Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas

Edward F. Chang, Gabriel Zada, Sang Kim, Kathleen R. Lamborn, Alfredo Quinones-Hinojosa, J. Blake Tyrrell, Charles B. Wilson, Sandeep Kunwar

Research output: Contribution to journalArticle

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Abstract

Object. Long-term outcomes following surgery for nonfunctional pituitary adenomas (NFPAs) are unclear. The role of adjuvant radiation therapy is therefore controversial because it is associated with higher tumor control but also carries known long-term morbidity. The authors' aim was to determine predictors of recurrence and overall survival and to define patient subgroups that may benefit from radiotherapy. Methods. The authors performed a retrospective cohort analysis of 663 patients who underwent surgery between 1975 and 1995 for treatment of primary NFPAs. The main outcome measures were disease progression after surgery, defined by clinical and/or imaging criteria, and all-cause mortality. Results. Over a median clinical follow-up of 8.4 years, there were 64 (9.7%) recurrences after treatment, with a median time to recurrence of 5.6 years. The 5-, 10-, and 15-year recurrence-free probabilities were 0.93, 0.87, and 0.81, respectively. Multivariate Cox proportional hazard regression analysis identified the following predictors as associated with increased recurrence: cavernous sinus invasion (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5-6.4; p < 0.001) and subtotal resection (STR) without radiotherapy (HR 3.6, 95% CI 1.4-14; p = 0.01). Using time-to-event estimates to adjust for differences in follow-up between groups, radiotherapy was found to reduce tumor recurrence in only those patients who received an STR (p < 0.001, log-rank test) but not gross-total resection (GTR; p = 0.63, log-rank test). Median follow-up for overall survival was 14.0 years. The 5-, 10-, 15- and 20-year overall survival estimates were 0.91, 0.81, 0.69, and 0.55, respectively. Within the study cohort and in age- and sex-adjusted comparison with the general US population, increased relative mortality was observed in patients who underwent radiotherapy or STR. Conclusions. Cavernous sinus invasion is an important prognostic variable for long-term control of NFPAs. Radiotherapy results in long-term tumor control for patients who undergo STR but does not affect recurrence rates and may increase the risk of death after GTR. Given the risks associated with radiotherapy, there is no role for its routine application in patients who have undergone GTR of their NFPA. In all patients, long-term monitoring is required.

Original languageEnglish (US)
Pages (from-to)736-745
Number of pages10
JournalJournal of Neurosurgery
Volume108
Issue number4
DOIs
StatePublished - Apr 2008
Externally publishedYes

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Adjuvant Radiotherapy
Pituitary Neoplasms
Radiotherapy
Recurrence
Mortality
Cavernous Sinus
Survival
Cohort Studies
Confidence Intervals
Neoplasms
Disease Progression
Regression Analysis
Outcome Assessment (Health Care)
Morbidity
Therapeutics
Population

Keywords

  • Endocrine-inactive pituitary adenoma
  • Nonfunctional pituitary adenoma
  • Radiation therapy
  • Recurrence
  • Survival
  • Transsphenoidal surgery

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas. / Chang, Edward F.; Zada, Gabriel; Kim, Sang; Lamborn, Kathleen R.; Quinones-Hinojosa, Alfredo; Tyrrell, J. Blake; Wilson, Charles B.; Kunwar, Sandeep.

In: Journal of Neurosurgery, Vol. 108, No. 4, 04.2008, p. 736-745.

Research output: Contribution to journalArticle

Chang, Edward F. ; Zada, Gabriel ; Kim, Sang ; Lamborn, Kathleen R. ; Quinones-Hinojosa, Alfredo ; Tyrrell, J. Blake ; Wilson, Charles B. ; Kunwar, Sandeep. / Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas. In: Journal of Neurosurgery. 2008 ; Vol. 108, No. 4. pp. 736-745.
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abstract = "Object. Long-term outcomes following surgery for nonfunctional pituitary adenomas (NFPAs) are unclear. The role of adjuvant radiation therapy is therefore controversial because it is associated with higher tumor control but also carries known long-term morbidity. The authors' aim was to determine predictors of recurrence and overall survival and to define patient subgroups that may benefit from radiotherapy. Methods. The authors performed a retrospective cohort analysis of 663 patients who underwent surgery between 1975 and 1995 for treatment of primary NFPAs. The main outcome measures were disease progression after surgery, defined by clinical and/or imaging criteria, and all-cause mortality. Results. Over a median clinical follow-up of 8.4 years, there were 64 (9.7{\%}) recurrences after treatment, with a median time to recurrence of 5.6 years. The 5-, 10-, and 15-year recurrence-free probabilities were 0.93, 0.87, and 0.81, respectively. Multivariate Cox proportional hazard regression analysis identified the following predictors as associated with increased recurrence: cavernous sinus invasion (hazard ratio [HR] 3.6, 95{\%} confidence interval [CI] 1.5-6.4; p < 0.001) and subtotal resection (STR) without radiotherapy (HR 3.6, 95{\%} CI 1.4-14; p = 0.01). Using time-to-event estimates to adjust for differences in follow-up between groups, radiotherapy was found to reduce tumor recurrence in only those patients who received an STR (p < 0.001, log-rank test) but not gross-total resection (GTR; p = 0.63, log-rank test). Median follow-up for overall survival was 14.0 years. The 5-, 10-, 15- and 20-year overall survival estimates were 0.91, 0.81, 0.69, and 0.55, respectively. Within the study cohort and in age- and sex-adjusted comparison with the general US population, increased relative mortality was observed in patients who underwent radiotherapy or STR. Conclusions. Cavernous sinus invasion is an important prognostic variable for long-term control of NFPAs. Radiotherapy results in long-term tumor control for patients who undergo STR but does not affect recurrence rates and may increase the risk of death after GTR. Given the risks associated with radiotherapy, there is no role for its routine application in patients who have undergone GTR of their NFPA. In all patients, long-term monitoring is required.",
keywords = "Endocrine-inactive pituitary adenoma, Nonfunctional pituitary adenoma, Radiation therapy, Recurrence, Survival, Transsphenoidal surgery",
author = "Chang, {Edward F.} and Gabriel Zada and Sang Kim and Lamborn, {Kathleen R.} and Alfredo Quinones-Hinojosa and Tyrrell, {J. Blake} and Wilson, {Charles B.} and Sandeep Kunwar",
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T1 - Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas

