Download Response evaluation when using targeted therapies

ROBERTO GARCÍA FIGUEIRAS, MD, PhD
DECISIONS IN ONCOLOGY
BLOOD and URINE
PATHOLOGIC
CIRCULATING Cells
PROTEOMICS
PHYSIOLOGIC
RADIOMICS
GENOMICS
EVALUATING RENAL CANCER
Imaging Technology: The perfection of anatomic imaging
RADIOGENOMICS – CONVENTIONAL IMAGING
Associations between CT Imaging Features and Mutations
NECROSIS
1. Understanding the biological correlates behind
image phenotypes.
VEIN INVASION
ILL-DEFINED MARGIN
NODULAR
ENHANCEMENT
1. Understanding how a biological process is
reflected in imaging.
1. Defining clinical biomarkers or biological
surrogates.
CALCIFICATION
MULTICYSTIC
GROSS
VESSELS
COLLECTING SYSTEM
INVASION
Karlo CA, et al.
Radiogenomics of Clear Cell Renal Cell Carcinoma: Associations between CT
Imaging Features and Mutations.
Radiology. 2014 Feb;270(2):464-71.
DECISIONS IN ONCOLOGY
Looking for non-responders and early progressors
BIOLOGY-MOLECULAR
ProteIns
GROUP A
RESPONDER TO DRUG
Increased TTP and OS
GROUP B
IMAGING FEATURES
IMAGING
ANALYSIS
NON-RESPONDER
Short TTP and OS
CLINICAL
DECISIONS IN ONCOLOGY
Looking for non-responders and early progressors
Is there any imaging finding that may suggest risk for early tumor
progression and, as a result, changing patient management?
Metastatic Renal Cancer
A GREAT CHANGE IN THE NATURAL HISTORY
10/07
09/08
03/09
IL-2
From 2005… to 04/2009
09/09
08/10
SORAFENIB
From 04/2009 to 02/2011
03/11
06/11
05/12
09/13
SUNITINIB
From 02/2011 to 11/2014
WHAT´S YOUR FEELING CONCERNING THE EVOLUTION OF THIS PATIENT?
10/14
EVALUATING RENAL CANCER
Technical Features
The use of an adequate imaging protocol, which must include an
arterial phase, is a key point to for the right evaluation of patients.
Arterial phase
Portal phase
WHAT´S YOUR OPINION CONCERNING THIS CT IMAGE IN A PATIENT WITH RENAL CANCER?
RECIST
(Response Criteria in Solid Tumors)
CASE 1
PRE
POST
CASE 2
PRE
POST
RECIST 1.1 is simple, objective, and reproducible. GOOD REASONS FOR USING RECIST.
EVALUATING RENAL CANCER
RECIST – LYMPH NODES
SHORT
AXIS
HOW MUST WE MEASURE LYMPH NODES IN RECIST EVALUATION?
EVALUATING RENAL CANCER
RECIST – BONE LESIONS
CAN WE USE BONE LESIONS AS TARGET LESIONS IN RECIST EVALUATION?
EVALUATING RENAL CANCER
RECIST – SIZE IS MY ONLY REASON
Baseline
Post-therapy with Sunitinib
Follow-up CT
04/12
07/12
02/13
WHAT´S YOUR OPINION ABOUT THE EVOLUTION OF THIS TUMOR UNDER THERAPY?
WHICH ARE THE RELEVANT QUESTIONS
EVALUATING TARGETED THERAPIES?
POST-TKIs THERAPY
EVALUATING RENAL CANCER
RECIST – IS SIZE THE KEY FEATURE?
- RECIST criteria had sensitivity of 16% for predicting
favorable PFS (Smith et al, AJR ‘10)
- Response rates by RECIST did NOT PREDICT SURVIVAL
*Sunitinib 31% (Motzer et al, NEJM 2007)
*Sorafenib 10% (Escudier et al, NEJM, 2007)
*Sunitinib or cediranib 25% (Nathan et al, CBT, 2010)
EVALUATING RENAL CANCER
RECIST limitations
1
2
3
4
5
The assessment of response to treatment in patients with mRCC has
been carried out using RECIST as the primary criteria.
Available data supported the implementation of RECIST 1.1 not only in
clinical research but also in clinical practice in many tumor types.
However, RECIST criteria have some limitations in the evaluation of
patients treated with molecular targeted therapies.
These therapies apparently lead to disease stabilization rather than to
substantial tumor regression.
Such limitations in RECIST criteria have encouraged the development of
new response evaluation criteria, which are more specific criteria to
cancer type and oncology treatment.
