Management of oral cavity cancer 23072018

Management of Oral Cavity
Cancer
Dr. Varshu Goel
Second Year Post-Graduate Resident
Department of Radiation Oncology
Maulana Azad Medical College, New Delhi

• Oral cavity cancers are approximately 30% of head and neck cancers.
• Occurs after the 5th decade of life
• 80% cases are tobacco related, 0 - 20% can be positive for HPV 16 DNA
• Oral leukoplakia (4–18%) and erythroplakia (30%) can proceed to cancer
• 1.5% will have synchronous cancers; 10–40% will develop second primaries.
• India:
• Approximately 1 lac new cases (out of 6 lacs worldwide) and more than
50,000 deaths occur yearly
• Ranks first among male and the third among female population
2
Introduction
Handbook Of Evidence-based Radiation Oncology, 3rd edition
Perez & Brady's Principles and Practice of Radiation Oncology, 6th ed.

1. Most common - buccal mucosa in India and oral tongue in West
2. Floor of the mouth
3. Alveolar Ridge
4. RMT and Hard Palate
LN drainage :
• Anterior oral tongue: IA, IB, and II, and also directly to levels III–IV.
• Floor of mouth and lower gingiva: levels I, II, and III.
• Bilateral node drainage is frequent, especially when the lesion approaches
midline.
4
OralCavityCancers : Subsitesand LN

Approximate risk of LN involvement :
• Lip: T1–2 = 5%, T3–4 = 33%
• Bucco-gingival mucosa: T1–2 = 10–20%, T3–4 = 33–67%
• Floor of mouth: T1–2 = 10–20%, T3–4 = 33–67%
• Oral tongue: T1–2 = 20%, T3–4 = 33–67%
• Retromolar trigone: 25–40%
LymphaticSpread
5
Level I Level II Level III Level IV Level V
cN0 20 17 9 3 0.5
cN+ 48 39 31 15 4
Incidence and distribution of regional metastasis for Levels I–V

Normally, Oral cavity is lined by non-keratinized stratified squamous
epithelium except dorsum of the tongue, hard palate and attached gingiva
lined by keratinized squamous epithelium.
• Squamous cell carcinoma – 90%
• Basaloid – worse prognosis
• Verrucous
• Sarcomatoid
• Minor salivary gland tumors – adenoid cystic carcinoma, mucoepidermoid
carcinoma, and adenocarcinoma
• Soft tissue tumours
• Lymphoepithelial carcinoma
• Haematolymphoid tumours
• Secondary tumours
6
Pathologicalclassification

7
Clinical Presentation
• Non-healing painful ulcer
• Poorly fitting dentures
• Advanced lesion:
• Neck lymphadenopathy – 30-40% (frequency of neck metastases can
range from 15% to 75%, depending on the size of the primary lesion)
• Dysphagia (difficulty in swallowing)/ Odynophagia (pain while
swallowing)
• Speech alteration or hoarseness
• Trismus (extension into pterygoid muscles)
• Otalgia (CN V)
• Facial Numbness (CN V)
• Hypoesthesia of the face, lips, or mandible (perineural spread along
inferior alveolar nerve after penetration of the mandible)
• Hypersalivation
• Limited tongue movements

8
Pathwayof Earache
V3 innervates the ear via the auriculotemporal
branch but also has sensory nerve fibers via the
lingual, buccal, and inferior alveolar nerves,
which serve to innervate the oral cavity and
floor of mouth, lower teeth, palate, mandible
including the temporomandibular joint (TMJ),
and the 3 major salivary glands

DiagnosticWorkup
9
• General –
• History
• Tobacco, Smoking, Alcohol
• Weight loss
• Dysphagia/ Odynophagia
• Physical examination
• Oral Cavity Palpation to assess bony involvement, tongue fixation and
bimanual assessment for depth of involvement
• Cervical lymph nodes
• Oral Hygiene
• Indirect laryngoscopy
• Mirror examination - nasopharynx
• Biopsy of tumor and FNAC of LN
• Blood investigations including CBC, KFT, LFT
• HPV testing in the biopsy specimen

