Clinical staging of lung cancer

 Non-small cell lung cancer staging
a lung cancer TNM staging TNM staging system is
for diagnosis, treatment and clinical research of the accurately reflect the patient's condition, accurate prognosis.
1966 of the International Union Against Cancer (UICC) TNM staging of lung cancer since the enactment of the first edition, lung cancer TNM staging system revised total of five. At present the clinical application of the Clifton F . Mountain1997 enacted the American Cancer Association (American Joint Committee on Cancer, AJCC) TNM 5th edition of lung cancer staging system
2002 年 AJCC 6th edition without making any amendments.
Clifton F. Mountain 1997 on Lung Cancer TNM staging system version 5 is based on clinical data from the MD Anderson Cancer Center, a medical center (University of Texas MD Anderson Cancer Center, 4,351 cases of lung cancer, National Cancer Institute study group 968 cases, a total of 5,319 cases), mostly for surgery treatment of cases, a longer time span (1975 to 1988). not fully reflect the real situation of the global lung cancer.
to reflect the results of the recent treatment of lung cancer and lung cancer staging system that has broad representation throughout the world, the 1998 International Study of Lung Cancer Association (IASLC) lung cancer staging Commission to proceed with the revision of the new staging system .1990 to 2000 worldwide (North America, Europe, Asia, Australia, a total of 19 countries) to collect the 100,869 patients with lung cancer data, which clearly pathological types, clinical stage, treatment and follow-up data complete new cases 81,015 cases, NSCLC 67725 cases of small cell lung cancer (SCLC) 13290 patients. Through statistical analysis of the different TNM definitions, Seoul, Korea in 2007, the tenth second report of the World Lung Conference on Lung Cancer of the seventh edition of TNM staging system (2009) amendments. San Francisco in 2009, the Thirteenth General Assembly adopted the World of lung cancer and global implementation in 2010.
1, T stage amendments
on 67,725 cases with complete data NSCLC primary tumor effects of factors on the long-term survival analysis, recommendations will be
T1 into T1a (l2cm), T1b (> 2cm, l3cm); < br> the T2 into T2a (> 3cm, l5cm),
T2b (> 5cm, l7cm);
will> 7cm were defined as T3.
lobe primary tumors occur within the host satellite the same prognosis and other T3 nodules, where the non-primary tumor lobe metastases occur within the same prognosis and the other T4 is better than the M1. It is therefore recommended where the original tumor nodules found in lungs is defined as T3; ipsilateral non-primary lung nodules occur within defined T4.
2, N staging of regional lymph node status revised
clear staging and treatment of lung cancer a vital component in .40 years, cancer researchers around the world under the intrathoracic anatomic site of lymph nodes to locate the regional lymph nodes of lung cancer, and that use different numbers to draw a map to represent the regional lymph nodes of lung cancer clinical and pathological lymph node metastasis.
through accurate, unified regional lymph node nomenclature is the development of lung cancer TNM sub- period, evaluate the therapeutic results in various medical centers to compare the clinical results, the design and analysis of clinical research and patient treatment options for different key factors.
a history of lung cancer is the Naruke lymph node map developed in 1967 , the first widely used in North America, Europe and Japan.
American Thoracic Society (the American Thoracic Society, ATS) will Naruke map was revised and regional lymph node dissection area to do a more precise description of the formation of the ATS map, is widely used in North America.
1996 年 Mountain and Dresler Naruke map and ATS map will be integrated to develop a new map of regional lymph nodes of lung cancer MD-ATS map, and is used by AJCC and UICC. after being in North America and widely used in Europe.
