Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

High proportion of circulating CD8 + CD28- senescent T cells is an independent predictor of distant metastasis in nasopharyngeal canrcinoma after radiotherapy.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a kind of epithelial carcinoma that is common in East and Southeast Asia. Distant metastasis after radiotherapy remains the main cause of treatment failure and preradiotherapy immune system function can influence prognosis. Our study aimed to identify immune-related prognostic factors for NPC after radiotherapy and establish a prognostic model to predict progression-free survival (PFS) and distant metastasis-free survival (DMFS). METHODS: We enrolled NPC patients and divided them into training and validation cohorts with follow-up. We collected clinical information and investigated immune cells, EBV DNA and cytokines in the peripheral blood of NPC patients before radiotherapy and EBV DNA after radiotherapy. Among these immune cells, we included CD8+CD28- T cells, which are a unique T-cell immunosenescent subset that increases in human peripheral blood with increasing age and declining immune function. Based on the detection results and clinical information, we utilized Cox regression and least absolute shrinkage and selection operator (LASSO) regression to screen the PFS and DMFS prognostic factors and build nomograms to predict the PFS and DMFS of NPC. We also verified the results in the validation set. RESULTS: Three factors associated with PFS were selected: proportion of CD8+CD28- T cells posttreatment EBV and N stage. Three factors associated with DMFS were screened: proportion of CD8+CD28- T cells, posttreatment EBV and N stage. CD8+CD28- T cells are correlated with systemic inflammation and posttreatment immunosuppression. The C-indexes were 0.735 and 0.745 in the training and validation cohorts for predicting PFS. For DMFS, the C-indexes were 0.793 and 0.774 in the training and validation cohorts. CONCLUSIONS: The pretreatment proportion of CD8+CD28- T cells is a candidate prognostic biomarker for NPC after radiotherapy. The constructed nomogram models based on CD8+CD28- T cells have good predictive value.

Involved site radiation therapy in stage I-III nasopharyngeal carcinoma with limited lymph node burden (ISRT-NPC) or elective region irradiation: a study protocol for a multicenter non-inferiority randomized controlled phase III clinical trial.

BACKGROUND: Current radiotherapy guidelines and consensus statements uniformly recommend elective region irradiation (ERI) as the standard strategy for nasopharyngeal carcinoma (NPC). However, given the scarcity of skip-metastasis, the improved assessment accuracy of nodal involvement, and the striking advancements in chemotherapy for NPC, a one-fits-all delineation scheme for clinical target volumes of the nodal region (CTVn) may not be appropriate anymore, and modifications of the CTVn delineation strategy may be warranted. Involved site irradiation (ISI) covering merely the initially involved nodal site and potential extranodal extension has been confirmed to be as effective as ERI with decreased radiation-related toxicities in some malignancies, but has not yet been investigated in NPC. This study aims to compare the regional control, survival outcomes, radiation-related toxicities, and quality of life (QoL) of ISI with conventional ERI in NPC patients with a limited nodal burden. METHODS: ISRT-NPC is a prospective, multicenter, open-label, noninferiority, phase III randomized controlled trial. A total of 414 patients will be randomly assigned in a 1:1 ratio to receive ISI or ERI. Randomization will be stratified by institution scale and N stage. Generally, in the ISI group, the high-risk CTV1 (dose: 60 Gy) includes a 1-cm expansion of the positive LN as well as the VIIa and the retrostyloid space above the bilateral transverse process of the atlantoaxial spine (C1), regardless of N status. The low-risk CTV2 (dose: 50 Gy) covers the cervical nodal region with a 3-cm caudal expansion below the transverse process of C1 for N0 disease and a 3-cm expansion below the positive LN for positive LNs. DISCUSSION: The results of this trial are expected to confirm that ISI is a non-inferior strategy to ERI in stage I-III patients with low LN burden, enabling the minimization of treatment-related toxicity and improvement of long-term QoL without compromising regional control. TRIAL REGISTRATION: ClinicalTrails.gov, NCT05145660. Registered December 6, 2021.

CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma.

BACKGROUND: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it's role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. METHODS: In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. RESULTS: As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05). CONCLUSION: In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.

