Development and validation of a nomogram for prediction of recovery from moderate-severe xerostomia post-radiotherapy in nasopharyngeal carcinoma patients.

PURPOSE: Aim to create and validate a comprehensive nomogram capable of accurately predicting the transition from moderate-severe to normal-mild xerostomia post-radiotherapy (postRT) in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We constructed and internally verified a prediction model using a primary cohort comprising 223 patients who were pathologically diagnosed with NPC from February 2016 to December 2019. LASSO regression model was used to identify the clinical factors and relevant variables (the pre-radiotherapy (XQ-preRT) and immediate post-radiotherapy (XQ-postRT) xerostomia questionnaire scores, as well as the mean dose (Dmean) delivered to the parotid gland (PG), submandibular gland (SMG), sublingual gland (SLG), tubarial gland (TG), and oral cavity). Cox proportional hazards regression analysis was performed to develop the prediction model, which was presented as a nomogram. The models' performance with regard to calibration, discrimination, and clinical usefulness was evaluated. The external validation cohort comprised 78 patients. RESULTS: Due to better discrimination and calibration in the training cohort, age, gender, XQ-postRT, and Dmean of PG, SMG, and TG were included in the individualized prediction model (C-index of 0.741 (95% CI:0.717 to 0.765). Verification of the nomogram's performance in internal and external validation cohorts revealed good discrimination (C-index of 0.729 (0.692 to 0.766) and 0.736 (0.702 to 0.770), respectively) and calibration. Decision curve analysis revealed that the nomogram was clinically useful. The 12-month and 24-month moderate-severe xerostomia rate was statistically lower in the SMG-spared arm (28.4% (0.230 to 35.2) and 5.2% (0.029 to 0.093), respectively) than that in SMG-unspared arm (56.8% (0.474 to 0.672) and 12.5% (0.070 to 0.223), respectively), with an HR of 1.84 (95%CI: 1.412 to 2.397, p = 0.000). The difference in restricted mean survival time for remaining moderate-severe xerostomia between the two arms at 24 months was 5.757 months (95% CI, 3.863 to 7.651; p = 0.000). CONCLUSION: The developed nomogram, incorporating age, gender, XQ-postRT, and Dmean to PG, SMG, and TG, can be used for predicting recovery from moderate-severe xerostomia post-radiotherapy in NPC patients. Sparing SMG is highly important for the patient's recovery.

A comparative study of functional MRI in predicting response of regional nodes to induction chemotherapy in patients with nasopharyngeal carcinoma.

Purpose: To identify and compare the value of functional MRI (fMRI) in predicting the early response of metastatic cervical lymph nodes (LNs) to induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients. Methods: This prospective study collected 94 metastatic LNs from 40 consecutive NPC patients treated with IC from January 2021 to May 2021. Conventional diffusion-weighted imaging, diffusion kurtosis imaging, intravoxel incoherent motion, and dynamic contrast-enhanced magnetic resonance imaging were performed before and after IC. The parameter maps apparent diffusion coefficient (ADC), mean diffusion coefficient (MD), mean kurtosis (MK), Dslow, Dfast, perfusion fraction (PF), Ktrans, Ve, and Kep) of the metastatic nodes were calculated by the Functool postprocessing software. All LNs were classified as the responding group (RG) and non-responding group (NRG) according to Response Evaluation Criteria in Solid Tumors 1.1. The fMRI parameters were compared before and after IC and between the RG and the NRG. The significant parameters are fitted by logistic regression analysis to produce new predictive factor (PRE)-predicted probabilities. Logistic regression analysis and receiver operating characteristic (ROC) curves were performed to further identify and compare the efficacy of the parameters. Results: After IC, the mean values of ADC, MD, and Dslow significantly increased, while MK, Dfast, and Ktrans values decreased dramatically, while no significant difference was detected in Ve and Kep. Compared with NRG, PF-pre and Ktrans-pre values in the RG were higher statistically. The areas under the ROC for the pretreatment PF, Ktrans, and PRE were 0.736, 0.722, and 0.810, respectively, with the optimal cutoff value of 222 × 10-4, 934 × 10-3/min, and 0.6624, respectively. Conclusions: The pretreatment fMRI parameters PF and Ktrans showed promising potential in predicting the response of the metastatic LNs to IC in NPC patients. Clinical Trial Registration: This study was approved by the ethics board of the Chinese PLA General Hospital, and registered on 30 January 2021, in the Chinese Clinical Trial Registry; http://www.chictr.org.cn/showproj.aspx?proj=121198, identifier (ChiCTR2100042863).

