Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67<55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.

No abstract

Somatostatin receptor imaging is a valuable tool in the diagnosis, follow-up, and treatment planning of neuroendocrine tumor (NET). PET-based tracers using 68 Ga as the radioisotope have in most centers replaced SPECT-based tracers as the gold standard. 64 Cu-DOTATATE is a new PET tracer that has been shown to be far superior to the SPECT tracer 111 In-diethylenetriaminepentaacetic acid-octreotide. Because of the advantages of 64 Cu over 68 Ga, we hypothesized that the tracer has a higher sensitivity than 68 Ga-based tracers. To test this hypothesis, we compared on a head-to-head basis the diagnostic performance of 64 Cu-DOTATATE with that of 68 Ga-DOTATOC in NET patients. Methods: Fifty-nine NET patients were scanned with both 64 Cu-DOTATATE and 68 Ga-DOTATOC PET/CT and compared on a head-to-head basis. Discordant lesions were verified during at least 30 mo of follow-up. Results: A total of 701 lesions were concordantly detected on both 64 Cu-DOTATATE and 68 Ga-DOTATOC PET/CT scans, whereas an additional 68 lesions were found by only one of the scans. 64 Cu-DOTATATE showed 42 lesions not found on 68 Ga-DOTATOC, of which 33 were found to be true-positive on follow-up. 68 Ga-DOTATOC showed 26 lesions not found on 64 Cu-DOTATATE, of which 7 were found to be true-positive on follow-up. False-positives were mainly lymph node lesions. Accordingly, 83% of the additional true lesions found on only one of the scans were found by 64 Cu-DOTATATE. On a patient-basis, additional true lesions were found by 64 Cu-DOTATATE and 68 Ga-DOTATOC in 13 and 3 patients, respectively. All patients with additional lesions also had concordant lesions found by both scans. Conclusion: 64 Cu-DOTATATE has advantages over 68 Ga-DOTATOC in the detection of lesions in NET patients. Although patient-based sensitivity was the same for 64 Cu-DOTATATE and 68 Ga-DOTATOC in this cohort, significantly more lesions were detected by 64 Cu-DOTATATE. Furthermore, the shelf life of more than 24 h and the scanning window of at least 3 h make 64 Cu-DOTATATE favorable and easy to use in the clinical setting.

The results from this first study on PET/CT in SCLC indicates that PET/CT can simplify and perhaps even improve the accuracy of the current staging procedure in SCLC. A larger clinical trial, preferably with consequent histological confirmation in case of discordance, however, is warranted.

Introduction: DLL3, an atypical Notch ligand, is expressed in SCLC tumors but is not detectable in normal adult tissues. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate containing a DLL3targeting antibody tethered to a cytotoxic agent pyrrolobenzodiazepine by means of a protease-cleavable linker. The efficacy and safety of Rova-T compared with topotecan as second-line therapy in patients with SCLC expressing high levels of DLL3 (DLL3-high) was evaluated.Methods: The TAHOE study was an open-label, two-to-one randomized, phase 3 study comparing Rova-T with topotecan as second-line therapy in DLL3-high advanced or metastatic SCLC. Rova-T (0.3 mg/kg) was administered intravenously on day 1 of a 42-day cycle for two cycles, with two additional cycles available to patients who met protocol-defined criteria for continued dosing. Topotecan (1.5 mg/m 2 ) was administered intravenously on days 1 to 5 of a 21-day cycle. The primary end point was overall survival (OS).Results: Patients randomized to Rova-T (n ¼ 296) and topotecan (n ¼ 148) were included in the efficacy analyses. The median age was 64 years, and 77% had the extensive disease at initial diagnosis. The median OS (95% confidence interval) was 6.3 months (5.6-7.3) in the Rova-T arm and 8.6 months (7.7-10.1) in the topotecan arm (hazard ratio, 1.46 [95% confidence interval: 1.17-1.82]). An independent data monitoring committee recommended that enrollment be discontinued because of the shorter OS observed with Rova-T compared with topotecan. Safety profiles for both drugs were consistent with previous reports.Conclusions: Compared with topotecan, which is the current standard second-line chemotherapy, Rova-T exhibited an inferior OS and higher rates of serosal effusions, photosensitivity reaction, and peripheral edema in patients with SCLC. A considerable unmet therapeutic need remains in this population.

To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type. Concentrating on GEP-NECs, we can conclude that survival times are poor, with a median of only 4–16 months depending on disease stage and primary site. Further, this aggressive disease appears to be on the rise, with incidence numbers increasing while survival times are stagnant. Treatment strategies concerning surgery are often undecided and second-line chemotherapy is not yet established. After an analysis of over 2600 articles, we can conclude that there is indeed more empirical literature concerning GEP-NECs available than previously assumed. This unique review is based on 333 selected articles and contains detailed information concerning all aspects of GEP-NECs. Namely, the classification, histology, genetic abnormalities, epidemiology, origin, biochemistry, imaging, treatment and survival of GEP-NECs are described. Also, organ-specific summaries with more detail in relation to disease presentation, diagnosis, treatment and survival are presented. Finally, key points are discussed with directions for future research priorities.

Background . The diagnostic work-up and treatment of patients with neuroendocrine neoplasms (NENs) has undergone major recent advances and new methods are currently introduced into the clinic. An update of the WHO classifi cation has resulted in a new nomenclature dividing NENs into neuroendocrine tumours (NETs) including G1 (Ki67 index Յ 2%) and G2 (Ki67 index 3 -20%) tumours and neuroendocrine carcinomas (NECs) with Ki67 index Ͼ 20%, G3. Aim . These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group ' s current view on how to diagnose and treat NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients.

Neuroendocrine tumors (NETs) can be visualized using radiolabeled somatostatin analogs. We have previously shown the clinical potential of 64 Cu-DOTATATE in a small first-in-human feasibility study. The aim of the present study was, in a larger prospective design, to compare on a head-to-head basis the performance of 64 In-diethylenetriaminepentaacetic acid (DTPA)-octreotide ( 111 In-DTPA-OC) as a basis for implementing 64 Cu-DOTATATE as a routine. Methods: We prospectively enrolled 112 patients with pathologically confirmed NETs of gastroenteropancreatic or pulmonary origin. All patients underwent both PET/CT with 64 Cu-DOTATATE and SPECT/CT with 111 In-DTPA-OC within 60 d. PET scans were acquired 1 h after injection of 202 MBq (range, 183-232 MBq) of 64 Cu-DOTATATE after a diagnostic contrast-enhanced CT scan. Patients were followed for 42-60 mo for evaluation of discrepant imaging findings. The McNemar test was used to compare the diagnostic performance. Results: Eightyseven patients were congruently PET-and SPECT-positive. No SPECT-positive cases were PET-negative, whereas 10 false-negative SPECT cases were identified using PET. The diagnostic sensitivity and accuracy of 64 Cu-DOTATATE (97% for both) were significantly better than those of 111 In-DTPA-OC (87% and 88%, respectively, P 5 0.017). In 84 patients (75%), 64 Cu-DOTATATE identified more lesions than 111 In-DTPA-OC and always at least as many. In total, twice as many lesions were detected with 64 Cu-DOTATATE than with 111 In-DTPA-OC. Moreover, in 40 of 112 cases (36%) lesions were detected by 64 Cu-DOTATATE in organs not identified as disease-involved by 111 In-DTPA-OC. Conclusion: With these results, we demonstrate that 64 Cu-DOTATATE is far superior to 111 In-DTPA-OC in diagnostic performance in NET patients. Therefore, we do not hesitate to recommend implementation of 64 Cu-DOTATATE as a replacement for 111 In-DTPA-OC.