Lung cancer is one of the major
causes of death. It is the 2nd most common cancer worldwide, more
common in men and the 2nd most common cancer in women.
There were more than 2.5 million
new cases of lung cancer in 2020.
In Malaysia lung cancer accounts
for approximately 10.6 % out of a total of 48,639 of all malignancies in 2020.
The most common cancers in Malaysia in 2020 are: breast (17.3 %) colorectal
(13.6 %), lung (10.6 %), nasopharyngeal (4.6 %), liver (4.4 %) and others (48.6
%)
The lifetime risk is
approximately 1 in 55 for Malaysian males. The risk is highest in Chinese males
(1 in 43), followed by Malays (1 in 62) and Indians (1 in 103). For women, the
risk is approximately 1 in 135, although in recent years the incidence of lung
cancer has shown an increase in women even though females are less likely to
smoke compared to males. The age-standardized incidence rate of lung
cancer increases rapidly from age 45 years and is highest in the 60- to
74-year-old age group. Nearly 90% of lung cancer patients in Malaysia are
diagnosed with stage III or IV disease.
Pathophysiology:
The classical bifurcation of lung
cancer is non-small cell lung cancer (NSCLC), the more common type, and small
cell lung cancer (SCLC). SCLC is typically less amenable to surgical resection,
whereas NSCLC can more often be treated with surgery. NSCLC can be divided into
three major histological subtypes, namely, squamous cell carcinoma,
adenocarcinoma, and large cell lung cancer. It is also possible for lung
cancers that have mixed features to be identified as mixed small cell and large
cell cancer.
Signs and Symptoms:
Symptoms do not normally occur
until the cancer is advanced and can include persistent cough, haemoptysis,
chest pain, voice change, example hoarseness, worsening shortness of breath,
recurrent pneumonia, or bronchitis.
Risk Factors:
Smoking and Tobacco Use:
Cigarette smoking is by far the
most important risk factor for lung cancer, wherein risk increases with both
the quantity and duration of smoking.1 Approximately 90 % of
lung cancers are the result of tobacco use, and the risk of a smoker developing
lung cancer is 25 times greater than that of a non-smoker. Smoking is strongly
linked with SCLC and squamous cell carcinoma, and adenocarcinoma is the most
common type in patients who have never smoked.3
Environmental Carcinogen:
Environmental risk factors that
have been implicated in lung cancer includes exposure to radon as the second
most common cause, second-hand smoke, asbestos, metals like chromium and
cadmium, tar exposure, arsenic, certain organic chemicals such as bis(chloromethyl)
ether, silica, radiation exposure, air pollution, and diesel exhaust. Certain
occupations may increase exposure to lung carcinogens, including rubber
manufacturing, paving, painting, and chimney sweeping in cold countries. In
addition to asbestos exposure, cigarette smoking greatly increases the chances
of an asbestos-related lung cancer.
Genetic and Biomarkers:
Lung cancer is a complex and
heterogeneous disease, not only at the biochemical level involving genes,
protein, metabolites, but also at the tissue, organism, and population level.4 There
are many early detection biomarkers for lung cancer, including both tissue
and biofluid-based biomarkers such as airway epithelium, sputum, blood, and
exhaled breath. Mutation in p53 has been seen in chronic smokers before there
is evidence of neoplasia, making it a potentially useful predictor of lung
cancer. Due to the heterogeneity of lung cancer, detection by one single
biomarker remains difficult. Panels of biomarkers can be useful, but these
frequently have overlap with other diseases, especially other cancers and
inflammatory conditions. 5
Screening and Detection:
Compared with standard chest X-ray
(CXR), screening with spiral computed tomography (CT) has been shown to reduce
lung cancer-related deaths by 16-20 % among adults with a 30 pack-year history
who were current smokers or who had quit within the past 15 years. Current
American Cancer Society guidelines suggest discussing utilization of low dose
helical CT (LDCT) in current or former smokers aged 55 - 74 years in good
health with at least a 30 pack-year history of smoking. A "pack-year
" is the packs of cigarettes smoked a day (1 pack = 20 cigarettes)
multiplied by the number of years smoked. "Clinicians with access to
high-volume, high -quality lung cancer screening and treatment centres should
initiate a discussion about lung cancer screening with apparently healthy
patients ages 55-74 who have at least a 30 pack-year smoking history and who
currently smoke or have quit within the past 15 years. A process of informed
and shared decision making with a clinician related to the potential benefit,
limitations, and harms associated with screening for lung cancer with LDCT
should occur before any decision is made to initiate lung cancer screening.
