Showing posts with label NSCLC. Show all posts
Showing posts with label NSCLC. Show all posts
Stage Information for NSCLC- BACKGROUND
Stage Information for NSCLC
NSCLC-Staging Evaluation
Staging Evaluation
Evaluation of mediastinal lymph node metastasis
Surgical evaluation
Surgical
staging of the mediastinum is considered standard if accurate evaluation of the
nodal status is needed to determine therapy.
Accurate
staging of the mediastinal lymph nodes provides important prognostic
information.
Evidence
(nodal status):
- The association between survival and the
number of examined lymph nodes during surgery for patients with stage I
NSCLC treated with definitive surgical resection was assessed from the
population-based Surveillance, Epidemiology and End Results database for the
period from 1990 to 2000.[3] A total of 16,800 patients were
included in the study.
o
The
overall survival (OS) analysis for patients without radiation therapy
demonstrated that in comparison to the reference group (one to four lymph
nodes), patients with five to eight lymph nodes examined during surgery had a
modest but statistically significant increase in survival, with a proportionate
hazard ratio (HR) of 0.90 (95% confidence interval [CI], 0.84–0.97). For
patients with 9 to 12 lymph nodes and 13 to 16 lymph nodes examined, HRs were
0.86 (95% CI, 0.79–0.95) and 0.78 (95% CI, 0.68–0.90), respectively. There
appeared to be no incremental improvement after evaluating more than 16 lymph
nodes. The corresponding results for lung cancer–specific mortality and for
patients receiving radiation therapy were not substantially different.
o
These
results indicate that patient survival following resection for NSCLC is
associated with the number of lymph nodes evaluated during surgery. Because
this is most likely the result of a reduction-of-staging error, namely, a
decreased likelihood of missing positive lymph nodes with an increasing number
of lymph nodes sampled, it suggests that an evaluation of nodal status should
include 11 to 16 lymph nodes.
CT imaging
CT scanning
is primarily used for determining the size of the tumor. The CT scan should
extend inferiorly to include the liver and adrenal glands. MRI scans of the
thorax and upper abdomen do not appear to yield advantages over CT scans.[4]
Evidence
(CT scan):
- A systematic review of the medical
literature relating to the accuracy of CT scanning for noninvasive staging
of the mediastinum in patients with lung cancer has been conducted. In the
35 studies published between 1991 and June 2006, 5,111 evaluable patients
were identified. Almost all studies specified that CT scanning was
performed following the administration of IV contrast material and that a
positive test result was defined as the presence of one or more lymph
nodes that measured larger than 1 cm on the short-axis diameter.[5]
o
The
median prevalence of mediastinal metastasis was 28% (range, 18%–56%).
o
The
pooled sensitivity and specificity of CT scanning for identifying mediastinal
lymph node metastasis were 51% (95% CI, 47%–54%) and 86% (95% CI, 84%–88%),
respectively. The corresponding positive and negative likelihood ratios were
3.4 and 0.6, respectively.
- The results from the systematic review are
similar to those of a large meta-analysis that reported the median
sensitivity and specificity of CT scanning for identifying malignant
mediastinal nodes as 61% and 79%, respectively.[6]
- An earlier meta-analysis reported average
sensitivity and specificity of 64% and 74%, respectively.[7]
FDG-PET scanning
The wider
availability and use of FDG-PET scanning for staging has modified the approach
to staging mediastinal lymph nodes and distant metastases.
Randomized
trials evaluating the utility of FDG-PET scanning in potentially resectable
NSCLC report conflicting results in terms of the relative reduction in the
number of noncurative thoracotomies.
Although
the current evidence is conflicting, FDG-PET scanning may improve results of
early-stage lung cancer by identifying patients who have evidence of metastatic
disease that is beyond the scope of surgical resection and that is not evident
by standard preoperative staging procedures.
