Einarsson syntes abstraktet indikerer at 100mg/m2 predosering beskytter beinmarg og 20/100 gir høyere opptak i tumor. Men han påpeker at det ikke er statistisk signifikans mellom arm 1 og 4 for Tumoropptak over beinmarg. p=0.12, betyr som jeg forstår at det er 12% sjanse for at disse resultatene er tilfeldige. Statistisk signifikans er p=<0.05
Ellers nevner de forumene veldig ofte, og det er tydelig at de er innom og leser. Hei Elisabeth og Jonas. (Prat enda mer om NANO, daaaa)
hehe, er sikkert noen som ryker på den slags teorier også! 
De er vel ikke innom her og leser? Og hva mener du, høyere opptak men ikke statistisk signifikant?
Forklar. Hva er forskjellen på dosering i arm 1 og 4?
De nevnte forum i flertall, og TekInvestor er jo ikke så vanskelig å finne frem til.
Jeg er ikke ekspert på statistikk, men for å få statistisk signifikans som er akseptert i forskermiljøer må man oppnå en p-verdi som er under 0.05. Det betyr at det er 5% sjans for at resultatet er tilfeldig. Jo lavere, jo bedre. Her kan garantert andre forklare hvorfor.
Litt usikker på hva du spør om egentlig, men jeg gjør et forsøk. De brukte forholdstallet mellom opptak i tumor og opptak i beinmarg i studien, og forholdstallet var “2.73” i arm 4, og noe sånn som “1.73” i arm 1. Jeg har ikke tid til å sjekke dette nå, men det indikerer jo at doseringen 20/100 i arm 4 bringer mer Betalutin inn i tumor i forhold til beinmarg enn arm 1. Så sammenlikner de disse resultatene med hverandre på statististisitsitistisik vis og får en p-verdi. Denne viste ikke at man kan stole på disse resultatene, men det kan muligens være at det var for få med i studien til at man kunne gjøre det.
Einarsson uttalte at han synes det indikerte at det var en sammenheng. Som en ekte aksjonær ville gjort. Og efficacy-resultatene vi venter på vil gi oss svaret.
Jeg etterlyser en ekspert på statistikk for å forklare bedre og korrigere hvor det er behov.
Fant frem de relevante tallene, jeg hadde blandet verdiene, men poenget står:
"The mean RM absorbed doses were 0.83, 0.91 and 1.39 mGy/MBq for arm 1, 4 and non-pre-dosing arms 2+3, respectively. There was a significantly higher RM dose for non-pre-dosing compared to arm 1 (p = 0.04), and arm 4 (p = 0.05). Mean tumour absorbed doses were 1.62, 2.78 and 1.37 mGy/MBq for arm 1, 4 and non-pre-dosing respectively. Tumour doses were higher in arm 4 patients compared to patients without pre-dosing (p = 0.04). Tumour doses in arm 1 were not significantly higher compared to non-pre-dosing (p = 0.71). The mean tumour to RM absorbed dose ratios were 2.16, 3.93 and 1.07 for arm 1, 4 and non-pre-dosing respectively. "
Riktig. Det er nettopp lavt n som gir en p på 0.12 og ikke <0.05. Så ja, det er en stor forskjell, men vi har sett på for få personer til å fastslå at dette ikke er tilfeldig. Fortsatt meget sterke tall.
"Especially when a study is small, even large effects may be “drowned in noise” and thus fail to be detected as statistically significant by a statistical test."
En ting jeg nylig la merke til som jeg hadde oversett tidligere, og som jeg ikke kan se har blitt diskutert noe sted: De oppgir tumoropptak i mGy/MBq, som impliserer at det tas hensyn til at strålingsdosene er forskjellige. Mener jeg leste et sted (tror det var HO) hvor noen nevnte at man jo måtte forvente i allefall 30% høyere tumoropptak med 20 vs 15 MBq (dersom predoseringen ikke gjør utslag). Men som jeg forstår det, er doseforskjellene hensyntatt ved å benytte verdier som er normalisert mht. MBq. Det vil i så fall si at resultatene er enda mer overbevisende, siden det ca.70% høyere tumoropptaket kun kan krediteres den høyere predosen og ikke den høyere strålingsdosen.
