The application of radiation therapy to the pediatric preclinical testing program (PPTP): Results of a pilot study in rhabdomyosarcoma

Rita Kaplon, Mersiha Hadziahmetovic, Jim Sommerfeld, Kathryn Bondra, Lanchun Lu, Justin Leasure, Phuong Nguyen, Kelsey McHugh, Ning Li, Christopher Chronowski, Nikhil Sebastian, Mamta Singh, Raushan Kurmasheva, Peter J Houghton, Christopher E. Pelloski

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: The Pediatric Preclinical Testing Program (PPTP) has been successfully used to determine the efficacy of novel agents against solid tumors by testing them within a mouse-flank in vivo model. To date, radiation therapy has not been applied to this system. We report on the feasibility and biologic outcomes of a pilot study using alveolar and embryonal rhabdomyosarcoma xenograft lines. Procedures: We developed a high-throughput mouse-flank irradiation device that allows the safe delivery of radiotherapy in clinically relevant doses. For our pilot study, two rhabdomyosarcoma xenograft lines from the PPTP, Rh30 (alveolar) and Rh18 (embryonal) were selected. Using established methods, xenografts were implanted, grown to appropriate volumes, and were subjected to fractionated radiotherapy. Tumor response-rates, growth kinetics, and event-free survival time were measured. Results: Once optimized, the rate of acute toxicity requiring early removal from study in 93 mice was only 3%. During the optimization phase, it was observed that the alveolar Rh30 xenograft line demonstrated a significantly greater radiation resistance than embryonal Rh18 in vivo. This finding was validated within the standardized 30Gy treatment phase, resulting in overall treatment failure rates of 10% versus 60% for the embryonal versus alveolar subtype, respectively. Conclusions: Our pilot study demonstrated the feasibility of our device which enables safe, clinically relevant focal radiation delivery to immunocompromised mice. It further recapitulated the expected clinical radiobiology.

Original languageEnglish (US)
Pages (from-to)377-382
Number of pages6
JournalPediatric Blood and Cancer
Volume60
Issue number3
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

Fingerprint

Rhabdomyosarcoma
Heterografts
Radiotherapy
Pediatrics
Alveolar Rhabdomyosarcoma
Embryonal Rhabdomyosarcoma
Radiation
Radiobiology
Equipment and Supplies
Treatment Failure
Disease-Free Survival
Neoplasms
Growth
Therapeutics

Keywords

  • Fractionated radiotherapy
  • PPTP
  • Preclinical testing
  • Rhabdomyosarcoma
  • Xenograft

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Kaplon, R., Hadziahmetovic, M., Sommerfeld, J., Bondra, K., Lu, L., Leasure, J., ... Pelloski, C. E. (2013). The application of radiation therapy to the pediatric preclinical testing program (PPTP): Results of a pilot study in rhabdomyosarcoma. Pediatric Blood and Cancer, 60(3), 377-382. https://doi.org/10.1002/pbc.24210

The application of radiation therapy to the pediatric preclinical testing program (PPTP) : Results of a pilot study in rhabdomyosarcoma. / Kaplon, Rita; Hadziahmetovic, Mersiha; Sommerfeld, Jim; Bondra, Kathryn; Lu, Lanchun; Leasure, Justin; Nguyen, Phuong; McHugh, Kelsey; Li, Ning; Chronowski, Christopher; Sebastian, Nikhil; Singh, Mamta; Kurmasheva, Raushan; Houghton, Peter J; Pelloski, Christopher E.

In: Pediatric Blood and Cancer, Vol. 60, No. 3, 01.03.2013, p. 377-382.

