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

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

99mTc-Tilmanocept performance for sentinel node mapping in breast cancer, melanoma, and head and neck cancer: a systematic review and meta-analysis from a European expert panel.

PURPOSE: Although multiple radiopharmaceuticals are currently available for sentinel node (SN) biopsy, 99mTc-tilmanocept is of particular interest due to its low molecular weight and specific binding capability for the mannose receptors of lymphatic reticuloendothelial cells. In the current systematic review and meta-analysis, we aimed to provide an update from a European expert panel on the performance of 99mTc-tilmanocept for SN biopsy. METHODS: A systematic literature search of the PubMed/Medline and Embase databases was performed to identify studies on the use of 99mTc-tilmanocept for SN identification in oncological patients. The articles' methodological quality was assessed before inclusion. The pooled estimates of the pre-/intraoperative detection rates (DR; proportion of patients with ≥ 1 SN identified) and/or pN + sensitivity (SN + /pN + patients ratio), with 95% confidence intervals (CIs), were calculated for breast cancer, melanoma, and head and neck cancer. RESULTS: Twenty-four articles were included in the systematic review, and twenty-one provided data for the meta-analysis. According to data availability, the 99mTc-tilmanocept-estimated pooled preoperative and intraoperative DRs were 0.94 (95%CI, 0.88-1.01) and 0.99 (0.98-1.00) for breast cancer, 0.98 (0.96-0.99) and 1.00 (0.99-1.00) for melanoma, and 0.97 (0.93-1.02) and 0.99 (0.96-1.01) for head and neck carcinoma. Finally, the pooled sensitivity for nodal metastasis in melanoma was 0.97 (95% CI, 0.92-1.03). CONCLUSION: 99mTc-tilmanocept is a promising radiotracer for SN mapping in patients with breast cancer, melanoma, or head and neck cancer. We strongly believe that multicenter trials are still needed to assess if 99mTc-tilmanocept is superior to other radiotracers used in clinical routine.

Lymphatic mapping and sentinel node biopsy in vulvar melanoma: the first multicenter study and systematic review.

OBJECTIVE: This multicenter study aimed to investigate the role of preoperative lymphatic mapping and sentinel node biopsy (SNB) as well as the impact of negative SNB on loco-regional control and survival in vulvar melanoma patients with clinically negative nodes (cN0). METHODS: Patients who had a proven vulvar melanoma with a Breslow thickness of 1-4 mm, cN0 and underwent a preoperative lymphatic mapping followed by SNB between July 2013 and March 2021 were retrospectively included. Groin recurrence and mortality rate were calculated as absolute and relative frequency. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. We provided a systematic review, searching among PubMed/Medline and Embase libraries. A total of 6 studies were identified (48 patients). RESULTS: A total of 18 women were included. Preoperative planar images showed 51 SNs in 28 groins. Additional SPECT/CT images were acquired in 5/18 cases; SNs were identified pre- and intra-operatively in all cases. A total of 65 SNs were excised from 28 groins. A total of 13/18 (72.2%) patients (21/28 groins, 75%) had negative SNs with no groin recurrences and 12/13 (92.3%) were still alive at last follow-up. Five out of the 18 (27.8%) patients (7/28 groins, 25%) had positive SNs, 2/5 (40%) patients died of cancer after 26.2 and 33.8 months, respectively. The median DFS and OS for the entire cohort were 17.9 months (95% CI, 10.3-19.9) and 65.0 months (95% CI, 26.2-infinite), respectively. The probability of DFS and OS at 3 years were 15.5% (95% CI, 2.6-38.7) and 64.3% (95% CI, 15.5-90.2), respectively. CONCLUSIONS: The use of preoperative lymphatic mapping followed by SNB permits a precise and minimally invasive surgical approach in cN0 vulvar melanoma patients. Negative SNB is associated with low risk of groin relapse and good survival.

