New possibilities for molecular imaging and intervention in breast cancer and other female malignancies
Angela Collarino is a PhD student in the research group Biomedical Photonic Imaging. Her Supervisor is professor Lioe-Fee de Geus-Oei from the Faculty Science and Technology
The work described in this thesis shows new possibilities for molecular imaging in breast and vulvar cancer and demonstrates how to simultaneously encompass all current and future applications of nuclear medicine in female cancers. General introduction and outline of this thesis are reported in Chapter 1. In part one of this thesis the reader is introduced to molecular imaging using 99mTc-sestamibi in breast cancer. Part two of this thesis describes the methodological aspects and clinical evaluation of 99mTc-sestamibi-guided biopsy. Part three presents the radioguided intervention in gynaecological malignancies. Discussion and future perspectives are reported in the fourth part of this thesis.
PART I
Chapter 2 provides a systematic review and meta-analysis on 99mTc-sestamibi imaging in the prediction of pathological nonresponse to neoadjuvant chemotherapy in primary locally advanced breast cancer. Up till now, only planar 99mTc-sestamibi imaging has been investigated, showing low sensitivity to predict pathologic nonresponse. 99mTc-sestamibi uptake during neoadjuvant chemotherapy seems highly sensitive, but the experience is limited to a few studies. The introduction of quantitative SPECT/CT imaging for early nonresponse monitoring could provide a new horizon. Chapter 3 presents the experimental validation of SPECT/CT quantification for response monitoring in breast cancer. Our results show that quantification using SPECT/CT is feasible when a 42% isocontour is used for delineation for tumour of at least 17 mm diameter. However, with tumour shrinkage, response evaluation should be handled with care, especially when using SUVmax. In chapter 4, the clinical use of MBI is evaluated in 287 patients with newly diagnosed breast cancer scheduled for lumpectomy. In this setting, MBI revealed more accurately the disease extent and presence of additional tumour foci, adjusting surgical management in 9% of the patients. Hence, incorporation of this modality in the clinical workup could improve the selection of patients for lumpectomy.
The general conclusion from part I is that technological advances in dedicated devices and SPECT/CT have the potential to lead to improvements in the detection and therapy monitoring in patients with breast cancer, and can also lead to relevant changes in patient management.
PART II
Part II of this thesis focuses on 99mTc-sestamibi guided biopsy in breast cancer. Chapter 5 addresses the methodological aspects of 99mTc-sestamibi MBI-guided biopsy. All procedure steps of this new biopsy modality are described and its advantages and limitations are discussed in comparison with radiology-guided modalities. Finally, future clinical applications, such as targeted biopsies in large and heterogeneous tumours, are discussed. In chapter 6, the first clinical experience using stereotactic biopsy guided by 99mTc-sestamibi is evaluated in 38 women. This biopsy procedure proved to be successful, acquiring representative samples in all patients. All samples were adequate for histopathological analysis. The procedure was well tolerated in all patients.
The general conclusion from part II of this thesis is that 99mTc-sestamibi MBI-guided biopsy is a valid tool for biopsy of breast lesions, complementary to radiology-assisted biopsy modalities. Moreover, the results of the above-described study show that this new biopsy tool is technically feasible and reliable. These promising results encourage a further validation in large (multicentre) studies.
PART III
Part III of this thesis discusses the issue of radioguided interventions in other female cancers. Chapter 7 provides an overview of the state-of-the-art of sentinel lymph node mapping in gynaecological malignancies, including vulvar cancer, cervical cancer and endometrial cancer. Currently, the sentinel node biopsy is a standard procedure in early stage vulvar- and cervical cancer, while it is considered investigational in endometrial cancer. This chapter also describes the methodological advances in preoperative and intraoperative imaging. In chapter 8, the lymphatic drainage pattern, using SPECT/CT, is evaluated in 83 patients with vulvar cancer scheduled for the sentinel lymph node procedure. Lymphatic drainage occurred mainly to the medial regions of the groin with only incidental drainage to the lateral inferior region. Therefore, in patients with metastatic sentinel node(s), scheduled for inguinal lymph node dissection, the lateral inferior region of the groin might be spared. In Chapter 9 we investigate the value of dual-time-point 18F-FDG PET/CT in the prediction of lymph node status in 33 patients with invasive vulvar cancer, scheduled for inguinofemoral lymph node dissection. The results underline that standard PET/CT (at 1 hour after 18F-FDG injection) is highly predictive of pathological negative groins and thus valuable for selecting patients suitable for minimal invasive surgery. Delayed PET/CT (at 3 hours after 18F-FDG injection) did not improve the specificity and positive predictive value of the modality.
From part III it can be concluded that preoperative SPECT/CT is a valid roadmap for surgeons and that PET/CT enables identification of patients for minimal invasive surgery.
PART IV
Part IV of this thesis presents the future perspective of nuclear medicine imaging in female tumours. Chapter 10 discusses the novel frontiers of dedicated molecular imaging in breast cancer diagnosis. In particular, targeted biopsy and precision breast cancer medicine will be the future application of dedicated breast devices. Additionally, new and specific radiotracers as well as the introduction of novel hybrid devices will facilitate cancer detection and therapy monitoring. Chapter 11 highlights some recent advances for gynaecological malignancies particularly in vulvar cancer. The combined use of radiotracer and fluorescence as well as the incorporation of new technological tools will improve the localisation of sentinel lymph nodes before and during the surgical procedure. A novel technique in quantitative PET/CT is texture analysis to evaluate intratumour heterogeneity. This technique may be of particular interest in the characterization and prediction of prognosis of locally advanced vulvar cancer and other gynaecological malignancies.
