This document summarizes information on radiosurgery for lung cancer. It discusses stereotactic body radiation therapy (SBRT) as a technique that uses precisely targeted radiation to treat small or moderate lung tumors with a large dose per fraction. Studies show SBRT provides better local control and survival rates than conventional radiation for early stage lung cancer and results similar to surgery with less toxicity. For central tumors, lower SBRT doses are safer to reduce risks of excessive toxicity. SBRT is shown to be effective for tumors over 4 cm and in elderly patients.

1. Radiosurgery
for Lung Cancer
Robert Miller MD
www.aboutcancer.com

2. 0%
20%
40%
60%
Local Regional Distant
Stage Distribution for Lung Cancer
16% 22%
57%
Very few are diagnosed at an early stage

3. 0%
20%
40%
60%
Local Regional Distant
5 Year Survival for Lung Cancer
55%
28%
4%
Cure rate is still poor even in early stages

4. Age Distribution at Diagnosis
SEER Data 2009-2013

8. 0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 1 2 3 4 5
Stage 1
Stage 2
Stage 3
Stage 4
Observed Survival in the US (2003-2009) NSCL
51%
31%
14%
3%

9. Survival by Stage with Surgery
Stage Clinical 5 Year Pathologic 5 Year
IA 60 months 50% 119 month 73%
IB 43 43% 81 58%
IIA 34 36% 49 46
IIB 18 25% 31 36%
IIIA 14 19% 22 24%
IIIB 10 7% 13 9%
IV 6 2% 17 13%
J Thorac Oncol 2007; 2:706

10. Conventional Radiation for
Stage I and II NSCL
Years Over All Survival Cancer Specific
Survival
2 years 22 – 72% 54 – 93%
5 years 0 – 42% 13 - 39%
Cochrane Database Syst Rev. 2001

11. Stereotactic body radiation therapy (SBRT) is a technique that utilizes precisely
targeted radiation to a tumor while minimizing radiation to adjacent normal
tissue. This targeting allows treatment of small- or moderate-sized tumors in
either a single or limited number of dose fractions.
SBRT has been defined by the American College of Radiology (ACR) and
American Society for Radiation Oncology (ASTRO) as the use of very large
doses per fraction
SBRT

12. Stereotactic Ablative Radiotherapy (SABR)
Radiation delivery to a demarcated tumor target using:
optimal immobilization
motion accounting
many small fields
accurate targeting
heterogeneous target dose
steep dose gradients outside targets
large dose per treatment with ablative intent

13. May use motion control
Upper Threshold
Lower Threshold
Playba
ck
Indicat
or
Breathing Signal
Beam On /
Off
Indicator

14. Conformal High Dose

15. Techniques for Hitting the Tumor with
a High Dose of Radiation
Highly Targeted Conventional (traditional)

17. Large dose per fraction = greater BED
(biologically effective dose)
Assume an alpha/beta ratio of 10 / from RTOG 0915

18. Tomotherapy

19. T1 Adenocarcinoma / 10Gy X 5 with Tomotherapy
Original CT Radiation Plan
Original PET 1 Year PET

20. Squamous Cancer
SBRT with Tomo
PET 8 months later

21. Contour in
the cancer
(GTV)
Use the CT
and PET to
identify the
gross tumor
volume
(GTV)
Or multiple
scans to
account for
movement
are combined
to create ITV
(internal
target
volume)

22. Add a
margin
around the
target (PTV)
Need to
make the
target a
little bigger
to account
for
movement
or set up
problems,
but keep the
PTV
(planning
target
volume) as
small as
possible

23. Add a
margin
around the
target (PTV)
Review the
images in
all
dimensions

24. Add in the other Organs to Measure the Radiation to Normal Structures
Computer will track doses to ensure the normal structures are protected

25. PET before SBRT Target PET 2 months Later
80 yo man with adenocarcinoma LUL / Tomo 10Gy X 5

26. Cyberknife

27. Cyberknife for Lung Cancer

28. Complications from CT Needle Biopsy or Fiducial Placement

29. Cyberknife for Lung Cancer

30. Radiosurgery or SBRT for Early Stage Lung
Cancer
Are the results better
than with
conventional
radiation?
Are the results as
good as conventional
surgery?

