Anlotinib reversed resistance to PD-1 inhibitors in recurrent and metastatic head and neck cancers: a real-world retrospective study.

Patients with recurrent or metastatic head and neck cancers (R/M HNCs) are prone to developing resistance after immunotherapy. This retrospective real-world study aims to investigate whether the addition of anlotinib can reverse resistance to PD-1 inhibitors (PD-1i) and evaluate the efficacy and safety of this combination in R/M HNCs. Main outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Potential biomarkers included PD-L1 expression, lipid index, and genomic profiling. Twenty-one patients with R/M HNCs were included, including 11 nasopharyngeal carcinoma (NPC), five head and neck squamous cell carcinoma (HNSCC), three salivary gland cancers (SGC), and two nasal cavity or paranasal sinus cancers (NC/PNC). Among all patients, ORR was 47.6% (95% CI: 28.6-66.7), with 2 (9.5%) complete response; DCR was 100%. At the median follow-up of 17.1 months, the median PFS and OS were 14.3 months (95% CI: 5.9-NR) and 16.7 months (95% CI:8.4-NR), respectively. The median DOR was 11.2 months (95% CI: 10.1-NR). As per different diseases, the ORR was 45.5% for NPC, 60.0% for HNSCC, 66.7% for SGC, and 50.0% for NC/PNC. Most treatment-related adverse events (TRAEs) were grade 1 or 2 (88.9%). The most common grades 3-4 TRAE was hypertension (28.6%), and two treatment-related deaths occurred due to bleeding. Therefore, adding anlotinib to the original PD-1i could reverse PD-1 blockade resistance, with a favorable response rate, prolonged survival, and acceptable toxicity, indicating the potential as a second-line and subsequent therapy choice in R/M HNCs.

Nomograms containing body dose parameters for predicting survival in patients with nasopharyngeal carcinoma.

PURPOSE: To assess the impact of body dose on survival outcomes in nasopharyngeal carcinoma (NPC) patients and to create novel nomograms incorporating body dose parameters for predicting survival. METHODS: 594 of non-metastasis NPC patients (training group, 396; validation group, 198) received intensity-modulated radiation therapy at our institution from January 2012 to December 2016. Patient characteristics, body dose parameters in dose-volume histogram (DVH) and hematology profiles were collected for predicting overall survival (OS) and progression-free survival (PFS). Nomograms for OS and PFS were developed using the selected predictors. Each nomogram was evaluated based on its C-index and calibration curve. RESULTS: Body dose-based risk score for OS (RSOS), N stage, age, and induction chemotherapy were independent predictors for OS, with a C-index of 0.784 (95% CI 0.749-0.819) in the training group and 0.763 (95% CI 0.715-0.810) in the validation group for the nomogram. As for PFS, the most important predictors were the body dose-based risk score for PFS (RSPFS), N stage, and induction chemotherapy. C-index of PFS nomogram was 0.706 (95% CI 0.681-0.720) in the training group and 0.691 (95% CI 0.662-0.711) in the validation group. The two models outperformed the TNM staging system in predicting outcomes. CONCLUSIONS: Body dose coverage is a useful predictor of prognosis in clinical routine patients. The novel nomograms integrating body dose parameters can precisely predict OS and PFS in NPC patients.

Radiation-induced nasopharyngeal ulcers after re-irradiation with intensity-modulated radiotherapy in locoregional recurrent nasopharyngeal carcinoma patients: a dose-volume-outcome analysis.

