1. SABR has emerged as an alternative to surgery for medically operable early-stage NSCLC based on case-control studies showing equivalence in outcomes. 2. Randomized trials are still needed to provide level 1 evidence of equivalence since residual differences remain between surgery and SABR cohorts in existing studies. 3. Ongoing trials such as STABLE-MATES, VALOR, and SABRTOOTH aim to address this evidence gap through randomized comparisons of SABR to surgery.

1. "Update on SABR for medically operable
early NSCLC: Current Status".
DR KANHU CHARAN PATRO
MD,DNB(Radiation Oncology),MBA,FICRO,FAROI(USA),PDCR,CEPC
HOD,RADIATION ONCOLOGY
Mahatma Gandhi Cancer Hospital And Research Institute, Visakhapatnam
drkcpatro@gmail.com /M- +91-9160470564
YROC 26th FEB 2023

2. Disclaimer
Dr Shyam Dr Ayush

3. Introduction
• Since decades, the gold standard for treatment of early-stage non-small
cell lung cancer is surgical lobectomy plus mediastinal lymph node
dissection
• Patients in worse health status are treated with sub lobar resection or
radiation treatment.
• With development of stereotactic-body-radiotherapy (SBRT), outcome
of patients treated with radiation was substantially improved.
• Comparison of SBRT and surgical techniques is difficult due to the lack of
randomized trials.
• However, all available evidence in form of case control studies of
population-based studies show equivalence between sub lobar resection
and SBRT indicating that SBRT—when performed by a trained and
experienced team—should be offered to all high-risk surgical patients.
• For patients not willing to take the risk of lobectomy and therefore
refusing surgery, SBRT is an excellent treatment option.

4. LEVELS OF EVIDENCE

5. What is SBRT?

6. The work flow
Pre-SBRT
work up
Simulation
(+/- 4DCT)
Tumor &
OAR
contouring
Plan
analysis &
acceptance
Trial setup
& off line
CBCT
Treatment
delivery &
review
Follow up &
data
collection

7. Patient selection for SBRT
SBRT is recommended in the NSCLC for patients
with
 Stage I and II (T1–3,N0,M0)
 NSCLC who are medically inoperable
 High risk- elderly
 Refuse surgery after appropriate consultation
SBRT has no established role in small cell lung
cancer
 PFT (FEV1 or
DLCO < 40%)
 DM/CAD
 Cerebral
disease
 Pul. HTN
 PS 0-2
 Able to lie flat for
at least one hour

8. 1. SABR for Node-Negative Early-Stage NSCLC
1. BED ≥100 Gy are associated with significantly better local control and
survival
2. For central and ultra-central tumors 4 to 10 fraction regimens are
effective and safe
3. SABR is most commonly used for tumors up to 5 cm in size
2. SBRT has a Developing role
1. Boost following definitive chemoradiation in management of LA-
NSCLC
2. Re-irradiation of locally recurrent disease
3. Intrathoracic oligometastases from various primary histologies
Role of SBRT

9. The
Timmerman

11. NCCN ALGORITHM

12. NCCN ALGORITHM

13. What NCCN SAYS?
1. Early-Stage NSCLC (Stage I, selected node-negative Stage IIA)
2. SABR (also known as SBRT) has achieved good primary tumor control rates and
overall survival, higher than conventionally fractionated radiotherapy.
3. Although SABR is not proven equivalent to lobectomy, some prospective
series have demonstrated similar overall and cancerspecific survival
4. SABR is also an appropriate option for patients with high surgical risk (able to
tolerate sublobar resection but not lobectomy [eg, age ≥75 years, poor lung
function])
5. More modestly hypofractionated or dose-intensified conventionally
fractionated 3D-CRT regimens are less preferred alternatives and may be
considered if referral for SABR is not feasible.
6. Close follow-up and therapy for isolated local and/or locoregional recurrence
after SABR have been shown to improve overall survival in a large
retrospective study

14. What NCCN SAYS?
SABR for Node-Negative Early-Stage NSCLC
1. The high-dose intensity and conformity of SABR require minimizing the PTV.
2. Dosing regimen For SABR, intensive regimens of BED ≥100 Gy are associated with
significantly better local control and survival than less intensive regimens
3. In the United States, only regimens of ≤5 fractions meet the arbitrary billing code
definition of SBRT, but slightly more protracted regimens are appropriate as well.
4. For centrally located tumors (defined variably as within 2 cm of the proximal bronchial
tree and/or abutting mediastinal pleura) and even ultra-central tumors (defined as
abutting the proximal bronchial tree), 4 to 10 fraction risk adapted SABR regimens
appear to be effective and safe, while 54 to 60 Gy in 3 fractions is unsafe and should be
avoided.
5. However, particular attention should be paid to tumors abutting the bronchial tree and
esophagus to avoid severe toxicity.
6. RTOG 0813 evaluated the toxicity of 5-fraction regimens and found no high-grade
toxicities at 50 Gy in 5 fractions
7. SABR is most commonly used for tumors up to 5 cm in size, though selected larger
isolated tumors can be treated safely if normal tissue constraints are respected.

