DR.

ABHIJEET KANJE

Introduction
Small cell lung cancer (SCLC) is a tumor of extremes. Un-treated, it is one of the most highly virulent malignancies known, with a life expectancy best measured in days to weeks.

On the other hand, it displays exquisite chemosensitivity, resulting in partial or complete responses in the vast majority of cases. Although many patients can be rendered free of clinical evidence of disease, most quickly relapse and die from this malignancy.

EPIDEMIOLOGY
Lung cancer is among the five main types of cancer

leading to overall cancer mortality contributing about 1.3 million deaths/year globally. In India trachea, bronchus, lung cancers are the most common cancers found in men. At a rate of 85 age-adjusted DALYs per 100,000 population, lung cancer accounts for 7% of total cancer DALYs in India.

Mortality, Incidence and Prevalence associated with Lung cancer

Globally in Males 0.85 million deaths in 2002. 29.4 age standardized death rates (world) per 100,000 in 2008. 34.0 age standardized incidence rates (world) per 100,000 in

2008. One year prevalence of 0.38 million and five year prevalence of 0.93 million in 2002. Globally in Females 0.33 million deaths in 2002. 11.0age standardized death rates (world) per 100,000 in 2008. 13.5 age standardized incidence rates (world) per 100,000 in 2008. One year prevalence of 0.16 million and five year prevalence of 0.42 million in 2002.

In India for Males 58,000 deaths in 2004. 549, 000 DALYs in 2004 9.8 age standardized deaths rates per 100,000 in 2008. 10.9 age standardized incidence rates per 100,000 in 2008. One year prevalence of 11,511 and five year prevalence of 27,477 in 2002.
In India for Females

12,500 deaths in 2004. 127,000 DALYs in 2004. 2.3 age standardized deaths rates per 100,000 in 2008. 2.5 age standardized incidence rates per 100,000 in 2008. One year prevalence of 2,646 and five year prevalence of 6,394 in 2002. Source: WHO, 2009b (6); GLOBOCAN 2002, 2008 database IARC (5)

 Lung cancer is the leading cancer among men in terms

of incidence rates in 6 out of the 12 Population Based Cancer Registries (PBCRs) in India (table 1). The age-adjusted incidence is highest in Kolkata, a metropolitan city in the west, and lowest in Barshi , a rural registry in Maharashtra(11)

Lung cancer and Demographic Status

A review of 32 Indian studies conducted by Behera

and Balamugesh in 2004, provides valuable data on the prevalence on lung cancer over two time periods: 1958-1985 and 1986 -2001(Table 2). Increases in lung cancer rate were predominantly observed among farmers, but lung cancer remained predominantly a disease of males with a male to female ratio of 6.7:1.5 and 5.7:1. The mean age was 54.6 years in males and 52.8 years in females which has remained the same over the years (15). Small Cell Carcinoma type was predominant than Non Cell Carcinoma with a ratio 2.5:1 and 2.7:1.

RISK FACTORS
1. Tobacco smoke : Like all other lung cancers, SCLC is linked to a variety of environmental risk factors. By far the strongest association is with the use of tobacco: Up to 98 percent of SCLC patients have a history of smoking. In most populations the incidence of SCLC rises with increasing tobacco exposure in a dose-dependent fashion, making the overall risk for smokers approximately 15-fold higher than for nonsmokers. If a person stops smoking before lung cancer starts, the lung tissue slowly repairs itself. Stopping smoking at any age may lower the risk of lung cancer.

 Cigar and pipe smoking has slightly reduced risk to

cause lung cancer as is cigarette smoking because less smoke is inhaled. There is concern that menthol cigarettes may increase the risk even more since the menthol allows smokers to inhale more deeply. Secondhand smoke(Passive smoking): People who don't smoke but who breathe the smoke of others may also be at a higher risk for lung cancer. Non-smokers who live with a smoker, for instance, have about a 20% to 30% greater risk of developing lung cancer. Non-smokers exposed to tobacco smoke in the workplace are also more likely to get lung cancer.

 In India, smoking of tobacco is mainly in the form of

bidi, followed by cigarette, hukah, chillum and chutta . Bidis accounts for three quarter (77%) of the market of smoking tobacco and 48% of the whole tobacco market . According to National Family Health Survey (NFHS)-3 carried out during 2005-06, prevalence of tobacco use (all forms) was 57% in men and 10.8% in women. The relative risk of developing lung cancer is 2.64 for bidi smokers and 2.23 for cigarette smokers with 2.45 as the overall relative risk . Hukah smoking has also been associated with lung cancer with an odds ratio (OR) of 1.94, (95% confidence interval 0.85-4.44) .