Correlation of somatostatin receptor PET/CT imaging features and immunohistochemistry in neuroendocrine tumors of the lung: a retrospective observational study.

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.

The impact of the COVID-19 pandemic on oncological disease extent at FDG PET/CT staging: the ONCOVIPET study.

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 < 0.001), N + or M + patients (rate 1.84 and 2.09, respectively, P < 0.001), and patients with a greater number of involved N stations or M (rate 2.01 and 2.06, respectively, P < 0.001) were found in 2020 compared with data of 2019. Analysis by tumour type showed a significant increase of advanced disease in lymphoma and lung cancer in 2020 compared with 2019 (P < 0.001). In addition, a significant increase of nodal involvement was found in lung, gastro-intestinal, and breast cancers, as well as in lymphoma patients (P < 0.02). A significant increase of distant metastases was found in lung cancers (P = 0.002). CONCLUSION: Cancer patients with advanced disease at FDG PET/CT staging increased in 2020 compared with 2019, following the national lockdown due to the COVID-19 pandemic, 1.5-fold with a significant increase of patients with N or M involvement. Targeted health interventions are needed to mitigate the effects of the pandemic on patient outcome.

Integration of molecular imaging in the personalized approach of patients with adrenal masses.

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, [18F]-FDG evaluation of tumor metabolism can be helpful to characterize them by distinguishing between benign nodules and primary malignant adrenal disease (mainly adrenocortical carcinoma), thus modulating the surgical approach. In oncologic patients, [18F]-FDG uptake can differentiate between benign nodule and adrenal metastasis from extra-adrenal primary malignancies.

Clinical impact of SARS-CoV-2 infection among patients with vulvar cancer: the Gemelli Vul.Can multidisciplinary team.

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. OBJECTIVE: To assess the clinical impact of the SARS-CoV-2 infection among patients scheduled for treatment for active vulvar cancer. METHODS: Data 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. RESULTS: One 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. CONCLUSIONS: In 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.

The role of apparent diffusion coefficient (ADC) in the evaluation of lymph node status in patients with locally advanced cervical cancer: our experience and a review.

Purpose: To evaluate the role of apparent diffusion coefficient (ADC) value measurement in the diagnosis of meta-static 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.

Diagnostic performance of preoperative [18F]FDG-PET/CT for lymph node staging in vulvar cancer: a large single-centre study.

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.

Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma.

The rarity of neoplastic cells in the biopsy imposes major technical hurdles that have so far limited genomic studies in classical Hodgkin lymphoma (cHL). By using a highly sensitive and robust deep next-generation sequencing approach for circulating tumor DNA (ctDNA), we aimed to identify the genetics of cHL in different clinical phases, as well as its modifications on treatment. The analysis was based on specimens collected from 80 newly diagnosed and 32 refractory patients with cHL, including longitudinal samples collected under ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy and longitudinal samples from relapsing patients treated with chemotherapy and immunotherapy. ctDNA mirrored Hodgkin and Reed-Sternberg cell genetics, thus establishing ctDNA as an easily accessible source of tumor DNA for cHL genotyping. By identifying STAT6 as the most frequently mutated gene in ∼40% of cases, we refined the current knowledge of cHL genetics. Longitudinal ctDNA profiling identified treatment-dependent patterns of clonal evolution in patients relapsing after chemotherapy and patients maintained in partial remission under immunotherapy. By measuring ctDNA changes during therapy, we propose ctDNA as a radiation-free tool to track residual disease that may integrate positron emission tomography imaging for the early identification of chemorefractory patients with cHL. Collectively, our results provide the proof of concept that ctDNA may serve as a novel precision medicine biomarker in cHL.

The role of 18F-FDG-PET/CT in predicting the histopathological response in locally advanced cervical carcinoma treated by chemo-radiotherapy followed by radical surgery: a prospective study.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Lung uptake of fluorine-18 fluoroethyl-choline PET-CT in patients with prostate cancer.