TUMOR GROWTH RATE (TGR)
TGR estimates the increase of the tumor volume over time. It incorporates the
time between the imaging examinations, allowing for a quantitative and
dynamic evaluation of the tumor response.
Tumor growth rate (TGR) is associated with prognosis (PFS and OS) independent of the Memorial Sloan-Kettering prognostic
score. The use of TGR allows for early and precise evaluation of drug activity compared with RECIST evaluation. TGR
suggests interesting drug-specific profiles at treatment discontinuation.
PRE
DRUG TRIAL
PD
TG = 3 log(Dt / D0) / t
(Dt) the sum of the longest
diameters of the target lesions
at time t per RECIST
(D0) the sum of the longest
diameters of the target lesions
at baseline per RECIST
Tumor growth rate (TGR) across specific treatment periods
Ferté Ch et al. European Urology 2014; 6 5 :713 – 20.
EPTIC
(Early Posttherapy Imaging Changes)
Early size change > 10% = RESPONDER
14 days post-therapy with Sunitinib
-66 mRCC patients with 165 lesions on clinical trials of VEGF-targeted
agents
Krajewski KM, et al. Eur Urol. 2011; 59(5):856-62.
Krajewski KM, et al. Oncologist 2014: 19(5):207-14
-More than -10% SLD significantly differentiated responders from nonresponders (median TTF 8.4 vs. 4.1 months, p = .001), whereas partial
response by RECIST did not). -10% SLD was also significantly predictive of
OS (median OS 35.1 vs. 15.0 months in responders vs. non-responders,
p = .003).
EVALUATING RENAL CANCER
RECIST – IS SIZE THE KEY FEATURE?
Pre
1m
4m
Courtesy MC Sebastiá, H Clínic
WHAT´S YOUR OPINION ABOUT THE EVOLUTION OF THIS TUMOR UNDER THERAPY?
- Tumor size is a late and inaccurate measurement.
- Non-measurable disease eg: bone mets.
- Key biological tumor hallmarks are not considered.
Choi Criteria
size >10% OR a decrease in tumor attenuation (HU) >15% on CT
Choi criteria defined more patients as responders than RECIST. However, they did
not differentiate between patients who did and those who did not have
therapeutic improvements in PFS or OS (*different data depending studies)
PROBLEMS WITH DENSITY BASE CRITERIA
• The reliability of Choi criteria decreases when fewer lesions are included for
analysis.
• The attenuation of heterogeneous lesions may be assessed inaccurately, as the
mean value is calculated in one region of interest in one slice.
• Measurements of relatively hypodense lesions at baseline may be less reliable,
because a 15% decrease in attenuation is less accurate than measurements in
lesions with higher pretreatment attenuation values.
• Attenuation measurements are not possible in lesions with sunitinib-induced
cavitations
EVALUATING RENAL CANCER
Beyond RECIST
Qualitative changes = density changes (necrosis) may precise
normalization of the enhancement
Choi, Nathan, SACT, and MASS criteria
132 UH (mass): 283 UH (aorta)
119 UH (mass): 245 UH (aorta)
Choi modified/Nathan Criteria
size >10% AND a decrease in tumor attenuation (HU) >15% on CT
• Neither the RECIST or CHOI criteria were able of effectively discriminating
between patients treated with sunitinib or cediranib with short or long term
clinical benefits. Patients who had a PR according to the modified Choi
criteria had a statistically significant longer TTP
• The response analysis, according to this study, combining both size reduction
and arterial phase density of the tumor in the mRCC treated with Tyrosine
Kinase Inhibitors (TKIs), can be correlated with TTP of the illness.
RECIST and CHOI criteria
were apparently inferior to NATHAN
1. Shinagare AB, et al. Am J Roentgenol. 2012; 199(5):W554-64. 2. Smith AD, et al. Am J Roentgenol. 2010; 194(1):157-65. 3. Nathan PD, et al. Cancer Biol
Ther. 2010; 9(1):15-9. 4. Krajewski KM, et al. Eur Urol. 2011; 59(5):856-62. 5. Smith AD, et al. Am J Roentgenol. 2010; 194(6):1470-8. 6. Fournier LS, et al.
Radiology. 2010; 256(2):511-8. 7. Van der Veldt AA, et al. Target Oncol. 2010; 5(2):95-112.
