AJCC update Disclosures. AJCC TNM staging system. Objectives:

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Disclosures AJCC update 2018 Remy Lobo, MD remylobo@med.umich.edu remy.lobo@hsc.utah.edu No relevant disclosures Information is based on the 8 th AJCC manual Amin MB, Edge SB, Greene FL et al, eds.

New York: Springer-Verlag; 2017 Objectives: Review the updated 8 th AJCC manual on the staging of head and neck cancers Describe changes from version 7, and rationale behind the changes Share tips

1 Disclosures AJCC update 2018 Remy Lobo, MD No relevant disclosures Information is based on the 8 th AJCC manual Amin MB, Edge SB, Greene FL et al, eds. AJCC Cancer Staging Manual. 8 th ed. New York: Springer-Verlag; 2017 Objectives: Review the updated 8 th AJCC manual on the staging of head and neck cancers Describe changes from version 7, and rationale behind the changes Share tips for radiology representatives at head and neck tumor boards (treatment planning conferences) AJCC TNM staging system T = tumor Characterize primary by size and extent N = node Characterize regional node involvement M = metastasis/metastases Presence/absence of metastasis/metastases Some non-anatomic factors also play a role What is the most important risk factor for the development of head and neck cancer? Male gender Age Tobacco use Alcohol use Genetic predisposition What is the most important risk factor for the development of head and neck cancer? Male gender Age Tobacco use Alcohol use Genetic predisposition 1

Head and neck risk factors Tobacco use Alcohol use Betel nut chewing Radiation Vitamin deficiencies Periodontal disease Immunosuppression Environmental/occupational exposures Head and neck risk

Pathology ctnm v ptnm Now separate clinical versus pathologic staging Clinical staging for all patients Pathologic only for cases that have gone to surgery High risk primary features, ENE,

com Cancer of Unknown Primary (CUP) T0 = tumor cannot be identified May have been a small mucosal primary the body attacked (and removed) These are non-hpv, non-ebv tumors Same system used for

2 Head and neck risk factors Tobacco use Alcohol use Betel nut chewing Radiation Vitamin deficiencies Periodontal disease Immunosuppression Environmental/occupational exposures Head and neck risk factors Tobacco use Field cancerization Alcohol use Betel nut chewing Radiation Vitamin deficiencies Periodontal disease Immunosuppression Environmental/occupational exposures Radiology versus Pathology ctnm v ptnm Now separate clinical versus pathologic staging Clinical staging for all patients Pathologic only for cases that have gone to surgery High risk primary features, ENE, laterality, volume of metastatic nodal disease Can help guide adjuvant treatment Well established in other body parts (e.g. breast), though new application in H&N Cancer of Unknown Primary (CUP) T0 = tumor cannot be identified May have been a small mucosal primary the body attacked (and removed) These are non-hpv, non-ebv tumors Same system used for salivary gland carcinoma (exclusions: melanoma, thyroid, sarcoma, OPSCCa, NPC) Staging is (primarily) based on nodal station N staging: non-hpv, non-ebv SCCa N1 = single ipsilateral node 3cm, and ENE- N2a = single ipsilateral node >3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE- N2c = bilateral (and/or) contralateral lymph node(s) 6cm, and ENE- N3a = lymph node >6cm, and ENE- N3b = any node(s) with overt ENE+ Nodes measured in GREATEST dimension / ENE = extranodal extension 2

N staging: non-hpv, non-ebv SCCa N1 = single ipsilateral node 3cm, and ENE- N2a = single ipsilateral node >3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE- N2c = bilateral

3 N staging: non-hpv, non-ebv SCCa N1 = single ipsilateral node 3cm, and ENE- N2a = single ipsilateral node >3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE- N2c = bilateral (and/or) contralateral lymph node(s) 6cm, and ENE- N3a = lymph node >6cm, and ENE- N3b = any node(s) with overt ENE+ N staging: non-hpv, non-ebv SCCa N1 = single ipsilateral node 3cm, and ENE- N2a = single ipsilateral node >3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE- N2c = bilateral (and/or) contralateral lymph node(s) 6cm, and ENE- N3a = lymph node >6cm, and ENE- N3b = any node(s) with overt ENE+ Nodes measured in GREATEST dimension / ENE = extranodal extension Nodes measured in GREATEST dimension / ENE = extranodal extension N staging: non-hpv, non-ebv SCCa ExtraNodal Extension (ENE+) N1 = single ipsilateral node 3cm, and ENE- N2a = single ipsilateral node >3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE- N2c = bilateral (and/or) contralateral lymph node(s) 6cm, and ENE- N3a = lymph node >6cm, and ENE- N3b = any node(s) with overt ENE+ Nodes measured in GREATEST dimension / ENE = extranodal extension ExtraNodal Extension (ENE+) Radiology often overestimates Poor prognostic indicator <10% 5yr survival Invasion of skin Dense tethering/infiltration of musculature Nerve dysfunction (phrenic, brachial plexus, sympathetic trunk, or cranial nerves) Important (neglected) nodes Suboccipital Retropharyngeal Parapharyngeal Buccinator (facial) Preauricular Peri/intraparotid 3

