New possibilities for molecular imaging and intervention in breast cancer and other female malignancies

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. 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. Chapter 3 presents the experimental validation of SPECT/CT quantification for response monitoring in breast cancer. In chapter 4, the clinical use of MBI is evaluated in 287 patients with newly diagnosed breast cancer scheduled for lumpectomy. Part two of this thesis describes the methodological aspects and clinical evaluation of 99mTc-sestamibi-guided biopsy. Chapter 5 addresses the methodological aspects of 99mTc-sestamibi MBI-guided biopsy. In chapter 6, the first clinical experience using stereotactic biopsy guided by 99mTc-sestamibi is evaluated in 38 women. Part three presents the radioguided interventions in gynaecological malignancies. 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. 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. 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. Discussion and future perspectives are reported in the fourth part of this thesis. Chapter 10 discusses the novel frontiers of dedicated molecular imaging in breast cancer diagnosis. Chapter 11 highlights some recent advances for gynaecological malignancies particularly in vulvar cancer

Intrapancreatic Accessory Spleen Detected by 68Ga DOTANOC PET/CT and 99mTc-Colloid SPECT/CT Scintigraphy

A 77-year-old man was referred to our center for a suspected neuroendocrine neoplasm in the pancreatic tail, incidentally detected at CT. Ga DOTANOC PET/CT showed intense tracer uptake in the pancreatic lesion. At MRI, the lesion was similar to the spleen on all sequences, suggesting the presence of intrapancreatic accessory spleen. A Tc-colloid SPECT/CT scan performed to differentiate spleen tissue from neuroendocrine tumor revealed a focal uptake in the pancreatic lesion, thus confirming the presence of ectopic spleen and avoiding unnecessary surgery

Is Technetium-99m Sestamibi Imaging Able to Predict Pathologic Nonresponse to Neoadjuvant Chemotherapy in Breast Cancer? A Meta-analysis Evaluating Current Use and Shortcomings

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Is Technetium-99m Sestamibi Imaging Able to Predict Pathologic Nonresponse to Neoadjuvant Chemotherapy in Breast Cancer?: A Meta-analysis Evaluating Current Use and Shortcomings

Background: Interest in technetium-99m (99mTc)-sestamibi imaging for neoadjuvant chemotherapy (NAC) response monitoring in locally advanced breast cancer (LABC) is increasing but remains matter of discussion. The present study conducted a meta-analysis of the diagnostic performance of 99mTc-sestamibi to predict pathologic nonresponse to NAC for primary LABC. Materials and Methods: A systematic data search was performed. Studies with a minimum of 10 LABC patients that had evaluated 99mTc-sestamibi imaging for NAC nonresponse using conventional planar scintimammography, breast-specific γ-imaging, and/or single photon emission computed tomography/computed tomography (SPECT/CT) were included. The histopathologic findings were the reference standard. The meta-analysis was performed using a mixed logistic regression model. Results: The search revealed 14 eligible studies with 529 patients. Of the 14 studies, 11 had evaluated scintimammography and 3 breast-specific γ-imaging. No studies examining SPECT or SPECT/CT were found. The overall estimated pooled sensitivity, specificity, and positive and negative likelihood ratios of 99mTc-sestamibi imaging to predict nonresponsiveness to NAC were 70.3% (95% confidence interval [CI], 56.5%-81.3%%), 90.1% (95% CI, 77.5%-96.0%), 7.13 (95% CI, 3.08-16.53), and 0.33 (95% CI, 0.22-0.49), respectively. Only 3 studies (107 patients) evaluated 99mTc-sestamibi imaging during NAC, reported an estimated pooled sensitivity of 87% (95% CI, 72%-100%) and specificity of 93% (95% CI, 85%-100%). Conclusion: Only planar 99mTc-sestamibi imaging has been investigated for NAC nonresponse in LABC but showed low sensitivity to predict pathologic nonresponse. However, most studies focused on the prediction of pathologic complete response after NAC. Although experience is limited, 99mTc-sestamibi uptake during NAC seems highly sensitivity for the prediction of nonresponsiveness. Features such as SPECT/CT imaging, standardized quantification, relation to tumor subtypes, and proper timing have been insufficiently evaluated and require further investigation

Molecular image–guided surgery in gynaecological cancer:where do we stand?

Purpose: The aim of this review is to give an overview of the current status of molecular image–guided surgery in gynaecological malignancies, from both clinical and technological points of view. Methods: A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image–guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices. Results: The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging. Conclusion: After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach.</p

First Clinical Experience Using Stereotactic Breast Biopsy Guided by Tc-99m-Sestamibi

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Novel frontiers of dedicated molecular imaging in breast cancer diagnosis

