PMC10282946_01
Radiological follow-up of breast lesion and metastases following IT-OV immunotherapy. PET/CT and CT images over the 17 months of treatment of four primary breast masses (A) and axillary lymph nodes (B) where intratumoral oncolytic virotherapy was administered, and two lung metastases (C, D). Graphic summary of chronological radiological pattern of hyperimmune response in the right chest wall, right axillary lymph node (LN) and right upper lung (RUL) nodules 1 and 2, as measured by PET (SUVmax) (see 
Figure 2
) (E).
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Re-assessment by PET/CT showed two sub-centimeter lung nodules in the right upper lobe, thus defining the tumor status as MBC ( Figure 1 ). PET/CT imaging showed typical radiological features of OV-associated immunotherapy ( Figure 1 ): After 3 and 6 months, increasing tumor size in CT and metabolic glucose uptake in PET were seen, followed by a steady decline in both parameters resulting radiologically in no evidence of disease (NED) ( Figures 1A, B ). The same response pattern was noted in PET analysis of the metastases, and manifested by increased standardized uptake values (SUV) in both lung nodules, showing mild metabolic uptake in lung nodules which were otherwise too small for PET resolution, likely reflecting a therapeutic abscopal effect ( Figures 1C, D ). Metabolic uptake in adjacent ribs showed the same chronological pattern, presumably reflecting systemic immune activation as seen in the bone marrow ( Figures 1B ,  2 ).
Hyperimmune reaction following IT-OV immunotherapy. Coronal PET showing an apparent OV-stimulated hyperimmune reaction in the local (A) and distant (B) lymph nodes (LN), in the liver-spleen (C), and in the axial skeleton (D). Graphic summary of chronological radiological pattern of the hyperimmune response, as measured by PET (SUVmax)
(E).
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Metabolic uptake in adjacent ribs showed the same chronological pattern, presumably reflecting systemic immune activation as seen in the bone marrow ( Figures 1B ,  2 ).
Immunological infiltration and necrotic/fibrotic changes after 9 months of intratumoral oncolytic virotherapy. (A) At diagnosis typical features of breast cancer are seen, with proliferation and mitotic cells (red arrows). (B) After 14 intratumoral oncolytic virotherapy administrations over 9 months some apoptotic tumor cells (white arrow) are seen along with a pronounced increase in the number of inflammatory cells, primarily in the tumor stroma, mainly lymphocytes and eosinophilic granulocytes (black arrows). Measuring bars equal 200microm. (C) Enlarged area from B with typical eosinophilic granulocytes.
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Comparison of biopsy after 9 months of IT-OV treatments to pre-treatment pathology illustrated infiltration of eosinophilic granulocytes along with some necrotic/fibrotic changes in the tumor mass ( Figure 3 ).