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Background: The impact of timing of PORT initiation for major salivary gland cancers on survival is unknown. We aim to examine the impact of PORT timeliness on overall survival (OS) of patients with major salivary gland cancers., Methods: This was a cross-sectional analysis using data from the National Cancer Database (2004-2017) and included patients with major salivary gland cancer treated with surgery and PORT., Results: In total, 5701 patients were included (3133 [55%] male, 4644 [82%] white, mean age 59 ± 16 years). For the overall cohort, PORT >6 weeks was not associated with decreased OS (1.00 aHR, 95% CI 0.89-1.11). When specifically examining patients with mucoepidermoid carcinoma, PORT >6 weeks was associated with a decreased OS (1.27 aHR, 95% CI 1.01-1.58)., Conclusions: Overall, this analysis did not demonstrate a survival benefit for initiating PORT within 6 weeks for patients with salivary gland malignancies. Subset analysis did support initiating PORT within 6 weeks after resection for patients with mucoepidermoid carcinomas. This was not demonstrated in other major salivary gland cancer histologies., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

There is an urgent need for novel systemic therapies for recurrent/systemic salivary gland cancer, as current treatment options are scarce. [ 68 Ga]Ga-PSMA-11 PET/CT revealed relevant uptake of prostate-specific membrane antigen (PSMA) in adenoid cystic carcinoma (AdCC) and salivary duct carcinoma (SDC). Therefore, we assessed the safety, feasibility, efficacy and radiation dosimetry of [ 177 Lu]Lu-PSMA-I&T treatment in AdCC and SDC patients in a prospective pilot study. Methods: This single-center, single-arm study intended to include 10 recurrent/metastatic AdCC patients and five recurrent/metastatic SDC patients. AdCC patients could only participate in case of progressive and/or symptomatic disease. Patients required ≥ 1 lesion ≥ 1.5 cm with an SUV max on [ 68 Ga]Ga-PSMA-11 PET/CT above liver SUV mean . Patients were planned to receive four cycles ~ 7.4 GBq [ 177 Lu]Lu-PSMA-I&T. In case of progressive disease per RECIST 1.1 at mid-treatment evaluation after two cycles, treatment was discontinued. Safety was the primary endpoint. Secondary endpoints included objective response rate (ORR), tumor- and organ-absorbed radiation doses and progression-free survival. Results: After screening, 10 out of 15 (67%) AdCC and two out of 10 (20%) SDC patients were eligible. Two patients (17%) demonstrated grade 3 treatment-related toxicity: lymphocytopenia (8%) and hyponatremia (8%). No dose-limiting toxicities occurred. In the AdCC cohort, six patients (60%) completed the four treatment cycles. Due to progressive disease, treatment was discontinued after two cycles in three patients (30%) and after one cycle in one patient (10%). No objective responses were observed (ORR: 0%). Three AdCC patients (30%) showed stable disease ≥ 6 months (7, 17 and 23 months). None of the two SDC patients completed the treatment: one patient deteriorated after the first cycle, while the other had progressive disease after two cycles. The high screen failure rate due to insufficient PSMA uptake resulted in premature closure of the SDC cohort. Dosimetry revealed low tumor-absorbed doses (median 0.07 Gy/GBq, range 0.001-0.63 Gy/GBq). Conclusions: [ 177 Lu]Lu-PSMA-I&T in AdCC and SDC patients was safe and generally well-tolerated. However, efficacy was limited, likely due to low tumor-absorbed doses. For SDC, [ 177 Lu]Lu-PSMA-I&T appears unfeasible due to insufficient PSMA uptake., Competing Interests: Competing Interests: NvR, MU, CD, SP, BP, AvEvG, MK, MK: nothing to declare. JN: has received research grants from ABX and Novartis, and has received consulting and teaching fees from ITM, POINT biopharma, CURIUM, Novartis and Bayer. CvH: has been member of advisory boards for Bayer, Bristol-Myers Squibb, Elevar, Ipsen, MSD and Regeneron, and has received research grants from Astra Zeneca, Bristol-Myers Squibb, MSD, Merck, Ipsen, Novartis and Sanofi., (© The author(s).)

Objective: Undergoing surgery and adjuvant radiotherapy (aRT) at the same facility has been associated with higher overall survival (OS) in head and neck squamous cell carcinoma. Our study investigates whether undergoing surgery and aRT at the same academic facility is associated with higher OS in major salivary gland cancer (MSGC)., Methods: The 2006-2018 National Cancer Database was queried for patients with MSGC undergoing surgery at an academic facility and then aRT. Multivariable binary logistic and Cox proportional hazards regression models were implemented., Results: Of 2801 patients satisfying inclusion criteria, 2130 (76.0%) underwent surgery and aRT at the same academic facility. Residence in a less populated area (adjusted odds ratio [aOR] 1.69, 95% confidence interval [CI] 1.16-2.45), treatment without adjuvant chemotherapy (aOR 1.97, 95% CI 1.41-2.76), and aRT duration (aOR 1.02, 95% CI 1.01-1.04) were associated with undergoing surgery and aRT at different facilities on multivariable logistic regression adjusting for patient demographics, clinicopathologic features, and adjuvant therapy (p < 0.01). Five-year OS was higher in patients undergoing surgery and aRT at the same academic facility (68.8% vs. 61.9%, p < 0.001). Undergoing surgery and aRT at different facilities remained associated with worse OS on multivariable Cox regression (aHR 1.41, 95% CI 1.10-1.81, p = 0.007)., Conclusion: Undergoing surgery and aRT at the same academic facility is associated with higher OS in MSGC. Although undergoing surgery and aRT at the same academic facility is impractical for all patients, academic physicians should consider same-facility treatment for complex patients who would most benefit from clear multidisciplinary communication., Level of Evidence: 4 Laryngoscope, 134:3620-3632, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To determine the indications for radiotherapy in salivary gland cancer and to specify the modalities and target radiation volumes., Material and Methods: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group which drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method., Results: Postoperatively, radiotherapy to the primary tumor site±to the lymph nodes is indicated if one or more of the following adverse histoprognostic factors are present (risk>10% of locoregional recurrence): T3-T4 category, lymph node invasion, extraglandular invasion, close or positive surgical margins, high tumor grade, perineural invasion, vascular emboli, and/or bone invasion. Intensity-modulated radiation therapy (IMRT) is the gold standard. For unresectable cancers or inoperable patients, carbon ion hadrontherapy may be considered., Conclusion: Radiotherapy in salivary gland cancer is indicated in postoperative situations in case of adverse histoprognostic factors and for inoperable tumors., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Salivary gland cancers are rare in general and salivary duct carcinoma and epithelial myoepithelial carcinomas are rare subtypes. This topic discussion will review the characteristics of these uncommon cancers. Additionally, it will briefly discuss available guidelines for salivary cancers and summarize author opinions on the role of adjuvant radiation therapy for these cases., Competing Interests: Disclosures None., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Adenoid cystic carcinoma (AdCC) is a rare and relatively heterogenous salivary gland malignancy, for which there is debate regarding grading, and clinical prognostic factors, including the role of adjuvant radiotherapy., Methods: Surveillance, Epidemiology, and End Results (SEER) data were reviewed for AdCC cases from 2000 to 2018., Results: A total of 1978 patients with AdCC were identified. Most patients were between 50 and 59 years of age (21.4 %), female (59.9 %), and Caucasian (76.8 %). Most tumors were localized at presentation (44.3 %), and moderately differentiated (or grade II) (43.7 %). Overall and DSS 5-year survival rates were 70.7 % (95 % CI, 69.9-78.8), and 78.6 % (95 % CI, 77.6-79.6). The best overall 5-year survival rate was observed for those treated with surgery plus radiation, 76.8 % (95 % CI, 75.5-78.1). Multivariate analysis revealed male sex, age > 65 (H.R. 2.659 (95 % CI,2.291-3.098), p < .001), grade III/IV (H.R.5.172 (95 % CI, 3.418-7.824), p < .001), nodal metastasis, distant metastasis (H.R. 2.400 (95 % CI, 2.178-2.645), p < .001), chemotherapy only, and combination therapy as negative prognostic factors, and receiving surgery plus radiation therapy (H.R.0.586 (95 % CI, 0.505-0.679), p < .001) as a positive prognostic factor. When limited just to the lungs, had much better survival than those patients with distant metastases to other sites such as the bones and liver (p < .001)., Conclusion: This SEER study identifies grade, particularly III and IV, to be the strongest single predictor of worse survival. Patients did best when treated with surgery and postoperative radiotherapy. These results can inform future management of patients with this challenging cancer type., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the effectiveness of radiotherapy and its association with second primary malignancies (SPMs) risk in major salivary gland carcinomas (MSGCs) patients., Methods: Cohort 1 included 7274 surgically treated MSGC patients from the Surveillance, Epidemiology, and End Results database, assessing the effectiveness of radiotherapy. Cohort 2 (n = 4213) comprised patients with ≥5-year survival in Cohort 1 to study SPMs., Results: Radiotherapy decreased overall survival in MSGCs patients, but improved it in high-grade MSGCs. Cumulative SPMs incidences at 25 years were 16.5% in the radiotherapy (RT) group compared to 14.5% in the non-radiotherapy (NRT) group. For second head and neck carcinomas (SHNCs), incidences were 3.4% in RT versus 1.6% in NRT. Radiotherapy increased the relative risks of tumors, particularly SHNCs (RR = 1.78). The 10-year OS rates of SHNCs after radiotherapy were significantly lower., Conclusion: Radiotherapy improves survival in advanced-stage MSGCs but increases the risk of developing SPMs, particularly SHNCs., (© 2024 Wiley Periodicals LLC.)

