Early Metabolic Response Assessment Research Articles

Abstract PO1-01-03: Pathological response according to early metabolic remission in an interim FDG-PET scan and to tumor infiltrating lymphocytes - A secondary analysis of the phase II trial ABCSG 52/ATHENE investigating atezolizumab in early HER2+ BC

Abstract Background: ABCSG-52/ATHENE investigated a neoadjuvant chemotherapy de-escalation/immunotherapy escalation approach with trastuzumab, pertuzumab, atezolizumab and epirubicin for early-stage HER2-positive breast cancer. The pathological complete response rate (pCR; ypT0/Tis, ypN0) - the primary endpoint of the trial - was 60.3% (95% CI 47.5% - 71.9%), and was higher than the predefined threshold for positivity (≥ 40%). Interestingly, higher pCR rates were observed in PD-L1 immune cell (IC) negative tumors (pCR 69.2%) as compared to PD-L1 IC positive tumors (pCR 55.2%). No new safety concerns were observed. Primary outcome data were reported at the ESMO Breast Cancer Conference 2023. Here, we present the correlation of pathological outcome according to early metabolic response in an interim fluorodeoxyglucose F18 positron emission tomography (FDG-PET) scan, and according to stromal tumor infiltrating lymphocytes (TILs) at baseline. Methods: Patients (pts) with previously untreated, histologically confirmed HER2-positive early breast cancer (EBC; clinical prognostic stage cT1c-4a-d, N0–3, M0) were randomized 1:1 to two 3-weekly cycles of a chemotherapy-free induction phase (Part 1) with trastuzumab and pertuzumab (TP) plus 1200 mg atezolizumab (TP+A), or TP alone. Subsequently, all pts received 4 cycles of TP+A in combination with epirubicin 90 mg/m² (Part 2). Randomization was stratified according to baseline TILs (< 5% vs ≥ 5%), hormone receptor status (positive vs. negative), and prognostic stage (≤ IIA vs. ≥ IIB; AJCC v.8.0). An FDG-PET assessment was performed at baseline and after 2 cycles of study treatment. According to PERCIST, early metabolic responses were classified as metabolic complete response (mCR) and metabolic partial response (mPR) and association with outcome was tested with Fisher’s exact test. TIL assessment in pretreatment biopsy specimen were performed according to the recommendations from the International TILs Working Group. Lymphocytic predominant phenotype was defined as a TIL proportion of ≥ 50%. Correlation of TILs and pCR was modeled with logistic regression. Results: Overall, 58 pts were randomized to TP-A (n=29) or TP (n=29) at 9 sites. In 45 patients, a protocol predefined PERCIST assessment was available. An early mCR was achieved in 14 pts (n=14/45, 31.1%): 5 pts (n=5/21, 23.8%) in the TP group and 9 pts (n=9/24, 37.5%) in the TP-A group. Pts with and without an early mCR achieved a pCR in 92.9% (n=13/14) and 54.8% (n=17/31) of cases (p=0.016), respectively. An early mCR/mPR was achieved in 37 pts (n=37/45, 82.2%). Pts with and without an early mCR/mPR achieved a Residual Cancer Burden (RCB) class 0 or I in 89.2% (n=33/37) and 50.0% (n=4/8) of cases (p=0.024), respectively. The mean stromal TIL proportion was 23.9% in the overall population, with 22.8% in TP group and 25.0% in TP-A group. A lymphocytic predominant phenotype was seen in 10.3% of pts treated in the TP group, and 17.2% of pts treated in the TP-A group. No association between TIL proportion at baseline and pCR could be detected (OR for a 10%-point increase = 1.02, 95% CI 0.78-1.34). A moderate positive correlation between numeric values of TILs and PD-L1 ICs was observed (spearman r=0.57, P< 0.0001). Exploratory correlation analyses of PD-L1 status, TIL proportion and metabolic responses in interim FDG-PET scans will be presented at the meeting. Conclusions: In ABCSG-52, chemotherapy de-escalation with intensified immunotherapy was effective and safe. Early metabolic response assessment was feasible and predicted pathologic response; therefore, incorporation of interim FDG-PET results into de-escalation trials merits further investigation. In contrast to regimens without immune-checkpoint inhibitors, TIL proportion at baseline did not correlate with pathological outcome. Funding: Provision of IMP and financial support by Roche Austria GmbH Citation Format: Gabriel Rinnerthaler, Daniel Egle, Rupert Bartsch, Clemens Schmitt, Andreas Petzer, Marija Balic, Edgar Petru, Ursula Denison, Christian F. Singer, Vesna Bjelic-Radisic, Simon Gampenrieder, Michael Knauer, Karl Sotlar, Christine Brunner, Florian Posch, Dominik Hlauschek, Lidija Sölkner, Zsuzsanna Bago-Horvath, Martin Filipits, Manuela Gili, Michael Gnant, Richard Greil. Pathological response according to early metabolic remission in an interim FDG-PET scan and to tumor infiltrating lymphocytes - A secondary analysis of the phase II trial ABCSG 52/ATHENE investigating atezolizumab in early HER2+ BC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-03.

