Disease free survival in lung cancer 7th,longest survival in the wilderness,emergency preparedness kits for home security - PDF 2016

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In 2012, it is estimated that 226,160 people in the United States will be diagnosed with lung cancer, including 116,470 men and 109,690 women. Exposure to side stream smoke, or passive smoking, might lead to an increased risk of lung cancer. An accurate prediction may help motivate smoking cessation, tailor early detection strategies, and identify patients to enroll in chemoprevention trials.
Dividing lung cancer into small and non-small cell groups is no longer sufficient for clinical purposes. The clinical manifestations of lung cancer result from the effects of local growth of the tumor, regional growth or spread through the lymphatic system, hematogenous distant metastatic spread, and remote paraneoplastic effects from tumor products or immune cross-reaction with tumor antigens (Box 2). Local growth in a central location can cause cough, hemoptysis, or features of large-airway obstruction. Paraneoplastic syndromes can occur before the primary tumor appears and thus can be the first sign of disease or an indication of tumor recurrence. Other paraneoplastic neurologic syndromes include cancer-associated retinopathy and the Lambert-Eaton myasthenic syndrome. Clinical features that suggest malignancy on initial evaluation include older age, current or past history of tobacco abuse, hemoptysis, and the presence of a previous malignancy.
The detection of lung nodules (<3cm) is likely to increase with CT based screening for lung cancer. Transthoracic needle biopsy, using fluoroscopic or CT guidance, can be used to obtain tissue.
Accurately characterizing the anatomic extent of disease in a patient with lung cancer guides the treatment and prognosis.
The extent of local regional spread is best evaluated using CT of the chest extending to the upper abdomen to include the liver and adrenals.
Because imaging tests have false-positive and negative results, tissue confirmation of imaging findings is necessary. The evaluation of metastatic disease also takes into consideration the history, physical examination, laboratory results (electrolytes, calcium, alkaline phosphatase, liver profile, and creatinine), and pathology results. Brain imaging should be performed if symptoms or signs of metastatic disease are present or when evaluating what appears to be stage IIIA or B disease. Coincident with the evaluation of the anatomic stage of disease should be an evaluation of the patient's performance status. Further evaluation of performance status may be necessary in those for whom surgical resection is indicated.
Traditional preoperative cutoff values are being replaced by percent predicted postoperative values.
When doubt remains, or when measured values and predictions seem discordant with a patient's reported activity tolerance, a cardiopulmonary exercise study should be performed. Given the high incidence of lung cancer, poor prognosis for advanced-stage lung cancer, and the high percentage of patients who present in an advanced stage, there has been great interest in early detection of lung cancer. Treatment of patients with lung cancer depends on the histology, tumor stage, and performance status. Traditional radiotherapy has been used with curative intent in early-stage non–small cell lung cancer, either in patients who cannot tolerate surgery or in those who elect not to undergo surgery.
Adjuvant therapy has been attempted in early-stage non–small cell lung cancer patients who have undergone surgical resection. Locally advanced tumors (T3) can often be completely resected, although central T3 tumors are somewhat less resectable than those involving the chest wall. When a Pancoast tumor is present, chemoradiotherapy followed by surgical resection are performed if possible. T4 disease without advanced nodal status (stage IIIB) may be considered surgical in a few settings.
In stage IV lung cancer, platinum-based doublet chemotherapy regimens have been shown to improve survival, enhance quality of life, and be cost effective.
Therapies targeting the consequences of alterations in normal physiology or driver oncogenes have been developed.
Palliation of symptoms related to lung cancer is an important aspect of the overall management. Lung cancer causes more cancer-related deaths in the United States than the next four causes of cancer-related mortality combined.
Symptoms are often absent until lung cancer has advanced; thus, only 15% of lung cancer patients live for 5 years after their diagnosis.
The histologic subtype, molecular markers, stage of lung cancer and the patient's performance status guide treatment decisions and influence the prognosis. Wahidi MM, Govert JA, Goudar RK, Gould MK, McCrory DC; American College of Chest Physicians.
