Post-Operative Medium- and Long-Term Endocrine Outcomes in Patients with Non-Functioning Pituitary Adenomas—Machine Learning Analysis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Population Statistics
3.2. Hormone Deficiency by Intervention
3.3. Hormone Deficiencies and Radiology Derived Timelines
3.4. Machine Learning for Determining Post-Operative Panhypopituitarism
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Fieldname | Description |
---|---|
date_of_birth | Patient’s date of birth |
age | Approximate decimal age of the patient in years on the date of diagnosis |
gender | Biological sex of the patient |
clinical_presentation | Clinical presentation of the patient. Conditions include: Incidental; Headache; Visual symptoms; Hypopituitarism; Apoplexy; Others; Unknown; Hyponatraemia; Hydrocephalus; facial numbness; cranial n palsy; Hyposmia. |
date_of_diagnosis | Date of Diagnosis |
date_first_surgery | Date of each of the patient’s surgeries, where applicable |
date_second_surgery | |
date_third_surgery | |
approach_first_surgery | Surgical approach taken for each surgery: transsphenoidal (TSS) or transcranial (TCS) |
approach_second_surgery | |
approach_third_surgery | |
surgeon_first_surgery | Lead neurosurgeon on each surgery |
surgeon_second_surgery | |
surgeon_third_surgery | |
preop_vision | Measure of the patient’s vision prior to first surgery. Possible options: Normal; Visual Loss; Unknown |
postop_vision | Measure of the patien’ts vision after first surgery. Possible options: Normal; Improved; No change; Unknown; Deteriorated |
date_radiotherapy_offered | Date on which radiotherapy was offered to the patient, where applicable (Not used in analysis) |
date_radiotherapy_given | Date on which radiotherapy treatment commenced, where applicable |
radiotherapy_type | Type of radiotherapy administered, where applicable. Possible options: Conventional radiotherapy; Gammaknife; Stereotactic radiotherapy |
date_ of_test_first | Date of each endocrine test |
date_ of_test_second | |
date_ of_test_third | |
date_ of_test_fourth | |
date_ of_test_fiveth | |
date_ of_test_sixth | |
hormone_deficit_first | Results of each endocrine test, categorised as described in Section 2: Materials and Methods |
hormone_deficit_second | |
hormone _deficit_third | |
hormone_deficit_fourth | |
hormone_deficit__fiveth | |
hormone_deficit_sixth | |
pathology_outcome_post_first_surgery | Endocrine profile taken immediately after surgery. Possible outcomes: FSH; LH; Not applicable; Null cell; ACTH. |
pathology_outcome_post_second_surgery | |
pathology_outcome_post_third_surgery | |
Ki 67_first_surgery | Ki67 mitotic proliferation measure, taken following each surgery. Possible outcomes: <1%; 1–3%; 3–5%; >5%. |
Ki 67_second_surgery | |
Ki 67_third_surgery | |
frequent_mitosis_first_surgery | Frequent mitosis proliferation measure, taken following each surgery. Possible outcomes: Normal; Increased; Unknown |
frequent_mitosis_second_surgery | |
frequent_mitosis_third_surgery | |
date_of_scan_first | Date of each radiology scan administered. Typically, the first scan occurred pre-operatively and second scan occurred post initial surgery, with subsequent scans taken over follow-up periods. |
date_of_scan_second | |
date_of_scan_third | |
date_of_scan_fourth | |
date_of_scan_fiveth | |
date_of_scan_Sixth | |
date_of_scan_seventh | |