Molecular imaging predicts lack of T-DM1 response in advanced HER2-positive breast cancer (final results of ZEPHIR trial)

Efficacy of the human epidermal growth factor receptor (HER)2-targeting trastuzumab emtansine (T-DM1) in breast cancer (BC) relies on HER2 status determined by immunohistochemistry or fluorescence in-situ hybridization. Heterogeneity in HER2 expression, however, generates interest in “whole-body” assessment of HER2 status using molecular imaging. We evaluated the role of HER2-targeted molecular imaging in detecting HER2-positive BC lesions and patients unlikely to respond to T-DM1. Patients underwent zirconium-89 (89Zr) trastuzumab (HER2) PET/CT and [18F]-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT before T-DM1 initiation. Based on 89Zr-trastuzumab uptake, lesions were visually classified as HER2-positive (visible/high uptake) or HER2-negative (background/close to background activity). According to proportion of FDG-avid tumor load showing 89Zr-trastuzumab uptake (entire/dominant part or minor/no part), patients were classified as HER2-positive and HER2-negative, respectively. Out of 265 measurable lesions, 93 (35%) were HER2-negative, distributed among 42 of the 90 included patients. Of these, 18 (19%) lesions belonging to 11 patients responded anatomically (>30% decrease in axial diameter from baseline) after three T-DM1 cycles, resulting in an 81% negative predictive value (NPV) of the HER2 PET/CT. In combination with early metabolic response assessment on FDG PET/CT performed before the second T-DM1 cycle, NPVs of 91% and 100% were reached in predicting lesion-based and patient-based (RECIST1.1) response, respectively. Therefore, HER2 PET/CT, alone or in combination with early FDG PET/CT, can successfully identify BC lesions and patients with a low probability of clinical benefit from T-DM1.

18F]-Fluorodeoxyglucose Positron Emission Tomography/CT to Assess the Early Metabolic Response in Patients with Hormone Receptor-Positive HER2-Negative Metastasized Breast Cancer Treated with Cyclin-Dependent 4/6 Kinase Inhibitors

Introduction: Addition of cyclin-dependent 4/6 kinase (CDK4/6) inhibitors to endocrine therapy is standard of care in the treatment of women with advanced hormone receptor-positive HER2-negative breast cancer. However, the predictive factors for the treatment response to CDK4/6 inhibitor therapy are poorly elucidated. Early changes in the by [¹⁸F]-fluorodeoxyglucose positron emission tomography (FDG-PET) uptake of tumors receiving different kinds of therapy have proven to reliably predict treatment outcomes in a variety of malignancies. Therefore, the feasibility of early metabolic response assessment to predict the long-term treatment response to CDK4/6 inhibitor therapy was evaluated in the present study. Methods: Eight patients underwent FDG-PET/CT before and after the initiation of CDK4/6 inhibitor therapy (ribociclib, palbociclib or abemcaciclib). CDK4/6 inhibitor therapy was combined with either aromatase inhibition or fulvestrant. The median interval between the treatment start (including baseline PET) and the follow-up PET examination was 14 days. Conventional radiographic staging was performed 3 months after the start of CDK4/6 inhibitor therapy. The percentual changes in molecular tumor volume, SUV_peak, the summed SUV_peak of up to 5 metastases (PERCIST-5), and total lesion glycolysis (TLG) were calculated for each patient. Results: Three patients showed progressive disease after 3 months of CDK4/6 inhibitor therapy, whereas 5 patients showed disease control (3 stable disease and 2 partial remission). Disease control was maintained in these patients (follow-up range 7–22 months). Patients with disease control had a significantly greater decline in TLG (–55.3 vs. 16.7%; p < 0.05). The same was true for the PERCIST-5 (–21.9 vs. 11.3%, p < 0.05). All patients with progressive TLG showed treatment failure and/or a poor outcome. Conclusion: Elevated TLG on early FDG-PET seems to be associated with long-term treatment failure and a poor outcome in patients undergoing CDK4/6 inhibitor therapy for metastatic breast cancer. Early findings indicate a potential prognostic value of early FDG-PET in this setting and warrant a prospective evaluation.

Early metabolic response assessment of breast cancer liver metastases: 4-week posttreatment FDG PET predicts survival after 90Y microsphere radioembolization.

