Locally Advanced Nasopharyngeal Carcinoma Research Articles

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.

Novel Index Combining Pan-Immune-Inflammatory Index and Hemoglobin Levels (PIV/Hb) Predicts Trismus Rates Efficiently after Chemoradiotherapy in Locally Advanced Nasopharyngeal Cancer.

To evaluate the predictive potency of a novel index combining the pan-immune-inflammatory index and hemoglobin levels (PIV/Hb) for the prevalence of radiation-induced trismus (RIT) in patients with locally advanced nasopharyngeal cancer (LA-NPC) receiving concurrent chemoradiotherapy (CCRT). Data from 228 LA-NPC patients were retrospectively examined. Maximum mouth openings (MMO) were measured to confirm the presence of RIT, defined as MMOs ≤35 mm. Complete blood test results from the first day of CCRT were used to calculate PIV/Hb levels. A potential relationship between pretreatment PIV/Hb and the RIT status was evaluated using receiver operating characteristic (ROC) curve analysis. Post-CCRT RIT was diagnosed in 20.2% of the patients. The ROC curve analysis determined 68.4 g/dL as the ideal PIV/Hb cutoff that effectively divided patients into two distinct groups (area under the curve: 94.7%; specificity: 86.4%; sensitivity: 87.4%). RIT was significantly more prevalent in the PIV/Hb > 68 group than in the PIV/Hb < 68 group (58.8% vs. 3.8%; P < 0.001). Multivariate logistic regression analysis showed that a pre-CCRT PIV > 68 was independently associated with significantly higher rates of RIT. Higher pretreatment levels of the novel PIV/Hb index predict increased RIT rates following definitive CCRT for LA-NPCs.

Topkan's CARWL Index Efficiently Predicts the Radiation-Induced Tooth Loss Rates in Radically Treated Locally Advanced Nasopharyngeal Cancer Patients.

To assess the usefulness of the novel CARWL index in predicting radiation-induced tooth loss (RITL) rates in locally advanced nasopharyngeal cancer (LA-NPC) patients undergoing concurrent chemoradiotherapy (C-CRT). The study retrospectively examined data from 323 LA-NPC patients. The patients were divided into two groups based on cutoff values for CAR and weight loss (WL). The ideal cutoff for RITL was 3.0 g/dL [AUC: 83.0%, sensitivity: 83.6%, specificity: 81.4%, J-index: 0.650]. CARWL index was created by combining pretreatment CAR and WL status (WL ≤ 5.0% vs > 5.0%, resulting in four groups: Group 1: CAR < 3.0 and WL ≤ 5.0%, Group 2: CAR < 3.0 and WL > 5.0%, Group 3: CAR ≥ 3.0 and WL ≤ 5.0%, and Group 4: CAR > 3.0 and WL > 5.0%. RITL was diagnosed in 67.2% of patients. Since the RITL rates of Groups 2 and 3 were statistically indistinguishable, we combined them and created the three-tiered CARWL score groups: CARWL-0: CAR < 3.0 and WL ≤ 5.0%; CARWL-1: CAR < 3.0 and WL > 5.0%, or CAR ≥ 3.0 and WL ≤ 5.0%; and CARWL-2: CAR > 3.0 and WL > 5.0%. Comparative analysis revealed that the RITL rates gradually and significantly increased from CARWL-0 to CARWL-2 score groups (49.4% vs 64.7% vs 83.0%; P <0.001) despite similar baseline disease and patient characteristics. Results of the multivariate analysis showed that higher CARWL score groups were independent and significant predictors of increased RITL rates (p < 0.001). Present results suggest that the novel CARWL index is a reliable biomarker for predicting RITL incidence in LA-NPC patients.

Pretreatment Masseter Muscle Volume Predicts Survival in Locally Advanced Nasopharyngeal Carcinoma Patients Treated with Concurrent Chemoradiotherapy.

