STEREOTACTIC RADIOSURGERY FOR LUNG

CANCER

Robert Sinha, M.D.Radiation Oncologist

Western Radiation OncolgyDorothy Schneider Cancer Center

Lung Cancer: The Problem

Incidence: Estimated 226,160 new cases in 2012

Mortality: Estimated 160,340 deaths in 2012

Survival by stage

Stage TNM 5-yr OS Literature**

IA-IB T1-T2N0M0 60-80%

IIA-IIB T1-T2N1M0 25-50%

IIIA T3N0-N1 or T1-3N2

10-40%

IIIB Any T4 or any N3

5%

IV M1=distant mets

<5%

**John D. Minna, Neoplasms of the Lung, in Harrison’s Principles of Internal Medicine, pt. 5 § 75, at 506-515 (Dennis L. Kasper, M.D. et al., eds, 16th ed 2005).

Survival: Only 15-20% of all lung cancer patients (all stages) will be alive 5 years after dx

Role of Radiotherapy

Palliation of symptoms for advanced disease Brain and bone mets, local symptoms

Curative Intent in Stage IIIA and IIIB disease 5 year survival rates of 10 to 30%

Curative Intent for medically inoperable patients Local control with traditional radiotherapy: 25-30%% New techniques like SBRT have local control ~ 90%

Radiotherapy in the 1970s to the 1990s

Step 1: Conventional simulator: diagnostic quality xrays to design fields

Step 2: Fabricate custom cerrobend blocks

Step 3: Perform Dose Calculations

Step 4: Treat patient on linac with mounted blocks

Typical radiation portal for lung cancer

Late 1990s to 2000s

CAT scan based planning 3 Dimensional conformal Therapy IMRT – Intensity Modulated Radiotherapy IGRT – Image Guided Therapy

3D conformal and IMRT: What did we achieve?

• Accuracy• Less side effects – normal tissue sparing• Dose escalation (60Gy to 70-74Gy)

Challenges

Target definition Target Motion

Respiratory motion/tracking Normal tissue tolerance/Increasing dose

Conventional XRT limited to 70Gy Duration of therapy

6 to 7 weeks for conventional therapy is difficult for medically inoperable patients

Highly focused radiation concentrated on the tumor – with sub-millimeter accuracy

Continuous tumor tracking – via respiratory gating Typically 5 or less treatments– high dose per

treatment Biologic Equivalent doses greater than 120Gy at

2Gy/fx

Stereotactic Body Radiosurgery (SBRT):The Ultimate “Targeted Therapy”

Challenge #1: Target Definition

Treatment Planning PET-CT scans

Time of Flight PET/CT

Challenge #2: Target MotionSolution: Respiratory Gating

Challenge #3: Normal Tissue Sparing

Stereotactic hypofractionated high-dose irradiation for stage I non-small cell lung carcinoma: Clinical outcomes in 281 cases of a Japanese multi-institutional

study

14 Institutions in Japan from 1993 to 20033yr OS 69% when BED>100 Gy3yr OS for “operable” patients = 81% when BED> 100

Stage I “Operable” NSCLC: Japanese Experience

IAIB

Baumann, P. et al. J Clin Oncol; 27:3290-3296 2009

• 57 patients• Median age 75• 90% inoperable due to COPD/CAD• 30% T2; 51% T1b; 19% T1a• Dose: 45Gy in 3 fxs (BED 113)

• Local control at 3yrs = 93%• Distant mets at 3yrs = 16%

• Overall survival @ 3yrs = 60%• DSS @ 3yrs = 88%

Scandinavian Study:

• 59 patients• Median age 72• All pts inoperable• T1 – 80%; T2- 20%• Dose: 60Gy in 3 fxs (BED 180)

Median FU 3 yrs:• Local control = 97.6%• Distant mets = 22.1%

• Overall survival @3yrs = 55.8%

• Median survival = 48 months

RTOG 0236:

• Lancet 2012

• 676 Patients, single institution

• Stage I and II patients

• 3 year survival 56%• Median survival: 41 months

• Local Control @5yrs – 90%• Distant mets@5yrs – 20%

Local Control for Primary NSCLC by Dose Fractionation Schemes

Historical Surgical Survival Stage I NSCLC

50-80%

Case Study: NSCLC Left Upper Lung

DEMOGRAPHICS & HISTOLOGY 76 yo Female, 1 month non-productive cough, mass on

CXR CT and PET show no other areas of disease Histology: Poorly differentiated non-small cell lung

carcinoma with squamous features . PET/CT staged as cT1N0M0 stage grouping IA

CLINICAL HISTORY: Referred by: Pulmonologist Previous Treatment: None Multiple medical co-morbidities (FEV1=1.12)

NSCLC Left Upper LungPreOp CT and Fiducial Placement: 1.0 mm CT slices with 1.5x2.0x2.1 cm tumor 4 fiducials are placed within and near the

tumor

TREATMENT PLANNING: • Axial, sagittal and coronal planning images showing the

tumor, lung parenchyma and isodose curves

NSCLC Left Upper Lung

TREATMENT DETAILS:• Rx Dose & Isodose: 60 Gy to 71%, 3 fractions QOD.• Tumor volume = 13.85 cc• Conformity Index (PIV/TV) = 1.37

RESULTS: • Near CR on CT 12 weeks post-treatment, PET negative at 3

months• PFTs unchanged at 3 months• Patient is NED at 3 years

Pre-treatment 3 months post

treatment

NSCLC Left Upper Lung

Solitary Lung Metastasis from Esophageal SCC

Demographics:• 67 yo s/p GTR resection 18 months prior, CAD &

FEV1=1.13 • Patient refused surgery after previous RML surgery

Solitary Lung Metastasis from Esophageal SCC

Pre-Treatment 1 mo post-CK 2 mo post-CK 6 mo post-CK

• Stable PFT’s & negative PET/CT >24 months after SBRT

Rx 54 Gy to 85% isodose in 3 fractions

Rusthoven, K. E. et al. J Clin Oncol; 27:1579-1584 2009

Fig 1. Images from a right lower lobe (RLL) lesion before and after stereotactic body radiation therapy (SBRT)

Pre - tx Post tx

• 38 patients with 63 lesions• Dose: 48 to 60Gy in 3fxs• Tumor volume included ITV, i.e. total

migration of tumor

• Local control at 2yrs = 96%• Median survival = 19 mo.

• Grade 3 toxicity 8% (almost all skin)• 1 case of symptomatic pneumonitis

Rusthoven, K. E. et al. J Clin Oncol; 27:1579-1584 2009

Fig 2. Actuarial local control in assessable patients

Why SBRT for Metastatic Disease?

Systemic therapies are improving, prolonging survival

But, systemic therapy still can’t durably control GROSS DISEASE (perhaps never will)

Residual disease can “re-seed” SBRT: A minimally toxic yet potent local

therapy to consolidate all gross disease

Summary

SBRT is emerging as the new “standard of care” for medically inoperable early stage NSCLC patients

Early data suggest that it may also achieve high local control and survival rates in operable patients

SBRT is a promising treatment modality for patients with oligiometastatic dz to the lung.

Future Directions

Randomized comparison of Surgery vs SABR for operable patients ACOSOG Z4099/RTOG 1021 – Wedge vs SABR STARS Trial – Lobectomy vs SABR for Stage I

Can adjuvant systemic therapy improve outcomes for early stage inoperable patients?

CALGB/RTOG – SABR +/- chemo for 2-5cm T1 tumors

Thank You