Federica Elisei

Current concepts on imaging in radiotherapy

New high-precision radiotherapy (RT) techniques, such as intensity-modulated radiation therapy (IMRT) or hadrontherapy, allow better dose distribution within the target and spare a larger portion of normal tissue than conventional RT. These techniques require accurate tumour volume delineation and intrinsic characterization, as well as verification of target localisation and monitoring of organ motion and response assessment during treatment. These tasks are strongly dependent on imaging technologies. Among these, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US) and positron emission tomography (PET) have been applied in high-precision RT. For tumour volume delineation and characterization, PET has brought an additional dimension to the management of cancer patients by allowing the incorporation of crucial functional and molecular images in RT treatment planning, i.e. direct evaluation of tumour metabolism, cell proliferation, apoptosis, hypoxia and angiogenesis. The combination of PET and CT in a single imaging system (PET/CT) to obtain a fused anatomical and functional dataset is now emerging as a promising tool in radiotherapy departments for delineation of tumour volumes and optimization of treatment plans. Another exciting new area is image-guided radiotherapy (IGRT), which focuses on the potential benefit of advanced imaging and image registration to improve precision, daily target localization and monitoring during treatment, thus reducing morbidity and potentially allowing the safe delivery of higher doses. The variety of IGRT systems is rapidly expanding, including cone beam CT and US. This article examines the increasing role of imaging techniques in the entire process of high-precision radiotherapy.

Tailoring systematic lymphadenectomy in high-risk clinical early stage endometrial cancer: The role of 18F-FDG PET/CT

OBJECTIVES To evaluate the role of FDG PET/CT in the preoperative N-staging of high-risk clinical stage I endometrial cancer. The correlation between the metabolic characteristics of endometrial tumor uptake as predictors of a) lymph-node (LN) metastases and b) recurrence, was also evaluated. METHODS Seventy-six high-risk (G2 with deep myometrial invasion, G3, serous/clear-cell carcinoma) clinical stage I endometrial cancer patients underwent preoperative PET/CT scan followed by total hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy. PET/CT images were analyzed and correlated to histological findings. Maximal and mean standardized uptake value (SUVmax, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG, defined as the product between SUVmean and MTV) of endometrial lesions were calculated and correlated to: a) presence of LN metastases, b) recurrences. RESULTS PET/CT resulted positive at LNs in 12/76 patients: 11/12 truly positive, 1/12 falsely positive. Conversely PET/CT was negative in 64/76 patients: 61/64 truly negative and 3/64 falsely negative. On pt-based analysis, sensitivity, specificity, accuracy, positive and negative predictive value of PET/CT in detecting LN metastases were 78.6%, 98.4%, 94.7%, 91.7%, 95.3%, respectively. A significant association was found between the presence of LN metastases and SUVmax (p=0.038), MTV (p=0.007), TLG (p=0.003) of the primary tumor. No correlations were found between the metabolic parameters and relapse (median follow-up 25.4months). CONCLUSIONS In high-risk clinical stage I endometrial cancer FDG PET/CT demonstrated moderate sensitivity, high specificity and accuracy for the nodal status assessment. SUVmax, MTV and TLG of the primary tumor are significantly correlated to LN metastases, while none of these parameters is predictor of recurrence.

Integration of hybrid single-photon emission computed tomography/computed tomography in the preoperative assessment of sentinel node in patients with cervical and endometrial cancer: our experience and literature review.

Objective The purpose of this study was to assess whether there is an additional value of single-photon emission computed tomography/computed tomography (SPECT/CT) over lymphoscintigraphy (LSG) alone for sentinel node (SN) mapping in endometrial and cervical cancer. Methods Ten women with clinically cervical stage IA2 to stage IB1 and 25 women with stage I endometrial cancer underwent preoperative LSG for SN mapping. Technetium Tc 99m albumin nanocolloid was injected submucosally at 4 points of the cervix. Patients underwent SPECT/CT emission-transmission study at least 3 hours after standard planar images. Methylene blue was injected into the cervix just before surgery under general anesthesia. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and radical regional nodal dissection. Hot and/or blue nodes were labeled as SNs. Results Conventional planar imaging detection rate was 50%, whereas the detection rate of at least one SN with SPECT/CT was 91% (32/35); bilateral detection was achieved in 7 (39%) of 18 women in planar and in 17 (53%) of 32 women in SPECT/CT imaging, respectively. Bilateral detection was achieved in 57% of women (20/35). Sentinel nodes were located in external and internal iliac nodes (66%), obturator nodes (5%), internal iliac nodes (11%), common iliac nodes (9%), and presacral nodes (9%). Lymph node involvement was identified in 5 patients (14%). Sentinel node correctly predicted lymph node involvement in all node-positive patients. Sentinel node sensitivity and negative predictive value of SPECT/CT were 100%. Conclusions Single photon emission computed tomography/computed tomography seems to improve intraoperative identification of SNs and provides additional useful information about the anatomic location of SNs compared to planar LSG in cervical and endometrial cancer.