Muscle loss is a significant indicator of cancer cachexia and is associated with a poor prognosis in cancer patients. Given the absence of comparable studies, the current retrospective study sought to examine the correlation between the total masseter muscle volume (TMMV) before treatment and the survival outcomes in locally advanced nasopharyngeal cancer (LA-NPC) patients who received definitive concurrent chemoradiotherapy (CCRT). A three-dimensional segmentation model was used to determine the TMMV for each patient by analyzing pre-CCRT magnetic resonance imaging. The optimal TMMV cutoff values were searched using receiver operating characteristic (ROC) curve analyses. The primary and secondary endpoints were the relationship between the pre-CCRT TMMV measures and overall survival (OS) and progression-free survival (PFS), respectively. Ninety-seven patients were included in this study. ROC curve analyses revealed 38.0 cc as the optimal TMMV cutoff: ≤38.00 cc (n = 42) and >38.0 cc (n = 55). Comparisons between the two groups showed that the TMMV>38.0 cc group had significantly longer PFS [Not reached (NR) vs. 28; p < 0.01] and OS (NR vs. 71; p < 0.01) times, respectively. The results of the multivariate analysis demonstrated that the T-stage, N-stage, number of concurrent chemotherapy cycles, and TMMV were independent associates of PFS (p < 0.05 for each) and OS (p < 0.05 for each) outcomes, respectively. The findings of the current retrospective research suggest that pretreatment TMMV is a promising indicator for predicting survival outcomes in LA-NPC patients receiving definitive CCRT.

Anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with chemoradiotherapy for induction chemotherapy resistant locally advanced nasopharyngeal carcinoma: A prospective phase II study

ObjectivesTo investigate the efficacy and safety of nimotuzumab (NTZ) combined with concurrent chemo-radiotherapy (CCRT) in induction chemotherapy (IC) resistant locally advanced nasopharyngeal carcinoma (LANPC). Materials and methodsA single-arm, open-label phase II clinical trial was conducted (NCT04508816). Eligible patients were 18–70 years old, pathologically confirmed NPC at stage III-IVA, stable disease or progressive disease after IC by imaging evaluation, and ECOG performance status with 0–1. All patients received intensity-modulated radiotherapy (IMRT) concurrent with chemotherapy and NTZ (200 mg/w). The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR) and safety. ResultsFrom May 2015 to July 2020, 56 NPC patients were enrolled. With the median follow-up of 34 months (range from 8 to 77 months), the 3-year and 5-year PFS and OS rates were 79.3 % and 72.1 %, 94.0 % and 87.2 %, respectively. ORR of the nasopharynx and cervical lymph nodes involvement were 98.2 % and 98.1 % three months after IMRT. Univariate analysis revealed that pretreatment PET/CT was the factor that influenced PFS (P = 0.038). Patients treated with ≥6 weeks of NTZ showed improved 3‐year PFS rate (83.0% vs. 73.9 %, P > 0.05) and 5-year PFS rate (83.0% vs. 61.6 %, P>0.05) compared with <6 weeks NTZ. The acute toxicities were mainly grade 1/2 hematologic. Severe toxicities were uncommon. The major grade 3/4 AE was neutropenia (26.8 %). ConclusionsThe results demonstrated that NTZ combined with CCRT in IC resistant LANPC was effective with mild toxicity.

Predictive function of tumor burden-incorporated machine-learning algorithms for overall survival and their value in guiding management decisions in patients with locally advanced nasopharyngeal carcinoma

ObjectiveAccurate prognostic predictions and personalized decision-making on induction chemotherapy (IC) for individuals with locally advanced nasopharyngeal carcinoma (LA-NPC) remain challenging. This research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival (OS) and their value in guiding treatment in patients with LA-NPC. MethodsIndividuals with LA-NPC were reviewed retrospectively. Tumor burden signature-based OS prediction models were established using a nomogram and two machine-learning methods, the interpretable eXtreme Gradient Boosting (XGBoost) risk prediction model, and DeepHit time-to-event neural network. The models' prediction performances were compared using the concordance index (C-index) and the area under the curve (AUC). The patients were divided into two cohorts based on the risk predictions of the most successful model. The efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy alone. ResultsThe 1 221 eligible individuals, assigned to the training (n = 813) or validation (n = 408) set, showed significant respective differences in the C-indices of the XGBoost, DeepHit, and nomogram models (0.849 and 0.768, 0.811 and 0.767, 0.730 and 0.705). The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS (0.881 and 0.760, 0.845 and 0.776, and 0.764 and 0.729, P < 0.001). IC presented survival benefits in the XGBoost-derived high-risk but not low-risk group. ConclusionThis research used machine-learning algorithms to create and verify a comprehensive model integrating tumor burden with clinical variables to predict OS and determine which patients will most likely gain from IC. This model could be valuable for delivering patient counseling and conducting clinical evaluations.

