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Patients with limited metastatic/advanced esophageal cancer not amenable for neoadjuvant therapy plus surgery have a poor prognosis and often receive palliative care. Alternatively, induction chemotherapy with response evaluation can be considered and in some patients surgery with curative intent may become feasible. The aim of this study was to evaluate the outcomes of patients treated with induction chemotherapy and to identify patient and/or tumor characteristics associated with survival. Patients with esophageal or junctional cancer who underwent induction chemotherapy between 2005 and 2021 were identified from an institutional database of a tertiary referral center. Response to therapy was assessed by (18F-FDG PET)/CT. Response to therapy and treatment options, including surgery or palliation, were discussed in the multidisciplinary tumor board. Overall survival (OS) was calculated using the Kaplan Meier method. Uni- and multivariable analyses were performed to identify prognostic factors for survival. 238 patients were identified. The majority had esophageal adenocarcinoma (68.9 %) and were treated with a taxane/platinum-based chemotherapy (79.4 %). Response evaluation was performed in 233 patients and 154 of 238 patients (64.7 %) underwent surgical exploration. Resection was performed in 127 patients (53.4 %) resulting in a median and 5-year OS of 26.3 months (95 % CI 18.8–33.8) and 29.6 %, respectively. Presence of T4b (HR = 2.01, 95 % CI 1.02–3.92) and poorly differentiated tumor (HR = 1.45, 95 % CI 1.02–2.10) was associated with worse survival (p = 0.04). In carefully selected patients with advanced disease not amenable for standard curative treatment, induction chemotherapy followed by esophagectomy may result in a 5-year overall survival of approximately 30 %. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Pancreatic cancer is among the five most lethal malignancies in the world. Unfortunately, many malignant tumors go undetected by the current primary diagnostic tools. 18FDG-PET and 18FDG-PET/CT might be useful to confirm suspected pancreatic cancer. Methods: A meta-analysis was performed using all major search engines. Methodological quality of included studies was assessed as well as quality of the PET-protocol. The following pooled estimates served as primary outcome measures: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. Results: Thirty-five studies were included. Pooled estimates for 18FDG-PET were: sensitivity 90%, specificity 76%, PPV 90%, NPV 76% and accuracy 86%. Pooled estimates for 18FDG-PET/CT were: sensitivity 90%, specificity 76%, PPV 89%, NPV 78% and accuracy 86%. The pooled sensitivity and specificity for 18FDG-PET to differentiate between pancreatic cancer and chronic pancreatitis were 90% and 84%, respectively. Conclusion: Both 18FDG-PET and 18FDG-PET/CT offer no benefit over the current primary diagnostic tools in diagnosing pancreatic cancer. However, the 18FDG-PET/CT systems are still improving. We should investigate the sensitivity and specificity of these new systems while reevaluating the tradeoff between false positive and false negative results. Yet, 18FDG-PET/CT may have a role in the staging of pancreatic cancer, in survival prediction, and may add to other diagnostic information, like histology. [Copyright &y& Elsevier]

In the 1980s, the 111In-labeled somatostatin analog OctreoScan (Covidien, Hazelwood, MO) was developed for imaging of somatostatin receptor subtype 2 (sst2) overexpressing tumors. On the basis of this success, peptide receptor radionuclide therapy (PRRT) was developed using similar somatostatin analogs with different therapeutic radionuclides. Clinical application of PRRT demonstrated impressive results on tumor response, overall survival, and quality of life in patients with gastroenteropancreatic neuroendocrine tumors. The peptides 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), Tyr3-octreotate (DOTATATE) and DOTA, Tyr3-octreotide (DOTATOC) (brand name Onalta), predominantly targeting sst2, have been granted Orphan Drug status by the European Medicines Agency and the US Food and Drug Administration for application in PRRT. Besides somatostatin receptor-targeting peptides, multiple other radiopeptide analogs were developed targeting several other receptors overexpressed on various tumors. Some of these peptide analogs, including cholecystokinin, gastrin, gastrin-releasing peptide, arginine-glycine-aspartate (RGD)-peptides, and glucagon-like peptide 1 analogs appeared very promising in preclinical and clinical imaging and PRRT studies. Although the success of PRRT with radiolabeled somatostatin analogs has been established, there is still room for improvement. The therapeutic window of PRRT could be enlarged by the use of new and improved targeting compounds, of which new antagonists with excellent tumor to background ratios are very promising. Furthermore, locoregional administration, improved healthy tissue protection, and combination treatment can be applied to increase the effectiveness of PRRT. Combination treatment might include cocktails of different peptide analogs of different therapeutic radionuclides and of radiolabeled peptides with chemotherapeutic or radiosensitizing agents. This review summarizes results of PRRT and describes clinical and preclinical studies regarding PRRT optimizing strategies. [Copyright &y& Elsevier]

