Cinzia Crivellaro

Integrated PET/CT as a first-line re-staging modality in patients with suspected recurrence of ovarian cancer

PurposeThe aims of this study were to compare CT with PET/CT results in patients with suspected ovarian cancer recurrence and to assess the impact of the PET/CT findings on their clinical management.MethodsThirty-two consecutive patients with suspected ovarian cancer recurrence were retrospectively included in the study. Abdominal contrast-enhanced CT and PET/CT with [18F]FDG, in addition to conventional follow-up, were performed in all 32 patients. After the comparison between CT and PET/CT results, based on clinical reports, changes in the clinical management of patients (intermodality changes) due to PET/CT information were analysed.ResultsTwenty of the 32 patients were positive at CT (62.5%) versus 29 (90.6%) at PET/CT. Intermodality changes in management, i.e. use of a different treatment modality, after PET/CT examination were indicated in 14/32 (44%) patients. In particular, before PET/CT study, the planned management was as follows: wait-and-see in 7/32 (22%), further instrumental examinations in 4/32 (12%), chemotherapy in 10/32 (31%), diagnostic surgical treatment in 6/32 (19%) and surgical treatment in the remaining 5/32 (16%). After PET/CT study, wait-and-see was indicated in 1/32 (3%), further instrumental examinations in 7/32 (22%), chemotherapy in 16/32 (50%), diagnostic surgical treatment in 2/32 (6%) and surgical treatment in the remaining 6/32 (19%).ConclusionIntegrated PET/CT could detect tumour relapse in a higher percentage of patients than could CT. A change in the clinical management was observed in 44% of cases when PET/CT information was added to conventional follow-up findings.

Clinical evidence on PET/CT for radiation therapy planning in prostate cancer

The present chapter is focused on the role of positron emission tomography/computed tomography (PET/CT) and [11C]-labelled Choline ([11C]Choline) for the management of prostate cancer patients for radiation therapy planning. Although still a matter of debate, PET/CT with [11C]Choline is not routinely recommended for selecting patients for prostate cancer primary radiation treatment. However, due to its high accuracy in detecting and localizing recurrences when a biochemical failure occurs, [11C]Choline PET/CT may play a role in the re-staging phase to distinguish patients with local versus distant relapse, thus influencing patient management (curative versus palliative therapy). Limited data are currently available on the role of [11C]Choline PET/CT in target volume selection and delineation. According to available literature, [11C]Choline PET/CT is not clinically recommendable to plan target volume both for primary prostate treatment and for local recurrence. Nevertheless, promising data suggested a potential role of [11C]Choline PET/CT as an image guide tool for the irradiation of prostate cancer relapse.

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.

Preoperative staging of cervical cancer: Is 18-FDG-PET/CT really effective in patients with early stage disease?

OBJECTIVE Nodal status is one of the most important findings in patients with early-stage cervical cancer that requires post-surgical adjuvant therapies and influences prognosis of patients. The purpose of this study was to determine the diagnostic accuracy of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG-PET/CT) in the detection of nodal metastases. METHODS From 2004 to 2010 women with Ib1-IIa <4cm cervical cancer underwent 18F-FDG-PET/CT followed by radical hysterectomy and pelvic lymphadenectomy in our institution. 18F-FDG-PET/CT images were analyzed and histopathological findings served as the reference standard. Diagnostic performance of 18F-FDG-PET/CT in nodal disease detection was reported in terms of accuracy value. A sub analysis of women with tumor diameter <2cm (group 1) or 2-4cm (group 2) was performed in order to verify the efficacy of 18F-FDG-PET/CT in each group. RESULTS One hundred fifty-nine women were enrolled. 65% had squamous histotype and 51% had grade 3 disease. Median number of nodes dissected was 29 (range 11-61). 28/159 women (18%) showed nodal metastases. Overall patient-based sensitivity, specificity, positive and negative predictive value of 18F-FDG-PET/CT for detection of nodal disease were 32.1%, 96.9%, 69.2%and 87.0% respectively. Among the 97 (61%) women included in group 1, 8 had nodal metastases (8.2%) and 2 was discovered through 18F-FDG-PET/CT (25%), while 20/62 women of the group 2 (32.3%) had nodal involvement, of which 7 (35%) was detected by 18F-FDG-PET/CT. CONCLUSIONS This study showed that 18F-FDG-PET/CT had low sensitivity and had a minimal clinical impact in the pretreatment planning of stage Ib1-IIa <4cm cervical cancer.

