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The necessity of level III irradiation in patients with node-negative advanced sinonasal squamous cell carcinoma (SNSCC) is unclear.Seventy-eight patients with advanced SNSCC were included. Survival rates were estimated and compared between treatment groups.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.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.

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.

To determine oncologic outcomes for patients with T4b sinonasal squamous cell carcinoma (SNSCC) treated with either surgery plus radiotherapy or definitive radiotherapy.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.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.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.III Laryngoscope, 2022.

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.

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.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.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).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.III Laryngoscope, 2022.

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.

Purpose Conditional survival (CS) and failure hazard estimations can provide important dynamic prognostic information for clinical decision‐making and surveillance counseling. The current study aimed to investigate the CS and dynamic failure hazard in non‐metastatic nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT). Methods Conditional overall survival (COS) and progression‐free survival (CPFS) estimates adjusted for age and gender against each AJCC 8th stage were calculated. Multivariable Cox regression (MCR) models were fitted in the entire population at baseline and subsequently separate MCR models were fitted in patients who have maintained event‐free time of 1 to 10 years to generate respective hazard ratio (HR). Annual hazard rates of death and progression over 10 years for each stage were also estimated. Results A total of 1993 patients were eligible for analysis. The estimated 5‐year OS and PFS for entire cohort were 79.0% and 70.7% at initial diagnosis. After 5 years of event‐free follow‐up, additional 5‐year COS and CPFS increased to 85.9% and 85.5%, respectively. Stage I/II maintained dramatically favorable CS and low hazard (< 5%) of death and progression over time. Relative to stage I/II, stage III manifested non‐significantly higher failure hazard for the first 3 years of survivorship and approached to similar level of stage I/II afterwards. Stage IVA presented most impressive improvement in terms of both COS (∆=9.8%) and CPFS (∆ = 16.8%) whereas still drastically inferior to that of stage I‐III across all conditional time points. After 4 years of follow‐up, progression hazard of stage IVA became relatively steady of approximate 6%. Conclusions Survival prospect of non‐metastatic NPC improves over years with distinct dynamic patterns across stages, providing important implications for personalized decision‐making in terms of both clinical management and surveillance counseling. Stage‐dependent and hazard‐adapted clinical management and surveillance are warranted., This study aimed to investigate the conditional survival (CS) and dynamic failure hazard in non‐metastatic nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT). Survival prospect of non‐metastatic NPC improved over years with distinct dynamic patterns across stage, providing important implications for personalized decision‐making in terms of both clinical management and surveillance counseling. Stage‐dependent and hazard‐adapted clinical management and surveillance are warranted.

Purpose: To evaluate prognosis for reducing postoperative radiotherapy (PORT) dose to lymph node levels of supraglottic cancer (SC) on real-word 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 60.06Gy/1.82Gy per fraction, while the other uninvolved levels (low-risk levels, LRL) received 50.96Gy/1.82Gy per fraction. In center 2, all received 50Gy/2Gy 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 50Gy for HRL may be an unfavorable treatment option for SC.

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).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 (8A total of 1907 LNs (1164 patients) were contoured. SD7 cm was an independent predictor of overall survival (OS), distant metastasis-free survival (DMFS), and progression-free survival (PFS), with hazard ratios of 1.851, 2.096, and 1.584, respectively. When patients with SD7 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 SD7 cm.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.

Objective To develop a nomogram for predicting the possibility of four or more positive nodes in breast cancer patients with 1–3 positive sentinel lymph nodes (SLN). Materials and methods Retrospective analysis of data of patients from two institutions was conducted. The inclusion criteria were: invasive breast cancer; clinically node negative; received lumpectomy or mastectomy plus SLN biopsy followed by axillary lymph node dissection (ALND); and pathologically confirmed T1-2 tumor, with 1–3 positive SLNs. Patients from one institution formed the training group and patients from the other the validation group. Univariate and multivariate analyses were performed to identify the predictors of four or more positive nodes. These predictors were used to build the nomogram. The area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of the model. Results Of the 1480 patients (966 patients in the training group, 514 in the validation group), 306 (20.7%) had four or more positive nodes. Multivariate stepwise logistic regression showed number of positive (p, Highlights • Five predictors of four or more positive nodes in breast cancer patients were identified. • A nomogram was built using these five factors. • The nomogram was validated on an external cohort. • The proposed nomogram predicts four or more positive nodes with high accuracy. • The nomogram can help in decision making on use of regional nodal irradiation.

