Advanced Nasopharyngeal Carcinoma Research Articles

143 neoadjuvant chemotherapy followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: real world data from the national institute of oncology, Morocco

143 neoadjuvant chemotherapy followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: real world data from the national institute of oncology, Morocco

107 Prognostic and Survival analysis of patients with locally advanced nasopharyngeal carcinoma with optic pathways involvement.

107 Prognostic and Survival analysis of patients with locally advanced nasopharyngeal carcinoma with optic pathways involvement.

The Application of Emodin Treatment on Nasopharyngeal Carcinoma Therapy.

Nasopharyngeal carcinoma (NPC) is a malignancy prevailing in Taiwan, Hong Kong, Southern China, Southeast Asia, and North Africa. Although early-stage NPC responds well to the primary treatment of radio-chemotherapy, the mortality rate of advanced NPC remains high. Therefore, developing new therapies for nasopharyngeal carcinoma is an urgent task. Emodin is an anthraquinone derivative mainly found in Rheum palmatum. Emodin has been found to possess many anti-cancer functions against various types of cancers, but they are less discussed in the treatment of NPC. This review organized the different studies about the anti-NPC activity of emodin and discussed the potential and challenges of emodin treatment in NPC therapy.

Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

This study aimed to investigate the efficacy and safety of using metronomic S-1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC). We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses. A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S-1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p < 0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S-1. The multivariate prognostic analysis revealed that metronomic S-1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR], 0.074; p=0.010), DFS (HR, 0.103; p=0.002) and OS (HR, 0.127; p=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S-1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2. It is worth conducting a randomized controlled trial to assess the effect of metronomic S-1 on survival outcomes and toxicities of LANPC.

Effect of waiting time for radiotherapy after last induction chemotherapy on prognosis of locally advanced nasopharyngeal carcinoma.

The effect of radiotherapy waiting time after last induction chemotherapy (IC-RT) on prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC) needs further discussion. Three hundred and six patients with LANPC diagnosed pathologically by induction chemotherapy (IC) and radiotherapy (RT) from 2013 to 2018 were selected for this study. The IC-RT was a risk factor for the post-treatment progression of LANPC (OR = 1.017 95%CI: 1.003-1.031), For patients with LANPC, the IC-RT > 40 days significantly reduced 5-year PFS (70% vs. 55%; p = 0.0012), 5-year OS (84% vs. 73%; p = 0.028), 5-year DMFS (80% vs. 66%; p = 0.003), 5-year LRFS (77% vs. 67%; p = 0.012). Indicating that patients with stage IVa who IC-RT > 40 days were found to be a significant predictor of aggravated PFS (HR = 2.69; 95%CI: 1.57-4.6), OS (HR = 2.55; 95%CI: 1.29-5.03), DMFS (HR = 3.07; 95%CI: 1.64-5.76) and LRFS (HR = 2.26; 95%CI: 1.21-4.21). The prognosis of patients will be adversely affected if the IC-RT exceeds 40 days, especially for stage IVa patients.

Neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in elderly patients with stage III-IVa nasopharyngeal carcinoma: A real-world study based on medical comorbidities.

To evaluate the outcomes and toxicities of adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) in elderly (≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (LANPC, stage III-IVa). Using an NPC-specific database, 245 elderly patients with stage III-IVa NPC, receiving CCRT +/- NAC, and an Adult Co-morbidity Evaluation 27 (ACE-27) score <2 were included. Recursive partitioning analysis (RPA) based on TNM stage and Epstein-Barr virus (EBV) DNA were applied for risk stratification. The primary end point was disease-free survival (DFS). Two risk groups were generated by the RPA model. In the high-risk group (EBV DNA < 4000 copy/ml with stage IVa & EBV DNA ≥4000 copy/ml with stage III-IVa), patients treated with NAC plus CCRT achieved improved 5-year DFS rates compared to those who received CCRT alone (56.9% vs. 29.4%; p = 0.003). But we failed to observe the survival benefit of additional NAC in the low-risk group (EBV DNA <4000 copy/ml with stage III). The most common severe acute toxic effects were leucopenia (46.8% vs. 24.4%) and neutropenia (43.7% vs. 20.2%) in the NAC plus CCRT group versus CCRT group with statistically significant differences. The addition of NAC to CCRT was associated with better DFS for the high-risk group of elderly LANPC patients with ACE-27 score <2. However, the survival benefit of additional NAC was not observed in low-risk patients.