17. TYPE OF LESIONS
• Peripheral lesions
• They are located > 2 cm from the primary bronchi or trachea
• Central lesions
• Located within 2 cm of the proximal bronchial tree and/or abutting
mediastinal pleura
• Ultra-Central lesions
• Lesions abutting the proximal bronchial tree

18. TYPE OF LESIONS

20. Evidences

23. STARS AND ROSEL

25. Pooed demographic

26. RFS AND OS

27. Local- regional
and distant
recurrences

28. SBRT VS SURGERY
Combined ROSEL/STARS analysis (Chang Lancet Oncol 2015):
• n=58 patients from two trials
• T1-T2 (<4 cm) N0 medically operable NSCLC
• SBRT (54 Gy in 3 fractions, 50 Gy in 4 fractions if central) vs
lobectomy and mediastinal lymph node dissection.
• 3-year OS improved for SBRT (95%) vs surgery (79%). Grade 3–4
toxicity 10% for SBRT vs 44% for surgery.

29. Indiana (Timmerman JCO 2006; Fakiris, IJROBP
2009)
• n=70
• T1–3N0 (≤7 cm)
• 60–66 Gy in 3 fx over 1–2 weeks.
• Three-year LC 88%, CSS 82%, OS 43%, regional failure 9%, and distant failure
13%.
• Patients with central tumors had increased risk of grade 3–5 toxicity (27% vs
10%).
• Established “no-fly-zone” of 2 cm surrounding proximal bronchial tree for
3-fraction treatment.

30. Onishi (Cancer, 2004)
• n=245
• T1–2N0 treated
• 18–75 Gy in 1–22 fx
• LF was 8% for BED ≥100 Gy vs 26% for BED <100 Gy.
• Three-year OS was 88% for BED ≥100 Gy vs 69% for BED <100 Gy.

31. RTOG 0236 (Timmerman 2010)
• T1–3N0 (≤5 cm), medically inoperable tumors >2 cm from proximal
bronchial tree treated
• SBRT 20 Gy × 3 over 1.5–2 weeks (54 Gy applying heterogeneity
correction).
• GTV = CTV. PTV = 0.5 cm axial margin and 1 cm superior/inferior
margin.
• 5-year LC 93%, LRC 62%, 31% DM, DFS 26%, OS 40%.

32. RTOG 0915 (Videtic IJROBP 2015)
• Phase II randomized study of 34 Gy in 1 fraction vs 48 Gy in 4
fractions
• Medically inoperable T1-3N0 (≤5 cm) NSCLC
• Single fraction arm had lower risk of serious adverse events (10.3 vs
13.3%).
• 2-year primary control, OS, and DFS were 97% vs 93%, 61% vs 77%,
and 56% vs 71%, respectively.

33. RTOG 0813 (Bezjak ASTRO 2016)
• Phase I/II dose escalation trial for medically inoperable early-stage
NSCLC with centrally located lesions (<2 cm from the bronchial tree)
• Arm I- 57.5 Gy (n=38), Arm II-60 Gy (n=33).
• Dose escalated from 50 Gy in 5 fractions to 60 Gy in 5 fractions.
• 2 yr LC 88–89%, PFS 52–55%, OS 70–73%, grade 3 toxicity 6–7%

34. VUMC (Senthi, Lancet Oncol 2012)
• n=676
• PET+ clinical stage T1–2 N0 NSCLC
• 2/5-yr LF 5/11%, regional failure 8/13%, DM 15/20%.

35. Conclusion
It is a form of high precision radiotherapy delivery technique
• Needs to account for tumor motion
• Needs to be accurate
• Needs to have reproducible setup prior to treatment
Indications
• Stage I–II, inoperable, T1-3N0M0   Definitive SBRT not 3D
• Medically inoperable
• Operable disease who are high risk, elderly
• Refuse surgery

37. RTOG 0618
• Single-arm phase 2 NRG Oncology Radiation Therapy
Oncology Group 0618 study enrolled patients from
December 2007 to May 2010 with median follow-up of 48.1
months (range, 15.4-73.7 months).
• The SBRT prescription dose was 54 Gy delivered in 3 at 18-
Gy fractions over 1.5 to 2.0 weeks.
• Primary end point was primary tumor control, with survival,
adverse events, and the incidence and outcome of surgical
salvage as secondary end points.

