Role of 18 F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in malignant ovarian germ cell tumors: a single-center experience with long term follow-up.

INTRODUCTION: 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a diagnostic tool widely used in oncology, but to date there are no established recommendations for its use in malignant ovarian germ cell tumors. The aim of this study was to evaluate the role of 18F-FDG PET/CT in the clinical management of patients with malignant ovarian germ cell tumors. METHODS: This was a retrospective review of 18F-FDG PET/CT scans performed in patients diagnosed with malignant ovarian germ cell tumors treated at the gynecology department of San Gerardo Hospital (Monza, Italy) from June 2006 to December 2016. Data collected included clinical history, radiological, biochemical and pathological evaluation, treatment, follow-up, outcome, and clinical indication for the PET/CT scan. PET/CT findings were categorized as negative/normal (no abnormal FDG uptake or physiological uptake), positive/abnormal (FDG uptake considered to indicate active germ cell malignancy), or equivocal (FDG uptake of uncertain significance, not clearly correlated to neoplastic disease). RESULTS: A total of 69 PET/CT scans in 37 patients were evaluated. The mean age at diagnosis was 25 years (range 20-48). The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage I (22/37) disease and had a diagnosis of dysgerminomas (18/37). Imaging indications were initial staging before treatment (4/69, 6%), staging after inadequate staging surgery (24/69, 35%), restaging after adjuvant chemotherapy (17/69, 25%), relapse suspect (9/69, 13%), and follow-up (15/69, 21%). Pathology confirmation of PET/CT results was available in 28/69 (40.5%) studies. All negative PET/CT (15/28) cases were confirmed with laparoscopy as true negative; among 13/28 positive PET cases, histopathology confirmed 7 (54%) as true positive and 6 (46%) as false positive (5 inflammatory and 1 mature teratoma implants). Patient-based analysis showed 100% sensitivity, 71% specificity, 54% positive predictive value, 100% negative predictive value, and 79% accuracy. Clinical follow-up was available in 41 (59.4%) of 69 PET/CT images: 28/41 studies were negative and 13/41 positive. A mean follow-up of 28 months (median 15, range 5-102) confirmed negative PET/CT studies. A total of 13 positive PET/CT patients underwent chemotherapy with subsequent evidence of disease response. DISCUSSION: PET/CT in malignant ovarian germ cell tumors was mainly performed for staging after inadequate staging surgery or for restaging after adjuvant chemotherapy. PET/CT was associated with high sensitivity and negative predictive value.

Predictive value of (18)F-FDG PET/CT in restaging patients affected by ovarian carcinoma: a multicentre study.

PURPOSE: Ovarian cancer is the eighth most common malignancy among women and has a high mortality rate. Prognostic factors able to drive an effective therapy are essential. (18)F-Fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has been investigated in patients with epithelial ovarian cancer and showed promise in diagnosing, staging, detecting recurrent lesions and monitoring treatment response. Conversely, its prognostic role remains unclear. We aimed at assessing the prognostic value of (18)F-FDG PET/CT performed in the restaging process in a multicentre study. METHODS: We evaluated 168 patients affected by ovarian carcinoma, who underwent a restaging (18)F-FDG PET/CT. The presence of local recurrences, lymph node involvement and distant metastasis was recorded as well as lesion dimensions, maximum and mean standardized uptake values (SUVmax and SUVmean, respectively). Progression-free survival (PFS) and overall survival (OS) at 3 and 4 years were computed by using Kaplan-Meier curves. Increased odds ratio was assessed using Cox regression analysis testing all lesion parameters measured by PET/CT. RESULTS: PFS was significantly longer in patients with a negative than a positive restaging PET/CT study (3- and 4-year PFS 64 and 53% vs 23 and 12%, respectively; p < 0.001). Similarly, a negative study was associated with a significantly higher OS rate after 4 years of follow-up (67 vs 25% in negative and positive groups, respectively; p < 0.001). Lymph node or distant involvement were also independently associated with an increased risk of disease progression [hazard ratio (HR) 1.6 and 2.2, respectively; p = 0.003]. Moreover, PET/CT showed an incremental prognostic value compared to the International Federation of Gynecology and Obstetrics (FIGO) staging system. In the analysis of patient subsets, individuals with the same FIGO stage I-II but with negative PET had a significantly better 4-year OS than patients with low FIGO stage but positive PET. This implies that patients with the same FIGO stage can be further prognostically stratified using PET (p = 0.01). At receiver-operating characteristic (ROC) analysis, no thresholds for semiquantitative parameters were predictive of a worse outcome. CONCLUSION: (18)F-FDG PET/CT has an important prognostic value in assessing the risk of disease progression and mortality rate. An efficacious therapy planning might therefore effectively rely on (18)F-FDG PET/CT findings. Semiquantitative data were not proven to be an effective tool to predict disease progression.

