Abstract
Background
The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer–specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%).
Purpose
To update the cure rate by determining the 20-year lung cancer–specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort.
Materials and Methods
For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer–specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke.
Results
Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61–72), with a median smoking history of 43.0 pack-years (IQR, 29.0–60.0). Median follow-up duration was 105 months (IQR, 41–182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer–specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer–specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer.
Conclusion
The 10-year lung cancer–specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer–specific survival for the expanded I-ELCAP cohort.
© RSNA, 2023
See also the editorials by Grenier and by Sequist and Olazagasti in this issue.
Summary
The estimated cure rate of 80% using the 10-year lung cancer–specific survival of 484 International Early Lung Cancer Action Program (I-ELCAP) participants reported in 2006 has persisted after 20 years of follow-up in the expanded cohort of 1257 participants.
Key Results
■ The estimated 10- and 20-year lung cancer–specific survival rates for the 1257 participants were 81% and 81%, respectively.
■ The Kaplan-Meier lung cancer–specific survival plateau was reached 10 years after diagnosis.
■ The 20-year follow-up provides an estimate of the cure rate achieved in annual screening programs using a well-defined protocol and comprehensive management system, which allows for identification of early lung cancer while it is still small and curable.
Introduction
In 1999, the initial results of the Early Lung Cancer Action Program (ELCAP) provided evidence supporting the benefit of annual low-dose CT as a screening modality for lung cancer in a predefined high-risk population (1). Starting in 1992, 1000 participants aged 60 years or older with a cigarette smoking history of at least 10 pack-years were prospectively enrolled in a cohort study that compared annual low-dose CT with annual chest radiography at two New York City institutions (2). Results of the baseline round of screening, reported in 1999 (1), found that 85% of the participants with newly diagnosed lung cancer detected with low-dose CT had stage I lung cancer (Lung Cancer TNM Classification, 6th edition), while 82% of these low-dose CT–detected stage I cancers had not been identified on chest radiographs obtained at the same time as the low-dose CT scans. The results gave renewed hope to people at risk for lung cancer (3) and led to low-dose CT screening research throughout the world (4–7).
By 2006, the International ELCAP (I-ELCAP), a multinational collaboration (7), and the expanded New York Early Lung Cancer Action Program (NY-ELCAP) (8) provided sufficient long-term follow-up to estimate the cure rate in 484 participants diagnosed with a first primary lung cancer under annual screening among 31 567 participants using the 10-year Kaplan-Meier lung cancer–specific survival, which was 80% (95% CI: 74, 85) (9).
Cure rates of different cancers are of increasing interest to screening participants and national public health policy authorities (10–14). The multinational Siracusa charter (12) defined cure of a cancer as “complete remission of a cancer regardless of the presence or absence of late sequelae of treatment.” The cure rate is estimated by the plateau reached in a cancer-specific Kaplan-Meier survival curve, and the number of years to reach this plateau varies by type of cancer (12–14). For lung cancer, the consensus was that the plateau is reached 8–10 years after treatment (12–14).
The aim of this report is to provide the updated 20-year lung cancer–specific survival of participants diagnosed with lung cancer in the prospectively enrolled I-ELCAP cohort, following the I-ELCAP protocol of annual screening (15), with a view toward strengthening confidence in the previously reported cure rate (9). As the prevalence of lung cancer in screening participants with different exposures to cigarette smoking was previously examined (16,17), 20-year lung cancer–specific survival was separately estimated for participants with a smoking history of 30 pack-years or more, those with a smoking history of 10–29 pack-years, and those with a smoking history of less than 10 pack-years, including those who had never smoked cigarettes but had passive exposure to cigarette smoke.
Materials and Methods
This Health Insurance Portability and Accountability Act–compliant study was conducted in accordance with the Declaration of Helsinki and received approval from the institutional review board of the Western Institutional Review Board (approval no. 1106439) and the institutional review boards of participating institutions. All enrolled participants provided written informed consent.
Study Participants
All participants consecutively enrolled between 1992 and 2022 in I-ELCAP (15) were reviewed. I-ELCAP is a prospective multi-institutional cohort study. Institutional enrollment criteria differed. Individuals with a history of any cancer other than nonmelanotic skin cancer were excluded from enrollment in this cohort. Race was self-reported by study participants. Included in this report are all participants aged at least 40 years who had current or former cigarette use or who had never smoked but were exposed to secondhand tobacco smoke. Some study participants were previously reported, including the 484 participants in the previous 2006 publication (9), but to our knowledge, the 20-year follow-up results have never been reported.
