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1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7-30. Review/Other-Dx N/A Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data. Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the National Center for Health Statistics. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2005-2014) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2006-2015) declined by about 1.5% annually in both men and women. The combined cancer death rate dropped continuously from 1991 to 2015 by a total of 26%, translating to approximately 2,378,600 fewer cancer deaths than would have been expected if death rates had remained at their peak. Of the 10 leading causes of death, only cancer declined from 2014 to 2015. In 2015, the cancer death rate was 14% higher in non-Hispanic blacks (NHBs) than non-Hispanic whites (NHWs) overall (death rate ratio [DRR], 1.14; 95% confidence interval [95% CI], 1.13-1.15), but the racial disparity was much larger for individuals aged <65 years (DRR, 1.31; 95% CI, 1.29-1.32) compared with those aged >/=65 years (DRR, 1.07; 95% CI, 1.06-1.09) and varied substantially by state. For example, the cancer death rate was lower in NHBs than NHWs in Massachusetts for all ages and in New York for individuals aged >/=65 years, whereas for those aged <65 years, it was 3 times higher in NHBs in the District of Columbia (DRR, 2.89; 95% CI, 2.16-3.91) and about 50% higher in Wisconsin (DRR, 1.78; 95% CI, 1.56-2.02), Kansas (DRR, 1.51; 95% CI, 1.25-1.81), Louisiana (DRR, 1.49; 95% CI, 1.38-1.60), Illinois (DRR, 1.48; 95% CI, 1.39-1.57), and California (DRR, 1.45; 95% CI, 1.38-1.54). Larger racial inequalities in young and middle-aged adults probably partly reflect less access to high-quality health care. 4
2. Leidl R, Wacker M, Schwarzkopf L. Better understanding of the health care costs of lung cancer and the implications. Expert Rev Respir Med. 2016:1-3. Review/Other-Dx N/A To provide Better understanding of the health care costs of lung cancer and the implications. No results stated in abstract. 4
3. Rami-Porta R, Ball D, Crowley J, et al. 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. J Thorac Oncol. 2007; 2(7):593-602. Observational-Tx 18,198 patients To propose changes in the seventh revision of the tumor, node, metastasis (TNM) classification for lung cancer. On the basis of the optimal cutpoints, pT1NOR0 was divided into pT1a =2 cm (n=1,816) and pT1b >2 to 3 cm (n=1,653) with 5-year survival rates of 77% and 71% (P<0.0001). The pT2NOR0 cutpoints resulted in pT2a >3 to 5 cm (n=2,822), pT2b >5 to 7 cm (n=825), and pT2c >7 cm (n=364). Their 5-year survival rates were 58%, 49%, and 35% (P<0.0001). For clinically staged N0, 5-year survival was 53% for cT1a, 47% for cT1b, 43% for cT2a, 36% for cT2b, and 26% for cT2c. pT3NO (n=711) and pT4 (any N) (n=340) had 5-year survival rates of 38% and 22%. pT4 (additional nodule(s) in the same lobe) (n=363) had a 5-year survival rate of 28%, similar to pT3 (P=0.28) and better than other pT4 (P=0.0029). For pM1 (ipsilateral pulmonary nodules) (n=180), 5-year survival was 22%, similar to pT4. For cT4-malignant pleural effusion/nodules, 5-year survival was 2%. Recommended changes in the T classification are to subclassify T1 into T1a and T1b, and T2 into T2a and T2b; and to reclassify T2c and additional nodule(s) in the same lobe as T3, nodule(s) in the ipsilateral nonprimary lobe as T4, and malignant pleural or pericardial effusions as M1. 2
4. Chansky K, Detterbeck FC, Nicholson AG, et al. The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol. 2017;12(7):1109-1121. Review/Other-Dx 612,534 NSCLC cases To externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons. The databases differed in terms of key factors related to data source. Survival was greater in the International Association for the Study of Lung Cancer (IASLC) database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage. 4
5. Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT. The Eighth Edition Lung Cancer Stage Classification. Chest. 2017;151(1):193-203. Review/Other-Dx N/A To summarize the eighth edition of lung cancer stage classification, which is the worldwide standard as of January 1, 2017. No results stated in abstract. 4
6. Goldstraw P, Chansky K, Crowley J, et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016;11(1):39-51. Review/Other-Dx N/A To describe the methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition. No results stated in abstract. 4
7. de Langen AJ, Raijmakers P, Riphagen I, Paul MA, Hoekstra OS. The size of mediastinal lymph nodes and its relation with metastatic involvement: a meta-analysis. Eur J Cardiothorac Surg. 2006;29(1):26-29. Meta-analysis 14 studies A meta-analysis of available studies reporting on the prevalence of metastatic involvement for different size categories of enlarged lymph nodes in patients with NSCLC. A post-test probability was found for N2 disease of 5% for lymph nodes measuring 10-15 mm on CT in patients with a negative FDG-PET result, suggesting that these patients should be planned for thoracotomy because the yield of mediastinoscopy will be extremely low. For patients with lymph nodes measuring =16 mm on CT and a negative FDG-PET result a post-test probability for N2 disease of 21% was found, suggesting that these patients should be planned for mediastinoscopy prior to possible thoracotomy to prevent too many unnecessary thoracotomies in this subset. Good
8. Satoh H, Ishikawa H, Kagohashi K, Kurishima K, Sekizawa K. Axillary lymph node metastasis in lung cancer. Med Oncol. 2009;26(2):147-150. Review/Other-Dx 1,340 patients To evaluate clinicopatholgical characteristics of such lung cancer patients, we performed a retrospective study of them, who had Axillary lymph node metastasis (ALNM) at the time of initial presentation or developed ALNM in their clinical courses. Ten (0.75%) of 1,340 patients had ALNM. In eight of them, ALNM was detected at the time of initial diagnosis, and two patients developed ALNM in their clinical courses. Lymphatic metastasis to mediastinum was evident in all patients. Supraclavicular and cervical lymph nodes were involved in five and three patients, respectively. One patient had direct chest wall invasion from the lung. Three patients had distant metastases other than axillary or cervical lymph nodes. Four patients received systemic chemotherapy, and another four patients received palliative chest irradiation or supportive care because of their poor performance status. Median survival time of 8 patients who were diagnosed as having ALNMs at initial presentation was 7 months. 4
9. Reck M, Heigener DF, Mok T, Soria JC, Rabe KF. Management of non-small-cell lung cancer: recent developments. [Review]. Lancet. 382(9893):709-19, 2013 Aug 24. Review/Other-Dx N/A To discuss the evolution of lung cancer staging towards more non-invasive, endoscopy-based, and image-based methods, and the development of stage-adapted treatment. No results stated in abstract. 4
10. Travis WD, Asamura H, Bankier AA, et al. The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol. 2016;11(8):1204-1223. Review/Other-Dx N/A To propose codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part-solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer. No results stated in abstract. 4
11. Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e211S-e250S. Review/Other-Dx N/A To provide guidelines for Diagnosis and management of lung cancer. The sensitivity and specificity of computed tomography (CT) scanning for identifying mediastinal lymph node metastasis were approximately 55% and 81%, respectively, confirming that CT scanning has limited ability either to rule in or exclude mediastinal metastasis. For Positron-Emission Tomography (PET) scanning, estimates of sensitivity and specificity for identifying mediastinal metastasis were approximately 77% and 86%, respectively. These findings demonstrate that PET scanning is more accurate than CT scanning, but tissue biopsy is still required to confirm PET scan findings. The needle techniques endobronchial ultrasound-needle aspiration, endoscopic ultrasound-needle aspiration, and combined endobronchial ultrasound/endoscopic ultrasound-needle aspiration have sensitivities of approximately 89%, 89%, and 91%, respectively. In direct comparison with surgical staging, needle techniques have emerged as the best first diagnostic tools to obtain tissue. Based on randomized controlled trials, PET or PET-CT scanning is recommended for staging and to detect unsuspected metastatic disease and avoid noncurative resections. 4
12. Toloza EM, Harpole L, McCrory DC. Noninvasive staging of non-small cell lung cancer: a review of the current evidence. Chest. 2003; 123(1 Suppl):137S-146S. Review/Other-Dx N/A Systematic review to determine the test performance characteristics of CT, PET, MRI, and endoscopic US for staging the mediastinum, and to evaluate the accuracy of the clinical evaluation. CT: sensitivity, 0.57; specificity, 0.82; PET: sensitivity, 0.84; specificity, 0.89; Endoscopic US: sensitivity, 0.78; specificity, 0.71. PET scanning is more accurate. 4
13. Cerfolio RJ, Bryant AS. Distribution and likelihood of lymph node metastasis based on the lobar location of nonsmall-cell lung cancer. Ann Thorac Surg. 2006;81(6):1969-1973; discussion 1973. Observational-Dx 954 patients A retrospective review of an electronic prospective database of patients with NSCLC. Patients with right middle lobe cancer were more likely to have N1 disease (P=0.014). Skip metastases (no N1, but N2 disease) was most common with left upper lobe lesions. Patients with right-sided cancers were more likely to have N2 disease compared with patients who had left-sided lesions (27% vs 21%, P=0.02). There is a distinct predilection for the location of N2 disease based on the lobar location of primary NSCLC. It is recommended to consider video-assisted thoracoscopy for biopsy of the 5 and 6 stations for patients with left upper lobe lesions, mediastinoscopy for right upper lobe lesions, and esophageal US with FNA for right lower lobe, left lower lobe, and right middle lobe lesions. Right-sided lesions are more likely to have N2 disease. 3
14. Watanabe S, Suzuki K, Asamura H. Superior and basal segment lung cancers in the lower lobe have different lymph node metastatic pathways and prognosis. Ann Thorac Surg. 2008;85(3):1026-1031. Observational-Tx 139 patients: 51 superior segment; 88 basal segment To reveal differences in the metastatic pathway to the mediastinum and in prognosis of N2 disease between lung cancers originating from superior and basal segment of the lower lobe. The superior segment group showed a significantly higher incidence of superior mediastinal metastasis than the basal segment group (64% vs 36%, P=0.0012). When superior mediastinal metastasis existed, the basal segment group showed a significantly higher incidence of synchronous subcarinal metastasis than the superior segment group (81% vs 39%, P=0.0006). Pneumonectomy was required significantly more often in the superior segment group than in the basal segment group (45% vs 17%, P=0.0003). The basal segment origin tumors with only subcarinal metastasis showed significantly better prognosis than other lower lobe N2 tumors (5-year survival, 43% vs 18%; P=0.0155). 2
15. Mayo-Smith WW, Song JH, Boland GL, et al. Management of Incidental Adrenal Masses: A White Paper of the ACR Incidental Findings Committee. J Am Coll Radiol. 2017;14(8):1038-1044. Review/Other-Dx N/A To represent an update to the adrenal component of the Journal of American College of Radiology (JACR) 2010 white paper on managing incidental findings in the adrenal glands, kidneys, liver, and pancreas. No results stated in abstract. 4
16. MacManus MP, Hicks RJ, Matthews JP, et al. High rate of detection of unsuspected distant metastases by pet in apparent stage III non-small-cell lung cancer: implications for radical radiation therapy. Int J Radiat Oncol Biol Phys. 2001;50(2):287-293. Observational-Dx 167 patients To compared the rates of positron emission tomography (PET)-detected distant metastases in patients with Stage I–II vs. Stage III disease on conventional imaging. Also to assess the accuracy of the PET scan by patient follow-up, serial imaging, and histopathologic correlations following PET. Stage distribution pre-positron emission tomography (PET) was n = 39 (Stage I), n = 28 (Stage II), and n = 100 (Stage III). In 32 patients (19%), PET detected distant metastasis, most commonly abdominal with 17 cases (adrenal, n = 7; liver, n = 4; other, n = 6). Other sites included lung (n = 10) and bone (n = 6). PET-detected metastasis increased with increasing pre-PET stage from I (7.5%) through II (18%) to III (24%, p = 0.016), and, in particular, was significantly higher in Stage III (p = 0.039). Biopsy confirmation was not routine, but progression occurred at PET-detected metastatic sites or other metastatic sites in all but 3 of the 32 patients by last review. 2
17. Reed CE, Harpole DH, Posther KE, et al. Results of the American College of Surgeons Oncology Group Z0050 trial: the utility of positron emission tomography in staging potentially operable non-small cell lung cancer. J Thorac Cardiovasc Surg. 2003;126(6):1943-1951. Observational-Dx 303 patients To ascertain whether FDG-PET could detect lesions that would preclude pulmonary resection in patients with documented or suspected NSCLC found to be surgical candidates by routine staging procedures. PET was significantly better than CT for the detection of N1 and N2/N3 disease (42% vs 13%, P=.0177, and 58% vs 32%, P=.0041, respectively). The NPV of PET for mediastinal node disease was 87%. In patients with suspected or proven NSCLC considered resectable by standard staging procedures, PET can prevent nontherapeutic thoracotomy in a significant number of cases. Use of PET for mediastinal staging should not be relied on as a sole staging modality, and positive findings should be confirmed by mediastinoscopy. Metastatic disease, especially a single site, identified by PET requires further confirmatory evaluation. 3
18. Viney RC, Boyer MJ, King MT, et al. Randomized controlled trial of the role of positron emission tomography in the management of stage I and II non-small-cell lung cancer. J Clin Oncol. 2004;22(12):2357-2362. Experimental-Dx 184 patients To investigate the impact of fluorodeoxyglucose (FDG) Positron emission tomography (PET) on clinical management of stage I and II non-small-cell lung cancer. One hundred eighty-four patients with stage I-II Non–small-cell lung cancer (NSCLC) were recruited and randomly assigned; 92% had stage I disease. Following exclusion of one ineligible patient, 92 patients were assigned to no PET and 91 to PET. Compared with conventional staging, PET upstaged 22 patients, confirmed staging in 61 and staged two patients as benign. Stage IV disease was rarely detected (two patients). PET led to further investigation or a change in clinical management in 13% of patients and provided information that could have affected management in a further 13% of patients. There was no significant difference between the trial arms in the number of thoracotomies avoided (P =.2). 1