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.

From Conventional Radiotracer Tc-99 m with Blue Dye to Indocyanine Green Fluorescence: A Comparison of Methods Towards Optimization of Sentinel Lymph Node Mapping in Early Stage Cervical Cancer for a Laparoscopic Approach

AbstractBackground The credibility of sentinel lymph node (SLN) mapping is becoming increasingly more established in cervical cancer. We aimed to assess the sensitivity of SLN biopsy in terms of detection rate and bilateral mapping in women with cervical cancer by comparing technetium-99 radiocolloid (Tc-99m) and blue dye (BD) versus fluorescence mapping with indocyanine green (ICG).MethodsData of patients with cervical cancer stage 1A2 to 1B1 from 5 European institutions were retrospectively reviewed. All centers used a laparoscopic approach with the same intracervical dye injection. Detection rate and bilateral mapping of ICG were compared, respectively, with results obtained by standard Tc-99m with BD.ResultsOverall, 76 (53 %) of 144 of women underwent preoperative SLN mapping with radiotracer and intraoperative BD, whereas 68 of (47 %) 144 patients underwent mapping using intraoperative ICG. The detection rate of SLN mapping was 96 % and 100 % for Tc-99m with BD and ICG, respectively. Bilateral mapping was achieved in 98.5 % for ICG and 76.3 % for Tc-99m with BD; this difference was statistically significant (p < 0.0001).ConclusionsThe fluorescence SLN mapping with ICG achieved a significantly higher detection rate and bilateral mapping compared to standard radiocolloid and BD technique in women with early stage cervical cancer. Nodal staging with an intracervical injection of ICG is accurate, safe, and reproducible in patients with cervical cancer. Before replacing lymphadenectomy completely, the additional value of fluorescence SLN mapping on both perioperative morbidity and survival should be explored and confirmed by ongoing controlled trials.

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.

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.

Role of PET/CT in the clinical management of locally advanced pancreatic cancer.

AIM To evaluate the role of 18F-fluorodeoxyglucose (FDG) PET/CT in: a) the selection of patients with locally advanced pancreatic cancer for helical tomotherapy with concurrent chemotherapy (HTT-ChT); b) monitoring HTT-ChT treatment efficacy in comparison with contrast-enhanced CT (c.e.CT). METHODS Forty-two consecutive patients with unresectable locally advanced pancreatic cancer referred for HTT-ChT were enrolled in the study. All patients were pretreated with induction ChT. Before the beginning of HTT-ChT treatment patients underwent diagnostic c.e.CT (CT0) and FDG PET/CT (PET/CT0) for staging. After staging, patients received HTT-ChT. Three months after the end of HTT-ChT a control c.e.CT (CT1) was done. FDG PET/CT (PET/CT1) was repeated only in patients with positive PET/CT0. PET/CT1 and CT1 were compared with baseline imaging results to assess treatment efficacy. RESULTS In 31/42 cases (74%) PET/CT0 documented pathological uptake in pancreatic lesions, while in the remaining 11/42 cases it showed no uptake. In 7/42 (17%) patients, PET/CT0 also detected distant metastases, prompting a change in the therapeutic approach. Compared to PET/CT0, PET/CT1 (n = 18) documented 3 complete metabolic responses, 9 partial metabolic responses, 2 instances of stable metabolic disease, and 4 instances of progressive metabolic disease. In the same group of 18 patients, CT1 showed 0 complete responses, 3 partial responses, 8 instances of stable disease, and 7 instances of progressive disease compared to CT0. Concordance between PET/CT and CT response was seen in 33% of cases. In 50% of cases, PET/CT1 documented a response to therapy that was not evident on CT. CONCLUSIONS PET/CT influenced the treatment strategy by detecting distant metastases not documented by CT, thus accurately selecting patients for HTT-ChT after induction ChT. In monitoring treatment efficacy, PET/CT can detect a metabolic response to treatment not identified by CT.