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Lung Cancer
Non Small Cell
Lung Cancer (NSCLC)
Small Cell Lung Cancer
Non Small Cell Lung Cancer (NSCLC)
Small Cell Lung Cancer
Lung cancer is the second most
prevalent cancer both in men and women, after prostate and breast
cancers respectively. The number of death from lung cancer is higher
than any other cancer.
1.
Smoking: Cigarette smoke contains numerous
carcinogens that were proved to induce cancer. Lung cancer incidence
increases markedly in smoking people relative to non-smoker. Passive
smoking is also correlated with lung cancer.
2.
Asbestos exposure: exposure to asbestos is
correlated with increased incidence of lung cancer as well as with
mesothelioma. Usually lung cancer appears starting 20 years after
exposure.
3.
Ionizing radiation
4.
Air pollution
Lung cancer is defined according to
the cells shape revealed my microscopic examination. The two main
variants of lung cancer are:
A.
Small cell lung
cancer (about 10-20% of lung cancer)
B.
Non-small cell lung cancer (NSCLC)
Non-small cell lung cancer has
several subtypes:
a.
Adenocarcinoma
b.
Squamous cell carcinoma
c.
Large cell carcinoma
d.
Combined squamous cell carcinoma and
Adenocarcinoma
Non-Small Cell Lung cancer
infiltrates regional lymph nodes and adjacent organs. Distant
metastasis occurs usually to the liver, bone, adrenals, and brain.
Small cell lung cancer frequently send metastasis to the liver,
brain, bone, adrenals, and mediastinal lymph nodes.
Several steps should be performed for diagnosis of lung
cancer:
1.
Careful history taking from the patient by
an experienced physician: the main presenting symptoms include
cough, dyspnea (difficulty breathing), weakness, weight loss,
hemoptysis (coughing up blood), chest pain and hoarseness (due to
involvement of specific nerves adjacent to the tumor).
2.
Careful physical examination should be
performed. Findings on examination may include cachexia (severe body
weight loss), pallor (anemia), tachypnea (increased breath rate),
hoarseness, enlarged lymph nodes, wheezes (due to bronchial
obstruction), pneumonia (due to airways obstruction), and clubbing
of fingers. On auscultation wheezes, or decreased breath sounds (due
to pleural effusion) may be noted.
3.
Laboratory tests may reveal anemia of
malignant disease; leukocyte count can be normal or elevated
(especially if pneumonia is also detected); hyponatremia (low blood
sodium level) is not uncommon, and is mainly due to inappropriate
secretion of anti diuretic hormone (ADH) by tumor cells;
hypercalcemia (elevated blood calcium level); elevated LDH levels.
4.
Radiological evaluation should include
initially chest x-ray and computerized tomography of the chest.
PET-FDG scan can be helpful in detecting metastatic disease.
5.
Pathological evaluation makes the final
diagnosis. Tissue biopsy should be obtained. Several methods are
available to get material for pathologic examination:
A.
Sputum cytology: the sputum is examined
under microscope for the presence of malignant cells.
B.
Bronchoscopy: in this method direct
inspection of the bronchial tree is performed, and biopsy is taken
directly from the tumor. Alternatively, the bronchi are washed with
saline, which is recollected and tested for malignant cells
(cytology).
C.
Fine needle aspiration (FNA): the lesion is
approached via a fine needle under the guidance of a radiological
facility (ultrasound or CT). The aspirated material is tested for
malignancy under microscope.
D.
Open biopsy: this is performed in operation
setting. This approach is usually good for lesions that can’t be
approached by FNA, and for localized tumors that may be totally
removed by surgery (tumors localized to single lobe, with no
metastasis).
Non Small Cell Lung
Cancer (NSCLC). NSCLC is classified according to the TNM
system suggested by the American Joint Committee on Cancer (AJCC).