19. van Tinteren H, Hoekstra OS, Smit EF, et al. Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomised trial. Lancet. 2002;359(9315):1388-1393. Experimental-Dx 188 patients from 9 hospitals: 96 conventional workup; 92 conventional workup plus PET A randomized controlled trial to test whether FDG-PET reduces the number of futile thoracotomies in patients with suspected NSCLC, scheduled for surgery after conventional workup. 18 patients in the conventional workup group and 32 in the conventional workup+PET group did not have thoracotomy. In the conventional workup group, 39 (41%) patients had a futile thoracotomy, compared with 19 (21%) in the conventional workup+PET group (relative reduction 51%, 95% CI 32-80%; P=0.003). Addition of PET to conventional workup prevented unnecessary surgery in one out of five patients with suspected NSCLC. 1
20. Marom EM, McAdams HP, Erasmus JJ, et al. Staging non-small cell lung cancer with whole-body PET. Radiology. 1999;212(3):803-809. Observational-Dx 100 patients To compare the accuracies of whole-body 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) and conventional imaging (thoracic computed tomography [CT], bone scintigraphy, and brain CT or magnetic resonance [MR] imaging) in staging bronchogenic carcinoma. PET staging was accurate in 83 (83%) patients; conventional imaging staging was accurate in 65 (65%) patients (P < .005). Staging with mediastinal lymph nodes was correct by using PET in 67 (85%) patients and by using CT in 46 (58%) patients (P < .001). Nine (9%) patients had metastases demonstrated by using PET that were not found with conventional imaging, whereas 10 (10%) patients suspected of having metastases because of conventional imaging findings were correctly shown with PET to not have metastases. 2
21. Antoch G, Vogt FM, Freudenberg LS, et al. Whole-body dual-modality PET/CT and whole-body MRI for tumor staging in oncology. JAMA. 2003;290(24):3199-3206. Observational-Dx 98 patients To determine the staging accuracies of both whole-body positron emission tomography (PET) /computed tomography (CT) and whole-body Magnetic resonance imaging (MRI) for different malignant diseases. Of 98 patients, the overall tumor, node and metastasis (TNM) stage was correctly determined in 75 with PET/CT (77%; 95% confidence interval [CI], 67%-85%) and in 53 with MRI (54%; 95% CI, 44%-64%) (P<.001). Compared with MRI, PET/CT had a direct impact on patient management in 12 patients. Results from MRI changed the therapy regimen in 2 patients compared with PET/CT. Separate assessment of T-stage (with pathological verification) in 46 patients revealed PET/CT to be accurate in 37 (80%; 95% CI, 66%-91%) and MRI to be accurate in 24 (52%; 95% CI, 37%-67%) (P<.001). Of 98 patients, N-stage was correctly determined in 91 patients with PET/CT (93%; 95% CI, 86%-97%) and in 77 patients with MRI (79%; 95% CI, 69%-86%) (P =.001). Both imaging procedures showed a similar performance in detecting distant metastases. 2
22. Fischer B, Lassen U, Mortensen J, et al. Preoperative staging of lung cancer with combined PET-CT. N Engl J Med. 2009;361(1):32-39. Experimental-Dx 189 patients: 98 received PET/CT; 91 conventional-staging group A randomized study to evaluate the clinical effect of combined PET/CT on preoperative staging of NSCLC. After PET/CT, 38 patients were classified as having inoperable NSCLC, and after conventional staging, 18 patients were classified thus. 60 patients in the PET/CT group and 73 in the conventional-staging group underwent thoracotomy (P=0.004). Among these thoracotomies, 21 in the PET/CT group and 38 in the conventional-staging group were futile (P=0.05). The number of justified thoracotomies and survival were similar in the two groups. The use of PET/CT for preoperative staging of NSCLC reduced both the total number of thoracotomies and the number of futile thoracotomies but did not affect overall mortality. 1
23. Hellwig D, Groschel A, Graeter TP, et al. Diagnostic performance and prognostic impact of FDG-PET in suspected recurrence of surgically treated non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2006;33(1):13-21. Observational-Dx 55 patients To evaluate the diagnostic performance and prognostic impact of Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) in cases of suspected relapse of lung cancer. FDG-PET correctly identified 51 of 55 relapses and gave true negative results in 16 of 18 remissions (sensitivity, specificity, accuracy: 93%, 89%, 92%). Standardised uptake value (SUV) in recurrent tumour was higher than in benign post-therapeutic changes (10.6+/-5.1 vs 2.1+/-0.6, p<0.001). Median survival was longer for patients with lower FDG uptake in recurrent tumour (SUV<11: 18 months, SUV > or = 11: 9 months, p<0.01). Long-term survival was observed mainly after surgical re-treatment (3-year survival rate 38%), even if no difference in median survival for surgical or non-surgical re-treatment was detected (11 vs 12 months, p=0.0627). For patients subsequently treated by surgery, lower FDG uptake predicted longer median survival (SUV<11: 46 months, SUV> or = 11: 3 months, p<0.001). SUV in recurrent tumour was identified as an independent prognostic factor (p<0.05). 1
24. Birim O, Kappetein AP, Stijnen T, Bogers AJ. Meta-analysis of positron emission tomographic and computed tomographic imaging in detecting mediastinal lymph node metastases in nonsmall cell lung cancer. Ann Thorac Surg. 2005;79(1):375-382. Meta-analysis 17 studies To perform a meta-analysis to estimate the diagnostic accuracy of fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) versus computed tomographic (CT) imaging on detecting mediastinal lymph node metastases in patients with nonsmall cell lung cancer (NSCLC). No results stated in abstract. Good
25. Darling GE, Maziak DE, Inculet RI, et al. Positron emission tomography-computed tomography compared with invasive mediastinal staging in non-small cell lung cancer: results of mediastinal staging in the early lung positron emission tomography trial. J Thorac Oncol. 2011;6(8):1367-1372. Observational-Dx 149 patients To determine the accuracy of positron emission tomography (PET)-computed tomography (CT) in staging the mediastinum compared with pathological staging based on observations made during a previously reported randomized trial of conventional staging versus PET-based staging All 149 patients had mediastinal nodal staging at mediastinoscopy alone (14), thoracotomy alone (64), or both (71). The sensitivity of PET-CT was 70% (95% confidence interval [CI], 48-85%), and specificity was 94% (95% CI, 88-97%). Of 22 patients with a PET-CT interpreted as positive for mediastinal nodes, 8 did not have tumor. The positive predictive value and negative predictive value were 64% (95% CI, 43-80%) and 95% (95% CI, 90-98%), respectively. Based on PET-CT alone, eight patients would have been denied potentially curative surgery if the mediastinal abnormalities detected by PET-CT had not been evaluated with an invasive mediastinal procedure. 2