Comparison of the Efficiency of Induction and Adjuvant Chemotherapy in Patients with Locally Advanced Nasopharyngeal Cancer.

To make a comparative evaluation of induction chemotherapy (ICT) or adjuvant chemotherapy (ACT) added to standard concurrent chemoradiotherapy in patients diagnosed with locally advanced nasopharyngeal cancer (LANPC) (Stage 3-4a patients, except T3N0). Observational study. Place and Duration of the Study: Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey, from April 2009 to June 2021. Clinicopathological features of adult patients diagnosed with LANPC were recorded from the hospital's patient registry database. Patients without the medical records were excluded. An assessment of the effectiveness of induction or ACT added to standard definitive chemoradiotherapy (CRT) was performed, and the application cycles were evaluated. Seventy-four patients (71.6% male, mean age 50.8±11.7) with LANPC were included in the study. There is no statistical difference in progression-free survival (PFS) between patients who applied ICT (before CRT) and ACT (after CRT) (p = 0.61). Female patients and patients aged ≤50 years had better PFS as independent factors (HR=3.82, 95% CI 1.14-12.74, p = 0.029; HR: 1.06 95% CI 1.02-1.10, p = 0.002, respectively). Also, patients aged 50 years and younger and female patients had a statistically longer overall survival (OS) (p = 0.045, and p = 0.012, respectively). While there was statistically no significant difference in PFS according to the number of cycles for EBER-positive patients received adjuvant Cisplatin-5FU (CF); 3 cycles compared to 2 showed a statistically higher OS (p = 0.06, and p = 0.022, respectively). Conclusion: LANPC patients were found to have a positive survival if they were young and females. There was a positive impact on survival of intensified adjuvant CF in EBER-positive nonkeratinising, undifferentiated LANPC patients. Locally advanced nasopharyngeal cancer, EBER, Induction chemotherapy, Adjuvant chemotherapy.

Treatment Outcomes of Concurrent Nimotuzumab with Intensity Modulated Radiotherapy in Advanced Nasopharyngeal Carcinoma Patients Unfit for Concurrent Chemoradiotherapy: A Single Institute Experience

To assess the safety and efficacy of intensity-modulated radiotherapy (IMRT) combined with nimotuzumab for patients with locally advanced nasopharyngeal carcinoma (LA-NPC) medically unfit to receive concomitant chemotherapy. From 2016.6 to 2020.9, 34 newly diagnosed patients with local-regional advanced NPC medically unfit for concurrent chemoradiation had undergone definitive radiotherapy and were retrospectively evaluated. All patients were treated with IMRT combined treatment modality of nimotuzumab with or without cisplatin-based induction chemotherapy. Nimotuzumab was administered concurrently with IMRT at a weekly dose of 200 mg. Acute and late radiation-related toxicities were evaluated based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 during and after IMRT. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate prognostic analyses were performed by using the Cox proportional hazard model. The median follow-up time for the entire group was 15 months (range 5 to 55 months). At the time of this analysis, a total of 2 cases developed loco-regional recurrence. In addition, 4 patients developed distant metastasis. There was a total of 5 deaths: 3 patients died from distant metastasis, 1 patient died from the progression of loco-regional disease after recurrence, and the causes of death for the additional 1 case was a nasopharyngeal ulcer and deadly bleeding. The 1-year OS rate of the whole cohort was 87.9%, and the 1-year LFFR, DFFR, and PFS rates were 100%, 91.0%, and 91.0%, respectively. During the period of concurrent nimotuzumab and IMRT, no grade 3-4 hematologic toxicities and dermatitis were observed. Grade 3-4 radiotherapy-related oral mucositis was reported in 7 patients (20.6%). No infusion reaction was observed. No acneiform eruptions were found among these patients. The most commonly observed late complication was xerostomia. The degree of dry mouth in most patients was mild-to-moderate at the time of the last follow-up. Finally, 7 patients developed either unilateral or bilateral hearing impairment. One female patient experienced a nasopharyngeal ulcer and deadly bleeding after 5 months of completion of radiotherapy. Concurrent nimotuzumab with IMRT for the treatment of LA-NPC was well tolerated, with encouraging survival data, and it could be an effective treatment alternative for patients with LA-NPC medically unfit for concomitant chemotherapy. Further clinical trials are needed to confirm these findings.