DiagnosticWorkup
• Nutrition, speech and swallowing evaluation/therapy, and baseline
audiogram as clinically indicated
• Dental evaluation
• Multidisciplinary consultation as clinically indicated
• Radiographic –
• Chest X-ray
• Plain radiograph of mandible (panoramic radiograph or pantomogram
or OPG)
• CECT (before biopsy) - method of choice – with “puffed cheek”
technique
• MRI (selected cases) - for tongue and hard palate – for soft tissue
delineation and perineural extension
• Ultrasound neck for screening enlarged neck nodes that are not
detected clinically ± USG guided FNAC of suspicious lymphadenopathy
• FDG-PET for stages III–IV. Otherwise CT chest to rule out metastatic
disease.
10

AJCCTNM Staging
11
AJCC Cancer Staging Manual, 8th ed.
• T0 (No evidence of primary tumor) removed in 8th edition
T
category
T criteria
Tx Primary tumor cannot be assessed
Tis Carcinoma in situ
T1 Tumor ≤ 2 cm in greatest dimension; DOI ≤ 5 mm
T2 Tumor ≤ 2 cm, DOI > 5 mm but ≤ 10 mm
OR
Tumor >2 cm but ≤ 4 cm in greatest dimension and ≤ 10 mm DOI
T3 Tumor > 4 cm OR any tumor > 10 mm DOI and ≤ 20 mm DOI
T4a Moderately advanced local disease OR any tumor > 20 mm DOI
T4b Very advanced local disease

AJCCTNM Staging
14
• T0 (No evidence of primary tumor) removed in 8th edition
T
category
T criteria
Tx Primary tumor cannot be assessed
Tis Carcinoma in situ
T1 Tumor ≤ 2 cm in greatest dimension; DOI ≤ 5 mm
T2 Tumor ≤ 2 cm, DOI > 5 mm but ≤ 10 mm
OR
Tumor >2 cm but ≤ 4 cm in greatest dimension and ≤ 10 mm DOI
T3 Tumor > 4 cm OR any tumor > 10 mm DOI
T4a Moderately advanced local disease

15
T
category
T criteria
T4a Moderately advanced local disease
Tumor invades adjacent structures
• cortical bone of mandible or maxilla, or
• maxillary sinus, or
• skin of face
Tumor invades masticator space, pterygoid plates, or skull base
and/or encases internal carotid artery
M
category
M criteria
M0 No distant metastasis
M1 Distant Metastasis
• Distant metastasis occurs in approximately 15% to 20% of patients
• 66% of distant metastases are to the lungs, 22% to the bones, and
9.5% to the liver

RegionalLymphNodes
16
N
category
Clinical N criteria (cN) Pathological N criteria (pN)
Nx Regional lymph nodes cannot be
assessed
Regional lymph nodes cannot be
assessed
N0 No regional lymph node
metastasis
No regional lymph node metastasis
N1 Metastasis in a single ipsilateral
lymph node ≤ 3 cm in greatest
dimension and ENE (-)
Metastasis in a single ipsilateral
lymph node ≤ 3 cm in greatest
N2a Metastasis in a single ipsilateral
lymph node > 3 cm but ≤ 6 cm in
greatest dimension and ENE (-)
Metastasis in a single ipsilateral
lymph node, larger than 3 cm but not
larger than 6 cm in greatest
OR
Metastasis in a single ipsilateral or
contralateral node ≤ 3 cm in greatest
dimension and ENE (+)

17
N
category
Clinical N criteria (cN) Pathological N criteria (pN)
N2b Metastasis in multiple ipsilateral
lymph nodes ≤ 6 cm in greatest
Metastasis in multiple ipsilateral
lymph nodes, none more than 6 cm in
N2c Metastasis in bilateral or
contralateral lymph nodes, none
> 6 cm in greatest dimension and
ENE (-)
Metastasis in bilateral or contralateral
lymph nodes, none more than 6 cm in
N3a Metastasis in a lymph node > 6
cm in greatest dimension and
ENE (-)
Metastasis in a lymph node, larger
than 6 cm in greatest dimension and
ENE (-)
N3b Metastasis in any lymph node(s)
with clinically overt ENE (+)
Metastasis in multiple ipsilateral,
contralateral or bilateral lymph
node(s) with ENE (+)
OR
Metastasis in single ipsilateral node,
larger than 3 cm in greatest
dimension and ENE (+)

