Molecular and Whole-body MR Imaging in Lymphomas (MILY)

June 18, 2019 updated by: Heikki Minn, Turku University Hospital

Lymphomas are classified as Hodgkin's or non-Hodgkin's lymphomas, of which especially the latter represent a heterogeneous group with varying patterns of prognosis, biological behaviour and response to treatment. 18F-FDG PET/CT is useful for staging and response monitoring but has the disadvantage of associated radiation exposure which may not be desirable for young patients. Advanced MRI techniques including diffusion weighted imaging (DWI) are increasingly used for improved lesion detection and characterisation of lymphomas and in the whole-body mode offer a promising radiation-free alternative to CT. Molecular imaging in turn is important in theranostics medicine where detection of therapeutic target is essential. The concept of theranostics has been successfully adapted to management of neuroendocrine tumors (NET) where peptide receptor radiotherapy (PRRT) is offered to patients progressing on treatment with long-acting somatostatin analogues.

Recently in the investigator's hospital a case of diffuse large B-cell lymphoma (DLBCL) was initially misdiagnosed as NET because of high uptake of 68Ga-DOTANOC in pancreatic tumor at PET/CT. A PubMed search revealed a similar case report in bronchial tumor which turned out to be DLBCL (Jain et al. Clin Nucl Med 2014;39:358-359). Bearing these two cases in mind the investigators now aim to systematically study somatostatin receptor status (ssr) by measuring uptake of 68Ga-DOTANOC with PET/CT in patients with newly diagnosed non-Hodgkin's and Hodgkin's lymphoma. The imaging findings will be compared to immunohistochemically determined ssr-subtypes 2,3 and 5 obtained from pre-treatment fresh tumor samples and 18F-FDG PET/CT which is part of standard diagnostic evaluation. Furthermore, whole-body MRI with DWI will be performed before, during and after chemotherapy to define the most sensitive and specific imaging method appropriate for routine diagnosis and follow-up. This study has potential implications for future response monitoring and follow-up imaging techniques in patients with malignant lymphoma and provides additional biologic characterization which may be useful for novel therapeutic approaches such as PRRT.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Lymphomas are malignant tumours of the immune system. Lymphomas are classified as Hodgkin's or non-Hodgkin's lymphomas with several subtypes. In Finland the amount of newly diagnosed Hodgkin's lymphomas is 120-150 new cases per year and it accounts for 12 % of all lymphomas. Non-Hodgkin's lymphoma is the sixth most common cancer in men and the eight most common cancer in women in Finland. There are approximately 1200 new cases per year and the incidence has been increasing during the last decade. (1, 2)

Etiology of lymphomas is mostly unknown but many risk factors have been identified. Diagnostics and classification to different subgroups is based on clinical, pathological, molecular, and radiological studies. Some of lymphoma's subtypes can be cured with current treatment methods, however, many of them remain still incurable. (1) Clearly, more accurate diagnostic tools with subsequent targeted therapies against lymphomas are needed.

Somatostatin receptors (SSTs) are expressed by a wide variety of different tumour cell types, including malignant lymphomas. (8, 9, 10, 11) Somatostatin receptor imaging by octreotide scintigraphy has showed a sensitivity of 95-100 % in Hodgkin's lymphoma and 80 % in non-Hodgkin's lymphoma. However, somatostatin receptor scintigraphy does not appear to have a significant role in diagnostic process because of the relatively low uptake of the used somatostatin analogue (octreotide) and limited sensitivity of the single photon emission computed tomography (SPECT) acquisition to detect and localise small involved nodes. (11, 25) Hence, somatostatin receptor imaging has been further developed with the advent of hybrid SPECT and positron emission tomography (PET) and computed tomography (CT) scanners. Several other radioligands have been studied to improve the binding affinity (15). This has also offered a new target for tumor cell-specific therapy using different somatostatin analogs labelled with therapeutic radionuclides such as 90Y-DOTATOC, a somatostatin receptor subtype 2 (SST2) -specific ligand. Clinical studies of peptide receptor radionuclide therapy (PRRT) have extensively focused on neuroendocrine tumors as a palliative treatment modality (12, 13, 14). Another new candidate for SST based imaging and treatment is 68Ga-DOTANOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 (SST2, SST3, SST5) (16). Neuroendocrine tumors are known to express SST2 and they show high uptake of radiolabeled somatostatin analogs on PET. However, lymphomas may mimick NETs on DOTANOC PET/CT as was shown in a recent case report (17). Therefore, further studies on SST2 status and DOTANOC uptake are in order to establish the role of peptide based imaging in diagnosis and possible PRRT in lymphomas.

