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Hodgkin lymphoma (HL) is a neoplastic disease in which the inflammatory microenvironment plays a pivotal role in the tumorigenesis. Neutrophilia is a typical finding in HL at diagnosis and, in particular, in association with lymphocytopenia, is a negative prognostic factor. As the immune checkpoint Programmed Death (PD)-L1/PD-1 has become an important therapeutic target, we were interested in the expression of PD-L1 in peripheral blood (PB) leukocytes using flow cytometry and RT-PCR in patients with HL and healthy controls. Granulocytes were the major PB cell fraction expressing PD-L1. PD-L1 expression on granulocytes was higher in patients with HL than in controls and correlated with lower T-cell numbers in PB. We analyzed for associations between PD-L1 expression in PB granulocytes at the time of diagnosis with patient characteristics and outcome in 126 patients with HL treated with standard chemotherapy adriamycin, bleomycin, vinblastine, and dacarbazine. Increased PD-L1 expression in PB associated with advanced disease, systemic symptoms, positive interim positron emission tomography, and inferior progression-free survival (PFS). PFS at 4 years was 81% (95% C.I., 71-87%) in patients with normal PD-L1 expression and 56% (95% C.I., 35-72%) in patients with higher-than-normal PD-L1 expression (p = 0.002). In conclusion, PD-L1 expression in PB could become a potentially actionable prognostic factor in HL.Expression of PD-L1 in peripheral blood reflects disease burden and predicts interim PET result and prognosis in classical HL.

Purpose: To evaluate the role of apparent diffusion coefficient (ADC) value measurement in the diagnosis of metastatic lymph nodes (LNs) in patients with locally advanced cervical cancer (LACC) and to present a systematic review of the literature. Material and methods: Magnetic resonance imaging (MRI) exams of patients with LACC were retrospectively eva luated. Mean ADC, relative ADC (rADC), and correct ADC (cADC) values of enlarged LNs were measured and compared between positron emission tomography (PET)-positive and PET-negative LNs. Comparisons were made using the Mann-Whitney U-test and Student’s t-test. ROC curves were generated for each parameter to identify the optimal cut-off value for differentiation of the LNs. A systematic search in the literature was performed, exploring several databases, including PubMed, Scopus, the Cochrane library, and Embase. Results: A total of 105 LNs in 34 patients were analysed. The median ADC value of PET-positive LNs (0.907 × 10-3 mm2/s [0.780-1.080]) was lower than that in PET-negative LNs (1.275 × 10-3 mm2/s [1.063-1.525]) (p < 0.05). rADC and cADC values were lower in PET-positive LNs (rADC: 0.120 × 10-3 mm2/s [–0.060-0.270]; cADC: 1.130 [0.980-1.420]) than in PET-negative LNs (rADC: 0.435 × 10-3 mm2/s [0.225-0.673]; cADC: 1.615 [1.210-1.993]) LNs (p < 0.05). ADC showed the highest area under the curve (AUC 0.808). Conclusions: Mean ADC, rADC, and cADC were significantly lower in the PET-positive group than in the PET-negative group. The ADC cut-off value of 1.149 × 10-3 mm2/s showed the highest sensitivity. These results confirm the usefulness of ADC in differentiating metastatic from non-metastatic LNs in LACC.

Gynecological malignancies currently affect about 3.5 million women all over the world. Imaging of uterine, cervical, vaginal, ovarian, and vulvar cancer still presents several unmet needs when using conventional modalities such as ultrasound, computed tomography (CT), magnetic resonance, and standard positron emission tomography (PET)/CT. Some of the current diagnostic limitations are represented by differential diagnosis between inflammatory and cancerous findings, detection of peritoneal carcinomatosis and metastases

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.

Purpose to correlate somatostatin receptor (SSTR) and proliferative activity profile (SSTR2, SSTR5, Ki-67) at immunohistochemistry (IHC) with SSTR-PET/CT imaging features in a retrospective series of lung neuroendocrine neoplasms (NEN). Proliferative activity by Ki-67 and 18F-FDG-PET/CT parameters (when available) were also correlated. Methods Among all consecutive patients who underwent SSTR-PET/CT with 68Ga-DOTA-somatostatin analogs (SSA) between July 2011 and March 2020 for lung NEN, 35 patients with a confirmed diagnosis were included. For 16 of them, 18F-FDG-PET/CT studies were available. PET/CT images were reviewed by qualitative and semi-quantitative analyses. Immunohistochemistry for SSTR2, SSTR5, and Ki-67 was assessed. An inferential analysis was performed including kappa statistic and Spearman's rank correlation test. Results Definitive diagnosis consisted of 32 low-intermediate-grade NEN (26 typical carcinoids-G1 and six atypical carcinoids-G2) and 3 high-grade NEN. Positive SSTR2-IHC was found in 63% of samples while SSTR5-IHC positivity was 17.6%. A correlation between SSTR2-IHC and SSTR-PET/CT was found in 26/35 cases (74.3%, p=0.003): 22 were concordantly positive, 4 concordantly negative. For positive IHC, 100% concordance with SSTR-PET/CT (both positive) was observed, while for negative IHC concordance (both negative) was 30.8%. In 9 cases, IHC was negative while SSTR-PET/CT was positive, even though with low-grade uptake in all but one. A significant correlation between SUVmax values at SSTR-PET/CT and the SSTR2-IHC scores was found, with low SUVmax values corresponding to negative IHC and higher SUVmax values to positive IHC (p=0.0007). When correlating 68Ga-DOTA-SSA or 18F-FDG SUVmax values with Ki-67, a significant result was found for 18F-FDG only (p=0.015). Conclusion This retrospective study showed an overall good agreement between SSTR2-IHC and tumor uptake at SSTR-PET/CT in lung NENs. SSTR-PET/CT SUVmax values can be used as a parameter of SSTR2 density. SSTR2-IHC may be proposed as surrogate of SSTR-PET/CT in selected lung NEN patients for clinical decision making when SSTR-PET/CT is not available.