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).Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100 mg/mA 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.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.

Background To investigate the clinical characteristics of metachronous second primary malignancies (Met‐SPMs) and its impact on prognosis in hypopharyngeal carcinoma (HPC). Methods We reviewed 593 newly diagnosed HPC patients without invasive synchronous SPMs (Syn‐SPMs) who were treated in our cancer center between 2009 and 2019. According to the status during follow‐up, patients were classified into three groups: (a) without SPMs (No‐SPMs, n = 440), (b) with tumors in situ in the esophagus or stomach (Tis, n = 80), or (c) with Met‐SPMs (n = 73). Results The median follow‐up time for entire cohort (n = 593) was 66.7 months. Met‐SPMs were present in 12.3% of the cohort (73/593). The predominant site of SPMs was esophagus, followed by lung, oral cavity, thyroid, stomach, and oropharynx. In Met‐SPMs group, both index tumor and SPMs were the main causes of death. Tis group exhibited comparable 5‐year overall survival (OS) and disease‐specific survival (DSS) with that of No‐SPMs group. The Met‐SPMs group had similar 5‐year OS rate and better 5‐year DSS rate of 47.3% versus 43.6% (odds ratio [OR], 0.931; 95% confidence interval [CI], 0.681–1.274, p = 0.657) and 66.3% vs. 46.2% (OR, 0.600; 95% CI, 0.402–0.896, p = 0.012), respectively, compared with the No‐SPMs group. Conclusion The overall incidence of Met‐SPMs in HPC was 12.3%. The occurrence of Met‐SPMs does not jeopardize the survival outcome of HPC. Routine surveillance of Met‐SPMs was requisite for patients with HPC.

Objective:To compare the long-term oncological outcomes of endoscopic resection versus open surgery in combination with radiotherapy for locally advanced sinonasal malignancies.Methods:Data for continuous patients with sinonasal epithelial tumors treated in our center between Jan 1999 and Dec 2016 were retrospectively reviewed. Those who received surgery (endoscopic or open surgery) combined with radiotherapy were identified, and 1:1 matching with propensity scores was performed. The primary endpoints of overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. The local recurrence rate (LRR) was assessed by competing risk analysis.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 surgical approach was not associated with lower OS, PFS or LRR. Age, histopathology and stage were independent risk factors for OS.Conclusion:For patients with locally advanced sinonasal carcinoma, 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.

Purpose: To define the clinical characteristics of irradiation-induced nasopharyngeal necrosis (INN) after intensity-modulated radiotherapy (IMRT) and identify the influence of treatment strategies on INN in primary nasopharyngeal carcinoma (NPC) patients.Patients and methods: From 2008 to 2019, NPC patients pathologically diagnosed with INN after primary IMRT were reviewed. Those patients were matched with propensity scores for patients without INN in our center. The impact of treatment strategies on INN occurrence was assessed using univariate and multivariate logistic regression analysis. Results: The incidence rate of INN was 1.9% among the primary NPC population, and 53 patients with INN were enrolled. Headache and foul odor were the main symptoms, and 71.7% of cases had pseudomembrane during or at the end of radiotherapy. All patients were in early or middle stage INN, and no one presented with skull-based osteoradionecrosis. Then 212 non-INN patients were included based on propensity scores match. Overall survival (p=0.248) and progression-free survival (p=0.266) curves were similar between the INN and non-INN groups. Treatment strategies including combining chemotherapy or molecular targeted therapy with radiotherapy were not associated with INN occurrence, while boost dose (OR 7.360; 95% CI 2.301-23.547; P = 0.001) was a predictor factor for it. However, the optimal threshold for an accumulated dose to predict INN's occurrence was failed to determine.Conclusion: In the IMRT era, the severity of INN in primary NPC patients is lessened. This study showed that treatment strategies contributed little to develop INN, while the accumulated dose of radiation may relate to its occurrence.

