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.

Loco-regional radiotherapy in de novo metastatic nasopharyngeal carcinoma with chemotherapy and immunotherapy: A real-world retrospective study from two cancer centers.

BACKGROUND: Immunochemotherapy has become the first-line treatment for initial diagnosed metastatic nasopharyngeal carcinoma (mNPC). Loco-regional radiotherapy combined with systemic chemotherapy significantly improves the survival. However, the safety and efficacy of loco-regional radiotherapy combined with immunochemotherapy remained unknown. METHODS: Patients with de novo mNPC who received immunochemotherapy followed by loco-regional radiotherapy were included from two cancer centers. Toxicity and treatment response were assessed using CTCAE 5.0 and RECIST 1.1, respectively. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. RESULTS: From 2019 to 2021, a total of 16 patients were retrospectively analyzed. The median follow-up was 28 months (range 14-47 months). No one died. One-year, 2-year, and 3-year PFS rate was 93.8%, 58.4% and 50.1%, respectively. Radiotherapy-related acute severe (grade 3 or higher) toxicity was dermatitis (1/16, 6.3%) and mucositis (2/16, 12.5%). CONCLUSIONS: Loco-regional radiotherapy provided a promising efficacy with modest toxicity for patients with mNPC who received immunochemotherapy.

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.

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.

Clinical Characteristics and Long-Term Outcomes following Surgery Combined with Adjuvant Radiotherapy for Patients with Frontal Sinus Malignancies.

Objectives Primary frontal sinus malignancies (FSMs) are the rarest sinonasal cancers. This study aimed to determine clinicopathologic characteristics of primary FSMs and provide long-term survival outcomes. Design This study is a retrospective review. Setting The study was conducted at a tertiary medical center. Participants Patients who participated in this study were diagnosed with primary FSMs. Main Outcome Measures Median survival time is the primary outcome measure of this study. Results In this series, the median age was 48 years (30-53 years) and all patients were male. There were five cases with squamous cell carcinoma and one with osteosarcoma. All cases presented with locally advanced disease without regional lymphatic metastasis, including five cases of stage III and one case of stage II. The two most common pathways of tumor invasion were as follows: local tumor broke posteriorly through bone wall and invaded dura mater, followed by frontal lobe; local tumor infiltrated downward through the floor of frontal sinus into ethmoid sinus, thereafter invaded laterally orbit and orbital contents. All patients received surgery followed by postoperative radiotherapy at the total doses of 50 to 75.95 Gy. Among them, only one patient underwent R0 resection, the rest of patients underwent R1/R2 resection. With a median survival time of 56 months (32-76 months), two patients receiving R1/R2 resection developed treatment failure and died within 5 years, including one case with local recurrence and one with local recurrence, thereafter distant metastasis. Conclusion The majority of FSMs presented with peripherally invasive progression lesions which led to a high ratio of R1/R2 resection. Surgery combined with postoperative radiotherapy might result in satisfactory efficacy.

Failure Patterns Within Different Histological Types in Sinonasal Malignancies: Making the Complex Simple.

OBJECTIVE: To analyze the failure patterns in patients with different histological subtypes of sinonasal malignancies (SNMs). STUDY DESIGN: Retrospectively gathered data. SETTING: Academic university hospital. METHODS: Patients with SNMs treated at a tertiary referral center between January 1999 and January 2019 were included. We assessed the failure patterns within different histological subtypes. RESULTS: The study included 897 patients. The median follow-up time was 100 months. Adenoid cystic carcinoma (ACC) had a moderate risk of developing local recurrence (LR) and distant metastasis (DM). Compared with ACC, squamous cell carcinoma (SCC), adenocarcinoma (AC), soft tissue sarcoma (STS), and mucosal melanoma (MM) were classified as a high LR risk group. For DM, neuroendocrine carcinoma (NEC), STS, and MM were in the high-risk group. CONCLUSIONS: ACC had intermediate local and distant failure risks, while SCC, AC, STS, and MM were at high LR risks. NEC, STS, and MM were at high DM risk.

[Clinical characteristics and efficacy of oropharyngeal carcinoma with secondary primary tumor].

Objective:To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. Methods:A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Results:Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%（42/66） were synchronous and 36.4%（24/66） were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%（P=0.001）; The second primary cancer accounted for 11.2%（12/107） of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%（9/12）. There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer（8.1%）. Among them, 65.0%（13/20） were synchronous and 35.0%（7/20） were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%（2/52） of all deaths in p16 positvie group. Conclusion:The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.

