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Case Reports
. 2021 Oct 27:5:PO.20.00438.
doi: 10.1200/PO.20.00438. eCollection 2021.

Clinical Utility of Functional Precision Medicine in the Management of Recurrent/Relapsed Childhood Rhabdomyosarcoma

Arlet M Acanda De La Rocha  1 , Maggie Fader  2   3 , Ebony R Coats  1 , Paula S Espinal  2 , Vanessa Berrios  1 , Cima Saghira  4 , Ileana Sotto  2 , Rojesh Shakya  1 , Michelin Janvier  2 , Ziad Khatib  2   3 , Haneen Abdella  2   3 , Mathew Bittle  2 , Cristina M Andrade-Feraud  1 , Tomás R Guilarte  1 , Jennifer McCafferty-Fernandez  2 , Daria Salyakina  2 , Diana J Azzam  1
Affiliations
Case Reports

Clinical Utility of Functional Precision Medicine in the Management of Recurrent/Relapsed Childhood Rhabdomyosarcoma

Arlet M Acanda De La Rocha et al. JCO Precis Oncol. .
No abstract available

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Conflict of interest statement

Maggie Fader Employment: Kidz Medical Services, Inc Travel, Accommodations, Expenses: Kidz Medical Services No other potential conflicts of interest were reported. Maggie Fader Employment: Kidz Medical Services, Inc Travel, Accommodations, Expenses: Kidz Medical Services No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Functional precision medicine in the management of recurrent childhood cancers. Illustration of our functional precision medicine program depicting the workflow, beginning with the sample collection, and processing, continuing with the establishment of patient-derived tumor cells that are subjected to single drug testing. In parallel, DNA is sent for targeted gene sequencing (UCSF500). The DSS are reported back to the MTB within 5-10 days, whereas the sequencing data take up to 3 weeks. The MTB reviews the data, likely off-label availability for candidate drugs, prior experience with candidate drugs, and treatment history of each patient. A final list of therapeutic options (ranked in order of preference together with suggested doses and schedules) is issued, and patients are treated with the best recommendations whenever possible. DSS, drug sensitivity score; MTB, Molecular Tumor Board.
FIG 2.
FIG 2.
Clinical course and response images of relapsed SRMS patient. Upper panel shows the timeline of treatments after relapse and progression in the patient. PET scans were obtained at relapse (January 2019) and after regimen 3 (March 2019), as well as before (April 2019) and after (June 2019) fourth-line DST-guided therapy. Before DST-guided therapy, there was progressive disease with PET demonstrating a large, FDG-avid right mass in the lower extremity with a right pelvic mass, right thigh lymph node, and right lung nodule (April 2019). PET scan obtained after 8 weeks of DST-guided therapy in June 2019 (vincristine in combination with irinotecan and temozolomide) demonstrated significantly decreased size of ill-defined soft tissue mass seen encasing the femoral neurovascular bundle (residual lower-level FDG uptake in the right thigh). In addition, interval improvement was observed in disease burden with residual masses throughout liver parenchyma, pancreatic head, and body as well as stable right middle lobe pulmonary nodule. Bottom panel shows results from our functional precision medicine platform (molecular tumor analysis and drug sensitivity testing) on the recurrent tumor. D, day; DST, drug sensitivity testing; FDG, fluorodeoxyglucose; FIU, Florida International University; IV, intravenous; NA, not available; PET, positron emission tomography; PFS, progression-free survival; SBRT, stereotactic body radiation therapy; SRMS, sclerosing and spindle cell rhabdomyosarcoma.
FIG 3.
FIG 3.
Ex vivo drug sensitivity results identify top effective drugs for treatment. (A) Representative image of original RMS tumor (left) and patient-derived tumor cells (right) as visualized under light microscope. Scale bars represent 400 µm, magnification 10×. (B) Immunohistochemical staining from the tumor tissue, H&E (left), myogenin (middle), and desmin (right) magnification 100×. (C) Immunofluorescence images show patient-derived cells express RMS markers, myogenin and desmin, scale bar is 20 µm, magnification 144×. (D) Top panel shows graph plot that highlights the most effective and potent drugs on the DST performed. Drugs selected for therapy are highlighted in red boxes. The bottom panel shows dose-response curves of vincristine and irinotecan. (E) The top panel shows most effective combination drugs including irinotecan and temozolomide in combination, as well as vincristine as a single agent (red boxes). The bottom panel shows the dose-response curves of the selected drugs highlighted in red boxes. The patient treatment regimen was modified based on DST results. DAPI, 4’,6-diamidino-2-phenylindole; DSS, drug sensitivity score; DST, drug sensitivity testing; H&E, hematoxylin and eosin; RMS, rhabdomyosarcoma.
See this image and copyright information in PMC

References

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