Standard Therapy vs. Individualized Therapy in Elderly Locally Advanced Nasopharyngeal Carcinoma: A Real-World Study

Concurrent chemoradiotherapy (CRT) with/without induction chemotherapy has been the standard therapy (ST) for locally advanced nasopharyngeal carcinoma (LA-NPC). However, most patients supporting these clinical trials were younger than 65 years of age. For the toxicity of CRT and the poor tolerance of elderly patients, it is still controversial whether ST could bring the most promising survival benefits for elderly NPC compared with individualized therapy (IT). Thus, in this real-world study we compared the survival and safety of ST with IT in elderly LA-NPC to explore an effective and tolerable treatment strategy for elderly LA-NPC. A total of 109 newly diagnosed elderly LA-NPC (>65 years old) from Jan. 2013-Jul. 2020 were retrospectively enrolled and divided into the ST group and IT group according to the original treatment tendency. ST refers to CRT with/without induction chemotherapy. IT group included patients not suitable for CRT and were given individualized treatment fully discussed by at least two oncologists from our head and neck team. A 1:1 propensity score matching (PSM) generated a matched cohort of ST and IT. The survivals and treatment related toxicities were compared between the two groups. There were 46 cases in the ST group and 63 cases in the IT group. The 5-year overall survival (OS) rate, cancer-specific survival (CSS) rate, progression- free survival (PFS) rate, local recurrence-free survival (LRFS) rate and distant metastasis-free survival (DMFS) rate were 68.64%, 76.42%, 73.69%, 85.67% and 86.82%, respectively. By 1:1PSM, 35 cases in each group were matched. No significant differences of OS, CSS, PFS, LRFS and DMFS were found between ST and IT groups in the PSM-matched cohorts (P = 0.87, P = 0.79, P = 0.51, P = 0.81 and P = 0.24, respectively). Compared with patients in the ST group, cases received IT were associated with less severe acute toxicities including anemia, leucopenia, neutropenia, and thrombocytopenia. For elderly LA-NPC, IT had similar survivals while less severe toxicities compared with ST, which revolutionarily challenged the role of ST for elderly LA-NPC. In the future, more studies are need to explore a less toxic treatment modality with noninferior efficacy for elderly LA-NPC.

Identification and Automated Delineation of Radioresistant Biological Tumor Volume in Nasopharyngeal Carcinoma Based on Magnetic Resonance Imaging Radiomics

Widespread use of intensity modulated radiotherapy (IMRT) has improved the tumor control rate of nasopharyngeal carcinoma (NPC). However, nearly 20% of the patients with local-advanced NPC would relapse after precise irradiation and 80% of the recurrent lesions occur within the high dose field, suggesting that there are radiation-resistant cancer cell subsets within the tumor. In this context, identification and contouring of radiation resistance region of NPC for dose escalation at primary IMRT could be advantageous. In this work, we proposed a two-step radiomics workflow to predict local relapse and the recurrent region of NPC before primary IMRT. In this single-center, retrospective study, pre-treatment magnetic resonance (MR) sequences of T1-weighted imaging (T1-w) and contrast-enhanced T1-weighted imaging (CET1-w) were collected from 800 patients of newly diagnosed and non-metastatic NPC between April 2009 and December 2015. The primary gross tumor volume (GTVp) of all patients and the actual recurrent lesion (GTVr) of patients who suffered from local recurrence were manually contoured for further analysis. A two-step complete radiomics workflow was designed to predict tumor recurrence and segment the region. First, least absolute shrinkage and selection operator (LASSO) was utilized for radiomics features selection of GTVp and support vector machine (SVM) was adopted to predict the recurrence. If the model predicts a recurrence, then the workflow utilizes an improved 3D U-Net to segment the recurrent region. Area under receiver operating characteristic curve (ROC-AUC) was used to evaluate the performance of tumor recurrence prediction, and Dice similarity coefficient (DSC) was used to assess the consistence between the actual and predicted GTVr. Of 800 NPC patients, 95 (11.9%) patients developed in-field local recurrence. For recurrence risk prediction, the SVM ensemble model (T1-w+CET1-w) was selected for further application with higher sensitivity. The average ROC-AUC, specificity, sensitivity of the SVM ensemble model in a 5-fold cross-validation and in the independent test set of 160 patients were 0.922, 0.922, 0.777 and 0.928, 0.915, 0.737, respectively. Moreover, for recurrent region segmentation, the multi-modality (T1-w+CET1-w) model was superior to the single-modality (T1-w or CET1-w) model. In an independent test set of 15 patients, the DSC, sensitivity and 95% Hausdorff Distance between actual and predicted GTVr was 0.549±0.176, 0.696±0.118 and 9.813±4.788 which was superior to 0.444±0.188, 0.497±0.218 and 12.047±5.361 of original 3D U-Net. The proposed two-step radiomics workflow showed a good performance in predicting tumor recurrence of NPC. The predicted location of the recurrence lesion was all accurate, but there was still a certain difference between the volume of the automated delineated and actual GTVr, which needed to be further optimized to be used as biological tumor volume.

