Background: Neuroendocrine tumours (NETs) are clinical heterogeneous. To date, no studies have focused on the genetic characteristics of NETs at different anatomical sites. We aim to explore the genetic similarities or differences between NETs at different sites. Methods:The patients were from a clinical study STEM (from a single institute, NCT03204032, NCT03204019). This cohort included 47 patients, including 14 Pancreatic NETs (pNETs), 11 Rectal NETs, 14 Thoracic NETs, and 8 Others. Whole exome sequencing (WES) was performed. The WES data of pancreatic cancer (PCa), rectal cancer (RC) and lung cancer (LC) from TCGA were used to compare the genetic characteristics with NETs.Results: Somatic mutational analysis showed that there were no differences in tumor mutation burden, intra-tumoral heterogeneity or mutation spectrum between different NETs. We found several specific driver mutations for pNETs (MEN1 et.al), Rectal NETs (APC et.al) and Thoracic NETs (CACNA1A). Compared with cancers, few significantly mutated genes were shared by pNET and PCa; mutations in APC mostly occurred in both Rectal NET and RC; and some common mutations were observed in Thoracic NET and LC. Copy number analysis showed that copy number loss frequently occurred in all NETs. Deletions of chromosomal regions 14q11. 2, 19p13.2, 19q13.31 and 1p36.21 were observed in all NETs. Moreover, we found several specific alterations of chromosomal regions for different NETs. Compared with NETs, counterpart cancers harbored copy number gain as well as copy number loss. Some altered chromosomal regions were shared by Thoracic NET and LC, while none were shared by NET and cancer at pancreas or rectum. Furthermore, we investigated the main altered pathways previously reported in pNETs or small intestine NETs. All NETs had frequent alterations in WNT pathway, PI3K/mTOR pathway, DNA repair pathway, chromatin remodeling pathway and cell cycle pathway. However, several differences in pathway alterations were observed between different NETs, indicating that pathway alterations may be achieved through different genetic routes.Conclusions: NETs at different sites had different genetic characteristics, which have the potential to distinguish the primary site of NETs.Legal entity responsible for the study: The authors.

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RAS status between plasma and tissue samples from metastatic colorectal cancer (mCRC) patients.Methods: We conducted a study to evaluate the concordance of RAS status between plasma and tissue samples of 301 patients from several hospitals in Galicia, Northwest of Spain. RAS genotyping in plasma was performed using the OncoBEAM RAS CRC kit (Sysmex) and compared to the standard of care technology for FFPE-tissue analysis. Clinical data were collected from electronic reports from each patient. We analyzed the clinical profiles of the mCRC patients to investigate the causes of discordance.Results: The overall percent of RAS agreement was 84.4%, with a sensitivity of 81.3% and a specificity of 88.5%. Evaluating the clinical features of the patients, the absence of liver metastasis was a significant factor of discordance of RAS status (71% vs 28%, p<0.0001). Patients with peritoneal disease alone showed the lowest level of agreement (71.4%), followed by those with lung metastasis alone (72%), as compared with patients with liver metastasis alone (88.9%). Taking into account the diagnosis timing of stage IV, the concordance (75.9% vs 88.4%) and the sensitivity (68.1 vs 86.3) were significantly lower in metachronous than synchronous patients. Conclusion:The overall concordance between plasma and tissue RAS mutation supports liquid biopsy technology as an alternative to tissue testing for RAS characterization in mCRC patients, especially in patients with liver metastasis. The RAS status obtained from plasma of patients with peritoneal or lung diseases, and particularly with those of metachronous stage IV, should be considered cautiously. These results reinforce the use of liquid biopsy as a non-invasive tool for guiding targeted therapy in selected patients.Legal entity responsible for the study: The author.

Background: 90Y-ibritumomab tiuxetan (Zevamab®; ZEV; Bayer-Schering Pharma- Argentina) has been approved for the treatment of relapsed, refractory and transformed (high grade) follicular lymphomas. Methods: Between Sep. 2005 and Feb. 2008, 45 patients (pts) [22 F & 23 M; median age 62 yrs (45–83)] with refractory/relapsed lymphoma were enrolled. Diagnoses: 37 follicular lymphoma (FL), 5 were mantle cell lymphoma (ML) and 3 transformed lymphoma (TL); 18 pts had bulky disease, 8 had bone marrow involvement and 21 had stage III–IV disease. Median time from diagnosis was 5 yrs (0.5– 29). Twenty two pts had received 1–2 previous treatments, and 23 pts had received 3–5 previous treatments including 5 pts with autologous bone marrow transplantation. All had previously received anti-CD20 monoclonal antibody therapy. Six pts received previous radiotherapy. ZEV was administered at 0.3 or 0.4 mCi, based on initial platelet count. Seven days before, and the same day of the ZEV administration, pts received standard rituximab 250 mg/m2. In 3 pt, ZEV was part of the conditioning regimen of autologous bone marrow transplantation. Results: Forty pts were evaluable for response: 34 (86%) pts responded – 19 CR (48%), 15 PR (38%). Overall survival and PFS for the entire group at 18 months was 63% and 37% respectively, with a median follow-up of 12 months (1–29 months). Of the 45 patients, 5 pts (11%) had died before third month and response was not assessed, 6 pts (13%) did not respond, 3 (7%) died with response from other causes, 14 pts (31%) responded and subsequently relapsed. Finally 17 pts (38%) continue to be in response, 9 (20%) lasting more than twelve months (long lasting responders). Slight differences in duration of response and survival were observed between FL vs ML and TL favouring FL (RR 2.047). Forty six per cent of pts required filgrastim for neutropenia, 24% required platelet transfusions, 22% had neutropenia plus fever and were admitted for complicated pancytopenia, and 20% required red blood cells transfusion. Two patient died 30 & 40 days after treatment with hypoplastic bone marrow complicated with sepsis in the post autologous bone marrow transplantation period. Four pts with previous bone marrow transplantation required filgrastim, transfusions and 2/3 had febrile neutropenia. Conclusion: Our experience with ZEV in relapsed and refractory FL shows 48 % CR. Even heavily treated pts that had previous bone marrow transplantation were able to receive ZEV, although they required extra support. Our experience supports the use of ZEV in relapsed and refractory lymphomas even after autologous bone marrow transplantation.