Staging of High-Risk Endometrial Cancer With PET/CT and Sentinel Lymph Node Mapping

Purpose The aim of this study was to evaluate the role of PET/CT and sentinel lymph node (SLN) biopsy in staging high-risk endometrial cancer patients (G2 and deep myometrial invasion, G3, serous clear cell carcinoma or carcinosarcoma) in early clinical stage. Patients and Methods From January 2006 to December 2012, high-risk early-stage endometrial cancer patients performing PET/CT scan followed by surgery (systematic pelvic ± aortic lymphadenectomy) were included. From December 2010, SLN mapping with 99mTc-albumin nanocolloid and blue dye cervical injection was included in our clinical practice and additionally performed. Histological findings were used as the reference standard. Results Ninety-three patients were included, of which 22 of 93 had both PET/CT and SLN biopsy. The median number of dissected lymph nodes (LNs) was 28. Nineteen women (20.4%) had pelvic LN metastases; 14 were correctly identified by PET/CT. Among 5 false-negative cases, 3 occurred after the introduction of SLN mapping due to detection of micrometastases by ultrastaging. On overall patient-based analysis, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for pelvic LN metastases were 73.7%, 98.7%, 93.6%, 93.3%, 93.6%, respectively. Conclusions PET/CT demonstrated moderate sensitivity and high specificity in detecting pelvic LN metastases; its high positive predictive value (93.3%) is useful to refer patients to appropriate debulking surgery. Sentinel LN mapping and histological ultrastaging increased the identification of metastases (incidence, 18.3%-27.3%) not detectable by PET/CT because of its spatial resolution. The combination of both modalities is promising for nodal staging purpose.

Detection of nodal metastases by 18F-FDG PET/CT in apparent early stage ovarian cancer: a prospective study

BACKGROUND The rate of nodal metastases in ovarian cancer macroscopically confined to the pelvis is about 15%-20%. Systematic pelvic and aortic lymphadenectomy improves staging but it is associated with increased morbidity and costs. The purpose of this study was to evaluate the role of 18F-FDG PET/CT in the pre-operative nodal metastases detection in ovarian cancer grossly confined to the pelvis. METHODS From 2006 to 2012, 68 consecutive women with epithelial ovarian cancer confined to the pelvis underwent 18F-FDG PET/CT followed by surgery inclusive of systematic pelvic and aortic lymphadenectomy (SAPL). 18F-FDG PET/CT images were analyzed and correlated to histological examination. RESULTS Twenty-six women underwent bilateral and 42 unilateral SAPL with 3165 nodes removed and analyzed. Median number of dissected nodes was 42 (range 16-91). Twelve women (17.6%) had nodal metastases. 18F-FDG PET/CT correctly identified 10 patients with nodal involvement. Sensitivity, specificity, accuracy, positive and negative-predictive value of 18F-FDG PET/CT in detecting nodal metastases were 83.3%, 98.2%, 95.6%, 90.9% and 96.5%, respectively, on overall patient-based, and 75.5%, 99.4%, 98.1%, 87.5% and 98.6%, respectively, on nodal lesion site-based analysis. CONCLUSION 18F-FDG PET/CT is an accurate tool for the detection of nodal metastases. Metabolic imaging could be used to select women who could benefit from systematic lymphadenectomy. The high negative predictive value allows avoidance of SAPL in the vast majority of women, minimizing operative and post surgical complications. Further larger prospective investigation is required to confirm our data.

