KEY LEARNING POINTS
- Radiotherapy in ENT (Ear, Nose, Throat) and Head and Neck Surgery has a rich history dating back to notable figures in the field such as Wilhelm Roentgen, Antoine Henri Becquerel, Marie Curie, and more.
- Mechanism of action involves damaging DNA cells directly or indirectly using two types of energy: photon (X-rays, gamma rays) and charged particles (proton, neutron, neon, carbon).
- Types of complications from radiotherapy include early effects like radiation sickness and mucositis, as well as late effects such as xerostomia, osteo-radionecrosis, and radiation-induced malignancies.
- Radiotherapy dosage is expressed in terms of absorbed dose, with the SI unit being gray (Gy). Different doses are prescribed based on the type of cancer and whether it's curative, preventive, or palliative.
- Fractionation, the process of dividing the total dose into smaller doses, is important in radiotherapy to maximize the treatment's effectiveness while minimizing side effects.
- Techniques in radiotherapy include external beam radiotherapy, brachytherapy, and unsealed radionuclide therapy, each tailored to target specific areas while sparing healthy tissues.
- Advanced methods like Intensity Modulated Radiotherapy (IMRT) and Image Guided Radiotherapy (IGRT) offer precise dose delivery and tumor targeting capabilities, enhancing treatment outcomes.
- Preoperative and postoperative radiation therapy have different indications and advantages, with the goal of reducing tumor size pre-surgery and targeting any residual disease post-surgery.
- Recommendations for elective lymph node irradiation in patients undergoing definitive radiotherapy for specific head and neck cancers are based on tumor stages and locations to ensure comprehensive treatment.- Pharyngeal/retropharyngeal lymph nodes are located in the upper part of the neck region.
- T1/T2 N0 refers to the tumor size and absence of lymph node involvement.
- Levels I, II, III, IV, and V are specific lymph node groups in the neck.
- RADPLAT is a treatment approach involving intra-arterial Cisplatin and systemic neutralization with i.v. sodium thiosulphate.
- Concomitant radiation therapy followed by surgery is recommended for advanced paranasal sinus cancer.
- Brachytherapy involves placing radioactive sources within tissues or body cavities for treatment.
- RTOG Trial 9615 showed high complete response rates for T4 squamous cell carcinomas in the oral cavity, oropharynx, hypopharynx, and larynx.
- Different radioactive sources like radium, cesium, and iridium can be used for brachytherapy implants.
- Complications of radiation therapy for head and neck cancer include early and late side effects like xerostomia, skin changes, and osteoradionecrosis.
- Reirradiation may be considered for recurrent diseases that are amenable to salvage surgery.
- Radioablation using Radioiodine (Iodine 131) is a common treatment for hyperthyroidism and thyroid cancer.
- Patient preparation for Radioiodine therapy includes thyroid mass calculation and low iodine diet.
- Sequelae of Radioiodine therapy may include early side effects like radiation thyroiditis and late effects like pulmonary fibrosis and secondary malignancies.
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SLIDES OUTLINE
Principles & Practice of radiotherapy
in ENT and Head Neck Surgery
History
Wilhelm Roentgen Germany (1845-1923)
Cont’d…
Antoine Henri Becquerel, France (1852 – 1908)
Cont’d…
Marie Sklodowska Curie (1867-1934)
Cont’d…
Emil Grubbe , USA
(1875-1960)
1st radiation oncologist
Irradiation cancer patient
Claude Regaud ,France
(1870-1940)
fractionation
Cont’d…
Henri Coutard, France
(1876-1950)
Advanced laryngeal cancers
Cont’d…
Medical linear accelerators since 1940
CT scan - Godfrey Hounsfield , 1971
PET, IMRT, IGRT- 1980
Mechanism of action
Damage the DNA of cells – directly or indirectly
Two types of energy
photon ( X-rays, gamma rays)
charged particle ( proton, neutron, neon, carbon)
Indirect ionization - ionization of water, forming free radicals, hydroxyl radicals- damage the DNA.
Cont’d…
Cont’d…
The DNA damage - inherited through cell division, accumulating damage to the cancer cells- to die or reproduce more slowly
Oxygen sensitizers – increase response by increasing free radicals
Hypoxic cell radiosensitizers –nimorazole,misonidazole and metronidazole and hypoxic cytotoxins, tirapazamine.