Preoperative 18F-FDG PET/CT in the management of advanced epithelial ovarian cancer.

OBJECTIVE: The introduction of 18-FDG-PET/CT during preoperative evaluation of patients with epithelial ovarian cancer (EOC) has led to an increase of the detection of extra-abdominal metastases. However, the clinical impact of this upstage remains unclear. METHODS: Patients with suspected advanced EOC underwent 18-FDG-PET/CT within two weeks prior to debulking surgery. RESULTS: Between 2006 and 2011 95 patients met the inclusion criteria. Based on the concordance or the discrepancy of clinical and PET/CT stage, patients were divided into 3 groups (A: clinical and PET III; B: clinical III and PET IV; C: clinical and PET IV). Twenty-five patients were upstaged from FIGO stage III to stage IV by PET/CT. The proportion of patients who achieved a residual tumor <1cm in group B and C was similar, whereas it was significantly lower compared to group A. Similarly, complete response to adjuvant chemotherapy was achieved more frequently in patients in group A. PFS was similar in the three groups (17, 17 and 12 months in group A, B and C), as well as OS (51, 41 and 35 months). CONCLUSIONS: PET/CT is able to detect distant metastases in EOC patients. The presence of extra-abdominal disease probably indicates a more aggressive disease which also shows a lower response to standard chemotherapy. However, upstaged patients have a similar prognosis compared to stage III patients, probably because intra-abdominal disease is more likely to lead patients to death. This might also explain why residual tumor is the most important prognostic factor for advanced EOC patients.

18F-FDG PET/CT can predict nodal metastases but not recurrence in early stage uterine cervical cancer.

OBJECTIVES: To evaluate the role of the metabolic characteristics of cervical tumor uptake as predictors of a) lymph node (LN) metastases, b) recurrence, in the preoperative staging of early-stage cervical cancer. METHODS: 89 patients with FIGO stage IB1 and IIA<4 cm cervical cancer were imaged with FDG-PET/CT before radical hysterectomy and pelvic lymphadenectomy. PET/CT images were analyzed and correlated to histological findings. Maximum and mean standardized uptake value (SUVmax, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) of cervical lesions were calculated by an iterative adaptive algorithm. These parameters were correlated to the presence of: a) LN metastases, b) relapse after primary treatment. RESULTS: Out of the 89 patients who underwent preoperative PET/CT scan for staging purpose, 16 were negative at cervical level: they were all pN0 and without recurrence during follow-up (mean 34.1±14.5 months). In 69 patients MTV and TLG were significantly higher (p=0.0006 and p=0.03) in pN1 patients in comparison to pN0 patients, while SUV values did not show significant differences between the two groups. No significant correlations were found between SUVmax, SUVmean, MTV, TLG and the evidence of relapse (mean follow-up 29.2±15.5 months). CONCLUSIONS: In early-stage cervical cancer MTV and TLG correlate with the presence of nodal metastases, but their clinical impact on patients management has to be clarified. The absence of pathological cervical uptake could be a good prognostic factor, while SUVmax, SUVmean, MTV, TLG of the cervical uptake have not been found predictors 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.

Advances in the Management of Medullary Thyroid Carcinoma: Focus on Peptide Receptor Radionuclide Therapy.

Effective treatment options in advanced/progressive/metastatic medullary thyroid carcinoma (MTC) are currently limited. As in other neuroendocrine neoplasms (NENs), peptide receptor radionuclide therapy (PRRT) has been used as a therapeutic option in MTC. To date, however, there are no published reviews dealing with PRRT approaches. We performed an in-depth narrative review on the studies published in this field and collected information on registered clinical trials related to this topic. We identified 19 published studies, collectively involving more than 200 patients with MTC, and four registered clinical trials. Most cases of MTC were treated with PRRT with somatostatin analogues (SSAs) radiolabelled with 90 yttrium (90Y) and 177 lutetium (177Lu). These radiopharmaceuticals show efficacy in the treatment of patients with MTC, with a favourable radiological response (stable disease, partial response or complete response) in more than 60% of cases, coupled with low toxicity. As MTC specifically also expresses cholecystokinin receptors (CCK2Rs), PRRT with this target has also been tried, and some randomised trials are ongoing. Overall, PRRT seems to have an effective role and might be considered in the therapeutic strategy of advanced/progressive/metastatic MTC.

Treatment response assessment in [18F]FDG-PET/CT oncology scans: Impact of count statistics variation and reconstruction protocol.