The aim of the study is to determine tumor uptake of 68Ga-DOTANOC in patients with non-Hodgkin's and Hodgkin's lymphoma to characterize the SST2, SST3 and SST5 receptor status of the tumour in vivo with 68Ga-DOTANOC PET/CT. In addition, immunohistochemical analysis of SST2, SST3 and SST5 subtype status will be made of the tumor specimens obtained in routine diagnostic biopsy resection. Furthermore, PET findings will be correlated with advanced MRI techniques, such as diffusion weighted imaging (DWI) in an attempt to find methods which limit radiation exposure especially in young patients. Hence, PET/CT will be performed with 68Ga-DOTANOC and 18F-FDG and compared with whole-body MRI (including DWI) to define the most sensitive and specific imaging method appropriate for routine diagnosis and follow-up of patients with lymphoma.

To the investigators knowledge, no prospective studies comparing octreodite analogue based PET/CT imaging with standard diagnostic procedures have been published until now. PET/CT offers a clear advantage over scintigraphy in terms of sensitivity and resolution which should be helpful in determining the SST status of various histologic forms of lymphomas The investigators hypothesize that a positive 68Ga-DOTANOC PET/CT scan correlates with the overexpression of all or some SST subtypes in lymphomas, which is possibly linked to a more indolent behavior of the disease. Furthermore, it is hypothesized that 68Ga-DOTANOC PET/CT imaging provides a valid method to select patients with lymphoma for radionuclide therapy with 177Lu-DOTATATE. Third, differential diagnosis with NETs may also improve after receiving information on SST status in lymphomas. Thus findings in this study may be useful not only for biologic characterization but also for diagnosis and management of these heterogenous diseases originating in the lymphatic system

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Finland
      • Turku, Finland, 20521
        • Turku University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age: 18-75 years old
  • Language spoken: Finnish or Swedish
  • Patients with diagnosed untreated non-Hodgkin's or Hodgkin's lymphoma with measurable disease (the diagnosis is based on radiological, histological and clinical grounds)
  • Before treatment CT and FDG-PET performed
  • Mental status: Patients must be able to understand the meaning of the study
  • The patient signs the appropriate Ethical Committee (EC) approved informed consent documents in the presence of the designated staff

Exclusion Criteria:

  • Any medical or psychiatric condition that compromises the subject's ability to participate in the study
  • Any other significant disease including liver or renal disease
  • Pregnant or lactating women
  • Contraindications for MR imaging

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lymphoma
Newly diagnosed lymphoma, all subtypes allowed
Other: 68Ga-DOTANOC PET/CT; Diffusion weighted MRI
PET/CT: Radionuclide imaging using short-lived isotope Ga-68; MRI imaging w/o gadolinium contrast

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
68Ga-DOTANOC Uptake in Lymphomas With PET/CT
Time Frame: Within 30 days prior to start of chemotherapy
Uptake of 68Ga-DOTANOC in lymphoma expressed as SUVmax
Within 30 days prior to start of chemotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Turku University Hospital

Investigators

  • Study Chair: Juhani Knuuti, M.D., Ph.D., Turku PET Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2014

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

September 1, 2016

Study Registration Dates

First Submitted

October 22, 2014

First Submitted That Met QC Criteria

March 9, 2015

First Posted (Estimate)

March 17, 2015

Study Record Updates

Last Update Posted (Actual)

August 5, 2019

Last Update Submitted That Met QC Criteria

June 18, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • T164/2014

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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