Salivary gland cancer: ESMO–European Reference Network on Rare Adult Solid Cancers (EURACAN) Clinical Practice Guideline for diagnosis, treatment and follow-up

• DOI: 10.1016/j.esmoop.2022.100602
• Publication Date: 2022-11-02T21:07:47Z
• Authors: C. van Herpen; V. Vander Poorten; A. Skalova; C. Terhaard; R. Maroldi; A. van Engen; B. Baujat; L.D. Locati; A.D. Jensen; L. Smeele; J. Hardillo; V. Costes Martineau; A. Trama; E. Kinloch; C. Even; J.-P. Machiels
• Keywords: Guideline; Clinical Practice; Salivary gland cancer

•This ESMO–EURACAN Clinical Practice Guideline provides key recommendations for managing salivary gland cancer.•The guideline covers clinical and pathological diagnosis, staging risk assessment, treatment follow-up.•Treatment algorithms parotid, submandibular, sublingual minor cancer are provided.•The author group encompasses a multidisciplinary of experts from different institutions countries in Europe.•Recommendations based on available scientific data the authors' collective expert opinion. Major cancers (SGCs) comprise 5% head neck Europe. The worldwide crude age-adjusted incidence rates 0.69 0.57 cases per 100 000 people year, respectively, with 53 583 new patients 2020. In Europe, 1.3 0.67 9917 2020.1Ferlay J. Ervik M. Lam F. et al.Global Cancer Observatory: Today. Lyon, France: International Agency Research Cancer.https://gco.iarc.fr/todayDate accessed: February 14, 2022Google Scholar Data SGCs limited, but RARECARENet project estimated gland-type to be 0.4 2000-2007 diagnosis period; have slight predominance males is highest elderly (>65 years).2RARECARENet. Information Network Rare Cancers.http://rarecarenet.istitutotumori.mi.it/Date History cervicofacial radiotherapy (RT) both been associated an increased major SGC [odds ratio (OR) 17.06, 95% confidence interval (CI) 4.34-67.05 OR 31.74, CI 2.48-405.25, respectively].3Radoi L. Barul C. Menvielle G. al.Risk factors results case-control study, ICARE study.Oral Oncol. 2018; 80: 56-63Crossref PubMed Scopus (15) Google Scholar,4Lin H.H. Limesand K.H. Ann D.K. Current state knowledge cancers.Crit Rev Oncog. 23: 139-151Crossref (38) Industries such as cereal other crop production, furniture manufacturing, interurban road transport industrial cleaning also SGC.3Radoi Scholar, 4Lin 5Cong X. Air pollution waste gas emissions incidences Shanghai, China.Environ Sci Pollut Res Int. 25: 13067-13078Crossref (48) Smoking only seems increase developing than mucoepidermoid carcinoma (MEC) (OR 5.15, 2.06-12.87)6Sawabe Ito H. Takahara T. al.Heterogeneous impact smoking according histopathological subtype: study.Cancer. 124: 118-124Crossref (18) Scholar; however, ionising radiation well-established factor.7Boukheris Curtis R.E. Land C.E. al.Incidence glands WHO classification, 1992 2006: population-based study United States.Cancer Epidemiol Biomarkers Prev. 2009; 18: 2899-2906Crossref (201) Scholar,8Alvi S. Chudek D. Limaiem Cancer, Parotid. Treasure. StatPearls Publishing, Island, FL2020Google include >20 distinct histological subtypes. Given their rarity heterogeneity, epidemiological studies providing histology limited. typically occurs sixth seventh decades life has male predominance2RARECARENet. age at gender vary by histology. MEC, adenoid cystic (AdCC) acinic cell (AcCC) tend occur earlier adenocarcinoma squamous (SCC). AdCC AcCC more common females up ∼50 years age; similar older ages, whereas MEC higher rate among males.7Boukheris tumour diagnoses subsites 100:10:10:1, proportion malignant tumours these sites 20%, 50%, 50% 80%, respectively.9Bradley P.J. McGurk Incidence neoplasms defined UK population.Br J Oral Maxillofac Surg. 2013; 51: 399-403Abstract Full Text PDF (139) not between 1995 2007 Europe10Gatta Capocaccia R. Botta al.Burden centralised Europe rare tumours: RARECAREnet – study.Lancet 2017; 1022-1039Abstract (230) or 2010 States.7Boukheris 5-year relative survival (estimated observed expected general population, matched age, sex, calendar year geographical area) 63% (95% 62% 63.7%) Europe.10Gatta This decreases ∼90% 91% 97%) aged <25 years, 70% 69% 71%) 25-64 53% 52% 55%) those >65 years. Five-year (72%, 71% 74%) (55%, 54% 56%). Furthermore, differs across European regions, 74% 78%) reported Nordic (Finland, Iceland, Norway) lowest 54%) Eastern (Bulgaria, Czech Republic, Estonia, Latvia, Lithuania, Poland, Slovakia). improved 1999 2007.2RARECARENet. 