Purpose To define the clinical characteristics of irradiation-induced nasopharyngeal necrosis (INN) after intensity-modulated radiotherapy (IMRT) and identify the influence of treatment strategies on INN in primary nasopharyngeal carcinoma (NPC) patients. Patients and methods From 2008 to 2019, NPC patients pathologically diagnosed with INN after primary IMRT were reviewed. Those patients were matched with propensity scores for patients without INN in our center. The impact of treatment strategies on INN occurrence was assessed using univariate and multivariate logistic regression analysis. Results The incidence rate of INN was 1.9% among the primary NPC population, and 53 patients with INN were enrolled. Headache and foul odor were the main symptoms, and 71.7% of cases had pseudomembrane during or at the end of radiotherapy. All patients were in early or middle stage INN, and no one presented with skull-based osteoradionecrosis. Then 212 non-INN patients were included based on propensity scores match. Overall survival (p = 0.248) and progression-free survival (p = 0.266) curves were similar between the INN and non-INN groups. Treatment strategies including combining chemotherapy or molecular targeted therapy with radiotherapy were not associated with INN occurrence, while boost dose (OR 7.360; 95% CI 2.301–23.547; p = 0.001) was a predictor factor for it. However, the optimal threshold for an accumulated dose to predict INN's occurrence was failed to determine. Conclusion In the IMRT era, the severity of INN in primary NPC patients is lessened. This study showed that treatment strategies contributed little to develop INN, while the accumulated dose of radiation may relate to its occurrence.

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). This phase Ⅱ trial was conducted to provide the direct evidence for the current practice of prescribing antiemetic in patients with LA-HNSCC receiving CCRT.Methods Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100 mg/m² every 3 weeks for two cycles. All patients were given orally aprepitant 125 mg once on d1, then 80mg once on d2-5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8mg 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 old, 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% 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 response and nausea-free response in 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 adverse event 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. Randomised phase 3 studies are required to further define the potential role of NK1RA in chemoradiotherapy setting.Trial registration: ClinicalTrials.gov, number NCT03572829. Registered 28 June 2018, https://clinicaltrials.gov/ct2/show/NCT03572829?term=NCT03572829&draw=2&rank=1.

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.

Purpose To provide a direct evidence for the current practice of prescribing antiemetic with aprepitant, dexamethasone and ondansetron in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) receiving concurrent chemoradiotherapy (CCRT). Methods Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100 mg/m² every 3 weeks for two cycles. All patients were given orally aprepitant 125 mg once on d1, then 80mg once on d2-5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8mg 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 old, 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% 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 response and nausea-free response in 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 adverse event 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 CCRT. Trial registration ID: NCT03572829.

Objective: This study aimed to determine clinicopathologic characteristics of primary frontal sinus malignancies (FSMs) and provide long-term survival results.Materials and methods: A retrospective study of six cases of primary FSMs at our center from 2006 to 2016 was performed. The demographics characteristics, tumor characteristics, treatment modalities and survival outcomes were recorded. 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 5 cases of stage Ⅲ and one 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 50Gy to 75.95Gy. 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 to 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.

Objective This study aimed to determine clinicopathologic characteristics of primary frontal sinus malignancies (FSMs) and provide long-term survival results. Materials and methods A retrospective study of six cases of primary FSMs at our center from 2006 to 2016 was performed. The demographics characteristics, tumor characteristics, treatment modalities and survival outcomes were recorded. 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 5 cases of stage Ⅲ and one 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 50Gy to 75.95Gy. 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 to 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.

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 P = .001) and DFS (P = .009), and decreased LRR (P 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.

