SBRT/SABR indications and results, just a brief overview; also, our results at NEARMC in Anniston, AL, 2013-2016

1. Stereotactic Body
Radiotherapy (SBRT) for
Early Stage Lung Cancer:
A Brief Overview
Todd J. Scarbrough, M.D. / Medical Director, NEARMC Rad Onc
COC Survey
April 26, 2016

2. A Payor’s Definition of SBRT
1. Tx with high degree of accuracy (i.e. use of image guidance)
2. Tx with high degree of precision (“conformality”)
3. Tx with a high fraction dose ≥5 Gy for ≤5 fractions

3. Precision vs. accuracy in radiation oncology:
IMRT (precise) vs. IGRT (accurate)
IMRT: intensity modulated radiotherapy
IGRT: image guided radiotherapy
Ting JY, Scarbrough TJ. Intensity-modulated radiation therapy and image-guided radiation therapy: small
clinic implementation. Hematol Oncol Clin North Am. 2006 Feb;20(1):63-86.

4. What’s so special
about SBRT?

5. *HOT TOPIC*
Already 622 published studies of
lung SBRT for lung CA by 2016!

7. DVH
(dose volume histogram; a
graphical representation of
doses delivered to tumor
targets and normal organs)
tumor
100% dose volume
50% dose volume
In general, we desire maximum dose conformality in our plans…
The relatively rapid fall-off of dose from the 100% to 50% region indicates a
relatively very conformal plan in this situation…

8. DVH
(dose volume histogram; a
graphical representation of
doses delivered to tumor
targets and normal organs)
tumor
100% dose volume
50% dose volume
In general, we desire maximum dose conformality in our plans…
The relatively rapid fall-off of dose from the 100% to 50% region indicates a
relatively very conformal plan in this situation…
Whether treating “standard dose” (e.g.
70 Gy/35 fx) or SBRT (e.g. 60 Gy/3 fx),
maximum conformality is desirable and
achievable. Increased conformality is
empirically expected to lower
complication probabilities (in this case,
lung and soft tissue) no matter the
fractionation scheme.

9. Again… “standard” XRT for early stage lung
CA is different how?
1. Tx with high degree of accuracy (i.e. use of image guidance)
2. Tx with high degree of precision (“conformality”)
3. Tx with a high fraction dose ≥5 Gy for ≤5 fractions

10. “[SBRT] techniques are unusual in the high
technology realm of radiation treatment in
that they require more specialized training
of physicians and physicists rather than
specialized equipment.”
Timmerman et al, Technology in Cancer Research and Treatment –
2003
SBRT: A complete paradigm shift in how we dose & prescribe radiation therapy,
and more of a revolution clinically than technologically…
ALTHOUGH… image guidance technology was not widely available in 2003,
and few would do SBRT without IGRT in2016!

11. IMAGING AT TREATMENT TIME:
The Cone Beam CT

12. Stereotactic Body
Radiotherapy
(SBRT):
Why more effective than older-style
XRT?
Technology, dose… and the immune system?

13. “Linear quadratic” formalism where
BED = biologically effective dose
n = number of treatment fractions
d = dose per fraction (Gy)
α/β = 10 Gy for tumor kill; 3 Gy for late effects
Total Dose
(Gy)
No. fractions Late effects
(Gy3)
Tumor kill
(Gy10)
Equiv. total
dose in 2 Gy
fractions for
tumor kill
70 35 117 84 70
48 4 240
105% hotter
106
26% hotter
88
50 5 217
85% hotter
100
19% hotter
84
60 4 360
208% hotter
150
79% hotter
126
60 3 460
293% hotter
180
114% hotter
150
SBRTregimens
We mitigate against this using conformality
(IMRT e.g.) and accuracy (IGRT e.g.).
This is desirable (i.e., the more the better), but
is tempered against late and/or acute effects.

14. Radiation “abscopal” effects are seen much more commonly with high-dose SBRT treatments
“… reduction of tumor burden after ablative RT largely depends on T-cell responses.
Ablative RT dramatically increases T-cell priming in draining lymphoid tissues, leading to
reduction/eradication of the primary tumor or distant metastasis in a CD8+ T cell-
dependent fashion.”

16. Generation of a tumour-specific
immune response through
modification of the tumour and
its microenvironment
Changes in an irradiated tumour (A) promote rejection
by effector T cells (B). Dendritic cells loaded with
tumour antigens migrate to lymph nodes (C) and
activate T cells that inhibit metastases (D). Tumour-
associated macrophages promote progression by
secreting factors that include matrix
metalloproteinases and immunosuppressive cytokines
(E). HMGB-1=high-mobility-group protein B1.
CXCL16=CXC chemokine 16. ICAM-1=intercellular
adhesion molecule 1. MHC-1=major histocompatibility
complex class I. VCAM-1=vascular cell adhesion
molecule 1. MDSC=myeloid-derived suppressor cells.

17. Radiation treatment field for a patient in the abscopal pilot trial with thymic carcinoma. Sagittal (A) and coronal (B) views of two metastatic
lesions in a case of poorly differentiated thymic carcinoma.Two parallel opposed radiation fields treated the most caudal metastasis, deliberately
excluding the apical one.