Oral cavity Mucosal lip Buccal mucosa Upper/lower alveolar ridge Retromolar gingiva (RMT) Floor of mouth Hard palate Oral tongue T staging: oral cavity (& lip) T1 = tumor 2cm, 5mm DOI T2 = tumor 2cm,

4 Oral cavity Mucosal lip Buccal mucosa Upper/lower alveolar ridge Retromolar gingiva (RMT) Floor of mouth Hard palate Oral tongue T staging: oral cavity (& lip) T1 = tumor 2cm, 5mm DOI T2 = tumor 2cm, DOI >5mm & 10mm OR the tumor is >2cm & 4cm, DOI 10mm T3 = tumor >4cm or DOI >10mm T4a = moderately advanced (into mandible, maxilla, sinus or skin) *tooth/bone erosion by gingival primary does not necessarily imply T4 T4b = very advanced (masticator space, pterygoid plates, skull base, internal carotid encasement) T staging: oral cavity (& lip) T1 = tumor 2cm, 5mm DOI T2 = tumor 2cm, DOI >5mm & 10mm OR the tumor is >2cm & 4cm, DOI 10mm T3 = tumor >4cm or DOI >10mm T4a = moderately advanced (into mandible, maxilla, sinus or skin) *tooth/bone erosion by gingival primary does not necessarily imply T4 T4b = very advanced (masticator space, pterygoid plates, skull base, internal carotid encasement) T staging: oral cavity (& lip) T1 = tumor 2cm, 5mm DOI T2 = tumor 2cm, DOI >5mm & 10mm OR the tumor is >2cm & 4cm, DOI 10mm T3 = tumor >4cm or DOI >10mm T4a = moderately advanced (into mandible, maxilla, sinus or skin) *tooth/bone erosion by gingival primary does not necessarily imply T4 T4b = very advanced (masticator space, pterygoid plates, skull base, internal carotid encasement) T staging: oral cavity (& lip) T1 = tumor 2cm, 5mm DOI T2 = tumor 2cm, DOI >5mm & 10mm OR the tumor is >2cm & 4cm, DOI 10mm T3 = tumor >4cm or DOI >10mm T4a = moderately advanced (into mandible, maxilla, sinus or skin) *tooth/bone erosion by gingival primary does not necessarily imply T4 T4b = very advanced (masticator space, pterygoid plates, skull base, internal carotid encasement) T staging: oral cavity (& lip) T1 = tumor 2cm, 5mm DOI T2 = tumor 2cm, DOI >5mm & 10mm OR the tumor is >2cm & 4cm, DOI 10mm T3 = tumor >4cm or DOI >10mm T4a = moderately advanced (into mandible, maxilla, sinus or skin) *tooth/bone erosion by gingival primary does not necessarily imply T4 T4b = very advanced (masticator space, pterygoid plates, skull base, internal carotid encasement) 4

T staging: oral cavity (& lip) T1 = tumor 2cm, 5mm DOI T2 = tumor 2cm, DOI >5mm & 10mm OR the tumor is >2cm & 4cm, DOI 10mm T3 =

does not necessarily imply T4 T4b = very advanced (masticator space, pterygoid plates, skull base, internal carotid encasement) Tx,

internal carotid encasement) Oral cavity T4a disease Locally advanced, osseous erosion (or skin) What muscle is arrowed?

5 T staging: oral cavity (& lip) T1 = tumor 2cm, 5mm DOI T2 = tumor 2cm, DOI >5mm & 10mm OR the tumor is >2cm & 4cm, DOI 10mm T3 = tumor >4cm or DOI >10mm T4a = moderately advanced (into mandible, maxilla, sinus or skin) *tooth/bone erosion by gingival primary does not necessarily imply T4 T4b = very advanced (masticator space, pterygoid plates, skull base, internal carotid encasement) Tx, Tis, T1, T2, T3 (not to scale) T staging: oral cavity (& lip) T1 = tumor 2cm, 5mm DOI T2 = tumor 2cm, DOI >5mm & 10mm OR the tumor is >2cm & 4cm, DOI 10mm T3 = tumor >4cm or DOI >10mm T4a = moderately advanced (into mandible, maxilla, sinus or skin) *tooth/bone erosion by gingival primary does not necessarily imply T4 T4b = very advanced (masticator space, pterygoid plates, skull base, internal carotid encasement) Oral cavity T4a disease Locally advanced, osseous erosion (or skin) What muscle is arrowed? Hyoglossus Oral cavity T4b disease Extrinsic tongue muscle involvement no longer heralds T4 disease (DOI) T4b Masticator PT plates Skull base Carotid encasement 5