Sentinel node mapping in high risk endometrial cancer after laparoscopic supracervical hysterectomy with morcellation

INTRODUCTION Occult endometrial cancer after supracervical hysterectomy is very uncommon. Even if optimal management of those rare cases is still unproven, to guide the need for further therapies, restaging should be recommended in this situation. PRESENTATION OF CASE We report of a 60-year old woman with occult high risk endometrial cancer after supracervical hysterectomy with morcellation. We describe the feasibility of laparoscopic intraoperative sentinel node identification with cervical stump removing to restage the suspicious early stage high risk endometrial cancer. DISCUSSION In high risk endometrial cancer surgical restaging is important, considering that 10-35% of cases can present pelvic nodal metastasis. To reduce the treatment related morbidity maintaining the benefit of surgical staging, with a negative preoperative PET/CT, we performed a laparoscopic SN mapping with cervical stump removing. CONCLUSION This report highlight the fact that SN mapping with cervical injection is a feasible and safe technique also without the uterine corpus after supracervical hysterectomy with morcellation.

Radiomics of the primary tumour as a tool to improve 18 F-FDG-PET sensitivity in detecting nodal metastases in endometrial cancer

BackgroundA radiomic approach was applied in 18F-FDG PET endometrial cancer, to investigate if imaging features computed on the primary tumour could improve sensitivity in nodal metastases detection. One hundred fifteen women with histologically proven endometrial cancer who underwent preoperative 18F-FDG PET/CT were retrospectively considered. SUV, MTV, TLG, geometrical shape, histograms and texture features were computed inside tumour contours. On a first group of 86 patients (DB1), univariate association with LN metastases was computed by Mann-Whitney test and a neural network multivariate model was developed. Univariate and multivariate models were assessed with leave one out on 20 training sessions and on a second group of 29 patients (DB2). A unified framework combining LN metastases visual detection results and radiomic analysis was also assessed.ResultsSensitivity and specificity of LN visual detection were 50% and 99% on DB1 and 33% and 95% on DB2, respectively. A unique heterogeneity feature computed on the primary tumour (the zone percentage of the grey level size zone matrix, GLSZM ZP) was able to predict LN metastases better than any other feature or multivariate model (sensitivity and specificity of 75% and 81% on DB1 and of 89% and 80% on DB2). Tumours with LN metastases are in fact generally characterized by a lower GLSZM ZP value, i.e. by the co-presence of high-uptake and low-uptake areas. The combination of visual detection and GLSZM ZP values in a unified framework obtained sensitivity and specificity of 94% and 67% on DB1 and of 89% and 75% on DB2, respectively.ConclusionsThe computation of imaging features on the primary tumour increases nodal staging detection sensitivity in 18F-FDG PET and can be considered for a better patient stratification for treatment selection. Results need a confirmation on larger cohort studies.

Motion Management in PET/CT: Technological Solutions

BACKGROUND AND OBJECTIVE Motion due to patients breathing can introduce heavy bias in PET/CT, both in image quality and quantitation. This paper is a review of the main technical solutions available to manage movement in PET/CT studies: a) Respiratory Gated (RG), b) Motion Free (MF), c) End Expiration (EE), d) Banana Artefact Management (BAM) and e) Data Driven Gating (DDG). METHODS The most diffused solutions (RG, MF and EE) are based on LIST mode acquisition of a PET Field of View (4D FOV), centered on the anatomical region of interest; to link PET data not only to time and to spatial position but also to the corresponding breathing phase, the synchronized acquisition of the patients breathing curve is performed by an external tracking device. Different commercial tools to track and to record patient breathing cycle are available to associate the internal organ motion with a measurable external parameter; for example these systems can measure the pressure on a chest elastic belt, the air flow trough patient nose, the breath-in and breath-out air temperature or the markers movement on the thorax/ abdominal region. Recently DDG techniques are developed to correct respiratory motion without the help of external motion tracking devices and to obtain a comparable result to that based on standard RG protocols. RESULTS The final result of an RG or DDG protocol is a sequence of 3D images showing organs and lesions movement; using the other motion management options a single 3D motion-free image is obtained without motion artefacts and degradation. Compared to the previously described options the BAM solution is not a real motion management protocol but just a Banana Artefact correction technique obtained using an Attenuation Correction Map calculated merging the Whole Body Helical CT with a Cine CT on the diaphragm area. CONCLUSION The motion management in PET/CT imaging shows benefits in terms of image quality, quantification and lesion detectability and it is useful both in diagnostic and radiotherapy planning.

