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Head and Neck Cancers Kazumi Chino, M.D. Radiation Oncology.

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Presentation on theme: "Head and Neck Cancers Kazumi Chino, M.D. Radiation Oncology."— Presentation transcript:

1 Head and Neck Cancers Kazumi Chino, M.D. Radiation Oncology

2 Epidemiology 52,000 people diagnosed in the US annually 3% of all cancers in the US Men are twice as likely as women to develop a head and neck cancer Dx is most common after age 50

3 Risk Factors Tobacco – approx. 85% of H&N Ca related to tobacco Alcohol HPV in oropharyngeal cancers Epstein-Barr virus in nasopharyngeal cancers Poor dental/oral hygiene Poor nutrition – vit A and B deficiency GERD in pharyngeal cancers

4 Histology 90% of H&N cancers are squamous cell carcinomas arising from the mucosal surfaces Salivary gland tumors are typically adenocarcinomas

5 Anatomy

6 Anatomy: Nasopharynx Eustachian tube Torus Tubaris Fossa of Rosenmuller

7 Anatomy: Oro/Hypopharynx From the uvula to hyoid bone Palatine tonsils, tonsillar pillars Base of tongue Epiglottis and vallecula

8 Anatomy: Laryngopharynx From the epiglottis to the inferior cricoid cartilage Vocal cords, piriform sinuses, arytenoid cartilage and aryepiglottic folds

9 Anatomy: Laryngopharynx

10 Cervical Lymph Nodes

11 Presentation: Nasopharynx

12 Nasopharyngeal Cancer Sx’s Nasal obstruction, bleeding, discharge Hearing problems if eustachian tube obstructed, otitis media Headaches Cranial nerve palsy with involvement of the base of skull Neck mass, particularly at the mastoid tip

13 Staging: Nasopharynx Primary tumor (T) TXPrimary tumor cannot be assessed T0No evidence of primary tumor TisCarcinoma in situ T1Tumor confined to the nasopharynx, or tumor extends to oropharynx and/or nasal cavity without parapharyngeal extension (eg, without posterolateral infiltration of tumor) T2Tumor with parapharyngeal extension (posterolateral infiltration of tumor) T3Tumor involves bony structures of skull base and/or paranasal sinuses T4Tumor with intracranial extension and/or involvement of cranial nerves, hypopharynx, or orbit, or with extension to the infratemporal fossa/masticator space

14 Staging: Nasopharynx Regional lymph nodes (N) NXRegional nodes cannot be assessed N0No regional lymph node metastasis N1Unilateral metastasis in cervical lymph nodes ≤6cm in greatest dimension, above the supraclavicular fossa, and/or unilateral or bilateral retropharyngeal lymph nodes ≤6 cm in greatest dimension (midline nodes are considered ipsilateral nodes) N2Bilateral metastasis in cervical lymph nodes ≤6cm in greatest dimension, above the supraclavicular fossa (midline nodes are considered ipsilateral nodes) N3Metastasis in a lymph node >6cm and/or to the supraclavicular fossa (midline nodes are considered ipsilateral nodes) N3a>6cm in dimension N3bExtension to the supraclavicular fossa

15 Staging: Nasopharynx StageTNM 0TisN0M0 IT1N0M0 IIT1N1M0 T2N0M0 T2N1M0 IIIT1N2M0 T2N2M0 T3N0M0 T3N1M0 T3N2M0 IVAT4N0M0 T4N1M0 T4N2M0 IVBT AnyN3M0 IVCT AnyN AnyM1

16 Tx & Prognosis: Nasopharynx Stage I/II tx’d RT alone: local control rates at 5 years for T1= 93%, T2 = 79%, T3 = 68% and T4 = 53% Intergroup 0099 compared RT alone vs cisplatin 100mg/ms day 1, 22, 43 + RT for Stage III/IV 3 yr progression free survival was 24% vs 69% in favor of concurrent chemo/RT 3 yr overall survival was 47% compared to 78% in favor or concurrent chemo/RT – Similar trial JCO 2005 showed OS 65%  80% with chemo

17 Nasopharynx NCCN Guidelines

18 Recurrent or Persistent Dz

19 Prognosis: Nasopharnx Keratinizing squamous cell carcinoma has a higher risk of local recurrence after tx than non-keratinizing SCCa or undifferentiated High EBV DNA titers after tx are associated with an increased risk of recurrence

20 Presentation: Oropharynx Globus sensation Difficultly swallowing Slurred speech Pain in throat or ear Neck mass

21 Staging: Oropharynx Primary tumor (T) Oropharynx: TXPrimary tumor cannot be assessed T0No evidence of primary tumor TisCarcinoma in situ T1Tumor ≤2cm in greatest dimension T2Tumor >2cm but ≤4cm in greatest dimension T3Tumor >4cm in greatest dimension or extension to lingual surface of the epiglottis T4a Moderately advanced, local disease Tumor invades the larynx, deep/extrinsic muscle of the tongue, medial pterygoid, hard palate, or mandible T4b Very advanced, local disease Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases the carotid artery