6 N staging: non-hpv, non-ebv SCCa N1 = single ipsilateral node 3cm, and ENE- N2a = single ipsilateral node >3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE- N2c = bilateral (and/or) contralateral lymph node(s) 6cm, and ENE- N3a = lymph node >6cm, and ENE- N3b = any node(s) with overt ENE+ Which salivary gland has the greatest incidence of neoplasms? Parotid Submandibular Sublingual Nodes measured in GREATEST dimension / ENE = extranodal extension Which salivary gland has the greatest incidence of neoplasms? Parotid Submandibular Sublingual Major salivary glands Parotids ~80% benign ~20% malignant Submandibular ~50% benign ~50% malignant Sublingual ~20% benign ~80% malignant T staging: major salivary glands T0 = no primary tumor T1 = tumor 2cm, NO extraparenchymal extension T2 = tumor >2cm and 4cm, NO extraparenchymal extension T3 = tumor >4cm and/or extraparenchymal extension T4a = moderately advanced (invades skin, mandible, ear canal, facial nerve) T4b = very advanced (invades skull base, pterygoid plates, encases carotid artery) T staging: major salivary glands T0 = no primary tumor T1 = tumor 2cm, NO extraparenchymal extension T2 = tumor >2cm and 4cm, NO extraparenchymal extension T3 = tumor >4cm and/or extraparenchymal extension T4a = moderately advanced (invades skin, mandible, ear canal, facial nerve) T4b = very advanced (invades skull base, pterygoid plates, encases carotid artery) 6

T staging: major salivary glands T0 = no primary tumor T1 = tumor 2cm, NO extraparenchymal extension T2 = tumor >2cm and 4cm, NO extraparenchymal extension T3 = tumor >4cm and/or extraparenchymal

advanced (invades skin, mandible, ear canal, facial nerve) T4b = very advanced (invades skull base, pterygoid plates, encases carotid artery) Major salivary glands Changes relate to ENE and nodal

node 3cm, and ENE- N2a = single ipsilateral node >3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE- N2c = bilateral (and/or) contralateral lymph node(s) 6cm, and ENE- N3a = lymph

7 T staging: major salivary glands T0 = no primary tumor T1 = tumor 2cm, NO extraparenchymal extension T2 = tumor >2cm and 4cm, NO extraparenchymal extension T3 = tumor >4cm and/or extraparenchymal extension T4a = moderately advanced (invades skin, mandible, ear canal, facial nerve) T4b = very advanced (invades skull base, pterygoid plates, encases carotid artery) T staging: major salivary glands T0 = no primary tumor T1 = tumor 2cm, NO extraparenchymal extension T2 = tumor >2cm and 4cm, NO extraparenchymal extension T3 = tumor >4cm and/or extraparenchymal extension T4a = moderately advanced (invades skin, mandible, ear canal, facial nerve) T4b = very advanced (invades skull base, pterygoid plates, encases carotid artery) Major salivary glands Changes relate to ENE and nodal staging Important T3 is > 4cm or beyond parenchyma T4a (skin, mandible, ear, and/or facial nerve) T4b (skull base, PT plates, encase carotid) N staging: non-hpv, non-ebv SCCa N1 = single ipsilateral node 3cm, and ENE- N2a = single ipsilateral node >3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE- N2c = bilateral (and/or) contralateral lymph node(s) 6cm, and ENE- N3a = lymph node >6cm, and ENE- N3b = any node(s) with overt ENE+ What virus is associated with nasopharyngeal carcinoma? HPV EBV HIV HSV CMV Nodes measured in GREATEST dimension / ENE = extranodal extension 7

8 What virus is associated with nasopharyngeal carcinoma? HPV EBV HIV HSV CMV Nasopharynx Medial/lateral recesses Soft palate to choanae Often extend to parapharyngeal fat Retropharyngeal and spinal accessory nodal spread is common Laterality, location, lowest 80% in Asian population T staging: nasopharynx (NPC) T0 = no tumor, but nodes are EBV+ T1 = confined to nasopharynx +/- oropharynx/nasal cavity without parapharyngeal involvement T2 = extends to parapharyngeal space, and/or adjacent tissues (pterygoid m, prevertebral m) T3 = infiltrates bony structures (skull base, cervical vertebra, pterygoid plates, paranasal sinuses) T4 = intracranial extension, cranial nerves, distal structures (orbit, parotid, hypopharynx or beyond lateral pterygoid muscle) T staging: nasopharynx (NPC) T0 = no tumor, but nodes are EBV+ T1 = confined to nasopharynx +/- oropharynx/nasal cavity without parapharyngeal involvement T2 = extends to parapharyngeal space, and/or adjacent tissues (pterygoid m, prevertebral m) T3 = infiltrates bony structures (skull base, cervical vertebra, pterygoid plates, paranasal sinuses) T4 = intracranial extension, cranial nerves, distal structures (orbit, parotid, hypopharynx or beyond lateral pterygoid muscle) T staging: nasopharynx (NPC) T0 = no tumor, but nodes are EBV+ T1 = confined to nasopharynx +/- oropharynx/nasal cavity without parapharyngeal involvement T2 = extends to parapharyngeal space, and/or adjacent tissues (pterygoid m, prevertebral m) T3 = infiltrates bony structures (skull base, cervical vertebra, pterygoid plates, paranasal sinuses) T4 = intracranial extension, cranial nerves, distal structures (orbit, parotid, hypopharynx or beyond lateral pterygoid muscle) T staging: nasopharynx (NPC) T0 = no tumor, but nodes are EBV+ T1 = confined to nasopharynx +/- oropharynx/nasal cavity without parapharyngeal involvement T2 = extends to parapharyngeal space, and/or adjacent tissues (pterygoid m, prevertebral m) T3 = infiltrates bony structures (skull base, cervical vertebra, pterygoid plates, paranasal sinuses) T4 = intracranial extension, cranial nerves, distal structures (orbit, parotid, hypopharynx or beyond lateral pterygoid muscle) 8

