Radiation Oncology: A Question-Based Review

Oral Cavity Cancer

Steven H. Lin and Gopal K. Bajaj

image Background

What is the incidence of oral cavity cancer (OCC) in the U.S.?

~23,000 cases/yr of OCC in the U.S. (2008 data)

What % of H&N cancers are OCCs?

OCCs comprise 25%–30% of all H&N cancers.

Of what structures does the oral cavity (OC) consist?

Lips, gingiva, buccal mucosa, retromolar trigone (RMT), hard palate, floor of mouth (FOM), and oral tongue

What is the most and least commonly involved site in OCC?

The lip is the most common site (45%), and the hard palate is the least common site (5%). The tongue is involved 16% of the time.

What CNs provide motor and sensory innervation to the oral tongue?

1.     Motor: CN XII

2.     Sensory: CN V (lingual branch)

What CNs provide the tongue with taste sensation?

1.     Anterior two thirds of tongue: CN VII (chorda tympani)

2.     Posterior one third of tongue: CN IX

What nerve provides motor innervation to the lips?

The facial nerve (CN VII) provides motor innervation to the lips.

What nerve provides motor innervation to the tongue?

The hypoglossal nerve (CN XII) provides motor innervation to the tongue.

Where is the ant-most border of the OC?

The vermilion border of the lips is the ant-most border of the OC.

Where is the post-most border of the OC?

The hard/soft palate border superiorly and the circumvallate papillae inferiorly are the post-most borders of the OC.

What are some premalignant lesions of the OC, and which type has the greatest propensity to progress to invasive cancer?

Erythroplakia (~30% progression rate) and leukoplakia (4%–18% progression rate) are premalignant lesions of the OC.

What are some risk factors that predispose to OCC?

Tobacco (smoked or chewed), betel nut consumption, alcohol, poor oral hygiene, and vitamin A deficiency

What are the sup and inf spans of level II–IV LN chains/levels?

1.     Level II: skull base to hyoid

2.     Level III: hyoid to bottom of cricoid

3.     Level IV: cricoid to clavicles

Where are the level IA–IB nodes located?

Level IA nodes are submental, and level IB nodes are submandibular.

Where are the level V–VI nodes located?

Level V nodes are in the post triangle, and level VI nodes are in the paratracheal/prelaryngeal region.

What is the delphian node?

The delphian node is a midline prelaryngeal level VI node.

What are some important risk factors for LN mets in OCC?

Increasing DOI, increasing T stage, muscle invasion, and high-grade histology

What is the estimated risk of LN involvement with a T1-T2 primary of the lip, FOM, oral tongue, and buccal mucosa?

The risk of LN involvement is ~5% for the lip, 20% for the oral tongue, and ~10%–20% for the other OC T1-T2 primaries.

What is the estimated risk of LN involvement with a T3-T4 primary of the lip, FOM, oral tongue, and buccal mucosa?

The risk of LN involvement is ~33% for the lip and ~33%–67% for the other OC T3-T4 primaries.

What is the nodal met rate for a T1 vs. T2 lesion of the oral tongue?

The nodal met rate is 14% for T1 tongue lesions and 30% for T2 tongue lesions. (Lindberg R et al., Cancer 1972)

What is the overall and stage-by-stage nodal met rate for FOM lesions?

1.     Overall: 20%–30%

2.     T1: 10%

3.     T2: 30%

4.     T3: 45%

5.     T4: >50%

(Lindberg R et al., Cancer 1972)

Lesions located where in the OC predispose to bilat LN mets?

Midline and anterolat OC lesions (tongue, FOM) predispose to bilat LN mets.

Which OC cancer has the greatest propensity for LN spread?

Oral tongue cancer has the greatest propensity for LN spread.

What OC subsite is 2nd only to the oral tongue in propensity for nodal spread?

The alveolar ridge/RMT has the 2nd highest propensity for LN spread (3rd highest is FOM).

Can ant oral tongue lesions involve other LN levels without involving level I LNs?

Yes. ~13% of ant tongue lesions skip the level I LNs. (Byers RM et al., Head Neck 1997)

Which anatomic structure divides the oral tongue from the base of tongue (BOT)?

The circumvallate papillae divide the oral tongue from the BOT (per the AJCC). Some use the sulcus terminalis as the border.