All identified participants were those diagnosed with a first primary lung cancer, either non–small cell or small cell cancer, regardless of stage or type of treatment, diagnosed under annual screening, that is resulting from baseline and annual screenings performed 7–18 months after the previous screening or from interim lung cancer diagnoses identified between rounds of screening (15,18). Participants diagnosed with lung cancer had a firmly established diagnosis of lung cancer and documentation in the management system. Updates have been made for each participant on an ongoing basis and have also been provided at each of the 44 International Conferences on Screening for Lung Cancer held since 1999 (7).
Study Design
The principal investigators and study coordinators at each participating institution observed participants diagnosed with lung cancer and submitted follow-up information to the I-ELCAP coordinating center, as required by the common standardized protocol. Date and cause of death were obtained from the participant’s physician, family members, and—in the United States—from the National Death Index.
Documented in the ELCAP Management System were: participant demographics, comorbidities, contact information, and referring physician information at enrollment; follow-up participant communications; low-dose CT findings; pathology findings; and treatment (19). The maximum tumor diameter of the lung cancer on axial, sagittal, and coronal CT images was measured on the last CT scan obtained before treatment. Lung cancer consistency was determined on the same pretreatment CT scan and was classified as solid or subsolid (part-solid or nonsolid) according to established criteria (15,20,21). For part-solid lung cancers, the maximum diameter of the largest solid component was also measured; when this diameter was more than 80% of the overall tumor diameter, tumor consistency was classified as solid (15). The I-ELCAP protocol required demonstration of growth of small nodules developed through a National Cancer Institute grant (R01-CA-78905; September 1999 to August 2002) since the beginning of the study (5,9,15,21). Reviews of the I-ELCAP database were made for protocol compliance at the semiannual conferences since 1999, which included multiple expert pathology panel reviews (22).
The documented diagnoses, treatment, and posttreatment follow-up information for all participants diagnosed with lung cancer and staging were available in the I-ELCAP Management System so that staging could be updated according to the Lung Cancer TNM Classification, 8th edition (23).
Clinical and Pathologic Stage
Clinical T status was defined by maximum tumor diameter on the last pretreatment CT scan (15); clinical N status was defined by lymph node location; N2 lymph nodes were defined as those with a short-axis diameter of more than 10 mm on pretreatment CT scans (15). Clinical stage I was defined as cT1a-c and cT2aN0M0 based on the last pretreatment CT scan. Pathologic T status was defined by maximum tumor diameter in the resected pathologic specimen: 10 mm or less (pT1a), 11–20 mm (pT1b), 21–30 mm (pT1c), and 31–40 mm or tumor with main bronchus involvement, invading visceral pleura or associated with atelectasis or obstructive pneumonitis (pT2a).
Many reports define stage I by using a hybrid definition of pathologic stage if resected or clinical stage if not resected. This means that the percentage diagnosed in stage I depends on the frequency of resection at any one institution. To avoid this bias, the clinical stage I definition was used, but the frequency of stage I using the hybrid definition was also provided.
Statistical Analyses
Statistical analyses were performed by a data scientist (R.Y.). Categorical variables were summarized as frequencies (percentages), continuous variables are presented as means ± SDs, and nonparametric variables are presented as medians and IQRs. Continuous variables for normal distribution were assessed with the Shapiro-Wilk test. Differences in demographic and sociomedical characteristics and CT findings were assessed using the χ2 or Fisher exact tests for categorical variables and using the two-sample t or Wilcoxon rank sum tests for parametric and nonparametric continuous variables.
Using Kaplan-Meier survival analysis, 10- and 20-year lung cancer–specific survival rates were calculated for all participants diagnosed with a first primary lung cancer through annual screening (15,17) using documented follow-up from diagnosis to death or last contact until December 31, 2022, whichever came first. The 95% Hall-Wellner bands were also computed. Deaths within 30 days of surgery or other lung cancer–related treatment were considered lung cancer deaths. Kaplan-Meier lung cancer–specific survival was calculated separately for participants with clinical stage I lung cancer and for the hybrid stage I definition. It was also calculated separately for three different cigarette smoking categories: (a) those with a smoking history of less than 10 pack-years, including those who had never smoked cigarettes but had passive exposure to cigarette smoke; (b) those with a smoking history of 10–29 pack-years; and (c) those with a smoking history of 30 or more pack-years. Factors associated with time to lung cancer death were analyzed using the Cox proportional hazards model; both crude and adjusted hazard ratios with 95% CIs are reported. P ≤ .05 was considered indicative of a significant difference. All statistical analyses were performed using SAS software (version 9.4; SAS Institute).