To evaluate the feasibility of early metabolic response assessment with 18F-FDG PET/CT in patients with breast cancer liver metastases 4 weeks after radioembolization with Yttrium-90 labeled microspheres. 25 patients (mean age 58y, range 40-74) with advanced stage liver metastases of breast cancer were treated with 1.9 ± 0.4 GBq of 90Y-microspheres in the salvage setting and underwent 18F-FDG PET/CT at baseline and 4 weeks post-radioembolization. 14 patients (56 %) had an excessive hepatic tumor burden (> 50 % of total liver volume), 21 patients (84 %) had extrahepatic disease. Liver lesions with the highest SUVmax were selected as target lesions and a cut-off was set at 50 % reduction to separate responders from non-responders. The predictive impact of metabolic response on overall survival (OS) was investigated along with other prognostic factors. The median OS in this highly advanced metastatic cohort was 7 months (95 % CI, 5-9). All patients had a reduction in SUVmax (mean ΔSUVmax: -49 ± 26 %) at 4 weeks post-treatment. Patients with > 50 % SUVmax reduction survived longer (median OS 13 mo, 95 % CI 8-18) than the remaining patients (median OS 4 mo, 95 % CI 2-6; p = 0.001). From all investigated baseline factors including age, performance status, and presence of extra-hepatic disease, only the hepatic tumor burden had a significant impact on OS (p = 0.02). This is the first preliminary evidence in breast cancer that early post-radioembolization molecular response assessment of treated liver metastases - as early as 4 weeks posttreatment - may predict survival. If confirmed by larger series, FDG PET/CT could be considered for early response-adapted treatment modifications.

Molecular imaging as a tool to investigate heterogeneity of advanced HER2-positive breast cancer and to predict patient outcome under trastuzumab emtansine (T-DM1): the ZEPHIR trial

Only human epidermal growth factor receptor (HER)2 status determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has been validated to predict efficacy of HER2-targeting antibody-drug-conjugate trastuzumab emtansine (T-DM1). We propose molecular imaging to explore intra-/interpatient heterogeneity in HER2 mapping of metastatic disease and to identify patients unlikely to benefit from T-DM1. HER2-positive mBC patients with IHC3+ or FISH ≥ 2.2 scheduled for T-DM1 underwent a pretreatment HER2-positron emission tomography (PET)/computed tomography (CT) with (89)Zr-trastuzumab. [(18)F]2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT was performed at baseline and before T-DM1 cycle 2. Patients were grouped into four HER2-PET/CT patterns according to the proportion of FDG-avid tumor load showing relevant (89)Zr-trastuzumab uptake (>blood pool activity): patterns A and B were considered positive (>50% or all of the tumor load 'positive'); patterns C and D were considered negative (>50% or all of the tumor load 'negative'). Early FDG-PET/CT was defined as nonresponding when >50% of the tumor load showed no significant reduction of FDG uptake (<15%). Negative (NPV) and positive predictive values (PPV) of HER2-PET/CT, early FDG response and their combination were assessed to predict morphological response (RECIST 1.1) after three T-DM1 cycles and time-to-treatment failure (TTF). In the 56 patients analyzed, 29% had negative HER2-PET/CT while intrapatient heterogeneity (patterns B and C) was found in 46% of patients. Compared with RECIST1.1, respective NPV/PPV for HER2-PET/CT were 88%/72% and 83%/96% for early FDG-PET/CT. Combining HER2-PET/CT and FDG-PET/CT accurately predicted morphological response (PPV and NPV: 100%) and discriminated patients with a median TTF of only 2.8 months [n = 12, 95% confidence interval (CI) 1.4-7.6] from those with a TTF of 15 months (n = 25, 95% CI 9.7-not calculable). Pretreatment imaging of HER2 targeting, combined with early metabolic response assessment holds great promise for improving the understanding of tumor heterogeneity in mBC and for selecting patients who will/will not benefit from T-DM1. NCT01565200.

Interim 18F-Fluorodeoxyglucose Positron Emission Tomography for Early Metabolic Assessment of Response to Cisplatin, Etoposide, and Bleomycin Chemotherapy for Metastatic Seminoma: Clinical Value and Future Directions

BackgroundIn patients with metastatic seminoma, designing a risk-adapted strategy that may help personalize the burden of treatment and follow-up is required. Patients and MethodsPatients who were administered cisplatin, etoposide, and bleomycin (PEB) were staged at baseline with computed tomography (CT), positron emission tomography (PET), and serum tumor markers. Restaging was then performed with PET after 2 cycles of PEB (PET2) and with CT after 3 to 4 cycles of treatment. The 20% cutoff of maximal standardized uptake value (SUVmax) changes and Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria were applied to define the response. The Wilcoxon rank sum test was used to analyze the association between metabolic response and the shrinkage of target lesions. ResultsBetween February 2009 and November 2013, 37 patients were enrolled. After 2 cycles of PEB, 27 patients (72.9%; 95% confidence interval [CI], 55.8-86.2) had a metabolic complete response (CR) and 10 patients had a partial response (PR; 27%; 95% CI, 13.8-44.1). A significant association was found between PET2 response and baseline (P = .003), final diameter (P < .001), and percentage of tumor shrinkage (P = .014) of target lesions. After 18 months' (interquartile range [IQR], 13-23) median follow-up, 2 patients with PET2 PR had relapsed disease; none of those with a CR had relapsed disease. ConclusionsA significant association was found between early metabolic response and tumor shrinkage in patients with advanced seminoma. Patients achieving a PET2 CR could be predicted not to need additional treatment after PEB, and simplifying their follow-up should be an end point. PET2 might also identify difficult to treat cases at an early stage.

