Transcript Diapositiva 1

IN RADIOTERAPIA BEST PAPERS
2014
FILIPPO ALONGI
Direttore Unità Operativa Complessa
Radioterapia Oncologica
PROSTATE RT:
WHERE WE ARE GOING?
Comments:
•RT has evolved from radium(1911)
to high Technology and high
precision
•RT became one of the standard
option for prostate cancer in
treatment panorama.
•Ballance between advantages and
sequele are differently reported by
urologists and radiation oncologists
in regard to the correct choice for
each patient.
PROSTATE RT:
IS DOSE ESCALATION EFFECTIVE?
FEBRUARY 2014
Comments:
•Largest dose escalation trial
•PHASE III trial for 862 pts randomized to receive
neoadv OT +: 64Gy in 32 fr vs 74Gy in 37 fr
FUP 10 years: dose escalation improve bDFS but
can increase acute and late toxicity.
Yes dose escalation is effective,
but could increase toxicity
(with old technology)
Further improvements in radiotherapy
techniques have been shown to reduce the effect
of dose-escalation on side-effects and should be
used to maintain the reported advantages of
dose-escalation while minimising treatment
sequelae
PROSTATE RT:
OT & DOSE ESCALATION?
Comments:
352 intermediate and hig risk pts randomized to: High RT
dose +STAD of 4 m vs High RTdose +LTAD of 2 years
56 th ASTRO MEETING
San Francisco 2014
•57 months of FUP
•Median dose 78 Gy
•LTAD + High RT dose is superior than STAD + High RT
dose
Long OT seems to be better also
with high RT doses
RADICAL RT:
IS NEW TECHNOLOGY REALLY MORE
EFFECTIVE?
Comments:
•On 42483 pts, IMRT vs observation analysis
documented an avantage for IMRT group.
•Advantage was high risk patients with younger age
and lower comorbidities
IMRT > SURVIVAL, BUT ONLY IN
HIGH RISK PTS
RADICAL RT:
IS NEW TECHNOLOGY REALLY MORE
EFFECTIVE?
COMMENTS:
1)The absence of any information about dose prescription, when IMRT is the key point of the data
interpretation, makes impossible to discern whether improved outcomes are related to IMRT by itself
2) 52.6% of the IMRT population also received androgen deprivation therapy, but ADT was not
considered as covariate in statistical evaluation. ADT has already showed a major impact on the
overall survival of intermediate and high risk PCa
RADICAL RT:
ARE WE READY FOR ROUTINE
HYPOFRACTIONATION?
AUGUST 2014
Comments:
•Current studies of moderate hypofractionation (20-30 fractions)
have sufficient follow-up to support the safety of moderate
hypofractionation. However, long term efficacy data are still
lacking because of the long natural history of PCa .
•Extreme hypofractionation (4-5 fractions) for low-risk PCa in
selected nonrandomized cohorts show good short-term
biochemical control comparable with current conventional
fractionation, but reports of high-grade urinary and rectal toxicity
are concerning.
-MODERATE HYPO IS ALLOWED
-EXTREME PREFERABLY WITHIN
PROTOCOLS
RADICAL RT:
ARE WE READY FOR ROUTINE
HYPOFRACTIONATION?
-MODERATE HYPO IS ALLOWED
-EXTREME PREFERABLY WITHIN PROTOCOLS
(CENTERS WITH EXPERIENCE AND TECHNOLOGY)
RADICAL RT:
ARE WE READY FOR EXTREME
HYPOFRACTIONATION?
Comments:
•Extreme hypofractionation in 5 sessions (SBRT)is
preferable within protocols.
•Nevertheless, at 7 years of FUP, results of
biochemical control are excellent
EXTREME HYPOFRACTIONATION
(SBRT) IS A PROMISING APPROACH
RADICAL RT:
WHAT IS THE BEST HIGH TECH APPROACH?
Comments:
SBRT seems to be more related to
GU toxicity, even if costs are less
than IMRT in conventional
fractionation
-EXTREME HYPOFRACTIONATION
(SBRT) IS A PROMISING
APPROACH(LOW COSTS)
-SELECTION OF PATIENTS IS CRUCIAL
TO REDUCE TOXICITY (GU)
RADICAL RT:
WHAT IS THE BEST HIGH TECH APPROACH?