BACKGROUND Esthesioneuroblastoma (ENB) is a rare malignant neoplasm. Currently, no consistent and universal staging system for ENB exists. The aim of this study is to propose a TNM-based classification. SUBJECTS AND METHODS Hundred and forty-two patients from our institution, with ENB pathologically confirmed between July 1978 and December 2018, were reviewed. All patients were restaged according to the Kadish stage, Morita stage and American Joint Committee on Cancer (AJCC) T classification from clinical and radiological data. Multivariate Cox proportional hazard regression analyses were performed to determine the impact of various factors. The goodness-of-fit and predictive accuracy of the different staging systems were calculated using R software. RESULTS The median follow-up time was 57 months (range: 4-229 months). According to the Kadish system, the 5-year overall survival (OS) for patients with stage A, B and C was 100%, 83.6% and 64.2%, respectively (P = .055). With respect to the Morita classification, 5-year OS for stages A, B, C and D was 100%, 83.6%, 70.7% and 50.0%, respectively (P = .004). Analysis based on the proposed staging model demonstrated 5-year OS for stage I, II, III and IV disease was 100%, 88.9%, 75.9% and 49.0%, respectively (P

Background The aim of this study is to evaluate the efficacy of different treatment strategies and the potential prognostic factors of esthesioneuroblastoma (ENB). Materials and methods Between April 1984 and December 2018, 138 patients with non-metastatic ENB were retrospectively analyzed. The treatment modalities mainly included surgery alone (n = 7), radiotherapy alone (n = 33), concurrent chemoradiotherapy (n = 17), surgery combined with current chemoradiotherapy (n = 32), and surgery plus radiotherapy (n = 49). Results The median follow-up time for the entire cohort was 61 months (range, 4–231 months). The 5-year overall survival (OS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS) rate were 69.6, 78.0 and 73.9%, respectively. Surgery combined with radiotherapy elicited superior survival results, and the combination of surgery and current chemoradiotherapy achieved the best prognoses for all patients, patients with advanced Kadish disease, patients receiving intensity modulated radiation therapy and those with positive surgical margin. Univariate analysis identified orbital invasion and treatment modalities were predictors for OS, LRFFS and DMFS. Lymph node metastasis was associated with OS and DMFS, but not LRFFS. Intracranial invasion, advanced Kadish stage and not receiving concurrent chemotherapy were also predictive of lower OS. Multivariate analyses indicated that lymph node metastasis was an independent prognostic factor affecting DMFS, whereas treatment modalities was independent prognostic factors for OS and LRFFS. Conclusion Orbital invasion, intracranial invasion, lymph node metastasis and advanced Kadish disease at initial diagnosis were significantly associated with inferior prognosis. Regarding the treatment modality, the optimal strategy remined surgery with radiotherapy-based multimodality treatment. The concurrent chemoradiotherapy may play a more beneficial role.

Purpose To investigate the effect of chemotherapy and radiotherapy timing after breast conserving surgery (BCS) on recurrence and survival of women with early-stage breast cancer. Patients and methods We retrospectively analyzed 900 patients who underwent BCS followed by both adjuvant chemotherapy and radiotherapy. Of these, 488 women received chemotherapy first (CT-first group) while the other 412 received radiotherapy first (RT-first group). Locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and further confirmed with propensity-score matching (PSM) and the Cox proportional hazards model. The optimal cut-off value of interval time from surgery to the start of chemotherapy was calculated by Maxstat. Results The median follow-up was 7.1 years. In pre-match analysis, the CT-first group had a significantly higher 8-year DFS than the RT-first group (90.4% vs. 83.1%, P = 0.005). PSM analysis of 528 patients indicated that the 8-year DFS (91.0% vs. 83.3%, P = 0.005) and DM (8.6% vs. 14.6%, P = 0.017) were significantly better in the CT-first group, but that the OS (P = 0.096) and LRR (P = 0.434) were similar. We found the optimal cut-off value of interval from surgery to chemotherapy was 12 weeks. Patients starting chemotherapy later than 12 weeks after surgery had significantly inferior survival outcomes. Conclusion For women with breast cancer who require both chemotherapy and radiotherapy after BCS, adjuvant chemotherapy should be started within 12 weeks. Delaying the initiation of radiotherapy, for administration of long-course chemotherapy, does not compromise outcomes.

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 p 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.