What type of tumors arise from the hard palate?

Primarily minor salivary gland tumors (adenoid cystic, mucoepidermoid, adenocarcinoma) arise from the hard palate.

What are common sites of DM for cancers of the OC?

Lungs, bones, and liver

What anatomic structure divides the FOM anteriorly into 2 halves?

The lingual frenulum divides the FOM anteriorly.

Where is the Wharton duct located, and what gland does it drain?

The Wharton duct opens at the ant FOM (midline) and drains the submandibular gland.

From where in the OC do most gingival cancers arise?

Most (80%) gingival cancers arise from the lower gingiva.

Do most lip cancers arise from the upper or lower lip?

Most (~90%) lip cancers arise from the lower lip.

What are some benign lesions that arise from the lip?

Benign lip lesions include keratoacanthoma, actinic keratosis, hemangiomas, fibromas, HSV, and chancre.

What nodal groups drain the tip of the tongue, the ant tongue, and the post tongue?

1.     Tip of tongue: level IA

2.     Anterior tongue: level IB and level III (mid jugular)

3.     Posterior tongue: level IB and level II

Which OC site lesions are notorious for skipped nodal mets?

Oral tongue lesions can skip levels II–III and involve only level IV (so a full neck dissection is typically needed).

What features of lip cancer predict for nodal spread?

DOI, high grade, large size, invasion of buccal mucosa/dermis, or recurrent Dz after resection

What nodal stations are involved with upper vs. lower lip lesions?

Upper lip lesions spread to preauricular, facial, parotid, and IA–IB LNs; lower lip lesions spread to level IA–IB and level II LNs.

image Workup/Staging

A pt presents with tongue deviation to the left. What CN is involved?

The left CN XII (hypoglossal) is involved with left tongue deviation (deviation is toward the involved nerve).

A pt presents with an OC lesion and ipsi ear pain. What nerve is responsible?

The auricotemporal nerve (branch of CN V3) causes ear pain in OCC.

Which lesions in the OC are most and least likely to present with +LNs?

1.     Most likely: tongue, FOM

2.     Least likely: lips, buccal mucosa, gingiva

What are some common presenting signs with OC lesions?

Asymptomatic red/raised lesion, ill-fitting dentures, bleeding mass, pain, dysphagia (due to tongue fixation), trismus (if pterygoids are involved), and otalgia

What does the typical workup of OC lesions entail?

OC lesion workup: H&P with palpation, direct endoscopy + Bx, CBC, CMP, CT/MRI H&N, and CT or PET/CT

What is the DDx for lesions of the OC?

Squamous cell carcinoma (SCC), minor salivary gland tumors, lymphoma, melanoma, sarcoma, plasmacytoma, and ameloblastoma

What defines T1–T3 lesions of the OC?

1.     T1: <2 cm

2.     T2: 2–4 cm

3.     T3: >4 cm

What defines T4a vs. T4b lesions of the OC?

1.     T4a: invasion of adjacent structures (bone, deep tongue muscles, maxillary sinus), resectable

2.     T4b: very advanced (invasion of masticator space, pterygoid plates, skull base, carotid artery) and typically unresectable

What is the nodal staging breakdown for OCC?

The nodal staging breakdown is the same system used for other H&N cancers (except for that of the nasopharynx):

1.     N1: single, ipsi, <3 cm

2.     N2a: single, ipsi, 3–6 cm

3.     N2b: multiple, ipsi, ≤6 cm

4.     N2c: bilat or contralat, ≤6 cm

5.     N3: >6 cm

What defines stage I–II OCC?

N0 OCC is either stage I or II (T1N0 or T2N0).

What defines stage III Dz in the OC?

T3N0 or T1-3N1 OC lesions are considered stage III.

What defines stages IVA–IVC OCC?

1.     Stage IVA: T4a or N2 Dz

2.     Stage IVB: T4b or N3 Dz

3.     Stage IVC: M1 Dz

If RT is anticipated for OCC, what should be done and when should it be done before starting Tx?

Dental evaluation (teeth extractions, fluoride trays) should be done 10–14 days before RT.

What is the most common location involved in oral tongue cancers?

The lat undersurface of the tongue in the middle to post 3rd is most commonly involved.

What is the overall bilat nodal involvement rate for oral tongue cancers?