BACKGROUND: Metastatic spreading to the lungs is a negative prognostic factor in patients with prostate cancer (PC). Aim of our study was to assess the prevalence of lung PC metastases in patients with fluorine-18 fluoroethyl-choline (F-18-FECh) PET-CT positive lung lesions and the role of Gleason Score (GS) and common biochemical markers in predicting metastatic spreading to the lungs. METHODS: We retrospectively evaluated the scans of 1283 patients ongoing (F-18-FECh) PET-CT for PC between May 2010 and July 2014. Patients with lung lesion with F-18-FECh uptake were included. Data concerning GS at diagnosis, "trigger" prostate-specific antigen (PSAtr), PSA doubling time (PSAdt), PSA velocity (PSAvel) and ongoing androgen deprivation therapy were collected. PET-CT findings were confirmed by histology or follow-up (FU) and classified as follows: inflammation, primary lung cancer or metastases from tumor other than PC, and lung metastases from PC. RESULTS: Twenty-two patients with F-18-FECh positive lung lesion and available histology or FU were identified. PSAdt was significantly (P=0.029) shorter in patients with lung metastases from PC (median PSAdt 1.7 months, interquartile range [IQR] 1.5-4.1 months) than in patients without lung PC relapse (median PSAdt 6.7 months, IQR 3.9-7.8); PSAvel was significantly (P=0.019) higher in patients with lung metastases from PC (median PSAvel 3.2 ng/mL/month, IQR 0.65-6.65 ng/mL/month) than in patients without lung PC relapse (median PSAvel 0.3 ng/mL/month, IQR 0.2-0.5 ng/mL/month). Patients with lung metastases from PC had significantly (P=0.006) higher GS at diagnosis (median GS 8) than the other ones (median GS 7). CONCLUSIONS: Our analysis shows that the prevalence of F-18-FECh positive lung metastases in patients with PC, especially with higher GS at diagnosis, is higher in presence of a steady increase in PSA values, confirmed by higher PSAvel and shorter PSAdt.

Are the simplified methods to estimate Ki in 18F-FDG PET studies feasible in clinical routine? Comparison between three simplified methods.

BACKGROUND: The aim of this study was to verify the feasibility, in clinical practice, of three simplified methods (Hunter, Sadato and another one proposed by our group) to calculate Ki and MRglu of 18F-FDG, comparing the results with those derived by the linear regression (LR) method (considered the golden standard), and also with SUV. METHODS: Forty-five patients (32males, mean age 69±9years) with non-small-cell-lung cancer prospectively enrolled, underwent dynamic 18F-FDG PET-CT over the thorax. Ki was estimated as follows: from a static acquisition and performing one venous blood sampling using the Hunter method; multiplying the SUV for the average plasma clearance rate (kP(T)) and for the initial distribution volume (V0bw) without performing any blood sampling using the Sadato method; multiplying the SUV for a factor F (which encompasses the mean value of haematocrit and plasma volume, both according to patient's sex) without performing any blood sample using ours method. Wilcoxon signed rank and coefficient of determination (R2) were used for statistical analysis. RESULTS: No significant difference was observed between the Ki and MRglu estimated by all three simplified methods and the Ki and MRglu estimated by LR. The highest P values and the lower values of mean differences were observed with our method compared with LR: Ki=0.0392±0.0178 min-1 vs. Ki=0.0392±0.0202 min-1 (P=0.897, MD=0.0001 min-1), respectively; MRglu= 4.47±2.23 ml/min/100g vs. MRglu= 4.43±2.38 ml/min/100g (P=0.839, MD= -0.0373 mL/min/100g), respectively. The highest correlation was observed between the Ki estimated by both Hunter and our methods and the Ki estimated by LR: R2=0.87, R2=0.86, respectively. A good correlation (R2=0.83) was observed between SUV and Ki estimated by LR. CONCLUSIONS: These three simplified methods represent a valid alternative to the more invasive and complex full kinetic analysis. Their "pros" are: the non-invasiveness, the feasibility, the good correlation with the golden standard; their "cons" is that full kinetic analysis provides highest accuracy in Ki determination. Therefore, in clinical oncology routine, the nuclear physicians can choose among different simplified methods especially for monitoring the response to treatment, for tumour grading, and for prognostic stratification, letting the full kinetic analysis to specific centre/studies.

