Graphic courtesy of Dr. Damien Dupuy.

Dupuy D. Radiofrequency ablation can destroy small lung tumors while avoiding the toxicity of thoracotomy or radiation. 42nd ASCO; June 2-6, 2006. Slide 14.

Progression-Free Interval After RFA Progression-Free Interval After RFA of Lung Tumorsof Lung Tumors

Size MattersSize Matters

100

80

60

40

20

00 12 24 36 48 60 72

≤ 3 cm

> 3 cm

P = .0002

Pro

gre

ssio

n-F

ree

(%)

Months Since Radiofrequency Ablation

Graphic courtesy of Dr. Damien Dupuy.

Dupuy D. Radiofrequency ablation can destroy small lung tumors while avoiding the toxicity of thoracotomy or radiation. 42nd ASCO; June 2-6, 2006. Slide 14.

Radiofrequency Ablation/Radiation Radiofrequency Ablation/Radiation Therapy in NSCLCTherapy in NSCLC

Pre-RFA 2 Weeks Post-RFA

6 Months Post-RFA/XRT

RFA = radiofrequency ablation; XRT = radiation therapy.

Copyright © Radiological Society of North America, 2005.

Wang H, et al. Radiology. 2005;235:289-298.

Before Cryotherapy After Cryotherapy

CT Images During Cryotherapy and at CT Images During Cryotherapy and at Follow-Up for Treatment of Small Follow-Up for Treatment of Small

Pulmonary MassPulmonary Mass

Stereotactic Body Radiation TherapyStereotactic Body Radiation Therapy(SBRT) for NSCLC(SBRT) for NSCLC

Graphic courtesy of Dr. Hak Choy.

BED = biological equivalent dose.

Optimization of Radiation Therapy Optimization of Radiation Therapy Stereotactic Body Radiation TherapyStereotactic Body Radiation Therapy

Indiana UniversityIndiana University11 JapanJapan22

~88%

~68%

100

80

60

40

20

00 12 24 36 48

Lo

cal

Tu

mo

r C

on

tro

l (%

)

Months from Therapy

100

80

60

40

20

0

0 1 2 3 4 5 6 7Time (Years)

P < .05

Ove

rall

Su

rviv

al (

%)

BED < 100 Gy (n = 23)

BED ≥ 100 Gy (n = 64)

1. Adapted from Cancer, Vol. 101, 2004: 1623-1631. Copyright © 2004 American Cancer Society. This material is reproduced with permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc. 2. Adapted from J Clin Oncol, 2006; 24: 4833, with permission from the American Society of Clinical Oncology.

Study DesignPCI

20–30 Gy in5–12 Fractions

No PCI

RandomAny response

Stratification: performance score and institute

<5 Weeks

4–6 Weeks

No ResponseChemotherapy

(4–6 Cycles)

Reprinted from Slotman BJ, et al. (ASCO 2007, #4; N Engl J Med. 357:664-672, 2007).

Prophylactic Cranial Irradiation in Prophylactic Cranial Irradiation in Extensive-Disease Small-Cell Lung CancerExtensive-Disease Small-Cell Lung Cancer

(EORTC 08993-22993)(EORTC 08993-22993)

0 4 8 12 16 20 24 28 32 360

10

20

30

40

50

60

70

80

90

100

PCI

Control

1 Year: 14.6% vs 40.4%

HR: 0.27 (0.16–0.44)

Sym

pto

mat

ic B

rain

Met

asta

ses

(%)

Prophylactic Cranial Irradiation in Extensive-Disease Small-Cell Lung Cancer

Symptomatic Brain Metastases

P < .001

Time Since Randomization (Months)Reprinted from Slotman BJ, et al. (ASCO 2007, #4; N Engl J Med. 357:664-672, 2007).