OBJECTIVE: To analyze the interrelation between radiation dose and radiation-induced nasopharyngeal ulcer (RINU) in locoregional recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: Clinical data were collected from 363 patients with locoregional recurrent NPC who received re-irradiated with definitive IMRT from 2009 to 2017. Twenty-nine patients were diagnosed with RINU. Univariate and multivariate analyses were used to re-evaluate the first and second radiotherapy plans and to identify predictive dosimetric factors. RESULTS: All dosimetric parameters were notably associated with the progression to RINU (p < 0.01) using paired samples Wilcoxon signed rank tests. Multivariate analysis showed that EQD2_ [Formula: see text]D80 (dose for 80 percent volume of the unilateral nasopharynx lesion) was an independent prognostic factor for RINU (p = 0.001). The area under the ROC curve for EQD2_ [Formula: see text]D80 was 0.846 (p < 0.001), and the cutoff point of 137.035 Gy could potentially be the dose tolerance of the nasopharyngeal mucosa. CONCLUSIONS: The sum of equivalent dose in 2 Gy fractions (EQD2) in the overlapping volumes between initial and re-irradiated nasopharyngeal mucosal tissue can be effective in predicting the hazard of developing RINU in NPC patients undergoing radical re­irradiation with IMRT and we propose a EQD2_ [Formula: see text]D80 threshold of 137.035 Gy for the nasopharynx.

Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy.

BACKGROUND: To review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT). METHODS: From April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28-30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0. RESULTS: Among the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153). CONCLUSION: Distant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.

Taxane/gemcitabine-containing chemotherapy plus locoregional IMRT for patients with de novo metastatic nasopharyngeal carcinoma: the treatment outcomes and prognostic factors analysis.

PURPOSE: To evaluate treatment outcomes of de novo metastatic nasopharyngeal carcinoma (mNPC) patients receiving taxane/gemcitabine-containing chemotherapy followed by locoregional intensity-modulated radiotherapy (IMRT) and analyze potential prognostic factors. METHODS: A total of 118 patients between March 2008 and November 2018 were retrospectively analyzed. All the patients were treated with taxane/gemcitabine-containing systemic chemotherapy followed by definitive locoregional IMRT. Potential prognostic factors including baseline absolute lymphocyte count (ALC) and the subdivision of metastasis were analyzed. RESULTS: The median follow-up time for the whole group was 31.5 months (range 5-138 months). Of the 118 patients, 9 (7.6%) patients experienced local regional failure and 60 (50.8%) patients had progression of distant metastasis. At the time of the last follow-up, 61 (51.7%) patients were dead. The 5-year actuarial progression free survival (PFS), overall survival (OS),distant metastasis relapse free survival (DMFS) and local regional recurrence free survival (LRFS) were 34.2%, 44%, 41.1% and 82.6%, respectively. Baseline lymphocyte count ≥ 1600/µl prior to the treatment conferred better locoregional control (5y-LRFS 96% vs. 64.7%, p < 0.001) and distant metastasis control (5y-MFS 50.4% vs. 32.4%, p = 0.023). The multivariate analysis showed that high lymphocyte count was the most relevant predictor of superior PFS (HR = 0.236, p < 0.001) and OS (HR = 0.518, p = 0.04). M subdivision was found as another independent prognostic factor for OS but not for PFS. CONCLUSION: Taxane/gemcitabine-containing chemotherapy combined with IMRT represents an effective treatment modality for mNPC. Baseline ALC is an independent significant prognostic factor for PFS and OS.

Long-Term Results of Intensity-Modulated Radiotherapy for T4 Nasopharyngeal Carcinoma: New Insight into the Value of Concurrent Chemotherapy.

The aim of the study was to report long-term results of intensity-modulated radiotherapy for patients with T4 classification nasopharyngeal carcinoma (NPC). From September 2007 to January 2013, 155 patients were retrospectively analyzed. The estimated 10-year local recurrent-free survival (LRFS), regional recurrent-free survival (RRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 79.4%, 93.2%, 69.0%, and 54.2%, respectively. Cycle number of chemotherapy was a significant predictor of LRFS, OS, and progression-free survival. There was no significant difference in survival rates between patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) and patients with IC plus IMRT and adjuvant chemotherapy (AC).

Clinical characteristics and prognosis of elderly nasopharyngeal carcinoma patients receiving intensity-modulated radiotherapy.