 Occupational risks for SCLC include exposure to

bischloromethyl ethers, nickel, vinyl chloride, asbestos, cadmium, and radon daughters (in uranium miners). Other types of radiation exposure also appear to be significant risk factors, with an in-creased incidence of SCLC in atomic bomb survivors and patients (typically those with breast cancer or Hodgkins lymphoma) exposed to therapeutic irradiation. Industrial nations in general have an increased incidence of SCLC, possibly secondary to higher levels of air pollutants.

SCLC classification history

 SCLC presents a proliferation

of small cells (less than 4 lymphocytes in diameter) with unique and strict morphologic features, scant cytoplasm, ill-defined borders, finely granular salt and pepper chromatin, absent or inconspicuous nucleoli, frequent nuclear molding, and a high mitotic count.

GENETICS
In SCLC the most common genetic abnormalities

include loss of chromosomal material associated with inactivation of specific tumor suppressor genes. This frees the cells from the normal growth constraint imposed by the gene products, resulting in unrestrained growth of the cancer cell. The chromosomal abnormalities most commonly associated with SCLC include loss of a portion of the short arm of chromosomes 3, 9, 11, and 17. Deletions in 3p are found in nearly all (90 percent) SCLC tumors and cell lines.

 SCLC has long been associated with the production of

numerous peptides, including ADH, ACTH, and calcitonin. The autocrine growth promotion potential of these peptides was first proposed almost 25 years ago. The classic autocrine agent in SCLC is gastrin-releasing peptide (GRP), a mammalian analog of the amphibian hormone bombesin. SCLCcells produce GRP, as well as neuromedin B, which bind to one of three receptors (GRP receptor, neuromedin B receptor, and bombesin receptor subtype 3) to active the autocrine-simulated growth loop. A murine anti-bombesin monoclonal antibody directed against GRP has been shown to inhibit the growth of SCLC in vitro and in a mouse model. Unfortunately, no clinically usable antibody is currently available.

 A second autocrine growth loop involves the c-kit

receptor, which is found in the majority of gastrointestinal stromal tu-mors (GIST), as well as up to 70 percent of SCLC tumors. The ligand stem-cell factor is produced by small cell cancers, which in turn binds to the c-kit receptor to stimulate cell Growth. The tyrosine kinase inhibitor imatinib, although effective in GIST, was not shown to have any antitumor activity in two phase II trials, and is not an option for treatment at present. Elevated levels of IGF-1 have been detected in more than 90 percent of SCLC tumors and cell lines, and receptors for IGF-1 are found on SCLC cell lines, suggesting autocrine growth activity.

Clinical Manifestations
No aspect of the clinical presentation of SCLC

distinguishes it from NSCLC or even from neoplasms metastatic to the lungs. However, the duration of symptoms of small cell cancer tends to be very short, due to the rapid dissemination of the disease. The typical patient is a middle-aged or elderly smoker who presents with symptoms attributable to their pulmonary and mediastinal disease: cough, dyspnea, chest pain, hoarse-ness, and/or hemoptysis. Because of the usual endobronchial location of the tumor, patients often have accompanying postobstructive pneumonia.

Clinical manifestations
Regionnal spread to hilar and mediastinal nodes may cause dysphagia due to esophageal compression, horseness due to recurrent laryngeal nerve compression, horners syndrome due to sympathetic nerve involvement, and elevation of the hemidiaphragm from phrenic nerve compression.

 Constitutional symptoms may include weakness,

anorexia, weight loss, and, rarely, fever. Symptoms may also arise from distant metastases, including headache or seizures in patients with central nervous system (CNS) disease, and abdominal or bone pain with hepatic and osseous metastases, or from regional disease with attendant superior vena cava obstruction, manifesting as facial fullness, upper extremity swelling, headache, and dysphagia. In rare instances, patients present with symptoms from a paraneoplastic syndrome.

Physical examinations
Usually in early stage, most of the patients with lung cancer have no positive physical findings. General findings include abnormal percussion, breath sounds changes, moist rales (when pneumonia happens) Digital clubbing, superior vena cava syndrome, horners syndrome(unilaterally constricted pupil, enophthalmos, narrowed palpebral fissure and

loss of sweating on the same side of the face.)