Time Since Randomization (Months)0 4 8 12 16 20 24 28 32 36

0

10

20

30

40

50

60

70

80

90

100

PCI

Control

1 Year: 27.1% vs 13.3%

HR: 0.68 (0.52–0.88)

Ove

rall

Su

rviv

al (

%)

Prophylactic Cranial Irradiation in Extensive-Disease Small-Cell Lung Cancer

Overall Survival

P = .003

Reprinted from Slotman BJ, et al. (ASCO 2007, #4; N Engl J Med. 357:664-672, 2007).

STRATIFY

RANDOMIZE

RPA Class2

1 (<65 y and no extracranial cancer vs 2

(>65 y or extracranial metastases)

Number of Brain Metastases2

1 vs 2/3

Extent of Extracranial Disease2

Yes vs no

WBRT + SRS

WBRT + SRS + Temozolomide

WBRT + SRS + Erlotinib

Eligibility1

NSCLC 1–3 brain metastases

Max. lesion: 4 cm

No brainstem metastases

No actively progressing

extracranial cancerx 1 month

WBRT = whole brain radiation therapy; SRS = stereotactic radiosurgery; RPA = recursive partitioning analysis.

1. ClinicalTrials.gov Web site. http://www.clinicaltrials.gov/ct/show/NCT00096265?order=1. 2. Sperduto PW, et al. Slide 4. www.rtog.org/members/protocols/0320/0320Presentation.pdf.

Phase III Trial of WBRT and SRS Phase III Trial of WBRT and SRS with Temozolomide or Erlotinib with Temozolomide or Erlotinib

RTOG 0320RTOG 0320

On multivariate analysis, PET response was a more significant predictor (P = .006) than Karnofsky performance status (P = .09) and weight loss (P = .14).

N = 57

MacManus M, et al. 36th ASCO; May 20-23, 2000. Abstract 1888; Slide 22.

Response to Chemoradiotherapy on Response to Chemoradiotherapy on FDG-PET Correlates with SurvivalFDG-PET Correlates with Survival

100

80

60

40

20

00 3 9 15 48

Est

imat

ed S

urv

ival

(%

)

Months Following PET Scan

2118126

CRPRNR/PD

P = .0033

18%

53%

36%

84%84%

REGISTER

PPEET T

Concurrent chemotherapy/radiation therapy(+/- adjuvant chemotherapy per MD)

PET or PET-CT to be done 12–16 weeks following radiation therapy PET or PET-CT to be done 12–16 weeks following radiation therapy and at least 4 weeks after adjuvant chemotherapy (if given)and at least 4 weeks after adjuvant chemotherapy (if given)

N = 250

PPEET T

Machtay M, et al. 2004. ACR Web site. p 3. http://www.acrin.org/files/protocol_docs/A6668partial_summary.pdf.

Lung Cancer PET StudyLung Cancer PET Study ACRIN 6668/RTOG 0235 DesignACRIN 6668/RTOG 0235 Design

AuthorAuthor NN MethodMethod ImpactImpact

HebertHebert11 2020 VisualVisual 6/206/20

KifferKiffer22 1515 VisualVisual 4/154/15

NestleNestle33 3434 VisualVisual 12/3412/34

MunleyMunley44 3535 VisualVisual 12/3512/35

VanuytselVanuytsel55 7373 DirectDirect 45/7345/73

GiraudGiraud66 1212 Image fusionImage fusion 5/125/12

BradleyBradley77 2626 Image fusionImage fusion 8/268/26

1. Hebert ME, et al. Am J Clin Oncol. 1996;19:416. 2. Kiffer JD, et al. Lung Cancer. 1998;19:167. 3. Nestle U, et al. Int J Radiat Oncol Biol Phys. 1999;44:593. 4. Munley MT, et al. Lung Cancer. 1999;23:105. 5. Vanuytsel LJ, et al. Radiother Oncol. 2000;55:317. 6. Giraud P, et al. Cancer Radiother. 2001;5:725. 7. Bradley J, et al. Int J Radiat Oncol Biol Phys. 2004;59:78.

Impact of PET on Radiation Therapy Impact of PET on Radiation Therapy Volumes in Lung CancerVolumes in Lung Cancer