Anastasia Zherlitsyna — timeline

		Helios Private Clinic Berlin-Buch
		Business premises of Helios Privatkliniken GmbH
	Helios Private Clinic Berlin-Buch Schwanebecker Chaussee 50 • 13125 Berlin Mr Nicolas Ziegenhagen Schwanebecker Chaussee 50 13125 Berlin
		Center for Haematology, Oncology and Palliative Medicine Clinic for Oncology and Palliative Medicine Chief Physician: Prof. Dr. medical Peter Reichardt Tel.: (030) 9401 - 54800 Fax.: (030) 9401 - 54809 E-Mail: peter.reichardt@helios-gesundheit.de
	Document date: 12.07.2023 Print date: 12.07.2023 Dear Mr Ziegenhagen, we report on our patient Zherlitsyna, Anastasiia, born on April 25, 1976, residing at Julii Zdanovskoi Street 26, 03022 Kiev, who was in our inpatient care from 26.06.2023 to 28.06.2023.

Diagnosis: Surgery: Tumor Formula: Histology: Immunohistochemistry: Molecular Pathology:	met. gastric GIST (HEP); ED 08/2022 no not present GIST (biopsy stomach/tail of pancreas RF) 04/2023 CD117, DOG1+, CD34+, SDH B+ Oncomine panel (tissue from 08/22): BRCA 1/2, CHEK2, PALB2 negative, KIT mut exon 11 (KIT Q556_V559DelinsHis mutation) so far 3 cases in the literature, KIF5B-MET translocation 284 copies/million; TMB 4.82 mut/Mb, MSS
Additional diagnoses:	Leiomyoma of the uterus Status after pazopanib-associated PRES 01/2023 - 2x grand mal, cerebral hemorrhages 01/2023 -currently 1 cm large post-hemorrhagic defect on the left occipital
Allergies:	not known
Date:	oncological course:
23.08.2022 24.08.2022 29.08.2022 09-12/22 10/2022	CT thorax/abdomen MRI Uterine leiomyosarcoma T2NxM1 (liver, sarcomatosis of the abdominal cavity, greater omentum) Biopsy liver: leiomyosarcoma 4 cycles Gemcitabine/Docetaxel Complication: psychosis under Dexamethasone MRI: Liver filiae, LL right S5/6 and 7 172x108mm, segment 8 82x61mm (77x51mm) and LLleft 75x57mm (66x42mm), tumor infiltrate in projection on left renal artery 74x60mm (53x58mm), uterus Rf 71x54x58mm (65x60x88mm)

11/2022 12/2022 12/2022 12/2022 04.01.2023 05.-12.01.2023 13.01.2023 09.02.2023 10.02.2023 13.02.2023 02.03.2023 09.03.2023 24.03.2023 11.04.2023 21.04.2023 25.04.2023 03.05.2023 since 05/2023 06/2023 01.06.2023 28.06.2023

2x ascites puncture CT-VK: Hepatic progression, peritoneal metastases in CR, Primarius stable failed liver biopsy Oncomine Panel (tissue from 08/22): BRCA 1/2, CHEK2, PALB2 negative, KIT mut exon 11 (KIT Q556_V559DelinsHis mutation) so far 3 cases in the literature !!!!! , KIF5B-MET translocation 284 copies/million; TMB 4.82 mut/Mb, MSS CT skull/thorax/abdomen: stable course compared to 12/22; Liver metastases and tumor mass in the area of the left mesogastrium and in projection on the right. Ovary, slight portal hypertension, sec. liver damage (!!) Pazopanib 800 mg daily Complication: loss of consciousness, 2x grand mal cMRI: PRES occipital, bihemispheric hemorrhage CT thorax/abdomen: hepatic metastases and RF regressing in the left mesogastrium 1.# cycle Trabectedin Complication: increase in transaminases 3x Fall on ice, fractured forearm 2.# cycle Trabectedin molecular tumor board Mainz: recommendation for therapy with Capmatinib or Imatinib 3.# cycle Trabectedin PET/CT: liver metastases LL right S5/6 and 7 with 19cm, Segment 8 101 mm and LL on the left with 75 mm, tumor between stomach/tail of pancreas slightly progressive with 58 mm and SUV increase (9-11); tumor manifestations of the uterus/ovary regressing with SUV Based on this assessment, the original histology of leiomyosarcoma was questioned repeat biopsy stomach/pancreas tail RF Immunohistochemistry: CD 117, DOG1+, CD34+, SDH B+ re-biopsy liver metastasis Immunohistochemistry: CD 117, DOG1+ Result: Revision of the diagnosis: GIST with KIT exon 11 mut., but also SDH deficiency detected (!) Tumor Conference (Issod Klinik/Israel): Report not available Beginning of Imatinib 400mg daily Revision: CT/MRI from 08/22: GIST of the stomach with Liver metastasis, incidental Leiomyoma uterus and endometrioma ovary on the right Reference histology of the first liver biopsy from 08/2023: IHC with CD 117 and DOG1+, SDH B deficiency thus confirming GIST CT thorax/abdomen: Largest in the right lobe of the liver up to 17 x 11 x 15 cm (4/105), further lesions here from cranial in liver segment VIII measuring approx. 75 x 52 mm (4/74) and approx. 52 x 39 mm measuring hypodense lesion in liver segment II Approx. 45 x 43 x 46 mm measuring hypodense lesion in the left upper abdomen with infiltration of the posterior gastric wall (4/107) and the duodenojejunal junction

