Perspectives on joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards for [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors.

Response assessment in the context of immunomodulatory treatments represents a major challenge for the medical imaging community and requires a multidisciplinary approach with involvement of oncologists, radiologists, and nuclear medicine specialists. There is evolving evidence that [18F]FDG PET/CT is a useful diagnostic modality for this purpose. The clinical indications for, and the principal aspects of its standardization in this context have been detailed in the recently published "Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0". These recommendations arose from a fruitful collaboration between international nuclear medicine societies and experts in cancer treatment. In this perspective, the key elements of the initiative are reported, summarizing the core aspects of the guidelines for radiologists and nuclear medicine physicians. Beyond the previous guidelines, this perspective adds further commentary on how this technology can advance development of novel therapeutic approaches and guide management of individual patients.

Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0.

PURPOSE: The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of [18F]FDG PET/CT in oncological patients undergoing immunotherapy, with special focus on response assessment in solid tumors. METHODS: In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard. CONCLUSIONS: The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of [18F]FDG PET/CT during immunotherapy. Local variations to this guideline should be taken into consideration. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association founded in 1985 to facilitate worldwide communication among individuals pursuing clinical and academic excellence in nuclear medicine. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote science, technology and practical application of nuclear medicine. The Australian and New Zealand Society of Nuclear Medicine (ANZSNM), founded in 1969, represents the major professional society fostering the technical and professional development of nuclear medicine practice across Australia and New Zealand. It promotes excellence in the nuclear medicine profession through education, research and a commitment to the highest professional standards. EANM, SNMMI and ANZSNM members are physicians, technologists, physicists and scientists specialized in the research and clinical practice of nuclear medicine. All three societies will periodically put forth new standards/guidelines for nuclear medicine practice to help advance the science of nuclear medicine and improve service to patients. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each standard/guideline, representing a policy statement by the EANM/SNMMI/ANZSNM, has undergone a thorough consensus process, entailing extensive review. These societies recognize that the safe and effective use of diagnostic nuclear medicine imaging requires particular training and skills, as described in each document. These standards/guidelines are educational tools designed to assist practitioners in providing appropriate and effective nuclear medicine care for patients. These guidelines are consensus documents based on current knowledge. They are not intended to be inflexible rules or requirements of practice, nor should they be used to establish a legal standard of care. For these reasons and those set forth below, the EANM, SNMMI and ANZSNM caution against the use of these standards/guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals considering the unique circumstances of each case. Thus, there is no implication that an action differing from what is laid out in the guidelines/procedure standards, standing alone, is below standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines/procedure standards. The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a particular treatment response to be predicted. Therefore, it should be recognized that adherence to these standards/ guidelines will not ensure a successful outcome. All that should be expected is that practitioners follow a reasonable course of action, based on their level of training, current knowledge, clinical practice guidelines, available resources and the needs/context of the patient being treated. The sole purpose of these guidelines is to assist practitioners in achieving this objective. The present guideline/procedure standard was developed collaboratively by the EANM, the SNMMI and the ANZSNM, with the support of international experts in the field. They summarize also the views of the Oncology and Theranostics and the Inflammation and Infection Committees of the EANM, as well as the procedure standards committee of the SNMMI, and reflect recommendations for which the EANM and SNMMI cannot be held responsible. The recommendations should be taken into the context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions.

PSMA-PET and micro-ultrasound potential in the diagnostic pathway of prostate cancer

To compare the diagnostic performance of 68Ga-PSMA PET/TC with PRI-MUS (prostate risk identification using micro-ultrasound) in the primary diagnosis of prostate cancer (PCa). Methods From September till December 2018, we prospectively enrolled 25 candidates to 68Ga-PSMA PET/TRUS (transrectal ultrasound) fusion biopsy and compared them with PRI-MUS. This included patients with persistently elevated PSA and/or PHI (prostate health index) suspicious for PCa, negative digital rectal examination, with either negative or contraindication to mpMRI, and at least one negative biopsy. The diagnostic performance of the two modalities was calculated based on pathology results. Results Overall, 20 patients were addressed to 68Ga-PSMA PET/TRUS fusion biopsy. Mean SUVmax and SUVratio for PCa lesions resulted significantly higher than in benign lesions (p = 0.041 and 0.011, respectively). Using optimal cut-off points, 68Ga-PSMA PET/CT demonstrated an overall accuracy of 83% for SUVmax ≥ 5.4 and 94% for SUVratio ≥ 2.2 in the detection of clinically significant PCa (GS ≥ 7). On counterpart, PRI-MUS results were: score 3 in nine patients (45%), score 4 in ten patients (50%), and one patient with score 5. PRI-MUS score 4 and 5 demonstrated an overall accuracy of 61% in detecting clinically significant PCa. Conclusion In this highly-selected patient population, in comparison to PRI-MUS, 68Ga-PSMA PET/CT shows a higher diagnostic performance (AU)