Results
Participant Characteristics
Among the 89 404 I-ELCAP screening participants enrolled in low-dose CT screening programs between 1992 and 2022, 62 722 (70.2%) participants were screened in North America, 16 082 (18.0%) were screened in Europe, and 10 600 (11.8%) were screened in Asia. A total of 1257 (1.4%) participants were diagnosed with first primary lung cancer under annual screening; 684 (54.4%) were male, and 573 (45.6%) were female (Table 1).
Table 1:
Characteristics of 1257 I-ELCAP Participants with Lung Cancer
At the time of diagnosis, the median age of these 1257 participants was 66 years (IQR, 61–72), with a median smoking history of 43 pack-years (IQR, 29–60). Median tumor diameter on the last pretreatment CT scan was 14.0 mm (IQR, 9.3–22.0 mm). Lung cancer consistency was solid for 1008 (80.2%) participants and subsolid for 249 (19.8%). Cancer cell type was adenocarcinoma in 843 (67.1%) participants, squamous cell carcinoma in 168 (13.4%), small cell carcinoma in 82 (6.5%), large cell carcinoma in 42 (3.3%), and carcinoid (both typical and atypical) in 27 (2.2%); other non–small cell types accounted for the remaining 95 (7.6%). Median follow-up in the 1257 participants was 105 months (IQR, 41–182). As of December 31, 2022, 212 (16.9%) participants had died of lung cancer; the rate of death from lung cancer was 18.8 deaths per 1000 person-years. Surgical resection was performed for 998 (79.4%) participants; it was performed within 1 month of diagnosis in 768 (77.0%), within 2–3 months of diagnosis in 179 (17.9%), within 4–6 months of diagnosis in 27 (2.7%), and more than 6 months after diagnosis in 24 (2.4%). Of the 998 surgical participants (Table 2), 142 (14.2%) underwent wedge resection, 82 (8.2%) underwent segmentectomy, 733 (73.4%) underwent lobectomy, 25 (2.5%) underwent bilobectomy, and eight (0.8%) underwent pneumonectomy; in eight participants (0.8%), the extent of surgery was not specified. The primary treatment for the remaining 259 (20.6%) participants was stereotactic body radiation therapy in 77 (6.1%), chemotherapy in 114 (9.1%), and concurrent radiation therapy and chemotherapy in 24 (1.9%); 44 (3.5%) participants underwent other treatments. The frequency of clinical stage I was 81% (1017 of 1257), which was higher than that using the hybrid definition (pathologic stage if resected, clinical stage if not resected) of 74.0% (930 of 1257).
Table 2:
Treatment and Pathologic Stage of the 998 I-ELCAP Participants with Resected Lung Cancers
The 10- and 20-year Lung Cancer–specific Survival
For all 1257 participants, the 10-year lung cancer–specific survival was 81% (95% CI: 79, 84) and the 20-year lung cancer–specific survival was 81% (95% CI: 78, 83) (Fig 1). For the 1017 participants with clinical stage I lung cancer (cT1a,b,cN0M0 or cT2aN0M0), the 20-year lung cancer–specific survival was 87% (95% CI: 85, 89) while for the 930 participants with stage I lung cancer defined by the hybrid definition of stage I, it was 87% (95% CI: 85, 89). The survival rate reached a plateau after 10 years of follow-up. When excluding the 22 adenocarcinoma in situ and minimally invasive adenocarcinoma (previously classified as bronchioloalveolar carcinoma) cases, the 20-year lung cancer–specific survival for the remaining 1235 participants was 80% (95% CI: 78, 83).
Figure 1:
Kaplan-Meier curve shows lung cancer–specific survival for all 1257 participants with lung cancer and for the 181 participants undergoing resection with resulting pT1aN0M0 and tumor size of 10 mm or less in the pathology specimen.
In the 998 participants who underwent surgical resection, 20-year lung cancer–specific survival was 87% (95% CI: 85, 90). In the 181 participants with the earliest pathologic stage of pT1aN0M0, it was 95% (95% CI: 91, 98) (Figs 1, 2). The 20-year lung cancer–specific survival was 83% (95% CI: 80, 86) in the 769 participants with resected solid cancers and 100% in the 228 participants with resected subsolid cancers. Of the 228 subsolid cancers, 71 (31%) were pathologic TisN0M0.