1998 年, IASLC set up a committee to establish an international lung cancer staging database in the world in 2006 to collect 100,869 valid cases of lung cancer cases. Based on the results of the international lung cancer database analysis, IASLC proposed 7th edition AJCC TNM staging of lung cancer amendments.
database through the lymph node staging of lung cancer IASLC international data analysis, we found Naruke map and the MD-ATS map regional lymph node classification for lung cancer there is a big difference in the definition.
more important differences include, Naruke map Group 1 corresponds to MD-ATS map in group 1 and group 2; Naruke map the first set of the corresponding 2,3,4 R and 4L MD-ATS map 4R and 4L group; is of great significance is the MD-ATS map Group 7 (subcarinal lymph nodes) corresponds to the Naruke map 7 group and 10 groups, resulting in some lung cancer staging by MD-ATS map for the N2, IIIA period, while the Naruke map stage was N1, II period. < br> IASLC Committee to develop revised lung cancer staging regional lymph node map, the MD-ATS map and Naruke map integration, and for each group of lymph nodes provided a precise definition of anatomy.
beginning in 2009, IASLC will This standard within the world of lung cancer data collection for 7 years after the AJCC TNM staging of lung cancer 8 edition standards.
compared to MD-ATS map and Naruke map, IASLC map has some significant changes, Table 3. For all of the regional lymph nodes, IASLC map provides clear anatomical boundaries, particularly for group 1 to 10 lymph nodes were clearly defined upper and lower boundaries of each group of lymph nodes in order to avoid duplication.
now 4, and 10 lymph nodes back off as no longer boundaries of the pleura, but provided a clear anatomic landmarks can be more reliable in imaging, endoscopy and surgery were identified.
the clavicle and sternum fossa lymph node before the packet is not clear to distinguish intrathoracic lymph nodes, IASLC map to the provisions of Section 1. unified by clearly defined and the MD-ATS map between the Naruke map of group 2 and group 4 naming difference. < br> taking into account more often upper mediastinal lymph node drainage area in the trachea and often across the right side of the trachea midline, IASLC map requirements right the first section 2,4 2,4 group and the group left the line to the left wall of the trachea, not then follow the MD-ATS map to the center line as the boundary marks the trachea.
cancel Naruke map in Group 3 (covering the middle of the surface of the trachea) the definition of lymph nodes, because the parts of the lymph nodes are not easily and accurately than group 2 or Group 4 lymph nodes, and often systematic lymph node dissection in group 4 with en bloc resection of lymph nodes along with. retain and further defined the vascular front (ie the anterior mediastinum) 3a and tracheal lymph 3p.
the bulge lymph node group (MD-ATS map is defined as Group 7, Naruke map is divided into 7 groups and 10 groups) and provides a clear anatomical boundaries. Similarly, for the past confused the right and 4, Section 10 the left and 10 of Group 5 Group and the bilateral group and 11 of 10 lymph nodes, a clear delineation of anatomy.
previous literature on the different regions of the lymph node metastasis and overall survival analysis of the relationship between the trigger of a specific groups of lymph nodes merged into and radiation oncology practitioner or integration for increased cross-group analysis of lymph nodes for help.
Table 3. Naruke, MD-ATS and IASLC Lymph Node Map Comparison of anatomically
Naruke Map
MD-ATS Map
IASLC Map
# 1 root of the neck, clavicle and sternum on the fossa lymph
intrathoracic trachea 1 / 3 of the surrounding area. upper bound for the pleural or subclavian artery on the top edge of the lower bound the left brachiocephalic vein crossing the center line on the edge and the level of the trachea.
the upper edge of the left brachiocephalic vein and trachea area above the center line level crossing.
upper bounds: the lower edge of cricoid cartilage; lower bound: Bilateral clavicle, the middle of the manubrium margin; trachea midline, and this regional lymph nodes are divided into 1R 1L.
# 2 paratracheal lymph nodes
# 2 on the paratracheal lymph nodes
in group 1 and 4 groups.
the aortic arch margin above the level of tangent plane, the following lower bound of group 1 lymph node area of the mediastinal lymph nodes.
2R: upper bounds: the top of the right lung and pleural tip, the upper edge of the middle of the manubrium; lower bound: innominate vein and trachea and the lower edge of the intersection; in sector: the left edge of the trachea.
2L: upper bound: the top left apical pleura, on the edge of the middle of the manubrium; lower bound: the upper edge of the aortic arch.