Aims: The aim of this study was to compare the efficacy of adjuvant radiotherapy (RT) versus adjuvant chemoradiotherapy (CRT) in patients with salivary gland tumors (SGTs)., Materials and Methods: Data from patients who underwent adjuvant RT for a diagnosis of SG cancer at Ankara Atatürk Education and Research Hospital, Ankara Numune Education and Research Hospital and Ankara Bilkent City Hospital between September 01, 2009 and September 01, 2022 were analysed retrospectively. We evaluated the efficacy of RT alone versus CRT in these patients in terms of acute response, treatment tolerance, overall survival (OS), and disease-free survival (DFS)., Results: Fifty-five patients who underwent RT between September 14, 2009 and August 04, 2022 at Ankara Atatürk Education and Research Hospital, Ankara Numune Education and Research Hospital and Ankara Bilkent City Hospital were included in this study. Eight patients who did not meet the study criteria were excluded; thus, the analysis was performed for 47 patients. The median follow-up period was 60 months (range: 6-160 months). The median patient age was 53 years (range: 18-86 years). Thirty-nine patients (83%) had parotid tumors and eight patients (17%) had submandibular cancer. The time from surgery to RT was 48 days (range: 20-126 days). Intensity-modulated radiotherapy was administered to all patients and the median RT dose was 66 Gy (range: 52-70 Gy). Concomitant chemotherapy (CCT) (40 mg/m 2 of cisplatin weekly) was administered to 13 patients (27.7%). Acute adverse events were observed in 17 patients (36.2%). Interruption of RT was noted for only six patients (12.8%), and this proportion did not differ significantly between the CRT and RT-only arms ( P = 0.538). Acute side effects were observed in 17 patients (36.2%), and there were no significant relationships between acute side effects and the administration of CCT ( P = 0.112). Recurrence was observed in 10 patients (21.3%). All recurrences were locoregional and no distant metastases were observed during the follow-up period. The median DFS of the patients was 48 months (range: 4-160 months), 1-year DFS was 86%, 2-year DFS was 83.5%, and 5-year DFS was 77.9%. There was no statistically significant difference in DFS between the adjuvant CRT and RT-alone arms ( P = 0.114). At the date of last follow-up, 14 patients (29.8%) had died. The median OS of the patients was 58.5 months (range: 6-160 months), 1-year OS was 91.4%, 2-year OS was 86.8%, and 5-year OS was 78%. There was no statistically significant difference in OS between the adjuvant CRT and RT-only arms ( P = 0.453)., Conclusion: Stage was identified as the most important prognostic factor for DFS and OS. No significant differences in OS, DFS, or acute side effects were observed between the CRT and RT-only arms. Additional studies are needed to identify the subgroup of SGT patients for which CRT is most warranted., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Background: Adenoid cystic carcinoma of the salivary glands is a relatively rare malignancy characterized by slow growth and a poor prognosis, and effective treatments remain challenging to identify. This systematic review, following the PRISMA guidelines, aimed to analyze the potential benefits of post-operative radiotherapy in terms of local control of recurrences and survival advantages when compared with surgery alone in patients with adenoid cystic carcinoma., Methods: A comprehensive systematic review was conducted by searching the MEDLINE, Cochrane, EMBASE, and OVID databases from January 1999 to July 2022. The goal was to identify articles comparing surgery alone with surgery plus postoperative radiotherapy for adenoid cystic carcinoma of the salivary glands. Downs and Black Checklist was used to assess the methodological quality and risk of bias of each included study. The data analysis was performed using Review Manager version 5.4.1., Results: This review included 8 studies comprising a total of 3103 patients, divided based on the analyzed outcomes. The pooled odds ratio for overall survival at 5 years was 0.87 (95% confidence interval 0.43-1.76, p = 0.70), and at 10 years was 1.23 (95% confidence interval 0.69-2.16, p = 0.48). In both cases, no statistically significant differences were observed. However, the pooled odds ratio for local control at 5 years was 3.37 (95% confidence interval 1.35-8.42, p = 0.009), providing strong support for the use of post-operative radiation., Conclusions: The findings from the meta-analysis suggest that post-operative radiotherapy significantly improves local control in patients with adenoid cystic carcinoma. However, there was no statistically significant increase in survival at 5 and 10 years. It is essential to note that the quality of the studies included in this meta-analysis ranged from fair to poor. To better clarify the indications for post-operative radiotherapy, future high-quality research is needed, particularly with improved stratification of patient groups. Additionally, it is important to recognize that achieving local control in adenoid cystic carcinoma is crucial for enhancing the overall quality of life for patients. We acknowledge that this review was not registered in the PROSPERO database, and the data pooling was conducted using a random effects model., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Postoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence., Objective: To evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins., Design, Setting, and Participants: The American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023., Main Outcomes and Measures: Main outcomes were risk factors for local recurrence., Results: A total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group., Conclusions and Relevance: In this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.

Purpose: Due to the rarity of adenoid cystic carcinoma (ACC) of the major salivary gland, there is no consensus on the extent of prophylactic neck irradiation (PNI) for patients with clinically negative lymph nodes (cN0) disease., Materials and Methods: We conducted a retrospective analysis of all patients with ACC of the major salivary gland who received treatment at our center between January 2010 and April 2020. The primary endpoint was regional failure-free survival (RRFS). Secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and acute toxicity., Results: A total of 139 patients were included in the analysis. For cN0 patients, the 5-year RRFS, OS, DMFS, and LRFS were 93.2%, 90.2%, 75.7%, and 91.4%, respectively. Multivariate analysis revealed that PORT was an independent prognostic factor for RRFS and LRFS. No statistically significant differences were observed between the Level III sparing PNI group and the Standard PNI group in terms of RRFS, OS, DMFS, and LRFS. The doses delivered to the larynx and thyroid in the Level III sparing PNI group were significantly lower than those in the Standard PNI group., Conclusion: In patients with cN0 ACC of the major salivary gland, PNI improves regional control, and the level III nodal region sparing radiotherapy does not increase the risk of level III recurrence, while potentially reducing toxicity., (© 2024. Italian Society of Medical Radiology.)

