Lung+(small,+NSC,+adeno,+squamous)


 * Epidemiology: || Cancers of the bronchial tree, lung, and pleural surfaces represent the most common invasive malignancies in the United States. According to the American Cancer Society, approximately 170,000 new cases are diagnosed and approximately 157,000 deaths are cause by the disease each year. As a group, these malignancies represent 13% of all new cancers in the United States and 28% of all cancer deaths. 1

Small cell carcinomas have a higher incidence of distant metastasis than non-small cell cancers; of the latter, adenocarcinoma has the highest potential for distant metastasis. 2

About 85 - 87% of all lung cancers diagnosed are non-small cell carcinomas, which grows more slowly than small cell lung carcinoma. Small cell lung carcinoma on the other hand makes up 13-15% of all lung cancers and are very aggressive and spreads quickly. 3 ||
 * Etiology: || The most common cause of lung cancer is significant tobacco exposure, which is defined as more thean one pack of cigarettes per day. There is a higher incidence of lung cancer with an increased durantion of smoking, an increased use of unfiltrated cigarettes, and an increased number of cigarettes consumed. Also occupational exposure can have an effect on the incidence of lung cancer. Some of these occupational exposures include fumes from coal tar, nickle, chromium, and aresnic and exposure to various radioactive materials. Especially dangerous agents with alpha emissions in their various daughter products, such as uranium and radon. The EPA has stated that radon is the second leading cause of lung cancer behind cigarette smoking in the United States. 1 ||
 * Signs & Symptoms: || Signs and symptoms of lung cancer can be from local tumor growth, invasion of surrounding structures, regional growth, distant mets, or from a secondary effect from the tumor. Coughing is a very prominent symptom (about 75% of patients) and is severe in 40%. Hemoptysis was a symptom in 57% of patients and was the first symptom experienced in 4%. Other likely symptoms (in approx. 40% of patients) are dyspnea and chest pain from involvement of the pleura, chest wall, and/or mediastinal structures. Other nonspecific initial symptoms include weight loss, weakness, anorexia, and malaise occured in 10% to 15% of patients.

Approximately 2% of patients that have lung cancer develop paraneoplastic symptoms (remote effects). Tumors located in the apex of the lung tend to grow by local extension and involve cervical and thoracic nerves, resulting in Pancoasts's or superior sulcus tumor (SST) syndrome. This consists of shoulder pain that radiates to the arm along the distribution of the ulnar nerve. Sympathetic nerve involvement leads to Horner's syndrome which is characterized by enophthalmos, ptosis, meiosis, and ipsilateral decrease in sweating. If the recurrent laryngeal lymph node is involved, it can lead to paralysis of the nerve and hoarseness. Involvement of the phrenic nerve can lead to paralysis of the hemidiaphragm resulting in difficulty breathing. Tumors that compress the esophagus can cause dysphagia. Prmary tumors of the right lung or metastatic tumors of the right mediastinal lymph nodes can cause Superior vena cava syndrome (SVC). "Large tumors in the upper lobes with massive upper mediastinal lymph adenopathy may cause thoracic inlet obstruction with severe respiratory distress." Tumors involving the pericardium and heart can result in CHF and pericardial tamponade.  4 || MRI has not been proven to be superior to CT studies for this treatment area because it has the same limitations as CT scans. Unless there are specific symptoms, multiple organ scans are not indicated for part of the initial work-up for lung cancer. One exception might be obtaining a CT or MRI of the brain because of the high incidence of brain mets. PET scans have become an important tool for staging and treatment planning of non-small cell lung cancer. There is not much data available for PET in Small cell lung cancer. In NSCLC, PET has mostly been used for evaluating lung nodules and staging the mediastinum. It has been shown to be more accurate than CT in determining nodal status. In addition, it is more sensitive and specific in displaying metastatic disease in normal-sized lymph nodes and in determining enlarged benign nodes from enlarged nodal mets. Pulmonary function tests are used to help predict the patients ability to undergo surgical resection or their ability to endure irradiation. Sputum cytology has the possibility of determining the presence of malignant cells and the cell type as well. The rate of success of this test depends on the quantity of sputum produced and the quality of technical procedures. This procedure has diagnosed malignancy in 65.2% of 75% of cases. Bronchoscopy can provide important information even when preoperative cytologic proof of cancer is already present. The false-positive rate is low. When a patient has a suspicious, undiagnosed peripheral lung lesion that was seen on an x-ray, a percutaneous biopsy can be performed under flouro. Other procedures that can be used to establish a diagnosis of lung cancer are scalene node biopsy, exploratory thoracotomy, and biopsy of an accessible metastatic site. 5 || ||
 * Diagnostic Procedures: || The most common x-ray exam used for diagnosing lung cancer is a PA and Lateral chest x-ray. CT is the best diagnostic tool for evaluating a lung tumor. This is because it is very accurate in predicting the resectability of tumors in most patients with bronchogenic carcinoma. In addition, CT helps with staging of lung cancer by demonstrating direct extension of the primary tumor into the mediastinum or chest wall along with detecting enlarged lymph nodes. A downfall of CT is that it cannot tell the difference between inflammatory disease and neoplasia. In addition, CT cannot detect metastatic disease within normal-sized lymph nodes. A staging CT exam for bronchogenic carcinoma should include a scan for assessment of the adrenal glands. If their is something suspicious seen, a percutaneous needle biopsy of the adrenal glands under ct-guidance is useful in determining distant mets.
 * Histology: || There are many histologic classifications that have been suggested and they are all variations of the World Health Organization (WHO) classification system. 4 
 * Lymph Node Drainage: || The lymphatic drainage system of the lungs is important because it can be the principal route of regional spread of lung cancer. The lymphatics actually connect with pulmonary arteries and veins at many points. The lymphatic drainage from the lungs, diaphragm, esophagus, pleural cavity, heart, stomach, and pancreas converge at the carina. All this drainage has access to the circulatory system at the aorta and thoracic duct. 6  This is why ,hematogenous spread with multiple organ involvement is frequent. The lymphatics of the lungs are classified into mediastinal and intrapulmonic nodes (see table below). 2