31. Does it Work?
• It’s better than doing nothing
• It’s better than conventional radiation (3D conformal or daily radiation for 6
weeks)
• It’s as good if not better that wedge resections or sub-lobar resections
• It’s probably better than risking surgery in ‘high risk’ patients (old or poor
medical status)
• It may be as good as lobectomy

32. A Comparison of Stereotactic Body Radiation Therapy (SBRT) Versus No Treatment
in Medically Inoperable Patients With Early-Stage Non-Small Cell Lung Cancer
(NSCLC)
From August, 2005 to June, 2013, 147 pts were treated with SBRT at a single
institution. The thoracic RT consisted of 45-66 Gy/3 F delivered in 9 days. The
control group of 43 untreated pts from Funen County, Denmark with early-stage
NSCLC, from 2000 to 2012, was extracted from the Danish Lung Cancer Register.
Jeppesen. IJROBP 2014;90:S642
SBRT No Rx
Survival 40 months 9.9 months
Survival/5y 37% 6%
Lung Cancer
cause of death
39% 77%

33. Conventional Radiation versus SBRT
Therapy Local Control Survival/3 Y
Conventional 30 – 40% 20 – 35%
SBRT 97.6% 56%
Timmerman RTOG 0236 / JAMA 2010;303:1070

34. Improved Local Control is Related to Improved Survival

35. Cause specific Survival
Radiosurgery Results
Robert Timmerman IJROBP 2009;75:677
Months

36. Years
Radiosurgery Results – Stage I
Cause Specific Survival
Onishi IJROBP 2011;81:1352

37. 0236 A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment
of Patients with Medically Inoperable Stage I/II Non-Small Cell Lung Cancer
0618 A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment
of Patients with Operable Stage I/II Non-Small Cell Lung Cancer
0813 Seamless Phase I/II Study of Stereotactic Lung Radiotherapy (SBRT) for Early
Stage, Centrally Located, Non-Small Cell Lung Cancer (NSCLC) in Medically
Inoperable Patients
0915 A Randomized Phase II Study Comparing 2 Stereotactic Body Radiation Therapy
(SBRT) Schedules for Medically Inoperable Patients with Stage I Peripheral Non-Small
Cell Lung Cancer

38. Long-term Results of RTOG 0236: A Phase II Trial of Stereotactic Body Radiation
Therapy (SBRT) in the Treatment of Patients with Medically Inoperable Stage I
Non-Small Cell Lung Cancer Timmerman IJROBP 2014;90:S30
n = 55 / 18 Gy per fraction X 3 fractions (54 Gy total)
5-year primary tumor failure rate was 7%
5 year survival 40% / median of 4 years
Grade 3 side effects in 27% . Grade 4 in 4% / no Grade 5

39. Timmerman JAMA 2010;303:1070
Stereotactic Body Radiation Therapy for Inoperable Early Stage Lung Cancer
RTOG 0236
18Gy X 3
OS 55.8%
DFS 48%

40. RTOG 0618: Stereotactic body radiation therapy (SBRT) to treat operable early-
stage lung cancer patients. The study opened December 2007 and closed May
2010 after accruing a total of 33 pts. Of 26 evaluable pts, 23 had T1, and 3 had T2
tumors. Median age was 72 years / dose 20Gy X 3
tumor failure rate of 7.7% / 2 years
2-year survival 84.4%
J Clin Oncol 31, 2013 (suppl; abstr 7523)