Focal congenital hyperinsulinism managed by medical treatment: a diagnostic algorithm based on molecular genetic screening.

OBJECTIVE: Congenital hyperinsulinism (CHI) requires rapid diagnosis and treatment to avoid irreversible neurological sequelae due to hypoglycaemia. Aetiological diagnosis is instrumental in directing the appropriate therapy. Current diagnostic algorithms provide a complete set of diagnostic tools including (i) biochemical assays, (ii) genetic facility and (iii) state-of-the-art imaging. They consider the response to a therapeutic diazoxide trial an early, crucial step before proceeding (or not) to specific genetic testing and eventually imaging, aimed at distinguishing diffuse vs focal CHI. However, interpretation of the diazoxide test is not trivial and can vary between research groups, which may lead to inappropriate decisions. Objective of this report is proposing a new algorithm in which early genetic screening, rather than diazoxide trial, dictates subsequent clinical decisions. PATIENTS, METHODS AND RESULTS: Two CHI patients weaned from parenteral glucose infusion and glucagon after starting diazoxide. No hypoglycaemia was registered during a 72-h continuous glucose monitoring (CGMS), or hypoglycaemic episodes were present for no longer than 3% of 72-h. Normoglycaemia was obtained by low-medium dose diazoxide combined with frequent carbohydrate feeds for several years. We identified monoallelic, paternally inherited mutations in KATP channel genes, and (18) F-DOPA PET-CT revealed a focal lesion that was surgically resected, resulting in complete remission of hypoglycaemia. CONCLUSIONS: Although rare, some patients with focal lesions may be responsive to diazoxide. As a consequence, we propose an algorithm that is not based on a 'formal' diazoxide response but on genetic testing, in which patients carrying paternally inherited ABCC8 or KCNJ11 mutations should always be subjected to (18) F-DOPA PET-CT.

Primary multifocal lymphoma of peripheral nervous system: case report and review of the literature.

INTRODUCTION: Primary lymphomas of peripheral nerves are extremely rare, and only a few cases have been reported. METHODS: We describe the clinical, neurophysiological, radiological, and pathological findings in a 61-year-old woman affected by primary multifocal lymphoma of the peripheral nervous system without systemic involvement. RESULTS: Fascicular left femoral nerve biopsy was decisive for the diagnosis of diffuse large B-cell non-Hodgkin lymphoma. Magnetic resonance imaging, fluorine-18 fluorodeoxyglucose positron emission tomography computed tomography, and nerve ultrasound contributed to the diagnosis. CONCLUSIONS: Primary lymphoma of peripheral nerves (PLPNs) is a rare but potentially treatable condition, which is frequently misdiagnosed. In the literature, there are very few descriptions of PLPNs, most of which are mononeuropathies. The possibility of a neuropathy associated with lymphoma should be considered in patients with poor response to treatment and severe pain symptoms.

Atypical Presentation of Splenic Tissue Mimicking Neuroendocrine Tumor Relapse.

ABSTRACT: A 61-year-old man underwent splenopancreasectomy for a 3-cm neuroendocrine tumor of the body of the pancreas (G2, pT1 pN0, Ki67 3%). Five months after surgery 68 Ga-DOTATOC PET/CT showed increased radiotracer uptake in a solid tissue of the splenic fossa, possibly referring to a splenosis nodule. After 19 months, a further 68 Ga-DOTATOC PET/CT showed a significant functional and dimensional increase of the previously detected tissue and the appearance of a new finding in the left lateral abdominal wall. In the suspicion of neuroendocrine tumor relapse, the patient underwent surgical excision of the documented lesions. Histology showed splenosis in both nodules.

