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Malignant conditions of oral cavity

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Terminology-types
 Neoplasia
 Dysplasia
 Carcinoma
 Sarcoma
 Carcinoma in situ
 Leukaemia
 Lymphoma
 Premalignant lesions and conditions

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NEOPLASIA

 Term ‘neoplasia’ means new growth; the new growth produced is called
‘neoplasm’ or ‘tumor’.
 Definition of neoplasm:- by WILLS
“an abnormal mass of tissue, the growth of which exceeds and is
uncoordinated with that of the normal tissues and persist in the same
excessive manner after the cessation of the stimuli which evoked the
change.

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Dysplasia
 Dysplasia means ‘disordered cellular development’.

 Often accompanied with metaplasia and hyperplasia.

 Also referred as atypical hyperplasia.

 Occurs most often in epithelial cells.

 Epithelial dysplasia is characterized by cellular proliferation and cytological

changes.

 In proportion of cases, the dysplasia progress into carcinoma in situ.

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These changes are :-
1. Loss of polarity of the basal cells.
2. Presence of more than one layer of cells having a basaloid appearance.
3. Increased nuclear cytoplasmic ratio.
4. Drop shaped rete processes.
5. Irregular epithelial stratification.
6. Increased number of mitotic figures.
7. Presence of mitotic figures in superficial half of epithelium.
8. Cellular pleomorphism.
9. Nuclear hyperchromatism.
10. Enlarged nucleoli.
11. Reduction of cellular cohesion.
12. Keratinization of single cells or cell groups in the prickle layer.

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Carcinoma

 Malignant tumors of epithelial origin are called carcinomas.


 Examples:- Squamous cell carcinoma
-Verrucous carcinoma
- Basaloid squamous cell carcinoma
- Adenoid squamous cell carcinoma
- Spindle cell carcinoma
- Adeno-squamous cell carcinoma
- Undifferentiated carcinoma

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Sarcoma
 Malignant tumors of mesenchymal origin are called sarcomas.
 Examples: - Fibrosarcoma
- Synovial sarcoma
- Liposarcoma
- Kaposi’s sarcoma
- Ewing’s sarcoma
- Chondrosarcoma
- Osteosarcoma

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Carcinoma in situ
 -Intraepithelial carcinoma.
 “Cancer that involves only at the place in which it began and that has not
spread. Carcinoma in situ is an early-stage tumor.”
 “When the cytological features of malignancy are present but the malignant
cells are confined to epithelium without invasion across the basement
membrane, it is called as carcinoma in situ.”
 The common sites are:
-Oral leukoplakia
-Bowen’s disease of skin.
.

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Leukemia
❑ “disease characterized by progressive overproduction of white blood cells
which usually appear in the circulating blood in an immature form.”
❑ Classified according to following types:-
1. Lymphoid ( lymphoblastic, lymphocytic)
-involving the lymphocytic series.
2. Myeloid (myelogenous) leukemia
-involving progenitor cell that gives rise to terminally differentiated
cells of myeloid series.
❑ Classification modified to indicate course of disease
a. acute
b. subacute
c. chronic

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Lymphoma

 “They constitute the group of neoplasms of varying degree of


malignancy which are derived from the basic cells of lymphoid tissue,
the lymphocytes, and the histiocytes in any of their developmental
stages.”
 Can arise from any type of lymphocytes (mostly B type)
 main types are:
- Hodgkin’s disease.
- Non Hodgkin’s lymphoma
- others are African jaw (Burkitt’s) lymphoma.

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Premalignant lesion
 A morphologically altered tissue in which cancer is more likely to occur
than its apparently normal counterpart.
- Leukoplakia
- Erythroplakia
- Palatal keratosis associated with reverse smoking.
- Squamous epithelial dysplasia
- Squamous cell carcinoma in situ
- Solar keratosis

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Premalignant condition
• A generalized state of body associated with increased risk of
developing cancer.
- Sideropenic dysphagia
- Lichen planus
- Oral submucous fibrosis
- Syphlis
- Discoid lupus erythematosus
- Xeroderma pigmentosum
- Epidermolysis bullosa
- Dyskeratosis congenita

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Routes of metastasis
 Cancers may spread to distant sites by following pathways:
1. lymphatic spread.
2. haematogenous spread.
3. other routes:
- transcoelomic spread.
- spread via cerebrospinal fluid.
- implantation.

