Non–Small-Cell Lung Cancer Diagnosis and Staging Evaluation

Physical examination Chest x-ray Bronchoscopy Fine-needle aspiration CT scan PET scan Laboratory analysis Mediastinoscopy

Purpose

Identify signs Determine position, size, number of tumors Determine location of tumor, obtain biopsy Cytology Identify chest-wall invasion, mediastinal lymphadenopathy, distant metastases Mediastinal, lymph-node and extrathoracic staging Detect changes in hormone production, and hematologic manifestations of lung cancer Visualize and sample mediastinal lymph nodes 1

TNM Staging of Non–Small-Cell Lung Cancer Stage IA Stage IB Stage IIA Stage IIB T1 T2 T1 T2 T3 N0 N0 N1 N1 N0 M0 M0 M0 M0 M0

T = primary tumor; N = nodal involvement; M = distant metastasis.

Mountain CF.

Chest.

1997;111:1710. 2

TNM Staging of Non–Small-Cell Lung Cancer Stage IIIA Stage IIIB T1 –3 T3 T4 Any T N2 N1 Any N N3 M0 M0 M0 M0 Stage IV Any T Any N M1

T = primary tumor; N = nodal involvement; M = distant metastasis.

Mountain CF.

Chest.

1997;111:1710. 3

Overview of NSCLC Treatment Options Early-stage tumor

  Surgery Radiation for inoperable patients

Locally advanced tumor

 Surgery   Chemoradiation Surgery + chemoradiation

Advanced tumor

 Chemotherapy   Targeted therapy Chemotherapy + targeted therapy NCCN Clinical Practice Guidelines in Oncology. NSCLC. V.I.2007. Available at: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed May 18, 2007.

4

Postoperative Radiation Therapy in NSCLC

Systematic Review and Meta-analysis of 9 Randomized Controlled Studies

No. Events/No. Entered

Trial

Belgium LCSG 773 CAMS Lille 88/98 84/110 83/153 59/81 EORTC 08861 MRC LU11 GETCB 04CB86 Slovenia 26/52 116/154 69/99 30/35 GETCB 05CB88 152/274 Total

PORT No PORT O-E Variance

80/104 81/120 100/164 45/82 20/54 59/90 33/39 16.04

4.77

1.07

10.87

5.53

123/154 -2.48

4.95

-2.56

120/265 25.13

707/1056 661/1072 63.33

40.67

41.02

44.88

25.66

11.20

59.39

31.59

15.63

67.08

337.12

Hazard ratio Hazard ratio = 1.21

P = .001

2.0

  Postoperative RT 30 – 60 Gy; diverse planning Survival data on 2128 patients – PORT  21% increase in risk of death 0 0.5

PORT better 1.0

1.5

No PORT better PORT Meta-analysis Trialists Group.

Lancet.

1998;352:257-263, with permission from Elsevier.

5

ANITA1: Evaluation of PORT in Patients With Node-Positive Disease

5 Year-Survival According to N Stage

Observation PORT Chemotherapy Chemotherapy + PORT

N0

62.3% 43.8% 59.7% 44.4%

N1

31.4% 42.6% 56.3% 40.0%

N2

16.6% 21.3% 34.0% 47.4% 232/840 received radiation after chemotherapy or surgery Doulliard J-Y, et al.

Int J Radiat Oncol.

2006;66:S2. Courtesy of Dr. Doulliard.

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PORT for Stage II or III NSCLC (SEER Database) Nodal Stage

N0 Radiotherapy Observation N1 Radiotherapy Observation N2 Radiotherapy Observation

HR

1.176

1.00 (Ref) 1.097

1.00 (Ref) 0.855

1.00 (Ref)

Overall Survival 95% Cl

1.005

1.015

0.762

–1.376

–1.186

–0.959

N = 7465; Hazard ratio (HR) <1 = improved overall survival.