Current:	CT follow-up: Large leiomyosarcoma in the cranial uterus as well as thickening of the cervical wall and suspected metastases in the ovarian algebra on both sides. 2. Extensive hepatic metastases in both lobes of the liver. 3. Extensive peritoneal metastases. Additional metastasis in the area of the dorsal gastric wall. MRI follow-up: no (oedematous) signs of activity, probably after PRES. Almost 1 cm large post-hemorrhagic defect on the left occipital and residual blood deposits on both sides frontal, well compatible with a status n. PRES with bleeding. Sarcoma conference: based on the available written findings (PET/CT as well as pathological assessments), the revision of the leiomyosarcoma into a GIST seems conclusive. Thus recommendation to continue therapy with imatinib. In principle, however, the patient was offered a new histological confirmation for independent analysis by our pathology colleagues. The patient decided to send the tissue material that would soon be available to her for further analysis.
Procedure:	Continuation of therapy with Imatinib 400 mg daily. Re-presentation of the patient for clinical and imaging follow-up in 3 months at the earliest after making an appointment via international patient management.

Anamnese:

The patient was admitted to hospital after obtaining a second opinion after a recent revision of the diagnosis of a metastatic leiomyosarcoma of the uterus originally made in 08/2022 into a metastatic GIST of the stomach. Ms. Zherlitsyna is in a stable general condition. Oral medication with Imatinib 400 mg daily is currently taking place. The patient experiences fatigue as a result. There is currently no fever or other signs of infection.

Physical state:

Generally:	Alert, cooperative, oriented to all qualities, EZ normal, AZ good.
Head/Neck:	Oral cavity, pharynx irritation-free, no cerv. LKS, pupils isocor, LR on both sides promptly
Pulmonary:	VAG bds, no RGs, no spasticity.
Cor:	Rhythmic, normal frequency
Abdomen:	Soft, no DS, DG sparse in all quadrants
Extremities:	Slim, warm.
Skin:	No efflorescens
Neurology:	No focal neurological deficit.

Therapy and progress:

The CT and MRT follow-up was carried out. Here, advanced abdominal tumor development is evident. Furthermore, according to the medical history of a PRES 01/2023, there was a residual hemorrhagic defect on the left occipital of approx. 1 cm.

We discussed the available imaging in our sarcoma conference in synopsis of the submitted external reports. Unfortunately, due to a lack of data, it was not possible to compare our imaging presentation with preliminary examinations, so that an assessment of the course after around 6 weeks of Imatinib therapy could not be made. From the point of view of our colleagues in radiology, however, the image morphology of the appearance of a GIST of the stomach plus hepatic and peritoneal metastases is very compatible with the current revision of the histology. The tumor findings on the uterus do not allow any further classification on the basis of CT morphology, but from our point of view the differentiation of these structures from the tumor findings of the upper abdomen in the context of PET/CT appears with a. e. Leiomyomas of the uterus understandable. Unfortunately, the external PET/CT was not available to us in digitized form, so that only the written report was evaluated here.

Likewise, no independent histological or immunohistochemical assessment of the externally removed tumor material could be carried out. At this point, too, our assessment was based on the submitted external reports, which we also judged to be conclusive.

We therefore recommended continuation of therapy with Imatinib. After a detailed discussion of our assessment, the patient rejected the immediately offered options for a new punch biopsy and histological analysis. However, she will endeavor to make the materials already taken available to our clinic for reference pathological assessment.

We discharge the patient in stable general condition to your valued outpatient care. A re-presentation of the patient for clinical and imaging follow-up is to be planned in about 3 months. Please make an appointment for this via international patient management. If you have any questions, we are always at your disposal under the telephone number: 030/9401-7966. Laboratory tests or written documents may be sent to the email address MFA.Onkologie-Buch@helios-gesundheit.de or by fax to: 030/755 455-7069. Thanks very much!