EVALUATING RENAL CANCER
RECIST – MUST BE SIZE MY ONLY REASON
Baseline
Post-therapy with Sunitinib
Follow-up CT
01/12
04/12
10/12
WHAT´S YOUR OPINION ABOUT THE EVOLUTION OF THIS TUMOR UNDER THERAPY?
SACT Criteria
- Size decrease ≥ 20%
- Size decrease ≥ 10% and average attenuation of ≥ 20 UH in over half of
the non-pulmonary treated lesions
- Decrease in average attenuation of ≥ 40 UH in at least one nonpulmonary treated lesion
Marked central necrosis was defined as more than 50% of the enhancing central portion of a predominantly solid enhancing mass subjectively
changing to near fluid attenuation (necrosis) after treatment
• Improved response assessment by changes in tumor SCAT criteria using CT
after target therapy for mRCC. They can suggest EARLY PD (<250d).
However:
• Need for contrast-enhanced CT evaluation in arterial phase and 3D
volumetric assessment.
• Time consuming, Complex criteria.
N
Favorableresponse SCAT
criteria
Partial-response
RECIST
Good-response
Modified Choi
Criteria
PFS >250d
44
75%
16%
93%
Early PD
<250d
9
0%
0%
56%
<0.0001
0.33
0.012
Disease
Status
P value
MASS Criteria
• The MASS “Morphology, Attenuation, Size and Structure” criteria
was created to compensate for some of the limitations of the
evaluation criteria, such as not taking into account specific
morphological or structural changes in the treated cases.
However
• Need for contrast-enhanced CT evaluation in portal phase.
• Complex parameters for indeterminate or unfavorable response.
MASS criteria are more reliable and may predict the
response of the illness measured as PFS
Qualitative evaluation
Central fill-in
EVALUATING RENAL CANCER
Beyond RECIST – Different response criteria
Partial response (PR)
Stable disease (SD)
Progressive disease (PD)
RECIST
Version 1.1
Choi Criteria
CLASSIC CATHEGORIES OF RESPONSE CRITERIA
Modified Choi
criteria (Nathan)
SACT criteria
MASS criteria
PROGNOSTIC VALUE CRITERIA
EPTIC
RECIST Response Evaluation Criteria in Solid Tumors, SACT evaluation criteria of size and attenuation EPTIC Early Posttherapy Imaging Changes MASS Morphology, Attenuation, Size and Structure
1. Shinagare AB, et al. Am J Roentgenol. 2012; 199(5):W554-64. 2. Smith AD, et al. Am J Roentgenol. 2010; 194(1):157-65. 3. Nathan PD, et al. Cancer Biol Ther. 2010;
9(1):15-9. 4. Krajewski KM, et al. Eur Urol. 2011; 59(5):856-62. 5. Smith AD, et al. Am J Roentgenol. 2010; 194(6):1470-8. 6. Fournier LS, et al. Radiology. 2010; 256(2):5118. 7. Van der Veldt AA, et al. Target Oncol. 2010; 5(2):95-112.
EVALUATING RENAL CANCER
Imaging-based evaluation criteria of the mRCC response
Criteria
RECIST
Version 1.1
Target
lesions
Complete
response
Tumor size ≥10mm per
CT
Disappearanc Size decrease ≥30%
e of all lesions
Tumor size ≥15mm per
Chest X-ray
Maximum 5 target
lesions
No new lesions
Choi Criteria Tumor size ≥15mm
Disappearanc Size decrease ≥10% OR attenuation
e of all lesions decrease in the tumor (UH) ≥15% in
CT
No new lesions No new lesions
Maximum of 10 target
lesions
Tumor size ≥15mm
Modified
Choi criteria
Maximum of 10 target
(Nathan)
lesions
SACT criteria
MASS
criteria
EPTIC (Early
Posttherapy
Imaging
Changes)
Partial response (PR)
Disappearanc Size decrease ≥10% AND attenuation
e of all lesions decrease in the tumor (UH) ≥15% in
CT
No new lesions No new lesions
Tumor size Arterial phase
≥10mm
Volumetric
measurements
Maximum
of 10
Portal phase
target
lesions
FAVOURABLE RESPONSE
Size decrease ≥20%
Size decrease ≥10% and average attenuation of ≥20 UH in
over half of the non-pulmonary treated lesions
Decrease in average attenuation of ≥40 UH in at least one
non-pulmonary treated lesion
RESPONDERS
- Decrease in size ≥10%
Stable
disease
Progressive
disease (PD)
Does not comply with
criteria of PR or PD
Increase in tumor size ≥20%
(the sum should show an
absolute increase in size of
at least 5mm)
Appearance of new lesions
Does not comply with
criteria of CR, PR or PD
Increase in tumor size ≥10%
and does not comply with
criteria for PR for tumor
attenuation
No symptomatic
deterioration due to PD
Does not comply with
criteria of CR, PR or PD
No symptomatic
deterioration due to PD
Does not comply with
criteria of PR or PD
Onset of new lesions
Increase in tumor size ≥10%
and does not comply with
criteria of PR for tumor
attenuation
Appearance of new lesions
UNFAVOURABLE RESPONSE
Increase in tumor size ≥20%
New metastases, increase
in necrosis
Central fill-in
NON-RESPONDERS
- No decrease in size ≥10%
EVALUATING RENAL CANCER
Beyond RECIST – The mess of response criteria
Which are the best imaging criteria for evaluating tumor response?