P

Multivariate Analysis

.0435

.0196

.0077

HR Disease-Specific Survival

1.361

1.00 (Ref) 1.082

1.00 (Ref) 0.850

1.00 (Ref)

95% Cl

1.134

0.990

0.748

–1.633

–1.182

–0.967

P

.0009

.0822

.0133

Conclusion

In a population-based cohort, PORT use is associated with an increase in survival in patients with N2 nodal disease but not in patients with N1 and N0 nodal disease.

Lally BE, et al.

J Clin Oncol.

2006;24:2998-3006. Reprinted with permission from the American Society of Clinical Oncology.

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Phase III Trial of Chemoradiation ± Surgery in Stage IIIA pN2 Patients (INT 0139) INDUCTION CHEMORADIOTHERAPY Cisplatin 50 mg/m 2 etoposide 50 mg/m 2 IV days 1, 8, 29, 36 + IV days 1 –5, 29–33 (PE) + RT to 45 Gy starting day 1 Resection if no progression, then PE x 2 (n = 202) Complete chemoradiotherapy to 61 Gy with PE x 2 (n = 194) 23.6

22.2

25 20 15 10 5 0

CT/RT/S CT/RT 12.8

10.5

5-y PFS 22.4% 11.1% Median PFS P = .017

HR 0.77 (0.62

–0.96)

Albain KS, et al.

J Clin Oncol.

2005;23:16S. Abstract 7014.

5-y OS 27.2% 20.3% Median OS P = .24

HR 0.87 (0.70

–1.10)

8

INT 0139: Overall Survival of the Lobectomy

Subset vs Matched CT/RT Subset

100 75

Deceased/Total CT/RT/S CT/RT 57/90 74/90

50 25 0 0

Median survival 5-y OS

/

CT/RT/S

/// /

P = .002

// / / / / / / / //

CT/RT/S

/ /

CT/RT 34 mo 22 mo 36% 18%

/ / / / /

CT/RT

12 24 36 48

Months from Randomization

60 Albain KS, et al.

J Clin Oncol.

2005;23:16S. Abstract 7014. Courtesy of Dr. K. Albain.

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Survival Comparison—Chemoradiation Sequencing

30 25 20 15 10 5 0

Sequential Concurrent Induction Concurrent Concurrent Consolidation

WJLCG LAMP GLOT 5 6 CZECH 1 RTOG 9410 2 CALGB 39801 BROCAT 7 4 SWOG 9504 RTOG 9801C RTOG 9801A 8 9 9 3 CALGB 30105A CALGB 30105B 10 10 1. Tada T, et al.

Radiat Med.

2004;22:163. 2. Curran WJ, et al.

Proc Am Soc Clin Oncol.

2003;22:621. Abstract 2499. 3. Vokes EE, et al.

J Clin Oncol.

2004;22(suppl):7005. 4. Huber RM, et al.

J Clin Oncol.

2006;24:4397. 5. Choy H, et al.

Proc Am Soc Clin Oncol.

2002;21:1160. 6. Gournel P, et al.

J Clin Oncol.

2005;23:5910. 7. Zatloukal P, et al. et al.

J Clin Oncol.

Lung Cancer.

2004;46:87. 8. Gandara DR, et al.

Clin Lung Cancer.

2006;8:116. 9. Movsas B, 2005;23:2145. 10. Blackstock AW, et al.

J Clin Oncol.

2006;24(suppl):7042.

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Confirmation of Consolidation Chemotherapy in Unresectable Stage III NSCLC

Hoosier Oncology Group (LUN01-24)

Chemoradiotherapy Induction

Cisplatin 50 mg/m 2 days 1, 8, 29, 36 Etoposide 50 mg/m 2 IV days 1–5, 29–33 Concurrent RT 59.4 Gy (1.8 Gy/d)

Complete Response, Partial Response, or Stable Disease ECOG PS 0 –1 Randomize Docetaxel 75 mg/m 2 every 3 weeks



3

http://www.clinicaltrials.gov/ct/show/NCT00216125?order=1

Observation

11