Breast cancer (BC) is the most common cancer in women worldwide. In the last years, the contribution of nuclear medicine has grown based on the use of dedicated molecular breast devices for diagnosis and biopsy. Recent technical improvements have been achieved in order to increase the detection of smaller breast lesions using lower doses of radiotracers as well as to facilitate accurate biopsy sampling. Furthermore, new prototypes have been developed combining anatomic and functional imaging. Although the gamma-emitting 99mTc-sestamibi (99mTc-MIBI) and the positron-emitting 18F-fluorodeoxyglucose (18F-FDG) are the most widely used radiotracers, several new tracers have been investigated to target more specific biologic features of BC like proliferation, angiogenesis and tumour receptor status. Dedicated molecular breast devices have been introduced as an adjunct imaging tool to mammography (MG) and ultrasound (US) in the clinical work-up for BC. Additionally, due to the increased interest in molecular tumour subtype analysis and ribonucleic acid (RNA)-based gene expression profiling tests in the routine clinical practice, a possible new clinical application of dedicated breast imaging concerns locally advanced BC, principally in order to visualise intra-tumour metabolic heterogeneity enabling selection of areas with highest tracer uptake (vital tissue) for core needle biopsy. Hence, it will be possible to more adequately tailor the individual treatment, also enabling therapy response monitoring. This review evaluates the current and future perspectives as well as the shortcomings of breast imaging using dedicated nuclear medicine devices

The Role of Multimodal Imaging in Pathological Response Prediction of Locally Advanced Cervical Cancer Patients Treated by Chemoradiation Therapy Followed by Radical Surgery

Purpose: This study aimed to develop predictive models for pathological residual disease after neoadjuvant chemoradiation (CRT) in locally advanced cervical cancer (LACC) by integrating parameters derived from transvaginal ultrasound, MRI and PET/CT imaging at different time points and time intervals. Methods: Patients with histologically proven LACC, stage IB2–IVA, were prospectively enrolled. For each patient, the three examinations were performed before, 2 and 5 weeks after treatment (“baseline”, “early” and “final”, respectively). Multivariable logistic regression models to predict complete vs. partial pathological response (pR) were developed and a cost analysis was performed. Results: Between October 2010 and June 2014, 88 patients were included. Complete or partial pR was found in 45.5% and 54.5% of patients, respectively. The two most clinically useful models in pR prediction were (1) using percentage variation of SUVmax retrieved at PET/CT “baseline” and “final” examination, and (2) including high DWI signal intensity (SI) plus, ADC, and SUVmax collected at “final” evaluation (area under the curve (95% Confidence Interval): 0.80 (0.71–0.90) and 0.81 (0.72–0.90), respectively). Conclusion: The percentage variation in SUVmax in the time interval before and after completing neoadjuvant CRT, as well as DWI SI plus ADC and SUVmax obtained after completing neoadjuvant CRT, could be used to predict residual cervical cancer in LACC patients. From a cost point of view, the use of MRI and PET/CT is preferable

Evaluating the Risk of Inguinal Lymph Node Metastases before Surgery Using the Morphonode Predictive Model: A Prospective Diagnostic Study in Vulvar Cancer Patients

Ultrasound examination is an accurate method in the preoperative evaluation of the inguinofemoral lymph nodes when performed by experienced operators. The purpose of the study was to build a robust, multi-modular model based on machine learning to discriminate between metastatic and non-metastatic inguinal lymph nodes in patients with vulvar cancer. One hundred and twenty-seven women were selected at our center from March 2017 to April 2020, and 237 inguinal regions were analyzed (75 were metastatic and 162 were non-metastatic at histology). Ultrasound was performed before surgery by experienced examiners. Ultrasound features were defined according to previous studies and collected prospectively. Fourteen informative features were used to train and test the machine to obtain a diagnostic model (Morphonode Predictive Model). The following data classifiers were integrated: (I) random forest classifiers (RCF), (II) regression binomial model (RBM), (III) decisional tree (DT), and (IV) similarity profiling (SP). RFC predicted metastatic/non-metastatic lymph nodes with an accuracy of 93.3% and a negative predictive value of 97.1%. DT identified four specific signatures correlated with the risk of metastases and the point risk of each signature was 100%, 81%, 16% and 4%, respectively. The Morphonode Predictive Model could be easily integrated into the clinical routine for preoperative stratification of vulvar cancer patients

The clinical impact of molecular breast imaging in women with proven invasive breast cancer scheduled for breast-conserving surgery

Purpose: To investigate the clinical utility of molecular breast imaging (MBI) in patients with proven invasive breast cancer scheduled for breast-conserving surgery (BCS). Methods: Following approval by the institutional review board and written informed consent, records of patients with newly diagnosed breast cancer scheduled for BCS who had undergone MBI for local staging in the period from March 2012 till December 2014 were retrospectively reviewed. Results: A total of 287 women (aged 30–88 years) were evaluated. MBI showed T stage migration in 26 patients (9%), with frequent detection of in situ carcinoma around the tumor. Surgical management was adjusted in 14 of these patients (54%). In 17 of 287 patients (6%), MBI revealed 21 proven additional lesions in the ipsilateral, contralateral breast or both. In 18 of these additional foci (86%), detected in 15 patients, malignancy was found. Thirteen of these 15 patients had ipsilateral cancer and 2 patients bilateral malignancy. In total, MBI revealed a larger tumor extent, additional tumor foci or both in 40 patients (14%), leading to treatment adjustment in 25 patients (9%). Conclusion: MBI seems to be a useful imaging modality with a high predictive value in revealing ipsilateral and bilateral disease not visualized by mammography and ultrasound. It may play an important role in delineating the extent of the index lesion during preoperative planning. Incorporation of MBI in the clinical work-up as an adjunct modality to mammography and ultrasound may lead to better selection of patients who could benefit from BCS