38. OS AND DFS

39. Summary
• RTOG 0618 demonstrated that high rates of intrathoracic control can
be achieved with a noninvasive, outpatient alternative to surgery in a
healthier group of patients with earlystage lung cancer.
• This tumor control was achieved with a relatively low rate of toxic
effects.
• Collectively, SBRT for this operable population may be a viable
alternative to surgical resection, which would ideally be compared in
a phase 3, randomized clinical trial.
• Further attempts to perform such a trial are ongoing (eg, VALOR,
Stablemates, and SAbRtooth).

42. HETEROGENOUS DATA

43. Toxicity

46. 23 observational studies
1 Chang et al, Pooled analysis

47. Residual important baseline differences in the surgery and SBRT cohorts could not be eliminated
• Only 8 studies capture PFT.
• Tumor size , location missing frequently.
• 2/3 of surgical pt were staged pathologically vs all SBRT were stages clinically
• Many trials <100BED

48. Lei Peng Metanalysis

49. Lei Peng Metanalysis

50. Lei Peng Metanalysis
• Six retrospective studies
• Total of 11,813 clinical stage I NSCLCs who received wedge resection
or SBRT were included
• The results showed that patients receiving wedge resection had a
significantly better OS (HR = 1.20, 95% CI = [1.07, 1.34], P = 0.002)
than those with SBRT, but no significant difference of DFS (HR 1.53,
95% CI = [0.83–2.83], P = 0.17) was observed
• Our meta-analysis showed that clinical stage I NSCLCs treated with
wedge resection had superior OS than those treated with SBRT.
• However, more prospective clinical trials should be well-designed to
evaluate the optimal treatment modality of early-stage NSCLCs

51. Michiel A. Ijsseldijk metanalysis

52. Michiel A. Ijsseldijk metanalysis
• A total of 100 studies with patients treated for clinical stage I non-
small-cell lung carcinoma were included.
• Long-term overall and disease-free survival after LR was superior
over SBRT in all comparisons
• SR was superior to SBRT. Noncomparative studies showed superior
long-term overall and disease-free survival for both LR and SR over
SBRT
• Results of this systematic review and meta-analysis showed that LR
has superior outcomes compared to SBRT for cI non-small-cell lung
carcinoma.
• New trials are underway evaluating long-term results of SBRT in
potentially operable patients.

53. Michiel A. Ijsseldijk metanalysis

54. Can Li Meta-analysis

55. Can Li Metanalysis
• We identified 11,110 articles, 17 of which were eventually included in
this study; these 17 articles had 17,973 patients (SBRT: 7395; CRT:
10,578).
• Compared to CRT for the treatment of inoperable stage I NSCLC, SBRT
had superior survival in terms of
• With better survival and a lower rate of dyspnea, esophagitis and
radiation pneumonitis than CRT, SBRT appears to be more suitable for
patients with inoperable stage I NSCLC.

56. Can Li Metanalysis

57. Take home message!!
• SBRT is SOC: Med. inoperable/Refuse Surgery: SOC
• Local control is equivalent to surgery.
• Regional/metastatic control: smaller T with properly staged =
Surgery
• Aggressive mediastinal staging is key.
• Need randomized trials for Level I evidence!!(VALOR, SABARTooth,
POSTLIVE..)

58. SBRT VS SURGERY-Trials undergoing
• JoLT-Ca STABLE-MATES trial (NCT02468024)
• VALOR (Veterans Affairs Lung cancer surgery Or stereotactic
Radiotherapy trial, NCT02984761)
• SABRTOOTH (NCT02629458)

59. STABLE MATES

60. STABLE MATES

61. VALOR STUDY

62. VALOR STUDY

63. SABRTooth

64. Summary
• SBRT is an evidence-based and effective treatment option for patients
with stage I NSCLC.
• Superiority to best supportive care and conventional radiotherapy has
been documented in prospective and retrospective studies.
• Local tumor control rates exceeding 90% is consistently achieved and
OS is mainly limited by comorbidities.
• Equivalence to surgery has been consistently reported in matched
pair analysis and studies using propensity score matching but level A
evidence is missing due to a lack of successfully completed randomized
trials: a multi-professional team experienced and trained in SBRT, and
image guided radiotherapy is essential for safe practice.
• Discussion in multidisciplinary tumor boards considering the
perioperative risk of the patient and patient’s preference is important.

65. Why not popular?
• No randomized trials
• Surgeon dominant
• Are we inefficient?
• Cases are coming through surgeon- all filtered

66. 10/20/12 01:12 PM 66
Whenever not
possible, make friends

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10/20/12 01:12 PM

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10/20/12 01:12 PM

69. THANKS