PRE-ART
PRE-PORT
50 UH
78 UH
PRE-ART
PRE-PORT
POST-ART
30 UH
POST-ART
POST-PORT
37 UH
POST-PORT
RECIST 1.1 -- PD / EPTIC – Non responder / CHOI – PR / CHOI modified – SD / SACT – Indeterminate response /MASS – Favorable response
BRAND NEW RESPONSE CRITERIA??
1
2
3
4
The assessment of response with Non-RECIST criteria may
improve the evaluation.
Every criteria include several conditions that must be
known (phase of contrast-enhanced of the evaluation,
type of lesions to evaluate, etc.)
We must consider the kind of evaluation that we are
performing (response?, prognosis?) with these criteria
Non-RECIST criteria are based on series with a small
number of patients.
TEXTURE CT ANALYSIS
• CT texture analysis reflecting tumor heterogeneity is an independent factor associated with
time to progression and has potential as a predictive imaging biomarker of response of
metastatic renal cancer to targeted therapy. Tumor entropy decreased by 3%–45% and
uniformity increased by 5%–21% for the different scale values after administration of a TKI.
Vicky Goh
Radiology 2011
Conventional CT image of a right upper lobe lung metastasis (upper left) and corresponding CT images selectively
displaying fine (upper middle), medium (lower left), and coarse (lower middle) texture obtained with filter values of 1.0
(width, 4 pixels), 1.5 (width, 6 pixels), and 2.5 (width, 12 pixels).
Genetic / Cancer / Imaging / Therapy
Genetic / Cancer / Imaging / Therapy
Tumor
Poor prognosis renal carcinoma. Baseline
BV
BV
BF
BF
Tumor
Early evaluation post-treatment with Tensirolimus = NO CHANGES
TUMOR IMAGING FEATURES
Usual findings in renal cancer
Angiogenic phenotype depends on tumor type
and shows a wide individual variability
BF
Prostate
Colon
Tumor
Lung
Renal
50
BV
Clear cell renal carcinoma. Perfusion CT
50
100
100
Breast
ml/100g/min
Blood flow (BF)
NEW IMAGING TECHNIQUES
RECIST
SIZE / DENSITY
-Choi
-Nathan
1.1
-SACT
-MASS
FUNCTIONAL
MOLECULAR
IMAGING
EVALUATING RENAL CANCER
BEYOND RECIST
PRE
Pharmacokinetic
End-points are
POST
focused on“what the
body does to the
drug,” in terms of
absorption,
distribution,
metabolism and
excretion
Pharmacodinamic
Biomarkers try to
evaluate “what the
drug does to the
body”
NEW IMAGING TECHNIQUES
Can functional and molecular imaging represent tumor biology?
BF 115 ml/min/100 g
PRE
BV 16.3 ml/100 g
PS 35 ml/min/100 g
VEGF
BF 23 ml/min/100 g
POST
PS 7.5 ml/min/100 g
BV 2.4 ml/100 g
VEGF
Parameters
Dynamic Contrast-Enhanced Computed Tomography as a Potential Biomarker in Patients With Metastatic Renal Cell Carcinoma
Invest Radiol 2014
High baseline BF and reductions in BF and BV during early treatment are
associated with improved outcome
PERFUSION-CT
Imaging as a biomarker of Early Response
Aorta
PRE
POST
Aorta
Tumor enhancement curve
Tumor enhancement curve
BV
BF
Metastatic renal Carcinoma (arrows). Baseline
BV
BF
14 days post-treatment with Sunitinib = Partial RESPONSE
As enhancement parameters of dynamic CT correlate with microvessel density (MVD) in RCC, DCECT may have additional value for early assessment of tumor response to antiangiogenic therapy.