PURPOSE: To investigate influences of reconstruction algorithms and count statistics variation on quantification and treatment response assessment in cancer patients, by using a large field of view-FOV scanner. METHODS: 54 cancer patients underwent PET/CT scan: 1) at baseline: 1.5 min/FOV, reconstructed by ordered-subset expectation maximization + point-spread-function-OSEM-PSF and bayesian penalised-likelihood-BPL algorithm 2) at restaging: 2 min/FOV, reconstructed also at 1.5 and 1 min/FOV, using OSEM-PSF and BPL. SUL (lean-body mass SUV) peak and max were measured for each target-lesion (n = 59). Differences in quantification obtained from datasets with different reconstruction algorithms and different time/FOV were evaluated. For any pair of PET datasets, metabolic response was assessed by using SULpeak, with a threshold of 30% in variation considered as significant. RESULTS: Both at baseline and restaging, SULpeak and max values were higher in BPL reconstructions than in OSEM-PSF (p < 0.0001). SULpeak at different time/FOV reconstructions showed no statistically significant differences both with OSEM-PSF and BPL; SULmax depended on acquisition time (p < 0.05). In 56/59 lesions (95%) therapy response was concordant regardless count statistics variation and reconstruction algorithm; 2/59 (3%) showed different responses according to count statistics, both for OSEM-PSF and BPL; in 1/59 lesion (2%) response was different depending on reconstruction algorithm used. CONCLUSIONS: BPL provided higher SULpeak and max than OSEM-PSF. With a large FOV/high sensitivity scanner, variation of time/FOV in restaging PET scans gave stable and reproducible results in terms of SULpeak, both for OSEM-PSF and BPL. Thus, metabolic response defined by SULpeak variation proved to be quite independent from count statistics.

Sentinel-node mapping in endometrial cancer patients: comparing SPECT/CT, gamma-probe and dye.

OBJECTIVE: The aim of this study was to compare preoperative SPECT/CT with gamma-probe and methylene blue-dye (MBD) in the identification of sentinel lymph node (SLN) in early stage endometrial cancer. METHODS: 40 stage-I EC patients (66.7 ± 9.7 years) underwent preoperative lymphoscintigraphy. After about 3 h from Tc-99m-albumin nanocolloid cervical injection, all patients underwent SPECT/CT study. MBD was injected into the cervix just before surgery under general anesthesia. All patients underwent SLN biopsy, hysterectomy, bilateral salpingo-oophorectomy, and radical regional lymphadenectomy. SPECT/CT findings were compared to those of gamma-probe and MBD techniques. RESULTS: In 2 patients no nodal migration was observed, neither with MBD nor radiotracer. Detection rate of at least one SLN was 90% (36/40 patients) with SPECT/CT, 88% (35/40) intra-operatively with gamma-probe and 80% (32/40) with MBD. Only in 7/40 patients a bilateral migration was obtained with all considered modalities. In particular, bilateral detection was achieved in 26 patients with SPECT/CT, in 24 with gamma-probe and in 10 patients with MBD. The concordance site between SPECT/CT and intraoperative gamma-probe was 73% (29/40 patients: 2 without migration, 21 bilateral and 6 monolateral SLNs); while concordance site with MBD was found in 40% (16/40: 8 bilateral, 6 monolateral SLNs, 2 without SLNs). Overall, 628 LNs were dissected (mean 18 LNs per patient). The median number of SLNs removed was 2 (mean 2.5 per patient). Out of 91 SLNs: 43 were "hot and blue (HB)", 10 were blue only and 38 were hot only. LN metastases rate was 16%: 9/90 SLNs (7 HB, 2 hot only) were positive for metastases in 6 patients. Four non-SLNs were found positive in 3 patients, and all presented concomitant positive SLNs. False negative rate was 0%. CONCLUSIONS: SPECT/CT had the highest detection rate and achieved the highest rate of bilateral mapping, compared to gamma-probe and MDB. SPECT/CT had moderate concordance with gamma-probe, and it can help the intraoperative detection of SLNs providing important information about their anatomic location.

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 Tc-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.

Uterine lymphatic drainage is unaffected from injection technique and operators: Identical sentinel node detection in two cases of endometrial cancer.

INTRODUCTION: Sentinel node (SN) mapping with cervical injection of 99m-technetium (99mTc) albumin nanocolloid in early endometrial cancer has been shown to be feasible and data emerging from recent large series support the incorporation of SN mapping algorithm in endometrial cancer staging. PRESENTATION OF CASE: We report two cases of SN mapping which demonstrated identical migration of both radioactive technetium and blue dye in the same patients that were re-injected because surgical intervention was postponed due to transitory cardiac contraindications. DISCUSSION: As clearly demonstrated in cervical cancer, SN mapping through intracervical injection of both radioactive technetium and blue dye seems to be effective and easy to perform, providing good results in patients with endometrial cancer. Our report highlights the reproducibility of SN mapping that has been strongly confirmed in both patients, even if re-injections were performed by different operators. Preoperative SPECT/CT imaging seems to enhance accuracy in SN localization and also improves its intraoperative detection in early endometrial cancer. CONCLUSION: The anatomically defined bilateral uterus drainage strongly confirms the reproducibility of SN mapping, that seems to be unaffected by after injection technique or operators.

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.