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Background <p>There are few studies on radiation-induced pituitary endocrine dysfunction (RIPD) for nasopharyngeal carcinoma (NPC) survivors. In this retrospective longitudinal cohort study, we explored dosimetric parameters associated with RIPD and its temporal distribution during follow-up in the era of intensity-modulated radiotherapy (IMRT).</p> Methods <p>NPC survivors who received curative IMRT between January of 2010 and December of 2018 were enrolled and randomly allocated to three cohorts at a ratio of 1:1:1. A dose of 7000&#xa0;cGy was then prescribed to the nasopharyngeal lesion and cervical lymph nodes; 212&#xa0;cGy per fraction were provided daily from Monday to Friday over seven weeks. Candidate risk factors related to RIPD were screened using univariate and multivariate logistic regression for cohort A, while the best thresholds of candidate risk factors were derived from receiver operating characteristic curve analysis for cohort B. Independent factors that were predictive of RIPD were subsequently selected by implementing a univariate and multivariate Cox proportional hazard model. For cohort C, we re-evaluated the prognostic role of independent factors. Temporal RIPD onset was ultimately revealed in the pooled cohort. This study was approved by the Ethics Boards of the Cancer Center and Fifth Affiliated Hospital of Sun Yat-sen University (2025-K189-1).</p> Results <p>RIPD occurred in 41.7% of all 302 NPC survivors, with the most prevalent RIPD observed as growth hormone deficiency (GHD) (40.4%)—followed by central hypogonadism (23.2%), hyperprolactinemia (19.5%), central hypothyroidism (10.3%), and adrenocorticotropic hormone (ACTH) deficiency (7.6%). V40 (i.e., the percentage of pituitaries that received above 4000&#xa0;cGy) was ≥ 60%, V60 (i.e., the percentage of pituitaries receiving above 6000&#xa0;cGy) was ≥ 50%, and V50 (i.e., the percentage of pituitaries receiving above 5000&#xa0;cGy) was ≥ 50%; and these indices were associated with hyperprolactinemia, ACTH deficiency, and GHD, respectively. A V50 ≥ 80% correlated with central hypothyroidism and hypogonadism. The C-indices of models that predicted hyperprolactinemia, central hypothyroidism, central hypogonadism, ACTH deficiency, and GHD were 0.74 (95% confidence interval [CI], 0.70–0.79), 0.66 (95% CI 0.61–0.71), 0.68 (95% CI 0.62–0.74), 0.67 (95% CI 0.61–0.74), and 0.69 (95% CI 0.63–0.76), respectively.</p> Conclusion <p>V40 ≥ 60%, V50 ≥ 50%, V50 ≥ 80%, and V60 ≥ 50% were associated with RIPD in adult survivors of NPC. These dosimetric thresholds served as a guide for IMRT plan optimization, but were not an absolute guarantee of pituitary sparing. Therefore, dynamic assessment of pituitary hormones was warranted.</p>

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Association between dosimetry and radiation-induced pituitary endocrine dysfunction among survivors of nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: a retrospective longitudinal cohort study

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  • 发表日期：

    2026年7月19日

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  • Xuexia Liang,
  • Yan Wang,
  • Dongping Pan,
  • Yunyu Zhou,
  • Xiaohong Wei,
  • Yun Deng,
  • Shuqin Zhu,
  • Youjuan Tang,
  • Qiaodan Liu

摘要

Background

There are few studies on radiation-induced pituitary endocrine dysfunction (RIPD) for nasopharyngeal carcinoma (NPC) survivors. In this retrospective longitudinal cohort study, we explored dosimetric parameters associated with RIPD and its temporal distribution during follow-up in the era of intensity-modulated radiotherapy (IMRT).

Methods

NPC survivors who received curative IMRT between January of 2010 and December of 2018 were enrolled and randomly allocated to three cohorts at a ratio of 1:1:1. A dose of 7000 cGy was then prescribed to the nasopharyngeal lesion and cervical lymph nodes; 212 cGy per fraction were provided daily from Monday to Friday over seven weeks. Candidate risk factors related to RIPD were screened using univariate and multivariate logistic regression for cohort A, while the best thresholds of candidate risk factors were derived from receiver operating characteristic curve analysis for cohort B. Independent factors that were predictive of RIPD were subsequently selected by implementing a univariate and multivariate Cox proportional hazard model. For cohort C, we re-evaluated the prognostic role of independent factors. Temporal RIPD onset was ultimately revealed in the pooled cohort. This study was approved by the Ethics Boards of the Cancer Center and Fifth Affiliated Hospital of Sun Yat-sen University (2025-K189-1).

Results

RIPD occurred in 41.7% of all 302 NPC survivors, with the most prevalent RIPD observed as growth hormone deficiency (GHD) (40.4%)—followed by central hypogonadism (23.2%), hyperprolactinemia (19.5%), central hypothyroidism (10.3%), and adrenocorticotropic hormone (ACTH) deficiency (7.6%). V40 (i.e., the percentage of pituitaries that received above 4000 cGy) was ≥ 60%, V60 (i.e., the percentage of pituitaries receiving above 6000 cGy) was ≥ 50%, and V50 (i.e., the percentage of pituitaries receiving above 5000 cGy) was ≥ 50%; and these indices were associated with hyperprolactinemia, ACTH deficiency, and GHD, respectively. A V50 ≥ 80% correlated with central hypothyroidism and hypogonadism. The C-indices of models that predicted hyperprolactinemia, central hypothyroidism, central hypogonadism, ACTH deficiency, and GHD were 0.74 (95% confidence interval [CI], 0.70–0.79), 0.66 (95% CI 0.61–0.71), 0.68 (95% CI 0.62–0.74), 0.67 (95% CI 0.61–0.74), and 0.69 (95% CI 0.63–0.76), respectively.

Conclusion

V40 ≥ 60%, V50 ≥ 50%, V50 ≥ 80%, and V60 ≥ 50% were associated with RIPD in adult survivors of NPC. These dosimetric thresholds served as a guide for IMRT plan optimization, but were not an absolute guarantee of pituitary sparing. Therefore, dynamic assessment of pituitary hormones was warranted.