Congenital hyperinsulinism (HI) is a life-threatening condition characterized by severe and recurrent episodes of hypoglycaemia due to defects in key genes involved in regulating insulin secretion. The delay in diagnosis and inappropriate management of HI lead to high risk of permanent hypoglycemic brain injury. The management of HI is challenging as each form of HI (focal, diffuse, and atypical) requires its own therapeutic strategy. In HI diagnostic work-up, integrated PET/CT scan is currently the first-line imaging technique allowing to differentiate between diffuse and focal form and, in the latter case, to localize the focus within the pancreas with high precision. Only in focal HI partial pancreatectomy is the treatment of choice and a curative surgical treatment means a real chance of transforming patient’s lives and HI patient’s future. The aim of this review is to discuss the role of PET/CT imaging in HI scenario, its technical advantages and limitations and how successful surgery is strongly dependent on accurate preoperative assessment (genetic analysis and PET/CT scan). A multidisciplinary approach in HI diagnosis and treatment inside a single team (involving different expertise) allows to manage children safely and properly, supporting their families in an organized care network.

Purpose To correlate somatostatin receptor (SSTR) and proliferative activity profile (SSTR2, SSTR5, Ki-67) at immunohistochemistry (IHC) with SSTR-PET/CT imaging features in a retrospective series of lung neuroendocrine tumors (NET). Proliferative activity by Ki-67 and 18F-FDG-PET/CT parameters (when available) were also correlated. Methods Among 551 patients who underwent SSTR-PET/CT with 68Ga-DOTA-somatostatin analogs (SSA) between July 2011 and March 2020 for lung neuroendocrine neoplasms, 32 patients with a confirmed diagnosis of NET were included. For 14 of them, 18F-FDG-PET/CT was available. PET/CT images were reviewed by qualitative and semi-quantitative analyses. Immunohistochemistry for SSTR2, SSTR5, and Ki-67 was assessed. Inferential analysis was performed including kappa statistics and Spearman’s rank correlation test. Results Definitive diagnosis consisted of 26 typical carcinoids-G1 and six atypical carcinoids-G2. Positive SSTR2-IHC was found in 62.5% of samples while SSTR5-IHC positivity was 19.4%. A correlation between SSTR2-IHC and SSTR-PET/CT was found in 24/32 cases (75.0%, p = 0.003): 20 were concordantly positive, 4 concordantly negative. For positive IHC, 100% concordance with SSTR-PET/CT (both positive) was observed, while for negative IHC concordance (both negative) was 33.3%. In 8 cases, IHC was negative while SSTR-PET/CT was positive, even though with low-grade uptake in all but one. A significant correlation between SUVmax values at SSTR-PET/CT and the SSTR2-IHC scores was found, with low SUVmax values corresponding to negative IHC and higher SUVmax values to positive IHC (p = 0.002). Conclusion This retrospective study showed an overall good agreement between SSTR2-IHC and tumor uptake at SSTR-PET/CT in lung NETs. SSTR-PET/CT SUVmax values can be used as a parameter of SSTR2 density. Within the limits imposed by the relatively small cohort, our data suggest that SSTR2-IHC may surrogate SSTR-PET/CT in selected lung NET patients for clinical decision making when SSTR-PET/CT is not available.

Adrenal masses are a frequent finding in clinical practice. Many of them are incidentally discovered with a prevalence of 4% in patients undergoing abdominal anatomic imaging and require a differential diagnosis. Biochemical tests, evaluating hormonal production of both adrenal cortex and medulla (in particular, mineralocorticoids, glucocorticoids and catecholamines), have a primary importance in distinguishing functional or non-functional lesions. Conventional imaging techniques, in particular computerized tomography (CT) and magnetic resonance imaging (MRI), are required to differentiate between benign and malignant lesions according to their appearance (size stability, contrast enhanced CT and/or chemical shift on MRI). In selected patients, functional imaging is a non-invasive tool able to explore the metabolic pathways involved thus providing additional diagnostic information. Several single photon emission tomography (SPET) and positron emission tomography (PET) radiopharmaceuticals have been developed and are available, each of them suitable for studying specific pathological conditions. In functional masses causing hypersecreting diseases (mainly adrenal hypercortisolism, primary hyperaldosteronism and pheochromocytoma), functional imaging can lateralize the involvement and guide the therapeutic strategy in both unilateral and bilateral lesions. In non-functioning adrenal masses with inconclusive imaging findings at CT/MR, [

Purpose Asymptomatic patients with follicular lymphoma (FL) and a low tumour burden can be followed without initial therapy, a strategy called watchful waiting (WW). Prediction of the time to treatment (TTT) is still a challenge. We investigated the prognostic value of baseline total metabolic tumour volume (TMTV) and whole-body total lesion glycolysis (WB-TLG) to predict TTT in patients with FL on WW. Methods We conducted a retrospective study of 54 patients with FL (grade 1–3a) diagnosed between June 2013 and December 2019, staged with FDG PET/CT, and managed on WW. Median age was 62 years (range 34–85), stage was advanced (III–IV) in 57%, and FLIPI score was intermediate to high (≥ 2) in 52% of the patients. Results The median TMTV and WB-TLG were 7.1 and 43.3, respectively. With a median follow-up of 59 months, 41% of patients started immuno-chemotherapy. The optimal cut-points to identify patients with TTT within 24 months were 14 for TMTV (AUC 0.70; 95% CI 51–88) and 64 for WB-TLG (AUC 0.71; 95% CI 52–89) (p p Conclusion Metabolic tumour volume parameters may add information to clinical scores to better predict TTT and better stratify patients for interventional studies.

