carcinoma oral cavity staging to amnagement, chemotherapy surgery radiotherapy dose conventional planning brachytherapy

1. Ca. Oral Cavity
(Staging to management)
Presenter:-
Dr. Durgesh kumar
Junior resident
Moderator:-
Dr. surabhi gupta
• Oral cavity cancers are approximately 40% of head and
neck cancers.
• Oral leukoplakia can proceed to cancer (4–18%) as can
erythroplakia (30%). 1.5% will have synchronous cancers;
10–40% will develop second primaries.

2. STAGING

3. Pathologic Classification
The predominant histopathologic type - squamous cell carcinoma.
There are several variants of squamous cell carcinoma--
• Basaloid squamous cell carcinoma -worse prognosis than
squamous cell carcinoma.
• Verrucous carcinoma- less common variant, low grade
malignancy with low metastatic potential and good overall
prognosis.
• Sarcomatoid carcinomas - can be found in the oral cavity
and larynx. poor prognosis with a mean survival of
approximately 2 years.
Less than 10% of neoplasms of the oral cavity have nonsquamous
histology. Most of these are minor salivary gland tumors, which
tend to arise in the hard palate.
.
Adenoid cystic carcinoma - 30% to 40% of minor salivary gland
cancers. Other histologies---
Adenocarcinomas, melanoma, ameloblastoma, lymphoma, and
Kaposi’s sarcoma
• Most lymphomas in the head and neck arise in Waldeyer’s ring
(tonsil, base of tongue, and nasopharynx).
• Only 2% of all lymphomas are found in the oral cavity.
• Melanoma of the oral cavity is very rare and represents only 0.2%
to 8% of all melanomas. Mucosal melanomas generally have a
worse prognosis than cutaneous melanomas

4. Nodal involvement
Approximate risk of LN involvement
• Lip: T1–2 = 5%, T3–4 = 33%
• Floor of mouth: T1–2 = 10–20%, T3–4 = 33–67%
• Oral tongue: T1–2 = 20%, T3–4 = 33–67%
• Bucco-gingival mucosa: T1–2 = 10–20%, T3–4 = 33–67%
• Retromolar trigone: 25–40%

5. • The aim of treatment is to combine optimal rates of cure with the best functional results. Where cure is not feaseble,
every attempt should be made to provide loco-regional disease control.
• Before begining treatment it is important to:
1. Establish the nutritional status- elective NG or enterostomy feeding tube
2. Dental assesment
3. Correct anemia- >12gm/dl for optimum results from radiotherapy
4. Smoking cessation- contnued smoking during treatment has multiple risks- higher complication rate during
radiotherapy, lower rate of local control, lower probablity of survival.
• Its Important to undergo evaluation by relevant members of the multidisciplinary team, including head and neck
surgery, radiation and medical oncology, nursing, dentistry, dietary, and social work, before treatment is delivered.
• The choice of tretment modality , either singly or in combination depends on the stage and size of tumor and
relevant patient factors such as toxicity , performance status , co morbid disease and convenience.
1. SURGERY
2. RADIOTHERAPY (EBRT , BRACHYTHERAPY)
3. ADJUVANT CT,
4. NEOADJUVANT CT ,
5. CONCURRENT CHEMORADIATION
Management

6. TREATMENT RECOMMENDATIONS
1. Lip
Stage T1-2N0 :-
• Preferred: surgical resection of primary.
• For positive margin only- re-excise if feasible. Post-op RT (including nodes if not dissected)
• For close margin, PNI, or LVSI. Post-op chemo-RT
• Alternative: definitive EBRT ± brachytherapy. Salvage surgery for residual disease
T3–4a or N1–3:-
• Preferred: surgical resection of primary and ipsilateral neck dissection (contralateral neck dissection if
tumor approaches midline or N2c). Reconstruction as indicated.
• Consider post-op RT for all, post-op chemo-RT for positive margin or ECE
• Alternatively: concurrent chemo-RT ± brachytherapy. If primary has < CR, consider salvage surgery and
neck dissection.
• If residual neck involvement by imaging at 6–12 weeks, consider salvage neck dissection