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Lymphatic Spread

 In general, carcinomas metastasize by lymphatic route.


 Exception : renal cell carcinoma (hematogenous spread).
 Walls of lymphatics are readily invaded by cancer cells.
 Form continuous growth in lymphatic channels called lymphatic
permeation .

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Haematogenous spread
 Metastasis through blood vessels common route for sarcomas.
 Exception : Rhabdomyosarcoma (occurs by lymphatics).
 Certain carcinomas such as those of lung, breasts, thyroid, kidney
and prostate also metastsise through this route.
 Cancer cells readily invade walls of capillaries, venules and veins.
 Arteries are comparatively resistant to tumor invasion
-thick walls.
-elastic tissue.

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T N M Classification

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Diagnosis of malignancy
1. Chairside examination.
2. Investigations
3. Imaging
4. histopathology

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Clinical/chair side examination

1.History taking
a. Duration:
1. Prolonged duration : may be congenital.
2. Long duration without pain : benign neoplasm
3. Short duration and rapid growth: malignant growth
b. Mode of onset:
- spontaneous swelling and rapid growing lesion may be malignant.
- very slowly growing may be benign.
- change in size, shape, color.

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c. Exact site and shape:
- In a huge swelling it is essential to know exact site and shape to know
Origin of lesion.
d. Progress of lesion:
- growing slowly.
- remained stationary for a long period
- growing again after stationary period or continuously increasing in
size (malignant).
e. Change in character of lesion
- ulceration over lesion.
- fluctuation, softening.
- painless swelling become painful.
- secondary infection may have set in lesion.

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f. Associated symptoms
- pain
- abnormal sensations
- anaesthesia
- paraesthesia over a region
- dysphagia
- nasal obstruction: difficulty in breathing
- tenderness
- lymphadenopathy.
g. Discharge
sero-sanguineous : carcinomatous ulcers

h. Loss of body weight (malignant growth)

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3. Family history
4 Personal history
Habits:
-Diet
-Brushing
-Tobacco: form of tobacco, consumption, duration of habit and
frequency of use.
-alcohol: duration of habit.
* smoking and alcohol are recognized carcinogens or cofactors for
oropharyngeal and other cancers.
* chronic smoking and tobacco are associated with various precancerous
lesions and conditions.
* these can be predisposing factors, initiating factors or precipitating
factors.

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EXAMINATION OF ULCERS
A. Duration: short –acute ulcer; long- chronic ulcer.
B. Pain: proportional to degree of inflammation.
-syphlitic ulcer and tropic ulcer resulting from nerve disease are quite
painless.
- tuberculous and aphtous ulcer are quite painful.
- carcinomatous ulcers including rodent ulcer have complete absence of
pain in early stages.
C. Position: eg.rodent ulcers are usually confined to upper part of face.
D. Site: malignant ulcer may occur anywhere but commo within lip, cheek
and tongue.
E. Size and shape: carcinomatous ulcers are irregular in size and shape.

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F. Floor: - it should be seen for pressence of slough or membrane.
- floor covered with red or florid granulation tissue- healing ulcer.
- floor covered with pale and smooth granulation- slow healing ulcer.
- fungation or cauliflower appearance- squamous cell carcinoma.
- ulcerated black mass- malignant melanoma.

G. Edge:
- edges of a spreading ulcer will be inflamed and oedematous.
- a healing ulcer is traced from granulation tissue in center and white zone
at periphery.
- tuberculous ulcer- undermined.
- syphlitic gumma - punched out.
- squamous cell carcinoma- raised and everted.

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Lymph node examination
• Lymphadenopathy refers to nodes that are abnormal in size, consistency or
number.
• Generalized: two or more lymph nodes are enlarged.
• Localized : if only one area is involved.

Consistency
-stony hard : carcinoma usually metastatic.
-firm rubbery nodes: lymphoma
-shotty nodes: small nodes feel like buckshot under the skin, as found in the
cervical nodes of children with viral illness.
-matting : group of nodes that feel connected and seem to move as a unit.
Can be bening eg. Sarcoidosis or
malignant like metastatic carcinoma.

