Nonoperative Treatment of Large (5–7 cm), Node-Negative Non–Small Cell Lung Cancer Commonly Deviates From NCCN Guidelines

Authors:
Craig S. Schneider Department of Radiation Oncology,

Search for other papers by Craig S. Schneider in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
Robert A. Oster Division of Preventative Medicine, Department of Medicine, and

Search for other papers by Robert A. Oster in
Current site
Google Scholar
PubMed
Close
 PhD
,
Aparna Hegde Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Search for other papers by Aparna Hegde in
Current site
Google Scholar
PubMed
Close
 MBBS
,
Michael C. Dobelbower Department of Radiation Oncology,

Search for other papers by Michael C. Dobelbower in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
John M. Stahl Department of Radiation Oncology,

Search for other papers by John M. Stahl in
Current site
Google Scholar
PubMed
Close
 MD
, and
Adam J. Kole Department of Radiation Oncology,

Search for other papers by Adam J. Kole in
Current site
Google Scholar
PubMed
Close
 MD, PhD
Restricted access

Background: Optimal treatment of nonoperative patients with large, node-negative non–small cell lung cancer (NSCLC) is poorly defined. Current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommend definitive radiotherapy (RT) with or without sequential chemotherapy and do not include concurrent chemoradiotherapy (chemoRT) as a treatment option. In this study, we identified factors that predict nonadherence to NCCN Guidelines. Patients and Methods: Patients who received definitive RT for nonmetastatic, node-negative NSCLC with tumor size of 5 to 7 cm were identified in the National Cancer Database from 2004 through 2016. Patients were evaluated by RT type (stereotactic body RT [SBRT], hypofractionated RT [HFRT], or conventionally fractionated RT [CFRT]) and chemotherapy use (none, sequential, or concurrent with RT). Patients were classified as receiving NCCN-adherent (RT with or without sequential chemotherapy) or NCCN-nonadherent (concurrent chemoRT) treatment. Demographic and clinical factors were assessed with logistic regression modeling. Overall survival was evaluated with Kaplan-Meier, log-rank, and univariable/multivariable Cox proportional hazards regression analyses. Results: Among 2,020 patients in our cohort, 32% received NCCN-nonadherent concurrent chemoRT, whereas others received NCCN-adherent RT alone (51%) or sequential RT and chemotherapy (17%). CFRT was most widely used (64% CFRT vs 22% SBRT vs 14% HFRT). Multivariable analysis revealed multiple factors to be associated with NCCN-nonadherent chemoRT: age ≤70 versus >70 years (odds ratio [OR] , 2.72; P<.001), treatment at a nonacademic facility (OR, 1.65; P<.001), and tumor size 6 to 7 cm versus 5 to 6 cm (OR, 1.27; P=.026). Survival was similar between the NCCN-nonadherent chemoRT and NCCN-adherent groups (hazard ratio, 1.00; P=.992) in multivariable analysis. Conclusions: A substantial proportion of inoperable patients with large, node-negative NSCLC are not treated according to NCCN Guidelines and receive concurrent chemoRT. Younger patients with larger tumors receiving treatment at nonacademic medical centers were more likely to receive NCCN-nonadherent therapy, but adherence to NCCN Guidelines was not associated with differences in overall survival.

Submitted August 19, 2020; final revision received March 31, 2021; accepted for publication April 5, 2021. Published online August 12, 2021.

Author contributions: Study concept: Schneider, Kole. Data acquisition: Stahl. Primary data analysis: Schneider, Kole. Manuscript preparation: Schneider, Kole. Support for statistical analyses: Oster. Contributed to data analysis and editing of the manuscript: All authors.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Data availability statement: The primary dataset from the National Cancer Database is available publicly through the American College of Surgeons (https://www.facs.org/quality-programs/cancer/ncdb). The statistic codes used during the present study are available from the corresponding author on reasonable request.

Correspondence: Adam J. Kole, MD, PhD, Department of Radiation Oncology, University of Alabama at Birmingham, 1700 Sixth Avenue South, Birmingham, AL 35233. Email: akole@uabmc.edu

Supplementary Materials

    • Supplemental Materials (PDF 552 KB)
  • Collapse
  • Expand
  • 1.