Background and Purpose: Salivary gland cancers (SGCs) are hard to treat when inoperable, and sole brachytherapy appears to be a promising therapeutic strategy. This study aimed to evaluate the effectiveness, safety, and capability of pain palliation using sole brachytherapy for inoperable, recurrent, and irradiated SGCs., Materials and Methods: Patients with inoperable SGCs treated using sole brachytherapy at Peking University School and Hospital of Stomatology were retrospectively included. Patients were divided into primary and recurrent groups and irradiated and non-irradiated groups. Local control (LC), overall survival (OS), radiation-relevant toxicities, and Visual Analogue Scale (VAS) score for pain, were recorded and evaluated., Results: A total of 176 patients from 2006 to 2020 were included. The 5-year LC rate was 48.6 %; for the primary, recurrent, non-irradiated and irradiated groups, the rates were 72.6 %, 39.5 %, 56.8 %, and 34.5 %, respectively. The 5-year OS rates was 52.6 %; for the primary, recurrent, non-irradiated, and irradiated groups, the rates were 62.9 %, 48.6 %, 58.9 %, and 42.3 %, respectively. The mean ± standard deviation of posttreatment VAS score of pain was 2.154 ± 2.989, which was significantly decreased from the score of 6.923 ± 2.280 prior to brachytherapy. Skin hyperpigmentation, mucositis, and dysphagia were the most frequently reported adverse events., Conclusions: Brachytherapy as a sole modality, was retrospectively proven effective and safe in the management of inoperable SGCs and was beneficial in multiple irradiation and pain control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background/aim: This study aimed to assess the effect of adjuvant radiotherapy on locoregional control, disease-free survival, and overall survival rates in patients with major salivary gland malignancies. The study also aimed to provide findings to guide clinicians in selecting appropriate candidates for adjuvant radiotherapy and optimizing treatment strategies for this challenging disease., Patients and Methods: A retrospective single-center analysis was conducted, reviewing the medical records of patients diagnosed with major salivary gland malignancies between November 2008 and May 2023. Inclusion criteria were histologically confirmed malignancy, surgical resection of the primary tumor, adjuvant radiotherapy, and availability of clinical and follow-up data. Survival analyses were performed using the Kaplan-Meier method, and Cox proportional hazards regression models were used to assess survival outcomes., Results: The study included 37 patients with major salivary gland malignancies. The most common site was the parotid gland, and the predominant histopathological diagnosis was salivary duct carcinoma. Adjuvant radiotherapy was generally well-tolerated, with the most common acute toxicities being grade 1-2 mucositis and dermatitis. The 5-year overall survival and progression-free survival rates were 93.8% and 62.9%, respectively. Locoregional control rate at five years was 89.1%. Recurrence occurred in 12 patients, with most cases observed within two years from the start of adjuvant radiotherapy. Distant metastasis was observed in nine patients., Conclusion: This retrospective analysis highlights the positive impact of adjuvant radiotherapy on locoregional control and survival outcomes in major salivary gland malignancies. The findings contribute to the existing body of evidence, aiding clinicians in treatment decision-making and potentially informing future prospective studies and treatment guidelines for this challenging disease., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands., Methods: The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution., Results: In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10 years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10 years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins., Conclusions: Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins., (© 2023 American Cancer Society.)

Background: There is limited information of radical radiotherapy (RT) on lymphoepithelial carcinoma of salivary gland (LECSG) regarding to the rarity of the disease. We conducted this retrospective study that evaluated the feasibility and efficacy of radical RT with/without surgery in LECSG., Methods: We retrospectively reviewed patients that were pathologically diagnosed of LECSG and had definite or suspicious residual disease. The prescribed dose given to P-GTV and/or P-GTV-LN was 66 to 70.4 Gy. The clinical target volume (CTV) involved ipsilateral salivary gland and corresponding lymph node drainage area., Results: A total of 56 patients were included. With a median follow-up of 60 months (range: 8 to 151 months), the 1-, 5-, and 10-year progression-free survival (PFS) rates were 94.6%, 84.7% and 84.7%; locoregional progression-free survival (LRPFS) rates were 98.2%, 87.4% and 87.4%; distance metastasis-free survival (DMFS) rates were 94.6%, 86.7% and 86.7%; and overall survival (OS) rates were 98.2%, 92.4% and 89.0%, respectively. A total of 7 patients without surgery were included. All patients were alive and only one patient experienced failure of distant metastasis four months after RT. The results of univariate analysis showed that compared with N stage, the number of positive lymph nodes (2 positive lymph nodes) was better prognostic predictor especially in PFS. There were no treatment-related deaths and most toxicities of RT were mild., Conclusions: Radical RT with/without surgery in LECSG for definite or suspicious residual disease is feasibility and efficacy. Most toxicities of RT were mild due to the target volume involved ipsilateral area., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Major salivary gland cancers (MSGCs) are often treated with primary surgery followed by adjuvant therapy for high-risk pathology. Patients with these cancers may opt out of recommended postoperative radiation therapy (PORT) for many reasons and consequently may suffer worse outcomes., Study Design: Retrospective cohort study., Setting: National Cancer Database., Methods: Patients diagnosed with MSGC from 2004 to 2016 were identified, and overall survival and risk factors for refusal of recommended PORT were analyzed based on demographic, socioeconomic, and clinical factors. Multivariable logistic regression and a Cox model were used to conduct the analysis., Results: 211 out of 4704 qualifying patients (4.5%) refused recommended PORT. Multivariable analysis demonstrated increased PORT refusal for age >74 years (odds ratio OR 4.34, confidence interval [CI] [2.43-7.85]), Asian race (OR 2.25, CI [1.10-4.23]), and certain facility types (comprehensive cancer center, OR 2.39, CI [1.08-6.34]; academic research program, OR 3.29, CI [1.49-8.74]; and integrated network cancer program, OR 2.75, CI [1.14-7.7]). N2 stage was associated with decreased PORT refusal (OR 0.67, CI [0.45-0.98]). The 5-year overall survival for patients who received and refused PORT were significantly different at 65.8% and 53.8%, respectively (p < .001). When controlling for several factors, PORT refusal was independently associated with significantly lower overall survival (HR 1.54, CI [1.21-1.98])., Conclusion: Patient refusal of recommended PORT in MSGC is rare, associated with various disease and socioeconomic factors, and may decrease overall survival. Our findings can assist clinicians in counseling patients and identifying those who may be more likely to opt out of recommended PORT., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

A systematic review was carried out to evaluate if adjuvant radiotherapy for acinic cell carcinomas (ACCs) of salivary glands improves survival. Twelve retrospective studies published between 2000 and 2020 that analysed the effect of radiotherapy on salivary gland neoplasms and ACCs of salivary glands and met the inclusion criteria were included in the review. The overall quality of the studies was moderate to low. There was no high-quality evidence for improved survival with radiotherapy for ACCs of the salivary gland. Some evidence suggests that there may be an advantage for patients with high-grade tumours, but these data should be interpreted with caution due to the small number of patients and low-quality evidence. Good quality of evidence is lacking. Recommendation for adjuvant radiotherapy for tumours with poor prognostic factors will require discussion and shared decision-making with the patients., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: The optimal treatment and associated clinical outcomes for lymphoepithelial carcinoma of the major salivary gland (LECSG) are currently unclear. As such, the purpose of this study was to assess the survival rates of LECSG patients who received either upfront surgery or upfront chemoradiotherapy (CRT)., Materials and Methods: In this retrospective study, we analyzed cases of LECSG patients treated at our center from January 2010 to April 2021. The cumulative incidences of overall survival rate (OS) and locoregional failure-free survival rate (LRFFS) were evaluated using the Kaplan-Meier method. In order to balance potential risk factors between the treatment groups, we conducted propensity score matching (PSM) at a 1:1 ratio., Results: The study enrolled a total of 107 patients, among whom 24 received surgery alone, 56 underwent surgery combined with postoperative radiotherapy, and 27 underwent definitive radiotherapy. The 5-year LRFFS rate and 5-year OS rate for the entire cohort were 86.6% and 84.4%, respectively. Following PSM, the 5-year LRFFS and OS rates for the upfront CRT cases were comparable to those of upfront surgery, both before and after matching. However, the upfront surgery group showed a tendency toward more de novo facial nerve injury and post-treatment facial nerve injury., Conclusion: The results of this study suggest that upfront CRT is as effective as upfront surgery in terms of locoregional control and overall survival for LECSG patients. Therefore, upfront CRT could be considered a viable treatment option, potentially avoiding the risks associated with surgical intervention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Acinic cell carcinomas (AciCCs) are malignant tumours of the salivary glands. The aim of this work was to analyse data from the national REFCOR multicenter cohort (i) to investigate the prognostic factors influencing survival outcomes in AciCC, (ii) to assess the impact on survival of postoperative radiotherapy (RT) in patients treated for AciCC without high-grade transformation and (iii) to explore the prognostic impact of prophylactic neck dissection (ND) in patients treated for AciCC of the major salivary glands., Patients and Methods: Data from all the patients treated for salivary AciCC between 2009 and 2020 were extracted from the REFCOR database. Survival outcomes and prognostic factors influencing Disease-Free Survival (DFS) and Overall Survival (OS) were investigated using univariate and multivariate analyses. Propensity score matching was used to assess the impact of postoperative RT and prophylactic ND on DFS., Results: A total of 187 patients were included. After a median follow-up of 53 months, their 5-year OS and DFS rates were 92.8% and 76.2%, respectively. In multivariate analysis, male sex, older age, higher T and N status, and high grade were independently associated with a worse DFS. In the subpopulation analysed after propensity score matching, patients with cN0 AciCC without high-grade transformation who were treated by surgery and RT did not have an improved DFS compared to patients who were treated by surgery alone (hazard ratio (HR) = 0.87, p = 0.8). Factors associated with nodal invasion were T3-T4 status and intermediate/high histological grade. After propensity score matching, prophylactic ND was associated with a trend toward a better DFS (HR = 0.46, p = 0.16)., Conclusions: These results suggest that (i) long-term follow-up (>5 years) should be considered in patients with AciCC, (ii) treatment by surgery alone could be an option in selected cN0 patients with AciCC without high-grade transformation and (iii) prophylactic ND may be considered preferentially in patients with T3-T4 status and/or intermediate/high histological grade., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Due to their rarity, histologic heterogeneity, and localization, treatment of malignant salivary gland tumors requires an interdisciplinary approach. First-line treatment includes complete tumor resection. Postoperative radiation therapy is advised in patients with risk factors, i.e., incomplete tumor resection, high-grade tumors, or perineural invasion. Definitive radiation therapy is only advised for inoperable tumors because of significantly lower local control and survival rates when compared to combined surgery and radiation therapy. In radiation oncology, modern techniques such as intensity-modulated radiation therapy (IMRT) or particle therapy with heavy ions (i.e., C12) have led to improved outcomes in the treatment of head and neck tumors, especially of adenoid cystic carcinomas. Given the biological and physical benefits of particles, particle therapy, particularly carbon ion radiation, is a promising therapeutic approach for salivary gland tumors that will be further investigated in prospective clinical studies., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