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Investigations
Routine examination of blood:-
-total count
-differential count of W.B.C
-haemoglobin percentage
-R.B.C count
-erythrocyte sedimentation rate (E.S.R).
-blood sugar estimation to rule out diabetes.

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Imaging
1. Conventional radiography
PA chest:
- important for head and neck cancer patients.
- high risk candidates for lung cancer.
- assess the chest when searching for occult primary, a second primary or
the presence of distant metastasis.
2. Magnetic resonance imaging- MRI
- most innovative, non invasive technique.
- employs radiofrequency radiation in presence of controlled magnetic
fields.
- shows superior soft tissue contrast.
- easier multiplanar imaging.
- modality of choice for nasopharynx, tongue, skull base pathology.
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3. Computed tomographic scan (CT SCAN)
-improved visualization of complex bony anatomy without
superimposition artifact
-high contrast discrimination of soft tissue.
-spiral CT is preferred technique, allowing rapid scan acquisition,
facilitating multiplanar scan reformats.
-has been shown that addition of CT improves staging of cancers with
clinical evluation.

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In the assessment of primary tumor , an anatomic scan may
be helpful to:-

1. Assess the sie of the primary lesion.


2. Assess the neck at same time.
3. Stage the disease accurately.
4. Assess the chest and abdomen when searching for an occult primary,
a second primary or the presence of distant metastasis.
5. Confirm the diagnosis e.g glomus tumors.
6. Aid assessment of conservation surgery.
7. Stage and assess inaccessible tumors such as those in the maxillary
sinus and the parapharyngeal space.
8. Aid baseline and postoperative assessment in tumors that have a high
risk of recurrence or recur slowly, i.e adenoid cystic carcinoma.

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Neck imaging (CT or MRI) may be useful in:

 If the neck is being scanned as part of the evaluation of the primary


tumor.
 If there is a high chance of occult disease (>20%) as an alternative to
elective treatment.
 In an N2a, N2b or N3 neck, when the presence of deep fixation or
contralateral neck disease may aalter therapy from surgery to no
surgical treatment at all.
 In the short, stocky neck where clinical examination is difficult.
 For restaging following previous surgery and irradiation.

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 To know about distant metastasis following can be performed:
-Bone scintigraphy
-Ultrasound abdomen

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Histopathology
 Biopsy:
-most important investigation.
-particularly done in case of suspected malignant tumors.
-taken from viable part of tumor, i.e not from the centre, which may be
necrotic, and not from edge, which may only show dysplasia.
 FNAC:
 -may be done on first draining lymph node; echelon node or centinal node.
 -if N0 neck – ultrasound guided FNAC. (deep cervical nodes)

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 Histologically tumor can be:
1.well differentiated.
-cells are having resemblance to cells of origin.
-cells are with distinct cell membrane and are
arranged in sheets or nests.
-mitotic figures are present but less in numbers.
- overall good prognosis.
2. moderately differentiated.
-somewhat lesser resemblance to cells.
-cells are still having distinct cell membrane
-increased mitotic figures.
- not so good prognosis.
3. poorly differentiated.
-poor resemblance to cells of origin.
-cells not having distinct cell membrane.
-mitotic figures increased further.
-bad prognosis
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Treatment options
 Treatment is planned after staging of tumor is done.
 Malignancies are treated with:
1. Surgery
2. Radiation
-radiotherapy as a definitive treatment.
- radiotherapy plus surgery.
3. Chemotherapy
-radiotherapy plus chemotherapy
-surgery plus chemotherapy
-surgery plus radiotherapy plus
chemotherapy

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Various incisions for neck dissection:
 1. Schobinger
 2. Horizontal-T (Hetter)
 3. McFee
 4. Lateral utility
 5. Utility
 6. Visor
 7. Extended neck
 8. H-incision

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Various neck dissections
1. Radical neck dissection (RND)
structures dissected out are:
-lymph nodes (level 1-5)
-sternocleidomastoid muscle.
-internal jugular vein
-spinal accessory nerve.