Purpose: To explore the efficacy of concomitant chemotherapy in intensity-modulated radiotherapy (IMRT) to treat stage II nasopharyngeal carcinoma (NPC). Methods and Materials: In this randomized phase 2 study [registered with ClinicalTrials.gov (NCT01187238)], eligible patients with stage II (2010 UICC/AJCC) NPC were randomly assigned to either IMRT alone (RT group) or IMRT combined with concurrent cisplatin (40 mg/m2, weekly) (CCRT group). The primary endpoint was overall survival (OS). The second endpoints included local failure-free survival (LFFS), regional failure-free survival (RFFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and acute toxicities. Results: Between May 2010 to July 2012, 84 patients who met the criteria were randomized to the RT group (n = 43) or the CCRT group (n = 41). The median follow-up time was 75 months. The OS, LFFS, RFFS, DFS, and DMFS for the RT group and CCRT group were 100% vs. 94.0% (p = 0.25), 93.0% vs. 89.3% (p = 0.79), 97.7% vs. 95.1% (p = 0.54), 90.4% vs. 86.6% (p = 0.72), and 95.2% vs. 94.5% (p = 0.77), respectively. A total of 14 patients experienced disease failure, 7 patients in each group. The incidence of grade 2 to 4 leukopenia was higher in the CCRT group (p = 0.022). No significant differences in liver, renal, skin, or mucosal toxicity was observed between the two groups. Conclusion: For patients with stage II NPC, concomitant chemotherapy with IMRT did not improve survival or disease control but had a detrimental effect on bone marrow function.

Background To analyze the patterns of locoregional recurrence in breast cancer patients after mastectomy. Methods The retrospective study included 7073 women with breast cancer without post-mastectomy radiotherapy: 4604 (65.1%) had pT1–2 N0 disease (low risk); 2042 (28.9%), pT1–2 N1 (intermediate risk); and 427 (6.0%), pT3–4 and/or pN2–3, or pT1–2 N1 after neoadjuvant chemotherapy (high risk). The distribution of cumulative locoregional recurrence was analyzed. The local recurrence and regional recurrence rates were estimated by the Kaplan-Meier method, and differences were compared with the log-rank test. Multivariate analysis was performed using Cox logistic regression analysis. Results In the median follow-up of 63.0 months, 469 patients had locoregional recurrence: chest wall recurrence in 238 (50.7%) cases, supraclavicular/infraclavicular nodes in 236 (50.3%) cases, axilla in 92 (19.6%), and internal mammary nodes in 50 (10.7%) cases. The 5-year local recurrence and regional recurrence rates were 2.5 and 4.4%, respectively. Subgroup analysis of the three risk groups and five molecular subtypes (luminal A, luminal B-Her2 negative, luminal B-Her2 positive, Her2-enriched, and triple negative) also showed that the chest wall and supraclavicular/infraclavicular nodes were the most common recurrence sites. Age, tumor location, T stage, N stage, and hormone receptor status were independent prognostic factors for both local recurrence and regional recurrence (p Conclusions The chest wall and supraclavicular/infraclavicular nodes are common sites of locoregional recurrence in breast cancer, irrespective of disease stage or molecular subtype, and the prognostic factors for local recurrence and regional recurrence are similar. Therefore, chest wall and supraclavicular/infraclavicular nodes irradiation should always be considered in post-mastectomy radiotherapy.

Additional file 1: Table S1. The univariate and multivariate analysis of prognostic factors for SCN recurrence

Laryngeal preservation strategies for resectable locally advanced hypopharyngeal carcinoma (LAHPC) have been explored. However, the optimal strategy remains unclear.To evaluate a response-adapted strategy based on an early response to radiotherapy (RT) in patients with resectable LAHPC.This cohort study was conducted from May 2009 to October 2019 with a median (IQR) follow-up period of 66.5 (44.7-97.0) months. The study was conducted at a tertiary academic medical center and included 423 patients pathologically confirmed stage III and IVB LAHPC. A total of 250 patients with previous cancer history, synchronous primary cancer, stage I or II, or with unresectable hypopharyngeal carcinoma were excluded.Patients who reached 80% or greater tumor regression when evaluated endoscopically and by imaging methods at 50 Gy received definitive RT or concurrent chemoradiotherapy, and those with less than 80% regression underwent surgery 4 to 6 weeks after RT.Five-year overall survival and survival with a functional larynx.Overall, 423 patients were included in the study (median [IQR] age, 55 [50-63] years; 408 [96.5%] men and 15 [3.5%] women). The response-adapted and primary surgery groups had significantly better survival than the primary RT group (52.7% and 54.4% vs 27.7%, respectively; P .001). The response-adapted and primary surgery groups had similar 5-year overall survival of 52.7% vs 54.4%, respectively (hazard ratio [HR], 1.02; 95% CI, 0.75 to 1.39; P = .89). The response-adapted group had better 5-year survival with functional larynx than the primary surgery group (40.6% vs 33.9%; HR, 0.64; 95% CI, 0.49 to 0.84, P = .001). Surgery complications did not significantly differ between the 2 groups. Among patients in the response-adapted group who required total laryngectomy (n = 186) as indicated by pretreatment evaluation, the 5-year cumulative Kaplan-Meier survival with functional larynx was 39.8%.In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, maximum tumor control, and higher laryngeal preservation compared with primary surgery and primary RT strategies. This approach could provide a feasible laryngeal preservation strategy in patients with LAHPC.

