Annual Meeting Proceedings Part 1 - American Society of Clinical ...

10512 Poster Discussion Session (Board #5), Tue, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Dynamic contrast-enhanced MRI versus 18F-misonidazol-PET/CT to predict
pathologic response in bevacizumab-based neoadjuvant therapy in
breast cancer. Presenting Author: Jesus Garcia-Foncillas, Oncology Department,
Hospital Universitario Fundación Jiménez Díaz, Universidad Autónoma
de Madrid, Madrid, Spain
Background: To investigate the role of DCE-MRI versus 18F-Misonidazole
(FMISO) positron emission tomography (PET/CT) in the prediction of
pathological response to bevacizumab-based neodajuvant therapy. Methods:
73 chemotherapy naïve, stage II and III breast cancer (BC) patients (pts)
were enrolled in a phase II, single-arm, multicenter, open-label and
prospective clinical trial. Pts received single infusion of bevacizumab (15
mg/ kg) (C1) 3 weeks prior to the beginning of neoadjuvant chemotherapy
(NAC) consisting of 4 cycles of docetaxel (60 mg/mq), doxorubicin (50
mg/mq) and bevacizumab (15 mg/ kg) every 21 days (C2-C5), followed by
surgery. Tumor proliferation, hypoxia and perfusion were evaluated respectively
using 18F-Fluorothymidine (FLT) and 18F-Misonidazole (FMISO)
positron emission tomography (PET/CT) and dynamic contrast enhancement
magnetic resonance (DCE-MR). Serial imaging studies were performed
in parallel at several time points including baseline (BL) and 14-21
days after bevacizumab alone (C1). Results: After only one administration of
bev, tumor proliferation and perfusion assessed using FLT-PET and
DCE-MRI significantly decrease (-26% and -46%, p�0.001) but these
changes were not found to be associated with final response. Most
important, changes in tumor hypoxia induced by bevacizumab was significantly
associated with pathological response (p� 0.004) and was an
independent predictor of response in multivariate analysis (RR�0.95, IC
95% 0.92-0.99, p�0.02). Decrease in FMISO uptake �10% yielded a
ROC curve area of 0.7 (95% CI: 0.56 - 0.85) with high specificity (94%).
Conclusions: Our findings suggest a significant value of early changes in
tumor hypoxia assessed by FMISO-PET as a biomarker of pathological
response in bevacizumab-based neoadjuvant therapy in breast cancer.
10514 Poster Discussion Session (Board #7), Tue, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
A translational study to investigate the association between smoking-induced
lung inflammation and lung metastases (LM) from breast cancer (BC). Presenting
Author: Patrick Glyn Morris, Memorial Sloan-Kettering Cancer Center, New
York, NY
Background: Retrospective and preclinical studies suggest that smokers are at
increased risk for LM from BC, possibly mediated by lung inflammation and the
bioactive lipid, PGE2. To investigate this link in pts, we examined urinary
PGE-M, a stable end metabolite of PGE2. Methods: A translational study was
conducted, consisting of pts with LM (n�100), pts with mets but no known lung
mets (NKL, n�100) and controls (CTRLS) with a history of BC (n�200). Pts
receiving steroids and radiotherapy were excluded. Pts gave urine (PGE-M),
blood (biomarkers), had BMI measured, and completed a validated questionnaire
(smoking, NSAIDs, confounders). PGE-M was measured by mass spectrometry,
normalized to urinary creatinine and compared between grps in both
univariate and multivariate models, correcting for covariates. Results: From
09/2010 to 06/2011, 400 pts, med age 58 yrs (range 24-88) enrolled. There
were no significant differences between grps in smoking and NSAID exposure
(table). PGE-M (med; range) was highest among pts with LM (6.7; 0.7 - 43.4)
compared to pts with NKL (4.6; 0.7 - 26.8) and CTRLS (4.2; 0.9 – 62.6,
P�0.001). In univariate analysis, smoking pack year was associated with PGE-M
(��0.13, P�0.01), and ever smokers with LM had the highest PGE-M (med 7.4;
range 0.8-28.9). In a multivariable model ever smokers with LM had higher
PGE-M than never smoking CTRLS (P�0.03). Pts with �24 pack year smoking
history and LM had the highest co-variate-adjusted log PGE-M (P�0.03). In this
model, age (P�0.001), pack year smoking hx (P�0.02), receipt of chemoRx �1
mth (P�0.003) and BMI (P�0.002) were all associated with higher PGE-M.
Conversely, receipt of NSAIDs �7 days was associated with lower PGE-M
(P�0.001). Conclusions: Increased lung inflammation, as characterized by
PGE-M, occurs in ever smokers with LM from BC, supporting the hypothesis that
changes in the lung microenvironment (“soil”) predispose to metastasis.
Baseline characteristics
LM
N�100
NKL
N�100
CTRLS
N�200 P
N(%) N(%) N(%)
Ever smokers 44 (44) 48 (48) 104 (52) 0.3
Pack year smoking Hx, med (range) 24 (1-126) 20 (1-150) 20 (1-150) 0.5
NSAIDs < 7 days 48 (48) 45(45) 92 (46) 0.9
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