Retrospective review of lung cancers diagnosed in annual rounds of CT screening.

Cardiopulmonar y Imaging • Original Research Xu et al. CT Lung Cancer Screening

Downloaded from www.ajronline.org by Washington State Univ. on 11/26/14 from IP address 69.166.47.134. Copyright ARRS. For personal use only; all rights reserved

Cardiopulmonary Imaging Original Research

Retrospective Review of Lung Cancers Diagnosed in Annual Rounds of CT Screening Dong Ming Xu1 Rowena Yip James P. Smith David F. Yankelevitz Claudia I. Henschke for the I-ELCAP Investigators Xu DM, Yip R, Smith JP, Yankelevitz DF, Henschke CI

Keywords: CT screening, early detection, lung cancer, lung cancer growth, small lung cancers DOI:10.2214/AJR.13.12115 Received October 22, 2013; accepted after revision March 16, 2014. Funded in part by the Flight Attendants Medical Research Institute. I-ELCAP pooled database supported in part by National Institutes of Health R01-CA-63393l and R01CA-78905; Department of Energy DE-FG02-96SF21260; City of New York, Department of Health and Mental Hygiene; New York State Office of Science, Technology and Academic Research (NYSTAR); American Cancer Society; Israel Cancer Association; Starr Foundation; New York Community Trust; Rogers Family Fund; Foundation for Lung Cancer: Early Detection, Prevention, and Treatment (primary source was an unrestricted gift in 2000–2003 from the Vector Group, the parent company of Liggett Tobacco); Dorothy R. Cohen Foundation, Research Foundation of Clinic Hirslanden; Yad-Hanadiv Foundation; Jacob and Malka Goldfarb Charitable Foundation; Auen/ Berger Foundation; Princess Margaret Foundation; Berger Foundation; Mills Peninsula Hospital Foundation, Tenet Healthcare Foundation; Ernest E. Stempel Foundation; Academic Medical Development Corporation; Empire Blue Cross and Blue Shield; Eastman-Kodak Corporation; GE Healthcare Corporation; Weill Medical College of Cornell University; Cornell University; New York Presbyterian Hospital; Clinic Hirslanden; Swedish Hospital; Christiana Care Helen F. Graham Cancer Center; Holy Cross Hospital; Eisenhower Hospital; Jackson Memorial Hospital Health System; Evanston Northwestern Healthcare. 1

All authors: Department of Radiology, Mount Sinai School of Medicine, One Gustave L. Levy Pl, Box 1234, New York, NY 10029. Address correspondence to C. I. Henschke ([email protected]).

AJR 2014; 203:965–972 0361–803X/14/2035–965 © American Roentgen Ray Society

OBJECTIVE. The purpose of this study was to review the records of patients with diagnoses of lung cancer in annual repeat rounds of CT screening in the International Early Lung Cancer Action Program to determine whether the cancer could have been identified in the previous round of screening. MATERIALS AND METHODS. Three radiologists reviewed the scans of 104 lung cancer patients and assigned the findings to one of three categories: 1, cancer was not visible at previous CT screening; 2, cancer was visible at previous CT screening but not identified; 3, abnormality was identified at previous CT screening but not classified as malignant. Nodule size, nodule consistency, cell type, and stage at the previous screening and when identified for further workup for each of the three categories were tabulated. RESULTS. Twenty-four (23%) patients had category 1 findings; 56 (54%) category 2; and 24 (23%) category 3. When diagnosed, seven (29%) category 1, 10 (18%) category 2, and four (17%) category three cancers had progressed beyond stage I. All cancers seen in retrospect were in clinical stage I at the previous screening. Category 1 cancers, compared with categories 2 and 3, had faster growth rates, were less frequently adenocarcinomas (29% vs 54% and 67%, p = 0.01), and were more often small cell carcinomas (29% vs 14% and 12%, p = 0.12). CONCLUSION. Lung cancers found on annual repeat screenings were frequently identified in the previous round of screening, suggesting that review of the varied appearance and incorporation of advanced image display may be useful for earlier detection.