41. 34Gy X1 12Gy X 4
Local Control/1y 97% 93%
Survival/2y 61% 78%
Side Effects 10% 13%
RTOG 0915
IJROBP 2015;93:757
A Randomized Phase 2 Study Comparing 2 Stereotactic Body Radiation
Therapy Schedules for Medically Inoperable Patients With Stage I
Peripheral Non-Small Cell Lung Cancer

42. CyberKnife with tumor tracking: an effective treatment for high-risk surgical
patients with stage I non-small cell lung cancer
Chen Front. Onc. Feb 2012
N = 45 / 42-60Gy in 3 fx
Local regional control at 3 years: 91%
Overall survival at 3 years: 75%
Overall Survival
Years

43. Outcomes After Stereotactic Lung Radiotherapy or Wedge Resection for Stage
I Non–Small-Cell Lung Cancer
Grills Journal of Clinical Oncology 28, no. 6 (February 2010) 928-935.
One hundred twenty-four patients with T1-2N0 NSCLC underwent wedge
resection (n = 69) or image-guided lung SBRT (n = 58) from February 2003
through August 2008. SBRT was volumetrically prescribed as 48 (T1) or 60 (T2)
Gy in four to five fractions.
SBRT reduced the risk of local recurrence (LR), 4% versus 20% for wedge (P =
.07). Overall survival (OS) was higher with wedge but cause-specific survival
(CSS) was identical.

44. Local Regional Control
Years
SBRT
Wedge
Resection
Grills Journal of Clinical Oncology 28, no. 6 (February 2010) 928-935.

45. Cause Specific Survival
Years
Grills Journal of Clinical Oncology 28, no. 6 (February 2010) 928-935.
SBRT
Wedge
Resection

46. Lobectomy, Wedge Resection, or Stereotactic Radiotherapy (SBRT) for Stage I
Non-small Cell Lung Cancer: Which Treatment Yields the Best Outcome?
Lobectomy Wedge SBRT
Local-regional recur/2y 2% 25% 9%
Overall Survival/2y 85% 91% 72%
Cause Specif Surv/2y 97% 96% 92%
Welsh. IJROBP 2010;78:S180

47. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-
small-cell lung cancer: a pooled analysis of two randomized trials
Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a (<4
cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to
SABR or lobectomy with mediastinal lymph node dissection or sampling
Chang in Lancet Oncology 16:630. June 2015

48. Outcome SABR Lobectomy
OS/3y (overall survival) 95% 79%
DFS/3y (progression free) 86% 80%
Toxicity
Grade 3 10% 44%
Grade 4 0% 4%
Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-
small-cell lung cancer: a pooled analysis of two randomized trials
Chang in Lancet Oncology 16:630. June 2015

49. Outcomes of stereotactic body radiotherapy (SBRT) in 175 patients with stage I
NSCLC aged 75 years and older
Since 2003, 175 consecutive patients (67% male; 32% female) were treated with SBRT at
a single center. The median age was 79 years, with 47% of patients aged 80 years or
older. 56% of patients had T1 lesions and 44% T2 tumors.
Risk-adapted SBRT schemes were used with the same total dose of 60 Gy in 3 (31%), 5
(53%) or 8 fractions (16%) depending upon risk for toxicity.
Senan Journal of Clinical Oncology 27, no. 15S (May 2009) 9545-9545.

50. All patients completed planned SBRT and survival rates at 1 and 3 years were
85% and 46%.
60% of patients reported no early side effects, and fatigue (31%), cough (6%),
dyspnea (5%), local chest wall pain (3%) and chest wall erythema (2%) were
observed in others.
Severe late toxicity was uncommon, with RTOG Grade 3 or higher radiation
pneumonitis observed in 2%, radiation-induced rib fractures in 2%, chronic chest
wall pain in 3%, and non-malignant pleural effusion in 2% of cases
Senan Journal of Clinical Oncology 27, no. 15S (May 2009) 9545-9545.
Outcomes of stereotactic body radiotherapy (SBRT) in 175 patients with stage I
NSCLC aged 75 years and older

