Guideline sources The following summarized guidelines for the evaluation and management of salivary gland cancer (SGC) are prepared by our editorial team based on guidelines from the European Reference Network on Rare Adult Solid Cancers (EURACAN/ESMO 2022), the American Society of Clinical Oncology (ASCO 2022; 2021; 2018), the American College of Radiology (ACR 2019), the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF 2017), the American Cancer Society (ACS 2016), and the United Kingdom National Multidisciplinary Guidelines (UKNMG 2016). 1 2 3 4 5 6 7 8 Guidelines 1. Classification and risk stratification Classification: classify SGC according to the WHO Classification of Head and Neck Tumors. A Show 2 more 2. Diagnostic investigations https://web.pathway.md/diseases/recuC3HKqLWLTLgUC 1/8 6/24/23, 3:06 PM Salivary gland cancer Pathway History and physical examination: elicit an initial history and perform a physical examination in adult patients with a neck mass to identify suspicious findings representing an increased risk for malignancy. B Show 4 more Diagnostic imaging: As per ESMO 2022 guidelines, obtain MRI in patients with a suspected malignant tumor. B Obtain contrast-enhanced CT where MRI is contraindicated. B Show 2 more As per ASCO 2021 guidelines, obtain neck ultrasound, CT with IV contrast and/or MRI of the neck and primary site in patients with suspected SGC. B Show 3 more As per ACR 2019 guidelines: Obtain contrast-enhanced neck CT or MRI for the initial imaging of nonpulsatile neck masses (not in the parotid region or thyroid). B Obtain contrast-enhanced neck CT or MRI or neck ultrasound for the initial imaging of neck masses (not in the parotid region or thyroid) in pediatric patients. B As per AAO-HNSF 2017 guidelines, obtain contrast-enhanced neck CT (or MRI) in patients with a neck mass deemed at increased risk for malignancy. B 3. Diagnostic procedures Biopsy and pathology: As per ESMO 2022 guidelines, obtain pathological confirmation of the salivary gland tumor. B Show 5 more As per ASCO 2021 guidelines, perform FNA or core needle biopsy to support distinction of SGCs from non-malignant salivary lesions. A Show 3 more As per AAO-HNSF 2017 guidelines, evaluate the upper aerodigestive tract under anesthesia before performing an open biopsy in patients with a neck mass deemed at increased risk for malignancy and without a diagnosis or primary site identified with FNA, imaging, and/or ancillary tests. B Show 2 more As per UKNMG 2016 guidelines: Perform US-guided FNA cytology by an expert histopathologist in all patients with salivary tumors. B Take into account the histologic grade when planning treatment in patients with mucoepidermoid carcinoma, as it correlates with the outcome. E Ancillary testing: As per ASCO 2022 guidelines: https://web.pathway.md/diseases/recuC3HKqLWLTLgUC 2/8 6/24/23, 3:06 PM Salivary gland cancer Pathway Obtain PD-L1 immunohistochemistry testing in patients with recurrent or metastatic head and neck SCC. Interpret PD-L1 CPS 1 as positive, recognizing that it correlates with a clinical benefit to PD-L1 inhibitors. A Consider obtaining tumor mutational burden testing in patients with recurrent or metastatic head and neck SCC when CPS is unavailable or in patients with rare tumors. Interpret tumor mutational burden 10 as high, recognizing that it correlates with a clinical benefit to PD-L1 inhibitors. B As per ASCO 2018 guidelines, do not obtain routine high-risk HPV testing in patients with non- oropharyngeal primary tumors of the head and neck. D 4. Medical management Adjuvant chemotherapy: As per ESMO 2022 guidelines, insufficient evidence to recommend adding chemotherapy to postoperative radiotherapy of the primary tumor and neck. I As per ASCO 2021 guidelines: Do not offer routine concurrent chemotherapy in patients undergoing adjuvant radiotherapy, outside of a clinical trial. D Do not offer routine adjuvant endocrine or targeted therapy in patients with salivary gland tumors expressing androgen receptor and/or HER2-Neu, outside of a clinical trial. D Definitive chemotherapy: As per ASCO 2022 guidelines, consider offering pembrolizumab in patients with PD-L1-positive metastatic SGC. C As per ESMO 2022 guidelines, insufficient evidence to recommend adding chemotherapy to primary radiotherapy in patients with