PURPOSE: To evaluate the clinical characteristics and prognosis of elderly nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT). METHODS: From June 2008 to October 2014, 148 newly diagnosed non-metastatic elderly NPC patients (aged ≥ 70 years) receiving IMRT were recruited. Comorbid condition was evaluated using the age-adjusted Charlson Comorbidity Index (ACCI). Kaplan-Meier method was used to estimate survival rates and the differences were compared using log-rank test. Hazard ratio (HR) and the associated 95% confidence interval (CI) were calculated using Cox proportional hazard model by means of multivariate analysis. RESULTS: The median follow-up time was 66.35 months. Estimated OS rate at 5 years for the entire group was 61.8% (95% confidence interval [CI] 0.542-0.703). The 5-year OS rate of RT alone group was 58.4% (95% [CI] 0.490-0.696) compared with 65.2% (95% [CI] 0.534-0.796) in CRT group (p = 0.45). In patients receiving IMRT only, ACCI score equal to 3 was correlated with superior 5-year OS rate in comparison with higher ACCI score 62.1% (95% [CI] 0.510-0.766) to 48.5% (95% [CI] 0.341-0.689), respectively; p = 0.024). A 5-year OS rate of 63.1% (95% [CI] 0.537-0.741) was observed in patients younger than 75 years old compared with 57.5% (95% [CI] 0.457-0.723) in patients older (p = 0.026). Patients with early-stage disease (I-II) showed better prognosis than patients with advanced-stage (III-IV) disease (5-year OS, 72.3-55.4%, respectively; p = 0.0073). The Cox proportional hazards model suggested that age independently predicted poorer OS (HR, 1.07; 95%CI 1.00-1.15, p = 0.04). CONCLUSION: The survival outcome of patients aged ≥ 70 years receiving IMRT only was similar to chemoradiotherapy with significantly less acute toxicities. Among the population, age is significantly prognostic for survival outcomes.

The prognostic value of preoperative prognostic nutritional index in patients with hypopharyngeal squamous cell carcinoma: a retrospective study.

BACKGROUND: To analyze the prognostic value of preoperative prognostic nutritional index (PNI) in predicting the survival outcome of hypopharyngeal squamous cell carcinoma (HPSCC) patients receiving radical surgery. METHODS: From March 2006 to August 2016, 123 eligible HPSCC patients were reviewed. The preoperative PNI was calculated as serum albumin (g/dL) × 10 + total lymphocyte count (mm-3) × 0.005. These biomarkers were measured within 2 weeks prior to surgery. The impact of preoperative PNI on overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: Median value of 52.0 for the PNI was selected as the cutoff point. PNI value was then classified into two groups: high PNI (> 52.0) versus low PNI (≤ 52.0). Multivariate analysis showed that high preoperative PNI was an independent prognostic factor for better OS (P = 0.000), PFS (P = 0.001), LRFS (P = 0.005) and DMFS (P = 0.016). CONCLUSIONS: High PNI predicts superior survival in HPSCC patients treated with radical surgery. As easily accessible biomarkers, preoperative PNI together with the conventional TNM staging system can be utilized to enhance the accuracy in predicting survival and determining therapy strategies in these patients.

Long-term survival and late complications of intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma.

BACKGROUND: To evaluate the effectiveness and toxicities of intensity-modulated radiotherapy (IMRT) for locally recurrent nasopharyngeal carcinoma (NPC). METHODS: One hundred and eighty-four previously irradiated NPC patients with recurrent disease and re-irradiated by IMRT between February 2005 to May 2013 had been reviewed. The disease was re-staged I in 33, II in 27, III in 70 and IV in 54 patients. Seventy-five percent of the patients received cisplatin-based chemotherapy. RESULTS: The median survival time was 33 months. The 3-year actuarial rates of local recurrence-free survival (LRFS), distant metastases-free survival (DMFS), and overall survival (OS) rates were 85.1, 91.1, and 46.0%, respectively. About 53% of the patients experienced Grade 3-4 late toxicities. Forty-four patients died of massive hemorrhage of the nasopharynx caused by radiation induced mucosal necrosis. Multivariate analysis indicated that chemotherapy and time interval between initial radiotherapy and re-irradiation were independent predictors for DMFS. CONCLUSION: IMRT is an effective method for patients with locally recurrent NPC. Massive hemorrhage of the nasopharynx is the major sever late complication and also the leading cause of death. Early recurrence is negative factor for DMFS. Combination of chemotherapy can improve DMFS, but not for OS. Optimal salvage treatment strategies focusing on improvement of survival and minimization of late toxicities are warranted.