PSMA-PET and micro-ultrasound potential in the diagnostic pathway of prostate cancer.

PURPOSE: To compare the diagnostic performance of 68Ga-PSMA PET/TC with PRI-MUS (prostate risk identification using micro-ultrasound) in the primary diagnosis of prostate cancer (PCa). METHODS: From September till December 2018, we prospectively enrolled 25 candidates to 68Ga-PSMA PET/TRUS (transrectal ultrasound) fusion biopsy and compared them with PRI-MUS. This included patients with persistently elevated PSA and/or PHI (prostate health index) suspicious for PCa, negative digital rectal examination, with either negative or contraindication to mpMRI, and at least one negative biopsy. The diagnostic performance of the two modalities was calculated based on pathology results. RESULTS: Overall, 20 patients were addressed to 68Ga-PSMA PET/TRUS fusion biopsy. Mean SUVmax and SUVratio for PCa lesions resulted significantly higher than in benign lesions (p = 0.041 and 0.011, respectively). Using optimal cut-off points, 68Ga-PSMA PET/CT demonstrated an overall accuracy of 83% for SUVmax ≥ 5.4 and 94% for SUVratio ≥ 2.2 in the detection of clinically significant PCa (GS ≥ 7). On counterpart, PRI-MUS results were: score 3 in nine patients (45%), score 4 in ten patients (50%), and one patient with score 5. PRI-MUS score 4 and 5 demonstrated an overall accuracy of 61% in detecting clinically significant PCa. CONCLUSION: In this highly-selected patient population, in comparison to PRI-MUS, 68Ga-PSMA PET/CT shows a higher diagnostic performance.

Does a 6-point scale approach to post-treatment 18F-FDG PET-CT allow to improve response assessment in head and neck squamous cell carcinoma? A multicenter study.

PURPOSE: Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale ("Cuneo score"). METHODS: We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients' information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. RESULTS: Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). CONCLUSIONS: In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

Prostate-specific antigen flare induced by 223RaCl2 in patients with metastatic castration-resistant prostate cancer.

PURPOSE: Prostate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer, but its impact during radium-223 dichloride (223RaCl2) therapy is still unclear. This radioisotope has shown to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC). We sought to evaluate the impact of PSA flare on survival and its relation with metabolic parameters on 18F-labeled sodium fluoride PET/CT. METHODS: We conducted a retrospective study of 168 patients with mCRPC (median age 69; median PSA 29.7) receiving 223RaCl2. Overall survival (OS) and progression-free survival (PFS), estimated by the Kaplan-Meier method and compared using a log-rank test, were evaluated for patient groups corresponding to different definitions of PSA flare. Metabolic 18F-fluoride PET/CT data were analyzed as well. RESULTS: Immediate PSA decline was observed in 49 patients (29.2%), whereas no PSA response was observed in 59 patients (35.1%). PSA flare (defined as rise after the first cycle followed by decrease below the baseline) was observed in 20 patients (11.9%) and PSA flare followed by a decrease from peak but not below baseline was observed in 40 (23.8%). The first flare subgroup had a median PFS and OS of 20.8 and 23.9 months, respectively. These outcomes were not significantly different from patients with immediate PSA decrease, but were significantly better than in patients with persistent PSA elevation (3.1 months for PFS and 11.5 months for OS, p < 0.001). Moreover, the PSA flare group showed an alkaline phosphatase (ALP) decrease significantly greater than non-responders (p = 0.003). Metabolic 18F-fluoride PET/CT data were available in 35 patients at baseline and during 233RaCl2 therapy. The tumor burden reduction, expressed by ΔTLF10 and ΔFTV10, was more evident within PSA flare group below baseline than non-responders (p = 0.005 and 0.001, respectively). CONCLUSIONS: This report suggests that a flare does not necessarily indicate lack of response to 223RaCl2 therapy.

