Macrophage Density Predicts Facial Nerve Outcome and Tumor Growth after Subtotal Resection of Vestibular Schwannoma

Christopher S. Graffeo, Avital Perry, Aditya Raghunathan, Trynda N. Kroneman, Mark Jentoft, Colin L. Driscoll, Brian A. Neff, Matthew L. Carlson, Jeffrey Jacob, Michael J. Link, Jamie Van Gompel

Research output: Contribution to journalArticle

Abstract

Introduction Vestibular schwannoma (VS) behavior following subtotal resection (STR) is highly variable. Overall progression rates have been reported as high as 44%, and optimal treatment is controversial. Correspondingly, identification of a reliable clinical or pathologic marker associated with progression after STR would help guide decision-making. Methods A prospectively maintained institutional VS registry from 1999 to 2014 was retrospectively reviewed for sporadic VS patients who underwent primary STR without preceding stereotactic radiosurgery (SRS) by a single neurosurgery-neurotology team. Primary endpoints included tumor progression and postoperative facial nerve function. Pathologic specimens were stained for Ki67, CD68, S100, and SOX10 and were quantitated by digital imaging analysis. Macrophage density was defined as the ratio of CD68 + macrophages to S100 + macrophages and Schwannian tumor cells. Clinical outcomes were correlated with pathologic markers. Results Forty-six patients met the study inclusion criteria. Thirteen (28%) progressed during a mean 57 months of follow-up (range 15–149). Favorable postoperative facial nerve function (House–Brackmann I–II) was achieved in 37 (80%). CD68 + cells were present at significantly higher concentrations in tumors that progressed ( p = 0.03). Higher macrophage density was significantly associated with both tumor progression ( p = 0.02) and unfavorable facial nerve function ( p = 0.02). Ki67 percent positivity was not significantly associated with either primary endpoint ( p = 0.83; p = 0.58). Conclusions Macrophage density may provide an important marker for individuals at the highest risk for progression of VS after STR, potentially prompting closer surveillance or consideration for upfront SRS following STR. This finding supports preceding conclusions that an intratumoral macrophage-predominant inflammatory response may be a marker for tumor growth and a potential therapeutic target.

Original languageEnglish (US)
JournalJournal of Neurological Surgery, Part B: Skull Base
DOIs
StateAccepted/In press - Feb 7 2018

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Acoustic Neuroma
Facial Nerve
Macrophages
Growth
Neoplasms
Radiosurgery
Neurotology
Neurosurgery
Tumor Biomarkers
Registries
Decision Making
Therapeutics

Keywords

  • macrophage density
  • macrophages
  • subtotal resection
  • tumor progression
  • tumor recurrence
  • vestibular schwannoma

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Macrophage Density Predicts Facial Nerve Outcome and Tumor Growth after Subtotal Resection of Vestibular Schwannoma. / Graffeo, Christopher S.; Perry, Avital; Raghunathan, Aditya; Kroneman, Trynda N.; Jentoft, Mark; Driscoll, Colin L.; Neff, Brian A.; Carlson, Matthew L.; Jacob, Jeffrey; Link, Michael J.; Van Gompel, Jamie.

In: Journal of Neurological Surgery, Part B: Skull Base, 07.02.2018.

Research output: Contribution to journalArticle

Graffeo, Christopher S. ; Perry, Avital ; Raghunathan, Aditya ; Kroneman, Trynda N. ; Jentoft, Mark ; Driscoll, Colin L. ; Neff, Brian A. ; Carlson, Matthew L. ; Jacob, Jeffrey ; Link, Michael J. ; Van Gompel, Jamie. / Macrophage Density Predicts Facial Nerve Outcome and Tumor Growth after Subtotal Resection of Vestibular Schwannoma. In: Journal of Neurological Surgery, Part B: Skull Base. 2018.
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abstract = "Introduction Vestibular schwannoma (VS) behavior following subtotal resection (STR) is highly variable. Overall progression rates have been reported as high as 44{\%}, and optimal treatment is controversial. Correspondingly, identification of a reliable clinical or pathologic marker associated with progression after STR would help guide decision-making. Methods A prospectively maintained institutional VS registry from 1999 to 2014 was retrospectively reviewed for sporadic VS patients who underwent primary STR without preceding stereotactic radiosurgery (SRS) by a single neurosurgery-neurotology team. Primary endpoints included tumor progression and postoperative facial nerve function. Pathologic specimens were stained for Ki67, CD68, S100, and SOX10 and were quantitated by digital imaging analysis. Macrophage density was defined as the ratio of CD68 + macrophages to S100 + macrophages and Schwannian tumor cells. Clinical outcomes were correlated with pathologic markers. Results Forty-six patients met the study inclusion criteria. Thirteen (28{\%}) progressed during a mean 57 months of follow-up (range 15–149). Favorable postoperative facial nerve function (House–Brackmann I–II) was achieved in 37 (80{\%}). CD68 + cells were present at significantly higher concentrations in tumors that progressed ( p = 0.03). Higher macrophage density was significantly associated with both tumor progression ( p = 0.02) and unfavorable facial nerve function ( p = 0.02). Ki67 percent positivity was not significantly associated with either primary endpoint ( p = 0.83; p = 0.58). Conclusions Macrophage density may provide an important marker for individuals at the highest risk for progression of VS after STR, potentially prompting closer surveillance or consideration for upfront SRS following STR. This finding supports preceding conclusions that an intratumoral macrophage-predominant inflammatory response may be a marker for tumor growth and a potential therapeutic target.",
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T1 - Macrophage Density Predicts Facial Nerve Outcome and Tumor Growth after Subtotal Resection of Vestibular Schwannoma