Evidence
(FDG-PET scan):
- A systematic review, an expansion of a
health technology assessment conducted in 2001 by the Institute for
Clinical and Evaluative Sciences, evaluated the accuracy and utility of
FDG-PET scanning in the diagnosis and staging of lung cancer.[8] Through a systematic search of the
literature, 12 evidence summary reports and 15 prospective studies of the
diagnostic accuracy of FDG-PET scanning were identified. FDG-PET scanning
appears to be superior to CT imaging for mediastinal staging in NSCLC.
FDG-PET scanning also appears to have high sensitivity and reasonable
specificity for differentiating benign from malignant lesions as small as
1 cm.
- A systematic review of the medical
literature relating to the accuracy of FDG-PET scanning for noninvasive
staging of the mediastinum in patients with lung cancer identified 44
studies published between 1994 and 2006 with 2,865 evaluable patients.[5] The median prevalence of mediastinal
metastases was 29% (range, 5%–64%). Pooled estimates of sensitivity and
specificity for identifying mediastinal metastasis were 74% (95% CI,
69%–79%) and 85% (95% CI, 82%–88%), respectively. Corresponding positive
and negative likelihood ratios for mediastinal staging with FDG-PET
scanning were 4.9 and 0.3, respectively. These findings demonstrate that
FDG-PET scanning is more accurate than CT scanning for staging of the
mediastinum in patients with lung cancer.
Cost effectiveness of FDG-PET
scanning
Decision
analyses demonstrate that FDG-PET scanning may reduce the overall costs of medical
care by identifying patients with falsely negative CT scans in the mediastinum
or otherwise undetected sites of metastases.[9-11] Studies concluded that the money saved by
forgoing mediastinoscopy in FDG-PET-positive mediastinal lesions was not
justified because of the unacceptably high number of false-positive results.[9-11] A randomized study found that the addition
of FDG-PET scanning to conventional staging was associated with significantly
fewer thoracotomies.[12] A second randomized trial evaluating the
impact of FDG-PET scanning on clinical management found that FDG-PET scanning
provided additional information regarding appropriate stage but did not lead to
significantly fewer thoracotomies.[13]
Combination of CT imaging and FDG-PET scanning
The combination
of CT imaging and FDG-PET scanning has greater sensitivity and specificity than
CT imaging alone.[14]
Evidence
(CT/FDG-PET scan):
- If there is no evidence of distant
metastatic disease on CT scan, FDG-PET scanning complements CT scan
staging of the mediastinum. Numerous nonrandomized studies of FDG-PET
scanning have evaluated mediastinal lymph nodes using surgery (i.e., mediastinoscopy
and/or thoracotomy with mediastinal lymph node dissection) as the gold
standard of comparison.
- In a meta-analysis evaluating the
conditional test performance of FDG-PET scanning and CT scanning, the
median sensitivity and specificity of FDG-PET scans were reported as 100%
and 78%, respectively, in patients with enlarged lymph nodes.[6] FDG-PET scanning is considered very
accurate in identifying malignant nodal involvement when nodes are
enlarged. However, FDG-PET scanning will falsely identify a malignancy in
approximately one-fourth of patients with nodes that are enlarged for
other reasons, usually as a result of inflammation or infection.[15,16]
- The median sensitivity and specificity of
FDG-PET scanning in patients with normal-sized mediastinal lymph nodes
were 82% and 93%, respectively.[6] These data indicate that nearly 20% of
patients with normal-sized nodes but with malignant involvement had
falsely negative FDG-PET scan findings.
For
patients with clinically operable NSCLC, the recommendation is for a biopsy of
mediastinal lymph nodes that were found to be larger than 1 cm in shortest
transverse axis on chest CT scan or were found to be positive on FDG-PET scan.
Negative FDG-PET scanning does not preclude biopsy of radiographically enlarged
mediastinal lymph nodes. Mediastinoscopy is necessary for the detection of
cancer in mediastinal lymph nodes when the results of the CT scan and FDG-PET
scan do not corroborate each other.
