Rare cancer treatment - the challenges: the radio ... › content › download › ...Courtesy of M. Witek, U. of Wisconsin, USA Oncology Outreach at University of Wisconsin, Madison,

RCE, Milan, Nov. 2017

Rare cancer treatment - the challenges:

the radio-therapist’s perspective

Vincent GREGOIRE, MD, PhD, hon. FRCR (UK), hon. FRCR (IE)

Radiation Oncology Dept. Head and Neck Oncology Program &

Center for Molecular Imaging, Radiotherapy and Oncology,

Université Catholique de Louvain, St-Luc University Hospital,

Brussels, Belgium


Radiation Oncologist’s

Vincent GREGOIRE, MD, PhD, hon. FRCR (UK), hon. FRCR (IE)

Radiation Oncology Dept. Head and Neck Oncology Program &

Center for Molecular Imaging, Radiotherapy and Oncology,

Université Catholique de Louvain, St-Luc University Hospital,

Brussels, Belgium



the Radiation Oncologist’s perspective

Volume and expertise matters for

patient outcome after Radiotherapy

for rare cancers…




Volume/expertise’s influence on patient outcome

after RxTh

• The “what”

• The “why”

• The “how to react”


Radiation Oncology: a technical discipline?


2-D Planning

≈ 1960

3-D Conformal

≈ 1990

IMRT

≈ 2000

Dose

Painting

≥ 2016

< 1950

Courtesy of John Schreiner, Kingston Regional Cancer Centre, Ontario

Evolution of Radiation Delivery


Volume/expertise’s influence on patient outcome: a 2017 view

Su

rviv

al p

rob

abil

ity

Years

Courtesy of L. Van Eycken, 2017

Relative survival for breast cancer in Belgium


Volume/expertise’s influence on patient outcome: a 2017 view

Leonard et al, BJS, 2014

Effect of hospital volume on quality of care and outcome after

rectal cancer: the Belgian PROCARE program and the Belgian

cancer registry

RCE, Milan, Nov. 2017 Gatta et al, Lancet Oncol, 2017

Volume/expertise’s influence on patient

outcome: list ofRare Tumours

Incidence:

< 6/100,000/year


Patients with Stage III or IV HNSCC

(stratified by stage, site, hemoglobin)

Randomization

Cisplatin, RT Tirapazamine,

cisplatin, RT

Rischin et al, JCO 2010

Volume/expertise’s influence on patient outcome: the TROG 02.02 trial

RCE, Milan, Nov. 2017 Peters et al, JCO 2010

TROG 02.02: clinical Impact of Radiotherapy non-

compliance


QARC review category

TMC Compliance status

TotalCompliant Non-

compliant

Not

evaluable

No plan submitted 109 32 25 166

Modification(s) not required 402 12 4 418

Modification(s) required and made 89 0 0 89

Modification(s) required and not made 12 95 1 108

Deviation subsequent to QARC review* 69 3 72

Total 612 208 33 853

*Incomplete plan submitted in week 1

Peters et al, JCO 2010

TROG 02.02 trial: result of interventional review



compliance


TROG 02.02: influence of “geography” on radiotherapy compliance

Country Number of

patients

Number with major

adverse impact

Percent

W Europe C 39 0 0.0%

Oceania A 154 8 5.2%

N America A 101 6 5.9%

E Europe A 48 5 10.4%

S America A 54 6 11.1%

W Europe B 67 8 11.9%

W Europe E 25 3 12.0%

Oceania B 16 2 12.5%

W Europe A 127 17 13.4%

S America B 42 6 14.3%

E Europe B 28 4 14.3%

N America B 63 10 15.9%

W Europe D 30 5 16.7%

W Europe F 6 2 33.3%

W Europe G 4 2 50.0%

E Europe C 14 13 92.9%



Enrolment bracket Number of

patients

Number with

major adverse

impact

Percent

1-4 (26 centres) 57 17 29.8%

5-9 (22 centres) 130 28 21.5%

10-19 (22 centres) 279 33 11.8%

> 20 (11 centres) 352 19 5.4%

Number of patients

enrolled

2P<0.0001


TROG 02.02: influence of investigator on radiotherapy compliance



compliance


RTOG 0129 trial: RT(7w)-cddp (x3) >< RT (6w)-cddp(x2)

Volume/expertise’s influence on patient outcome: the RTOG 0129 trial

Wuthrick et al, JCO, 2015


Radiotherapy

Capocaccia, RARECARENet

Surgery

Head & Neck cancer treatment

Volume/expertise’s influence on patient outcome: the Belgian Cancer Registry database

RCE, Milan, Nov. 2017Capocaccia, RARECARENet

Volume/expertise’s influence on patient outcome: the Belgian Cancer Registry database

Nasal cavities, Nasopharynx, Salivary glands, Oral cavity, Oropharynx -

Adjusted by period of follow-up, age and subsite

2055 (26%) 3653 (46%) 256 (3%) 1958 (25%)

Rel

ativ

e ex

cess

ris

k o

fm

ort

alit

y





after RxTh

• The “why”


Processes involved in

Radiation Treatment

PRE-RADIOTHERAPY WORKUP

Diagnosis 3-D Imaging and

Staging Multi-Disciplinary

Tumor Board

Patient History

RADIOTHERAPY PREPARATION

Immobilization 3-D Planning

Images

Delineation of Volumes

of Interest (VOIs), E.g. GTV, CTV, OAR

PLANNING

Planning Aims Optimized

Treatment Plan

Modification of Aims

and Creation of TV Or Avoidance

Structures

DELIVERY

Setup Patient

With Immobilization

Image Verification

Adjust Setup

Treat

PLAN ADAPTATION (if necessary)