Twitterstorm i kveld om kostnadene ved CAR-T
https://endpts.com/cascade-of-costs-could-push-new-gene-therapy-above-1-million-per-patient/
Så, hvordan får vi den gjengen til å tweete om Betalutin etter ASH? 
Det var Merlin som tidlig i år rimelig antok linært 30% høyere effetkt (vi snakket ikke om tumoropptak da).
Den siste setningen din er slik resultatene allerede har blitt forstått, men ikke presiseringen/forståelsen av doseringsekvivalent måling med mGy/MBq er ny. Takk for den. Fin studie egentlig:)
Log the manhours, opprett en twitterkonto og kjør på med tweets på hashtagen for konferansene
Du svarte på det jeg lurte på: hvorfor man ikke får en signifikant forskjell når absorbert stråledose er høyere og det er mindre toksisitet til benmarg. Når vi får data fra hele pasientsettet vil nok dette endre seg…
Mer og mer taler for at det ligger an til Home run her…
Kom det fram noe nytt, bekreftelser etc i helgen?
Nanomelding! Ser vel bra ut dette?
Press releases
Nordic Nanovector: Presentations at European Association of Nuclear Medicine annual meeting (EANM)
23.10.2017 07:00
Oslo, Norway, 23 October 2017
Nordic Nanovector ASA (OSE: NANO) announces the following presentations by the company’s research collaborators at the European Association of Nuclear Medicine annual meeting (EANM; 21-25 October; Vienna, Austria).
Abstract: OP-012
Title: Pre-dosing with lilotomab prior to antibody-radionuclide conjugate therapy with 177Lu-lilotomab satetraxetan significantly increases the ratio of tumour to red marrow absorbed dose in non-Hodgkin lymphoma patients Authors: J. Blakkisrud et al.
Abstract: OP-054
Title: Involvement of cell cycle checkpoints in the therapeutic efficacy of 177Lu-lilotomab in non-Hodgkin B-cell lymphoma Authors: A. Pichard et al.
Abstract: EP-0814
Title: FDG uptake at baseline may predict absorbed dose in tumor lesions in indolent Non-Hodgkin lymphoma patients treated with the novel antibody-radionuclide conjugate 177Lu-lilotomab satetraxetan Authors: A. Londalen et al.
In addition, Jostein Dahle, Nordic Nanovector’s CSO presented in Pre-Congress Symposium 3 - Clinical Introduction of New Radiotherapeutics: Challenges and Opportunities
Title: PS23 - Treatment of NHL with Lutetium-177 Labelled Anti-CD37 Antibodies
The abstracts are available by clicking here
http://onsite.eanm.org/index.php?p=recorddetail&rid=90eb2f5b-236a-43c0-b77e-071de7de07b8&t=browsesessions
OP-054
11:41
Involvement of cell cycle checkpoints in the therapeutic efficacy of 177Lu-lilotomab in non-Hodgkin B-cell lymphoma
Add presentation to my schedule A. Pichard1, A. Courteau2, S. Marcatili2, G. Cartron3, I. Isabelle Navarro-Teulon1, A. Repetto-Llamazares4, H. Heyerdahl4, M. Bardiès2, J. Dahle4, J. POUGET1; 1IRCM/INSERMU1194, MONTPELLIER, FRANCE, 2Centre de Recherche en Cancérologie de Toulouse, TOULOUSE, FRANCE, 3Centre Hospitalier Universitaire de Montpellier, MONTPELLIER, FRANCE, 4Nordic Nanovector ASA, OSLO, NORWAY.