Figure 2:
(A, B) Two annual repeat low-dose CT scans in a woman who was 60 years old at baseline enrollment in 1999. At baseline enrollment, she was currently smoking and had a 30-pack-year smoking history. No nodules were identified on baseline low-dose CT scans. On the sixth annual low-dose CT scan (B), a right lower lobe solid nodule (arrow) measuring 4.5 mm in maximum diameter was identified. The nodule could be identified in retrospect on the prior annual CT scan (arrow in A), when it measured 2.0 mm in maximum diameter. Estimated tumor volume doubling time was 161 days. Lobectomy was performed 2 months later, and diagnosis of stage 1aN0M0 moderately differentiated adenocarcinoma measuring 6.0 mm in maximum diameter was made. Expert pathologic panel review (22) of the pathologic specimen updated the diagnosis to adenocarcinoma with mixed subtype (80% acinar, 20% bronchoalveolar carcinoma components) with 5 mm of invasion.
The 20-year lung cancer–specific survival for the three categories of cigarette smoking was (a) 85% (95% CI: 78, 91) in 136 participants who had a smoking history of less than 10 pack-years, including those who had never smoked cigarettes but had passive exposure to cigarette smoke; (b) 83% (95% CI: 77, 89) in 196 participants with a smoking history of 10–29 pack-years; and (c) 79% (95% CI: 77, 82) in 925 participants with a smoking history of at least 30 pack-years (P = .26) (Fig 3). After adjusting for sex and age, there was no evidence of a difference in the risk of lung cancer death among participants who had smoked for at least 30 pack-years when compared with participants who had a smoking history of less than 10 pack-years, including those who had never smoked (hazard ratio, 1.2; 95% CI: 0.65, 2.17; P = .59) and participants who had smoked for 10–29 pack-years (hazard ratio, 1.3; 95% CI: 0.82, 2.22; P = .25).
Figure 3:
Kaplan-Meier curve shows lung cancer–specific survival for all 1257 participants with lung cancer, organized by smoking categories (participants who never smoked or who smoked less than 10 pack-years, participants who smoked 10–29 pack-years, and participants who smoked at least 30 pack-years).
Discussion
Among 89 404 participants in the International Early Lung Cancer Action Program (I-ELCAP) annual program of low-dose CT screening, 20-year lung cancer–specific survival for 1257 (1.4%) participants diagnosed with a first primary lung cancer under annual screening was 81% (95% CI: 78, 83), and in the subset of 181 participants who underwent surgical resection and had T1aN0M0 lung cancer confirmed via pathology, 20-year lung cancer–specific survival was 95% (95% CI: 91, 98) (Fig 1). The survival rate reached the plateau after 10 years of follow-up, and the 10-year lung cancer–specific survival for all 1257 participants was 81% (95% CI: 79, 84). These updated survival rates allow us to confirm our previously reported estimated cure rate of 80% reported in 2006 based on the 10-year lung cancer–specific survival of 484 participants (9). This high cure rate was anticipated using a mathematic model prior to the start of the Early Lung Cancer Action Program (ELCAP) screening program in 1992 (24), as well as the initial ELCAP stage distribution reported in 1999 (1). To reach this high cure rate of 80%, however, requires that low-dose CT screening follows a well-defined regularly updated protocol for the work-up of CT findings, a comprehensive data management system for the entire screening program, and training to ensure appropriate follow-up and adherence to continued annual screening (21).
Lung cancer cure rates achieved in screening programs have received increased attention as low-dose CT screening has begun to be implemented globally (10–14,23,25,26). For lung cancer, the consensus is that the survival curve plateau for estimating the cure is reached 8–10 years after treatment (12–14). To the best of our knowledge, no other studies have reported 20-year lung cancer–specific survival for low-dose CT screening programs. Sufficiency of 10 years of follow-up to reach the plateau had been demonstrated by the I-ELCAP 10-year lung cancer–specific survival of 80% for the original 484 participants in 2006 (9) and again by the 10-year survival of 81% (95% CI: 79, 84) for the 1257 participants in this report. The plateau is also evident in the 10-year lung cancer–specific survival of 73.4% among stage I participants in the National Lung Screening Trial (27). The 10-year survival in the National Lung Screening Trial is lower due to many factors, including that screenings were performed from 2002 to 2008, that screenings were limited to a maximum of two annual rounds and thus were predominantly baseline cases, and that there was a lack of consensus in the work-up protocol among the 33 participating institutions (28), as detailed in a previous report (29). In summary, the 20-year follow-up provides strong added empirical support of the consensus that 8–10 years of follow-up after diagnosis is sufficient to estimate cure rates for lung cancer (12–14).
