CyberKnife: A New Option In the Treatment of Lung Cancer
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Transcript of CyberKnife: A New Option In the Treatment of Lung Cancer
William R. Silveira, M.D., Ph.D.
Department of Radiation OncologyOncology Care ProvidersCommunity Medical Centers
CyberKnife: A New Option In the Treatment of Lung Cancer
Conventional radiation therapyDevelopment of radiosurgery • Stereotactic body radiosurgery (SBRT)
SBRT for inoperable patients• Early results & Phase II data• Cases/Examples
SBRT for operable patients
Early stage non-small cell lung cancer (NSCLC)
The Gold Standard for Early Stage Lung Cancer: Surgery
Peripheral T1N0 NSCLC247 patientsLobectomy vs. Limited resection3 year OS ~75-80%Limited resection tripledLocoregional recurrence: 6% → 18%
Ginsberg et al. Annals of Thoracic Surgery (1995) 60:615-623
LCSG 821
Does conventional radiation therapy help?
The Other End of the Spectrum: The Inoperable Patient
Does conventional radiation therapy help?
The Other End of the Spectrum: The Inoperable Patient
Linear Accelerator (Linac)
Timmerman JCO 32: 2847-2854
2D/3D Conventional Radiation
60 Gy in 30 treatments
Author Dose 5-year OS 5-year LC Intercurrent death
Dosoretz et al.
60-69 Gy 10% N/A 11%
Krol et al. 60-65 Gy 15% 25% 34%
Kaskowitz et al.
63 Gy 6% 0% 27%
Sibley et al. 55-70 Gy 13% N/A 43%
Graham et al.
60 Gy 13% N/A 28%
Conventional Radiation Therapy for Stage I/II NSCLC
Death: ~30% of distant metastases,~30% of local failure, ~30% intercurrent Sibley GS. Radiotherapy for patients with medically inoperable Stage I nonsmall cell lung carcinoma:
smaller volumes and higher doses--a review. Cancer 1998;82:433-438.
The Richard L. Roudebush VAMC, Indianapolis, IN
RT ObsMedian Survival (mos) 20 14Death (from cancer) 43% 53%
Conventional RT for Early Stage (I/II) NSCLCIs it better than nothing?
CHEST 2002; 121:1155–1158
The Richard L. Roudebush VAMC, Indianapolis, INRT Obs
Median Survival (mos) 20 14Death (from cancer) 43% 53%
Conventional RT for Early Stage (I/II) NSCLCIs it better than nothing?
CHEST 2002; 121:1155–1158
SEER (Chest 2005): 4,300 patientsRT improved MS vs. ObsStage I 14 → 21 monthsStage II 9 → 14 months
Didn’t help 5-year CSSStage I 15%Stage II 10%
An Improvement with Hypofractionation
Slotman et al. (1996)• 31 pts, T1–2N0 tx w/ 4 Gy/day to 48 Gy • Peripheral lesions only, poor PS.• “Postage Stamp Field” – No nodes
• 3-year OS 42%• 3 year DFS 76%• 6% regional failure
Why? Radiobiology
48 Gy in 12 treatments
Challenge: maximize dose, minimize toxicity
It’s more of a problem in the CNS
Intracranial Radiosurgery – Gamma Knife
Gamma Knife
Beautiful plans & excellent outcomes
Cumbersome & limited to the CNS
What is a “CyberKnife?” Linear accelerator + robotic arm • Sub-mm accuracy• 6 degrees of freedom
Treat anywhere in the body• Stereotactic Body Radiation Therapy• SBRT or SABR
Inventor: Dr. John Adler, Stanford
What is a “CyberKnife?” Linear accelerator + robotic arm • Sub-mm accuracy• 6 degrees of freedom
Treat anywhere in the body• Stereotactic Body Radiation Therapy• SBRT or SABR
Inventor: Dr. John Adler, Stanford
CyberKnife by Accuray
Versatile – initially used for CNS disease
Outside the CNS: “There’s plenty of room at the bottom.”
-Richard Feynman
Small beams, highly targeted
Multiple beams converge
Conformal/Steep fall-off
Hypo-fractionated
Account for motion• 6D skull, fiducials, synchrony,
X-sight spine, X-sight lung
SBRT (SABR) via CK: Another Way to give 60 Gy
Team effort: from tumor board to
treatment delivery
Planning: Radiation Oncologist & PhD
physicist
Author Dosing Local control 3-year OS
Onishi et al. Multiple 84% (3 yr) 57%Nyman et al. 15 Gy x3 80% (3.5 yr) 55%Uematsu et al. 50-60 Gy in 5-
1094% (5 yr) 66%
Timmerman et al.
T1: 20 Gy x3T2: 22 Gy x3
88% (3 yr) 43%
Early SBRT Data for Inoperable IA/B NSCLC
BED >/= 100 Gy was superior• 5 year LC 57% vs. 95%• 5 year OS 30% vs. 71%
Dose ResponseOnishi et al. JTO (2007)
And then came toxicity…
Time to Grade 3 to 5 toxicity
Response & Toxicity JCO 24:4833-4839 (2006)
2 year freedom from toxicity: 83% vs. 54%11x higher risk
Phase II: 70 patients, T1-2 NSCLC, inoperable3 month response (PR + CR): 60%, 2-yr LC 95%Median OS 33 months, 2 year OS 55%
(8) Grade 3-4: pericardial effusions, decline in PFTs, pneumonia, effusions, apnea, skin reaction
(6) Grade 5 (death): 4 pneumonia, pericardial effusion, carina w/ hemoptysis
First major phase II trialRTOG 02-36
Dose: 18 Gy x3T1-3N0 NSCLC, <5 cm, peripheral, 55 pt w/ medical conditions precluding surgery
3-year Control Rates• Primary tumor control rate: 98%• Local control: 91%• Local & regional control: 87%
• Rate of disseminated failure: 22%• 15% for T1 vs. 47% for T2• 6% for SCC vs. 31% for non-SCC
JAMA. 2010 March 17; 303(11): 1070–1076.
