Heterogeneity of Metabolic Response to Systemic Therapy in Metastatic Breast Cancer Patients

doi:10.1016/j.clon.2010.05.021

Clinical Oncology

Volume 22, Issue 10, December 2010, Pages 818-827

https://doi.org/10.1016/j.clon.2010.05.021 Get rights and content

Abstract

Aim

The aim of this retrospective study was to describe the intra-individual heterogeneity of the ¹⁸F-labelled fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) response among lesions in bone-dominant metastatic breast cancer patients treated with systemic therapies.

Patients and methods

The metabolic response was analysed by comparing PET/CT scans carried out before and during a new treatment phase (n = 46) in 25 bone-dominant metastatic breast cancer patients. Patients presented both bone and extra-bone metastases in 48% treatment phases. The metabolic response was analysed according to European Organization for Research and Treatment of Cancer (EORTC) criteria. A heterogeneous response was defined as the coexistence of responding and non-responding lesions within the same patient.

Results

The lesion-based response analysis showed a heterogeneous metabolic response in 48% of treatment phases. In the subset with both bone and extra-bone metastases (n = 20), PET/CT showed discordant responses between bone and extra-bone metastases in 6/20 (30%) treatment phases. Considering all the cases included in the study, the time to progression (TTP) was longer in cases with a metabolic response compared with the cases with a metabolic non-response (P = 0.02). In cases with a PET/CT non-response, TTP seemed to be lower in those with a homogeneous non-response compared with those with a heterogeneous metabolic response (P = 0.07).

Conclusion

Whole-body FDG-PET allows frequent heterogeneous responses after systemic therapy to be identified in bone-dominant metastatic breast cancer patients.

Introduction

Accurate monitoring of systemic disease in patients with metastatic breast cancer (MBC) should help to identify the subset of non-responding patients and allow early discontinuation of ineffective and toxic treatment. Assessing the treatment response in these patients is hampered by the fact that up to 70% of them have bone metastases [1], which are notoriously problematic to monitor [2]. The size of bone metastases is difficult to estimate and does not necessarily change with treatment response. For this reason, the Response Evaluation Criteria In Solid Tumors (RECIST) considers bone lesions as non-measurable [3]. New RECIST criteria recently published specify that only lytic or mixed lesions with identifiable soft tissue components can be considered as measurable lesions [4].

Bone scintigraphy remains an excellent imaging tool to detect bone metastases. However, the assessment of the treatment response by bone scintigraphy is generally difficult to interpret.

Changes occur slowly and sometimes a paradoxically increased activity in responding bone lesions (flare phenomenon) within 3 months of a new therapy can occur, which cannot be distinguished from progressive disease [5], [6].

Circulating tumour markers (CTM) are widely used to monitor MBC patients. The American Society of Clinical Oncology updated the clinical practice guidelines for the use of CTM in these patients. It states that for monitoring MBC patients during active therapy, CTM can be used in conjunction with history, physical examination and diagnostic imaging [7]. Increasing CTM levels may indeed indicate a local or systemic treatment failure. However, a stable or decreasing CTM level in a patient with multiple metastases is more difficult to interpret because heterogeneous responses among lesions might occur.

A recent advance for assessing disease extent in MBC patients is positron emission tomography (PET) with ¹⁸F-labelled fluorodeoxyglucose (FDG), a whole-body functional imaging tool. The modality has been upgraded by the introduction of hybrid PET/computed tomography (CT) technology, which allows the simultaneous assessment of the metabolic and structural-anatomical aspects of suspected disease sites, thereby increasing the overall diagnostic accuracy. PET/CT is today the most accurate technique for assessing the extent of recurrent MBC [8]. Encouraging data are becoming available on the use of FDG-PET for treatment monitoring. Its performance has been validated in the neoadjuvant setting where the early FDG-PET response of the primary breast tumour correlates with the histopathological response [9], [10], [11], [12], [13]. However, only a few studies have evaluated FDG-PET for the assessment of treatment response in bone-dominant MBC patients, but the results of these studies are promising [14], [15], [16].

Repeating whole-body FDG-PET during systemic treatment in bone MBC should allow a metabolic response assessment on a lesion-by-lesion basis, including bone and visceral sites, in one imaging session. The aim of this study was to describe the intra-individual heterogeneity of response among metastatic lesions, and to correlate the overall PET/CT response with the clinical time to progression (TTP) and the CTM response.

Section snippets

Patients

A search of the database of the PET centre of the Bordet Institute, a comprehensive cancer centre, identified 110 histopathologically proven breast cancer patients who underwent at least two PET/CT between November 2004 and September 2007. These medical records were studied to select bone-dominant MBC patients defined as patients presenting distant lesions confined to the bone, with or without extra-bone lesions. Among these patients, we selected those who had undergone a baseline PET/CT,

Overall and Lesion-based Positron Emission Tomography Response Analysis

Figure 1 illustrates how FDG-PET can be used to monitor the treatment effects on a whole-body level by showing different metabolic responses during consecutive treatment phases in the same patient. Based on the analysis of treatment phases, PET/CT indicated a homogenous metabolic response in 8/46 (17%) of the treatment phases (complete response in one, partial response in seven cases). In all other treatment phases (83%), PET/CT showed non-responsive disease (stable disease in 17; progressive

Heterogeneous Metabolic Responses

The originality and the principal aim of our study was to study the intra-individual heterogeneity of response among metastatic lesions as measured by serial whole-body FDG-PET/CT in bone MBC patients undergoing different types of systemic treatment. This is the first study describing the intra-individual variability of the metabolic responses among lesions in these patients. Surprisingly, we observed a frequent occurrence of heterogeneous PET responses: responding and non-responding metastatic

Conclusions

PET/CT allows the intra-individual heterogeneity of a tumour response among metastatic lesions to be identified. In our study, heterogeneous responses were frequent, particularly in bone lesions, and seems to be associated with an intermediate treatment outcome. Prospective studies should now be conducted to confirm our observations and research in this domain should be led to determine the implicated mechanisms that could explain the origin of these heterogeneous responses. Also, metabolic

Acknowledgement

The authors wish to thank Dr Jan Berneim for his editorial assistance.

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Original ArticleHeterogeneity of Metabolic Response to Systemic Therapy in Metastatic Breast Cancer Patients

Abstract

Aim

Patients and methods

Results

Conclusion

Introduction

Section snippets

Patients

Overall and Lesion-based Positron Emission Tomography Response Analysis

Heterogeneous Metabolic Responses

Conclusions

Acknowledgement

Eur J Cancer

Ann Oncol

Acad Radiol

Eur J Cancer

Clinical features of metastatic bone disease and risk of skeletal morbidity

Clin Cancer Res

Bone imaging in metastatic breast cancer

J Clin Oncol

New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada

J Natl Cancer Inst

Bone scan flare predicts successful systemic therapy for bone metastases

J Nucl Med

Flare on bone scintigraphy following Taxol chemotherapy for metastatic breast cancer

J Nucl Med

American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer

J Clin Oncol

Is there a role for positron emission tomography in breast cancer staging?

J Clin Oncol

Tumor metabolism and blood flow changes by positron emission tomography: relation to survival in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer

J Clin Oncol

Original Article
Heterogeneity of Metabolic Response to Systemic Therapy in Metastatic Breast Cancer Patients