Goldstraw P, Crowley J, Chansky K, et al; on behalf of the International Association for the Study of Lung Cancer International Staging Committee and Participating Institutions.
Ung YC, Maziak DE, Vanderveen JA, et al; Lung Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-Based Care.
Rami-Porta R, Ball D, Crowley J, et al; on behalf of the International Staging Committee, Cancer Research and Biostatistics, Observers to the Committee, and Participating Institutions. Georgoulias V, Papadakis E, Alexopoulos A, et al; for the Greek Oncology Cooperative Group (GOCG) for Lung Cancer. In the United States, 31% of cancer deaths in men and 26% of cancer deaths in women are secondary to lung cancer. Lung cancer is the second most frequently diagnosed cancer in both men and women; prostate and breast cancers are the most frequent in men and women, respectively (Figure 1).
It surpassed colon cancer in the early 1950s in men and breast cancer in the late 1980s in women. Many tobacco-related carcinogens have been identified; the two major classes are the N-nitrosamines and polycyclic aromatic hydrocarbons. Higher consumption of fruits and vegetables is associated with a reduced lung cancer risk, and an increased dietary fat intake might lead to a higher risk. Top right, Squamous cell carcinoma characterized by the presence of cytokeratin differentiation with keratinization and intercellular bridges. The current standard of care for advanced non-small cell lung carcinoma is to determine the chemotherapies to use on the basis of precise histologic subtype. The genes influenced in the pathogenesis of lung cancer produce proteins involved in cell growth and differentiation, cell cycle processes, apoptosis, angiogenesis, tumor progression, and immune regulation.
Neurologic symptoms can suggest brain metastases or spinal cord compression, and pain could indicate bone metastases.
An immune response to tumor antigens that cross-react with common antigens expressed in the nervous system seems to take place. In cancer-associated retinopathy (most common with small cell carcinoma), rapid vision loss, ring scotomata, photosensitivity, night blindness, and color vision loss can occur in association with autoantibodies directed against retinal proteins.
In the remainder, lung cancer is detected by radiographic evaluation initiated for an unrelated problem.
Radiographic features suggesting malignancy include the absence of a benign pattern of calcification in the detected lesion, a nodule or mass that is growing, a nodule with a spiculated or lobulated border, a larger lesion (>3 cm is considered malignant unless proven otherwise), and a cavitary lesion that is thick walled.
The probability of malignancy in a solid lung nodule is related to patient age, risk factors and radiographic features (size, border, calcification, density, growth and ground glass appearance).14,15 Solid nodules that have low probability for malignancy will generally be followed with serial imaging. Due to advances in the treatment of non-small cell cancer, appropriate and sufficient tumor specimens are required to allow accurate histologic subtyping and molecular characterization of the cancer. The addition of endobronchial needle aspiration to conventional sampling techniques (washing, brushing, and endobronchial biopsy) improves this yield. The positive predictive value of this procedure is high, the negative predictive value is modest, and the rate of establishing a specific benign diagnosis is low. Non-small cell lung cancer is staged using the TNM system (T for extent of primary tumor, N for regional lymph node involvement, and M for metastasis) (Figure 5).
All patients should have their chest CT scanning extended through the adrenals, because metastatic disease to these glands is usually asymptomatic, and often no alterations are seen in routine laboratory tests.
Brain imaging is often performed despite a lack of symptoms, in deference to the published guidelines. This is important in determining an individual patient's ability to tolerate any proposed treatment. To determine if a patient will tolerate lung resection surgery, reports of activity tolerance and pulmonary function testing are used. Percent predicted postoperative values of FEV1 and DLCO can be calculated by multiplying the percent predicted preoperative value by the fraction of the total number of lung segments that will remain postoperatively. In the 1970s and 1980s, chest x-ray with or without sputum cytology have been studied as screening tools.