Applications of PET imaging with radiolabelled choline (11C/18F-choline).

The use of radiopharmaceuticals is the distinguishing characteristics of nuclear medicine. Among the panel of available radiopharmaceuticals in many PET centers around the world, choline is well represented, being widely used to image prostate cancer. Carbon-11 labelled choline can only be produced in centres with a cyclotron available, but the 18F-labelled radiopharmaceutical is distributed and licensed in several countries in Europe. Besides prostate cancer, other possible uses of choline are related to its ability to indirectly evaluate the cell proliferation as a measure of the synthesis of lipids required for cell membrane. In particular, the radiopharmaceutical can be successfully used in those districts where 18F-FDG has a high uptake, like the brain. Moreover, slow growing tumors, not always taking up 18F-FDG, like hepatocellular carcinoma, can also be imaged. We will evaluate possibly uses of this molecule in patients affected by prostate cancer, brain tumors and hepatocellular carcinoma.

11C-Methionine uptake in secondary brain epilepsy / Captación de la 11C-metionina en la epilepsia cerebral secundaria

Carbon-11 methionine (11C-Methionine) is a radio-labeled amino acid currently utilized in Positron Emission Tomography (PET) for imaging primary and metastatic brain tumors. Its clinical use relies mostly on oncologic applications, but the tracer has the potential to investigate other non-malignant conditions. So far, very limited evidence concerns the use of 11C-Methionine in patients suffering from seizure; however, the tracer can find a proper utilization in this setting especially as a diagnostic complement to 18F-Fluorodeoxyglucose (18F-FDG). Herein we report the case of a 57-year-old patient presenting with epileptic crises secondary to a brain metastasis from bladder carcinoma, who was investigated in our institution with 11C-Methionine PET. The scan documented the disease recurrence in the left parietal lobe associated with a diffused tracer uptake in the surrounding cerebral circumvolutions, derived from the comitial status. After surgical removal of the metastatic lesion, the patient experienced a complete recovery of symptoms and no further onset of secondary seizure (AU)

La 11C-metionina es un aminoácido radiomarcado que se utiliza actualmente en la tomografía por emisión de positrones (PET) para obtener imágenes de tumores cerebrales primarios y metastáticos. Su aplicación clínica más extendida es la oncología, pero tiene el potencial de investigar otras situaciones no oncológicas. Hasta el momento existe una limitada evidencia del uso de 11C-metionina en pacientes con crisis convulsiva; sin embargo, el radiotrazador puede tener utilidad en este campo especialmente como complemento diagnóstico de la 18F-fluorodeoxiglucosa (18F-FDG). Presentamos el caso de un paciente de 57a˜nos de edad con crisis epilépticas secundarias a metástasis cerebrales de un carcinoma de vejiga que fue explorado en nuestra Institución con 11C-metionina PET. El estudio demostró la recidiva de la enfermedad en el lóbulo parietal izquierdo asociada con captación difusa en las circunvoluciones cerebrales de alrededor, derivada del status comicial. Después de la extirpación quirúrgica de la metástasis cerebral, el paciente experimentó una recuperación completa de los síntomas sin posterior inicio de crisis convulsivas secundarias (AU)

(11)C-Methionine uptake in secondary brain epilepsy.

Carbon-11 methionine ((11)C-Methionine) is a radio-labeled amino acid currently utilized in Positron Emission Tomography (PET) for imaging primary and metastatic brain tumors. Its clinical use relies mostly on oncologic applications, but the tracer has the potential to investigate other non-malignant conditions. So far, very limited evidence concerns the use of (11)C-Methionine in patients suffering from seizure; however, the tracer can find a proper utilization in this setting especially as a diagnostic complement to (18)F-Fluorodeoxyglucose ((18)F-FDG). Herein we report the case of a 57-year-old patient presenting with epileptic crises secondary to a brain metastasis from bladder carcinoma, who was investigated in our institution with (11)C-Methionine PET. The scan documented the disease recurrence in the left parietal lobe associated with a diffused tracer uptake in the surrounding cerebral circumvolutions, derived from the comitial status. After surgical removal of the metastatic lesion, the patient experienced a complete recovery of symptoms and no further onset of secondary seizure.