Nasopharynx changes Old T4 is now T2 NPC T0 = for EBV+ nodes (T1, Tx) T2 now includes pterygoid and/or prevertebral muscle involvement T4 more explicit (distal structures) N staging uses cricoid

Cancer 2016; 122:546-58 N staging: NPC N1 = unilateral cervical and/or bilateral retropharyngeal nodes 6cm (above cricoid) N2 = bilateral cervical nodes 6cm (above cricoid) N3 = cervical nodes

9 Nasopharynx changes Old T4 is now T2 NPC T0 = for EBV+ nodes (T1, Tx) T2 now includes pterygoid and/or prevertebral muscle involvement T4 more explicit (distal structures) N staging uses cricoid cartilage as a marker for lower neck +/- nodes greater than 6cm (N3) Merging of prognostic groups Pan JJ et al. Proposal for the 8th Edition of the AJCC/UICC Staging System for NPC in the Era of IMRT. Cancer 2016; 122: N staging: NPC N1 = unilateral cervical and/or bilateral retropharyngeal nodes 6cm (above cricoid) N2 = bilateral cervical nodes 6cm (above cricoid) N3 = cervical nodes (unilateral or bilateral) >6cm and/or extending below caudal cricoid margin N staging: NPC N1 = unilateral cervical and/or bilateral retropharyngeal nodes 6cm (above cricoid) N2 = bilateral cervical nodes 6cm (above cricoid) N3 = cervical nodes (unilateral or bilateral) >6cm and/or extending below caudal cricoid margin N staging: NPC N1 = unilateral cervical and/or bilateral retropharyngeal nodes 6cm (above cricoid) N2 = bilateral cervical nodes 6cm (above cricoid) N3 = cervical nodes (unilateral or bilateral) >6cm and/or extending below caudal cricoid margin N staging: NPC N1 = unilateral cervical and/or bilateral retropharyngeal nodes 6cm (above cricoid) N2 = bilateral cervical nodes 6cm (above cricoid) N3 = cervical nodes (unilateral or bilateral) >6cm and/or extending below caudal cricoid margin 9

N staging: NPC N1 = unilateral cervical and/or bilateral retropharyngeal nodes 6cm

(unilateral or bilateral) >6cm and/or extending below caudal cricoid margin Human

(OPSCCa) Makes up ~80% of head and neck cancers in US HPV-16 is the primary subtype

(biphasic 30, 55) Men > women (3-5x more likely to have OPSCCa) Vaccinations decrease

N3 disease in OPSCCa (p16+) behaves like what stage?

10 N staging: NPC N1 = unilateral cervical and/or bilateral retropharyngeal nodes 6cm (above cricoid) N2 = bilateral cervical nodes 6cm (above cricoid) N3 = cervical nodes (unilateral or bilateral) >6cm and/or extending below caudal cricoid margin Human papilloma virus (HPV) Causative viral agent for oropharyngeal squamous cell carcinoma (OPSCCa) Makes up ~80% of head and neck cancers in US HPV-16 is the primary subtype (18, 31, 33 as well) Usually do NOT have classic risk factors Younger age at onset (biphasic 30, 55) Men > women (3-5x more likely to have OPSCCa) Vaccinations decrease HPV expression, protective Tumor suppressor p16 is overexpressed in OPSCCa Pathologic N3 disease in OPSCCa (p16+) behaves like what stage? Stage I Stage II Stage III Stage IV Pathologic N3 disease in OPSCCa (p16+) behaves like what stage? Stage I Stage II Stage III Stage IV 10