597 Interim [18F] Fluorodeoxyglucose Positron Emission Tomography (PET) for early metabolic assessment of response to PEB chemotherapy for metastatic seminoma: Preliminary findings

597 Interim [18F] Fluorodeoxyglucose Positron Emission Tomography (PET) for early metabolic assessment of response to PEB chemotherapy for metastatic seminoma: Preliminary findings

Interim [18f] fluorodeoxyglucose positron emission tomography (PET) for early metabolic assessment of response to PEB chemotherapy for metastatic seminoma: Preliminary findings.

381 Background: A risk-adapted strategy for metastatic seminoma may further refine the necessary burden of chemotherapy while sparing futile treatment. The objective of this study was to evaluate the association of the early metabolic response to cisplatin, etoposide, and bleomycin (PEB) and dimensional response. Methods: Patients (pts) with newly-diagnosed seminoma and who were candidate to PEB were staged at baseline by computed tomography (CT), PET and serum tumor markers (STM). Then, restaging with PET after 2 cycles of PEB (PET2), and with CT after treatment (3-4 cycles [CT3-4]) were provided. One (greatest) target lesion was chosen to evaluate metabolic/dimensional changes. Wilcoxon rank sum test was used to analyze the association between PET response and either the shrinkage of target lesion (primary endpoint) or baseline, or final dimensions. Results: In the time-frame 02/2009-11/2013, 37 pts have been enrolled. Two pts had CSIIA, 13 CSIIB, 13 CSIIC, and 9 CSIII. 3 had an intermediate prognosis because of liver (n=1) and bone (n=2) disease. The latter were recognized by PET while having a bone-negative CT scan. 4 had a retroperitoneal and 1 a mediastinal primary. All pts had a PET-positive target disease. After 2 cycles of PEB, 27 pts (72.9%) had a metabolic complete response (CR), 10 a partial response (PR). 12 pts had a CR at CT3-4. Median follow up was 18 months (IQR: 13-23). A significant association was found between PET2 response and baseline (p=0.003), final diameter (p&lt;0.001), and % of tumor shrinkage (p=0.014). Pts with PET2 CR had a median residual diameter of 1.2 cm (IQR: 1-1.9) while pts with PET2 PR 3.75 cm (IQR: 2.6-6.1, p=0.002). 6 Pts received RT after PEB. 2/10 pts with PET2 PR had a relapse (0/27 CR). Conclusions: A significant association was found between PET2 response and tumor shrinkage in pts with metastatic seminoma. PET2 CR pts could be predicted not to need additional re-imaging or treatment after PEB, and simplifying the follow up should be an endpoint. PET2 PR category includes pts yielding a difficult-to-treat disease. A detailed cost-efficacy analysis of the strategy will be required further.

Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol

IntroductionRegorafenib was recently approved for patients with pretreated advanced colorectal cancer (aCRC), despite a moderate improvement of the patients’ outcome, and significant toxicities. Based on previous studies showing that early...

Accuracy and Efficacy of Whole-Body 18 F-FDG PET in Patient with Recurrent Colorectal Cancer: A Case Report

Background: A 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) is useful for early metabolic response assessment in various malignancies, including Colorectal Cancer (CRC). Herein, we express that Positron Emission Tomography/Computed (PET-CT) with 18FDG was very useful for early diagnosis, accuracy and additional value of whole-body in recurrent CRC. Case Report: A 50 years old woman was diagnosed with an adenocarcinoma of the left side colon. She selected for surgery with left sided hemicolectomy. Final pathologic report of adenocarcinoma high risk stage 2 patient, candidate for adjuvant chemotherapy with Folinic acid, Fluorouracil and Oxaliplatin regimen. Her carcino embryonic antigen (CEA) marker at beginning of diagnosis was in normal range but during last year of follow up her CEA marker increased and rising progressive without any complaints by patient. Gastroenterologist tried to diagnosis further secondary staging with lung, brain, abdominal and pelvic contrast computed tomography (CT) scanning but he could not find any lesion in these areas. But After second staging by whole body PET- CT that we suggested it could reveal a multiple lesion uptake in the left lateral sided of the rectum according to a stage IVB disease. For intraperitoneal metastasis adjuvant chemotherapy (CTX) with capecitabine and oxaliplatin was started. At now she is alive without significant abdominal complaint and therefore she treated with maintenance regimen CTX with capecitabine and regorafenib. Conclusion: A 18F-FDG PET/CT scan was very effective in early diagnosis and High accuracy in finding the precise location of lesion in adenocarcinoma CRC and it can prepare better survival to patients with correctly therapeutic management.

