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Computed Tomography Screening for Lung Cancer: Mediastinal Lymph Node Resection in Stage IA Nonsmall Cell Lung Cancer Manifesting as Subsolid and Solid Nodules

Flores, Raja M. MD*; Nicastri, Daniel MD*; Bauer, Thomas MD; Aye, Ralph MD; Andaz, Shahriyour MD§; Kohman, Leslie MD; Sheppard, Barry MD||; Mayfield, William MD**; Thurer, Richard MD††; Korst, Robert MD‡‡; Straznicka, Michaela MD§§; Grannis, Fred MD¶¶; Pass, Harvey MD||||; Connery, Cliff MD***; Yip, Rowena MPH*; Smith, James P. MD†††; Yankelevitz, David F. MD*; Henschke, Claudia I. PhD, MD*,‡‡‡; Altorki, Nasser K. MD§§§Writing committee for the I-ELCAP Investigators

doi: 10.1097/SLA.0000000000001802
Original Articles

Objective: To compare long-term survival rates of patients with first, primary, clinical stage IA nonsmall cell lung cancer from a large cohort undergoing computed tomography screening with and without mediastinal lymph node resection (MLNR) under an Institutional Review Board-approved common protocol from 1992 to 2014.

Background: Assessing survival differences of patients with and without MLNR manifesting as solid and subsolid nodules.

Methods: Long-term Kaplan-Meier (K-M) survival rates for those with and without MLNR were compared and Cox regression analyses were used to adjust for demographic, computed tomography, and surgical covariates.

Results: The long-term K-M rates for 462 with and 145 without MLNR was 92% versus 96% (P = 0.19), respectively. For 203 patients with a subsolid nodule, 151 with and 52 without MLNR, the rate was 100%. For the 404 patients with a solid nodule, 311 with and 93 without MLNR, the rate was 87% versus 94% (P = 0.24) and Cox regression showed no statistically significant difference (P = 0.28) when adjusted for all covariates. Risk of dying increased significantly with increasing decades of age (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.4–3.8), centrally located tumor (HR 2.5, 95% CI 1.2–5.2), tumor size 21 to 30 mm (HR 2.7, 95% CI 1.2–6.0), and invasion beyond the lung stroma (HR 3.0, 95% CI 1.4–6.1). For the 346 patients with MLNR, tumor size was 20 mm or less; K-M rates for the 269 patients with and 169 patients without MLNR were also not significantly different (HR 2.1, P = 0.24).

Conclusions: It is not mandatory to perform MLNR when screen-diagnosed nonsmall cell lung cancer manifests as a subsolid nodule.

*Departments of Thoracic Surgery and Radiology, Mount Sinai School of Medicine, New York, NY

Department of Surgery, Christiana Care, Helen F. Graham Cancer Center, Newark, DE

Department of Surgery, Swedish Medical Center, Seattle, WA

§Department of Surgery, South Nassau Communities Hospital, Long Island, NY

Department of Surgery, Upstate Medical Center, Syracuse, NY

||Deprtment of Surgery, Mills-Peninsula Health Services, San Mateo, CA

**Department of Surgery, Wellstar Health System, Marietta, GA

††Department of Surgery, Jackson Memorial Hospital, University of Miami, Miami, FL

‡‡Department of Surgery, The Valley Hospital Cancer Center, Paramus, NJ

§§Department of Surgery, John Muir Cancer Institute, Concord, CA

¶¶Department of Surgery, City of Hope National Medical Center, Duarte, CA

||||Department of Surgery, New York University Medical Center, New York, NY

***Department of Surgery, Beth Israel Hospital Center, New York, NY

†††Department of Medicine, Weill Cornell Medical College, New York, NY

‡‡‡Phoenix Veterans Health Care System, Phoenix, AZ

§§§Department of Cardiothoracic Surgery, Weill Cornell Medical College, New York, NY.

Reprints: Claudia I. Henschke, PhD, MD, Department of Radiology, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1234, New York, NY 10029. E-mail:

Funding: This study was sponsored in part by the generous gift from Sonia Lasry Gardner given in loving memory of her father, Moise Lasry, to support lung cancer research, outreach, and treatment.

