SBRT is the New Brachy - ABG 2018

‘SBRT is the New Brachy’ A/Prof Jarad Martin @DocJarad Radiation Oncologist 17 February 2018

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

Outline • Prostate Brachy is awesome! – Evidence of efficacy – Keeps Dr Bucci occupied – Except that it’s a dying art…

• SBRT democratizes Brachy-like dose delivery

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

Low and intermediate risk patients treated with radiotherapy alone 100

FFBF(%)

80

60

40

20 low risk intermediate risk

0 55

Trada et al JMIRO 2013

60

65

70 dose (Gy)

75

80

85

Grimm et al BJUI 2012 Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

HDRB + EBRT

Morton et al Clin Onc 2013 Department of Radiation Oncology, Calvary Mater Newcastle, Australia

ACSENDE RT

“Ultra Dose Escalation”

TOXICITY - GU Grade 3 19% vs 5%

Morris et al IJROBP 2017

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

• Rise of the Robot • Negative Press regarding complications • ‘Poor getting poorer’ – lower volume = less training & less awareness • Rise of Active Surveillance • EBRT Improving Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

Department of Radiation Oncology, Calvary Mater Newcastle, Australia

Department of Radiation Oncology, Calvary Mater Newcastle, Australia

Stereotactic Prostate Monotherapy

Multi-institutional Median dose 36.25 Gy in 5 fractions 14% had ADT 1100 patients 3 yr median follow-up

King Rad Onc 2013 15

Katz et al Front Onc 2014 Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

16

Randomized Trials • Hypo-RT-PC (n=1200, 78/39 v 42.7/7) • PACE (n=1716, 74/37 or 62/20 v 36.25/5) • NRG GU005 (70/28 v 36.25/5)

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

TROG 15.01 SPARK Stereotactic Prostate Adaptive Radiotherapy utilising

Kilovoltage Intrafraction Monitoring (KIM)

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

KIM in Action

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

PROMETHEUS Early results of Australian multicentre phase 2 trial of stereotactic “virtual HDR” radiation therapy for intermediate and high risk prostate cancer

Mark Sidhom, Sankar Arumugam, Joseph Bucci, Sarah Gallagher, Mel Grand, Peter Greer, Sarah Keats, David Pryor, Lee Wilton, Jarad Martin

PROMETHEUS PROstate Multicentre External beam radioTHErapy Using Stereotactic boost • Multicentre phase 2 trial to investigate the feasibility and safety of utilising SBRT as a boost technique in men with intermediate and high risk prostate cancer

PROMETHEUS - Patient selection

• Inclusion criteria: – Intermediate risk (T1c-T2b, PSA 10-20, GS 7) – High risk (T2c-T3b, PSA >20, GS 8-10)

• Exclusion criteria: – – – – –

Severe urinary obstructive symptoms T4 Hip prosthesis Inability to have fiducial seeds or MRI Inability to meet planning objectives

PROMETHEUS

- Treatment technique

• “Virtual HDR”: – 19-20Gy/2# VMAT SBRT – 46/23 or 36/12 EBRT (Equivalent to 110Gy)

• ADT and WPRT: – at clinician discretion

Rectal displacement

PROMETHEUS

- Treatment technique

• Fiducial seeds • MRI fusion • CTV to PTV: – 5mm all directions, except 3mm posterior

• IGRT: – recommended at least every 2 mins during SBRT – Real time becoming standard

Summary • Brachy is awesome, but a dying art • Potentially can resurrect Brachy with SBRT • SBRT is more Pt and staff friendly

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

27TH ANNUAL SCIENTIFIC MEETING AUSTRALASIAN BRACHYTHERAPY GROUP

Rydges Sydney Central Hotel 15 – 17 February 2018

Simple Debate  Modern brachytherapy is the New Brachytherapy!

 SBRT is just new EBRT

Why not to do SBRT as first choice?  Follow up - short  No randomised trials  5-10yrs to get results that will compare with currently superseded treatment

 Prostate motion remains an issue – technology solutions may overcome these – but complex

 No ablative effect due to relative homogeneity of dose

Why do Brachytherapy?  Choice of LDR or HDR  Long follow up  Large studies  Multi-institutional results  Toxicity improvements  Retrospective and randomised data  Exciting technology that will improve toxicity and patient selection

Why do Brachytherapy?  Radiobiology  Dosimetry  Technology  Results  Follow up  Toxicity  Other factors  Evidence

Why do Brachytherapy?  Radiobiology

α/β= >30Gy - 5.2Gy possibly >30Gy - 0.6Gy

Radiobiology  If true value of α/β is not < than that of the

rectum, hypofractionation would have no benefit on the therapeutic ratio.