Induction Chemotherapy Followed by Radiotherapy vs Chemoradiotherapy in Nasopharyngeal Carcinoma

Induction chemotherapy plus concurrent chemoradiotherapy is recommended for locoregionally advanced nasopharyngeal carcinoma but is associated with higher rates of acute toxic effects and low compliance. Evidence on de-escalating treatment intensity after induction chemotherapy is limited. To assess if radiotherapy was noninferior to chemoradiotherapy after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma. From April 2015 to March 2018, a multicenter, open-label, randomized, noninferiority, phase 3 trial was conducted at 5 Chinese hospitals. A total of 383 patients aged 18 to 70 years with an untreated histologically confirmed nonkeratinizing tumor, Karnofsky performance status score not worse than 70, proper organ function, and stage III to IVB nasopharyngeal cancer were enrolled. Data were analyzed from April 2023 to June 2023. Patients were assigned randomly. Both groups received 3 cycles of induction chemotherapy consisting of intravenous administration (on day 1) of cisplatin at 60 mg/m2 and docetaxel at 60 mg/m2 and continuous intravenous infusion (from day 1 to day 5) of daily fluorouracil (600 mg/m2), repeated every 21 days. Subsequently, the patients received radiotherapy alone (induction chemotherapy in combination with radiotherapy [IC-RT] group) or concomitant cisplatin (30 mg/m2/week) with radiotherapy for 6 to 7 weeks (induction chemotherapy combined with chemoradiotherapy [IC-CCRT] group). The primary end point was 3-year progression-free survival (time from the initiation of therapy until the first indication of disease progression or death), with a noninferiority margin of 10%. The secondary end points included overall survival, locoregional failure-free survival, distant metastasis-free survival, response rate, and toxic effects. A total of 383 patients (median [range] age, 48 [19-70] years; 100 women [26%]). Median follow-up time was 76 months (IQR, 70-89 months). The 3-year progression-free survival was 76.2% and 76.8% in the IC-RT (n = 193) and IC-CCRT groups (n = 190), respectively, in the intention-to-treat population, showing a difference of 0.6% (95% CI, -7.9% to 9.1%; P = .01 for noninferiority). Identical outcomes were reported in the per-protocol population. The incidence of grade 3 to 4 short-term toxic effects in the IC-RT group was less than the IC-CCRT group. No differences were observed in late toxic effects. The results of this randomized clinical trial suggest that after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma, radiotherapy alone was noninferior to chemoradiotherapy in terms of 3-year progression-free survival. ClinicalTrials.gov Identifier: NCT02434614.

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.

Neutrophil-to-lymphocyte ratio and monocyte-to-eosinophil ratio as prognostic indicators for advanced nasopharyngeal carcinoma.

To determine the predictive value of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-eosinophil ratio (NER), lymphocyte-to-eosinophil ratio (LER), monocyte-to-eosinophil ratio (MER), systemic inflammatory response index (SIRI), and ratio of inflammatory cells before and after treatment for predicting survival in advanced nasopharyngeal carcinoma (NPC) and to provide a reference for treatment. A retrospective review of 70 patients was performed. Serological indexes were obtained by drawing blood before and after systemic therapy. The cutoff values of these indexes were determined by receiver operating characteristic (ROC) curves. The prognostic value of the indexes for overall survival (OS) and distant metastasis free survival (DMFS) was evaluated. Survival analysis showed that a smaller pretreatment LMR value was associated with poor OS; larger pretreatment NER, LER, MER, and SIRI values were associated with poor OS; a smaller posttreatment LMR value was associated with poor OS; larger posttreatment NLR, NER, MER, and SIRI values were associated with poor OS; a smaller pretreatment LMR value was associated with poor DMFS; larger pretreatment NLR, NER, LER, and MER values were associated with poor DMFS; and larger posttreatment NLR, NER, LER, and MER values were associated with poor DMFS. Furthermore, a larger neutrophil after treatment-to-neutrophil before treatment ratio was associated with poor OS and DMFS. Logistic regression analysis showed that pretreatment MER and posttreatment NLR were independent predictors of OS in patients with advanced NPC; moreover, pretreatment and posttreatment MER and NLR were independent prognostic factors for DMFS in patients with advanced NPC. The NLR, NER and MER can be used to predict survival in advanced NPC patients. Eosinophils might be one of the factors for the good prognosis of NPC patients. In addition, an increased number of neutrophils after treatment may indicate a favorable prognosis.