Antiemetic prophylaxis for chemoradiotherapy-induced nausea and vomiting in locally advanced head and neck squamous cell carcinoma: a prospective phase II trial.

BACKGROUND: There is sparse research reporting effective interventions for preventing nausea and emesis caused by concurrent chemoradiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). METHODS: Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100 mg/m2 (33 mg/m2/days [d]1-3) every 3 weeks for two cycles. All patients were given oral aprepitant 125 mg once on d1, then 80 mg once on d2-5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8 mg on d2-5. The primary endpoint was complete response (CR). Pursuant to δ = 0.2 and α = 0.05, the expected CR rate was 80%. RESULTS: A total of 43 patients with LA-HNSCC were enrolled. The median age was 53 years, and 86.0% were male. All patients received radiotherapy and 86.0% of patients completed both cycles as planned. The overall CR rate was 86.0% (95% confidence interval [CI]: 72.1-94.7). The CR rates for cycles 1 and 2 were 88.4% (95% CI: 74.9-96.1) and 89.2% (95% CI: 74.6-97.0). The complete protection rate in the overall phase was 72.1% (95% CI: 56.3-84.7). The emesis-free and nausea-free responses in the overall phase were 88.4% (95% CI: 74.9-96.1) and 60.5% (95% CI: 44.4-75.0), respectively. The adverse events related to antiemetics were constipation (65.1%) and hiccups (16.3%), but both were grade 1-2. There was no grade 4 or 5 treatment-related toxicity with antiemetic usage. CONCLUSION: The addition of aprepitant into ondansetron and dexamethasone provided effective protection from nausea and emesis in patients with LA-HNSCC receiving radiotherapy and concomitant high-dose cisplatin chemotherapy.

Induction TPF followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locally advanced hypopharyngeal cancer: a preliminary analysis of a randomized phase 2 trial.

PURPOSE: Concurrent chemoradiotherapy (CCRT) is a standard treatment choice for locally advanced hypopharyngeal carcinoma. The aim of this study was to investigate whether induction chemotherapy (IC) followed by CCRT is superior to CCRT alone to treat locally advanced hypopharyngeal carcinoma. METHODS AND MATERIALS: Patients (n = 142) were randomized to receive two cycles of paclitaxel/cisplatin/5-fluorouracil (TPF) IC followed by CCRT or CCRT alone. The primary end point was overall survival (OS). The secondary end points included the larynx-preservation rate, progression-free survival (PFS), distant metastasis-free survival (DMFS), and toxicities. RESULTS: Ultimately, 113 of the 142 patients were analyzed. With a median follow-up of 45.6 months (interquartile range 26.8-57.8 months), the 3-year OS was 53.1% in the IC + CCRT group compared with 54.8% in the CCRT group (hazard ratio, 1.004; 95% confidence interval, 0.573-1.761; P = 0.988). There were no statistically significant differences in PFS, DMFS, and the larynx-preservation rate between the two groups. The incidence of grade 3-4 hematological toxicity was much higher in the IC+ CCRT group than in the CCRT group (54.7% vs. 10%, P < 0.001). CONCLUSIONS: Adding induction TPF to CCRT did not improve survival and the larynx-preservation rate in locally advanced hypopharyngeal cancer, but caused a higher incidence of acute hematological toxicities. TRIAL REGISTRATION: ClinicalTrials.gov , number NCT03558035. Date of first registration, 15/06/2018.

Delineation of neck node levels for patients with locally advanced supraglottic cancer receiving radical intensity-modulated radiotherapy: a cross-sectional study in Mainland China.

Background: To survey the diversity of clinical target volumes (CTVs) for locally advanced supraglottic cancer (LA-SGC) with radical radiotherapy in mainland China. Methods: Radiation oncologists from 30 provinces and four representative cases (T2N1, T3N2b, T4N0, T4N2c) were included. Results: High risk (HR)-CTV included involved and the lower adjacent level was followed by most physicians (n = 160, 97.6%). In the N0-1 stage, whether contralateral levels II-III should be included in HR- or low risk (LR)-CTV was controversial. In the N2 stage, the bilateral levels II-IVb were included in LR-CTV (75-92.5% agreement). Levels Ib, V or VIb were included in CTV requiring certain conditions. Conclusion: Involved and lower adjacent levels were as HR-CTV. Whether bilateral levels II-IV are included in HR- or LR-CTV remain controversial.

