (IC) due to a higher metastasis rate. However, additional IC may lead to immunosuppression and can negatively affect the prognosis. We evaluated whether receiving IC improved the prognosis of patients with NPC co-infected with HBV, on the basis of concurrent chemoradiotherapy (CCRT).MethodsThis large-scale retrospective cohort study included data of patients with pathologically confirmed NPC that were collected from two hospitals between January 2010 and March 2014. Patients were followed-up every 3 months during the first 2 years and once every 6 months thereafter. Univariate analysis identified confounding factors associated with prognosis. Stage-based subgroup analyses and 1:1 random-matched pair analyses were performed to compare the survival differences between patients treated with IC + CCRT and those treated with CCRT alone.ResultsAmong the 1,076 enrolled patients, 16.6% were hepatitis B surface antigen (HBsAg)-positive. Among HBsAg-positive patients with stage II/III/IV NPC, distant metastasis-free survival (DMFS) (79.3% vs. 89.9%; P=0.045) and progression-free survival (PFS) (70.6% vs. 83.7%; P=0.025) were lower in patients who received IC + CCRT than in those who received CCRT alone. After adjusting for confounding factors, IC + CCRT was validated as a negative prognosticator for DMFS and PFS, while matched-pair analysis with HBsAg-negative patients showed a better overall survival (OS) for IC + CCRT (88.4% vs. 82.6%; P=0.04).ConclusionsCompared with CCRT alone, IC + CCRT negatively affects DMFS and PFS in patients with NPC with chronic HBV infection. We advocate withholding IC but administering stronger initial treatment in NPC patients complicated with HBV infection.

A spectral CT-based nomogram for predicting the response to induction chemotherapy in nasopharyngeal carcinoma

To establish a spectral computed tomography (CT)-based nomogram for predicting the response to induction chemotherapy (ICT) in nasopharyngeal carcinoma (NPC). Fifty-four patients with NPC who underwent spectral CT examination before ICT were enrolled prospectively. Patients were assigned to response and non-response groups according to response evaluation. The predictive indicators were spectral CT parameters of venous phase, including iodine concentration (IC), normalised IC (NIC), slope of the spectral attenuation curve in Hounsfield units (λHU), effective atomic number (Eff-Z), and water concentration. Multivariate logistic regression was used to construct a predictive model. The receiver operating characteristic (ROC) and calibration curves were used to evaluate the robustness of model, while the bootstrap method was used for internal validation. The Hosmer-Lemeshow test was used to test the goodness of fit of the discriminant model. Multivariate logistic regression analysis showed that NIC, λHU, and Eff-Z were the potential predictors, and the three indicators were further used to establish a predictive model. The nomogram was evaluated to have good predictive performance, the area under the ROC curve was 0.909 (95% confidence interval [CI]: 0.799-0.970), and the model was well calibrated (χ2=8.149, p=0.419). The spectral CT nomogram has potential clinical value in predicting response to ICT in NPC and may help guide individualised treatment decisions.

Survival outcomes for patients with nasopharyngeal carcinoma in non–endemic region in the UK treated with intensity modulated based radiotherapy 65 Gy in 30 fractions ± weekly cisplatin chemotherapy

BackgroundNasopharyngeal carcinoma (NPC) is rare in the UK. The aim of the current study was to investigate survival outcomes for patients with NPC treated with (chemo)radiotherapy using 65 Gy in 30 fractions in a non-endemic region.Materials and methodsAll consecutive 62 patients with histology proven non-metastatic nasopharyngeal carcinoma diagnosed between January 2009 to June 2019 were included in this retrospective analysis.ResultsMedian age was 59 years (range:19–81). The majority of patients had stage III disease (66.1%). Induction chemotherapy was given in 21% of patients and 82.3% of patients received concomitant systemic therapy. All patients were treated with 65 Gy in 30 fractions. There was disease recurrence in 17.4% patients. The 5-year disease-free, disease-specific and overall survival were 81.9%, 79.2% and 76.4%, respectively. On univariate analysis, disease recurrence was associated with N-stage (p = 0.047) and overall stage group (p = 0.023).ConclusionTo the best of authors’ knowledge, this is the first report of the use of 65 Gy in 30 fractions of radiotherapy ± weekly cisplatin chemotherapy in NPC in a real-world setting. Our results are comparable to that from other non-endemic regions of the world using different dose fractionation of (chemo)radiotherapy. Future randomised control trials are warranted to compare various dose fractionations in these settings.

De-escalating elective nodal irradiation for nasopharyngeal carcinoma.