Criticisms of our estimated cure rate in 2006 (9) were biases due to length time, overdiagnosis, and lead time biases, as described by Morrison (30). Length bias is introduced, as slower-growing cancers are more frequently detected in the asymptomatic participants presenting for screening, while participants with aggressive cancers may have symptom-prompted diagnoses outside of screening rounds (30). Thus, to determine lung cancer–specific survival, it is important to include all lung cancers diagnosed by screening as well as those diagnosed in between screening rounds. Length bias was demonstrated in the Dutch-Belgian Lung Cancer Screening (NELSON) trial (31), as the frequency of stage I diagnoses decreased as symptom-prompted diagnoses in between rounds of screening increased when longer intervals were used between screening rounds. In both our 2006 report and our current report, we included all lung cancers diagnosed at baseline and annual screening rounds, as well as all those diagnosed between screening rounds. Overdiagnosis bias, a severe form of length bias, occurs when screening reveals cancers that would otherwise never have exhibited clinical symptoms, leading to a diagnostic work-up in the patient’s lifetime (30). Overdiagnosis in I-ELCAP was mitigated by the requirement to demonstrate growth of small nodules using growth assessment developed through a National Cancer Institute grant (R01-CA-78905; September 1999 to August 2002) which was incorporated from the beginning in the I-ELCAP protocol (5,9,15,21). There were also expert pathology panel reviews of I-ELCAP lung cancers (22), and these expert panel members stimulated the development of the revised adenocarcinoma classification (32). Further, analysis of the Surveillance, Epidemiology, and End Results (SEER) database demonstrated the low rate of overdiagnosis (33); the National Lung Screening Trial protocol, which did not require growth assessment prior to diagnosis, revised its estimate of overdiagnosis to 3% when excluding the nonsolid cancers (34); and Raz et al (35) reported that patients with untreated clinical stage I lung cancer in the California Cancer Registry had a 5-year all-cause survival of 7% (median survival, 9 months). To further address concerns about overdiagnosis, we presented 20-year survival separately for resected solid and subsolid lung cancers and showed that lung cancer–specific survival remained high after excluding adenocarcinoma in situ and minimally invasive adenocarcinoma as had been done in the National Lung Screening Trial survival analysis (34). We avoided lead-time bias, as we did not compare the survival rates achieved under screening with those achieved in the absence of screening.
Our study had limitations. First, a limitation of long-term follow-up is that advances in CT and PET technology, as well as other diagnostic and treatment innovations that improve outcomes, are not fully recognized. Second, staging has changed from the 6th to the current 8th edition of Lung Cancer TNM Classification (23); however, because we had an ongoing management system for data and image acquisition, we were able to review the images and treatment reports of all participants diagnosed with lung cancer to update the Lung Cancer TNM Classification, 8th edition, criteria. Third, compliance with the annual screening protocol was variable among the institutions, as illustrated by the reports from the Pamplona (25) and Valencia (26) sites; however, training and monitoring using a common management system, as well as follow-up reporting of I-ELCAP results at each semiannual conference (7), were important for protocol compliance. Fourth, only 556 of the 1257 participants with lung cancer had more than 10 years of follow-up data, which might have affected the precision of the survival estimates; however, the estimates include about three times the number of participants used to make the 2006 estimate of 80%, which had only two participants with 10 years of follow-up data (9).
In conclusion, the estimated cure rate of 80% reported in 2006 based on the 10-year survival of 484 participants in I-ELCAP diagnosed with a first primary lung cancer under annual low-dose CT screening has persisted after 20 years of follow-up in the expanded I-ELCAP cohort of 1257 participants and enables us to confirm the benefit of annual low-dose CT screening. Future focus should be on identifying lung cancer even earlier, perhaps during the first 20 doublings rather than the last 20 doublings, as can currently be achieved using low-dose CT. Blood biomarkers and new imaging tests will continue to improve. We eagerly await new innovations that can be rapidly evaluated by comparison with low-dose CT using the ELCAP approach.
Acknowledgments
Acknowledgments
We express our deepest gratitude to the many physicians, nurses, patient coordinators, academicians, and technical and administrative staff members whose dedicated and meticulous work over the past decades has provided the platform on which I-ELCAP research is built. Our very, very special thanks to the thousands of screening participants who have allowed us to follow their progress over the years so that others could benefit from the information gleaned from their experiences. We greatly appreciate their generosity of spirit.
