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SECTION VIII — Recent Advances
Figure 71.4. Treatment at hyperbaric chamber. (Courtesy Tarun Sahni, Indraprastha Apollo Hospital, New Delhi.)
9. Osteomyelitis
10. Thermal burns
11. Clostridial myonecrosis
12. Intracranial abscess
13. Exceptional blood loss (anaemia)
14. Sensorineural hearing loss
Research-based Indications
1. Bell palsy
2. Burns
3. Anoxic encephalopathy
4. Traumatic brain injury
5. Stroke
6. Spinal cord injury
7. Cerebral palsy/Autism
PATIENTS SELECTION CRITERIA FOR SSNHL
Patients with moderate to profound SSNHL (≥ 41 dB) who
present within 14 days of symptom onset should be considered for HBOT. While patients presenting after this time
may experience improvement when treated with HBOT,
the medical literature suggests that early intervention is associated with improved outcomes. The best evidence supports the use of HBOT within 2 weeks of symptom onset.
CLINICAL MANAGEMENT
The recommended treatment profile consists of 100%
O2 at 2.0–2.5 atmospheres absolute for 90 min daily for
10–20 treatments. However, the optimal number of HBO
treatments will vary, depending on the severity and duration of symptomatology and the response to treatment.
COST IMPACT
There is no formal detailed cost analysis for SSNHL in
the literature. However, the World Health Organization
(WHO) has described the cost impact of hearing loss.
Hearing impairment makes it difficult to obtain, perform and keep jobs, and the hearing impaired are often
stigmatized and socially isolated. Adult onset hearing
loss is the 15th leading cause of burden of disease, and
is projected to move up to 7th by the year 2030 (WHO,
2008). Although additional studies are recommended to
further define the pathology and optimize the treatment
of SSNHL, based on the current medical evidence, the use
of HBOT outweighs the risk. Furthermore, significantly
improving a patient’s hearing and minimizing the social
and economic burden of this disease outweighs treatment costs.
IV. COBLATION
The term coblation was derived from controlled ablation or
cold ablation, as the temperature used in ablation of tissues
is much lower than that used in electrosurgical ablation or
even coagulation. Coblation uses a radiofrequency above
200 kHZ to break tissue bonds. It is a chemical process
whereby highly energized ions are created in a saline medium. A plasma field causes dissolution of tissue, unlike
that in electrosurgical dissection which works on thermal
reaction causing tissue burning or coagulation with collateral damage (Figures 71.5 and 71.6A and B).
The differences between coblation and electrosurgery
are shown in Table 71.3.
Chapter 71 — Laser Surgery, Radiofrequency Surgery, Hyperbaric Oxygen Therapy and Coblation
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Figure 71.5. A flowchart showing the principle of coblation.
USES
Coblation can be used for dissection, ablation and coagulation with a single apparatus using a setting for coblation and coagulation. This gives a bloodless field.
It has been used to perform:
• adenotonsillectomy,
• a reduction of tongue base,
• uvulopalatoplasty for sleep disordered breathing,
• turbinate reduction in nose,
• nasal polypectomy,
• cordectomy,
• laryngeal papillomas and other benign lesions of
larynx and
• transverse cordectomy (Kashima operation) for bilat-
eral abductor paralysis.
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Figure 71.6. (A) Coblator II machine probes. (B) Various types of
wands used in coblation. (Courtesy of Smith & Nephew, Inc.)
TABLE 71.3 DIFFERENCES BETWEEN COBLATION AND ELECTROSURGERY
Coblation Electrosurgery
Temperatures generated 40–70°C 400–600°C
Mechanism of action Chemical Thermal
Effects on tissue Gentle dissolution of molecular bonds of soft tissue Thermal charring and burning of tissues due to
high temperature
Collateral damages Works superficially with no collateral or deep-tissue
damage
Causes deep collateral damage
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Chapter 72
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Cryosurgery
Rapid freezing of tissues to temperatures of −30 °C and
below and their slow thawing causes destruction. This fact
has been used to treat various lesions of the head and neck
including benign, premalignant and malignant neoplasms.