Prognostic values of hematological biomarkers in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.

PURPOSE: In this study, we evaluated the prognostic values of hematological biomarkers in primary nasopharyngeal carcinoma (NPC) patients receiving definitive intensity-modulated radiotherapy (IMRT). METHODS: There were 427 NPC patients enrolled between January 2010 and March 2013 at Fudan University Shanghai Cancer Center. Pre-treatment absolute neutrophil count (ANC), platelet count (APC), lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were collected as prognostic biomarkers. The Kaplan-Meier method and log-rank test were utilized to calculate progression-free survival (PFS) and overall survival (OS). The Cox proportional hazard models were applied to assess variables. RESULTS: ANC, APC and ALC were declined, while NLR and PLR were elevated significantly after therapy (P < 0.001 each). On multivariate analysis, pre-treatment NLR ≥ 2.32 was associated with shortened OS (P = 0.048) and PFS (P = 0.008), whereas PLR ≥ 123.0 was related with inferior OS (P = 0.032), yet it was not correlated with PFS (P = 0.161). CONCLUSIONS: High pre-treatment NLR and PLR indicated poor survival in NPC patients treated with IMRT-based therapy. As easily accessible and economically feasible biomarkers, NLR and PLR can be applied into clinical practice, in combination with current TNM staging, to design a more personalized treatment in these patients.

Outcome after intensity modulated radiotherapy for anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. We reviewed our recent clinical experience with intensity modulated radiotherapy (IMRT) combined with surgery and chemotherapy for the management of ATC. METHODS: 13 patients with ATC who were treated by IMRT in our institution between October 2008 and February 2011, have been analyzed. The target volume for IMRT was planned to include Gross tumor volume (GTV): primary tumor plus any N + disease (66 Gy/33 F/6.6 W), with elective irradiation of thyroid bed, bilateral level II through VI and mediastinal lymph nodes to the level of the carina (54-60 Gy). Seven patients received surgical intervention and eleven patients had chemotherapy. RESULTS: The median radiotherapy dose to GTV was 60 Gy/30 fractions/6 weeks. The median survival time of the 13 patients was 9 months. The direct causes of death were distant metastases (75%) and progression of the locoregional disease (25%). Ten patients were spared dyspnea and tracheostomy because their primary neck lesion did not progress. CONCLUSION: The results showed that IMRT combined by surgery and chemotherapy for ATC might be beneficial to improve locoregional control. Further new therapies are needed to control metastases.

Preliminary results of nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: a retrospective study of 364 patients.

The aim of the study was to evaluate the survival and toxicity of 364 patients with nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). Cisplatin-based chemotherapy was given to patients with local-regionally advanced disease. The median follow-up was 26 months (range 3-62 months). The 2-year local failure-free survival, regional failure-free survival (RFFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 97.6, 96.8, 89.1 and 93.5 %, respectively. Overall disease failures (at any site) were found in 60 patients. Eighteen patients experienced locoregional failures: seven were local only, seven were regional only and four were both local and regional. Forty-two patients developed distant metastases. Of these, 30 patients had single organ metastasis and 12 had multiple organ metastases. The most common acute toxicities were dermatitis, mucositis and xerostomia. Grade 0-2 dermatitis, mucositis and xerostomia occurred in 337 patients (92.6 %), 204 patients (56.1 %) and 364 patients (100 %), respectively. Grade 3 dermatitis, mucositis and xerostomia were seen in 27 patients (7.4 %), 160 patients (44 %) and 0 patients. No Grade 4 acute toxicities were observed. N stage was an independent prognostic factor for RFFS, DMFS and OS. Our preliminary results showed that IMRT provides excellent local-regional control for NPC, with acceptable acute toxicities. Distant metastasis remains the most difficult treatment challenge. More effective systemic chemotherapy should be explored.