# 3 tracheal blood vessels before the lymph nodes before and
# 3 tracheal tube after the lymph nodes
in front of group 1 below. # 3a anterior mediastinal lymph nodes,
# 3p mediastinal lymph nodes after airway.
lymph vessel is defined as before 3a, tracheal lymph nodes defined as 3p. in the middle ipsilateral lymph nodes were considered.
3a: the right side of the upper bound: pleural top, the lower bound: carina level, the former world: chest, back boundary: the left superior vena cava on the boundary edge
: pleural top , lower bound: carina level, the former world: chest, back boundary: left common carotid artery
3p: the upper bound: pleural top, the lower bound: carina level.
# 4 tracheobronchial lymph nodes
# 4
in the trachea carina lymph node on the right side of the inside of the azygos vein, left the inside of the aorta.
right in the middle right side of the trachea, aortic arch tangent plane on the edge of the level below, right upper lobe bronchus plane above the upper edge of the opening, including in the mediastinal pleura or less. the left side of the center line at the left side of the trachea, aortic arch tangent plane on the edge of the level below the left upper lobe bronchus on the edge of the opening above the level of arterial medial ligaments, including the mediastinal pleura or less. Youyi azygos vein arch level of the upper edge of the boundary is divided into 4s and 4i.
4R: including the right paratracheal lymph nodes and trachea before. the world: the intersection of innominate vein and trachea and the lower edge of the lower bound: azygos vein under edge.
4L: the left edge of the trachea between the ligaments and arteries. the world: on the edge of the aortic arch, the lower bound: the upper edge of the left pulmonary artery.
# 5 near the aortic arch arteries
ligament lymph nodes, located in the aortic arch and between the pulmonary trunk.
pulmonary artery and the left lateral ligament, to the first branch of the left pulmonary artery, including within the mediastinal pleura.
artery lateral ligament lymph nodes. upper bounds: the lower edge of the aortic arch, the lower bound: the left pulmonary artery on the edge.
# 6
aortic lymph nodes along the ascending aorta, aortic arch lateral to the vagus nerve after the community.
located in the ascending aorta, aortic arch or the innominate artery and the outside front, in the aortic arch cutting edge level below the level.
ascending aorta and aortic arch anterior lateral lymph node. the world: cutting edge of the aortic arch and lower bounds: the lower edge of the aortic arch.
# 7 subcarinal lymph nodes in the subcarinal
.
in the lymph nodes below the carina, not related to the lower lobe bronchus and pulmonary artery.
upper bound: carina, the lower bound: the left lower lobe bronchus on the edge of the right bronchus to the lower edge of the middle of dry .
# 8
paraesophageal lymph nodes in the subcarinal lymph nodes below the surrounding esophagus.
lymph nodes near the esophagus, except for subcarinal lymph nodes.
in the esophageal surface, except for subcarinal lymph nodes. upper bound: the left lower lobe bronchus on the edge of the right bronchus to the lower edge of the middle dry, the lower bound: the diaphragm.
# 9 in the lower pulmonary ligament lymph nodes
pulmonary vein, the rear.
included in the pulmonary ligament , including the rear and below the lymph nodes.
pulmonary ligament lymph nodes. Upper Bound: inferior pulmonary vein, the lower bound: the diaphragm.
# 10 hilar lymph nodes
located around the left or the right main bronchus.
mediastinal pleura back off the roots of lymph nodes outside the lung. On the right side near the middle of dry bronchial
adjacent main bronchus and hilar vessels (including the distal pulmonary veins and the pulmonary artery). upper bound: the lower edge of the right side of the azygos vein, left the pulmonary artery on the edge of the lower bound: bilateral interlobar region.
# 11 leaves of the lymph nodes in the lobar bronchus
between:
# 11s: located on the middle between the bronchus, # 11i: located in between the lower lobe bronchus.
lobe bronchus is located between the openings between
lobe bronchus. # 11s: right upper lobe bronchus and intermediate between the dry, # 11i: right between the middle and lower lobe bronchus.
# 12 leaves in the leaf nodes
bronchi:
# 12u: the upper lobe bronchi,
# 12m: middle bronchi,
# 12l: lower lobe bronchi.
distal lobar bronchus lobar bronchus close to the surrounding lymph nodes
.