NEW IMAGING TECHNIQUES
Can functional and molecular imaging represent tumor
biology?
The importance of an evaluation based on multiple parameters
PRE-PS
PRE-BF
70 ml/min/100 g
7.2 ml/min/100 g
POST- BF
POST-PS
50%
36 ml/min/100 g
VEGF
50%
10.3 ml/min/100 g
NEW IMAGING TECHNIQUES
Technique
CT
ADVANTAGES
Availability
Easy quantification
DISADVANTAGES
Radiation dose
Limited in patients with renal insufficiency
Not predictive for early response
DCE-CT
DCE-US
MRI
PET
Availability
Straightforward quantification
Predictive of early response
High radiation dose
Limited in patients with renal insufficiency
Predictive value for OS not yet established
Cost
No radiation
Simple standardised quantification using bolus
injection
Largest clinical data with strong evidence
No renal failure contraindication
Acquisition window restricted to 10-15 cm
Not a whole-body technique (bone, lung, and
brain not evaluable)
No radiation
Can be done without contrast agent injection
(ASL)
Multiparametric evaluation (DCE, DWI)
Predictive of early response
Potentially predictive of OS
No standardised acquisition
Imaging of metabolic activity
Availability
Cost
Radiation dose
Very limited experience with data not validated
Allow for studying different metabolic pathways
Quantification more complex
Cost
Availability
Predictive value for OS not yet validated in larger studies
Limited experience
DCE-US
AUC >40% RELATED TO TTP Y OS
Lassau, N., Vilgrain, V., Taieb, S., Lacroix, J., Aziza, R.,
Cuinet, M. et al. (2012) Evaluation with DCE-US of antiangiogenic treatments in 539 patients allowing the selection of
one surrogate marker correlated to overall survival. J Clin Oncol 30(Suppl.): abstract 4618.
Williams, R., Hudson, J., Lloyd, B., Sureshkumar, A.,
Lueck, G., Milot, L. et al. (2011) Dynamic microbubble contrast-enhanced US to measure tumor response to targeted
therapy: a proposed clinical protocol with results from renal cell carcinoma patients receiving antiangiogenic therapy.
Radiology 260: 581–590.
METASTATIC RENAL CANCER to the liver: pre and post Sunitinib
LIMITED EVALUATION
DCE-MRI
- Elevated baseline Ktrans was a statistically significant
predictive marker for favorable response to treatment
- Change in Ktrans or IAUGC90 with treatment were not
significantly related to PFS
Flaherty, K., Rosen, M., Heitjan, D., Gallagher, M., Schwartz, B., Schnall, M. et al. (2008) Pilot study of DCE-MRI to predict
progression-free survival with sorafenib therapy in renal cell carcinoma. Cancer Biol Ther 7: 496–501.
Hahn, O., Yang, C., Medved, M., Karczmar, G., Kistner, E., Karrison, T. et al. (2008) Dynamic contrast-enhanced magnetic
resonance imaging pharmacodynamic biomarker study of sorafenib in metastatic renal carcinoma. J Clin Oncol 26: 4572–
4578.
COMPLEX QUANTIFICATION
NON-CE MRI
- Changes in blood flow detected by ASL-MRI at 1 month
correlated with the change in tumor size measured at 4 months
or at disease progression (p < 0.01)
ASL
De Bazelaire, C., Rofsky, N., Duhamel, G., Michaelson, M., George, D. and Alsop, D. (2005) Arterial spin labeling blood
flow magnetic resonance imaging for the characterization of metastatic renal cell carcinoma1. Acad Radiol 12: 347–
357.
DWI - IVIM
Desar, I., ter Voert, E., Hambrock, T., van Asten, J., van Spronsen, D., Mulders, P. et al. (2011) Functional MRI techniques
demonstrate early vascular changes in renal cell cancer patients treated with sunitinib: a pilot study. Cancer Imaging
11: 259–265.
ASL
IVIM
RENAL CANCER: Arterial Spin Labelling and IVIM-DWI
WHOLE BODY-DWI
67 F. Metastatic renal cancer (lung, liver and lymph nodes) treated with Sunitinib.
Courtesy AR Padhani (UK)
10 July/12
18 Sept/12
Renal tumor: volume 1249.7 ml, ADC 1617 ± 530 µm2/s
Metastases: volume 212.5 ml, ADC 942 ± 300 µm2/s
Renal tumor: volume 1636.7 ml, ADC 1651 ± 650 µm2/s
Metastases: volume 85.4 ml, ADC 1090 ± 300 µm2/s
MRI - MULTIPARAMETRIC
Is there any added value in using multiparametric imaging?
