presentación de powerpoint - fundacionareces.es · volume108, issue 3 march 2017 5-, 10- and...
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Deploy… desplegar, avanzar, implementar, expandir…
Radiotherapy in Precision Medicine: clinical facts (models 2020)
o Medical practice: State-of-the-Art o Photons, protons and ions o Protons and ions: clinical facts o Opportunities for deploy…
clinical challenges
precision medicine
personalized oncology
patient centered
cancer medicine for clinicians…2020 and more…
…your cancer… your cure… your care…
60-70% indicated; ½ for cure; 80% organ preservation; >90% + systemic therapy
Technological RT evolution: < 5 decades
…started my residency training…
Evidence vs Innovation
The academic dilema in medical progress: technology…
> 80 %
< 7 %
radiotherapy, is … radiation oncology, is … clinical oncology, is… advanced medicine
RO identity: ionizing radiation + modulating agents + cancer biology + patient bio-environment
Precision RT: techno-precision + bio-precision
Ionizing radiation + technology + bioengineering = techno-progress
photons electrons protons h-ions
Automatization Robotics
Miniaturization
Image fussion 4D 5D
PET bio-guided RT
> 30% RT dose/volumen changes
VMAT/IMRT techno-guided RT systemic-control guided RT
100% dose/volumen changes
Radiotherapy in Precision Medicine: clinical facts (models 2020)
o Medical practice: State-of-the-Art o Photons, protons and ions o Protons and ions: clinical facts o Opportunities for deploy…
Photons in personalized oncology: models 2020
from improved precision to improved practice
Volume precision: cranial RT Dose precision: escalation lung Fractionation precision: breast
30% vs 7% memory loss
66 vs 70 Gy
cancer death 25 / 30 vs 15 / 5
Protons in personalized oncology: models 2020
from improved precision to improved practice
Volume precision: pediatrics Dose precision: hepatocarcinoma Fractionation precision: lung
70 Gy / 10 fractions Shirato personal com.
Phase 1 CR + PR 60 Gy 20fr 67% 66 Gy 22fr 63% 72 Gy 24fr 100%
558 pts x 2 cohorts 6.5 y fu
5,2% vs 7,5% 2nd cancer
Stage I 4fr x 12 Gy 10fr x 6 Gy
Heavy ions in personalized oncology: models 2020
from improved precision to improved practice
Volume precision: protons vs carbon Dose precision: multi-ion p + He + C
HTA 2011-2019
CIRT 5 reports
27 studies (1 RCT) qualitative synthesis.
biophysically feasible combine heavy and light physical dose distributions vs single ion species
further improve target conformality
Radiotherapy in Precision Medicine: clinical facts (models 2020)
o Medical practice: State-of-the-Art o Photons, protons and ions o Protons and ions: clinical facts o Opportunities for deploy…
William Henry Bragg (1862-1942)
Cavendish Laboratory 1904 – 1989
29 Nobel Prizes…
Protons vs Electrons: the ionizing power
vs x 55
IMPT
IMPT = IMRT
- Cambio de corte < 100 ms
(1 litro de tumor se trata en < 6 segundos)
- Rango de profundidad de 5 cm a 32 cm.
- Tamaño en el aire del punto es 4 a 7 mm
- Velocidad de administración:
volumen tumoral de 1 litro recibe 2 Gy en 1 minuto.
Healthy tissue preservation… survivors…
(low-intermediate doses, unnecesary radiation exposure…)
radiation induced cancer Neuro-cognitive function
> 3.000 siblings
> 15 y follow-up; 72% RT
62% vs 27% on active therapy 28% vs 9% grade 3-4
2015 12 countries
dosimetry plans comparisons 19 questionaires (protons?, photons?)
24 expert pediatric radiation oncologists
“Cure is not enough” 50 % ?
Volume108, Issue 3 March 2017
5-, 10- and 20-year grade 2 or higher late toxicities were 18%, 35% and 45% grade 3 or higher late toxicities were 6%, 17% and 17% Univariate analysis irradiated site (head and neck, brain) associated late toxicities
No malignant secondary tumors occurred within the irradiated field. 10- and 20-year all secondary tumors: 8% and 16% PBT has the potential to reduce the risk of late mortality and secondary malignancy
4 institutions > 400 pediatric patients
> 5 years alive
Non-pediatric clinical models: improved tolerance… improved cancer control
243,822 patients photon radiation therapy: 243,474 proton radiation therapy: 348 Non-PT significantly worse survival compared to PT (P<.01) univariate analysis
PT (n=309) better 5-year overall survival vs non-PT (n=1549): 22% vs 16% (P=.025) propensity matched analysis
stage II and III non-PT associated worse survival vs PT (P<.01). Thoracic PT is associated with better survival in this retrospective analysis; validation in the randomized setting is needed (imbalances in patient characteristics).
11 % vs 27 % grade 3-4 CRT toxicity
JASTRO, ASTRO, ESTRO, SEOR… Status
2020 medical recommendations update
international scientific societies
…growing fast, but no recommendations…
JASTRO 2017
125 proton references 35 cancer sites / histologies / stages
58 % hypofractionated schemes 45 % pediatric cancer
11 clinical scenarios 5 new additions in 2017
6 clinical scenarios CED
Demographics… 2020 – 2030
Spain: cancer care expectations
…2019
2% - 15% cancer patients
Holanda…sus datos
Aprox 20.000 pts / year
Photons vs Protons vs Carbon: the ionizing power
vs x 55 vs x ????