P

rimary carcinoma of the lung that is not mentioned in a CT report but can be identified at retrospective review of previous scans once the cancer is diagnosed is an important diagnostic concern, particularly in the context of a screening program. Early identification of a malignant nodule is important because the cancer is typically more curable when it is smaller and in stage I [1, 2]. Possible reasons for not identifying a malignant nodule are therefore important concerns of radiologists and have been extensively studied, first on chest radiographs [3–9] and then on CT scans [10–13]. Understanding the reasons for not identifying a malignant nodule in the context of screening will help in finding lung cancer earlier. To investigate the frequency of and possible reasons for not identifying a malignant nodule earlier, we reviewed the CT images of patients with lung cancer diagnosed in annual rounds of screening in the International Early Lung Cancer Action Program (I-ELCAP)

to determine how often the lung cancer could have been identified in the previous round of screening and the possible reasons for not reporting a malignant nodule earlier. Materials and Methods I-ELCAP is a consortium of institutions throughout the world that have agreed to follow a common protocol for CT screening for lung cancer [14]. Consent had been obtained from all participants in I-ELCAP according to HIPAA-compliant protocols, and the study was approved by the institutional review boards of the collaborating institutions. The protocol for CT screening in annual rounds is different from the protocol for the first, baseline round. For annual repeat rounds of screening, the definition of a positive result is any newly seen solid or partially solid nodule 3 mm in diameter or larger. If all newly seen solid or partially solid nodules are smaller than 3 mm or there are nonsolid nodules of any size, the result is considered semipositive, and the recommendation to the patient is to return for further evaluation in 12 months.

AJR:203, November 2014 965


Xu et al. Fig. 1—61-year-old woman with cancer not visible at previous CT screening (category 1). A, CT image shows no nodule in left lower lobe. B, CT image 11 months after A shows new nodule measuring 22.0 × 19.0 mm. Diagnosis was large cell carcinoma (stage I).

A

B

The recommendations for workup of a positive result of annual repeat screening are based on nodule diameter. If the result is positive and the largest nodule is larger than 3.0 but smaller than 5.0 mm in diameter, CT is to be performed 6 months later. If no growth is seen in any of the nodules, the recommendation is to return for annual repeat screening. If at least one of the noncalcified nodules is 5.0 mm in diameter or larger, an immediate 2-week course of broad-spectrum antibiotics is given and followed by CT 1 month later. If the nodules have grown, biopsy or PET is performed. If the biopsy or PET result is indeterminate or negative, CT is performed 3 months later. For all those for whom the workup does not result in a diagnosis of lung cancer, repeat CT 12 months after the previous annual repeat CT examination is performed.

From the I-ELCAP database of 41,846 annual repeat screenings for 1993–2009, we identified the records of 111 patients who underwent annual repeat screening (time T N) that resulted in workup and ultimately in the diagnosis of a first primary lung cancer and reviewed the previous screening CT scans, which has been obtained 7–18 months earlier (time TN – 1). For seven patients, either TN – 1 or T N scans were available because imaging had been performed outside the participating institutions. This report thus focuses on the 104 patients whose CT scans at both time points were available. Of the 104 patients, seven received the diagnosis before 2000, 54 in 2000–2006, and 43 in 2007–2009. Before 2000, CT scans were obtained at 10.0-mm slice thickness overlapping at 4.0-mm intervals. If nodules were found, another low-dose

CT acquisition at a slice thickness of 1.25 mm or less was performed. After 1999, MDCT scanners were used with a slice thickness of 2.5 mm; by 2001, the slice thickness had decreased to 1.25 mm or less. The clinical stage of the cancer, its location, consistency (solid, subsolid), and size were documented at the annual CT screenings for the 104 patients at times T N and T N – 1. Nodule size was defined as the average of the length and width of the nodule on the CT image containing the largest cross-sectional area of the nodule. The location was documented according to the lobe containing the cancer and whether it was in the lung periphery, that is, in the outer one third of the lung; otherwise it was considered central. Consistency of the nodule was classified as solid or subsolid, the

A

B

C

Fig. 2—Category 2 CT images. A, 74-year-old man with visible but unidentified 2.9-mm nodule (arrow) in left lower lobe. B, CT image 12 months after A shows nodule diameter has increased to 14.6 mm. Diagnosis was small cell carcinoma (stage I). C, 57-year-old man with visible but unidentified 6.3-mm nodule (arrow) in left lower lobe similar in size and shape to surrounding blood vessels. (Fig. 2 continues on next page)

