Object

Title: Application of new forms of radioisotope therapy with 90Y in oncology

Abstract:

The oncological diseases are still a challenge to clinicians and inspire the search for new diagnostic and therapeutic procedures. Lately radioisotope therapy with 90Y-labelled compounds has been introduced in the treatment of neuroendocrine tumours and non-Hodgkin’s lymphomas. 90Y is the emitter of beta radiation of the energy high enough to directly influence the tumour biology. Its properties enable the treatment without necessity of the patient’s hospitalisation. For the successful therapy an appropriate ligand should be chosen to carry the isotope to the place of its action. Ligands influence both the course and the side effects of the treatment. Yttrium connected by chelating agent Tiuxetan to the monoclonal antibody against antigen CD20+ expressed on the surface of type B lymphocytes is used in the non-Hodgkin lymphomas therapy. It enables the direct action of the radiation not only on the tumour, but on the adjacent neoplasmatic cells not expressing the antigens on their surface as well (so called cross-fire effect). In the treatment of neuroendocrine tumours the somatostatin analogue labelled with radioactive isotope is utilised. Ligand - chelator - [DOTA, Tyr3] complex is characterised by the greatest affinity to somatostatin receptor type 2, which is expressed in most of the NETs. The radioisotope therapy of NETs is used in the patients with disseminated disease or with inoperable primary tumour with positive results of the pre-therapeutic scintigraphy with labelled somatostatin analogues. Radioimmunotherapy is an alternative method of treatment of lymphomas resistant to the standard treatment. The aim of the study was to assess the effectiveness of the therapy with 90Y combined with the different types of ligands in two groups of patients: with neuroendocrine tumours and with non-Hodgkin lymphomas, as well as the side effects of the treatment depending on the exposure of the critical organs. 32 patients (19 females and 13 males - 59,37% and 40,63% of the study subgroup respectively) aged 37-75 years (mean age 58,03±10,75 years) with histopathologically confirmed NET treated in Endocrinology Department of the University Hospital in Krakow between 2001 and 2007 were included in the study. 90,6% of patients were diagnosed with disseminated disease. In 3 patients the tumour was inoperable. Radioimmunotherapy was instituted in 30 patients (16 females and 14 males - 53,33% and 46,67% of the study subgroup respectively) aged 41-82 years (mean age 58,73 ± 11,26 years) diagnosed with non-Hodgkin lymphoma CD20+ of III and IV stage according to Ann Arbor classification. All patients were followed-up by the Haematology Department of the University Hospital in Krakow. The isotope therapy (1) was the first line of the treatment, (2) was initiated after achieving partial remission after the first or second line of the treatment or (3) was commenced in recurrent disease after non-successful immunotherapy or chemotherapy. Before implementation of the treatment in the patients of the NET subgroup, receptor scintigraphy was performed to confirm the somatostatin receptors expression in the tumour, as well as the computed tomography (CT) of the involved area. Both procedures were essential to the treatment implementation. In every patient the serum level of AlAT, creatinine and chromogranin A together with completed blood count was estimated. Glomerular filtration rate (GFR) was also estimated. In every patient in the non-Hodgkin lymphoma (NHL) subgroup CT of the abdomen and chest, complete blood count and bone marrow trepanobiopsy were performed to qualify the patient to the therapy. The serum AlAT and creatinine were also assessed. The dose of the 90-DOTA-TATE in NET patients was calculated according to the body surface area (BSA). The maximum dose did not exceed 7,4 GBq/m2 (200 mCi/m2) of BSA. In all patients the implementation of the therapeutic dose divided into 4 - 5 cycles were planed. ; 22 patients received planed treatment, 2 patients received the therapy divided into 3 cycles, the other 1 patient received 7 cycles. The most often instituted dose was 100 mCi per treatment cycle. The cycles were repeated every 4 to 9 week, most commonly every 6-7 week. Two hours before the injection of the labelled somatostatin analogue, the infusion of