Lutathera® Orphans: State of the Art and Future Application of Radioligand Therapy with 177Lu-DOTATATE.

Lutathera® is the first EMA- and FDA-approved radiopharmaceutical for radioligand therapy (RLT). Currently, on the legacy of the NETTER1 trial, only adult patients with progressive unresectable somatostatin receptor (SSTR) positive gastroenteropancreatic (GEP) neuroendocrine neoplasms (NET) can be treated with Lutathera®. Conversely, patients with SSTR-positive disease arising from outside the gastroenteric region do not currently have access to Lutathera® treatment despite several papers in the literature reporting the effectiveness and safety of RLT in these settings. Moreover, patients with well-differentiated G3 GEP-NET are also still "Lutathera orphans", and retreatment with RLT in patients with disease relapse is currently not approved. The aim of this critical review is to summarize current literature evidence assessing the role of Lutathera® outside the approved indications. Moreover, ongoing clinical trials evaluating new possible applications of Lutathera® will be considered and discussed to provide an updated picture of future investigations.

Prognostic Implications of 18-FDG Positron Emission Tomography/Computed Tomography in Resectable Pancreatic Cancer.

There are currently no known preoperative factors for determining the prognosis in pancreatic cancer. The aim of this study was to examine the role of 18-fluorodeoxyglucose (18-FDG) positron emission tomography/computed tomography (18-FDG-PET/CT) as a prognostic factor for patients with resectable pancreatic cancer. Data were obtained from a retrospective analysis of patients who had a preoperative PET scan and then underwent pancreatic resection from January 2007 to December 2015. The maximum standardized uptake value (SUVmax) of 18-FDG-PET/CT was calculated. Patients were divided into high (>3.65) and low (≤3.65) SUVmax groups, and compared in terms of their TNM classification (Union for International Cancer Contro classification), pathological grade, surgical treatment, state of resection margins, lymph node involvement, age, sex, diabetes and serum Carbohydrate Antigen 19-9 (CA 19-9) levels. The study involved 144 patients, 82 with high SUVmax pancreatic cancer and 62 with low SUVmax disease. The two groups' disease-free and overall survival rates were significantly influenced by tumor stage, lymph node involvement, pathological grade, resection margins and SUVmax. Patients with an SUVmax ≤ 3.65 had a significantly better survival than those with SUVmax > 3.65 (p < 0.001). The same variables were independent predictors of survival on multivariate analysis. The SUVmax calculated with 18-FDG-PET/CT is an important prognostic factor for patients with pancreatic cancer, and may be useful in decisions concerning patients' therapeutic management.

Prognostic value of PET/CT in patients with lymphoma treated with autologous stem cell transplantation for relapsed/refractory or high risk disease.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT scan) has increasingly been used for management of lymphoma, however few and conflicting data have been provided in the setting of high dose therapy with autologous stem cell transplantation (ASCT) so far. METHODS: We retrospectively evaluated the outcome of 47 NHL patients who underwent ASCT for relapsed/refractory disease or high risk disease or partial response after first line treatment, with the aim of testing sensitivity, specificity, positive and negative prognostic value of PET/CT performed before and after ASCT. RESULTS: In our experience pre ASCT-PET/CT predicts outcome of non-Hodgkin's lymphoma patients with chemosensitive relapse, whereas post ASCT-PET showed a better prognostic value for relapsed disease. CONCLUSIONS: Results of our study, if confirmed by studies on a larger scale, could significantly contribute to design future trials and optimize the management of lymphoma patients.

PET/CT incidental detection of second tumor in patients investigated for pancreatic neoplasms.

BACKGROUND: Positron Emission Tomography/computed tomography (PET/CT) is an imaging technique which has a role in the detection and staging malignancies (both in first diagnosis and follow-up). The finding of an unexpected region of FDG (Fluorodeoxyglucose) uptake can occur when performing whole-body FDG-PET, raising the possibility of a second primary tumor. The aim of this study was to evaluate our experience of second primary cancer incidentally discovered during PET/CT examination performed for pancreatic diseases, during the initial work-up or follow-up after surgical resection. METHODS: In this study, a retrospective evaluation of a prospectively collected data base was performed. Three hundred ninety- nine patients with pancreatic pathology were evaluated by whole body PET/CT imaging from January 2004 to December 2014. Among them, 348 patients were scanned before surgical resection and 51 during the course of their follow-up (pancreatic cancer). Median follow-up time was 29 months (range 14-124). RESULTS: Fifty-six patients (14%) had incidental uptake of FDG in their organs: 31 patients had focal uptake and 25 showed diffuse with or without focal uptake. All patients with focal uptake were investigated, and invasive malignancy was diagnosed in 22 patients: 14 colon, 4 lung, 1 larynx, 1 urothelial, 1 breast cancer, and 1 colon metastasis from pancreatic cancer. Twenty patients underwent resection, and 6 endoscopic removal of colonic polyps. Three patients were not operated for advanced disease, and two patients did not show any pathology (PET/CT false positive). Of the 10 patients investigated for diffuse uptake, no malignancy was found; none of these patients developed a second cancer during the follow-up. CONCLUSIONS: As in other malignancies, unexpected FDG uptake can occur in patients having PET/CT investigation for pancreatic diseases. Focal uptake is likely to be a malignancy and deserves further investigations, although the stage and the poor prognosis of primary pancreatic cancer should be kept in mind. Some selected patients may benefit from the aggressive treatment of incidental lesions and show survival benefit.