Prognostic Value of Pre-Chemoradiotherapy Pan-Immune-Inflammation Value (PIV) in Locally Advanced Nasopharyngeal Cancers.

To examine the prognostic relevance of pan-immune-inflammation value (PIV) in locally advanced nasopharyngeal carcinomas (LA-NPC) patients treated with concurrent chemoradiotherapy (CCRT) definitively. We used receiver operating characteristic (ROC) curve analysis to determine an optimal PIV cutoff that could effectively divide the patient cohort into two distinct groups based on distant metastasis-free (DMFS) and overall survival (OS) results. For this purpose, receiver operating characteristic (ROC) curve analysis was employed. Our primary and secondary endpoints were to investigate the potential correlations between pre-CCRT PIV measurements and post-CCRT OS and DMFS outcomes, respectively. This retrospective cohort study included 179 LA-NPC patients. The optimal PIV cutoff was 512 (area under the curve: 74.0%; sensitivity: 70.8%, specificity: 68.6%; J-index: 0.394) in ROC curve analysis, creating two patient groups: Group-1: PIV < 512 (N = 108); vs Group-2: PIV ≥ 512 (N = 71). In the comparative analysis, although there were no significant differences between the two groups regarding the patient, disease, and treatment characteristics, the PIV ≥ 512 group had significantly poorer median OS [74.0months vs not reached yet (NR); HR: 2.81; P < 0.001] and DMFS (27.0 months vs NR; HR: 3.23; P < 0.001) than the PIV < 512 group. Apart from PIV ≥ 512, the N2-3 nodal stage and ≥ 5% weight loss within the preceding 6months were significant predictors of unfavorable outcomes for DMFS (P < 0.05 for each) and OS (P < 0.05 for each) in univariate analyses. The results of the multivariate analysis showed that each of the three variables had independent negative impacts on both DMFS and OS outcomes (P < 0.05 for each). The present findings indicate that PIV, which classifies these patients into two groups with significantly different DMFS and OS, might be a potent prognostic biological marker for LA-NPC patients.

Deletion of concurrent chemotherapy on the basis of sequential chemoradiotherapy for non-metastatic stage T4 nasopharyngeal carcinoma in IMRT era.

Intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy is deemed as the mainstay treatment in locoregionally advanced nasopharyngeal carcinoma (NPC). Nevertheless, the tolerance of severe acute toxicity of concurrent chemotherapy was unsatisfied. In addition, T4 is the predicting factor of poor prognosis for NPC patients. In this retrospective analysis, the long-term outcomes IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy for T4 non-metastatic NPC were analyzed. From January 2005 to November 2016, a total of 145 biopsy-proven non-metastatic T4 NPC was treated with IMRT combined by induction chemotherapy with or without adjuvant chemotherapy. The survival and side effects of the patients were analyzed. Median follow-up time was 74 months (ranges, 8-186 months). 10.0%, 61.3%, 27.3%, and 1.3% developed grade 1, 2, 3, and 4 mucositis during IMRT, respectively. 5.5% and 2.0% patients experienced grade 1 and 2 nausea and vomiting; no patients developed grade 3 or 4 nausea and vomiting. Of 145 patients enrolled, 5-year and 10-year overall survival(OS) rates were 73.7% and 53.9%, local progression-free survival(LPFS) rates were 86.1% and 71.6%, regional progression-free survival(RPFS) rates were 96.7% and 92.8%, distant metastasis-free survival (DMFS) rates were 86.7%, 78.2%, respectively. At the last follow-up, five patients developed cranial nerve injury, one patient developed mandibular bone necrosis, four patients developed temporal lobe injury, four patients developed nasopharyngeal massive hemorrhage (three cases after recurrence and one case without recurrence), and five patients developed second primary tumor. The survival outcomes of treating T4 NPC IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy are encouraging. Moreover, mucosal reaction, nausea, and vomiting reaction were reduced during IMRT.

