- Novel RT techniques such as SBRT, IMRT, IGRT and particle beam therapy can provide high local control rates for lung cancer with reduced toxicity compared to conventional RT. - SBRT achieved 90% local control and favorable 5-year survival for primary and metastatic lung cancers at SMC with very low complication risks. - IMRT may be beneficial for large or centrally-located tumors but further study is needed due to the study's retrospective nature and heterogeneous patient population. - Particle beam therapy, such as proton therapy, can further reduce dose to organs-at-risk compared to photon therapies and may allow dose escalation for improved outcomes, particularly for locally advanced lung cancers.

1. Novel RT Techniques
For Lung Cancer Treatment
Yong Chan Ahn, MD, PhD
Dept. of Radiation Oncology
Samsung Medical Center
Sungkyunkwan University School of Medicine

3. Fundamental of RT
• To deliver high dose to tumor
• To limit dose to normal tissues

4. From Classic to Conformal
•
•
•
•
Better local control
Enhanced quality of life and reduced morbidity
Improve accuracy of every step!
Patient-specific:
– Individualized
– Customized
– Adaptive

5. 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

6. Preparation for Radiation Therapy
• Acquisition of CT (MR, PET-CT)
• Contouring

7. Novel Technology in RT
Image guided RT (IGRT)
Stereotactic Ablative RT (SABR, SBRT)
Intensity Modulated RT (IMRT)
Particle Beam Therapy (Proton; Carbon)

8. Image guided RT (IGRT)
Stereotactic Ablative RT (SABR, SBRT)
Intensity Modulated RT (IMRT)
Particle Beam Therapy (Proton; Carbon)

9. 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.

10. To identify and correct problems
arising from inter- and intrafractional variations in patient setup
and anatomy

11. Electronic Portal Image (EPI)

12. KV Cone-beam CT (CBCT)

13. In-Room CT

14. MV CT (Tomotherapy)

15. Fluoroscopy-based IGRT

16. CyberKnife (Synchrony)

17. Image guided RT (IGRT)
Stereotactic Ablative RT (SABR, SBRT)
Intensity Modulated RT (IMRT)
Particle Beam Therapy (Proton; Carbon)

18. Ablative RT (by conventional technique)

19. Stereotactic Ablative (Body) RT

20. SABR

21. Conventional RT
SABR
1.8~3.0 Gy
10~20 Gy
10~30 fractions
1~5 fractions
GTV, CTV, (ITV), PTV
GTV, CTV, ITV, PTV
(GTV  CTV)
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
Dose/fraction
Fraction number
Target delineation
Margins

22. 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.

23. Importance of tumor size
Importance of RT duration

24. SABR Indications at SMC
•
•
•
•
cT1-2,N0
Single metastasis or recurrence
≤ 5 cm in size (preferably ≤ 3 cm)
Location (peripheral > central, upper > lower)

25. Respiratory Training
(Respiratory Signal Analysis Program)

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

29. Patients’ Characteristics II
(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%)

30. Survival
Probability
66.4%
53.8%
p = 0.036
Months

31. 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.

34. Acta Oncologica, 2012

35. 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.

36. Image guided RT (IGRT)
Stereotactic Ablative RT (SABR, SBRT)
Intensity Modulated RT (IMRT)
Particle Beam Therapy (Proton; Carbon)

37. Multi-leaf Collimator

38. LINAC-based IMRT
• Static MLC (“step-and-shoot”)
• Dynamic MLC (“sliding window”)
• Volumetric modulated arc (VMAT)

39. Tomotherapy

40. Example Case: Sq, cT2N3

42. 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)