AU - Chang, Edward F.

AU - Zada, Gabriel

AU - Kim, Sang

AU - Lamborn, Kathleen R.

AU - Quinones-Hinojosa, Alfredo

AU - Tyrrell, J. Blake

AU - Wilson, Charles B.

AU - Kunwar, Sandeep

PY - 2008/4

Y1 - 2008/4

N2 - Object. Long-term outcomes following surgery for nonfunctional pituitary adenomas (NFPAs) are unclear. The role of adjuvant radiation therapy is therefore controversial because it is associated with higher tumor control but also carries known long-term morbidity. The authors' aim was to determine predictors of recurrence and overall survival and to define patient subgroups that may benefit from radiotherapy. Methods. The authors performed a retrospective cohort analysis of 663 patients who underwent surgery between 1975 and 1995 for treatment of primary NFPAs. The main outcome measures were disease progression after surgery, defined by clinical and/or imaging criteria, and all-cause mortality. Results. Over a median clinical follow-up of 8.4 years, there were 64 (9.7%) recurrences after treatment, with a median time to recurrence of 5.6 years. The 5-, 10-, and 15-year recurrence-free probabilities were 0.93, 0.87, and 0.81, respectively. Multivariate Cox proportional hazard regression analysis identified the following predictors as associated with increased recurrence: cavernous sinus invasion (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5-6.4; p < 0.001) and subtotal resection (STR) without radiotherapy (HR 3.6, 95% CI 1.4-14; p = 0.01). Using time-to-event estimates to adjust for differences in follow-up between groups, radiotherapy was found to reduce tumor recurrence in only those patients who received an STR (p < 0.001, log-rank test) but not gross-total resection (GTR; p = 0.63, log-rank test). Median follow-up for overall survival was 14.0 years. The 5-, 10-, 15- and 20-year overall survival estimates were 0.91, 0.81, 0.69, and 0.55, respectively. Within the study cohort and in age- and sex-adjusted comparison with the general US population, increased relative mortality was observed in patients who underwent radiotherapy or STR. Conclusions. Cavernous sinus invasion is an important prognostic variable for long-term control of NFPAs. Radiotherapy results in long-term tumor control for patients who undergo STR but does not affect recurrence rates and may increase the risk of death after GTR. Given the risks associated with radiotherapy, there is no role for its routine application in patients who have undergone GTR of their NFPA. In all patients, long-term monitoring is required.

AB - Object. Long-term outcomes following surgery for nonfunctional pituitary adenomas (NFPAs) are unclear. The role of adjuvant radiation therapy is therefore controversial because it is associated with higher tumor control but also carries known long-term morbidity. The authors' aim was to determine predictors of recurrence and overall survival and to define patient subgroups that may benefit from radiotherapy. Methods. The authors performed a retrospective cohort analysis of 663 patients who underwent surgery between 1975 and 1995 for treatment of primary NFPAs. The main outcome measures were disease progression after surgery, defined by clinical and/or imaging criteria, and all-cause mortality. Results. Over a median clinical follow-up of 8.4 years, there were 64 (9.7%) recurrences after treatment, with a median time to recurrence of 5.6 years. The 5-, 10-, and 15-year recurrence-free probabilities were 0.93, 0.87, and 0.81, respectively. Multivariate Cox proportional hazard regression analysis identified the following predictors as associated with increased recurrence: cavernous sinus invasion (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5-6.4; p < 0.001) and subtotal resection (STR) without radiotherapy (HR 3.6, 95% CI 1.4-14; p = 0.01). Using time-to-event estimates to adjust for differences in follow-up between groups, radiotherapy was found to reduce tumor recurrence in only those patients who received an STR (p < 0.001, log-rank test) but not gross-total resection (GTR; p = 0.63, log-rank test). Median follow-up for overall survival was 14.0 years. The 5-, 10-, 15- and 20-year overall survival estimates were 0.91, 0.81, 0.69, and 0.55, respectively. Within the study cohort and in age- and sex-adjusted comparison with the general US population, increased relative mortality was observed in patients who underwent radiotherapy or STR. Conclusions. Cavernous sinus invasion is an important prognostic variable for long-term control of NFPAs. Radiotherapy results in long-term tumor control for patients who undergo STR but does not affect recurrence rates and may increase the risk of death after GTR. Given the risks associated with radiotherapy, there is no role for its routine application in patients who have undergone GTR of their NFPA. In all patients, long-term monitoring is required.

KW - Endocrine-inactive pituitary adenoma

KW - Nonfunctional pituitary adenoma

KW - Radiation therapy

KW - Recurrence

KW - Survival

KW - Transsphenoidal surgery

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