date_of_scan_eighth | |
Scan_first | Results of the first radiology scan. Possible outcomes: Macroadenoma; Optic n compression; Cavernous sinus invasion; Sphenoid sinus invasion; Clivus invsion; Ethmoid invsion; Hydrocephalus; Unknown; Nasopharynx; Ventricle |
Scan_second | Results of the second radiology scan. Possible outcomes: Complete resection; Residual tumour (RT); RT + Optin n compression; RT + Cavernous invasion; RT + Sphenoid sinus; Unknown; RT + Op n + CS invasion; Rt + Clivus. |
Scan_third | Results of follow-up radiology scans. Possible outcomes: No recurrence; Residual tumour Stable; increase in size; optic contact/compression; Cavernous invasion; Sphenoid; Clivus/skull base; Recurrence; Reduction in size; Residual tumour. |
Scan_fourth | |
Scan_fiveth | |
Scan_Sixth | |
Scan_seventh | |
Scan_eighth | |
date_last_seen | Date of last clinical visit |
cc | Estimated tumour volume (cc) |
transverse | Transverse tumour length (mm) |
ap | Anterior-posterior tumour length (mm) |
Time Relative to First Surgery | ||||||
---|---|---|---|---|---|---|
Pre-Operative | 0–6 Months | 6–12 Months | 1–1.5 Years | 5 Years | 10 Years | |
No Deficiency | 39.2% | 29.1% | 30.3% | 29.5% | 29.1% | 27.0% |
GH | 24.3% | 26.7% | 28.2% | 30.3% | 30.4% | 33.1% |
FSH/LH | 43.5% | 45.5% | 44.6% | 43.9% | 44.4% | 46.6% |
ACTH | 36.5% | 42.7% | 39.4% | 39.2% | 39.4% | 41.5% |
TSH | 42.2% | 47.1% | 49.3% | 49.3% | 51.4% | 53.2% |
AVP | 0.6% | 9.4% | 8.1% | 7.6% | 6.3% | 6.1% |
Panhypopituitarism | 15.8% | 14.4% | 13.3% | 12.8% | 14.2% | 15.1% |
Panhypopituitarism + AVP | 0.0% | 2.9% | 3.4% | 3.4% | 2.4% | 2.4% |
References
- Ntali, G.; Wass, J.A. Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas. Pituitary 2018, 21, 111–118. [Google Scholar] [CrossRef] [PubMed]
- Snyder, P.J. Gonadotroph Adenomas. In The Pituitary; Academic Press: Cambridge, MA, USA, 2011; pp. 637–654. [Google Scholar]
- Chen, Y.; Wang, C.D.; Su, Z.P.; Chen, Y.X.; Cai, L.; Zhuge, Q.C.; Wu, Z.B. Natural History of Postoperative Nonfunctioning Pituitary Adenomas: A Systematic Review and Meta-Analysis. Neuroendocrinology 2012, 96, 333–342. [Google Scholar] [CrossRef]
- Nomikos, P.; Ladar, C.; Fahlbusch, R.; Buchfelder, M. Impact of primary surgery on pituitary function in patients with non-functioning pituitary adenomas—A study on 721 patients. Acta Neurochir. 2004, 146, 27–35. [Google Scholar] [CrossRef]
- Arafah, B.M. Reversible Hypopituitarism in Patients with Large Nonfunctioning Pituitary Adenomas. J. Clin. Endocrinol. Metab. 1986, 62, 1173–1179. [Google Scholar] [CrossRef]
- Pedersen, M.B.; Dukanovic, S.; Springborg, J.B.; Andreassen, M.; Krogh, J. Systematic Review Endocrine Function after Transsphenoidal Surgery in Patients with Non-Functioning Pituitary Adenomas: A Systematic Review and Meta-Analysis. Neuroendocrinology 2022, 112, 823–834. [Google Scholar] [CrossRef]
- Jahangiri, A.; Wagner, J.R.; Han, S.W.; Tran, M.T.; Miller, L.M.; Chen, R.; Aghi, M.K. Improved versus worsened endocrine function after transsphenoidal surgery for nonfunctional pituitary adenomas: Rate, time course, and radiological analysis. J. Neurosurg. 2016, 124, 589–595. [Google Scholar] [CrossRef]
- Pekic, S.; Miljic, D.; Popovic, V.; Hypopituitarism Following Cranial Radiotherapy. Endotext 2021. Available online: https://www.ncbi.nlm.nih.gov/books/NBK532082/ (accessed on 7 December 2021).