7. 2. Oral cavity
T1-2N0:-
• Preferred: surgical resection of primary with ipsilateral or bilateral selective neck dissection (consider
bilateral for midline, oral tongue, or floor of mouth). Neck treatment (dissection or RT) for lesions >2–3
mm thick. For positive margin only, re-excise if feasible.
• Post-op RT alone (including neck if not dissected) For close margin (< 5 mm),
• For positive margin, PNI, or LVSI. Post-op chemo-RT
Alternatively: definitive EBRT ± brachytherapy. Salvage surgery for residual disease
T3–4a or N1–3:-
• Preferred: surgical resection of primary with ipsilateral or bilateral selective neck dissection (consider
bilateral for tumors approaching midline, oral tongue, floor of mouth, N2c). Reconstruction as
indicated.
• Consider post-op RT for all, post-op chemo-RT for positive margin or ECE

8. Unresectable
• Preferred: concurrent chemo-RT with cisplatin based regimen
• Alternative: induction chemotherapy followed by chemo-RT, or altered fractionation RT if unable to
tolerate chemo
If residual neck involvement by imaging at 6–12 weeks, consider salvage neck dissection

9. Surgical management:
• Cancer of the oral cavity is most commonly treated surgically when the disease is in its early stages.
• Postoperative radiation or chemoradiation is administered to those patients with pathologic evidence of
extensive nodal disease and/or extracapsular spread.
• Surgical approaches to cancers of the oral cavity may either be transoral, transcervical (pull-through), or,
alternatively, via mandibulectomy,
• A tracheotomy is often necessary to maintain a patent airway.
• Tumors that approximate the gingiva should be resected with the gingiva and periosteum, while those that
appear to involve the periosteum should be resected with an additional deep margin of bone (marginal
mandibulectomy).
• May involve resection of a bi-cortical rim of bone at the upper aspect of the alveolus (rim
mandibulectomy) ,
• Selective removal of the inner cortex using a vertical or oblique resection (sagittal mandibulectomy).

10. Management of neck node
• Lymphadenectomy in the presence of known neck disease can be therapeutic as well as provide
prognostic information (i.e., presence of extracapsular extension).
• Elective neck surgical treatment - for management of the clinically node-negative patient,
• Therapeutic neck dissections- for patients with clinically apparent nodal disease.
• For midline tumors, regardless of the type of dissection, bilateral surgical management is recommended.
However, for well-lateralized tumors, unilateral dissection, followed by bilateral postoperative radiation, is
reasonable.
• In patients with nodal disease ≥6 cm (N3), extracapsular extension, or clinically evident disease in levels IV
or V, the most common approach is a modified radical nodal dissection (MRND). This includes the
removal of nodal levels I through V with sparing of the sternocleidomastoid muscle, internal jugular vein,
and accessory nerve, if they are uninvolved with disease.
• Selective neck dissection- favored in patients with more limited nodal disease. involves the removal of at
least levels I through III, with the possible addition of level IV depending on the interpretation of the
surgeon.
• Similar to other cancer types, SLNB provides excellent sensitivity (~90% to 100%) and negative predictive
value (~95%) with no compromise of local control in the neck.

11. Chemotherapeutic management
• Neither induction therapy followed by surgery nor adjuvant chemotherapy following surgery has
improved survival.

12. RADIOTHERAPY
Radical RT
Conventional (7-8 weeks)
Hyperfractionation (5-6 weeks)
Hypofractionation (1-2 Gap 1-2 weeks)
Pre Operative RT (2-5 weeks)
Post Operative RT (5-7 weeks)
Palliative RT
Short Course (1-2 weeks)

13. POST-OP EBRT
• Post-op RT superior to pre-op RT. (RTOG 73–03 (Kramer Head Neck Surg 1987, Tupchong IJROBP 1991)
• Indications for post-op RT:
1. pT3–4,
2. close margin,
3. N2/3,
4. level IV–V nodes
• 60–66 Gy if no gross residual disease, otherwise 70 Gy.
• Indications for post-op chemo-RT:
1. ECE and/or
2. positive margins.
EORTC 22931, RTOG 95–01, and combined analysis. Concurrent cisplatin 100 mg/m2 q3 weeks ×3c (alternatively, cisplatin 40 mg/m2
weekly ×6c).
ALTERED FRACTIONATION
• Improved local control and survival with accelerated or hyperfractioned/dose escalated in definitive RT ± chemo.