966

AJR:203, November 2014


CT Lung Cancer Screening

D

E

F Fig. 2 (continued)—Category 2 CT images. D, CT image obtained 12 months after C shows substantial increase in diameter to 56 mm. Diagnosis was small cell carcinoma with N1 lymph node metastasis (stage II). E, 62-year-old woman with visible but unidentified nodule (arrow) 5.6 mm in diameter that was initially similar size and shape to surrounding blood vessels. F, CT image obtained 12 months after E shows nodule diameter (arrow) has increased to 11 mm. Diagnosis was adenocarcinoma (stage I). G, 66-year-old man with 2.5 mm slice thickness CT images shows visible but unidentified right lower lobe solid nodule measuring 7.8 mm in diameter. H, CT image obtained 13 months after G shows slight increase in diameter (8.8 mm). Diagnosis was adenocarcinoma (stage I).

G

H

latter including partially solid and nonsolid subtypes. The cell type at the time of diagnosis after the screening (T N) was also documented. Three radiologists reviewed the CT images of each patient at TN – 1 and TN with the corresponding axial images displayed side by side (Figs. 1–3) to develop a consensus opinion on whether the malignant nodule identified at TN had been identifiable at TN – 1. Each patient was assigned to one of three mutually exclusive categories based on review of the CT scans at TN – 1. Category 1 indicated the nodule was not identified at TN – 1, even though the location of the cancer was known and the CT images were available at both TN – 1 and TN. Category 2 indicated the nodule was not reported at TN – 1 but was identified on review of the images from the previous screening. Category 3 indicated the nodule was reported at TN – 1 but was not recognized as a potentially malignant lesion but instead was clas-

sified as a nonmalignant finding, such as fibrosis, apical scarring, bulla, or pleural thickening. Category 2 was further subclassified as to possible reasons for missing a nodule at the previous screening (T N – 1). Each patient was assigned to one of the following three mutually exclusive groups based on nodule diameter at T N – 1: diameter less than 3 mm, diameter 3 mm or larger but not greater than the cross-sectional diameter of the surrounding blood vessels, diameter 3 mm or larger and larger than the cross-sectional diameter of the surrounding blood vessels. The diameter of 3 mm was chosen because it has been generally recognized as the limit of detectability on CT scans [10, 11]. All statistical analyses were performed with SAS software (version 9.2, SAS Institute). Comparisons were made between category 1 patients and category 2 and 3 patients and separately be-

tween category 2 and 3 patients. Because of the small sample size, the Fisher exact test was used for analysis of stage, nodule consistency, and cell type. The Kruskal-Wallis test was used for assessment of nodule diameter differences.

Results The consensus of the three radiologists was that 24 (23%) of the 104 patients had a category 1 finding because no nodule was identified on the earlier CT scan at TN – 1, even after side-by-side review of the CT images obtained at both TN – 1 and TN (Fig. 1). Another 56 (54%) patients had a category 2 finding because no nodule was reported at TN – 1, but review of the images obtained at TN – 1 and TN revealed that the nodule could have been identified at the previous screening (Fig. 2). The other 24 (23%) patients had



Xu et al.

A

B

C

E

968

D

F

Fig. 3—Category 3 CT images. A, 75-year-old man with area (arrow) interpreted as fibrotic changes in left upper lobe. B, CT image obtained 9 months after A shows increase in diameter of lesion. Diagnosis was squamous cell carcinoma with N2 lymph nodes (stage IIIA). C, 61-year-old woman with finding interpreted as linear scarring in right lung apex. D, CT image obtained 13 months after C shows increase in diameter of lesion. Diagnosis was adenocarcinoma (stage I). E, 72-year-old woman with finding of isolated cystic airspace in left lower lobe with irregular wall thickening. F, CT image obtained 12 months after E shows further thickening of wall. Further workup led to diagnosis of adenocarcinoma (stage I).