Dose
Radiotherapy dosage - expressed in terms of absorbed dose
The SI unit of absorbed dose- gray (Gy), defined as an energy absorption of
1 joule/kg
One gray = absorption of one joule of energy, in the form of ionizing radiation by one kilogram of matter
(100 rads = 100 cGy = 1 Gy)
Cont’d…
For curative/radical cases:
Solid epithelial tumour 60-80 Gy in 1.8-2Gy/fraction in 6-7 weeks
Lymphoma 20-40 Gy
For preventive (adjuvant) doses:
Breast, head and neck cancers 45-60Gy in 1.8-2Gy/ fraction
For palliative doses:
30-40Gy in 15-20 fractions over 3-4 weeks
Complications of Radiotherapy
Early-
Radiation sickness
Mucositis
Dryness of mucous membranes
Skin reactions (erthyema, dry or wet desquamation)
Laryngeal oedema
Candida infections
Haematopoietic suppression
Acute tranverse myelitis
Lethargy
Late complications
xerostomia
Skin changes
Decaying of teeth
Osteo-radionecrosis
Trismus (fibrosis of TM Joint & muscles)
Transverse myelitis
Radiation deficit(thyroid, pituitary)
Radiation induced malignancy(thyroid cancer, osteosarcoma of orbit)
Hypoglossal nerve palsy
Temporal bone necrosis
Laryngeal cartilage necrosis
Cartilage necrosis (nose and pinna)
Retinal damage
Optic nerve damage
Cataract, deafness
Carotid artery stenosis
Cont’d…
Fractionation of dose
Total dose divided into a no. small doses
Gross disease : 66-70 Gy, 2Gy/#, 1#/day, 5#/wk
Microscopic disease: 44-50Gy, 2Gy/#, 1#/day, 5#/wk
Cont’d…
5R’s of Radiotherapy
Repair
Redistribution ( Re-assortment)
Re-oxygenation
Repopulation
Intrinsic radiosensitivity
Conventional fractionation
Use of individual treatments (fractions) of 1.8-2Gy each given daily for 5 days per week
Curative doses : 66-70Gy delivered in 33-35 fractions over 6.5-7 wks
Historically, post op doses have been 10% lower, of 60-64Gy delivered in 30-32 fractions over 6-6.5 wks
Altered fractionation
Cont’d…
CHART( continuous hyper-fractionated accelerated radiotherapy)
RT at 1.5Gy per fraction is given three times daily and continuously for 12 days to a total dose of 54Gy (i.e. without a weekend break)
Intense acute reaction develops in most patients
Repopulation of malignant cells reduced
Reduced fractions size to prevent increased late tissue damage
Relative effectiveness of altered fractionation
A RCT of CHART Vs conventional RT to 66Gy in pts with locally advanced cancers of larynx and pharynx demonstrated approx. equivalence of the two regimes
Dische S, Saunders M, Barett A et al., 1997
In a meta analysis of different fractionation schedules, there was a significant advantage of altered fractionation over conventional fractionation, amounting to a 6.5 % improvement in 5 year survival
Bourhis J, Overgaard J, Audry H et al., 2006
Scheduling of radiotherapy
Neo-adjuvant
Synchronous, concomitant
Adjuvant
Types of radiotherapy
Curative
Palliative
Combination
Modes of radiotherapy
External beam radiotherapy or teletherapy
Conventional, stereotactic, fractionated, virtual simulation, 3D conformal RT, IMRT, IGRT
Interstitial or intracavitary brachytherapy
Unsealed radionuclide therapy :
radioiodine therapy
External beam therapy/teletherapy
Conventional
Ttreatment planned or simulated on a specially calibrated diagnostic x-ray machine known as a simulator to achieve a desired plan
Photon or electron beams- projected to the target area through the skin
Delivery of radiation from a unit located external to the body
Two-dimensional beams using linear accelerator machines
Consists of a single beam of radiation delivered to the patient from several directions: often front or back, and both sides
Cont’d…
Aim - accurately target or localize the volume to be treated, quick and reliable
Linear accelerators ,Cobalt 60 teletherapy
Types of external beam radiation
Photon beams
X – rays
Gamma rays
Particle beams
Electrons
Neutrons
Protons
Photon beams
Most common form
X- rays and gamma rays
Photon- a packet of electromagnetic radiations
X-rays : produced by X-ray machines when high energy electrons bombard a metallic target
Gamma rays : emitted by radioactive sources, e.g. cobalt 60
Cont’d…
X – ray :
Superficial : 100 KV
Ortho-voltage : 200-500 KV