The National Lung Screening Study is the first lung cancer screening study to show that screening for lung cancer with low-dose CT in a well-define high risk cohort, leads to a reduction in lung cancer mortality.40 This large trial of very high risk subjects compared annual low-dose chest CT to chest x-ray screening over 2 years. With the more recent personalized approach, specific histologic subtyping and molecular characterization also determine the choice of treatment. A 5-year survival rate in combined stages I and II disease approaches 15% with radiotherapy alone. Adjuvant radiotherapy might improve local control but it does not improve survival (with the possible exception of those who have undergone incomplete resection).
The survival rates in T3 patients with chest-wall involvement and negative nodes approximates those of other stage IIB patients. The invasion of local structures (rib, vertebral body, subclavian artery, or sympathetic chain) is a poor prognostic sign. Unselected patients have a low rate of complete resection with primary surgery, and patients with incompletely resected lesions do poorly. T4 disease involving the main carina may be considered for resection at centers with expertise.


The decision to treat with chemotherapy and the agents selected must consider each patient's comorbidites and overall performance status. The addition of a VEGF inhibitor to treatment in those without squamous cell carcinoma, hemoptysis, or brain metastases, has led to improved outcomes.
In limited-stage disease, combination chemotherapy with concurrent hyperfractionated radiotherapy is recommended. The judicious use of analgesic agents for pain, antiemetics for nausea, and antidepressants can improve quality of life. Effect of cigar smoking on the risk of cardiovascular disease, chronic obstructive pulmonary disease, and cancer in men.
Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study [published online ahead of print January 28, 2005]. Environmental tobacco smoke and tobacco related mortality in a prospective study of Californians, 1960-98. Association between lung cancer incidence and family history of lung cancer: data from a large-scale population-based cohort study, the JPHC study.
Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. Low lung function and incident lung cancer in the United States: data from the First National Health and Nutrition Examination Survey follow-up.
Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis. Lung cancer risk prediction: Prostate, Lung, Colorectal And Ovarian Cancer Screening Trial models and validation [published online ahead of print May 23, 2011].
The Liverpool Lung Project: a molecular epidemiological study of early lung cancer detection. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. The probability of malignancy in solitary pulmonary nodules: application to small radiologically indeterminate nodules. Determining the likelihood of malignancy in solitary pulmonary nodules with Bayesian analysis. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Natural history of pure ground-glass opacity after long-term follow-up of more than 2 years.
Clinical, pathological and thin-section CT features of persistent multiple ground-glass opacity nodules: comparison with solitary ground-glass opacity nodule [published online ahead of print September 16, 2008]. Evaluation of F-18 fluorodeoxyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images. Seeking a home for a PET, part 1: defining the appropriate place for positron emission tomography imaging in the diagnosis of pulmonary nodules or masses. Acquisition and processing of endobronchial ultrasound-guided transbronchial needle aspiration specimens in the era of targeted lung cancer chemotherapy [published online ahead of print October 27, 2011]. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition). Mediastinal lymph node staging with FDG-PET scan in patients with potentially operable non-small cell lung cancer: a prospective analysis of 50 cases.
Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography.
Real-time endobronchial ultrasound guided transbronchial needle aspiration for sampling mediastinal lymph nodes [published online ahead of print May 31, 2006]. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. 18Fluorodeoxyglucose positron emission tomography in the diagnosis and staging of lung cancer: a systematic review [published online ahead of print November 27, 2007]. Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial [published online ahead of print October 26, 2011]. Reduced lung-cancer mortality with low-dose computed tomographic screening [published online ahead of print June 29, 2011]. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Safety and efficacy of video-assisted versus conventional lung resection for lung cancer [published online ahead of print May 9, 2009]. Early experience with robotic lung resection results in similar operative outcomes and morbidity when compared with matched video-assisted thoracoscopic surgery cases [published online ahead of print March 20, 2012]. Stereotactic body radiation therapy: rationale, techniques, applications, and optimization. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group [published online ahead of print May 27, 2008]. The IASLC Lung Cancer Staging Project: proposals for the revision of the T descriptors in the forthcoming (seventh) edition of the TNM classification for lung cancer.
Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study [published online ahead of print September 18, 2009].
Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Mortality rates in men declined significantly in the 1990s, whereas a slow increase occurred in women. A dose-response relation exists between the degree of exposure to cigarette smoke and the development of lung cancer. The risk of developing lung cancer decreases over time after smoking cessation, although it never reaches that of a lifelong nonsmoker. Bottom left, Large cell carcinoma characterized by sheets and nests with extensive necrosis, large nuclei with prominent nucleoli, and lack of definitive evidence of squamous or glandular differentiation. The nona€“small cell cancer category consists of adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and variants (Figure 4). Unveiling these mechanisms should translate into novel means of risk stratification, prevention, early detection, and therapy. The three most common are ectopic Cushing's syndrome, the syndrome of inappropriate antidiuretic hormone (SIADH), and humoral hypercalcemia of malignancy.
This leads to manifestations that vary depending on where in the nervous system these antigens are expressed. Lambert-Eaton myasthenic syndrome is the most common of the neurologic paraneoplastic syndromes and is present in 3% of small cell carcinomas. This proportion might change in the future with the development of lung cancer screening programs. Modern imaging techniques are used to alter the clinical probability of malignancy and hence influence biopsy decisions. Indeterminate nodules need a decision between observation, further characterization, biopsy or resection. Flexible bronchoscopy and transthoracic needle biopsy are the invasive, nonsurgical approaches used to obtain tissue. The most recent revision to this staging system occurred in 2009 (Tables 1 and 2).29 Small cell lung cancer can also be staged with the TNM system. The detection of parietal pleural, chest wall, and mediastinal invasion by the primary tumor is limited with CT.
A contrast-enhanced CT scan, ultrasound, or MRI of the liver should be performed if the chest CT, laboratory results, or clinical evaluation suggests metastatic disease to this organ.
This is probably justifiable in small cell carcinoma, but it is debatable in other lung cancers.
Although no one pulmonary function study or absolute cutoff has proved ideal, the FEV1 and diffusing capacity for carbon monoxide (DLCO) are the most commonly used measures. Despite considerable debate about the design and analysis of these randomized studies, they have been interpreted to show that screening chest x-ray, sputum examination, or both, did not have a beneficial effect on mortality from lung cancer. After 6 to 7 years of follow-up, lung cancer-associated mortality was found to be 20% lower in the CT screened group. Surgical resection offers the best chance of cure for early-stage non–small cell lung cancer (stages I and II).
Adjuvant chemotherapy has improved survival in select patients with completely resected stages IIA to IIIA lung cancers (and possibly large stage IB).
Patients without radiographic evidence of N2 disease but who are found at surgery to have N2 disease do better than those with preoperative evidence of N2 disease. In addition, it has been recognized that chemotherapy choices should be based on the specific histologic subtype.
The presence of activating mutations in the epidemeral growth factor receptor is a marker of improved response to EGFR inhibitors as upfront therapy.
Radiotherapy can be used to palliate bone pain related to metastatic disease, hemoptysis, or symptoms of airway obstruction. The age at which smoking began, the number of cigarettes smoked per day, and the duration of smoking all influence the likelihood of developing lung cancer. Since the 1980s, the proportions of lung cancers that are adenocarcinomas and squamous cell carcinomas have changed. Regional growth can lead to esophageal compression (dysphagia), recurrent laryngeal nerve paralysis (hoarseness), phrenic nerve paralysis with an elevated hemidiaphragm (dyspnea), and sympathetic nerve paralysis leading to Horner's syndrome (ptosis, miosis, anhidrosis, and enophthalmos). Proximal muscle weakness (which might improve with exercise) is most prominent in the lower extremities, and autonomic features predominate.