We analyzed the diagnostic performance of prostate-specific membrane antigen (PSMA) PET/CT and the dosimetry, efficacy, and safety of 177 Lu-PSMA-617 radioligand therapy (RLT) in salivary gland malignancies (SGMs). Methods: We identified 28 SGM patients with PSMA PET/CT from our database. CT and PSMA PET/CT images were evaluated separately by 3 masked readers in joint reading sessions. Pathologic findings were grouped into 6 TNM regions, and lesion-based disease extent was classified as no disease ( n  = 1, 4%), unifocal ( n  = 2, 7%), oligometastatic ( n  = 9, 32%), multifocal ( n  = 3, 11%), or disseminated ( n  = 13, 47%). For each region, the SUV max of the lesion with the highest uptake was measured and the visual PSMA expression score was evaluated on a per-patient basis using PROMISE criteria. The association between PSMA expression and clinical and histopathologic markers was tested using the Student t test. Five patients underwent PSMA RLT with intratherapeutic dosimetry. Response was assessed using RECIST 1.1, and adverse events were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events. Results: Compared with CT, PSMA PET/CT demonstrated additional metastatic lesions in 11 of 28 (39%) patients, leading to upstaging of TNM and lesion-based disease extent in 3 (11%) and 6 (21%) patients, respectively. PSMA PET/CT detected CT-occult local tumor, regional lymph nodes, nonregional lymph nodes, and bone metastases in 1 (4%), 4 (14%), 2 (7%), and 4 (14%) patients, respectively; no additional lesions were detected in the other predefined regions. PSMA expression level was higher than liver in 6 patients (25%). A significantly higher SUV max was observed in male than female patients (15.8 vs. 8.5, P  = 0.007) and in bone than lung lesions (14.2 vs. 6.4, P  = 0.006). PSMA RLT was discontinued after 1 cycle in 3 of 5 patients because of insufficient tumor doses. No adverse events of grade 4 or higher occurred. Conclusion: In SGMs, PSMA PET/CT demonstrated a superior detection rate and led to upstaging in about one third of patients when compared with CT. The male sex and the presence of bone metastases were associated with significantly higher PSMA expression. PSMA RLT was well tolerated, but most patients did not have more than 1 cycle because of insufficient tumor doses., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

This study aimed to compare survival of patients with advanced major salivary gland cancers treated with adjuvant chemoradiation therapy (CRT) versus radiotherapy (RT) alone, after surgical resection. The Taiwan Cancer Registry database was used to identify patients (2009-2017) with advanced (T3-4 or nodal positivity) major salivary gland cancers, treated post-surgically with adjuvant CRT or RT alone. Overall survival (OS) and disease-specific survival (DSS) evaluated using Kaplan-Meier. Stratified analyses conducted on clinicopathological features. A total of 395 patients were analyzed: 178 (45.1%) received adjuvant CRT; 217 (54.9%) received adjuvant RT alone. Median radiation dose was 66 Gy in 33 fractions. Cisplatin was most common chemotherapy regimen. After a median follow-up of 3.37 years, there was no significant difference in OS or DSS (p = 0.1354 and 0.3361, respectively) between groups. Adding chemotherapy to adjuvant RT was not significantly associated with improved OS (adjusted hazard ratio [aHR] 0.94; 95% CI 0.72-1.23) and DSS (aHR 0.96; 95% CI 0.72-1.28). Stratified analysis of clinicopathological features found no significant advantages for improved OS or DSS from adding chemotherapy to adjuvant RT. Thus, in this population database, the use of chemotherapy provided limited survival benefits in advanced major salivary gland cancers after surgical resection., (© 2022. The Author(s).)

Background: This study investigated the effects of adjuvant radiotherapy on outcomes in early-stage major salivary gland cancers., Methods: A total of 655 patients were identified, including 355 (54.2%) received adjuvant radiotherapy and 300 (45.8%) had surgery alone. The effect of adjuvant radiotherapy on 5-year locoregional recurrence and disease-specific survival (DSS) was calculated using the Kaplan-Meier method, Wilcoxon rank sum test, and Cox proportional hazards model., Results: There were no significant differences in locoregional recurrence and DSS between patients receiving adjuvant radiotherapy and those not in both univariate and multivariable analysis. Although patients with positive margin status had a higher locoregional recurrence and those with moderate/poor differentiation had a worse DSS, stratified analysis still indicated there were no protective effects from the use of adjuvant radiotherapy., Conclusions: The use of adjuvant radiation therapy was not associated with improved locoregional recurrence and DSS, even for those with high-risk histopathological factors., (© 2022 Wiley Periodicals LLC.)

Background: To evaluate the predicting factors associated with distant metastasis (DM) for lymphoepithelial carcinoma of salivary gland (LECSG) following postoperative radiotherapy (PORT)., Methods: We retrospectively collected 160 eligible patients from two cancer institutions. The DM rate was evaluated using competing risk method., Results: The median follow-up time was 65.6 months. Elevated preradiotherapy serum LDH (ratio >0.5) (p = 0.006) and N classification (N2-3) (p = 0.001) were independently associated with DM for the LECSG. After the risk stratification, the high-risk subgroup was defined as the patients presented higher risk score (score >0), whereas 5-year cumulative incidence of DM in the high- and low-risk group was 30.9% and 6.0%, respectively (p < 0.001). Moreover, a significantly worse overall survival (OS) was observed in the high-risk patients compared with the low-risk subgroup (5-year OS: 83.9% vs. 97.8%, p = 0.006)., Conclusion: Elevated preradiotherapy serum LDH could serve as a predictive factor for DM in the LECSG following PORT., (© 2022 Wiley Periodicals LLC.)