Background‘Severe acute respiratory syndrome coronavirus-2’ (SARS-CoV-2) infection has dramatically affected the management of patients with cancer, who are most vulnerable to the consequences of the infection. Patients with vulvar cancer are frequently elderly and affected by multiple co-morbidities, thus representing a particularly frail population.ObjectiveTo assess the clinical impact of the SARS-CoV-2 infection among patients scheduled for treatment for active vulvar cancer.MethodsData on patients with vulvar tumors referred to Fondazione Policlinico Universitario Agostino Gemelli IRCCS between February 2020 and July 2021 were retrospectively analyzed. Patients with a positive reverse transcription polymerase chain reaction in nasopharyngeal swab were considered as positive for SARS-Cov-2.ResultsOne hundred and ninety-one patients with vulvar cancer were evaluated and scheduled for treatment. The median age was 72 years (range 35–94). Seven (3.7%) patients were diagnosed with SARS-Cov-2 infection: three (42.9%) had their treatment delayed, with no apparent consequences, two (28.6%) had their treatment delayed and later abandoned because of clinical worsening due to oncologic disease progression, and two (28.6%) contracted the infection in the post-operative period and died due to respiratory complications.ConclusionsIn most cases the infection had major clinical implications, being associated with significant delays in oncologic treatments and extremely high mortality when contracted in the post-operative period.

Solitary fibrous tumor of the pleura (SFTP) is a rare mesenchymal neoplasm. Preoperative diagnosis is usually difficult and based on radiological findings only. We report the imaging results observed in 5 patients with SFTP (2 malignant) obtained by 68Ga-DOTATOC PET/CT. At qualitative analysis, all tumors showed uptake of 68Ga-DOTATOC. Mean tumor SUVmax was 9.9 ± 5.7. The expression of SST2 (somatostatin receptors subtype 2) was confirmed by immunohistochemistry in 2 tumor samples, and by gene amplification of SST2 mRNA in all cases. These data suggest a diagnostic role of radioreceptor PET/CT in SFTP, and open novel potential treatment options in unresectable/metastatic disease.

Introduction/Background* Sentinel node biopsy (SNB) is the standard of care for vulvar cancer patients clinically N0 (cN0) at preoperative assessment, with unifocal primary tumor, Methodology According to the Grosnapet study design, lymph node status was assessed by pre-operative PET/CT scan and cN0 patients were enrolled on the base of the following criteria: a) Tumor > 4 cm, b) Multifocal tumors, c) previous complete excision; d) contralateral nodal involvement, e) previous RTCT treatment or f) vulvar recurrence. Vulvar surgery was performed according to current recommendations, as appropriate. Sentinel lymph node was detected by radiotracer and blue dye to reach the maximum detection rate. Radical lymphadenectomy was always provided after SNB, according to the standard of care. Both PET/CT scan and SNB were compared to final pathology report. Patients were followed up quarterly, undergoing clinical visit, groin ultrasound and PET/CT scan. Result(s)* During the study period, 72 patients were considered eligible for a total of 111 groins included. Median patient’s age was 73yrs. Histopathology revealed 16 (14.4%) groins with metastatic sentinel nodes (SLNs). Only one case had further involved non SLNs. Overall, 18/274 (6.5%) SLN excised were positive at histology. Median metastasis diameter was 4.8 (1.5-12). One false negative SN was identified (NPV 99%). PET/CT showed an NPV of 92%. After a median follow-up of 38 months (range 1-97 months), 19 recurrences and 6 deaths were registered. The 3-year disease-free survival (DFS) was 72.6%. Conclusion* This is the largest series that strongly support the use of SNB in cN0 patients currently excluded. A careful preoperative study could safely select eligible patients. Further validation is advisable.

Introduction/Background* The first prototype of the “Multidisciplinary Tumor Board Smart Virtual Assistant” is presented. Methodology Data from patients affected by invasive carcinoma of the cervix (LACC), FIGO stage IB2-IVa, treated between 2015 and 2018 were extracted. Magnetic Resonance (MR), Gynecologic examination under general anesthesia (EAU), and Positron Emission Tomography–Computed Tomography (PET-CT) performed at the time of diagnosis were the items from the Electronic Health Records (eHRs) considered for analysis. An automated extraction of eHR that capture the patient’s data before the diagnosis and then, through Natural Language Processing (NLP), analysis and categorization of all data to transform source information into structured data has been performed. Thereafter, an Artificial Intelligence method was developed to support the clinical staff in their decision with regards to tumor staging and to help them identifying the most complex cases where deeper analysis and discussion were required (e. g. conflicting information from different exams). Result(s)* In the first round, the system has been used to retrieve all the eHR for the 96 patients with LACC. This was the training set of the study, with validated 2009 FIGO staging classification ranging from I B2 to IV A as output. For these patients, available eHR included MR, EUA, and PET-CT diagnostic reports. The system has been able to classify all patients belonging to the training set and - through the NLP procedures - the clinical features were analyzed and classified for each patient. A second important result was the setup of a predictive model to evaluate the patient’s staging. Our approach has led to predict patient’s staging within an accuracy of 94%. Lastly we created a user-oriented operational tool targeting the MTB who are confronted with the challenge of large volumes of patients to be diagnosed in the most accurate way. The resulting decision support system is summarized in figure 1. Furthermore, the MTB Smart DA was tested in a 13 LACC patients validation cohort showing an accuracy of 93%, in line with the training set performances. Conclusion* This is the first proof of concept concerning the possibility of creating a smart virtual assistant for the MTB. A significant benefit could come from the integration of these automated methods in the collaborative, crucial decision stages.