67% males. children (>90%) then decrease 60% during period 1999-2007, remained stable was (84%) (55%).2RARECARENet. should classified World Health Organization (WHO) Classification Head Neck Tumours.11El Naggar A.K. Chan J.K. Grandis J.R. al.World Tumours.4th ed. IARC Press, France2017Google Including benign tumours, there over 30 types latest classification system (see Supplementary Table S1, https://doi.org/10.1016/j.esmoop.2022.100602, types). symptoms depend location. Symptoms that prompt consideration pain face mouth, externally submucosally growing lump (facial) nerve paralysis. Cytology mandatory. Ultrasound-guided fine-needle aspiration (FNA) cytology become accepted minimally invasive method evaluating parotid submandibular preoperatively. can distinguish disease 90% if examined pathologist experienced disease.12Faquin W. Rossi E.D. Milan System Reporting Salivary Gland Cytopathology. Springer, New York, NY2018Crossref (0) reporting cytopathology recommended. It facilitates standardised links each diagnostic category malignancy (ROM); risks were recently confirmed large meta-analysis.13Farahani S.J. Baloch Z. Retrospective assessment effectiveness cytology: systematic review meta-analysis published literature.Diagn Cytopathol. 2019; 47: 67-87Crossref (45) ROM-associated therapeutic approaches, e.g. initial intensified when high-grade suspected (one 99% accuracy14Kim B.Y. Hyeon Ryu al.Diagnostic accuracy fine needle tumors.Ann Surg 20: 2380-2387Crossref (44) Scholar) S2, https://doi.org/10.1016/j.esmoop.2022.100602).12Faquin If FNA non-diagnostic situation requires information histotype, core biopsy, while demanding slightly complications,15Howlett D.C. Triantafyllou A. Evaluation: cytology, ultrasound-guided biopsy open techniques.Adv Otorhinolaryngol. 2016; 78: 39-45PubMed less inadequate sampling (risk 0.85) yield FNA.16Cho Kim Lee J.S. al.Comparison neoplasm: meta-analysis.Head Neck. 2020; 42: 3041-3050Crossref thus next step work-up.17Romano E.B. Wagner J.M. Alleman A.M. al.Fine-needle selective use tumors.Laryngoscope. 127: 2522-2527Crossref (23) Open biopsies avoided lesions due complicating definitive surgical spillage, exception skin ulcerating tumours. For surgeon take surrounding stroma.18Ihrler Agaimy Guntinas-Lichius O. al.Why histomorphological much difficult?.Histopathology. 2021; 79: 779-790Crossref (9) Incisional recommended extending incisional forceps taken lesions. Ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) [18F]2-fluoro-2-deoxy-D-glucose–positron emission (FDG–PET) techniques most commonly used assess glands, MRI being preferred modality Figure 1). Diagnostic described Section 1 Material, https://doi.org/10.1016/j.esmoop.2022.100602. type essentially defines its biological behaviour, which influences prognosis patterns recurrence, management. Some types, basal adenocarcinoma, low-grade intraductal conventional AcCC, indolent, high locoregional recurrence low nodal involvement distant metastases.19Seethala R.R. An update grading carcinomas.Head Pathol. 3: 69-77Crossref (229) Immunohistochemistry (IHC) specimen supplementary visualisation compartments populations, improving taxonomy. role molecular diagnostics evolving. Many monomorphic now known harbour defining balanced translocations, some readily evaluable paraffin-embedded materials either FISH, RT–PCR next-generation sequencing (NGS).20Skalova Stenman Simpson R.H.W. al.The testing differential carcinomas.Am e11-e27Crossref (126) Recently, NGS provided significant input characterisation subtypes, differentiation morphologically identifying novel driver pathways determine biology may amenable targeted therapy [see Society Medical Oncology (ESMO) Scale Actionability Molecular Targets (ESCAT) further details S3, https://doi.org/10.1016/j.esmoop.2022.100602]. subtypes detail 2 Key alterations S4, •Classification carried out Tumours [I, A].•Clinical examination confirmation mandatory [IV, A].•FNA screening; inadequate, [III, including ROM suggested approaches A].•For stroma. A].•When suspected, A].•Contrast-enhanced CT mostly limited whom contraindicated B].•Regardless technique used, extended ipsilateral contralateral levels integrated ultrasound lymph nodes A].•FDG–PET–CT detection metastases A].•IHC tools appropriate A]. Confirmation androgen receptor human epidermal growth factor (HER2) status duct otherwise specified (NOS) A; ESCAT score: II-B].•Analysis NTRK fusion whole genome secretory I-C].•NGS (or exome sequencing) recurrent metastatic (R/M) all actionable mutations genes identified 40%-50% [V, C]. [cTNM (clinical tumour–node–metastasis)] before referring physician patient evaluation using Union Control (UICC) TNM eighth edition classification.21O'Sullivan B. glands.in: Brierley J.D. Gospodarowicz M.K. Wittekind UICC Malignant Tumours. 