[Comparison of different laryngeal preservation strategies based on chemoradiotherapy in locally advanced hypopharyngeal carcinoma].

Objective:This study aimed to evaluate the clinical features and treatment outcomes of the value of response-adapted treatment following radiotherapy and induction chemotherapy follwing subsequent comprehensive therapy in patients with resectable locally advanced hypopharyngeal carcinoma. Methods:This cohort study was conducted from September 2010 to September 2020 in our hospital, 231 patients pathologically confirmed stage Ⅲ and ⅣB resectable locally advanced hypopharyngeal carcinoma included. For the IC-directed ART strategy, IC is used to select good candidates to receive radical RT or CCRT, and others undergo surgery. He response-adapted strategy was determined based on the primary tumor response, which was evaluated at a dose of 50 Gy. If the response reached complete response or partial response（more than 80% tumor regression）, patients received radical RT or CCRT; otherwise, they received surgery, if possible, at 4 to 6 weeks after RT. The end points of the study were OS（overall survival）, progression free survival（PFS）, locoregional recurrence-free survival（LRRFS） and LDFS. Results:In IC-directed group, 75.0%（57/76） patients reached PR after 2 cycles of induction chemotherapy. While in RT-directed group, 70.3%（109/155） patients reached large PR at dose of 50 Gy. The median interquartile range follow-up period of the whole cohort was 63.8 months. The 5-year OS, PFS, LRRFS and SFL of the whole cohort were 47.9%、39.6%、44.3% and 36.2%, respectively. In evaluations based on the different treatment strategies, the 5-year OS and SFL were 51.3% versus 37.0%（HR 0.67; 95%CI 0.43-1.05; P=0.07） and 27.8% versus 39.8%（HR 0.68; 95%CI 0.46-0.99; P=0.04） between IC-directed and RT-directed groups. In additional, surgery complications did not significantly differ between these two groups. Conclusion:In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, and higher laryngeal preservation compared with IC-directed strategies. This approach could provide a feasible laryngeal preservation strategy in patients with resectable locally advanced hypopharyngeal carcinoma.

Feasibility of omitting contralateral neck irradiation in patients with node-negative sinonasal squamous cell carcinoma crossing the midline.

BACKGROUND: Identifying the lymph node target volume in patients with node-negative sinonasal squamous cell carcinoma (SNSCC) crossing the midline poses a challenge. This study aims to address this. METHODS: We retrospectively reviewed clinically N0 patients with tumors crossing the midline who received elective neck irradiation (ENI) from two centers between 1999 and 2019. The main endpoint was regional relapse-free survival (RRFS). RESULTS: We included 104 patients: 64 received bilateral ENI, and 40 received ipsilateral-only ENI (median follow-up time was 89.99 and 95.01 months, respectively). At 5 years, the RRFS rates were comparable (57.68% vs. 55.83%, p = 0.372), as were the contralateral RRFS (57.68% vs. 61.62%, p = 0.541). Five-year OS, LRFS, and DMFS showed no significant difference between two groups. CONCLUSIONS: Our findings provide preliminary evidence suggesting the potential for avoiding contralateral ENI in SNSCC patients with midline crossing tumors who undergo ipsilateral ENI, covering at least level II. Validation through future prospective studies is necessary.

A subregion-based prediction model for local-regional recurrence risk in head and neck squamous cell carcinoma.

BACKGROUND AND PURPOSE: Given that the intratumoral heterogeneity of head and neck squamous cell carcinoma may be related to the local control rate of radiotherapy, the aim of this study was to construct a subregion-based model that can predict the risk of local-regional recurrence, and to quantitatively assess the relative contribution of subregions. MATERIALS AND METHODS: The CT images, PET images, dose images and GTVs of 228 patients with head and neck squamous cell carcinoma from four different institutions of the The Cancer Imaging Archive(TCIA) were included in the study. Using a supervoxel segmentation algorithm called maskSLIC to generate individual-level subregions. After extracting 1781 radiomics and 1767 dosiomics features from subregions, an attention-based multiple instance risk prediction model (MIR) was established. The GTV model was developed based on the whole tumour area and was used to compare the prediction performance with the MIR model. Furthermore, the MIR-Clinical model was constructed by integrating the MIR model with clinical factors. Subregional analysis was carried out through the Wilcoxon test to find the differential radiomic features between the highest and lowest weighted subregions. RESULTS: Compared with the GTV model, the C-index of MIR model was significantly increased from 0.624 to 0.721(Wilcoxon test, p value < 0.0001). When MIR model was combined with clinical factors, the C-index was further increased to 0.766. Subregional analysis showed that for LR patients, the top three differential radiomic features between the highest and lowest weighted subregions were GLRLM_ShortRunHighGrayLevelEmphasis, GRLM_HghGrayLevelRunEmphasis and GLRLM_LongRunHighGrayLevelEmphasis. CONCLUSION: This study developed a subregion-based model that can predict the risk of local-regional recurrence and quantitatively assess relevant subregions, which may provide technical support for the precision radiotherapy in head and neck squamous cell carcinoma.