Chest radiography and computed tomography (CT) are performed at most patients' initial evaluation. Positron emission tomography (PET) using 18F fluorodeoxyglucose is the most-studied ancillary imaging technique. Serial imaging is usually appropriate for a solid nodule smaller than 1 cm given the low probability for malignancy and absence of accurate adjuvant testing. Conventional sampling techniques and peripheral transbronchial needle aspiration complement each other. Traditionally, small cell carcinoma of the lung has been staged instead as limited or extensive disease. Magnetic resonance imaging (MRI) is not more accurate except in the setting of a Pancoast tumor.
Many choose to use MR imaging of the brain because it has greater sensitivity to detect metastatic disease. The two most commonly employed scales of performance status are the Zubrod scale and the Karnofsky scale.
If the percent predicted postoperative FEV1 and DLCO are greater than 40%, then the patient should be able to tolerate surgery. This was confirmed recently in a large multi-center randomized trial (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial).39 Thus standard chest radiography should not be used for lung cancer screening. Survival after resection in pathologic stage IA is 73% at 5 years, and in pathologic stage IB is 58%. Advances in stereotactic body radiotherapy have provided an additional tool for treating this group.
The more advanced the node involvement (number, extension, or location), the poorer the prognosis.
For example, pemetrexed combined with a platinum agent has been shown to be more effective and less toxic than traditional agents combined with a platinum in the treatment of advanced nonsquamous cell carcinomas.
EGFR mutations are most commonly found in women, those who have never smoked, and those with adenocarcinoma. Prophylactic cranial radiation (PCI) is recommended for patients who have a complete response to chemoradiotherapy. There were an estimated 158,590 deaths in 2008 in the United States secondary to lung cancer. Also, the intensity of smoking, the depth of inhalation, and the composition of the cigarette influence the risk. An inherited genetic predisposition has epidemiologic support as a risk factor, but the mechanisms are theoretical at this time.5 Women appear to have a higher baseline risk of developing lung cancer as well as a greater susceptibility to the effects of smoking.
In North America, approximately 40% of all lung cancers are adenocarcinomas, and 20% to 25% are squamous cell.
Apical growth can lead to Pancoast's syndrome, with shoulder pain radiating in an ulnar distribution.
The clinical manifestations are less prominent than in Cushing's disease; biochemical abnormalities predominate, whereas the physical changes are less prominent. Each of these is more common with small cell carcinoma, can occur in the presence of anti-Hu antibodies, and can occur as part of a more diffuse anti-Hu syndrome (the encephalomyelitis and subacute sensory neuropathy syndrome). It has a sensitivity of 97% and a specificity of 78% as used in clinical practice.13 Single-photon emission CT and lung nodule enhancement with contrast-enhanced CT are less well established.
A solid nodule with an intermediate probability for malignancy that is 1 cm or larger may benefit from further characterization with PET imaging. Factors that influence the diagnostic yield of flexible bronchoscopy for peripheral lesions include the size of the lesion, its location, and a bronchus sign on CT. Limited-stage disease is present when the tumor is confined to a hemithorax (including ipsilateral mediastinal and supraclavicular lymph nodes), and thus can be encompassed in a radiotherapy port. The sensitivity and specificity of CT for evaluating regional lymph node involvement are modest, commonly noted to be as low as 60% and rarely greater than 75%. Despite the advances in imaging technology and sampling techniques, definitive surgical resection and mediastinal dissection remains the gold standard.
Although their definitions differ, their general principles are the same, with ratings based on activity level, independence in daily activities, and severity of symptoms.
Thus, as would be expected, a pneumonectomy requires better preoperative lung function than does a lobectomy.
This tool gives us the ability to target the tumor with minimal effect on surrounding normal lung tissue.
Advances in induction therapy might alter this notion in time, and trials of multimodality therapy are ongoing. Similarly, the presence of an EML4-ALK translocation, identified by FISH testing, is a marker of improved response to an ALK inhibitor.