Sparing submandibular gland to alleviating acute xerostomia in patients with nasopharyngeal carcinoma treated with helical tomotherapy: Evaluation by diffusion kurtosis imaging.

PURPOSE: To identify the clinical significance of sparing submandibular glands (SMG) for the amelioration of acute xerostomia using diffusion kurtosis imaging (DKI) in nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT). MATERIALS AND METHODS: The prospective study enrolled 42 participants treated with HT. All patients underwent five times of DKI scans before HT (pre-HT), in the middle of the HT course (mid-HT), immediately after HT (post-HT), and 1 months (1m-HT), 3 months post-HT(3m-HT). Mean diffusion (MD) and mean kurtosis (MK) of SMG, parotid glands (PG) and sublingual glands (SLG), saliva flow rate measures under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire scores (XQ) were recorded. Comparisons between the SMG-spared and -unspared groups were analyzed using two-factor repeated-measures ANOVA for the group as the inter-subject factor and the time as the intra-subject factor. RESULTS: When sparing SMG, the dose of spared-SMG and ipsilateral SLG was lower compared to that of unspared glands (p < 0.001). MD of spared-SMG and ipsilateral SLG in SMG-spared group were lower than that of SMG-unspared group (the simple effect for the group, p-value at mid-HT, post-HT, 1m- and 3m-HT was 0.014, 0.011, 0.000 and 0.000, respectively), MK of spared-SMG was higher conversely (the main effect for the group, p < 0.001), while uSFR and sSFR were significantly lower in SMG-unspared group (the main effect for the group, p = 0.002, and p = 0.045, respectively). No significant differences were detected in MK of SLG, MD/MK of PG, and XQ between the two groups (the main effect for the group, p values were 0.9, 0.37, 0.15, 0.86, respectively). There were significant differences in the effect of the time for all MD/MK of the salivary glands and for uSFR, sSFR, and XQ between the SMG-spared and -unspared groups (p values were all <0.001). CONCLUSION: Sparing SMG is of great clinical significance in alleviating acute xerostomia for NPC patients treated by helical tomotherapy as evaluated by diffusion kurtosis imaging and saliva flow rate.

Response of Tonsil Follicular Dendritic Cell Sarcoma to Multimodal Treatment Including Pembrolizumab: A Case Report and Literature Review.

Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm that was classified by the World Health Organization (WHO) under histiocytic and dendritic cell neoplasms in the 2016 revision. Considering the rarity of this tumor, there is no standardized treatment. It is usually treated by complete surgical resection. Adjuvant chemotherapy and radiotherapy are alternative methods. Immune checkpoint inhibitors (ICIs) represented by the programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) antibody have achieved significant clinical benefits in a variety of solid tumors. However, reports on the treatment of FDCS with ICIs are rare. FDCS often expresses high levels of PD-L1, which provides a rationale to use immunotherapy in cases of FDCS. Here, we present a 51-year-old Filipino-Chinese man with FDCS who was treated with multimodal treatment, including the PD-1 inhibitor pembrolizumab and achieved a relatively long disease-free survival of 24 months. This case emphasizes that the application of ICIs under the guidance of NGS technology seems to be a meaningful treatment option for patients with FDCS.

[Clinical significance of tumor chemosensitivity assay in patients with head and neck cancer].