Smoking cessation counselling remains a high priority for clinical attention in
discussions with current smokers, who should be informed of their continuing
risk for lung cancer. Screening should be viewed as an alternative to smoking
cessation.
Low-dose helical CT (LDCT) is
recommended annually starting at age of 55 till 79 in those with a 30 pack-year
smoking history. This recommendation continues if a nodule measuring </- 4
mm is found. For nodules that measure 4-6 mm repeat LDCT in 6 months. If the
nodule grows to 6 -8 mm or greater, radiology may recommend positron emission
tomography (PET) / CT or bronchoscopy based on nodule characteristics.
Chest Radiography:
CXR is no longer recommended as the
screening technique for lung cancer and is less useful than newer technologies
such as LDCT. According to the large Prostate, Lung, Colorectal, and Ovarian
cancer screening trial published in 2011, annual screening with chest
radiography did not reduce lung cancer mortality when compared with a
"usual care" group who did not receive an annual chest radiography.7
Sputum Cytology:
This technique is more likely to be
helpful in the detection of cancer that start in the major airways, such as
squamous cell lung cancer.8 According to four prospective randomized
controlled studies of lung cancer screening using a combination of CXR and
sputum cytology there is no significant reduction in lung cancer mortality
associated with an invitation to undergo sputum cytology screening.
Positron Emission Tomography (PET):
Not all patients with lung cancer
will require a PET scan; however, it can be a useful tool for determining
cancer staging.9 It can be effective for determining the level
of tissue activity and is more effective than CT in distinguishing between
benign and malignant lesion. 10 Glucose uptake alone is
nonspecific because it can be increased with inflammatory conditions.
Laser Bronchoscopy:
Conventional white-light
bronchoscopy (WLB) alone identifies the lesion in only 29 % of cases. 11
Conventional Treatment:
Conventional treatment includes
surgery, radiofrequency ablation (RFA), radiation therapy, chemotherapies,
targeted therapies, and immunotherapy. Palliative therapies may also be used to
help with symptoms.
Surgery:
Surgery to remove lung cancer may
be an option for early-stage NSCLC. More advanced lung cancer, especially with
metastasis, may not be helpful by surgery. If surgery can be done early, it
provides the best chance to cure NSCLC. The risk for serious consequences is
high 8 Types of lung surgery includes pneumonectomy,
lobectomy, and segmentectomy (wedge resection).
Radiofrequency Ablation:
RFA may be useful for some small
cell NSCLC tumours that are near the edge of the lungs, especially in people
who cannot tolerate surgery. In RFA, a thin probe is used to heat the tumour to
destroy the cancer cells. This is typically done as an outpatient procedure.
Major complications are uncommon but can include a partial collapse of the
lungs or bleeding into the lungs. 8
Chemotherapy:
Patients with SCLC are frequently
treated with chemotherapy. If the disease is in a limited stage, radiation
therapy and rarely surgery may be used for SCLC. 20 The side effects
of treatment with chemotherapy for SCLC include hair loss, mouth scores, loss
of appetite, nausea, vomiting, diarrhoea, constipation, immunodeficiency such
as myelosuppression (decreased blood cell counts).