Physical examinations
Endobronchial obstruction may result in a localized

wheeze. Lobar collapse may result in an area of decreased breath sounds and dullness to percussion. Supra clavicular and scalene lymphadenopathy.

INVESTIGATIONS
Laboratory evaluation reveals mild abnormalities of

liver function (usually elevated alkaline phosphatase, and less commonly SGOT, SGPT, or bilirubin) and/or elevated lactate dehydrogenase in about 50 percent of patients. Leukopenia and thrombocytopenia are unusual and hardly ever seen in the absence of widespread disease at a number of sites beside the bone marrow.

 Chest X-ray The xray examination is the most important method. It can detect the presence of lung cancer. The most frequent finding is a mass in the lung

field. Since small cell ca are mostly central tumours(75%cases),slight prominence of hilar shadow is an early feature. Postobstructive atelectasis and pneumonia are very common with small cell lung cancer, but cavitation on chest radiograph suggests the alternative diagnosis of squamous cell lung cancer.

SPUTUM CYTOLOGY
Sputum cytology can give definitive diagnosis in 60-70%

cases of lung cancer. Small cell tumor being centrally placed have a higher positive yield. First sputum in morning or one produced after FOB has higher yield. Yield from single sample is 40% and can be increased by repeated collections to in excess of 80% with 4 specimens.

Small Cell Carcinoma

Epithelial cells are small with scanty cytoplasm,

ill-defined cell borders, finely granular nuclear chromatin (salt and pepper pattern), and absent or inconspicuous nucleoli . The cells are round, oval, and spindle-shaped with nuclear molding, high mitoses & necrosis. Basophilic staining of vascular walls due to encrustation by DNA from necrotic tumor cells is frequently present .

Small Cell Carcinoma

Dark blue cells with minimal cytoplasm are packed together in sheets Hemotoxylin- Eosin stain

Small cell carcinoma

Electron microscopy shows dense-core neurosecretory granules. Immunohistochemical stains for neuroendocrine markers such as chromogranin, synaptophysin ,and leu-7 are positive in most cases. Commonly associated with ectopic hormone production. Strong relationship with cigarette smoking. Most aggressive of lung tumors, metastasize widely, and are virtually incurable by surgical means.

Diagnosis Of SCLC

Abstract
Diagnosis of lung cancer requires: A: detecting the tumor B: establish the cell type C: define the stage of the tumor among these, Determing cell type is the most important because it influences the treatment.

Many methods we used to detect the tumor,

including chest X-ray, computer Tomo graphy(CT),Magnetic resounce imaging (MRI), PET, histologic examination (mainly sputum examination, bronchoscopy biopsy,bronchial brushing , bronchial washings, transbronchial needle aspiration and transthoracic needle).

If a diagnosis is not established by these imaging examination and cytologic study , we can use thoracotomy. Before we make the decision , we must weigh some foctors,for example , the importance, age of the patient and other
complicating illness.

Chest X-ray
It is the most important method to find lung cancer. If a patient with chronic cough, sputum with few blood, and dyspnea, lower fever he should adopt a chest X-ray. The most frequent finding is a mass in the lung field.

On chest X-ray, secondary manifestations include lobar collapse, pleural effusion, pneumonitis, elevation of the hemidiaphragm, hilar and mediastinal adenopathy, and erosion of ribs or vertebrae due to metastases.

Lung cancer on CT
CT is the most useful in evaluating patients with pulmonary and mediastinal masses. It is also useful for detecting multiple metastases. CT can show a mass to be located in which lobe of lung field and the size of the mass. It also shows the nodule in the mediastinum. Sometimes,when a mass locate behind the heart, chest X-ray can`t detect it .CT can detect some secret sites of lung cancer.

 Current guidelines call for computed tomography (CT)

scans of the chest to assess for adenopathy, contralateral parenchymal disease, and pleural effusion. Liver metastases occur in roughly 25 percent of SCLC patients, and adrenal metastases in 5 to 30 percent; therefore, the initial CT of the chest should be extended caudally to include the liver and both adrenal gland Patients with any neurological abnormality should immediately undergo MRI or CT of the brain and MRI of the spinal cord, as 80 to 90 percent of these SCLC patients have disease in the central nervous system

Radionuclide bone scans

Radionuclide bone scans are called for in any patient

with bony pain. As 25 to 40 percent of patients have bony metastases on presentation, and most of these patients are asymptomatic with normal serum alkaline phosphatases, a bone scan can be considered an integral part of the staging workup.