51. Survival With Stereotactic Body Radiation Therapy (SBRT) and Conventional
Radiation Therapy (CRT) in Stage I Non-Small Cell Lung Cancer Patients in the
Veterans Affairs System
2001 to 2010 along with increased SBRT utilization from 15.6% to 47.3%,
and PET utilization from 12.0% to 69.4%.
Boyer IJROBP 2016;96:S9
SBRT Conventional
Overall Survival/4y 30% 19.2%
DSS/ Survival / 4 y 54.7% 33.7%

52. Stereotactic Body Radiotherapy (SBRT) for Lung Lesions > 4 cm: Safety and
Efficacy
Woody. IJROBP 2011;81:S603 Cleveland Clinic
Between 2005 and 2010, 51 lesions ranging from 4 to 7.2cm (20 > 5 cm) in 51 pts
were treated. Forty (78%) were non small cell lung cancer (NSCLC) and 11
(22%) were oligometastatic disease.
Local control at 12 and 24 months was 100 and 80.8% respectively. Loco-regional
control at 12 and 24 months was 88% and 71% respectively.
SBRT appears safe for lung lesions >4cm. Local control was excellent, with
distant failure the primary form of failure. There appears to be an association
between higher doses and tumor control.

53. 3 X 18 or 20 Gy
5 x 10Gy

54. Side Effects and
Toxicity of SBRT for
Lung Cancer

55. Stereotactic body radiation therapy of early-stage non–small-cell lung
carcinoma: Phase I study
McGarry IJROBP 2005;63:1010
8.0 Gy/fraction for 3 fractions (total dose: 24 Gy / Radiation was given once
daily with fractions separated by 2–3 days.
The maximum tolerated dose was not achieved in the T1 stratum (maximum
dose = 60 Gy), but within the T2 stratum, the maximum tolerated dose was
realized at 72 Gy for tumors larger than 5 cm.
Dose-limiting toxicity included predominantly bronchitis, pericardial effusion,
hypoxia, and pneumonitis.

56. Excessive Toxicity When Treating Central Tumors in a Phase II Study of
Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage
Lung Cancer
Timmerman JCO 2006:24:4833
staged T1 or T2 (≤ 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients
had comorbid medical problems that precluded lobectomy. SBRT
treatment dose was 60 to 66 Gy total in three fractions during 1 to 2
weeks.
Patients treated for tumors in the peripheral lung had 2-year freedom
from severe toxicity of 83% compared with only 54% for patients with
central tumors.

57. Timmerman JCO 2006:24:4833
“No Fly Zone” Avoiding High Dose Centrally

58. What dose is safe for central
cancer

59. Efficacy and Toxicity Analysis of NRG Oncology/RTOG 0813 Trial of Stereotactic
Body Radiation Therapy (SBRT) for Centrally Located Non-Small Cell Lung Cancer
(NSCLC)
Bezjak IJROBP 2016;96:S8
PET staged T1-2 (<5 cm) N0M0 centrally located NSCLC (within or touching the
zone of the proximal bronchial tree or adjacent to mediastinal or pericardial pleura)
were successively accrued onto a dose-escalating 5 fraction SBRT schedule ranging
from 10-12 Gy/fraction (fr) delivered over 1.5-2 weeks.
Phase I data analysis revealed that maximum tolerated dose was the highest dose
level allowed on the study, 12 Gy/fr x 5 fractions. Two-year OS rates of 70% in this
medically inoperable group of elderly pts with comorbidities were comparable to
pts with peripheral early stage tumors.

61. Author Local Control Rate
Timmerman 95%
Chang 57-100%
Milano 73%
Song 85%
Haasbeek 93%
Rowe 94-100%
Nuyttens 76-85%
Chang 97%
Radiosurgery for Central Lesions
Chang. IJROBP 2014;88:1120

62. Instead of 50Gy in 4 fractions they are using 70Gy in 10 fractions
Results: Local Control (3y) WAS 96.5% and overall survival (3y)
was 70.5%
Conclusion: as long as lower dose constraints are used the
outcome for central lesions is as good as peripheral
Is it safe to use
radiosurgery for
central lesions?