43. Characteristics
Gender
Male
IMRT (29)
p-value
62 (44-72) yrs
Median age (range)
3D-CRT (48)
59 (40-80) yrs
0.7441
35 (72.9%)
18 (62.1%)
0.3904
Female
11 (37.9%)
34 (70.8%)
Smoking history
13 (27.1%)
17 (58.6%)
Yes
0.2722
No
Median FEV1 (range)
2.49 (1.17-3.90) L 2.50 (1.46-3.71) L
ECOG performance 0
10 (20.8%)
0.7909
6 (20.7%)
0.9880
1
Primary site lobe
38 (79.2%)
23 (79.3%)
Upper/middle
39 (81.3%)
13 (44.8%)
0.0009
Lower
16 (55.2%)
Adenoca
31 (64.6%)
22 (75.9%)
Sq cell ca
Histology
9 (18.7%)
15 (31.2%)
3 (10.3%)
2 (4.2%)
4 (13.8%)
3.8 (1.3-12.2) cm
3.7 (1.0-9.2) cm
34 (70.8%)
23 (79.3%)
Others
Median tumor size (range)
cT stage
cT1-2
0.0533
0.7852
0.4111
cT3-4
Involved N3 region
14 (29.2%)
6 (20.7%)
Contralateral mediastinum
29 (60.4%)
7 (24.1%)
0.0020
Supraclavicular
26 (54.2%)
24 (82.8%)
0.0108

44. Dosimetric Parameters
Variable
3D-CRT (48)
IMRT (29)
p-value
CTV
Median
279.3 (89-1,543) cm3 357.5 (89-763) cm3 0.7064
<300 cm3
28 (59.3%)
10 (34.5%)
≥300 cm3
20 (41.7%)
19 (65.5%)
0.0425
Dose to lung
Mean
18.4 (9.3-28.0) Gy
19.6 (14.6-25.2) Gy 0.0306
V5
57.2 (29.8-72.9)%
65.1 (48.4-90.0) %
0.0002
V10
48.6 (24.5-63.5)%
51.8 (41.8-62.9) %
0.1072
V15
40.6 (18.1-54.5)%
42.3 (34.7-53.6) %
0.0519
V20
32.8 (14.3-50.0)%
35.6 (28.2-45.9) %
0.0612

45. Clinical Outcomes
3D-CRT (48) IMRT (29) Total (77)
Disease progression
24 (50.0%)
Failure pattern LR
4 (8.3%)
Distant
Both
17 (35.4%)
3 (6.3%)
21 (72.4%) 45 (58.4%)
2 (6.9%)
6 (7.8%)
15 (51.7%) 32 (41.6%)
4 (13.8%)
7 (9.1%)
9.1 months
6.0 months 8.2 months
Grade ≤2
41 (85.4%)
21 (72.4%) 62 (80.5%)
Grade 3
7 (14.6%)
8 (27.6%) 15 (19.5%)
Grade 1
32 (66.7%) 22 (75.9%) 54 (70.1%)
Grade ≥2
16 (33.3%)
Median time to progression
Esophagitis
Pneumonitis
7 (24.1%) 23 (29.9%)

46. 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

47. Image guided RT (IGRT)
Stereotactic Ablative RT (SABR, SBRT)
Intensity Modulated RT (IMRT)
Particle Beam Therapy (Proton)

48. Why Proton Beam Therapy?
• Bragg peak (1946, Wilson et al. first proposed PBT)
• RBE=1.1

49. 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. 50

51. PBT for Stage I NSCLC

55. 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

57. Dose-volume Histogram (DVH)
100
Proton PTV
90
Proton Spinal Cord
Normalized volume (%)
80
Proton Both Lungs
70
IMRT PTV
IMRT Spinal Cord
60
IMRT Both Lungs
50
3DCRT PTV
40
3DCRT Spinal Cord
30
3DCRT Both Lungs
Tomo PTV
20
Tomo Spinal Cord
10
Tomo Both Lungs
0
0
10
20
30
40
50
Dose (Gy)
60
70
80

58. Normal Tissue DVH

59. Normalized volume (%)
CTV DVH

60. CTV DVH

61. 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

64. 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

65. Proton Therapy Center
Samsung Medical Center

67. Multidisciplinary
approach

69. Importance of Target Delineation
• Target contouring errors generate systematic errors
which no level of image guidance will eliminate.
• Target delineation accuracy cannot be overemphasized!