Principles of Oncology

Riyadh et al.
Notes
Head and Neck:

1- Principles of Head and Neck Oncology
2- Thyroid - Embryology, Anatomy and Physiology
3- Approach for Evaluation of Thyroid Nodules
4- Benign Thyroid Diseases
5- Malignant Thyroid Tumors
6- Parathyroid - Embryology, Anatomy and Physiology
7- Diseases of Parathyroid Glands
8- Salivary Glands - Embryology, Anatomy and Physiology
9- Approach to Salivary Gland Pathology
10- Benign Salivary Gland Diseases
11- Salivary Glands Tumors
12- Parapharyngeal Space Tumors
13- Paraganglioma
14- Anatomy of Oral Cavity
15- Tongue - Embryology, Anatomy and Physiology
16- Common Disorders of Oral Cavity
17- Premalignant Oral Ulcers & Lesions
18- Oral Cavity Cancer
19- Nasopharyngeal Tumors
20- Oropharyngeal Tumors
21- Hypopharyngeal Cancer
22- Early Laryngeal Cancer
23- Advanced Laryngeal Cancer
24- Lymphoma
25- Orbital Anatomy and Tumors
26- Odontogenic Cysts and Tumors
27- Cutaneous Malignancy
28- Melanoma
29- Head and Neck Reconstruction Pearls
2267
rapid note
- palliative Chemotherapy Must be weighed carefully with regard to factors such as morbidity, expected
improvement in symptoms, performance status, and realistic patient/family expectations
- Palliative chemotherapy may involve single or multiple agents; the choice depends on carefully weighing
the risks and benefits. Improvement in symptoms can be observed in the absence of overt response in
lesion size.
- Resistance to apoptosin in head and neck squamous cell carcinoma is conferred in part by BcL-2
overexpression. Disequilibrium between cell proliferation and cell death is characteristic of cancer. These
proteins are currently being studied as targets for cancer therapy
the most common presenting symptom(s) for tracheal squamous cell carcinoma (SCCA) is Cough
with hemoptysis
disadvantage of elective neck irradiation (ENI) versus elective neck dissection

(END = Prognostic information from histopathology is not known
disadvantage of elective neck dissection (END) versus elective neck irradiation

(ENI) = The inability to adequately treat retropharyngeal and parapharyngeal
lymph nodes
the most common complication of tracheoesophageal (TE) voice restoration = TE

puncture granulation
postcricoid mucosa (57%), and subglottis is associated with metastasis in the paratracheal and
paraesophageal nodes.
the most accurate predictor of disease-related survival for patients with head and
neck squamous cell carcinoma= Presence of cervical lymph node metastasis
Riyadh et al. Notes
chapter 1
Principles of Head and Neck Oncology:
- H&N cancers makes up about 10% of all malignancies excluding skin.

- SCC arises from genetic alterations to genes regulates cellular growth
and death.
o Mainly acquired from exposure to environmental agents.
o Less commonly inherited.
- Risk Factors for H&N Cancers:

1. Alcohol and Tobacco Abuse:
o Common etiologic factors in cancers of oral cavity, oropharynx,
hypopharynx, and larynx.
o Tobacco abuse includes smoking cigarettes, cigars, pipes or
chewing and snuffing tobacco.
o High risk for developing second primary neoplasms of H&N,
lung, esophagus due to exposure of entire aerodigestive tract
to these carcinogens.
2. Human Papilloma Virus (HPV):

o Risk factor for oropharygeal SCC (Lingual and palatine tonsils,
and base of tongue) in younger men who are nonusers of
tobacco and alcohol.
o Mainly HPV type 16.
3. Epstein-Barr Virus (EBV):

o Primary risk factor for Nasopharyngeal carcinoma and oral hairy
leukoplakia.
4. Human Immunodeficiency Virus (HIV):

o 2-3 fold increase in incidence of HNSCC.
o Increases incidence of non-AIDS-defining malignancies:
 Anogenital Cancer, Hodgkin Lymphoma, Testicular Germ
Cell Tumors, Non-small-cell Lung Cancer, Hepatocellular
Cancer.
5. Herpes Simplex Virus (HSV):

o Less strongly correlated with development of Oral Cancer than
EBV or HPV.
o HSV can transform cells in vitro to a malignant phenotype.
6. Radiation:
o Prior irradiation is risk factor for thyroid, salivary gland tumors,
HNSCC and sarcomas.
7. Betel Nut Chewing:

o Independent risk factor for HNSCC, esophageal and
hepatocellular Cancer.
o Synergistic effect with tobacco and alcohol.
2268
Riyadh et al. Notes
8. Occupational Rxposure:
o Dry cleaning agent perchloroethylene, asbestos, pesticides,
wood workers, plastic and rubber products, naphthalene
refiners, ethanol, formaldehyde, sulfuric acid mist, leather and
paint workers, automobile mechanics, cement and metal
workers.
9. Diet:
o Protective effect of H&N cancers is associated with increased
consumption of fruits and vegetables.
o Risk of Nasopharyngeal carcinoma is increased in frequent
consumers of preserved meats contains high levels of added
nitrites.
10. Genetic Factors:

o H&N cancers in these patients tend to arise at an earlier age and
in the absence of other risk factors.
11. Other Risk Factors:

o Poor oral hygiene and Periodontal disease are linked with
carcinoma of oral cavity.
o Dental prostheses or poorly fitting dentures do not appear to be
an independent risk factor for development of oral carcinoma.
- HNSCC starts on the surface and spreads superficially, deeply, and

submucosally.
o Lymphatic metastasis are common in advanced tumors.
o Distant metastasis are rare
o Status of the cervical lymph nodes is the most important
prognostic factor in SCCA of the upper aerodigestive tract.
 Cure rates drop in half (50%) when there is
regional lymph node involvement.
- General Classification of H&N Tumors:

o Mucosal Tumors:
1. Sinonasal
2. Oral.
3. Pharyngeal.
4. Laryngeal
o Non-Mucosal Tumors:
1. Thyroid and Parathyroid.
2. Salivary Glands.
3. Paragangliomas.
4. Skin.
2269
Riyadh et al. Notes
Evaluation of H&N Patient in Clinic:
History (8 Points):
1. Age and Gender
2. Chief complain
3. History of Present Illness:
 Site
 Onset
 Duration
 Progression
 Associated symptoms.
4. Past Medical and Surgical History.
5. Medications:
 Blood Thinners.
6. Allergies
7. Social History:
 Alcohol and smoking
8. Family History of Tumors.
- Important Keypoints in History:

o Any neck mass in an adult over the age of 40 years is
malignant until proven otherwise.
o Any unilateral ENT Sign and Symptom is malignant until
proven otherwise.
2270
Riyadh et al. Notes
- Otological Symptoms:
o Persistent otalgia (referred pain with normal otologic exam).
o Hearing loss.
o Aural fullness.
o Pulsatile tinnitus.
- Nasal/Paranasal/Nasophargeal Symptoms:
o Recurrent Epistaxis.
o Unilateral Nasal Obstruction.
o Persistent Rhinorrhea or Sinusitis.
- Oral/Pharyngeal Symptoms:
o Persistent sore throat (>3 weeks).
o Odynophagia.
o Dysphagia.
o Trismus.
o Presence of nonhealing ulcers.
o Halitosis.
o Numbness in the lower teeth.
- Laryngeal Symptoms:
o Persistent hoarseness and throat pain (>3 weeks).
o Difficulty breathing.
- Neck Symptoms:
o Character and duration of neck masses.
- Neurological Symptoms:
o Diplopia.
o Cranial nerve palsies.
o Mental status changes.
- Risk Factors:
o Pack-year history of smoking.
o Alcohol use.
o Tobacco abuse.
o Sun exposure.
o Previous cancers.
o Family history of cancer.
o Radiation exposure.
o Exposure to wood dust or heavy metals.
- Constitutional Symptoms:
o Extent of weight loss.
o Bone pain.
o Hemoptysis
o Malaise.
o Anorexia.
2271
Riyadh et al. Notes
Physical Examination (8 Areas):

- Complete H&N examination including All cranial nerves.
1. Head:
1. Skin and Scalp.
2. Parotid.
2. Neck:
1. Five Lymph Node Levels.
2. Thyroid.
3. Oral Cavity (7 sub-sites):
1. Floor of mouth.
2. Tongue.
3. Alveolar Ridge.
4. Lips
5. Hard Palate.
6. Buccal area.
7. Retro-molar triangle.
4. Nasal cavity:
1. Vestibule.
2. Septum.
3. Floor.
4. Lateral wall.
5. Nasopharynx:
1. Postro-superior wall (Skull base to soft palate).
2. Lateral wall (Fossa of Rosenmuller).
3. Inferior wall (superior surface of soft palate).
6. Oropharynx:
1. Base of Tongue.
2. Soft palate.
3. Tonsills.
4. Posterior pharyngeal wall.
7. Hypopharynx:
1. Postcricoid area.
2. Piriform sinus.
3. Posterior pharyngeal wall.
8. Larynx:
1. Supraglottis:
1. Epiglottis.
2. Aryepiglottic fold.
3. Arytenoids.
4. Ventricular bands.
2. Glottis:
1. Vocal cords.
3. Subglottis:
1. From lower border of glottis to inferior border of
cricoid.
2272
Riyadh et al. Notes
- Important Keypoints in Physical Examination:

o Ipsilateral otalgia with normal otoscopy:
 Direct attention to:
1. Tonsil.
2. Tongue base.
3. Supraglottis.
4. Hypopharynx.
o Unilateral OME:
 Direct examination of Nasopharynx.
Levels of Investigations:
1. Diagnostic:
o CT with Contrast from Skull base to thoracic inlet for all neck
masses EXCEPT Thyroid (US Thyroid).
o FNA.
2. Staging (TNM):
o CXR or CT Chest.
o LFT or CT Abdomen.
3. Treatment (Pre-op Assessment):
o CBC.
o U&E.
o Coagulation profile.
- Ultrasonography (US):
o Indications:
1. Thyroid masses.
2. Pediatric Neck masses
o Advantages:
1. Differentiates between Solid vs. cystic masses.
2. Noninvasive
3. Avoids ionizing radiation
4. Not required sedation.
o Characteristics of Benign Lymph node in US:

1. Small
2. Well-defined
3. Oval shape
4. Presence of fatty hilum.
o Characteristics of Pathologic Lymph node in US:

1. Large
2. Ill defined
3. Round shape
Mcq 4. Loss of fatty hilum
5. Microcalcifications
6. Focal necrosis
2273
Riyadh et al. Notes
- Computed Tomography (CT) with Contrast:

o Indications:
1. 1st imaging modality in diagnosis of H&N masses.
2. Helps in staging.
3. Detects Recurrence and Metastasis.
o Advantages:
1. Evaluates characteristics and extent of primary tumor.
2. Evaluates involvement of adjacent structures.
3. Best for evaluation of bone invasion.
4. Evaluates lymph nodes status (Requires contrast).
5. Evaluates vascularity.
o Disadvantages:
1. Ionizing radiation.
2. Can miss small metastases and early recurrence.
3. Poor soft tissue and Peri-neural evaluation.
4. Better to avoid contrast in Thyroid lesions.
2274
Riyadh et al. Notes
o Pathologic LN in CT:
1. Size > 1cm, EXCEPT:
 > 1.5cm in Level 1-2.
 > 8mm in Retropharynx.
2. Ill defined
3. Round shape.
4. Central Necrosis
5. Enhancement with contrast
6. Rim enhancement
7. Extra Capsular Invasion
o Indications of CT in Thyroid :
1. Huge Thyroid Mass.
2. Retrosternal Extension.
3. For completion thyroidectomy.
4. Pathological Lymph Node.
5. Involvement of Adjacent Structures.
- Magnetic Resonance Imaging (MRI) with Contrast:

o Advantages:
 Evaluation of Soft tissue.
 Evaluation of Cartilage and Pre-vertebral fascia (Larynx).
 Evaluation of Bone marrow invasion.
 Evaluation of Peri-neural invasion:
1. Abnormal nerve thickening.
2. Enhancement of nerve sheath.
3. Expansion of skull base foramina.
4. Sclerotic changes in nerve canal.
o Disadvantages:
1. Expensive.
2. Can miss small metastases and early recurrence.
3. Poor evaluation of Bone invasion.
4. Artifacts with breathing or swallowing.
o Indications of MRI in H&N Tumors:

1. Sinonasal tumors with intra-cranial or intra-orbital
involvement.
2. Nasopharyngeal tumors.
3. Deep parotid lobe tumors.
4. Parapharyngeal tumors.
5. Vascular tumors.
6. Laryngeal tumors with cartilage or pre-vertebral fascia
involvement.
7. Parathyroid adenoma.
2275
Riyadh et al. Notes
- Positron Emission Tomography (PET):

o Functional imaging with 18F-fluorodeoxyglucose (FDG).
o Defines tissues with increased metabolic rate.
o Improve characterization of both primary tumors and metastatic
disease.
o Poor spatial resolution of PET and the lack of anatomic
landmarks can make exact localization of disease difficult.
- Combined PET/CT:
o Advantages:
 Allows for both anatomic and functional characterization
of disease at the same time.
 More accurate than either modality alone for detection of
malignancy in H&N.
 Improved localization of abnormalities.
 Better differentiation of therapeutic changes from
residual disease.
 Improved assessment of tumor extent.
o Disadvantages:
 More expensive.
 Some H&N cancers do not uniformly accumulate FDG.
 Numerous false positive results.
 Inflammatory and infectious lesions.
 Warthin’s and pleomorphic adenomas.
o Indications of PET/CT in H&N:

1. Modality of choice for evaluation of Recurrence.
 Initial surveillance should be performed at least 3
months after conclusion of therapy.
2. Modality of choice for identifying Second primary.
3. Useful in detection of Unknown primary tumors.
 PET/CT is a supplement, not a substitute, for
endoscopy and biopsy in unknown primary tumors.
 Finds 20-30% of unknown primary tumors above
and beyond the traditional search.
4. Treated Differentiated Thyroid Carcinoma with elevated
thyroglobulin levels and negative RAI scan.
5. Treated Medullary Thyroid Carcinoma with persistent
measurable calcitonin levels and equivocal or negative
sonography.
2276
Riyadh et al. Notes
o Keypoints:
 PET/CT is superior to standard anatomic imaging
modalities in staging advance (T3 and T4) primary tumor.
 PET/CT is not sufficiently accurate to avoid neck
dissection in patients with advanced primaries and N0.
 PET/CT is superior to conventional imaging modalities for
radiation treatment planning, allowing for improved tumor
coverage and sparing of normal tissues.
 PET/CT is useful for monitoring treatment response in
HNSCC.
 PET/CT is useful for restaging, including nodal disease
and distant metastases.
 PET/CT has the potential to avoid unnecessary neck
dissections in patients with nodal disease that responds
completely to therapy.
- Miscellaneous investigations:
o Modified Barium Swallow with Esophagram:
 Evaluates aspiration and swallow.
 Indicated for suspicion of esophageal carcinoma or
lesions.
o Videostroboscopy:
 Provides documentation of laryngeal tumors and allows
for patient education.
o Nuclear Medicine Studies:

 Considered in evaluating thyroid, parathyroid, mandible
invasion, and metastatic bone disease.
 Usually not indicated as a screening tool for head and
neck cancer.
2277
Riyadh et al. Notes
- Biopsy:
o Histologic confirmation of the diagnosis is mandatory before
pursuing definitive therapy.
o Fine Needle Aspiration (FNA):

 Standard of diagnosis.
 Utilizes small (21-25) gauge needle.
 Allows cytology evaluation of cells aspirated from the
lesion.
 Indications:
1. Any neck mass that is not an obvious abscess.
2. Persistence of Neck mass after a 2 weeks course of
antibiotics.
 Advantages:
 Easy, quick, inexpensive.
 Less pain.
 Low risk of hematoma
 Low risk of seeding of tumor along the biopsy tract.
 Can be performed in a palpable node without US.
 Disadvantages:
 Provides information on cytology rather than nodal
architecture.
 Does not allow for histological subtyping.
 Accuracy varies depending on disease entity.
 Contraindicated in vascular lesions.
 Steps required to improve accuracy of FNA results:

1. Proper collection and skilled cytopathologist.
2. Minimum of 4 separate passes.
3. On-site review for adequacy.
 Sensitivity and specificity rates are 85-90%.

 FNA results may contribute to establishing the
diagnosis but should not be accepted as absolute
when clinical or other information contradicts the
FNA findings.
 Measurement of Thyroglobulin (Tg) in needle
washout fluid enhances the sensitivity of FNA of
cervical nodes in patients with thyroid nodule and
suspicious LN on Neck US.
2278
Riyadh et al. Notes
 Selective results with FNA:

 Follicular Thyroid Neoplasms:
o Difficult to differentiate between Follicular
Thyroid Adenoma and Carcinoma.
o Does not evaluate for capsular or vascular
invasion.
 Salivary Gland Neoplasms:
o Interpretation of salivary gland pathology is
difficult and requires greater experience.
o On average, FNA has high specificity (98%)
but lower sensitivity (80%).
 Lymphomas:
o Accurate diagnosis of lymphoma depends on
changes in architecture, which requires
morphologic examination of entire node.
o Combination FNA with flow cytometry and
immunohistochemistry may increase the
accuracy of lymphoma diagnosis without the
need for excisional biopsies.
o Core Needle Aspiration (CNA):

 Utilizes larger (18-20) gauge needle.
 Advantages:
 Improves the accuracy of diagnosis.
 Provides a sufficient amount of material for
conventional histopathology and immunotyping as
well as for molecular examinations.
 Higher diagnostic accuracy for diagnosis of the
following:
1. Lymphoma.
2. Salivary gland tumors.
3. Tuberculosis
 Disadvantages:
 Expensive.
 Requires experience.
 Painful.
 High risk of hematoma.
 Requires U/S to avoid complications and to ensure
suitable targeting.
 Risk for seeding malignant cells along needle tract.
o Lower incidence in Lymphoma compared to
SCC.
o One treatment strategy is to consider
excision of the needle tract site at the time
of definitive surgery and/or inclusion of the
biopsy site in the radiation field.
2279
Riyadh et al. Notes
o Excisional Biopsy:
 Remove the tumor with its capsule.
 No risk for tumor seeding.
 Indications:
1. Three negative FNA with highly suspension of
malignancy.
2. Lymphoma.
o Incisional Biopsy:
 Violates tumor capsule.
 High Potential risk for tumor seeding.
 Increase the mortality 50%.
 Indicated only when all diagnostic modalities have failed
to establish a diagnosis and excisional biopsy of the mass
is not technically feasible.
2280
Riyadh et al. Notes
- Immunohistochemistry:
o Utilizes antigen-antibodies reactions that bind to specific cellular
components that aid in the histological diagnosis.
o Most markers are not tumor-specific and not utilized on a
routine basis (due to expense).
o Useful for paranasal malignancy and poorly differentiated
cancers (small- and large-cell tumors).
o SCC typically is not difficult to distinguish, possible False
Positives include:
 Necrotizing sialometaplasia
 Mucoepidermoid carcinoma
o Common Immunohistochemical Markers:

 Lymphoma:
 Common leukocyte antigens
 T-cell and B-cell markers
 Carcinoma:
 Cytokeratin.
 Melanoma:
 S-100 (High sensitivity, Low specificity, also found
in neural and cartilaginous tumors).
 HMB-45 (Sensitive and specific, does not stain
spindle cell type).
 Mitf and Tyrosinase (Sensitive and specific).
 MART-1 and melan-A (Newer, sensitive and specific
for melanocytes).
 Neuroendocrine:
 Chromogranin.
 Neuronspecific endolase (NSE).
 Sarcomas:
 Vimentin.
 Desmin (smooth and skeletal muscle).
 Myoglobin (skeletal muscle, rhabdomyosarcoma).
 Actin (Skeletal muscle).
 S-100.
2281
Riyadh et al. Notes
- Diagnostic and Ancillary Procedures:
o Triple Endoscopy:
 Direct Laryngoscopy, Esophagoscopy, and Bronchoscopy.
 Considered as routine screening for:
1. Unknown primary
2. Second primary.
 Controversial for negative CXR and no signs or symptoms
of esophageal or tracheobronchial involvement.
o Feeding Tube:
 Allows enteral feedings with lower risk of aspiration, may
place with anticipation of radiation effects, postoperative
effect, and tumor growth.
 Temporary (Nasogastric tube) or Permanent
(Gastrostomy tube).
o Tracheostomy:
 Low threshold for surgical airway management in
anticipation of radiation effects, postoperative effect, and
tumor growth.
2282
Riyadh et al. Notes
- Determine Classification of Neoplasms:

- Based on histological specimen and evaluation of size and spread of
primary tumor (tumor mapping).
o Histological Grading:
- Categorizes the histological type of cancer according to the
degree of differentiation.
- Not significant to prognosis.
- Classification:
 Gx: Grade cannot be assessed.
 G1: Well-differentiated.
 G2: Moderately differentiated.
 G3: Poorly differentiated.
 G4: Undifferentiated.
o TNM:
- Categorizes size and spread of cancer.
 Extent of Primary Tumor (T0-4):
- Criteria varies for each type of cancer.
 Tx: Primary tumor cannot be assessed.
 T0: No evidence of primary tumor.
 Tis: Carcinoma in situ.
o Lip and Oral Cavity (T):

 T1: Tumor ≤2cm.
 T2: Tumor > 2 ≤4cm.
 T3: Tumor > 4cm.
 T4 (Lip): Tumor invades through cortical bone,
inferior alveolar nerve, floor of mouth, or
skin of face.
 T4a (Oral Cavity): Tumor invades adjacent
structures , cortical bone, into
deep [extrinsic] muscle of
tongue, maxillary sinus, skin
of face.
 T4b (Oral Cavity): Tumor invades masticator
space, pterygoid plates, or
skull base and/or encases the
internal carotid artery.
2283
Riyadh et al. Notes
o Nasopharynx (T):
 T1: Tumor is confined to nasopharynx or tumor
extends to oropharynx and/or nasal cavity,
without parapharyngeal extension.
 T2: Tumor extends into Parapharyngeal space.
 T3: Tumor involves bony structures and/or
paranasal sinuses.
 T4: Tumor has intracranial extension and/or
involves cranial nerves, infratemporal fossa,
hypopharynx, orbit, or masticator space.
o Oropharynx (T):
 T1: Tumor ≤2cm.
 T2: Tumor > 2 ≤4cm.
 T3: Tumor > 4cm.
 T4a: Tumor invades the larynx, deep/extrinsic
muscle of the tongue, medial pterygoid, hard
palate, or mandible.
 T4b: Tumor invades the lateral pterygoid muscle,
pterygoid plates, lateral nasopharynx, or skull
base or encases the carotid artery.
o Hypopharynx (T):
 T1: Tumor limited to one subsite and/or ≤2cm.
 T2: Tumor invades more than one subsite or an
adjacent site, or measures > 2 ≤4cm without
fixation of hemilarynx.
 T3: Tumor > 4cm or with fixation of hemilarynx or
extension to esophagus.
 T4a: Tumor invades thyroid/cricoid cartilage, hyoid
bone, thyroid gland, or central compartment
soft tissue.
 T4b: Tumor invades prevertebral fascia, encases
the carotid artery, or involves mediastinal
structures.
2284
Riyadh et al. Notes
o Supraglottis (T):
 T1: Tumor limited to one subsite with normal
vocal cord mobility.
 T2: Tumor invades invades mucosa of more than
one adjacent subsite of the supraglottis or
glottis or region outside the supraglottis
without fixation of the larynx.
 T3: Tumor limited to the larynx with vocal cord
fixation and/or invades any of the following:
postcricoid area, pre-epiglottic tissues,
paraglottic space, and/or inner cortex of
thyroid cartilage.
 T4a: Tumor invades through the thyroid cartilage
and/or invades tissues beyond the larynx
(e.g., trachea, soft tissues of neck, including
deep extrinsic muscle of the tongue, strap
muscles, thyroid, or esophagus).
 T4b: Tumor invades prevertebral space, encases
the carotid artery, or invades mediastinal
structures.
o Glottis (T):
 T1a: Tumor limited to one vocal cord with normal
mobility.
 T1b: Tumor involves both vocal cords with normal
mobility.
 T2: Tumor extends to the supraglottis and/or
subglottis, and/or with impaired vocal cord
mobility.
fixation and/or invades paraglottic space
and/or inner cortex of thyroid cartilage.
 T4a: Tumor invades through the thyroid cartilage
structures.
2285
Riyadh et al. Notes
o Subglottis (T):
 T1: Tumor limited subglottis.
 T2: Tumor extends to the vocal cords with
normal or impaired mobility.
fixation.
 T4a: Tumor invades cricoid or thyroid cartilage
structures.
o Maxillary Sinus (T):