Objective:To evaluate the clinical significance of OncoDrug-Seq™ tumor gene detection in patients with head and neck malignancies. Methods:A retrospective analysis of 338 patients with locally advanced or unresectable head and neck malignancies admitted to the Department of Otorhinolaryngology Head and Neck Surgery, Chinese PLA General Hospital from April 2011 to February 2021. Among them, 301 patients were pathologically diagnosed as squamous cell carcinoma, 37 cases were non-squamous cell carcinoma. All patients underwent OncoDrug-Seq™ gene detection, combined with the test results and the treatment response after induction chemotherapy to evaluate whether to change the chemotherapy regimen, and to calculate the accuracy of the gene detection and the survival rate of the patient. Results:Among 301 patients with head and neck squamous cell carcinoma, the results of the drug sensitivity test were compared with the actual clinical response, the true positive rate（TP）, true negative rate（TN）, positive predictive value（PPV）, negative predictive value（NPV） and total predictive accuracy rates were 85.37%, 65.45%, 91.70%, 50.00% and 81.73%, respectively. For patients who changed chemotherapy regimen（TN+FP） and did not change（TP+FN）, the 5-year progression-free survival（PFS） was 63.45% and 80.58%（P<0.05）, respectively, the 5-year overall survival（OS） was 54.18% and 84.74%（P<0.05）. Among 37 patients with non-squamous cell carcinoma, the TP, TN, PPV, NPV and total predictive accuracy rates were 88.46%, 72.73%, 88.46%, 72.73%, and 83.78%, respectively. The 5-year PFS of the patients who changed（TN+FP） and did not change the treatment regimen（TP+FN） were 68.57% and 56.00%, and the 5-year OS was 69.26% and 48.72%, the difference was not statistically significant. Conclusion:OncoDrug-Seq™ testing has certain significance in guiding clinicians to formulate personalized chemotherapy regimens. Timely replacement of the treatment plan can enable the patient to obtain a more ideal curative effect. Compared with patients with squamous cell carcinoma, patients with non-squamous cell carcinoma can obtain greater survival benefit from this testing. However, there are still some deviations in the accuracy of the test results compared with the actual clinical situation. Therefore, the decision should be made based on the test results in combination with the clinical reality.

Multimodal Treatment With Orbital Organ Preservation in Adult Patients With Locally Advanced Small-Round-Cell Malignancy of the Nasal Cavity and Paranasal Sinus.

BACKGROUND: To investigate the efficacy of induction chemotherapy followed by concurrent chemotherapy and helical tomotherapy in adult patients with locally advanced small-round-cell malignancy of the nasal cavity and paranasal sinus in regard to orbital organ preservation and quality of life. METHODS: The clinical data of 49 patients with orbital involvement of locally advanced small-round-cell malignancy of the nasal cavity and paranasal sinus who received multimodal treatment for orbital organ preservation between December 2009 and January 2019 were retrospectively analyzed. Treatment efficacy and side effects were assessed. The study included three different pathological types. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy. Helical tomotherapy was applied as radiotherapy. Adverse reactions to the chemotherapy were assessed according to Common Terminology Criteria for Adverse Events, Version 3. The overall survival (OS) rate, progression-free survival (PFS) rate, and orbital preservation rate were calculated using the Kaplan-Meier method. RESULTS: After multimodal treatment, the 3- and 5-year OS rates of the 49 patients were 63.8% and 54.5%, respectively, and the 3- and 5-year total PFS rates were 66.8% and 63.1%, respectively. CONCLUSIONS: Multimodal treatment can preserve the orbital organs of adult patients with small-round-cell malignancy of the nasal cavity and paranasal sinus, achieve relatively ideal organ protection and survival rates, and improve quality of life, thus providing a new treatment option for these patients.

Induction and Regulation of the Immunoproteasome Subunit ß5i (PSMB8) in Laryngeal and Hypopharyngeal Carcinoma Cells.