AJCCPrognosticStageGrouping
18
T N M Stage
Tis N0 M0 0
T1 N0 M0 I
T2 N0 M0 II
T3 N0 M0 III
T1, T2, T3 N1 M0 III
T4a N0, N1 M0 IVA
T1, T2, T3, T4a N2 M0 IVA
Any T N3 M0 IVB
T4b Any N M0 IVB
Any T Any N M1 IVC

19
• Location/thickness/depth of primary tumor
• Staging
• Type of histology
• Grading
• Presence of perineural spread
• Mandibular invasion
• LN extension (Level, size, extracapsular)
PrognosticFactors

21
Treatmentof Oral CavityCancer
• AIM : Highest loco-regional control (anatomical) with functional
preservation and minimize sequelae of treatment
• Stage I / II disease - Single modality ( Surgery or RT )
• Comparable results
• Choice depends on:
• Tumor factors - Site, Size, Type
• Patient factors
• Facilities available
• Stage III / IV disease – Combined modality
• Surgery + post-op RT (in most patients)
• Chemotherapy + RT in selected patients

22
CombinedModality
• RT  Surgery (Pre-op RT)
• Surgery + RT (Intra-operative RT)
• Surgery  RT (Post-op RT) – standard of care
• Radical RT  Salvage Surgery

Surgeryfor OralCavityCancers
23
• Excision of primary with neck dissection
• Surgical approaches to cancers of the oral cavity may either be
transoral, transcervical (pull-through) or via mandibulectomy
• Tracheotomy is often necessary
• It is commonly recommended to leave at least a 1-cm-thick
segment of bone inferiorly following a rim mandibulectomy to
reduce the risk of pathologic fracture
Segmental mandibulectomy
Marginal mandibulectomy

ReconstructiveSurgery
24
• Skin graft – small defects
• Regional flap-
• large defects
• include pectoralis major flap, trapezius flap and lattismus dorsi
flap
• Free flap –
• radial forearm flap, antero-lateral thigh flap, rectus abdominis
flap and fibula flap.
• Total glossectomy defects are well suited.
• Reconstruction of mandible requires free flap from fibula flap,
iliac crest flap and scapular flap

25
Managementof the Neck
• 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) - removal of nodal levels
I through V (including the submental nodes), with sparing of the SCM,
IJV, and accessory nerve
• Types
• RND
• Modified RND
• Selective ND
• Supra-omohyoid SND (Level I-III/IV)
• Lateral SND (Level II-IV)
• Posterolateral SND (Level II-V)
• Anterior SND (Level VI)
• Extended ND

Managementof clinicallynegativeNeck
28
• SND usually guided by invasion of primary oral tumor
• Depth of invasion > 2 to 4mm – require surgical intervention.
• Recently, role of sentinel lymph node biopsy (SLNB) in patients with
small volume (T1–2) oral squamous cell carcinoma have been
studied
• SLNB provides excellent sensitivity (∼90% to 100%) and negative
predictive value (∼95%) with no compromise of local control in the
neck

• A clear margin is defined as the distance from the invasive tumor
front that is 5 mm or more from the resected margin.
• A close margin is defined as the distance from the invasive tumor
front to the resected margin that is less than 5 mm.
• A positive margin is defined as carcinoma in situ or as invasive
carcinoma at the margin of resection.
29
SurgicalMargins
NCCN V2.2018

• Applications:
• Radical : early stage
• Palliative : advanced total control not possible.
• Combined therapy
• Preoperative (neoadjuvant)
• Postoperative (adjuvant)
• Mode of delivery:
• External beam radiation therapy (EBRT)
• Brachytherapy
30
Radiotherapy