Evaluate

Dose

Delivered

Evaluate

Images and

Create New VOIs

RECORD AND REPORT

Record Level 2 or 3 Reporting

Optimizer

Prescription

and Technical

Data

Treatment Plan


Volume/expertise’s influence on patient outcome:

heterogeneity in target volume delineation-international

survey on H&N cancers

Harari et al., 2004 & 2012


Mean

Parameter Vol. STD CV

CTV1 cm3 74 78 105%

CTV2 cm3 144 50 35%

CTV3 cm3 254 47 19%

PTV1 cm3 169 105 62%

PTV2 cm3 279 63 23%

PTV3 cm3 508 83 16%

V70.6 Gy cm3 0 0 -

V62.7 Gy cm3 222 112 50%

V57.0 Gy cm3 362 105 29%

V47.5 Gy cm3 767 131 17%

V40.0 Gy cm3 1059 185 17%

V30.0 Gy cm3 1403 230 16%

Max dose Spinal Cord Gy 42 2 5%

Mean dose left parotid Gy 42 5 12%

Mean dose right parotid Gy 27 6 22%

Max dose Mandible Gy 67 1 1%

Courtesy of C. Grau, 2016


heterogeneity in target volume delineation in H&N tumors

(DAHANCA)

RCE, Milan, Nov. 2017 Wills, Rad. Oncol, 2017


heterogeneity in target volume delineation in the

oesophageal SCOP trial


Mailed TLD dosimetry program in EORTC centres as QA-RT of

beam

Radiation dose variation

Hansson, R&O, 1993


loss of local

control

excess mild to

moderate complications

65 high-energy

treatment units

have been checked :

• 22 underdosing

• 41 overdosing 3,3 %7 %

10 %

23,7%

Bentzen, R&O, 48 (S1): 728, 1998

average

worst 10%

EORTC TLD QA program for breast cancer radiotherapy

Radiation dose variation





after RxTh

• The “how to react”

RCE, Milan, Nov. 2017 David et al, Cancer , 2017

Volume effect Academic facility effect

46,567 H&N patients from National Cancer Data Base (USA) treated by

RxTh for oropharynx, hypopharynx and larynx SCC from 2004 to 2012


benefit of patient centralization and academic referral



benefit of patient centralization

• Clinical and planning experience

• Full infrastructure support and bespoke facilities

• Multiple radiation oncologists site-specific practice with cross cover and no more than 2 areas of sub-specialisation

• Critical mass for QA, service and research leadership, data collection and outcomes, innovation and trial participation

A lack of evidence for benefice is NOT the

same as evidences for lack of benefit!


Volume/expertise’s influence on patient outcome: a

role for tele-medicine?

Courtesy of M. Witek, U. of Wisconsin, USA

Oncology Outreach at University

of Wisconsin, Madison, USA


Volume/expertise’s influence on patient outcome: a

role for tele-medicine?

Maguire et al., J; Oncol. Practice, 2016



Clinical Target Volumes (CTV) in the neck

Grégoire et al, R&O, 2013


consensus guidelines on target volume delineation


Mean

Parameter 2004 STD CV 2013 STD CV Change %

CTV1 cm3 74 78 105% 104 9 9% 40%

CTV2 cm3 144 50 35% 190 7 4% 32%

CTV3 cm3 254 47 19% 291 18 6% 15%

PTV1 i cm3 169 105 62% 229 32 14% 36%

PTV2 i cm3 279 63 23% 338 25 7% 21%

PTV3 i cm3 508 83 16% 567 50 9% 12%

V70.6 Gy cm3 0 0 - 0 0 -

V62.7 Gy cm3 222 112 50% 267 44 16% 20%

V57.0 Gy cm3 362 105 29% 398 36 9% 10%

V47.5 Gy cm3 767 131 17% 823 114 14% 7%

V40.0 Gy cm3 1059 185 17% 1161 228 20% 10%

V30.0 Gy cm3 1403 230 16% 1591 350 22% 13%

Max dose Spinal Cord Gy 42 2 5% 43 3 7% 1%

Mean dose left parotid Gy 42 5 12% 46 3 7% 10%

Mean dose right parotid Gy 27 6 22% 28 7 25% 5%

Max dose Mandible Gy 67 1 1% 67 1 1% 1%

Courtesy of C. Grau, 2016


benchmarking among experts: the Danish experience in

H&N tumor


Site A Site C Site D Site E Site F Site G Site H Site I Site J Site K Site L Site O Site P Site Q Site RSite M Site N

1st patient

registered

Last patient

registered (n= 188)

= acceptable (58%)

= acceptable variation (12%)

= unacceptable (30%)

Site B


benchmarking among experts: the EORTC QA-RT program

EORTC 1219 H&N trial



Conclusion

•Volume/expertise effect on outcome well demonstrated

•Centralization as a straightforward solution

•Use of radiotherapy guidelines and QA program

•Audit of radiotherapy department

•Benchmarking at institutional/national/international level(s)

Documents

Rare cancer treatment - the challenges: the radio ... › content › download › ...Courtesy of M. Witek, U. of Wisconsin, USA Oncology Outreach at University of Wisconsin, Madison,