Lessons Learned.
Percutaneous thermal ablation combined with in situ granulocyte‐macrophage colony‐stimulating factor cytokine therapy was technically feasible and well tolerated.No significant clinical or immunologic responses were seen.Background.Melanoma tumor‐derived heat‐shock proteins (HSPs) and HSP‐peptide complexes can elicit protective antitumor responses. The granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) chemokine can also promote uptake and processing by professional antigen presenting cells (APCs). On this basis, we designed a pilot study of percutaneous thermal ablation as a means to induce heat‐shock protein vaccination plus GM‐CSF to determine safety and preliminary antitumor activity of this combination.Materials and Methods.This study was designed to assess overall safety of percutaneous ablation combined with GM‐CSF for unresectable, metastatic melanoma including uveal and mucosal types. All patients received heat‐shock therapy (42°C for 30 minutes), then received one of three treatments: (a) intralesional GM‐CSF (500 mcg standard dose); (b) radiofrequency ablation (RFA) + GM‐CSF; or (c) cryoablation plus GM‐CSF. The primary endpoint of the study was the induction of endogenous HSP70 and melanoma‐specific cytotoxic T lymphocytes (CTL).Results.Nine patients (three per study arm) were enrolled. No dose‐limiting toxicity was observed as specified per protocol. All patients developed progressive disease and went on to receive alternative therapy. Median overall survival (OS) was 8.2 months (95% confidence interval [CI] 2–17.2). The study was not powered to detect a difference in clinical outcome among treatment groups.Conclusion.Percutaneous thermal ablation plus GM‐CSF was well tolerated, technically feasible, and demonstrated an acceptable adverse event profile comparable to conventional RFA and cryoablation. While HSP70 was induced following therapy, the degree of HSP70 elevation was not associated with clinical outcome or induced CTL responses. While percutaneous thermal ablation plus GM‐CSF combinations including checkpoint inhibitors could be considered in future studies, the use of GM‐CSF remains experimental and for use in the context of clinical trials.
Bristol-Myers Squibb; and ownership interest with Tetralogic Pharmaceuticals. Reviewers "A" and "B" disclose no financial relationships. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. On the basis of disclosed information, all conflicts of interest have been resolved.
LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Explain the difference in survival prediction between response criteria (WHO) when used as a two-level variable (CR/PR vs. other) and as a three-level variable (CR/PR vs. SD vs. PD).2. Describe the limited benefit of using actual tumor measurements over traditional criteria (as a three-level variable) in predicting survival in colorectal cancer.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME Results. Tumor status at 12 weeks by WHO criteria (three or two levels) or actual TM were all strongly associated with OS. Actual TM provided no meaningful additional benefit compared with the three-level WHO criteria. Tumor status at 24 weeks was also strongly associated with survival, but added no additional prognostic value compared with the 12-week assessment. At 12 weeks, actual TM improved prognostic characterization of patients with WHO status of response, but provided no additional value in patients with stable disease or progression.
ABSTRACTConclusions. In N9741, the use of actual TM, or following tumor status beyond 12 weeks, did not improve survival prediction compared with a single three-level response assessment at 12 weeks, suggesting that 12-week tumor status could be an appropriate phase II trial endpoint in metastatic CRC. The Oncologist 2011;16:859 -867
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