26. Booth K, Hanna GG, McGonigle N, et al. The mediastinal staging accuracy of 18F-Fluorodeoxyglycose positron emission tomography/computed tomography in non-small cell lung cancer with variable time intervals to surgery. Ulster Med J. 2013;82(2):75-81. Observational-Dx 64 patients To compare varying time frames from Positron emission tomography (PET)/computerised tomography (CT) to surgery with the accuracy of the PET/CT analysis and suggest an optimal timing of the using of PET/CT information or a “best before” time interval. Sensitivity of PET/CT scans for indentifying involved N2 lymph nodes was 39%, specificity 96% and overall accuracy 90%. For individual lymph node analysis, logistic regression demonstrated a significant linear association between PET/CT sensitivity and time from scanning to surgery (p=0.031) but not for specificity and accuracy. Those scanned <9 weeks before pathological sampling were significantly more sensitive (64% >9 weeks, 0% >/= 9 weeks, p=0.013) and more accurate (94% <9 weeks, 81% >/= 9 weeks, p=0.007). Differences in specificity were not seen (97% <9 weeks, 91% >/= 9 weeks, p=0.228). No significant difference in specificity was found at any time point. 3
27. Gomez DR, Liao KP, Swisher SG, et al. Time to treatment as a quality metric in lung cancer: Staging studies, time to treatment, and patient survival. Radiother Oncol. 2015;115(2):257-263. Review/Other-Dx 28,732 patients To determine if predictors of treatment delay after diagnosis were associated with prognosis. Median diagnosis-to-treatment interval was 27days. Receipt of positron emission tomography (PET) was associated with delays (57.4% of patients with PET delayed [n=6646/11,583] versus 22.8% of those without [n=3908/17,149]; adjusted OR=4.48, 95% CI 4.23-4.74, p<0.001). Median diagnosis-to-PET interval was 15days; PET-to-clinic, 5days; and clinic-to-treatment, 12days. Diagnosis-to-treatment intervals <35days were associated with improved survival for patients with localized disease and those with distant disease surviving 1year but not for patients with distant disease surviving <1year. 4
28. NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. Version 3.2018.  Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Review/Other-Dx N/A To provide clinical practice guidelines in non-small cell lung cancer. No results stated in abstract. 4
29. Hishida T, Yoshida J, Nishimura M, Nishiwaki Y, Nagai K. Problems in the current diagnostic standards of clinical N1 non-small cell lung cancer. Thorax. 2008;63(6):526-531. Observational-Dx 143 patients To evaluate the surgical and pathological results of patients with cN1 NSCLC to determine if there are problems in the current diagnostic standards. Patients with pN2-3 showed a significantly worse 5 year survival rate of 38% compared with patients with pN0 (68%) and pN1 (60%) (P=0.017 and 0.007, respectively). Multivariate analysis showed that adenocarcinoma histology was a significant predictor for pN2-3 disease (OR 3.312, 95% CI 1.439 to 7.784; P=0.005). The presence of N1 node separate from the main tumor on CT scans tended to predict pN2-3 disease although this did not reach statistical significance (OR 2.103, 95% CI 0.955 to 4.693; P=0.066). Pathological N2-3 disease was found in 53% of patients with adenocarcinoma with a separate N1 pattern and in only 12% of patients with non-adenocarcinoma with a continuous N1 pattern. The diagnosis of N1 status by contrast enhanced CT scans is unsatisfactory with a high rate of unexpected pN2 disease. To avoid infertile lung resection, patients with CT diagnosed N1 adenocarcinoma, especially with a separate N1 pattern on CT, should be considered for additional invasive node biopsy modalities, including mediastinoscopy. 3
30. Lee PC, Port JL, Korst RJ, Liss Y, Meherally DN, Altorki NK. Risk factors for occult mediastinal metastases in clinical stage I non-small cell lung cancer. Ann Thorac Surg. 2007;84(1):177-181. Observational-Dx 224 patients A retrospective review during a 7-year period to identify patients with potentially operable clinical stage I NSCLC screened by CT and PET scans. The overall prevalence of histologically confirmed N2 disease was 6.5% in clinical T1 patients and 8.7% in clinical T2 patients. Central tumors had a higher prevalence of N2 disease compared with peripheral tumors, 21.6% vs 2.9% (P<0.001). Larger clinical T size predicted a higher prevalence of occult N2 disease (P<0.001). All 16 patients with occult N2 metastases had adenocarcinoma as the primary tumor cell type. When the PET maximum SUV(max) of the primary tumors was analyzed, patients with occult N2 metastases had a higher median SUV(max) of the primary tumor compared with patients without N2 metastases, 6.0 g/mL vs 3.6 g/mL (P=0.017). For patients deemed at clinical stage I NSCLC by CT and PET, the prevalence of missed N2 metastases increased significantly with larger tumor size and central location. Adenocarcinoma cell type and a high PET SUV(max) of the primary tumor were other risk factors. Mediastinoscopy may have improved yield in the select subset of patients with one or more risk factor. 3
31. Boland GW, Dwamena BA, Jagtiani Sangwaiya M, et al. Characterization of adrenal masses by using FDG PET: a systematic review and meta-analysis of diagnostic test performance. [Review]. Radiology. 259(1):117-26, 2011 Apr. Meta-analysis 21 studies To perform a systematic review and meta-analysis of published data to determine the diagnostic utility of adrenal fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for distinguishing benign from malignant adrenal disease. A total of 1391 lesions (824 benign, 567 malignant) in 1217 patients from 21 eligible studies were evaluated. Qualitative (visual) analysis of 841 lesions (in 14 reports) and quantitative analyses based on standardized uptake values (SUVs) for 824 lesions (in 13 reports) and standardized uptake ratios (SURs) for 562 lesions (in eight reports) were performed. Resultant data were highly heterogeneous, with a model-based inconsistency index of 88% (95% confidence interval [CI]: 79%, 98%). Mean sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio values for differentiating between benign and malignant adrenal disease were 0.97 (95% CI: 0.93, 0.98), 0.91 (95% CI: 0.87, 0.94), 11.1 (95% CI: 7.5, 16.3), 0.04 (95% CI: 0.02, 0.08), and 294 (95% CI: 107, 805), respectively, with no significant differences in accuracy among the visual, SUV, and SUR analyses. Good
32. Bury T, Barreto A, Daenen F, Barthelemy N, Ghaye B, Rigo P. Fluorine-18 deoxyglucose positron emission tomography for the detection of bone metastases in patients with non-small cell lung cancer. Eur J Nucl Med. 1998;25(9):1244-1247. Observational-Dx 110 patients To evaluate the utility of the fluorine-18 deoxyglucose positron emission tomography (FDG PET) for the detection of bone metastasis. Among these, 21 (19% of total group) had one or several bone metastases confirmed by biopsy (n = 8) or radiographic techniques (n = 13). Radionuclide bone scanning correctly identified 54 out of 89 cases without osseous involvement and 19 out of 21 osseous involvements. On the other hand, FDG PET correctly identified the absence of osseous involvement in 87 out of 89 patients and the presence of bone metastasis in 19 out of 21 patients. Thus using PET there were two false-negative and two false-positive cases. PET and bone scanning had, respectively, an accuracy of 96% and 66% in the evaluation of osseous involvement in patients with nonsmall cell lung cancer (NSCLC). 2