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 * Metastatic Spread: || The routes of spread include: direct ( local extension), Lymphatic, and hematogenic ( circulatory system). Metastatic spread can occur when malignant cells pass into the blood vessels. Once the disease reaches the circulatory system it has access to the entire body. The most common sites for metastasis occur in the liver, brain, bones, adrenal glands, kidneys, and contralateral lung. 6 <span style="color: #0000ff; font-family: Georgia,serif;"> Adenocarcinoma carcinoma has the highest incidence of distant metastasis, followed by small cell then non-small cell carcinomas. <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">2 ||
 * Grading: || <span style="color: #0000ff; font-family: Georgia,serif;">The American Joint Commission on Cancer recommends the following guidelines for grading tumors. <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">5 <span style="color: #0000ff; font-family: Georgia,serif;">

__**Grade**__


 * Gx -** Grade cannot be assessed ( undetermined grade)
 * G1 -** Well differentiated ( low grade)
 * G2 -** Moderately differentiated ( intermediate grade)
 * G3 -** Poorly differentiated ( high grade)
 * G4 -** Undifferentiated ( high grade) ||
 * Staging: || <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 120%;">AJCC Lung Staging System

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 150%;">Primary tumor (T) TX: Primary tumor connot be assessed, or tumor proven by presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy T0: No evidence of primary tumor Tis: Carcinoma //in situ// T1: Tumor less than or equal to 3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion mor proximal than the lobar bronchus T2: Tumuor with any of the following features of size or extent: greater than 3 cm in greatest dimension; Involves main bronchus, greater than or equal to 2 cm distal to the carina; Invades the visceral pleura; Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung T3: Tumor of any size that directly invades any of the following: chestwall (including superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or tumor in the main bronchus less than 2 cm distal to the carina but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung T4: Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina; or tumor with a malignant pleural effusion

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 150%;">Lymph nodes (N) NX: Regional lymph nodes cannot be assessed N0: No regional lymph node metastasis N1: Metastasis in the ipsilateral peribronchial or ipsilateral hilar lymph nodes, including direct extension N2: Metastasis in the ipsilateral mediastinal or subcarinal lymph node(s) N3: Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph node(s)

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 150%;">Distant metastasis (M) MX: Presence of distant metastsis cannot be assessed M0: No distant metastasis M1: Distant metastasis

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">

Staging as seen in Radiation Oncology Management Decisions. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">2 || Acute effects are going to appear sooner and will most likely go away shortly after treatment is complete. Later effects have more of a chronic nature and do not appear until much later after treatment is complete.
 * Radiation Side Effects: || <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Side effects of radiation to the lung can be broken down into two categories: acute (short term) and later (long term).