Multiply-mesoporous hydrophilic titanium dioxide nanohybrid for the highly-performed enrichment of N-glycopeptides from human serum.

N-glycopeptide is considered as one of significant biomarkers which provide guidance for the diagnosis and drug design of diseases. However, the direct analysis of N-glycopeptides is nearly impracticable mainly owing to their extremely low abundance and grave signal suppression from other interfering substances in the bio-samples. In this research, a multiply-mesoporous hydrophilic TiO2 nanohybrid (mM-TiO2@Cys) was synthesized by immobilizing Cys on a TiO2 substrate with hierarchical mesopores to achieve the highly-performed enrichment of N-glycopeptides. With the advantages of superior hydrophilicity and multiply-mesoporous structure, the obtained material exhibited an excellent selectivity (IgG digests and BSA digests at the molar ratio of 1/500), a high sensitivity (1 fmol µL-1 for IgG digests) and a good size-exclusion ability (IgG digests, IgG and BSA at the molar ratio of 1/500/500) in the enrichment of N-glycopeptides from IgG digests. As a result, 281 N-glycopeptides corresponded with 109 glycoproteins were identified from 2 µL serum digests of the patients with nasopharyngeal carcinoma, and 181 N-glycopeptides corresponded with 78 glycoproteins were identified from 2 µL serum digests of the healthy volunteers, revealing the potential application value of mM-TiO2@Cys in glycoproteomics.

Prognostic value of lymph node-to-primary tumor ratio of PET standardized uptake value for nasopharyngeal carcinoma: a recursive partitioning risk stratification analysis.

Background: Induction chemotherapy (IC) combined with concurrent chemoradiotherapy has become the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Data on the prognostic value of the lymph node-to-primary tumor ratio (NTR) of positron emission tomography (PET) standardized uptake value (SUV) for patients treated with IC were limited. Objectives: To evaluate the prognostic value of the SUV NTR for patients with LA-NPC treated with IC. Design: In all, 467 patients with pretreatment 18F-fluorodeoxyglucose PET/computed tomography (CT) scans between September 2017 and November 2020 were retrospectively reviewed. Methods: The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value of SUV NTR. Kaplan-Meier method was used to evaluate survival rates. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. Results: The optimal cutoff value of SUV NTR was 0.74. Multivariate analyses showed that SUV NTR and overall stage were independent predictors for distant metastasis-free survival (DMFS) and regional recurrent-free survival (RRFS). Therefore, an RPA model based on the endpoint of DMFS was generated and categorized the patients into three distinct risk groups: RPA I (low risk: SUV NTR < 0.74 and stage III), RPA II (medium risk: SUV NTR < 0.74 and stage IVa, or SUV NTR ⩾ 0.74 and stage III), and RPA III (high risk: SUV NTR ⩾ 0.74 and stage IVa), with a 3-year DMFS of 98.9%, 93.4%, and 84.2%, respectively. ROC analysis showed that the RPA model had superior predictive efficacy than the SUV NTR or overall stage alone. Conclusion: SUV NTR was an independent prognosticator for distant metastasis and regional recurrence in locoregionally advanced NPC. The RPA risk stratification model based on SUV NTR provides improved DMFS and RRFS prediction over the eighth edition of the TNM (Tumor Node Metastasis) staging system.