CT Lung Cancer Screening TABLE 1: Distribution of 104 Patients by Category


Category

p

1, Not Seen in Retrospect (n = 24)

2, Seen in Retrospect (n = 56)

3, Seen but Not as a Nodule (n = 24)

1 vs 2 and 3

2 vs 3

I

17 (71)

46 (82)

20 (83)

0.25a

1.00a

II or greater

7 (29)

10 (18)

4 (17)

Average

14.3

11.5

12.3

0.81b

0.40b

SD

13.5

9.6

8.0

22 (92)

45 (80)

24 (100)

0.73a

0.03a

2 (8)

11 (20)

0 (0)

7 (29)

30 (54)

16 (67)

0.01

0.28

4 (17)

0.78a

1.00a 1.00a 0.42a

Characteristic Annual repeat screening (TN) Stage

Diameter (mm)

Consistency Solid Subsolid Cell type Adenocarcinoma Squamous cell

5 (21)

11 (20)

Small cell

7 (29)

8 (14)

3 (12)

0.12a

Other

5 (21)

7 (12)

1 (4)

0.17a

56 (100)

24 (100)

Average

4.9

5.8

SD

2.6

2.8

Solid

44 (79)

24 (100)

Subsolid

12 (21)

0 (0)

Previous screening (TN – 1) Stage I Diameter (mm) 0.10b

Consistency (TN – 1) 0.51a

0.01a

Note—Except for diameter, values are numbers of patients with percentages in parentheses. aFischer exact test. bKruskal-Wallis test.

a category 3 finding because the CT abnormality was reported at TN – 1 but was identified as nonmalignant (Fig. 3). At TN, 83 (80%) of the 104 patients had clinical stage I disease, and 21 (20%) had disease that had progressed beyond stage I (four, stage II; 13, stage IIIA; three, stage IIIB; one, stage IV). In all of these patients, the manifestation of higher-stage disease was a solid nodule. For the 104 patients, the distribution by stage, nodule diameter, consistency, and cell type on CT scans at TN just before diagnosis are shown in Table 1. The frequency of stage I disease at TN was lowest for category 1 (17/24 [71%]) and higher for category 2 (46/56 [82%]) and category 3 (20/24 [83%]). These values were not significantly different, either in comparisons of category 1 with categories 2 and 3 combined (p = 0.25) or of category 2 with category 3 (p = 1.00). The average nodule diameters for category 1 ver-

sus 2 and 3 (p = 0.81) and category 2 versus 3 (p = 0.40) were also not significantly different. Nodule consistency, although not significantly different for category 1 versus 2 and 3 (p = 0.73), was significantly different for category 2 versus 3 because 20% of the nodules in category 2 were subsolid, whereas there were no subsolid nodules in category 3 (p = 0.03). Category 1 patients had a significantly lower proportion of adenocarcinomas than category 2 and 3 patients (29% vs 54% and 67%; p = 0.01) and a higher proportion of small cell carcinoma (29% vs 14% and 12%; p = 0.12). Table 1 also shows the clinical stage, nodule diameter, and consistency at the previous CT screening (T N – 1). All patients in whom the nodule was identified at that earlier time (category 2 and 3) had clinical stage I disease at that earlier time. The average diameters of the nodules were 4.9 mm in category

2 and 5.8 mm in category 3. By TN, the nodules in categories 2 and 3 had grown, and the average diameters were 11.5 mm in category 2 and 12.3 mm in category 3. The nodules in category 1, however, had not been visible at the earlier time. By T N, however, the average nodule diameter was 14.3 mm. Assuming that all nodules in category 1 were 2 mm in diameter or smaller at T N – 1, there was a significant difference (p < 0.0001) in the average nodule diameter for category 1 versus 2 and 3 combined at T N – 1. The growth rate of nodules in category 1 was clearly faster than that in category 2 or 3. It is not surprising that a higher proportion of category 1 than category 2 and 3 disease progressed beyond stage I. As for nodule consistency, it was essentially the same at T N – 1 and T N. Table 2 focuses on the 56 category 2 patients in whom a malignant nodule was missed at TN – 1. The nodule was in the out-



