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The aim of the study is to evaluate the response to four schemes of treatment with novel diagnostic tools - Immuno-PET and proteomics as well as standard imaging (magnetic resonsonce imaging and computed tomography). Two fractionation schedules of radiotherapy will be used. The first will be a common standard of palliative irradiation - 20 Gy delivered in five fractions of 4 Gy (SHORT). The other is called Spatially Fractionated Radiotherapy (SFRT). SFRT is delivered in one fraction of 20 Gy but the dose is diversified inside the tumor to produce areas of high and low doses distributed alternately. This kind of irradiation may be able to stimulate immune response and improve the efficiency of immunotherapy. A drug belonging to the class of immunotherapeutic agents - Pembrolizumab will be added to the treatment scheme in two arms of the study to check that assumption. The response of the target tumor will be evaluated with PET study using Pembrolizumab labeled with zirconium-89 which will show the spatial distribution of immune receptors within the target tumor and other involved sites if there are any. The examination will be repeated after the treatment to evaluate changes in distribution of the immune receptors necessary for the drug to work. Additionally, the researchers will repeatedly test the presence and concentration of a wide panel of proteins in blood to evaluate response to the treatment more precisely.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SFRT with immunotherapy | Experimental |
| |
| SHORT with immunotherapy | Active Comparator |
| |
| SFRT | Experimental |
| |
| SHORT | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Baseline 89-Zr Pembrolizumab Immuno PET-CT | Diagnostic Test | Diagnostic imaging with novel radiotracer - drug (Pembrolizumab) labeled with zirconium-89 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in expression of PD-1 receptors expressed as a ratio of SUV values | The expression of PD-1 receptors will be measured with Immuno-PET basing on Zr-89 labeled Pembrolizumab and expressed as the ratio of initial and post-treatment SUV | one year |
| Change in number of areas with PD-1 receptors expressed as number of lesions | The localization of regions expressing PD-1 receptors will be identified with Immuno-PET basing on Zr-89 labeled Pembrolizumab and expressed as the number of lesions | one year |
| Change of proteome expression profile after treatment expressed in NPX (Normalized Protein eXpression) values | The difference between proteome expression profile before treatment and after the last infusion of Pembrolizumab or after a year in arms without immunotherapy. The Proximity Extension Assay (PEA) technology will be used. Following sequencing, the raw data will be converted to counts, assigning an integer value to each assay-sample combination based on the detected copy numbers. These raw data counts will be converted into NPX values, enabling the identification of protein level changes within different sample sets, and establishing protein signatures. | one year |
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Inclusion Criteria:
Exclusion criteria
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sławomir Blamek, MD, PhD, MBA | Contact | +48322788052 | slawomir.blamek@gliwice.nio.gov.pl | |
| Marzena Gawkowska, MD, PhD | Contact | +48322788625 | marzena.gawkowska@gliwice.nio.gov.pl |
| Name | Affiliation | Role |
|---|---|---|
| Sławomir Blamek, MD, PhD, MBA | Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch | Principal Investigator |
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The individual patient data can be shared upon request. The basic demographic data, type of intervention and outcome measures will be available.
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| Proteomic assay | Diagnostic Test | Assessment of the proteomic profile before and periodically after treatment |
|
| Follow-up 89-Zr Pembrolizumab Immuno PET-CT | Diagnostic Test | Diagnostic imaging with novel radiotracer - drug (Pembrolizumab) labeled with zirconium-89 after radiotherapy performed in patients who are not treated with immunotherapy |
|
| ID | Term |
|---|---|
| D064726 | Triple Negative Breast Neoplasms |
| D002583 | Uterine Cervical Neoplasms |
| D008545 | Melanoma |
| D002292 | Carcinoma, Renal Cell |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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