 T1: Tumor limited to the maxillary sinus mucosa,
with no erosion or destruction of bone.
 T2: Tumor causing bone erosion or destruction,
including extension into the hard palate and/or
middle nasal meatus, except extension to the
posterior wall of the maxillary sinus and
pterygoid plates.
 T3: Tumor invades any of the following: bone of
the posterior wall of the maxillary sinus,
subcutaneous tissues, floor, or medial wall of
the orbit, pterygoid fossa, or ethmoid sinuses.
 T4a: Tumor invades anterior orbital contents, skin
of cheek, pterygoid plates, infratemporal
fossa, cribriform plate, sphenoid or frontal
sinuses.
 T4b: Tumor invades any of the following: orbital
apex, dura, brain, middle cranial fossa,
cranial nerves other than maxillary division
of trigeminal nerve (V2), nasopharynx, or
clivus.
2286
Riyadh et al. Notes
o Nasal Cavity and Ethmoid Sinus (T):

 T1: Tumor limited to any one subsite with or
without bone erosion.
T2: Tumor invades two subsites in a single region
or extends to involve an adjacent region within
the nasoethmoidal complex, with or without
bony invasion.
 T3: Tumor extends to invade the medial wall or
floor of the orbit, maxillary sinus, palate, or
cribriform plate.
 T4a: Tumor invades anterior orbital contents, skin
of cheek, pterygoid plates, infratemporal
fossa, cribriform plate, sphenoid or frontal
sinuses.
 T4b: Tumor invades any of the following: orbital
apex, dura, brain, middle cranial fossa,
cranial nerves other than maxillary division
of trigeminal nerve (V2), nasopharynx, or
clivus.
o Salivary Glands (T):

 T1: Tumor ≤2cm without extraparenchymal
extension.
 T2: Tumor > 2 ≤4cm without extraparenchymal
extension.
 T3: Tumor > 4cm and/or with extraparenchymal
extension.
 T4a: Tumor invades the skin, mandible, ear canal,
and/or facial nerve.
 T4b: Tumor invades the skull base and/or
pterygoid plates and/or encases the carotid
artery.
o Thyroid Gland (T):

 T1: Tumor ≤2cm Limited to Thyroid only.
 T2: Tumor > 2 ≤4cm Limited to Thyroid only.
 T3: Tumor > 4cm Limited to Thyroid only or
Tumor of Any size with Minimal Extra-thyroid
Extension (e.g., extension to SCM or
Perithyroid soft tissues).
 T4a: Tumor of Any size extends beyond Thyroid
capsule to invade Subcutaneous soft tissues,
Larynx, Trachea, Esophagus, or RLN.
 T4b: Tumor invades Prevertebral Fascia or encases
Carotid Artery or Mediastinal vessels.
 All Anaplastic carcinomas are considered T4.
2287
Riyadh et al. Notes
o Mucosal Melanoma (T):

 T3: Mucosal disease.
 T4a: Tumor involving deep soft tissue, cartilage,
bone, or overlying skin.
 T4b: Tumor involving brain, dura, skull base, lower
cranial nerves (IX, X, XI, XII), masticator space,
carotid artery, prevertebral space, or mediastinal
structures.
 Regional Lymph Node Metastasis (N0-3):

- Most important prognostic indicator for HNSCC.
- Consistent for all Head and Neck Mucosal tumors EXCEPT
Thyroid, Nasopharynx and Mucosal Melanoma.
 Nx: Regional LN cannot be assessed.
 N0: No regional LN metastasis.
 N1: Single ipsilateral LN ≤3cm.
 N2a: Single ipsilateral LN > 3-6cm.
 N2b: Multiple ipsilateral LN ≤6cm.
 N2c: Bilateral or contralateral LN ≤6cm.
 N3: Any LN >6cm.
 Thyroid Regional Lymph Node Metastasis (N):

 N1a: Metastasis to Level VI (pretracheal,
paratracheal, prelaryngeal/Delphian LN).
 N1b: Metastasis to cervical (Level I-V) or superior
Mediastinal lymph nodes (Level VII).
2288
Riyadh et al. Notes
 Nasopharynx Regional Lymph Node Metastasis (N):

 N1: Unilateral LN ≤6cm
 N2: Bilateral LN ≤6cm
 N3a: Any LN >6cm
 N3b: Extension to Supraclavicular fossa:
o Supraclavicular fossa (Ho's Triangle) is
bounded by medial (A) and lateral (B) ends
of clavicle and the point (C) where neck
meets the shoulder.
o It includes caudal portions of levels IV and V
 Mucosal Melanoma Regional Lymph Node

Metastasis (N0-1):
 N1: Regional LN metastasis present.
 Distant Metastasis (M0-1):

- Any SCC involves Level VII lymph node is considered
Distant Metastasis for palliative therapy.
- Lung Metastasis is NOT a contraindication for surgical
excision in Thyroid and Salivary glands tumors.
 Mx: Distant metastasis cannot be assessed.
 M0: No distant metastasis.
 M1: Distant metastasis present.
2289
Riyadh et al. Notes
o Staging:
- Grouped TNM classification.
- Used to guide treatment plan and apply statistical data such as
prognosis and treatment effectiveness.
o Early Stage (I-II):
 Single modality treatment plan:
o Surgery or Radiation.
o Advanced Stage (III-IV):
 Double modality treatment plan:
o Surgery and Radiation
or
o Chemotherapy and Radiation.
o TNM Staging Table is applied for All Head and Neck

Cancers Except Thyroid and Nasopharynx.
 Any T4 is considered Stage IV (Advance Stage).
 Any N1 is considered Stage III (Advance Stage).
 Any N2-3 is considered Stage IV (Advance Stage).
 Any M1 is considered Stage IV (Advance Stage).
o Pathological staging > Radiological > Clinical staging.

o Up-Staging Theory:
 If in doubt about the staging  Upstage.
2290
Riyadh et al. Notes
Management Plan of H&N Cancers:
- Discuss the case in H&N Tumor Board.

- Consultations:
o Dental:
 Evaluate dentition and possibility of teeth extraction
before radiation therapy.
o Plastic/Reconstructive Surgery:
 Evaluate complex reconstructive issues including free-flap
transfer if needed.
o Neurosurgery:
 Assist in certain skull base and cranial procedures.
o Ophthalmology:
 Assist in surgical management of the eye.
o Prosthodontics:
 Preoperative consultation if oral-maxillary, orbital, and
other head and neck prostheses needed.
o Dermatology:
 Mohs micrographic surgery for dermal lesions.
o Vascular Surgery:
 Consultation for possible carotid resection or bypass.
o Medicine:
 Preoperative evaluation (preoperative clearance),
management of coexisting medical conditions.
o Dietitian:
 Considered preoperatively for malnourished patients to
assess nutrition status and recommend methods to obtain
a positive nitrogen balance.
o Speech and Swallow Therapy:
 Considered postoperatively to assess swallowing and
speech and provide therapy.
- Treatment Concepts:
o Goal of treatment is maximizing survival with preservation of
form and function.
o Treat the Neck mets with same modality used for treatment of
the primary tumor.
o Single-modality Therapy (Stage I-II):
 Primary surgery or radiation therapy alone.
o Double-modality Therapy (Stage III-IV):
 Surgery and Radiation
 Chemotherapy and Radiation.
o Surgical treatment is better for:

 Sinonasal + Oral.
o Non-Surgical treatment is better for:

 Pharyngeal + Laryngeal.
2291
Riyadh et al. Notes
Principles of Oncologic Surgical Therapy:

- The goal of oncologic surgery is complete tumor resection with
histologic verification of tumor-free margins.
- If surgery is the chosen modality of treatment, think of 4 points:
1. Primary Tumor:
 Resection with 1cm safe margin.
 Approach.
2. Neck Dissection:
 Type.
 Unilateral or Bilateral.
3. Reconstruction.
4. Airway i.e. Tracheotomy.
- Operability vs Resectability:
- Operability is with regard to the patient:
o Inoperable: Operation cannot be done because of either:
 Poor general condition of the patient (unfit), or
 Surgery can not cure the malignant disease.
 Ex: Distant metastasis.
- Resectability is with regard to the tumor:

o Unresectable: Tumor infiltrates vital structures (T4b).
 Ex: Encasement of common or internal carotid artery.
- Inoperable disease may still be resectable, but that is not going to

offer a cure for the malignant disease.
o SCC with distant metastasis is considered inoperable, but the
lesion may be locally resectable.
- Assessment of Resectability:
- Unresectable tumors are associated with poor prognosis.
- Based on ability to obtain clear margins due to involvement of (T4b):
1. Skull base:
 Erosion of pterygoid plates or sphenoid, widening of
foramen ovale.
2. Nasopharynx:
 Deep extension into eustachian tube and lateral
nasopharyngeal walls.
3. Pterygoid muscles with severe trismus or pterygopalatine
fossa involvement with cranial neuropathy.
4. Direct extension to mediastinum , prevertebral fascia, or
cervical vertebrae.
5. Encasement of common or internal carotid artery.
 Encasement is assessed radiologically and defined as a
tumor surrounding the carotid artery by 270 degrees or
greater.
6. Direct extension of neck disease to involve external skin.
7. Presence of subdermal metastases.
2292
Riyadh et al. Notes
- Primary Tumor Resection:

- En-bloc resection is recommended.
- Peri-neural invasion is suspected when tumors are adjacent to nerves.
o Nerve should be dissected both proximally and distally and
should be resected to obtain clearance of disease.
o Frozen section determination of proximal and distal nerve
margins may prove helpful to facilitate tumor clearance.
- Primary tumor should be assessed histologically for:

o Depth of invasion.
o Distance from invasive tumor to margin of resection, including
peripheral and deep margins.
- Tumor Margins:
- Tumor-free margins are essential to decrease risk of local recurrence.
o Positive margins are an indication for post-op adjuvant therapy.
- Achievement of adequate wide margins may require resection of an
adjacent structure.
- Clear Margin: ≥5mm from invasive tumor to resection margin.