Megavoltage : 1-25 MV
Gamma ray :
Cobalt : 2 MV
Particle therapy
Direct damage to cancer cell DNA through high - LET (linear energy transfer)
Antitumour effect independent of tumour oxygen supply
Electron beams
Second most common
Rapid dose build up and sharp dose fall off with very little scatter (main characteristic)
Used to boost up radiation dose to the target area avoiding radiation to adjoining vital structures, e.g. spinal cord
Produced by linear accelerator, betatron and microtron
Cont’d…
Types: external beam therapy
Superficial RT:
100 kV
Poorly penetrating ( depth of only about 1 cm)
Exclusively used for small skin tumours
Orthovoltage RT:
200-500 kV (deep X-rays)
Megavoltage/Supervoltave RT:
Megavoltage machines such as linear accelerators are universally used now
Operate at 1-25 MV& produce much more penetration than by orthovoltage era
Cont’d…
Advantages of Megavoltage RT
Increased dose at depth
Skin sparing
Better precision (less penumbra)
Diminished bone absorption
60Cobalt machines
Gamma rays with energies of 1.17 and 1.33 MeV are emitted from the artificially produced radionuclide Cobalt-60
Some of these machines are still in use, but most have been replaced by linear accelerators
Linear accelerators
High energy radiation - X-rays (photons) (4-40 MV) and electrons
Allows the treatment head to rotate 3600, allowing treatment of the patient at any angle
Good tissue penetration coupled with a skin sparing effect
Also produce electron beams
Stereotactic Radiosurgery (SRS)
Stereotactic Radiosurgery (SRS)
A high dose of radiation - a single session
A single radiosurgery dose - more damaging than multiple fractionated doses
The target area must be precisely located and completely immobilized with a stereotactic head or body frame
Cont’d…
Extreme accuracy, limit the effect of the radiation on healthy tissues, suitable for certain small tumours.
CPA Tumours
CyberKnife Robotic Radiosurgery System
Cont’d…
Benefits :
Sub-millimeter accuracy– minimal harm to surrounding healthy tissue in high doses of radiation
Continuous imaging– ensures targeting accuracy throughout the treatment the slightest patient or tumour movement
Track, detect and correct– tumour position, any movement, beam delivery and reposition the patient or interrupt the treatment
Anywhere in the body– in the body including the brain, spine, lungs, liver, pancreas and prostate
Virtual simulation, 3-dimensional conformal radiotherapy(3D-CRT)
Ability to delineate tumours and adjacent normal structures in three dimensions using specialized CT and/or MRI scanners and planning software
Cont’d…
Radiation beam should conform (adapt) as closely as possible to shape of tumour using multileaf collimators(MLC)
More important when associated tumour masses coexist e.g. primary tumour with locally involved nodes surrounded by normal tissue
3-D software allows the radiation beam to be shaped by linear accelerator to achieve this objective hence term “conformal RT”
Drawback:
No modulation of beams as per complex structures to preserve structures like spinal cord, salivary glands eg. Ca nasopharynx
Intensity modulated RT (IMRT)
Intensity modulated RT (IMRT)
More advance than 3D- CRT
Multiple beam of varying intensities used to create irregular shape if necessary with concave contour
Linear accelerator-based radiation therapy
Primary objective
to reduce dose to selected normal tissue structures in an effort to preserve function
maintaining full dose delivery to tumour targets
Cont’d…
Oropharyngeal carcinoma
Laryngeal , hypopharyngeal carcinoma
Nasopharyngeal carcinoma
Paranasal sinus tumours
Cont’d…
Cont’d…
Cont’d…
Cont’d…
Cont’d…
Image guided radiotherapy (IGRT)
Image guided radiotherapy (IGRT)
Regular portal imaging - to improve the precision and accuracy of the delivery of treatment
Linear accelerator (for x-ray or photon) or cyclotron/synchrotron (for proton), are equipped with imaging technology
CT, MRI, PET, USG and X-rays
Cont’d…
Real time tumour tracking
Mainly useful in organs with movement
Often in conjunction with IMRT, proton beam therapy, stereotactic radiosurgery, or stereotactic body radiotherapy (SBRT)
