PMID- 33569310
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220420
IS  - 2218-6751 (Print)
IS  - 2226-4477 (Electronic)
IS  - 2218-6751 (Linking)
VI  - 10
IP  - 1
DP  - 2021 Jan
TI  - Synergy between early-incorporation immunotherapy and extracranial radiotherapy 
      in metastatic non-small cell lung cancer.
PG  - 261-273
LID - 10.21037/tlcr-20-537 [doi]
AB  - BACKGROUND: Combining radiotherapy (RT) and immunotherapy (IT) may enhance 
      outcomes for metastatic non-small cell lung cancer (mNSCLC). However, data on the 
      immunomodulatory effects of extracranial RT remains limited. This retrospective 
      database analysis examined real-world practice patterns, predictors of survival, 
      and comparative effectiveness of extracranial radioimmunotherapy (RT + IT) versus 
      early-incorporation immunotherapy (eIT) in patients with mNSCLC. METHODS: 
      Patients diagnosed with mNSCLC between 2004-2016 treated with eIT or RT + IT were 
      identified in the National Cancer Database. Practice patterns were assessed using 
      Cochrane-Armitrage trend test. Cox proportional hazards and Kaplan-Meier method 
      were used to analyze overall survival (OS). Propensity score matching was 
      performed to account for baseline imbalances. Biologically effective doses (BED) 
      were stratified based on the median (39 Gy(10)). Stereotactic body radiotherapy 
      (SBRT) was defined as above median BED in </=5 fractions. RESULTS: eIT utilization 
      increased from 0.3% in 2010 to 13.2% in 2016 (P<0.0001). Rates of RT + eIT 
      increased from 38.8% in 2010 to 49.1% in 2016 among those who received eIT 
      (P<0.0001). Compared to eIT alone, RT + eIT demonstrated worse median OS (11.2 
      vs. 13.2 months) while SBRT + eIT demonstrated improved median OS (25 vs. 13.2 
      months) (P<0.0001). There were no significant differences in OS based on 
      sequencing of eIT relative to RT (log-rank P=0.4415) or irradiated site (log-rank 
      P=0.1606). On multivariate analysis, factors associated with improved OS included 
      chemotherapy (HR 0.86, P=0.0058), treatment at academic facilities (HR 0.83, 
      P<0.0001), and SBRT (HR 0.60, P=0.0009); after propensity-score multivariate 
      analysis, SBRT alone showed improved OS (HR 0.28, P<0.0001). CONCLUSIONS: 
      Utilization of RT + eIT in mNSCLC is increasing. SBRT + eIT was associated with 
      improved OS on propensity-score matched analysis. There were no significant 
      differences in OS based on RT + eIT sequencing or site irradiated. Whether these 
      observations reflect patient selection or possible immunomodulatory benefits of 
      RT is unclear and warrants further study.
CI  - 2021 Translational Lung Cancer Research. All rights reserved.
FAU - Chodavadia, Parth A
AU  - Chodavadia PA
AD  - School of Medicine, Duke University, Durham, NC 27710, USA.
FAU - Jacobs, Corbin D
AU  - Jacobs CD
AD  - Department of Radiation Oncology, Duke University, Durham, NC 27710, USA.
FAU - Wang, Frances
AU  - Wang F
AD  - Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 
      27710, USA.
FAU - Salama, Joseph K
AU  - Salama JK
AD  - Department of Radiation Oncology, Duke University, Durham, NC 27710, USA.
FAU - Kelsey, Chris R
AU  - Kelsey CR
AD  - Department of Radiation Oncology, Duke University, Durham, NC 27710, USA.
FAU - Clarke, Jeffrey M
AU  - Clarke JM
AD  - Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.
FAU - Ready, Neal E
AU  - Ready NE
AD  - Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.
FAU - Torok, Jordan A
AU  - Torok JA
AD  - Department of Radiation Oncology, Duke University, Durham, NC 27710, USA.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Transl Lung Cancer Res
JT  - Translational lung cancer research
JID - 101646875
PMC - PMC7867754
OTO - NOTNLM
OT  - Database analysis
OT  - immunotherapy
OT  - non-small cell lung cancer (NSCLC)
OT  - radioimmunotherapy
OT  - radiotherapy
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/tlcr-20-537). Dr. NER reports 
      personal fees from BMS, personal fees from Celgene, grants and personal fees from 
      Merck, personal fees from Astrazeneca, personal fees from G1 therapeutics, 
      personal fees from Novartis, personal fees from Genentech, personal fees from 
      Roche, personal fees from Abbvie, outside the submitted work. Dr. JMC reports 
      grants from Bristol-Myers Squibb, grants from Genentech, grants from Spectrum, 
      grants from Adaptimmune, grants from Medpacto, grants from Bayer, grants from 
      Abbvie, grants from Moderna, grants from Array, grants and personal fees from Eli 
      Lilly, personal fees from Merck, personal fees from AstraZeneca, personal fees 
      from Guardant Merck, personal fees from Achilles Therapeutics, outside the 
      submitted work. The other authors have no conflicts of interest to declare.
EDAT- 2021/02/12 06:00
MHDA- 2021/02/12 06:01
PMCR- 2021/01/01
CRDT- 2021/02/11 05:54
PHST- 2021/02/11 05:54 [entrez]
PHST- 2021/02/12 06:00 [pubmed]
PHST- 2021/02/12 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - tlcr-10-01-261 [pii]
AID - 10.21037/tlcr-20-537 [doi]
PST - ppublish
SO  - Transl Lung Cancer Res. 2021 Jan;10(1):261-273. doi: 10.21037/tlcr-20-537.