Transcript Radiation Therapy - Lancaster General

1
Controversies in Prostate Cancer
Radiation Therapy
Curtiland Deville, MD
Assistant Professor
April 24, 2013
Lancaster General Health CME
Disclosures
 None
3
Outline
 Objective: to review current controversies and
hot topics in prostate RT:
• Background
• Conformality
– 3DCRT vs. IMRT
• Motion management (IGRT)
• Dose escalation
– Hypofractionation
– SBRT
• Modality
– Proton vs. IMRT
4
Outline
 Controversies and Hot Topics in Prostate RT (not covered):
• Erectile dysfunction prophylaxis using a PDE-5 inhibitor
• Brachytherapy:
– Role in high risk prostate cancer
– Benefit of androgen deprivation (ADT)
• Post-prostatectomy RT
– Adjuvant vs. early salvage
• Clinically node positive (N1M0)
– Benefit of definitive RT with ADT
• Intermediate risk prostate cancer
– Benefit of short-term ADT in the setting of dose escalation
• High risk prostate cancer
– Benefit of elective pelvic nodal irradiation
– Duration of long-term ADT (are 28-36 months needed)
5
Background
 The role of radiotherapy across all risk groups as curative
management for prostate cancer is well-established.
6
Evolution of conformality
2D RT
IMRT
3DCRT
Rapid
Arc
7
IMRT vs. 3D-CRT
 No randomized trials comparing IMRT with 3D-CRT for localized
prostate cancer.
 Retrospective data suggest an improved toxicity profile.
• Medicare Surveillance, Epidemiology, and End Results (SEER) analysis
of 12,000 men.
– IMRT less GI “morbidity,” hip fractures, and additional cancer therapy
Sheets NC, et al, JAMA 2012
• MSKCC series of 1571 men
– IMRT 81 Gy vs. 3D-CRT at lower doses (358 at ≤70.2 Gy and 472 at
75.6 Gy).
– IMRT significantly reduced grade ≥2 GI toxicity at 10 years (5% vs.
13% 3D-CRT).
Zelefsky M, et al, Red Journal 2008
8
Motion Management
 Interfraction Motion
•
•
•
•
Changes in position between fraction, “day to day”
External: set-up error
Internal: Mostly due to daily changes in rectal and bladder volume
Image-guided radiotherapy (IGRT) - daily imaging to provide prostate
localization to account variable motion
 Intrafraction Motion
• Changes in position while the treatment beam is on, “second by second”
9
Motion Management (pre-IGRT era)
 Rectal size at RT planning prognostic for PSA-free
survival
de Crevoisier, Red Journal 2005
10
Motion Management
 Daily localization IGRT techniques to account for interfraction
motion:
•
•
•
•
intraprostatic fiducial markers with daily imaging
transabdominal US
daily in-room CT imaging
endorectal balloon immobilization
 All of these methods employ daily imaging of the prostate in the
treatment room.
11
Motion Management
reference (simulation film)
online (port film)
co-registered (right)
In this technique, the isocenter is shifted until the bony contours (setup error) or the implanted markers
are in agreement (total error).
Graf, RO Journal 2009
12
Motion Management
 Cone beam
computerized
tomography (CBCT)
allows volumetric
visualization of the
prostate and adjacent
organs.
• Daily online correction
allows for PTV margins:
– 4 mm in all directions and 3
mm posterior (Pawlowski, Red
Journal 2010)
– 5 mm all around and 3 mm
posterior (Hammoud, Red Journal
2008)
2 stages of image registration: Top: pelvic bone region of interest
Bottom: prostate/sv represented by masked area.
13
Motion Management
 Intrafraction Motion
• Changes in position while the treatment beam is on (“second by second”)
• Mostly from peristalsis/gas, pelvic floor movement, respiration coughing, etc.
• Techniques to account for intrafraction motion:
– RGRT (radiofrequency-guided RT techniques)
– Rectal balloon
– Bowel prep (anti-gas tablets and daily bm)
– Consistent Bladder filling
14
15
16
17
18
19
20
21
22
23
Motion management
 Electromagnetic transponders
 Benefits:
• localize the prostate similar to
fiducial markers but without
additional radiation dose
• real-time tracking, allowing for
immediate intervention if prostate
moves outside the radiation field.
 Limitations:
• Subsequent difficulty of prostate
post-treatment follow-up with MRI
• Patient factors: pacemakers,
obese/abdominal girth.
24
Motion management
 Endorectal balloon
• Used for prostate
immobilization/fixation
• Ensures reproducibility of
rectal filling and spares
posterior rectum
Teh, Red Journal 2001
78 Gy IMRT plans without (left) and with
balloon (right)
Contours: rectal wall (green), anal wall
(purple) and PTV (blue).
25
Dose escalation
 Biologic models support dose escalation beyond 80 Gy
 Improved conformality and IGRT techniques have allowed for dose
escalation
 Multiple randomized trials show improved control rates:
• MD Anderson: 8-yr freedom from biochemical or clinical failure improved
significantly with dose escalation from 70 to 78 Gy (59% vs. 78%).