unresectable SGC or unsuitable for surgery. I As per ASCO 2021 guidelines, do not offer routine concurrent chemotherapy in patients undergoing radiotherapy for inoperable SGC, outside of a clinical trial. D 5. Therapeutic procedures Adjuvant radiotherapy: As per ESMO 2022 guidelines: Offer postoperative local radiotherapy in patients with T3-T4 and intermediate/high-grade tumors and in cases with close resection margins (1-5 mm; 30 2 Gy), incomplete resection margins (33 2 Gy), or perineural growth. B Offer postoperative regional radiotherapy in cases with pN+ (30 2 Gy) and extranodal extension (33 2 Gy). Offer unilateral elective neck irradiation (25 2 Gy) based on the inclusion criteria for elective neck dissection. B As per ASCO 2021 guidelines, offer postoperative radiotherapy in all patients with resected adenoid cystic carcinoma. B https://web.pathway.md/diseases/recuC3HKqLWLTLgUC 3/8 6/24/23, 3:06 PM Salivary gland cancer Pathway Show 3 more As per UKNMG 2016 guidelines, offer adjuvant radiotherapy after surgery in all patients with malignant submandibular tumors except in patients with completely excised small, low-grade tumors. B Show 2 more Definitive radiotherapy: As per ESMO 2022 guidelines, offer curative primary radiotherapy in patients with functionally unresectable disease or unsuitable for surgery due to comorbidities. B Show 2 more As per ASCO 2021 guidelines, offer radiotherapy in patients with salivary gland malignancy not fit for surgical resection because of extent of disease or medical comorbidity. B Technical considerations for radiotherapy: As per ASCO 2021 guidelines, consider covering the associated nerves with an elective or intermediate dose to the skull base in patients with perineural invasion. C Show 4 more As per UKNMG 2016 guidelines, set a low threshold for adjuvant radiotherapy if malignant parotid tumors lie close to the facial nerve. E 6. Surgical interventions General principles: As per ESMO 2022 guidelines: Collect as much information as possible about the tumor before surgery, discuss scenarios with the patient, and be prepared for doing a graft during the ablative procedure. B Consider performing intraoperative frozen sections to evaluate margins of resection, perineural invasion, and lymph nodes, but only if the result is expected to alter management at the time of surgery. C As per ASCO 2021 guidelines, perform open surgical excision in patients with histologically confirmed salivary gland malignancies. A Show 2 more Parotid gland resection: As per ESMO 2022 guidelines: Perform total parotidectomy as the procedure of choice for primary resectable SGC. B Consider performing superficial parotidectomy in patients with low-grade tumors, especially when discovered postoperatively. B As per ASCO 2021 guidelines: Consider performing partial superficial parotidectomy in patients with appropriately located superficial T1 or T2 low-grade SGCs. C https://web.pathway.md/diseases/recuC3HKqLWLTLgUC 4/8 6/24/23, 3:06 PM Salivary gland cancer Pathway Perform at least superficial parotidectomy with consideration of a total or subtotal parotidectomy in patients with any high-grade or advanced (T3-T4) parotid cancer because of the risk of intraparotid nodal metastases. B Facial nerve preservation: As per ESMO 2022 guidelines: Preserve the facial nerve if it is not infiltrated or grossly encased by the tumor. B Resect the facial nerve and perform primary reconstruction and/or reanimation procedures in patients with a preoperatively paralyzed facial nerve. B As per ASCO 2021 guidelines: Preserve the facial nerve in patients with intact preoperative facial nerve function if a dissection plane can be created between the tumor and the nerve. B Perform resection of involved facial nerve branches in patients with impaired facial nerve movement preoperatively or if branches are encased or grossly involved by a confirmed malignancy. B As per UKNMG 2016 guidelines, attempt to preserve the facial nerve function during parotidectomy if the facial nerve function is normal preoperatively. Consider performing immediate microsurgical repair (with an interposition nerve graft if required) if the facial nerve is divided intraoperatively. E Submandibular gland resection: Perform at least a resection of the gland and the surrounding level Ib lymph nodes in patients