18F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival to Preoperative Radiochemotherapy with Bevacizumab in High Risk Locally Advanced Rectal Cancer

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Abstract

There is an unmet need for predictive biomarkers of the clinical benefit of anti-angiogenic drugs.The aim of the present study was to prospectively evaluate the value of FDG-PET/CT performed during and after preoperative radiochemotherapy (CRT) with bevacizumab for the prediction of complete pathologic tumor regression and survival in magnetic resonance imaging (MRI)-defined high-risk locally advanced rectal cancer (LARC) patients Methods: Sixty-one patients treated in a non-randomized phase II study (BRANCH) with concomitant or sequential (4 days before CRT) administration of bevacizumab with preoperative CRT were included. 18F-FDG PET/CT was performed at baseline, 11 days after the beginning of the CRT (early) and before surgery (late). Metabolic changes were compared with pathological complete (TRG1) vs incomplete (TRG2-5) tumor regression, progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS). Receiver operating characteristic (ROC) curves were calculated for those FDG-PET/CT parameters that significantly correlated with TRG1. Results: Early total lesion glycolysis (TLG-early) and its percent change compared to baseline (ΔTLG-early %) could discriminate TRG1 from TRG2-5. Only ROC analysis of ΔTLG-early % showed an AUC > 0.7 (0.76), with an optimal cutoff at 59.5% (80% sensitivity, 71.4 specificity) for identifying TRG1. Late metabolic assessment could not discriminate between the two groups. After a median follow-up of 98 months (range 77-132) metabolic responders (ΔTLG-early % ≥ 59.5 %) demonstrated a significantly higher 10-year PFS (89.3 vs 63.6 %, P = 0.02) and CSS (92.9 vs 72.6 %, P = 0.04) compared to incomplete metabolic responders . Conclusion: Our results suggest that early metabolic response can act as a surrogate marker of the benefit of antiangiogenic therapy and provide further support for the use of early -FDG-PET/CT evaluation to predict pathological response and survival in the preoperative treatment of patients with LARC. ΔTLG-early% showed the best accuracy in predicting TRG and may be particularly useful in guiding treatment modifying decisions during preoperative CRT based on expected response.

Original languageEnglish
JournalJournal of Nuclear Medicine
DOIs
Publication statusE-pub ahead of print - Mar 15 2019

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Fluorodeoxyglucose F18
Chemoradiotherapy
Rectal Neoplasms
Survival
Neoplasms
ROC Curve
Disease-Free Survival
Biomarkers
Angiogenesis Inhibitors
Glycolysis
Area Under Curve
Therapeutics
Magnetic Resonance Imaging
Bevacizumab
Sensitivity and Specificity

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@article{51f88b4e759145baa693090fab2a977c,
title = "18F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival to Preoperative Radiochemotherapy with Bevacizumab in High Risk Locally Advanced Rectal Cancer",
abstract = "There is an unmet need for predictive biomarkers of the clinical benefit of anti-angiogenic drugs.The aim of the present study was to prospectively evaluate the value of FDG-PET/CT performed during and after preoperative radiochemotherapy (CRT) with bevacizumab for the prediction of complete pathologic tumor regression and survival in magnetic resonance imaging (MRI)-defined high-risk locally advanced rectal cancer (LARC) patients Methods: Sixty-one patients treated in a non-randomized phase II study (BRANCH) with concomitant or sequential (4 days before CRT) administration of bevacizumab with preoperative CRT were included. 18F-FDG PET/CT was performed at baseline, 11 days after the beginning of the CRT (early) and before surgery (late). Metabolic changes were compared with pathological complete (TRG1) vs incomplete (TRG2-5) tumor regression, progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS). Receiver operating characteristic (ROC) curves were calculated for those FDG-PET/CT parameters that significantly correlated with TRG1. Results: Early total lesion glycolysis (TLG-early) and its percent change compared to baseline (ΔTLG-early {\%}) could discriminate TRG1 from TRG2-5. Only ROC analysis of ΔTLG-early {\%} showed an AUC > 0.7 (0.76), with an optimal cutoff at 59.5{\%} (80{\%} sensitivity, 71.4 specificity) for identifying TRG1. Late metabolic assessment could not discriminate between the two groups. After a median follow-up of 98 months (range 77-132) metabolic responders (ΔTLG-early {\%} ≥ 59.5 {\%}) demonstrated a significantly higher 10-year PFS (89.3 vs 63.6 {\%}, P = 0.02) and CSS (92.9 vs 72.6 {\%}, P = 0.04) compared to incomplete metabolic responders . Conclusion: Our results suggest that early metabolic response can act as a surrogate marker of the benefit of antiangiogenic therapy and provide further support for the use of early -FDG-PET/CT evaluation to predict pathological response and survival in the preoperative treatment of patients with LARC. ΔTLG-early{\%} showed the best accuracy in predicting TRG and may be particularly useful in guiding treatment modifying decisions during preoperative CRT based on expected response.",
author = "Antonio Avallone and Luigi Aloj and Biagio Pecori and Corradina Caraco and {De Stefano}, Alfonso and Fabiana Tatangelo and Lucrezia Silvestro and Vincenza Granata and Francesco Bianco and Carmela Romano and {Di Gennaro}, Francesca and Alfredo Budillon and Antonella Petrillo and Paolo Muto and Gerardo Botti and Paolo Delrio and Secondo Lastoria",
note = "Copyright {\circledC} 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.",
year = "2019",
month = "3",
day = "15",
doi = "10.2967/jnumed.118.222604",
language = "English",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",