14. RADIATION TECHNIQUES
SIMULATION AND FIELD DESIGN
• Simulate supine with neck extended, shoulders down. (For patients with a short neck, the shoulders are depressed by having the
patient pull on a tensioning device looped beneath the feet)
• Immobilize with thermoplastic head and shoulder mask. (Custom masking of the head and neck and shoulders can also help
accomplish optimal positioning. )
• Cork and tongue blade to depress tongue from palate if appropriate. 2–5 mm bolus may be applied to scars.
RADIOTHERAPY DOSE
1. External :
a. Alone : 7000 cGy to 7600 cGy /6-8 wks.
(microscopic - 4600 - 5000 cGy)
b. Pre-op. : 46-50 Gy/ 4 1/2 - 5 1/2 wks.
c. Post-op.: 60-66 Gy/ 6-7 wks.
2. Brachytherapy :
a. Alone : 6000 - 7000 cGy in 6 to 7 days.
b. External + Brachytherapy
Ext : 46-50 Gy in 4 1/2 - 5 1/2 wks. +
Brachy : 2000-3000 cGy in 2-3 days
DOSE LIMITATIONS
• Spinal cord max ≤45 Gy (≤ 35 Gy for BID),
• brainstem max ≤54 Gy (≤ 30 Gy to dorsal vagal complex),
• parotid gland mean ≤ 26 Gy and V20 Gy ≤ 50%,
• submandibular mean ≤ 39 Gy,
• mandible max ≤70 Gy,
• retina max ≤45 Gy,
• larynx mean ≤ 32 Gy and V50 Gy ≤ 66%,
• cochlea mean (max) ≤ 37 (45) Gy,
• thyroid mean (max) ≤ 35 (45) Gy.

15. Conventional:
• Carcinoma of the oral cavity has traditionally been treated with opposed lateral fields, using either two-dimensional or three-
dimensional (CT-based) techniques. Generally, the oral cavity tumor bed and upper echelon lymph nodes are included within the
initial lateral Fields.
• The upper border -a 1.5- to 2.0-cm border on the tumor bed in an attempt to partially spare parotid glands and the hard palate if
possible without compromising coverage of the tumor bed and regional lymphatics.
• The inferior border- at approximately the thyroid notch, just above the true vocal cords.
• The posterior border- at the midvertebral body level if level V nodal coverage is not required.
• The nodal volume should include level Ia–b, II, and III. For patients with more advanced neck disease or positive level V lymph nodes,
where the posterior chain requires radiation, the initial fields should be set behind the C1 vertebral body spinous process.
• The portals are then reduced at approximately 45 Gy to spare high dose to the spinal cord.
• If patients harbor cervical lymph node metastases, or high-risk disease, then the lower neck will also be treated.
• 3-field technique (opposed laterals superiorly, AP inferiorly).
• Beam split at thyroid notch/arytenoids (not through gross disease).
• Small anterior block to avoid double treatment of cord at the match line
• Superior: Include skull base and mastoid processes.
• Anterior: Include faucial arch and 2 cm margin on tumor.

16. • N0: Include levels II–IV and retropharyngeal nodes (RPN).
• N1: Include levels IB–IV and RPN.
• N2-3: Include levels IB–V and RPN.
• Spinal cord shielding after 42–45 Gy with posterior block on lateral fields.
IMRT
IMRT volumes
• GTV = Clinical or radiographic gross disease, if present (primary and nodes).
• CTV1 = Entire postoperative bed, including ≥0.5–2 cm margin on GTV
(depending on anatomic boundaries to microscopic spread),
and areas of close/positive margins, ECE. Entire flap is covered if reconstructed.
• CTV2 = Elective neck (dissected neck, high risk cN0, contralateral neck).
• PTV = CTV + 3–5 mm (depending on tumor motion and setup error).

17. Lip
 T1–2 may be treated with EBRT (100–250 kV photons or 6–12 MeV electrons), with brachytherapy or both.
 Appositional field for EBRT. Borders determined clinically with 1–1.5 cm margin for orthovoltage or 2–2.5 cm margin for electrons.
Bolus for superficial tumors. Wax-coated lead shield behind lip to reduce dose to mandible and oral cavity.
 T3–4 tumors typically treated with IMRT or opposed lateral 4–6 MV photons.
 Suggested nodal coverage: Levels I–II for T3, levels I–IV for T4 or LN+. May consider “moustache field” of elective RT to perifacial
lymphatics for advanced upper lip lesions.
 HDR brachytherapy typically Ir-192 in catheters spaced 1 cm apart. A dental roll is placed between the lip and the gingiva to minimize
dose to mandible and oral cavity.