Evaluation of brain metastasis
Patients at
risk for brain metastases may be staged with CT or MRI scans. One study
randomly assigned 332 patients with potentially operable NSCLC and no
neurological symptoms to brain CT or MRI imaging to detect occult brain
metastasis before lung surgery. MRI showed a trend towards a higher
preoperative detection rate than CT scan (P = .069), with an overall detection
rate of approximately 7% from pretreatment to 12 months after surgery.[17] Patients with stage I or stage II disease
had a detection rate of 4% (i.e., eight detections out of 200 patients);
however, individuals with stage III disease had a detection rate of 11.4%
(i.e., 15 detections out of 132 patients). The mean maximal diameter of the
brain metastases was significantly smaller in the MRI group. Whether the
improved detection rate of MRI translates into improved outcome remains
unknown. Not all patients are able to tolerate MRI, and for these patients
contrast-enhanced CT scan is a reasonable substitute.
Evaluation of distant metastasis other than the
brain
Numerous
nonrandomized, prospective, and retrospective studies have demonstrated that
FDG-PET scanning seems to offer diagnostic advantages over conventional imaging
in staging distant metastatic disease; however, standard FDG-PET scans have
limitations. FDG-PET scans may not extend below the pelvis and may not detect
bone metastases in the long bones of the lower extremities. Because the
metabolic tracer used in FDG-PET scanning accumulates in the brain and urinary
tract, FDG-PET scanning is not reliable for detection of metastases in these
sites.[17]
General Information About Non-Small Cell Lung Cancer (NSCLC)
General Information About Non-Small Cell Lung
Cancer (NSCLC)
·
Anatomy
NSCLC is any type of epithelial lung
cancer other than small cell lung cancer (SCLC). The most common types of NSCLC
are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma, but
there are several other types that occur less frequently, and all types can
occur in unusual histologic variants. Although NSCLCs are associated with
cigarette smoke, adenocarcinomas may be found in patients who have never smoked.
As a class, NSCLCs are relatively insensitive to chemotherapy and radiation
therapy compared with SCLC. Patients with resectable disease may be cured by
surgery or surgery followed by chemotherapy. Local control can be achieved with
radiation therapy in a large number of patients with unresectable disease, but
cure is seen only in a small number of patients. Patients with locally advanced
unresectable disease may achieve long-term survival with radiation therapy
combined with chemotherapy. Patients with advanced metastatic disease may
achieve improved survival and palliation of symptoms with chemotherapy,
targeted agents, and other supportive measures.
Incidence and Mortality
Estimated new cases and deaths from
lung cancer (NSCLC and SCLC combined) in the United States in 2014:[1]
·
New cases: 224,210.
·
Deaths: 159,260.
Lung cancer is the leading cause of
cancer-related mortality in the United States.[1] The 5-year relative survival rate from 1995
to 2001 for patients with lung cancer was 15.7%. The 5-year relative survival rate
varies markedly depending on the stage at diagnosis, from 49% to 16% to 2% for
patients with local, regional, and distant stage disease, respectively.[2]
Anatomy
NSCLC arises from the epithelial
cells of the lung of the central bronchi to terminal alveoli. The histological
type of NSCLC correlates with site of origin, reflecting the variation in
respiratory tract epithelium of the bronchi to alveoli. Squamous cell carcinoma
usually starts near a central bronchus. Adenocarcinoma and bronchioloalveolar
carcinoma usually originate in peripheral lung tissue.
Anatomy of the
respiratory system.
Pathogenesis
Smoking-related lung carcinogenesis
is a multistep process. Squamous cell carcinoma and adenocarcinoma have defined
premalignant precursor lesions. Before becoming invasive, lung epithelium may
undergo morphological changes that include the following:
·
Hyperplasia.
·
Metaplasia.
·
Dysplasia.
·
Carcinoma in situ.
