Giving Induction Radiation in Addition to Chemotherapy Is Not Associated with Improved Survival of NSCLC Patients
with Operable Mediastinal Nodal Disease
Chi-Fu Jeffrey Yang MD, Brian Gulack MD, Paul Speicher MD, Xiaofei Wang PhD, Mark Onaitis MD, David Harpole MD, Thomas D’Amico MD, Mark Berry MD,
Matthew Hartwig MD
Duke Cancer InstituteDurham, NC
Disclosures
Dr. Thomas D’Amico is a consultant for Scanlan
No conflicts related to this presentation
Introduction For patients selected for surgery for stage IIIA-N2
non-small cell lung cancer (NSCLC), the optimal induction therapy strategy is not well-established1
1. J Natl Compr Canc Netw 2012; 10: 599-613
Introduction For patients selected for surgery for stage IIIA-N2
non-small cell lung cancer (NSCLC), the optimal induction therapy strategy is not well-established1
Few prospective studies have evaluated induction therapy regimens
1. J Natl Compr Canc Netw 2012; 10: 599-613
Introduction For patients selected for surgery for stage IIIA-N2
non-small cell lung cancer (NSCLC), the optimal induction therapy strategy is not well-established1
Few prospective studies have evaluated induction therapy regimens
Previous studies have shown that the addition of radiation to chemotherapy enhances mediastinal nodal down-staging but does not improve survival when compared to induction chemotherapy alone2
2. Ann Thorac Surg 2012; 93:1807-121. J Natl Compr Canc Netw 2012; 10: 599-613
Objective Assess outcomes of patients with operable
stage IIIA-N2 disease who received induction chemotherapy (Chemo) vs induction chemoradiation (ChemoRT)
National Cancer Data Base
Objective Assess outcomes of patients with operable
stage IIIA-N2 disease who received induction chemotherapy (Chemo) vs induction chemoradiation (ChemoRT)
National Cancer Data Base
Hypothesis: No significant improvement would be observed with the addition of radiation to induction chemotherapy
Methods National Cancer Data Base (NCDB)
Prospective database jointly sponsored by the American College of Surgeons and the American Cancer Society,
Data abstracted by certified tumor registrars from approved Tumor Registries
Captures ~70% of cancer cases in the U.S.
Inclusion Criteria: Patients with cT1-3, N2 NSCLC from 2003-2006
All patients underwent induction chemotherapy or induction chemoradiation
Patients had at least a lobectomy or pneumonectomy (n=1362) Post-resection pathologic nodal data collected
Start: Comorbidity data available since 2003 End: Long-term survival data available for
patients diagnosed until the end of 2006
Methods
Exclusion Criteria: History of previous unrelated malignancy in last 5
years Patients with T4 or N3 NSCLC
Statistical analyses Kaplan-Meier Analysis Multivariable Cox proportional hazards modeling
Methods
Patient Characteristics
No significant differences observed between induction chemotherapy and induction chemoradiation for:
• Gender• Race• Co-morbidity scores
Patient Characteristics
Variable Chemo(N = 528)
Chemo+RT (N = 834) p-value
Age, mean ± SD 62 ± 10 60 ± 10 <0.01Facility Type (% of total) <0.01 Academic/Research Program 56% 43% Non Academic Program 44% 57%
• Induction chemoradiation patients were younger
• More patients in the induction chemoradiation group were treated at community cancer programs
Clinical T Status
Variable Chemo(N = 528)
Chemo+RT(N = 834) p-value
Clinical T Status (% of total) <0.01 T1 30% 21% T2 60% 61% T3 10% 18%
• Induction chemotherapy group had lower clinical T status
Perioperative Outcomes
VariableChemo (N = 528)
Chemo+RT (N = 834) p-value
Type of Surgery (% of total) 0.04 Pneumonectomy 16% 20% Lobectomy 84% 80%
• More patients in the induction chemoradiation group underwent pneumonectomy
Perioperative Outcomes
Variable Chemo(N = 528)