63. Pulmonary VeinBronchus
Esophagus
Cord Skin
Chestwall
Lung
Published dose limits for the normal
structures near the target

65. Normal structures that
need to be identified
(contoured) so that the
computer can keep
track of the radiation
exposure and ensure it
stays in a safe range

67. Maximum Dose Constraints (to normal structures) for SABR
(from Stablemates Trial)

68. RTOG 0236 Timmerman JAMA 2010:303:1070
Side Effects of SBRT

69. Rib Fractures After Stereotactic Body Radiation Therapy for Primary Non-
small Cell Lung Cancer
Oguir IJROBP 2012;84:S596
Between November 2001 and April 2009, 177 patients who had
undergone SBRT were assessed for clinical symptoms and underwent
follow-up thin-section computed tomography (CT).
Forty-one patients were found to have rib fractures on follow-up thin-
section CT. The frequency of rib fractures was 23.2%, appearing at a
mean of 21.2 months (range, 4 -58 months) after completion of SBRT.
The frequency of chest wall pain in patients with rib fractures was
34.1% (14/41), and was classified as Grade 1 or 2.

70. Limiting Chest Wall Toxicity by Adapting the Dose Schedule and Dose
Constraints in Stereotactic Body Radiation Therapy for Early-Stage Lung
Cancer
IJROBP 2016:96:E457
60 Gy (range, 54 – 60). SBRT was delivered in 3 fractions for patients with a
CW V30 of less than 30cc. If the CW V30 exceeded 30cc, 5 fractions were
delivered and the SBRT plan was optimized on the biologically equivalent
parameter of CW V30: CW V37 <30cc.
Three hundred and eighty-one lesions were treated in a cohort of 363 patients
with a median follow-up of 17 months (range, 1 - 62). Twenty patients (6%) had
CW toxicity: 13 patients (4%) developed CW pain and 9 patients (3%)
developed rib fractures.

71. Dose–effect analysis of radiation induced rib fractures after thoracic SBRT
Barbara Stam
N = 466 / Dose was 18 Gy X 3
Based on Max dose to ribs
37.5Gy = 50%
<22.5Gy = < 5%
http://www.thegreenjournal.com/article/S0167-8140(17)30009-9

72. Side Effects of SBRT
80 yo 2.7 cm adenocarcinoma / 10Gy X 5 with Tomo
Tomo Radiation CT CT 4 months later
Note: mediastinal mass was thyroid goiter

73. Same patient, PET at 4 months, not hypermetabolic and assumed to be radiation
fibrosis

74. Same patient, PET at 12 months, not hypermetabolic and assumed to be radiation
fibrosis

75. Compare 3-year
survival in high risk
stage I NSCL between
SAbR (18Gy X 3) and
Sublobar resection

76. High-Risk =
Minimum of 1 major
or two minor criteria

77. • SABR/SBRT has achieved primary tumor control rates and
survival , comparable to lobectomy and higher than 3D-CRT
In non-randomized comparisons in medically inoperable
or older patients
• SBRT is an option if they cannot tolerate a lobectomy,
with local control and survival comparable to wedge resections
• In partially completed randomized trials found
outcome similar to lobectomy with lower toxicity

78. • Intensive Regimens (BED >100Gy) have better local
control and survival
• For central lesions 4-10 fraction risk-adapted regimens
appear to be safe and effective (while 54-60Gy/3 should
be avoided)
• For central lesions (from RTOG 0813) 50Gy in 5 fx appears
safe
• Most commonly used up to 5cm but larger lesions can be treated safely if
the dose constraints are met

79. Comparable Survival Data for Stage I Lung Cancer