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S482

ESTRO 36 2017

_______________________________________________________________________________________________

1

San Raffaele Scientific Institute, Medical Physics, Milan,

Italy

2

San Raffaele Scientific Institute, Radiotherapy, Milan,

Italy

3

San Raffaele Scientific Institute, Nuclear Medecine,

Milan, Italy

Purpose or Objective

To investigate the predictive role of early changes of

18

F-

fluorodeoxyglucose (FDG) positron emission tomography

(FDG-PET) based biomarkers in locally advanced

pancreatic carcinoma (LAPC) patients (pts) treated with

induction and concomitant chemo-radiotherapy (CRT) on

overall survival (OS), local relapse free survival (LRFS),

distant relapse free survival (DRFS) and progression free

survival (PFS).

Material and Methods

Data of 39 pts included in an Institutional trial were

considered. Most pts (92%) received neoadjuvant

chemotherapy, followed by CRT. Pts received 44.25Gy in

15 fractions to the tumor: a simultaneous integrated boost

(SIB) to the sub-volume infiltrating the great abdominal

vessels up to 48-58Gy was delivered in 17/39 pts. FDG-

PET-CT was performed in all pts before (PET_pre) and

after CRT (PET_post), at a median time of 3-months after

the end of CRT. The predictive value of the % difference

of FDG-PET parameters between PET_post and PET_pre

was investigated, including maximum standard uptake

value (∆SUVmax), metabolic tumor volume (∆MTV) and

total lesion glycolysis (∆TLG), these last twos estimated

considering different uptake thresholds (40-50-60%) of

SUVmax. The % difference between gastrointestinal

cancer-associated antigen (GICA) levels measured at

roughly the same timing of PET scan (pre and post) was

also considered. For each parameter, median ∆ values

were used to categorize the pts in high vs low risk groups:

logrank tests and univariable Cox regression analyses were

performed to assess the prognostic value of the considered

parameters on OS, LRFS, DRFS and PFS.

Results

The median follow-up was 11 months (range: 3.7-106); the

median age was 63 years (35-84). Median OS, LRFS, DRFS

and PFS after the start of CRT were 22, 10, 4.3, 5.3

months, respectively. No uptake was present at PET_pre

in 9 pts: a longer median time to progression for PET

negative pts (9.0 vs 3.7 months,

p

=0.06) was found

compared to pts with positive PET_pre. Focusing on the

30/39 pts with positive PET-pre, ∆MTV-60 was the most

significant predictor of LRFS (

p

=0.007; RR=0.16) and PFS

(

p

=0.04; RR=0.41). Median LRFS were 4.3 and 23 months

for pts with ∆MTV-60< 35% and pts with ∆MTV-60> 35%,

respectively

(

p

=0.002;

RR=3.8,

Figure1);

the

corresponding median PFS were 3.2 vs 6.7 months (

p

=

0.03; RR=2.2, Figure2). ∆TLG-50 and ∆TLG-60 showed

borderline significance in predicting OS (

p

= 0.05;

RR=0.33). No correlation was found between the %

variation of PET parameters and DRFS while the % change

of GICA levels was a significant predictor (

p

=0.03;

RR=0.28).

Conclusion

The early assessment of FDG-PET biomarkers response

predicts clinical outcome in LAPC pts, except DRFS. The

early variation of GICA values predicts DRFS suggesting

that the integration of the information concerning early

changes of PET biomarkers and GICA may be useful in

identifying patients at higher risk of early local and/or

distant relapse and to discriminate the pattern of relapse.

PO-0887 Experimental validation of a 3D model to

simulate FMISO spatial retention in HNSCC tumor

xenografts

L.J.M. Wack

1

, A. Menegakis

2

, R. Winter

1

, S. Boeke

2

, K.

Trautmann

3

, A. Leun

1

, M. Krueger

4

, B. Pichler

4

, D.

Mönnich

1

, D. Zips

2

, D. Thorwarth

1

1

Clinic for Radiation Oncology- University Hospital

Tübingen, Section for Biomedical Physics, Tübinge n,

Germany

2

University Hospital Tübingen, Department of Radiation

Oncology, Tübingen, Germany

3

University Hospital Tübingen, Department of Pathology

and Neuropathology, Tübingen, Germany

4

Preclinical Imaging and Radiopharmacy, Werner Siemens

Imaging Center, Tübingen, Germany

Purpose or Objective

Tumor hypoxia is prognostic for poor outcome after

radiotherapy (RT). A method for non-invasi ve assessment

of hypoxia is PET using hypoxia radiotracers such as FMISO.

For this study, we evaluated a tool to simulate 2D and 3D

FMISO accumulation on realistic vessel architectures,

which can be compared against experimental

pimonidazole (pimo) stainings of the same tumor.

Material and Methods

Dynamic PET/MR imaging was performed in FaDu tumors

(human HNSCC) grown in the right hind leg of nude mice

for about 5 weeks, using an injected FMISO activity of

~12MBq. Pimo and hoechst 33342 were injected 1h and

1min prior to tumor excision, respectively, to allow

staining for tumor hypoxia and perfusion status of blood

vessels. After excision, two tumors were snap frozen and

the central part was cut into 120 consecutive sections of

10µm. Immunofluorescence staining was performed for

pimo and endothelial marker CD31. Sections were

subsequently scanned on a Zeiss Axiovert fluorescence

microscope to detect pimo, CD31 and hoechst. The

fluorescence images were rigidly registered, manually