Dysplasia and carcinoma in
situ are considered the principal premalignant lesions because they
are more likely to progress to invasive cancer and less likely to spontaneously
regress.
In addition, after resection of a
lung cancer, there is a 1% to 2% risk per patient per year that a second lung
cancer will occur.[3]
Pathology
NSCLC is a heterogeneous aggregate
of histologies. The most common histologies include the following:
·
Epidermoid or squamous cell
carcinoma.
·
Adenocarcinoma.
·
Large cell carcinoma.
These histologies are often
classified together because approaches to diagnosis, staging, prognosis, and
treatment are similar.
Risk Factors
Several risk factors contribute to
the development of lung cancer. These risk factors may include the following:
·
Cigarette, pipe, or cigar smoking.
·
Exposure to second-hand smoke,
radon, arsenic, asbestos, chromates, chloromethyl ethers, nickel, polycyclic
aromatic hydrocarbons, radon progeny, other agents, and air pollution.[4]
·
Radiation therapy to the breast or
chest.
The single most important risk
factor for the development of lung cancer is smoking. For smokers, the risk for
lung cancer is on average tenfold higher than in lifetime nonsmokers (defined
as a person who has smoked <100 cigarettes in his or her lifetime). The risk
increases with the quantity of cigarettes, duration of smoking, and starting
age.
Smoking cessation results in a
decrease in precancerous lesions and a reduction in the risk of developing lung
cancer. Former smokers continue to have an elevated risk for lung cancer for
years after quitting. Asbestos exposure may exert a synergistic effect of
cigarette smoking on the lung cancer risk.[4]
Prevention
A significant number of patients
cured of their smoking-related lung cancer may develop a second malignancy. In
the Lung Cancer Study Group trial of 907 patients with stage T1, N0 resected
tumors, the rate was 1.8% per year for nonpulmonary second cancers and 1.6% per
year for new lung cancers.[5] Other studies have reported even higher
risks of second tumors in long-term survivors, including rates of 10% for
second lung cancers and 20% for all second cancers.[6]
Because of the persistent risk of
developing second lung cancers in former smokers, various chemoprevention
strategies have been evaluated in randomized control trials. None of the phase
III trials with the agents beta carotene, retinol, 13-cis-retinoic acid,
[alpha]-tocopherol, N-acetylcysteine, or acetylsalicylic acid has demonstrated
beneficial, reproducible results.[7-11][Level of evidence: 1iiA] Chemoprevention of
second primary cancers of the upper aerodigestive tract is undergoing clinical
evaluation in patients with early-stage lung cancer.
Refer to the PDQ summaries on Lung Cancer Prevention and Smoking in Cancer Care for more
information.
Screening
In patients considered at high risk
for developing lung cancer, the only screening modality for early detection
that has been shown to alter mortality is low-dose helical CT scanning.[12] Studies of lung cancer screening with
chest radiography and sputum cytology have failed to demonstrate that screening
lowers lung cancer mortality rates.
(Refer to the Screening by low-dose helical computed tomography subsection
in the PDQ summary onLung Cancer Screening for more
information.)
Clinical Features
Lung cancer may present with
symptoms or be found incidentally on chest imaging. Symptoms and signs may
result from the location of the primary local invasion or compression of
adjacent thoracic structures, distant metastases, or paraneoplastic phenomena. The
most common symptoms at presentation are worsening cough or chest pain. Other
presenting symptoms include the following:
·
Hemoptysis.
·
Malaise.
·
Weight loss.
·
Dyspnea.
·
Hoarseness.