BACKGROUND The ubiquitin-proteasome pathway (UPP) is closely associated with the occurrence and progression of cancer, and the 5i immunoproteasome subunit is an important antitumor target in UPP. This study aimed to characterize the regulation of the immunoproteasome subunit ß5i (PSMB8) in JHU-011 laryngeal carcinoma cells and FaDu hypopharyngeal carcinoma cells to explore a new target for the treatment of laryngeal and hypopharyngeal carcinomas. MATERIAL AND METHODS JHU-011 and FaDu cells were used as effector cells in this study. By means of 6°Co γ-irradiation, the construction of stable cell lines of the silenced proto-oncogene c-Abl, and the addition of exogenous tyrosine kinase inhibitor (TKI) and activator, the transcription and protein expression levels of PSMB8 and its alternatively spliced isoforms in both cell lines were detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and Western blot. RESULTS Ionizing radiation upregulated the transcription level of the alternatively spliced isoform of PSMB8, E2, in both cell lines, thereby upregulating the mRNA and protein levels of PSMB8. The silencing of the proto-oncogene c-Abl and the activation and inhibition of its kinetic kinase product can affect the transcription and protein levels of PSMB8. CONCLUSIONS Ionizing radiation can significantly upregulate the mRNA and protein levels of PSMB8, which happens through the upregulation of its splicing isoform E2. The proto-oncogene c-Abl and its kinetic kinase protein product can regulate the transcription and protein expression levels of PSMB8 and its alternatively spliced isoforms.

Clinical significance of circulating tumor cells in patients with locally advanced head and neck squamous cell carcinoma.

The present study aimed to investigate the clinical relevance of circulating tumor cells (CTCs) in patients with locally advanced head and neck squamous cell carcinoma (LA­HNSCC), particularly in patients with nasopharyngeal and hypopharyngeal squamous cell carcinoma. CTCs were isolated using negative immunomagnetic bead enrichment and were identified by fluorescence in situ hybridization. Youden's index and the receiver operating characteristic (ROC) curve were used to select the optimal CTC baseline value. χ2 test or Fisher's test were used to determine the association between CTC counts and clinical parameters, curative effects and prognosis. The Kaplan­Meier estimator was used to analyze overall survival (OS) and progression­free survival (PFS). In the present study, 356 peripheral blood samples (178 pretreatment samples and 178 post­treatment samples) from 178 patients were examined. The results revealed that the pretreatment CTC detection rate was 73.8%. The minimum, maximum and median CTC counts were 1, 22 and 2/3.2 ml, respectively. The number of polyploid CTCs was associated with distant metastasis (P=0.026). In addition, patients with undetectable CTCs, and decreasing or negative CTCs post­treatment tended to have a good prognosis (P<0.05). For nasopharyngeal squamous cell carcinoma, the PFS of patients with increased CTCs and CTCs ≥2/3.2 ml after treatment was significantly lower (P<0.05). For hypopharyngeal squamous cell carcinoma, it was suggested that CTCs with a cutoff value of 3 may be used to evaluate PFS and OS before and after treatment. In conclusion, CTCs may be used to monitor disease progression and the response to chemoradiotherapy for patients with LA­HNSCC. Furthermore, CTCs are a better predictor of the prognosis of hypopharyngeal squamous cell carcinoma than that of nasopharyngeal squamous cell carcinoma.

A clinical study of multimodal treatment for orbital organ preservation in locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinus.

OBJECTIVE: This study aimed to investigate the efficacy of induction chemotherapy followed by concurrent chemotherapy and helical tomotherapy in patients with T4b squamous cell carcinoma of the nasal cavity and paranasal sinus in regard to orbital organ preservation and quality of life. METHODS: Clinical data of 28 cases of patients with orbital involvement of T4b squamous cell carcinoma of the nasal cavity and paranasal sinus who received multimodal treatment for orbital organ preservation between May 2008 and September 2015 were retrospectively analysed. The treatment efficacy and side effects were assessed. The study included 18 male and 10 female patients. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy and/or epidermal growth factor receptor inhibitor. Helical tomotherapy was applied as radiotherapy. Adverse reactions to the chemotherapy were assessed according to Common Terminology Criteria for Adverse Events, Version 4. The overall survival rate, local control rate and rate of effective orbital preservation were calculated using the Kaplan-Meier method. RESULTS: All patients completed the planned chemotherapy, and 27 (96.4%) of the patients completed the planned radiotherapy cycle. After the multimodal treatment, the 3-year overall survival, local control rate and rate of effective orbital preservation of the patients were 59.2%, 80.2% and 77.8%, respectively. CONCLUSIONS: Multimodal treatment could preserve the orbital organs of patients with T4b squamous cell carcinoma of the nasal cavity and paranasal sinus, achieve relatively ideal organ protection and survival rates and improve the quality of life of patients with advanced squamous cell carcinoma of the nasal cavity and paranasal sinus, thus providing a new treatment option for these patients.