Objectives: To develop and validate a prediction model to estimate overall survival (OS) with and without postoperative radiotherapy (PORT) for resected major salivary gland (SG) cancers., Materials and Methods: Adults in the National Cancer Database diagnosed with invasive non-metastatic major SG cancer between 2004 and 2015 were identified. Exclusion criteria included prior malignancy, pT1N0 or unknown stage, no or unknown surgery, and neoadjuvant therapy. Cox proportional hazards models evaluated the effect of covariates on OS. A multivariate regression model was utilized to predict 2-, 5-, and 10-year OS. Internal cross-validation was performed using 50-50 hold-out and Harrell's concordance index., Results: 18,400 subjects met inclusion criteria, including 9,721 (53%) who received PORT. Distribution of SG involvement was 86% parotid, 13% submandibular, and 1% sublingual. Median follow-up for living subjects was 4.9 years. PORT was significantly associated with improved OS for the following subgroups by log-rank test: pT3 (p < 0.001), pT4 (p < 0.001), high grade (p < 0.001), node-positive (p < 0.001), and positive margin (p < 0.001). The following variables were incorporated into a multivariate model: age, sex, Charlson-Deyo comorbidity score, involved SG, pathologic T-stage, grade, margin status, ratio of nodal positivity, and PORT. The resulting model based on data from 6,138 subjects demonstrated good accuracy in predicting OS, with Harrell's concordance index of 0.73 (log-rank p < 0.001)., Conclusion: This cross-validated prediction model estimates 2-, 5-, and 10-year differences in OS based on receipt of PORT for resected major SG cancers using readily available clinicopathologic features. Clinicians can utilize this tool to aid personalized adjuvant therapy decisions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Lymphoepithelial carcinoma of salivary gland (LECSG) is a rare malignant tumor. Whether postoperative radiotherapy (PORT) can improve locoregional control and which patients can benefit from PORT are unknown. This study aimed to evaluate the role of PORT and provide individualized suggestions for postoperative therapy in patients with LECSG., Patients and Methods: We retrospectively reviewed patients with nonmetastatic LECSG who underwent surgery with or without PORT. Recursive partitioning analysis (RPA) was performed to categorize the patients and predict progression-free survival (PFS)., Results: A total of 223 patients were included, 34 (15.2%) received surgery alone, whereas the remaining 189 (84.8%) underwent PORT in the initial treatment. Although patients in the PORT group were with advanced T stage and N stage, the PORT group had an advantage over the non-PORT group on 1-year, 5-year and 10-year PFS and locoregional control (LRC). PORT was an independent prognostic factor for PFS and LRC. Furthermore, compared with T stage and N stage, the size of the primary tumor and the number of positive lymph nodes were better prognostic predictors. The RPA model was generated according to the endpoint of PFS and categorized patients into 3 prognostic groups: low-risk (maximum diameter of primary lesion (≤3 cm) and number of positive lymph nodes (≤2)), intermediate-risk (maximum diameter of primary lesion (>3 cm) and number of positive lymph nodes (≤2)), and high-risk (number of positive lymph nodes (>2)), with corresponding 5-year PFS rates of 90.0%, 75.0%, and 51.0%, respectively. Significant improvement in PFS was observed in the PORT group among intermediate-risk (P = 0.000) and high-risk patients (P = 0.000)., Conclusions: PORT was shown to be a positive prognostic factor for PFS and LRC of LECSG. PORT was an essential treatment especially for patients with >3 cm maximum diameter of primary lesion and/or >2 positive lymph nodes., Competing Interests: Conflict-of-interest statement The authors declare no potential conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: This study presents the experience of the National Cancer Institute, Cairo University, in diagnosis and management of ACC of the head and neck., Methods: This is a retrospective review of 57 patients with ACC managed during the period from January 2011 to January 2016. Data about the characteristics and management of the disease were recorded. All patients were followed up to detect the development of local recurrence and distant metastasis and their management., Results: The mean age was 45.5 ± 15.1, with a femaleto-male ratio of 1.5:1. The minor salivary glands were affected in 61.4% of cases. Four patients (7%) were metastatic at presentation. The main presenting symptom was swelling, followed by pain. Surgical resection was performed in 48 patients (84.2%) followed by adjuvant radiotherapy in 36 of them. Four patients received radical radiotherapy. Treatment failed in 3 patients. Recurrences were recorded in 21 out of the 50 cured patients; 9 had locoregional recurrence, 9 had distant metastases, and 3 had both. The overall survival (OS) and disease-free survival (DFS) at three years were 79% and 57.1%, respectively. Surgical resection improved OS (p<0.001). Advanced T-stage, lymph node invasion, solid tumors, close or positive margins worsened OS. Adjuvant radiotherapy was associated with better DFS (p = 0.003), while solid tumors were associated with worse DFS., Conclusion: Despite aggressive management with radical surgery and adjuvant radiotherapy, recurrence affects 42% of the patients within three years. Patients with unresectable tumors have a poor prognosis. Adjuvant radiotherapy improves DFS but not OS.

Background: No international consensus has been reached regarding delineation of postoperative intensity-modulated radiotherapy (PO-IMRT) clinical target volumes (CTV) for major salivary gland carcinoma (SGC). The purpose of this article was to report our experience according to surgical principles., Methods: Between June 2010 and June 2018, 54 consecutive patients were enrolled. Reserved tissues around the margin of resection that were less than 5 mm from the invasive tumour edge before surgery were defined as high-risk clinical target volumes (CTV-HD), those less than 10 mm away were defined as medium-risk CTV (CTV1), and those 10-20 mm away were defined as low-risk CTV (CTV2), and were irradiated with 63-65 Gy, 59.5-61 Gy, and 45-54 Gy, respectively. Target volume distributions of reserved tissues were analysed and actuarial estimates of overall survival (OS), recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were obtained with the Kaplan-Meier method., Results: In parotid gland tumours, the percentages of defined CTV-HD in the styloid process, mandibular ramus, posterior venter of the digastric muscle, carotid sheath and stylomastoid foramen reached 34.29%, 25.71%, 54.29%, 40.00%, and 37.10%, respectively. The median follow-up was 33 months (range, 5-98 months). The 3-year and 5-year Kaplan-Meier estimates of OS, RFS and DMFS were 85.4% and 77.8%, 97.4%, and 97.4%, and 82.0% and 82.0%, respectively., Conclusions: It is feasible to delineate CTVs according to distances between various reserved tissues and the primary tumour edge before operation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The role of radiotherapy (RT) for oligometastases is currently established in different oncological settings but data on salivary gland cancer (SGC) are lacking. We evaluated the role of RT in oligometastatic SGC patients, focusing on stereotactic body radiation therapy (SBRT)., Materials and Methods: We performed a retrospective, multicentric study of oligometastatic SGC treated with palliative RT or SBRT. Endpoints included response evaluation and local control (LC)., Results: Between 2006 and 2016, 64 patients were collected from 9 Italian Cancer Centers, on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Working Group. 37 patients (57.8%) were suffering from adenoid cystic carcinoma (ACC) and 27 patients (42.2%) had non-ACC. Thirty-four patients underwent palliative RT (53,1%), and 30 received SBRT (46,9%). Most common metastatic sites were bone for palliative RT and lung for SBRT. Among patients treated with SBRT, an objective response or a stability was observed in all treated lesions. After a median follow-up of 29.2 months (range 2.3-117.1), LC at 12 months was 57.5% for patients treated with SBRT and was higher in ACC subgroup., Conclusion: We confirmed the potential role of SBRT in the management of oligometastatic SGC patients to control limited burden of disease considering the absence of effective systemic therapies., (© 2020 Wiley Periodicals LLC.)