Treatment outcomes for endemic nasopharyngeal carcinoma have steadily improved over the past two decades with routine use of intensity-modulated radiotherapy (IMRT), concurrent chemotherapy, and MRI staging. 1 Peng G Wang T Yang KY et al. A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma. Radiother Oncol. 2012; 104: 286-293 Summary Full Text Full Text PDF PubMed Scopus (420) Google Scholar , 2 Blanchard P Lee A Marguet S et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015; 16: 645-655 Summary Full Text Full Text PDF PubMed Scopus (459) Google Scholar In the past decade, trials have primarily focused on treatment escalation with induction and consolidative chemotherapy. 3 Zhang Y Chen L Hu GQ et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med. 2019; 381: 1124-1135 Crossref PubMed Scopus (312) Google Scholar , 4 Pan JJ Ng WT Zong JF et al. Proposal for the 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy. Cancer. 2016; 122: 546-558 Crossref PubMed Scopus (164) Google Scholar , 5 Chen YP Liu X Zhou Q et al. Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. Lancet. 2021; 398: 303-313 Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar However, with modern treatment, fewer than 20% of patients with non-metastatic nasopharyngeal carcinoma develop disease recurrence. In this population with few competing risks, these excellent outcomes have promoted renewed interest in individualised treatment de-intensification. Elective upper-neck versus whole-neck irradiation of the uninvolved neck in patients with nasopharyngeal carcinoma: an open-label, non-inferiority, multicentre, randomised phase 3 trialElective UNI of the uninvolved neck provides similar regional control and results in less radiation toxicity compared with standard WNI in patients with N0–N1 nasopharyngeal carcinoma. Full-Text PDF

Effect of Hydrogen Inhalation Therapy on Hearing Loss of Patients With Nasopharyngeal Carcinoma After Radiotherapy.

ObjectiveTo evaluate the clinical efficacy and safety of hydrogen inhalation in improving hearing loss in patients with long-term survival of nasopharyngeal carcinoma after radiotherapy.MethodsThe eustachian tube dysfunction score, pure tone air conduction threshold, bone conduction threshold, the score of tympanogram and otoscope were prospectively observed in patients with deafness after radiotherapy only or combined radiotherapy and chemotherapy for nasopharyngeal carcinoma. Paired t test and one-way analysis of variance were used to analyze the data before and after treatment.ResultsA total of 17 patients were observed. The median time from radiotherapy to now was 228 months, and the median time from the diagnose of deafness to now was 92 months. After 4 weeks of hydrogen inhalation, the score of eustachian tube dysfunction, air conduction and bone conduction hearing thresholds were significantly reduced, P values were 0.0293, 0.0027, 0.0404, respectively. The mean air-bone gap, the score of otoendoscopy and tympanogram were also decreased, but the differences were not significant (P = 0.2079, P = 0.0536, P = 0.1056). Patients with radiotherapy alone and concurrent chemo-radiotherapy had significantly lower air conduction hearing threshold after hydrogen absorption (P = 0.0142, P = 0.0495). The results of air and bone hearing thresholds before, 4 and 12 weeks after hydrogen inhalation showed a descending trend. The air and bone hearing thresholds before hydrogen inhalation were 74.69 ± 27.03 dB and 45.70 ± 21.58 dB, respectively. At the 12th week, the mean values of air and bone hearing thresholds were the lowest, which were 66.88 ± 20.88 dB and 40.94 ± 18.93 dB, respectively, but there was no significant difference in air and bone hearing thresholds among all groups (P = 0.6755, P = 0.7712). After hydrogen inhalation treatment, no adverse reactions such as nosebleed, chest pain, dyspnea, nausea, vomiting, dizziness, earache and allergic reaction were observed.ConclusionThis is the first prospective study on the effect of hydrogen inhalation on hearing improvement in patients with deafness after radiotherapy/chemotherapy for nasopharyngeal carcinoma, suggesting that continuous hydrogen inhalation may be an alternative rehabilitation therapy for these patients.

Comparison of Platelet-Lymphocyte Ratio Before and After Chemotherapy in Nasopharyngeal Carcinoma Based on Histopathology

