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Pre-surgical assessment of mediastinal lymph node metastases in Stage IA non-small-cell lung cancers

  • Author Footnotes
    1 Yong Wang and Yeqing Zhu are both first authors.
    Yong Wang
    Footnotes
    1 Yong Wang and Yeqing Zhu are both first authors.
    Affiliations
    Department of Radiology, Mount Sinai School of Medicine, NY, NY, USA

    Department of Radiology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, China
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  • Author Footnotes
    1 Yong Wang and Yeqing Zhu are both first authors.
    Yeqing Zhu
    Footnotes
    1 Yong Wang and Yeqing Zhu are both first authors.
    Affiliations
    Department of Radiology, Mount Sinai School of Medicine, NY, NY, USA

    Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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  • Rowena Yip
    Affiliations
    Department of Radiology, Mount Sinai School of Medicine, NY, NY, USA
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  • Dong-Seok Lee
    Affiliations
    Department of Thoracic Surgery, Mount Sinai School of Medicine, NY, NY, USA
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  • Raja M. Flores
    Affiliations
    Department of Thoracic Surgery, Mount Sinai School of Medicine, NY, NY, USA

    Tisch Center Institute, Mount Sinai School of Medicine, NY, NY, USA

    Center for Thoracic Oncology, Mount Sinai School of Medicine, NY, NY, USA
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  • Andrew Kaufman
    Affiliations
    Department of Thoracic Surgery, Mount Sinai School of Medicine, NY, NY, USA

    Tisch Center Institute, Mount Sinai School of Medicine, NY, NY, USA

    Center for Thoracic Oncology, Mount Sinai School of Medicine, NY, NY, USA
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  • Claudia I. Henschke
    Correspondence
    Corresponding author at: Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
    Affiliations
    Department of Radiology, Mount Sinai School of Medicine, NY, NY, USA

    Tisch Center Institute, Mount Sinai School of Medicine, NY, NY, USA

    Center for Thoracic Oncology, Mount Sinai School of Medicine, NY, NY, USA

    Phoenix Veterans Affairs Health Care System, Phoenix, AZ, USA
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  • David F. Yankelevitz
    Affiliations
    Department of Radiology, Mount Sinai School of Medicine, NY, NY, USA

    Phoenix Veterans Affairs Health Care System, Phoenix, AZ, USA
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  • for theI-ELCAP Investigators
    Author Footnotes
    2 I-ELCAP Investigators: Mount Sinai School of Medicine, New York, NY: Claudia I. Henschke, Principal Investigator, David F. Yankelevitz, Rowena Yip, Artit Jirapatnakul, Raja Flores, Andrea Wolf; Weill Cornell Medical College: Daniel M. Libby, James P. Smith, Mark Pasmantier; 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: Shusuke Sone, Takaomi Hanaoka; Clinica Universitaria de Navarra, Pamplona, Spain: Javier Zulueta, Juan P. de-Torres, Maria D. Lozano; Swedish Medical Center, Seattle, WA: Ralph Aye, Kristin Manning; 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; LungenZentrum 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: Dorith Shaham; 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: Diana 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: 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: James Walsh, David Bertsch; 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; University of Toledo, Toledo OH: James C. Willey.
  • Author Footnotes
    1 Yong Wang and Yeqing Zhu are both first authors.
    2 I-ELCAP Investigators: Mount Sinai School of Medicine, New York, NY: Claudia I. Henschke, Principal Investigator, David F. Yankelevitz, Rowena Yip, Artit Jirapatnakul, Raja Flores, Andrea Wolf; Weill Cornell Medical College: Daniel M. Libby, James P. Smith, Mark Pasmantier; 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: Shusuke Sone, Takaomi Hanaoka; Clinica Universitaria de Navarra, Pamplona, Spain: Javier Zulueta, Juan P. de-Torres, Maria D. Lozano; Swedish Medical Center, Seattle, WA: Ralph Aye, Kristin Manning; 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; LungenZentrum 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: Dorith Shaham; 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: Diana 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: 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: James Walsh, David Bertsch; 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; University of Toledo, Toledo OH: James C. Willey.

      Highlights

      • None of the patients with nonsolid or part-solid NSCLCs had N1-N3 metastases.
      • FDG-PET has low sensitivity but high specificity for MLN metastases.
      • CT short axis of MLN > 20 mm was a better predictor of N2/N3 metastases than FDG-PET.
      • Further prospective evaluation of clinical Stage IA staging criteria is needed.

      Abstract

      Objective

      Evaluation of sensitivity and specificity of CT and fluorodeoxyglucose-positron emission tomography for pre-surgical staging of mediastinal lymph node metastases (N2/N3) of non-small-cell-lung-cancers ≤30 mm.

      Methods

      We reviewed a total of 263 patients from a prospective cohort study, who underwent resection including mediastinal lymph nodes, for first primary non-small-cell-lung-cancer ≤30 mm in maximum diameter on pre-surgical CT. Cutoff criteria for short-axis diameter on CT of the largest N2/N3 node of 10, 15, and 20 mm and positron emission uptake of 2.5, 3.0, and 4.0 were evaluated using Area-Under-the-Curve (AUC) assessment. Accuracy criterion was used to determine the optimal cutoffs.

      Results

      Of 263 patients, 9 had nonsolid, 42 part-solid, and 212 solid non-small-cell-lung-cancers. Post-surgically, none of the 51 patients with nonsolid or part-solid cancers had mediastinal lymph node metastases. Among the 212 patients with solid cancers, 23 had N2 node metastases. For the 212 patients with solid cancers, the AUC for CT lymph node measurements was 0.67 (95% CI: 0.57–0.77), significantly higher (p = 0.001) than chance alone, while the AUC for SUVmax measurements, 0.56 (95% CI: 0.48–0.65), was not (p = 0.13). Optimal CT cutoff was >20 mm had low sensitivity of 30.4% (95% CI: 11.6%–49.2%) but high specificity of 99.5% (95% CI: 98.4%–100.0%).

      Conclusion

      Based on these results, clinical Stage IA for non-small-cell-lung-cancers with nonsolid, part-solid, or solid consistency should be based on pre-surgical CT maximum tumor diameter and lymph node short-axis measurements on CT ≤20 mm. Further prospective evaluation of these clinical Stage IA staging criteria is needed.

      Abbreviations:

      AUC (area under the receiver operating characteristic curve), CT (computed tomography), FDG-PET (fluorodeoxyglucose-positron emission tomography), I-ELCAP (International Early Lung Cancer Action Program), NSCLC (non-small-cell-lung-cancer), NPV (negative predictive value), PPV (positive predictive value), SUV (standardized uptake value)

      Keywords

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