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Lung cancer• Early lung cancer: Surgery & Radiosurgery have similar results
• However, NO level I evidence regarding role of Surgery or SBRT in early NSCLC
• In meta-analysis, SBRT is similar to surgery after match pair analysis
• RT dose should be BED10 >100 Gy
• 54-60Gy/3# is preferred treatment fractionation schedule
• Fiducial based Robotic Radiosurgery (CyberKnife) have not ITV & irradiated volume is lowest
• Prospective ongoing studies will provide answers
Carcinoma lung: Management option
Majority (80%) of NSCLC present with advanced disease (stage III & IV)2-Yr Survival in advanced NSCLC is ONLY 30-40%
ONLY 20% of NSCLC present at early stage (Stage I&II)
Stage I NSCLC: treatment is surgery & 5 Yr-OS is 70-80%
However, a proportion of patient with poor lung function or PS are not suitable for urgery and are candidate for alternative treatment, eg: Conf RT, Cryotherapy, ---therapy & SBRT
So, SBRT in primary lung cancer is suitable in only a very small cohort of patient
With modern SBRT techniques, RT has become more relevant option in early lungBut, surgery has also become more effective and less risky with VATS
NSCLC: SURGERY is the best option• Morbidity and mortality in elderly and in patients with co-morbidities
• Requirement for extensive resection in 10-20%
• Deterioration in QOL
• Relapses 30%, second tumors 1-2% patients per year
• VATS is equally effective
• Overall surgical mortality-5.2 %
• Guidelines by the British Thoracic Society “ Surgery-related mortality considered acceptable if < 4 % for lobectomy , < 8 % for pneumonectomy”
Conformal RT dose: 60-66 Gy/30-33#Survival function: 2-Yr OS is 60-70% 5-Yr OS is 20-30%Lung toxicity: Symptomatic pneumonitis in 15-25%Lung toxicity depends upon mean lung dose & V20, V10Oesophageal toxicity 5%
Crabtree et al, J Thorac Cardiovasc Surg 2010
Surgery Vs Radiosurgery: Ph II studySurgery, n=462; Radiosurgery, n=76
Overall Survival: Surgery better than Radiosurgery
Surgery Vs Radiosurgery: Ph II study
Crabtree et al, J Thorac Cardiovasc Surg 2010
Disease free Survival: Surgery similar to [email protected]
Crabtree et al, J Thorac Cardiovasc Surg 2010
Surgery Vs Radiosurgery: Ph II studyPropensity matched analysis
OS, DFS: Surgery= Radiosurgery
Early lung cancer: Surgery Vs Radiosurgery: Meta-analysis (n=864)Meta-analysis of matched pair analysis
Jhang B et al, Radiat Oncol 2014 [email protected]
Early lung cancer: Surgery Vs Radiosurgery: OVERALL SURVIVALMeta-analysis of matched pair analysis
SURGERY: BETTER
Early lung cancer: Surgery Vs Radiosurgery: DFSMeta-analysis of matched pair analysis
DFS SIMILAR
Early lung cancer: Surgery Vs Radiosurgery: Distant Control Meta-analysis of matched pair analysis
DC: SBRT BETTER
Early lung cancer: Surgery Vs Radiosurgery: LOCAL CONTROLMeta-analysis of matched pair analysis
LC: SBRT BETTER
Improving efficacy of RT in early NSCLC
Definite dose response relation- higher the dose higher the control
SBRT allows dose escalationHigher dose/Fr allows more BED
BED>100 Gy- local control 84%, BED<100Gy- LC- 37%.
Majority of hypofractionation schedules are 3 fractions of 15-20Gy/Fr
Dose Prescription
All doses were prescribed at the PTV encompassing
80% isodose.
T1 tumor- 20Gy(18)X3Without extensive
contact with chest wall and mediastinum
180Gy
T2 tumor and T1 with broad contact with thoracic
wall- 12Gy(11)X5
132Gy
Tumors close to heart, hilus or mediastinum
7.5GyX8
105Gy
421 patients
2 yr. OS -70%3 yr. LC-97%
Optimum dose for SBRT in early NSCLC•Meta-analysis of Thirty-four observational studies with a total of 2,587 pts
•BED divided into four dose groups: A) low (<83.2 Gy) B) medium (83.2–106 Gy) C) medium to high (106–146 Gy) D) high (>146 Gy)
•The OS for the medium or medium to high BED (range, 83.2–146 Gy) was higher than those for the low or high
BED group
•BED10 need to be between 100-150Gy
Zhang, IJROBP [email protected]
SBRT in early lung cancer studies
• There are many single institution studies
• No multicentric study available
• No prospective comparison between Conv RT Vs SBRT
• No prospective study between Surgery Vs SBRT
SBRT studies:• 2 Yr OS 70-80%• 5 Yr OS 20-30%Toxicity:Gr-3/4 Pnuemonitis <5%Rib fracture/ plexopathy <1%
Timmerman et al JCO 2006
Central lung tumours: Poor prognosis
• Poor prognosis of central lung tumours are mostly because of critical structures• Lower total RT dose (BED)• Lower dose per fraction• Poor contouring Milano et al , Radiat Oncol , 2009
Failure pattern after SBRT
• 91 patients (Washington Univ)• Most had comorbidities (poor PS or LF)• 83 peripheral (18GyX3), 8 central (9Gy X5) • Median FU 18 m, 2 yr LC 86 %• 45% failures are distant ONLY• ONLY 3% had local ONLY failure