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.

Predictive potential of pan-immune-inflammation value / hemoglobin index as biomarker for osteoradionecrosis risk in locally advanced nasopharyngeal carcinomas

ObjectiveWe aimed to investigate whether the Pan-Immune-Inflammation-Value/Hemoglobin (PIV/Hb) index could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal cancer (LA-NPC). Materials and methodsThis retrospective analysis included LA-NPC patients who underwent CCRT and pre-CCRT oral exams at our institution's Departments of Radiation Oncology and Dentistry between January 2010 and December 2022. The relationship between ORN rates and PIV-Hb levels was explored using receiver operating characteristic curve analysis. The primary objective was to establish a correlation between pre-CCRT PIV-Hb levels and ORN rates, while the secondary objective was to identify other risk factors for ORN. ResultsOf 249 eligible patients, 21 (8.4 %) were diagnosed with ORN. The optimal pre-CCRT PIV/Hb cutoff was 73.8, which divided patients into two subgroups with distinctive ORN risk estimates: Group 1: PIV/Hb < 73.8 (N = 206), and Group 2: PIV/Hb ≥ 73.8 (N = 43). The results of the comparative analysis indicated that the cohort with PIV/Hb ≥ 73.8 exhibited substantially higher rates of ORN than the PIV/Hb < 73.8 cohort (44.2 % vs. 1.0 %; P < 0.001). The multivariate logistic regression analysis indicated that the pretreatment PIV/Hb ≥ 73.8 was independently associated with higher ORN rates (P < 0.001). ConclusionThe results of our current investigation indicate that higher levels of pretreatment PIV/Hb were associated with a significant independent increase in ORN rates in LA-NPC patients who received CCRT.

Retracted: Clinical Effect of Apatinib Mesylate Tablets Combined with Paclitaxel Concurrent Radiotherapy and Chemotherapy in the First-Line Treatment of Locally Advanced Nasopharyngeal Carcinoma.

[This retracts the article DOI: 10.1155/2022/6293816.].

Toripalimab (Loqtorzi) for nasopharyngeal carcinoma.

Toripalimab-tpzi (Loqtorzi – Coherus Biosciences), a programmed death receptor-1 (PD-1)-blocking antibody, has been approved by the FDA for use in combination with cisplatin and gemcitabine for first-line treatment of recurrent locally advanced or metastatic nasopharyngeal carcinoma and for use as monotherapy for treatment of recurrent unresectable or metastatic nasopharyngeal carcinoma in adults with disease progression on or after platinum-based chemotherapy. It is the first immune checkpoint inhibitor to be approved in the US for treatment of nasopharyngeal carcinoma.

Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma.

To compare target area delineation schemes in intensity-modulated radiotherapy (IMRT) effect on patients with locally advanced nasopharyngeal carcinoma (NPC). A total of 88 NPC patients received IMRT and were assigned into control group (n = 44) and observation group (n = 44) based on MRI and CT imaging. In the control group, the treatment range was determined as the clinical target volume (CTV) as the gross tumor volume (GTV) + 5 mm. In the observation group, high-risk target areas CTVp1 was GTVp + 5 mm, lymphatic drainage area CTVn1 was GTVn + 5 mm, medium-risk CTVp2 was CTVp1 + 5 mm margin + the whole nasopharyngeal area, CTVn2 was CTVn1 + 5 mm. Radiotherapy treatment course was 6-8 weeks, four times a week. The observation group had higher total effective rate, with fewer complications. Neutrophil lymphocyte ratio (NLR), interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels were lower after radiotherapy in both groups compared to before radiotherapy, with the observation group demonstrating lower levels than the control group. The effective group exhibited lower serum NLR, IL-6, and TNF-α compared to the non-effective group. T stage, target location, serum NLR, IL-6, and TNF-α were risk factors for the effect of radiotherapy. Serum NLR, IL-6, and TNF-α have predictive significance for radiotherapy effect.