Chemo+RT(N = 834) p-value
Perioperative Mortality (% of total) Lobectomy 1% 3% 0.14 Pneumonectomy 8% 6% 0.59Re-admission in 30 days (% of total) 6% 7% 0.38Length of Stay Median, IQR 6 (4, 8) 6 (4, 8) 0.37
• No significant differences in perioperative mortality, length of stay and hospital re-admission between the groups
Pathologic Results
Variable Chemo(N = 528)
Chemo+RT(N = 834) p-value
Size of Tumor (cm) Median, IQR 3.5, (2.5, 5.0) 4 (2.6, 6.0) <0.01Lymph Nodes Examined Median, IQR 10 (5, 16) 7 (5, 16) <0.01Positive Margin 8% 7% 0.55
• Patients that underwent induction chemotherapy alone had smaller tumor size
• Induction radiation was associated with fewer nodes examined
Down-staging
Variable Chemo(N = 528)
Chemo+RT(N = 834) p-value
T stage down-staging 24% 38% <0.01N2 to N0/N1 down-staging 46% 58% <0.01
• T stage down-staging was more common with induction chemoradiation
• Nodal down-staging from N2 to N1/N0 was more common with the induction chemoradiation
Overall Survival of Patients with Operable N2 NSCLC who Underwent Induction Chemotherapy vs. Induction
Chemoradiation
p = 0.78
Treatment Median survival
5-year survival
Induction CRT 3.3 years 41.4 %
Induction CT 3.4 years 40.8 %
Induction CRT – 834 698 533 406 356 299 205 110 49 Induction CT – 528 445 341 278 227 188 130 62 29
Impact of Induction Therapy in Multivariable Analysis
* Adjusted for: age, sex, race, comorbidity score, facility type, insurance type, clinical T status, type of operation, histology and tumor location
Adjusted hazard ratio* 95% CI P-valueLower Upper
1.03 0.89 1.18 0.73
Induction Chemoradiation vs Chemotherapy
p = 0.54
Overall Survival after Induction Therapy Followed by Lobectomy
Treatment Median survival
5-year survival
Induction CRT 3.9 years 44.0 %
Induction CT 3.6 years 42.3 %
Induction CRT – 666 573 447 346 305 255 169 89 39 Induction CT – 445 388 300 243 201 167 115 56 27
aHR 1.01; 95% CI: 0.86-1.18
Overall Survival after Induction Therapy Followed by Pneumonectomy
p = 0.99
Treatment Median survival
5-year survival
Induction CRT
2.1 years 32 %
Induction CT 2.4 years 33 %
IC – 83 57 41 35 26 21 15 6 2ICR – 168 125 86 60 51 44 36 21 10
aHR 1.15; 95% CI: 0.80-1.65
Limitations
Retrospective study
No histologic verification of N2 disease prior to induction therapy
No data on type of N2 disease (multi-station vs single station)
Survival was not cancer-specific and no data on location of recurrence
Summary No significant differences in perioperative
mortality between induction chemotherapy and induction chemoradiation
Summary No significant differences in perioperative
mortality between induction chemotherapy and induction chemoradiation
Induction chemoradiation was associated with a higher rate of primary tumor (T) and mediastinal nodal down-staging
However, there was no survival benefit associated with addition of radiation to induction chemotherapy
Conclusion
The addition of radiation to induction chemotherapy for operable stage IIIA-N2 NSCLC is not associated with a significant improvement in overall survival
Conclusion
The addition of radiation to induction chemotherapy for operable stage IIIA-N2 NSCLC is not associated with a significant improvement in overall survival
The use of induction chemoradiation should be reexamined in the context of randomized trials
Conclusion
The addition of radiation to induction chemotherapy for operable stage IIIA-N2 NSCLC is not associated with a significant improvement in overall survival
The use of induction chemoradiation should be reexamined in the context of randomized trials
Future studies should focus on identifying characteristics that can be used to indicate if and when radiation is needed in addition to chemotherapy
Notes
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