C.I.H. and R.Y. contributed equally to this work.
International Early Lung Cancer Action Program Investigators are listed at the end of the article.
Supported in part by the Simons Foundation International and the Flight Attendant Medical Research Institute. The screenings in the I-ELCAP pooled database have been supported in part by National Institutes of Health (R01-CA-63393l, R01-CA-78905); U.S. Department of Energy (DE-FG02-96SF21260); New York City Department of Health and Mental Hygiene; New York State Foundation for Science, Technology and Innovation; American Cancer Society; Instituto de Salud Carlos III (PI10/01652, PI07/0792, RD12/0036/0062); Starr Foundation; New York Community Trust; Rogers Family Foundation; Foundation for Lung Cancer: Early Detection, Prevention, and Treatment (primary source from an unrestricted gift in 2000-2003 from the Vector Group, the parent company of Liggett Tobacco); Dorothy R. Cohen Foundation; Jacob and Malka Goldfarb Charitable Foundation; Auen/Berger Foundation; Berger Foundation; Mills Peninsula Hospital Foundation; Tenet Healthcare Foundation; Ernest E. Stempel Foundation; Academic Medical Development Corporation; Columbia University Medical Center; Empire Blue Cross and Blue Shield; Eastman-Kodak; GE HealthCare; Weill Cornell Medical College; Cornell University; New York-Presbyterian Hospital; Swedish Hospital; Christiana Care Helen F. Graham Cancer Center; Holy Cross Hospital; Eisenhower Hospital; Jackson Memorial Hospital Health System; and Evanston Northwestern Healthcare. The views presented in this article are those of the authors and do not reflect the views of the U.S. government or the Department of Veterans Affairs.
The I-ELCAP Investigators: Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY: Claudia I. Henschke (principal investigator), David F. Yankelevitz, Rowena Yip, Artit Jirapatnakul, Raja Flores, Andrew Kaufman, Andrea Wolf, Daniel Nicastri, Timothy Harkin, Javier J. Zulueta, Emanuela Taioli; Cornell University, Ithaca, NY: Anthony P. Reeves; Weill Cornell Medical College, New York, NY: Nasser K. Altorki, James P. Smith, Daniel M. Libby, Mark Pasmantier; Center for the Biology of Natural Systems, Barry Commoner Center for Health and the Environment, Queens College, City University of New York, Queens, NY: Steven Markowitz, Albert Miller; Fundacion Instituto Valenciano de Oncologia, Valencia, Spain: Jose Cervera Deval; Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel: Dorith Shaham; Clinica Universidad de Navarra, Pamplona, Spain: Luis Seijo, Gorka Bastarika, Luis M Montuenga; Holy Cross Hospital Cancer Institute, Silver Spring, MD: Cheryl Aylesworth; LungenZentrum Hirslanden, Zurich, Switzerland: Karl Klingler, Othmar Schöb; Mount Sinai South Nassau, Long Island, NY: Shahriyour Andaz; John Muir Cancer Institute, Concord, Calif: Michaela Straznicka; White Plains Hospital, White Plains, NY and St Luke’s Cornwall, Cornwall, NY: Cynthia Chin and Todd Weiser; Azumi General Hospital, Nagano, Japan: Shusuke Sone, Takaomi Hanaoka; University of Toronto, Princess Margaret Hospital, Toronto, Ontario, Canada: Heidi Roberts, Demetris Patsios; St Barnabas Lung Institute, West Orange NJ; M. Scopetuolo, Andrew Brown; ChristianaCare Helen F. Graham Cancer Center, Newark, Del: Thomas Bauer; Regina Elena National Cancer Institute, Rome, Italy: Stefano Canitano, Salvatore Giunta; National Cancer Center of China/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China: Ning Wu; St Agnes Cancer Center, Baltimore, Md: Enser Cole; Nebraska Methodist Hospital, Omaha, Nebr: Patrick Meyers; Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan: Diana Yeh; St Joseph Cancer Care (SSM Health System), St