    Butts CA, Ding K, Seymour L, et al. Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: updated survival analysis of JBR-10. J Clin Oncol 2010;28:2934.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Fibla JJ, Cassivi SD, Brunelli A, et al. Re-evaluation of the prognostic value of visceral pleura invasion in stage IB non-small cell lung cancer using the prospective multicenter ACOSOG Z0030 trial data set. Lung Cancer 2012;78:259262.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Lakha S, Gomez JE, Flores RM, et al. Prognostic significance of visceral pleural involvement in early-stage lung cancer. Chest 2014;146:16191626.

  • 4.

    Park SY, Lee JG, Kim J, et al. Efficacy of platinum-based adjuvant chemotherapy in T2aN0 stage IB non-small cell lung cancer. J Cardiothorac Surg 2013;8:151.

  • 5.

    Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 2008;26:35523559.

  • 6.

    Strauss GM, Herndon JE II, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol 2008;26:50435051.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Ettinger DS, Wood DE, Aisner DL, et al. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 3.2020. Accessed January 5, 2020. To view the most recent version, visit NCCN.org

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Timmerman RD, Hu C, Michalski JM, et al. Long-term results of stereotactic body radiation therapy in medically inoperable stage I non-small cell lung cancer. JAMA Oncol 2018;4:12871288.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 2010;303:10701076.

  • 10.

    Videtic GM, Paulus R, Singh AK, et al. Long-term follow-up on NRG Oncology RTOG 0915 (NCCTG N0927): a randomized phase 2 study comparing 2 stereotactic body radiation therapy schedules for medically inoperable patients with stage I peripheral non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2019;103:10771084.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Bezjak A, Paulus R, Gaspar LE, et al. Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non-small-cell lung cancer: NRG Oncology/RTOG 0813 Trial. J Clin Oncol 2019;37:13161325.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Ball D, Mai GT, Vinod S, et al. Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial. Lancet Oncol 2019;20:494503.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Jacobs CD, Gao J, Wang X, et al. Definitive radiotherapy for inoperable stage IIB non-small-cell lung cancer: patterns of care and comparative effectiveness. Clin Lung Cancer 2020;21:238246.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Newman NB, Brett CL, Kluwe CA, et al. Immortal time bias in National Cancer Database studies. Int J Radiat Oncol Biol Phys 2020;106:512.

  • 15.

    Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst 2011;103:14521460.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Furuse K, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol 1999;17:26922699.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Fournel P, Robinet G, Thomas P, et al. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d’Oncologie Thoracique-Groupe Français de Pneumo-Cancérologie NPC 95-01 Study. J Clin Oncol 2005;23:59105917.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med 2017;377:19191929.

  • 19.

    Bradley JD, Paulus R, Komaki R, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol 2015;16:187199.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Seok Y, Yang HC, Kim TJ, et al. Frequency of lymph node metastasis according to the size of tumors in resected pulmonary adenocarcinoma with a size of 30 mm or smaller. J Thorac Oncol 2014;9:818824.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Lopez Guerra JL, Gomez DR, Lin SH, et al. Risk factors for local and regional recurrence in patients with resected N0-N1 non-small-cell lung cancer, with implications for patient selection for adjuvant radiation therapy. Ann Oncol 2013;24:6774.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Verma V, Shostrom VK, Kumar SS, et al. Multi-institutional experience of stereotactic body radiotherapy for large (≥5 centimeters) non-small cell lung tumors. Cancer 2017;123:688696.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Woody NM, Stephans KL, Marwaha G, et al. Stereotactic body radiation therapy for non-small cell lung cancer tumors greater than 5 cm: safety and efficacy. Int J Radiat Oncol Biol Phys 2015;92:325331.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Peterson J, Niles C, Patel A, et al. Stereotactic body radiotherapy for large (> 5 cm) non-small-cell lung cancer. Clin Lung Cancer 2017;18:396400.

  • 25.

    Aupérin A, Le Péchoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 2010;28:21812190.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Dudani S, Zhu X, Yokom DW, et al. Radical treatment of stage II non-small-cell lung cancer with nonsurgical approaches: a multi-institution report of outcomes. Clin Lung Cancer 2018;19:e1118.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Verma V, McMillan MT, Grover S, et al. Stereotactic body radiation therapy and the influence of chemotherapy on overall survival for large (≥5 centimeter) non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2017;97:146154.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Ko EC, Raben D, Formenti SC. The integration of radiotherapy with immunotherapy for the treatment of non-small cell lung cancer. Clin Cancer Res 2018;24:57925806.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 2932 676 23
PDF Downloads 1104 218 23
EPUB Downloads 0 0 0