Abstract
Aims To elucidate the mechanisms of action of radioimmunotherapy with 177Lu-labeled lilotomab (Betalutin®) directed against the CD37 receptor on non-Hodgkin lymphoma (NHL) B-cells, we have developed a radiobiological approach that discriminates between the cytotoxic effects of unlabelled antibodies and of radiation. Comparison was done with 177Lu-rituximab. Materials and methods. In vitro, Ramos (Burkitt), DOHH2 (follicular) and Rec-1 (mantle) lymphoma cell lines were exposed for 18 hours to increasing activities (0—6 MBq/mL) of 177Lu-rituximab, of 177Lu-lilotomab, of the non-specific 177Lu-cetuximab or to unlabelled mAbs (0-40µg/mL). A radiobiological model considering the contribution of cytotoxic effects of 177Lu (radiation only) and of unlabelled antibody (mAb only) to the cytotoxicity of 177Lu-mAbs was established. We next investigated in which B-cell NHL subtypes 177Lu-lilotomab would be the most efficient and how biological (genetic background, cell cycle, apoptosis) and/or physical (tumour absorbed doses) parameters could affect the final therapeutic outcome. In vivo, mice bearing subcutaneous Ramos or DOHH2 tumour xenografts, were treated at MTA of 177Lu-mAbs and tumour growth was monitored. Organ and tumour absorbed doses were determined according to MIRD formalism. Results. We showed in the three lymphoma cell lines that unlabelled rituximab was more cytotoxic than lilotomab. When antibodies were radiolabeled, 177Lu-lilotomab was as cytotoxic as 177Lu-rituximab in the radiosensitive DOHH2 cells, but not in the most radioresistant Ramos cells. The higher response to 177Lu-lilotomab in DOHH2 cells than in Ramos cells was mainly mediated by lack of G2/M cell cycle arrest followed by strong induction of apoptosis in DOHH2 cells. Inhibition of signal pathways involved in cell cycle control radiosensitized Ramos cells. These results were supported by in vivo data. 177Lu-lilotomab was as efficient as 177Lu-rituximab in Ramos tumour xenograft models only if tumour absorbed radiation dose was increased over a certain limit. Conversely, in DOHH2 tumour xenografts, 177Lu-lilotomab was as efficient as 177Lu-rituximab for similar absorbed radiation doses, although lilotomab was less efficient than rituximab. Conclusion. A radiobiological approach identified the parameters determining 177Lu-lilotomab therapeutic efficacy in different subtypes of lymphoma.
OP-012
08:00
Pre-dosing with Lilotomab Prior to Antibody-Radionuclide Conjugate Therapy with 177Lu-Lilotomab Satetraxetan Significantly Increases the Ratio of Tumour to Red Marrow Absorbed Dose in non-Hodgkin Lymphoma Patients
Add presentation to my schedule J. Blakkisrud1, A. Løndalen2, J. Dahle3, A. C. Martinsen4,1, H. Holte5, A. Kolstad5, C. Stokke1,6; 1Department of Diagnostic Physics, Oslo University Hospital, Oslo, NORWAY, 2Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, NORWAY, 3Nordic Nanovector ASA, Oslo, NORWAY, 4The Department of Physics, University of Oslo, Oslo, NORWAY, 5Department of Oncology, Radiumhospitalet, Oslo University Hospital, Oslo, NORWAY, 6Oslo and Akershus University College of Applied Science, Oslo, NORWAY.
Abstract
Introduction: 177Lu-lilotomab satetraxetan is a novel anti-CD37 antibody radionuclide conjugate for treatment of non-Hodgkin lymphoma. Four different combinations of pre-dosing and pre-treatment have been investigated in the phase 1 study. All patients were pre-treated with different regimens of rituximab. Two arms included cold lilotomab pre-dosing (arm 1 and 4; 40 mg fixed and 100 mg/m2 BSA dosage respectively) and two did not (arm 2 and 3). Patients received either 10, 15 or 20 MBq 177Lu-lilotomab satetraxetan per kg body weight. Previously, we have shown that absorbed red marrow (RM) doses were lower in arm 1 vs arm 2, and that haematological toxicity was more severe for patients receiving higher RM doses. The aim of this work was to compare the ratios of tumour to RM absorbed doses between arm 1, 4 and non-pre-dosed patients (arm 2 + 3). Subjects and Methods: A total of 16 patients were included for RM dosimetry, of these 14 were included for tumour dosimetry. A total of 35 tumour lesions were included, 1 to 5 from each patient (mode 3). RM and mean tumour absorbed doses per administered activity were determined from multiple SPECT/CT-images for each patient. Two-sided student-t-tests were used for all statistical analyses. Results: The mean RM absorbed doses were 0.83, 0.91 and 1.39 mGy/MBq for arm 1, 4 and non-pre-dosing arms 2+3, respectively. There was a significantly higher RM dose for non-pre-dosing compared to arm 1 (p = 0.04), and arm 4 (p = 0.05). Mean tumour absorbed doses were 1.62, 2.78 and 1.37 mGy/MBq for arm 1, 4 and non-pre-dosing respectively. Tumour doses were higher in arm 4 patients compared to patients without pre-dosing (p = 0.04). Tumour doses in arm 1 were not significantly higher compared to non-pre-dosing (p = 0.71). The mean tumour to RM absorbed dose ratios were 2.16, 3.93 and 1.07 for arm 1, 4 and non-pre-dosing respectively. Ratios were significantly higher in both arm 1 and 4 compared to non-pre-dosing (p = 0.05 and p = 0.04). No statistically significant difference between arm 1 and 4 was found for any parameters (p >= 0.12). Conclusion: Pre-dosing with lilotomab has a mitigating effect on red marrow absorbed dose for 177Lu-lilotomab satetraxetan patients, and increased pre-dosing amounts was found correlated with a higher tumour dose. While the optimal amount of lilotomab is yet to be investigated, both pre-dosage levels significantly increased the tumour to RM absorbed dose ratio.