11 HPV OPSCCa Biologically aggressive, but better prognosis For HPV+ disease, survival is similar between I, II, III, IV-A disease (81-88% 5yr survival), 60% in IV-B Recurs less commonly (23% vs 41%) Risk groups: Tobacco use Retropharyngeal adenopathy (worse survival) Treatment: Chemotherapy, radiation, +/- (transoral) surgery T staging: oropharynx (HPV+) T0 = unable to identify primary T1 = tumor 2cm in greatest dimension T2 = tumor >2cm and 4cm in greatest dimension T3 = tumor >4cm or extends to lingual epiglottis T4 = moderately advanced (invades larynx, extrinsic tongue muscles, medial pterygoid, hard palate, mandible or beyond) T staging: oropharynx (HPV+) T0 = unable to identify primary T1 = tumor 2cm in greatest dimension T2 = tumor >2cm and 4cm in greatest dimension T3 = tumor >4cm or extends to lingual epiglottis T4 = moderately advanced (invades larynx, extrinsic tongue muscles, medial pterygoid, hard palate, mandible or beyond) T staging: oropharynx (HPV+) T0 = unable to identify primary T1 = tumor 2cm in greatest dimension T2 = tumor >2cm and 4cm in greatest dimension T3 = tumor >4cm or extends to lingual epiglottis T4 = moderately advanced (invades larynx, extrinsic tongue muscles, medial pterygoid, hard palate, mandible or beyond) T staging: oropharynx (HPV+) T0 = unable to identify primary T1 = tumor 2cm in greatest dimension T2 = tumor >2cm and 4cm in greatest dimension T3 = tumor >4cm or extends to lingual epiglottis T4 = moderately advanced (invades larynx, extrinsic tongue muscles, medial pterygoid, hard palate, mandible or beyond) N staging: HPV related OPSCCa N1 = ipsilateral node(s), ALL 6cm N2 = contralateral/bilateral nodes, ALL 6cm N3 = lymph node(s) > 6cm 11

12 N staging: HPV related OPSCCa N1 = ipsilateral node(s), ALL 6cm N2 = contralateral/bilateral nodes, ALL 6cm N3 = lymph node(s) > 6cm N staging: HPV related OPSCCa N1 = ipsilateral node(s), ALL 6cm N2 = contralateral/bilateral nodes, ALL 6cm N3 = lymph node(s) > 6cm N staging: HPV related OPSCCa N1 = ipsilateral node(s), ALL 6cm N2 = contralateral/bilateral nodes, ALL 6cm N3 = lymph node(s) > 6cm N staging: HPV related OPSCCa N1 = ipsilateral node(s), ALL 6cm N2 = contralateral/bilateral nodes, ALL 6cm N3 = lymph node(s) > 6cm Note: ENE is not evaluated in HPV related OPSCCa Oropharyngeal sites Base of tongue (includes lingual tonsil) Soft palate (and uvula) Anterior/posterior tonsillar pillars (palatine tonsils) Glossotonsillar sulci Lateral/posterior pharyngeal walls Oropharyngeal sites Base of tongue (includes lingual tonsil) Soft palate (and uvula) Anterior/posterior tonsillar pillars (palatine tonsils) Glossotonsillar sulci Lateral/posterior pharyngeal walls 12

OPSCCa PET/CT eases nodal detection T3 (lingual epiglottis), though ~2cm From 1 chapter to 3 7 th AJCC had 1 pharynx chapter (NP/OP/HP) 8 th edition

indicators T staging: oropharynx (HPV-) T1 = tumor 2cm in greatest dimension T2 = tumor >2cm and 4cm in greatest dimension T3 = tumor >4cm or extends

advanced (invades lateral pterygoid m, pterygoid plates, lateral nasopharynx, skull base or encases carotid artery) T staging: oropharynx (HPV-) T1 =

>2cm and 4cm in greatest dimension T3 = tumor >4cm or extends advanced (invades lateral pterygoid m, pterygoid plates, lateral nasopharynx, skull

13 OPSCCa PET/CT eases nodal detection T3 (lingual epiglottis), though ~2cm From 1 chapter to 3 7 th AJCC had 1 pharynx chapter (NP/OP/HP) 8 th edition has 3 chapters Nasopharynx EBV related Oropharynx HPV related Hypopharynx and oropharynx (non-hpv related) Based on different genetic, prognostic indicators T staging: oropharynx (HPV-) T1 = tumor 2cm in greatest dimension T2 = tumor >2cm and 4cm in greatest dimension T3 = tumor >4cm or extends to lingual epiglottis T4a = moderately advanced (invades larynx, extrinsic tongue muscles, medial pterygoid, hard palate, mandible) T4b = very advanced (invades lateral pterygoid m, pterygoid plates, lateral nasopharynx, skull base or encases carotid artery) T staging: oropharynx (HPV-) T1 = tumor 2cm in greatest dimension T2 = tumor >2cm and 4cm in greatest dimension T3 = tumor >4cm or extends to lingual epiglottis T4a = moderately advanced (invades larynx, extrinsic tongue muscles, medial pterygoid, hard palate, mandible) T4b = very advanced (invades lateral pterygoid m, pterygoid plates, lateral nasopharynx, skull base or encases carotid artery) T staging: oropharynx (HPV-) T1 = tumor 2cm in greatest dimension T2 = tumor >2cm and 4cm in greatest dimension T3 = tumor >4cm or extends to lingual epiglottis T4a = moderately advanced (invades larynx, extrinsic tongue muscles, medial pterygoid, hard palate, mandible) T4b = very advanced (invades lateral pterygoid m, pterygoid plates, lateral nasopharynx, skull base or encases carotid artery) 13