Multiple large osteolytic lesions in a patient with systemic mastocytosis: a challenging diagnosis.

Patients with advanced variants of Systemic Mastocytosis may develop destructive bone lesions when massive mast cell (MC) infiltrates are present. Finding of large osteolyses in indolent systemic mastocytosis, typically characterized by low MC burden, should prompt investigations for an alternative explanation.

Comparison of International Consensus Guidelines versus 18-FDG PET in detecting malignancy of intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVE: To assess the reliability of the International Consensus Guidelines (ICG) and 18-fluorodeoxyglucose positron emission tomography (PET) in distinguishing benign from malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. BACKGROUND: Since 2006 the ICG have been used to choose immediate surgery or surveillance for IPMN patients, but their low specificity increases the number of benign IPMNs that undergo resective surgery. PET has proved highly sensitive and specific in detecting malignancy in cystic neoplasms of the pancreas, including IPMNs. METHODS: Patients suspected with IPMNs of the pancreas seen at our Department from January 1989 to July 2010 were identified and classified as cases of main duct, mixed type and branch type IPMN. The indication for resection or surveillance was verified a posteriori for all patients according to the ICG. PET was considered positive for a Standardized Uptake Value ≥2.5. Surveillance included clinical examination, laboratory tests, CA 19-9 serum levels, and computed tomography and/or magnetic resonance and magnetic resonance cholangiopancreatography every 6 months for 2 years and yearly thereafter. Endoscopic ultrasound was rarely performed. PET was repeated in clinically or radiologically suspect cases, or if tumor markers increased. RESULTS: Sixty-one main duct or mixed type and 101-branch type IPMNs were included in the study. A histological diagnosis was available for 81 of 162 patients, missing for 1 locally advanced IPMN, whereas 62 patients are under surveillance and it proved impossible to contact 18. Conservative surgery was performed in 16 of 68 patients with benign IPMNs. The sensitivity, specificity, positive and negative predictive value, and accuracy of the ICG in detecting malignancy were 93.2, 22.2, 59.4, 72.7, and 61.2, whereas for PET they were 83.3, 100, 100, 84.6, and 91.3. CONCLUSIONS: PET is more accurate than the ICG in distinguishing benign from malignant (invasive and noninvasive) IPMNs. Prophylactic IPMN resection in young patients fit for surgery should be guided by the ICG, whereas PET should be performed in older patients, cases at increased surgical risk, or when the feasibility of parenchyma-sparing surgery demands a reliable preoperative exclusion of malignancy.

Tumor relapse after pancreatic cancer resection is detected earlier by 18-FDG PET than by CT.

INTRODUCTION: Pancreatic cancer recurrence is often difficult to detect by conventional imaging. Our aim was to evaluate the impact of fluorodeoxyglucose-positron emission tomography (FDG-PET) in the diagnosis of recurrent pancreatic cancer. METHODS: One-hundred thirty-eight patients were followed after resection for pancreatic cancer. Sixty-six underwent only CT and were excluded. Seventy-two patients also had FDG-PET. Recurrent patients were divided in two groups: group-1, CT positive and group 2, CT non diagnostic, FDG-PET positive. Characteristics and survival curves of the two groups were compared. Significance was set at p < 0.05. RESULTS: Overall, tumors recurred in 63 of 72 (87.5%) patients; two patients had a second cancer resected, thanks to FDG-PET. Tumor relapse was detected by CT in 35 patients and by FDG-PET in 61. Prognostic factors were similar in groups 1 and 2. Five out of 35 group 1 patients underwent surgery (two R0, two bypass, and one exploratory). Ten out of 28 group 2 patients underwent surgery (four R0, two R2, two bypass, and two exploratory). FDG-PET influenced treatment strategies in 32 of 72 patients (44.4%). Group 2 patients survived longer (P = 0.09), but the difference was not significant. Disease-free survival was similar in groups 1 and 2. CONCLUSION: Tumor relapse is detected earlier by FDG-PET than by CT. FDG-PET can help select the best candidates for surgical exploration, although the real benefit is still to be defined. It influences treatment strategies in a significant percentage of patients. An earlier diagnosis did not influence survival due to the lack of effective therapies.