Symptoms may result from local
invasion or compression of adjacent thoracic structures such as compression
involving the esophagus causing dysphagia, compression involving the laryngeal
nerves causing hoarseness, or compression involving the superior vena cava
causing facial edema and distension of the superficial veins of the head and
neck. Symptoms from distant metastases may also be present and include
neurological defect or personality change from brain metastases or pain from
bone metastases. Infrequently, patients may present with symptoms and signs of
paraneoplastic diseases such as hypertrophic osteoarthropathy with digital
clubbing or hypercalcemia from parathyroid hormone-related protein. Physical
examination may identify enlarged supraclavicular lymphadenopathy, pleural
effusion or lobar collapse, unresolved pneumonia, or signs of associated
disease such as chronic obstructive pulmonary disease or pulmonary fibrosis.
Diagnosis
Treatment options for patients are
determined by histology, stage, and general health and comorbidities of the
patient. Investigations of patients with suspected NSCLC focus on confirming
the diagnosis and determining the extent of the disease.
The procedures used to determine the
presence of cancer include the following:
·
History.
·
Physical examination.
·
Routine laboratory evaluations.
·
Chest x-ray.
·
Chest CT scan with infusion of
contrast material.
·
Biopsy.
Before a patient begins lung cancer
treatment, an experienced lung cancer pathologist must review the pathologic
material. This is critical because SCLC, which responds well to chemotherapy
and is generally not treated surgically, can be confused on microscopic
examination with NSCLC.[13] Immunohistochemistry and electron microscopy
are invaluable techniques for diagnosis and subclassification, but most lung
tumors can be classified by light microscopic criteria.
(Refer to the Staging Evaluation section of this
summary for more information on tests and procedures used for staging.)
Molecular Features
The identification of mutations in
lung cancer has led to the development of molecularly targeted therapy to
improve the survival of subsets of patients with metastatic disease.[14] In particular, subsets of adenocarcinoma
now can be defined by specific mutations in genes encoding components of the
epidermal growth factor receptor (EGFR) and downstream mitogen-activated
protein kinases (MAPK) and phosphatidylinositol 3-kinases (PI3K) signaling
pathways. These mutations may define mechanisms of drug sensitivity and primary
or acquired resistance to kinase inhibitors.
Other genetic abnormalities of
potential relevance to treatment decisions include translocations involving the
anaplastic lymphoma kinase (ALK)-tyrosine kinase receptor, which are sensitive
to ALK inhibitors, and amplification of MET (mesenchymal
epithelial transition factor), which encodes the hepatocyte growth factor
receptor. MET amplification has been associated with secondary
resistance to EGFR tyrosine kinase inhibitors.
Prognostic Factors
Multiple studies have attempted to
identify the prognostic importance of a variety of clinicopathologic factors.[6,15-18] Factors that have correlated with adverse
prognosis include the following:
·
Presence of pulmonary symptoms.
·
Large tumor size (>3 cm).
·
Nonsquamous histology.
·
Metastases to multiple lymph nodes
within a TNM-defined nodal station.[19-29] (Refer to theEvaluation of Mediastinal Lymph Node Metastasis section
of this summary for more information.)
For patients with inoperable
disease, prognosis is adversely affected by poor performance status and weight
loss of more than 10%. These patients have been excluded from clinical trials
evaluating aggressive multimodality interventions.
In multiple retrospective analyses
of clinical trial data, advanced age alone has not been shown to influence
response or survival with therapy.[33]
Refer to the separate treatment
sections for each stage of NSCLC in this summary for more information about
prognosis.
Because treatment is not
satisfactory for almost all patients with NSCLC, eligible patients should be
considered for clinical trials. Information about ongoing clinical trials is
available from the NCI
Web site.
Related Summaries
Other PDQ summaries containing
information related to lung cancer include the following:
References
1.
American Cancer Society: Cancer
Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online . Last accessed November 24, 2014.
2.
Ries L, Eisner M, Kosary C, et al.,
eds.: Cancer Statistics Review, 1975-2002. Bethesda, Md: National Cancer
Institute, 2005. Available online. Last accessed May 30, 2013.
3.
Johnson BE: Second lung cancers in
patients after treatment for an initial lung cancer. J Natl Cancer Inst 90
(18): 1335-45, 1998. [PUBMED Abstract]
4.