14 T staging: oropharynx (HPV-) T1 = tumor 2cm in greatest dimension T2 = tumor >2cm and 4cm in greatest dimension T3 = tumor >4cm or extends to lingual epiglottis T4a = moderately advanced (invades larynx, extrinsic tongue muscles, medial pterygoid, hard palate, mandible) T4b = very advanced (invades lateral pterygoid m, pterygoid plates, lateral nasopharynx, skull base or encases carotid artery) T staging: oropharynx (HPV-) T1 = tumor 2cm in greatest dimension T2 = tumor >2cm and 4cm in greatest dimension T3 = tumor >4cm or extends to lingual epiglottis T4a = moderately advanced (invades larynx, extrinsic tongue muscles, medial pterygoid, hard palate, mandible) T4b = very advanced (invades lateral pterygoid m, pterygoid plates, lateral nasopharynx, skull base or encases carotid artery) T staging: hypopharynx T1 = tumor 2cm and in one subsite T2 = tumor >2cm and 4cm OR invades >1 subsite T3 = tumor >4cm OR extends to esophagus OR demonstrates hemilarynx fixation T4a = moderately advanced (invade thyroid/cricoid cartilage, hyoid, thyroid gland or central compartment including strap muscles/fat) T4b = very advanced (invades prevertebral fascia, encases carotid artery or extends to mediastinum) T staging: hypopharynx T1 = tumor 2cm and in one subsite T2 = tumor >2cm and 4cm OR invades >1 subsite T3 = tumor >4cm OR extends to esophagus OR demonstrates hemilarynx fixation T4a = moderately advanced (invade thyroid/cricoid cartilage, hyoid, thyroid gland or central compartment including strap muscles/fat) T4b = very advanced (invades prevertebral fascia, encases carotid artery or extends to mediastinum) T staging: hypopharynx T1 = tumor 2cm and in one subsite T2 = tumor >2cm and 4cm OR invades >1 subsite T3 = tumor >4cm OR extends to esophagus OR demonstrates hemilarynx fixation T4a = moderately advanced (invade thyroid/cricoid cartilage, hyoid, thyroid gland or central compartment including strap muscles/fat) T4b = very advanced (invades prevertebral fascia, encases carotid artery or extends to mediastinum) T staging: hypopharynx T1 = tumor 2cm and in one subsite T2 = tumor >2cm and 4cm OR invades >1 subsite T3 = tumor >4cm OR extends to esophagus OR demonstrates hemilarynx fixation T4a = moderately advanced (invade thyroid/cricoid cartilage, hyoid, thyroid gland or central compartment including strap muscles/fat) T4b = very advanced (invades prevertebral fascia, encases carotid artery or extends to mediastinum) 14

T staging: hypopharynx T1 = tumor 2cm and in one subsite T2 = tumor >2cm and 4cm OR invades >1 subsite T3 = tumor >4cm OR

thyroid gland or central compartment including strap muscles/fat) T4b = very advanced (invades prevertebral fascia, encases

HP: pyriform sinuses, L/P hypopharyngeal walls, post cricoid region T4b oropharyngeal cancer T4b oropharyngeal cancer T4a

>3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE- N2c = bilateral (and/or) contralateral lymph node(s) 6cm,

15 T staging: hypopharynx T1 = tumor 2cm and in one subsite T2 = tumor >2cm and 4cm OR invades >1 subsite T3 = tumor >4cm OR extends to esophagus OR demonstrates hemilarynx fixation T4a = moderately advanced (invade thyroid/cricoid cartilage, hyoid, thyroid gland or central compartment including strap muscles/fat) T4b = very advanced (invades prevertebral fascia, encases carotid artery or extends to mediastinum) OPSCCa (HPV-), HP OP: BoT, SP, A/P tonsil pillars, GTS, L/P pharyngeal walls, tonsils HP: pyriform sinuses, L/P hypopharyngeal walls, post cricoid region T4b oropharyngeal cancer T4b oropharyngeal cancer T4a hypopharyngeal cancer N staging: non-hpv, non-ebv SCCa N1 = single ipsilateral node 3cm, and ENE- N2a = single ipsilateral node >3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE- N2c = bilateral (and/or) contralateral lymph node(s) 6cm, and ENE- N3a = lymph node >6cm, and ENE- N3b = any node(s) with overt ENE+ Nodes measured in GREATEST dimension / ENE = extranodal extension 15

T staging: cutaneous SCCa (H&N) T1 = tumor <2cm T2 = tumor 2cm and <4cm T3 = tumor 4cm, or minor bone erosion, or perineural invasion or deep extension (6mm beyond subcutaneous fat) T4a = gross