amino-acids formula was given to every patient for nephroprotection. The infusion time of the pre-prepared somatostatin analogue preparation labelled with radioisotope (manufacturer: Research and Development IAE Radioisotope Centre Otwock-Świerk) was 30 minutes. It was followed by 6-hour infusion of the amino-acids. The NHL patients received the dose of 90Y-Ibritumomab-tiuxetan (Zevalin) calculated based on the platelet count and body mass. If the platelet count (PLT) exceeded 150 000 per µl, the patient was administered 15 MBq (0,4 mCi) per kg of the body mass. If the PLT was within the range 100 000 – 150 000 per µl, the dose of 11 MBq (0,3 mCi) per kg of the body mass was given. The maximum dose was 1200 MBq (32 mCi). The radioimmunotherapy was preceded by Rituximab injection (250 mg per m2 of the BSA) administered one week earlier. Rituximab injection (the dose of 250 mg per m2 of the BSA) was repeated again 4 hours before the treatment with Zevalin. The preparation was labelled with Yttrium isotope in Nuclear Medicine Unit of the Endocrinology Department of University Hospital in Krakow. The radiochemical purity of the pharmaceutical was assessed after the labelling procedure, Zevalin was injected only when its purity was higher than 95%. Every patient with mantle cell lymphoma was given every 21 days 3 to 6 cycles of FCM+/-Rituximab chemotherapy. After first 3 cycles of the therapy the patient was qualified for radioimmunotherapy (RIT). If the patient did not fulfill the criteria for RIT, next 3 cycles of the therapy were given. Additional bridging dose of Rituximab was administered if the rise of neutrophil count or PLT count was not observed. The 90Y-Ibritumomab tiuxetan was not implemented in patients not meeting the criteria of the qualification. Statistical analysis was performed using STATISTICA PL (version 6.0) package. After the treatment in subgroup of NET patients no statistically important changes in creatinine level and GFR were observed. After 5 months an increase in creatinine level was noticed (from 73,37 µmol/l to 86,63 µmol/l). A slightly higher rise in creatinine levels was observed in a small subset of patients with longer, 24-month follow-up period. Mean creatinine level was 101,66 µmol/l. None of the patient showed the signs and symptoms related to the deterioration of the kidney function. However, literature data on the delayed nephrotoxicity suggest that the prolonged observation after the treatment with labelled somatostatin analogues is needed. Only minor changes in complete blood count (CBC) were seen after completion of the therapy. Mean haemoglobin level decreased after subsequent therapy cycles. The lowest mean values of haemoglobin (11,65 g/dL) were found during the 4 month after initiation of the treatment (mean pre-therapy level was 12,4 g/dL). Increase in haemoglobin level was observed 1 month after nadir values were reached. Normal haemoglobin levels or mild anaemia were present in most of the patients. 2 persons developed severe anaemia (3rd grade of toxicity) after 1 month after initiation of the treatment and after 3 cycle respectively. Similarly, after subsequent cycles of the therapy decrease in the PLT count was seen, but the mean values were within normal range. Only in 1 patient single measurement of PLT was assessed as the 3 grade toxicity according to WHO.The lowest values of white blood cell count (WBC) were seen after 3 and 4 cycle of the treatment. In the subgroup of NET patients WBC decreased by at least one toxicity grade according to WHO in 20 patients. No 4 grade toxicity was observed. Three patients developed 3 grade

Level of degree:

2 - studia doktoranckie

Degree discipline:

onkologia ; radiologia ; endokrynologia

Degree grantor:

Wydział Lekarski

Promoter:

Alicja Hubalewska-Dydejczyk

Date issued:

2008

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:1030

Call number:

ZB-107988

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nieograniczony

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego - Collegium Medicum

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Last modified:

Feb 12, 2020

In our library since:

Nov 21, 2012

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http://dl.cm-uj.krakow.pl:8080/publication/1030

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ZB-107988 Feb 12, 2020
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