- Fang, Y.; Wang, H.; Feng, M.; Zhang, W.; Cao, L.; Ding, C.; Wang, S. Machine-Learning Prediction of Postoperative Pituitary Hormonal Outcomes in Nonfunctioning Pituitary Adenomas: A Multicenter Study. Front. Endocrinol. 2021, 12, 748725. [Google Scholar] [CrossRef] [PubMed]
- Collins, G.S.; Reitsma, J.B.; Altman, D.G.; Moons, K.G.M. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): The TRIPOD Statement. BMC Med. 2015, 162, 55–63. [Google Scholar] [CrossRef] [PubMed]
- Glynn, N.; Agha, A. Diagnosing Growth Hormone Deficiency in Adults. Int. J. Endocrinol. 2012, 2012, 972617. [Google Scholar] [CrossRef] [PubMed]
- Shalet, S.M.; Toogood, A.; Rahim, A.; Brennan, B.M.D. The diagnosis of growth hormone deficiency in children and adults. Endocr. Rev. 1998, 19, 203–223. [Google Scholar] [CrossRef]
- Husebye, E.S.; Pearce, S.H.; Krone, N.P.; Kämpe, O. Adrenal insufficiency. Lancet 2021, 397, 613–629. [Google Scholar] [CrossRef]
- Arlt, W.; Allolio, B. Adrenal insufficiency. Lancet 2003, 361, 1881–1893. [Google Scholar] [CrossRef]
- Fleseriu, M.; Hashim, I.A.; Karavitaki, N.; Melmed, S.; Murad, M.H.; Salvatori, R.; Samuels, M.H. Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2016, 101, 3888–3921. [Google Scholar] [CrossRef]
- Jayasena, C.N.; Anderson, R.A.; Llahana, S.; Barth, J.H.; MacKenzie, F.; Wilkes, S.; Quinton, R. Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism. Clin. Endocrinol. 2022, 96, 200–219. [Google Scholar] [CrossRef]
- Ferreira, L.; Silveira, G.; Latronico, A.C. Approach to the patient with hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 2013, 98, 1781–1788. [Google Scholar]
- Littley, M.D.; Shalet, S.M.; Beardwell, C.G. Radiation and hypothalamic-pituitary function. Baillieres. Clin. Endocrinol. Metab. 1990, 4, 147–175. [Google Scholar] [CrossRef] [PubMed]
- Pedregosa, F.; Varoquaux, G.; Gramfort, A.; Michel, V.; Thirion, B.; Grisel, O.; Duchesnay, E. Scikit-Learn: Machine Learning in Python. J. Mach. Learn. Res. 2011, 12, 2825–2830. [Google Scholar]
- Kim, S.Y. Diagnosis and Treatment of Hypopituitarism. Endocrinol. Metab. 2015, 30, 443. [Google Scholar] [CrossRef]
- Darzy, K.H.; Shalet, S.M. Hypopituitarism following Radiotherapy Revisited. Endocr. Dev. 2009, 15, 1–24. [Google Scholar] [CrossRef] [PubMed]
- Sherlock, M.; Ayuk, J.; Tomlinson, J.W.; Toogood, A.A.; Aragon-Alonso, A.; Sheppard, M.C.; Stewart, P.M. Mortality in Patients with Pituitary Disease. Endocr. Rev. 2010, 31, 301–342. [Google Scholar] [CrossRef] [PubMed]
- Tomlinson, J.W.; Holden, N.; Hills, R.K.; Wheatley, K.; Clayton, R.N.; Bates, A.S.; Stewart, P.M. Association between premature mortality and hypopituitarism. Lancet 2001, 357, 425–431. [Google Scholar] [CrossRef] [PubMed]
- Drummond, J.B.; Ribeiro-Oliveira, J.A.; Soares, B.S.; Non-Functioning Pituitary Adenomas. Endotext 2018. Available online: https://www.ncbi.nlm.nih.gov/books/NBK534880/ (accessed on 21 February 2021).
