'Is radiotherapy,chemotherapy or surgery a more effective treatment for non small cell lung
cancer?''
Introduction:
What started as a relatively unknown disease at the end of the nineteenth century, lung cancer has
become the most common worldwide cancer. In just over 100 years lung cancer has transformed
into a modern epidemic. It is currently thought to account for over 3,000,000 deaths each year
worldwide and roughly 33,400 deaths in the UK.1 Out of all the types of cancer that currently exist,
Lung cancer is currently the most common form worldwide. Life expectancy for the disease is usually
between three to seven months from diagnosis.2 In order to understand treatment for this disease it
is important to understand how cancer develops.
A cancer is formed when the control of the cell cycle goes wrong. The cell contains a nucleus which
holds the DNA that contains the genetic code. Cancer is fundamentally caused by damage to a DNA
molecule which leads to an unregulated, abnormal growth of cells3. Unlike normal cells, cancer cells
do not follow an orderly pattern of growth division and death. The cell death known as apoptosis is
not experienced by cancer cells which lead to it growing out of control. The growth of these cells
leads to lumps or masses of tissue called tumours which grow and can interfere with the digestive,
nervous and circulatory systems. More dangerous, malignant tumours form when either a cell that is
cancerous moves throughout the body using the blood systems in a process called invasion or that it
manages to divide and grow, making new blood vessels to feed on in what is called angiogenesis.
When a tumour has spread to other parts of the body, destroying various tissues it has
metastasized.4
Lung cancer:
In general there are two types of Lung cancer. These are small cell lung cancer (SCLC) and non-small
cell lung cancer (NSCLC). The most common form of lung cancer however is Non small cell lung
cancer which accounts for roughly 87% of all lung cancer cases in the UK. Of this type there are three
more subtypes of cancer which are squamous cell carcinoma, large cell carcinoma and
adenocarcinoma though these are all treated similarly.5
Symptoms of Non-small cell lung cancer include a persistent cough that may get worse, trouble
breathing, chest pain, hoarseness, fatigue and various infections such as bronchitis that may keep
coming back. Due to the nature of the symptoms of lung cancer it is easy to get it confused with a
less severe pathological disease which is why it is so hard to detect. Furthermore symptoms are
usually only presented after the disease has advanced to a far point which makes treatment for it
more difficult as the cells have usually metastasized by quite an extent and the stage of Lung cancer
will be high.The methods of detection are generally imaging tests which help doctors locate possible
tumours inside the lungs. Imaging may include X-rays, MRIs, Ultrasounds, PET scans or CT scans.
1
Lung cancer: a multidisciplinary approach, First edition. Edited by Alison Leary.
Textbook of Lung cancer from Boyle et al. (2000)
3
Cancer: a very short introduction by Nicholas James
4
Medical news today: ‘What is cancer? What causes cancer? written by Peter Crosta
http://www.medicalnewstoday.com/info/cancer-oncology/ accessed 15/6/14
5
‘Types of Lung cancer’ http://www.cancerresearchuk.org/cancer-help/type/lung-cancer/about/types-oflung-cancer 15/6/14
2
Once a tumour has been discovered the main treatment options for NSCLC are surgery, radiotherapy
and chemotherapy.6
Surgery:
For patients with Stage I or II of the disease, surgery gives the best chance of a cure although it is
quite hard to detect Non-small cell lung cancer in its early stages. In attempting surgery the doctor
will perform a thoracotomy, which involves leaving an opening in the chest wall. This leaves a scar
around the side of the chest. The surgeon will then identify and agree upon a method of pain control
which is important for the patient’s comfort. This will most likely involve local anaesthesia and
medication with paracetamol.
On the whole there are three main types of surgery for non-small cell lung cancer which include a
Lobectomy, Pneumonectomy and a wedge resection. Lobectomy involves getting surgically removing
half of or the whole section of a lung.