Pre-operative radiation
Advantages :
Reduces bulk of tumor
Oxygenation of tissues not hampered
Lymphatic's are blocked by radiation –dissemination of tumor cells less during surgery
Eliminates microscopic spread beyond palpable tumor mass or occult metastasis
Cont’d…
Disadvantages
Preoperative radiation reduces vitality of tissues by dealing healing tissues
Flap necrosis, fistulae formation
Carotid blow outs in post-op period
Loss of tissue plane and exact margin while surgery
Delayed wound healing
Postoperative radiation
Indications
High risk disease i.e. presence of nodal disease with extracapsular spread
Presence of an involved surgical margin or 4 of the following:
Excision margin<5 mm, stage 3 /4, peri-neural or vascular invasion, poor differentiation, oral cavity primary, multicentre primary, >4 nodes +ve, soft tissue invasion and dysplasia or carcinoma in situ at the resection margin
Additional risk factors: post laryngectomy- presence of transglottic disease, a preoperative tracheostomy and LN involvement in level 6
Cont’d…
Advantages
More effective, bulk of tumor mass removed by surgery
Extent of tumour defined and radiation can be applied in suspected residual disease or areas of positive margins
Few complications of flap necrosis
Disadvantages-
After surgery -blood supply to the tissues interfered, hypoxic cells not respond to radiation
Recommendations for elective lymph node irradiation in patients undergoing definitive RT for head and neck cancer
Larynx
T1/T2 N0 Glottic No elective nodal irradiation
T3/T4 N0 Glottic Levels Ib to IV bilaterally
T1/T2 N0 Supraglottic Levels Ib to V bilaterally
All other stages Levels Ib to V bilaterally
Oropharynx
T1 N0 tonsil Levels Ib, II ipsilateral
T2 N0 tonsil (lateralized) Levels Ib to IV ipsilateral
T1/T2 N1 tonsil (lateralized) Levels Ib to V ipsilateral
T2 N0 tonsil (approaching midline)
+ other sites Levels Ib to V bilaterally
All other stages and subsites Levels Ib to V bilaterally
Hypopharynx
All stages and subsites Levels Ib to V bilaterally
Nasal cavity
Any T, N0 No elective nodal irradiation
Any T, N+ Levels Ib to V bilaterally
Paranasal sinuses
Any T, N0
Any T, N+ Lateral pharyngeal/retropharyngeal lymph node
Oral cavity
T1/T2 N0 ( lateralized primary) Levels I, II ipsilateral
T2N1 (lateralized primary) Levels I to V ipsilateral
T2N0 (primary approaching midline ) Levels I to V B/L
All other stages Levels I to V B/L
Stell and Maran, 5th edition
RADPLAT
Intra-arterial Cisplatin with systemic neutralization by i.v. sodium thiosulphate and Concomitant Radiation Therapy Followed by Surgery for Advanced Paranasal Sinus Ca
Advantages:
Allows very high cisplatin dose intensities to be used
Minimizing adverse systemic effects.
Excellent locoregional control rates are achievable in patients with unresectable disease
Favorable side-effect profile when compared with conventional chemoradiation protocols
Supradose Intra-Arterial Cisplatin and Concurrent Radiation Therapy for the Treatment of Stage IV Head and Neck Squamous Cell Carcinoma Is Feasible and Efficacious in a Multi-Institutional Setting: Results of RTOG Trial 9615
Robbins et al.,2005
Journal of clinical oncology
T4 squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
Complete response (CR) rate 85% at the primary site and 88% at nodal regions, and the overall CR rate was 80%.
At a median follow-up of 3.9 years for alive patients (range, 0.9 to 6.1 years), the estimated 1-year and 2-year locoregional tumor control rates - 66% and 57%
Brachytherapy
Radioactive sources placement within tissues/tumours (interstitial therapy) or body cavities (intracavitary therapy)
Radioactive material is applied in the form of
A mould (epithelial surfaces)
Interstitial implant
Radioactive material in the form of needles, wires, ribbons or seeds
Sometimes permanently left in the tissues due to shorter half life
Intracavitary implant
Radioactive material placed in a hollow cavity next to tumour, e.g. nasopharynx, maxillary antrum
Greater dose can be delivered to the tumor at a continuously low dose rate.