Role of FDG PET/CT in assessing response to targeted therapy in metastatic lung cancers: Morphological versus metabolic criteria.

Introduction:Targeted therapeutic agents are indicated in metastatic lung cancers. These being receptor specific therapies, manifestation of response can be best assessed by estimating the metabolic activity of tumor, rather than the size. This retrospective analysis studied metabolic and morphological response on Positron Emission Tomography (PET) and Computed Tomography (CT), respectively to these agents.Materials and Methods:Thirty-one patients (23 males, 8 females with an age range of 42–77 years) with Epidermal Growth Factor Receptor (EGFR) positive metastatic lung cancer on Gefitinib, who underwent PET/CT, at baseline and at 4–6 weeks, were assessed by Response Evaluation Criteria In Solid Tumors [RECIST] 1.1 and European Organization for Research and Treatment of Cancer (EORTC) criteria.Results:Concordance between RECIST 1.1 and EORTC was seen in 26 (83.7%) patients. Discordance was seen in 5 (16.3%) patients. In patients with discordance, the results were confirmed by follow-up imaging. Metabolic EORTC criteria changed the disease status from stable disease to partial response (3 out of 5) and progressive disease (2 out of 5) in these five patients.Conclusions:Metabolic criteria using PET/CT could accurately predict response as well as disease progression early in the course of targeted therapy, compared to morphologic criteria. In addition, early metabolic response assessment can predict refractoriness of therapy.

857P - Interim [18F] Fluorodeoxyglucose Positron Emission Tomography (Pet) for Early Metabolic Assessment of Response to Peb Chemotherapy for Metastatic Seminoma: Preliminary Findings

ABSTRACT Aim: A risk-adapted strategy for metastatic seminoma may further refine the necessary burden of chemotherapy while sparing futile treatment for early recognized good responders. The objective of this proof-of-principle study was to evaluate the association of an early metabolic response to PEB and the dimensional response at the end of treatment. Methods: Patients (pts) with newly-diagnosed seminoma and who were candidate to PEB were staged at baseline by computed tomography (CT), PET and serum tumor markers (STM). Then, restaging with PET after 2 cycles of PEB (PET2), and with CT after treatment (3-4 cycles [CT3-4]) were provided. One (greatest) target lesion was chosen to evaluate metabolic/dimensional changes in each case. The primary endpoint was the association between PET2 (EORTC criteria) and CT3-4 response. Secondary endpoints were progression-free survival (PFS) and ability to detect visceral metastases. An analysis after the initial 35 pts was planned. Results: In the time-frame 06/2010-11/2013, 35 pts have been enrolled in this single-site study. Two pts had CSIIA, 12 CSIIB, 13 CSIIC, and 8 CSIII. 3 had an intermediate prognosis because of liver (1) and bone (2) disease. These two were recognized by PET while having a bone-negative CT scan. 4 had a retroperitoneal and 1 a mediastinal primary. All pts had a PET-positive target disease (retroperitoneal in 33 and mediastinal in 2). After 2 cycles of PEB, 25 pts (71.4%) had a metabolic complete response (CR), 10 a partial response (PR). 10 pts had a CR at CT3-4. PET2-negative pts had a significantly smaller residual disease at CT3-4 scan (median 1.2 cm [IQR: 2.8-6] vs 4 cm [IQR: 1-1.9], p Conclusions: PET2 early identified pts having the greatest response to chemotherapy and who finally reached the cut off for observation only ( Disclosure: All authors have declared no conflicts of interest.

Regorafenib assessment guided by metabolic imaging in refractory advanced colorectal cancer (aCRC): REGARD-C study.