- Close Margin: <5mm from invasive tumor to resection margin.
- Positive Margin: Carcinoma in situ or invasive carcinoma at resection
margin.
- Margin assessment can be done by:

1. Frozen section:
 Done intra-op (Real time).
 Indicated if there is uncertain clear margins due to:
 Indistinct tumor margins
 Suspected residual disease (soft tissue, cartilage,
carotid artery, or mucosal irregularity).
2. Formalin-fixed tissues.
- Surgical Management of Cranial Nerves (VII, X, XI, XII):

- Influenced by pre-op clinical function.
o Pre-op Functioning Nerve:
 Preserve structure and function of the nerve even if
otherwise adequate tumor margins are not achieved.
 Should not leave any gross residual disease.
 Adjuvant post-op Radiation or Chemoradiation is
prescribed when a microscopic residual or gross residual
tumor is suspected.
o Pre-op Paralyzed Nerve (Direct Nerve Invasion):

 Segmental resection (and nerve grafting) if tumor-free
margins are assured throughout the remainder of the
procedure.
2293
Riyadh et al. Notes
- Neck Dissection:
- Removal of regional lymphatics and surrounding fibrofatty tissue.
- Indicated in positive neck or tumors with high risk to develop occult
metastasis.
- Indications of Neck Dissection:

1. Tumors with N+.
2. Tumors with N0 and high risk of occult disease.
3. Salvage surgery
- Indications of Bilateral Neck Dissection:

1. Midline tumors
2. Tumors crossing the midline
- Regional Lymph Nodes of the Neck:

- Level Ia (Submental LN):
o Anatomical Landmark:
 Bounded by bilateral anterior bellies of
digastric muscles and hyoid.
o Radiological Landmark:
 Lymph nodes located anterio-medially
to horizontal line passing from posterior
border of submandibular gland.
o Drainage Sites:
 Floor of mouth, Anterior tongue,
Anterior mandibular alveolar ridge, and
Lower Lip.
- Level Ib (Submandibular LN):

 Bounded by anterior and posterior
bellies of digastric and body of
Mandible.
 Lymph nodes located anterio-laterally
to horizontal line passing from posterior
border of submandibular gland.
o Drainage Sites:
 Oral cavity, Anterior Nasal Cavity, soft
tissue structures of the mid face, and
Submandibular gland.
2294
Mcq The hypoglossal nerve lies in level II of the neck immediately
below and deep to the posterior belly of the digastric tendon.
Riyadh et al. Notes Attempts to control bleeding in this area without nerve
identification place the nerve at risk.
- Level II (Upper Jugular / Jugulodigastric LN):
o Related to upper third of internal jugular vein.
o Spinal Accessory Nerve (CN-XI) travels obliquely across this
area.
o Level IIa:
 Clinical Landmark:
 From Skull base to Hyoid bone.
 Surgical Landmark:
Inferomedial to  From posterior belly of digastric to
Carotid bifurcation.
accessory nerve
 Anterior to Spinal Accessory Nerve
(CN-XI).
 Radiological Landmark:
 Lymph nodes located between 2
horizontal lines passing from posterior
border of submandibular gland and
posterior border of SCM from Skull
base to hyoid.
 Drainage Sites:
 Oral cavity, nasal cavity, nasopharynx,
oropharynx, hypopharynx, larynx, and
parotid gland.
Level IIb:
o
 Clinical Landmark:
 From Skull base to Hyoid bone.
 Surgical Landmark:
 From posterior belly of digastric to
Superolateral Carotid bifurcation.
to accessory  Posterior to Spinal Accessory Nerve
nerve (CN-XI).
 Lymph nodes located between 2
horizontal lines passing from
posterior border of submandibular
gland and posterior border of SCM
from Skull base to hyoid.
 Drainage Sites:
 Oral cavity, nasal cavity,
nasopharynx, oropharynx,
hypopharynx, larynx, and parotid gland.
2295
Riyadh et al. Notes
- Level III (Middle Jugular LN):

o Related to Middle third of internal jugular vein.
o Clinical Landmark:
 From Hyoid bone to Cricoid.
o Surgical Landmark:
 From Carotid bifurcation to Omohyoid.
 Lymph nodes located between 2 horizontal
lines passing from posterior border of
submandibular gland and posterior border of
SCM from hyoid to cricoid.
o Drainage Sites:
 Oral cavity, nasopharynx, oropharynx,
hypopharynx, and larynx.
- Level IV (Lower Jugular LN):

o Related to Lower third of internal jugular vein.
o Clinical Landmark:
 From Cricoid to Clavicle.
o Surgical Landmark:
 From Omohyoid mucle to Clavicle.
 Lymph nodes located anterior to horizontal
line passing from posterior border of SCM
from hyoid to cricoid lateral the carotids.
o Drainage Sites:
 Larynx, hypopharynx, thyroid, and cervical
esophagus.
- Level V (Posterior Triangle LN):

o Located along lower half of the spinal accessory
nerve and transverse cervical artery.
o Level Va:
 Anatomical Landmark:
 From Apex of Convergence of SCM and
trapezius muscle to horizontal plane
crossing the inferior border of cricoid.
 LN Associated with Spinal accessory
nerve (CN-XI)
 Lymph nodes located posterior to
horizontal line passing from posterior
border of SCM.
 Drainage Sites:
 Drains nasopharynx, oropharynx, and
skin of the posterior scalp and neck.
2296
Riyadh et al. Notes
o Level Vb:
 Anatomical Landmark:
 From horizontal plane crossing the
inferior border of cricoid to Clavicle.
 LN Associated with Transverse Cervical
and supraclavicular nodes.
 Lymph nodes located posterior to
horizontal line passing from posterior
border of SCM.
 Drainage Sites:
 Drains nasopharynx, oropharynx, and
skin of the posterior scalp and neck.
 Virchow's lymph node is located in
left supraclavicular fossa and drains
internal abdominal organs (Stomach mainly).
- Level VI (Central Compartment):

 Extend in midline from hyoid bone to
Suprasternal notch between the carotids.
 Paratracheal LN:
o Located in Tracheoesophageal
groove.
 Pretracheal LN:
o Located in front of the trachea
 Parathyroidal LN:
o Located around the thyroid gland
 Precricoid or Delphian LN:
o Located on Cricothyroid
membrane.
 Lymph nodes located anterior to horizontal line passing
from posterior border of SCM medial to carotids.
o Drainage Sites:
 Drains Thyroid gland, subglottic larynx, cervical trachea,
hypopharynx, and cervical esophagus.
- Level VII (Anterior Superior Mediastainal):

 Landmark:
 Extends from suprasternal notch to Innominate
artery, behind manubrium and between
Common carotid arteries.
 Clinical Importance:
 Any SCC involves Level VII is considered
Distant Metastasis for palliative therapy.
2297
Riyadh et al. Notes
- Classification of Neck Dissections:
1. Radical Neck Dissection (RND):

o Removes all the followings:
submandibular 1. Level (I-V) Lymph Nodes.
salivary gland, tail 2. Spinal Accessory Nerve (SAN)
of the parotid and 3. Internal Jugular Vein (IJV).
omohyoid muscle. 4. Sternocleidomastoid Muscle (SCM).
o Indications:
1. Recurrence or Residual disease.
2. Involvement of SAN, IJV and SCM.
3. Advance nodal disease (N3).
o Advantages:
1. Technically easier.
2. Lower risk of residual disease
o Disadvantages:
1. Neck deformity (Removal of SCM).
2. Shoulder drop (Removal of SAN).
3. Risk of facial edema (Removal of IJV).
4. Hyposthesia of Neck and periauricular region.
2298
Riyadh et al. Notes
2. Modified Radical Neck Dissection (MRND):

o Indicated in patients with N1-N2.
o Types:
1. Type I:
 Removes the following:
1. Level (I-V).
2. IJV.
3. SCM.
 Spares SAN.
 Indicated in N1 and N2 with involvement of these
structures (Intra-op Decision).
submandibular salivary
2. Type II:
 Removes the following:
gland, tail of the parotid
1. Level (I-V). and omohyoid muscle.
2. SCM.
 Spares SAN and IJV.
 Indicated in N1 and N2 with involvement of these
structures (Intra-op Decision).
3. Type III (Functional/Bocca):
 Removes level (I-V) only.
 Spares SAN, IJV and SCM.
 Indicated in N1 and N2 without involvement of
these structures.
o Advantages:
1. Lower morbidity.
o Disadvantages:
1. Technically more difficult.
2. Higher risk of residual disease.
2299
Riyadh et al. Notes
3. Selective Neck Dissection:

o Neck dissection with preservation of one or more LN groups.
o Indicated only in N0 with high risk of occult metastasis (≥20%).
o Levels removed depend on the location of the primary lesion
and its known pattern of spread.
o Subtypes:
1. Supraomohyoid (Anterolateral) Neck Dissction:
 Removes levels I–III.
 Extended supraomohyoid removes level IV.
 Indications:
1. N0 Oral cavity.
2. N0 Salivary glands.
2. Lateral Neck Dissection:
 Removes levels II–IV.
 Typically bilateral.
 Indications:
1. N0 Oropharynx.
2. N0 Hypopharynx.
3. N0 Larynx.
3. Posterlateral Neck Dissection:
 Removes levels II–V.
 Indications:
1. Scalp.
2. Nasopharynx.
3. N1b Thyroid.
4. Anterior (Central) Neck Dissection:
 Removes Level VI.
 Indications:
1. N1a Thyroid.
2. Parathyroid.
3. Subglottic.
4. Cervical esophagus.
4. Extended Neck Dissection:

o Any Neck dissection with additional removal of any structure
other than Lymph node levels I-V, SAN, IJV and SCM.
2300
Riyadh et al. Notes
- Clinically Negative Neck (N0):

o Tumors with Low risk (<20%) of occult metastasis:
 Management is observation.
 No Neck Dissection in N0 Sinonasal tumors.
 Lymphatic drainage is mainly to Retropharyngeal.
o Tumors with High risk (≥20%) of occult metastasis:
 All tumors with N0 and ≥T2, Except:
 N0 and ≥T1:
o Oral tongue.
o Piriform sinus.
 N0 and ≥T3:
o Glottic.
 N0 and ≥T4:
o Hard palate.
o Subglottic.
 Management:
 Selective Neck Dissction (SND).
- Indications of ND in N0 Oral cavity Ca (Supraomohyoid ND):

o Oral Tongue ≥T1
o Others ≥T2
Mcq o Hard Palate ≥T4
- Indications of ND in N0 Pharyngeal Ca (Bilateral Lateral ND):

o Piriform sinus ≥T1
o Hypopharynx and Oropharynx ≥T2
- Indications of ND in N0 Laryngeal Ca (Bilateral Lateral ND):

o Supraglottic ≥T2
o Glottic ≥T3
o Subglottic ≥T4
- Indications of ND in Nasopharyngeal Ca:

o Reccurence.
o If primary tumor was treated surgically.
- Indications of ND in Thyroid Ca:

o DTC N1a  Central (VI) ND.
o DTC N1b:
 If Ipsilateral LN:
 Ipsilateral Posterolateral + Central (II-VI) ND.
 If Contralateral LN:
 Ipsilateral Posterolateral + Central (II-VI) ND.
 Contralateral Lateral (II-VI) ND.
o Medullary Thyroid Ca:
 Bilateral Posterolateral + Central (II-VI) ND.
2301
Riyadh et al. Notes
- Indications of ND in Salivary Glands Ca:

o High Grade Tumors:
 N0 and ≥T1  Supraomohyoid ND.
 N+ve  MND.
o Low Grade Tumors:
 N0 and ≥T3  Supraomohyoid ND.
 N+ve  MND.
- Complications of Neck Dissection:
- Wound infection:
o Higher incidence in:
 Irradiated neck
 Soilage of wound by saliva, tracheal or gastric secretions.
 Tight wound closure
 Immunocompromised
 Malnourished
 Presence of foreign body
 Hematoma
 Seroma
o Treatment:
 Aggressive antibiotic regimen
 Monitor for fistula
 Control diabetes
 Optimize nutrition
 Meticulous wound care (debridement, wet to dry
dressings)
 Evaluate potential for carotid blowout.
- Shoulder dysfunction:
o Most commonly in patients underwent RND due to removal of
spinal accessory nerve supplying the trapezius muscle.
o However, any type of neck dissection may result in impairment
of function of the shoulder.
o Results in:
 Shoulder pain
 Shoulder drop
 Winged scapula
 Inability to abduct the shoulder above 90 degrees.
o If any deficit is detected, the patient should be properly
counseled and coached to ensure proper rehabilitation of the
shoulder.
2302
Riyadh et al. Notes
- Hematoma:
o Prevented by:
 Meticulous hemostasis
 Placement of suction drains.
o If detected early:
 Milking the drains may result in evacuation of
accumulated blood.
o If massive hematoma or blood re-accumulates quickly:
 Best to be managed in OR by exploration of the wound
under sterile conditions and evacuating the hematoma
after controlling the bleeding.
o Failure to recognize or manage postoperative hematoma
properly may predispose to development of wound infection.
- Facial/Cerebral Edema:
o Resulted from synchronous bilateral RNDs due to IJVs ligation.
o Facial or cerebral edema results from a mechanical problem of
venous drainage which may resolves with time as collateral
circulation is established.
o More common and more severe in previously irradiated patients.
o Cerebral edema presents with syndrome of inappropriate
secretion of antidiuretic hormone (SIADH), impaired neurologic
function or coma that occur after bilateral RND.
o Prevented by:
 Preserving at least one EJV whenever bilateral RND is
anticipated.
 Reconstructing one IJV using saphenous vein graft.
- Chyle Leak:
o Occurs in 1-2% of neck dissections.
o Typically left-sided in 95–97%.
o Chyle consists of fat, protein, electrolytes and lymphocytes.
o Results from injury to the thoracic duct:
 Thoracic duct is the conduit for lymph and dietary fat to
reach the venous bloodstream.
o Clinical picture:
 Odorless milky appearance fluid in the drain.
 Apparent after few days of starting enteral feeding.
o Fluid analysis:
 Total fat composition of 0.4-4 g/L.
 Total protein greater than 30 g/L. triglyceride level > 110
 Lymphocyte predominance. mg/ dl is diagnostic of a
o Complications: chyle leak. Scott
 Electrolyte disturbance
 Hypovolemia
 Hypoalbuminemia
 Wound infection
 Chylothorax
2303
The thoracic duct is located at the base of the
neck, medial and deep to the carotid artery and
Riyadh et al. Notes Mcq vagus nerve” Posterior to the carotid artery”. It
may have multiple branching tributaries.
o Prevented intraoperatively by:
avoided by meticulous  Bloodless operative field while dissecting around the
dissection in Level IV thoracic duct.
to avoid injuring the  Observing the area of the thoracic duct while asking the
thoracic duct anesthesiologist to do Valsalva maneuver.
 Intraoperative control of any apparent leak with ligation
or clipping of any visualized or potential lymphatic
tributaries.
o Management: This complication is best
 Conservative management: treated if recognized
 Head elevation. intraoperatively with suture
 Closed-wound drainage ligature or oversewing local
 Pressure dressings muscle flaps
 Enteral diet modification:
o Low-fat nutritional support.
o Medium-chain triglycerides:
 Absorbed directly into the portal
circulation bypassing the lymphatic
system.
 Replace fluid and electrolytes.
 Octreotide administration.
 Parenteral alimentation through central line:
o Indicated for high-output or intractable
fistulae.
 Indications of early surgical exploration:
 Daily output of chyle exceeds 600 ml.
 Failure of conservative measures (>1 week).
 Cachexia.
 Chylothorax.
Mcq The mainstay of all management strategies is nutritionally based. It is based

on the theory that reducing formation of chyle slows down the flow and
thus allows the fistula to heal.
2304
Riyadh et al. Notes
- Surgical Defect Reconstruction:

- Primary closure is recommended.
o Should not be done at expense of obtaining wide, tumor-free
margins.
- Follow the Reconstructive ladder:
1. Primary closure
2. Delayed closure
3. Split thickness skin graft (STSG)
4. Full thickness skin graft (FTSG)
5. Random pattern flap
6. Pedicled flap
7. Free flap
- Indications of Post-op Adjuvant Radiation alone in H&N

Cancers:
1. Advance Stage (III -IV).
2. Peri-neural invasion.
Mcq 3. Vascular invasion
4. Positive margin.
5. Depth > 4mm (Oral cavity)
6. High grade (Salivary glands)
- Indications of Post-op Adjuvant ChemoRadiation in H&N

Cancers:
1. Nodal extra-capsular invasion.
2. Positive margin.
2305
Riyadh et al. Notes
- Post-treatment Follow-up Plan:
- Regular Follow-up every:

o 1 month for 1st year post-therapy.
o 2 months for 2nd year post-therapy.
o 3 months for 3rd year post-therapy.
o 6 months for 4th year post-therapy.
o 1 year for 5th year and afterward post-therapy.
- PET/CT:
o Initial post-treatment surveillance done >3 months after
conclusion of therapy then Annually.
- Annual investigations:
o Chest Radiographs (Consider CT of primary site and chest)
o Thyroid function tests (Post radiation therapy to the neck)
o Liver enzymes.
o EBV monitoring for Nasopharynx.
Prognostic Evaluation of H&N Cancers:

- Overall 5-year survival of H&N cancers is <40%.
o 50–60% of mortality is from failed loco-regional control.
o 20–30% of mortality is from metastatic disease.
o 10–20% of mortality is from second primaries.
- Premorbid conditions account for mortality of:

o 30–35% of early-staged H&N cancers patients.
o 10–15% of late-staged H&N cancers patients.
2306
Riyadh et al. Notes
- Risk Factors for Poor Prognosis in H&N cancer:
1. Presence of regional nodal disease

 The strongest predictor of prognosis for H&N cancers.
 Decrease survival as much as 50%.
2. Invasiveness (T) and metastasis (M) within each site:

 T1 H&N cancers survival rates is 80%.
3. Increased tumor thickness and volume determined by

CT/MRI:
 Especially if >4mm in depth.
4. Presence of abundant lymphatic drainage at primary site:

 Increases risk of regional disease.
5. Character of Nodal Disease:

1. Presence of nodal extracapsular spread.
2. Increased number of positive nodes.
3. Presence of metastasis to lower nodal levels (level IV-V).
4. Skipped nodes (Nodal involvement of level II and IV
without involvement of level III).
5. Lymphocyte-depleted pattern immunomorphology of the
lymph node.
6. Vascular and Perineural Invasion:

 Histological predictors of cancer spreading beyond the
margins of resection, indicate aggressive cancer behavior.
7. Cytomorphometric Parameters: (controversial)

 Number of chromosome set (ploidy) may predict
prognosis.
 Aneuploid is associated with worse prognosis than
diploidy.
o Grade of Tumor differentiation is not an important

determinant in prognosis for most head and neck
cancers.
2307
Riyadh et al. Notes
- Unknown Primary Tumors:

- Malignant neoplasm metastatic to cervical lymph nodes without an
identifiable primary tumor following a comprehensive evaluation.
o In most cases, primary tumor will be found by physical exam,
imaging, or endoscopic evaluation.
- 5-10 % of patients presenting with nodal metastases will have an
occult primary tumor.
o Tumor regression due to patient immunity.
o Too small tumor (5 mm) to be seen on endoscopy and imaging.
o Tumor located in a location that may escape notice:
 Tonsillar crypts.
 Cutaneous primary tumors.
 Tumors outside H&N.
- Squamous cell carcinoma (SCC) is the most common histotype,

followed by adenocarcinoma, undifferentiated carcinoma and others.
- Pattern of Nodal involvement:

o Most commonly Level II then level III.
o Unilateral lymph node involvement is more common.
o Bilateral adenopathy is present in about 10% of patients.
o Location of neck nodes may provide information regarding
location of primary tumor:
 Level I: Not Oropharynx.
 Levels II-III: Oropharynx.
 Level IV: Thyroid, Infraclavicular primary.
 Level V: Nasopharynx.
- By using a thorough physical examination, Panendoscopy, and imaging
findings, Occult primary site is discovered in 20–40% of cases.
- Most common site of occult primary tumor:
o Tonsil:
 75% from ipsilateral tonsillar fossa.
 5% from contralateral tonsillar fossa.
 10% from bilateral tonsillar fossa.
o Base of tongue.
o Pyriform sinus.
- Evaluation of patients with unknown primary:

o Full History and Complete H&N physical examination:
1. All cranial nerves.
2. Head and scalp.
3. Neck.
4. Oral cavity.
5. Nasal cavity.
6. Nasopharynx.
7. Oropharynx.
8. Hypopharynx.
9. Larynx.
2308
Riyadh et al. Notes
o Imaging studies:
 CT or/and MRI with contrast.
 Head and Neck.
 Chest, Abdomen and Pelvis.
 PET/CT:
 Detects tumor ≥5mm in size.
 Helps to direct site of the biopsy.
 Supplement but not a substitute, for endoscopy
and biopsy in the setting of an unknown primary
due to risk of false negative results.
 False positive results:
o Lymphoid tissue.
o Salivary glands
o Prior biopsy.
o FNA:
 U/S guidance helps to target solid component.
 Immunohistochemical stain to exclude Lymphoma.
 EBV detection for Nasopharyngeal primary.
 HPV detection for Oropharyngeal primary.
o EUA + Panendoscopy:
1. Direct Laryngoscopy.
2. Esophagoscopy.
3. Bronchoscopy.
o Multiple Biopsies:
- Ideally, biopsies should be performed after PET scan.
o Allows biopsy of suspected area in PET.
o Avoids false positive PET-scans at biopsy site.
- Biopsy sites:
1. All suspicious sites clinically and radiologically.
2. Sites of possible origin of the primary:
1. Nasopharynx.
2. Base of the tongue.
3. Pyriform sinus.
4. Supraglottic area
5. Bilateral Tonsillectomy
o Other diagnostic procedures:

- Upper and Lower GI endoscopy mainly in patients with
metastases to the left lower cervical (supraclavicular)
lymph nodes.
2309
Riyadh et al. Notes
- Management of Unknown Primary Tumors:

- If no primary tumor site was identified (Tx), the standard therapy
consists of:
1. Radiation therapy to all mucosal surfaces of H&N.
2. Neck:
 If N1:
 Ipsilateral Modified Radical Neck Dissection
(MRND).
OR
 Ipsilateral radiation of the neck.
 If N2-3:
 Ipsilateral Modified Radical Neck Dissection
(MRND).
AND
 Ipsilateral radiation of the neck.
- If occult primary tumor can be identified, treatment will be directed

according the primary site.
- Second Primary Tumors:

- Patients with primary HNSCC have a high rate (3-5% per year) of
developing second primary tumors than any other group of cancer
patients.
o Due to distribution of toxic effects from tobacco and alcohol.
- Major sites of involvement:

o Other H&N sites.
o Lung.
o Esophagus.
- Types of Second primary:

1. Synchronous:
 Second cancer occurs around the same time as the
primary tumor.
2. Metachronous:
 Second cancer occurs ≥ 6 months after the primary
tumor.
- Post-treatment surveillance can diagnose second primary lesions