Xu et al. er third of the lung (peripheral location) in 36 (64%) of these patients. The nodule diameter was less than 3 mm in 17 patients (Fig. 2A), and 15 of the 17 (88%) still had stage I disease at the next screening (time TN). Had these nodules been identified in the previous screening, the patient would have been classified as having a semipositive result and been referred for the next annual repeat screening [14]. For another 21 patients, the nodule was larger than 3 mm in diameter but not larger than the cross-sectional sizes of surrounding blood vessels (Figs. 2C and 2E). Fourteen of these 21 patients (67%) still had stage I disease at TN. Seventeen of the 18 patients (94%) with a nodule diameter larger than 3 mm and larger than the crosssectional size of surrounding blood vessels (Fig. 2G) still had stage I disease at TN. Nine of these 18 patients had a subsolid nodule, and all still had stage I disease at TN. All of these nodules could be seen on CT images obtained at the baseline screening. Eight of the nine patients (89%) with solid nodules still had stage I disease at TN. Discussion This report focused on lung cancers identified in annual rounds of repeat screening because such cancers typically have faster growth rates and are more aggressive than those identified in the baseline round [15– 17]. Because screening is a repetitive process, identifying and diagnosing these cancers as early as possible ultimately determines the benefit of screening itself. Among the 104 patients in this report, 80 (77%) could have had the cancer identified at the previous screening given the images of the cancer 1 year later. All 80 patients had clinical stage I disease on review of the previous screening images, but by the time the cancer was first identified at the next annual screening, it had progressed beyond stage I in 14 patients (18%). The cancers in these 80 patients grew from an average diameter of 5.2 mm to an average diameter of 11.8 mm, equivalent to a volume doubling time of 103 days. In comparison, among the 24 patients with a nodule that could not be identified at the previous screening (assuming a nodule size of 2 mm in the previous screening), the cancer grew to an average diameter of 14.3 mm, which corresponds to a volume doubling time of 43 days or faster. Although the stage, nodule consistency, and average nodule diameter of the cancers in category 1 versus categories 2 and 3 were not significantly different at the time of

970

TABLE 2: Distribution of Nodule Characteristics in Category 2 Diameter of Nodules Not Identified at Time TN – 1

Total

< 3 mm

Same as Surrounding Blood Vessels

No.

56

17

21

18

Solid

45

15

21

9

Characteristic

Peripheral Beyond stage I at diagnosis

Larger Than Surrounding Blood Vessels

36

12

10

14

10 (18)

2 (12)

7 (33)

1 (6)

Note—Category 2 is nodules not reported at the previous screening (time T N – 1) but seen in retrospective review. Values are numbers of nodules; values in parentheses are percentages.

diagnosis, the category 1 cancers clearly had faster growth rates, explaining the higher proportion that progressed beyond stage I. It is well known that there are cancers so aggressive that they have progressed to the advanced stage when they become visible on CT scans, as has been found in other screening studies [18–21]. It should be noted, however, that all of the patients in those studies had cancers that were still smaller than those typically found in usual care in the absence of screening, and thus overall they still had a better cure rate [22–24]. Among the 56 category 2 patients, 17 had nodules that were smaller than 3 mm in diameter, and thus even if the nodule had been identified in the previous year, these patients would not have been referred for further workup because the nodules were smaller than the minimum threshold of 3 mm defined as a positive result [14]. Only 2 of these 17 patients (12%), both with small cell carcinomas, had disease progression beyond stage I by the following year. Naidich and colleagues [10] found that nodules smaller than 3 mm are rarely identified. This finding was also summarized later by Gurney [11], who in a review of missed lung cancers considered 3 mm the detectability threshold. These findings are in accord with our definition of a positive result at annual repeat screening. Another 21 patients had nodules larger than 3 mm that were similar in size to the adjacent blood vessels. In seven (33%) of these patients, disease had progressed beyond stage I. For these patients, earlier detection would have been useful. This finding suggests that use of computer-assisted diagnosis, which is particularly useful for separating nodules from blood vessels, would have led to even earlier diagnosis. Perhaps in the future such visualization techniques will become an integral part of the reading process. On a more immediate basis, addi-

tional imaging in maximum intensity projection, which is not routinely used in screening, may facilitate discrimination between blood vessels and nodules because the images show a longer portion of the vessel than do conventional images [25–27]. In 9 of the 18 patients with missed nodules larger than the surrounding blood vessels, the nodules had a subsolid consistency, and none had progressed beyond stage I. Twenty-four (23%) patients had category 3 findings. Although the nodules were recognized, they were considered to represent benign rather than malignant findings. This may be partly due to lack of experience in identifying findings suspicious for small lung cancers or identifying small cancer with an unusual appearance. In this study, these nodules were misclassified as fibrosis, scarring (Figs. 3A and 3C), and a simple bulla (Fig. 3E) until growth was seen. However, in the context of screening, such benign findings are frequently identified, particularly in older individuals, and are rarely malignant. Distinguishing features such as convex borders and marked asymmetry of apical scarring (Fig. 3C) should alert the radiologist to recommend short-term follow-up. Similarly, the presence of a small cystic airspace with irregularly thickened walls deserves an alert (Fig. 3E), as has been previously reported [28]. Other unusual appearances of early lung cancer will most likely be identified as experience in screening accumulates. This study was limited by the use of consensus of three radiologists in assigning a reason the cancer had not been identified 1 year earlier. Each of the three radiologists, however, had at least 10 years of experience in reading screening CT scans. In addition, the main goal was to broadly place these cases in a limited number of mutually exclusive categories in an attempt to better understand the possible reasons for failing to identify