- Esposito, D.; Olsson, D.S.; Ragnarsson, O.; Buchfelder, M.; Skoglund, T.; Johannsson, G. Non-functioning pituitary adenomas: Indications for pituitary surgery and post-surgical management. Pituitary 2019, 22, 422. [Google Scholar] [CrossRef] [PubMed]
- Ivan, C.; Ann, R.; Craig, B.; Debi, P.; Ciric, I. Complications of Transsphenoidal Surgery: Results of a National Survey, Review of the Literature, and Personal Experience. Neurosurgery 1997, 40, 225–237. [Google Scholar]
- Fernandez, A.; Brada, M.; Zabuliene, L.; Karavitaki, N.; Wass, J.A.H. Radiation-induced hypopituitarism. Endocr. Relat. Cancer 2009, 16, 733–772. [Google Scholar] [CrossRef]
- Darzy, K.H.; Shalet, S.M. Hypopituitarism following radiotherapy. Pituitary 2009, 12, 40–50. [Google Scholar] [CrossRef] [PubMed]
- Chieng, P.U.; Huang, T.S.; Chang, C.C.; Chong, P.N.; Tien, R.D.; Su, C.T. Reduced hypothalamic blood flow after radiation treatment of nasopharyngeal cancer: SPECT studies in 34 patients. AJNR Am. J. Neuroradiol. 1991, 12, 661. [Google Scholar]
Measure | Value |
---|---|
Total patients | 383 |
Mean age | 56.8 |
Std age (years) | 13.5 |
Sex ratio (male:female) | 67:33 |
% of patients receiving one or more surgeries | 100 |
% of patients receiving two or more surgeries | 22 |
% of patients receiving three surgeries | 4 |
% of patients receiving radiotherapy | 17 |
Accuracy | AUC-ROC | |||
---|---|---|---|---|
Mean | Std | Mean | Std | |
Logistic regression | 0.89 | 0.03 | 0.79 | 0.07 |
KNN | 0.87 | 0.04 | 0.61 | 0.06 |
SVM | 0.94 | 0.03 | 0.88 | 0.06 |
Decision tree | 0.92 | 0.03 | 0.84 | 0.06 |
Time from First Surgery | Early Endocrine Test Period | Mean Accuracy | Std Accuracy | Mean AUC-ROC | Std AUC-ROC |
---|---|---|---|---|---|
6 Months | Pre-operative | 0.89 | 0.04 | 0.77 | 0.09 |
1 Year | Pre-operative | 0.88 | 0.04 | 0.77 | 0.09 |
5 Years | 1 year post-operative | 0.97 | 0.03 | 0.95 | 0.03 |
10 Years | 1 year post-operative | 0.94 | 0.02 | 0.92 | 0.06 |
Prediction Period | Feature | Mean Importance | Std Importance |
---|---|---|---|
6-months post-operative | Panhypop @ Pre-operative: True | 0.40 | 0.38 |
Panhypop @ Pre-operative: False | 0.32 | 0.37 | |
Age | 0.07 | 0.02 | |
Tumour Volume (cc) | 0.04 | 0.02 | |
1 year post-operative | Panhypop @ Pre-operative: True | 0.39 | 0.36 |
Panhypop @ Pre-operative: False | 0.33 | 0.37 | |
Age | 0.08 | 0.04 | |
Tumour Volume (cc) | 0.07 | 0.03 | |
5 years post-operative | Panhypop @ 1 year Post-operative: True | 0.76 | 0.03 |
Panhypop + AVP @ 1 year Post-operative: True | 0.18 | 0.03 | |
Radiotherapy already given: True | 0.02 | 0.01 | |
10 years post-operative | Panhypop @ 1 year Post-operative: True | 0.71 | 0.04 |
Panhypop + AVP @ 1 year Post-operative: True | 0.19 | 0.06 | |
Radiotherapy already given: True | 0.02 | 0.01 |
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Hussein, Z.; Slack, R.W.; Marcus, H.J.; Mazomenos, E.B.; Baldeweg, S.E. Post-Operative Medium- and Long-Term Endocrine Outcomes in Patients with Non-Functioning Pituitary Adenomas—Machine Learning Analysis. Cancers 2023, 15, 2771. https://doi.org/10.3390/cancers15102771
Hussein Z, Slack RW, Marcus HJ, Mazomenos EB, Baldeweg SE. Post-Operative Medium- and Long-Term Endocrine Outcomes in Patients with Non-Functioning Pituitary Adenomas—Machine Learning Analysis. Cancers. 2023; 15(10):2771. https://doi.org/10.3390/cancers15102771
Chicago/Turabian StyleHussein, Ziad, Robert W. Slack, Hani J. Marcus, Evangelos B. Mazomenos, and Stephanie E. Baldeweg. 2023. "Post-Operative Medium- and Long-Term Endocrine Outcomes in Patients with Non-Functioning Pituitary Adenomas—Machine Learning Analysis" Cancers 15, no. 10: 2771. https://doi.org/10.3390/cancers15102771