with a malignant tumor confined within the submandibular gland. B Include the gland in a selective neck dissection involving levels I, II, and III in patients with high- grade malignancy without clinical evidence of cervical lymph node involvement. B Management of regional lymph nodes: As per ESMO 2022 guidelines, perform a comprehensive lymph node dissection involving levels I-V in patients with positive lymph nodes (clinical or radiological). B Show 6 more As per ASCO 2021 guidelines, consider performing elective neck dissection or offering elective neck irradiation in patients with cN0 T3-T4 cancer or high-grade malignancy. C Show 2 more As per UKNMG 2016 guidelines, perform neck dissection in all patients with malignant parotid tumors except for low-grade small tumors. B 7. Follow-up and surveillance Follow-up, clinical assessment: As per ASCO 2021 guidelines: Obtain clinical follow-up with history and physical examination regularly with decreasing frequency as the time elapses from completion of treatment of SGC. B https://web.pathway.md/diseases/recuC3HKqLWLTLgUC 5/8 6/24/23, 3:06 PM Salivary gland cancer Pathway Obtain long-term follow-up (beyond 5 years) with an annual examination in all patients with SGC. B As per ACS 2016 guidelines, educate and counsel all head and neck cancer survivors about the signs and symptoms of local recurrence. B Show 4 more As per UKNMG 2016 guidelines, obtain long-term follow-up for clinical observation in patients with intraoperative tumor spillage. Discuss initiation of adjuvant radiation therapy in a multidisciplinary team. E Follow-up, imaging assessment: As per EURACAN/ESMO 2022 guidelines, consider obtaining follow-up imaging with MRI for locoregional recurrence and chest CT for lung metastases. C Show 3 more As per ASCO 2021 guidelines, obtain post-treatment CT or MRI (if not contraindicated) of the primary site and/or positron emission tomography/CT 3 months after completion of all treatment. B Show 3 more Management of recurrent locoregional disease: consider performing revision resection and appropriate reconstruction and rehabilitation in patients with resectable, recurrent locoregional disease and no distant metastatic disease, regardless of prior treatment type. B Show 2 more Management of recurrent metastatic disease: As per ASCO 2022 guidelines, consider offering pembrolizumab in patients with PD-L1-positive recurrent SGC. C As per ESMO 2022 guidelines, consider obtaining sequencing (next-generation sequencing) of the tumor in case of recurrent/metastatic disease. Encourage participation in clinical trials. C Show 4 more As per ASCO 2021 guidelines, consider evaluating patients with metastatic disease for further treatment such as local ablative treatment or systemic therapy. Decide on treatment option after discussion with the patient and depending on the patient and tumor factors. C Show 9 more Survivorship and rehabilitation (general principles): offer a multidisciplinary recovery program in all patients with SGC. B Survivorship and rehabilitation (lifestyle modifications): advise achieving and maintaining a healthy weight in head and neck cancer survivors, B including offering nutrition strategies to maintain a healthy weight if at risk for cachexia. B Advise limiting consumption of high-calorie foods and beverages and increase physical activity to promote and maintain weight loss if overweight or obese. A Show 4 more Survivorship and rehabilitation (neuromuscular complications): refer patients with spinal accessory nerve palsy occurring after radical neck dissection to a rehabilitation specialist to https://web.pathway.md/diseases/recuC3HKqLWLTLgUC 6/8 6/24/23, 3:06 PM Salivary gland cancer Pathway improve their ROM and ability to perform daily tasks. A Show 3 more Survivorship and rehabilitation (neurosensory complications): Refer patients with altered or loss of taste to a registered dietitian for dietary counseling and assistance in additional seasoning of food, avoiding unpleasant food, and expanding dietary options. B Refer patients to appropriate specialists (audiologists) for loss of hearing, vertigo, or vestibular neuropathy related to treatment. B Survivorship and rehabilitation (speech disturbance): assess patients for speech disturbance B and refer to an experienced speech-language pathologist if a