Post-Procedural Anticoagulation After Primary Percutaneous Coronary Intervention for Anterior Acute Myocardial Infarction With Severe Left Ventricular Dysfunction.

BACKGROUND: Patients with anterior acute myocardial infarction (AMI) and left ventricular (LV) dysfunction have an increased risk of LV thrombus (LVT). In the thrombolytic era, short-term anticoagulation using low-molecular-weight heparin during hospitalization proved to significantly reduce LVT formation, but, the effect of this prophylactic approach remains unclear in the current era. Therefore, we conducted a study to evaluate the effects of post-procedural anticoagulation (PPAC) using enoxaparin in addition to dual antiplatelet therapy (DAPT) after primary percutaneous coronary intervention (PCI) in such patients.Methods and Results:A total of 426 anterior AMI patients with LV ejection fraction ≤40% were retrospectively enrolled and classified into 2 groups based on whether they received PPAC (enoxaparin SC for at least 7 days). All patients received primary PCI and DAPT. The primary endpoint was definite LVT at 30 days diagnosed by echocardiography. The secondary endpoints were 30-day mortality, embolic events, and major bleeding events. PPAC was independently associated with a lower incidence of LVT (odds ratio 0.139, 95% confidence interval 0.032-0.606, P=0.009). The 30-day mortality, embolic events, and major bleeding events were not statistically different between groups. CONCLUSIONS: Short-term PPAC using enoxaparin after primary PCI may be an effective and safe way to prevent LVT in patients with anterior AMI and LV dysfunction.

A Phase II Trial of Concurrent Temozolomide and Hypofractionated Stereotactic Radiotherapy for Complex Brain Metastases.

PURPOSE: Complex brain metastases (BMs), such as large lesions, lesions within or close to eloquent locations, or multiple recurrent/progressive BMs, remain the most challenging forms of brain cancer because of decreased intracranial control rates and poor survival. In the present study, we report the results from a single institutional phase II trial of concurrent temozolomide (TMZ) with hypofractionated stereotactic radiotherapy (HFSRT) in patients with complex brain metastases, including assessment of its feasibility and toxicity. PATIENTS AND METHODS: Fifty-four patients with histologically proven primary cancer and complex BMs were enrolled between 2010 and 2015. All the patients were treated with concurrent HFSRT and TMZ (administrated orally at a dosage of 75 mg/m2 per day for at least 20 days). The primary endpoint was overall survival (OS). RESULTS: The median follow-up time was 30.6 months. The local control rates at 1 and 2 years were 96% and 82%, respectively. The median OS was 17.4 months (95% confidence interval [CI], 12.6-22.2), and the OS rates at 1 and 2 years were 65% (95% CI, 52%-78%) and 33% (19%-47%). Only six patients (15.8%) died of intracranial disease. The median brain metastasis-specific survival was 46.9 months (95% CI, 35.5-58.4). Treatment-related grade 3-4 adverse events were rare and included one grade 3 hematological toxicity and two grade 3 liver dysfunctions. CONCLUSION: Treatment using HFSRT concurrent with TMZ was well tolerated and could significantly extend OS compared with historical controls in complex BMs. Large randomized clinical trials are warranted. Trial registration ID: NCT02654106. IMPLICATIONS FOR PRACTICE: The treatment using hypofractionated stereotactic radiotherapy concurrent with temozolomide appeared to be safe and could significantly extend overall survival compared with historical control in complex brain metastases. Large randomized clinical trials are warranted to verify our results.

Pretreatment nutritional risk as a prognostic factor in head and neck cancer patients receiving radiotherapy or chemoradiotherapy.

