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