18. ORAL TONGUE AND FLOOR OF MOUTH
 Low RT tolerance due to increased risk of soft tissue injury and osteoradionecrosis.
 Use cork and tongue blade to depress tongue from palate. Need secure setup due to
tongue mobility.
 For superficial T1–2 lesions, brachytherapy or intraoral cone RT may be used in lieu of
surgery.
 LDR brachytherapy dose is 60–70 Gy. Intraoral cone dose is 3 Gy × 15–20 fractions.
 For definitive treatment of larger lesions, 3DCRT or IMRT techniques are generally
recommended for advanced lesions in order to spare adjacent normal structures.
 Brachytherapy (21–30 Gy) or intraoral cone (15–24 Gy) may be used for boost after EBRT (40–50 Gy).
 Suggested nodal coverage (all bilateral): Levels I–IV, include level V for +LN.

19. BUCCAL MUCOSA
 The oral commissures and lips are excluded or shielded if possible. Consider intraoral device to displace and shield tongue. May insert
metal seeds into the periphery of the tumor for localization.
 Suggested nodal coverage: ..T1-T4N0: Ipsilateral levels I–IV if well lateralized, otherwise consider covering contralateral neck.
 LN+: Ipsilateral levels I–V, consider contralateral neck.

20. GINGIVA, HARD PALATE, AND RETROMOLAR TRIGONE
 Brachytherapy is generally avoided due to risk of osteoradionecrosis.
 EBRT superior border must include pterygoid plates (exception: inferior gingiva).
 For gingival tumors, if PNI is present the entire hemimandible from mental foramen to TMJ is included.
 MRI can help identify perineural spread along major nerves (e.g., inferior alveolar nerve). If radiographically or clinically involved, or
extensive PNI present, cover nerve pathway at least to the base of skull foramina and consider covering to trigeminal ganglion.
 Suggested nodal coverage:
 T1-4N0: ipsilateral levels I–IV if well lateralized, otherwise consider covering contralateral neck.
 LN+: ipsilateral levels I–V, consider contralateral neck

21. management of recurrent disease
 management of recurrent oral cavity cancer depends largely on the extent of disease,the prior
therapy administered, and whether the recurrences are local, regional, or both.
 For distant disease recurrence, systemic therapy approaches will likely assume primary importance.
 Small recurrences at the primary site- treated with primary excision only, further excision with or
without postoperative radiotherapy is often recommended.
 Larger recurrences- who received radiation as part of their initial management, the rate of surgical
salvage is quite low. Systemic therapy,reirradiation, and palliative care are other options for this group
of patients.

22. management of metastatic disease
 Poor prognosis with median survival- 6 to 9 months
 Certain chemotherapeutic agents have been shown to be effective
 Single agent therapy:
Median survival is around 6 months—
MTx, cisplatin, or cituximab
 Combination regimes
Survival advantage over single agent treatment has not been consistently demonstrated
Considered in patients with good performance status
Platinum agent with fluorouracil or with taxens

23. Supportive care

24. Oral mucostis
Grade 1 (Mild) Irritation / may experience mild pain not
requiring analgesic
Grade 2 (Moderate) Patchy mucositis that may produce an
inflammatory serosanguinous discharge
/ may experience moderate pain
requiring analgesia
Grade 3 (Severe) Confluent fibrinous mucositis / may
include severe pain requiring narcotic
Grade 4 (Potentially Life-Threatening) Ulceration, hemorrhage or necrosis

25. Xerostomia (dry mouth) Management
Grade 1 (Mild) Symptomatic (e.g., dry or thick saliva) without significant
dietary alteration; unstimulated saliva flow >0.2 mL/min
Advise ongoing basic oral hygiene
Advise avoidance of hot, spicy, acidic foods
Anticipate possible alternative treatment(s)
Zinc supplements or 0.2% zinc sulfate mouthwash
Probiotics with Lactobacillus
Benzydamine HCI
Grade 2 (Moderate) Moderate symptoms; oral intake alterations (e.g.,
copious water, other lubricants, diet limited to purees
and/or soft, moist foods); unstimulated saliva 0.1 to 0.2
mL/min)
Advise moistening agents
Saliva substitute
Synthetic saliva
Oral lubricants
Advise secretagogues
Nonpharmacologic
Sugarless gum
Sugarless hard candies
Natural lemon
Pharmacologic
Pilocarpine
Cevimeline HCI
Grade 3 (Severe) Inability to adequately aliment orally; tube feeding or
total parenteral nutrition indicated; unstimulated saliva
<0.1 mL/min
hospitalization
Unclear role of systemic corticosteroids
Anticipate need for supplemental nutrition
Enteral, Parenteral
Analgesics
Systemic opioids may be indicated
Oral care
Grade 4 (Potentially Life-
Threatening)
Life-threatening consequences; urgent intervention
indicated