Agents used in freezing the tissue are used either by
an open method (liquid nitrogen spray or carbon dioxide
snow) or through a closed system such as a cryoprobe. A
cryoprobe is based on Joule-Thomson effect, i.e. rapid expansion of compressed gas through a small hole produces
cooling. Probes in current use produce a tip temperature
of −70 °C or below and are available in different sizes and
designs to suit the area of cryoapplication. Some probes
also have thermocouples which can be inserted into the
tissue to monitor the temperature. The clinically available closed systems employ liquid nitrogen, nitrous oxide
or carbon dioxide.
MECHANISM OF TISSUE DESTRUCTION
Freezing causes cell death through several mechanisms:
1. dehydration. The pure water inside and outside the
cell crystallizes with consequent rise in the concentration
of electrolytes. The pH of the medium also changes as the
buffering substances crystallize out. Urea and dissolved
gases also reach toxic concentrations and cause cell death.
2. denaturation. Cell membranes are made up of lipo-
proteins. Their denaturation makes cell membrane permeable to cations. Thawing of cells, now engorged with
cations result in cell lysis.
3. thermal shock. This arrests the respiratory function
of cell.
4. Vascular stasis. Both arterial and venous supply
of blood is occluded leading to ischaemic infarct. Microthrombosis of capillaries is seen within a few hours
of cryoapplication. It is because of this mechanism that
cryosurgery is useful to treat vascular tumours, e.g. haemangioma, angiofibroma or glomus tumours.
5. cryoimmuniZation. Autoantibodies, specific to the
tissues frozen, have been seen experimentally. This is supposed to provide tissue specific immunity to subsequent
challenges with the same tumour.
be insulated. A suitable cryoprobe is applied into or upon
the tissues and the latter frozen quickly for 3–8 min and
then allowed to thaw slowly. The procedure is repeated
once or twice. Area frozen should include a margin of
normal tissue. A thermocouple can be implanted to ensure freezing at an adequate depth. After cryotherapy,
the area is allowed to heal by secondary intention. The
necrotic slough falls off in 3–6 weeks. Repeat cycles of
cryotherapy may be required to achieve the desired result.
USES OF CRYOTHERAPY
1. benign Vascular tumours. Cryotherapy has been
found useful to treat haemangiomas involving skin, oral
cavity or oropharynx. It has also been used as an adjunct
to treat vascular tumours such as angiofibroma and glomus tumour.
2. premalignant lesions. Leukoplakia, involving the
cheek, tongue, floor of mouth, has been effectively treated by cryotherapy. It is preferred to electrosurgery because
of less scarring, better quality of regenerated epithelium
and no recurrence of lesion. It is also used to treat solar
keratosis, a precancerous condition of skin.
3. malignant lesions. Skin cancers like Bowen disease (intraepithelial carcinoma) and basal cell carcinoma
have been treated successfully with a cure rate of 94–97%.
Cryotherapy is particularly useful when tumour overlies
the cartilage as the latter does not undergo necrosis with
freezing. It is also useful for skin cancers which are multiple. Recurrent skin cancers or lesions which do not have
well-defined margins should not be treated by this method.
Major role of cryotherapy has been in the palliation
of advanced cancers or recurrent or residual tumours. In
these cases, aim is to debulk the tumour mass to facilitate
deglutition or respiration, to reduce tendency of tumours
to bleed and to relieve pain.
Role of curative cryotherapy in primary malignant lesion of the oral cavity and oropharynx is limited though
some success is reported in early lesions (T1 N0) involving
floor of mouth, tongue and palate. For this, cryotherapy
should be used very selectively, in patients who are otherwise high-risk groups and have a short expectancy of life
due to other concurrent disease.
TECHNIQUE
Cryotherapy can be applied under local or light general
anaesthesia. Sometimes, no anaesthesia is used as freezing itself causes numbness. The area to be frozen should
4. other uses. Cryotherapy has been applied to nasal
turbinates to reduce their size and improve the airway.
It has also been used in allergic rhinitis to control sneezing and rhinorrhoea. Cryodestruction of tonsils has been
done in poor risk patients.