[quote=“Amatouren, post:5575, topic:560”]
EP-0814
[/quote]EP-0814
FDG uptake at baseline may predict absorbed dose in tumor lesions in indolent Non-Hodgkin lymphoma patients treated With the novel antibody-radionuclide-conjugate 177Lu-lilotomab satetraxetan
Add presentation to my schedule A. Londalen1,2, J. Blakkisrud2, J. Dahle3, M. Revheim1,4, H. Holte5, A. Kolstad5, C. Stokke2,6; 1Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, NORWAY, 2Department of Diagnostic Physics, Oslo University Hospital, Oslo, NORWAY, 3Nordic Nanovector ASA, Oslo, NORWAY, 4Faculty of Medicine, University of Oslo, Oslo, NORWAY, 5Department of Oncology, Radiumhospital, Oslo University Hospital, Oslo, NORWAY, 6Oslo and Akershus University College of Applied Science, Oslo, NORWAY.
Abstract
Aim: 177Lu-lilotomab satetraxetan is a novel anti-CD37 antibody-radionuclide-conjugate (ARC) under development for treatment of indolent non-Hodgkin lymphoma. Four different treatment regimens have been investigated in a dose escalating phase 1 study. Patients in arm 1 and 4 received cold lilotomab as pre-dosing; 40 mg fixed and 100 mg/m2, respectively, on the same day as 177Lu-lilotomab satetraxetan, while patients in arm 2 and 3 did not. Administered activity of 177Lu-lilotomab satetraxetan was 10, 15 or 20 MBq/kg. FDG PET/CT imaging was performed at baseline, and at 3 and 6 months after treatment. The aim of this work was to investigate correlations between baseline FDG uptake and tumour absorbed dose at the lesion level. Material and methods: In eleven patients, a total of 33 lesions were eligible for tumour dosimetry (1-5 lesions/patient). Lesions were included based on visual identification on low dose CT and activity on SPECT. Tumour absorbed doses were determined from SPECT/CT images obtained at different time points. Peak standardized uptake value (SUVpeak ) according to EANM procedure guidelines for tumour imaging:version 2.0 at baseline PET/CT were registered for each lesion. Based on pre-dosing, patients were separated into two groups: lilotomab(+) and lilotomab(-), with and without pre-dosing respectively. Tumours were further grouped into two as, “high” and “low” FDG-avid tumours based on the SUVpeak 50% percentile cut-off and the absorbed dose was corrected for ARC dosage. Results: Mean SUVpeak for all lesions at baseline was 7.34 (range 3.5 - 12.3). Mean dosage-corrected tumour absorbed doses for the lilotomab(+) group were 19.2 and 25.7 cGy/(MBq/kg) for tumours with high and low-SUVpeak, respectively (P = 0.34). For the lilotomab(-) patients the mean absorbed tumour doses were 12.3 and 20.2 cGy/(MBq/kg) for high and low-SUVpeak tumours respectively (P = 0.18). Conclusion: A tendency towards higher absorbed doses in tumours with low FDG uptake at baseline PET/CT was observed. The difference seemed to decrease when pre-dosing with cold lilotomab before 177Lu-lilotomab satetraxetan treatment was given. This may indicate that pre-dosing increases the availably of 177Lu-lilotomab satetraxetan for tumours and evens out the difference in relative absorbed doses between high and low FDG avid lesions.