review of stereotactic body radiotherapy (sbrt ... · max≤ 26 gy = 8% (p = 0.04) •...

CORECanadian Oncology Resident Education Program

Review of Stereotactic Body Radiotherapy(SBRT)/Stereotactic Ablative Radiotherapy

(SABR) for Lung Cancer

Houda Bahig, MD, FRCPCCentre Hospitalier de l’Université de Montréal

Canadian Lung Cancer ConferenceFebruary 9th 2017


Disclosures

• Relationships with commercial interests:

o Grants/Research Support: Variano Speakers Honoraria : Siemens/Varian


Lung SABR reviewOutline

Definition Indications Work-up

Planning Dose Outcomes

Toxicities Follow-up


SABR/SBRT definitionqAdvanced imaged-guided radiotherapy (RT)

• 4D-CT• Cone beam CT, orthogonal X-ray (robotic tracking)

qAblative dose of RT in typically 1 to 8 fractions

qAccurate in the order of 3-5 mm

è Tumor dose escalationè Healthy tissues sparing


Lung SABR Indications

1. Gold standard for inoperable ES-NSCLC• 25% unfit (elderly, co-morbidities)

2. Equipoise for (borderline) operable ES-NSCLC?• Standard = lobectomy + mediastinal LN sampling or dissection• Early RCT closure (ROSEL, STARS, RTOG 1021/ACOSOG Z4099)

• Matched comparisons/systematic reviews… conflicting results

3. (Oligometastatic disease)


• Results from 2 prematurely closed trials: STARS and ROSEL o Lobectomy vs. SABR

• 58 patients with operable T1–2a (<4 cm) N0M0 NSCLC

Operable Patients: Surgery vs. SABR?


Chang et al. Lancet, 2015• 3-year OS in favour of SABR, similar 3-year RFS• Small sample size, underpowered for these end points

Median follow-up 40 mo SABR vs. 35 mo surgery


Moghanaki and Chang, Translational lung cancer research, April 2016

Meanwhile…Treatment decisionè Physician-to-patient discussions (outcomes/toxicities/QoL)è Multidisciplinary tumor board discussion è Inclusion in clinical trials

Operable Patients: Surgery vs. SABR?


ES-NSCLC- Work-up

Mediastinal evaluation includes EBUS/EUS, mediastinoscopy, mediastinotomy, CT guided biopsy.


Histological diagnosis before SABR?

• Favoured whenever possible

• Literature: histological confirmation in 35%-100%

Patients at high risk of complications• Hazardous transthoracic biopsy/repeat biopsy

• FDG-PET + serial CT growth: ≤5% false diagnosis (Ashraf et al. 2011)• Expert opinion + decision model (Louie et al. 2014)

èPrior probability of lung cancer is > 85%• Multidisciplinary tumor board• Not valid in regions with high rates of benign disease


Treatment Planning


Technique• Several technologies possible:o Robotic linear accelerator (Cyberknife)o Arc therapy technique o Conventional linear accelerator

• Specific advantages in particular situationso Likely similar outcomes across platforms (Meta-analysis, Solda et al. 2013)


Planning CT and contouring• Planning CT in treatment position

o Contrast injection for central tumors

• 4D-CT

• IGTV (Lung window WL; -600/1500 HU) o All phaseso Maximum intensity projection (MIP)o End inspiration / expiration

• Typically no CTV expansion

• PTV : 3-5 mm

IGTV

Carri 2014, JTD


Motion management

• Good immobilization o Dual vacuum body immobilisation system

• Good image guidanceo On board Cone beam CT prior to each fractiono Near real-time kV image pair intra-fraction

• Good intra-fraction motion management strategy


Managing RespirationWhat to do in case of large respiratory motion?

1. Use larger internal target volume

1. Abdominal compression

1. Breath-hold technique

1. Respiratory Gating

1. Tumor tracking

Treatment field

Tumor


Managing Respiration:1. Abdominal compression

• Abdominal pressure at planning CT + during treatment

• Scaled screw for reproducible position of the compression plate

• Can reduce tumor motion range ≤ 5 mm (motion up to 20 mm)

• Good lung function to tolerate device

http://ecatalog.elekta.com/oncology/


Managing respiration:2. Breath-hold and Respiratory gating

• Breath-hold techniqueo Treatment planning on a particular phase of 4D CT

o Phase selection

• End-expiration more reproducible (within 2-3 mm)

• End-inspiration decreases lung dose

o Requires good respiratory function and cooperation

• Respiratory gatingo RT during portion of respiratory cycle (30%)

o Patient breathes freely (beam on periodically)

o Respiratory gating system

www.varian.com/oncology/


Managing Respiration:3. Tumor tracking

• Near-real time tumor motion monitoring• Available in some commercial equipment

o Ex: Cyberknife (Accuray, Inc., Sunnyvale, CA)§ In room X-ray system

o Fiducial markers placement (risk of pneumothorax) ORo Direct soft tissue tracking

Direct soft-tissue trackingFiducial tracking


Dose- Prescription

60 Gy (70%) at surface of

PTV

X

86 Gy

60 Gy – Green line covering PTV (70% isodose line)Maximum dose = (60 Gy x 100%)/ 70% = 86 Gy

1. Rapid dose fall-off2. Much higher dose to GTV


Onishi et al. JTO 2007 Retrospective analysis from 14 institutions 257 patients with T1–2 NSCLC

Unclear if éé BED10≥ 100 Gy betterMeta-analysis Zhang et al. Red J, 201134 observational studies BED10 > 146 Gy was associated ê OS