Charles, Mo: Dan Luedke; The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China: Xueguo Liu; Mercy Medical Center, Rockville Center, NY: Gary Herzog; Swedish Medical Center, Seattle, Wash: Ralph Aye; State University of New York at Stony Brook, Stony Brook, NY: Matthew Rifkin; Humanitas Research Hospital, Milano, Italy: Giula Veronesi, Maurizio Infante; Eisenhower Lucy Curci Cancer Center, Rancho Mirage, Calif: Davood Vafai; Health Group John Maimonides Medical Center, Brooklyn, NY: Samuel Kopel; Physimed/McGill University, Montreal, Quebec, Canada: Jana Taylor; Jackson Memorial Hospital, University of Miami, Miami, Fla; Richard Thurer, Nestor Villamizar; Columbia University Medical Center, New York, NY: John H. M. Austin, Gregory D. N. Pearson; Roswell Park Cancer Institute, Buffalo, NY: Donald Klippenstein, Alan Litwin, Peter A. Loud; Upstate Medical Center, Syracuse, NY: Leslie J. Kohman, Ernest M. Scalzetti; North Shore-Long Island Jewish Health System, New Hyde Park, NY: Arfa Khan, Rakesh Shah; Wellstar Health System, Marietta, Ga: William Mayfield; Central Main Medical Center: Carmine Frumiento; Georgia Institute for Lung Cancer Research, Atlanta, Ga: Michael V. Smith; ProHealth Care Regional Cancer Center, Waukesha and Oconomowoc Memorial Hospitals, Oconomowoc, Wis: M. Kristin Thorsen, Richard Hansen; New York University Medical Center, New York, NY: David Naidich, Georgeann McGuinness; Atlantic Health Morristown Memorial Hospital, Morristown, NJ: Mark Widmann; The Valley Hospital Cancer Center, Paramus, NJ: Robert Korst; State University of New York, Staten Island University Hospital, Staten Island, NY: Joseph Lowry, Mary Salvatore; Guthrie Cancer Center, Sayre, Pa: James Walsh, David Bertsch; St Joseph’s Hospital, Emory Healthcare, Atlanta, Ga: Paul Scheinberg; Dorothy E. Schneider Cancer Center, Mills-Peninsula Health Services, San Mateo, CA: Barry Sheppard; Alta Bates Summit Medical Center, Berkeley, CA: Gary Cecchi; Memorial Sloan Kettering Cancer Center, New York, NY: Michelle S. Ginsberg; William W. Backus Hospital, Norwich, Conn: Dennis Slater; Building Trades, Oak Ridge, Tenn: Laura Welch; City of Hope National Medical Center, Duarte, Calif: Fred Grannis, Arnold Rotter; Vassar Brothers Medical Center, Poughkeepsie, NY; Cliff Connery; New York Medical College, Valhalla, NY: Terence A.S. Matalon; Baylor University Medical Center, Dallas, Tex: Edson H. Cheung; Atlantic Medical Imaging, Atlantic City, NJ: Robert Glassberg; Aurora St Luke’s Medical Center, Milwaukee, Wis: David Olsen; Greenwich Hospital, Greenwich, Conn: David Mullen; Mount Sinai Comprehensive Cancer Center, Miami Beach, Fla: Shari-Lynn Odzer; Our Lady of Mercy Medical Center, Bronx, NY: Peter H. Wiernik; Evanston Northwestern Healthcare Medical Group, Evanston, Ill: Daniel Ray; Glens Falls Hospital, Glens Falls, NY: Louis DeCunzo; Monmouth Medical Center, St Barnabas Health, Long Branch, NJ: Seth Cohen; Karmanos Cancer Institute, Detroit, Mich: Harvey Pass, Carmen Endress; Saint Mary’s Good Samaritan, Mt Vernon, Ill: Anthony Vacca and M. Kondapaneni; Sequoia Hospital, Redwood City, Calif: Melissa Lim; Sharp Memorial Hospital, San Diego, Calif: Michael Kalafer; Newark Beth Israel Medical Center, Newark, NJ: Jeremy Green; Rush University, Chicago, Ill: Mark Yoder and Palmi Shah; Comprehensive Cancer Centers of the Desert, Palm Springs, Calif: Elmer Camacho; Novant Health, Presbyterian Cancer Center Healthcare, Charlotte, NC: James O’Brien; University of Toledo, Toledo, Ohio: James C. Willey; Samaritan Albany General Hospital, Albany, Ore; Matthew Rifkin; State University of New York Downstate, Brooklyn, NY; David Gordon; Bend Memorial Hospital, Bend, Ore: Albert Koch.
