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.

Effectiveness of the AJCC 8th edition staging system for selecting patients with T1-2N1 breast cancer for post-mastectomy radiotherapy: a joint analysis of 1986 patients from two institutions.

BACKGROUND: The role of post-mastectomy radiotherapy (PMRT) in the treatment of patients with T1-2N1 breast cancer is controversial. This study's purpose was to evaluate the risk of recurrence of T1-2N1 breast cancer and the efficacy of PMRT in low-, medium- and high-risk groups of patients. METHODS: Post-mastectomy patients with T1-2N1 breast cancer were restaged according to the American Joint Committee on Cancer Staging Manual, 8th edition (AJCC 8th ed.) staging system. Recurrence scores were generated using prognostic factors identified for loco-regional recurrence and distant metastasis in patients without PMRT, and three risk groups were identified. Rates of loco-regional recurrence and distant metastasis were calculated with a competing risk model and compared using Gray's test. Disease-free survival and overall survival were calculated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards regression model was used for the multivariate analysis. RESULTS: Data from 1986 patients (1521without PMRT; 465 with PMRT) were analyzed. Patients without PMRT were stratified into low-, intermediate- and high-risk groups by age, tumor location, AJCC 8th ed. stage, number of positive nodes and lympho-vascular invasion. The 5-year loco-regional recurrence rate and distant metastasis rates for the three risk groups were significant at 2.5, 5.4 and 16.2% (p <  0.001) respectively, and 4.9, 8.4 and 18.6% (p <  0.001) respectively. In the high-risk group, loco-regional recurrence (p <  0.001), and distant metastasis (p = 0.044) were significantly reduced, and disease free survival (p = 0.004), and overall survival (p = 0.029) were significantly improved after PMRT. In the low- and intermediate-risk groups, PMRT had no significant effect on loco-regional recurrence (p = 0.268), distant metastasis (p = 0.252), disease free survival (p = 0.608) or overall survival (p = 0.986). CONCLUSION: Our results showed no benefits of PMRT in the low-risk group, and thus, omitting PMRT radiotherapy in this population could be considered.

Radiotherapy plays an important role in improving the survival outcome in patients with T1-2N1M0 breast cancer - a joint analysis of 4262 real world cases from two institutions.

BACKGROUND: To compare the survival outcomes between breast-conserving surgery (BCS) and modified radical mastectomy (MRM), and to investigate the role of radiotherapy (RT) in patients with pT1-2N1M0 breast cancer. METHODS: A total of 4262 women with T1-2N1M0 breast cancer treated at two institutions were retrospectively reviewed. A total of 3858 patients underwent MRM, and 832 (21.6%) of them received postoperative RT (MRM + RT). A total of 404 patients received BCS plus postoperative RT (BCS + RT). All patients received axillary lymph node dissection, while 3.8% of them had upfront sentinel node biopsy. The association of survival outcomes with different surgical modalities (BCS vs. MRM) and the role of RT were evaluated using multivariable proportional hazards regression and confirmed by the propensity score-matching (PSM) method. RESULTS: At a median follow-up of 71 months (range of 6-230 months), the 5-year overall survival (OS) rates of the BCS and MRM groups were 96.5 and 92.7%, respectively (P = .001), and the corresponding 5-year disease-free-survival (DFS) and locoregional recurrence (LRR) rates were 92.9 and 84.0%, and 2.0 and 7.0% (P = .001), respectively (P < .001). Multivariate analysis revealed that RT was an independent prognostic factor for improved OS (P = .001) and DFS (P = .009), and decreased LRR (P < .001). However, surgery procedure was not independently associated with either OS (P = .495), DFS (P = .204), or LRR (P = .996), which was confirmed by PSM analysis. CONCLUSION: Postoperative radiotherapy rather than the surgery procedures was associated with superior survival outcomes in patients with T1-2N1M0 breast cancer.

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.

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.

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.

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.

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.

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.

[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.

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.

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.

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 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.