Gallium-68 DOTANOC imaging in paraganglioma/pheochromocytoma: presentation of sample cases and review of the literature.

Gallium-68 DOTANOC is a high affinity somatostatin receptor ligand, first introduced in 2005 for imaging neuroendocrine tumors. Due to its technically simple production, broad availability, favourable biodistribution and advantageous dosimetry, although not approved yet in all European countries, gallium-68 DOTANOC has rapidly gained acceptance in the diagnostic and therapeutic work-flow of different types of neuroendocrine tumors. Principal indications in clinical practice in countries where it is officially approved include diagnosis and staging, restaging after treatment, identification of sites of unknown primary and selection of patients with neuroendocrine tumors eligible for therapy with somatostatin analogues.

PET/CT imaging in neuroblastoma.

123Iodine-metaiodobenzylguanidine (123I-MIBG) scintigraphy is currently the tracer of choice for neuroblastoma (NB). It has high diagnostic accuracy and prognostic value for the assessment of patients after chemotherapy. A positive 123I-MIBG scan is also used for the basis of targeted radionuclide therapy with 131I-MIBG. I-123 MIBG scan however has some limitations which should be taken into account. Moreover the reasons for false negative MIBG results have not been entirely elucidated. Meticulous correlation with radiological examinations and recognition of the normal distribution pattern of 123I-MIBG in children is vital to obtain optimal results. With its technical superiorities, positron emission tomography/computed tomography (PET/CT) can be successfully introduced into the diagnostic workup of NB. Different PET tracers have been offered for imaging in patients with NB, and the efficacy of this modality has been compared with that of 123I-MIBG scan. Our review aims to analyze the present role of PET/CT imaging and radiopharmaceuticals in NB.

[18F]FDG-PET/CT monitoring early identifies advanced ovarian cancer patients who will benefit from prolonged neo-adjuvant chemotherapy.

AIM: The most accepted standard duration of neoadjuvant chemotherapy (na-CHT) before debulking surgery for advanced ovarian cancer (AOC) is 3 courses. However a percentage of patients could benefit from additional courses. [(18)F]FDG-PET/CT monitoring during na-CHT could predict early pathological response and allow the delivery of an optimal na-CHT duration. METHODS: Consecutive patients with AOC unsuitable for optimal up front surgery and fit for na-CHT were monitored by FDG-PET/CT at baseline and after 3 and 6 courses of carboplatin-paclitaxel CHT. At the end of na-CHT patients were re-evaluated to undergo definitive optimal surgery (i.e. without post-surgical residual disease). Percentage changes in maximal standardized uptake value (∆-SUVmax) were compared with the pathological response. Only patients with pathological complete response (pCR) or minimal residual disease (pMRD) were considered as pathological responders (pR), while all the other cases were considered non-responders (NR). RESULTS: Baseline FDG-PET/CT was abnormal in all 42 enrolled patients (median SUVmax 11, range 3-20). After 3 and 6 courses median SUVmax decreased to 3 (<2-21) and <2, i.e. value equal to normal surrounding tissues uptake (<2-17), respectively. After 3 courses, 17 (40%) patients presented ∆-SUVmax=100%, (i.e. SUVmax <2): 15 of them (88%) subsequently resulted pR and achieved no postsurgical residual disease at the end of na-CHT, while 2 (12%) were NR with postsurgical residual tumor ≤ 1cm. Out of 25 patients with ∆-SUVmax <100% after 3 courses, 6 (24%) were pR and 19 (76%) NR at the end of na-CHT. CONCLUSION: Patients with AOC who present normalization of SUVmax after 3 courses of na-CT have a high likelihood of benefiting from 3 additional courses in order to obtain pCR or pMDR and receiving optimal surgery.

FDG PET and 90Y ibritumomab tiuxetan in patients with follicular lymphoma.