18-fluorodeoxyglucose positron emission tomography enhances computed tomography diagnosis of malignant intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVE: To assess the reliability of 18-fluorodeoxyglucose positron emission tomography (18-FDG PET) in distinguishing benign from malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and its contribution to surgical decision making. SUMMARY BACKGROUND DATA: Pancreatic IPMNs are increasingly recognized, often as incidental findings, especially in people over age 70 and 80. Computed tomography (CT) and magnetic resonance (MR) are unreliable in discriminating a benign from a malignant neoplasm. 18-FDG PET as imaging procedure based on the increased glucose uptake by tumor cells has been suggested for diagnosis and staging of pancreatic cancer. METHODS: From January 1998 to December 2005, 64 patients with suspected IPMNs were prospectively investigated with 18-FDG PET in addition to conventional imaging techniques [helical-CT in all and MR and magnetic resonance cholangiopancreatography (MRCP) in 60]. 18-FDG PET was analyzed visually and semiquantitatively using the standard uptake value (SUV). The validation of the diagnosis was made by a surgical procedure (n = 44), a percutaneous biopsy (n = 2), main duct cytology (n = 1), or follow-up (n = 17). Mean and median follow-up times were 25 and 27.5 months, respectively (range, 12-90 months). RESULTS: Twenty-seven patients (42%) were asymptomatic. Forty-two patients underwent pancreatic resection, 2 palliative surgery, and 20 did not undergo surgery. An adenoma was diagnosed in 13 patients, a borderline tumor in 8, a carcinoma in situ in 5, and an invasive cancer in 21; in 17 patients a tumor sampling was not performed and therefore the histology remained undetermined. Positive criteria of increased uptake on 18-FDG PET was absent in 13 of 13 adenomas and 7 of 8 borderline IPMNs, but was present in 4 of 5 carcinoma in situ (80%) and in 20 of 21 invasive cancers (95%). Conventional imaging technique was strongly suggestive of malignancy in 2 of 5 carcinomas in situ and in 13 of 21 invasive carcinomas (62%). Furthermore, conventional imaging had findings that would be considered falsely positive in 1 of 13 adenomas (8%) and in 3 of 8 borderline neoplasms (37.5%). Therefore, positive 18-FDG PET influenced surgical decision making in 10 patients with malignant IPMN. Furthermore, negative findings on 18-FDG PET prompted us to use a more limited resection in 15 patients, and offered a follow-up strategy in 18 patients (3 positive at CT scan) for the future development of a malignancy. CONCLUSIONS: 18-FDG PET is more accurate than conventional imaging techniques (CT and MR) in distinguishing benign from malignant (invasive and noninvasive) IPMNs. 18-FDG PET seems to be much better than conventional imaging techniques in selecting IPMNs patients, especially when old and asymptomatic, for surgical treatment or follow-up.

Clinical usefulness of 18-fluorodeoxyglucose positron emission tomography in the management of patients with nonpancreatic periampullary neoplasms.

BACKGROUND: 18-Fluorodeoxyglucose positron emission tomography (18-FDG PET) has been investigated for the diagnosis and staging of gastrointestinal malignancies including pancreatic adenocarcinoma. The aim of this study was to examine the clinical usefulness of 18-FDG PET in the diagnosis and follow-up evaluation of patients with periampullary neoplasms. METHODS: Twenty-five patients underwent whole-body 18-FDG PET and abdominal computed tomography (CT). Pathologic confirmation was obtained in all patients by surgical resection or biopsy examination. The 18-FDG PET was analyzed visually and semiquantitatively using the standard uptake value (SUV). Positivity was assumed when a focal uptake occurred with an SUV of 2.5 or greater. RESULTS: Between January 1998 and December 2003, 14 ampullary, 7 bile duct, and 4 duodenal tumors were included in the study. PET showed increased focal uptake in 22 patients (88%): 11 of 14 (79%) ampullary tumors, and 100% of bile duct and duodenal tumors. PET showed a focal uptake in 11 of 12 patients without detectable mass at CT scan, and lymph node metastases in 6 patients. An SUV value of 2.7 discriminated adenomas or noninvasive cancers (n = 6) from invasive malignancies (n = 14). Follow-up evaluation including CT scan and PET was performed in 12 patients: PET showed recurrent disease not seen by CT in 4 patients, confirmed CT findings in 6 patients, and showed an unsuspected primary lung cancer in 1 patient and colon cancer in another patient. CONCLUSIONS: 18-FDG PET is very sensitive for detecting periampullary neoplasms. It may be useful to differentiate benign or borderline lesions from invasive tumors when no mass has been identified by traditional imaging. Finally, it is very useful in the follow-up evaluation of resected patients to identify recurrent disease or other malignancies.

A case of advanced Hodgkin lymphoma with breast involvement treated with a combination of gemcitabine and pegylated liposomal doxorubicin.

Gemcitabine in combination with pegylated liposomal doxorubicin has been recognized as an effective treatment in patients with refractory solid tumors. To our knowledge, this is the first case of relapsed Hodgkin lymphoma with breast involvement successfully treated with this association.