Sinonasal mucosal melanoma: Is there a need for elective neck irradiation?

BACKGROUND AND PURPOSE: Sinonasal mucosal melanoma (SNMM) is a rare malignant neoplasm. The regional failure pattern and effectiveness of elective neck irradiation (ENI) were not well defined. Here, we would assess the value of ENI for clinical node negative (cN0) SNMM patients. MATERIALS AND METHODS: A total of 107 SNMM patients treated at our institution over a period of 30 years was retrospectively analyzed. RESULTS: Five patients had lymph node metastases at diagnosis. Among the 102 cN0 patients analyzed, 37 patients had received ENI, and 65 patients had not. ENI significantly reduced the regional recurrence rate from 23.1% (15/65) to 2.7% (1/37). Ipsilateral levels Ib and II were the most common locations of regional relapse. Multivariate analysis also showed that ENI was the only independent favorable predictor for the achievement of regional control (HR: 9.120; 95% CI: 1.204-69.109; P = 0.032). CONCLUSION: This is the largest cohort of SNMM patients from a single institution analyzed for the assessment of the value of ENI on regional control and survival. ENI significantly reduced the regional relapse rate in our study. Ipsilateral levels Ib and II might be considerable when deliver elective neck irradiation, more evidence is needed in the future.

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.

Postoperative radiotherapy for supraglottic cancer on real-world data: can we reduce dose to lymph node levels?

PURPOSE: To evaluate prognosis for reducing postoperative radiotherapy (PORT) dose to lymph node levels of supraglottic cancer (SC) on real-world data. METHOD AND MATERIALS: Patients were derived from two cancer centers. In center 1, the involved nodal levels (high-risk levels, HRL) and the next level received a dose of 60.06 Gy/1.82 Gy per fraction, while the other uninvolved levels (low-risk levels, LRL) received 50.96 Gy/1.82 Gy per fraction. In center 2, all received 50 Gy/2 Gy per fraction. The rates of high-risk levels control (HRC), regional control (RC), overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier method. RESULT: Totally, 124 patients were included (62 in center 1, 62 in center 2). Most patients (106, 85.5%) had a stage T3/N + tumor. The median follow-up was 45 months (range 1-163 months). There were no significant differences in terms of OS (p = 0.126), RC (p = 0.514), PFS (p = 0.195) and DMFS (p = 0.834). Most regional recurrences (4, 80%) occurred within three years of treatment, and all occurred within the target volumes. No regional failure occurred in HRL in center 1, while three (3/4) failures occurred in center 2. Dose reduction prescription to HRL led to a lower HRC rate (100% vs. 90.6%, p = 0.009). While the rates of LRL control (98.4%) were equal between the two centers. CONCLUSION: Compared with a standard dose, the reduced dose to involved nodal levels showed inferior regional control for PORT, while uninvolved nodal levels showed equal outcomes. A dose of 50 Gy for HRL may be an unfavorable treatment option for SC.

Improved Cancer-Specific Risk Stratification by the Lymph Node Ratio-Based Nomogram: A Potential Role in Guiding Postoperative Management Decisions for Oral Cavity Carcinoma.

PURPOSE: To develop and validate a nomogram integrating lymph node ratio (LNR) to predict cancer-specific survival (CSS) and assist decision making for postoperative management in nonmetastatic oral cavity squamous cell carcinoma (OCSCC). MATERIALS AND METHODS: We retrospectively retrieved 6,760 patients with OCSCC primarily treated with surgery from surveillance, epidemiology, and end results database between 2010 and 2015. They were randomly divided into training and validation cohorts. Performance of the nomogram was evaluated by calibration curve, consistency index, area under the curve, and decision curve analysis and was compared with that of the LNR, positive lymph nodes (PLN) and tumor node metastasis (TNM) staging. According to the individualized nomogram score, patients were classified into three risk cohorts. The therapeutic efficacy of postoperative radiotherapy and chemotherapy was evaluated in each cohort. RESULTS: The nomogram incorporated six independent variables, including race, tumor site, grade, T stage, PLN, and LNR. Calibration plots demonstrated a good match between the predicted and observed CSS. C-indices for training and validation cohorts were 0.746 (95% CI, 0.740 to 0.752) and 0.726 (95% CI, 0.713 to 0.739), compared with 0.687, 0.695, and 0.669 for LNR, PLN, and TNM staging, respectively (P < .001). Decision curve analyses confirmed that nomogram showed the best performance in clinical utility. Postoperative radiotherapy presented survival benefit in medium-and high-risk groups but showed a negative effect in the low-risk group. Chemotherapy was only beneficial in the high-risk group. CONCLUSION: The LN status-incorporated nomogram demonstrated good discrimination and predictive accuracy of CSS for patients with OCSCC and could identify those most likely to benefit from adjuvant therapy.