2. Extended neck dissection


structures dissected are– those removed in RND plus
-lymph nodes level (6-7)
-parotid lymph nodes
-retrppharyngeal nodes.
-non lymphatic structures which may get involved: parotid gland, mastoid tip, prevertebral
fascia, pharynx, external carotid artery, skin, digastric muscle.

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• Modified RND:-structures removed are:
TYPE 1 : lymph node (level 1-5) + sternoceidomastoid + internal jugular
vein + submandibular gland.

TYPE 2 : Lymph node (level 1-5) + sternocleidomastoid muscle +


submandibular gland.

TYPE 3 : Lymph node (level 1-5) + submandibular gland


- also called as Comprehensive or Functional Neck
Dissection.

• Commando operation:
-Operation in which along with Radical Neck Dissection partial
hemimandibulectomy and hemiglossectomy are performed.

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Contraindications to neck dissections

 Those patients whose primary tumors are untreatable.

 Any patients who is unfit for major surgery because of a serious medical
condition which would render anaesthesia and major surgery unsafe.

 Patients with inoperable neck disease.

 Patients with distant metastasis.

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Radiotherapy
• Definition: (ray-dee-oh-THER-a-pee) The use of high-energy radiation
from x-rays, gamma rays, neutrons, and other sources to kill cancer cells
and shrink tumors.
• Local treatment modality.
• Complementary with surgery.
• Radiation causes damage to DNA of both normal and malignant cells.
Malignant cells devide more frequently and less efficiently.
• Before undergoing next division if the damage is not repaired the
malignant cells die in mitosis.

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PREOPERATIVE AND POSTOPERATIVE RADIOTHERAPY

 Radiotherapy is best at eradicating small volumes of diseases and more likely to fail if there
is large bulky tumors.
 Two modalities combined usefully, the advantage of each overcoming the shortcomings of
other.
PREOPERATIVE RADIOTHERAPY
 Tumors will shrink prior to surgery making operation easier.
 Sterilizing majority of viable cells , risk of tumor dissemination at time of surgery was
reduced.
Advantages
-Blood supply may be better than after surgery, leading improved oxygenation.
-tumor seeding during surgery decreased.
Disadvantage
-loss of definitive tumor staging and lower doses given concerning increase in surgical
morbidity.
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POSTOPERATIVE RADIOTHERAPY
• Considered preferable.
-proper pathological staging of tumors and nodes.
-introduction of free flaps in reconstructive surgery.
-following surgery only microscopic tumor left behind, relatively easy to cure
with radiation.
 INDICATIONS
-Large infiltrating tumors.
-compromised margins of surgical resection.
-perineural spread.
-extension of tumor into deep soft tissues or bone destruction.
-multiple lymph nodes, large lymph nodes, and extracapsular nodal spread.

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TYPES OF RADIATION TREATMENT
 External beam Radiotherapy.

 Interstitial or Intracavitary Brachytherapy.

 Unsealed Radionuclide Therapy.

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EXTERNAL BEAM RADIOTHERAPY
 Also known as TELETHERAPY.
 Beam of radiation directed by a machine to tumor bearing part of
patient.
 Variety of different types of radiations are in current use.

TYPES OF EXTERNAL BEAM RADIOTHERAPY.


 Photons [x-ray or gamma rays]
 particles[ e.g. electrons]
-common in use

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INTERSTITIAL RADIOTHERAPY

 Also known as BRACHYTHERAPY.


 Sealed sources of radioactive isotopes either implanted into tumor.
OR
placed in natural body cavity.
For example; maxillary antrum or nasopharynx.
{intracavitary therapy}

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Oral cavity is the most common site for Interstitial implantation.

- many oral tumors, being small, relative well demarcated

- anatomically accessible.

-Interstitial therapy treats small, localized volume with


rapid fall off dose remote from implant.

-Enables higher radiation dose.

-Diminishes doses to adjacent structures such as bone


and salivary glands.

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USES OF UNSEALED SOURCES
 Radioactive isotopes can be used in form of drugs given orally or
intravenously.
 These drugs are then concentrated by metabolic pathway in
malignant tissue, enabling larger radiation doses to be given to
tumor.
 Example: treatment of differentiated thyroid carcinoma of
follicular cell origin with radioactive iodine.

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CONVENTIONAL FRACTIONATION

 Maximum amount of radiation given as single dose is limited by NORMAL


TISSUE TOLERANCE.