CT Lung Cancer Screening cancer earlier and to consider ways of improving the screening protocol. The findings of this report confirm the aggressive nature of lung cancers identified in annual repeat rounds of screening that are different from those identified in the baseline round [15–17]. These findings also suggest caution and the need for further research before the interval between repeat screenings is increased to more than 12 months for individuals at high risk of lung cancer. The results also provide an impetus for the routine use of additional imaging display methods and further development of advanced image-processing techniques. We believe these cases have educational value for the imaging community and are working to provide a subset of them in a public database. We hope that other large screening programs will contribute to such databases. Acknowledgments The I-ELCAP locations and investigators are the Mount Sinai School of Medicine, New York, Claudia I. Henschke (principal investigator), David F. Yankelevitz; Raja Flores, Rowena Yip, Ali Farooqi, Dongming Xu, David S. Mendelson; Weill Cornell Medical College, New York, Dorothy I. McCauley, Mildred Chen, Daniel M. Libby, James P. Smith, Mark Pasmantier; Cornell University, A. P. Reeves, A. Biancardi; Center for the Biology of Natural Systems, City University of New York at Queens College, Steven Markowitz, Albert Miller; Azumi General Hospital, Nagano, Japan, Shusuke Sone, Takaomi Hanaoka; University of Toronto, Princess Margaret Hospital, Heidi Roberts, Demetris Patsios; Clinica Universitaria de Navarra, Pamplona, Spain, Javier Zulueta, Maria D. Lozano, Juan de Torres; Christiana Care, Helen F. Graham Cancer Center, Newark, Delaware; Thomas Bauer; National Cancer Institute, Regina Elena, Rome, Italy, Salvatore Giunta; Lungen Zentrum Hirslanden, Zurich, Switzerland, Karl Klingler; Swedish Medical Center, Seattle, Ralph Aye; Columbia University Medical Center, New York, John H. M. Austin, Belinda M. D’Souza, Gregory D. N. Pearson; Hadassah Medical Organization, Jerusalem, Dorith Shaham; St. Agnes Cancer Center, Baltimore, Enser Cole; New York University Medical Center, David Naidich, Georgeann McGuinness; Holy Cross Hospital Cancer Institute, Silver Spring, Maryland, Cheryl Aylesworth; State University of New York at Stony Brook, Matthew Rifkin; Maimonides Medical Center, Brooklyn, New York, Samuel

Kopel; Roswell Park Cancer Institute, Buffalo, Donald Klippenstein, Peter Loud, Alan Litwin; State University of New York, Upstate Medical Center, Syracuse, Leslie J. Kohman, Ernest M. Scalzetti; Dorothy E. Schneider Cancer Center, Mills-Peninsula Health Services, San Mateo, California, Barry Sheppard; ProHealth Care Regional Cancer Center, Waukesha & Oconomowoc Memorial Hospitals, Wisconsin, M. Kristin Thorsen, Richard Hansen; North Shore-Long Island Jewish Health System, New Hyde Park, New York, Arfa Khan, Rakesh Shah; Jackson Memorial Hospital, University of Miami, Richard Thurer, Tammy Baxter; Eisenhower Lucy Curci Cancer Center, Rancho Mirage, California, Davood Vafai; 5th Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China, Xueguo Liu; South Nassau Communities Hospital, New York, Shahriyour Andaz; Fundacion Instituto Valenciano de Oncologia, Valencia, Spain, Jose Cervera Deval; Georgia Institute for Lung Cancer Research, Atlanta, Michael V. Smith; Nebraska Methodist Hospital, Omaha, Patrick Meyers; Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Diane Yeh; St. Joseph Health Center, St. Charles, Missouri, Dan Luedke; Memorial Sloan- Kettering Cancer Center, New York, Robert T. Heelan, Michelle S. Ginsberg; New York Medical College, Valhalla, Terence A. S. Matalon; Mount Sinai Comprehensive Cancer Center, Miami Beach, Shari-Lynn Odzer; Wellstar Health System, Marietta, Georgia, William Mayfield; City of Hope National Medical Center, Duarte, California, Fred Grannis, Arnold Rotter; Evanston Northwestern Healthcare Medical Group, Illinois, Daniel Ray; Aurora St. Luke’s Medical Center, Milwaukee, David Olsen; Staten Island University Hospital, Mary Salvatore; Our Lady of Mercy Medical Center, Bronx, Peter H. Wiernik; Valley Hospital Cancer Center, Paramus, New Jersey, Robert Korst; Greenwich Hospital, Connecticut, David Mullen; Glens Falls Hospital, New York, Louis DeCunzo; Karmanos Cancer Institute, Detroit, Harvey Pass, Carmen Endress; Sharp Memorial Hospital, San Diego, Michael Kalafer; John Muir Cancer Institute, Concord, California, Michaela Straznicka; Comprehensive Cancer Center, Sequoia Hospital, Redwood City, California, Melissa Lim; Alta Bates Summit Medical Center, Berkeley, California, Gary Cecchi; Bend Memorial Hospital, Oregon, Albert Koch; St. Joseph’s Hospital, Atlanta, Paul Scheinberg; Baylor University Medical Center, Dallas, Edson Cheung.