Wingo PA, Ries LA, Giovino GA, et
al.: Annual report to the nation on the status of cancer, 1973-1996, with a
special section on lung cancer and tobacco smoking. J Natl Cancer Inst 91 (8):
675-90, 1999. [PUBMED Abstract]
5.
Thomas P, Rubinstein L: Cancer
recurrence after resection: T1 N0 non-small cell lung cancer. Lung Cancer Study
Group. Ann Thorac Surg 49 (2): 242-6; discussion 246-7, 1990. [PUBMED Abstract]
6.
Martini N, Bains MS, Burt ME, et
al.: Incidence of local recurrence and second primary tumors in resected stage
I lung cancer. J Thorac Cardiovasc Surg 109 (1): 120-9, 1995. [PUBMED Abstract]
7.
van Boxem AJ, Westerga J, Venmans
BJ, et al.: Photodynamic therapy, Nd-YAG laser and electrocautery for treating
early-stage intraluminal cancer: which to choose? Lung Cancer 31 (1): 31-6,
2001. [PUBMED Abstract]
8.
Blumberg J, Block G: The
Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study in Finland. Nutr Rev 52
(7): 242-5, 1994. [PUBMED Abstract]
9.
Omenn GS, Goodman GE, Thornquist MD,
et al.: Effects of a combination of beta carotene and vitamin A on lung cancer
and cardiovascular disease. N Engl J Med 334 (18): 1150-5, 1996. [PUBMED Abstract]
10.
Lippman SM, Lee JJ, Karp DD, et al.:
Randomized phase III intergroup trial of isotretinoin to prevent second primary
tumors in stage I non-small-cell lung cancer. J Natl Cancer Inst 93 (8):
605-18, 2001. [PUBMED Abstract]
11.
van Zandwijk N, Dalesio O, Pastorino
U, et al.: EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in
patients with head and neck cancer or lung cancer. For the EUropean
Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer
Cooperative Groups. J Natl Cancer Inst 92 (12): 977-86, 2000. [PUBMED Abstract]
12.
Aberle DR, Adams AM, Berg CD, et
al.: Reduced lung-cancer mortality with low-dose computed tomographic
screening. N Engl J Med 365 (5): 395-409, 2011. [PUBMED Abstract]
13.
Travis WD, Colby TV, Corrin B, et
al.: Histological typing of lung and pleural tumours. 3rd ed. Berlin:
Springer-Verlag, 1999.
14.
Pao W, Girard N: New driver
mutations in non-small-cell lung cancer. Lancet Oncol 12 (2): 175-80,
2011. [PUBMED Abstract]
15.
Albain KS, Crowley JJ, LeBlanc M, et
al.: Survival determinants in extensive-stage non-small-cell lung cancer: the
Southwest Oncology Group experience. J Clin Oncol 9 (9): 1618-26, 1991. [PUBMED Abstract]
16.
Macchiarini P, Fontanini G, Hardin
MJ, et al.: Blood vessel invasion by tumor cells predicts recurrence in
completely resected T1 N0 M0 non-small-cell lung cancer. J Thorac Cardiovasc
Surg 106 (1): 80-9, 1993. [PUBMED Abstract]
17.
Ichinose Y, Yano T, Asoh H, et al.:
Prognostic factors obtained by a pathologic examination in completely resected
non-small-cell lung cancer. An analysis in each pathologic stage. J Thorac
Cardiovasc Surg 110 (3): 601-5, 1995. [PUBMED Abstract]
18.
Fontanini G, Bigini D, Vignati S, et
al.: Microvessel count predicts metastatic disease and survival in non-small
cell lung cancer. J Pathol 177 (1): 57-63, 1995. [PUBMED Abstract]
19.
Sayar A, Turna A, Kiliçgün A, et
al.: Prognostic significance of surgical-pathologic multiple-station N1 disease
in non-small cell carcinoma of the lung. Eur J Cardiothorac Surg 25 (3): 434-8,
2004. [PUBMED Abstract]
20.
