Current strategies in treatment of oligodendroglioma

Evolution of molecular signatures of response

Kurt Jaeckle, Karla V. Ballman, Ravi D. Rao, Robert B. Jenkins, Jan C. Buckner

Research output: Contribution to journalReview article

51 Citations (Scopus)

Abstract

Oligodendroglioma frequently (≥ 70%) responds to radiation and chemotherapy, and is the first CNS neoplasm in which a genetic signature dp and 19q deletion) has been associated with outcome within the context of large clinical trials. Current translational investigations focus on deletions or mutations of potential tumor suppressor genes, epigenetic alterations, amplification or mutation of growth factor and regulatory genes, and characterization of signaling events and regulatory protein expression. The most compelling data has involved 1p and 19q loss, which is observed in over 50% of anaplastic oligodendrogliomas. In two randomized phase III trials (Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951), the addition of neoadjuvant or adjuvant procarbazine, lomustine, and vincristine (PCV; respectively) to radiotherapy did not produce superior survival as compared with radiotherapy alone. A modest increase in progression-free survival was observed with the addition of PCV, but at the cost of increased toxicity. Combined 1p and 19q loss identified a favorable prognostic group in both studies, which appeared to be independent of treatment arms. However, it is unclear whether these deletions represent surrogate markers of a favorable biologic tumor behavior, or are predictive of outcome after specific treatment. Currently, there is insufficient data to allow therapeutic decisions to be made solely on the basis of 1p and 19q gene deletion status. Future phase III trials are evaluating other chemotherapeutic and targeted agents, including temozolomide, and include correlative investigations of aberrant molecular events in these neoplasms, which may lead to future therapeutic strategies that are based on specific molecular signatures.

Original languageEnglish (US)
Pages (from-to)1246-1252
Number of pages7
JournalJournal of Clinical Oncology
Volume24
Issue number8
DOIs
StatePublished - Mar 10 2006

Fingerprint

Oligodendroglioma
Molecular Evolution
Radiotherapy
temozolomide
Lomustine
Procarbazine
Neoplasms
Radiation Oncology
Sequence Deletion
Gene Deletion
Vincristine
Therapeutics
Regulator Genes
Tumor Suppressor Genes
Epigenomics
Disease-Free Survival
Intercellular Signaling Peptides and Proteins
Biomarkers
Clinical Trials
Radiation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jaeckle, Kurt ; Ballman, Karla V. ; Rao, Ravi D. ; Jenkins, Robert B. ; Buckner, Jan C. / Current strategies in treatment of oligodendroglioma : Evolution of molecular signatures of response. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 8. pp. 1246-1252.
@article{45ec43ee34f140d38cb140e4675577f4,
title = "Current strategies in treatment of oligodendroglioma: Evolution of molecular signatures of response",
abstract = "Oligodendroglioma frequently (≥ 70{\%}) responds to radiation and chemotherapy, and is the first CNS neoplasm in which a genetic signature dp and 19q deletion) has been associated with outcome within the context of large clinical trials. Current translational investigations focus on deletions or mutations of potential tumor suppressor genes, epigenetic alterations, amplification or mutation of growth factor and regulatory genes, and characterization of signaling events and regulatory protein expression. The most compelling data has involved 1p and 19q loss, which is observed in over 50{\%} of anaplastic oligodendrogliomas. In two randomized phase III trials (Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951), the addition of neoadjuvant or adjuvant procarbazine, lomustine, and vincristine (PCV; respectively) to radiotherapy did not produce superior survival as compared with radiotherapy alone. A modest increase in progression-free survival was observed with the addition of PCV, but at the cost of increased toxicity. Combined 1p and 19q loss identified a favorable prognostic group in both studies, which appeared to be independent of treatment arms. However, it is unclear whether these deletions represent surrogate markers of a favorable biologic tumor behavior, or are predictive of outcome after specific treatment. Currently, there is insufficient data to allow therapeutic decisions to be made solely on the basis of 1p and 19q gene deletion status. Future phase III trials are evaluating other chemotherapeutic and targeted agents, including temozolomide, and include correlative investigations of aberrant molecular events in these neoplasms, which may lead to future therapeutic strategies that are based on specific molecular signatures.",
author = "Kurt Jaeckle and Ballman, {Karla V.} and Rao, {Ravi D.} and Jenkins, {Robert B.} and Buckner, {Jan C.}",
year = "2006",
month = "3",
day = "10",
doi = "10.1200/JCO.2005.04.9874",
language = "English (US)",
volume = "24",
pages = "1246--1252",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "8",

}

Current strategies in treatment of oligodendroglioma : Evolution of molecular signatures of response. / Jaeckle, Kurt; Ballman, Karla V.; Rao, Ravi D.; Jenkins, Robert B.; Buckner, Jan C.