33. Cheran SK, Herndon JE, 2nd, Patz EF, Jr. Comparison of whole-body FDG-PET to bone scan for detection of bone metastases in patients with a new diagnosis of lung cancer. Lung Cancer. 2004;44(3):317-325. Observational-Dx 257 patients To compare the accuracy and agreement of whole-body PET scan to bone scintigraphy for the detection of bony metastases in staging patients with newly diagnosed lung cancer. The accuracies of PET and bone scan were 94% and 85%, respectively (P<0.05), sensitivity values were 91% and 75%, and specificity values were 96% and 95%, respectively. The weighted-kappa statistic suggested moderate agreement between the two modalities KW = 0.510, 95% CI, 0.402-0.618). The use of both whole-body PET and bone scintigraphy as initial staging studies in lung cancer patients provides redundant information about the presence of bony metastases. The improvement in accuracy and sensitivity with PET suggests bone scan can be eliminated from the staging evaluation at presentation. Due to its retrospective nature, the results of this study are subject to several forms of bias including selection bias, verification bias, test review bias, and incorporation bias. A prospective trial with appropriate verification of bony metastases is suggested to confirm the results. 3
34. Qu X, Huang X, Yan W, Wu L, Dai K. A meta-analysis of (1)(8)FDG-PET-CT, (1)(8)FDG-PET, MRI and bone scintigraphy for diagnosis of bone metastases in patients with lung cancer. Eur J Radiol. 2012;81(5):1007-1015. Meta-analysis 17 studies To evaluate and compare the capability for bone metastasis assessment of [(18)F] fluoro-2-d-glucose positron emission tomography with computed tomography ((18)FDG-PET-CT), [(18)F] fluoro-2-d-glucose positron emission tomography ((18)FDG-PET), magnetic resonance imaging (MRI) and bone scintigraphy (BS) in lung cancer patients, a meta-analysis is preformed. A total of 17 articles (9 (18)FDG-PET-CT studies, 9 (18)FDG-PET studies, 6 MRI studies and 16 BS studies) that included 2940 patients who fulfilled all of the inclusion criteria were considered for inclusion in the analysis. The pooled sensitivity for the detection of bone metastasis in lung cancer using (18)FDG-PET-CT, (18)FDG-PET, MRI and BS were 0.92 (95% CI, 0.88-0.95), 0.87 (95% CI, 0.81-0.92), 0.77 (95% CI, 0.65-0.87) and 0.86 (95% CI, 0.82-0.89), respectively. The pooled specificity for the detection of bone metastasis from lung cancer using (18)FDG-PET-CT, (18)FDG-PET, MRI and BS were 0.98 (95% CI, 0.97-0.98), 0.94 (95% CI, 0.92-0.96), 0.92 (95% CI, 0.88-0.95), 0.88 (95% CI, 0.86-0.89), respectively. The pooled DORs estimates for (18)FDG-PET-CT 449.17 were significantly higher than for (18)FDG-PET (118.25, P<0.001), MRI (38.27, P<0.001) and BS (63.37, P<0.001). The pooled sensitivity of BS was not correlated with the prevalence of bone metastasis. Good
35. Song JW, Oh YM, Shim TS, Kim WS, Ryu JS, Choi CM. Efficacy comparison between (18)F-FDG PET/CT and bone scintigraphy in detecting bony metastases of non-small-cell lung cancer. Lung Cancer. 2009; 65(3):333-338. Observational-Dx 1,000 patients Retrospective study to compare the efficacies of integrated whole-body FDG-PET/CT and bone scintigraphy for the detection of bone metastases in patients with NSCLC. Bone metastases were confirmed in 105 (10.5%) patients. The respective accuracy, sensitivity, and specificity of PET/CT and bone scan in detecting bone metastases were 98.3% and 95.1% (P<0.001), 94.3% and 78.1% (P=0.001), and 98.8% and 97.4% (P=0.006). PET/CT also showed lower incidence of false positive (1.2% vs 2.9%) and false-negative results (5.7% vs 21.9%) than bone scan. Agreement between PET/CT and bone scan findings was good with calculated kappa=0.732. PET/CT was superior to bone scan in the detection of bone metastases of NSCLC with the lower incidence of false-positive as well as false-negative results. 3
36. Kagohashi K, Satoh H, Ishikawa H, Ohtsuka M, Sekizawa K. Liver metastasis at the time of initial diagnosis of lung cancer. Med Oncol. 2003;20(1):25-28. Review/Other-Dx 1,073 lung cancer patients; 62 liver metastasis To evaluate clinicopathological features associated with liver metastases from lung cancer. Of the 62 patients, 17 had sole liver metastasis, and the remaining 45 had synchronous spread to the liver and one or more other organs. In morphological liver metastasis, 26/28 SCLC patients had multiple nodules, whereas 16/34 NSCLC patients had a solitary liver nodule (P=0.0006). Liver is a possible site of extrathoracic spread of disease for some patients with lung cancer, especially with SCLC. When the histological types are squamous cell carcinoma or SCLC, it would also be considered likely that an isolated liver mass represents a metastasis even though there is no metastatic disease elsewhere. 4
37. Hustinx R, Paulus P, Jacquet N, Jerusalem G, Bury T, Rigo P. Clinical evaluation of whole-body 18F-fluorodeoxyglucose positron emission tomography in the detection of liver metastases. Ann Oncol. 1998;9(4):397-401. Observational-Dx 64 patients To evaluate the potential role of fluorodeoxyglucose positron emission tomography (FDG PET) in the detection of liver metastases. PET demonstrated a 97% sensitivity, an 88% specificity and a 92% accuracy, compared to 93%, 75% and 85%, respectively, for computed tomography (CT) (P = NS). Concordant results were obtained in 44 of 64 patients (69%: 19 TP. 25 TN). PET provided new and accurate information in 15 of 64 patients (23.4%). PET demonstrated liver metastases in 11 patients in whom conventional methods yielded negative (two cases) or doubtful (nine cases) results. Four patients free of liver involvement were correctly staged with PET, while CT/ ultrsound (US) were equivocal. PET was erroneous in five of 64 cases (7.8%, four FP, one FN). 3
38. Liu T, Xu JY, Xu W, Bai YR, Yan WL, Yang HL. Fluorine-18 deoxyglucose positron emission tomography, magnetic resonance imaging and bone scintigraphy for the diagnosis of bone metastases in patients with lung cancer: which one is the best?--a meta-analysis. Clin Oncol (R Coll Radiol). 