20131225-

Cynthia asked a valid question in response to a prior blog post: what new treatments look most promising for relapsed metastatic alveolar rhabdomyosarcoma?

The most relevant answer is that the human relapsed rhabdomyosarcoma study ARST-0921 (bevacizumab vs temsirolimus) may have early results worth discussing with one's physician.

The second most relevant answer is that the human newly-diagnosed metastatic rhabdomyosarcoma trial ARST-08P1 will eventually have results concerning, among other questions, the value of IGF1R inhibitors.

More preliminary (pre-clinical) results come from an assortment of labs, often without the same kinds procedures used in deriving their results. Thus, it's hard to compare one lab's results to the others. Still, the best first place to go might be the Pediatric Preclinical Testing Program (sponsored by the National Cancer Institute's CTEP office) which is very consistent in the way they test drugs against rhabdomyosarcoma. Their results page is at http://pptp.nchresearch.org/comparison.html.

In evaluating results from a preclinical lab, the aRMS tumor lines Rh3 & Rh28, Rh30 and Rh41 apply most relavently to metastatic or relapsed aRMS. Rh3 and Rh28 are from the same patient but are lung and lymph node metastasis derived; Rh30 is from bone marrow metastasis at diagnosis; Rh30R is relapsed bone marrow metastasis; Rh41 is a post-treatment metastasis as well (probably from the lung).

A lot of lay press has followed conversation in the scientific journals who now have concerns that preclinical testing results (in petri dishes or in mice) are not reproducible. Many of these concerns are warranted. Standardization of the types of experiments performed are needed as much in rhabdomyosarcoma as in other types of research. These benchmarks might be determined by the researchers with input from the funding agencies as well as the journals (time for a Summit, perhaps?) As a potential funding agency, the community might itself have an influence to ask for studies using metastatic and/or relapsed cell lines and animal models, or even better, patient-derived xenograft mouse models from metastatic, relapsed tumors. And not just one model - but 5 or more distinct models (to ensure any result is consistent across the biological diversity of many patients).

In the absence of benchmarking, there is opinion based on the best possible assessment of existing preclinical data. Some recent publications (below) discuss these options.

Click here - http://www.ncbi.nlm.nih.gov/pubmed/?term=24326270

Click here - http://www.ncbi.nlm.nih.gov/pubmed/?term=23255356

Click here - http://www.ncbi.nlm.nih.gov/pubmed/?term=22378628

Click here - http://www.ncbi.nlm.nih.gov/pubmed/?term=23665679