• Tumor classified as T1 and early T2 tumors.
• Combined approach including both external beam radiation and
interstitial brachytherapy is often recommended for optimal
outcome.
• The normal tissue toxicity may render radiation therapy a less
attractive option or single modality treatment.
• Sites- lip, floor of mouth, oral tongue.
• The outcome for advance lesion of the oral cavity (T3 and T4) are
less than satisfactory with either surgery or radiation alone.
31
Radiotherapyalone

32
Indication Irradiation
Oral cavity
T2N0 with well-lateralized primary
T2N1 with well-lateralized primary
T2N0 with primary approaching
midline, all T3N0 and T4N0
All others
Levels I and II on the same side
Levels I to V on the same side
Levels I, II and III bilaterally
Levels I to V bilaterally
Walter & Miller’s Textbook of Radiotherapy, 7th ed.
Nodal TreatmentBy TumorSite

• High risk:
• Primary tumor and involved lymph nodes (this includes possible
local subclinical infiltration at the primary site and at the high risk
level lymph node(s)):
• Fractionation: 66 Gy (2.2 Gy/fraction) to 70 Gy (2.0 Gy/fraction);
daily Monday–Friday in 6–7 weeks
• Concomitant boost accelerated RT:
• 72 Gy/6 weeks (1.8 Gy/fraction, large field; 1.5 Gy boost as
second daily fraction during last 12 treatment days)
• 66–70 Gy (2.0 Gy/fraction; 6 fractions/wk accelerated)
• Hyperfractionation: 81.6 Gy/7 weeks (1.2 Gy/fraction, twice daily)
• Low to intermediate risk:
• Sites of suspected subclinical spread
• 44–50 Gy (2.0 Gy/fraction) to 54–63 Gy (1.6–1.8 Gy/fraction)
33
Definitive RT alone : PTV
NCCN Version 2.2018

Post-opRT
34
• Takes care of microscopic disease after removal of gross disease.
• Considered when risk of loco regional failure > 20%
• Commonly done in stage III, IV tumors and selectively in early stages.
• Advantages:
• Better information about the tumor pathology
• Knowledge of tumor spread
• Tailoring of radiation dose and volume
• Disadvantages:
• Potential delay in starting RT
• Tumor hypoxia
• Wound healing

35
• Post-op RT superior to pre-op RT in H&N Cancer (RTOG, 73-03) trial,
1991)
• Timing of postop RT critical - Within 3-6 weeks of surgery, >6 weeks delay
detrimental
• Optimal dose considerations (60-64 Gy/30-32#/6-6.5 wks)
• Absolute Indications :
• Microscopically involved mucosal margins of resection
• Extra capsular extension
• Relative indications :
• Close margins (<5mm)
• Multiple positive neck nodes (2 or more)
• pT3-T4 with negative margins
• Perineural spread or microvascular emboli
• Mandibular bone involvement
• Level IV-V nodes

36
• With Concurrent chemotherapy :
• Microscopically involved mucosal margins of resection
• Extra capsular extension
• Concurrent cisplatin 100 mg/m2 q3 weeks x 3c (alternatively, cisplatin
40 mg/m2 weekly x 6c)
• Drug Radiation Interaction Mechanisms:
1. Enhancement of tumour Radio-response
2. Inhibition of repair of Sublethal radiation damage or recovery from
Potentially lethal damage
3. Cell cycle redistribution & synchronization