Delta magnetic resonance imaging radiomics features­based nomogram predicts long­term efficacy after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: To establish and validate a delta-radiomics-based model for predicting progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) following induction chemotherapy (IC). METHODS AND MATERIALS: A total of 250 LA-NPC patients (training cohort: n = 145; validation cohort: n = 105) were enrolled. Radiomic features were extracted from MRI scans taken before and after IC, and changes in these features were calculated. Following feature selection, a delta-radiomics signature was constructed using LASSO-Cox regression analysis. A prognostic nomogram incorporating independent clinical indicators and the delta-radiomics signature was developed and assessed for calibration and discrimination. Risk stratification by the nomogram was evaluated using Kaplan-Meier methods. RESULTS: The delta-radiomics signature, consisting of 12 features, was independently associated with prognosis. The nomogram, integrating the delta-radiomics signature and clinical factors demonstrated excellent calibration and discrimination. The model achieved a Harrell's concordance index (C-index) of 0.848 in the training cohort and 0.820 in the validation cohort. Risk stratification identified two groups with significantly different PFS rates. The three-year PFS for high-risk patients who received concurrent chemoradiotherapy (CCRT) or radiotherapy plus adjuvant chemotherapy (RT+AC) after IC was significantly higher than for those who received RT alone, reaching statistical significance. In contrast, for low-risk patients, the three-year PFS after IC was slightly higher for those who received CCRT or RT+AC compared to those who received RT alone; however, this difference did not reach statistical significance. CONCLUSIONS: Our delta MRI-based radiomics model could be useful for predicting PFS and may guide subsequent treatment decisions after IC in LA-NPC.

Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial.

PURPOSE: The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitor in locally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: This is a single-arm phase II study. Patients with histopathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and Eastern Cooperative Oncology Group Performance Status 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175 mg/m2 d1, cisplatin 25 mg/m2 d1-3) combined with PD-1 inhibitor (toripalimab 240 mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with a complete/partial response of the primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo) radiation and maintenance therapy of toripalimab. The primary endpoint is a larynx preservation rate at 3 months postradiation. RESULTS: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy because of impaired larynx function. Overall response rate of induction chemoimmunotherapy was 85.2%. At 3 months postradiation, the larynx preservation rate was 88.9%. With a median follow-up of 18.7 months, the 1-year overall survival rate, progression-free survival rate, and larynx preservation rate were 84.7%, 77.6%, and 88.7%, respectively. When excluding those with pretreatment tracheostomy, the 1-year larynx preservation rate was 95.5%. Exploratory analysis revealed that relapse correlated with enrichment of RNA signature of hypoxia and M2 macrophage-associated genes. CONCLUSIONS: Induction toripalimab combined with chemotherapy provided encouraging activity, promising larynx preservation rate and acceptable toxicity in this cohort of extensively locally advanced laryngeal and hypopharyngeal cancer.

Experience with combination of docetaxel, cisplatin plus 5-fluorouracil chemotherapy, and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: Our aim was to evaluate the efficacy and toxicity of cisplatin, fluorouracil, and docetaxel chemotherapy plus intensity-modulated radiotherapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with locoregionally advanced NPC were enrolled. Patients received IMRT plus three courses of neoadjuvant chemotherapy and two courses of adjuvant chemotherapy consisting of docetaxel (60 mg/m(2)/day on day 1), cisplatin (25 mg/m(2)/day on days 1-3), and 5-fluorouracil (500 mg/m(2)/day on days 1-3). RESULTS: The overall response rate to neoadjuvant chemotherapy was 89 %. Three months after the completion of radiotherapy, 53 (93 %) patients achieved complete regression, 3 (5 %) achieved partial response (PR), and 1 experienced liver metastasis. However, among the 3 PR patients, 2 patients had no evidence of relapse in the follow-up. With a median follow-up of 27 months (range, 6-43), the 2-year estimated locoregional failure-free survival, distant failure-free survival, progression-free survival, and overall survival were 96.6, 93.3, 89.9, and 98.3 %, respectively. Leukopenia was the main adverse effect in chemotherapy; 14 patients experienced grade 3 or grade 4 neutropenia, and 1 patient developed febrile neutropenia. The nonhematological adverse events included alopecia, nausea, vomiting, anorexia, and diarrhea. The incidence of grade 3 acute radiotherapy-related mucositis was 28.3 %; no grade 4 acute mucositis was observed. No grade 3 or grade 4 hematological toxicity occurred during radiotherapy. None of the patients had interrupted radiotherapy. The common late adverse effects included xerostomia and hearing impairment. CONCLUSIONS: Neoadjuvant-adjuvant chemotherapy using cisplatin, fluorouracil, plus docetaxel combined with IMRT was an effective and well-tolerated alternative for advanced NPC.