8th Wiley-Blackwell, Oxford, UK2017Google Preoperative mainly methods findings, especially FNA. Pathological after resection primary tumour. There currently no clear recommendation intraparotid versus cervical metastases; findings recent suggest differences addressed future editions classification.22Lombardi Tomasoni Paderno carcinoma: multicenter experience proposal N-classification.Oral 112105076Crossref correct management SGC, report follow Collaboration guidelines.23Seethala Altemani Ferris R.L. al.Data set carcinomas glands: explanations guidelines Reporting.Arch Pathol Lab Med. 143: 578-586Crossref (13) Operative procedure; specimens submitted; site, focality dimensions; grade; perineural invasion; lymphovascular extent invasion margin required 3 https://doi.org/10.1016/j.esmoop.2022.100602).23Seethala (pTNM) presented S5, Minor staged similarly SCC, site they arise (e.g. oral cavity, pharynx, sinuses, etc.). •Clinical pTNM A].•Intra-operative frozen sections indicated evaluate margins resection, nodes, result alter time surgery B].•The complicated subgroup cancers. As such, local/locoregional managed surgeons, oncologists, medical oncologists specialists working team specialised units, centres designated members Reference Adult Solid Cancers. Proposed gland, cancer, shown Figures 2, 4, respectively.Figure 3Treatment algorithm SGC. Purple: categories stratification; red: surgery; dark green: radiotherapy; white: aspects management; blue: systemic anticancer therapy. ChT, chemotherapy; END, elective dissection; ND, node RT, cancer. aDefinition https://doi.org/10.1016/j.esmoop.2022.100602.View Large Image ViewerDownload Hi-res image Download (PPT)Figure 4Treatment CNB, biopsy; FNA, aspiration; radiotherapy. (PPT) complete excision free margins.24Lombardi Vander Poorten V. al.Surgical tumors.Oral 65: 102-113Crossref (65) difficulty this lies achieving without functional aesthetic sequelae. Revision following unexpected post-operative carries great already dissected facial nerve; therefore, every effort made identify preoperatively, allowing immediately adequate removal.25Sood Vaz Management Kingdom National Multidisciplinary Guidelines.J Laryngol Otol. 130: S142-S149Crossref imperative, preoperative MRI, suggests malignancy, warn possibly extensive procedure. case extraparotid extension, sacrificing elements [e.g. (nVII), infratemporal fossa, mandible, skin] possible reconstruction must considered. Functional disorders arising considered planning.24Lombardi Resectability assessed meeting, bearing mind surgery, possible, optimal treatment. A unresectable macroscopic likely left behind. reference procedure total parotidectomy. low-grade, early-stage (cT1-T2N0) superficial lobe, parotidectomy suffice, discovery advanced-stage (all cT1-T2N0) and/or preoperatively intermediate- preferable. No consensus exists literature how many millimetres thick 'free'. presence absence paralysis choice procedure: it logical try preserve sacrifice paralysis.24Lombardi intra-operative nerve, preservation decided case-by-case basis, depending well wishes patient. important collect about discuss scenarios able do graft ablative remote dissection branches section analysis limits necessary, AdCC, characterised extensions along nerves.26Dillon P.M. Chakraborty Moskaluk C.A. al.Adenoid advances, targets, trials.Head 38: 620-627Crossref (168) negative prognostic factor.24Lombardi imposes wide often unsatisfactory excisional limits. Addressing deficit approach.24Lombardi Scholar,27Renkonen Sayed Keski-Santti al.Reconstruction radical parotidectomy.Acta Otolaryngol. 2015; 135: 1065-1069Crossref (17) entity, mucous membranes (including nasal nasopharynx, oropharynx, hypopharynx, oesophagus, larynx, trachea cavity). 10 times frequent SGC.9Bradley Surgery mainstay resectable traditional approach widely although endoscopic robot-assisted described.28Bollig Wang K. Llerena P. al.National oropharyngeal malignancies treated transoral robotic surgery.Otolaryngol 2022; 166: 886-893Crossref (1) series 450 multivariate showed advanced stage unfavourable subtype poor disease-specific survival.29Hay A.J. Migliacci Karassawa Zanoni al.Minor tumors neck-Memorial Sloan Kettering experience: outcomes type.Cancer. 125: 3354-3366Crossref (59) Surveillance, Epidemiology End Results (SEER) database 1426 oropharynx.30Goel A.N. Badran K.W. Braun A.P.G. oropharynx: patients.Otolaryngol 158: 287-294Crossref generally 1-cm tumours; millimetric achievable. particularly spread (as earlier), requiring detailed planning margins, bony structures.24Lombardi AdCC.31Han M.W. Cho K.J. Roh J.L. al.Patterns metastasis influence carcinoma.J 2012; 106: 475-480Crossref (26) Scholar,32Aro Tarkkanen Saat al.Submandibular cancer: specific features considerations.Head 40: 154-162Crossref confined within require level Ib ensure margins. evidence involvement, involving I, II III standard prevalence high, exceeding malignancies.24Lombardi Scholar,33Vander V.L. Balm Hilgers F.J. al.Prognostic long term tumors.Cancer. 1999; 85: 2255-2264Crossref (72) Careful needed structures lingual, hypoglossal marginal mandibular nerves, floor mouth muscles skin. Although low, propensity infiltrating adjacent spread.24Lombardi Scholar,31Han Sur