Acute Radiation Side Effects: <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Late Radiation Side Effects: - Stage and extent of the disease - Clinical performance status (measured by scales such as the Karnofsky Performance Scale) - Weight loss, especially greater than 5% of the total body weight over 3 months <span style="color: #ff0000; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">2 Lung cancer has a poor prognosis. On average, people with untreated advanced non-small cell lung cancer survie only 6 months. Even with treatment, people with extensive small cell lung cancer or advanced non-small lung cancer do especially poorly, with a 5-year survival rate of less than 1%. Early diagnosis improves survival. People with early non-small lung cancer have a 5-year survival rate of 60 to 70%. <span style="color: #ff0000; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">3 || -The first decision needs to be whether treatment is palliative or curative, followed by resectable or not. -If possible non-small cell lung cancers should be treated with surgery. There has been **no evidence in improved survival** with treatment of preoperative irradiation or chemoirradiation. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">2 -**Post operative radiation** is used for positive or close surgical margins and/or positive hilar or mediastinal lymph nodes. Recommended doses include 60 to 70 Gy in 2 Gy fractions. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">2 -A complete and through resection of mediastinal nodes (all nodes negative), the irradiation can have a small treatment volume without lymph node areas being treated prophylactically. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">2 -A complete resection of a T2 or T3 tumor has a high incidence of hilar and mediastinal lymph node involvement and requires lymph node irradiation. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.56pt; vertical-align: super;"> 2 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;"> -**Postoperative Chemotherapy** used in the treatment of non-small cell lung cancer includes cisplatin, carboplatin, vindesine and etoposide. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">2 ** -Unresectable tumors ** – Standard of care includes radiation doses up to 70 Gy with reduced fields to gross tumor volume. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">2 **-Doses**- tumor doses of 50 to 79.3 Gy have been used in 1.8 to 2 Gy fractions depending upon tumor. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">2 Small cell lung cancer is sensitive to many chemotherapy agents; multidrug agents have proven to be more effective in treatments. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">1 -Advantages have been shown when using irradiation either concurrently or early in chemotherapy treatments. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">2 - **Concomitant irradiation and chemotherapy** (radiation doses of 45 to 60 Gy), must not contain doxorubicin or methotrexate (associated with a higher complication rate). <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">2 - **Elective cranial irradiation**- there is a high incident of brain metastases with small cell lung cancer (up to 50%). Whole brain irradiation decreases this incidence with doses of 30 to 35 Gy in 2 to 2.5 Gy fractions. This, however, provides no survival advantage. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">2 - ** Treatment volumes ** - are determined by the size and location of the tumor, areas of lymphatic drainage, histological type and equipment available. Treatment portals are usually designed with 2 cm margin around both the primary tumor and nodal volumes. Irregular fields are almost always used to protect as much normal tissue as possible. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 90%; vertical-align: super;">7
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Acute toxicites include esophagitis, cough, skin reaction, and fatigue. These symptoms are more likely to occur during treatment or within a month of completing treatment.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Acute esophagitis usually begins in the third week of radiation therapy, at approximately 30 Gy. Chemotherapy in combination of radiation therapy can cause esophageal symptoms to surface earlier.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Cough is common but usually not severe.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">An acute phase of radiation pneumonitis could be a side effect of radiation treatment.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Lhermitte syndrome, observed in 10- 15% of patients, is transient and of no clinical importance.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Skin reaction, if any, is usually mild to moderate.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Late side effects include pneumonitis and pulmonary fibrosis (both symptomatic and radiographic), esophageal stricture, pericardial effusion, constrictive pericarditis, cardiomyopathy, spinal cord myelopathy, and brachial plexopathy.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Pneumonitis and pulmonary fibrosis are the most frequently reported side effects in RTOG trails.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Statistically speaking close to 10 % of patients with a grade 2 tumor and 4.6% with a grade 3 tumor reported having pneumonitis. Approximately 20% of patients with a grade 2 tumor and 8% of patients with a grade 3 tumor reported having pulmonary fibrosis.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">The threshold dose for radiation pneumonitis is approximately 20-22 Gy. The incidence and degree of the condition depends on the total dose, fractionation, and volume of lung irradiated.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Long-term esophageal problems such as stenosis, ulceration, perforation, and fistula formation are seen in 5-15 % of patients.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">A combination a carboplatin and conventional or accelerated fractionation resulted in greater hematologic and esophageal morbidity compared to radiation alone.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Radiation-induced cardiac disease after irradiation for lung cancer is rare; pericarditis is most common. Certain chotherapeutic agents, such as doxorubicin, having synergistic cardiotoxicity with radiation. Extreme caution is required when irradiation is combined with such drugs.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Spinal cord myelopahty may occur with doses higher than 45 Gy in 1.8-2.0- Gy fractions; factors important in its causation are total irradiation dose, length of the irradiated cord, and frationation schedule. ||
 * Prognosis: || There are many factors that effect prognosis, some of the factors are...
 * Treatments: || **__ Non-Small Cell Lung Cancer __**
 * -Chemoirradiation ** - is considered the treatment of choice for locally advanced, inoperable non small cell cancer. Cisplatin and visblastine is given for two cycles, followed by 60 Gy irradiation in 6 weeks. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">2
 * __Small Cell Lung Cancer__ **