Peptide receptor radionuclide therapy with radiolabelled somatostatin analogues is an emerging and convincing treatment modality for patients with unresectable, somatostatin-receptor-positive neuroendocrine tumours. Using radiolabelled somatostatin analogues for imaging became the gold standard for staging of neuroendocrine tumours. The somatostatin receptor is strongly over-expressed in most tumours, resulting in high tumour-to-background ratios. Consequently, the next step was to try to treat these patients by increasing the radioactivity of the administered radiolabelled somatostatin analogue in an attempt to bring about tumour cure. Many patients have been treated successfully with this approach, roughly 25% of them achieving objective tumour shrinkage >50%. Serious side-effects have been rare. This article reviews the effectiveness and safety of the different radiolabelled somatostatin analogues used. Furthermore, clinical issues – including indication and timing of therapy – are discussed. Finally, important directions for future research are mentioned to illustrate new strategies for increasing therapy efficacy. [Copyright &y& Elsevier]

Because the role of chemotherapy, interferon, or somatostatin analogs as antiproliferative agents is uncertain, currently few treatment options exist for patients with metastatic or inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NET). Fifty-eight patients with somatostatin receptor-positive GEP-NET were treated in a phase I dose-escalating study with cumulative doses of 47 mCi to 886 mCi of the radiolabeled somatostatin analog [90Y-DOTA0,Tyr3]-octreotide. At baseline, 47 patients had progressive disease, and 36 were symptomatic. The extent of disease was: 4 patients without liver metastases and 52 patients with liver metastases, including 16 patients with very advanced disease, qualified as “end-stage,” and 2 end-stage patients without liver metastases. The objective responses were 5 partial response (PR), 7 minor response (MR), 29 stable disease (SD), and 17 PD. Overall, 33 patients (57%) experienced some improvement in their disease status, including conversion from PD into SD and improvement from SD into MR. Accordingly, 21 of 36 patients (58%) had improvement in Karnofsky performance score or symptoms. The median overall survival (OS) was 36.7 months (95% confidence interval [CI] 19.4-54.1 months). The median progression-free survival in 41 patients who had at least stable disease at the end of the treatment period was 29.3 months (95% CI 19.3-39.3 months). Patients who had SD at baseline had a significantly better OS than patients who had PD at baseline. The extent of disease at baseline also was a significant predictive factor for OS. The OS after therapy with [90Y-DOTA0,Tyr3]-octreotide was significantly better than in a historic control group of 32 comparable patients with GEP-NET who had been treated with another radiolabeled somatostatin analog, [111In-DTPA0]-octreotide (median OS 12.0 months, 95% CI 6.2-17.8 months). The difference in OS for both therapies remained highly significant in a multivariate Cox proportional hazard model including progression status and extent of disease at baseline as covariates. Although the objective response after therapy with [90Y-DOTA0,Tyr3]-octreotide by standard criteria seems modest, the significantly longer OS compared with historic controls is most encouraging. [Copyright &y& Elsevier]

Peptide receptor radionuclide therapy is a new treatment modality for patients with inoperable or metastasised neuroendocrine gastroenteropancreatic tumours. After the successful implementation of somatostatin receptor scintigraphy in daily clinical practice, the next logical step was to increase the radiation dose of the administered radiolabelled somatostatin analogue in an attempt to induce tumour shrinkage. Since then, an increasing number of patients has been successfully treated with this approach, resulting in a substantial numbers of patient with objective tumour shrinkage. Serious side-effects have been rare. This article reviews the effectiveness of the different radiolabelled somatostatin analogues used, the currently known side-effects and the survival data available. Furthermore, clinical issues, including indication and timing of therapy, are discussed. Finally, important directions for future research are briefly mentioned to illustrate that, although the currently available results already suggest a favourable outcome compared with other systemic therapies, new strategies are being developed to increase efficacy. [ABSTRACT FROM AUTHOR]

Peptide receptor radionuclide therapy is a new treatment modality for patients with inoperable or metastasised neuroendocrine gastroenteropancreatic tumours. After the successful implementation of somatostatin receptor scintigraphy in daily clinical practice, the next logical step was to increase the radiation dose of the administered radiolabelled somatostatin analogue in an attempt to induce tumour shrinkage. Since then, an increasing number of patients has been successfully treated with this approach, resulting in a substantial numbers of patient with objective tumour shrinkage. Serious side-effects have been rare. This article reviews the effectiveness of the different radiolabelled somatostatin analogues used, the currently known side-effects and the survival data available. Furthermore, clinical issues, including indication and timing of therapy, are discussed. Finally, important directions for future research are briefly mentioned to illustrate that, although the currently available results already suggest a favourable outcome compared with other systemic therapies, new strategies are being developed to increase efficacy. [Copyright &y& Elsevier]