AIM: Despite its established utility in non-Hodgkin's lymphoma, not much is reported on FDG positron emission tomography (PET) with respect to radioimmunotherapy (RIT). In this paper we investigate its value in patients affected by follicular lymphoma (FL) before and after treatment with [90Y]Ibritumomab Tiuxetan (Zevalin(R)). METHODS: We evaluated 38 relapsed or refractory FL patients. All had a PET scan performed before and 3 months after radioimmunotherapy. Final assessment was done 9 months post-RIT, including clinical evaluation, other imaging techniques and/or biopsy, when necessary. RESULTS: At the first PET scan 20 patients out of 38 had a limited disease (nodal involvement on one side of the diaphragm: 7 above and 13 below), 11 patients had nodal findings on both sides of the diaphragm and the remaining 7 patients had both nodal and extra-nodal findings. At three months post-RIT, 21 patients (55%) were in complete remission, 13 patients (34%) had a partial response (PR) and four patients (11%) had a progression disease (PD). The corresponding rates at final assessment were all consistent with the 3-month evaluation: 55% CR, 13% PR and 32% PD. FDG PET scan revealed maximal predictive values. When comparing the disease extent at relapse and the response to treatment, we could testify a higher rate of CR (75%) in patients with limited disease, while in patients with diffused nodal and/or extra-nodal findings, it was more frequent a PR or PD (66%). CONCLUSION: Our data are concordant with the expected results on RIT, and FDG PET is confirmed to be useful in assessing treatment response. Potential correlation can also be picked out between the disease extent at relapse and the CR rate, with reasonable PET predictivity for the final outcome.

FDG-PET in the assessment of patients with follicular lymphoma treated by ibritumomab tiuxetan Y 90: multicentric study.

BACKGROUND: The aim of this study is the 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) evaluation following radioimmunotherapy (RIT) with ibritumomab tiuxetan Y 90 in patients with non-Hodgkin's follicular lymphoma (FL). MATERIALS AND METHODS: We retrospectively analyzed data from 59 relapsed or refractory FL patients treated with ibritumomab tiuxetan Y 90 in four different PET centers who had a PET scan carried out before and after RIT. Possible predictive factors of progression-free survival (PFS) were studied through univariate and multivariate analysis. RESULTS: The post-RIT PET documented 45.8% complete responders (CR), 25.4% partial responders (PR) and 28.8% nonresponders [stable disease + progressive disease], with an overall survival of 71.2% (range 59.5%-90.9%). With a median follow-up period of 23 months, the univariate analysis documented a statistically significant relation between disease extent before RIT and response to treatment with respect to PFS (P = 0.015), while all the other prognostic factors showed no significant correlation. When carrying out the multivariate analysis, post-RIT PET resulted as the lonely independent predictor of PFS (P < 0.00001). CONCLUSIONS: RIT is an effective therapy in FL patients, as confirmed in our study too. Disease extension before treatment and response to RIT, as assessed by FDG-PET, result as main predictors of PFS, with the post-RIT PET result being the only independent predictive factor.

MACOP-B regimen in the treatment of adult Langerhans cell histiocytosis: experience on seven patients.

BACKGROUND: Adult Langerhans cell histiocytosis (LCH) is a rare disease. The combination of vinblastine and prednisone, given in a 6-month course, is the standard of care but prospective randomized trials are lacking. PATIENTS AND METHODS: We report our monocentric experience in the treatment of seven adult patients with multisystem (MS) LCH (n = 3) or single-system multifocal (SS-m) LCH (n = 4) with the short-course intensive chemotherapy regimen methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomicin (MACOP-B). RESULTS: The overall response rate was 100% [five complete response (CR), two partial response (PR)]. After a median follow-up of 6.5 years, four patients are in first continuous CR and three patients relapsed after 5, 8 and 62 months, respectively. Four patients were evaluated with positron emission tomography (PET) scan: all three PET-negative patients at the end of treatment had a long-lasting response with only one patient relapsing after 5 years. PET scan detected additional bone lesions at diagnosis in two of four patients, changing the treatment program in one of them. CONCLUSIONS: MACOP-B regimen seems to be very active in the treatment of adult MS or SS-m LCH, with long-lasting responses in five of seven patients. PET scan merits further evaluation in the initial staging and in the evaluation of the response to chemotherapy.

Clinical applications of 68Ga-DOTANOC in neuroendocrine tumours.