Purpose: To investigate whether the COVID-19 pandemic and national lockdown had an impact on the extent of cancer disease at staging using FDG PET/CT as surrogate marker.Methods: Retrospective observational study including cancer patients submitted to FDG PET/CT for staging purposes from June 1 to October 31, 2020, and June 1 to October 31, 2021, respectively. Data regarding primary tumour, nodal (N) status and number of involved nodal stations, presence and number of distant metastases (M) were collected. Each scan was classified in limited vs advanced status. Data were aggregated across the study population and tumour type. Bi-weekly frequencies of the observed events were analysed. Results: 611 patients were included in the study (240 in 2019 vs. 371 in 2020, respectively). A significant increase in the rate of advanced disease patients in 2020 compared to 2019 was found (rate 1.56, pConclusion: The rate of cancer patients with advanced disease at staging FDG PET/CT increased by 1.5-fold in 2020, following the national lockdown due to the COVID-19 pandemic, compared to 2019 with a significant increase of patients with N involvement or M. Targeted health interventions are needed to mitigate the effects of the pandemic on patient outcome.

Purpose To investigate whether the COVID-19 pandemic and national lockdown had an impact on the extent of cancer disease at FDG PET/CT staging as surrogate marker. Methods Retrospective observational study including cancer patients submitted to FDG PET/CT staging from June 1 to October 31, 2020, and June 1 to October 31, 2019, respectively. Data regarding primary tumour, nodal (N) status and number of involved nodal stations, and presence and number of distant metastases (M) were collected. Each scan was classified in limited vs advanced status. Data were aggregated across the study population and tumour type. Bi-weekly frequencies of the observed events were analysed. Results Six hundred eleven patients were included (240 in 2019 vs 371 in 2020, respectively). A significant increase of advanced disease patients (rate 1.56, P

Aim. The first prototype of the “Multidisciplinary Tumor Board Smart Virtual Assistant” is presented, aimed to (i) Automated classification of clinical stage starting from different free-text diagnostic reports; (ii) Resolution of inconsistencies by identifying controversial cases drawing the clinician's attention to particular cases worthy for multi-disciplinary discussion; (iii) Support environment for education and knowledge transfer to junior staff; (iv) Integrated data-driven decision making and standardized language and interpretation.Patients and Method. Data from patients affected by invasive carcinoma of the cervix (LACC), FIGO stage IB2-IVa, treated between 2015 and 2018 were extracted. Magnetic Resonance (MR), Gynecologic examination under general anesthesia (EAU), and Positron Emission Tomography–Computed Tomography (PET-CT) performed at the time of diagnosis were the items from the Electronic Health Records (eHRs) considered for analysis. An automated extraction of eHR that capture the patient’s data before the diagnosis and then, through Natural Language Processing (NLP), analysis and categorization of all data to transform source information into structured data has been performed. Results. In the first round, the system has been used to retrieve all the eHR for the 96 patients with LACC. The system has been able to classify all patients belonging to the training set and - through the NLP procedures - the clinical features were analyzed and classified for each patient. A second important result was the setup of a predictive model to evaluate the patient’s staging (accuracy of 94%). Lastly we created a user-oriented operational tool targeting the MTB who are confronted with the challenge of large volumes of patients to be diagnosed in the most accurate way. Conclusion. This is the first proof of concept concerning the possibility of creating a smart virtual assistant for the MTB. A significant benefit could come from the integration of these automated methods in the collaborative, crucial decision stages.