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SECTION VIII — Recent Advances
ADVANTAGES OF CRYOTHERAPY
1. Useful in poor risk patients and can be applied without
anaesthesia or under local anaesthesia.
2. Useful in patients with bleeding disorders or
coagulopathies.
3. Can be used in multiple cancers, palliation of recurrent cancers where second course of radiation is not
advisable.
4. Causes minimal post-treatment discomfort or pain.
5. Causes minimal scarring. Can be used at sites, notorious for keloid formation, e.g. presternal region.
6. It is an outpatient procedure.
DISADVANTAGES OF CRYOTHERAPY
1. No tissue is available for biopsy in case of small lesions.
2. Not possible to assess margins of tumour to know
whether free of malignant cells.
3. No control on depth of freezing.
4. When used for skin lesions, cryotherapy causes depigmentation and loss of hair due to destruction of hair follicles.
5. Anaesthesia of the part is required when lesion is near
the nerve, e.g. ulnar or digital.
With the advent of laser therapy, many of the indica-
tions for cryotherapy will be reduced; however, its lower
cost will be an important factor in developing countries.
Chapter 73
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Radiotherapy in Head
and Neck Cancers*
Head and neck cancers comprise those of the oral cavity,
oropharynx, larynx, nasopharynx and hypopharynx and
also of the paranasal sinuses, salivary glands and the ear.
Head and neck cancer is the eighth most common malignancy globally (sixth among males) and the third most
common cancer in India, mostly in males. The clinical
manifestations vary according to the stage and primary
site of involvement. In the Indian setting, more than 70%
of patients present in locally advanced stages (stage III
and IV). Surgery is the most common treatment of choice
and is effective in small- to moderate-sized lesions. Radiation therapy can also be considered for patients with:
1. early-stage disease,
2. those who are not surgical candidates and
3. those who refuse surgery.
For patients with advanced lesions, a combined mo-
dality of radiation and chemotherapy is used.
The propagation of energy from a radioactive source
to another medium is termed as radiation. The various
forms of radiation originating from atoms (including visible light, X-rays and γ-rays) are grouped under the term
electromagnetic radiation (Figure 73.1). Electromagnetic
radiation can also be subdivided into ionising and non-ionising radiations. Non-ionising radiations have wavelengths
of ≥10−7 m and energies of <12 eV (12 eV is considered to
be the lowest energy that an ionising radiation can possess). The radiation is measured in gray (Gy). This is the SI
unit for absorbed energy and 1 Gy = 1 J/kg. The older term
‘rad’ is no longer used (1 Gy = 100 rad). Cobalt 60 emits
γ-rays and has a fixed 1.3 × 106 or 1.7 × 106 eV of energy.
TYPES OF RADIATION BEAMS
malignant salivary gland tumours. Particle radiation
are not yet available in India.
Linear accelerator (LINAC) can produce high-voltage
energy of both photons and electrons (Figure 73.2).
Energy of photon beams (X-rays and γ-rays) is expressed
in kilovolts (kV) or megavolts (MV), whereas energy of
electrons is expressed in megaelectron volts (MeV).
X-ray energies used are:
• Diagnostic X-ray: 20–50 kV
• Superficial X-ray: 50–200 kV
• Orthovoltage X-ray: 200–500 kV
• Supervoltage X-ray: 500–1000 kV
• Megavoltage X-ray: 1–25 MV
Currently megavoltage is used in radiotherapy.
MECHANISM OF ACTION OF RADIOTHERAPY
Radiation causes cellular death by various mechanisms such
as break in DNA strands, genetic mutation and apoptosis.
Water surrounding the DNA is ionised, creating hy-
droxyl and oxygen radicals which damage DNA strands.
Radiation can directly damage cell mitochondria and
trigger apoptosis. It can also directly stop cellular multiplication by cell cycle arrest.
RADIOSENSITISERS AND RADIOPROTECTORS
RADIOSENSITISERS
They are the agents which sensitise tumour cells to the
effects of radiation and increase tumour cell killing. The
various mechanisms and measures taken are discussed here.