T4b = skull base invasion and/or foraminal extension cortical bone/marrow invasion T4b = skull base invasion and/or foraminal extension T staging: cutaneous SCCa (H&N) Cutaneous malignancies T1 =

16 T staging: cutaneous SCCa (H&N) T1 = tumor <2cm T2 = tumor 2cm and <4cm T3 = tumor 4cm, or minor bone erosion, or perineural invasion or deep extension (6mm beyond subcutaneous fat) T4a = gross cortical bone/marrow invasion T4b = skull base invasion and/or foraminal extension T staging: cutaneous SCCa (H&N) T1 = tumor <2cm T2 = tumor 2cm and <4cm T3 = tumor 4cm, or minor bone erosion, or perineural invasion or deep extension (6mm beyond subcutaneous fat) T4a = gross cortical bone/marrow invasion T4b = skull base invasion and/or foraminal extension T staging: cutaneous SCCa (H&N) T1 = tumor <2cm T2 = tumor 2cm and <4cm T3 = tumor 4cm, or minor bone erosion, or perineural invasion or deep extension (6mm beyond subcutaneous fat) T4a = gross cortical bone/marrow invasion T4b = skull base invasion and/or foraminal extension T staging: cutaneous SCCa (H&N) T1 = tumor <2cm T2 = tumor 2cm and <4cm T3 = tumor 4cm, or minor bone erosion, or perineural invasion or deep extension (6mm beyond subcutaneous fat) T4a = gross cortical bone/marrow invasion T4b = skull base invasion and/or foraminal extension T staging: cutaneous SCCa (H&N) Cutaneous malignancies T1 = tumor <2cm T2 = tumor 2cm and <4cm T3 = tumor 4cm, or minor bone erosion, or perineural invasion or deep extension (6mm beyond subcutaneous fat) T4a = gross cortical bone/marrow invasion T4b = skull base invasion and/or foraminal extension 16

Cutaneous malignancies N staging: non-hpv, non-ebv SCCa N1 = single ipsilateral node 3cm, and ENE- N2a = single ipsilateral node >3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE-

Prognostic staging groups Vary depending on malignancy and site of origin IV-A usually with N2 or T4a IV-B usually with N3 or T4b There are exceptions to this generalization Example: HPV related

17 Cutaneous malignancies N staging: non-hpv, non-ebv SCCa N1 = single ipsilateral node 3cm, and ENE- N2a = single ipsilateral node >3cm and 6cm, and ENE- N2b = multiple ipsilateral nodes 6cm, and ENE- N2c = bilateral (and/or) contralateral lymph node(s) 6cm, and ENE- N3a = lymph node >6cm, and ENE- N3b = any node(s) with overt ENE+ Nodes measured in GREATEST dimension / ENE = extranodal extension Prognostic staging groups Vary depending on malignancy and site of origin IV-A usually with N2 or T4a IV-B usually with N3 or T4b There are exceptions to this generalization Example: HPV related OPSCCa N3 (and any T) = III T4 (any N) = III M1 (any T,N) = IV Prospective data being gathered Overall health of patients Comorbidities Performance scores (Karnofsky) Lifestyle factors Tobacco, alcohol Weight loss Depression Many other demographic, histopathologic and epidemiological details are also acquired Before dictating a case Need to know: age of patient, other cancer history and any treatment (radiation/surgery) Current cancer primary location (with suspected laterality referenced) Histopathology p16 status (for OPSCCa), EBV for NPC TNM T assess primary site according to selected table, ensure LONG axis for T measurement N look for size (>10mm), rounded shape, loss of fatty hilum, necrosis or cystic change N evaluation for ENE (non p16, non-ebv cases), assess for infiltration/tethering M often requires PET/CT or dedicated whole body imaging 17

18 Useful points OP HPV positive (p16+) cancers have a better prognosis, chemoradiation sensitive NPC nodal system is simplified (no 3a/3b) OC tumors are no longer upstaged based on the presence of extrinsic tongue muscle involvement, DOI is now the dominant factor (determined on histopathology) Lip cancers is now part of cutaneous H&N Other details 90% CUP (cancer of unknown primary) are HPV+, presumed to arise from OP. This requires nodal evaluation and in situ hybridization evaluation Larynx/salivary/sinus/nasal are similar to 7 th AJCC Pathology specific staging tables will take precedence after surgery has been performed Summary AJCC 8 th edition Separates HPV and non-hpv related OPSCCa Simplified tumor staging (4b = locally advanced) Simplified nodal staging (1, 2a/b/c, 3a/b) Extranodal extension (a new descriptor) Goal is to create a more personalized approach Thank you for your time AJCC update 2018 Remy Lobo, MD remylobo@med.umich.edu remy.lobo@hsc.utah.edu remy.lobo@hsc.utah.edu remylobo@med.umich.edu Abbreviations AJCC = American Joint Committee on Cancer UICC = Union for International Cancer Control TNM = tumor, node, metastasis (staging system) SCCa = squamous cell carcinoma OP = oropharynx, NP = nasopharynx, HP = hypopharynx HPV = Human Papilloma virus (p16+) ENE = extranodal extension (poor prognosis) NPC = nasopharyngeal cancer/carcinoma EBV = Epstein Barr virus DOI = depth of invasion (pathological feature) Muscle (m), Nerve (n), base of tongue (BoT), anterior/posterior commissures AC/PC 18