37
• Trial • Description
EORTC 22931 (Bernier
NEJM 2004):
• 334 patients with operable H&N SCC stage pT3–4, pT1-
2N2-3, oral cavity/ oropharynx with levels IV–V
involved, or T1-2N0-1 with ECE, +margin, LVSI, or PNI.
Randomized to post-op RT 2/60–66 Gy or chemo-RT (+
cisplatin for 3 cycles).
• Chemo-RT improved 5-year DFS (36 → 47%), OS (40 →
53%), and LRC (69 → 82%).
• Chemo-RT increased acute grade ≥ 3 toxicity (21 →
41%).
RTOG 95–01 (Cooper
NEJM 2004, IJROBP
2012):
• 459 patients with operable H&N SCC who had ≥2 LN,
ECE, or +margin randomized to post-op RT (2/60–66
Gy) vs. chemo-RT (2/60–66 + cisplatin Å~3 cycles).
• Chemo-RT improved 2-year DFS (43 → 54%) and LRC
(72 → 82%); only in ECE and/or +margin subset
improved 10-year DFS (12 → 18%) and LRC (21 → 33%).
• Trend only for OS improvement.
• Chemo-RT increased acute toxicity, no significant
increase in late toxicity.

Post-opRT Doses
38
NCCN Version 2.2018
PTV
• High risk: Adverse features such as positive margins
• 60–66 Gy (2.0 Gy/fraction); daily Monday–Friday in 6–6.5 weeks
• Low to intermediate risk: Sites of suspected subclinical spread
• 44–50 Gy (2.0 Gy/fraction) to 54–63 Gy (1.6–1.8 Gy/fraction)

39
TargetedTherapy
• Cetuximab with RT
• Cetuximab: 400 mg/m2 IV loading dose, 1 week before radiation
therapy, then 250 mg/m2 IV weekly
• Radiation therapy: 200 cGy/day for 5 days per week (total dose,70
Gy)
• Over expression of EGFR in SCCHN
• Synergistic action of cetuximab and RT
• Inhibits radiation-induced DNA damage repair
• Decreases tumor repopulation and improves re-oxygenation

40
TargetedTherapy
• CONCERT trials (CONcomitant Chemotherapy and/or EGFR inhibition
with Radiation Therapy)
• Panitumumab cannot replace cisplatin in the combined treatment
with radiotherapy for unresected stage III–IVb HNSCC
• EXTREME trial: Erbitux in First-Line Treatment of Recurrent or
Metastatic Head and Neck Cancer 2009
• Platinum/5-FU with or without cetuximab in recurrent/metastatic
SCCHN
• Addition of Cetuximab to first-line therapy therapy resulted in
significantly prolonged OS with a median of 2.7 months compared to
chemotherapy alone
• Gefitinib and Erlotinib in patients of recurrent/metastatic HNSCC : good
response, better survival and longer PFS, and can be used in patients
with poor PS
• Nimotuzumab, Afatinib, Lapatinib : Phase II results

Pre-opRT followedby Surgery
NCCN Guidelines Version 2.2018
41
• Borderline operable lesions
• Have been used for RMT tumors
• Advantages:
• Well oxygenated tumors
• Reduces the viability of tumor
• Improves resectability
• Disadvantage:
• Delayed wound healing

ChemotherapyDoseSchedules
Physician’s Cancer Chemotherapy Drug Manual 2015
TPF Induction Chemotherapy  Carboplatin + Radiation Therapy
• Docetaxel: 75 mg/m2 IV on day 1
• Cisplatin: 75–100 mg/m2 IV on day 1
• 5-Fluorouracil: 1000 mg/m2/day IV continuous infusion on days 1–4
• Repeat cycle every 3 weeks for 3 cycles followed by:
• Carboplatin: AUC of 1.5, IV weekly for 7 weeks during radiation
therapy
• Radiation therapy: 200 cGy/day to a total dose of 7400 cGy
• At the completion of chemoradiotherapy, surgical resection as
indicated

43
NeoadjuvantTherapy
• Largely experimental
TAX 324 (Posner
NEJM 2007, Lorch
Lancet Oncol 2011):
• Randomized 501 patients with stage III–IV H&N SCC
to TPF (docetaxel, cisplatin, 5-FU) vs. PF induction
chemotherapy followed by carboplatin chemo-RT
(70–74 Gy).
• TPF improved median PFS (13 → 38 months) and
OS (35 → 71 months).
• More acute hematologic toxicity with TPF, but more
treatment delays with PF.
• No significant difference in late toxicity

44
IS NACT+CTRTbetterthan CTRT?
2012-DeCide
• A phase III randomized trial of docetaxel (D), cisplatin (P), 5-
fluorouracil (F) (TPF) induction chemotherapy (IC) in patients with
N2/N3 locally advanced squamous cell carcinoma of the head
and neck (SCCHN).
• CRT Vs 2#TPF f/b CRT
• Conclusions: High survival rates were observed in both arms.
• Further analysis and follow-up may provide insight into why the
significant decrease in DF did not translate into improved OS.