Beams are of three types.
1. Photon beams. They are the most common form and in-
clude both X-rays and γ-rays. Photons are produced by
machines and γ-rays are emitted by radioactive cobalt.
2. Electron beams. Their main characteristic is rapid dose
build up and sharp dose fall off with little scatter and
are thus used in places where vital structures are to be
avoided.
3. Particle radiation. It is an emission of protons, neutrons
and pions by machines. Neutron emission is used for
* This chapter is co-authored by Dr GK Jadhav, DMRT, MD, DNB,
MNAMS, FAGE, FICRO, Senior Consultant Radiation Oncology,
Indraprastha Apollo Hospital, New Delhi and Dr Sapna Manocha
Verma, MD (Radiotherapy), Senior Consultant Radiation Oncology,
Indraprastha Apollo Hospital, New Delhi.
Reduce Hypoxia
Hypoxic cells are 2.5–3 times less radiosensitive than
well-oxygenated cells. Attempts to make them more responsive include:
• Use of hyperbaric oxygen. The patient is placed in a special
hyperbaric O2 chamber (100% O2 under two times the
atmospheric pressure) and then radiated. Hyperbaric
oxygen improves function of white cells and also their
phagocytic activity. It increases neovascularization of
the hypoxic area.
• Inhalation of carbogen (95% O2 + 5% CO2).
• Use of nicotinamide. It improves blood flow and thus
oxygenation.
• Maintenance of good haemoglobin levels during radiother-
apy. Patient should preferably have 12 g of haemoglobin before radiation.
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SECTION VIII — Recent Advances
Figure 73.1. Electromagnetic spectrum.
Figure 73.2. Novalis–Tx linear accelerator. Dual energy with photon and electron beam and 6D robotic couch. It is used for both cancerous and
non-cancerous lesions. It generates photons (6 and 15 MV) and electrons (6, 9, 12, 15 and 18 MeV). It can be used for:
• 3DCRT–3Dconformalradiotherapy
• IMRT–Intensity-modulatedradiotherapy
• IGRT–Image-guidedradiotherapy
• SRT–Stereotacticradiotherapy
• SRS–Stereotacticradiosurgery(singlesession),e.g.acousticneuromaandtrigeminalneuralgia
• SBRT–Stereotacticbodyradiotherapy,e.g.tospine,liver,lung,prostate,etc.
(Courtesy Drs GK Jadhav and Sapna Manocha Verma, Indraprastha Apollo Hospital, New Delhi).
Chapter 73 — Radiotherapy in Head and Neck Cancers
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Hypoxic Cell Sensitisers
Nimorazole and tirapazamine are hypoxic cell sensitisers.
They have been used in concomitant chemotherapy.
Chemotherapeutic Drugs
Drugs such as cisplatin, mitomycin-C, 5-fluorouracil,
pacititaxel, docetaxel and hydroxyurea have been used in
concomitant chemoradiation. They act as radiosensitisers
and potentiate the effect of radiation by their additive or
synergistic effect.
Cetuximab is a monoclonal antibody which acts
against the receptors of epidermal growth factor. As the
latter is overexpressed in head and neck cancers, use of
cetuximab would inhibit the receptors by blocking them.
Cetuximab has been used as a targeted chemotherapy
along with radiation.
RADIOPROTECTORS
These compounds are designed to reduce damage to the
normal tissues by scavenging highly reactive free radicals
caused by radiation. The most commonly used radioprotectors are amifostine, antioxidants (such as glutathione and
vitamin A, C and E), lipoic acid and drugs such as cysteine.
Radiation Fractionation
Conventional radiotherapy involves delivering 2 Gy/
day for 5 days in a week. It comes to 5 fractions, i.e.
1000 Gy in a week.
Hyperfractionation is delivering multiple daily doses
of such a size that the overall treatment time is about the
same as in conventional radiotherapy. Dose of each fraction is reduced typically to a dose 1.1–1.2 Gy/fraction, 2
fractions/day are given. A total dose of 74–80 Gy can be
used. The studies conducted on hyperfraction gave better locoregional control of disease and decreased delayed
side effects. However, acute toxicity was significantly
more.