Treatment of hypoxic or slowly proliferating tumours
Cont’d…
Radium needles – removable implants,
radon – permanent implants
Caesium (pellets) and iridium (wire)
Radon – replaced by gold (seeds or grain)
Afterloading technique
Oral cavity tumours, lips, oropharynx, nasopharynx recurrent previously irradiated neck nodes
Ca Oral cavity/Lip
Interstitial implants: 60-70Gy over 6-7 days - Cesium
Irridium : 60Gy for 5 days
Planning & quality control of radiation therapy
Selecting the treatment volume
Preparation of a shell
Simulation
Beam shaping
Wedges & compensators
Isodense plans
Treatment verification
Cont’d …
Methods of tackling the oxygen effect
in radiotherapy of head and neck cancer
Breathing oxygen and carbon dioxide (carbogen)
Hyperbaric oxygen
Neutron therapy
Hypoxic cell sensitizing drugs
Raising haemoglobin level
Carbogen plus a vasodilator (ARCON- Accelerated rdiotherapy carbogen and nicotinamide)
Factors affecting effectiveness of RT for head and neck cancer
Complications of Radiotherapy
Early-
Radiation sickness
Mucositis
Dryness of mucous membranes
Skin reactions (erthyema, dry or wet desquamation)
Laryngeal oedema
Candida infections
Haematopoietic suppression
Acute tranverse myelitis
Lethargy
Late complications
Permanent xerostomia
Skin changes
Decaying of teeth
Osteo-radionecrosis
Trismus (fibrosis of TM Joint & muscles)
Transverse myelitis
Radiation deficit(thyroid, pituitary)
Radiation induced malignancy(thyroid cancer, osteosarcoma of orbit)
Hypoglossal nerve palsy
Temporal bone necrosis
Laryngeal cartilage necrosis
Cartilage necrosis (nose and pinna)
Retinal damage
Optic nerve damage
Cataract, deafness
Carotid artery stenosis
Cont’d…
Reirradiation
For recurrent diseases which can be
Operated , not irradiated
Irradiated but amenable to salvage surgery
Irradiated not amenable for surgery
Associated with distance metastasis
Recurrence
Radiation resistance
Geographical miss : in regions of penumbra, low dose
Development of secondary primary after tumour free interval for years
Patient and treatment factors to consider for irradiation
Cont’d…
Brachytherapy :
rT1/rT2 oropharynx /nasopharynx without e/o nodal metastasis
External beam radiotherapy
rT1/rT2 larynx
Can also be salvage TL
Concomitant chemotherapy : increase effectiveness of reirradiation
IMRT
For site not suited for salvage surgery
Skull base
Infratemporal fossa
Radioablation
Radioablation
Hyperthyroidism
Differentiated thyroid cancer
Radioablation in hyperthyroidism
Graves’ disease
Toxic MNG
AFTN
Radioiodine
Iodine131
Physical half life : 8 days
Medium energy beta-particle emission (Emax=0.61 meV) with a path length of about 0.8 mm tissue.
Destroys follicular cells
Preparation
ATD
Carbimazole: 3-5 days
PTU: 7-20 days
Medicine:
Expectorants
Amiodarone
Contrast
Radioiodine dose
Controversial
Goal of treatment (control of hyperthyroidism vs. avoidance of hypothyroidism)
Thyroid mass and RAIU
Dose = (80-120µCi x thyroid wt in gms)/RAIU
Empirical: 10-15mCi
Side effects
Hypothyroidism
Nausea
Radiation thyroiditis (transient)
Exacerbation of thyrotoxicosis
Worsening of active opthalmopathy
Radiation induced gastritis
Hepatitis
Follow up
At 2-months
TFT
Repeat dose if hyperthyroidism persists after 6 months or if there is minimal response after 3 months
Contraindications
Pregnancy
Lactation
Severe Grave’s ophthalmopathy
Suspicion of thyroid cancer
Females planning pregnancy
DTC
Aim
Remnant Ablation
Destruction of neoplastic tissue
Whole body scan and detection of micrometastases
Patient preparation
Thyroxine withdrawal
Low iodine diet
Iodized salt, foods high in salt, baking soda
Vitamins or supplements that contain iodine
Milk or other dairy products including ice cream, cheese, yogurt and butter
Seafood including fish, sushi, shellfish, seaweed
Egg yolks, whole eggs and foods containing whole eggs
Dried fruits
Soy products (soy sauce, soy milk, tofu)
rhTSH
Protocol
Surgery Day1
Thyroxine withdrawl Day 1-35
Low Iodine diet Day 15-35
Diagnositc I-131, Day 29
TSH, Tg, ATA
Diagnostic WBS Day 30
Therapy Day 30
Post therapy Scan Day 35
Dose
Remnant ablation: 30-100mCi
Suspected/known residual disease: 100-200mCi
Metastasis: 100-300mCi
Cumulative dose: 1000mCi
Sequelae- early
Radiation thyroiditis
Sialadenitis
Gastritis
Abnormality of taste/smell
Nausea, vomiting
Hypospermia
Transient pancytopenia
Cerebral edema or spinal cord compression
Transient alopecia
Thyroid storm
Sequelae- Late
Pulmonary fibrosis
2nd Primary
Leukemia , bladder ca, breast ca, salivary carcinomas
Chronic sialadenitis with xerostomia
Hypoparathyroidism
Chronic hypospermia or azoospermia
Early menopause
Chronic dry eye