Primary tumours of the salivary glands account for about 5 to 10% of tumours of the head and neck. These tumours represent a multitude of situations and histologies, where surgery is the mainstay of treatment and radiotherapy is frequently needed for malignant tumours (in case of stage T3-T4, nodal involvement, extraparotid invasion, positive or close resection margins, histological high-grade tumour, lymphovascular or perineural invasion, bone involvement postoperatively, or unresectable tumours). The diagnosis relies on anatomic and functional MRI and ultrasound-guided fine-needle aspiration for the diagnostic of benign or malignant tumors. In addition to patient characteristics, the determination of primary and nodal target volumes depends on tumor extensions and stage, histology and grade. Therefore, radiotherapy of salivary gland tumors requires a certain degree of personalization, which has been codified in the recommendations of the French multidisciplinary network of expertise for rare ENT cancers (Refcor) and may justify a specialised multidisciplinary discussion. Although radiotherapy is usually recommended for malignant tumours only, recurrent pleomorphic adenomas may sometimes require radiotherapy based on multidisciplinary discussion. An update of indications and recommendations for radiotherapy for salivary gland tumours in terms of techniques, doses, target volumes and dose constraints to organs at risk of the French society for radiotherapy and oncology (SFRO) was reported in this article., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Importance: Salivary gland cancer comprises a diverse group of histologic types with different biological behavior. Owing to this heterogeneity, the association of margin status and postoperative adjuvant radiotherapy has been poorly studied., Objective: To examine the association between surgical margin status and oncologic outcomes and the subsequent outcome of adjuvant radiotherapy in patients with salivary gland carcinomas., Design, Setting, and Participants: This cohort study analyzed data from institutional records at Memorial Sloan Kettering Cancer Center from 1985 to 2015. Statistical analysis was completed on October 31, 2020. After exclusions, 837 patients with surgically treated salivary gland carcinoma were identified. Surgical margins and histologic characteristics identified from pathology reports were recorded, with margins classified as negative, close, and positive, and individual histologic types classified into 3 risk groups: low, intermediate, and high., Exposures: The outcome of adjuvant radiotherapy was determined in patients with close margins with low- and intermediate-risk histologic type and overall pathologic stage I/II disease., Main Outcomes and Measures: Disease-specific survival (DSS) and local recurrence-free survival (LRFS) outcomes were calculated using the Kaplan-Meier method. Multivariable analysis was performed using the Cox proportional hazards regression model. A planned subgroup analysis of patients with close margins was conducted., Results: Among the 837 patients identified, 438 were women (52.3%); median age at surgery was 58 years (range, 6-98). A total of 399 tumors (47.7%) originated from major salivary glands, and 438 (52.3%) from minor salivary glands. Margin positivity rates were not different between minor and major salivary gland tumors. Positive surgical margins were identified in 252 patients (30.1%), with nasal cavity/paranasal sinuses and trachea/larynx subsites as the most common sites. Close margins were recorded in 203 patients (24.3%). Adjuvant radiotherapy was administered in 80.5% (103 of 128) of patients with major salivary gland cancer with positive margins, 58.8% (60 of 102) with close margins, and 30.7% (52 of 169) with negative margins and in 70.2% (87 of 124), 36.6% (37 of 101) , and 19.7% (42 of 213) patients with minor salivary gland cancer. With median follow up time of 57 months (range, 1-363 months), patients with positive margins had poorer DSS and LRFS. However, after controlling for overall stage, histologic risk group, and adjuvant radiotherapy, margin status was not a factor associated with poorer DSS or LRFS. In patients with close margins, low-risk and intermediate-risk histologic type, and overall pathologic stage I/II, patients who did not have adjuvant radiotherapy had comparable local control with those who received adjuvant radiotherapy., Conclusions and Relevance: The findings of this cohort study suggest that patients with salivary gland cancer who have either close or positive surgical margins are at increased risk for poorer local control and survival. After controlling for tumor stage, histologic risk group, and the use of adjuvant radiotherapy, margin status was not an independent factor associated with poorer outcome. Subgroup analyses showed that care for patients with close margins with low-risk or intermediate-risk histologic type who have stage I/II cancers might be managed safely without adjuvant radiotherapy.

Background: Salivary gland cancer (SGC) is rare and a heterogeneous type of cancer. Prospective randomized trials are lacking. No guideline focusing on standard procedures of radiotherapy (RT) in the treatment of SGC exists. Therefore, we surveyed the members of the German Society of Radiation Oncology (DEGRO) to gain information about current therapeutic strategies of SGC., Methods: An anonymous questionnaire was designed and made available on the online platform umfrageonline.com. The corresponding link was sent to all DEGRO members who provided their user data for contact purposes. Alternatively, a PDF printout version was sent. Frequency distributions of responses for each question were calculated. The data were also analyzed by type of institution., Results: Sixty-seven responses were received, including answers from 21 university departments, 22 non-university institutions, and 24 radiation oncology practices. Six participants reported that their departments (practice: n = 5, non-university hospital: n = 1) did not treat SGC, and therefore the questionnaire was not completed. Concerning radiation techniques, target volume definition, and concomitant chemotherapy, treatment strategies varied greatly among the participants. Comparing university vs. non-university institutions, university hospitals treat significantly more patients with SGC per year and initiated more molecular pathological diagnostics., Conclusion: SGC represents a major challenge for clinicians, as reflected by the inhomogeneous survey results regarding diagnostics, RT approaches, and systemic therapy. Future prospective, multicenter clinical trials are warranted to improve and homogenize treatment of SGC and to individualize treatment according to histologic subtypes and risk factors., (© 2021. The Author(s).)

Objectives: Timely administration of postoperative radiation therapy (PORT) impacts oncologic outcomes in resected squamous cell carcinomas of the head and neck. Salivary gland cancers (SGCs) are uncommon, and timing of PORT has not been extensively explored. We aimed to determine if the interval between surgery and PORT impacts outcomes in SGCs., Materials and Methods: This is a retrospective study of patients with SGCs who underwent curative intent surgical resection followed by adjuvant PORT. Locoregional recurrence free survival (LRFS), disease free survival (DFS), and overall survival (OS) were estimated using the Kaplan Meier method. A multivariate analysis explored the association between demographics, tumor characteristics, and PORT timing with oncologic outcomes using a stepwise Cox proportional hazards model., Results: 180 eligible patients were identified. The median time to PORT start was 61 (range 8-121) days. 169 (93.5%) of patients received neutron radiation. With a median follow up of 8.2 years in surviving patients, the 10-year OS and LRFS estimates were 61% and 53%. In a multivariate analysis, nodal involvement, histologic grade, and age at diagnosis were associated with OS, while nodal involvement, tumor size, and age at diagnosis were associated with LRFS and DFS. Time to PORT start or completion was not statistically associated with survival outcomes., Conclusion: SGC patients who underwent surgery in our tertiary institution received PORT within a median of 61 days after surgery. With long term follow up, PORT timing in this retrospective series was not associated with worse oncologic outcomes, and support timely administration of PORT., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Distant metastasis (DM) indicates a poor outcome from cancer treatment. The present study estimated the incidence of DM and identified risk factors associated with development of DM in patients with salivary gland carcinoma that achieved locoregional control after surgery combined with 125 I internal brachytherapy., Materials and Methods: A retrospective cohort study was performed using consecutive patients treated with surgery combined with 125 I internal brachytherapy at the Peking University School and Hospital of Stomatology. Variables that might be associated with DM, including clinical, treatment characteristics, pathologic findings, and time to DM were recorded. Kaplan-Meier was performed to estimate incidence of DM, and Cox proportional hazard model was used to identify factors associated with DM., Results: Data from 156 patients were obtained for statistical analysis. The DM was observed in 16 of 156 with rate being 10.3%. The median interval from diagnosis of primary tumor to DM was 30.0 months. The 3-, 5-, 10-year overall survival rates were 97.0, 94.6, 85.2%, respectively, for patients without DM compared with 60.9, 52.2, 26.1%, respectively, for those with DM (P < .001). Univariate analysis revealed that the factors that significantly influenced DM were primary tumor site (P = .012) and histologic grade (P = .001). Multivariate Cox proportional hazard model indicated that histologic grade was the most important risk factor for predicting the risk of DM (P = .005; hazard ratio: 2.79; 95% confidence interval: 1.36 to 5.72)., Conclusions: Histologic grade was the major risk factor that significantly influenced DM in patients with salivary gland carcinoma that achieved locoregional control. Patients with high-grade tumors should be under close evaluation for DM., (Copyright © 2021 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Despite modern treatment techniques, radiotherapy (RT) in patients with head and neck cancer (HNC) may be associated with high rates of acute and late treatment-related toxicity. The most effective approach to reduce sequelae after RT is to avoid as best as possible healthy tissues and organs at risk from the radiation target volume. Even small geometric changes can lead to a significant dose reduction in normal tissue and better treatment tolerability. The major objective of the current study is to investigate 3D printed, tooth-borne tissue retraction devices (TRDs) compared to conventional dental splints for head and neck RT., Methods: In the current two-arm randomized controlled phase II trial, a maximum of 34 patients with HNC will be enrolled. Patients will receive either TRDs or conventional dental splints (randomization ratio 1:1) for the RT. The definition of the target volume, modality, total dose, fractionation, and imaging guidance is not study-specific. The primary endpoint of the study is the rate of acute radiation-induced oral mucositis after RT. The quality of life, local control and overall survival 12 months after RT are the secondary endpoints. Also, patient-reported outcomes and dental status, as well as RT plan comparisons and robustness analyzes, will be assessed as exploratory endpoints. Finally, mesenchymal stem cells, derived from the patients' gingiva, will be tested in vitro for regenerative and radioprotective properties., Discussion: The preliminary clinical application of TRD showed a high potential for reducing acute and late toxicity of RT in patients with HNC. The current randomized study is the first to prospectively investigate the clinical tolerability and efficacy of TRDs for radiation treatment of head and neck tumors., Trial Registration: ClinicalTrials.gov; NCT04454697; July 1 st 2020; https://clinicaltrials.gov/ct2/show/record/NCT04454697 .