Background: Regorafenib, an oral multi-tyrosine kinase inhibitor that shares with sorafenib several targets on tumor angiogenesis, oncogenesis, and tumor microenvironment, was recently approved for patients (pts) with pretreated advanced colorectal cancer (aCRC). The drug improves the pts’ outcome, but with significant toxicities, underscoring the need to identify those who will not benefit. A previous study (SoMore trial) showed that early FDGPET-based metabolic response assessment (MRA) may adequately discriminate pts with chemorefractory aCRC unlikely to benefit from a sorafenib-capecitabine combination. RegARd-C aims to explore early MRA in pts treated with regorafenib as a clinical tool to spare pts from needless toxicity from a drug that gives them little or no benefit and as a translational tool to guide comprehensive genomic and epigenetic research on the determinants of drug resistance. Methods: RegARd-C’s (EUDRACT 2012-005655-16) is a multi-centric prospective study. Its primary objective is to identify in a population of pts with pretreated aCRC, those who will not benefit from regorafenib given at 160 mg/day, three weeks/4. Baseline PET is repeated at D14 of the first treatment course. MRA results are blinded for the investigators. Tumor tissues, optionally obtained from a PET-measurable lesion, and blood samples (at baseline; after the first chemotherapy course; and every two months) are collected. Overall survival (OS) is the primary endpoint and will be correlated with metabolic parameters, and genetic, epigenetic and molecular aberrations assessed from tumor biopsies and blood samples using gene expression and methylation profiling, RNA and exome sequencing. As the study is exploratory, no formal hypothesis was formulated. We arbitrarily decided to have a sample size of 105 evaluable pts with 70 pts as a derivation set and 35 pts as a validation set. Taking into account an expected 20-25% drop-out rate, between 124 and 140 pts will be accrued.This sample size is, however, sufficient to validate the hypothesis generated by the SoMore study, which found a prognostic impact of homogeneous metabolic response on OS, with an estimated HR of 0.59. RegARd-C has accrued 76 pts since August 2013. Clinical trial information: NCT01929616.

SoMore trial: Early metabolic response assessment of a sorafenib (SOR) and capecitabine (CAP) combination in chemorefractory metastatic colorectal cancer (mCRC).

524 Background: The SOR-CAP combination has shown clinical activity in several phase I-II trials involving metastatic breast cancer and mCRC patients (pts). SoMore aims to substantiate the combination’s effects in mCRC refractory to all medications and the predictive value of early metabolic response (MR) on survival. Methods: SoMore (EUDRACT 2010-023695-91) has 2 coprimary objectives: 1) to demonstrate an overall survival (OS) rate at 6 months (mths) &gt; 30%, and 2) to compare OS between pts with and without MR. CAP was given at 1700 mg/m²/day (D), 2 weeks out of 3. SOR was administered at 600mg/D for the first cycle, then at 800mg/D until progression or unacceptable toxicity. FDGPET-CT was performed at baseline and before the 2nd cycle. MR analysis was centralized and blinded for the investigators. Results: From February to October 2011, 92 eligible pts were prospectively recruited in 6 Belgian centers: M/F: 54%/46%; ECOG PS 0/1: 55%/45%; median age: 61. A median of 5 treatment cycles were given (0-28+). Grade 3-4 toxic reactions were reported in 61.2%, mainly fatigue (18%), hand-foot skin reaction (14%) and diarrhea (11%), but no toxic death. 6.9% of the pts stopped therapy due to toxicity. 6 mths OS was 71% (95% CI: 61%-79%), significantly &gt;30% (p&lt;0.001). 47% of the 79 pts evaluable for metabolic assessment showed homogeneous MR (HMR) of all metastatic lesions, 32% mixed MR and 21% homogeneous non-MR. Median overall OS and PFS of the intent-to-treat population and of pts with and without HMR are shown in the table below. Hazard ratio for HMR was 0.34 (95% CI, 0.21 to 0.56) p-value &lt;0.001 for PFS and 0.59 (95% CI, 0.37 to 0.96) p-value 0.03 for OS. Conclusions: These data suggest robust efficacy for the SOR-CAP combination in heavily pretreated mCRC, associated with high but manageable toxicity. Early MR assessment, by detecting unresponsive lesions within the whole body tumoral load, is able to capture the pts’ likelihood of benefit, opening the path to personalized medicine. Clinical trial information: NCT01290926. [Table: see text]

362P - Might Early Metabolic Response by 18F-FDG-PET/CT be Useful to Select Patients (PTS) With Breast Cancer (BC) who Will not Optimally Respond to Preoperative Chemotherapy (PCT)?

