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.

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.

[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.

Voluntary Deep Inspiration Breath-Hold (VDIBH) Whole-Breast Irradiation Assisted by Optical Surface Monitoring System (OSMS) in Patients With Left-Sided Breast Cancer: A Prospective Phase II Study.

Objectives: To investigate the dosimetric advantages of the voluntary deep inspiration breath-hold technique assisted by optical surface monitoring system for whole breast irradiation in left breast cancer after breast-conserving surgery and verify the reproducibility and acceptability of this technique. Methods: Twenty patients with left breast cancer receiving whole breast irradiation after breast-conserving surgery were enrolled in this prospective phase II study. Computed tomography simulation was performed during both free breathing and voluntary deep inspiration breath-hold for all patients. Whole breast irradiation plans were designed, and the volumes and doses of the heart, left anterior descending coronary artery, and lung were compared between free breathing and voluntary deep inspiration breath-hold. Cone beam computed tomography was performed for the first 3 treatments, then weekly during voluntary deep inspiration breath-hold treatment to evaluate the accuracy of the optical surface monitoring system technique. The acceptance of this technique was evaluated with in-house questionnaires completed by patients and radiotherapists. Results: The median age was 45 (27-63) years. All patients received hypofractionated whole breast irradiation using intensity-modulated radiation therapy up to a total dose of 43.5 Gy/2.9 Gy/15f. Seventeen of the 20 patients received concomitant tumor bed boost to a total dose of 49.5 Gy/3.3 Gy/15f. Voluntary deep inspiration breath-hold showed a significant decrease in the heart mean dose (262 ± 163 cGy vs 515 ± 216 cGy, P < .001) and left anterior descending coronary artery (1191 ± 827 cGy vs 1794 ± 833 cGy, P < .001). The median delivery time of radiotherapy was 4 (1.5-11) min. The median deep breathing cycles were 4 (2-9) times. The average score for acceptance of voluntary deep inspiration breath-hold by patients and radiotherapists was 8.7 ± 0.9 (out of 12) and 10.6 ± 3.2 (out of 15), respectively, indicating good acceptance by both. Conclusions: The voluntary deep inspiration breath-hold technique for whole breast irradiation after breast-conserving surgery in patients with left breast cancer significantly reduces the cardiopulmonary dose. Optical surface monitoring system-assisted voluntary deep inspiration breath-hold is reproducible and feasible and showed good acceptance by both patients and radiotherapists.

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.

Two-Step Preparation of CCF/PEEK Wrapped Yarn for 3D Printing Composites with Enhanced Mechanical Properties.

Continuous fiber reinforced thermoplastic composites (CFTPCs) have shown advantages such as high strength, long life, corrosion resistance, and green recyclability. Three-dimensional printing of CFTPCs opened up a new strategy for the fabrication of composites with complicated structures, low cost, and short production cycles. However, a traditional 3D printing process usually causes poor impregnation of the fiber or surface damage of the fiber due to the short impregnation time or high viscosity of the thermoplastic resin. Here, continuous carbon fiber/poly(ether-ether-ketones) (CCF/PEEK) wrapped yarn was fabricated via powder impregnation and using double spinning technology for the 3D printing. The concentration of PEEK powder suspension and wire speed were optimized as 15% and 2.0 m/min. The twist of wrapped yarn was optimized as 1037 T/m. Mechanical testing showed that the 3D-printed composite wire had excellent tensile and bending strength, which was about 1.6~4.2 times larger than those without the powder pre-impregnation process. It is mainly attributed to the improved impregnation of the CF which took place during the powder pre-impregnation process. We believe that our research on wrapped yarn for 3D-printed composites provides an effective strategy for the 3D printing of composites with enhanced mechanical properties.

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.

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.

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.

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.

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.

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.

Spatial architecture of regulatory T-cells correlates with disease progression in patients with nasopharyngeal cancer.

Purpose: This study aims to investigate the prognostic value of composition and spatial architecture of tumor-infiltrating lymphocytes (TILs) as well as PDL1 expression on TILs subpopulations in nasopharyngeal carcinoma (NPC). Methods: A total of 121 patients with NPC were included and divided into two groups: favorable (n = 68) and unfavorable (n = 53). The archived tumor tissues of the included patients were retrieved, and a tissue microarray was constructed. The density and spatial distribution of TILs infiltration were analyzed using the multiplex fluorescent immunohistochemistry staining for CD3, CD4, CD8, Foxp3, cytokeratin (CK), PDL1, and 4',6-diamidino-2-phenylindole (DAPI). The infiltration density of TILs subpopulations and PDL1 expression were compared between the two groups. The Gcross function was calculated to quantify the relative proximity of any two types of cells. The Cox proportional hazards regression model was used to identify factors associated with overall survival (OS) and disease-free survival (DFS). Results: The densities of regulatory T-cells (Tregs), effector T-cells (Teffs), PDL1+ Tregs, and PDL1+ Teffs were significantly higher in patients with unfavorable outcomes. PDL1 expression on tumor cells (TCs) or overall TILs was not associated with survival. Multivariate analysis revealed that higher PDL1+ Tregs infiltration density was independently associated with inferior OS and DFS, whereas Tregs infiltration density was only a prognostic marker for DFS. Spatial analysis revealed that unfavorable group had significantly stronger Tregs and PDL1+ Tregs engagement in the proximity of TCs and cytotoxic T lymphocyte (CTLs). Gcross analysis further revealed that Tregs and PDL1+ Tregs were more likely to colocalize with CTLs. Moreover, increased GTC : Treg (Tregs engagement surrounding TCs) and GCTL : PDL1+ Treg were identified as independent factors correlated with poor outcomes. Conclusion: TILs have a diverse infiltrating pattern and spatial distribution in NPC. Increased infiltration of Tregs, particularly PDL1+ Tregs, as well as their proximity to TCs and CTLs, correlates with unfavorable outcomes, implying the significance of intercellular immune regulation in mediating disease progression.

Sinonasal Inverted Papilloma-Associated and De Novo Squamous Cell Carcinoma: A Tale of Two Cities or Not.

BACKGROUND: Sinonasal squamous cell carcinoma (SNSCC) can arise as either inverted papilloma-associated SCC (IP-SCC) or as de novo SCC (DN-SCC). It is controversial as to whether survival differences between IP-SCC and DN-SCC exist. METHODS: Between January 2000 and December 2016, 234 patients with SNSCC were analyzed retrospectively, including 68 with IP-SCC and 166 with DN-SCC. Propensity score matching (PSM) was performed to balance baseline characteristics. The Kaplan-Meier method and Cox proportional hazard model were used to determine risk factors on survival outcomes. RESULTS: The median follow-up time was 98.4 months. Before PSM, lymph node metastasis was noted to be lower in patients with IP-SCC. After PSM, the 5-year DFS, DSS and OS between IP-SCC and DN-SCC were 43.0% vs. 44.5% (p = 0.701), 49.2% vs. 56.2% (p = 0.753), and 48.2% vs. 52.9% (p = 0.978). The annual hazards of local failure, respectively, peaked at 28.4% and 27.8% for IP-SCC and DN-SCC within 12 months after treatment. Afterward, the hazards gradually decreased and the hazard for IP-SCC was always higher before approaching null. CONCLUSIONS: This study provides novel evidence to support the clinical utility of improved distinction between IP-SCC and DN-SCC. Further studies are necessary to validate these findings before considering escalation of IP-SCC.