Novel RT techniques for treating lung cancer 1403

Novel RT Techniques

For Lung Cancer Treatment

Yong Chan Ahn, MD, PhD

Dept. of Radiation Oncology

Samsung Medical Center

Sungkyunkwan University School of Medicine

Fundamental of RT

• To deliver high dose to tumor

• To limit dose to normal tissues

From Classic to Conformal

• Better local control

• Enhanced quality of life and reduced morbidity

• Improve accuracy of every step!

• Patient-specific:

– Individualized

– Customized

– Adaptive

RT Process

Steps in RT that can be represented by links in a chain.

Tx accuracy will be limited by the weakest link in the chain

Preparation for Radiation Therapy

• Acquisition of CT (MR, PET-CT)

• Contouring

Novel Technology in RT

Image guided RT (IGRT)

Stereotactic Ablative RT (SABR, SBRT)

Intensity Modulated RT (IMRT)

Particle Beam Therapy (Proton; Carbon)

Image guided RT (IGRT)

Stereotactic Ablative RT (SABR, SBRT)

Intensity Modulated RT (IMRT)

Particle Beam Therapy (Proton; Carbon)

Image Guided RT (IGRT)

If you can’t see it, you can’t hit it.

If you can’t hit it, you can’t cure it.

To identify and correct problems

arising from inter- and intra-

fractional variations in patient setup

and anatomy

Electronic Portal Image (EPI)

KV Cone-beam CT (CBCT)

In-Room CT

MV CT (Tomotherapy)

Fluoroscopy-based IGRT

CyberKnife (Synchrony)

Image guided RT (IGRT)

Stereotactic Ablative RT (SABR, SBRT)

Intensity Modulated RT (IMRT)

Particle Beam Therapy (Proton; Carbon)

Ablative RT (by conventional technique)

Stereotactic Ablative (Body) RT

SABR

Conventional RT SABR

Dose/fraction 1.8~3.0 Gy 10~20 Gy

Fraction number 10~30 fractions 1~5 fractions

Target delineation GTV, CTV, (ITV), PTV GTV, CTV, ITV, PTV

(GTV CTV)

Margins cm range mm range

Need for mechanical

accuracy Low to medium Very high

Need for respiratory

motion control Moderate High

Radiobiology Well understood Still poorly understood

Interaction with

systemic therapy Currently active Will become active

Rationale of SABR in Stage I NSCLC

• RT is better than doing nothing.

• (+) dose-response relationship in local control.

• The smaller the tumor, the higher the local control

and survival by RT.

• LN metastasis incidence is very low.

• Shorter RT is better than protracted RT in survival.

Importance of tumor size Importance of RT duration

SABR Indications at SMC

• cT1-2,N0

• Single metastasis or recurrence

• ≤ 5 cm in size (preferably ≤ 3 cm)

• Location (peripheral > central, upper > lower)

Respiratory Training (Respiratory Signal Analysis Program)

Characteristics # Pt (%)

Age Median 69 (39~88) years

Sex Male 98 (84.5%)

Female 18 (15.5%)

Tumor nature Primary 38 (32.8%)

Metastatic 78 (67.2%)

Lung 32 (41.0 %)

GI Track 24 (30.8 %)

Head & Neck 9 (11.5 %)

Others 13 (16.7 %)

Patients’ Characteristics I (116 Patients: ’01/Feb~’10/Nov)

Characteristics # Pt (%)

Tumor size ≤ 2.0 cm 58 (50.0%)

> 2.0 cm 58 (50.0%)

RT dose 50 Gy/5 Fx’s (’01/Jun~’02/May) 8 ( 6.9%)

60 Gy/5 Fx’s (’02/June~’09/Dec) 72 (62.1%)

60 Gy/4 Fx’s (’10/Jan~’10/Dec) 36 (31.0%)

Patients’ Characteristics II (116 Patients: ’01/Feb~’10/Nov)

Survival

Months

Pro

bab

ilit

y

p = 0.036

66.4%

53.8%

Summary

• SBRT to lung cancer at SMC:

– High local control (90%)

– Favorable 5 year survival (primary/metastatic –

66.4%/53.8%)

– Very low risk of complication (Grade 2/3 –

3.4%/1.7%)

– Highly effective and curative modality to patients

who are unfit for surgery.

Acta Oncologica, 2012

Summary

• SBRT for single or oligo-metastasis seems

quite effective and safe.

• Tumor size, disease-free interval, and presence

of extrathoracic disease are prognosticators for

survival.

Image guided RT (IGRT)

Stereotactic Ablative RT (SABR, SBRT)

Intensity Modulated RT (IMRT)

Particle Beam Therapy (Proton; Carbon)

Multi-leaf Collimator

LINAC-based IMRT

• Static MLC (“step-and-shoot”)

• Dynamic MLC (“sliding window”)

• Volumetric modulated arc (VMAT)

Tomotherapy

Example Case: Sq, cT2N3

SMC Experience of IMRT

• May 2010~November 2012

• 77 patients with N3 (+) stage IIIB NSCLC

• Definitive CCRT by 3DCRT or LINAC- IMRT

– 66 Gy/33 Fx’s to CTV

– 3DCRT (48); IMRT (29)

– Weekly pacli-/docetaxel + cis-/carboplatin (67)

– 3 weekly pemetrexed/etoposide + cisplatin (10)

Characteristics 3D-CRT (48) IMRT (29) p-value

Median age (range) 62 (44-72) yrs 59 (40-80) yrs 0.7441

Gender Male

Female

35 (72.9%)

13 (27.1%)

18 (62.1%)