EBV abortive lytic cycle promotes nasopharyngeal carcinoma progression through recruiting monocytes and regulating their directed differentiation.

Epstein-Barr virus (EBV) is associated with several types of human cancer including nasopharyngeal carcinoma (NPC). The activation of EBV to the lytic cycle has been observed in advanced NPC and is believed to contribute to late-stage NPC development. However, how EBV lytic cycle promotes NPC progression remains elusive. Analysis of clinical NPC samples indicated that EBV reactivation and immunosuppression were found in advanced NPC samples, as well as abnormal angiogenesis and invasiveness. To investigate the role of the EBV lytic cycle in tumor development, we established a system that consists of two NPC cell lines, respectively, in EBV abortive lytic cycle and latency. In a comparative analysis using this system, we found that the NPC cell line in EBV abortive lytic cycle exhibited the superior chemotactic capacity to recruit monocytes and polarized their differentiation toward tumor-associated macrophage (TAM)-like phenotype and away from DCs, compared to EBV-negative or EBV-latency NPC cells. EBV-encoded transcription activator ZTA is responsible for regulating monocyte chemotaxis and TAM phenotype by up-regulating the expression of GM-CSF, IL-8, and GRO-α. As a result, TAM induced by EBV abortive lytic cycle promotes NPC angiogenesis, invasion, and migration. Overall, this study elucidated the role of the EBV lytic life cycle in the late development of NPC and revealed a mechanism underlying the ZTA-mediated establishment of the tumor microenvironment (TME) that promotes NPC late-stage progression.

The Use of Pre-Chemoradiotherapy Total Masseter Muscle Volume as a Novel Predictor of Radiation-Induced Trismus in Locally Advanced Nasopharyngeal Carcinoma Patients.

We sought to determine whether pretreatment total masseter muscle volume (TMMV) measures can predict radiation-induced trismus (RIT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT). We retrospectively reviewed the medical records of LA-NPC patients who received C-CRT and had pretreatment maximum mouth openings (MMO) greater than 35 mm. MMO of 35 mm or less after C-CRT were considered RIT. We employed receiver operating characteristic (ROC) curve analysis to explore the correlation between pre-treatment TMMV readings and RIT status. Out of the 112 eligible patients, 22.0% of them received a diagnosis of RIT after C-CRT. The optimal TMMV cutoff that was significantly linked to post-C-CRT RIT rates was determined to be 35.0 cc [area under the curve: 79.5%; sensitivity: 75.0%; and specificity: 78.6%; Youden index: 0.536] in the ROC curve analysis. The incidence of RIT was significantly higher in patients with TMMV ≤ 5.0 cc than in those with TMMV > 35.0 cc [51.2% vs. 8.7%; Odds ratio: 6.79; p < 0.001]. A multivariate logistic regression analysis revealed that pre-C-CRT MMO ≤ 41.6 mm (p = 0.001), mean masticatory apparatus dose V56.5 ≥ 34% group (p = 0.002), and TMMV ≤ 35 cc were the independent predictors of significantly elevated rates of RIT. The presence of a smaller pretreatment TMMV is a reliable and independent novel biological marker that can confidently predict higher RIT rates in LA-NPC patients who receive C-CRT.

Worth of pan-immune-inflammation value in trismus prediction after concurrent chemoradiotherapy for nasopharyngeal carcinomas.