Role of 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma: Current Evidence and Innovative Applications.

This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head-neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head-neck imaging interpretation are described. In the initial work-up, 18F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various 18F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, 18F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, 18F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than 18F-FDG, which can answer specific clinical needs.

Pancreas as an Unusual Metastatic Site of Medullary Thyroid Carcinoma: A Case of Very Long-term Follow-up Under Prolonged Treatment with Somatostatin Analogues.

BACKGROUND: Pancreatic metastases from medullary thyroid carcinoma (MTC) are exceptional. Imaging and treatment based on somatostatin receptors may play a role, though the evidence is unconvincing. CASE PRESENTATION: We have, herein, documented a unique case of metastatic MTC, where pancreatic metastasis was identified by 68Ga-PET/CT, with the disease showing very slow progression during treatment with lanreotide autogel. A 51-year-old woman underwent total thyroidectomy for goiter in 2000, with a postoperative diagnosis of MTC. Due to persistent disease, somatostatin analogues (SSA) treatment commenced in 2005, following a positive acute octreotide test. In 2012, a pathology-confirmed pancreatic metastasis was diagnosed via 68Gallium-positron emission tomography (68Ga-PET/CT). The disease progressed very slowly over 17 years of SSA treatment. CONCLUSION: This uncommon case of pancreatic metastasis from MTC indicates that nuclear medicine techniques might offer valuable additional information. Extended treatment with lanreotide autogel appears to correlate with very slow disease progression in selected patients.

Is PET Radiomics Useful to Predict Pathologic Tumor Response and Prognosis in Locally Advanced Cervical Cancer?

This study investigated whether radiomic features extracted from pretreatment [18F]FDG PET could improve the prediction of both histopathologic tumor response and survival in patients with locally advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed by surgery compared with conventional PET parameters and histopathologic features. Methods: The medical records of all consecutive patients with LACC referred between July 2010 and July 2016 were reviewed. [18F]FDG PET/CT was performed before neoadjuvant chemoradiotherapy. Radiomic features were extracted from the primary tumor volumes delineated semiautomatically on the PET images and reduced by factor analysis. A receiver-operating-characteristic analysis was performed, and conventional and radiomic features were dichotomized with Liu's method according to pathologic response (pR) and cancer-specific death. According to the study protocol, only areas under the curve of more than 0.70 were selected for further analysis, including logistic regression analysis for response prediction and Cox regression analysis for survival prediction. Results: A total of 195 patients fulfilled the inclusion criteria. At pathologic evaluation after surgery, 131 patients (67.2%) had no or microscopic (≤3 mm) residual tumor (pR0 or pR1, respectively); 64 patients (32.8%) had macroscopic residual tumor (>3 mm, pR2). With a median follow-up of 76.0 mo (95% CI, 70.7-78.7 mo), 31.3% of patients had recurrence or progression and 20.0% died of the disease. Among conventional PET parameters, SUVmean significantly differed between pathologic responders and nonresponders. Among radiomic features, 1 shape and 3 textural features significantly differed between pathologic responders and nonresponders. Three radiomic features significantly differed between presence and absence of recurrence or progression and between presence and absence of cancer-specific death. Areas under the curve were less than 0.70 for all parameters; thus, univariate and multivariate regression analyses were not performed. Conclusion: In a large series of patients with LACC treated with neoadjuvant chemoradiotherapy followed by surgery, PET radiomic features could not predict histopathologic tumor response and survival. It is crucial to further explore the biologic mechanism underlying imaging-derived parameters and plan a large, prospective, multicenter study with standardized protocols for all phases of the process of radiomic analysis to validate radiomics before its use in clinical routine.