3-year Survival Rates•Disease-free survival 48.3%•Overall survival 55.8%(18% died of lung cancer)
•Median DFS 34 months31 months if T2
•Median OS 48 months34 months if T2
JAMA. 2010 March 17; 303(11): 1070–1076.
Toxicity•Grade 3 toxicity: 13%• Severe cough not responsive to
intervention, dyspnea at rest, intermittent O2/steroids needed
•Grade 4 toxicity: 4%• Continuous oxygen or assisted ventilation
•Grade 5 toxicity: No deaths from toxicity
JAMA. 2010 March 17; 303(11): 1070–1076.
Author Dose Local control 3-year OS
Timmerman et al. 2010
18 Gy x3 98% 56%
Baumann et al.
2009
15 Gy x 3 92% 60%
Ricardi et al. 2010
15 Gy x3 88% 57%
Nagata et al. 12 Gy x 3 98% 83%
Additional Phase II Data for Unresectable IA/B NSCLC
Comparative Effectiveness of 5 Treatment Strategies for Early-Stage NSCLC in the Elderly (SEER)
IJROBP; 84 (5) 1060-1070
100%
80%
50%
40%
20%
Years
10,923 patients aged ≥66 years Stage IA-IB NSCLC
In the propensity-score matched analysis, survival after SBRT was similar to that after lobectomy
Lobectomy
SBRT
Increased use of SBRT and a
decline (12%) in the proportion of
untreated elderly patients
Palma et al. JCO 2010
Overall Survival is increasing (16%) for this
population with historically poor
outcomesPalma et al. JCO 2010
RTOG 08-13: Phase II• Question: How to treat central tumors
safely?• Dose escalation trial• 9, 10, 11, 12 Gy x5
RTOG 09-15, Phase II• Question: Single session safety?• T1-2 inoperable, peripheral• Randomize: 34 Gy vs. 12 Gy x4• Winning arm to face 20 Gy x3
Pending Data For Inoperable Patients
A few cases…
53 M, COPD, cT1aN0M0 (1.3 cm), Stage IA, moderately differentiated adenocarcinoma of the RUL, FEV1 1.45 L, DLCO 23%.
6 months post treatment
67 F, COPD, pulmonary HTN, cT2aN0M0 (4.5 cm), Stage IB, poorly diff SCC of the LUL, 2L NC at baseline, wheelchair bound, FEV1 0.6 L, DLCO 11%
2 months post treatment
66 F, cT2aN0M0 (4.7 cm), Stage IB, poorly differentiated SCC of the LUL, FEV1 1.3 L, DLCO 50%.
66 F, cT2aN0M0 (4.7 cm), Stage IB, poorly differentiated SCC of the LUL, FEV1 1.3 L, DLCO 50%.
6 months post treatment
12 months post treatment
Metastatic disease (briefly)
2 months post treatment
Operable Early Stage NSCLC
Retrospective Data: SBRT can approach limited resection & lobectomy
RTOG 06-18 Phase II, operable I/II NSCLC, 18 Gy x3• PRELIMINARY: 2 year LF (primary lobe) 19.2%, OS 84.4%
PHASE III Studies• ROSEL (Dutch): SBRT vs. Surgery, CLOSED EARLY• STARS (Accuray/MDACC): CK vs. Surgery CLOSED EARLY• ACOSOG 4099/RTOG 1021: Sublobar resection +/- brachy vs.
SBRT: CLOSED
Operable Patients
Retrospective Data: SBRT can approach limited resection & lobectomy
RTOG 06-18 Phase II, operable I/II NSCLC, 18 Gy x3• PRELIMINARY: 2 year LF (primary lobe) 19.2%, OS 84.4%
PHASE III Studies• ROSEL (Dutch): SBRT vs. Surgery, CLOSED EARLY• STARS (Accuray/MDACC): CK vs. Surgery CLOSED EARLY• ACOSOG 4099/RTOG 1021: Sublobar resection +/- brachy vs.
SBRT: CLOSED
Operable Patients
cT1-2aN0M0, operable NSCLC, 58 pts , SBRT vs. Lobectomy
SABR versus lobectomy for operable stage I NSCLC: A pooled analysis of 2 randomized trials
SBRT Lobectomy
Deaths 1 6 (1 of surgical comp)
3-year OS 95% 86%Local recurrence 1 N/A
Regional recurrence 4 (13%) 1 (4%)Distant metastases 1 2Grade 3/4 toxicity 10% 44%
Inoperable patients: it’s an easy choice
Operable: Choose wisely – more data is needed• Low risk upfront, likely higher risk of regional recurrence• Consider: tumor size, pathology, full staging
Question remains: What is the role for systemic therapy?
Thoughts on SBRT for Early Stage NSCLC
Surgery is the standard of care for early stage NSCLC
Conventional radiotherapy fairs poorly for early NSCLC
SBRT/SABR has proven to help tremendously• Higher effective doses to be delivered safely• Increased LC and OS for inoperable early stage NSCLC • Promising for operable early stage NSCLC
We have a lot to learn: Surgery vs. SBRT for operable pts.
Summary
Oncology Care Providers, Drs. Brent Kane and Uma SwamyPhysics: Dr. Georg Weidlich, Ph.D.CCC Radiation Therapists & NursingLung Nodule ProgramCommunity Medical CentersAll of our referring physicians
Acknowledgements