[Effective analysis of non-surgical combined treatments for laryngeal organ preservation in locally advanced laryngeal carcinoma].

OBJECTIVE: To evaluate the therapeutic effects, larynx preservation and adverse events of non-surgical combined treatments for laryngeal organ preservation in locally advanced laryngeal squamous cell carcinomas(SCCs). METHODS: Forty-six patients with locally advanced laryngeal carcinoma (T2-4, N0-N3) were treated individually with non-surgical combined treatments for larynx preservation (LP). These treatments included concurrent chemoradiotherapy (CCRT)(±epidermal growth factor receptor (EGFR) inhibitor), induction chemotherapy (ICT) followed by CCRT(± EGFR inhibitor), or concurrent radiotherapy and EGFR inhibitor. Radiation therapy was given to a total dose of 60-70 Gy. The Kaplan-Meier method was used to determine the overall survival. Side-effects were evaluated with the established Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. RESULTS: The average follow-up time was 31.8 months (range 6-95 months). All patients completed the planned radiotherapy without treatment breaks, and 45(97.8%) of 46 patients completed the planned chemotherapy.The 3-year and 5-year overall survival rates were 87.3%and 67.2%, respectively.The 5-year larynx preservation rate was 100.0%. The 3-year and 5-year progression free survival rates were 95.1% and 87.7%, respectively. The most common acute side effect in grade 3 was oropharyngeal mucositis. After treatment, tracheotomy was still required in 2 patients with glottis cancer for laryngeal edema or stenosis. No patient depended on a percutaneous gastrostomy and experienced speech impairment. CONCLUSION: Patients with locally advanced laryngeal cancer can be offered non-surgical combined treatments for laryngeal preservation and the high quality of life, showing a higher laryngeal preservation survival rate with minimal toxicities.

Safe dose reduction of steroid pre-medication for docetaxel in head and neck neoplasm treatment.

CONCLUSION: The results suggest that the rate of severe hypersensitivity reactions did not increase when the dexamethasone pre-medication dose was reduced to 11 mg prior to docetaxel infusion. OBJECTIVES: Dexamethasone is commonly used to prevent the adverse effects of docetaxel in head and neck neoplasm treatment. The recommended dexamethasone dose is 8 mg orally twice daily for 3 days for each injection of docetaxel. This pre-medication reduces the incidence of adverse effects to 1-2% of treated patients. However, many adverse events have been observed with long-term steroid use. In an attempt to balance the benefits and harms of steroid prophylaxis without affecting the safety of docetaxel, this study tried to reduce the duration and dose of dexamethasone. METHODS: In this study, a total of 336 patients underwent docetaxel-containing protocols (TP or TPF regimens) to treat head and neck neoplasms. Docetaxel was given in doses of 70 mg/m(2) once every 3 weeks. Dexamethasone (0.75 mg/tablet) pre-medication was given in different doses (45, 24, 18, and 11 mg); the minimum dose included 6 mg orally in the morning and 5 mg intravenously immediately before docetaxel infusion. RESULTS: Severe hypersensitivity reactions were experienced by none of 30 patients who received 45 mg (7.5 mg orally twice for 3 days) dexamethasone pre-medication in 125 cycles, none of 20 patients who received 24 mg (6 mg orally twice for 2 days) dexamethasone in 77 cycles, and none of 20 patients who received 18 mg (4.5 mg orally twice for 2 days) dexamethasone in 79 cycles. Three of 266 patients who received 11 mg dexamethasone in 1054 applications developed a severe hypersensitivity reaction with bronchospasm and hypotension, two of the 266 patients developed a severe rash, and four developed severe oedema.