26. Follow up

27. Induction chemotherapy for advanced head and neck SCC
and supporting clinical evidence
TAX 324 was a randomised, open-label phase 3 trial comparing
three cycles of TPF induction chemotherapy (docetaxel 75 mg/m2,
followed by intravenous cisplatin 100 mg/m2 and fluorouracil 1000
mg/m2 per day, administered as a continuous 24-h infusion for 4
days) with three cycles of PF (intravenous cisplatin 100 mg/m2,
followed by fluorouracil 1000 mg/m2 per day as a continuous 24-h
infusion for 5 days) in patients with stage III or IV squamous-cell
carcinoma of the head or neck.
Median follow-up was 72·2 months (95% CI 68·8–75·5). Overall
survival was significantly better after treatment with TPF versus PF
(hazard ratio [HR] 0·74, 95% CI 0·58–0·94), with an estimated 5-year
survival of 52% in patients treated with TPF and 42% in those
receiving PF. Median survival was 70·6 months (95% CI 49·0–89·0) in
the TPF group versus 34·8 months (22·6–48·0) in the PF group
(p=0·014).
Progression-free survival was also significantly better in patients
treated with TPF

28. Phase III Study Comparing Cisplatin Plus Fluorouracil to Paclitaxel, Cisplatin, and Fluorouracil
Induction Chemotherapy Followed by Chemoradiotherapy in Locally Advanced Head and Neck
Cancer
Ricardo Hitt, Antonio López
A total of 382 eligible patients were randomly assigned to CF (n = 193) or PCF (n = 189). The CR rate was
14% in the CF arm v 33% in the PCF arm (P < .001). Median time to treatment failure was 12 months in the
CF arm compared with 20 months in the PCF arm (log-rank test, P = .006; Tarone-Ware, P = .003). PCF
patients had a trend to longer overall survival (OS; 37 months in CF arm v 43 months in PCF arm; log-rank
test, P = .06; Tarone-Ware, P = .03). This difference was more evident in patients with unresectable disease
(OS: 26 months in CF arm v 36 months in PCF arm; log-rank test, P = .04; Tarone-Ware, P = .03). CF
patients had a higher occurrence of grade 2 to 4 mucositis than PCF patients (53% v 16%, respectively; P <
.001).
Conclusion
Induction chemotherapy with PCF was better tolerated and resulted in a higher CR rate than CF.

29. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised
trials and 17,346 patients
Jean-PierrePignon
Twenty-four new trials, most of them of concomitant chemotherapy, were included with a total of 87 trials and 16,485 patients. The
hazard ratio of death was 0.88 (p < 0.0001) with an absolute benefit for chemotherapy of 4.5% at 5 years, and a significant
interaction (p < 0.0001) between chemotherapy timing (adjuvant, induction or concomitant) and treatment. Both direct (6 trials) and
indirect comparisons showed a more pronounced benefit of the concomitant chemotherapy as compared to induction
chemotherapy. For the 50 concomitant trials, the hazard ratio was 0.81 (p < 0.0001) and the absolute benefit 6.5% at 5 years. There
was a decreasing effect of chemotherapy with age (p = 0.003, test for trend).
Conclusion
The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.

30. Chemotherapy added to locoregional treatment for head and neck squamous-cell
carcinoma: three meta-analyses of updated individual data
DrJPPignonMD
Despite more than 70 randomised trials, the effect of chemotherapy on non-metastatic head and neck
squamous-cell carcinoma remains uncertain.
The main meta-analysis of 63 trials (10 741 patients) of locoregional treatment with or without
chemotherapy yielded a pooled hazard ratio of death of 0·90 (95% CI 0·85–0·94, p<0·0001),
corresponding to an absolute survival benefit of 4% at 2 and 5 years in favour of chemotherapy.
There was no significant benefit associated with adjuvant or neoadjuvant chemotherapy.
Chemotherapy given concomitantly to radiotherapy gave significant benefits.
Interpretation- Because the main meta-analysis showed only a small significant survival benefit in
favour of chemotherapy, the routine use of chemotherapy is debatable