T2
DCE
T1 out
T1 in
DWI – b 800
ADC
Multiparametric MR imaging – DCE + DWI + T1 + T2
MR Imaging can perform a multiparametric approach, including anatomy, T1 and T2 contrast, in/out of phase sequences, fat saturation,
DCE imaging and diffsuion weighted imaging
MOLECULAR IMAGING
Tumor cells
Ramona
GLUCOSE metabolism – Aerobic Glycolysis
FDG-PET
Tumor cells
Integrins αvβ3 expressed on TUMOR
cells potentiate metastasis by
facilitating invasion and movement
across blood vessels. Tumor cells
produces VEGF
“Non-tumoral” cells in tumor
matrix
Inflammatory cells (such as macrophages) or
platelets also express integrins
Tumor Vessels
ANGIOGENIC pathways –
Integrins αvβ3 expressed
on ENDOTHELIAL cells
modulate cell migration
and survival during tumor
angiogenesis. They are
upregulated on tumor
vasculature but not on
quiescent endothelium
Endothelial cells also
express VEGF receptors
MOLECULAR IMAGING is mainly based on FDG-PET. However, new PETradiotracers which target integrins or VEGF pathway and may opens new
opportunities specifically on imaging of the angiogenesis
PET - IMAGING
One prospective study involving 67 mRCC patients further supports that survival is
predicted by SUVmax
Several studies have shown that early assessment by FDG-PET/CT of
response to TKIs using a combination of FDG uptake and tumor size predicted both
PFS and OS in mRCC patients
Specific radiotracers of angiogenesis may improve these data
Liver metastasis pancreatic
cancer: [68Ga]TRAP-RGD(3)
PET/MR: fusion PET + Anatomic
T2
Courtesy Ambors Beer, Tulm,
Germany
NEW IMAGING TECHNIQUES
CHALLENGES
Renal Cancer
16 days post
Sunitinib
70% change in BV
Which threshold must be consider response?
Which one is linked to patient improvement?
SIGNIFICANCE represents the variability of a parameter that may be consider a true change,
NEW IMAGING TECHNIQUES
Tumor enhancement
CHALLENGES
100
tBF change ≤ -50%
Overall Survival (%)
90
tBF change > -50%
80
70
60
50
40
30
20
10
0.0
HR,1.25, 95%CI, 0.46 to 3.57; p=0.64
0
12
24
36
48
Time since the beginning of the treatment (months)
Which one is the right threshold?
Progression-free survival curves in patients given antiangiogenic drugs according to their
change (>50% or ≤ 50%) in tumor blood flow (TBF) after a single cycle of treatment. There
was no significant difference in survival between the two groups of patients.
1. Fournier LS, et al. Radiology. 2010; 256(2):511-8
“IN GOD WE TRUST.
ALL THE OTHERS BRING DATA”
W. Edwards Deming
James P.B. O'Connor and Gordon C. Jayson
Do Imaging Biomarkers Relate to Outcome in Patients Treated with VEGF Inhibitors?
Clin Cancer Res; 18(24) December 15, 2012
No phase I (mixed population) study
has shown significant association
between imaging biomarkers and
TTP or OS.
Non-progression has an association
with some imaging biomarkers but is
a weak clinical endpoint.
Pretreatment (Ktrans) and acute
change biomarkers [size, Hounsfield
units (HU), Ktrans] show promise as
predictive and/or prognostic
indicators.
“Why Most Published Research Findings Are False?”
-The smaller the studies conducted in a scientific field, the less
likely the research findings are to be true.
-The smaller the effect sizes in a scientific field, the less likely
the research findings are to be true.
-The greater the financial and other interests and prejudices
in a scientific field, the less likely the research findings are to be
true.
-The hotter a scientific field (with more scientific teams
involved), the less likely the research findings are to be true.
John P. A. Ioannidis, PLoS Medicine August 2005 Volume 2 lssue 8 e124
CONCLUSIONS
- Non-RECIST criteria improve the evaluation of mRCC patients.
- Several criteria seem to be able to identified patients with a poor
prognosis.
- These criteria have been only evaluated in a reduced number of
patients
-There are several promising novel techniques for the assessment of
response to treatment in patients with mRCC treated with targeted
therapies.
- Functional and molecular imaging techniques provide quantitative
evaluation parameters.
- High values of perfusion related parameters are usually associated to
a good response to antiangiogenic therapies
- However, these techniques need to be standardized