# 13 segments around the lymph nodes

segmental bronchi segmental bronchi segmental bronchi lymph node
lymph nodes.
# 14 sub-section of lymph node
subsegmental bronchi

subsegmental bronchi adjacent to sub-segmental bronchi.
3, M
Statistics found that the amendment stage, malignant pleural effusion and contralateral lung nodules 5 year survival rate was the same, only 2%, defined as M1a, other distant metastasis is defined as M1b. the TNM staging combinations, as shown in Table 4:
Table 4. IASLC recommended a new version of NSCLC TNM staging
N0
N1
N2
N3
M1a
M1b
T1a
Ⅰ A
Ⅱ A
Ⅲ A
Ⅲ B
Ⅳ
Ⅳ
T1b
Ⅰ A
Ⅱ A
Ⅲ A
Ⅲ B
Ⅳ
Ⅳ
T2a
Ⅰ B
Ⅱ A
Ⅲ A
Ⅲ B
Ⅳ
Ⅳ
T2b
Ⅱ A
Ⅱ B
Ⅲ A
Ⅲ B
Ⅳ
Ⅳ
T3
Ⅱ B
Ⅲ A
Ⅲ A
Ⅲ B
Ⅳ
Ⅳ
T4
Ⅲ A
Ⅲ A
Ⅲ B
Ⅲ B
Ⅳ
Ⅳ
Second, NSCLC mediastinal lymph node staging method Evaluation
no distant metastasis for NSCLC, a clear decision without mediastinal lymph node metastasis is a key factor in treatment of lung cancer mediastinal lymph node staging method N is divided into two non-invasive and invasive.
1, NSCLC mediastinal Non-invasive lymph node staging
past studies have shown that chest CT, CT scan images on the morphological features of mediastinal lymph nodes, such as the lymph node shape, density, degree of edge enhancement on the situation and determine whether the transfer has occurred not help much, only the size of lymph nodes CT diagnosis of mediastinal lymph node metastasis help.
CT diagnosis of metastatic lymph nodes the size of the field value has not yet have a unified opinion, at present mostly in the axial CT, and lymph node short axis diameter g1cm CT diagnosis of lymph node metastasis as the standard.
1991 to 2006 with complete data of 35 clinical studies, a total of 5111 cases of NSCLC, mediastinal lymph node metastasis was found in 28% (18 ~ 56%), CT mediastinal lymph nodes to determine the overall sensitivity and specificity were 51% and 86%.
two large meta-analysis to determine mediastinal lymph node metastasis CT sensitivity and specificity were 61%, 79% and 64%, 74%. Although chest CT to determine the accuracy of mediastinal lymph node metastasis and not high, but it is the best of mediastinal non-invasive anatomical methods, mediastinal lymph nodes can provide more information for suspicious lymph nodes targeted for further invasive inspection to improve the diagnostic accuracy and guide the surgical dissection.
positron emission tomography (PET) PET through quantitative analysis of glucose metabolism in tissues and cells to determine the benign and malignant lesions, with a high degree of sensitivity, the drawback is the spatial resolution is not high, only a new generation of PET spatial resolution 7 ~ 10 mm .2001 PET / CT advent of integrated PET's high sensitivity and high resolution CT, and quickly became a variety of tumor diagnosis and staging of the best non-invasive imaging methods.
18F-deoxy glucose (18 F-FDG) is currently the only recognized mediastinal staging of lung cancer imaging agent for positron. in order to change glucose metabolism in the cell as a roadmap, 18F-FDG can be sensitive to show a variety of lymph nodes and the pathological change .18 F- FDG PET may be sensitive to the detection of normal-sized lymph nodes, effectively reducing ineffective chest. University of diagnosis and treatment of cancer Multidisciplinary Center statistics show, PET images that reflect the metabolic information of 72.2% making the diagnosis and treatment of lung cancer.
for CT scan of mediastinal lymph nodes of cases, PET sensitivity and specificity were 100% and 78%. In other words, PET to determine the accuracy of high metastatic lymph nodes enlarged, but there are nearly 1 / 4 of the false positive, granulomatous and inflammatory diseases, mostly.