2011;23(5):350-358. Meta-analysis 34 studies To carry out a meta-analysis to compare fluorine-18 deoxyglucose ((18)FDG) positron emission tomography (PET), magnetic resonance imaging (MRI) and bone scintigraphy imaging for the diagnosis of bone metastases in patients with lung cancer In total, 14 articles that consisted of 34 studies fulfilled all inclusion criteria. On a per-patient basis, the pooled sensitivity estimates for PET, MRI and bone scintigraphy were 91.9, 80.0 and 91.8%, respectively. The sensitivity for PET and bone scintigraphy were significantly higher than for MRI (P<0.05). There was no significant difference between PET and bone scintigraphy (P>0.05). The pooled specificity estimates for PET, MRI and bone scintigraphy were 96.8, 90.6 and 68.8%, respectively. The specificity for PET was significantly higher than for MRI and bone scintigraphy (P<0.05), and the specificity for MRI was significantly higher than for bone scintigraphy (P<0.05). The pooled DOR estimates for PET, MRI and bone scintigraphy were 365.5, 53.8 and 34.4, respectively. The DOR for PET was significantly higher than for MRI and bone scintigraphy (P<0.05). There was no significant difference between MRI and bone scintigraphy (P>0.05). The SROC curve for PET showed better diagnostic accuracy than for MRI and bone scintigraphy. The SROC curve for MRI was better than for bone scintigraphy. The *Q index estimates for PET, MRI and bone scintigraphy were 0.933, 0.903 and 0.857, respectively. The *Q index for PET and MRI were significantly higher than for bone scintigraphy (P<0.05). There was no significant difference between PET and MRI (P>0.05). On a per-lesion basis, the pooled sensitivity estimates for PET, MRI and bone scintigraphy were 95.0, 83.8 and 71.5%, respectively. The sensitivity for PET was significantly higher than for MRI and bone scintigraphy (P<0.05), and the sensitivity for MRI was significantly higher than for bone scintigraphy (P<0.05). The pooled specificity estimates for PET, MRI and bone scintigraphy were 94.6, 96.3 and 91.0%, respectively. The specificity for MRI was significantly higher than for PET and bone scintigraphy (P<0.05), and the specificity for PET was significantly higher than for bone scintigraphy (P<0.05). The pooled DOR estimates for PET, MRI and bone scintigraphy were 431.9, 158.1 and 9.0, respectively. The DOR for PET was significantly higher than for MRI and bone scintigraphy (P<0.05) and the DOR for MRI was significantly higher than for bone scintigraphy (P<0.05). The SROC curve for PET and MRI showed better diagnostic accuracy than for bone scintigraphy. There was no significant difference between PET and MRI. The *Q index estimates for PET, MRI and bone scintigraphy were 0.953, 0.962 and 0.778, respectively. The *Q index for PET and MRI were significantly higher than for bone scintigraphy (P<0.05). There was no significant difference between PET and MRI (P>0.05). Good
39. Goldstraw P, Crowley J, Chansky K, et al. 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. J Thorac Oncol. 2007; 2(8):706-714. Review/Other-Tx 67,725 cases Proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumors. Suggestions include additional cutoffs for tumor size, with tumors >7 cm moving from T2 to T3; reassigning the category given to additional pulmonary nodules in some locations; and reclassifying pleural effusion as an M descriptor. In addition, it is suggested that T2b N0 M0 cases be moved from stage IB to stage IIA, T2a N1 M0 cases from stage IIB to stage IIA, and T4 N0-1 M0 cases from stage IIIB to stage IIIA. 4
40. Hochstenbag MM, Twijnstra A, Hofman P, Wouters EF, ten Velde GP. MR-imaging of the brain of neurologic asymptomatic patients with large cell or adenocarcinoma of the lung. Does it influence prognosis and treatment? Lung Cancer. 2003;42(2):189-193. Observational-Dx 91 patients To investigate the impact of neurologic examination by the neurologist and of the Magnetic resonance imaging (MRI) of the brain on the staging of neurologic asymptomatic patients with large cell carcinoma or adenocarcinoma of the lung. Patients were followed up for at least 6 months. Evidence of metastatic brain disease was documented in 13 (14%) patients. Two of these patients were found suspective of brain metastases (BM) by the neurologist. The detection of BM resulted in upstaging of 1 (3%) patient in stage I/II, 4 (21%) patients in stage IIIA and 2 (11%) patients in IIIB. Especially for patients in stage III this upstaging is of importance as aggressive locoregional treatment can be abandoned. 3
41. Earnest Ft, Ryu JH, Miller GM, et al. Suspected non-small cell lung cancer: incidence of occult brain and skeletal metastases and effectiveness of imaging for detection--pilot study. Radiology. 1999;211(1):137-145. Observational-Dx 29 patients To estimate the incidence of occult metastases to the brain and skeleton in patients suspected of having non-small cell lung cancer (NSCLC) (stage higher than T1Nomo) with surgically resectable disease, to assess the accuracy of screening magnetic resonance (MR) imaging and radionuclide bone scanning for help in identifying occult metastases, and to determine the effectiveness of a high dose of MR contrast material. Eight (28%) patients had occult metastatic disease to the brain or skeleton. Brain metastases were identified on MR images in five of six patients. Bone metastases were identified on MR images in four of five patients and on bone scans in three of five patients. MR imaging was no more accurate than bone scanning for skeletal evaluation. A high dose of MR contrast material allowed detection of more metastases and of small lesions. 2
42. Mintz BJ, Tuhrim S, Alexander S, Yang WC, Shanzer S. Intracranial metastases in the initial staging of bronchogenic carcinoma. Chest. 1984;86(6):850-853. Review/Other-Dx 66 patients To evaluate the effectiveness of neurologic examination, EEG, and CT in the initial staging of patients with non-small cell carcinoma. 8/66 patients had evidence of intracranial metastases. Three of these had no other metastases and would otherwise have been surgical candidates. Thorough investigation for evidence of intracranial metastases is warranted at the time of initial staging. The CT proved to be more effective than clinical evaluation or EEG, alone or in combination, in detecting intracranial metastases. The CT screening of patients prior to curative resection should increase the success rate for such procedures by eliminating patients with preexisting metastases. 4
43. Davis PC, Hudgins PA, Peterman SB, Hoffman JC, Jr. Diagnosis of cerebral metastases: double-dose delayed CT vs contrast-enhanced MR imaging. AJNR Am J Neuroradiol. 1991;12(2):293-300. Review/Other-Dx 23 patients To compare double-dose delayed CT with contrast-enhanced MRI in the diagnosis of cerebral metastases. Contrast-enhanced MRI was better than double-dose delayed CT for lesion detection, anatomic localization of lesions, and differentiation of solitary vs multiple lesions. 4
44. Yokoi K, Kamiya N, Matsuguma H, et al. Detection of brain metastasis in potentially operable non-small cell lung cancer: a comparison of CT and MRI. Chest. 1999;115(3):714-719. Observational-Dx 332 patients Prospective study to compare the usefulness of MRI and CT in the detection of brain metastases during preoperative evaluation and postoperative follow-up. MRI detected brain metastases preoperatively in 6/12 patients (3.4% of the total MRI group), whereas CT detected brain metastases preoperatively in 1/11 patients (0.6% of the total CT group). MRI showed a trend toward a higher preoperative detection rate of brain metastases than CT (P=0.069). There was no significant difference between the groups in survival time. 3
45. Bruzzi JF, Komaki R, Walsh GL, et al. Imaging of non-small cell lung cancer of the superior sulcus: part 2: initial staging and assessment of resectability and therapeutic response. Radiographics. 2008;28(2):561-572. Review/Other-Dx N/A Summary of the resectability, determination of the optimal approach to disease management, and evaluation of the response to therapy of imaging. MRI is superior for evaluating tumor extension to the intervertebral neural foramina, the spinal cord, and the brachial plexus, primarily because of the higher contrast resolution and multiplanar capability available with MRI technology. Use of PET/CT enables the detection of unsuspected nodal and distant metastases. However, imaging has only limited usefulness for evaluating the response of a tumor to induction therapy and detecting local recurrence, and surgical biopsy often is necessary to verify the results of therapy. 4