18. The Standard of Care in Early Stage Lung CA
• American College of Chest Physicians Evidence-based Clinical Practice Guidelines in 2007
determined that “surgical resection remains the treatment of choice for stage I and II
NSCLC.”
• Lobectomy or greater anatomical resection has consistently been reported to achieve local
control rates of >90% for stage I NSCL. ACCP guidelines: lobectomy preferred over sublobar
resections (with wedge resection or segmentectomy).
• In patients able to tolerate operative interventions but thought not to be able to undergo a
lobectomy, ACCP clinical practice guidelines recommend sublobar resection over radiation
therapy or other ablative techniques if medically operable.
• HOWEVER… resection as “the” standard does have several limitations.
• 15-20% of patients are unable to undergo or refuse definitive surgical resection.
• National Cancer Data Base study assessing 124,418 major lung resections from 2007
to 2011 found a 30-day mortality rate of 2.8% and 90-day mortality rate of 5.4%
(whereas these rates are ~0% with radiation approaches). Pezzi et al. Ninety-day mortality after
resection for lung cancer is nearly double 30-day mortality. J Thorac Cardiovasc Surg 2014;148:2269-77.
• Although lobectomy is considered the standard-of-care surgical procedure for stage I
NSCLC, 5-15% of patients require a bilobectomy and another 4-15% require a
pneumonectomy which are known to increase the risk of perioperative mortality
compared with lobectomy.

20. Stereotactic Body
Radiotherapy
(SBRT):
Selected Results for Early Lung CA

21. Timmerman et al
RTOG 0236
2004-06
N = 55
Phase II prelim results
Estimated 3 year “lobar”
control rate: 91%
3y LRC: 87%

22. Retrospective cohort,
from Wm. Beaumont,
2003-08
Stage IA/B NSCLC
Median f/u = 2.5y
Surgery N=69
SBRT N=58
Surgery: wedge
resection, “ineligible” for
lobectomy
SBRT: Medically
inoperable, but
technically resectable

23. TUMOR LYMPH NODES
TUMOR or NODES ANY FAILURE

25. Chang et al. Lancet Oncol 2015;16:630-7.
• The STARS (in the US @ MD Anderson) and ROSEL (@VU Netherlands) trials were
designed to analyze the SBRT vs. surgery question.
• Patients had to have path dx in the STARS but not in the ROSEL. All patients had to be
medically/surgically operable and have T1-2N0 (assessed by staging with suspicious
nodes assessed by sampling) tumors <4 cm.

27. • 19 lobectomies
5 VATS lobectomies
1 wedge
1 VATS N+
1 aborted (distant dz)

30. • Small patient numbers, OS p=0.037 in favor of SBRT. Not overwhelming! Recent
matched pair analyses (abstract only, 286 patients total… http://bit.ly/1QxmuyO)
suggest better OS for surgery… but, again, selection bias?
• The idea of radiation and surgery being equals is provocative however… or maybe
not (head/neck cancer, anal cancer, cervical CA, breast mastectomy vs
lumpectomy+XRT, bladder CA, skin CA, etc etc).

31. • Overall survival (OS)
and local control (LC)
outcomes on 8
patients over a ~2.5
year period
• Low patient numbers,
but remember two
international trials
over several years at
large cancer centers
accrued 31 patients!
• OS = 100%
• LC = 100%
• Median survival and
LC not calculable at
this point due to zero
death or failure
events
NEARMC Anniston
SBRT outcomes
2013-2016

32. Stereotactic Body
Radiotherapy
(SBRT):
Would you use a cute baby in
a presentation about lung cancer?

34. Pre-SBRT, March 2010 Post-SBRT, December 2011

35. SBRT patient A.B.
Stage IA NSCLC
(adenosquamous)
56 Gy/4 fx
PET SUV Max 7.8
PRE-TREATMENT
AUGUST 2013
POST-TREATMENT
APRIL 2016
PET SUV Max 1.6
NEARMC 1st SBRT patient
Alive & well ~2.5 years after treatment 

36. SUMMARY
•Lung SBRT differs primarily from standard lung XRT (in the “modern clinic”) in
terms of dose/fractionation (this difference is large!)… the difference in terms of
“lung sparing” and precision/accuracy is small because high precision/high accuracy
treatments were already being utilized.
•Lung SBRT is a valid (superior?) treatment option for all patients with Stage I
NSCLC based on the available data. It seemed clear in the past that surgical
methods had higher control rates than radiation therapy… but with SBRT, this
seems much less clear now.
•SBRT dose regimens deliver lower (15-30% less) total treatment regimen doses
than standard radiation therapy, but much higher (500 to 1000% more) daily
fractional doses. It’s the latter difference that likely accounts for higher local control
rates.
•Abscopal effects of XRT are found to be higher at “ablative” doses secondary to T-
cell mediated immune responses. These effects may have clinical implications.
•Active trials in America and Europe are underway looking at surgery vs. SBRT for
Stage I NSCLC. But based on available evidence, SBRT for lung cancer patients is
likely being under-offered/underutilized.