Metabolic imaging and early response assessment by positron emission tomography (PET) are gaining importance in guiding treatment of localised and metastatic gastrointestinal tumours. During a workshop organised by the European Organisation of Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Group the most relevant research questions, methodological aspects and unmet clinical needs in this disease were discussed. Potential future trials were drafted. This paper reviews the lectures and discussions held during this workshop and summarises the action points for the further investigation of metabolic imaging to guide treatment in gastrointestinal tumours.
"Monitoring of the individual tumor response is crucial for optimizing systemic treatment in patients with cancer, particularly as treatments trend toward individualized patient care    . Therapy response assessment is generally performed by anatomic imaging using the standardized Response Evaluation Criteria In Solid Tumors criteria on the basis of changes in anatomic tumor size . "
[Show abstract][Hide abstract] ABSTRACT: Anatomic imaging alone is often inadequate for tuning systemic treatment for individual tumor response. Optically based techniques could potentially contribute to fast and objective response monitoring in personalized cancer therapy. In the present study, we evaluated the feasibility of dual-modality diffuse reflectance spectroscopy-autofluorescence spectroscopy (DRS-AFS) to monitor the effects of systemic treatment in a mouse model for hereditary breast cancer.
Brca1(-/-); p53(-/-) mammary tumors were grown in 36 mice, half of which were treated with a single dose of cisplatin. Changes in the tumor physiology and morphology were measured for a period of 1 week using dual-modality DRS-AFS. Liver and muscle tissues were also measured to distinguish tumor-specific alterations from systemic changes. Model-based analyses were used to derive different optical parameters like the scattering and absorption coefficients, as well as sources of intrinsic fluorescence. Histopathologic analysis was performed for cross-validation with trends in optically based parameters.
Treated tumors showed a significant decrease in Mie-scattering slope and Mie-to-total scattering fraction and an increase in both fat volume fraction and tissue oxygenation after 2 days of follow-up. Additionally, significant tumor-specific changes in the fluorescence spectra were seen. These longitudinal trends were consistent with changes observed in the histopathologic analysis, such as vital tumor content and formation of fibrosis.
This study demonstrates that dual-modality DRS-AFS provides quantitative functional information that corresponds well with the degree of pathologic response. DRS-AFS, in conjunction with other imaging modalities, could be used to optimize systemic cancer treatment on the basis of early individual tumor response.
"In general, the role of metabolic imaging and early response assessment to anticancer therapy is one of oncology's key questions today. The implications for therapeutic management and treatment strategies, especially in patients with gastrointestinal cancer, are a point of intensive discussion . For example, in locally advanced adenocarcinoma of the esophagogastric junction, the MUNICON trial showed the value of early metabolic response evaluation and demonstrated the feasibility of a PET-guided treatment algorithm in clinical practice . "
[Show abstract][Hide abstract] ABSTRACT: The epidermal growth factor receptor monoclonal antibody cetuximab has proven activity in metastatic colorectal cancer. To date, the mechanisms of action are not completely understood. Especially the impact on tumor glucose metabolism, or tumor vascularization remains largely unclear. The understanding of mechanisms such as early changes in tumor metabolism is of clinical importance since there may be a substantial influence on choice and sequence of drug combinations. Early signals of response to cetuximab may prove useful to identify patients having a relevant clinical treatment benefit. The objective of this trial is to evaluate the predictive relevance of the relative change in (18)F-Fluorodeoxyglucose tumor uptake for early clinical response during short-term single agent treatment with cetuximab. Early clinical response will be routinely measured according to the response evaluation criteria in solid tumors. Accompanying research includes cytokine immune monitoring and analysis of tumor proteins and tumor genes.
The REMOTUX trial is an investigator-initiated, prospective, open-label, single-arm, single-center early exploratory predictive study. The first (18)F-FDG PET-CT is conducted at baseline followed by the run-in phase with cetuximab at days 1 and 8. At day 14, the second (18)F-FDG PET-CT is performed. Subsequently, patients are treated according to the Folfiri-cetuximab regimen as an active and approved first-line regimen for metastatic colorectal carcinoma. At day 56, clinical response is evaluated with a CT-scan compared to the baseline analysis. Tracer uptake is assessed using standardized uptake values (SUVs). The main hypothesis to be tested in the primary analysis is whether or not the relative change in the SUV from baseline to day 14 has any predictive relevance for early clinical response determined at day 56. Patients are followed until death from any cause or until 24 months after the last patient has ended trial treatment.
The aim of this trial is to evaluate metabolic changes in metastatic colorectal cancer during short-term single agent treatment with cetuximab and to analyse their potential of predicting early clinical response. This could be helpful to answer the question if early identification of patients not responding to cetuximab is possible.
ClinicalTrials.gov NCT200811021020; EudraCT 200901327923.
BMC Cancer 03/2012; 12(1):108. DOI:10.1186/1471-2407-12-108 · 3.36 Impact Factor
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