Objective To evaluate the feasibility and clinical application of fusion imaging with virtual navigation, combining 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) with real-time ultrasound imaging, in assessing superficial lymph nodes in breast-cancer and gynecological-cancer patients. Methods This was a pilot study of breast- and gynecological-cancer patients with abnormal uptake of 18 F-FDG by axillary or groin lymph nodes on PET/CT scan, examined at our institution between January 2017 and May 2019. Fusion imaging was performed, uploading preacquired PET/CT DICOM images onto the ultrasound machine and synchronizing them with real-time ultrasound scanning performed at the lymph-node site. In the first phase, we assessed the feasibility and reliability of fusion imaging in a series of 10 patients with suspicious lymph nodes on both PET/CT and ultrasound, and with full correspondence between both techniques in terms of size, shape and morphology of the lymph nodes (Group A). In the second phase, we included 20 patients with non-corresponding findings between PET/CT and ultrasound: 10 patients with lymph nodes that were suspicious or pathological on PET/CT scan but not suspicious on ultrasound assessment (Group B), and 10 patients with suspicious or pathological lymph nodes on both PET/CT and ultrasound but with no correspondence between the two techniques in terms of number of affected lymph nodes (Group C). Results In the 30 selected patients, fusion imaging was assessed at 30 lymph-node sites (22 inguinal and eight axillary nodes). In the first phase (Group A), the fusion technique was shown to be feasible in all 10 lymph-node sites evaluated. In the second phase, fusion imaging was completed successfully in nine of 10 cases in Group B and in all 10 cases in Group C. In all groups, fusion imaging was able to identify the target lymph node, guiding the examiner to perform a core-needle aspiration biopsy or to inject radiotracer for selective surgical nodal excision, according to the radio-guided occult lesion localization technique. Conclusion Fusion imaging with virtual navigation, combining PET/CT and real-time ultrasound imaging, is technically feasible and able to detect target lymph nodes even when PET/CT and ultrasound findings are inconsistent. Fusion imaging can also be used to guide the performance of core-needle aspiration biopsy, avoiding further surgical diagnostic procedures, or the injection of radiotracer for selective surgical nodal excision, enabling more sparing, selective surgery. This innovative technique could open up multiple diagnostic and therapeutic opportunities in breast and gynecological oncology. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Aim The aims of this study were to determine the role of 18F-FDG PET/CT in vulvar cancer patients and to extract summary estimates of its diagnostic performance for preoperative lymph node staging. Patients and methods PubMed/Medline and Embase databases were searched to identify studies evaluating 18F-FDG PET/CT in vulvar cancer patients. The assessment of methodological quality of the included articles was performed. Per-patient and per-groin pooled estimates, with 95% confidence intervals (CIs), of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (DOR) were calculated. Results Ten articles were included in the systematic review, 7 among which evaluated the diagnostic performance of preoperative 18F-FDG PET/CT for lymph node staging. Qualitative per-patient analysis (72 patients from 4 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.70 (95% CI, 0.44-0.95), 0.90 (95% CI, 0.76-1.04), 0.86 (95% CI, 0.66-1.06), 0.77 (95% CI, 0.56-0.97), and 10.49 (95% CI, 1.68-65.50), respectively. Qualitative per-groin analysis (245 groins from 5 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.76 (95% CI, 0.57-0.94), 0.88 (95% CI, 0.82-0.94), 0.70 (95% CI, 0.55-0.85), 0.92 (95% CI, 0.86-0.97), and 19.43 (95% CI, 6.40-58.95), respectively. Conclusions Despite limited literature data, this systematic review and meta-analysis revealed that a negative preoperative PET/CT scan may exclude groin metastases in at least early-stage vulvar cancer patients currently unfit for sentinel node biopsy and select those eligible for a less invasive surgical treatment. A positive PET/CT result should otherwise be interpreted with caution. Larger prospective studies are needed to confirm these results and to evaluate the diagnostic value of standardized semiquantitative analysis compared with the qualitative one.

Purpose This retrospective study aimed to assess the diagnostic performance of preoperative [18F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients. Methods Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [18F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUVmax). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard. Results All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3–92.8), 65.5% (59.0–72.0), 71.6% (66.5–76.8), 52.0% (44.0–60.1) and 91.2% (86.7–95.8) for visual assessment; 78.9% (70.5–87.3), 78.2% (72.5–83.8), 78.4% (73.7–83.1), 61.2% (52.3–70.1) and 89.4% (85.0–93.9) for overall assessment; and 73.3% (64.2–82.5), 85.0% (80.1–89.8), 81.4% (77.0–85.8), 68.0% (58.8–77.3) and 87.9% (83.4–92.5) for semi-quantitative analysis (SUVmax cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis. Conclusion In this large single-centre series of vulvar cancer patients, [18F]FDG-PET/CT showed good values of sensitivity and NPV in discriminating metastatic from non-metastatic LNs. In routine clinical practice, qualitative analysis is a reliable interpretative criterion making unnecessary commonly used semi-quantitative methods such as SUVmax.

We assessed the prognostic value of several FDG PET/CT parameters, measured within the primary tumor and the involved lymph nodes, before definitive radio-chemotherapy (RCT) in anal cancer patients. Anal cancer patients with positive baseline FDG PET/CT who underwent definitive RCT from May 2011 to February 2018 were retrospectively assessed. Primary tumour (T)-SUVmax, T-SUVpeak, T-SUVmean, T-MTV, T-TLG, whole-body (WB) MTV, and WB-TLG were measured. Kaplan–Meier curves, Cox-regression analysis, and logistic regression machine-learning technique were used to test for associations between clinical data, metabolic parameters, and outcomes as overall survival (OS), disease-specific survival (DSS), metastatic-free survival (MFS), disease-free survival (DFS), local relapse-free survival (LRFS), and colostomy-free survival (CFS). Fifty-nine patients were included in the study. Median follow-up was 28 months. Higher pre-treatment WB-MTV, T-TLG, and WB-TLG were associated with worse OS (p = 0.025, 0.021, and 0.02, respectively). PET parameters resulted also statistically significant for DSS, DFS, and CFS (p = 0.032, 0.043, 9 × 10−4 for WB-TLG). Cox analysis showed that PET parameters are significant predictors of OS, DSS, DFS, CFS, and LRFS. On multivariate analysis, age, stage, T-SUVpeak, WB-MTV, and T-TLG resulted significantly related to OS. A further stratification for patients with advanced stage (cT3-4 any N or any cT, N + ) showed that MTV and TLG, measured within the primary tumor and the involved nodes, are significantly higher in patients with a worse prognosis. In this subgroup, cut-off values of T- and WB-TLG as well as T- and WB-MTV showed a statistically significant correlation with clinical outcomes. Pre-treatment metabolic parameters measured within the primary tumor and the involved nodes may represent additional new biomarkers for estimating prognosis in anal cancer patients, especially in advanced stage patients.