}

TY - JOUR

T1 - 18F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival to Preoperative Radiochemotherapy with Bevacizumab in High Risk Locally Advanced Rectal Cancer

AU - Avallone, Antonio

AU - Aloj, Luigi

AU - Pecori, Biagio

AU - Caraco, Corradina

AU - De Stefano, Alfonso

AU - Tatangelo, Fabiana

AU - Silvestro, Lucrezia

AU - Granata, Vincenza

AU - Bianco, Francesco

AU - Romano, Carmela

AU - Di Gennaro, Francesca

AU - Budillon, Alfredo

AU - Petrillo, Antonella

AU - Muto, Paolo

AU - Botti, Gerardo

AU - Delrio, Paolo

AU - Lastoria, Secondo

N1 - Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PY - 2019/3/15

Y1 - 2019/3/15

N2 - There is an unmet need for predictive biomarkers of the clinical benefit of anti-angiogenic drugs.The aim of the present study was to prospectively evaluate the value of FDG-PET/CT performed during and after preoperative radiochemotherapy (CRT) with bevacizumab for the prediction of complete pathologic tumor regression and survival in magnetic resonance imaging (MRI)-defined high-risk locally advanced rectal cancer (LARC) patients Methods: Sixty-one patients treated in a non-randomized phase II study (BRANCH) with concomitant or sequential (4 days before CRT) administration of bevacizumab with preoperative CRT were included. 18F-FDG PET/CT was performed at baseline, 11 days after the beginning of the CRT (early) and before surgery (late). Metabolic changes were compared with pathological complete (TRG1) vs incomplete (TRG2-5) tumor regression, progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS). Receiver operating characteristic (ROC) curves were calculated for those FDG-PET/CT parameters that significantly correlated with TRG1. Results: Early total lesion glycolysis (TLG-early) and its percent change compared to baseline (ΔTLG-early %) could discriminate TRG1 from TRG2-5. Only ROC analysis of ΔTLG-early % showed an AUC > 0.7 (0.76), with an optimal cutoff at 59.5% (80% sensitivity, 71.4 specificity) for identifying TRG1. Late metabolic assessment could not discriminate between the two groups. After a median follow-up of 98 months (range 77-132) metabolic responders (ΔTLG-early % ≥ 59.5 %) demonstrated a significantly higher 10-year PFS (89.3 vs 63.6 %, P = 0.02) and CSS (92.9 vs 72.6 %, P = 0.04) compared to incomplete metabolic responders . Conclusion: Our results suggest that early metabolic response can act as a surrogate marker of the benefit of antiangiogenic therapy and provide further support for the use of early -FDG-PET/CT evaluation to predict pathological response and survival in the preoperative treatment of patients with LARC. ΔTLG-early% showed the best accuracy in predicting TRG and may be particularly useful in guiding treatment modifying decisions during preoperative CRT based on expected response.

AB - There is an unmet need for predictive biomarkers of the clinical benefit of anti-angiogenic drugs.The aim of the present study was to prospectively evaluate the value of FDG-PET/CT performed during and after preoperative radiochemotherapy (CRT) with bevacizumab for the prediction of complete pathologic tumor regression and survival in magnetic resonance imaging (MRI)-defined high-risk locally advanced rectal cancer (LARC) patients Methods: Sixty-one patients treated in a non-randomized phase II study (BRANCH) with concomitant or sequential (4 days before CRT) administration of bevacizumab with preoperative CRT were included. 18F-FDG PET/CT was performed at baseline, 11 days after the beginning of the CRT (early) and before surgery (late). Metabolic changes were compared with pathological complete (TRG1) vs incomplete (TRG2-5) tumor regression, progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS). Receiver operating characteristic (ROC) curves were calculated for those FDG-PET/CT parameters that significantly correlated with TRG1. Results: Early total lesion glycolysis (TLG-early) and its percent change compared to baseline (ΔTLG-early %) could discriminate TRG1 from TRG2-5. Only ROC analysis of ΔTLG-early % showed an AUC > 0.7 (0.76), with an optimal cutoff at 59.5% (80% sensitivity, 71.4 specificity) for identifying TRG1. Late metabolic assessment could not discriminate between the two groups. After a median follow-up of 98 months (range 77-132) metabolic responders (ΔTLG-early % ≥ 59.5 %) demonstrated a significantly higher 10-year PFS (89.3 vs 63.6 %, P = 0.02) and CSS (92.9 vs 72.6 %, P = 0.04) compared to incomplete metabolic responders . Conclusion: Our results suggest that early metabolic response can act as a surrogate marker of the benefit of antiangiogenic therapy and provide further support for the use of early -FDG-PET/CT evaluation to predict pathological response and survival in the preoperative treatment of patients with LARC. ΔTLG-early% showed the best accuracy in predicting TRG and may be particularly useful in guiding treatment modifying decisions during preoperative CRT based on expected response.

U2 - 10.2967/jnumed.118.222604

DO - 10.2967/jnumed.118.222604

M3 - Article

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

ER -