Purpose of Review: To give an overview of recent advances in therapeutic approaches of radiation-induced salivary gland cancers (ri-SGCs)., Recent Findings: Reirradiation with protons and carbon ions demonstrated to be feasible, safe and to offer good local control rates, with the possibility of overcoming radioresistance and dosimetric issues in previously irradiated cancer patients. Chromosomal rearrangements, gene fusions and expression profiles are important to identify specific cancer subtypes and can guide tailored systemic therapy., Summary: Ri-SGCs are rare and heterogeneous. Patients are often heavily pretreated and at risk of toxicities, and their management remain challenging. A multidisciplinary approach in referral centers is mandatory. Knowledge about SGCs cellular and molecular mechanisms is constantly evolving. In the last years, novel advances in therapeutic approaches, such as carbon ion radiotherapy, are emerging as safe and effective options in active treatment, but further efforts are needed to offer tailored personalized treatments and to improve survival., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Proton beam radiation therapy (PBRT) has dosimetric advantages compared to photon radiation therapy for the treatment of major salivary gland tumors (MSGTs)., Methods: Patients with non-metastatic MSGTs treated at a single proton therapy center from October 2013 to October 2018 were retrospectively reviewed., Results: Sixty-eight patients with MSGTs were included and the most common site and histology were the parotid gland (75.0%) and adenoid cystic carcinoma (22.1%), respectively. The 3-year rates of locoregional control, progression-free survival, and overall survival were 95.1% (95% CI: 89.9%-100.0%), 80.7% (70.2%-92.7%), and 96.1% (95% CI: 90.9%-100.0%), respectively., Conclusion: In a large cohort of MSGTs treated with PBRT, the rates of locoregional control were high in short-term follow-up and treatment was well tolerated., (© 2021 Wiley Periodicals LLC.)

Objectives/hypothesis: Our primary objective was to compare differences in survival of patients with high-grade salivary gland carcinomas (SGCs) receiving adjuvant neutron versus photon radiotherapy using a hospital-based national cohort and restricted mean survival time (RMST) analysis. Our secondary objective was to compare survival of similar patients treated with primary neutron versus photon radiation., Study Design: Multicenter, retrospective population-based study of patients within the National Cancer Database from 2004 to 2014., Methods: One thousand eight hundred forty-four patients were selected on diagnosis of high-grade parotid and submandibular malignancies. One thousand seven hundred seventy-seven patients receiving photon and 67 patients receiving neutron therapy were identified who met inclusion criteria. Patients were then categorized as having primary surgery with adjuvant radiation or primary radiation without prior surgery. Bivariate analysis was performed to assess for differences between groups, and RMST analysis was performed at 1-, 2-, and 5-year timepoints with controlling for available covariate data., Results: There was no significant difference in RMST for patients receiving neutrons over photons at 1, 2, and 5 years in the adjuvant setting. Among patients undergoing primary radiotherapy, there was a difference in RMST of 2.29 months at 1 year and 5.05 months at 2 years for neutrons over photons, though this benefit was not observed at 5 years post-therapy., Conclusions: For patients with high grade SGCs undergoing adjuvant photon versus neutron radiotherapy, there was no difference in RMST. There was observed to be a significant difference in RMST at 1 and 2 years among patients undergoing primary neutron therapy of up to 5 months. Given the benefit observed with primary neutron therapy, it should be considered in both the primary and adjuvant treatment setting., Level of Evidence: 4 Laryngoscope, 131:541-547, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Background and Purpose: To evaluate oncological outcomes and treatment-related toxicities of elderly salivary gland cancer patients undergoing (chemo)radiotherapy., Material and Methods: Local/locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) of elderly patients ≥ 65 years with primary salivary gland cancers undergoing (chemo)radiotherapy between 2005 and 2020 at three tertiary cancer centers were calculated. The impact of clinicopathological and treatment parameters on outcomes were analyzed, and acute and chronic toxicities were quantified., Results: 288 elderly salivary gland cancer patients were included in this multicenter analysis, and their median LRC, PFS and OS amounted to 113, 39 and 75 months, respectively. Age, performance status, comorbidities, definitive vs. adjuvant (chemo)radiotherapy as well as locally/locoregionally advanced cancers and distant metastases correlated with reduced outcomes in elderly salivary gland patients. Patients receiving dose-escalated radiotherapy (total doses > 70 Gy EQD2 ) with carbon ion boost radiation resulted in improved LRC, but no improvements in PFS or OS. Concomitant chemoradiotherapy did not improve treatment outcomes in elderly salivary gland carcinoma patients. Radiotherapy of elderly salivary gland cancer patients resulted in moderate higher-grade toxicities despite dose escalation with 70 (24.3%) and 48 patients (16.7%) experiencing acute and chronic grade 3 toxicities, respectively. No grade 4/5 toxicities were observed in this patient cohort., Conclusion: Data from the largest multicenter analysis of elderly salivary gland cancer patients undergoing (chemo)radiotherapy demonstrate favorable LRC and tolerable toxicity rates. Decision-making for these vulnerable patients should be based on patient performance rather than chronological patient age., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Head and neck adenoid cystic carcinoma (ACC) is a rare malignant tumor that is prone to local recurrence. The NCCN Guidelines for Head and Neck Cancers recommend that all patients with ACC receive postoperative radiotherapy (PORT). However, whether PORT can improve local control and which patients can benefit from PORT are unknown. This study aimed to assess the role of PORT and provide individualized suggestions for postoperative therapy in patients with ACC., Patients and Methods: We retrospectively reviewed patients with nonmetastatic head and neck ACC who underwent surgery with or without PORT. Recursive partitioning analysis (RPA) was performed to categorize the patients and predict local recurrence-free survival (LRFS). The survival outcome was compared between non-PORT and PORT groups., Results: A total of 319 patients were included. PORT was identified as a prognostic factor for LRFS in univariate (P=.01) and multivariate analysis (P<.01). However, it did not improve distant metastasis-free survival, disease-free survival, or overall survival in univariate analysis. RPA categorized patients into 3 prognostic groups: low-risk (negative margin, T1-T2, primary location = major or minor salivary gland), intermediate-risk (negative margin, T1-T2, primary location = other locations instead of a major or minor salivary gland; negative margin, T3-T4; positive margin, without bone invasion), and high-risk (positive margin, with bone invasion). Significant LRFS improvements in the PORT group were observed among intermediate-risk (P<.01) and high-risk patients (P<.05). LRFS improvements among low-risk patients were relatively insignificant (P=.10)., Conclusions: PORT was shown to be a positive prognostic factor for improved LRFS in ACC. Furthermore, PORT could significantly improve LRFS in intermediate-risk and high-risk patients with ACC, but whether low-risk patients could benefit from PORT needs further study.

Objective: To investigate the clinical application and efficacy of 125 Ⅰ radioactive seeds implantation in the treatment of recurrent salivary gland carcinoma after external radiotherapy., Methods: From July 2004 to July 2016, 43 cases of recurrent salivary gland carcinoma of the neck after external radiotherapy or surgery combined with external radiotherapy were treated. According to the conventional segmentation radiotherapy for head and neck cancer (once a day, 1.8-2.0 Gy each time, 5 days per week), the cumulative radiation dose of the patients in this group was calculated. In the study, 26 patients received 50-60 Gy, 7 patients received less than 50 Gy, 4 patients received 60-70 Gy, and 6 patients received more than 80 Gy (range: 80-120 Gy). The interval between the last external irradiation and local recurrence was 4-204 months, and the median interval was 48 months. Among them, 25 cases were treated with 125 Ⅰ radioactive seeds implantation only and 18 cases were treated with 125 Ⅰ radioactive seeds implantation after operation. The prescription dose was 100-140 Gy. The control rate, survival rate and disease-free survival rate were recorded to evaluate the side effects., Results: The median follow-up time was 27 months (ranging from 2.5 to 149.0 months). Among them, the median follow-up time of adenoid cystic carcinoma patients was 31 months (range: 2.5-112.0 months), and the median follow-up time of mucoepidermoid carcinoma patients was 18 months (range: 5-149 months). The local control rates for 1, 3 and 5 years were 66.5%, 48.8% and 42.7%, respectively. The 1-, 3- and 5- year survival rates were 88.0%, 56.7% and 45.8%, respectively. The disease-free survival rates of 1, 3 and 5 years were 58.3%, 45.4% and 38.1%, respectively. There was no statistically significant difference in local control rate, survival rate, and disease-free survival between the radioactive seeds implantation group and the radioactive seeds implantation group after surgical resection. There were 2 cases of acute radiation reaction Ⅰ/Ⅱ and 3 cases of reaction Ⅲ or above. In the late stage of radiotherapy, there were 8 cases with Ⅰ/Ⅱ grade reaction and 3 cases with Ⅲ grade or above reaction. The incidence of radiation reactions of Grade Ⅲ and above was 7%., Conclusion: 125 Ⅰ radioactive seeds implantation provides an alternative method for the treatment of recurrent salivary gland carcinoma after external radiotherapy. The local control rate and survival rate are improved on the premise of low incidence of side effects.