Surgery is limited to cases in which the diagnosis is in doubt, there is a solitary lung nodule focus, or in cases that have not responded to chemoradiotherapy but remain resectable. Unfortunately, data on worldwide tobacco consumption suggest that lung cancer will remain an epidemic for years to come.
The superior vena cava can become obstructed and the heart and pericardium can become involved. Several new bronchoscopic technologies have improved the yield of biopsies for the diagnosis of peripheral nodules and have become the standard of care in large centers. The assigned clinical stage (determined by testing, including mediastinoscopy) is often lower than the pathologic staging (assigned after surgery).
However, debate over the cost-effectiveness of low-dose CT screening programs and the potential harms of screening are ongoing. There does not seem to be a difference in survival in patients who have adenocarcinoma and those who have squamous cell carcinoma.
Induction with chemotherapy with or without radiotherapy leads to objective responses in most patients, many of whom are downstaged. When surgery is not considered in stage IIIA or IIIB disease, concurrent chemoradiotherapy, using a platinum-based regimen, is the standard of care in a patient with a reasonable performance status. Other novel agents targeting alterations in the pathobiology of the cancer cell are being developed.
Recent advances in early detection and targeted therapies have changed evaluation and treatment paradigms, leading to a meaningful impact on patient outcomes. In men, lung cancer becomes the leading cause of cancer-related mortality from age 40 onward. The increased incidence of lung cancer in women (who are more likely to have adenocarcinomas) and changes in smoking habits are believed to account for this change. The manifestations of hyponatremia (mental status changes, lethargy, or seizures) are often absent despite very low sodium levels, because the rate of decline is typically prolonged. These are defined as a focal, hazy lung opacity on CT, that have preserved bronchial and vascular markings.
They include electromagnetic navigation, virtual bronchoscopy, radial and convex endobronchial ultrasound, the use of an ultrathin bronchoscope, and guide sheath. The overall condition of the patient should be considered as well as the anatomic extent of the tumor.
In patients with extensive-stage disease, combination chemotherapy improves the quality of life and median survival. Humoral hypercalcemia of malignancy, resulting from the production of parathyroid hormone-related protein by the tumor, is most commonly associated with squamous cell carcinoma. These guided bronchoscopic techniques have a higher yield than traditional transbronchial biopsies, approaching that of transthoracic needle aspiration.25 The small samples obtained by bronchoscopic techniques appear to be adequate for histologic and molecular characterization of the tumor. Survival after resection in pathologic stage IIA is 46% at 5 years, and that in pathologic stage IIB is 36%. A greater percentage of patients treated with induction therapy are able to undergo complete resection. There is a suggestion that newer agents may be as effective with less toxicity.51 Further studies are ongoing.
Fatigue, mental status changes, weakness, gastrointestinal symptoms, polyuria, and electrocardiogram changes may occur. However, a persistent GGN may represent a slow growing malignancy, specifically an adenocarcinoma. Patients with adenocarcinoma may have poorer survival rates than those with squamous cell carcinoma.
Although multimodality therapy is often offered to those who can tolerate it, the selection of patients and therapy is best served in the setting of a study.
A poor performance status and an elevated lactate dehydrogenase level portend a poor prognosis. A pure GGN ≤10mm in diameter has a 25% chance of being an adenocarcinoma in situ (AIS) and less than 5% chance of being an invasive adenocarcinoma.
A semisolid GGN (part ground glass and part solid) has approximately a 50% chance of being AIS and 25% chance of being adenocarcinoma if ≤10 mm.
Growth of the GGN, the development of a solid component, or growth of an existing solid component are all highly related to the presence of malignancy. The benefits in this group includes the preservation of lung function and lower perioperative morbidity.42 However, lobectomy is still considered a superior method. It is more likely to be performed in large, high volume academic centers.43,44 Robotic lung resection seems to have comparable results to VATS.




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