46. Akata S, Kajiwara N, Park J, et al. Evaluation of chest wall invasion by lung cancer using respiratory dynamic MRI. J Med Imaging Radiat Oncol. 2008;52(1):36-39. Observational-Dx 61 patients To evaluate chest wall invasion by lung cancer using respiratory dynamic MRI. At pathological examination, the respiratory dynamic MRI findings were proved correct in all patients. Pathologically, 20 patients had chest wall invasion and their respiratory dynamic MRI was positive (sensitivity 100%). There were 7 false-positive results among the 41 patients without chest wall invasion (specificity 82.9%). Respiratory dynamic MRI may improve the accuracy of conventional CT scan or MRI in the prediction of chest wall invasion of lung cancer, especially in patients in whom the results of conventional CT scan or MRI appear equivocal in the presence of a peripheral mass abutting the chest wall surface without obvious chest wall invasion. 3
47. Seo JS, Kim YJ, Choi BW, Choe KO. Usefulness of magnetic resonance imaging for evaluation of cardiovascular invasion: evaluation of sliding motion between thoracic mass and adjacent structures on cine MR images. J Magn Reson Imaging. 2005;22(2):234-241. Observational-Dx 26 patients To determine the feasibility and usefulness of MRI for evaluating cardiovascular invasion of a thoracic mass by demonstrating the sliding motion between the mass and adjacent structures. The cine MR images showed the presence of sliding motion in 39 structures in 20 patients, which were surgically confirmed as not being invaded, and 15 structures in 6 patients with the absence of sliding motion noted as tumor invasion. The accuracy of the cine MRI was 94.4% (51/54) for evaluating cardiovascular invasion of a thoracic mass. MRI can provide additional information and improve the accuracy of preoperative staging for predicting cardiovascular invasion of a thoracic mass by evaluating the sliding motion. 3
48. Yang RM, Li L, Wei XH, et al. Differentiation of central lung cancer from atelectasis: comparison of diffusion-weighted MRI with PET/CT. PLoS One 2013;8:e60279. Observational-Dx 38 patients To assess the performance of diffusion-weighted magnetic resonance imaging (DW-MRI) for differentiation of central lung cancer from atelectasis. PET/CT and DW-MR allowed differentiation of tumor and atelectasis in all 38 cases, but T2WI did not allow differentiation in 9 cases. Comparison of conventional T2WI and DW-MRI indicated a higher contrast noise ratio of the central lung carcinoma than the atelectasis by DW-MRI. ADC maps indicated significantly lower mean ADC in the central lung carcinoma than in the atelectasis (1.83±0.58 vs. 2.90±0.26 mm(2)/s, p<0.0001). ADC values of small cell lung carcinoma were significantly greater than those from squamous cell carcinoma and adenocarcinoma (p<0.0001 for both). 2
49. Koyama H, Ohno Y, Seki S, et al. Magnetic resonance imaging for lung cancer. J Thorac Imaging. 2013;28(3):138-150. Review/Other-Dx N/A To review Magnetic resonance imaging for lung cancer. No results stated in abstract. 4
50. Carter BW, Glisson BS, Truong MT, Erasmus JJ. Small cell lung carcinoma: staging, imaging, and treatment considerations. Radiographics. 2014;34(6):1707-1721. Review/Other-Dx N/A To review the staging, imaging, and treatment considerations of small cell lung carcinoma. No results stated in abstract. 4
51. Jett JR, Schild SE, Kesler KA, Kalemkerian GP. Treatment of small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e400S-e419S. Review/Other-Dx 9 studies To revise the evidence-based guidelines on staging and best available treatment options. The staging classification should include both the old Veterans Administration staging classification of limited stage (LS) and extensive stage (ES), as well as the new seventh edition American Joint Committee on Cancer/International Union Against Cancer staging by TNM. The use of PET scanning is likely to improve the accuracy of staging. Surgery is indicated for carefully selected stage I SCLC. LS disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle 1 or 2 of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. ES disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in those individuals with both LS and ES disease who achieve a complete or partial response to initial therapy. To date, no molecularly targeted therapy agent has demonstrated proven efficacy against SCLC. 4
52. Kalemkerian GP, Gadgeel SM. Modern staging of small cell lung cancer. J Natl Compr Canc Netw. 2013;11(1):99-104. Review/Other-Dx N/A To review the Modern staging of small cell lung cancer. No results stated in abstract. 4
53. NCCN Clinical Practice Guidelines in Oncology. Small Cell Lung Cancer. Version 2.2018.  Available at: https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Review/Other-Dx N/A To provide Clinical Practice Guidelines in Oncology. No results stated in abstract. 4
54. NCCN Clinical Practice Guidelines in Oncology. Small Cell Lung Cancer. NCCN Evidence Blocks™. Version 2.2018.  Available at: https://www.nccn.org/professionals/physician_gls/pdf/sclc_blocks.pdf. Review/Other-Dx N/A To provide Clinical Practice Guidelines in Oncology. No results stated in abstract. 4
55. Mirvis SE, Whitley NO, Aisner J, Moody M, Whitacre M, Whitley JE. Abdominal CT in the staging of small-cell carcinoma of the lung: incidence of metastases and effect on prognosis. AJR. 1987;148(5):845-847. Observational-Dx 72 patients Retrospective study to assess the role of abdominal CT in staging. Statistical analysis of patients with extensive disease revealed a significant increase in complete therapeutic response (P=.0054) and in the length of survival (P=.001) among those who had extensive disease without abdominal metastases as compared with those who had abdominal metastases on their initial abdominal CT examination. The development of new or recurrent abdominal metastases in general or in specific organs on follow-up scans obtained in 35 patients did not significantly decrease their survival time as compared with that of patients without such metastases. The findings suggest that CT of the abdomen is beneficial in the initial staging of patients with SCLC and provides prognostic information concerning response to therapy and length of survival. 3
56. Arslan N, Tuncel M, Kuzhan O, et al. Evaluation of outcome prediction and disease extension by quantitative 2-deoxy-2-[18F] fluoro-D-glucose with positron emission tomography in patients with small cell lung cancer. Ann Nucl Med. 2011;25(6):406-413. Observational-Dx 25 patients To determine whether 2-deoxy-2-[18F] fluoro-D: -glucose with positron emission tomography (FDG-PET) imaging and quantitative PET parameters can predict outcome and differentiate patients with limited disease (LD) from extensive disease (ED) in patients with small cell lung cancer (SCLC). By conventional methods 14 of 25 (56%) patients were reported to have LD and 11 of 25 (44%) had ED. FDG-PET scan upstaged 9 out of 25 (36%) and downstaged 2 out of 25 (%8) patients. Among the quantitative PET parameters, total lesion glycolysis (TLG) were the only PET parameters that differentiated between Group A and Group B patients. FDG-PET staging (p = 0.019) could predict significant survival difference between stages on contrary to conventional staging (p = 0.055). Moreover, TLG [SUV(max) > %50] was the only quantitative PET parameter that could predict survival (p = 0.027). 3