Positron emission tomography scan

Positron emission tomography (PET) scans have

recently been show to have utility in SCLC. SCLC is fluorodeoxy-d-glucose (FDG) avid at both primary and metastatic sites. PET appears to be more sensitive and specific than CT scans in detecting nonbrain distant metastases, but less sensitive than MRI or CT in detecting brain metastases. Approximately 10 percent of limited stage patients can be upstaged to extensive stage disease through the use of PET scans, and therein lies the best defined clinical utility for this modality

Bronchoscopy
It is important both for determining if a tumor is present and for obtaining tissue for histologic diagnosis. Usually, the combination of bronchial brushing and forceps biopsy is positive 90 to 93 percent of the tumors located in proximal airway.

Bronchoscopic appearances of Small Cell Carcinoma

Tumors may be infiltrating, nodular, and obstructive

Thoracotomy
If the methods mentioned above are not useful for detecting the cell type of lung cancer,thoracotomy may be used. But we should analyse some other factors before we adopt the method, for example the age of the patient,the pulmonary function, and complicating illness.

Immunohistochemistry
Immunohistochemistry plays an important role in the

diagnosis of SCLC. Nearly all small cell cancers are positive for the epithelial markers keratin, epithelial membrane antigen, and BER-EP4. (Non-Hodgkins lymphoma is suggested by antibodies against the common leukocyte antigen, with negative epithelial markers.) Given their neuroendocrine derivation,many of the tumors will stain positively for one of a variety of neuroendocrine markers, with neuron-specific enolase and chromogranin A being the two most common. Other neuroendocrine markers that can be found include dopa decarboxylase, calcitonin, Leu-7, CD56 (neural cell adhesion molecule [NCAM]), gastrin releasing peptide (GRP), andinsulin-like growth factor-I (IGF-I). One or more of these markers can be found in approximately 75 percent of SCLCs.

SCLC diagnostic criteria (1)

Cytological features of paramount importance Small cell size, <3 resting lymphocytes
Occasional large, pleomorphic nuclei accepted

Cell borders not seen High N/C ratio Finely granular chromatin Absent or at best inconspicuous nucleoli Cell shape varies from oval to spindled

SCLC diagnostic criteria (2)

Architectural features
Growth patterns: Solid sheets Nested Trabecular Rosettes Palisading

SCLC diagnostic criteria (3)

Architectural features Necrosis Encrustation of nuclear material on vessel walls (Azzopardi phenomenon (10%)

Staging of lung cancer

Small cell lung cancer has often metastasized at the time of diagnosis. TNM staging is not suited to small cell lung cancer. Small cell lung cancer is divided into limited and extensive stage disease.

SCLC
Limited Stage

Defined as tumor involvement of one lung, the mediastinum and ipsilateral supraclavicular lymph nodes or disease that can be encompassed in a single radiotherapy port.
Extensive Stage

Defined as tumor that has spread beyond one lung, mediastinum, and supraclavicular lymph nodes. Common distant sites of metastases are the adrenals, bone, liver, bone marrow, and brain.

PROGNOSTIC FACTORS
Since the aggressiveness of therapy may depend on this

perceived outcome, it is important to determine before treatment how a patient is likely to do Strongest and most consistent prognosticators from nearly all studies have been stage of disease (limited vs. extensive) and Karnofsky performance status at presentation. In general, extensive-stage patients have a lower chance of achieving a complete response to chemotherapy, shorter median survival times, and a much smaller chance of being cured. However, patients with extensive-stage disease, by virtue of having a single site of metastasis (especially in soft tissue, bone, or brain),often behave more like limited-stage patients and should be treated accordingly.

 The performance status or ability of the patient to

carry out normal daily activities has a profound effect both on the ability to tolerate chemotherapy and the efficacy of those drugs administered. In general, patients with poor performance status have a lower chance of response to chemotherapy and a higher chance of having clinical toxicity.

 Similar to performance status, substantial weight loss

(usually qualified as at least 10 percent of total body weight) is an independent prognostic factor for an adverse outcome. In many epidemiologic studies, female gender has been suggested to be a favorable prognostic factor in patients with SCLC. Women have a higher likelihood of responding to chemotherapy and obtaining a complete response. Their overall survival is also better than that of male patients.