ABSTRACT Purpose To evaluate 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) changes between baseline and after 2 cycles of PCT in pts with early/locally advanced (E/LA) BC, with the aim to verify whether early metabolic assessment of response during PCT may have a role in clinical practice to enable early changes in the therapeutic strategy. Patients and methods Sixty pts with newly diagnosed E/LA BC received 6-8 cycles of anthracycline and taxane-based PCT. Fifty-eight pts underwent surgery, which consisted in breast conserving surgery or radical mastectomy; axillary node dissection was performed in all cases. Optimal pathologic response (pR) to PCT was defined as absence of cancer cells in breast and ipsilateral axillary lymph nodes. All other conditions were defined as nonresponders (pNR). Maximum standardized uptake value (SUV max) with 18F-FDG PET/CT was measured for each pathologic lesion at baseline and after 2 cycles of PCT. SUV max percentage changes (Δ-SUV) were compared with pR rate according to immunohistochemical (IHC) BC characteristics. Δ-SUV >50% defined a metabolic response (MetR). Results Thirteen (22%) of 60 pts achieved pR. According to IHC, pR rates where 16% in ERpositive/HER2negative (ER + /HER2-) pts, 29% and 27% in HER2-positive (HER2+) and triple negative (TN) pts respectively. Sensitivity of metR to identify pR was 100% in all three subgroups, but the specificity was low: 38% in ER + /HER2- pts (38%) was the highest value. In this subgroup of pts PET had a low positive predictive value (24%), while the negative predictive value was 100%, showing, compared to HER2+ and TN pts, the highest ability to correctly predict pNR (32%). At a median follow-up of 36.6 months, recurrence rate was higher in metabolic non-responders, particularly in the ER + /HER2- subgroup, in which Kaplan-Meier analysis of disease-free survival confirmed a significant difference (p = 0.0490). Conclusions PET assay after 2 cycles of PCT correctly predicted pNR in 32% of ER + /HER2- pts, identifying a subgroup of BC pts with worse prognosis who might benefit from an early change of the therapeutic strategy. Disclosure All authors have declared no conflicts of interest.

FDG-PET/CT based response-adapted treatment.

It has been shown that [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) provides robust and reproducible data for early metabolic response assessment in various malignancies. This led to the initiation of several prospective multicenter trials in malignant lymphoma and adenocarcinoma of the esophagogastric junction, in order to investigate whether the use of PET-guided treatment individualization results in a survival benefit. In Hodgkin lymphoma and aggressive non-Hodgkin lymphoma, several trials are ongoing. Some studies aim to investigate the use of PET in early identification of metabolic non-responders in order to intensify treatment to improve survival. Other studies aim at reducing toxicity without adversely affecting cure rates by safely de-escalating therapy in metabolic responders. In solid tumors the first PET response-adjusted treatment trials have been realized in adenocarcinoma of the esophagogastric junction. These trials showed that patients with an early metabolic response to neoadjuvant chemotherapy benefit from this treatment, whereas metabolic non-responders should switch early to surgery, thus reducing the risk of tumor progression during chemotherapy and the risk of toxic death. The trials provide a model for designing response-guided treatment algorithms in other malignancies. PET-guided treatment algorithms are the promise of the near future; the choice of therapy, its intensity, and its duration will become better adjusted to the biology of the individual patient. Today’s major challenge is to investigate the impact on patient outcome of personalized response-adapted treatment concepts.

Induction Chemotherapy in Barrett Cancer

To study the impact of induction chemotherapy on surgical risk and outcome in locally advanced Barrett cancer. Induction chemotherapy has become an accepted choice for the treatment of locally advanced adenocarcinoma of the esophagus and the esophagogastric junction. It has been shown that early assessment of metabolic response using positron emission tomography predicts response to chemotherapy. Metabolic response has also been revealed to be an independent prognostic factor. Surgical risk and outcome in metabolic responders were compared with those in nonresponders. The study design predefined a 12-week multicourse preoperative chemotherapy regimen in metabolic responders. In contrast, chemotherapy was stopped after a 2-week induction period in metabolic nonresponders. All patients were scheduled for surgical resection. Of 110 evaluable patients, 50 metabolic responders and 54 nonresponders underwent resection. Postoperative complications occurred in 34%. Two patients (1.8%) died. There were no significant differences between responders and nonresponders in terms of postoperative morbidity and mortality. Major histologic remissions were seen in 58% of metabolic responders. Metabolic responders had an increased chance of having an R0 resection (96% vs. 74%; P=0.002) and a decreased risk of developing hematogenous or distant lymphatic recurrence (32% vs. 54%, P=0.019). This translated into better recurrence-free and overall survival. Induction chemotherapy and early metabolic response assessment is a new concept in the treatment of locally advanced Barrett cancer. Metabolic responders undergoing multicourse preoperative chemotherapy have a good prognosis. The best treatment strategy for nonresponders remains to be defined.

Visualisation of metastatic oesophageal and gastric cancer and prediction of clinical response to palliative chemotherapy using 18FDG PET

This study assessed the value of (18)F-deoxyglucose positron emission tomography (FDG-PET) for visualisation and early metabolic response assessment in metastatic gastro-oesophageal cancer. Twenty-six patients who were treated for metastatic disease (20 adenocarcinomas, 6 squamous cell cancers) underwent FDG-PET before and two weeks after the onset of palliative chemotherapy with either oxaliplatin + 5-FU/LV or with docetaxel + capecitabine. PET results were validated according to clinical response based on RECIST criteria. Twenty-four tumours (92%) could be visualised by FDG-PET and were also assessable by a second PET scan at 2 weeks. The 2 tumours that were not detectable by PET were both gastric cancers belonging to the non-intestinal subtype according to Lauren. Median time to progression and overall survival were not significantly different for metabolic responders and non-responders (6.3 vs 5.3 months and 14.1 vs 12.5 months, respectively). In this heterogeneous study population, FDG-PET had a limited accuracy in predicting clinical response. However, the metabolic response prediction was particularly good in the subgroup of patients with oesophageal squamous cell cancer. Therefore, FDG-PET and assessment of cancer therapy clearly merits further investigation in circumscribed patient populations with metastatic disease.