Advance in integrating platinum-based chemotherapy with radiotherapy for locally advanced nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant tumor characterized by the malignant transformation of nasopharyngeal epithelial cells. It is highly sensitive to radiation therapy, making radiotherapy the primary treatment modality. However, 60-80% of patients are initially diagnosed with locally advanced NPC (LA-NPC), where radiotherapy alone often fails to achieve desirable outcomes. Therefore, combining radiotherapy with chemotherapy has emerged as an effective strategy to optimize treatment for LA-NPC patients. Among the various chemotherapy regimens, concurrent chemoradiotherapy (CCRT) using platinum-based drugs has been established as the most commonly utilized approach for LA-NPC patients. The extensive utilization of platinum drugs in clinical settings underscores their therapeutic potential and emphasizes ongoing efforts in the development of novel platinum-based complexes for anticancer therapy. The aim of this review is to elucidate the remarkable advances made in the field of platinum-based therapies for nasopharyngeal carcinoma, emphasizing their transformative impact on patient prognosis.

Utility of pre-chemoradiotherapy Pan-Immune-Inflammation-Value for predicting the osteoradionecrosis rates in locally advanced nasopharyngeal cancers.

The aim of this retrospective study was to explore whether pretreatment Pan-Immune-Inflammation-Value (PIV) measurements might predict the risk of mandibular osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal cancer (LA-NPC). The platelet, monocyte, neutrophil, and lymphocyte counts acquired on the first day of CCRT were used to compute pretreatment PIV levels: PIV = (Platelets × Monocytes × Neutrophils) ÷ Lymphocytes. Receiver operating characteristic curve analysis was used to determine the association between ORN rates and PIV levels. Spearman correlation analysis was used to examine the probable intergroup correlations. The potential link between the pretreatment PIV levels and the post-treatment ORN rates was determined as the primary objective. 21 (10.0%) of 210 eligible patients were diagnosed with ORN. The optimal pre-CCRT PIV cutoff was 833, which separated patients into two PIV groups with divergent ORN prevalence estimates: Group1: PIV < 833 (N = 153), and Group2: PIV ≥ 833 (N = 57). The comparison analysis found that the PIV ≥ 833 cohort had significantly higher ORN rates than the PIV < 833 cohort (29.8% vs. 2.6%; P < 0.001). Other characteristics linked to significantly higher ORN rates were the patient's continuing smoking, the use of the Three-dimensional conformal radiation therapy technique, the mean mandibular dose of ≥ 58.1 Gy, the number of tooth extractions before CCRT ≥ 4, and the presence of tooth extractions after CCRT. The independent importance of all factors on higher ORN occurrence rates were retained in multivariate analysis (P < 0.05). Our findings revealed astrong link between aggravated inflammatory response and ORN genesis, with high pretreatment PIV levels related to significantly higher ORN rates.