Caudal distribution pattern of metastatic neck lymph nodes in nasopharyngeal carcinoma and prognostic significance of nodal spread distances.

OBJECTIVE: To investigate the caudal distribution pattern of metastatic neck lymph nodes (LNs) in nasopharyngeal carcinoma (NPC) and the prognostic significance of nodal spread distances (SDs). MATERIALS AND METHODS: NPC patients with neck metastatic LNs were enrolled. The most caudally located LNs were marked. SD was defined as the distance from marked LNs to the lateral process of the atlantoaxial spine (LPC1). Univariate and multivariate analyses were performed to assess association between MRI-identified nodal features and survival. Harrell's concordance index (C-index) and area under the curve (AUC) were used to compare AJCC (8th edition) N staging with the proposed N staging. Survival after induction chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) versus CCRT alone was compared between different SD groups. RESULTS: A total of 1907 LNs (1164 patients) were contoured. SD > 7 cm was an independent predictor of overall survival (OS), distant metastasis-free survival (DMFS), and progression-free survival (PFS), with hazard ratios of 1.725, 1.553 and 1.414, respectively. When patients with SD > 7 cm were upgraded one N stage higher, the proposed N classification showed better stratification in OS, DMFS, and PFS between N1 and N2 stages. C-indices and AUCs of the proposed N staging were superior to AJCC N staging. IC + CCRT showed negative effect in N1-2 patients with SD ≤ 7 cm but improved OS in those with SD > 7 cm. CONCLUSION: SD of metastatic LNs can predict survival in NPC. Integration of SD into AJCC N staging could improve its prognostic value and help identify patients requiring IC.

Synchronous Second Primary Cancers of Hypopharyngeal Carcinoma in the Image-Enhanced Endoscopy Era.

OBJECTIVES: To explore the prevalence of hypopharyngeal carcinoma (HPC) with synchronous second primary malignancies (Syn-SPMs), their impact on clinical outcomes, and associated risk factors in the image-enhanced endoscopy era. MATERIALS AND METHODS: We retrospectively analyzed 673 patients newly diagnosed with HPC at our cancer center between 2009 and 2019. The patients were divided into three groups: (a) no second primary malignancies (N-SPMs, n = 533); (b) synchronous carcinoma in situ (Syn-Tis, n = 60); (c) synchronous invasive tumors (Syn-invasive, n = 80). Propensity score matching was conducted to balance the N-SPMs and Syn-invasive groups at a 3:1 ratio. RESULTS: Most (96.1%) underwent pretreatment esophagogastroduodenoscopy evaluation with image-enhanced endoscopy. The incidence rates were: Syn-SPMs, 20.8%; Syn-Tis, 8.9%; Syn-invasive, 11.9%. At a median follow-up of 66.7 months, the Syn-Tis and N-SPMs groups had a similar 5-year overall survival (OS; 45.6% vs. 44.5%; hazard ratio [HR], 0.956; 95% confidence interval [CI], 0.660-1.385; p = 0.806). Compared to the N-SPMs group, the Syn-invasive group had poorer 5-year OS (27.0% vs. 52.9%; HR, 2.059; 95% CI, 1.494-2.839; p < 0.001). Alcohol consumption was significantly associated with Syn-SPMs occurrence (odds ratio, 2.055, 2.414, and 3.807 for light, intermediate, and heavy drinkers, respectively). CONCLUSION: The prevalence of Syn-SPMs among patients with HPC was high. Syn-invasive SPMs decreased the survival of patients with HPC. Routine screening with image-enhanced endoscopy should be recommended to detect early-stage SPMs, especially for heavy alcohol drinkers. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1906-1913, 2023.

Feasibility of ipsilateral elective neck irradiation of levels Ib and II without level III in patients with node-negative sinonasal squamous cell carcinoma.

