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Patterns of Failure and Optimal Treatment Paradigm for Large, Inoperable, Node-Negative Non–small Cell Lung Cancer

  • Craig S. Schneider
    Affiliations
    Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL

    O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
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  • Haris Hatic
    Affiliations
    Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL

    O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
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  • Devika Das
    Affiliations
    Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL

    O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
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  • Rex A. Cardan
    Affiliations
    Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL

    O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
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  • John M. Stahl
    Affiliations
    Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL

    O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
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  • James A. Bonner
    Affiliations
    Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL

    O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
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  • Adam J. Kole
    Correspondence
    Address for correspondence: Adam J. Kole, MD, PhD, Department of Radiation Oncology, University of Alabama at Birmingham, 1700 6th Ave South, Birmingham, AL 35294.
    Affiliations
    Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL

    O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
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      Highlights

      • Little is known about optimal treatments and patterns of failure for non-operative patients with large, node-negative non–small cell lung cancer as this group is commonly excluded from major prospective clinical trials.
      • Patients treated with definitive radiation therapy have high rates of both regional and distant progression.
      • Systemic chemotherapy use is associated with significant reductions in the risk of regional and distant failure.
      • Ablative radiotherapy (i.e., stereotactic body radiotherapy, or SBRT) is associated with the highest rates of local control.
      • For inoperable patients in this cohort, strong consideration should be made to treat with SBRT and adjuvant systemic therapy when feasible.

      Abstract

      Objectives

      The ideal non-operative treatment for patients with large, node-negative non–small cell lung cancer (NSCLC) is poorly defined. To inform optimal treatment paradigms for this cohort, we examined patterns of failure and the impact of radiation therapy (RT) and chemotherapy receipt.

      Materials and Methods

      Node-negative NSCLC patients with 5+ cm primary tumors receiving definitive RT at our institution were identified. Sites of initial progression were analyzed. Local progression, regional/distant progression, progression-free survival, and overall survival were analyzed via cumulative incidence function and Kaplan-Meier. Associations between local vs. regional/distant progression with treatment and clinicopathologic variables were assessed via univariable and multivariable competing risks regression.

      Results and Conclusion

      We identified 88 patients for analysis. Among patients with recurrent disease (N = 36), initial patterns of failure analysis showed that isolated distant (27.8%) and isolated regional progression (22.2%) were most common. Distant or regional failure as a component of initial failure was seen in 88.9% of patients who progressed, while isolated local failure was uncommon (11.1%). Univariable and multivariable competing risks regression showed that receipt of SBRT was associated with reduced risk of local progression (HR 0.23, P = .012), and receipt of chemotherapy was associated with reduced risk of regional/distant progression (HR 0.12, P = .040). In conclusion, patients with large, node-negative NSCLC treated with definitive RT are at high risk of regional and distant progression. SBRT correlates with a reduced risk of local failure while chemotherapy is associated with reduced regional/distant progression in this patient population. Ideal treatment may include SBRT when feasible with appropriate systemic therapy.

      Keywords

      Abbreviations:

      CFRT (Conventionally-Fractionated Radiotherapy), COPD (Chronic Obstructive Pulmonary Disease), ECOG (Eastern Cooperative Oncology Group), EMR (Electronic Medical Record), GTV (Gross Tumor Volume), HFRT (Hypofractionated Radiotherapy), HR (Hazard Ratio), NCCN (National Comprehensive Cancer Network), NSCLC (Non-Small Cell Lung Cancer), OS (Overall Survival), PFS (Progression-Free Survival), PS (Performance Status), RT (Radiation Therapy), SBRT (Stereotactic Body Radiotherapy)
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