September2014
Comments:
1)First, the authors did not report the scale and the
grade of the toxicity. This represents a crucial bias.
2)Radiotherapy-related toxicities are highly dependent
on the radiation dose, fields used, and dose-volume
constraints.
The lack of these data makes any considerations about
toxicity rather speculative
RADICAL RT:
HOW WE CAN IMPROVE OUTCOME IN
HIGH RISK PATIENTS?
Comments:
The feasibility of weekly docetaxel
associated to high dose RT + long
term OT was confirmed
High risk pts
could deserve a multidisicplinary
integration that seems to be
feasible
RADICAL RT:
IS USEFUL RT IN N+ PATIENTS?
Comments:
56 th ASTRO MEETING
San Francisco 2014
Observational Study
3682N+ pts 1/3 OT alone, ½ RT + OT.
5 y OS 71% in OT, 85% in Rt + OT
RT+ OT approach in N+ is
more effective than OT
alone
RADICAL RT:
WHAT ABOUT RELATED TOXICITIES?
January2014
Comments:
-32465 pts evaluated
-Patients submitted to RT had higher incidence
of complications
-However, patients submitted to RT had lower
incidence of urological procedures during
hospitalization.
- Limitations are the absence of specific type of
RT (several patients treated with 2D RT)
Complication after RT and
prostatectomy could be
frequent
and depend on age,
comorbidities and treatment
procedure
RADICAL RT:
WHAT ABOUT RELATED TOXICITIES?
RADICAL RT:
WHAT ABOUT RELATED TOXICITIES?
Biases of the study
• This study has generated much discussion because
of several selection bias:
• retrospective comparisons
• selection biases
• patients given radiotherapy:
• were older,
• have more comorbidities,
• have more advanced disease.
• no differences between radiotherapy tecniques (EBRT,
BRT)
• no clear definitions of toxicities
RADICAL RT:
QUALITY OF LIFE?
August 2014
Comments:
•Randomized trial 3994 pts:
•Surgery had the worst results in terms of sexual
and urinary function
•Radiation has the worst results in terms of bowel
function
•In both age influences after 3 years
SURGERY AFFECTS MORE SEXUAL AND GU
RT AFFECTS MORE INTESTINE
AGE IS CRUCIAL
RADICAL RT:
QUALITY OF LIFE?
Comments:
•First randomized published trial for Sexual
disfunction rehabilitation during RT:
•Sexual function could be improved by daily
viagra during and after RT
WE ARE LEARNING THAT SEXUAL
ACTIVITY COULD BE IMPROVED
FOR RT PATIENTS
POST-OPERATIVE RT:
IS ADJUVANT EFFECTIVE?
AUGUST 2014
Comments:
-388 pts randomized to receive RT or observation
with 10 years FUP.
-compared with observation RT < 51% risk of
biochemical relapse
-ART was safe
RT is better than
observation in pT3
and it is safe
POST-OPERATIVE RT:
RANDOMIZED TRIALS
Studio randomizzato
Pazienti
FUP mediano
Outcome
considerazioni
RTOG 8794
(J Urology 2009)
431
12.7 anni
Metastasis free survival and
overall survival a favore di RT
Vantaggio di sopravvivenza
solo a lungo termine
EORTC 22911
(Lancet 2012)
1005
10.6 anni
RT meglio di osservazione per
PFS e LC a 5 anni, a 10 anni
perso il vantaggio della RT vs
osservazione.
Margini positivi e età < 70 anni:
unici forti fattori prognostici a
favore di RT.
No vantaggio sopravvivenza
ARO 9602
(European Urology 2014)
388
10 anni
RT meglio di osservazione per
PFS
RT riduce il rischio di recidiva
biochimica del 51%
POST-OPERATIVE RT:
WHO IS THE PERFECT CANDIDATE?
POST-OPERATIVE RT:
WHO IS THE PERFECT CANDIDATE?
Comments:
November 2014
-Endoresement of AUA/ASTRO GUIDELINES
-adding one qualifying statement:
not all candidates for adjuvant or salvage RT have the
same risk of recurrence or disease progression, and
thus, risk-benefit ratios are not the same for all men.
