Locally Advanced Nasopharyngeal Carcinoma Research Articles

Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study

Background and PurposeTo investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC).MethodsA total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated.ResultsThe median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively.ConclusionsPatients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

Impact of chrono-radiotherapy on the prognosis and treatment-related toxicity in patients with locally advanced nasopharyngeal carcinoma: A multicenter propensity-matched study

ABSTRACT The timing of radiotherapy (RT) delivery has been reported to affect both cancer survival and treatment toxicity. However, the association among the timing of RT delivery, survival, and toxicity in locally advanced nasopharyngeal carcinoma (LA-NPC) has not been investigated. We retrospectively reviewed patients diagnosed with LA-NPC who received definitive RT at multiple institutions. The median RT delivery daytime was categorized as morning (DAY) and night (NIGHT). Seasonal variations were classified into the darker half of the year (WINTER) and brighter half (SUMMER) according to the sunshine duration. Cohorts were balanced according to baseline characteristics using propensity score matching (PSM). Survival and toxicity outcomes were evaluated using Cox regression models. A total of 355 patients were included, with 194/161 in DAY/NIGHT and 187/168 in WINTER/SUMMER groups. RT delivered during the daytime prolonged the 5-year overall survival (OS) (90.6% vs. 80.0%, p = 0.009). However, the significance of the trend was lost after PSM (p = 0.068). After PSM analysis, the DAY cohort derived a greater benefit in 5-year progression-free survival (PFS) (85.6% vs. 73.4%, p = 0.021) and distant metastasis-free survival (DMFS) (89.2% vs. 80.8%, p = 0.051) in comparison with the NIGHT subgroup. Moreover, multivariate analysis showed that daytime RT was an independent prognostic factor for OS, PFS, and DMFS. Furthermore, daytime RT delivery was associated with an increase in the incidence of leukopenia and radiation dermatitis. RT delivery in SUMMER influenced only the OS significantly (before PSM: p = 0.051; after PSM: p = 0.034). There was no association between toxicity and the timing of RT delivery by season. In LA-NPC, the daytime of radical RT served as an independent prognostic factor. Furthermore, RT administered in the morning resulted in more severe toxic side effects than that at night, which needs to be confirmed in a future study.

Addition of nimotuzumab to concurrent chemoradiotherapy after induction chemotherapy improves outcomes of patients with locally advanced nasopharyngeal carcinoma.

To investigate the survival outcomes and toxicities associated with the addition of nimotuzumab to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LANPC) patients who received induction chemotherapy (IC). Patients with stage III-IVA nasopharyngeal carcinoma who received IC and CCRT between January 2017 and October 2021 were retrospectively included. We aimed to compare the locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) between patients treated with CCRT+nimotuzumab and CCRT alone. We included 411 patients in the analysis. Of these patients, 267 (65.0%) and 144 (35.0%) had CCRT+nimotuzumab and CCRT alone, respectively. Similar LRFS was found between those with and without nimotuzumab (92.9% vs. 92.6%, p = 0.855). The 3-year DMFS was 88.2% and 76.2% in those with and without nimotuzumab (p = 0.002). The 3-year DFS was 83.4% and 70.6% in those with and without nimotuzumab treatment (p = 0.003). The 3-year OS was 92.1% and 81.1% in those with and without nimotuzumab (p = 0.003). The multivariate Cox regression analysis indicated that the addition of nimotuzumab was independently associated with better DMFS (hazard ratio [HR] 0.606, p = 0.049), DFS (HR 0.613, p = 0.028), and OS (HR 0.497, p = 0.019). No significant differences in major toxicities were found between the two treatment arms, including hematologic toxicities, hepatoxicity, nephrotoxicity, gastrointestinal reactions, and mucositis (all p > 0.05). The addition of nimotuzumab to CCRT after IC in LANPC has shown promising results in improving treatment outcomes and acceptable toxicities.

Pre-chemoradiotherapy high platelet counts predict jaw osteoradionecrosis in locally advanced nasopharyngeal carcinoma patients

IntroductionThis retrospective study aimed to investigate if pretreatment platelet (PLT) levels can predict the risk of osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) who received concurrent chemoradiotherapy (CCRT). Material &MethodsORNJ instances were identified from LA-NPC patients' pre- and post-CCRT oral exam records. All pretreatment PLT values were acquired on the first day of CCRT. Receiver operating characteristic curve analysis was used to determine the optimal PLT cutoff that divides patients into two subgroups with distinctive ORNJ rates. The primary outcome measure was the association between pretreatment PLT values and ORNJ incidence rates. ResultsThe incidence of ORNJ was 8.8 % among the 240 LA-NPC patients analyzed. The ideal pre-CCRT PLT cutoff which divided the patients into two significantly different ORNJ rate groups was 285,000 cells/µL (PLT ≤ 285,000 cells/µL (N = 175) vs. PLT > 285,000 cells/µL (N = 65)). A comparison of the two PLT groups revealed that the incidence of ORNJ was substantially higher in patients with PLT > 285,000 cells/L than in those with PLT≤285,000 cells/L (26.2% vs. 2.3 %; P < 0.001). The presence of pre-CCRT ≥3 tooth extractions, any post-CCRT tooth extractions, mean mandibular dose ≥ 34.1 Gy, mandibular V57.5 Gy ≥ 34.7 %, and post-CCRT tooth extractions > 9 months after CCRT completion were also associated with significantly increased ORNJ rates. A multivariate Cox regression analysis demonstrated that each characteristic had an independent significance on ORNJ rates after CCRT. ConclusionAn affordable and easily accessible novel biomarker, PLT> 285,000 cells/L, may predict substantially higher ORNJ rates after definitive CCRT in individuals with LA-NPC.

Prediction of severe radiation-induced oral mucositis in locally advanced nasopharyngeal carcinoma using the combined systemic immune-inflammatory index and prognostic nutritional index.

Severe radiation-induced oral mucositis (sRIOM) can seriously affect patients' quality of life and treatment compliance. This study was to investigate the utility of the systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) in predicting sRIOM in patients with locally advanced nasopharyngeal carcinoma (LANPC). 295 patients with LANPC were retrospectively screened. The pre-radiotherapy SII and PNI were calculated based on peripheral blood samples. A receiver operating characteristic (ROC) curve was used to determine the cut-off value. Logistic regression was used for univariate and multivariate analyses. Patients were classified into three groups based on the SII-PNI score: score of 2, high SII (> cut-off value) and low PNI (≤ cut-off value); score of 1, either high SII or low PNI; score of 0, neither high SII nor low PNI. The SII-PNI demonstrated significant predictive ability for sRIOM occurrence, as evidenced by an area under the curve (AUC) of 0.738. The incidence rates of sRIOM with SII-PNI score of 2, 1, and 0 were 73.86%, 44.35%, and 18.07%, respectively. Multivariate analysis confirmed that the SII-PNI score was an independent risk factor for sRIOM. The SII-PNI score is a reliableand convenient indicator for predicting sRIOM in patients with 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.

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.

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.