AU - Graffeo, Christopher S.

AU - Perry, Avital

AU - Raghunathan, Aditya

AU - Kroneman, Trynda N.

AU - Jentoft, Mark

AU - Driscoll, Colin L.

AU - Neff, Brian A.

AU - Carlson, Matthew L.

AU - Jacob, Jeffrey

AU - Link, Michael J.

AU - Van Gompel, Jamie

PY - 2018/2/7

Y1 - 2018/2/7

N2 - Introduction Vestibular schwannoma (VS) behavior following subtotal resection (STR) is highly variable. Overall progression rates have been reported as high as 44%, and optimal treatment is controversial. Correspondingly, identification of a reliable clinical or pathologic marker associated with progression after STR would help guide decision-making. Methods A prospectively maintained institutional VS registry from 1999 to 2014 was retrospectively reviewed for sporadic VS patients who underwent primary STR without preceding stereotactic radiosurgery (SRS) by a single neurosurgery-neurotology team. Primary endpoints included tumor progression and postoperative facial nerve function. Pathologic specimens were stained for Ki67, CD68, S100, and SOX10 and were quantitated by digital imaging analysis. Macrophage density was defined as the ratio of CD68 + macrophages to S100 + macrophages and Schwannian tumor cells. Clinical outcomes were correlated with pathologic markers. Results Forty-six patients met the study inclusion criteria. Thirteen (28%) progressed during a mean 57 months of follow-up (range 15–149). Favorable postoperative facial nerve function (House–Brackmann I–II) was achieved in 37 (80%). CD68 + cells were present at significantly higher concentrations in tumors that progressed ( p = 0.03). Higher macrophage density was significantly associated with both tumor progression ( p = 0.02) and unfavorable facial nerve function ( p = 0.02). Ki67 percent positivity was not significantly associated with either primary endpoint ( p = 0.83; p = 0.58). Conclusions Macrophage density may provide an important marker for individuals at the highest risk for progression of VS after STR, potentially prompting closer surveillance or consideration for upfront SRS following STR. This finding supports preceding conclusions that an intratumoral macrophage-predominant inflammatory response may be a marker for tumor growth and a potential therapeutic target.

AB - Introduction Vestibular schwannoma (VS) behavior following subtotal resection (STR) is highly variable. Overall progression rates have been reported as high as 44%, and optimal treatment is controversial. Correspondingly, identification of a reliable clinical or pathologic marker associated with progression after STR would help guide decision-making. Methods A prospectively maintained institutional VS registry from 1999 to 2014 was retrospectively reviewed for sporadic VS patients who underwent primary STR without preceding stereotactic radiosurgery (SRS) by a single neurosurgery-neurotology team. Primary endpoints included tumor progression and postoperative facial nerve function. Pathologic specimens were stained for Ki67, CD68, S100, and SOX10 and were quantitated by digital imaging analysis. Macrophage density was defined as the ratio of CD68 + macrophages to S100 + macrophages and Schwannian tumor cells. Clinical outcomes were correlated with pathologic markers. Results Forty-six patients met the study inclusion criteria. Thirteen (28%) progressed during a mean 57 months of follow-up (range 15–149). Favorable postoperative facial nerve function (House–Brackmann I–II) was achieved in 37 (80%). CD68 + cells were present at significantly higher concentrations in tumors that progressed ( p = 0.03). Higher macrophage density was significantly associated with both tumor progression ( p = 0.02) and unfavorable facial nerve function ( p = 0.02). Ki67 percent positivity was not significantly associated with either primary endpoint ( p = 0.83; p = 0.58). Conclusions Macrophage density may provide an important marker for individuals at the highest risk for progression of VS after STR, potentially prompting closer surveillance or consideration for upfront SRS following STR. This finding supports preceding conclusions that an intratumoral macrophage-predominant inflammatory response may be a marker for tumor growth and a potential therapeutic target.

KW - macrophage density

KW - macrophages

KW - subtotal resection

KW - tumor progression

KW - tumor recurrence

KW - vestibular schwannoma

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