Radiation-induced trismus (RIT), one of the rare but serious side effects of concurrent chemoradiotherapy (C-CRT), is difficult to predict with high accuracy. We aimed to examine whether the pretreatment pan-immune-inflammation value (PIV) measures predict RIT in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving C-CRT. Data of patients with LA-NPC who underwent C-CRT and had maximum mouth openings (MMO) > 35 mm were reviewed. Any MMO of 35 mm or less after C-CRT was considered RIT. All PIV values were computed using the complete blood count test results: PIV = (Platelets × Monocytes × Neutrophils) ÷ Lymphocytes. The receiver operating characteristic analysis was employed to dissect a possible association between pre-treatment PIV readings and RIT status. Confounding variables were tested for their independent relationship with the RIT rates using logistic regression analysis. The research comprised 223 participants, and RIT was diagnosed in 46 (20.6%) at a median time from C-CRT to RIT of 10 months (range: 5-18 months). Pre-C-CRT PIV levels and RIT rates were analyzed using receiver operating characteristic curve analysis, with 830 being the optimal cutoff (area under the curve: 92.1%; sensitivity: 87.5%; specificity: 85.5%; Youden index: 0.730). RIT was significantly more prevalent in the PIV > 830 cohort than its PIV ≤ 830 counterpart (60.3% vs. 5%; hazard ratio 5.79; P < 0.001). Multivariate logistic regression analysis revealed that advanced T-stage (P = 0.004), masticatory apparatus dose V58Gy≥%32 (P = 0.003), and PIV > 830 (P < 0.001) were independently linked with significantly elevated rates of RIT. The presence of elevated pre-C-CRT PIV is a unique biological marker that independently predicts increased RIT rates in LA-NPC undergoing C-CRT.

Chronomodulated chemotherapy for locoregionally advanced nasopharyngeal carcinoma: A phase II randomized controlled trial

ObjectiveTo validate the safety and efficacy of chronochemotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC). MethodsParticipants for this phase II randomized controlled trial were recruited from the Department of Head and Neck Oncology at the Affiliated Cancer Hospital of Guizhou Medical University. Patients enrolled (128 in total, 112 in the final analysis) between April 1, 2017, and February 28, 2018, were randomly divided into the chronochemotherapy and conventional chemotherapy groups. In the chronochemotherapy group, docetaxel was intravenously administered between 3:30 a.m. and 4:30 a.m. on day 1, followed by intravenous administration of cisplatin between 10:00 a.m. and 10:00 p.m. from day 1to day 5. In addition, 5-fluorouracil was administered through a continuous intravenous pump between 10:00 p.m. and 10:00 a.m. (2nd day) from day 1 to day 5. In the conventional chemotherapy group, docetaxel (on day 1), cisplatin (on day 2), and 5-fluorouracil (from day 1 to day 5, 120 ​h in total) were administered without time-specific constraints. Both groups underwent intensity-modulated radiation therapy with 6-MV X-rays. The gross target volume (GTV) comprised the nasopharyngeal GTV and cervical lymph node GTV. The primary endpoint was immune function, quantified by measuring dendritic cell and lymphocyte subsets, whereas the secondary endpoints were therapeutic efficacy and incidence of adverse events. Pearson Chi-square test was applied to compare total events between the groups, Mann-Whitney U test was used to compare the DC subsets and toxicities, and Wilcoxon signed-rank test ​was used to compare the continuous variables between the two groups. ResultsChronochemotherapy preserved immune function, as evidenced by elevated levels of myeloid dendritic cells (P ​= ​0.394) and higher CD4/CD8 ratio (P ​= ​0.781). No significant difference in overall response rate, measured as the sum of complete and partial response rates, was observed between the groups (P ​= ​0.711). A reduction in the incidence of vomiting (P ​= ​0.002), stomatitis (P ​= ​0.028), and mucositis (P ​= ​0.028) was observed in the chronochemotherapy group. Leukopenia incidence rate was 83.3 ​% and 92.3 ​% in the chronochemotherapy and conventional chemotherapy groups, respectively (P ​= ​0.232). ConclusionsIn patients with locoregionally advanced NPC, the overall response rate of chronochemotherapy is comparable to that of conventional chemotherapy; however, chronochemotherapy shows fewer adverse events.