5% of oral tongue cancers present with bilat neck Dz (most nodal Dz is ipsi). If N1-N2 ipsi Dz, there is an ~30% risk for bilat Dz.

What 2 factors are most predictive of nodal involvement in oral tongue cancers?

DOI and tumor thickness (not T stage) are most predictive of LN mets in oral tongue cancers.

What are the 2 most important prognostic factors after surgery alone for buccal mucosa cancers?

DOI≥3 mm or tumor thickness ≥6 mm are the most important prognostic factors for buccal mucosa cancers. (Urist MM et al., Am J Surg 1987)

image Treatment/Prognosis

In general, what is the Tx paradigm for OCC?

OCC Tx paradigm: surgery +/− PORT (+/− chemo)

In what circumstances should chemo be added to PORT?

Chemo should be administered with RT if there is a + margin, +ECE, and/or PNI (per Bernier and Cooper adjuvant chemoradiation data).

What pathologic features of the OCC primary lesion call for prophylactic/elective neck management?

Tumor thickness >3 mm, grade III Dz, +LVI, and a recurrent lesion are features that increase the need for prophylactic neck management.

What are the indications for PORT to the ipsi neck in OCC?

>N2a (>3-cm LN) or >2 LN levels, ECE, no neck dissection in high-risk pts, and a DOI (primary) >3mm are indications for PORT.

When should bilat neck irradiation be considered for OC lesions?

Bilat neck RT should be considered for midline primaries, for ant tongue tumors, and with ipsi LAD.

When is bilat neck dissection recommended for lesions of the OC?

Bilat neck dissection is recommended with ≥N2c Dz (bilat or bulky LNs).

For what OC sites is definitive RT preferred and why?

Definitive RT is preferred (over surgery) for lip commissure, buccal mucosa, and RMT lesions with tonsillar pillar involvement. There is better cosmesis with RT (surgery is too morbid).

What is an adequate surgical margin for OC cancers?

The adequate surgical margin is typically 1 cm (1.5 cm for the oral tongue).

What are the indications for PORT to the primary site for OC lesions?

or close ( <2 mm) margin, DOI >2 mm, PNI/perivascular invasion, and T3-T4 Dz are indications for PORT.

What RT doses are typically used in OCC, and how is RT delivered?

1.     PORT54 (–margins) to 66 Gy (+margins) in 2 Gy/fx

2.     Definitive RT54 → 70 Gy to gross Dz +/− chemo

RT has been typically delivered via opposed lat fields (IMRT can now be considered for T3-T4 tumors).

When is brachytherapy indicated for OCC?

1.     Definitive: early (T1-T2) lip/early oral tongue/FOM lesions–LDR to 66–70 Gy in 1 Gy/hr

2.     As a supplement: T4 tongue/FOM lesions, 40% of total dose or ~30 Gy

For oral tongue lesions, which modality is associated with better LC: LDR or HDR?

Both modalities yield similar results. 5-yr LC was 76%–77% for both HDR and LDR techniques in a phase III comparison. (Inoue T et al., IJROBP 2001)

What are the common LDR and HDR doses used with an interstitial implant for OCC?

1.     Low dose rate: 60–70 Gy (40–60 cGy/hr)

2.     High dose rate: 60 Gy (5 Gy bid × 12 fx)

What alternate teletherapy modalities can be employed for superficial OC lesions?

An intraoral cone can be employed for superficial OC lesions: orthovoltage (100–250 keV) or electrons (6–12 MeV).

What are the borders of the standard lat fields for oral tongue lesions?

1.     Superior: 1–1.5 cm above dorsum of tongue or 2 cm above tumor

2.     Inferior: thyroid notch

3.     Posterior: spinous process

4.     Anterior: 2 cm ant to tumor

What beam-modifying device is used with standard opposed lat fields for the Tx of OC lesions? What beam energy is typically used?

Wedges (usually 30 degree with heels ant) are typically used with standard fields, and the beam energy is 6 MV.

How can the lat fields be tilted to spare the contralat parotid gland, and what wedge angle is used if this is done?

The lat fields are tilted obliquely away from contralat parotid, and a 15-degree wedge is typically used if this is done.

Why is a tongue depressor/bite block used when irradiating the OC?

