Endogenous heat-shock protein induction with or without radiofrequency ablation or cryoablation in patients with stage IV melanoma

Evidio Domingo-Musibay, James M. Heun, Wendy K. Nevala, Matthew R Callstrom, Thomas Atwell, Evanthia Galanis, Lori A. Erickson, Svetomir Nenad Markovic

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalOncologist
Volume22
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Cryosurgery
Heat-Shock Proteins
Melanoma
Hot Temperature
Cytotoxic T-Lymphocytes
Safety
Antigen-Presenting Cells
Complementary Therapies
Chemokines
Vaccination
Proteins
Therapeutics
Clinical Trials
Confidence Intervals
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Endogenous heat-shock protein induction with or without radiofrequency ablation or cryoablation in patients with stage IV melanoma. / Domingo-Musibay, Evidio; Heun, James M.; Nevala, Wendy K.; Callstrom, Matthew R; Atwell, Thomas; Galanis, Evanthia; Erickson, Lori A.; Markovic, Svetomir Nenad.

In: Oncologist, Vol. 22, No. 9, 01.09.2017.

Research output: Contribution to journalArticle

@article{a17f5a3dc47342dc8e0e91479d120265,
title = "Endogenous heat-shock protein induction with or without radiofrequency ablation or cryoablation in patients with stage IV melanoma",
abstract = "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.",
author = "Evidio Domingo-Musibay and Heun, {James M.} and Nevala, {Wendy K.} and Callstrom, {Matthew R} and Thomas Atwell and Evanthia Galanis and Erickson, {Lori A.} and Markovic, {Svetomir Nenad}",
year = "2017",
month = "9",
day = "1",
doi = "10.1634/theoncologist.2017-0060",
language = "English (US)",
volume = "22",
journal = "Oncologist",
issn = "1083-7159",
publisher = "AlphaMed Press",
number = "9",

}

TY - JOUR

T1 - Endogenous heat-shock protein induction with or without radiofrequency ablation or cryoablation in patients with stage IV melanoma

AU - Domingo-Musibay, Evidio

AU - Heun, James M.

AU - Nevala, Wendy K.

AU - Callstrom, Matthew R

AU - Atwell, Thomas

AU - Galanis, Evanthia

AU - Erickson, Lori A.

AU - Markovic, Svetomir Nenad

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85029689026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029689026&partnerID=8YFLogxK

U2 - 10.1634/theoncologist.2017-0060

DO - 10.1634/theoncologist.2017-0060

M3 - Article

C2 - 28679643

AN - SCOPUS:85029689026

VL - 22

JO - Oncologist

JF - Oncologist

SN - 1083-7159

IS - 9

ER -