Introduction: Nasopharyngeal carcinoma (NPC) is a non-lymphomatous squamous cell carcinoma in the nasopharyngeal epithelial layer which can be classified into three categories with different prognosis based on histopathological examination. This study aimed to compare platelet-lymphocyte ratio (PLR) in NPC patients before and after chemotherapy based on histopathological type. Method: this cohort study recorded data from medical records. The histopathological type, chemotherapy regimen, clinical stage, and PLR of NPC patients were recorded and compared before and after therapy using paired T-test and Wilcoxon test. The prognostic strength of PLR and the value of the cut-off point was determined by looking at the Area Under Curve (AUC) value using the Receiver Operating Characteristic (ROC) curve method. Results: A total of 44 NPC patients received chemotherapy for three cycles, including 21 patients with NPC type-2 and 23 patients with NPC type-3. There were significant differences in the average PLR before and after undergoing three cycles of chemotherapy in type III NPC (p=0.023). At the same time, there were no statistically significant differences in type-II NPC (p=0.131). The prognostic ability of pre-chemotherapy PLR in assessing disease progression in type II NPC was good (AUC=0.763) with 100.0% sensitivity and 73.68% specificity. In type III NPC, the prognostic ability of PLR was very good (AUC 0.881) with 100% sensitivity value and 76.19% specificity. Conclusion: A significant PLR decrease was obtained after the 3rd cycle of chemotherapy in type III NPC following brexel-cisplatin regimen but not in type II NPC. This is probably due to the use of a cisplatin therapy regimen that is more responsive to type III NPC. In addition, examining PLR value before undergoing chemotherapy can be a predictor in assessing disease progression in type III NPC patients.

Baseline Amide Proton Transfer Imaging at 3T Fails to Predict Early Response to Induction Chemotherapy in Nasopharyngeal Carcinoma.

BackgroundEarly identification of nasopharyngeal carcinoma (NPC) patients with high risk of failure to induction chemotherapy (IC) would facilitate prompt individualized treatment decisions and thus reduce toxicity and improve overall survival rate. This study aims to investigate the value of amide proton transfer (APT) imaging in predicting short-term response of NPC to IC and its potential correlation with well-established prognosis-related clinical characteristics.Methods and MaterialsA total of 80 pathologically confirmed NPC patients receiving pre-treatment APT imaging at 3T were retrospectively enrolled. Using asymmetry analysis, APT maps were calculated with mean (APTmean), 90th percentile (APT90) of APT signals in manually segmented NPC measured. APT values were compared among groups with different histopathological subtypes, clinical stages (namely, T, M, N, and overall stages), EBV-related indices (EBV-DNA), or responses to induction chemotherapy, using Mann–Whitney U test or Kruskal–Wallis H test.ResultsNPC showed significantly higher APTmean than normal nasopharyngeal tissues (1.81 ± 0.62% vs.1.32 ± 0.56%, P <0.001). APT signals showed no significant difference between undifferentiated and differentiated NPC subtypes groups, different EBV-DNA groups, or among T, N, M stages and overall clinical stages of II, III, IVA and IVB (all P >0.05). Similarly, baseline APT-related parameters did not differ significantly among different treatment response groups after IC, no matter if evaluated with RECIST criteria or sum volumetric regression ratio (SVRR) (all P >0.05).ConclusionNPC showed significantly stronger APT effect than normal nasopharyngeal tissue, facilitating NPC lesion detection and early identification. However, stationary baseline APT values exhibited no significant correlation with histologic subtypes, clinical stages and EBV-related indices, and showed limited value to predict short-term treatment response to IC.

Differential benefit of induction chemotherapy according to body mass index in nasopharyngeal carcinoma – Pooled analysis of two randomized trials

ObjectiveInduction chemotherapy followed by concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, survival benefits from additional induction chemotherapy varied significantly among patients. This study aimed to determine the predictive value of body mass index (BMI) in induction chemotherapy in NPC. Materials and methodsThis post-hoc analysis included patients from two multicenter, randomized, phase 3 trials (NCT01245959 and NCT01872962), in which patients were randomized to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone. ResultsAmong 960 patients participated, 957 were included in this analysis. 82 (8.6%) patients had baseline BMI < 18.5 kg/m2 (underweight) and 875 (91.4%) had BMI ≥ 18.5 kg/m2 (normal /overweight). Higher proportion of normal/overweight patients completed ≥2 cycles of induction chemotherapy than underweight patients (96.5% vs. 88.4%, p = 0.042). A strong trend for interaction was observed between BMI and induction chemotherapy regarding failure-free survival (FFS) and overall survival (OS, both pinteraction < 0.001). Normal/overweight patients benefited from induction chemotherapy regarding FFS (83.8% vs. 72.9%, p < 0.001) or OS (93.1% vs. 86.9%, p < 0.001), while underweight patients did not (p = 0.24 and p = 0.65, respectively). These results were confirmed in multivariate analysis and multiple sensitivity analyses. ConclusionUsing pooled data from two landmark phase III trials, we found that underweight patients might not benefit from additional induction chemotherapy in locoregionally advanced NPC. If confirmed in prospective studies, this could help guide individual treatment in the clinic.