BACKGROUND AND OBJECTIVES: Head and neck cancer patients often experience nutritional deterioration, which decreases their treatment tolerance and is associated with poor outcomes. We analyzed nutritional status in head and neck cancer patients before and during treatment, and its impact on clinical outcomes. METHODS AND STUDY DESIGN: Between January 2009 and April 2012, 336 head and neck cancer patients receiving radiotherapy or chemoradiotherapy were prospectively entered into the study. The Nutritional Risk Screening 2002 (NRS 2002) assessment was used to evaluate their nutritional status. RESULTS: A total of 227 patients with nasopharyngeal carcinoma and 109 patients with head and neck cancers were analyzed. The proportion of patients receiving radiotherapy or chemoradiotherapy at nutritional risk was 61.3%, with 11.9% at risk before treatment and 49.4% developing risk during treatment. In multivariate analysis, nutritional risk before treatment was associated with T stage for the two groups. Risk was significantly higher in patients receiving concurrent chemoradiotherapy during treatment for nasopharygeal carcinoma patients. The prognosis of pretreatment nutritional risk patients was worse than those becoming at risk during treatment and those without nutritional risk (3-year overall survival 62.9% vs 81.7% vs 80.6%, p=0.026; 3-year disease-free survival 64.8% vs 84.5% vs 84.4%, p=0.019). CONCLUSIONS: The incidence of nutritional risk is high in head and neck cancer patients receiving radiotherapy or chemoradiotherapy, especially during treatment. Pretreatment nutritional risk evaluated using the NRS 2002 can predict patient prognosis.

Nasopharyngeal carcinoma with intracranial extension in the era of intensity-modulated radiotherapy: case-control study using propensity score matching method.

The objective of the study was to evaluate long-term survival outcomes and toxicity of T4 classification nasopharyngeal carcinoma (NPC) with intracranial extension (IE group) or without intracranial extension (non-IE group) after intensity-modulated radiotherapy (IMRT) using the propensity score matching method. After generating propensity scores given the covariates of age, sex, N classification, and concurrent chemotherapy, 132 patients in each group were matched. The 5-year local failure-free survival rate and the 5-year overall survival rate in the IE group were lower than the patients in the non-IE group (74.6 vs. 88.9 %, p = .008; 51.1 vs. 71.9 %, p = .005). Grade 2 hypothyroidism was more common in the IE group (13.2 vs. 3.4 %, p = .029). For patients with T4 classification NPC after IMRT, patients with intracranial extension need more attention to the thyroid gland function and are more likely to experience local failure and death than patients without intracranial extension.

Intensity-modulated radiotherapy for cervical esophageal squamous cell carcinoma: clinical outcomes and patterns of failure.

The objective of the study was to report clinical outcomes and patterns of failure for these patients with cervical esophageal squamous cell carcinoma (CESCC) treated with intensity-modulated radiotherapy (IMRT). A total of 64 patients with CESCC treated with definitive IMRT from May 2005 to March 2012 in our center were analyzed. Forty-two patients received radiotherapy alone and 22 patients received concurrent chemoradiotherapy. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. For all patients, the overall 2-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 74.5, 88.0, 66.6 and 42.5 %, respectively. Twenty-eight patients had developed treatment failure. Of the 28 patients, 14, 5, and 18 had developed local failure, regional failure, and distant metastasis, respectively. All of the 14 local failures were considered in-field failures. Of the five regional failures, three were considered in-field failures and two were marginal failures. The most frequently observed acute toxicity was mainly Grade 1 or 2. The incidence of acute Grade 3 mucositis (including pharyngitis), skin reaction, and leukopenia was 4.7, 12.5 and 10.9 %, respectively. IMRT provides satisfactory locoregional control for CESCC. Distant metastasis remains the predominate pattern of failure and the predominate pattern of locoregional failures is in-field failure.

Definitive intensity-modulated radiotherapy compared with definitive conventional radiotherapy in cervical oesophageal squamous cell carcinoma.