 Total dose divided in small doses, called FRACTIONS, given for e.g, daily,
the maximum dose tolerated by normal tissues increases

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CONVENTIONAL AND ALTERNATIVE
FRACTIONATION SCHEDULE
 Conventional : 60 Gy in 30x2 Gy fractions over 42
days.
 Hypo fractionation : Smaller number of fractions each
larger than 2 Gy.
 Hyper fractionation: Larger number of fractions each
smaller than 2 Gy.
 Acceleration : Shortened overall time.
 Split course : Gap to allow acute reactions to
settle.

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Radiotherapy in management of metastatic neck
disease
 Radiotherapy may be used to treat the neck in the following clinical
situations:-
-The clinically negative neck (N0 neck).
-The clinically positive neck.
- Elective after surgery.
- Neck disease developing/recurring after initial treatment:
1. nodal metastasis developing in the untreated neck
after initial treatment of the primary tumor alone.
2. recurrence after previous surgery to the neck.
3. nodal recurrence after combined treatment.

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COMPLICATIONS
• ACUTE:- during or immediately after a course of
treatment.
 skin reactions
1.cutaneous erythema.
2. blistering or moist desquamation and hyperpigmentation.
mucosal reactions.
1.xerostomia.
2. Mucositis.
Other acute complications are
Swelling.
- infertility.
- generalized fatigue
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• Late effects:-which may come on in subsequent months or
years.
 Dental and bone effects.
bone and soft tissue necrosis.
xerostomia.
periodontal disease.
Wide spread radiation caries .
 Osteoradionecrosis. (radiation osteomyelitis.)
 Skin and soft tissue effects
Telengiectasia
Atrophy
Hypo-pigmentation and fibrosis

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 Neurological effects.
spinal cord compression.
optic neuropathy.
neurotoxicity.
 Hypothyroidism
 Visual problems.
Dry eyes, corneal ulcerations, cataracts, retinal damage.
 Other complications:
- Fibrosis.
- Hair loss.
- Cancer.
- Death.

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CHEMOTHERAPY
 Chemotherapy is the treatment by chemicals that act by interfering with
rapidly growing tumor cells .

 For squamous cancers of head and neck, chemotherapy may be used in


combination with surgery and radiotherapy as an adjunct in radical
treatments.

 Many patients with lymphoma , for e.g, rhabdomyosarcoma may be cured


with chemotherapy alone.

 Most agents are given intravenously, recently intra arterial injections have
been given.
 The drugs are introduced through various branches of external carotid
artery in retrograde fashion.
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Classes of chemotherapeutic agents
• Alkylating agents: - Reactive compounds bind covalently to DNA,
interrupting DNA replication.
example: cyclophosphamide, ifosfamide, melphan, chlorambucil,
nitrosoureas, carmustine and lomustine.

• Antimetabolites :-These are simple chemicals with a structural


similarity to normally occuring cellular compounds.
Act by interfering with essential cellular metabolism.
example: Methotrexate is an antifoliate compound acts as a false substrate
for enzyme dihydrofolate reductase.
other examples are purine antagonists 6-mercaptopurine and 6-
thioguanine.
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• Plant derivatives: various substances derived from plants are cytotoxic.
for example vinca alkaloids vincristine and vinblastine come from the
Madagascar pink periwinkle and act by binding to protein tubulin.

• Antitumor antibiotics: Various naturally occuring drugs extracted from


bacterial and fungal cultures.
for example actinomycin D, bleomycin and the anthracyclines
doxorubicin and daunorubicin.

• Miscellaneous drugs: The platinum derivatives carboplatin and cisplatin


form cross-links with DNA.

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Scheduling of chemotherapy

 Before definitive treatment (surgery/radiotherapy)


-neoadjuvant; induction; up-front.

 During definitive treatment


-synchronous; concomitant.

 After definitive treatment


-adjuvant; subsequent.

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Follow-up policies

• Reasons for follow-up:


1. To detect relapse and institute salvage treatment.

2. For speech and swallowing rehabilitation.

3. For patient support and education.

4. For prevention and treatment of late morbidity.

5. To collect outcome data systematically.

6. For training.
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