Lobectomy
Pneumonectomy
Wedge resection
Pneumonectomy is the removal of a whole lung as shown in the diagram above. Despite the
impression that it will be difficult to cope without a lung, it is possible to breathe normally with only
one lung present but only if there were no previous breathing difficulties pre-operation. Finally a
wedge resection can take place if the cancer is not far enough which involves removing only a small
portion of the lungs. Surgery is usually combined with chemotherapy and radiotherapy to achieve
the best effect. Soon after the patient will be able to go home but they will only get fully better a
long while after the operation takes place. If a Pneumonectomy has been performed then the
patient will have to check in with his/her local doctor to check that breathing difficulties are not
present.
Surgery does provide clear benefits, the main one being that it can eradicate the tumour if it is
localised in a small area. The five year survival rate with surgery alone approaches to 60-70%7 if the
patient presents an early stage localized disease. Unfortunately most patients present symptoms
that are in the range of stage III to IV since detection rate is low at early stages. The drawbacks of
surgery are that usually there are common side effects after which include the chest being sore and
feeling short in breath due to the lack of lung tissue. In severe cases pneumonia and bleeding can
6
‘Non-small Cell Lung cancer’ by Winston W tan http://emedicine.medscape.com/article/279960-overview
accesed 15/6/14
7
Lung cancer by Frank V Fosella et al.
occur as a result of this surgery or a leak of air from the lung wall. DVT (deep vein thrombosis) is also
a side effect of surgery and further surgery and medicine is likely to be used to overcome these
issues. Furthermore if the cancer has metastasized to multiple tumours in a stage IV lung cancer
condition then surgery is unlikely to be effective but is still possible if they are all localised close to
each other and they have not spread to other internal organs.
Radiotherapy:
Radiotherapy is the use of ionising radiation to kill cells. It is packets of energy which takes several
forms of photons such as x-rays or gamma rays. It can also be particles i.e. protons, electrons or
neutrons. Radiation deposits energy in tissues and produces ionisation. Radiation kills cells by
producing secondary charged particles and free radicals in the cell nucleus which produce a form of
DNA damage. DNA can be damaged when high energy x-rays collide with electrons of the biological
molecules which causes the electrons of these molecules to be ejected. This leads to DNA damage
which causes cells to die almost immediately.8 Radiotherapy is carried out via intensive radiation
therapy which involves a thin wire being sealed in an object and placed in a catheter which is
inserted into the lungs via the bronchi. It is then placed at the site of the tumour and is left there for
several minutes until removal so as to maximise the effect of it killing cancer cells but not to leave it
too long to damage normal tissue.
The doses of radiation are usually split into smaller doses per session with a doctor. This process is
known as fractionation, and the dose is gradually increased as treatment progresses in order to
achieve the same amount of cell kill. The most desirable use of radiotherapy involves using generally
lower doses per fraction to kill the cancer cells but allow the normal cells to recover.
Methods of delivering radio treatment include Brachytherapy that is delivered by placing a source of
radiation next to the treatment area, in this case the lungs. Due to their precisely placed position the
irradiation only affects a localised area of the lungs so healthy tissues are less exposed to harmful
radiation. This has advantages to external beam radiation therapy since the tumour will be treated
with localised radiation that lowers the probability of damage to surrounding tissue9. Since
brachytherapy is completed in a lower amount of time than other radiation therapy courses it
lowers the chance of lung cancer cells surviving and dividing between doses of radiation which
increases the chance for patient survival as a result.
External beam therapy, the alternative method for delivery of radiation uses electron beam therapy,
orthovoltage and megavoltage therapy. Orthovoltage produces low energy beams of x rays that
treat tumours since the dose of radiation is within a few centimetres of the skin. Electron beam
therapy is delivered using a linear accelerator which fires charged particles (electrons) towards the
site of the tumour after the area of the cancer has been marked on the patient’s skin. Megavoltage
is below the skin surface which allows the skin to be spared of damage from the radiation and is
used to treat deep seated tumours.
Radiotherapy has clear advantages as it is seen as a last resort for those medically inoperable due to
the location or size of their tumour. Radiotherapy is a painless procedure (though the side effects
8
‘Lung Cancer a multidisciplinary approach’ by Alison leary page 67
9
Stewart AJ et al. (2007). "Radiobiological concepts for brachytherapy".
may be painful) that helps prevent the spread of cancer cells in the body and is super effective due
to its precise localised nature in being able to treat the cancer. As a result of new technology
computer imaging can help locate the tumour and assist machines in administering localised
radiation which can be more effective since the target area is pinpointed easily so the damage to
surrounding tissue is minimised.