PURPOSE The aim of this retrospective study was to determine, by dynamic acquisition, the optimal scan time of F-DOPA PET/CT in patients with recurrent medullary thyroid carcinoma (MTC). METHODS Twenty-one patients with suspected recurrent MTC underwent dynamic F-DOPA PET/CT (lasting 45 minutes) followed by whole-body scan. Three different time intervals of dynamic acquisition were evaluated: ultra-early phase (2-5 minutes), early phase (5-10 minutes), and late phase (40-45 minutes). The number and SUVmax of all detected lesions among the 3 dynamic acquisition phases were compared on qualitative and semiquantitative analyses. Time-activity curves, SUVmax washout rate between ultra-early or early phase and late phase, and signal-to-noise ratio (SNR) between lesion and background activity were also calculated. RESULTS At dynamic acquisition, 15 of 21 patients were classified as PET-positive and 6 of 21 as PET-negative, with overall 21 detected lesions. Ultra-early and early imaging provided a better lesion visualization than late phase in more than 70% of cases, as also reflected by SNR (mean SNR reduction between 2 and 45 minutes, -45% ± 19%). Time-activity curves showed a rapid tracer accumulation in MTC lesions, with an average maximum uptake at 2 minutes after injection. Mean lesion SUVmax was 2-fold higher in ultra-early frames compared with last frames (mean washout rate, -44% ± 33%). Finally, compared with whole-body imaging in the same field of view, dynamic acquisition identified 1 additional positive patient and 3 additional lesions in 2 patients. CONCLUSIONS Our study, showing a very fast F-DOPA uptake in MTC lesions, suggests the utility to obtain early PET/CT images, already at 2 to 5 minutes after tracer injection, when maximum lesion tracer uptake is reached.

To assess the diagnostic performance of conventional and DW-MRI parameters in the detection of residual tumor in locally advanced cervical cancer (LACC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and radical surgery Between October 2010 and June 2014, 88 patients with histologically documented cervical cancer (FIGO stage IB2–IVA) were prospectively included in the study. Maximum tumor diameters (maxTD), tumor volume (TV), DWI signal intensity (SI), and ADCmean were evaluated at MRI after nCRT. Histology was the reference standard. Treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney, χ2, and Fisher’s exact tests. ROC curves were generated for variables to evaluate diagnostic ability to predict PR and to determine the best cutoff value to predict PR. For each diagnostic test, sensitivity, specificity, and accuracy were calculated. TV and maxTD were significantly smaller in the CR than in the PR group (p

To determine the diagnostic performance of two-dimensional (2D) ultrasound parameters, three-dimensional (3D) power Doppler and contrast-enhanced indices in detecting residual disease in locally advanced cervical cancer patients triaged to neoadjuvant treatment followed by radical surgery.Between October 2010 and June 2014, we screened 108 women with histologically documented locally advanced cervical cancer Stage IB2-IVA, of whom 88 were included in the final analysis. 2D ultrasound parameters, 3D power Doppler and contrast-ultrasound parameters were assessed 5 weeks after the end of neoadjuvant chemoradiation therapy. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (including microscopic and/or macroscopic residual tumor at pathology examination). The two response groups were compared and receiver-operating characteristics (ROC) curves generated to determine the best cut-off value of sonographic tumor diameter to predict residual disease. Histology was considered as reference.Complete pathological response to chemoradiation was observed in 40 (45.5%) patients and partial response in 48 (54.5%). The presence of residual disease, as confirmed at pathology examination, was detected by 2D grayscale ultrasound with a sensitivity of 64.6% and specificity of 65%. Color Doppler examination in the cases with lesions visualized on grayscale imaging detected the presence of residual disease, confirmed at pathology, with a sensitivity of 87.1% and specificity of 21.4%. The best area under the ROC curve (0.817) was for the detection of pathological residual disease of at least 6 mm in diameter, using a cut-off value of 12 mm for the largest tumor diameter assessed using 2D grayscale ultrasound (sensitivity, 95%; specificity, 70.6%). Neither 3D vascular indices nor contrast-ultrasound parameters obtained for lesions suspected at ultrasound following chemoradiation differed significantly between patients with histological complete and those with partial response.Our results show that grayscale and color Doppler ultrasound have a low level of diagnostic performance in detecting residual disease after neoadjuvant chemoradiation in patients with locally advanced cervical cancer. The best performance was achieved in detection of macroscopic (≥ 6 mm) residual disease. Copyright © 2018 ISUOG. Published by John WileySons Ltd.

Objective Chemoradiation-based neoadjuvant treatment followed by radical surgery is an alternative therapeutic strategy for locally advanced cervical cancer (LACC) –stage ≥ IB2 (except of IIA1)– but ultrasound variables used to predict neoadjuvant partial response are not well defined. The goal of this study was to prospectively analyze the potential role of transvaginal ultrasound (TVUS) in early predicting pathologically assessed residual disease in a large, single-institution series of LACC patients triaged to neoadjuvant treatment followed by radical surgery. Methods Between October 2010 and June 2014, 108 women with histologically documented LACC were screened and 88 of them were included in the final analysis. Tumor volume, 3D power Doppler indices and contrast parameters were obtained before (baseline examination) and after two weeks of treatment (early examination). The pathological response was defined as complete (absence of any residual tumor after treatment) or partial, including both microscopic and macroscopic residual tumor at pathological examination. Comparisons between the two groups (complete response group versus partial response group) were made with Mann–Whitney-test or Wilcoxon-test and χ2-test, as appropriate. Receiver–operating characteristic (ROC) curves were generated for statistically significant ultrasound variables on univariate analysis to evaluate their diagnostic ability to predict pathological partial response. Results Complete and partial pathological responses to neoadjuvant therapy were documented in 40 (45.5%) and 48 (54.5%) patients respectively. At baseline examination, tumor volume did not differ between patients with a complete and those with a partial response. However, after two weeks of neoadjuvant treatment, the tumor volume was significantly higher in patients with partial response than in those with complete response (p = 0.019). Among the 3D vascular indices, vascularization index (VI) was significantly lower in partial response group than in complete response group both before and two weeks after treatment (p = 0.037 and p = 0.024 respectively). In the contrast analysis, a lower tumor peak enhancement (PE) as well as a lower tumor Wash in Rate (WiR), and a longer tumor Rise Time (RT) were observed at baseline examination in women with partial response than in those with complete response (p = 0.006, p = 0.003, p = 0.038, respectively). No difference was found in terms of contrast parameters at early examination. Receiver operating characteristic (ROC) curve analysis of baseline parameters showed that the best cut-off for predicting pathological partial response was 41.5% for VI (sensitivity 63.6% and specificity 66.7%); 16123.5 for tumor PE (sensitivity 47.9% and specificity 84.2%); 7.8 s for tumor RT (sensitivity 68.8% and specificity 57.9%); and 4902 for tumor WiR (sensitivity 77.1% and specificity 60.5%). ROC curves of early parameters showed that the best cut-off for predicting pathological partial response was 18.1 cm3 for tumor volume (sensitivity 71% and specificity 60%) and 39.5% for VI (sensitivity 63% and specificity 74%). Conclusions Ultrasound and contrast parameters differ between patients with complete response and those with partial response before and after two weeks of neoadjuvant treatment. However, neither ultrasound parameters performed before treatment nor those performed two weeks after treatment have shown a cut-off value with acceptable sensitivity and specificity for predicting pathological partial response to neoadjuvant therapy.