References 1. Henschke CI, McCauley DI, Yankelevitz DF, et al. Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet 1999; 354:99–105 2. International Early Lung Cancer Action Program Investigators; Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006; 355:1763–1771 3. Muhm JR, Muhm JR, Miller WE, Fontana RS, Sanderson DR, Uhlenhopp MA. Lung cancer detected during a screening program using four-month chest radiographs. Radiology 1983; 148:609–615 4. Woodring JH. Pitfalls in the radiologic diagnosis of lung cancer. AJR 1990; 154:1165–1175 5. Wu MH, Gotway MB, Lee TJ, et al. Features of non-small cell lung carcinomas overlooked at digital chest radiography. Clin Radiol 2008; 63:518–528 6. Austin JH, Romney BM, Goldsmith LS. Missed bronchogenic carcinoma: radiographic findings in 27 patients with a potentially resectable lesion evident in retrospect. Radiology 1992; 182:115–122 7. Kundel HL, Revesz G. Lesion conspicuity, structured noise, and film reader error. AJR 1976; 126:1233–1238 8. Kundel HL, Nodine CF, Carmody D. Visual scanning, pattern recognition and decision-making in pulmonary nodule detection. Invest Radiol 1978; 13:175–181 9. Samuel S, Kundel HL, Nodine CF, Toto LC. Mechanism of satisfaction of search: eye position recordings in the reading of chest radiographs. Radiology 1995; 194:895–902 10. Naidich DP, Rusinek H, McGuinness G, et al. Variables affecting pulmonary nodule detection with computed tomography: evaluation with three-dimensional computer simulation. J Thorac Imaging 1993; 8:291–299 11. Gurney JW. Missed lung cancer at CT: imaging findings in nine patients. Radiology 1996; 199:117–122 12. White CS, Romney BM, Mason AC, Austin JH, Miller BH, Protopapas Z. Primary carcinoma of the lung overlooked at CT: analysis of findings in 14 patients. Radiology 1996; 199:109–115 13. Davis SD. Through the “retrospectoscope”: a glimpse of missed lung cancer at CT. Radiology 1996; 199:23–24 14. Henschke CI. International Early Lung Cancer Action Program: enrollment and screening protocol. www.ielcap.org/sites/default/files/ielcap.pdf. July 1, 2011. Accessed January 12, 2014 15. Carter D, Vazquez M, Flieder DB, et al. Comparison of pathologic findings of baseline and annual repeat cancers diagnosed on CT screening. Lung