BED10 ≥ 100 Gy associated with improved local control

5-year LC84% : BED10 ≥ 100Gy36% : BED10 < 100Gyp<0.001

5-year OS72% : BED10 ≥ 100Gy50% : BED10 < 100Gyp<0.05

BED10 of 100 Gy= 50 Gy in 5 fx48 Gy in 4 fx = BED10 = 10660 Gy in 8 fx = BED10 = 10554 Gy in 3 fx = BED10 = 151


Dose: Risk-adapted strategy• Doses from 48 to 60 Gy in 3–8 fractions

• CHUM guidelinesa) T1N0 no OAR

60 Gy in 3 fractions

b) T1N0 with chest wall contact or T2N060 Gy in 5 fractions

c) Central lesions

50-60 Gy in 5 fractions

60 Gy in 8 fractions

Central per RTOG 0813≤2 cm to proximal bronchial tree or

PTV touchingmediastinal/pericardial pleura


Time between fractions?

CHUM guidelines: > 40 hours between fractions


Outcomes


Initial results (Timmerman, 2010)• 55 patients - Phase 2 multicentric• Peripheral T1-2N0 ≤5cm NSCLC – Inoperable• 54 Gy in 3 fractions • 3-year primary tumor control rate was 98%


RTOG 0236- Long term results

• 5y primary tumor + involved lobe failure (local) 20%• 5y locoregional failure 38%• 5y disseminated failure 31%• 5y DFS 26%

Median follow-up 4 years (7 years for survivors)

5y primary tumorrecurrence 7%

5y OS 40%


45 studies, 3771 patientsSABR for stage I NSCLC from 2006-2013

2y LC 91% 2y OS 70%


Toxicities


SABR ToxicitiesLung

Chest wall

Skin

Brachial plexus

Central Airway

Esophageal

Vascular

Vagus nerve

Central tumors


SABR Toxicities• < 5-10% risk grade ≥ 3 toxicities• 90-day mortality rate < 1% (Chang, Lancet 2015)

o Severe COPD : 0% 30-day mortality (Palma, Red J. 2012)

• Various dose constraints (adapted to fractionation)o Prospective data (RTOG 0236, RTOG 0813)

• Vary witho Doseo Fractionationo Localisationo Volumeo Combination with systemic therapies


Radiation Pneumonitis

• 2% grade ≥ 3 RPo Risk factors

o Mean lung dose and V20 (In clinic, also V5 and V10)o Older ageo Larger tumor size

88 studies, 7752 patients


• Systematic review (Chen et al. ASTRO 2016)o 13 SABR studies (122 patients with ILD)- mostly inoperableo 16% treatment related deatho 26% ILD-related grade 3 ≥ toxicity

Advanced cystic changes

Severe Toxicities with ILD

SABR in ILD +è 20% mortality from grade 5 RP


Chest wall toxicities• Most frequent

o Chest wall pain 5-25% (any grade) / Rib fracture <5% o 2% ≥ grade 3

• Within first 2 years post-SABR• Tumors ≤1–2 cm from chest wall at higher risk


Chest Wall Toxicities Review

Limit V30 to <30 cc and V60 to <3 cc

Siva et a.l J Med Im RO, 2012


Skin Toxicities• Hoppe et al. 2008

• 8% (4/50 patients) grade ≥ 2• Much rarer in our practice…

• Risk factors • Tumor < 5 cm to posterior skin• High back dose (>50%)• Small number of beams (3 vs. more)• Obesity

Always check skin dose for posteriortumor close to skin!


Central airway: Life threateningcomplications

• Proximal bronchial treeo Bronchial stenosis and atelectasiso Fistulao Necrosis and fatal hemoptysis

• Risk-adapted dose regimen for central tumorso Systematic review (Senthi, 2013)

o 563 central tumors• 60 Gy in 8 or 50 Gy in 5 most common

• ≤ 3% treatment-related mortality 1% with BED3 �210 Gy

• < 9% grade 3-4 toxicity • Strict observance of available dose constraints

Kang et al. Cancers, 2015


Other toxicities• Brachial plexopathy (Forquer et al. Rad Onc 2009)

o 7/37 apical tumors with grade 2-4o 2-year brachial plexopathy risk (3-4 fractions)

• Dmax > 26 Gy = 46% • Dmax≤ 26 Gy = 8% (p = 0.04)

• Vagal/recurrent laryngeal neuropathy (Shultz et al. PRO 2014)o 2/67 upper lobe lesions

• Vocal cord paralysis• No clear dose response• 1 re-irradiation et 1 connective tissue disease


Follow-upESMO guidelines (2014)• Chest CT q6 months for 3 y• Then annual

High risk features

1. Enlarging opacity2. Sequential growth3. Enlargement after 12-m4. Bulging margin; 5. Loss of linear margin6. Air bronchogram loss7. Sup/inf growth

�3 è ≥90% sensitivity & specificity

• SUVmax >5 highly suggestive of recurrence(Bollineni 2012)

Huang et al. Green J, 2013


Lung SABR: Conclusion• Gold standard inoperable ES-NSCLC

o Option in (borderline) operable patientsèProspective studies will provide definitive answers

• Requires robust IGRT and motion management methodso To avoid tumor miss and increased toxicities to OAR

• Risk adapted dose selection strategyo Based on location and sizeo BED10 ≥ 100 Gy = improved LC

• Generally minimal severe toxicitieso Caution in ILD and central/ultracentral tumors


Thank you!

v Radiation Oncologistso Dr Edith Filiono Dr Marie-Pierre Campeau

v Medical Physicisto Karim Zerouali

Aknowledgements:

review of stereotactic body radiotherapy (sbrt ... · max≤ 26 gy = 8% (p = 0.04) •...

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