The staging system takes into account the primary tumor
characteristics (T1-T4, see table below), lymph nodes involvement
(N0-N3, see table below), and the presence (M1) or absence (M0) of
distant metastasis.
The combination of the different
characteristics of the tumor (the specific T, N, and M) gives the
stage of the disease in each patient. Presence of distant metastasis
denotes stage IV disease. The TNM combinations indicating Stages
I-III diseases are described in the table below.
Small Cell Lung
Cancer
Small cell lung cancer staging
defines “limited” (limited to one hemi-thorax) versus “extensive”
disease. Most patients present with extensive disease (60-70%), and
about 30-40% with limited disease.
NSCLC
Surgery
Surgery is the best treatment for
limited lung cancer. Resection usually includes the entire lung, a
lung’s lobes (most used), or a lobe segment. Patients with advanced
cancer or metastatic disease rarely gain from surgery. In very
specific and rare cases, resection of limited primary lung tumor and
single distant metastasis may be considered.
Radiotherapy
Radiotherapy is a pivotal modality
for the treatment of lung cancer. It is used both for curative and
palliative treatments. Radiotherapy is also used preoperatively in
some patients (with or without chemotherapy) to shrink the tumor
size so that surgery become feasible. Side effects of radiotherapy
include toxicity to: the normal lung tissue (radiation pneumonitis),
heart, esophagus (esophagitis) and spinal cord. These toxicities are
more prominent with increased radiation dose and/or intensity, and
in patients undergoing concomitant chemotherapy and radiation.
Chemotherapy
Chemotherapy for NSCLC usually
includes combination of drugs containing cisplatin (or carboplatin).
Other drugs used together with platinum include etoposide,
paclitaxel, vinorelbine or gemcitabine. Chemotherapy improve
survival in metastatic disease, as well as in locally advanced
disease. Recently, clinical trails showed that the use of
chemotherapy after resection of lung cancer, improve the survival of
patients. Overall, chemotherapy (platinum based) have a role in
treatment of lung cancer, but the prognosis for the long term,
remains disappointing.
Biologic therapy
1)
Bevacizumab (Avastin): Avastin is used in
treatment of advanced non squamous NSCLC (stage III, IV). In
squamous cell lung cancer, avastin resulted in high rate of
pulmonary hemorrhage (12) and hence its use was restricted to non
squamous non-small-cell-lung-cancer. Phase III study by Sandler et
al. (5) showed that adding bevacizumab to paclitaxel and carboplatin
compared to paclitaxel and carboplatin alone resulted in
prolongation of median survival from 10.3 months to 12.3 months.
There was though a 6 fold increase in significant bleeding, a 10
fold increase in severe hypertension, and a higher rate of febrile
neutropenia in the group that received
paclitaxel-carboplatin-bevacizumab compared to the
paclitaxel-carboplatin control group (5). Interestingly, women who
participated in this trail didn't benefit from avastin, with median
overall survival of 13.1 months in the paclitaxel-carboplatin group,
compared to 13.2 months in the paclitaxel-carboplatin-bevacizumab
group (5).
Small Cell Lung Cancer
Surgery
SCLC usually develops in the central
airways. Most patients present with metastatic disease. Surgery
usually is not applicable to most patients, except for patients with
“very limited’ and operable disease.
Radiation
Radiotherapy is integral part of the
treatment of SCLC (limited disease). Prophylactic radiation to the
brain is used in some patients, especially in near or complete
responders to induction chemotherapy.
Radiation also plays a pivotal role
in palliation (e.g. radiotherapy to painful bone lesion).
Chemotherapy
Several drugs have a role in
treatment of SCLC. Cisplatin or carboplatin are usually combined
with etoposide (VP-16), and were proved to give favorable results in
limited stage disease. Other regimens of chemotherapy for SCLC
include the ICE protocol (Ifosfamide, Carboplatin, Etoposide), VIP
(VP16=Etoposide, Ifosfamide, Platinol), and cisplatin& Irinotecan.
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