Accelerated fractionation uses multiple daily radiation
fractions, and dose of each fraction is also increased. Thus
the total treatment time is reduced to give the total dose.
However with this schedule incidence of severe late side
effects increased, and survival of patient decreased and
this was attributed to these complications.
INDICATIONS OF RADIOTHERAPY
IN HEAD AND NECK CANCER
DEFINITIVE RADIOTHERAPY
The aim is organ preservation with radiation only. Usually it is recommended in early-stage laryngeal cancer
(with the aim of voice preservation) or tumours of the
nasopharynx and base of the tongue where function is to
be preserved.
Advantages of Preoperative Radiotherapy
1. It reduces the tumour bulk, making questionably resectable tumours definitely resectable.
2. Vascularity and oxygenation of tumour is not affected
and response is better than would be in the case of a
scarred area after surgery.
3. Lymphatics are blocked, therefore tumour dissemination is less during surgery. It also reduces the risk of
distant metastases.
4. It helps to eliminate microscopic disease beyond tumour mass and occult metastases in lymph nodes.
5. Treatment portals are smaller than would be required
in postoperative radiation for residual tumour or one
with positive margins.
Disadvantages of Preoperative Radiotherapy
1. It reduces the vitality of tissues and interferes with the
healing process; thus increasing the chances of flap necrosis, fistula formation and carotid blow out.
2. It cannot be given in cases where surgical margins are
reported positive after surgery, as the patient has already received radiation.
3. Preoperative dose is usually 4500 cGy delivered in
4–5 weeks. It is sufficient to eradicate nearly 90% of
micrometastases. Higher doses interfere with wound
healing.
POSTOPERATIVE RADIOTHERAPY
Its aim is to improve locoregional control and is recommended in the following indications:
1. positive resection margins or close resection margins
(i.e. <5 mm),
2. extracapsular lymph node spread,
3. invasion of soft tissues,
4. involvement of two or more lymph nodes or more
than one nodal level,
5. size of involved node >3 cm in diameter,
6. vascular invasion and/or perineural invasion,
7. poorly differentiated tumour,
8. stage III/IV disease,
9. multicentric primary and
10. in-situ carcinoma at resection margin.
Advantages of Postoperative Radiotherapy
1. It is more effective, as the bulk of disease has been removed during surgery.
2. Extent of tumour has been defined at surgery and radiation is given to the suspected areas of residual disease
or areas of positive margins.
3. Surgical resection is technically easier and postoperative healing better.
4. A greater dose of radiation can be delivered to the
target area and adjusted on the basis of residual disease
and positive margins.
PREOPERATIVE RADIOTHERAPY
It is usually recommended in borderline operable lesions.
It improves resectability by reducing the viability of tumours. It is mainly used in cancers of retromolar trigone
and paranasal sinuses.
Disadvantages of Postoperative Radiotherapy
1. Blood supply to the tissues is affected due to fibrosis
after surgery. Moreover, cancer cells are hypoxic and
do not respond well.
2. If surgical complications occur, postoperative radiation
is delayed which may allow tumour cells to regrow.
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SECTION VIII — Recent Advances
Results of radiation are poor, if it gets delayed beyond
6 weeks.
3. Tumour cells are squeezed into blood vessels and lymphatics at the time of surgery, increasing the chances
of distant metastases.
4. There are a few complications of flap necrosis, wound
dehiscence and infection, as surgery is done on nonradiated tissues.
PALLIATIVE RADIOTHERAPY
In advanced lesions where total control of disease is not
possible, palliative radiotherapy is used to control pressure symptoms on air and food passages or on the nerves
to provide relief from pain.
RADIOTHERAPY PLANNING
Patient is assessed for radiation with clinical examination, staging and performance status. Radiotherapy planning includes:
1. Establishing the patient’s treatment position by
making an immobilization cast, so that the patient’s
position remains stable during delivery of radiation
(Figure 73.3).