PURPOSE: The authors compared definitive intensity-modulated radiotherapy (IMRT) with definitive conventional radiotherapy (2D-RT) in cervical oesophageal squamous cell carcinoma (CESCC). MATERIALS AND METHODS: A total of 101 patients with CESCC treated with definitive radiotherapy from January 2001 to April 2012 were analysed. 37 patients were irradiated using 2D-RT, whereas 64 cases were treated using IMRT. RESULTS: The median follow-up time was 15.5 months for all the patients. For all patients, the overall 2-year local failure-free survival (LFFS), regional failure-free survival (RFFS), and overall survival (OS) rate was 67.4, 85.2 and 46.2%, respectively. The 2-year LFFS rate and the 2-year RFFS rate in the IMRT group were higher than the 2D-RT group, although no statistically significant difference was observed in LFFS and RFFS. No statistically significant difference was observed in overall survival (OS) between the groups. Compared with 2D-RT, the rate of grade 3 dysphagia after radiotherapy was lower (6.3 vs. 8.1%) and none had hypothyroidism requiring lifelong thyroxine replacement in the IMRT group. Matched-cases analysis did not show a statistical difference in terms of LFFS, RFFS and OS between the groups. CONCLUSIONS: Although no statistically significant difference was observed in OS, LFFS and RFFS between the IMRT group and the 2D-RT group, the incidence of late toxicity declined using IMRT, thereby resulting in an improved therapeutic ratio for patients with CESCC.

[Analysis of the effectiveness of radiotherapy in postoperative residual tumors in patients with thyroid papillary carcinoma].

OBJECTIVE: The aim of this study was to assess the impact of radiotherapy on patients with postoperative residual or recurrent papillary thyroid cancer (PTC). METHODS: We retrospectively reviewed the medical records of 34 patients with PTC, who underwent surgery and radiotherapy in other hospitals, and treated at the Department of Head and Neck Surgery at Cancer Institute & Hospital CAMS from January 2011 to January 2014. Among the 34 cases, 22 were in stage I, 5 in stage II and 7 in stage IVa. The 34 patients received 1.5 times of surgery before radiotherapy in average. All the cases received radiotherapy (mean, 56 Gy; range, 50-70 Gy). The patients were re-operated in our hospital, and the specimens were examined by pathology. The pre- and post-radiotherapy images (CT and B-ultrasound) were compared, and the changes of tumor volume were examined. The objective effect of treatment on the tumor residual focus was evaluated using RECIST, and analyzed by t-test (SPSS 17.0). RESULTS: All the re-resected lesions after radiotherapy were proved by pathology to be papillary thyroid cancer (PTC) or metastatic PTC in cervical lymph nodes. Among the 34 patients, 22 cases showed mild or moderate cell degeneration and the other 12 cases showed no obvious degeneration. The largest tumor diameter was 27.18 mm before radiotherapy and 27.76 mm after radiotherapy, with a non-significant difference between them (t=-1.618, P>0.05). Among the 34 patients, only 3 patients received reoperation, all other 31 cases had complete resection, and no severe complications were observed except recurrent laryngeal nerve injury in one case. CONCLUSIONS: Radiotherapy has few therapeutic benefit to PTC patients after surgery with residual tumor or local recurrence. It should be used in the PTC patients, in which the tumor invasion involves important organ tissues and is difficult for a single operation to achieve safe resection margin, or in patients who can't bear a surgery because of severe coronary heart disease or others.

Long-Term Outcomes of Endoscopic Resection versus Open Surgery for Locally Advanced Sinonasal Malignancies in Combination with Radiotherapy.

Objective Our objective was to compare the long-term outcomes of endoscopic resection versus open surgery in combination with radiotherapy for locally advanced sinonasal malignancies (SNMs). Methods Data for continuous patients with sinonasal squamous cell carcinoma and adenocarcinoma who received surgery (endoscopic or open surgery) combined with radiotherapy in our center between January 1999 and December 2016 were retrospectively reviewed. A 1:1 matching with propensity scores was performed. Overall survival (OS), progression-free survival (PFS), and local recurrence rate (LRR) were evaluated. Results We identified 267 eligible patients, 90 of whom were included after matching: 45 patients in the endoscopy group and 45 in the open group. The median follow-up time was 87 months. In the endoscopic group, 84.4% of patients received intensity-modulated radiotherapy (IMRT), with a mean gross tumor volume (GTV) dose of 68.28 Gy; in the open surgery group, 64.4% of patients received IMRT, with a mean GTV dose of 64 Gy. The 5-year OS, PFS, and LRR were 69.9, 58.6, and 24.5% in the endoscopic group and 64.6, 54.4, and 31.8% in the open surgery group, respectively. Multivariable regression analysis revealed that the surgical approach was not associated with lower OS, PFS, or LRR. The overall postoperative complications were 13% in the endoscopic group, while 21.7% in the open group. Conclusion For patients with locally advanced SNMs, minimally invasive endoscopic resection, in combination with a higher radiation dose and new radiation techniques such as IMRT, yields survival outcomes similar to those of open surgery in combination with radiotherapy.