11 (37.9%) 0.3904

Smoking history Yes

No 34 (70.8%) 17 (58.6%) 0.2722

Median FEV1 (range) 2.49 (1.17-3.90) L 2.50 (1.46-3.71) L 0.7909

ECOG performance 0

1

10 (20.8%)

38 (79.2%)

6 (20.7%)

23 (79.3%) 0.9880

Primary site lobe Upper/middle

Lower

39 (81.3%)

9 (18.7%)

13 (44.8%)

16 (55.2%) 0.0009

Histology Adenoca

Sq cell ca

Others

31 (64.6%)

15 (31.2%)

2 (4.2%)

22 (75.9%)

3 (10.3%)

4 (13.8%)

0.0533

Median tumor size (range) 3.8 (1.3-12.2) cm 3.7 (1.0-9.2) cm 0.7852

cT stage cT1-2

cT3-4

34 (70.8%)

14 (29.2%)

23 (79.3%)

6 (20.7%) 0.4111

Involved N3 region Contralateral mediastinum

Supraclavicular

29 (60.4%)

26 (54.2%)

7 (24.1%)

24 (82.8%)

0.0020

0.0108

Dosimetric Parameters Variable 3D-CRT (48) IMRT (29) p-value

CTV

Median

<300 cm3

≥300 cm3

279.3 (89-1,543) cm3

28 (59.3%)

20 (41.7%)

357.5 (89-763) cm3

10 (34.5%)

19 (65.5%)

0.7064

0.0425

Dose to lung

Mean

V5

V10

V15

V20

18.4 (9.3-28.0) Gy

57.2 (29.8-72.9)%

48.6 (24.5-63.5)%

40.6 (18.1-54.5)%

32.8 (14.3-50.0)%

19.6 (14.6-25.2) Gy

65.1 (48.4-90.0) %

51.8 (41.8-62.9) %

42.3 (34.7-53.6) %

35.6 (28.2-45.9) %

0.0306

0.0002

0.1072

0.0519

0.0612

Clinical Outcomes 3D-CRT (48) IMRT (29) Total (77)

Disease progression 24 (50.0%) 21 (72.4%) 45 (58.4%)

Failure pattern LR

Distant

Both

4 (8.3%)

17 (35.4%)

3 (6.3%)

2 (6.9%)

15 (51.7%)

4 (13.8%)

6 (7.8%)

32 (41.6%)

7 (9.1%)

Median time to progression 9.1 months 6.0 months 8.2 months

Esophagitis Grade ≤2

Grade 3

41 (85.4%)

7 (14.6%)

21 (72.4%)

8 (27.6%)

62 (80.5%)

15 (19.5%)

Pneumonitis Grade 1

Grade ≥2

32 (66.7%)

16 (33.3%)

22 (75.9%)

7 (24.1%)

54 (70.1%)

23 (29.9%)

Summary

• Limitations:

– Small number of patients

– Heterogeneous patient population

– Retrospective nature

• IMRT group:

– More extensive disease and larger CTV

– More frequent early distant metastasis

• Careful case selection and intensified systemic Tx

maybe considered

Image guided RT (IGRT)

Stereotactic Ablative RT (SABR, SBRT)

Intensity Modulated RT (IMRT)

Particle Beam Therapy (Proton)

Why Proton Beam Therapy?

• Bragg peak (1946, Wilson et al. first proposed PBT)

• RBE=1.1

History of PBT

• 1950: 1st clinical application

to suppress pituitary

function and to reduce

metastases from breast ca

• 1950’s: Uppsala Group

(Sweden) pioneered proton

RT for cancer

• Early 1960’s: Harvard

Cyclotron Group (US)

developed most current

techniques

50

PBT for Stage I NSCLC

PBT for Stage III NSCLC

• Need for dose escalation:

– RTOG trials (X-rays): 8311 (+) and 0617 (-)

• Few dosimetric comparison studies:

– Advantage of PBT over X-rays seems more

significant in stage III than stage I

• Recent on-going trials of high-dose PBT with

concurrent chemotherapy

– Safe and effective

Dose (Gy)

No

rmal

ized

vo

lum

e (%

)

Dose-volume Histogram (DVH)

0

10

20

30

40

50

60

70

80

90

100

0 10 20 30 40 50 60 70 80

Proton PTV

Proton Spinal Cord

Proton Both Lungs

IMRT PTV

IMRT Spinal Cord

IMRT Both Lungs

3DCRT PTV

3DCRT Spinal Cord

3DCRT Both Lungs

Tomo PTV

Tomo Spinal Cord

Tomo Both Lungs

Normal Tissue DVH

No

rmal

ized

vo

lum

e (%

)

CTV DVH

CTV DVH

PBT for III NSCLC

• Need for dose escalation:

– RTOG trials (X-rays): 8311 (+) and 0617 (-)

• Few dosimetric comparison studies:

– Advantage of PBT over X-rays seems more

significant in stage III than stage I

• Recent on-going trials of high-dose PBT with

concurrent chemotherapy

– Safe and effective

Summary

• PBT can give excellent dose distribution using less ports (Bragg peak)

• PBT maybe more widely applicable than SABR even with pulmonary comorbidity and difficult tumor location in stage I

• PBT may save more normal tissue in stage III than in stage I

• Pencil beam scanning seems promising

• Dose-escalated PBT with concurrent CTx may be safe and effective

Proton Therapy Center

Samsung Medical Center

Multidisciplinary

approach

Importance of Target Delineation

• Target contouring errors generate systematic errors

which no level of image guidance will eliminate.

• Target delineation accuracy cannot be overemphasized!