Research output: Contribution to journalArticle

Kaplon, R, Hadziahmetovic, M, Sommerfeld, J, Bondra, K, Lu, L, Leasure, J, Nguyen, P, McHugh, K, Li, N, Chronowski, C, Sebastian, N, Singh, M, Kurmasheva, R, Houghton, PJ & Pelloski, CE 2013, 'The application of radiation therapy to the pediatric preclinical testing program (PPTP): Results of a pilot study in rhabdomyosarcoma', Pediatric Blood and Cancer, vol. 60, no. 3, pp. 377-382. https://doi.org/10.1002/pbc.24210
Kaplon, Rita ; Hadziahmetovic, Mersiha ; Sommerfeld, Jim ; Bondra, Kathryn ; Lu, Lanchun ; Leasure, Justin ; Nguyen, Phuong ; McHugh, Kelsey ; Li, Ning ; Chronowski, Christopher ; Sebastian, Nikhil ; Singh, Mamta ; Kurmasheva, Raushan ; Houghton, Peter J ; Pelloski, Christopher E. / The application of radiation therapy to the pediatric preclinical testing program (PPTP) : Results of a pilot study in rhabdomyosarcoma. In: Pediatric Blood and Cancer. 2013 ; Vol. 60, No. 3. pp. 377-382.
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AU - Bondra, Kathryn

AU - Lu, Lanchun

AU - Leasure, Justin

AU - Nguyen, Phuong

AU - McHugh, Kelsey

AU - Li, Ning

AU - Chronowski, Christopher

AU - Sebastian, Nikhil

AU - Singh, Mamta

AU - Kurmasheva, Raushan

AU - Houghton, Peter J

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N2 - Background: The Pediatric Preclinical Testing Program (PPTP) has been successfully used to determine the efficacy of novel agents against solid tumors by testing them within a mouse-flank in vivo model. To date, radiation therapy has not been applied to this system. We report on the feasibility and biologic outcomes of a pilot study using alveolar and embryonal rhabdomyosarcoma xenograft lines. Procedures: We developed a high-throughput mouse-flank irradiation device that allows the safe delivery of radiotherapy in clinically relevant doses. For our pilot study, two rhabdomyosarcoma xenograft lines from the PPTP, Rh30 (alveolar) and Rh18 (embryonal) were selected. Using established methods, xenografts were implanted, grown to appropriate volumes, and were subjected to fractionated radiotherapy. Tumor response-rates, growth kinetics, and event-free survival time were measured. Results: Once optimized, the rate of acute toxicity requiring early removal from study in 93 mice was only 3%. During the optimization phase, it was observed that the alveolar Rh30 xenograft line demonstrated a significantly greater radiation resistance than embryonal Rh18 in vivo. This finding was validated within the standardized 30Gy treatment phase, resulting in overall treatment failure rates of 10% versus 60% for the embryonal versus alveolar subtype, respectively. Conclusions: Our pilot study demonstrated the feasibility of our device which enables safe, clinically relevant focal radiation delivery to immunocompromised mice. It further recapitulated the expected clinical radiobiology.

AB - Background: The Pediatric Preclinical Testing Program (PPTP) has been successfully used to determine the efficacy of novel agents against solid tumors by testing them within a mouse-flank in vivo model. To date, radiation therapy has not been applied to this system. We report on the feasibility and biologic outcomes of a pilot study using alveolar and embryonal rhabdomyosarcoma xenograft lines. Procedures: We developed a high-throughput mouse-flank irradiation device that allows the safe delivery of radiotherapy in clinically relevant doses. For our pilot study, two rhabdomyosarcoma xenograft lines from the PPTP, Rh30 (alveolar) and Rh18 (embryonal) were selected. Using established methods, xenografts were implanted, grown to appropriate volumes, and were subjected to fractionated radiotherapy. Tumor response-rates, growth kinetics, and event-free survival time were measured. Results: Once optimized, the rate of acute toxicity requiring early removal from study in 93 mice was only 3%. During the optimization phase, it was observed that the alveolar Rh30 xenograft line demonstrated a significantly greater radiation resistance than embryonal Rh18 in vivo. This finding was validated within the standardized 30Gy treatment phase, resulting in overall treatment failure rates of 10% versus 60% for the embryonal versus alveolar subtype, respectively. Conclusions: Our pilot study demonstrated the feasibility of our device which enables safe, clinically relevant focal radiation delivery to immunocompromised mice. It further recapitulated the expected clinical radiobiology.

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