easy bruising, and
fatigue
The list of chemo drugs used
are:
- Platinum-Based Chemotherapy:
- Cisplatin
- Carboplatin
- Paclitaxel and Docetaxel:
- Paclitaxel
- Docetaxel
- Vinorelbine
- Gemcitabine
- Epidermal Growth Factor Receptor (EGFR) Inhibitors:
- Erlotinib
- Gefitinib
- Afatinib
- Osimertinib (for patients with EGFR mutations)
- Anaplastic Lymphoma Kinase (ALK) Inhibitors:
- Crizotinib
- Ceritinib
- Alectinib
- Lorlatinib
- Programmed Death-Ligand 1 (PD-L1) Inhibitors:
- Pembrolizumab
- Atezolizumab
- Durvalumab
- Nivolumab
- Tyrosine Kinase Inhibitors (TKIs):
- Bevacizumab (targets vascular endothelial growth
factor, VEGF)
Side effects of these drugs can
vary, and not everyone will experience the same side effects. Common side
effects may include fatigue, nausea and vomiting (antiemetic) diarrhoea, hair
loss, and myelosuppression (decreased blood cell counts).
Radiation Therapy:
The two major types of radiation
therapy include external beam radiation therapy (EBRT) and brachytherapy, a
type of internal radiation therapy. The use of EBRT is less common than in the
past because there are newer treatments that allow for greater accuracy. 8 When
radiation is given with chemotherapy, the side effects are often worse.
Fever therapy or
pyrotherapy (artificial fever):
Induced fever is another method of
treatment by raising the body temperature or sustaining an elevated
body temperature using a fever. In general, the body temperature was
maintained at 41 ° C (105 ° F). Many diseases were treated by
this method in the first half of the 20th century. In general, it was done by
exposing the patient to hot baths, warm air, or (electric) blankets. The
technique reached its peak of sophistication in the early 20th
century with malariotherapy, in which Plasmodium vivax, a causative
agent of malaria, was allowed to infect already ill patients in order to
produce intense fever for therapeutic ends. The sophistication of this approach
lay in using effective anti-malarial drugs to control the P. vivax infection,
while maintaining the fever it causes to the detriment of other, ongoing, and
then-incurable infections present in the patient, such as
late-stage syphilis. This type of pyrotherapy was most famously used by
psychiatrist Julius Wagner-Jauregg, who won the Nobel Prize for
Medicine in 1927 for his elaboration of the procedure in treating
neurosyphilis. However, this method of using malarial parasite to induce a
fever is no longer used but is replaced by the term ‘hyperthermia therapy’
today which is essentially the same thing serving the same purpose of elevating
the body temperature to levels higher than normal (typically around 41-45° C)
using external methods such as heat blankets, warm water immersion, or focused
microwave or radiofrequency energy. Today fever therapy is used as a treatment
for cancer because high temperatures can damage and kill cancer cells.
It's commonly used in cancer
treatment as a complementary therapy alongside other treatments like
chemotherapy or radiation therapy. The elevated temperature can help in several
ways:
- Direct Cell Damage: High temperatures can directly
damage and kill cancer cells.
- Sensitizing Effect: Hyperthermia can make cancer
cells more sensitive to radiation or chemotherapy, enhancing the
effectiveness of these treatments.
- Immune System Stimulation: It may also stimulate
the body's immune response, aiding in the destruction of cancer cells.
Overall, hyperthermia treatment can
be effective in certain cases of cancer treatment, especially when combined
with other therapies. However, its effectiveness varies depending on factors
such as the type and stage of cancer, as well as individual patient factors.
It's often used as part of a comprehensive treatment plan tailored to each
patient's specific needs.
Alternative Therapies to Consider:
Research is ongoing at various
stages with herbal and natural preparations with astragalus, ginseng,
pomegranate, rosemary, sage, parsley, oregano, and various combinations of
Chinese herbs, although conclusive evidence may not be apparent yet. Another potential
anti-cancer herb is Sabah snake grass (Clinacanthus nutans) and lemon
grass or serai, in the Malay language. See some of the many scientific papers
published on the use of lemon grass for the treatment of cancers here:
https://www.scielo.br/j/cta/a/YwZrtspBFZZMFxrPrMK9Lvs/?format=pdf&lang=en#:~:text=Lemongrass%20extract%20possesses%20potent%20anticancer,Cancer%20Therapies%2C%2018%2C%201534735419889150.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918039/
https://www.nature.com/articles/nindia.2014.45
https://www.sciencedirect.com/science/article/abs/pii/S1773224723000357
Here is just one research paper
among several dozen published on the use of Clinacanthus nutans (Sabah snake
grass) for treating cancers. https://www.hindawi.com/journals/ecam/2021/5560502/
Patients with lung cancer and other
poor-outlook cancers are particularly vulnerable to heavily promoted claims for
unproven or disproven "alternatives". Inquiring about the patients'
uses of these therapies should be routine because these practices may be
harmful and can delay or impair treatment. However, physician-guided mind-body
modalities and massage therapy can reduce anxiety, mood disturbances, and
chronic pain. Acupuncture can assist in the control of pain and other side
effects and help reduce quantities of pain medication that may be
required.