Disclosures of conflicts of interest: C.I.H. On the advisory board of LungLife AI; named inventor on patents and patent applications owned by Cornell Research Foundation; president and serves on the board of the Early Diagnosis and Treatment Research Foundation. R.Y. No relevant relationships. D.S. Payment from AstraZeneca made through the institution for lecturing and organizing an educational event. S.M. No relevant relationships. J.C.D. No relevant relationships. J.J.Z. Consulting fees from American Heart Technologies and Median Technologies for service on the medical advisory board; small amount of equity from American Heart Technologies. L.M.S. Grants from Serum Median Technologies, SEPAR (Spanish Thoracic Society), and SOLACE (Strengthening the Screening of Lung Cancer in Europe) Consortium (Funded by EU4Health); consulting fees from Sabartech, Serum Median Technologies, and Lung Ambition Alliance; honoraria from AstraZeneca, Merck Sharp & Dohme, Roche, Grupo Español de Cáncer de Pulmón, Menarini, GlaxoSmithKline, and Chiesi Fundación Respira; support for attending meetings from AstraZeneca; participation on the Serum Median Technologies and Lung Ambition Alliance DataSafety Monitoring Board or advisory board; leadership or fiduciary role in SEPAR (Spanish Thoracic Society). C.A. No relevant relationships. K.K. No relevant relationships. S.A. No relevant relationships. C.C. No relevant relationships. J.P.S. No relevant relationships. E.T. No relevant relationships. N.A. Grants NCI/UH3CA244697, NIH/NCILC200388, AstraZeneca: Investigator-Initiated Clinical Trial, New York Genome Center LC200388, NIH/R01 CA271545-01A1, and NIH/U54 CA272688-01; honoraria from Peer View, AstraZeneca, Roche, and Regeneron. R.M.F. No relevant relationships. D.F.Y. Royalties from HeartLung and General Electric; consulting fees from Genentech, AstraZeneca, and Pfizer; named inventor on patents and patent applications owned by General Electric; on the advisory board of HeartLung, on the medical advisory boards of Median Technology and Carestream; consultant and co-owner of Accumetra; owns equity in HeartLung.
Abbreviations:
- ELCAP
- Early Lung Cancer Action Program
- I-ELCAP
- International ELCAP
Contributor Information
Claudia I. Henschke, Email: Claudia.Henschke@mountsinai.org.
Collaborators: Claudia I. Henschke, David F. Yankelevitz, Rowena Yip, Artit Jirapatnakul, Raja Flores, Andrew Kaufman, Andrea Wolf, Daniel Nicastri, Timothy Harkin, Javier J. Zulueta, Emanuela Taioli, Anthony P. Reeves, Nasser K. Altorki, James P. Smith, Daniel M. Libby, Mark Pasmantier, Steven Markowitz, Albert Miller, Jose Cervera Deval, Dorith Shaham, Luis Seijo, Gorka Bastarika, Luis M Montuenga, Cheryl Aylesworth, Karl Klingler, Othmar Schöb, Shahriyour Andaz, Michaela Straznicka, Cynthia Chin, Todd Weiser, Shusuke Sone, Takaomi Hanaoka, Heidi Roberts, Demetris Patsios, M. Scopetuolo, Andrew Brown, Thomas Bauer, Stefano Canitano, Salvatore Giunta, Ning Wu, Enser Cole, Patrick Meyers, Diana Yeh, Dan Luedke, Xueguo Liu, Gary Herzog, Ralph Aye, Matthew Rifkin, Giula Veronesi, Maurizio Infante, Davood Vafai, Samuel Kopel, Jana Taylor, Richard Thurer, Nestor Villamizar, John H. M. Austin, Gregory D. N. Pearson, Donald Klippenstein, Alan Litwin, Peter A. Loud, Leslie J. Kohman, Ernest M. Scalzetti, Arfa Khan, Rakesh Shah, William Mayfield, Carmine Frumiento, Michael V. Smith, M. Kristin Thorsen, Richard Hansen, David Naidich, Georgeann McGuinness, Mark Widmann, Robert Korst, Joseph Lowry, Mary Salvatore, James Walsh, David Bertsch, Paul Scheinberg, Barry Sheppard, Gary Cecchi, Michelle S. Ginsberg, Dennis Slater, Laura Welch, Fred Grannis, Arnold Rotter, Cliff Connery, Terence A.S. Matalon, Edson H. Cheung, Robert Glassberg, David Olsen, David Mullen, Shari-Lynn Odzer, Peter H. Wiernik, Daniel Ray, Louis DeCunzo, Seth Cohen, Harvey Pass, Carmen Endress, Anthony Vacca, M. Kondapaneni, Melissa Lim, Michael Kalafer, Jeremy Green, Mark Yoder, Palmi Shah, Elmer Camacho, James O’Brien, James C. Willey, Matthew Rifkin, David Gordon, and Albert Koch
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