Although it is effective in destroying a tumour there are several side effects of radiotherapy. It can
cause tiredness and also chest pain and flu-like symptoms. The side effects range from the mild to
the more severe depending on how strong the radiation dose that you have taken is. Radiothearpy
will occasionally cause the oesophagus to become inflamed which consequently leads to problems
with swallowing and being uncomfortable. A further side effect would include tiredness due to loss
of cells.10 External radiotherapy can also cause extreme side effects since the radiation used
damages healthy tissues which can lead to chest pain.
Further disadvantages include the expensive nature of radiotherapy as it involves the use of high
tech machinery, lots of different sessions, several registered practitioners monitoring your progress
and lots of different treatments. The cost therefore is high and this too can also vary depending on
the cost of the health service in your area which you may not be able to afford. Also there are
restrictions to the diet of a patient which require that they eat lots of calories so they don’t lose
weight during treatment. After radiotherapy has finished the patient will need to have care for the
rest of his life as checkups will be carried out to check for signs of the cancer or whether the therapy
has worked, which it might not have.
Chemotherapy:
Chemotherapy is considered to be relatively insensitive to non-small cell lung cancer but is used in
combination with radiotherapy and surgery anyway since it does have an effect although a minor
one anyway. Chemotherapy is a treatment involving the use of drugs to prevent the growth of
cancer cells in the lungs which is done either by killing the cells or to stop them from dividing.
Chemotherapy is usually taken in orally or intravenously since it can enter the bloodstream and
reach the cancer cells throughout the body. When it is placed directly into an organ such as the lungs
the drugs affect the cells in that area. The method of delivery for these drugs depends on the stage
of the non-small cell lung cancer present at the time of patient treatment.11
The drugs then travel through the bloodstream at a rapid rate and destroy cell micrometastases and
the spread of cancer cells which cannot be detected by scans since they have moved away from the
tumour and are too small to see. This makes the treatment somewhat effective in eliminating cancer
cells from other parts of the body which is why it is readily prescribed as a means of treatment for
patients with stage iv of NSCLC and this is good because at this stage the cancer has been spread to
other parts of the body and so is effective in tackling this issue as after the cancer has spread to the
other parts of the body it is hard to control and monitor it so chemotherapy helps diminish the
effect that the cancer cells have when it has spread to the other areas.
10
‘Radiotherapy for non small cell lung cancer’ accessed 15/6/14
http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Lung/Treatingnonsmallcelllungcancer/Radiotherapy.aspx
11
http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/Patient/page4#Keypoint23
Chemotherapy improves significantly 1-year survival for patients with advanced NSCLC. It is mostly
recommended for patients with either stage iii or stage iv of NSCLC. The treatment is generally
known as combination chemotherapy since a combination of drugs are taken which are docetaxel
and gemcitabine which are the major drugs used. It is important to note that most chemotherapy
drugs have an existing toxicity which makes choosing the dosage an important job as too low a dose
would be too ineffective yet too high a dose could damage cell tissue seriously and could lead to side
effects.
Chemotherapy is often used after surgery to lower the risk of the cancer coming back. The
treatment of chemotherapy and radiotherapy together is sometimes used to banish the early stages
of Non small cell lung cancer for those who are not able to have a surgery. For a healthy person the
best chance of survival is a combined therapy of chemotherapy and radiotherapy since they will be
able to potentially maximise the effect of survival and although being cured is unlikely it will
certainly help to live longer.
The two approaches of taking chemotherapy in patients have been preoperative (neoadjuvant) and
postoperative (adjuvant). Studies have been conducted on adjuvant treatment but no real benefit
was discovered from patients with this treatment despite the stage they were in proving it to be
relatively ineffective. A study was conducted on 52 randomized trials where adjuvant chemotherapy
was utilized in patients with the disease and there was only a 5% positive treatment effect and in
some cases it was even considered detrimental to overall survival.12 Neoadjuvant treatment has also
been studied by scientists and has been shown to have demonstrated a significant survival benefit to
patients with around a stage III disease of non small cell lung cancer that has had its preliminary
results been approved of.