 May be time to turn away from hypofractionation, or even toward hyperfractionation (i.e. seeds)

 Tumours are heterogeneous probably different α/β  Brachytherapy dose is heterogeneous – hedges against tumour variability of radiobiological behaviour by combination of radiotherapeutic and ablative effect

Why do Brachytherapy?  Dosimetry

Laws== of Physics

Why do Brachytherapy?  Follow up

Why do Brachytherapy?  Other factors

Why do Brachytherapy?  Other factors - Cost

 14 articles between 2003 and 2013 that discussed cost effectiveness of prostate radiotherapy in men over the age of 65

 Costs of radiation treatments in order of increasing cost are: brachytherapy, SBRT, IMRT, and Protons

Why do Brachytherapy?  Results- Randomised trials

Probability of biochemical or clinical failure (BCF) by randomized treatment arm.

Sathya J R et al. JCO 2005;23:1192-1199 ©2005 by American Society of Clinical Oncology

 220 pts. randomised to:  55Gy/20# EBRT, or  37.5Gy/13# + 17Gy/2# HDR

 Initial results with 30 months FU

 Equivalent acute and late toxicity

 Improved biochemical control in HDR group

ASCENDE RT PSA PFS (Phoenix)at 5y – primary outcome

proportion free of recurrence

1.0

LDR + EBRT + ADT bNED 83% @9y

0.8

0.6 Kaplan-Meier (95% CI)

0.4

0.2

PFS

0.0 0

Randomization (N=398) DE-EBRT LDR-PB (N=200) (N=198)

5 yr

83.8 (±5.6)

88.7 (±4.8)

7 yr

75.0 (±7.2)

86.2 (±5.4)

9 yr

62.4 (±9.8)

83.3 (±6.6)

EBRT 78Gy + ADT bNED 62% @ 9y

2 4 6 8 10 time since first LHRH injection (yrs)

12

Absolute difference 5y – 4.9% 7y – 11.2% 9y – 20.95%

ASCENDE RT PSA PFS >0.2 PSA threshold surgical definition 1.0

proportion free of recurrence

LDR+EBRT + ADT – bNED 80%@9y 0.8

0.6

EBRT 78Gy + ADT bNED 20% @ 9y

0.4

Log rank P < 0.0001

0.2

0.0

0 200 198

2 3 4 5 6 7 8 9 10 Time 186 168 145 119 93 74 52 27 11 DE-EBRT 184 168 147 127 106 86 59 38 14 LDR- PB

0

2 4 6 8 10 time since first LHRH injection (years)

12

Absolute difference 5y – 38.9% 7y – 42.9% 9y – 47.8%

Nadir+2 vs. PSA>0.2 failure definition for PB vs. EBRT boost arms

PB BOOST

ACENDE RT

EBRT BOOST

Submitted to IJROBP Jan 2018. Morris,Kkeyes Pickles

Overall survival

P = 0.293

Multivariate analysis - all cause mortality

Of the 35 metastatic events, 30 (86%) occurred within 2 years of biochemical failure

Why do Brachytherapy?  Toxicity

Cumulative incidence vs. Prevalence

 More G2+ GU toxicity after dose escalation:

 OR 1.2  (p = 0.054)

Why do Brachytherapy?  Technology

BrachyView for LDR Brachytherapy  Interface allows fast seed location reconstruction and comparison with anatomy

 Seed positions determined to within 2mm of their true location

ASCO Summary of Recommendations

 Low-risk prostate cancer who require or choose active treatment

 LDR alone, EBRT alone, or RP should be offered to eligible patients

 Intermediate-risk prostate cancer choosing EBRT with or without androgen-deprivation therapy (ADT)

 brachytherapy boost (LDR or high–dose rate) should be offered to eligible patients.

 For low-intermediate risk prostate cancer (Gleason 7,

prostate-specific antigen, 10 ng/mL or Gleason 6, prostatespecific antigen, 10 to 20 ng/mL) LDR brachytherapy alone may be offered as monotherapy.

 High-risk prostate cancer receiving EBRT and ADT,

 brachytherapy boost (LDR or HDR) should be offered to eligible patients.

www.asco.org/brachytherapy-guideline ©American Society of Clinical Oncology 2017. All rights reserved.

Why use stereotactic radiotherapy?  Patients not suitable for brachytherapy    

Can treat bigger prostates Obstructive urinary symptoms Not suitable for anaesthesia – comorbidities Where potential survival advantage is unlikely to be attained eg older men, co-morbidity etc

Brachytherapy under siege!

We may have a battle!

Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation Informed Consent Six months total ADT

Unfavourable Intermediate or LowHigh risk prostate cancer

Substudies

ARM 1: SBRT Monotherapy - 40 Gy in 5 fractions

R

Primary Endpoint: 5yr BiochemicalClinical Control ARM 2: Virtual HDR 20 Gy in 2 fractions + 36 Gy in 12 fractions

-KBP RTR QA -MRI only planning

Department of Radiation Oncology, Calvary Mater Hospital, Newcastle, Australia

Rebuttal

Why do Brachytherapy?  “Serious problem requires serious people, not idiots”



 

JAROD WE WELCOME YOU TO THE BRACHYTHERAPY COMMUNITY – THE FORCE IS STRONG IN YOU