Xu et al. Cancer 2007; 56:193–199 16. Henschke CI, Shaham D, Yankelevitz DF, et al. CT screening for lung cancer: significance of diagnoses in the baseline cycle of screening. Clin Imaging 2006; 30:11–15 17. Henschke CI, Yankelevitz DF, Yip R, et al. Lung cancers diagnosed at annual CT screening: volume doubling times. Radiology 2012; 263:578–583 18. Kakinuma R, Ohmatsu H, Kaneko M, et al. Detection failures in spiral CT screening for lung cancer: analysis of CT findings. Radiology 1999; 212:61–66 19. Li F, Sone S, Abe H, MacMahon H, Armato SG 3rd, Doi K. Lung cancers missed at low-dose helical CT screening in a general population: comparison of clinical, histopathologic, and imaging findings. Radiology 2002; 225:673–683 20. van Klaveren RJ, Oudkerk M, Prokop M, et al. Management of lung nodules detected by volume

CT scanning. N Engl J Med 2009; 361:2221–2229 21. National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, et al. Reduced lung cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011; 365:395–409 22. Wisnivesky JP, Yankelevitz DF, Henschke CI. Stage of lung cancer in relation to its size. Part 2. Evidence. Chest 2005; 127:1136–1139 23. Henschke CI, Yankelevitz DF, Miettinen OS; The International Early Lung Cancer Action Program Investigators. CT screening for lung cancer: the relationship of disease stage to tumor size. Arch Intern Med 2006; 166:321–325 24. National Cancer Institute, Surveillance, Epidemiology, and End Results Program website. Lung and bronchus cancer statistics review. seer.cancer. gov/csr/1975_2010/results_merged/sect_15_lung_ bronchus.pdf. Accessed February 28, 2014

25. Gruden JF, Ouanounou S, Tigges S, et al. Incremental benefit of maximum-intensity-projection images on observer detection of small pulmonary nodules revealed by multidetector CT. AJR 2002; 179:149–157 26. Peloschek P, Sailer J, Weber M, et al. Pulmonary nodules: sensitivity of maximum intensity projection versus that of volume rendering of 3D multidetector CT data. Radiology 2007; 243:561–569 27. Jankowski A, Martinelli T, Timsit JF, et al. Pulmonary nodule detection on MDCT images: evaluation of diagnostic performance using thin axial images, maximum intensity projections, and computer-assisted detection. Eur Radiol 2007; 17:3148–3156 28. Farooqi AO, Cham M, Zhang L, et al. Lung cancer associated with cystic airspaces. AJR 2012; 199:781–786

F O R YO U R I N F O R M AT I O N

The AJR has made getting the articles you really want really easy with an online tool, Really Simple Syndication, available at www.ajronline.org. It’s simple. Click the RSS button located in the menu on the right side of the page. You’ll be on your way to syndicating your AJR content in no time.

972


Annual or biennial lung cancer CT screening?

Small pulmonary nodules in baseline and incidence screening rounds of low-dose CT lung cancer screening.

Fecal Immunochemical Test Program Performance Over 4 Rounds of Annual Screening: A Retrospective Cohort Study.

Autoantibody profiling for lung cancer screening longitudinal retrospective analysis of CT screening cohorts.

Lung cancers overdiagnosed with low-dose CT.

Molecular understanding of lung cancers-A review.

Correlation between CT and DNA contents in peripheral lung cancers.

Spectrum of early lung cancer presentation in low-dose screening CT: a pictorial review.

Deciphering Crosstalk Circuits in Non-small Cell Lung Cancers with an Increasing Interval Length of Low Dose CT Screening.

Early screening of lung cancers: an effort arduous but worthwhile.

Management of subsolid pulmonary nodules in CT lung cancer screening.

CT and thin-section CT.

Differences in Patient Outcomes of Prevalence, Interval, and Screen-Detected Lung Cancers in the CT Arm of the National Lung Screening Trial.

Histological review of skin cancers in African Albinos: a 10-year retrospective review.

Cost-effectiveness of CT screening in the National Lung Screening Trial.

Automated pulmonary nodule CT image characterization in lung cancer screening.

Nodule size and overdiagnosis in lung cancer CT screening.

Cost-effectiveness of CT screening in the National Lung Screening Trial.

Cost-effectiveness of CT screening in the National Lung Screening Trial.

Low-dose CT screening in an Asian population with diverse risk for lung cancer: A retrospective cohort study.

Performance of ACR Lung-RADS in a clinical CT lung screening program.

Lung Cancer Screening Using Low Dose CT Scanning in Germany. Extrapolation of results from the National Lung Screening Trial.

CT-diagnosed emphysema and prognosis of chronic airflow obstruction: a retrospective study.

DNA ploidy patterns of tumors diagnosed as metachronous or recurrent lung cancers.