In contrast to radiotherapy and surgery, chemotherapy is a systemic treatment used to treat the
entire body rather than a small area. Chemotherapy drugs vary widely in composition,
administration and side effects. Cancer is made of living tissue, so the destruction of cancer depends
on the destruction of its cells. Chemotherapy destroys either cancerous and normal cells which is
unavoidable, therefore it is not recommended for unfit people or people who are very weak since it
will make them more unfit and maybe ill. Every time chemotherapy is administered there needs to
be a compromise between the destruction of the cells of cancer and the control of undesirable side
effects.
Chemotherapy has certain benefits for patients and that would be that it can be used to control the
growth of tumours and to prevent it spreading throughout the body and metastasizing though it
cannot be considered an effective cure since the cancer will resurface. It can however make the area
of cancer small enough so that a team of surgeons can operate on the tumour which makes it work
very effectively when combined with the use of surgery or radiotherapy. It is also beneficial since it
reduces the other symptoms of the cancer which include the patient’s stress due to being hurt by
the cancer. Reducing stress and pain can be significantly important since it increases his quality of
life which is most important when considering a patient and his needs even though he is unable to
be cured from the cancer.
12
Lung cancer by Frank V fosella
The disadvantages presented from the use of chemotherapy in the treatment of non small cell lung
cancer are much more severe. Most people experience tiredness that gets worse as the treatment
progresses and will even last for quite a few months after the treatment has ended known as
fatigue. Patients will lack energy and will struggle to cope with excessive feelings of tiredness as a
result of the chemotherapy which will cause it. Furthermore chemotherapy stops the bone marrow
from making enough blood cells to be produced. This means that white blood cell production is
significantly reduced so the patient is more prone to infection due to low white blood cell count, the
patient is anaemic due to low red blood cell count and the patient is at risk of severe bleeding due to
the lack of platelets to help clot the blood and thus prevent excessive bleeding from occurring. Signs
of infection amongst patients will include a high temperature, headache, coughs and a fever. 13
Most commonly observed amongst chemotherapy patients and cancer patients in general are a loss
of hair. Some drugs make your hair fall out by making it thinner while other make all your hair fall off
including the eyebrows and the eyelashes. Hair loss is very distressing for the patient’s self esteem
and can be one of the worst side effects encountered since most patients can’t cope without their
hair. Furthermore chemotherapy also makes the skin more sensitive and dry which causes rashes
and increased risk of sunburn when exposed to the sun for too long. People often find that nails
become brittle during treatment and the hair is found with white streaky lines going straight through
it. The mouth can also be affected since it can become quite sore with bulges developing on the side
of it. A final disadvantage is that chemo drugs can damage nerves and cause pins and needles in your
hands and feet.
Conclusion:
It is difficult to conclude which treatment is most effective since the treatments listed are the main
treatments for the disease and are usually used in combinations with each other. Surgery is an
immediately effective short term solution for treating localised areas of the cancer but in roughly
40% of cases lung cancer is inoperable and this is not a viable solution, therefore a combination of
chemotherapy and radiotherapy is used as treatment. Surgery can allow the 5 year survival rate for a
patient to greatly increase however the cancer will inevitably return and surgery will no longer be a
viable option as a significant portion of the lung has been cut out at this point. Chemotherapy is
fairly effective though is almost useless on its own neoadjuvant or adjuvant but combined with
radiotherapy is effective in preventing the cancer cells from metastasizing and for the tumour to
spread which makes it useful but only as a combination with another option. The side effects of
chemotherapy alone make it an undesirable option to be used by itself and therefore are the
weakest of my three proposed methods. Finally I believe radiotherapy to be the most effective
solution for the treatment of non-small cell lung cancer since it is both a localised form of cancer
treatment that also prevents metastatisation of the tumour to other parts of the body without
posing the same risks as surgery. Although a lot of tumours are considered surgically inoperable due
to their position in the lungs, radiotherapy is often considered to be able to treat all tumours since
the charged particles can penetrate anywhere in the body without an incision needing to be made in
order to reach the tumour.
13
http://www.cancerresearchuk.org/cancer-help/about-cancer/treatment/chemotherapy/chemotherapyside-effects