"Old-school" radiotherapy alone can cure lung cancer!

“OLD-SCHOOL” RADIOTHERAPY ALONE CAN CURE LUNG CANCER!

• SELECTION

• LUCK?

• “The real reason we use conventionally fractionated RT is in fact because of the normal tissues, not the tumor.” Bob Timmerman, 2007

Improving RT Results in the Inoperable Early Lung CA patient

INTRODUCTION

• What is SBRT? Technical

• Multiple convergent beams of RT aimed at target
• Requires rigid patient immobilization
• MUST account OR compensate for organ motion
• Precise localization of target via stereotactic coordinate system
• Size-restriction for target

INTRODUCTION

• What is SBRT? Technical

• Typically few-fraction (1 to 5) RT using large individual fraction doses
• High dose conformality, i.e., “tight around target”
• Rapid dose fall-off from target to surrounding normal tissue.

INTRODUCTION

SBRT and Early Lung Cancer

• CLINICAL EXPERIENCE

• Numerous series document efficacy and safety of SBRT in early lung cancer

• Recent review of rationale, techniques, applications and optimization of SBRT for various extracranial sites (Song et al. Oncology, 2004)

• -Includes lung cancer (primary/metastatic)

SBRT and Early Lung Cancer- The radiobiological dose matters, I.e., >100Gy equivalent

SBRT and Early Lung Cancer

• Treatment Toxicities

• Reported rates generally low
• > grade 3 pneumonitis, hypoxia: < 5%
• Related to tumor location
• RTOG SBRT eligibility
• Tumors must be at “2 cm or beyond the zone of the proximal bronchial tree”
• Restriction due to high bronchial injury rates
• Based on work of Timmerman et al at U Indiana

SBRT and Early Lung Cancer

• Interesting SBRT data from Japan in operable pts who declined surgery

• (Onishi et al)

• 5 year survivals for stage IA and IB comparable to surgery

• Stage IA=77%
• Stage IB=68%

SBRT for Early Lung Cancer: The Cleveland Clinic program

SBRT for Early Lung Cancer: The Cleveland Clinic program

• PATIENT SELECTION

• Defined as early stage AND medically inoperable following

• Review by the Thoracic Multidisciplinary Lung Team
• Surgeon
• Pulmonologist
• Radiation Oncologist
• Medical Oncologist
• (Cardiothoracic service/Cardiology)
• Staging (complete) to include
• PET
• +(/-) Mediastinoscopy
• +(/-) Biopsy- morbidity of procedure of importance

SBRT for Early Lung Cancer: The Cleveland Clinic program

• Treatment Regimen Model

• Uematsu et al. IJROBP 2001; 51:666-670
• 5 yr. reported experience with Stage I NSCLC
• 50 patients (medically inoperable / refused surgery)
• Dose 50-60 Gy / 5-10# /1-2 wks
• T size 0.8-5.0 cm
• Staged by CXR, CT chest, no PET, no mediastinoscopy
• Results:
• 3 yr o.s. 66% for 50 patients
• 3 yr o.s. 86% for the 29 medically inoperable patients
• 3 yr c.s.s. 80% for 50 patients

SBRT for Early Lung Cancer: The Cleveland Clinic program

• Treatment Unit

• Novalis BrainLab System

• 6MV Linac
• Special characteristics
• “Automated image-guided radiation therapy system, utilizes high-resolution X-rays to pinpoint internal tumor sites seconds before treatment, robotically corrects patient set-up errors and tracks any patient movement throughout the treatment, all within a standard treatment time slot”

SBRT for Early Lung Cancer: The Cleveland Clinic program

• SBRT on NOVALIS

• By restriction (immobilization)
• By tumor motion studies
• By creating reference frame to provide real-time verification of patient positioning and set-up

SBRT for Early Lung Cancer: The Cleveland Clinic program

• Novalis patient immobilization

SBRT for Early Lung Cancer: The Cleveland Clinic program

• Abdominal compression/breathing restriction

SBRT for Early Lung Cancer: The Cleveland Clinic program

• Abdominal compression/breathing restriction

SBRT for Lung Cancer: Sample cases from CCF

• 76 y.o AAF

• 1992 RUL for CA, 1998 R pneumonectomy with 2nd CA
• On chronic O2
• F/U surveillance CT shows new LUL lesion, increasing in size and PET SUVs
• No biopsy (!)
• FEV1 32% predicted

SBRT for Early Lung Cancer: The Cleveland Clinic program

• Follow-up schedule for control and assessment of toxicity

• 6 weeks,then Q3m for 2 yrs
• CT chest + contrast Q 3months
• PFTs/DLCO Q 6months