Individualized neoadjuvant treatment strategy in adenocarcinoma of the esophago-gastric junction (AEG): Interim report on the MUNICON trial

4060 Background: 18-Fluorodeoxyglucose-PET (FGD-PET) was found to be a valuable tool for the prediction of response during neoadjuvant chemotherapy (CTx) in locally advanced AEG. Major histological remissions were seen in 53% of metabolic responders whereas in unselected patients the rate was found to be only 24% (Weber et al. JCO 2001: 3058–65). The MUNICON trial implements response prediction by means of FDG-PET into clinical decision making. Methods: Patients (pts) with cT3 AEG receive platin-based neoadjuvant CTx. Metabolic responders (decline of FDG tumor uptake > 35% 2 weeks after the onset of CTx compared to baseline PET) continue with CTx for a duration of 3 months. Metabolic non-responders discontinue CTx and proceed to surgery. Clinical response is assessed according to RECIST. Major histological response is defined as <10% vital tumor cells in the resected tumor. The recruitment goal is 108 pts within 3 yrs. The primary endpoint is survival. Results: From 6/02–3/03 34 pts (median age 62 yrs, range 36–75; 32 males) have been enrolled. 22 pts (65%) were classified as metabolic responders. 11 pts (32%) were non-reponders. 1 patient (3%) died before metabolic response assessment. 31 pts (91%) underwent resection. R0 resection was achieved in 26/34 pts (76%), thereof 18/22 responders (82%) and 8/11 non-responders (73%). In metabolic responders, clinical remission was achieved in 14 pts (64%; 95% CI 0.41–0.83) and major histological response was seen in 11 pts (50%, 95% CI 0.28 – 0.72). In all metabolic non-reponders clinical staging (cT3) was confirmed histopathologically (pT2b/3). None of the metabolic non-responders had achieved any grade of histological regression. After a median follow-up of 12 (8–18) months 6 pts have died. Further survival endpoints were not subject of this interim analysis. Conclusion: The interim analysis of the MUNICON trial confirms previous findings. An individualized treatment approach in locally advanced AEG proves to be feasible. Early metabolic response assessment aids to select patients for neoadjuvant chemotherapy who have a good chance for clinical and histological response. No significant financial relationships to disclose.

Individualized neoadjuvant treatment strategy in adenocarcinoma of the esophago-gastric junction (AEG): Interim report on the MUNICON trial

4060 Background: 18-Fluorodeoxyglucose-PET (FGD-PET) was found to be a valuable tool for the prediction of response during neoadjuvant chemotherapy (CTx) in locally advanced AEG. Major histological remissions were seen in 53% of metabolic responders whereas in unselected patients the rate was found to be only 24% (Weber et al. JCO 2001: 3058–65). The MUNICON trial implements response prediction by means of FDG-PET into clinical decision making. Methods: Patients (pts) with cT3 AEG receive platin-based neoadjuvant CTx. Metabolic responders (decline of FDG tumor uptake > 35% 2 weeks after the onset of CTx compared to baseline PET) continue with CTx for a duration of 3 months. Metabolic non-responders discontinue CTx and proceed to surgery. Clinical response is assessed according to RECIST. Major histological response is defined as <10% vital tumor cells in the resected tumor. The recruitment goal is 108 pts within 3 yrs. The primary endpoint is survival. Results: From 6/02–3/03 34 pts (median age 62 yrs, range 36–75; 32 males) have been enrolled. 22 pts (65%) were classified as metabolic responders. 11 pts (32%) were non-reponders. 1 patient (3%) died before metabolic response assessment. 31 pts (91%) underwent resection. R0 resection was achieved in 26/34 pts (76%), thereof 18/22 responders (82%) and 8/11 non-responders (73%). In metabolic responders, clinical remission was achieved in 14 pts (64%; 95% CI 0.41–0.83) and major histological response was seen in 11 pts (50%, 95% CI 0.28 – 0.72). In all metabolic non-reponders clinical staging (cT3) was confirmed histopathologically (pT2b/3). None of the metabolic non-responders had achieved any grade of histological regression. After a median follow-up of 12 (8–18) months 6 pts have died. Further survival endpoints were not subject of this interim analysis. Conclusion: The interim analysis of the MUNICON trial confirms previous findings. An individualized treatment approach in locally advanced AEG proves to be feasible. Early metabolic response assessment aids to select patients for neoadjuvant chemotherapy who have a good chance for clinical and histological response. No significant financial relationships to disclose.