SBRT In Lung and Oligometastatic Cancer...•SBRT and immunotherapy combination appears very...

SBRT In Lung and Oligometastatic Cancer

Dr. Andrea BezjakBMedSc, MD CM, MSc, FRCPC

Staff Radiation Oncologist, Princess Margaret Cancer CentreProfessor, Department of Radiation Oncology

University of Toronto, CanadaFeb 2021.

Disclosures

• No commercial interests

• Acknowledgment of support from the Addie MacNaughton Chair in Thoracic Radiation Oncology at PMH/UT (2004-2019) and contributions from members of the PMH/UHN Thoracic group

• Thank you to Dr Aisling Barry (RMP) for some of the slides

Overview

• SBRT for Early Stage Lung Cancer• Including results of NRG/RTOG 0813 study

• SBRT for Lung Metastases

• SBRT to other sites of (oligo)Metastases

• Future Directions

Take Home Messages

• SBRT lung is safe and well tolerated

• Careful selection of doses depending on Organs at risk (OARs)

• Especially for lymph nodes, adrenal, bone, central tumors

• Goals in oligometastatic disease = Local control, prolonged PFS, QOL

• SBRT and immunotherapy combination appears very promising

SBRT for early stage Lung cancer - Curative

J Clin Oncol 2019

NRG/RTOG 0813 Phase I/II study of 5 fr SBRT for central tumors

SBRT Dose

# pts

accrued

# pts

eligible

# pts

evaluable for

DLT

10Gy X5fr 8 8 8

10.5X5 8 7 6

11X5 18 14 13

11.5X5 43 38 32

12X5 43 33 30

Result - Demographics

•Median age was 72 yrs (range 52- 89)

•57% were female

•45% had squamous cell carcinoma

•39% had adenocarcinoma

•65% had T1 tumors

•84% had PS 0-1

•Median follow up was 26.6 months

•All tumors were central but in different locations -- different OARs at risk

SBRT

dose

# of

evaluable

pts

#of DLTs

(Probability*)

DLT Details

10x5 8 0 (2.0%)

10.5x5 6 1 (2.7%) Hemoptysis (G5)

11x5 13 1 (4.3%) Bradycardia (G5)

11.5x5 32 2 (5.7%) Hypoxia (both G3)

12x5 30 1 (7.2%) Pneumonitis (G3)

*Probability based on a Bayesian logistic model with a=1.266 and 95%

CI = (1.089,1.049).

Results – Dose Limiting Toxicity (DLT)

Results – Worst treatment related Adverse events (AE) at any time

SBRT

Dose # pts

Grade 2

n (%)

Grade 3

n (%)

Grade 4

n (%)

Grade 5*

n (%)

10X5 8 5 (62.5) 0 0 0

10.5X5 7 1 (14.3) 0 0 1 (14.3)

11X5 14 4 (28.6) 1 (7.1) 0 0

11.5X5 38 11 (28.9) 4 (10.5) 0 2 (5.3)

12X5 33 4 (12.1) 5 (15.2) 1 (3.0) 1 (3.0)

*grade 5 AEs = hemoptysis at a mean 13 mo postSBRT

(range 5.5-14mo)

Careful with ultra-central tumors

SBRT for Lung Metastases

SBRT for Lung Metastases

• Technical aspects similar to SBRT for early stage lung ca• Patients often have better pulmonary reserve, better

PS and fewer co-morbidities• Lesions frequently peripheral• However, multiple lesions may present planning

challenges

Previous T2N3 oropharyngeal ca

• 54 year old woman with stage IV colorectal carcinoma

• S/p preoperative chemo-RT + surgery

•Now presenting with low-volume metastatic lung disease, with a dominant right hilar metastasis

• SBRT? Dose?

SBRT Lung or Lymph Nodes?

SBRT for Lung Metastases

• Challenges are more clinical than technical:• Patient selection• Goals of therapy• Benefit/risk in comparison to other options• Level of evidence needed –• Trials for lung metastases from any cancer• Trials of metastases to any organ from a specific cancer

Examples of studies - Colorectal Cancer

• PMH data, 60 pts, CRC liver mets

• Med F/U 28M, med OS 16m

• Improved OS - smaller GTV, PS 0/1, no extrahep dz

Gomez Phase II study of local consolidative therapy for oligometastatic NSCLC (Lancet Oncology 2016)

• 1:1 randomization to local therapy to all sites vs Maintenance /SOR

• 29 pts (study closed early • due to results)• PFS – 12 mo in local

consolidation arm vs 4 mo in standard of care arm

Gomez Long-term results of Phase II studyJ Clin Onc 2019

Iyengar – Phase II trial of consolidative RT for oligometastatic NSCLC (JAMA Oncology 2018)

• Single center study – 28 pts (closed early due to results)

• Standard of care +/- SBRT to 1-5 metastases (or primary)

• PFS 9.7 vs 3.5 mo

Palma – SABR COMET trial (Lancet 2019)

• Ph II RCT, 99 pts

• Primary treated definitely, >3m prior

• Up to 5 mets, up to 3 in any organ

• SOC +/- SBRT (1:2 randomization)

• Median F/U 25 m

• Medan OS 28 vs 41m (p=0.09)

• Median PFS 6 vs 12m

• 3 (4.5%) treatment related mortalities

• 16 key questions

• OMD and the relationship to• Disease characteristics• Disease burden• Timing of OMD• Relation to other treatments• Endpoints• Impact of technology

Radiotherapy and Oncology 2020

The Use of SBRT in (Oliogo)Metastatic Disease

1. Motion Management

2. Simulation and Image Fusion

• CT simulation and MRI simulation

3. Targets and Normal Tissues

4. Planning

• Conformal beams

• From many locations

• Steep dose gradients

Current Studies and Future Directions

• Combination of SBRT with systemic therapy

• Eg in Mutation-driven NSCLC - Early introduction of consolidative SBRT

• SBRT and Immunotherapy combinations

• Clintrials.gov search Feb 2020 = 33 studies actively accruing to RT and IO combinations in thoracic cancers

• Phase I, II, III trials

• Questions being explored : timing, dose, efficacy, ability to deal with IO resistance, oligometastatic setting, abscopal effect etc etc

31

Theelen JAMA Oncology 2019Phase II RCT of Pembro +/- SBRT for stage IV NSCLC

92 pts (76 randomized)SBRT 8Gy x 3Pembro 200mg/kg q 3 w

Primary outcome = ORR at 12 wExpectation = 20% to 50% improvement

Results = 18% vs 26% ORR1.9 mo vs 6.6 mo PFS7.6 mo vs 15.9 mo OS

Welsh et al - Phase I/II Study of Pembro +/- RT in NSCLC with lung or liver metastases (J Immunother Cancer 2020)

20 pts in phase I, 80 pts in randomized phase II – SBRT (50Gy. 4fr) if possible, or standard moderate dose RT (45Gy/15 fr)

How to Translate Innovation into Practice?

How to Translate Innovation into Practice?

We are only as strong as our weakest link….

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Safety, Quality, Peer Review, Standardization, Processes, Raising the Bar…

Advances in Radiation Oncology 2021

Take Home Messages

• SBRT lung is safe and well tolerated

• Careful selection of doses depending on OARs

• Especially for lymph nodes, adrenal, bone, central tumors

• Goals in oligometastatic disease = Local control, prolonged PFS, QOL

• SBRT and immunotherapy combination appears very promising