22 Staging: Hypopharynx Hypopharynx: TXPrimary tumor cannot be assessed T0No evidence of primary tumor TisCarcinoma in situ T1Tumor limited to 1 subsite of the hypopharynx and/or ≤2cm in greatest dimension T2Tumor invades more than 1 subsite of the hypopharynx or an adjacent site or measures >2cm but ≤4cm in greatest dimension, without fixation of the hemilarynx T3Tumor >4cm in greatest dimension or with fixation of the hemilarynx or extension to the esophagus T4a Moderately advanced, local disease Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophagus, or central compartment soft tissue (including prelaryngeal strap muscles and subcutaneous fat) T4b Very advanced, local disease Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures

23 Staging: Oro/Hypopharynx Regional lymph nodes (N) NXRegional nodes cannot be assessed N0No regional lymph node metastasis N1Metastasis in a single ipsilateral lymph node ≤3cm in greatest dimension N2Metastasis in a single ipsilateral lymph node >3cm but ≤6cm in greatest dimension; or in multiple ipsilateral lymph nodes, none >6cm in greatest dimension; or in bilateral or contralateral lymph nodes, none >6cm in greatest dimension N2aMetastasis in a single ipsilateral lymph node >3cm but ≤6cm in greatest dimension N2bMetastasis in multiple ipsilateral lymph nodes, none >6cm in greatest dimension N2cMetastasis in bilateral or contralateral lymph nodes, none >6cm in greatest dimension N3Metastasis in a lymph node >6cm in greatest dimension

24 Staging: Oro/Hypopharynx StageTNM 0TisN0M0 IT1N0M0 IIT2N0M0 IIIT3N0M0 T1N1M0 T2N1M0 T3N1M0 IVAT4aN0M0 T4aN1M0 T1N2M0 T2N2M0 T3N2M0 IVBT AnyN3M0 T4bN AnyM0 IVCT AnyN AnyM1

25 Tx & Prognosis: Oro/Hypopharynx RTOG randomized advanced oropharyngeal tumors to surgery with or without post-op RT – Post-op RT better LRC (48 vs 65%) & OS (26% vs 38%) RTOG and EORTC studies on locally advanced H&N Ca’s (excluding NPX) showed improved LC with concomitant boost with RT

26 Tx & Prognosis: Oro/Hypopharynx GORTEC (JCO 2004) for Stage III/IV showed benefit of 3 cycles carboplatin/5-FU + RT vs RT alone – Chemo-RT improved LC (25 vs 48%), DFS (15 vs 27%) OS (16 vs 23%) Intergroup Trial (JCO 2003) and Duke trials (NEJM 1998) showed similar benefit for cisplatin +/- 5FU Bonner (NEJM 2006) showed benefit of cetuximab with RT over RT alone – Cetuximab increased 3 yr LRC (34 vs 47%) OS (45 vs 55%).

27 Tx & Prognosis: Oro/Hypopharnx EORTC Stage III/IV operable H&N Ca’s (excluding NPX) pT3-4 N0/+ Tl­-2N2-3, or Tl-2 N0-1 with ECE, + margin, or PNI randomized to post-op cisplatin 100mg/ms days 1, 11, 43 + RT vs RT alone – Chemo­RT improved 3/5 yr DFS (41/36 vs 59/47%) OS (49/40 vs 65/53%) 5yr LRC (69 vs 82%) RTOG operable H&N cancer who had > 2 LN, ECE, or + margin randomized to RT vs RT + cisplatin – Chemo-RT improved 2yr DFS (43 vs 54%), LRC (72 vs 82%) & trend for improved OS (57 vs 63%) – No difference in distant mets for either study

28 NCCN Guidelines Orophyarnx

29 NCCN Guidelines Oropharyx

30 NCCN Guidelines Oropharynx

31 NCCN Guidelines Hypophyarnx

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33

34 NCCN Guidelines Hypopharynx

35 Presentation: Larynx Hoarse voice Stridor Cough, hx of GERD Trouble swallowing For glottic tumors – T1-2 5% LN involvement – T3-4 20% LN involvement

36 Staging: Larynx Supraglottis: TXPrimary tumor cannot be assessed T0No evidence of primary tumor TisCarcinoma in situ T1Tumor limited to 1 subsite of the supraglottis, with normal vocal cord mobility T2Tumor invades mucosa of more than 1 adjacent subsite of the supraglottis or glottis or region outside the supraglottis (eg, mucosa of base of the tongue, vallecula, medial wall of piriform sinus), without fixation of the larynx T3Tumor limited to the larynx, with vocal cord fixation, and/or invades any of the following: postcricoid area, preepiglottic space, paraglottic space, and/or inner cortex of the thyroid cartilage T4a Moderately advanced, local disease Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of the neck, including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus) T4b Very advanced local disease Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