Background: Owing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified., Methods: In this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists., Results: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy., Conclusions: A higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.

Surgical treatment in patients with rare adenoid cystic carcinoma (ACC) of the salivary glands is considered to be the state of the art. With respect to an additional radiotherapy there are different approaches regarding the type of radiotherapy and timing. In this study the overall survival and recurrence-free survival in 52 individuals with salivary gland ACC who were treated at the University Hospital in Essen and received irradiation with fast neutrons and photons (mixed beam technique) either A) immediately following surgical treatment or B) only after the appearance of local recurrence were compared. Group A (n = 28, first diagnosis, FD September 1991-September 2009) received adjuvant radiotherapy immediately postoperative, group B (n = 24, FD June 1979-November 2001) underwent primarily surgical tumor resection according to the treatment regimen at that time and were irradiated only on the appearance of a local recurrence. In comparison to group B, patients in group A showed a lower recurrence rate and a significantly longer local relapse-free survival. Group B, however, showed a significantly higher overall survival. The frequency of distant metastasis occurred equally in both groups but the onset of distant metastasis was significantly earlier in group A. In general, overall survival was negatively influenced by distant metastasis. The local recurrence rate was very high after primary surgical treatment only. The immediate adjuvant high-linear energy transfer (LET) radiotherapy reduced the local recurrence rates. Irradiation after the appearance of a recurrence had a positive influence on overall survival. Overall, definitive high-LET radiotherapy in the mixed beam technique enabled high local control rates both primarily postoperative and also locoregional recurrences.

Objective: To evaluate the biological effectiveness of dose associated with interruption time; and propose the dose compensation method based on biological effectiveness when an interruption occurs during photon radiation therapy., Methods: The lineal energy distribution for human salivary gland tumor was calculated by Monte Carlo simulation using a photon beam. The biological dose (D bio ) was estimated using the microdosimetric kinetic model. The dose compensating factor with the physical dose for the difference of the D bio with and without interruption (Δ) was derived. The interruption time (τ) was varied to 0.1, 0.2, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, 75, and 120 min. The dose per fraction and dose rate varied from 2 to 8 Gy and 0.1 to 24 Gy/min, respectively., Results: The maximum Δ with 1 Gy/min occurred when the interruption occurred at half the dose. The Δ with 1 Gy/min at half of the dose was over 3% for τ >= 20 min for 2 Gy, τ = 10 min for 5 Gy, and τ = 10 min for 8 Gy. The maximum difference of the Δ due to the dose rate was within 3% for 2 and 5 Gy, and achieving values of 4.0% for 8 Gy. The dose compensating factor was larger with a high dose per fraction and high-dose rate beams., Conclusion: A loss of biological effectiveness occurs due to interruption. Our proposal method could correct for the unexpected decrease of the biological effectiveness caused by interruption time., Advances in Knowledge: For photon radiotherapy, the interruption causes the sublethal damage repair. The current study proposed the dose compensation method for the decrease of the biological effect by the interruption.

Aims: To report oncologic and functional outcomes in terms of tumor control and toxicity of carbon ion radiotherapy (CIRT) in reirradiation setting for recurrent salivary gland tumors at CNAO., Methods: From November 2013 to September 2016, 51 consecutive patients with inoperable recurrent salivary gland tumors were retreated with CIRT in the frame of the phase II protocol CNAO S14/2012C for recurrent head and neck tumors., Results: Majority of pts (74.5%) had adenoid cystic carcinoma, mainly rcT4a (51%) and rcT4b (37%). Median dose of prior photon based radiotherapy was 60 Gy. Median dose of CIRT was 60 Gy [RBE] at a mean of 3 Gy [RBE] per fraction. During reirradiation, 19 patients (37.3%) experienced grade G1 toxicity, 19 pts (37.3%) had G2 and 2 pts (3.9%) had G3. Median follow up time was 19 months. Twenty one (41.2%) patients had stable disease and 30 (58.8%) tumor progression at the time of last follow up. Furthermore, 9 (18%) patients had G1 late toxicity, 19 (37%) had G2 and 9 (17. 5%) had G3. Using the Kaplan Meier method, progression free survival (actuarial) at one and two years were 71.7% and 52.2% respectively. Estimated overall survival (actuarial) at one and two years were 90.2% and 64%, respectively., Conclusions: CIRT is a good option for retreatment of inoperable recurrent salivary gland tumors with acceptable rates of acute and late toxicity. Longer follow up time is needed to assess the effectiveness of CIRT in reirradiation setting of salivary gland tumors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Proton beam therapy (PBT) reduces normal organ dose compared to intensity-modulated radiation therapy (IMRT) for patients with major salivary gland tumors. It is not known whether this dosimetric advantage is clinically meaningful for reducing acute toxicity. Methods: We evaluated treatment parameters and acute toxicity outcomes of patients with major salivary gland cancers enrolled on the Proton Collaborative Group REG001-09 trial (NCT01255748). Results: One-hundred and five patients with a median age of 61 years were included. The majority had parotid ( N  = 90) versus submandibular gland ( N  = 15) tumors. The patients were treated across seven institutions in the United States between 2010 and 2017, most commonly in the postoperative setting (70.5%) although a minority were treated definitively (29.5%). Median PBT dose was 66.5 GyE in 33 fractions; only one patient was prescribed less than 50 GyE. Chemotherapy was given concurrently to 20%. Median follow-up was 14.3 months. Acute grade 2 or higher toxicity included nausea (1.5%), dysgeusia (4.8%), xerostomia (7.6%), mucositis (10.5%) and dysphagia (10.5%). Conclusions: PBT should be strongly considered when ipsilateral radiation therapy is indicated for major salivary gland cancer based on a considerably lower incidence of acute grade 2 or higher toxicity in this analysis compared to historical IMRT outcomes.

Sinonasal adenoid cystic carcinoma is a rare malignancy characterized by an insidious growth pattern and a tendency for perineural spread along major and minor nerves, resulting in invasion of the skull base and intracranial extension. Therefore, many patients present with advanced disease and involvement of critical structures, making treatment difficult and potentially associated with high morbidity. Surgery represents the mainstay of treatment of the primary tumor. Complete resection of the tumor with negative margins, whenever feasible, is associated with better survival outcomes. However, in the case of extensive involvement of vital structures (e.g., carotid artery, cavernous sinus, optic nerve, Meckel's cave) or when radical surgery could seriously affect the patient's quality of life, a function-preserving subtotal removal of the tumor followed by irradiation can be proposed. The role of surgery is limited to a biopsy in unresectable lesions that are more suitable for non-surgical treatments (e.g., exclusive chemoradiation). Given the difficulty in obtaining negative margins and the propensity for submucosal and perineural spread, adjuvant radiotherapy is strongly recommended. Recently, heavy-particle radiotherapy using protons or carbon ions has emerged as a promising treatment with improved local control. Local failures (60%) and distant metastases (40%) are common and can occur even decades after definitive treatment. The 5-year overall survival ranges from 55 to 70% and it exceeds that of other sinonasal malignancies, but dramatically drops down at 10 years (40%) and further decreases at 20 years (15%). Therefore, a prolonged follow-up of at least 15 years, and possibly lifelong, is mandatory., (© 2020 S. Karger AG, Basel.)

Particle therapy is a comparatively new radiotherapy treatment form allowing the application of extremely conformal treatment plans. In head and neck malignancies, especially in the paranasal sinus and anterior skull base, this technology is very valuable in order to maintain normal tissue tolerance of critical structures while still applying high doses to the tumour. The following paper will further explore the rationale of particle therapy and available clinical experience of the most commonly treated malignancies arising in these anatomical sites. The potential of particle therapy for re-irradiation in tumours of the paranasal sinus and anterior skull base will also be summarised., (© 2020 S. Karger AG, Basel.)