19 T staging: maxillary sinus T1 = tumor limited to maxillary sinus mucosa without osseous erosion or destruction T2 = tumor erodes/destroys bone, extends into hard palate/middle meatus T3 = tumor invades posterior maxillary sinus wall, subcutaneous tissue, inferior/medial orbit, pterygoid fossa, or ethmoid sinuses T4a = moderately advanced (anterior orbit, skin, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses T4b = very advanced (orbital apex, dura, brain, cranial nerves [beyond V2], nasopharynx, or clivus) T staging: nasal cavity/ethmoids T1 = tumor limited to one subsite, +/- bony invasion T2 = tumor in two subsites or adjacent extension in nasoethmoidal complex, +/- bony invasion T3 = tumor invades inferior/medial orbit, maxillary sinus, palate or cribriform plate T4a = moderately advanced (anterior orbit, skin, pterygoid plates, sphenoid/frontal sinuses, or minimal anterior cranial fossa extension) T4b = very advanced (orbital apex, dura, brain, cranial nerves [beyond V2], nasopharynx, clivus) T staging: supraglottic larynx T1 = tumor in one supraglottic subsite; normal cord mobility T2 = tumor invades one adjacent supraglottic mucosal subsite, glottis or adjacent site (BoT, vallecula, pyriform); normal cord mobility T3 = vocal cord fixation and/or invasion of post cricoid, preepiglottic space, paraglottic space, or inner thyroid cartilage cortex T4a = moderately advanced (through outer cortex of thyroid, or beyond larynx [trachea, extrinsic tongue muscles, strap muscles, thyroid, esophagus]) T4b = very advanced (prevertebral space, encases carotid artery, invades mediastinum) T staging: glottis T1a = one vocal cord (AC/PC, normal mobility) T1b = both vocal cord (AC/PC, normal mobility) T2 = supra/subglottic extension, +/- impaired mobility T3 = vocal cord fixation, and/or invade paraglottic space, and/or inner cortex of thyroid T4a = moderately advanced (through outer thyroid cartilage cortex, beyond larynx [trachea, cricoid, tongue, strap muscles, thyroid, esophagus]) T4b = very advanced (invades prevertebral space, encases carotid artery, invades mediastinum) T staging: subglottis T1 = limited to subglottis T2 = extends to vocal cord, +/- impaired mobility T3 = vocal cord fixation, and/or invades paraglottic space, and/or inner thyroid cartilage cortex T4a = moderately advanced (invades cricoid or thyroid cartilage, beyond larynx [trachea, tongue, strap muscles, thyroid, esophagus]) T4b = very advanced (invades prevertebral space, encases carotid artery, invades mediastinum) T staging: thyroid T0 = no primary tumor T1a = tumor 1cm, limited to thyroid T1b = tumor >1cm and 2cm, limited to thyroid T2 = tumor >2cm and 4cm, limited to thyroid T3a = tumor >4cm limited to thyroid T3b = extrathyroidal extension (any size) into the strap muscles (sternohyoid, sternothyroid, thyroihyoid, omohyoid) T4a = extrathyroidal extension (subcutaneous tissue, larynx, trachea, esophagus, recurrent laryngeal n.) T4b = extrathyroidal extension (prevertebral fascia, encasing carotid or other mediastinal vessels) 19

20 N staging: thyroid Nx = nodes cannot be assessed N0a = confirmed benign lymph nodes N0b = no radiologic or clinical locoregional metastasis N1a = level VI or VII (pretracheal, paratracheal, prelaryngeal, upper mediastinum), can be unilateral or bilateral N1b = involvement in I, II, III, IV or V stations or retropharyngeal nodes Thyroid stage groups Age dependent (above/below 55 years old) Under 55, M1 is stage II (all others are stage I) Better overall prognosis T4a is III T4b is IV-A M1 is IV-B Exception is for anaplastic (all are stage IV) T1-3a is IV-A T3b or N1 is IV-B T4 is IV-B M1 is IV-C AJCC update 2018 Remy Lobo, MD remylobo@med.umich.edu remy.lobo@hsc.utah.edu 20

AJCC Staging of Head & Neck Cancer (7 th edition, 2010) -LIP & ORAL CAVITY-

TX: primary tumor cannot be assessed T0: no evidence of primary tumor Tis: carcinoma in situ. T1: tumor is 2 cm or smaller AJCC Staging of Head & Neck Cancer (7 th edition, 2010) -LIP & ORAL CAVITY- T2: