Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response.

BACKGROUND: Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent. METHODS: Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) by receiver operating characteristic (ROC) analysis and logistic regression) for prediction of benefit (PFS) from sunitinib. RESULTS: Data for 237 patients (85 placebo; 152 sunitinib (n=66.50 mg \u274-weeks on/2-weeks off\u27 schedule; n=86 \u2737.5 mg continuous daily dosing (CDD)\u27)) and 788 scans were analysed. The median PFS for sunitinib and placebo were 9.3 months (95% CI 7.6-12.2) and 5.4 months (95% CI 3.5-6.01), respectively (hazard ratio (HR) 0.43 (95% CI 0.29-0.62); P CONCLUSIONS: A 10% reduction within marker lesions identifies pNET patients benefiting from sunitinib treatment with implications for maintenance of dose intensity and future trial design

Respiratory syncytial virus as a cause of pulmonary hemorrhage in a low birth weight infant - strategies for protection and prevention: a case report

A case study of 39-year old man with persistent wheezing, episodes of haemoptysis and dry cough unsuccessfully treated with inhaled beta2-agonists and steroids for about 10 months. Chest radiograph revealed a disproportion in dimensions between both lungs, with the left one being smaller than the right one. Spirometry demonstrated a restrictive pattern. During bronchoscopy, a polypoid endobronchial tumor, localized in the left main bronchus, completely occluding its lumen, was found. The tumor was diagnosed as carcinoid. In this case, due to the lack of characteristic symptoms, diagnosis of carcinoid was delayed. Patients unsuccessfully treated for bronchial asthma or chronic obstructive pulmonary disease should undergo bronchoscopic examination

Non-prostatic pathology on prostate needle-biopsy – colorectal carcinoid: a case report

Introduction: Prostate needle-biopsies are among the most common specimens in routine histopathological practice; in 15% colorectal tissue is also present. Rectal pathology is described to be found in 17% of this coincidentally obtained material. Case presentation: We present a case in which colorectal carcinoid was found in the rectal mucosa obtained via transrectal prostate biopsies in a screening program for prostate cancer in a 71-year old Caucasian male. To the best of our knowledge, this was the first time that such a coincidental finding was discovered. Besides a colonoscopy with polypectomy, this coincidental detection remained without any further clinical consequences for this patient until today. Conclusion: As there is a considerable chance that abnormalities are found in the rectal tissue of prostate biopsies, it is advisable for all pathologists to include this tissue in the histology evaluation and look for potential irregularities in this simultaneously collected material

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11

Carcinoid tumor of the minor papilla in complete pancreas divisum presenting as recurrent abdominal pain

<p>Abstract</p> <p>Background</p> <p>Tumors of the minor papilla of the duodenum are extremely rare, and they are mostly neuroendocrine tumors, such as somatostatinomas and carcinoid tumors. However, true incidence of carcinoid tumors in minor papilla might be much higher, because patients with minor papillary tumors usually remain asymptomatic. We report a very unusual case of carcinoid tumor in a patient with complete pancreas divisum with a review of the literature.</p> <p>Case presentation</p> <p>A 56-year-old female patient was referred for evaluation of pancreatic duct dilatation noted on abdominal ultrasonography and computerized tomography. She complained of intermittent epigastric pain for 6 months. A MRCP and ERCP revealed complete pancreas divisum with dilatation of the main pancreatic duct. On duodenoscopy, a small, yellows, subepithelial nodule was visualized at the minor papilla; biopsy of this lesion revealed a carcinoid tumor. She underwent a pylorus-preserving pancreaticoduodenectomy. The histologic evaluation showed a single nodule, 1 cm in diameter, in the submucosa with duodenal and vascular invasion and metastasis to the regional lymph nodes.</p> <p>Conclusion</p> <p>Although the size of the carcinoid tumor was small and the tumor was hormonally inactive, the concomitant pancreas divisum led to an early diagnosis, the tumor had aggressive behavior. Carcinoid tumors of the minor papilla should be included in the differential diagnosis of recurrent abdominal pain or pancreatitis of unknown cause.</p

The prognostic role of WHO classification, urinary 5-hydroxyindoleacetic acid and liver function tests in metastatic neuroendocrine carcinomas of the gastroenteropancreatic tract

The World Health Organisation (WHO) classification (2000) is widely used to classify neuroendocrine carcinomas (NECs), yet its prognostic value needs to be confirmed. In this study, patients with metastatic NECs (n=119) were classified according to WHO guidelines into well differentiated and poorly differentiated (WDNECs and PDNECs). Histological differentiation based on WHO criteria had the highest impact on overall survival (OS) (PDNECs : WDNECs hazard ratio (HR)=4.02, P=0.02); however, PDNECs represented only a small percentage of patients (8%). In a WDNEC-restricted analysis, abnormal liver function tests (LFTs) and elevated urinary 5-hydroxyindoleacetic acid (u5HIAA) were independent prognostic factors for survival (HR=2.65, P=0.006 and HR=2.51, P=0.003, respectively) and were used to create a WDNEC-specific prognostic model (low risk=both normal, intermediate risk=one of them abnormal, high risk=both abnormal). Low-risk WDNECs had the most favourable prognosis (median OS, mOS 8.1 years), which was significantly better compared to both intermediate-risk and high-risk WDNECs (mOS 3.2 and 1.4 years, with P=0.01 and P<0.001, respectively). High-risk WDNECs displayed the shortest OS (1.3 years), which was similar to that of PDNECs (P=0.572). This analysis supports the prognostic value of WHO classification for metastatic NECs arising from the gastroenteropancreatic tract; however, risk stratification using readily available u5HIAA and LFTs may be necessary for the heterogeneous group of WDNECs

Neuroendocrine carcinoma arising in soft tissue: three case reports and literature review

<p>Abstract</p> <p>Background</p> <p>Neuroendocrine tumours (NET) are tumours arising from neuroendocrine cells of neural crest origin. They are characterised by the presence of neurosecretory granules which react positively to silver stains and to specific markers including neuron specific enolase, synaptophysin and chromogranin. Metastasis to the skin occurs infrequently but primary soft tissue NET is excessively rare.</p> <p>Case presentation</p> <p>We report our experience with 3 such cases. In the first case, the NET originated in muscle and was treated with wide surgical excision and adjuvant radiotherapy. The second case presented as a subcutaneous mass in the foot and the tumour was positive on ¹²³I mIBG scan. She has had prolonged recurrence-free survival following primary hypo-fractionated radiotherapy. In the third case, a cutaneous nodule proved to be a NET and at surgery, lymph node disease was present. He has remained disease-free after surgical excision without the need for external beam radiotherapy.</p> <p>Conclusion</p> <p>These tumours appear to have a good prognosis. Complete excision offers potentially curative treatment. Adjuvant radiotherapy may be helpful when the tumour margin is narrow. For patients with unresectable disease or where surgery would not be appropriate, radiotherapy appears to be an effective therapeutic option.</p