Developing Lung SBRT: An approach to Research

• 1. Establish IRB approved prospective data registry of all SBRT patients

• 2. Demonstrate efficacy

• Videtic GMM, Stephans K, Reddy CA, Gajdos S, Kolar M, Clouser E, Djemil T. IMRT-based Stereotactic Body Radiotherapy for Medically Inoperable Early Stage Lung Cancer: Excellent Local Control. Int J Radiat Oncol Biol Phys. 2010; 77:344-349.
• Stephans KL, Djemil T, Reddy CA, Gajdos SM, Kolar M, Mason D, Murthy S, Rice TW, Mazzone P, Machuzak M, Mekhail T, Videtic GM.A comparison of two stereotactic body radiation fractionation schedules for medically inoperable stage I non-small cell lung cancer: the Cleveland
• Clinic experience. J Thorac Oncol. 2009; 4:976-982

Developing Lung SBRT: An approach to Research

• 3. Establish acute safety

• Stephans KL, Djemil T, Reddy CA, Gajdos SA, Kolar M, Mazzone P, Videtic GMM. Comprehensive assessment of Pulmonary Function Test (PFT) Changes after Stereotactic Body Radiotherapy (SBRT) for Stage I Lung Cancer in Medically Inoperable Patients. J Thorac Oncol. 2009; 4:838-844.

• 4. What about long-term safety?

• Woody NM, Djemil T, Adelstein DJ, Mason DP, Rice TW, Videtic GMM. Severe Local Toxicity after Lung Stereotactic Body Radiation Therapy (SBRT): Lesional abscess leading to bronchocutaneous fistula requiring surgical marsupialization. J Thorac Oncol. 2010; 5:1874-1875.
• Stephans KL, Djemil T, Tendulkar RD, Robinson CG, Reddy CA, Videtic GM. Prediction of Chest Wall Toxicity From Lung Stereotactic Body Radiotherapy (SBRT). Int J Radiat Oncol Biol Phys. 2011 Feb 5. [Epub ahead of print]

Developing Lung SBRT: An approach to Research

• 5. Advancing the discipline

• Burdick MJ, Stephans KL, Reddy CA, Djemil T, Srinivas SM, Videtic GMM. SUVmax from Staging FDG- PET/CT Does Not Predict Treatment Outcome for Early Stage NSCLC Treated with SBRT. Int J Radiat Oncol Biol Phys. 2010 Nov 15;78(4):1033-9.
• Videtic GM, Stephans K, Woody N, Pennell N, Shapiro M, Reddy C, Djemil T. A Stereotactic body radiotherapy-based treatment model for stage I medically inoperable small cell lung cancer. IASLC- 14th World Conference on Lung Cancer, July 3-7, 2011; Amsteram, The Netherlands.
• Videtic GM, Reddy C, Sorenson L. Prospective Study of Fatigue and Quality of Life after Stereotactic Body Radiotherapy for Medically Inoperable Early-Stage Lung Cancer. 52nd Annual meeting of ASTRO, October 31-November 4, 2010; San Diego, CA.

Developing Lung SBRT: An approach to Research

• 5. Advancing the discipline

• C. Robinson, K. Stephans, C. Reddy, T. Djemil, G. Videtic. Stereotactic Body Radiotherapy (SBRT) for Radiographically Diagnosed Primary Lung Cancer without Histologic Confirmation. 51st Annual Meeting of the American Society for Therapeutic Radiology and Oncology, November 3, 2009; Chicago, IL.
• Woody NM, Stephans KL, Videtic GMM, Djemil T, Xia P. Defining Target Volume for Lung Stereotactic Body Radiotherapy (SBRT): Fixed or Motion-derived Margins? IJROB. Provisionally accepted.

Developing Lung SBRT: An approach to Research

• 6. Setting standards

• Videtic GMM, Stephans KL. The role of stereotactic body radiotherapy in the management of non-small cell lung cancer: An emerging standard for the medically inoperable patient? Curr Oncol Rep. 2010; 12:235-241.

Developing Lung SBRT: An approach to Research

• ASTRO 2011

• - Videtic: early experience with single fraction lung radiosurgery

• - Stephans: bronchial toxicity with SBRT:moving beyond RTOG 0813 parameters

• -Woody: SBRT outcomes for tumors >4cm

• - Haque: outcomes for SBRT pts with PET borderline abnormalities in the mediastinum

Conclusions

• Morbidity of treatment strikingly minimal in the acute phase

• LATE TO VERY LATE TOXICITY:

• Clearly highlights necessity of long term follow-up (years)
• Will be critical to define for operable patients