 Karnofsky Scale Adapted from Karnofsky, Abelmann, Craver, & Burchenal, 1948 100 Normal; No complaints; No evidence of disease. Able to

work. 90 Able to carry on normal activity; Minor symptoms. Able to work. 80 Normal activity with effort; Some symptoms. Able to work. 70 Cares for self; Unable to carry on normal activity. Independent; not able to work. 60 Disabled; dependent. Requires occasional assistance; cares for most needs. 50 Moderately disabled; dependent. Requires considerable assistance and frequent care. 40 Severely disabiled; dependent. Requires special care and assistance. 30 Severely disabled. Hospitalized, death not imminent. 20 Very sick. Active supportive treatment needed. 10 Moribund. Fatal processes are rapidly progressing

 WHO/ECOG PERFORMANCE STATUS* Grade ECOG 0 Fully active, able to carry on all pre-disease

performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work 2 Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours 3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 4 Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair

 The continued use of tobacco is an adverse prognos-tic

factor. Second malignancies, often smoking related, are a significant cause of death in long-term survivors of SCLC. Chronic tobacco use puts these patients at risk for chronic obstructive pulmonary disease and ischemic heart disease, which worsen with continued tobacco exposure. These two conditions represent significant sources of morbidity and mortality in patients with SCLC both during and after treatment.

 high serum lactate dehydrogenase, suggestive of more

bulky disease, is an independent predictor of poor outcome for extensive-stage disease. Hypoalbuminemia, hyponatremia, elevated alkaline phosphatase, and leukocytosis have been associated in various studies with poor prognosis. The serum tumor marker neuron-specific enolase (NSE) is more often elevated in extensive-stage than in limitedstage patients. Di-agnostic specificity of this marker, however, is only 40 to 70 percent in limited SCLC, but specificity reaches to 80 to 100 percent in extensive disease.

DOUBLING TIME
Growth of lung cancer is exponential,duration of

survival being a function of both size of tumour at diagnosis and its doubling time. Doubling time for small cell ca is 50 days(sq &large cell-100,adenoca-180).the shorter doubling time in small cell ca acounts for its worse prognosis. A tumour cell with diam 10 micrometres produces 1cm nodule weighing aprox 1gm after 30 doublings. Therefore a small cell lesion may have existed for upto 3 yrs before it is clinicaly or radiologically detectable.

Treatment
Including: A:Surgery B:Chemotherapy C:Radiation therapy D:Some other therapy immunologic therapy, Endoscopic stent placement

Surgery
More than 90 percent of small cell lung cancer has often metastasized at the time of diagnosis. So these patients usually adopt radiation therapy or chemotherapy before surgery. Surgery for early stage small cell carcinoma, particularly those cancers presenting as small single pulmonary nodules, may be more appropriate, as these tumors may be biologically distinct from advanced disease. The benets of surgical resection in SCLC are mainly seen in patients with TNM stageI disease with peripheral tumors and no nodal involvement, and who are able to tolerate the procedure. Adjuvant chemotherapy should be offered post operatively.

Chemotherapy
SCLC is classically associated with exquisite chemosensitivity. In limited stage (LS) disease, chemotherapy combined with thoracic radiation achieves a response in over 80% of patients, and a complete response in the range of 40 to 60 %. In ES disease, the response rate is lower (6080 %), with a rate of complete response around 15 to 35 %. Chemotherapy has been shown to improve survival compared with supportive care. In LS disease, median survival in treated patients is 15 to 20 months, with 5-year survival rates of 10 to 13%. The median survival for ES patients treated with chemotherapy remains at 7 to 9 months, with few long-term survivors.

 Drugs used: Cyclophoshamide Doxorubicin Vincristine Cisplatin Ifosphamide Etopiside

Combined chemotherapy

Drug regimen with predictable results include: Cyclophoshamide/Doxorubicin/Vincristine Cyclophoshamide/Doxorubicin/Etopiside Cisplatin/etoposide .

To be administerde 3-4 weekly, can be done on OPD basis. Response assesed after 2-3 cycles; Activity of treatment measured in terms of response rates;

either complete or partial. Partial response: shrinkage of tumor by atleast 50% of diameter. Complete response: total removal of all tumor as evaluated by physical examination, radiography, scanning or FOB

HIGH DOSE CHEMOTHERAPY

This is strategy to increase initial dose of induction

chemotherapy to try to prevent later relapses. Fit pts with LS given double dose 1.5g/m2 of cyclo in a regimen also containing methotrexate and lomustine at conventional doses. Toxicity involved is myelosupression prevented by autologus BMT and use of hematopoetic growth factors.
Scheduling : no less than 4 and no more than 6 courses

of induction chemoterapy.