<span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 120%;">Figures 1-5 treatment borders based on tumor locations. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 96%; vertical-align: super;">7 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 120%;">

** Superior Vena Cava Syndrome ** - is an obstruction of the superior vena cava by a mediastinal mass. Immediate treatment (irradiation is the treatment of choice) is needed to allow the return of the blood to the heart from the upper thorax, head, neck and extremities. Treatment includes initial high fraction doses of 3 to 4 Gy and followed by conventional fractionation (1.8 to 2 Gy). Total doses depend on histology of tumor. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10.8pt; vertical-align: super;">7 7 || Kim is the <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 121%;"> teal green <span style="font-family: 'Times New Roman',Times,serif; font-size: 131.76%;">. <span style="font-family: 'Times New Roman',Times,serif; font-size: 119.79%;">Kristy is the <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 119.79%;">fushia/bright purple <span style="font-family: 'Times New Roman',Times,serif; font-size: 119.79%;">. <span style="font-family: 'Times New Roman',Times,serif; font-size: 121%;">Stacy is the <span style="color: #298000; font-family: 'Comic Sans MS',cursive; font-size: 120%;">darker green <span style="font-family: 'Times New Roman',Times,serif; font-size: 121%;">. Shae is the <span style="color: #ff0000; font-family: 'Times New Roman',Times,serif; font-size: 121%;"> red <span style="font-family: 'Times New Roman',Times,serif; font-size: 121%;">. <span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;"> || References: 1. Washington,C.M & Leaver, D.(Eds.).(2004). //Principles and Practice of Radiation Therapy// (Second ed). St. Louis, Missouri; Mosby Inc: pg. 654. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">2. Chao KC, Perez CA, Brady LW. Radiation Oncology Management Decisions. 2nd ed. Philadelphia, PA; Lippincott Williams & Wilkins. 1999, 2002: 303, <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 110%;">307 <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">-318. 3. Merck Online Medical Library: Lung Cancer. Available at: []. Accessed January 20, 2010. <span style="color: #008000; font-family: 'Comic Sans MS',cursive; font-size: 120%;">4. Perez CA, Brady LW, Halperin EC, Schmidt-Ullrich RK. //Principles and Practice of Radiation Oncology.// 4th edition. Philadelphia, PA: Lippincott Williams & Wilkins. 2004: 1204-1206. <span style="color: #0000ff; font-family: Georgia,serif;">5. National Cancer Institute. Available at []. <span style="color: #0000ff; font-family: Georgia,serif;">Accessed Jan. 21, 2010. 6. Washington CM, Leaver DT. //Principles and Practice of Radiation Therapy Practical Applications.// St. Loiis, Missouri: Mosby. 1997; 129, 137, 159. 7. <span style="color: fuchsia; font-family: 'Arial','sans-serif'; font-size: 10pt;"> Dasher, BG & Vann, AM. //<span style="font-family: 'Arial','sans-serif';">Portal Design in Radiation Therapy //. 2nd edition. Philadelphia, PA: DWV Enterprises. 2006: 99-102, 216-219.
 * Brachytherapy**- is an alternative for large, unresectable tumors or a boost (usually three 5 Gy fractions or one 10 Gy fraction). Usually used in combination with external radiation. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 108%; vertical-align: super;">2
 * TD5/5: || [[image:lungtd55new.jpg width="268" height="160"]] 7 ||
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