57. Azad A, Chionh F, Scott AM, et al. High impact of 18F-FDG-PET on management and prognostic stratification of newly diagnosed small cell lung cancer. Mol Imaging Biol. 2010;12(4):443-451. Observational-Dx 46 patients To the impact on stage classification and management, in this study, we sought to evaluate the association between stage classification with Positron-Emission Tomography (PET) and prognosis in newly diagnosed small cell lung cancer (SCLC). PET altered stage classification in 12 of 46 (26%) patients. PET altered treatment modality in nine patients, and the target mediastinal radiation field in another three patients. Therefore, PET altered management in 12 of 46 (26%) patients. Patients with limited disease (LD) on pre-PET staging had significantly longer overall survival (OS) than those upstaged to extensive disease (Extensive disease (ED); median 18.6 months versus 5.7 months; log-rank p < 0.0001). In patients with ED on pre-PET staging, those downstaged to LD by PET had significantly longer OS than those with ED on PET (median 10.9 months versus 5.9 months; log-rank p = 0.037). 3
58. Blum R, MacManus MP, Rischin D, Michael M, Ball D, Hicks RJ. Impact of positron emission tomography on the management of patients with small-cell lung cancer: preliminary experience. Am J Clin Oncol. 2004;27(2):164-171. Observational-Dx 15 patients To review the Impact of positron emission tomography (PET) on the management of patients with small-cell lung cancer. Of 15 patients who had PET for staging, 5 (33%) were upstaged from limited to extensive disease and treated without thoracic radiotherapy. Twenty-five patients underwent 32 restaging PET scans, of which 20 (63%) were discordant with conventional imaging. In 8 cases PET showed more extensive disease than conventional imaging, and in 12 cases PET-apparent disease appeared less extensive. In 13 patients, 14 untreated discordant lesions were evaluable; PET was confirmed accurate in 11 (79%) sites by last follow-up. Restaging PET influenced management in 13 cases (52%). PET-complete remission (CR) conferred longer median time to progression (13.7 months) than no CR (9.7 months). 3
59. Bradley JD, Dehdashti F, Mintun MA, Govindan R, Trinkaus K, Siegel BA. Positron emission tomography in limited-stage small-cell lung cancer: a prospective study. J Clin Oncol. 2004;22(16):3248-3254. Observational-Dx 24 patients To determine how often FDG-PET detects extensive-stage SCLC in patients considered to have limited-stage disease based on conventional staging procedures, and to determine the impact of PET on treatment planning for presumed limited-stage SCLC. FDG-PET demonstrated findings consistent with extensive-stage SCLC in 3/24 patients. FDG-PET correctly upstaged two (8.3%) of 24 patients to extensive-stage disease (95% CI, 1.03% to 27.0%). PET correctly identified tumor in each SCLC mass (primary or nodal) that was suspected on CT, thus giving a lesion-based sensitivity relative to CT of 100%. PET identified unsuspected regional nodal metastasis in 6 (25%) of 24 patients, and the radiation therapy plan was significantly altered to include the PET-positive/CT-negative nodes within the high-dose region in each of these patients. FDG-PET has high sensitivity for SCLC and appears to be of value for initial staging and treatment planning of patients with presumed limited-stage disease. 2
60. Brink I, Schumacher T, Mix M, et al. Impact of [18F]FDG-PET on the primary staging of small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2004;31(12):1614-1620. Observational-Dx 120 consecutive patients To evaluate the impact of FDG-PET on the primary staging of patients with SCLC. Sensitivity of FDG-PET was significantly superior to that of CT in the detection of extrathoracic lymph node involvement (100% vs 70%, specificity 98% vs 94%) and distant metastases except to the brain (98% vs 83%, specificity 92% vs 79%). However, FDG-PET was significantly less sensitive than cranial MRI/CT in the detection of brain metastases (46% vs 100%, specificity 97% vs 100%). The introduction of FDG-PET in the diagnostic evaluation of SCLC will improve the staging results and affect patient management, and may reduce the number of tests and invasive procedures. 2
61. Hochstenbag MM, Twijnstra A, Wilmink JT, Wouters EF, ten Velde GP. Asymptomatic brain metastases (BM) in small cell lung cancer (SCLC): MR-imaging is useful at initial diagnosis. J Neurooncol. 2000;48(3):243-248. Observational-Dx 112 patients To evaluate the usefulness of Magnetic Resonance (MR)-imaging in the detection of asymptomatic brain metastases (BM) at the initial diagnosis in patients with small cell lung cancer (SCLC) and studied the follow-up of these patients. In 112 patients with normal neurological findings, MR-imaging of the brain demonstrated BM in 17 patients (15%). Six of these 17 patients were therefore upgraded to extensive disease (ED). Two of these 17 patients died during chemotherapy because of progressive disease and 3 patients became neurologic symptomatic with progressive disease on MR-imaging of the brain. After completion of chemotherapy a repeated MR-imaging of the brain in the remaining 12 patients showed 1 complete remission, 4 partial remission and 7 progressive disease of the BM. 2
62. Adjei AA, Marks RS, Bonner JA. Current guidelines for the management of small cell lung cancer. Mayo Clin Proc. 1999;74(8):809-816. Review/Other-Tx N/A Guidelines for the management of SCLC. Combined modality approaches, such as radiotherapy administered concomitantly with the initiation of chemotherapy, induction chemotherapy followed by radiotherapy administered during the subsequent courses of chemotherapy, sequential chemotherapy and radiotherapy, and courses of radiotherapy split between cycles of chemotherapy, are important for improving survival in patients with SCLC. 4
63. Conen K, Hagmann R, Hess V, Zippelius A, Rothschild SI. Incidence and predictors of Bone Metastases (BM) and Skeletal-Related Events (SREs) in Small Cell Lung Cancer (SCLC): A Swiss patient cohort. J Cancer. 2016;7(14):2110-2116. Observational-Dx 92 patients To review the Incidence and predictors of Bone Metastases (BM) and Skeletal-Related Events (SREs) in Small Cell Lung Cancer (SCLC) We identified 92 consecutive patients with SCLC diagnosed between 2000 and 2010 at our institution. Overall, 36.9% presented with BM at first diagnosis. Median time to BM from first diagnosis was 14.8 months (range) in limited disease (LD) and 0.9 months (range) in extensive disease (ED). The overall incidence of SRE was 18.4%. Only 19.6% of patients with BM were initially treated with bisphosphonates. 3
64. Johnson DH, Hainsworth JD, Greco FA. Pancoast's syndrome and small cell lung cancer. Chest. 1982;82(5):602-606. Review/Other-Dx N/A To review Pancoast's syndrome and small cell lung cancer. No results stated in abstract. 4
65. American College of Radiology. ACR Appropriateness Criteria® Radiation Dose Assessment Introduction. Available at: https://www.acr.org/-/media/ACR/Files/Appropriateness-Criteria/RadiationDoseAssessmentIntro.pdf. Review/Other-Dx N/A To provide guidelines on exposure of patients to ionizing radiation. No abstract available. 4