1994 ~ 2006 年 44 clinical studies with complete data, a total of 2,865 cases of NSCLC, mediastinal lymph node metastasis rate was 29%, PET mediastinal N staging of NSCLC to determine the sensitivity and specificity were 74% and 85%, 20% of normal-sized lymph nodes were false negative PET scans.
a comparison of PET / CT and PET for staging of lung cancer diagnosis study shows PET / CT sensitivity and specificity significantly better than PET, were 85% and 84% vs 70% and 69%.
2, NSCLC mediastinal lymph node staging
invasive mediastinoscopy (Mediastinoscopy) mediastinoscopy is mediastinal lymph node staging in NSCLC ; gold standard , 4L, 4R and 7 lymph nodes before carina biopsies. but can not reach 3A, 3P, 5,6, 7,8,9 post carina lymph nodes. should routinely check the 2R, 2L, 4R, 4L and 7 groups lymph node. on the 5,6 group before the implementation of lymph node biopsy be mediastinotomy (Chamberlain operation), expanded by cervical mediastinoscopy incision can replace the anterior mediastinal lymph node biopsies of 5,6.
video-assisted mediastinal mirror technology to expand the traditional scope of mediastinoscopy in the exploration, application of video-assisted mediastinoscopy now have to complete systematic mediastinal lymphadenectomy.
the sensitivity of mediastinoscopy lymph node biopsy and false negative rates were 80% and 10% specificity and false-positive rate was 100% and 0%. about half (42 ~ 57%) false-negative due to mediastinoscopy can not reach the lymph nodes. The video-assisted mediastinoscopy in the sensitivity of lymph node biopsy and false negative rates were 90 % and 7%.
N0 for the clinical diagnosis of NSCLC to mediastinoscopy, mediastinal lymph node metastasis, the sensitivity of diagnosis and false negative rates were 45% and 8%, found that about 15% of the patients had lymph node metastases. As lower false negative rate, it is recommended to exclude normal-sized mediastinal lymph nodes.
bronchoscopic needle aspiration biopsy (transbronchial needle aspiration, TBNA) bronchoscopic needle aspiration can be easily and safely in the clinic, and less serious complications. mainly used to evaluate the subcarinal lymph nodes, paratracheal lymph node biopsy has difficulty .80 ~ 90% of cases have access to adequate specimens.
Patelli other use of TBNA in the diagnosis of 194 patients with NSCLC mediastinal N2 lymph nodes , the sensitivity and accuracy were 71% and 73%. complication rate of about 2% -5%, including bleeding and pneumothorax.
Hermens integrated 17 clinical studies found that the sensitivity and TBNA false negative rates were 78% and 28%; specificity and false positive rates were 100% and 7%. TBNA and more used in CT scanning in patients with mediastinal lymph nodes, because of its high false negative, not suitable for normal size mediastinal lymph node biopsy, and negative results can not completely rule out lymph node metastasis.
bronchoscopy guided needle aspiration biopsy (endobronchial ultrasound needle aspiration, EBUS-NA) early in the EBUS-NA can not do real-time ultrasound guided bronchoscopic biopsy of mediastinal lymph node biopsy, with advances in technology have been able to do real-time guide the puncture process. can be safely puncture 1R, 1L, 2R, 2L, 4R, 4L, 7, and 10R and 10L. mediastinal lymph node to determine its sensitivity and specificity , respectively 90% and 24%.
a study of 100 patients diagnosed as stage Ⅰ NSCLC, application of EBUS-NA were 2R, 2L, 4R, 4L, 7, 10R, 10L, 11R and 11L lymph node biopsy and found 9 patients with lymph node metastasis, all patients underwent subsequent surgical resection, confirmed the clinical diagnosis of EBUS-NA Ⅰ lymph node metastasis of lung cancer the accuracy, specificity and negative predictive values were 89%, 100% and 98.9%. Tip EBUS-NA may be used to evaluate the normal size of the mediastinal lymph nodes. Real-time EBUS-NA performed 3 times on the same node biopsy, allows the diagnostic accuracy, sensitivity and negative predictive values were increased to 98.4%, 95.3% and 97.6%.