Osaki T, Nagashima A, Yoshimatsu T,
et al.: Survival and characteristics of lymph node involvement in patients with
N1 non-small cell lung cancer. Lung Cancer 43 (2): 151-7, 2004. [PUBMED Abstract]
21.
Ichinose Y, Kato H, Koike T, et al.:
Overall survival and local recurrence of 406 completely resected stage IIIa-N2
non-small cell lung cancer patients: questionnaire survey of the Japan Clinical
Oncology Group to plan for clinical trials. Lung Cancer 34 (1): 29-36,
2001. [PUBMED Abstract]
22.
Tanaka F, Yanagihara K, Otake Y, et
al.: Prognostic factors in patients with resected pathologic (p-) T1-2N1M0
non-small cell lung cancer (NSCLC). Eur J Cardiothorac Surg 19 (5): 555-61,
2001. [PUBMED Abstract]
23.
Asamura H, Suzuki K, Kondo H, et
al.: Where is the boundary between N1 and N2 stations in lung cancer? Ann
Thorac Surg 70 (6): 1839-45; discussion 1845-6, 2000. [PUBMED Abstract]
24.
Riquet M, Manac'h D, Le
Pimpec-Barthes F, et al.: Prognostic significance of surgical-pathologic N1
disease in non-small cell carcinoma of the lung. Ann Thorac Surg 67 (6):
1572-6, 1999. [PUBMED Abstract]
25.
van Velzen E, Snijder RJ, Brutel de
la Rivière A, et al.: Lymph node type as a prognostic factor for survival in T2
N1 M0 non-small cell lung carcinoma. Ann Thorac Surg 63 (5): 1436-40, 1997. [PUBMED Abstract]
26.
Vansteenkiste JF, De Leyn PR,
Deneffe GJ, et al.: Survival and prognostic factors in resected N2 non-small
cell lung cancer: a study of 140 cases. Leuven Lung Cancer Group. Ann Thorac
Surg 63 (5): 1441-50, 1997. [PUBMED Abstract]
27.
Izbicki JR, Passlick B, Karg O, et
al.: Impact of radical systematic mediastinal lymphadenectomy on tumor staging
in lung cancer. Ann Thorac Surg 59 (1): 209-14, 1995. [PUBMED Abstract]
28.
Martini N, Burt ME, Bains MS, et
al.: Survival after resection of stage II non-small cell lung cancer. Ann
Thorac Surg 54 (3): 460-5; discussion 466, 1992. [PUBMED Abstract]
29.
Naruke T, Goya T, Tsuchiya R, et
al.: Prognosis and survival in resected lung carcinoma based on the new
international staging system. J Thorac Cardiovasc Surg 96 (3): 440-7,
1988. [PUBMED Abstract]
30.
Thomas P, Doddoli C, Thirion X, et
al.: Stage I non-small cell lung cancer: a pragmatic approach to prognosis after
complete resection. Ann Thorac Surg 73 (4): 1065-70, 2002. [PUBMED Abstract]
31.
Macchiarini P, Fontanini G, Hardin
MJ, et al.: Relation of neovascularisation to metastasis of non-small-cell lung
cancer. Lancet 340 (8812): 145-6, 1992. [PUBMED Abstract]
32.
Khan OA, Fitzgerald JJ, Field ML, et
al.: Histological determinants of survival in completely resected T1-2N1M0
nonsmall cell cancer of the lung. Ann Thorac Surg 77 (4): 1173-8, 2004. [PUBMED Abstract]
33.
Earle CC, Tsai JS, Gelber RD, et
al.: Effectiveness of chemotherapy for advanced lung cancer in the elderly:
instrumental variable and propensity analysis. J Clin Oncol 19 (4): 1064-70,
2001. [PUBMED Abstract]
Subscribe to:
Posts (Atom)