Cervical injection for sentinel lymph nodes detection in endometrial cancers is controversial: response to comments

We thank Abdelazim and Zhurabekova [1] for their interest in our recent paper in Clinical and Translational Imaging on sentinel lymph nodes (SLNs) in endometrial cancer [2]. As discussed in their comment, the injection site is controversial. In endometrial cancer patients one of the main criticisms regards cervical site injection and whether it maps the organ rather than the tumor [3]. The study of Khoury-Collado et al. [4] challenged the reservations about the effectiveness of cervical site injection, since after a cervical site injection, SLNs were three times more likely to harbour disease than non-SLNs. Abu-Rustum et al. demonstrated that the addition of a fundal injection to the cervical injection did not appear to produce a higher detection rate [5]. In the study by Rossi et al., women were injected with indocyanine green (ICG) either into the cervix or into the endometrium during hysteroscopy, and the authors concluded that cervical injection achieved a higher SLN detection rate and a similar anatomic nodal distribution [6]. Our data are consistent with those of Bodurtha Smith et al. [7], showing that cervical injection is associated with higher rates of bilateral SLN detection. In addition, they found that it was associated with a significantly lower detection rate in the aortic area [7]. In our analysis, we focused on bilateral migration rate (a selective lymphadenectomy is required in presence of unilateral mapping) rather than on the aortic detection rate considering that studies in which the protocol includes a systematic para-aortic lymphadenectomy demonstrated a higher rate of detection of para-aortic SLNs, as well as isolated aortic node involvement [8]. In published series including more than 100 cases of endometrial cancer patients (6858 evaluated patients), the overall rate of isolated aortic metastasis recorded was 1.7% [3]. Cormier et al. showed that deeper (≥ 3 cm), as opposed to superficial (≤ 2 cm) cervical injection may increase the detection of para-aortic SLN, and that the use of ICG increases the detection rate of para-aortic SLN [8]. Our meta-analysis described advantages and disadvantages of different techniques. Although the site of injection is still a question to be definitively addressed, NCCN guidelines based on available data, suggest that combination of a superficial (1–3 mm) and deep (1–2 cm) cervical injection leads to dye delivery to the main layers of lymphatic channel origins in the cervix and corpus [9].

18F-FDG PET/CT in preoperative staging of vulvar cancer patients: Is it really effective?

Abstract The aim of this study was to assess the role of 18F-FDG PET/CT in preoperative staging of vulvar cancer patients. 29 pts (69 years, range 51–88) with vulvar cancer (clinical apparent stage I-II), underwent preoperative FDG-PET/CT scan followed by radical vulvectomy and bilateral (or monolateral in case of tumor >2 cm from midline) inguinal lymphadenectomy ± sentinel node biopsy. PET/CT images were analyzed in consensus and correlated to histological findings according to a pt-based and a groin-based analyses. SUVmax of the nodal uptake of each inguinal area (if present) was calculated and correlated to histological findings. The presence of distant metastases was also considered and confirmed. PET/CT analysis in consensus resulted negative at the inguinal LN level in 17 pts (10 true negative, 7 false negative) and positive in 12 pts (7 true positive, 5 false positive). Incidence of LN metastases resulted 48%. On pt-based analysis, sensitivity, specificity, accuracy, and negative and positive predictive value of PET/CT in detecting LN metastases were 50%, 67%, 59%, 59%, and 58%, respectively. On a groin-based analysis, considering overall 50 LN-sites, sensitivity, specificity, accuracy, and negative and positive predictive value of PET/CT were 53%, 85%, 73%, 67%, and 76%, respectively. The mean value of SUVmax was 6.1 (range 0.7–16.2) for metastatic nodes, whereas 1.6 (range 0.7 – 5.4) for negative lymph-nodes (P = .007). PET/CT detected pelvic (n = 1) and both pelvic/paraortic (n = 1) nodal metastases. In clinical early stage vulvar cancer FDG PET/CT showed low sensitivity and moderate specificity for N-staging; therefore, it is not an accurate tool for the nodal status assessment. PET/CT may not be cost-effective in detecting the rare event of distant metastases, but further studies are needed.