Valero’s host index is useful in predicting radiation-induced trismus and osteoradionecrosis of the jaw risks in locally advanced nasopharyngeal carcinoma patients

BackgroundIn the absence of previous research, we sought to assess the H-Index’s predictive significance for radiation-induced trismus (RIT) and osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT).Patients and methodsThe research comprised 295 LA-NPC patients who had C-CRT and pre- and post-C-CRT oral exams between June 2010 and December 2021. The H-Index was calculated using neutrophils, monocytes, lymphocytes, hemoglobin, and albumin measurements obtained on the first day of C-CRT. Patients were divided into three and two H-index groups, respectively, based on previously established cutoff values (1.5 and 3.5) and the cutoff value determined by our receiver operating characteristic (ROC) curve analysis. The primary objective was the presence of any significant connections between pretreatment H-Index groups and post-C-CRT RIT and ORNJ rates.ResultsRIT and ORNJ was diagnosed in 46 (15.6%) and 13 (7.8%) patients, respectively. The original H-Index grouping could only categorize RIT and ORNJ risks at a cutoff value of 3.5, with no significant differences in RIT and ORNJ rates between groups with H-Index 1.5 and 1.5 to 3.5 (P < 0.05 for each). The ideal H-Index cutoff for both RIT and ORNJ rates was found to be 5.5 in ROC curve analysis, which divided the entire research population into two groups: H-Index ≤ 5.5 (N = 195) and H-Index > 5.5 (N = 110). Intergroup comparisons revealed that patients in the H-Index > 5.5 group had significantly higher rates of either RIT (31.8% vs. 5.9%; P < 0.001) or ORNJ (17.3% vs. 2.2%; P < 0.001) than their H-Index ≤ 5.5 counterparts. The results of the multivariate analysis showed that H-Index > 5.5 was independently linked to significantly higher RIT (P < 0.001) and ORNJ (P < 0.001) rates.ConclusionPre-C-CRT H-Index > 5.5 is associated with significantly increased RIT and ORNJ rates in LA-NPC patients receiving definitive C-CRT.

Nab-paclitaxel plus cisplatin versus docetaxel plus cisplatin and 5-FU induction chemotherapy followed by concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: A multicenter parallel controlled phase III trial.

6071 Background: Although several large phase III clinical trials and meta-analysis have demonstrated significant clinical benefit of docetaxel combined with cisplatin and 5-FU (TPF) chemotherapy in head and neck cancer, serious adverse reactions are unsatisfactory. Therefore, this study was designed to evaluate the efficacy and safety of nab-paclitaxel plus cisplatin (TP) versus TPF induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: In this open-label, phase 3 trial, patients were randomized 1:1 to received TP (260 mg/m2 nab-paclitaxel and 80 mg/m2 cisplatin on days 1 and 22) or TPF (60 mg/m2 docetaxel and 60 mg/m2 cisplatin on days 1 and 22; 3 g/m2 5-Fu on days 1-5 and 22-26) every 3 weeks for 2 cycles, both groups of patients received CCRT (100mg/m2 cisplatin and IMRT on days 43 and 64) every 21 days for 2 cycles. The primary endpoint was failure-free survival. Secondary endpoints included overall survival, objective response rate (ORR), quality of life and safety. Results: From January 2019 to July 2021, 281 patients were randomized to TP (n = 142, TP arm) or TPF (n = 139, TPF arm). The median age was 44 years (range, 20-63) in the TP arm and 45 years (range, 18-69) in the TPF arm. The pathological stages were 40.85% stage III and 59.15% stage IVA in the TP arm, while those of the TPF arm were 43.17% stage III and 56.83% stage IVA. There were 99.30% and 97.12% undifferentiated nonkeratinizing carcinoma in the two groups, respectively. All patients had Karnofsky performance status of 90. ICT was completed in 98.93% (100% in the TP arm and 97.84% in the TPF arm). The median relative dose intensity of nab-paclitaxel and cisplatin were 99.96% and 99.81% in the TP arm, 99.83%, 100% and 100% for docetaxel, cisplatin and 5-FU in the TPF arm, respectively. The ORR were 80.28% in the TP arm and 78.26% in the TPF arm after two cycles of ICT. 85.77% (83.10% in the TP arm and 88.49% in the TPF arm) completed the CCRT. After two cycles of CCRT, the ORR were 99.25% and 99.24%, respectively. 3 months after completion of all treatment, the ORR were 99.25% and 99.25%, respectively. During ICT, all treatment-related adverse events occurred in 40.14% of patients in the TP arm and 57.55% in the TPF arm. The most frequent grade 3 adverse events were neutropenia (0.70% vs 2.16%), leucopenia (0 vs 2.88%), diarrhea (0 vs 0.72%) in the TP arm and in the TPF arm. Over the entire course of treatment, the most common was 1 grade adverse events, and no patient developed grade 4 adverse events in the two groups. Conclusions: In this study, TP regimen showed similar trends in the ORR but excellent safety profile in patients with LA-NPC compared with TPF regimen, suggesting a potential therapeutic option for this population. Clinical trial information: ChiCTR1800019922 .