earlier and more accurately allowing for potentially higher cure rates.
o PET/CT is modality of choice for identifying second
primary tumors.
o Routine post-treatment Panendoscopy has not been shown to be
effective in detecting second primary tumors.
2310
Chapter 103 (9) Hosam’s Note
extra chapter
PRINCIPLES OF CHEMOTHERAPY IN THE MANAGEMENT
OF HEAD AND NECK CANCER
Introduction
 Aimed at eradication of systemic cancer, or at an increase in locoregional
control
 Chemo can cure the following:
o Testicular cancer, Small-cell lung cancer, Ovarian cancer
o Lymphoma
o Leukemia
o Sarcomas of childhood or young adulthood
o Occasionally lymphoepithelial subtype of NPC
 Effective as adjuvant therapy in the following:
o Breast cancer
o Colon cancer
o Osteosarcoma
o Many solid tumors of childhood, as well as H&N to some extent
 Also effective in combo with rads for H&N and other intermediate-stage solid
tumours
 Success factors for chemo:
I. Tumour burden
II. Percentage of cells in a chemo-responsive phase of cell cycle
III. Number of cells with inherent/acquired resistance
IV. May dependent on specific mutation or protein expression
(cetuximab)
 Chemotherapeutic agent categories:
1. Alkylating agents: cross-link DNA; interfere with replication
 Nitrogen mustard; cyclophosphamide; chlorambucil
2. Antitumour antibiotics: also bind DNA
 Bleomycin; doxorubicin; mitomycin C
3. Platinum agents: also bind DNA
 Cisplatin; carbaplatin
MCQp 4. Antimetabolites: interfere with cellular metabolism
 Methotrexate; 5-FU; hydroxyurea; gemcitabine
5. Vinca alkaloids: interfere with mitotic spindle formation
 Vincristine; vinblastine; vinorelbine
6. Taxanes: stabilize microtubules; can’t do mitosis/cell division
 Paclitaxel; docetaxol
7. Topoisomerase I inhibitors: prevent unwinding of DNA
 Topotecan; irinotecan
8. Molecular targeted therapy
 Epidermal growth factor receptor (EGFR) inhibitor –
cetuximab
9. Vascular endothelial GF receptor inhibitor
I. sunitinib
10. Biologic response modifiers
 Including IFs and ILs, and tumor vaccines have a role in
renal cell carcinoma, melanoma, and some forms of
leukemia and lymphoma
 Ideal combination drugs: spectra of toxicity that do not overlap
H&N
1
Clinical Trials
 Phase I:
o Study tolerance and pharmacologic properties; study endpoint is
maximally tolerated dose and spectrum of toxicity
o Maximally tolerated dose: the dose at which 1/3 or fewer of the
patients have severe toxic reactions, is reached
o Typically, cohorts of 3-6 patients are treated with escalating doses of a
drug, usually starting with 1/10 the dose that was lethal to 1/10 of the
mice
 Phase II:
o Determine therapeutic activity or “efficacy” of new drug or combo in
specific disease at defined dose; endpoint is response rate
 Phase III:
o Compare successes in phase II with gold standard; usually randomized
and multi-centered
o Endpoints:
 Survival is most frequent endpoint
 Disease-free survival
 Disease-specific survival
 Overall survival
 Therapeutic activity and toxicity
 For example, a new treatment with similar activity but
less toxicity is considered superior
 Palliation of defined symptoms
Chemotherapeutic Response Definitions Using “Response Evaluation Criteria

in Solid Tumors” (RECIST)
 Complete response:
o Complete disappearance of all clinically detectable disease for at least
28 days
 Histologic/pathologic complete response:
o Complete disappearance of microscopic disease (at surgery/biopsy) for
at least 28 days
 Partial response:
o 50% or greater reduction in average tumor size, measured by means
of multiplying the two largest perpendicular dimensions or
o At least 30% decrease in the sum of the longest diameters (LD) of
target lesions, taking as reference the baseline sum LD
 Stable disease:
o Any reduction in average tumor size of less than 50% (30% by
RECIST).
o Neither a response or progression
 Progressive disease:
o Appearance of new lesions or
o A 25% (20% linear increase by RECIST) or greater increase of target
lesions
 Overall response rate: all CRs and PRs over all pts enrolled
H&N
2
Roles of Chemotherapy in H&N Ca

 Palliative: if presentation with distant mets or untreatable recurrence; 1/3 of
patients have response for 3-6/12
 Locoregional stage III/IV:
o Improves survival
 Unresectable: improved survival if used with RT v. RT alone
o Organs preservation
 Advanced disease of larynx/pharynx: chemo followed by RT can
preserve organs in 2/3 of pts without decreasing survival;
concurrent chemo/rads may be as good or better at preserving
organs with equivalent survival rates to surgery
Standard Chemo for Recurrence or Mets

 These agents generate response rates of 30% or less, with responses that are
almost exclusively partial and of short duration (2 to 6 months)
 Only potential cure is occasional metastatic NPC
 Paclitaxel and Docetaxel

o Among the most active drugs against head and neck cancer
o Stabilize tubulin polymers; prevent cell division
o Dose (Paclitaxel): 175 mg/ m2 Q 3 wks
Oxaliplatin is a
o Considered by many to be “first-line” agents for treatment of advanced
third-generation H&N ca (RR ~35%)
cisplatin analogue o S/E nausea & vomiting, joint pain, bleeding, hair loss, numbness RC
that is not
associated with  Cisplatin
nephrotoxicity or o Mainstay of treatment for H&N Ca
ototoxicity o Intracellular binding to DNA to interfere with function
o Dose: 60-120 mg/m2; over 2-6 hrs; Q3-4 wks
o S/E: nephro, neuro, ototoxic, N&V and myelosuppression
o PR of 15-30% for single agent given every 3-4/52
MCQp o Mildly better than methotrexate but more toxic
o Carboplatin is a little less effective, but has fewer side effects (less
nephro, neuro & N&V)
 5-fluorouracil
o S-phase specific uracil analogue that blocks both the enzyme
thymidylate synthase and conversion of uridine into thymidine
compounds
o DNA can not be synthesized due to lack of thymidine
o At most a 13% response rate when used alone
o Clearly potentiates effect of cisplatin; given in a 5-days continuous
MCQP infusion
o S/E: myelosuppression, mucositis, diarrhea, dermatitis, cardiac
toxicity and if high dose will be ataxia
 Methotrexate
o S-phase specific; binds to dihydrofolate reductase; inhibits
metabolism of folate and thereby inhibits DNA synthesis
H&N
3
o Inhibition of conversion of folic acid to tetrahydrofolate; result in

depletion of reduced folates which inhibit DNA synthesis
o It selectively affects tissues with more rapid cell turnover
o Leucovorin (reduced folates) within 36 hrs of drug admin can
significantly reduce side effects
o Weekly doses of 40-50 mg/m2
o PR of ~ 10%, duration 1-6/12; high dose no better, more toxic
o Usually given with cisplatin, 5-FU, Paclitaxel
o It is the minimal standard treatment; not first line
o S/E: myelosuppression, mucositis, dermatitis, N&V, diarrhea, and
hepatic fibrosis
Other Chemotherapeutic Drugs

 Bleomycine
o Combined with cisplatin or mtx
o Interstitial Pneumonitis MCQp
 Ifosfamide
o Alkylating agent
o Given in combination
Biologic Therapies Under Investigation

 Targets: growth factor receptors and receptor tyrosine kinases (RTK)
 EGFR is an RTK; monoclonal Ab and TK inhibitors are being developed
 Cetuximab (400 mg/m2 initially, followed by 250 mg/m2 weekly)
o AE’s: rash, infusion reactions, magnesium wasting, cardiac,
mucositis
o Most H&N Ca over express EGFR
o This drug is a monoclonal Ab that binds/blocks ligand bind site
o Currently under investigation as a single agent, in combination with
chemotherapy, and as a radiation sensitizer
 Gefitinib and Erlotinib
o Both are orally active small molecule TK inhibitors
Combination Chemotherapy
 Rational: cells resistant to one agent may be sensitive to another; also may
get some synergistic effect (cisplatin and 5-FU in vitro)
 In the management of H&N ca, most combinations are based on methotrexate
or cisplatin, and most recently on cisplatin or carboplatin, paclitaxel or
docetaxel, and 5-FU
 One of the “standard” combination is cisplatin followed by a 4- to 5-day
continuous IV infusion of 5-FU (RR ~35%)
 In the palliative setting, carboplatin is often substituted for cisplatin in
combination with a taxane
 Conclusions re combo therapy:
o They produce stat. sig. response rates over all single agents
o No combo has been shown to increase survival
o Cisplatin and 5-FU combo is more toxic than any single agent
o Treat metastatic pts in clinical trial whenever possible
Concomitant Chemoradiation Therapy (CRT)

 Both used together or in rapidly alternating sequence
 The early use of chemotherapy also can sterilize distant micrometastasis.
H&N
4
 Better than RT alone in the following settings:

 Unresectable advanced local disease
 Post-op in those likely to recur
 Surgery refusal
 CRT v. surgery + RT being studied currently
BENEFITS AND MECHANISMS OF CRT
1. Drugs and rads active against different tumour cell

subpopulations based on cell cycle specificity, pH, and O2
supply
2. CRT can increase tumour cell recruitment from G0 into rads
responsive cell-cycle phase
3. Shrinkage decreases tumour interstitial pressure and increases
drug/O2 delivery to the tumour
4. Early eradication prevents emergence of resistant
subpopulations
5. Cell-cycle synchronization increases efficacy of both therapies
6. Chemo inhibits repair of sub-lethal rads damage
Unresectable H&N Ca
 Long-term survival with rads alone is 10-30%
 Most frequently used single-agent drugs are 5-FU and cisplatin. Paclitaxel and
docetaxel also are commonly used. Cetuximab added to RT shown to be
superior to RT alone
 Most frequently used combination is cisplatin and 5-FU
 Metaanalysis of Chemotherapy on H&N Ca Collaborative Group (MACH-NC);
10,000 pts; 5-yr survival increase from 32% to 40% with CRT over RT alone
in unresectable disease
 Mechanisms are same as above
 Toxicities are higher, but only in the short-term; long-term adverse effects are
similar to RT alone
Post-op Adjuvant Chemoradiation Therapy

 Again, we’re comparing post-op CRT to post-op RT alone
 Several studies show clear increases in LR control and 5-yr survival in “high
risk” pts (extracapsular spread, etc.)
 European Organization for the Research and Treatment of Cancer
(EORTC); 334 high risk pts (see bullets below for definition) with resected
SCC of OC, OP, L and HP; post-op RT alone v. CRT with cisplatin (100
mg/m2); overall survival of 53% v. 40% with 18% LR relapses v. 31%; 41%
v. 21% severe mucositis
o All T3 or T4 except T3N0 laryngeal
o Positive margins
o Extracapsular extension
o Perineural invasion
o Vascular invasion
o OC or OP primaries with level IV or V nodes
 Radiation Therapy Oncology Group (RTOG); 459 high risk pts (see bullets
for definition) with resected SCC of OC, OP, L or HP; CRT with cisplatin v.
H&N
5
post-op RT alone; 40% v. 30% 4-yr disease-free survival; 19% v. 30% LR

relapses; overall survival not significantly different; 77% v. 34% acute severe
mucosal toxicities; long-term toxicity rates were comparable.
o Positive resection margins
o Involvement of two or more lymph nodes
o Extracapsular nodal extension
Preoperative/Induction/Neoadjuvant Chemotherapy
 Most important: lower systemic tumour cell burden earlier, hopefully before
they become chemo-resistant
 Conclusions from many big randomized trials:
1) Overall response rates > 80% frequently achieved
2) Complete responce from 20-50%, averaging 30%
3) Toxicity is moderate to severe, but subsequent local therapy is not
compromised; small percentage of CR refuse further Tx
4) CR (especially Pathological confiirmed) have better prognosis
5) Laryngeal and HP SCC have higher potential for preservation
6) Rate of distant mets is decreased
7) Survival is not consistently improved (the decreased rate of distant
mets did not translate into a survival benefit)
 Veterans Affairs Laryngeal Cancer Study Group; advanced laryngeal Ca;
randomized to surgery followed by rads or chemo then rads, with salvage
surgery; identical survival (68%) with higher organ preservation in study arm
(64%)
 RTOG 91-11; stage 3 or 4 laryngeal Ca; three arms: RT with induction
chemo (5-FU and cisplatin), RT alone and CRT with cisplatin; 54-56% 5-yr
survival in all 3 groups; 84% laryngeal preservation in CRT group, 72% in
induction group and 67% for RT alone
 Final word: neoadjuvant not shown to be better than CRT, so it is
therefore still considered experimental
ADVANTAGES AND DISADVANTAGES OF INDUCTION CHEMO