2. Planning a radiation treatment on CT scan for contouring
target volume(s) and organs at risk (OAR) (Figure 73.4).
3. Planning radiation on a treatment planning system after specifying a prescription dose for the tumour volume. Various treatment techniques such as
conventional radiation therapy, three-dimensional
conformal radiation therapy (3D-CRT), intensitymodulated radiation therapy (IMRT), image-guided
radiation therapy (IGRT), stereotactic body radiation
therapy (SBRT), stereotactic radiosurgery (SRS) and
adaptive radiotherapy (ART) are planned depending
upon the tumour stage, extent and proximity to the
critical organs.
RADIOTHERAPY TECHNIQUES
CONVENTIONAL RADIATION THERAPY
In the past, conventional planning for head and neck
radiotherapy has involved orthogonal films taken in the
simulator with fields defined directly. It comprises anatomically marking parallel opposed lateral fields or two
orthogonal fields depending upon the site including primary and nodal disease.
THREE-DIMENSIONAL CONFORMAL
RADIATION THERAPY
With developments in radiotherapy planning, it has become possible to shape beams to confirm the dimensions
of the tumour mass, shield the normal structures and
thereby reduce the toxicity. A CT scan with the patient
positioned in the immobilization device is a requisite for
the process. Target volumes and structures to be avoided
(such as spinal cord) are outlined directly on the CT. This
process allows for some conformality and sparing the
normal tissues; with 3D radiation conforming with the
dose to the tumour using multiple fields (five or seven
in number). This is done by a computerised treatment
planning system.
Figure 73.3. (A, B) Head and neck immobilization with thermoplastic mask.
INTENSITY-MODULATED RADIATION
THERAPY
Highly precise and conformal inverse planning aims at
the maximum dose delivery to the tumour and sparing
the critical organs in radiation field such as spinal cord,
parotids, brainstem, etc. It uses 3D scans of the body to
guide the beams of radiation to the tumour from several
different angles. At each of these angles, the intensity of
the radiation is varied (modulated) and the shape of the
beam is changed to match the shape of the tumour. These
adjustments enable the prescribed amount of radiation to
be delivered to each part of the tumour, while minimizing
exposure to the surrounding healthy tissue.
IMAGE-GUIDED RADIATION THERAPY
It is basically IMRT planning under image guidance
done on the treatment machine during daily treatment
delivery. It helps in reducing the daily treatment set-up
errors and thus aims at more precision and accuracy.
Chapter 73 — Radiotherapy in Head and Neck Cancers
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Figure 73.4. (A, B) Contouring and planning of the tumour and critical organs on the treatment planning system.
This is usually recommended for small tumours close
to very critical organs such as eyes, optic nerves, spinal
cord, etc. In IGRT an image is acquired inside the treatment room and the positional information of the target
is also determined. Target surrogates or avoidance structures do the needful rectification right up to millimetre
accuracy.
STEREOTACTIC BODY RADIATION THERAPY
SBRT is a specially designed stereotactic coordinate system used in treatment planning of tumours anywhere in
the body. Re-irradiation of head and neck cancers and juvenile angiofibromas can be treated by SBRT for one to
five sessions.
STEREOTACTIC RADIOSURGERY
SRS is a stereotactic radiation treatment for brain lesions,
and is usually done in one or up to five sessions of radiation as in acoustic neuroma of the cerebellopontine
angle.
ADAPTIVE RADIOTHERAPY
Adaptive radiotherapy is defined as changing the radiation
treatment plan delivered to a patient during the course of
radiotherapy to account for changes in anatomy, e.g. tumour shrinkage, weight loss or internal motion.
TREATMENT MACHINES
The main machines are cobalt 60 (the source is radioactive isotope cobalt which emits γ-rays) and LINAC (emits
X-rays and electrons), but some centres are equipped with
Gamma Knife, Cyber Knife and Tomotherapy. Proton
therapy and heavy particle therapy are not yet available
in India.
DOSE AND FRACTIONATION
• Conventional dose of radiotherapy: 1.8–2.0 Gy/day for
5 days in a week (Monday to Friday).
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