2013-PARADIGM
Lancet Oncol 2013; 14: 257–
64
3# TPF f/b
CRT(Carboplatin
or Docetaxel)
Vs
CRT
(2# Cisplatin)

46
Intra-op RT
• IORT-Electron
• Accessible lesion
• More homogenous dose distribution
• IORT – HDR
• Less accessible
• Heterogeneous dose (200% of prescribed dose at surface)

47
RadiotherapyTechniques
• Simulation :
• Patient is treated in supine position with extended neck
• Palpable lymph nodes are marked with wire
• Depress the tongue away from hard palate
• Immobilize with a thermoplastic head and shoulder mask, neck
rest and shoulder retractors

48
Conventionalfields
• Superior: 2 cm above primary tumor
• Inferior: below hyoid bone.
• Lymph node (+): level III is included
• Anterior: 2 cm in front of primary tumor (usually in front of
mandible).
• Posterior: Back of vertebral corpuses.
• Lymph node (+): back of vertebral spinous processes.
• Two lateral parallel–opposed fields are used.
• Lymph node (+): neck and supraclavicular field is also treated

50
Anterior and I/L field with wedges
for small tumors of buccal mucosa 2 anterior wedged fields for
anterior T1 and small T2 floor of
mouth tumors

Role of 3D CRT
51
• Achievement of dose escalation:
• To improve loco-regional control
• To increase overall survival
• Reduction of normal tissue complications:
• To improve quality of life

Role of IMRT
52
• Despite high dose PORT in patients with locally advanced HNC with
certain high risk factors, locoregional recurrences rate is about
30%.
• IMRT has a potential to reduce the radiation accompaniments -
damage to major salivary glands (xerostomia) and to the mandible
(osteoradionecrosis)
• Ideal candidates for IMRT include patients with T1–4 primary
lesions with less than or equal to N2b neck disease
• In lateralized disease, contralateral neck be included when
ipsilateral neck involvement is greater than N1

• Interstitial brachytherapy is considered for selected cases.
• May be useful as an adjunct to EBRT or as definitive therapy in early
stage tumors, especially in cases of re-irradiation.
• LDR brachytherapy (0.4–0.5 Gy per hour):
• Consider LDR boost 20–35 Gy if combined with 50 Gy EBRT or 60–
70 Gy over several days if using LDR as sole therapy.
• HDR brachytherapy:
• Consider HDR boost 21 Gy at 3 Gy/fraction if combined with 40–
50 Gy EBRT or 45–60 Gy at 3–6 Gy/fraction if using HDR as sole
therapy.
• For lesions >2.5 cm, part of the treatment should be given with
external-beam radiation to supplement the dose to the cold spots.
• For lesions that are very close to the mandible, brachytherapy is
contraindicated because of the risk of osteoradionecrosis.
53
Brachytherapy
NCCN Version 2.2018

.
Techniquesof Implantation
• The commonest techniques used for brachytherapy in the oral
tongue are:
• Hypodermic needle technique
• Guide-gutter technique
• Plastic loop technique

HypodermicNeedles
• Hollow, bevelled needles with outer diameter
of 0.8mm and variable length (4 to 8 cm),
open at both ends.
• Cause little trauma - can be directly inserted
in the tissues
• The rigid steel and template system avoids
displacement of the sources due to the
elasticity of the soft tissues
• Can be used in lip tumours of ≤3cm in largest
diameter, not involving the lateral
commissurae.