Long-term outcomes and prognosis of neuroendocrine neoplasms of the head and neck: a cohort from a single institution.

BACKGROUND: Neuroendocrine neoplasm is a rare cancer of head and neck. This study aimed to evaluate clinical features, treatment outcomes, and prognostic factors of neuroendocrine neoplasm of head and neck treated at a single institution. METHODS: Between Nov 2000 and Nov 2021, ninety-three patients diagnosed with neuroendocrine neoplasms of head and neck treated at our institution were reviewed retrospectively. The initial treatments included chemotherapy (induction, adjuvant, or concurrent) combined with radiotherapy in 40 patients (C + RT group), surgery followed by post-operative RT in 34 (S + RT group), and surgery plus salvage therapy in 19 patients (S + Sa group). RESULTS: The median follow-up time was 64.5 months. 5-year overall survival rate (OS), progression-free survival rate (PFS), loco-regional relapse-free survival free rate (LRRFS) and distant metastasis-free survival rate (DMFS) were 64.5%, 51.6%, 66.6%, and 62.1%, respectively. For stage I-II, the 5-year LRRFS for patients' treatment regimen with or without radiotherapy (C + RT and S + RT groups versus S + Sa group) was 75.0% versus 12.7% (p = 0.015) while for stage III-IV, the 5-year LRRFS was 77.8% versus 50.0% (p = 0.006). The 5-year DMFS values for patients with or without systemic therapy (C + RT group versus S + RT or S + Sa) were 71.2% and 51.5% (p = 0.075). 44 patients (47.3%) experienced treatment failure and distant metastasis was the main failure pattern. CONCLUSIONS: Radiotherapy improved local-regional control and played an important role in the management of HNNENs. The optimal treatment regimen for HNNENs remains the combination of local and systemic treatments.

A deep learning-based method for the prediction of temporal lobe injury in patients with nasopharyngeal carcinoma.

PURPOSE: To establish a deep learning-based model to predict radiotherapy-induced temporal lobe injury (TLI). MATERIALS AND METHODS: Spatial features of dose distribution within the temporal lobe were extracted using both the three-dimensional convolution (C3D) network and the dosiomics method. The Minimal Redundancy-Maximal-Relevance (mRMR) method was employed to rank the extracted features and select the most relevant ones. Four machine learning (ML) classifiers, including logistic regression (LR), k-nearest neighbors (kNN), support vector machines (SVM) and random forest (RF), were used to establish prediction models. Nested sampling and hyperparameter tuning methods were applied to train and validate the prediction models. For comparison, a prediction model base on the conventional D0.5cc of the temporal lobe obtained from dose volume (DV) histogram was established. The area under the receiver operating characteristic (ROC) curve (AUC) was utilized to compare the predictive performance of the different models. RESULTS: A total of 127 nasopharyngeal carcinoma (NPC) patients were included in the study. In the model based on C3D deep learning features, the highest AUC value of 0.843 was achieved with 5 features. For the dosiomics features model, the highest AUC value of 0.715 was attained with 1 feature. Both of these models demonstrated superior performance compared to the prediction model based on DV parameters, which yielded an AUC of 0.695. CONCLUSION: The prediction model utilizing C3D deep learning features outperformed models based on dosiomics features or traditional parameters in predicting the onset of TLI. This approach holds promise for predicting radiation-induced toxicities and guide individualized radiotherapy.

Epidermal growth factor receptor­targeted antibody nimotuzumab combined with chemoradiotherapy improves survival in patients with locally advanced head and neck squamous cell carcinoma: a propensity score matching real-world study.

Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) have poor survival outcomes. The real-world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)-based chemoradiotherapy in patients with LA-HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3-year overall survival (OS) rate. Log-rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow-up time was 54.2 (95% confidence interval [CI]: 52.7-55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57-0.99, p = 0.038) and progression-free survival (PFS) (HR = 0.74, 95% CI: 0.58-0.96, p = 0.021). Subgroup analysis revealed that aged 50-60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab-related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA-HNSCC patients in an IMRT era.

Optimizing Cervical Target Volume in Patients with Nasopharyngeal Cancer Based On Nodal Drainage Distance.

PURPOSE: To determine the potential nodal drainage distances of nasopharyngeal carcinoma (NPC) by investigating spatial distribution of metastatic lymph nodes (LN). EXPERIMENTAL DESIGN: Patients with NPC harboring at least two ipsilateral metastatic LNs were enrolled. LN spreading distances were analyzed in nonrestricted direction, cranial-to-caudal direction, and between the two most caudal LNs. Euclidean distance (ED) and vertical distance (VD) between any two LNs were computed. The nearest-neighbor ED and VD covering 95% of LNs or patients (p95-ED and p95-VD) were considered drainage distances, and were further validated by independent internal and external cohorts with recurrent LNs. RESULTS: In all, 5,836 metastatic LNs in 948 patients were contoured. Corresponding to the three scenarios, per-LN level, the p95-EDs were 2.83, 3.28, and 3.55 cm, and p95-VDs were 2.17, 2.32, and 2.63 cm, respectively. Per-patient level, the p95-EDs were 3.25, 3.95, and 3.81 cm, and p95-VDs were 2.67, 2.81, and 2.73 cm, respectively. In internal validation, over 95% of recurred LNs occurred within ED of 2.91 cm and VD of 0.82 cm to the neighbor LN, and the corresponding distances in external validation were 2.77 and 0.67 cm, respectively. CONCLUSIONS: In NPC, the maximum LN drainage distance was 3.95 cm without considering the direction. Specifically, in cranial-to-caudal direction, the sufficient vertical drainage distance was 2.81 cm, indicating that a 3-cm extension from the most inferior node may be rational as caudal border of the prophylactic clinical target volume (CTV). These findings promote in-depth understanding of nodal spreading patterns, uncovering paramount evidence for individualized CTV.

Efficacy and Safety of Nimotuzumab in Combination with Radiotherapy or Chemoradiotherapy for Local Advanced Head and Neck Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: The present meta-analysis aimed to evaluate the efficacy and safety of adding nimotuzumab to radiotherapy (RT) or chemoradiotherapy (CRT). METHODS: Prospective randomized controlled studies at EMBASE, PubMed, and the Cochrane Library from January 1, 2010, to October 1, 2022, were searched. Data on the overall survival (OS), progress-free survival (PFS), disease-free survival (DFS), complete response rate (CRR), objective response rate (ORR), and all grade adverse events were collected from the enrolled publications. OS was the primary measurement indicator. Pooled analysis was performed with relative risks (RRs), hazard risks (HRs), and their corresponding 95% confidence intervals (CIs) in the software Stata SE 16.0. RESULTS: Six randomized controlled studies were included in the analysis of the overall pooled effect. As compared to the control group, the nimotuzumab intervention group exhibited improved OS by 21% (pooled HR=0.79,95% CI: 0.64-0.98, P=0.028), along with PFS up to 31% (HR=0.69, 95% CI: 0.55-0.86, P=0.001) and DFS up to 29% (HR=0.71, 95% CI: 0.56-0.91, P=0.006), increased CRR as 50% (RR=1.50, 95%CI:1.09-2.04; P=0.012), and ORR as 35% (RR=1.35, 95%- CI:1.04-1.73; P=0.022). Regarding safety, nimotuzumab in combination with RT or CRT did not increase the incidence of all grade adverse events (pooled-RD=-1.27, 95%CI:-2.78-0.23, P=0.099). CONCLUSION: The present meta-analysis has demonstrated that nimotuzumab, in combination with RT or CRT, could provide survival benefits and increase response rates. Its safety profile has been found to be controllable.