Yoga:
Some controlled trials suggest yoga
is beneficial for chemotherapy-induced nausea, anticipatory nausea, pain,
invigoration, acceptance, fatigue, and appetite loss, and can decrease salivary
cortisol levels. Investigators also report a positive dose-response
relationship.
Massage:
Massage therapy, an effective
adjunct to cancer supportive care, can reduce anxiety, depression, and pain.
The evidence that supports its effect on anxiety is stronger than that on
depression.
Exercise-Based Pulmonary
Rehabilitation:
Overall, the studies published to
date suggest that short-term (6 - 8 weeks), low-intensity, multidisciplinary,
exercise-based rehabilitation is potentially feasible and safe for select
patients with inoperable NSCLC. The preliminary data further suggest that
low-intensity, multidisciplinary, exercise-based rehabilitation is associated
with modest improvements in exercise tolerance and functional capacity
endpoints in select patients who are able to tolerate and achieve reasonable
adherence.
Acupuncture:
Acupuncture is a relatively safe
and minimally invasive modality that may be useful for treating symptoms of
lung cancer and side effects of anticancer treatment. A small case series
showed some improvement in both an analogue pain scale and well-being score for
patients with lung cancer. Overall, there is a lack of data on whether
acupuncture could be useful in the treatment of chemotherapy-induced peripheral
neuropathy.
Nutrition:
Nausea and vomiting are common side
effects of chemotherapy treatments. There are numerous methods for treating
chemotherapy-related nausea, including corticosteroids, dopamine antagonists,
serotonin antagonists, benzodiazepines, aprepitant, and cannabinoids. One of
the best natural medicines for nausea is ginger. Ginger can also be recommended
for both its anti-nausea and anti-cancer benefits 15 Generally
a diet rich in non-starchy vegetables and fruits and low in red meat is
recommended B-complex vitamins, tea, and cruciferous vegetables can also be
recommended. For patients with weight loss, nutritional supplements may be
recommended along with a diet rich in protein while still limiting red meat
consumption. In patients with sarcopenia, supplementation with n-3 fatty
acids may be beneficial.13 Oral supplementation of
eicosapentaenoic acid (EPA) in patients with NSCLC significantly improves
energy, protein intake, and body composition, while decreasing fatigue,
neuropathy, loss of appetite, according to a randomized trial. 16
Curcumin is a food and herbal
medicine, scientifically called diferuloylmethane. It is a hydrophobic
polyphenol that is the main curcuminoid of turmeric. "The mechanism
implicated as a good natural anticancer medicine in the inhibition of tumour
genesis by curcumin are diverse and appear to involve a combination of
anti-inflammatory, antioxidant, immunomodulatory, proapoptotic, and
anti-angiogenic properties via pleiotropic effects on genes and signalling
pathways at multiple levels. 17 Gene inhibition of cyclooxygenase
(COX)-2 is thought to be the main anti-inflammatory activity of curcumin.
Curcumin tends to be well tolerated, however, its systemic bioavailability
after dosing is poor, which may limit its effectiveness outside the gastrointestinal
tract. However, pipevine, a major component of black pepper, has been shown to
increase the bioavailability of curcumin.18
Prevention:
Smoking cessation continues to be
the most important factor in reducing the risk for lung cancer. People who
discontinue smoking, even well into middle age, avoid most of the subsequent
risk for lung cancer, and discontinue smoking before middle age avoids
more than 90 % of the risk attributable toobacco.19
However, in recent years women who
hardly smoke unlike men are also found to develop lung cancer for reasons
unknown to medical scientists.
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