-highest risk for recurrence after radical
prostatectomy include men with seminal vesicle
invasion, Gleason score 8 to 10, extensive positive
margins, and detectable postoperative PSA.
-The decision to administer radiotherapy should be
made by the patient and multidisciplinary treatment
team, keeping in mind that not all men are at equal
risk of recurrence or clinically meaningful disease
progression.
PERSONALIZED
APPROACH BASED ON
RISK FACTORS
POST-OPERATIVE RT
MOST SIGNIFICANT RISK FACTORS?
September 2014
COMMENTS:
In conclusion, the beneficial impact of aRT on
survival in patients pN1 can depend on
individualized tumor characteristics.
Specifically, patients who benefited from aRT were
those with:
- low-volume LNI ( two PLNs) in the presence of
intermediate- to high-grade non–specimen-confined
disease
-intermediate-volume LNI (3 to 4 PLNs), regardless of
other tumor characteristics.
Conversely, all other patients with LNI did not seem to
benefit significantly from aRT
aRT is effective for
pN1
up to 4 positive LN
ADJUVANT RT:
HOW WE CAN IMPROVE OUTCOME IN
HIGH RISK PATIENTS?
Comments:
RT after RP in case of PSA >0.2, GS>7-8,pT3
ADT+RT(66.6Gy)+6 Docetaxel
56 th ASTRO MEETING
San Francisco 2014
RESULTS: 70% 3-years FFP vs 50 % of Hystorical data.
Intentification of adiuvant
approach in very high risk is
feasible and seems to be
effective
POST-OPERATIVE RT
SALVAGE TIME?
SALVAGE RT FOR PSA RISE: WHAT IS THE CUT
OFF???
POST-OPERATIVE RT
SALVAGE TIME?
“A PSA value greater than 0.2 ng/mL is an appropriate
cutpoint to define PSA recurrence after RRP”
Freedlan et al, Urology 61 : 365-369, 2003
POST-OPERATIVE RT
EARLY SALVAGE OR ADJUVANT AT ALL?
COMMENTS:
Ultrasensitive serum PSA measurements plays in
determining who will develop BCR after radical
prostatectomy and, such as, be candidates for
secondary treatment.
Postoperative PSA levels achieved significant
predictive accuracy already on day 30. PSA >0.073
ng/ml at day 30 increased significantly the risk of BCR
The kinetics of postoperative PSA decline may allow
better stratification of patients who would benefit
from immediate RT.
EARLY SALVAGE MAY
REPLACE UPFRONT
ADJUVANT AT ALL BY
ULTRASENSIVE PSA
POST-OPERATIVE RT
HAVE WE PREDICTORS FOR SALVAGE SUCCESS?
COMMENTS:
-7616 pts pT3/4N0/N1
-Early RT reduced cancer specific mortality only in
patients with a hig risk score due to Gleason score 8–
10; pT3b/4, lymph node
Invasion
- However, because of the lack of detailed data on
PSA and clinical progression, these results should be
interpreted with caution.
EARLY SALVAGE
MAY BE MORE USEFUL IN MORE
AGGRESSIVE POSTOPERATIVE
SETTING
OLIGOMETASTASES/RECURRENCES
ROLE OF LOCAL THERAPY
September 2014
COMMENTS:
New imaging to detect early
relapse(multiparametric MRI and Choline PET).
Metastasis directed Treatment (SURGERY OR RT) is a
promising approach for oligometastatic PCa
recurrence
RT PROMISING TO DELAY
SISTEMIC TREATMENTS IN
OLIGOMTS/OLIGORECURRENCE
OLIGOMETASTASES/RECURRENCES
LOCAL THERAPY AND WHAT ABOUT RT?
COMMENTS:
Metastasis directed Treatment (SURGERY OR RT) is a
promising approach for oligometastatic PCa
recurrence
This is the first randomized phase 2 trial that will
asses the possibility of deferring palliative ADT and
cancer progression with metastasis directed therapy
by means of SBRT or surgery.
RT PROMISING TO DELAY
SISTEMIC TREATMENTS IN
OLIGOMTS/OLIGORECURRENCE