Predict Glioma tese – pro
Going back years, the article by Schrag et al criticized the field of chemosensitivity and chemo resistance(SRA), concluding that these types of in vitro assays are not yet ready for prime time. The panel of authors attempted to present evidence that in vitro drug response assays should not be used clinically. This issue was first addressed by an exhaustive Medicare Coverage Advisory Committee (MCAC) in 1999. A panel of physicians selected by the Department of Health and Human Services reviewed hundreds of articles from the literature and heard two days of testimony by experts in the field in an open hearing. The panel voted unanimously that although chemosensitivity assays should not be covered, drug resistance assays should be paid for. This became a cause celebre with a vigorous debate in the literature and variant opinions offered by professional bodies. The American Society of Clinical Oncology vigorously objected and recommended: ”
The use of chemotherapy sensitivity and resistance assays to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting. Oncologists should make chemotherapy treatment recommendations on the basis of published reports of clinical trials and a patient’s health status and treatment preferences. Because the in vitro analytic strategy has potential importance, participation in clinical trials evaluating these technologies remains a priority.”
The scientific evidence consists of validation studies that generally support the ability of this test based on retrospective analyses. Lipnski did a study that prospectively flowed patients, but it was not a study of prospective assignment of therapy. Ldford pursued a similar approach in a 2024 article. These were predicitve studies, and a study that upfront randomized patients to different therapies based on the test results had not yet been done.
There is still an ongoing study, https://clinicaltrials.ucsf.edu/trial/NCT03561207, albeit it no longer accepts patients, rendering this an E.I approach. It is also registry study.
Stephen Shuford, Lindsay Lipinski, Ajay Abad, Ashley M Smith, Melissa Rayner, Lauren O’Donnell, Jeremy Stuart, Laszlo L Mechtler, Andrew J Fabiano, Jeff Edenfield, Charles Kanos, Stephen Gardner, Philip Hodge, Michael Lynn, Nicholas A Butowski, Seunggu J Han, Navid Redjal, Howland E Crosswell, Cecile Rose T Vibat, Lillia Holmes, Matthew Gevaert, Robert A Fenstermaker, Teresa M DesRochers, Prospective prediction of clinical drug response in high-grade gliomas using an ex vivo 3D cell culture assay, Neuro-Oncology Advances, Volume 3, Issue 1, January-December 2021
Schrag D, Garewal HS, Burstein HJ, et al: American Society of Clinical Oncology technology assessment: Chemotherapy sensitivity and resistance assays. J Clin Oncol 22 : 3631 -3638, 2004
Lindsay J. Lipinski et al, Clinical application of a functional 3D ex vivo test to predict therapeutic response in patients with HGG: A progression-free survival analysis. Journal of Clinical Oncology Volume 40, Number 16_suppl June 2022
Ledford, A., Rodriguez, A., Lipinski, L. et al. Functional prediction of response to therapy prior to therapeutic intervention is associated with improved survival in patients with high-grade glioma. Sci Rep 14, 19474 (2024).
Luckett PH, Olufawo M, Lamichhane B, Park KY, Dierker D, Verastegui GT, Yang P, Kim AH, Chheda MG, Snyder AZ, Shimony JS, Leuthardt EC. Predicting survival in glioblastoma with multimodal neuroimaging and machine learning. J Neurooncol. 2023 Sep;164(2):309-320.