BACKGROUND: The necessity of level III irradiation in patients with node-negative advanced sinonasal squamous cell carcinoma (SNSCC) is unclear. METHODS: Seventy-eight patients with advanced SNSCC were included. Survival rates were estimated and compared between treatment groups. RESULTS: Twenty-five patients received ipsilateral levels Ib and II irradiation (group 1) and 53 patients received ipsilateral levels Ib and II plus level III irradiation (group 2). The median follow-up time was 75.56 months. Five-year survival rates (regional relapse-free survival, overall survival, local relapse-free survival, and distant metastasis-free survival) were similar between groups 1 and 2 (all p > 0.05). Irradiation doses to the thyroid and larynx were significantly lower in group 1 than in group 2. CONCLUSIONS: Ipsilateral irradiation of levels Ib and II neck provides similar regional control and results as irradiation of these levels plus level III, with lower irradiation doses to normal neck tissue, in patients with node-negative advanced SNSCC.

T4b Sinonasal Squamous Cell Carcinoma: Surgery Plus Radiotherapy May Contribute to Prolonged Survival.

PURPOSE: To determine oncologic outcomes for patients with T4b sinonasal squamous cell carcinoma (SNSCC) treated with either surgery plus radiotherapy or definitive radiotherapy. MATERIALS AND METHODS: Between January 1999 and December 2016, 85 patients with T4b SNSCC were analyzed retrospectively, there were 54 who received surgery plus radiotherapy (S + RT group) ± chemotherapy and 31 with definitive radiotherapy (RT group) ± chemotherapy. A 1: 2 propensity score matching (PSM) was performed to balance clinical factors and match patients. Kaplan-Meier method and Cox proportional hazard model were used to determine risk factors on survival outcomes. RESULTS: The median follow-up time was 76.7 months. The cumulative rates of locoregional control (LRC), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) at 5 years for entire cohort were 44.6%, 33.1%, 38.8%, and 33.9% respectively. After PSM, a total of 50 patients in S + RT group and 25 patients in RT group were analyzed. The 5-year LRC, DMFS, CSS, and OS between S + RT and RT group were 58.6% versus 27.5% (p = 0.035), 42.8% versus 20.0% (p = 0.006), 50.3% versus 22.0% (p = 0.005), 44.5% veruss 20.0% (p = 0.004). The 5-year survival rates with orbital retention between groups were 32.7% and 15.0%, p = 0.080. Multivariate Cox analysis revealed non-surgical therapy (HR = 3.678, 95%CI 1.951-6.933) and invasion of cranial nerves (other than maxillary division of trigeminal nerves) (HR = 2.596, 95%CI 1.217-5.535) were associated with decreased OS. CONCLUSION: The inclusion of surgery in the multimodal management of T4b SNSCC might confer a survival benefit. Further prospective studies comparing the oncologic outcomes of S + RT with RT are warranted. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2222-2231, 2023.

MRI-identified multidimensional nodal features predict survival and concurrent chemotherapy benefit for stage II nasopharyngeal carcinoma.

BACKGROUND: Reliable predictors are urgently needed to identify stage II nasopharyngeal carcinoma (NPC) patients who could benefit from concurrent chemoradiotherapy (CCRT). We aimed to develop a nomogram integrating MRI-identified multidimensional features of lymph nodes to predict survival and assist the decision-making of CCRT for stage II NPC. PATIENTS AND METHODS: This retrospective study enrolled 242 stage II NPC patients treated from January 2007 to December 2017. Overall survival (OS) was the primary endpoint. Performance of nomogram was evaluated using calibration curves, Harrell Concordance Index (C-index), area under the curve (AUC) and decision curves analysis (DCA) and was compared with TNM staging. According to the individualized nomogram score, patients were classified into two risk cohorts and therapeutic efficacy of CCRT were evaluated in each cohort. RESULTS: Three independent prognostic factors for OS: age, number and location of positive lymph nodes were included into the final nomogram. T stage was also incorporated due to its importance in clinical decision-making. Calibration plots demonstrated a good match between the predicted and our observed OS rates. C-index for nomogram was 0.726 compared with 0.537 for TNM staging (p < 0.001). DCAs confirmed the superior clinical utility of nomograms compared with TNM staging. CCRT compared to intensity-modulated radiotherapy (IMRT) delivered OS benefit to patients in the high-risk group (5-year: 89.9% vs. 72.1%; 10-year: 72.5% vs. 34.2%, p = 0.011), but not in the low-risk group. CONCLUSIONS: This lymph node features-based nomogram demonstrated excellent discrimination and predictive accuracy for stage II patients and could identify patients who can benefit from CCRT.

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.