TUMOR # studies # CARBON pts Local Control 5y
cordoma 9 237 77 %
condrosarcoma 6 79 90 %
meningioma 4 6 96 %
total 19 322 77 – 96 %
46 CARBON pts prostate cáncer: data on tolerance
1580 patients carbon radiotherapy prostate cancer NIRS
38 594 patients prostate cancer Osaka registry 1983 (5%) photon radiotherapy
5948 (15%) surgery
acute gastrointestinal toxicities: radiation proctitis grade 1 12.1% (13.0% in A; 11.1% in B) grade 2 5.5% (8.7% in A; 2.2% in B)
acute genitourinary toxicities: radiation cystitis grade 1 34.1% (39.1% in A; 28.9% in B) grade 2 17.6% (21.7% in A; 13.3% in B)
92 pts localized prostate cancer randomized A = protons B = carbon
66 Gy [RBE]/ 20 fr (1fr dose of 3.3 Gy)
spacer gel
Radiotherapy in Precision Medicine: clinical facts (models 2020)
o Medical practice: State-of-the-Art o Photons, protons and ions o Protons and ions: clinical facts o Opportunities for deploy…
1st Linac
(1960)
2-D Planning &
MV Port Films
(1970)
CT-Based
Planning
(1987)
3-D Planning
(1990)
IMRT
Implementation
(1992)
75% of RO
using IMRT
(2002)
kV Imaging
VMAT Implementation
(2006)
CBCT & VMAT Growth
(2010)
VMAT Maturation
(2014 )
MDACC
(#5)
(2006) LLUMC (#1)
(1990)
1st USA Spot
Scanning
(2008)
1st USA IMPT
(MDACC)*
(2009)
UCSF (#2)
(1994)
MGH (#3)
(2001)
Proton Therapy Development Lag = ~17 Yrs.
39 New PT
Centers (45%)
(2014 - 2018)
7 w/
Spot Scanning &
0 w/ CBCT
(2014)
Single Room
PT Growth
(2018)
Future Potential of Proton Therapy
…started my residency training…
Value =
(Outcomes)
(Costs)
Thaker N et al. Oncology Payers 2014
Equivalent
at 21 Days
Value Proposition- H&N
Finantial toxicity !
Value Proposition- Esophagus
Lin SH et al., ASTRO 2015
Protons reduces hospital stay by > 2 days
Finantial toxicity !
Evidence vs Innovation
The academic dilema in medical progress
“Would we agree to receive 25 Gy
to a large fraction of our brain or abdomen . . .
with no known credibly hypothesized medical benefit?”
122 active PTB trials 42.000 patients
79 % interventional studies
Background: consensus (Evidence + Consensus) 10 most common cancers in the US 2019 vs 2010 guidelines.
Methods: 2019 NCCN guidelines.
Category 1 (high level evidence randomized controlled trials + uniform consensus),
Category 2A (phase I-II + uniform consensus) Category 2B (lower level of evidence + no-uniform consensus)
Category 3 (any level of evidence + major disagreement).
Results:
recommendations increased by 77% from 1023 (2010) to 1818 (2019)
19% category 1 EC (65%) initial therapy
category 1 EC were breast (30%), lung (10%), and kidney (10%) cancers
Conclusions: 2019 NCCN lower levels of evidence with uniform expert opinion.
© 2019 American Society of Clinical Oncology
Abstr 14 2019
NCI + Patients CORI 7 RCTs
6 cancer sites Outcomes including tolerance
Evidence in proton therapy: bibliometrics of clinical results with synchrotron technology
PubMed “proton”, “cancer”, “synchroton”
2008 – 2019 = 192 publications
2008 – 2014 49
2015 – 2019 143
1q 58%
2q 13%
pediatric 49 (30%)
lung 44 (30%)
gastrointestinal 18 (9%)
prostate 15 (5%)
miscelaneus 14 (6%)
sarcoma 8 (5%)
breast 4 (2%)
Mayo Clinic Rochester 2019… 100 patients/day… real-time innovation (4D)
53
Mayo Clinic Rochester August 2019
Real-life proton therapy practice…
Transparency policy…
!!!
54
Ewing sarcoma: bilateral lung IMPT with multiple SIB (≥20 nodules)
55
Ewing sarcoma: bilateral lung IMPT with multiple SIB (≥20 nodules) and respiratiory gaiting guided proton beam delivery
Heavy ions clinical data available…
protons vs heavy ions ?
Protons Carbon ions single field multiple fields
Non-comparative 25 studies Comparative 9 studies
…More than deploy… Deep thinking…Think different…
Radioinmunogenicity and precision radiotherapy
new paradigm
pCR ! 1 out of 3
Impact factor 2017… 244.585
64 y breast cancer
(Koriyama, Japan)
“APSCOPALIST !”
Nat Rev Clin Oncol. 2016 Jun 1. Radio-immunogenicity… Clinical development of new drug-radiotherapy combinations
Immunotherapy + protons
50 CGyE/25 fr protons
Pre PT Post PT 1,5 months Post PT 5 months
18 months NED
> =
CUN Madrid Proton Project: METRICS m, m2, m3…
SINCROTRON GANTRY
150 m2
236 m2
64 m2
100 m2 81 m3
318 m3
770 m3
944 m3
Protocols are comfortable…
Ion therapy in Precision Medicine: clinical facts (models 2020)
The “st” (superlatives) of protons @present
o Medical practice: state-of-the-art proton-must pediatrics o Photons, protons and ions proton-best conformality o Protons and ions: clinical facts proton-fast “cost-icity” o Opportunities for deploy… proton-boost immunogenicity