Guide GutterTechnique
• Iridium hairpins with a fixed separation
of 12 mm are used
• This limits width of volume which can
be treated to approximately 15 mm and
the technique can therefore only be used
for smaller tumours (≤30 mm in length).
• The guide gutter is first inserted and
when they are in position, the
radioactive hairpins can be cut to the
desired length
• The pre-prepared suture is then tied
over the bridge of the hairpin to secure
it within the tongue

PlasticTube Loop Technique
• This allows a wider separation
between the sources - can be
used to treat larger volumes.
• Remote after-loading that
reduces the risk of exposure
• In case of local oedema
inducing the risk of
displacement of the plastic
tubes, we can wait for an
acceptable local status before
loading the iridium wire.
• Self retaining assembly, no
suturing required

58

• Enable boosting of radiation dose to sites within the oral cavity while
avoiding direct dose to the mandible
• Anterior oral cavity lesions upto 3 cm in edentulous patients
• Either 100- to 250-kilovolt (peak) x-rays or electron beams in the 6- to
12-mev range
• Major advantage - highly focal to the tumor bed and non-invasive
• Requires careful daily positioning and verification - equipped with a
periscope to visualize the lesion.
• Cone abuts the mucosa and is centered directly over the lesion.
• Intraoral cone treatment should take place prior to external beam
radiation so that the lesion can be adequately visualized.
59
Intraoral Cone
NCCN Version 2.2018

60

Fractionationin Headand Neck
61
• Squamous cell carcinoma - higher α/β ratio as compared to late
responding normal tissues
• Propensity for accelerated repopulation after onset of therapy
• Accelerated repopulation starts around 28 days after starting
radiation
• Suboptimal results in locally advanced carcinomas
• Compensate with dose increase of about 0.6Gy/day

Hyperfractionation
• Total tumour dose: INCREASED
• No. of fractions: INCREASED
• Dose/fraction: DECREASED
• Overall time: UNCHANGED
• For comparable toxicity in fibrovascular tissues, 2Gy/# replaced
by two # per day, 1.15 – 1.2Gy/#
• Inter-fraction interval not less than 6 hours
• Useful when α/β ratio of tumour greater than dose limiting
normal tissue
• Inevitably, more severe acute reactions

AcceleratedFractionation
• Overall treatment time: significantly reduced
• Total dose, fraction size: some change
• Aim is to minimize tumour regeneration during therapy
• ‘Pure’ and ‘hybrid’ types of schedules
• No. of fractions/day varies

Pure Acceleration
• Reduction of overall treatment time
• No change in fraction size or total dose
• Once daily fraction, 6-7 days a week
• Two fractions per day during some or all weekdays

HybridAcceleration
• Overall treatment reduced along with changes in fraction size and
total dose
• Aim is to make treatment more tolerable
• Three main types of schedule tested with different strategies to
avoid acute reactions

Type A HybridAcceleration
• Intensive short course treatment
• Overall treatment time markedly reduced
• Multiple fractions delivered per day
• Total dose reduced in order to decrease acute reactions
• Spinal cord, if included, may not have full repair within 6 hours

Type B HybridAcceleration
• Split course regimen
• Two short courses of multi-fraction radiation with a planned gap
of two weeks
• Initially, the second part of treatment was given by once a day
fractions
• Total treatment time lasted about 6 weeks

Type C HybridAcceleration
• Concomitant boost
• Designed in MD Anderson Cancer Centre
• Boost dose to a smaller area delivered concomitantly
• Boost given as a second daily dose 4 – 6 hours after initial
radiation
• May be given throughout the main treatment or at the beginning
or end

