1. The Role of Cyberknife Stereotactic Body Radiation Therapy in the Treatment of Prostate Cancer
Jay L. Friedland, MD

2. History of Modern Prostate Radiotherapy
LDR Brachytherapy
Late 80’s-Present
3D-CRT
Early 90’s - Present
HDR Brachytherapy
Mid-90’s - Present
IMRT
Late 90’s to Present
IGRT (Cyberknife)
Present
Jay L. Friedland, M.D.

3. The Balancing Act Convenience Invasive Toxicity Efficacy IMRT Low No
High
LDR
BrachyTx
Yes X 1
Mod
HDR
Moderate
Yes X 2
Low/Mod
Very High CK
Very Low
TBD
Jay L. Friedland, M.D.

4. Dose Calculations for Cyberknife Stereotactic Body Radiation Therapy
Perform BED dose calculations
For CK, one can fractionate the therapy yet remain convenient and non-invasive for the patient
CK doses are most like HDR, since the dose/fraction, total doses and time factors are similar
SHARP trial from Virginia Mason Hospital with good results (33.5Gy/5fx)
Thus, since we have intermediate and long term results with HDR, CK appears to be a reasonably well founded treatment option
Jay L. Friedland, M.D.

5. BED Calculations External Beam Radiation Therapy / HDR
BED = nd [ 1 + (d/ α/β) ]
Low Dose Rate Permanent Decaying Implants
BED = (Ro/ λ) { 1 + [ Ro/(μ+ λ)(α/β)] }
Definitions of parameters
n = # fractions
d = daily dose
Ro = initial dose rate of implant
λ = radioactive decay constant = 0.693/T1/2
T1/2 = radioactive half-life of isotope
μ = repair rate constant = 0.693/t1/2
t1/2 = tissue repair half-time
Jay L. Friedland, M.D.

6. Calculating BED For Low Risk CaP Monotherapy Treatment Regimens
81Gy IMRT/ 45fx / 9 weeks
(BED 1.5 = 178.2, BED 3 = )
HDR 9.5Gy X 4fx
(BED 1.5 = 278.7, BED 3 = 158.3)
HDR 8.55Gy X 4fx
(BED 1.5 = 229.1, BED 3 = 131.7)
HDR 7.25Gy X 6fx
(BED 1.5 = 253.7, BED 3 = 148.6)
Cyberknife 7Gy X 5fx
(BED 1.5 = 198.3, BED 3 = )
Cyberknife 7.25Gy X 5fx (BED 1.5 = 211.5, BED 3 = )
Biologically Equivalent Dose
BED = D (1 + d/alpha beta ratio)
D = total dose
d = dose/fraction
alpha/beta ratio =
1.5 for prostate
3 for late effects
10 for acute effects
NCH Hospital, Naples, FL
Jay L. Friedland, M.D.

7. Effectiveness and Applicability of CK
CK monotherapy: Low risk and low intermediate risk CaP
EBRT + CK boost: High risk and high intermediate risk CaP
Basically, CK reproduces dose distributions very much like HDR, except more homogeneous and non-invasively
May reduce the need for androgen deprivation therapy (ADT) for volume reduction or some patients with more extensive disease
Jay L. Friedland, M.D.

8. Prostate PTV: gland expanded 5 mm in each direction except posteriorly where it is expanded 3 mm
Jay L. Friedland, M.D.

9. Cyberknife Stereotactic Body Radiation Therapy
Part 2: Results

10. Prostate Experience to Date Cyberknife SBRT
First patient treated in Jan. 2005
Initiated Monotherapy protocol in Feb. 2005
Total patients treated: 200
Monotherapy: 162
Boost: 38
(Jan May 2007)
Jay L. Friedland, M.D.

11. Basic Demographics Will only present monotherapy results
Stage cT1cNoMo to cT2bNoMo
All patients treated between 1/5/2005 and 5/25/2007
Total number of Patients = 162
All patients treated by 2 Urologists and
2 Radiation Oncologists
NCH Hospital, Naples, Florida
Jay L. Friedland, M.D.