Failures
Bradley IJROBP [email protected]
Toxicity of SBRT (n=206)
Chest wall pain 11 (5%)
Radiation pneumonitis 7 (4%)
Rib fracture 4 (2%)
Pleural effusion 4 (2%)
Atelectasis 1 (1%)
No toxicity 51%
Fatigue 28%
Chest wall pain 12%
Nausea 9%
Dyspnea 6%
Cough 6%
Erythema 2%
Hemoptysis 1%
Palpitations 1%
(Sub)acute
Late
≥ Grade 3 Radiation Pneumonitis 0-5 %Radiation induced plexopathy (upper lobe tumours)Late Chest wall toxicity – Up to 10 % Lagerwaard FJ, IJROBP, 2008
Petterson et al, Radiother Oncol 2009
Ong CL et al, Radiat Oncol 2010
Lung toxicity: Dose-effect relationship
Symptomatic pneumonitis depends upon V20, V15Asymptomatic pneumonitis depends upon low dose volume
Yamashita H et al, WJR 2014
Lung toxicity: Dose-effect relationship
Radiation pneumonitis Gr 3-4: 2-21%Depends upon mean lung dose, V20 & damaged lung vol dose
Jin JY IJROBP 2009
Lung toxicity depends upon relative lung damage vol
Damaged lung is the volume receiving threshold dose of RT
High dose SBRT: higher dose per fraction will deliver less dose to lungLow dose RT: lower dose per fraction
Small volume peripheral tumour need high dose per fraction to increase efficacy (high BED; >100Gy) & low damaged lung volume
Hence high local control, low toxicity
Hypo fractionated SRT in lung cancerLikely candidates:•Small lesions (< 5 cm)•Histologically proven (especially in India!)•Poor performance status•No nodes/distant metastasis
Medically Inoperable patients:•Compromised Pulmonary Function
– Pulmonary spirometry, Arterial Blood gases– TLCO, maxi O2 uptake– Prior major resection as pneumonectomy– Ventialtion/Perfusion scan
•Ischemic heart disease•Left ventricular dysfunction (2 D Echo)•Pulmonary vascular diseases
– Precapillary PAH– Postcapillary PAH
Robotic Radiosurgery
Pencil beam: small lesions
Melanoma eye, Trigiminal
Multiple isocentre: Irregular tumour
Skull tracking: brain tumours
Fiducial based tracking: prostate
Fiducial tracking with syncrony: lung cancer
Real time tracking for fiducialNO ITV marginTreated lung volume low
Treatment Margins
GTV
PTV
Conventional SBRT Fiducial based Robotic Radiosurgery
ITV
CTV
NO ITV for fiduicial based real time tracking
• Stage I NSCLC treated with SBRT between 2004 and 2011 in National Cancer Database
• Overall mean BED10 = 134.5 and median BED10 =132 Gy • 94.5% were prescribed a regimen with a BED10≥100 Gy• • Most common prescriptions: 60 Gy/3# = 24%, 48 Gy /4#
=17.8%; 50 Gy/5# = 13.0%; 54 Gy/3# =12.8%
• Decreased utilization of 54 to 60 Gy in 3 fractions (47.9% in 2006 to 27.9% in 2011, combined) and increased utilization of 50 Gy in 5 fractions (3.1% in 2006 to 20.4% in 2011).
• Majority of patients being treated with regimens employing a BED10≥100 Gy.
• Since 2006, decline in the use of 54- 60 Gy /3#, increase in use of 50 Gy/5#
• Possible explanations: 1) concern for increased toxicity with higher BED regimens, 2) increasing treatment of centrally located tumors.
Corso CD et al, Am J Clin Oncol 2014
Stage I Lung SBRT Clinical Practice Patterns (n=5246)
• National Cancer Database from 2003-2011
• T1-T2N0M0 inoperable lung cancer (n= 39,822)
• Logistic regressions were performed to determine predictors of receiving any 1) radiation vs. No Tx and 2) receiving SBRT vs. ConvRT.
• Treatment with RT significantly less likely in blacks (OR 0.65) and Hispanics (OR 0.42) compared to whites.
• Treatment with SBRT vs ConvRT was more likely in an academic research program (OR: 2.62) and a high-volume facility (OR: 7.00) compared to community cancer programs or low-volume facilities.
Koshy M et al; J Thoracic Oncol 2014
Disparities in Treatment of Patients with Inoperable Stage I Non-Small Cell Lung Cancer: A Population-Based Analysis (n=39822)
Marked institutional and socioeconomic variations in the treatment of inoperable stage I NSCLC
Yr-2011
Surgery Vs Radiosurgery studies:-ROSEL study-STARS study-JCOG 0403 study
Radiosurgery Vs Conv RT studies:-RTOG 0915 Arm 1: 37Gy/1# Arm 2: 48Gy/4#-RTOG 0813 Dose escalation study -TROG 09.02 Arm 1: 66Gy/33# Arm 2: 54Gy/3# -SPACE Arm 1: 70Gy/35# Arm 2: 45Gy/3#
On going studies in SBRT lung
Lung cancer• Early lung cancer: Surgery & Radiosurgery have similar results
• However, NO level I evidence regarding role of Surgery or SBRT in early NSCLC
• In meta-analysis, SBRT is similar to surgery after match pair analysis
• RT dose should be BED10 >100 Gy
• 54-60Gy/3# is preferred treatment fractionation schedule
• Fiducial based Robotic Radiosurgery (CyberKnife) have not ITV & irradiated volume is lowest
• Prospective ongoing studies will provide answers