Chemotherapy with median survival in weeks in lung cancer at a tertiary care centre (Post Graduate Institute of Medical Education and Research Chandigarh)

SFRT: Single fraction radiotheSFRT: Single fraction radiotherapy of 1000rads; CTX Cyclophosphamide; V: vincristin Cisplatin;B:bleomycin;M:methotrexate;A:ad riamycin;VB:vinblastin;MIt;mitomycin;CC: CCNU;IFO:Ifosamide,E:etoposide. rapy of 1000rads; CTX Cyclophosphamide; V:

 Duration of treatment
The optimal duration of initial chemotherapy for

patients with small cell lung cancer is not well defined. The number of cycles is determined by how the cancer is responding to treatment, and how the patient's body tolerates the treatment. Typically, four to six cycles of chemotherapy are recommended. Additional cycles of chemotherapy (called maintenance chemotherapy) have not been shown to significantly improve survival or quality of life

Side effects
Chemotherapy affects normal cells as well as the cancer

cells, resulting in a wide range of side effects. While receiving chemotherapy, patients are closely monitored for these side effects and any signs of toxicity. The most important side effect of chemotherapy is a transient drop in the blood counts due to the effect of chemotherapy on the bone marrow. This typically occurs one to two weeks after a dose of chemotherapy is given. During this time, the patient or a family member should report any fever or chills to the physician; having low blood counts can increase a person's chances of developing infections, such as pneumonia. Other possible side effects of chemotherapy include fatigue, hair loss, numbness in the fingers and toes, hearing loss, diarrhea, and changes in kidney function.

RADIATION THERAPY
Radiation therapy (RT) involves the use of focused, high

energy x-rays to destroy cancer cells. The x-rays are delivered from a machine (called a linear accelerator) that is outside of the patient, and individual treatments are brief (typically 10 to 15 minutes) and not painful. The damaging effect of radiation is cumulative, and a certain amount of radiation must be delivered before the cancer cells are so damaged that they die. To accomplish this, small radiation doses are administered daily, five days per week, for five to seven weeks. Radiation is only administered to the areas of the body that are affected by the tumor. Thus, in contrast to chemotherapy, which is a systemic or body-wide treatment, radiation is a local treatment, and side effects are generally limited to the area undergoing radiation.

 Chest radiation Studies of patients with limited

stage lung disease have shown that RT of the chest can help decrease the chance of the tumor regrowing in the chest (a recurrence) after chemotherapy. Furthermore, the use of radiation may improve the likelihood of surviving the cancer by approximately five percent . The best way of combining chest RT with chemotherapy is a matter of debate, although in general, chemotherapy and radiation therapy are usually started at the same time (called concurrent therapy). Chest RT can sometimes be given after chemotherapy has been completed (called sequential therapy

Fractionation
Therapeutic ratio of radiotherapy improves with division

of total dose into fractions. Larger than std fraction dose (>2 GY) reduces larger kill of tumor cells, but causes increase effects on normal tissue. Hyperfractionation dividing daily dose into smaller doses improves therapeutic index. Accelerated fractionation: allows for frequent treatment in shorter time spent. Theory behind these schedules is to optimise effects of radiotherapy on tumor cells while allowing normal cells to recover.

 Brain radiation The brain is a common site of

tumor spread (termed metastasis) in people with small cell lung cancer. Having preventive radiation treatment of the brain after chemotherapy, before evidence of metastases develop, substantially reduces the chances of developing brain metastases and prolongs survival . This type of radiation therapy is called prophylactic cranial irradiation, or PCI. PCI is often recommended for people with limited or extensive disease if the tumor has partially or completely responded to the initial course of chemotherapy.

 Using modern techniques, PCI causes a tolerable level

of short term side effects, including redness and itching of the scalp, fatigue, and hair loss, all of which are usually self-limited. Long-term side effects may include mild neurologic and intellectual difficulties (including short-term memory loss and difficulty concentrating). The likelihood of these long-term effects is lessened when PCI and chemotherapy are given at different times. In patients who already have spread of small cell lung cancer to the brain and in those who subsequently develop brain metastases, radiation therapy to the brain is often recommended to control symptoms.