Magnetic resonance sialography for investigating major salivary gland duct system after intensity-modulated radiotherapy of nasopharyngeal carcinoma.

BACKGROUND: We investigated the value of magnetic resonance sialography for evaluating xerostomia induced by intensity-modulated radiotherapy for nasopharyngeal carcinoma. METHODS: Fourteen patients with nasopharyngeal carcinoma were treated with intensity-modulated radiotherapy. Salivary function was assessed by magnetic resonance sialography and subjective evaluation criteria pre-treatment, 1 week and 1 year post-radiotherapy. A magnetic resonance sialography categorical scoring system was used to compare the visibility of salivary ducts. RESULTS: The average mean dose was 38.93 Gy to the parotid glands and 59.34 Gy to the submandibular glands. Before radiotherapy, the visibility scores of both the parotid and submandibular ducts increased after secretion stimulation. The scores decreased and the response to stimulation was attenuated 1 week post-radiotherapy. For most of the parotid ducts, the visibility score improved at 1 year post-radiotherapy both at rest and under stimulation, but not for the submandibular ducts. With a median follow-up of 12.3 months, 8/12 patients had grade 1 xerostomia and 4/12 had grade 2 xerostomia. CONCLUSIONS: Magnetic resonance sialography allows non-invasive evaluation of radiation-induced ductal changes in the major salivary glands and enables reliable prediction of radiation-induced xerostomia.

Radiotherapy Alone Versus Concurrent or Adjuvant Chemoradiotherapy for Nasopharyngeal Carcinoma Patients with Negative Epstein-Barr Virus DNA after Induction Chemotherapy.

The purpose of this study was to compare the efficacy and toxicity of induction chemotherapy (IC) plus radiotherapy (RT) and IC plus concurrent or adjuvant chemoradiotherapy (CCRT/AC) in nasopharyngeal carcinoma (NPC) patients with negative Epstein-Barr virus DNA (EBV DNA) after IC. A total of 547 NPC patients with negative plasma EBV DNA post-IC were included. Patients were classified into the IC + RT group and the IC + CCRT/AC group. Locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS) were estimated and compared using the Kaplan-Meier method. Propensity score matching (PSM) was performed to balance the variables. The median follow-up time was 37 months. The 3-year LRFS, DMFS, OS, and PFS rates for the whole group were 92.2%, 92.4%, 96.4%, and 84.4%, respectively. There was no significant difference in LRFS, DMFS, OS, and PFS between the IC + RT and the IC + CCRT/AC groups, both before PSM (3-year rates of 91.1% vs. 92.6%, p = 0.94; 95.6% vs. 91.5%, p = 0.08; 95.2% vs. 96.8%, p = 0.80; 85.9% vs. 84.0%, p = 0.38) and after PSM (90.7% vs. 92.7%, p = 0.77; 96.8% vs. 93.7%, p = 0.29; 94.5% vs. 93.9%, p = 0.57; 84.7% vs. 85.6%, p = 0.96). Multivariate analysis demonstrated that the treatment schedule was not an independent predictor for survival rates. Patients in the IC + RT group had fewer treatment-related acute toxicities and better tolerance. IC + RT displayed similar survival outcomes as IC + CCRT/AC for NPC patients with negative post-IC EBV DNA.

Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides.

The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. In this work, a facile and timesaving route was introduced in which COFTP-TAPT served as a carrier and poly (ethylenimine) (PEI) and carrageenan (Carr) were successively coated on the surface via electrostatic interaction. The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol µL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 µL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 22 glycopeptides were identified only from the normal controls and 53 glycopeptides were detected only from the other set. The results demonstrated that this hydrophilic material was promising on a large scale and further N-glycoproteome research.