by comparing EBUS-NA, and mediastinoscopy in the diagnosis of NSCLC value of mediastinal lymph node metastasis prospective controlled study found that both the accuracy of N staging was no significant difference (93% vs 82%, P = 0.083), However, EBUS-NA of the sensitivity and negative predictive value were higher than the CM. Therefore, to determine paratracheal and subcarinal lymph nodes whether there is metastasis, EBUS-NA is better than the diagnostic value of mediastinoscopy.
esophageal Mirror ultrasound-guided needle aspiration biopsy (esophageal endoscopic ultrasound needle aspiration, EUS-NA) has high security, the probability of infection and bleeding is very low. EUS-NA groups of lymph nodes can be evaluated, especially for in section 9, 8,7 and 5 lymph node biopsy and the metastasis of the left adrenal gland, even the lymph nodes smaller than 1 cm in diameter can be accurately puncture. but because of the trachea, bronchus gas interference, EUS is usually unable to detect 1,2,3 and 4R group of lymph. but hard on the 2R, 2L, 4R, 4L reliable biopsy.
Detterbeck summed up the 16 EUS-NA of mediastinal lymph node staging in NSCLC line reports, the overall sensitivity and false negative rates were 84% and 19%; specificity and false positive rate was 99.5% and 0.4%. For the CT scan in patients with mediastinal lymphadenopathy, EUS-NA sensitivity and false negative rates were 87% and 22%; specificity and false positive rate 98% and 2%. For the CT scan in patients with normal-sized mediastinal lymph nodes, EUS-NA sensitivity and false negative rates were 66% and 14%; specificity and false-positive rate was 100% and 0%.
EUS-FNA complications are rare, the occurrence rate of only 0.8%, and are fever, cough, sore throat, nausea and vomiting and other minor complications. So for CT in patients with lymph node-positive NSCLC, EUS-FNA is a safe, effective method for diagnosis of mediastinal lymph node. despite negative CT in the mediastinal lymph nodes when the sensitivity is low, but EUS-FNA or CT, can avoid a lot of negative results as a result of unnecessary thoracotomy.
yet No single imaging method can accurately evaluate the potential availability of NSCLC patients with mediastinal lymph node metastasis, and a variety of invasive examination methods are dangerous and there is a special operation requires a certain skill, the choice of invasive staging methods, the technical equipment should be based on the hospital operator's skill level and the transfer of suspicious mediastinal lymph nodes depending on the specific site.
in actual clinical work, should first be enhanced chest CT scans, mediastinal lymph nodes are found, then the need for PET / CT examination, if no significant metabolic increase in mediastinal lymph nodes, the conventional surgical treatment for lung cancer; otherwise, in need of invasive inspection including TBNA, EBUS-TBNA and mediastinoscopy in mediastinal lymph node biopsy TV to exclude N2 and N3. from the surface point of view, seems to increase the patient's hospital medical costs, but the health economics point of view, that is saving the government medical expenses, but also reduce the rate of unnecessary thoracotomy; particularly for PET / CT examinations showed false-positive mediastinal lymph node metastasis in patients with radical surgery offers the opportunity for treatment.
Zhi Xiuyi Director of lung cancer patient with special needs telephone booking:
,
Zhi Xiuyi CMU director of Capital University of Medical Oncology
Deputy Director, Department of Science and lung cancer, head cancer treatment center
Capital University of Medical Director and Director of Thoracic Surgery, Xuanwu Hospital, Beijing Medical Association
vice president of Thoracic Surgery, Beijing Medical Branch of Chinese Medical Association, chairman of thoracic
CATS surgeon Branch Director
executive vice president and the Ministry of Health Clinical Pathway Audit Committee of Experts and Thoracic Surgery, Xuanwu Hospital, the team leader
special needs clinic hours: Mondays 8:30-11:30 am < br> Beijing 305 Hospital outpatient special needs: Every Thursday morning 9:00-11:00