Age is a significant biomarker for the selection of neoadjuvant chemotherapy plus radiotherapy versus concurrent chemoradiotherapy in patients with advanced nasopharyngeal carcinoma.

The optimal timing of combined chemotherapy with radiotherapy for locally advanced nasopharyngeal carcinoma (LA-NPC) is undetermined. This study aimed to compare the therapeutic efficacy of neoadjuvant chemotherapy (NACT) followed by radiotherapy (RT) and concurrent chemoradiotherapy (CCRT). Five hundred and thirty-eight patients diagnosed with LA-NPC and treated with NACT + RT or CCRT alone were enrolled in the study. Restricted cubic spline regression (RCS) was used to determine the relationship between age and the hazard Ratio of death. A Kaplan-Meier analysis was performed to evaluate overall survival (OS) related to NACT + RT or CCRT alone. Cox proportional hazards models were used to adjust for potential confounding factors. Compared with the CCRT alone regimen, the NACT + RT regimen showed a significantly better OS rate with a 62% decreased risk of death in a subgroup of patients aged ⩾ 45 years (hazard ratio, HR: 0.38; 95% confidence interval, CI: 0.24-0.61). In patients aged < 45 years, the risk of death was significantly increased when NACT + RT was chosen compared with CCRT (HR: 4.10; 95% CI: 2.09-8.07). Age is a significant biomarker when selecting NACT + RT or CCRT alone in patients with advanced NPC.

Low hemoglobin levels predict increased radiation-induced trismus rates in nasopharyngeal cancer.

To investigate the predictive significance of hemoglobin (Hb) values in the incidence of radiation-induced trismus (RIT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients who received concurrent chemoradiotherapy (C-CRT). Data of LA-NPC patients were examined before and after C-CRT and to confirm the presence of RIT, maximum mouth openings (MMO) were measured; RIT is defined as an MMO of ≤35 mm. All Hb values were derived from complete blood count tests obtained on the first day of C-CRT. The receiver operating characteristic (ROC) curve analysis was used to scrutinize a possible connection between pre-treatment Hb values and RIT status. Two hundred and twenty three patients were included in the study and RIT was diagnosed in 46 (20.6%) patients. The Hb cutoff in ROC curve analysis that separated the patients into two groups was 12.05 g/dL [Area under the curve (AUC): 82.7%; sensitivity: 72.9%; and specificity: 71.3%]. RIT was significantly more prevalent in the Hb ≤ 12 g/dL group than in its counterpart (41.9% vs. 7.3%; p < 0.001). In multivariate analysis, Hb ≤ 12, anemia, pre-C-CRT MMO < 41.4 mm, and masticatory apparatus doseV58 Gy < 32% groups were found to be independently associated with significantly increased rates of RIT. Low pre-C-CRT Hb and anemia status are novel biological markers that independently predict higher RIT rates in LA-NPC undergoing C-CRT.

The predictive value of pretreatment hemoglobin-to-platelet ratio on osteoradionecrosis incidence rates of locally advanced nasopharyngeal cancer patients managed with concurrent chemoradiotherapy