The screenings in the I-ELCAP pooled database have been supported in part by National Institutes of Health R01-CA-63393l and R01-CA-78905; Department of Energy DE-FG02–96SF21260; The City of New York, Department of Health and Mental Hygiene; New York State Office of Science, Technology and Academic Research (NYSTAR); American Cancer Society; The Starr Foundation; The New York Community Trust; The Rogers Family Fund; The 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 Corporation; General Electric Corporation; Weill Medical College of Cornell University; 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; Evanston Northwestern Healthcare.

Conflicts of interest: Dr Yankelevitz is a named inventor on a number of patents and patent applications relating to the evaluation of diseases of the chest including measurement of nodules. Some of these, which are owned by Cornell Research Foundation (CRF), are nonexclusively licensed to General Electric. As an inventor of these patents, Dr Yankelevitz is entitled to a share of any compensation which CRF may receive from its commercialization of these patents. He also serves on the scientific advisory board (unpaid) for Give-A-Scan, Lung Cancer Alliance and serves as a consultant for Accumetra, LLC.

Dr Henschke is the President and serves on the board of the Early Diagnosis and Treatment Research Foundation. She receives no compensation from the Foundation. The Foundation is established to provide grants for projects, conferences, and public databases for research on early diagnosis and treatment of diseases. Recipients include, I-ELCAP, among others. The funding comes from a variety of sources including philanthropic donations, grants and contracts with agencies (federal and non-federal), imaging and pharmaceutical companies relating to image processing assessments. The various sources of funding exclude any funding from tobacco companies or tobacco-related sources. Dr Claudia Henschke is also a named inventor on a number of patents and patent applications relating to the evaluation of pulmonary nodules on CT scans of the chest which are owned by CRF. Since 2009, Dr Henschke does not accept any financial benefit from these patents including royalties and any other proceeds related to the patents or patent applications owned by CRF.