FOR LOCALLY ADVANCED H&N CA
Advantages
1. Unimpaired drug delivery to tumour (vessels in tact)
2. Prompt elimination of micromets may aid in cure
3. Tumour may be downsized; allows better LR control
4. Patient performance status at surgery may be improved
Disadvantages
1. Original extent of tumour may be obscured
2. Performance status may decline
3. Tumour size may increase (progression) during
chemotherapy  a resectable tumor may become
unresectable, and the chance for cure is lost
4. Duration, toxicity and cost of treatment all increased
5. Cell that survive chemo may not respond to subsequent RT
H&N
6
Resectable H&N Ca
 No RCTs exist comparing CRT to surgery +/- RT. Results of several
indirect comparisons suggest CRT can be an alternative to surgery
 Lots of data comparing RT to CRT
 Those with stage III or IV disease who are likely to have functional or
cosmetic sequelae of the surgery and who need post-op radiation therapy
anyway should be offered an aggressive CRT regimen, as primary therapy, if
they are medically able.
Nasopharyngeal Ca
 Chemo considered standard therapy for all but the few early ones
 Metastatic, undifferentiated carcinoma, or lymphoepithelioma, of the
nasopharynx is highly sensitive to chemotherapy
 Intergroup trial in US: 147 pts randomized to RT, CRT with cisplatin, or RT
followed by cisplatin and 5-FU; RT alone did much worse (47% v. 78% 3-yr
survival); trial stopped early
Chemotherapy Complications
 ENT usually involved in some complications include:
o Chemotherapy-induced mucositis
o Tooth abscesses from dental caries in a neutropenic patient.
o Tonsillar or retropharyngeal abscesses.
o Chemotherapy commonly causes dysguesia
o Stridor and airway obstruction can be caused by allergic reactions to
chemotherapeutic drugs
H&N
7
Questions
1. What are the classes of chemotherapeutic action and their
mechanisms of action? Give an example of each.
2. Define phase I, II and III clinical trials.
3. What are the common chemotherapeutics used in H&N?
4. What are the common dosages and toxicities?
5. What are the advantages of combined chemo-XRT?
6. What is induction or neo-adjuvant chemotherapy?
7. What are the chemotherapeutic emergencies?
8. What is a new chemotherapeutic agent used for melanoma?
9. What is the only chemo agent shown to have an effect on thyroid Ca?
10. Name three genes that can be mutated to cause cancer.
11. Draw the staging table for H&N Ca.
H&N
8
Answers
1. See text
2. Phase I: assessing toxicities and maximum tolerated dose; Phase II:
assessing efficacy and response rates; Phase III: compare efficacy to gold
standard; Phase IV: new gold-standard gets more testing in large trials to get
more toxicity-related data
3. Methotrexate, cisplatin, 5-FU, paclitaxel
4. Dosage:
a. Cisplatin: 100 mg/m2; N/V, anemia, oto/nephro/neurotoxicity and
neutropenia
b. 5-FU: 1000 mg/day continuous infusion; mucositis, diarrhea,
myelosuppression, nausea and coronary spasm (5%)
c. Docetaxel: 60 mg/m2; alopecia, myelosuppression, mucositis,
neuropathy and allergic reaction
d. Methotrexate: 30 mg/m2 IV push; similar SE to 5-FU
5. May be active against different sub population (cell cycle, pH, O2 supply);
can increase tumor cell recruitment from G0 to XRT sensitive phase; tumour
shrinkage from XRT can increase blood flow and O2 and drug delivery;
chemo inhibits sub-lethal repair prior to next dose of XRT
6. Chemotherapy prior to XRT or surgery; it decreases local disease for improved
XRT or surgery; it may lead to improved response rates, but there is no
survival benefit
7. Emergencies include:
a. Neutropenic fever
b. Thrombocytopenia with bleed
c. Allergic reaction
d. Overdose
e. Extravasation
f. Tumor lysis syndrome (hydrate; alkalinize urine)
8. Interferon -2b; adjuvant therapy; high dose given daily for 5/52, then Q2-3D
for up to 11 months (Also imatinib – Gleevec in future)
9. Adriamycin
10. P53 deletion; RAS mutation; RET proto-oncogene translocation
11. Stging table
N0 N1 N2 N3 M1
T1 I IVc
T2 II
T3 III
T4a IVa
T4b IVb
Mimi Davis talk:

MACH-NC metanalysis 2009 – 6.5% benefit, 5yr vs. RT alone
H&N
9
The most commonly used particle for radiation therapy is= Photon
extra chapter
PRINCIPLES OF RADIATION ONCOLOGY
Radiation Physics
 Rads deposits energy in tissue by producing 2 charged particles
o X-rays (aka photons), gamma rays produce electrons
 Ionizing radiation deposits its energy in biologic material through the
production of secondary charged particles. With primary x-rays, gamma rays,
and electrons, the secondary particles are electrons, and these secondary
particles are ultimately responsible for inflicting the biologic injury
 Can be delivered through external beam (teleradiotherapy) or through
implant or mold (brachytherapy)
 External beam irradiation

o Most common beams and energies:
 Low-energy megavoltage x-rays (4-6 MV); not very deep
penetration; good for 7-8 cm deep (H&N)
 High-energy megavoltage x-rays (15-25 MV); very penetrating;
good for cancers 12-15 cm deep (pelvis)
 Range of electron beams (6-18 or 6-25 MeV); finite range;
spare deep tissue; used for superficial lesions
 6 MeV: skin or lip
 6-9 MeV: cervical nodes over spinal cord
 9-12 MeV: buccal mucosa
 15-18 MeV: tonsillar fossa and parotid
o X-rays and gamma rays are penetrating; very versatile
o Important characteristics include:
 Skin-sparing properties
 Depth dose (penetration)
 Isodose distribution (beam uniformity)
o Protons: immediate drop off distal to target; used for choroidal
melanoma and chordomas and clival tumours
o Neutrons: not useful; sledge hammers
 Brachyradiotherapy
o Interstitial: within tumour; intracavitary: within body cavity;
surface molds: onto epithelial surfaces
o Implants can be temporary (long-lived isotopes like radium 226,
cesium 137, iridium 192) or permanent (short-lived like gold 198,
iodine 125 or palladium 103)
o Advantages:
 Irradiation confined to the implant volume – higher dose to
tumour and lower dose to surrounding tissues
 Continuous delivery at low dose rate – better for hypoxic or
slowly proliferating lesions (see bio for why)
o Disadvantages:
 Must be able to implant entire tumour volume
 Lesion must be accessible and clearly demarcated
o If it’s the sole treatment, leave in for 5-7 days (70-80 Gy)
o Can be combined with ext beam; 40-50 Gy from beam, followed by 2-4
days of implant giving additional 30-40 Gy
H&N
1
The use of IMRT

employs multiple
 Conformal radiation therapy
o Better computing and imaging allow more targeted delivery beams to allow
o IMRT (intensity modulated radiation therapy) is one method effective tumor dose
 Treatment fields divided into hundreds of pencil beams while reducing dose
 Computer controls rads in each beam; machine rotates to uninvolved
tissues.
Radiation Biology
 Cell death
o All viable cancer cells must be eliminated; “dead” implies that they
can no longer proliferate indefinitely (doesn’t have to be lysed)
o Forms of cell death post rads include:
 Mitotic death (most common form): cells die while
attempting division; likely from DNA damage; may take a few
division cycles before death
 Apoptosis: rads induced apoptosis occurs in normal marrow
and salivary glands; also in lymphoid/hematopoietic tumours
 Random nature of cell kill

o Every cell has same chance of being killed by given dose
o Therefore a given dose kills a proportion of cells, not a number
 Reduction from 100 to 10 cells = same dose as reduction from
10 billion to 1 billion cells
o So, a 3 cm tumour needs more rads than a 1 cm tumour
 Repair of sublethal injury (Repair)

o Areas of dense ionization cause irreparable damage, but sparse
ionization causes sublethal damage – more hits needed
o Sublethal injury usually repaired in 3 hrs; can take 24 hrs
o Because of potential for repair, greater overall dose needed if given in
fractions v. giving it all at once
 More fractions = more repair = higher total dose
 The fewer the fractions, the smaller is the opportunity for repair
between fractions
o Flip side: normal tissue repairs better than tumour and needs the time
between fractions to recover
o Some melanomas have remarkable ability to repair – radioresistance;
may need hypofractionation
 Tumour cell hypoxia (Reoxygenation)

o Indirect damage: O2 combined with an electron in the outer shell of
free radicals (very labile) and forms stable O- radicals that cause tissue
damage; increases rads effect
o Need 2.5-3 fold higher dose to kill hypoxic tissue
o Tumour hypoxia is common
 Acute: capillaries get compressed or collapse
 Chronic: tumour outgrows blood supply
o Hypoxic cells usually reoxygenate during rads as others die
o Reoxygenation is one of the most important reasons for giving
rads over time in fractions
H&N
2
 Cell-cycle effect (Redistribution)