12. Hormonal Therapy
Hormonal Therapy administered at discretion of Urologist
135 Patients treated without Hormonal therapy
27 Patients treated with Neoadjuvant Hormonal Therapy
NCH Hospital, Naples, Florida
Jay L. Friedland, M.D.

13. Histology Gleason grade 3 + 3 = 121 Patients
NCH Hospital, Naples, Florida
Jay L. Friedland, M.D.

14. Prostate Volumes Range = 15.5cc to 109cc Mean initial volume = 45.7 cc
Median initial volume = 46.1 cc
N= 111
NCH Hospital, Naples, Florida
Jay L. Friedland, M.D.

15. Prostate Cyberknife MonoTx Dose
Mean Dose = 3503 cGy (n=162)
Median Dose = 3500 cGy
Range = 3500cGy to 3755 cGy
Number of Fractions = 5
NCH Hospital, Naples, Florida
Jay L. Friedland, M.D.

16. Initial PSA’s Range = 1.1 to 17.2 ng/ml Mean initial PSA = 5.87 ng/ml
Median initial PSA = 5.75 ng/ml
N= 160
NCH Hospital, Naples, Florida
Jay L. Friedland, M.D.

17. PSA Response to Cyberknife Monotherapy Only
Jay L. Friedland, M.D.

18. PSA Response to Cyberknife (All 231 Patients treated between 12/7/2004 and 9/24/2007)
Jay L. Friedland, M.D.

19. Case Review Patient with Recurrence after CK monotherapy
65 y/o wm with h/o rising PSA’s.
Initial Presentation
cT1cNoMo, PSA=4.3 in 2/2005, GG 4+3 in 2/12 cores (Lt lat base 10%, Lt med apex 20%) and GG 3+4 in 1/12 cores (Lt med base 5%), BS- and CT-
Tx with CK monotherapy (35Gy/5 fx) completed on 6/10/05
PSA = 5.4 on 6/30/05
PSA = 10.2 on 9/15/05, repeat TRUS bx’s all negative (0/12) on 10/27/05
PSA = 24.1 on 11/14/05, repeat bone scan negative on 11/3/05 and CT abd/pelvis negative except small sclerotic lesion in head of Lt femur. MRI Lt hip on 12/6/05 negative but suspicious at L5
PSA = 87.5 on 3/31/06, Prostascint/CT fusion scan of abd/pelvis negative on 4/7/06, Started HTx in 3/2006
PSA declined to 2.6 on 6/26/206 but increased to 14 in 10/2006
Repeat bone scan +L5 on 11/28/06 and repeat CT abd/pelvis +blastic mets at T8, T10 and L5. Started systemic chemoTx in 11/2006.
Jay L. Friedland, M.D.

20. Acute Toxicity Urinary hesitancy, urgency, frequency (Day 3-10)
Tenesmus/ rectal discomfort (Day 5-8)
Diarrhea (Day 5-8)
Rx: Flomax
Lomotil
Decadron
Anusol-HC supp.
Jay L. Friedland, M.D.

21. Acute Toxicity Scoring (IPSS/RAS/SHIM)
Baseline, days 2 and 5, post-treatment day 10, 1 month and 4 months
Acute effects generally return to baseline by 1 months
Urinary symptoms more marked in patients with IPSS baseline scores >20
No urethral strictures/ persistent rectal bleeding observed
Jay L. Friedland, M.D.

22. IPSS Scores After Cyberknife SBRT
Jay L. Friedland, M.D.

23. RAS and SHIM Scores after Cyberknife SBRT
Jay L. Friedland, M.D.

24. Summary
Cyberknife is a new and innovative treatment technique for prostate cancer.
Cyberknife monotherapy appears to produce a reasonable early decline of PSA’s in low risk patients.
The acute toxicity of Cyberknife monotherapy is acceptable.
Cyberknife therapy is a noninvasive and convenient treatment option for patients with early stage prostate cancer.
Prostate cancer patients treated with Cyberknife should be enrolled on research protocols, and the data collectively analyzed.
Jay L. Friedland, M.D.

25. Thank You for Your Kind Attention