A tongue depressor is used to spare the sup OC/hard palate and to surround the lat oral tongue lesion with other mucosa to minimize any buildup effect on the lat surfaces.

What kind of surgical resection is typically performed for leukoplakia or CIS of the lip?

Vermilionectomy with advancement of the mucosal flap (“lip shave”), which involves simple excision from the vermilion to the orbicularis muscle

When is surgery an option for cancers of the lip?

Surgery is an option if the lesion involves <30% of the lip, if it is a T1 lesion, or the lesion does not involve the oral commissure; otherwise use RT, typically WLE with primary closure (W-shaped excision) and with a 0.5-cm gross margin.

When is definitive RT used for cancers of the lip?

Definitive RT is used for lip tumors >2 cm, large lesions (>50% of the lip), upper lip lesions, or if the lesion involves the oral commissure.

Is elective nodal RT of the neck required for T1-T2 cancers of the lip?

No. Elective nodal RT is not needed b/c the occult nodal positivity rate is only ~5%.

What are the doses used for the Tx of T1-T2 cancers of the lip?

1.     T1: 50 Gy (2.5 Gy × 20)

2.     T2: 60 Gy (2.5 Gy × 24) with 100–250 keV photons or 6–9 MeV electrons + 1-cm bolus

When is PORT indicated for lip cancers?

PORT is indicated for lip cancers in case of T4 Dz (bone invasion), +margin, extensive PNI, +ECE, ≥2 nodes+, or T3-T4 Dz without dissection of the neck.

What randomized evidence supports PORT over surgery alone for stage III–IV SCC of the buccal mucosa?

Indian data. Mishra et al. showed improved 3-yr DFS with PORT (68% vs. 38%). (Eur J Surg Oncol 1996)

Is bilat neck RT required for stage III–IV buccal mucosa lesions?

No. Ipsi RT may be sufficient for stage III–IV buccal mucosa lesions. (Lin CY et al., IJROBP 2008)

For buccal mucosa lesions, when is surgery preferred and when is RT preferred?

Surgery is preferred for small T1 lesions and RT is preferred for >T1 lesions b/c of better cosmetic outcomes.

What must the PORT field include for gingival lesions with PNI?

PORT fields for gingival lesions with PNI must include the entire hemimandible (from the mental foramen to the temporomandibular joint).

What randomized data supports the need for PORT for OC lesions based on specific risk factors?

MDACC series (Ang KK et al., IJROBP 2001): pts with a +margin, PNI, and ECE had higher failure rates.

What are the standard RT field borders for the postop Tx of oral tongue lesions?

1.     Anterior: incisors

2.     Posterior: vertebral spinous processes

3.     Superior: 1.5 cm above dorsum of tongue

4.     Inferior: thyroid notch

For RMT/alveolar ridge tumors, in what circumstances is RT preferred over surgery and vice versa?

Definitive RT preferred if there is no bone erosion or if the lesion extends to the ant tonsillar pillar, soft palate, or buccal mucosa. If there is bone erosion, then surgery is preferred → PORT.

What is the preferred management approach for hard palate lesions?

Generally, surgery is preferred 1st for all cases, except if there is extension to the soft palate or RMT, in which case definitive RT can be considered.

Per NCCN guidelines, what is the recommended time interval between surgery and PORT for OCC?

Per NCCN guidelines, the recommended time interval between surgery and PORT for OCC is 6 wks.

image Toxicity

Why is brachytherapy generally avoided for gingival lesions?

There is a high risk of osteoradionecrosis with brachytherapy for gingival lesions.

To avoid malnutrition during a course of RT or CRT, pts need at least how many calories/day?

To avoid malnutrition during a course of RT or CRT, pts need at least 2,000 calories/day

What are the side effects of amifostine, if used?

Side effects of amifostine include hypotension (especially if given intravenously) and nausea.

The mandible should be kept at or below what RT dose?

The mandibular RT dose should be ≤70 Gy.

What does the follow-up for OCC pts entail?

OCC follow-up: H&P + laryngoscopy (q1–3mos for yr 1, q2–4mos for yr 2, q4–6mos for yrs 3–5, and q6–12mos if >5 yrs), imaging (for signs/Sx), TSH (if the neck is irradiated), speech/hearing/dental evaluation, and smoking cessation