37 Staging: Larynx Glottis: TXPrimary tumor cannot be assessed T0No evidence of primary tumor TisCarcinoma in situ T1Tumor limited to the vocal cord(s) (may involve anterior or posterior commissure), with normal mobility T1aTumor limited to 1 vocal cord T1bTumor involves both vocal cords T2Tumor extends to the supraglottis and/or subglottis, and/or with impaired vocal cord mobility T3Tumor limited to the larynx with vocal cord fixation and/or invasion of the paraglottic space and/or inner cortex of the thyroid cartilage T4a Moderately advanced, local disease Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of the neck, including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus) T4b Very advanced, local disease Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

38 Staging: Larynx Subglottis: TXPrimary tumor cannot be assessed T0No evidence of primary tumor TisCarcinoma in situ T1Tumor limited to the subglottis T2Tumor extends to vocal cord(s), with normal or impaired mobility T3Tumor limited to the larynx, with vocal cord fixation T4a Moderately advanced, local disease Tumor invades cricoids or thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of the neck, including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus) T4b Very advanced, local disease Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

39 Staging: Larynx Regional lymph nodes (N) NXRegional nodes cannot be assessed N0No regional lymph node metastasis N1Metastasis in a single ipsilateral lymph node ≤3cm in greatest dimension N2Metastasis in a single ipsilateral lymph node >3cm but ≤6cm in greatest dimension; or in multiple ipsilateral lymph nodes, none >6cm in greatest dimension; or in bilateral or contralateral lymph nodes, none >6cm in greatest dimension N2aMetastasis in a single ipsilateral lymph node >3cm but ≤6cm in greatest dimension N2bMetastasis in multiple ipsilateral lymph nodes, none >6cm in greatest dimension N2cMetastasis in bilateral or contralateral lymph nodes, none >6cm in greatest dimension N3Metastasis in a lymph node >6cm in greatest dimension

40 Staging: Larynx StageTNM 0TisN0M0 IT1N0M0 IIT2N0M0 IIIT3N0M0 T1N1M0 T2N1M0 T3N1M0 IVAT4aN0M0 T4aN1M0 T1N2M0 T2N2M0 T3N2M0 T4aN2M0 IVBT AnyN3M0 T4bN AnyM0 IVCT AnyN AnyM1

41 Tx & Prognosis: Larynx Stage I tx’d with RT with salvage surgery if needed: 5 yr OS 80-98% Stage II tx’d with RT with salvage surgery: 5 yr OS 68-93% VA Laryngeal Trial: Stage III/IV laryngeal tumors randomized to surgery + post-op RT vs induction chemo with cisplatin/5FU followed by RT – 2 yr OS was 68% for both groups – Laryngeal preservation rate was 64% (36% in the chemo/RT group required salvage laryngectomy)

42 Tx & Prognosis: Larynx RTOG compared RT alone vs sequential chemo/RT vs concurrent chemo + RT – LRC 56% RT alone, 61% sequential, 78% concurrent – Decreased distant mets with chemo Bonner trial for cetuximab included laryngeal tumors as well RTOG and EORTC for post-op chemoRT included laryngeal tumors – Benefit for > 2LN, T3-4, + ECE, + margins

43 NCCN Guidelines Supraglottic Larynx

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47

48

49 NCCN Guidelines Glottic Larynx

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52

53

54 Overview of Treatment Surgery: First choice when possible, but often limited by disfigurement and preservation of organ function such as speech and swallowing Radiation: Most head and neck cancer is sensitive to radiation while preserving organ function – Side effects can be severe; Mucositis, permanent xerostomia, osteoradionecrosis of the mandible, altered taste, weight loss, and tooth decay Chemotherapy: Can have dramatic response to treatment, but is often not a durable response – Side effects can also be severe; decreased blood counts, anemia, infections, weight loss, nausea, vomiting, and hair loss – Newer targeted therapies have lower side effects

55 IMRT

56 Recent Advances and Future Directions PET imaging may allow detection of occult LN metastasis negating the need for post-RT neck dissection Sentinel LN bx in the neck is showing use especially in oral cancers IMRT improves SE’s from radiation therapy Taxanes are showing some promise with cisplatin Targeted therapies: phase III trials with zalutumumab and panitumumab, sorafenib (an inhibitor of the intracellular domain of VEGFR, PDGFR and c-Kit) and afatinib (an irreversible inhibitor of pan-HER tyrosine kinase)


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