Kuban, Red Journal 2008
• Proton Radiation Oncology Group (PROG) 95-09 collaborative trial compared
70.2 GyE to 79.2 GyE using proton beam after standard photon 50.4/28, finding
significantly improved 10-year biochemical PFS.
Zietman, JCO 2010
26
Hypofractionation
 Shorter courses of RT using larger treatment fractions
• 2.5 - 3.1 Gy per fraction, rather than standard 1.8 - 2.0 Gy
 Method of dose escalation
 Preliminary reports suggest similar outcomes and favorable toxicity
profiles:
• Fox Chase
• Cleveland Clinic
• Italian NCI
27
Hypofractionation
 Italian NCI randomized trial
• 168 men with high-risk prostate
cancer.
• 3DCRT + 9 mo ADT
• 80 Gy/40 vs. 62 Gy/20 fractions
• Median f/u 70 months
• No differences in biochemical, local,
or distant failure (right).
• No differences in toxicity.
Arcangeli, Red Journal 2010, 2012
28
Hypofractionation
 Multiple multi-institutional randomized trials are ongoing:
• RTOG 0415 clinicaltrials.gov NCT00331773
– Patients: cT1-T2c, PSA <10
– Arms: 73.8/41 vs. 70/28
– Closed: 12/2009
• Ontario Clinical Oncology Group clinicaltrials.gov NCT00304759
– Patients: Intermediate risk PCA
– Arms: 78/39 vs. 60/20
– Target: 1204 patients, completion by 6/2013
• UK clinicaltrials.gov NCT00392535
– Patients: cT1b-T3a, PSA <= 30, risk of SV+ <30%
– Arms: 37 fxs vs. 20 fxs vs. 19 fxs
– Target: 2163 men, completion by 9/2012
 Long-term results are required before hypofractionation can be
considered a standard alternative
29
Hypofractionation (at Penn Medicine)
 Mild Hypofractionation With Proton Therapy or Intensity
Modulated Radiation Therapy (IMRT) for Intermediate-Risk
Prostate Cancer





70 Gy/ 28 fractions (2.5 Gy per fractions)
currently recruiting
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01352429
Eligibility:
• Clinical stages T1a-T2c N0 M0
• Gleason score must be in the range 2-7
• PSA values < 20 ng/ml within 90 days prior to registration.
 Androgen deprivation at discretion of the treating radiation
oncologist.
30
Stereotactic Body Radiotherapy (SBRT)
 Extreme hypofractionation
 Entire dose is administered in a
very limited number (~5) of
fractions.
 Requires high degree of
precision in defining the target
and administering the radiation
• Immobilization
• Imaging
• Motion management
31
SBRT
32
SBRT
 Longer follow-up in larger numbers of patients is required to establish
the safety and efficacy of this approach
 Presently SBRT should be performed within the context of a clinical
trial
33
Proton Therapy vs. IMRT
34
Proton Therapy
 Theoretical advantage is its
dose distribution.
 The physical characteristics of
the proton beam result in the
majority of the energy being
deposited at the end of a linear
track, “Bragg peak”
 Dose then falls rapidly to zero
beyond the Bragg peak.
35
Proton Therapy vs. IMRT
 Dosimetric study:
 10 IMRT vs.10 proton
beam to 78 Gy
 Mean rectal dosevolume histograms
Vargas et al. IJROBP 2007
36
Proton Therapy
37
Proton Therapy vs. IMRT
 No randomized trials comparing proton therapy to photon therapy
or brachytherapy in men with clinically localized prostate cancer.
 Retrospective analyses have not established whether proton beam
therapy (either alone or in combination with photon therapy) is less
toxic than photon therapy alone or brachytherapy
38
Proton Therapy vs. IMRT (retrospective)
 Medicare-SEER analysis of 684 men treated with proton therapy
2002-2007 vs. matched IMRT cohort
• IMRT associated with less GI “morbidity”
• No significant differences in other toxicities
• No difference in additional cancer therapy
Sheets NC, et al, JAMA 2012
 Medicare analysis of 421 men treated with proton therapy with 842
2008-2009 vs. matched IMRT cohort
• Less GU toxicity at 6 mo for protons, which disappeared by 1 yr
• No other significant differences
• Proton therapy associated Medicare reimbursement costs were 75%
higher than IMRT
Yu JB, et al, JNCI 2013
39
Proton Therapy vs. IMRT (at Penn Medicine)
 Proton Therapy vs. IMRT for Low or Low-Intermediate Risk
Prostate Cancer
 Currently recruiting
 Sponsor: Massachusetts General Hospital
 Collaborators:
• University of Pennsylvania
• National Cancer Institute (NCI)
 ClinicalTrials.gov Identifier: NCT01617161
 Anticipated enrollment: 461
 Primary Outcome Measures:
• Compare the reduction in mean EPIC bowel scores at 24 mo
40
Thank You
41
42