Treatment Options by Stage

Limited-Stage Small Cell Lung Cancer Treatment of limited-stage small cell lung cancer may include

the following: Combination chemotherapy{ most commonly used drug combination is cisplatin plus etoposide.} and radiatiotherapy to the chest. Radiation therapy to the brain may later be given to patients with complete responses. Combination chemotherapy for patients with lung problems or who are very ill. Radiation therapy to the brain may later be given to patients with complete responses. Surgery followed by chemotherapy or chemotherapy plus radiation therapy to the chest. Radiation therapy to the brain may later be given to patients with complete responses. Clinical trials of new chemotherapy, surgery, and radiation treatments are going on.

 Extensive-Stage Small Cell Lung Cancer Treatment of extensive-stage small cell lung cancer

may include the following: Combination chemotherapy{treated with cisplatin or carboplatin in combination with either etoposide or irinotecan}. Radiation therapy to the brain may later be given to patients withcomplete responses. Radiation therapy to the brain, spine, bone, or other parts of the body where the cancer has spread, as palliative therapy to relieve symptoms and improve quality of life. Clinical trials of new chemotherapy treatments are going on.

 Treatment Options for Recurrent Small Cell Lung

Cancer. include the following: Chemotherapy. Radiation therapy as palliative therapy to relieve symptoms and improve quality of life. Laser therapy, stent placement to keep airways open, and/or internal radiation therapy as palliative therapy to relieve symptoms and improve quality of life

PREVENTING LUNG CANCER

Cigarette smoking is responsible for almost 90 percent of

cases of lung cancer. Exposure to certain substances, such as asbestos, has also been linked to the development of lung cancer. Exposure to secondhand smoke and other environmental factors may play a role. The best way to avoid getting lung cancer is not to smoke. Some smokers believe that once they have smoked for a long while, it does little good to quit. However, studies have shown that smokers who quit decrease their risk of lung cancer when compared to those who continue to smoke. Smokers who quit for more than 15 years have an 80 to 90 percent reduction in their risk of lung cancer compared to people who continue to smoke.

 IS SCREENING WORTHWHILE?
Screening is a way to detect a disease in its earliest

stages, before a person becomes ill. To be recommended, it must be clear that screening is useful in identifying patients who have the disease in the early stages, and that this discovery can reduce the number of patients who die from the disease. Some screening exams have proven to make a clear difference in outcomes. Examples are the Pap smear for detection of cervical cancer in women, and colonoscopy for detection of colon or rectal cancer in people over 50 years old.

LUNG CANCER SCREENING EXAMS

Chest x-ray Although many healthcare providers

recommend an annual chest x-ray for patients who smoke, studies to date have not shown a clear benefit. In patients who had more frequent chest x-rays, more lung cancers were found at early stages, the cancers were more frequently removable by surgery, and the patients had longer five-year survival (from time of diagnosis) than patients with less frequent x-rays. However, since overall death from lung cancer was not significantly different, these findings may represent overdiagnosis (finding cancer that would not affect health during a persons lifetime). Chest x-ray is not recommended for lung cancer screening

 Computed tomography (CT scan) A large randomized

trial in the United States compared the benefits of screening by low-dose CT scan or chest x-ray in smokers (at least a 30 pack-year history, including current smokers or people who had quit in the previous 15 years). Compared to chest x-ray, low-dose CT scan reduced the risk of death from lung cancer by 20 percent, and the overall risk of death by about 7 percent. However, nearly a quarter of the patients who had annual CT screening for three years had an abnormal test, and more than 95 percent of the abnormal tests were false positive meaning that they did not represent cancer. False positive tests require follow-up tests, such as more xrays or biopsies, and these follow-up tests carry risks such as increasing radiation exposure, and complications from biopsy procedures. Thus, there are significant downsides to screening.

 Sputum tests Some studies have looked at the efficacy

of analyzing a patient's sputum for evidence of cancer cells in order to detect lung cancer. So far, no clear benefit to this approach has been found. Additional studies that use new technologies to examine the sputum are underway. PET scan Researchers are looking at a number of other tools in an effort to help identify patients with lung cancer. Positron Emission Tomography (or PET scanning, which uses a small amount of radioactivity to provide a detailed picture of an organ's function) has been used in combination with CT scanning (PET/CT). However it involves a higher dose of radiation than CT alone and benefit has not been shown for screening purposes. Other studies Direct visualization of the lungs with bronchoscopy and breath analysis for cancer markers are two tests that may be used in future studies.