To analyse the role of DW-MRI in early prediction of pathologically-assessed residual disease in locally-advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed by radical surgery. Between October 2010–June 2014, 108 women with histologically-proven cervical cancer were screened; 88 were included in this study. Tumour volume (TV) and ADCmean were measured before (baseline-MRI) and after 2 weeks of chemoradiotherapy (early-MRI). According to histopathology, treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney, Wilcoxon and χ2 tests. ROC curves were generated for statistically significant parameters on univariate analysis. CR and PR were documented in 40 and 48 patients. At baseline-MRI, TV did not differ between groups. At early-MRI, TV was higher in PR than in CR (p=0.001). ΔTV reduction after treatment was lower in PR than in CR (63.6% vs. 81.1%; p=0.001). At baseline-MRI and early-MRI, ADCmean did not differ between PR and CR. ROC curve showed best cut-off for predicting pathological PR was ΔTV reduction of 73% with sensitivity, specificity, accuracy, NPV, PPV of 73%, 72.5%, 72.7%, 76%, 69%. TV evaluated before and early after treatment could predict pathological response in LACC. ADCmean did not correlate with treatment outcome. • Early-MRI tumour volume assessment could predict pathological response to nCRT in LACC. • Best cut-off for predicting pathological PR was ΔTV reduction of 73 %. • Early-MRI ADC mean measurements did not correlate with treatment outcome.

A 75-year-old man, who had been diagnosed with small lymphocytic lymphoma with cervical localization, underwent F-FDG PET/CT with iodinated contrast medium due to the appearance of cervical swelling suspected of illness relapse. PET/CT revealed intense F-FDG uptake in multiple cervical and subdiaphragmatic lymph nodes and in the left parotid. Moreover, diffuse uptake and wall thickening of the colon were evident; endoscopy with biopsy revealed a diffuse large B-cell lymphoma. Transformation into a more aggressive lymphoma occurs in 2% to 8% of small lymphocytic lymphoma, the so-called Richter syndrome. Extranodal localization in the sigmoid colon is an extremely rare site for transformed lymphoma.

Hodgkin Lymphoma (HL) is a tumor of B-cell origin characterized by Hodgkin and Reed-Stenberg (H/RS) cells embedded in an inflammatory tissue where numerous cytokines/chemokines contribute to shape the microenvironment, leading to the typical clinical symptoms. We investigated: i) the expression of Interleukin-IL-31 (IL-31) and Thymic Stromal Lymphopoietin (TSLP), two Th2-related cytokines with tumor-promoting and pruritogenic functions, and of the respective receptors in HL invaded lymph nodes by flow cytometry, and ii) the potential association of IL-31/TSLP plasma concentrations with clinical characteristics by ELISA. H/RS cells and the major immune cell types infiltrating HL lymph nodes expressed intracytoplasmic and surface IL-31/TSLP, and their receptors. A subgroup of patients showing at diagnosis elevated IL-31 and TSLP plasma levels had an International Prognostic Score > 2, indicative of high risk of relapse, and a subsequent positive interim PET-scan, indicative of insufficient response to chemotherapy. No correlation was found between IL-31/TSLP plasma levels and overall or event-free survival. In conclusion, IL-31/TSLP and their receptors are expressed in HL cells and in immune cells infiltrating affected lymph nodes, where both cytokines may contribute to local immune suppression. The clinical impact of IL-31 and TSLP plasma levels has to be further defined in larger patient cohorts.

Objective The aim of the study was to assess the value and potential pitfalls of Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) in patients with suspected pancreatic neuroendocrine neoplasms (pNEN). Methods Consecutive patients referred for Ga-DOTANOC PET/CT for suspected pNEN between May 1, 2011, and October 31, 2014, were retrospectively assessed. Scan data were compared with cytological/histological final diagnosis. Pancreatic neuroendocrine neoplasm detection rate was determined on per-patient and per-lesion basis. Maximum standardized uptake values of lesions were determined. Results Fifty-eight patients with 65 lesions were enrolled. Twelve patients had nonconfirmed diagnosis; of these, 7 were positive and 5 negative at PET/CT. Of 46 patients with confirmed diagnosis, 36 had pNEN; of these, 33 were positive, 1 negative, and 2 nonevaluable at PET/CT. Ten patients had non-NE lesions, of which 8 were positive, 1 negative, and 1 nonevaluable at PET/CT. Of 48 patients with positive PET/CT, 8 proved to have non-NE lesions, of which 6 were intrapancreatic accessory spleen. No significant maximum standardized uptake values difference was found between pNEN and non-NE lesions. Conclusions Intrapancreatic accessory spleen is an important pitfall in Ga-DOTANOC PET/CT for suspected pNEN. Cytological/histological confirmation is mandatory before any surgical procedure is undertaken.

