Patient-derived xenografts for individualized care in advanced sarcoma.
BACKGROUND
Patients with advanced, metastatic sarcoma have a poor prognosis, and the overall benefit from the few standard-of-care therapeutics available is small. The rarity of this tumor, combined with the wide range of subtypes, leads to difficulties in conducting clinical trials. The authors previously reported the outcome of patients with a variety of common solid tumors who received treatment with drug regimens that were first tested in patient-derived xenografts using a proprietary method ("TumorGrafts").


METHODS
Tumors resected from 29 patients with sarcoma were implanted into immunodeficient mice to identify drug targets and drugs for clinical use. The results of drug sensitivity testing in the TumorGrafts were used to personalize cancer treatment.


RESULTS
Of 29 implanted tumors, 22 (76%) successfully engrafted, permitting the identification of treatment regimens for these patients. Although 6 patients died before the completion of TumorGraft testing, a correlation between TumorGraft results and clinical outcome was observed in 13 of 16 (81%) of the remaining individuals. No patients progressed during the TumorGraft-predicted therapy.


CONCLUSIONS
The current data support the use of the personalized TumorGraft model as an investigational platform for therapeutic decision-making that can guide treatment for rare tumors such as sarcomas. A randomized phase 3 trial versus physician's choice is warranted.
Department of Oncology, Imperial College and Imperial Healthcare National Health Service Trust, Hammersmith Hospital, London, United Kingdom.
Justin
J
Stebbing
Keren
K
Paz
Gary K
GK
Schwartz
Leonard H
LH
Wexler
Robert
R
Maki
Raphael E
RE
Pollock
Ronnie
R
Morris
Richard
R
Cohen
Arjun
A
Shankar
Glen
G
Blackman
Victoria
V
Harding
David
D
Vasquez
Jonathan
J
Krell
Stergios
S
Zacharoulis
Daniel
D
Ciznadija
Amanda
A
Katz
David
D
Sidransky
D000368:Aged; D000818:Animals; D002648:Child; D002813:Chondrosarcoma / Q000601:surgery; D005260:Female; D064593:Heterografts; D006801:Humans; D007890:Leiomyosarcoma / Q000601:surgery; D008080:Liposarcoma / Q000601:surgery; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009232:Myxoma / Q000601:surgery; D057285:Precision Medicine / Q000379:methods*; D012208:Rhabdomyosarcoma / Q000601:surgery; D012509:Sarcoma / Q000235:genetics / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D012512:Sarcoma, Ewing / Q000601:surgery; D013584:Sarcoma, Synovial / Q000601:surgery; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
TumorGraft; biomarker; chemotherapy; mice; prediction; response; sarcoma; trial