o S-phase (DNA synthesis) cells are more resistant than others
o Therefore, a single large dose of radiation is less effective in
controlling a tumor than is a fractionated course of radiation
o More fractions = greater chance of hitting sensitive phases
o This effect tends to offset repair benefit in fractionation
o Redistribution better for rapidly cycling cells
 Repopulation
o Accelerated repopulation occurs if tumour burden reduced – don’t stop
halfway with treatment (surgery or rads)
o This is theory behind hyperfractionation and the short delay
between incomplete resection and post-op rads
 Regression rates
o Cell loss after irradiation is due to lysis at the time of mitosis, and most
cells divide 4 or 5 times before lysis occurs.
o Rapidly proliferating tumors tend to regress quickly after irradiation
o Because lethally injured cells and surviving cells are morphologically
indistinguishable, biopsies are of little value in the early postirradiation
period, (may take a while before all tumour dies; Bx no good for 3/12)
 Radiosensitivity
 The biologic factors that determine the probability of local tumor control
are:
I. The number of malignant cells
II. The proportion of hypoxic cells
 Large  more cancer cells  more (hypoxic) tumours  less
radiosensitive
 If it looks exophytic, it’s probably relatively small, well
vascularized and oxygenated, and therefore
radiosensitive
 If it looks infiltrative and ulcerative, it’s likely bigger,
poorly oxygenated, and therefore resistant
 The probability of controlling a cancer with irradiation depends on the size
of a neoplasm and the dose of radiation
o 65 Gy in 6.5/52 controls 70% of 2-4 cm tumours
o 60 Gy in 6/52 controls 80-90% of 1-2 cm tumours
o 50 Gy in 5/52 controls > 90% of subclinical lesions
 The dose–response relation for small well-vascularized tumors is often quite
steep. A modest increase in dose can increase the probability of local tumor
control from 25 to 75%; because they are relatively homogeneous in size and
oxygenation.
 The dose–response relation for bulky tumors is not as steep as it is for small
tumors, however, because large tumors are much more heterogeneous, with
considerable variability in the number of cells and the state of oxygenation
 Histology has little to no effect on radiosensitivity
H&N
3
Treatment
 Selection of treatment modality
o Based on:
1) Size/location of primary
2) Node status
3) Pt condition
o Early lesions usually treated with one modality (Sx v. RT)
 Choice based on functional outcome post treatment
o More advanced get Sx and RT, or CRT with surgical salvage
o Palliative for bad recurrence or distant mets
 Radiation doses required for palliative are similar to those
required for definitive treatment
 RT alone
o The neck is irradiated if clinically positive or if a greater than a
15% risk of subclinical mets exists
o Dose depends on tumour size
 Small cancer  60 to 65 Gy in 6 to 6.5 weeks may be
adequate.
 Larger tumors  65 to 70 Gy in 6.5 to 7.5 weeks)
 Massive disease  ~70 to 75 Gy in 7.5 to 8 weeks)
o Shrinking field technique for boost as tumour regresses
o Spinal cord is limited to 45-50 Gy (radiation myelitis)
 Combined surgery and rads
o Rads fail because you can’t get all of bulky mass
o Surgery fails because of residual microscopic disease
o The dose of preoperative rads is usually smaller (45 Gy in 4.5/52)
o Presence of disease within 0.5 cm of the surgical margins has the same
prognostic implication as positive margins
o If the postoperative radiation therapy is delayed beyond 6 weeks, the
results are poor (typical post-op dose is 60-65 Gy in 6-7 wks)
o For the advantages & disadvantages of pre-op and post-op rad (see
the questions).
o See table 104.3 for recurrence rates based on margins
H&N
4
MCQp
radiation therapy used and the accompanying
chemotherapy. Such effects include mucositis,
odynophagia, dysphagia, hoarseness,
xerostomia, dermatitis, and weight loss.
MCQp cumming
Complications
 Acute – during course; subside a few weeks after rads done
 Late – permanent
o Salivary glands
 Xerostomia if glands get 35 Gy or more in 3.5/52
 Also causes dental damage “decay”
o Ulcers and soft tissue necrosis
 Caused by damage to vascular connective tissue
o Skin
 Severe reactions unusual with today’s technology
 Epilation (loss of hair) and dryness are common (loss of
sweat/sebaceous glands; epidermal thinning; telangiectasia)
 Early: moist desquamation
 Late: dry desquamation
o Fibrosis
 Major problem; dose limiting in H&N Ca Tx
 Woody texture; fixed into single hard mass
o Bone and cartilage necrosis (ORN)
 Most cases are secondary to necrosis of overlying soft tissue
o Eye
 Cataracts (6 Gy), radiation retinopathy (50 Gy), optic nerve
injury (50 Gy) and lacrimal gland damage (30 Gy) all possible
 The nasolacrimal system is usually quite radioresistant
o Ear
 Transient serous OM common
 SNHL rarely reported; likely more common than realized
o CNS
 Brain and SC injury are serious and can happen
 Transient myelopathy (electronic shock sensation triggerd by
flexing the cervical spine “Lhermitte sign” from as little as 30
Gy
 Transverse myelitis is rare; 50-60 Gy
 Somnolence syndrome (lethargy, nausea, HA, CN palsies and
ataxia) typically transient; appears 2-3 months after treatment
and lasts 2-4/52
 Brain necrosis is perminant injury; 65-70 Gy
Mcq
The lens of the eye is affected by 10 Gy and the optic chiasm at 55 Gy.
Permanent parotid salivary dysfunction can be expected after what total dose of
radiation 25 Gy
H&N
5
Questions
1. What is a Gray?
2. List the various types of external beam XRT.
3. What source is used most often for cancer of the H&N?
4. What is a guideline for the useful range in depth of penetration (cm)
with electron beams?
5. What are the advantages and disadvantages of brachytherapy?
6. What are the two mechanisms of injury in XRT?
7. What is the minimum number of cells required for a tumour to be palpable?
8. What are the four R’s of XRT?
9. What type of tumor is the most radio-sensitive?
10.What are the different types of fractionation?
11. What are the advantages and disadvantages of pre-op XRT?
12. What are the advantages and disadvantages of post op XRT?
13. What are some of the complications of XRT?
14. Name four ocular tissues that can be damaged by H&N XRT and state how
much energy is required to damage them.
15. What is the only true emergency of radiation therapy (bad enough to fire up
the machine in the middle of the night)?
16. What is bad enough to fire it up first thing the next morning?
17. What is IMRT?
18. What is the difference between IMRT and stereotactic radiosurgery?
19. What does radiotherapy do other than kill tumour cells?
20.How do you classify osteoradionecrosis?
21. What are the complications of stereotactic radiosurgery for CPA lesions?
22.How is mucositis graded according to the RTOG?
23. List some problems with the RTOG 91-11 trial.
24. What is shrinking-field technique? (ADDED)
25. Describe IMRT (ADDED)
H&N
6
Answers
1. One joule of energy absorbed per kg of tissue (1 Gray = 100 Centigray = 100
Rads); typically daily dose in 2 Gy
2. XRT beams include:
a. Mega-voltage x-rays
b. Low-energy (4-6 MeV) for 7 cm penetration
c. High energy (15-20 MeV) for 14 cm penetration (pelvis)
d. Photons (Gamma rays)
e. Electrons, protons, and neutrons
3. 6 MV (megaelectron volts) gamma ray beams
Rajaraman: x-rays do not equal gamma rays. Gamma rays have high
energy and are ionizing. These are used.
Gamma rays are photons and are what is most commonly used with
external beam radiation.
4. Energy in MeV divided by 3 (example: 9 MeV ÷ 3 = 3 cm)
5. Brachytherapy:
a. Advantages
1) Higher dose to tumour
2) Lower dose to surrounding normal tissue
3) Shorter treatment duration
b. Disadvantages
1) Technical expertise required for implantation
2) No good near bone (can cause osteoradionecrosis)
3) No good if regional LN involved
6. Direct (33%; x-ray directly damages critical target by knocking out electrons);
Indirect (66%; x-ray knocks electron out of O2 creating a free O- radical; it
then damages target tissue
7. 105 cells
8. Four R’s include:
a. Repair: sublethal injury; allows repair of normal tissue; most cells can
repair within 3 hours
b. Reoxygenation: hypoxic cells more radio resistant; fractionation allows
revascularization and relieves the pressure occluding vessels
c. Redistribution: cells in S-phase are less radiosensitive; fractionation
increases the likelihood that cells will be treated during their
radiosensitive phases
d. Repopulation: increased rate of growth if tumor population decreased
and treatment suddenly stopped; do not delay or halt XRT unless
necessary
Note: Repair & repopulation spare normal tissues
Reoxygenation & redistribution enhance tumour cell kill
9. Small, well-vascularized, rapidly-proliferation & homogeneous lesion
10. Fractionation (see picture on next page):
a. Conventional: 2 Gy OD x 5 days/wk for 6-8/52
b. Accelerated (same total dose; shorter time period): 2 Gy BID x 5
days/wk 3.5/52
c. Hyperfractionated (smaller individual fractions; same or slightly higher
total dose; same total time): 1.2 Gy BID-TID x 5 days/wk 6-8/52
d. Hypofractionation: higher daily dose
e. Concomitant boost (form of accelerated hyperfractionation): smaller
field given additional daily fraction for the last 12 days
H&N
7
11. Preoperative XRT (45 Gy in 4.5/52):

a. Advantages
1) Unresectable tumours may become resectable
2) May diminish extent of surgical resection
3) Treatment portals usually smaller preop than postop
4) Better blood supply preop so microscopic disease more sensitive
than in postop setting
5) Viability of disseminated cells during surgery is diminished, thus
decreasing likelihood of distant mets
b. Disadvantages
1) Decreased wound healing (smaller dose allowable)
2) Surgery more difficult
3) Lower dose available if margins positive postoperatively
12. Postoperative XRT:
a. Advantages
1) Better staging and anatomic extent
2) Can give a higher dose post-op
3) Surgery easier
4) Tissue heals better
5) Dose can be adjusted based on post-op tumour burden
b. Disadvantages
1) Theoretical increase in rate of distant mets
2) Potential delay in XRT if complications
13. Complications include:
a. Acute: mucositis (2nd week); skin (5th week)
b. Chronic: xerostomia; dental; soft tissue fibrosis/osteonecrosis; ocular
(see next quesition); otologic (SNHL; OME with CHL); CNS
(myelopathy; transverse myelitis; brain necrosis; somnolence
syndrome)
14. Ocular complications:
a. Lens: 6 Gy
b. Retina: 50 Gy
c. Optic nerve: 50 Gy
d. Lacrimal gland: 30 Gy
15. Spinal cord compression from radiosensitive lesion
H&N
8
16. SVC syndrome

17. Intensity-modulated radiotherapy
18. The beams in IMRT have variable intensities throughout the various pixels
within the beams (intensity modulated beams); in stereotactic radiosurgery,
the beams are of equal intensity throughout (like a normal beam), but there
are more of them and they are smaller
19. Antiinflammatory effect by modulating cytokines and prostaglandins; can
improve pain
20. Healing v. chronic (stable) v. acute (progressive); or early v. late
21. CPA radiosurgery complications:
a. Hearing loss (hearing preservation in 1/3)
b. Facial weakness (delayed facial weakness in 1/5)
c. Trigeminal dysfunction (1/5)
d. Prolonged imbalance (1/3)
e. Risk of malignancy induction (1/200 over 10 years)
22. Mucositis grading scheme:
a. Grade I: injection; may experience mild pain not requiring analgesics
b. Grade II: patchy mucositis which may produce an inflammatory
serosanguinous discharge; may experience moderate pain requiring
analgesia
c. Grade III: confluent fibrinous mucositis; severe pain; needs narcotics
for analgesia
d. Grade IV: ulceration, hemorrhage or necrosis
e. Grade V: death due to mucositis
23. RTOG 91-11:
a. Large T4 lesions were excluded
b. TL was the only surgical option offered
c. High rates of complications in those treated with salvage Sx
d. The best arm of the study had poor swallowing results
24. Shrinking-field technique:
 An initial dose of 45 to 50 Gy is delivered in 4 to 5 weeks through large
portals covering the clinically involved region and areas of potential
regional LN mets.
 After this, the fields are reduced to encompass only the gross tumor
with a small margin, and an additional 15 to 25 Gy is delivered,
bringing the total tumor dose to 60 to 70 Gy in 6 to 7.5 weeks.
 With massive tumors, often a second field reduction is given at 60 to
65 Gy. An additional 5 to 10 Gy is given with the final boost fields,
which cover the residual disease with small or no margins. The total
tumor dose is 70 to 75 Gy in 7 to 8 weeks.
25. Use CT & complex software using inverse planning, multi-leaf collimated
device consisting of beams with varying intensities to highly conform 3-D
tumour, sparing normal tissues.
26. SRT – rigid mobilization of structures to get precision to within 1mm.Many
beams, high precision.
Read over rest of Rajaraman’s lecture.
H&N
9

Principles of Oncology

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Riyadh et al.

Head and Neck:

disadvantage of elective neck irradiation (ENI) versus elective neck dissection

disadvantage of elective neck dissection (END) versus elective neck irradiation

the most common complication of tracheoesophageal (TE) voice restoration = TE

- H&N cancers makes up about 10% of all malignancies excluding skin.

- Risk Factors for H&N Cancers:

2. Human Papilloma Virus (HPV):

3. Epstein-Barr Virus (EBV):

4. Human Immunodeficiency Virus (HIV):

5. Herpes Simplex Virus (HSV):

7. Betel Nut Chewing:

10. Genetic Factors:

11. Other Risk Factors:

- HNSCC starts on the surface and spreads superficially, deeply, and

- General Classification of H&N Tumors:

Evaluation of H&N Patient in Clinic:

- Important Keypoints in History:

Physical Examination (8 Areas):

- Important Keypoints in Physical Examination:

o Characteristics of Benign Lymph node in US:

o Characteristics of Pathologic Lymph node in US:

- Computed Tomography (CT) with Contrast:

- Magnetic Resonance Imaging (MRI) with Contrast:

o Indications of MRI in H&N Tumors:

- Positron Emission Tomography (PET):

o Indications of PET/CT in H&N:

o Nuclear Medicine Studies:

o Fine Needle Aspiration (FNA):

 Steps required to improve accuracy of FNA results:

 Sensitivity and specificity rates are 85-90%.

 Selective results with FNA:

o Core Needle Aspiration (CNA):

o Common Immunohistochemical Markers:

- Diagnostic and Ancillary Procedures:

- Determine Classification of Neoplasms:

o Lip and Oral Cavity (T):

o Maxillary Sinus (T):

o Nasal Cavity and Ethmoid Sinus (T):

o Salivary Glands (T):

o Thyroid Gland (T):

o Mucosal Melanoma (T):

 Regional Lymph Node Metastasis (N0-3):

 Thyroid Regional Lymph Node Metastasis (N):

 Nasopharynx Regional Lymph Node Metastasis (N):

 Mucosal Melanoma Regional Lymph Node

 Distant Metastasis (M0-1):

o TNM Staging Table is applied for All Head and Neck

o Pathological staging > Radiological > Clinical staging.

Management Plan of H&N Cancers:

- Discuss the case in H&N Tumor Board.

o Surgical treatment is better for:

o Non-Surgical treatment is better for:

Principles of Oncologic Surgical Therapy:

- Resectability is with regard to the tumor:

- Inoperable disease may still be resectable, but that is not going to

- Primary Tumor Resection:

- Primary tumor should be assessed histologically for:

- Clear Margin: ≥5mm from invasive tumor to resection margin.

- Margin assessment can be done by:

- Surgical Management of Cranial Nerves (VII, X, XI, XII):

o Pre-op Paralyzed Nerve (Direct Nerve Invasion):