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)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Lung CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Uptake of minimally invasive surgery and stereotactic body radiation therapy for early stage non-small cell lung cancer in the USA: an ecological study of secular trends using the National Cancer Database.BMJ Open Respir Res. 2020; 7
- The Academic facility type is associated with improved overall survival for early-stage lung cancer.Ann Thorac Surg. 2021; 111: 261-268
- Durvalumab after Chemoradiotherapy in stage III non-small-cell lung cancer.N Engl J Med. 2017; 377: 1919-1929
- Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410.J Natl Cancer Inst. 2011; 103: 1452-1460
- Long-term results of stereotactic body radiation therapy in medically inoperable stage I non-small cell lung cancer.JAMA Oncol. 2018; 4: 1287-1288
- 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: 1316-1325
- 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: 1077-1084
National Comprehensive Cancer Network. Non-small cell lung cancer (v1.2022). Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl_blocks.pdf, Accessed January 12, 2022.
- 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: 5043-5051
- Nonoperative Treatment of Large (5-7 cm), node-negative non-small cell lung cancer commonly deviates from NCCN guidelines.J Natl Compr Canc Netw. 2021; https://doi.org/10.6004/jnccn.2021.7043
- Multi-institutional experience of stereotactic body radiotherapy for large (>/=5 centimeters) non-small cell lung tumors.Cancer. 2017; 123: 688-696
- 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: 325-331
- Stereotactic body radiotherapy with adjuvant systemic therapy for early-stage non-small cell lung carcinoma: a multi-institutional analysis.Radiother Oncol. 2019; 132: 188-196
- 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: 494-503
- Definitive radiotherapy for inoperable stage IIB non-small-cell lung cancer: patterns of care and comparative effectiveness.Clin Lung Cancer. 2020; 21: 238-246
- A proportional hazards model for the subdistribution of a competing risk.J Am Stats Assoc. 1999; 94: 496-509
- Immortal time bias: a frequently unrecognized threat to validity in the evaluation of postoperative radiotherapy.Int J Radiat Oncol Biol Phys. 2012; 83: 1365-1373
- 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: 146-154
Article info
Publication history
Published online: May 10, 2022
Accepted:
May 4,
2022
Received in revised form:
April 30,
2022
Received:
February 18,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