Neuroendocrine tumours (NET) are relatively rare neoplasms affecting principally the gastroenteropancreatic tract, but with potential ubiquitary location, as the neural crest cells, origin of this group of tumours, are dispersed in various organs and tissues. After the discovery of somatostatin receptors (SSTR) over-expression in this group of neoplasms, NET management has significantly improved. This is witnessed by the development of new tracers in positron emission tomography (PET) imaging of NETs belonging to the family of radio-labelled somatostatin analogues, that significantly improved the accuracy of diagnosis and, more recently, opened the way to the innovative targeted radionuclide therapies. First introduced in clinical application in 2005, 68Ga-DOTANOC (one of the most used radio-labelled somatostatin analog for PET imaging) has revealed promising results in preliminary studies for the main clinical indications: staging NET; suspected NET of unknown primary; follow-up, restaging and, finally, for pre- and post-treatment evaluation of receptor radionuclide therapies. Due to its technically simple production, favourable biodistribution, biokinetics, dosimetry and high affinity for SSTR and thanks to the possibility of hybrid scans PET/computed tomography (CT) with better spatial resolution and localisation of the lesions, 68Ga-DOTANOC can advance as the new gold standard for imaging in neuroendocrine tumours.

Molecular imaging and targeted therapies in oncology: new concepts in treatment response assessment. a collection of cases.

The widespread use of several new non-cytotoxic drugs and the significant improvements in functional imaging highlights a number of difficulties in monitoring, interpreting and predicting treatment response in clinical practice. Certain guidelines for disease assessment after therapy are already available: the traditional Response Evaluation Criteria in Solid Tumours guidelines based on tumour size variations using conventional imaging technologies, the recent combined method developed by Choi and colleagues in gastrointestinal stromal tumour treated with tyrosine kinase inhibitors based on tumour density variations using computed tomography (CT), and the European Organization for Research and Treatment of Cancer criteria based on tumour glucose metabolism variations using fluorodeoxyglucose (FDG) positron emission tomography (PET). At the moment combined PET/CT response criteria are still not available. A number of new PET compounds other than FDG are also currently being developed to visualize specific cellular and molecular tumour pathways but their role in assessment and prediction of cancer treatment response has not yet been thoroughly investigated in a large series. However, in clinical practice many oncologists treat cancer patients with targeted therapies or chemotherapy and evaluate the response using conventional or functional imaging without appropriate and standardized guidelines. The aim of this study was to present a selection of clinical cases that illustrate the usefulness of new PET tracers and efficacy evaluation of new drugs. In the era of molecular imaging and molecular therapies, these cases highlight the urgency to develop new criteria for treatment assessment and the exigency of correctly interpreting the biological information obtained from new technologies, and introduce new concepts that require further investigation in clinical trials.

[Video-assisted treatment for biliary atresia]. / Trattamento videoassistito dell'atresia delle vie biliari.

BACKGROUND: The surgical treatment of biliary atresia is still a great challenge for pediatric surgeons. Kasai's operation usually needs a wide, painful, muscle-cutting laparotomies that quite often are followed by pain and peritoneal adhesion. These possible complications may disturb the post-operative course and humper liver transplantation. Advancements in minimally invasive surgery have allowed even the most complex procedures to be approached using these techniques. METHODS: The authors present a case of successful Roux-en-Y laparoscopic portoenterostomy for the treatment of biliary atresia. We report a case of a 3-month-old patient with biliary atresia who weighted Kg 5,300 at the operation. The patient was placed in supine position. The procedure was performed with 4 trocars of 3 mm and 1 of 10 mm. The umbilical site was used for extracorporeal Roux-en-Y enteroenterostomy. CO2 was insufflated at a pressure of 8 mmHg and a flow of 0.5 L/min. A drain was placed through the lower trocar site with the tip near the anastomosis. RESULTS: The procedure was free of neither intraoperative nor post-operative complications. Feeding by nasogastric tube was started after 2 days. Total oral feeding was possible after 8 days. CONCLUSION: Laparoscopic approach to perform Kasai's operation is technically feasible and thanks to a magnified vision, it allows to abtain a good visualization of the portal structures with an adequate retraction of the liver. This procedure can avoid or decrease the post-operative complications such as pain, breathing difficulty, adhesions and resulting in very small scars. Anyway laparoscopic Kasaiportoenterostomy should be done by a surgeon with a good experience in laparoscopic hand-suturing and neonatal experience and with the support of an experienced in neonatal and infantile videosurgery anaesthesiologist.