The I-ELCAP Investigators: Mount Sinai School of Medicine, New York, NY: Claudia I. Henschke, Principal Investigator, David F. Yankelevitz, Rowena Yip, Dongming Xu, Kunwei Li, Mary Salvatore, Raja Flores, Andrea Wolf; Daniel Nicastri, Emanuela Taioli; Weill Cornell Medical College: Dorothy I. McCauley, Mildred Chen, Daniel M. Libby, James P. Smith, Mark Pasmantier Nasser K. Altorki; Cornell University: A. P. Reeves; CBNS, City University of New York at Queens College, Queens, NY; Steven Markowitz, Albert Miller; Fundacion Instituto Valenciano de Oncologia, Valencia, Spain: Jose Cervera Deval; University of Toronto, Princess Margaret Hospital, Toronto, Canada: Heidi Roberts, Demetris Patsios; Azumi General Hospital, Nagano, Japan: ShusukeSone, Takaomi Hanaoka; ClinicaUniversitaria de Navarra, Pamplona, Spain: Javier Zulueta, Luis Montuenga, Maria D. Lozano; Swedish Medical Center, Seattle, WA: Ralph Aye; Christiana Care, Helen F. Graham Cancer Center, Newark, DE: Thomas Bauer; National Cancer Institute Regina Elena, Rome, Italy: Stefano Canitano, Salvatore Giunta; St. Agnes Cancer Center, Baltimore, MD: Enser Cole; Lungen Zentrum Hirslanden, Zurich, Switzerland: Karl Klingler; Columbia University Medical Center, New York, NY: John H.M. Austin, Gregory D. N. Pearson; Hadassah Medical Organization, Jerusalem, Israel: DorithShaham; Holy Cross Hospital Cancer Institute, Silver Spring, MD: Cheryl Aylesworth; Nebraska Methodist Hospital, Omaha NE: Patrick Meyers; South Nassau Communities Hospital, Long Island, NY: Shahriyour Andaz; Eisenhower Lucy Curci Cancer Center, Rancho Mirage, CA; Davood Vafai; New York University Medical Center, New York, NY: David Naidich, Georgeann McGuinness; Dorothy E. Schneider Cancer Center, Mills-Peninsula Health Services, San Mateo, CA: Barry Sheppard; State University of New York at Stony Brook, Stony Brook, NY: Matthew Rifkin; ProHealth Care Regional Cancer Center, Waukesha & Oconomowoc Memorial Hospitals, Oconomowoc, WI: M. Kristin Thorsen, Richard Hansen; Maimonides Medical Center, Brooklyn, NY: Samuel Kopel; Wellstar Health System, Marietta GA: William Mayfield; St. Joseph Health Center, St. Charles, MO: Dan Luedke; Roswell Park Cancer Institute, Buffalo, NY: Donald Klippenstein, Alan Litwin, Peter A. Loud; Upstate Medical Center, Syracuse, NY: Leslie J. Kohman, Ernest M. Scalzetti; Jackson Memorial Hospital, University of Miami, Miami, FL; Richard Thurer, Nestor Villamizar; State University of New York, North Shore-Long Island Jewish Health System, New Hyde Park, NY: Arfa Khan, Rakesh Shah; The 5th Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China: Xueguo Liu; Mercy Medical Center, Rockville Center, NY: Gary Herzog; Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan: Diane Yeh; National Cancer Institute of China, Beijing, China: Ning Wu; Staten Island University Hospital, Staten Island NY: Joseph Lowry, Mary Salvatore; Central Main Medical Center: Carmine Frumiento; Mount Sinai School of Medicine, New York, NY: David S. Mendelson; Georgia Institute for Lung Cancer Research, Atlanta, GA: Michael V. Smith; The Valley Hospital Cancer Center, Paramus NJ: Robert Korst; Health Group Physimed/McGill University, Montreal, CA: Jana Taylor; Memorial Sloan-Kettering Cancer Center, New York, NY: Robert T. Heelan, Michelle S. Ginsberg; John Muir Cancer Institute, Concord CA: Michaela Straznicka; Atlantic Health Morristown Memorial Hospital, Morristown NJ: Mark Widmann; Alta Bates Summit Medical Center, Berkeley CA: Gary Cecchi; New York Medical College, Valhalla, NY: Terence A.S. Matalon; St. Joseph's Hospital, Atlanta GA: Paul Scheinberg; Mount Sinai Comprehensive Cancer Center, Miami Beach, FL: Shari-Lynn Odzer; Aurora St. Luke's Medical Center, Milwaukee WI: David Olsen; City of Hope National Medical Center, Duarte, CA: Fred Grannis, Arnold Rotter; Evanston Northwestern Healthcare Medical Group, Evanston, IL: Daniel Ray; Greenwich Hospital, Greenwich, CT: David Mullen; Our Lady of Mercy Medical Center, Bronx, NY: Peter H. Wiernik; Baylor University Medical Center, Dallas TX: Edson H. Cheung; Sequoia Hospital, Redwood City CA: Melissa Lim; Glens Falls Hospital, Glens Falls NY: Louis DeCunzo; Atlantic Medical Imaging, Atlantic City NJ: Robert Glassberg; Karmanos Cancer Institute, Detroit, MI: Harvey Pass, Carmen Endress; Rush University, Chicago IL: Mark Yoder, Palmi Shah; Building Trades, Oak Ridge TN: Laura Welch; Sharp Memorial Hospital, San Diego, CA: Michael Kalafer; Newark Beth Israel Medical Center, Newark NJ Jeremy Green; Guthrie Cancer Center, Sayre PA: Comprehensive Cancer Centers of the Desert, Palm Springs CA: Elmer Camacho; Dickstein Cancer Treatment Center, White Plains Hospital, White Plains NY: Cynthia Chin; Presbyterian Healthcare, Charlotte NC: James O’Brien; SUNY Downstate, Brooklyn NY: David Gorden; Bend Memorial Hospital, Bend OR: Albert Koch; University of Toledo, Toledo OH: James C. Willey, Good Samaritan Regional Health Center, Mt. Vernon IL: Anthony Vacca; Mt. Sinai Doctors North Shore Medical Group, Huntington NY: Peter DeLuca; Monmouth Medical Center, Long Branch NJ: Seth Cohen; Saint Barnabas Medical Center, Livingston NJ: Michael Scoppetuolo, Andrew Brown; Samaritan Albany General Hospital, Albany NY: George Giacoppe.

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