BackgroundThis retrospective study aimed to investigate whether the pretreatment hemoglobin-to-platelet ratio (HPR) could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (C-CRT) for locally advanced nasopharyngeal carcinoma (LA-NPC).MethodsORN cases were reported from the records of LA-NPC patients who had oral examinations before and after C-CRT. The pretreatment HPR values were calculated on the first day of C-CRT. The connection between HPR values and ORN occurrences was determined using receiver operating characteristic curve analysis. The primary endpoint was the relationship between the pretreatment HPR values and post-C-CRT ORN incidence rates, while secondary endpoints included the identification of other putative ORN risk factors.ResultsWe distinguished 10.9% incidences of ORN during the post-C-CRT follow-up period among 193 LA-NPC patients. The optimal cutoff for pre-C-CRT HPR was 0.48 that grouped the patients into two HPR groups with fundamentally different post-C-CRT ORN incidence rates: Group 1: HPR ≤ 0.48 (N = 60), and Group 2: HPR > 0.48 (N = 133). The comparative analysis indicated a significantly higher ORN incidence in HPR ≤ 0.48 group (30%; P < 0.001). The other factors associated with meaningfully increased ORN rates included the presence of pre-C-CRT ≥ 5 teeth extractions, mandibular volume receiving ≥ 64 Gy, post-C-CRT tooth extractions, mean mandibular dose ≥ 50.6 Gy, and C-CRT to tooth extraction interval > 5.5 months.ConclusionLow pretreatment HPR levels were independently and unequivocally linked to significantly increased incidence of ORN post-C-CRT. Pre-C-CRT HPR levels may be used to estimate the incidence of ORN and be useful for taking preventive and therapeutic measures in these patients such as monitoring oral hygiene with strict follow-up, avoidance of unnecessary tooth extractions, particularly after C-CRT, and use of more rigorous mandibular RT dose limits.

Pre-chemoradiotherapy low hemoglobin levels indicate increased osteoradionecrosis risk in locally advanced nasopharyngeal cancer patients.

We aimed to determine whether pretreatment hemoglobin (Hb) levels can predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal carcinoma (LA-NPC). ORN cases were identified from the records of LA-NPCs who had oral exams before and after CCRT. All Hb measurements were obtained on the first day of treatment. Receiving operating characteristic curve analysis was used to determine the relationship between Hb levels and ORN rates. The relationship between pretreatment Hb levels and ORN rates served as the primary endpoint, and secondary endpoints included the discovery of additional potential ORN risk factors. Among the 263 eligible LA-NPCs, we identified 8.7% ORN cases. The ideal cutoff Hb before CCRT was 10.6g/dL. It was revealed that HPR ≤ 10.6 group had a significantly higher ORN rate (32.5% vs. 1.5% for Hb > 10.6; P < 0.001). The mandibular V59.8 ≥ 36% Gy, pre-CCRT ≥ 4 tooth extractions, the presence of post-CCRT tooth extractions, and the time of post-CCRT tooth extractions > 8months were the other factors associated with significantly increased ORN rates (P < 0.05 for each). Low pre-CCRT Hb levels appeared to be independently linked to significantly higher ORN rates. Pretreatment Hb levels may be used to establish preventive measures and predict ORN.

Assessment of Response to Different Induction Chemotherapy Regimens in Locally Advanced Nasopharyngeal Carcinoma.

To compare the short-term treatment response and survival of the three induction chemotherapy (IC) regimens, including gemcitabine and cisplatin (GP), docetaxel and cisplatin (TP), and docetaxel, cisplatin, and fluoropyrimidines (TPF) in locally advanced nasopharyngeal carcinoma (LANPC). We included stage III-IVA NPC patients who received ≥3 cycles of IC in this study. The chi-square test, multivariate logistic regression analysis, and Kaplan-Meier method were used for statistical analysis. A total of 227 patients were included. The overall response rate (ORR) of the primary nasopharyngeal tumors after IC with GP, TP, and TPF was 91.9%, 83.8%, and 91.7%, respectively (P=0.729), and the ORR of the cervical lymph nodes was 94.6%, 72.3%, and 85.0%, respectively (P<0.001). For the primary nasopharyngeal tumor, there was no significant difference in the ORR among the three IC regimens. For cervical lymph nodes, patients treated with GP had significantly higher ORR compared to those treated with the TP regimen (P=0.014), and comparable ORR was found between TPF and GP regimens (P=0.161). Similar progression-free survival (PFS) (P=0.501) and overall survival (OS) (P=0.504) were found among three IC regimens. There were comparable PFS (P=0.123) and OS (P=0.478) among those with complete response (CR), partial response (PR), and stable disease (SD)/progressive disease (PD) in the primary nasopharyngeal tumors. However, patients who had CR in the primary nasopharyngeal tumor (P=0.014) and the cervical lymph nodes (P=0.022) had better PFS compared to those who had PR or SD/PD. GP and TPF regimens are equivalent to the TP regimen in the response to primary nasopharyngeal tumors after IC, but with better ORR in the cervical lymph nodes than the TP regimen. The response to IC may be a powerful indicator for predicting prognosis and developing individualized follow-up and treatment strategies for LANPC patients.