communication disorder is present. B Survivorship and rehabilitation (oral and dental care): advise maintaining regular dental care, including frequent visits to dental professionals, early interventions for dental complications, and meticulous oral hygiene. Test fitting dentures to ensure proper fit and advise removing them at night to avoid irritation. B Show 9 more Survivorship and rehabilitation (gastroesophageal complications): refer patients with complaints of dysphagia, postprandial cough, unexplained weight loss, or pneumonia to an experienced speech-language pathologist for instrumental evaluation of swallowing function to assess and manage dysphagia and possible aspiration. Recognize the potential for psychosocial barriers to swallowing recovery and refer to an appropriate clinician if barriers are present. Refer patients to a speech-language pathologist for videofluoroscopy as the first-line test in patients with suspected stricture due to the high degree of coexisting physiologic dysphagia. B Show 2 more Survivorship and rehabilitation (thyroid dysfunction): measure TSH every 6-12 months to monitor thyroid function in head and neck cancer survivors. B Survivorship and rehabilitation (lymphedema): use the National Cancer Institute Common Toxicity Criteria for Adverse Events v.4.03 or refer for endoscopic evaluation of mucosal edema of the oropharynx and larynx, tape measurements, ultrasound, or external photographs for the assessment of lymphedema. Refer patients to a rehabilitation specialist for treatment consisting of manual lymphatic drainage and, if tolerated, compressive bandaging. B Survivorship and rehabilitation (fatigue): Assess for fatigue and treat any causative factors, including anemia, thyroid dysfunction, and cardiac dysfunction. B Offer treatment for factors that may impact fatigue, such as mood disorders, sleep disturbance, and pain, in patients without an otherwise identifiable cause of fatigue. A Advise regular physical activity and offer CBT as appropriate. A Survivorship and rehabilitation (sleep disorders): ask patients and their partners about snoring and symptoms of sleep apnea to screen for sleep disturbance. Refer patients with suspected sleep apnea to a sleep specialist for a sleep study (polysomnography). B https://web.pathway.md/diseases/recuC3HKqLWLTLgUC 7/8 6/24/23, 3:06 PM Salivary gland cancer Pathway Show 2 more Survivorship and rehabilitation (psychosocial distress): assess head and neck cancer survivors for body and self-image concerns. Refer for psychosocial care as indicated. A Show 3 more References 1. Ezra E W Cohen, Samuel J LaMonte, Nicole L Erb et al. American Cancer Society Head and Neck Cancer Survivorship Care Guideline. CA Cancer J Clin. 2016 May;66 3 203 39. Open 2. Jessica L Geiger, Nofisat Ismaila, Beth Beadle et al. Management of Salivary Gland Malignancy: ASCO Guideline. J Clin Oncol. 2021 Jun 10;39 17 1909 1941. Open 3. C van Herpen, V Vander Poorten, A Skalova et al. Salivary gland cancer: ESMO European Reference Network on Rare Adult Solid Cancers EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up. ESMO Open. 2022 Dec;7 6 100602. Open 4. S Sood, M McGurk, F Vaz. Management of Salivary Gland Tumours: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol. 2016 May;130 S2 S142 S149. Open 5. Melissa A Pynnonen, M Boyd Gillespie, Benjamin Roman et al. Clinical Practice Guideline: Evaluation of the Neck Mass in Adults. Otolaryngol Head Neck Surg. 2017 Sep;157 2_suppl):S1 S30. Open 6. Emrullah Yilmaz, Nofisat Ismaila, Julie E Bauman et al. Immunotherapy and Biomarker Testing in Recurrent and Metastatic Head and Neck Cancers: ASCO Guideline. J Clin Oncol. 2023 Feb 10;41 5 1132 1146. Open 7. Expert Panel on Neurologic Imaging:, Joseph M Aulino, Claudia F E Kirsch et al. ACR Appropriateness Criteria Neck Mass-Adenopathy. J Am Coll Radiol. 2019 May;16 5S S150 S160. Open 8. Carole Fakhry, Christina Lacchetti, Lisa M Rooper et al. Human Papillomavirus Testing in Head and Neck Carcinomas: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists Guideline. J Clin Oncol. 2018 Nov 1;36 31 3152 3161. Open 9. Maria K. Gule-Monroe, MDa, Susana Calle et al. ACR Appropriateness Criteria Staging and Post- Therapy Assessment of Head and Neck Cancer. ACR. 2023. Open https://web.pathway.md/diseases/recuC3HKqLWLTLgUC 8/8