To explore the effects of elective neck irradiation (ENI) in clinically node-negative (cN0) sinonasal adenoid cystic carcinoma (SNACC).Between January 2000 and December 2016, 60 patients with cN0 sinonasal adenoid cystic carcinoma receiving surgery combined with radiotherapy were analyzed retrospectively, there were 39 received ENI (ENI group) and 21 with no ENI (non-ENI group). Propensity score matching (PSM) was performed to balance clinical factors and match patients. Kaplan-Meier method and Cox proportional hazard model were used to evaluate the impact of ENI on regional relapse risk and survival outcomes.The median follow-up time for our cohort was 82.0 months (12.4-190.7 months). Four patients (6.7%) developed neck nodal relapses, with a median time to progression of 38.8 months. Among them, two patients in ENI group but failed out-field. After PSM, 21 patients were matched in each group. The 7-year regional relapse-free survival (RRFS), distant metastasis free survival (DMFS), progression-free survival (PFS), and overall survival (OS) between ENI group and non-ENI group were 85.4% vs 73.3% (p = 0.845), 65.2% vs 65.6% (p = 0.548), 68.3% vs 66.2% (p = 0.425), and 87.3% vs 84.0% (p = 0.953). Multivariate Cox analysis showed ENI was not an independent prognostic factor associated with RRFS, DMFS, PFS and OS.Our findings firstly demonstrated the omission of elective neck irradiation in the management of cN0 sinonasal adenoid cystic carcinoma might be safe without compromising disease control and should be further investigated.

The energy release of aluminized explosives was impeded by the aggregation of aluminum powders, especially for nano-aluminum powders. The core-shell HMX@(Al@GAP) explosives with 5 wt.% to 15 wt.% aluminum were fabricated, with systematical investigation of morphology, mechanical properties, thermal decomposition, combustion and detonation properties. Compared with the physical mixtures, the aluminized explosives with core-shell microstructure showed better creep resistance and mechanical strength. The thermal decomposition of HMX in core-shell HMX@(Al@GAP)was slightly advanced due to good dispersion of Al@GAP particles. Delayed but more vigorous and longer burning during combustion process was witnessed for the core-shell explosive. For HMX@15wt%(Al@GAP) aluminized explosives, the detonation velocity and specific kinetic energy was 8567 m/s and 1.412 kJ/g, which was 1.3% and 5.1% higher than the corresponding physical mixtures. The reaction of the core-shell HMX@(Al@GAP) and the physical mixtures were calculated by ReacFF-/g force field, showing remarkable dependent of the average temperature on the microstructure. Present research might provide new insight for synergistically improvement of mechanical and detonation properties in aluminized explosives.

To assess prognostic benefits of intraoperative electron beam radiation therapy (IOERT) in patients with nonmetastatic locally advanced pancreatic cancer (LAPC) and evaluate optimal adjuvant treatment after IOERT. A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Two hundred forty-seven consecutive patients with nonmetastatic LAPC who underwent IOERT between January 2008 and May 2015 were identified and included in the study. Overall survival (OS) was calculated from the day of IOERT. Prognostic factors were examined using Cox proportional hazards models. The 1-, 2-, and 3-year actuarial survival rates were 40%, 14%, and 7.2%, respectively, with a median OS of 9.0 months. On multivariate analysis, an IOERT applicator diameter