In: Journal of Clinical Oncology, Vol. 24, No. 8, 10.03.2006, p. 1246-1252.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Current strategies in treatment of oligodendroglioma

T2 - Evolution of molecular signatures of response

AU - Jaeckle, Kurt

AU - Ballman, Karla V.

AU - Rao, Ravi D.

AU - Jenkins, Robert B.

AU - Buckner, Jan C.

PY - 2006/3/10

Y1 - 2006/3/10

N2 - Oligodendroglioma frequently (≥ 70%) responds to radiation and chemotherapy, and is the first CNS neoplasm in which a genetic signature dp and 19q deletion) has been associated with outcome within the context of large clinical trials. Current translational investigations focus on deletions or mutations of potential tumor suppressor genes, epigenetic alterations, amplification or mutation of growth factor and regulatory genes, and characterization of signaling events and regulatory protein expression. The most compelling data has involved 1p and 19q loss, which is observed in over 50% of anaplastic oligodendrogliomas. In two randomized phase III trials (Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951), the addition of neoadjuvant or adjuvant procarbazine, lomustine, and vincristine (PCV; respectively) to radiotherapy did not produce superior survival as compared with radiotherapy alone. A modest increase in progression-free survival was observed with the addition of PCV, but at the cost of increased toxicity. Combined 1p and 19q loss identified a favorable prognostic group in both studies, which appeared to be independent of treatment arms. However, it is unclear whether these deletions represent surrogate markers of a favorable biologic tumor behavior, or are predictive of outcome after specific treatment. Currently, there is insufficient data to allow therapeutic decisions to be made solely on the basis of 1p and 19q gene deletion status. Future phase III trials are evaluating other chemotherapeutic and targeted agents, including temozolomide, and include correlative investigations of aberrant molecular events in these neoplasms, which may lead to future therapeutic strategies that are based on specific molecular signatures.

AB - Oligodendroglioma frequently (≥ 70%) responds to radiation and chemotherapy, and is the first CNS neoplasm in which a genetic signature dp and 19q deletion) has been associated with outcome within the context of large clinical trials. Current translational investigations focus on deletions or mutations of potential tumor suppressor genes, epigenetic alterations, amplification or mutation of growth factor and regulatory genes, and characterization of signaling events and regulatory protein expression. The most compelling data has involved 1p and 19q loss, which is observed in over 50% of anaplastic oligodendrogliomas. In two randomized phase III trials (Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951), the addition of neoadjuvant or adjuvant procarbazine, lomustine, and vincristine (PCV; respectively) to radiotherapy did not produce superior survival as compared with radiotherapy alone. A modest increase in progression-free survival was observed with the addition of PCV, but at the cost of increased toxicity. Combined 1p and 19q loss identified a favorable prognostic group in both studies, which appeared to be independent of treatment arms. However, it is unclear whether these deletions represent surrogate markers of a favorable biologic tumor behavior, or are predictive of outcome after specific treatment. Currently, there is insufficient data to allow therapeutic decisions to be made solely on the basis of 1p and 19q gene deletion status. Future phase III trials are evaluating other chemotherapeutic and targeted agents, including temozolomide, and include correlative investigations of aberrant molecular events in these neoplasms, which may lead to future therapeutic strategies that are based on specific molecular signatures.

UR - http://www.scopus.com/inward/record.url?scp=33644869823&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644869823&partnerID=8YFLogxK

U2 - 10.1200/JCO.2005.04.9874

DO - 10.1200/JCO.2005.04.9874

M3 - Review article

VL - 24

SP - 1246

EP - 1252

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 8

ER -