Medication orally	Dosing	Indication	Application
Imatinib	400mg	GIST	1-0-0
Apixaban	2,5mg		1-0-1

Emergency medication:	Dosing	Indication	Application
Ondansetron	8mg	Nausea	1-2x daily
Dimenhydrinat	50mg	Nausea	1-3x daily

Best regards,

Prof. Dr. medical Peter Reichardt Chief Physician	Nicholas Ziegenhagen Senior Physician

Attachment:

cran. MRT native + KM i.v. + Reko from 28.06.2023

Leiomyosarcoma of the uterus T2NxM1 (liver, peritoneum). Pres diagn. Jan. 2023 under TKI - follow-up requested There is no preliminary study available for comparison.

Brainstem and cerebellum with proper signaling. Cerebellopontine angle unremarkable. 4. Ventricle normally wide. Free basal cisterns. Age-appropriate width of the inner and outer liquor spaces, no liquor accumulation. Normal pith-cortical differentiation. Left occipital 9 mm large T2 hyperintense lesion left occipital with adjacent, presumably gliotic perifocal signal increase and cortical defect, central annular T1 native hyperintense border. No contrast enhancement. No edematous changes. Ring-shaped susceptibility artefact of about 1 cm in size in this region. Intersulcal susceptibility artifacts on both sides frontal. No diffusion disturbance. Normal formation and free pneumatization of the paranasal sinuses, slight swelling of the mucous membrane in the mastoid cells on both sides of the posterobasal. No preliminary study for comparison. With probably Z.n. PRES no (oedematous) signs of activity. Almost 1 cm large posthemorrhagic defect on the left occipital and residual blood deposits on both sides frontal, well compatible with a condition after PRES with bleeding.

CT thorax/abdomen + KM 2 series from 28.06.2023

Thorax: Inserted port catheter on the right pectoral with tip in the VCS. Thoracic soft-tissue coat proper. No pathologically enlarged thoracic lymph nodes. No central LAE. No pericardial effusion. No pleural effusions. Regular contrasting of the supraaortic vessels. No pneumonic consolidations. No pneumothorax. Bullous changes in the right upper lobe apical dorsal (5/15). Bullous changes also in the left upper lobe (8/49). Bipulmonary micronodules, exemplary micronodules in the right upper lobe ventral (8/78), another micronodules in the right upper lobe dorsal (8/61) peri-fissural micronodules in the lower lobe on the right (8/180). Another micro nodulus in the left lower lobe (8/84). No pulmonary nodules.

Abdomen:

Abdominal soft tissue coat proper. No significant amount of free fluid intra-abdominal. No free air intra-abdominal. Liver with multiple low-density, partially septated liver lesions, the largest in the right liver lobe measuring up to 17 x 11 x 15 cm (4/105), further lesions of this cranial in liver segment VIII measuring approx. 75 x 52 mm (4/74) and a hypodense lesion measuring approx. 52 x 39 mm in liver segment II (4/89).

Another small hypodense liver lesion in the caudate lobe measuring approx. 15 mm (4/82). Multiple other small hypodense liver lesions accentuated in the right lobe of the liver. No signs of cholestasis. hepatomegaly. Gallbladder not delimitable. Pancreatic parenchyma literally. spleen unremarkable. Adrenal gland plump on the left Adrenal gland slim on the right. Kidneys on both sides are orthotopic. Normal corticomedullary differentiation. No urinary retention. Bladder moderately full. No wall thickening. Uterus with clearly inhomogeneous contrasting anteflected and cranial inhomogeneous mass measuring approx. 82 x 53 mm, partly with low-density liquid parts (4/150), measuring approx. 29 x 28 mm inhomogeneous to the uterus corpus slightly hypodense lesion on the right in the uterus (4/168) also inhomogeneous contrasting and thickening of the cervix uteri additionally right dorsal in the Ovarian allologist low-dense mass measuring approx. 59 x 50 mm (4/158) but also small septated low-dense lesions in the left ovarian allologist (10/67). Approx. 45 x 43 x 46 mm measuring hypodense lesion in the left upper abdomen with infiltration of the gastric posterior wall (4/107) and the duodenojejunal transition (4/110), the rest of the gastrointestinal tract with partly stool-filled, non-irritated colon framework and fluid-filled small bowel loops. No pathologically enlarged abdominal lymph nodes. Regular contrasting of the large abdominal vessels.

Skeleton: No fresh fracture. No osteodestructions suspected of being malignant. No higher grade degenerative changes.

1. Large leiomyosarcoma in the cranial uterus and thickening of the cervical wall and suspected metastases in the ovarian alogue on both sides.

2. Extensive hepatic metastases in both lobes of the liver.

3. Extensive peritoneal metastases. Additional metastasis in the area of the dorsal gastric wall.

4. No pulmonary nodules.

NB: Gallbladder not delimitable. Bullous changes in the upper lobe apically on both sides