RTOG 90–03 (Fu
IJROBP 2000; Beitler
IJROBP 2014):
• 268 patients with locally advanced H&N SCC
randomized to standard 2/70 Gy vs.
hyperfractionated 1.2 BID/81.6 Gy vs. concomitant
boost 72 Gy (1.8/54 Gy plus BID 1.5 Gy last 12 days)
vs. split-course 1.6 BID/67.2 Gy (2 week break).
• At 5 years, reduction in LRF vs. standard was 6.5%,
6.6%, and 1.1%. Overall survival was
nonsignificantly improved for hyperfractionated
and concomitant boost.
• All non-standard fractionation increased acute side
effects, and accelerated fractionation increased late
side effects
MARCH meta-analysis
(Bourhis Lancet
2006):
• 15 phase III trials of 6515 patients with H&N SCC.
Significantly improved OS (3.4% benefit) and LRC
(6.4% benefit) at 5 years for altered fractionation
vs. conventional fractionation, with most benefit
seen for hyperfractionation.
• Decreasing benefit with increasing age
AlteredFractionation

Trial Description
MACH-NC Meta-
analysis (Pignon
Radiother Oncol
2009) :
• 93 phase III trials and 17,346 patients. 5-year OS
benefit 4.5% with chemo-RT vs. RT alone.
• Greater OS benefit for concurrent (6.5%) vs.
induction chemo (2.4%), no benefit from adjuvant
chemo.
• Similar results with post-op RT, conventional, and
altered fractionation.
• More benefit with regimens containing platinum.
Decreasing chemo-RT benefit with age; none
observed if age > 70 years
ChemoRT+/- AlteredFractionation

71
DoseLimitations
• Spinal cord ≤ 45 Gy
• Brainstem ≤ 54 Gy
• D50 of total parotid < 30 Gy and mean dose atleast in one gland <26 Gy;
V20 ≤ 50%
• Submandibular ≤ 39 Gy
• Cochlea mean ≤ 37 Gy, max ≤ 45 Gy
• Retina ≤ 35 Gy
• Mandible and TMJ max ≤ 70Gy or 1cc PTV not more than 75Gy
• Larynx ≤ 32 Gy and V50 ≤ 66%
Handbook of Evidence-based Radiation Oncology, 3rd ed.

72
Followup
• H&P q 2–3 months for first 2 years, q 6 months for next 3 years, and
then annually
• 85–90% of locoregional recurrences occur within 3 years.
• If recurrence suspected but biopsy is negative, follow up monthly until
resolved
• Work up at follow up :
• History/physical examination at each follow-up
• Imaging of the head and neck (whenever patients develop new signs
or symptoms suggestive of recurrence) – Post treatment PET/CT has
high predictive value for long-term outcomes
• Imaging of the thorax recommended annually
• Speech, swallow, and hearing evaluations and rehabilitation
• Smoking cessation counseling
• Dental care after treatment : non invasive 3 and invasive 6 months
Handbook of Evidence-based Radiation Oncology, 3rd ed.

73
TreatmentSequelae
• Acute
• Mucositis
• Xerostomia
• Loss of taste
• Skin reaction
• Late
• Trismus
• Dental caries
• Osteoradionecrosis
• Grade I- Exposed alveolar bone is observed.
• Grade II- ORN that does not respond to
hyperbaric oxygen therapy and requires
sequestrectomy/ saucerization.
• Grade III- Full thickness involvement or
pathologic fracture
HYPOVASCULARITY
HYPOCELLULARITYHYPOXIA

74
Recurrence
• Appropriate 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
• Systemic therapy, reirradiation, and palliative resection can be
considered

SystemicTherapy
Physician’s Cancer Chemotherapy Drug Manual 2015
TIP
• Paclitaxel: 175 mg/m2 IV over 3 hours on day 1
• Ifosfamide: 1000 mg/m2 IV over 2 hours on days 1–3
• Mesna: 400 mg/m2 IV before ifosfamide and 200 mg/m2 IV, 4 hours after
ifosfamide
• Cisplatin: 60 mg/m2 IV on day 1
• Repeat cycle every 21–28 days
Paclitaxel + Carboplatin
• Paclitaxel: 175 mg/m2 IV over 3 hours on day 1
• Carboplatin: AUC of 6, IV on day 1
• Repeat cycle every 21 days

77
NCCN guidelines V2.2018
• Follow
up

78
NCCN guidelines V2.2018
• Follow
up

Management of oral cavity cancer 23072018

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