This prospective study aimed to evaluate whetherBetween October 2010 and June 2014, 88 patients with LACC were enrolled. For each patient, threeAt histopathology, 40 patients had complete response (CR, pR0), 48 had partial response (PR: 21 microscopic [pR1] and 27 macroscopic [pR2]). At baseline, SUVIn LACC patients treated with CRT followed by surgery, early variations in metabolic parameters effectively discriminate histopathological PR of the primary tumor, suggesting the potential role of

This study investigated whether radiomic features derived from preoperative PET images could predict both tumor biology and prognosis in women with invasive squamous cell carcinoma of the vulva. Methods: Patients were retrospectively included if they had a unifocal primary cancer at least 2.6 cm in diameter, received a preoperative 18F-FDG PET/CT scan followed by surgery, and had at least 6 mo of follow-up data. 18F-FDG PET images were analyzed by semiautomatically drawing a volume of interest on the primary tumor in each PET image, followed by extraction of 83 radiomic features. Unique radiomic features were identified by principal-component analysis (PCA), after which they were compared with histopathology using nonpairwise group comparison and linear regression. Univariate and multivariate Cox regression analyses were used to correlate the identified features with progression-free survival (PFS) and overall survival (OS). Survival curves were estimated using the Kaplan–Meier method. Results: Forty women were included. PCA revealed 4 unique radiomic features, which were not associated with histopathologic characteristics such as grade, depth of invasion, lymph-vascular space invasion, and metastatic lymph nodes. No statistically significant correlation was found between the identified features and PFS. However, Moran’s I, a feature that identifies global spatial autocorrelation, correlated with OS (P = 0.03). Multivariate Cox regression analysis showed that extracapsular invasion of the metastatic lymph nodes and Moran’s I were independent prognostic factors for PFS and OS. Conclusion: Our data show that PCA is usable to identify specific radiomic features. Although the identified features did not correlate strongly with tumor biology, Moran’s I was found to predict patient prognosis. Larger studies are required to establish the clinical relevance of the observed findings.

This prospective study aimed to evaluate whether 18F-FDG-PET/CT performed before, during and after neoadjuvant chemo-radiotherapy (CRT) could predict histopathological response in patients with locally advanced cervical cancer (LACC) treated with CRT followed by radical surgery. Between October 2010 and June 2014, 88 patients with LACC were enrolled. For each patient, three 18F-FDG-PET/CT scans (baseline, early and final) were acquired and evaluated by qualitative and quantitative analysis. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured as absolute values and their percentage variation (delta) (early vs. baseline and final vs. baseline). The role of 18F-FDG-PET/CT in predicting lymph node (LN) residual disease was evaluated by qualitative analysis only. Histopathology was the reference standard. At histopathology, 40 patients had complete response (CR, pR0), 48 had partial response (PR: 21 microscopic [pR1] and 27 macroscopic [pR2]). At baseline, SUVmax and SUVmean were significantly higher in pR0 than in pR1–pR2 patients. At early evaluation, MTV and TLG were significantly higher in pR1–pR2 than in pR0 patients. At final evaluation, SUVmax, SUVmean and TLG were significantly higher in pR1–pR2 than in pR0 patients. Delta SUV parameters and delta TLG were significantly lower in PR group both during and after CRT. Delta MTV was significantly lower in patients with PR in the early phase only. In receiver operating characteristic (ROC) curve analysis, baseline SUVmean, early delta TLG, and final delta SUVmax better discriminated PR, providing 83.3%, 67.6% and 85% positive predictive value (PPV) and 60.3%, 90% and 70.8% negative predictive value (NPV), respectively. For LN assessment, high NPV was observed at early and final 18F-FDG-PET/CT (93.5% and 92.3%, respectively). In LACC patients treated with CRT followed by surgery, early variations in metabolic parameters effectively discriminate histopathological PR of the primary tumor, suggesting the potential role of 18F-FDG-PET/CT in early personalized treatment. The high NPV of early and final PET/CT could enable “tailored surgery” by avoiding lymphadenectomy in selected patients.

To evaluate the prognostic role of the ratio between target lesion and liver SUVmax (rPET) in patients with Hodgkin lymphoma (HL) undergoing interim FDG-PET/CT and to compare rPET with the 5-point Deauville Score (5p-DS). Sixty-eight patients with HL undergoing interim FDG-PET/CT after first courses of chemotherapy were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cutpoint of rPET with respect to progression free survival (PFS). The prognostic significance of rPET was compared with 5p-DS (scores 4 and 5 considered as positive). Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of an adverse event as the gold standard. The ROC analysis for rPET as a predictor of progression showed an optimal rPET cutpoint of 1.14. Both 5p-DS and rPET were strong outcome predictors (p 1.14 had a 2-year PFS of 15 %. 5p-DS and rPET cutoff of 1.14 showed a PPV of 58 versus 70 %, and a NPV of 85 versus 86 %, respectively. rPET could be considered an accurate prognostic factor in patients with HL undergoing interim FDG-PET/CT. Larger prospective studies are needed to confirm these data.