Machine Learning in Preoperative Prediction of Postoperative Immediate Remission of Histology-Positive Cushing’s Disease

BackgroundThere are no established accurate models that use machine learning (ML) methods to preoperatively predict immediate remission after transsphenoidal surgery (TSS) in patients diagnosed with histology-positive Cushing’s disease (CD).PurposeOur current study aims to devise and assess an ML-based model to preoperatively predict immediate remission after TSS in patients with CD.MethodsA total of 1,045 participants with CD who received TSS at Peking Union Medical College Hospital in a 20-year period (between February 2000 and September 2019) were enrolled in the present study. In total nine ML classifiers were applied to construct models for the preoperative prediction of immediate remission with preoperative factors. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the performance of the models. The performance of each ML-based model was evaluated in terms of AUC.ResultsThe overall immediate remission rate was 73.3% (766/1045). First operation (p<0.001), cavernous sinus invasion on preoperative MRI(p<0.001), tumour size (p<0.001), preoperative ACTH (p=0.008), and disease duration (p=0.010) were significantly related to immediate remission on logistic univariate analysis. The AUCs of the models ranged between 0.664 and 0.743. The highest AUC, i.e., the best performance, was 0.743, which was achieved by stacking ensemble method with four factors: first operation, cavernous sinus invasion on preoperative MRI, tumour size and preoperative ACTH.ConclusionWe developed a readily available ML-based model for the preoperative prediction of immediate remission in patients with CD.

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Outcomes of Therapy for Cushing’s Disease due to Adrenocorticotropin-Secreting Pituitary Macroadenomas1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.1.4525 ◽

1998 ◽

Vol 83 (1) ◽

pp. 63-67 ◽

Cited By ~ 1

Author(s):

Lewis S. Blevins ◽

James H. Christy ◽

Masheed Khajavi ◽

George T. Tindall

Keyword(s):

Confidence Interval ◽

Cavernous Sinus ◽

Cushing’S Disease ◽

Odds Ratio ◽

Remission Rate ◽

Cushing's Disease ◽

Tumor Diameter ◽

Cavernous Sinus Invasion ◽

Free Cortisol ◽

Acth Secreting

We reviewed our experience with 21 patients who had Cushing’s disease due to ACTH-secreting macroadenomas to clarify the natural history of this disease. All patients had typical clinical and biochemical features of ACTH-dependent hypercortisolism. Their mean maximal tumor diameter was 1.6 ± 0.1 cm, and the range was 1.0–2.7 cm. Six patients had cavernous sinus invasion, three had invasion of the floor of their sella, and nine had suprasellar extension. The observed remission rate was significantly lower in macroadenoma patients than in microadenoma patients (67% vs. 91%; χ2 = 5.7; P < 0.02). Cavernous sinus invasion (odds ratio, 35; 95% confidence interval, 2.6–475; P < 0.008) and presence of a maximum tumor diameter 2.0 cm or more (odds ratio, 12.9; 95% confidence interval, 1.4–124; P< 0.02) emerged as the only predictors of residual disease after surgery. The observed recurrence rate was significantly higher in macroadenoma patients than in microadenoma patients (36% vs. 12%; χ2 = 4.2; P< 0.05). Macroadenoma patients tended to suffer from recurrences earlier than did microadenoma patients (16 vs. 49 months). Stepwise multiple logistic regression did not identify any predictors of disease recurrence in macroadenoma patients. Eight macroadenoma patients underwent a total of nine repeat surgical procedures, but none of these resulted in clinical remissions. Only four of seven (57%) patients followed for a sufficient period of time achieved normal urinary free cortisol levels after conventional radiotherapy. Three (75%) of these four patients had re-recurrent hypercortisolism after brief periods of eucortisolism. Pharmacological agents and adrenalectomy were effective in the management of hypercortisolism in patients with residual and recurrent disease. Our results indicate that ACTH-secreting macroadenomas are more refractory to conventional treatments than are ACTH-secreting microadenomas.

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Factors associated with recurrence after endoscopic transphenoidal surgery for Cushing’s disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2015.186 ◽

2015 ◽

Vol 42 (S1) ◽

pp. S41-S41

Author(s):

Y Meng ◽

S Suppiah ◽

L Gonen ◽

G Klironomos ◽

F Gentili ◽

...

Keyword(s):

Cavernous Sinus ◽

Cushing’S Disease ◽

Univariate Analysis ◽

Cushing's Disease ◽

Serum Cortisol Level ◽

Surgical Removal ◽

Significant Variable ◽

Safe Procedure ◽

Sinus Wall

Introduction: Surgical removal is the standard treatment for Cushing’s disease. Although endoscopic transsphenoidal surgical (ETS) approach has grown in popularity, its efficacy has not yet been established. Furthermore, achieving long-term remission remains challenging. Methods: We conducted a retrospective chart review of 39 consecutive patients who underwent ETS for Cushing’s disease at our institution between 2005 and 2014. Univariate analysis using Pearson’s χ2 test was carried out on variables of patient demographics, radiology, pathology, biochemical markers versus recurrence. Results: The mean age was 40, with 82% females. Average length of follow-up was 44.8 months. Based on serum cortisol level, 28 patients (71%) achieved mid to long-term remission after ETS. Of them, 25 experienced an immediate remission, and 3 achieved a delayed remission as long as 4 months postoperatively. MRI findings of (1) microadenomas or no detectable abnormality, (2) adjacency to the cavernous sinus wall were associated with significantly higher recurrence rate (p<0.05). Histologically, MIB-1 >5% was not a significant variable (p=0.55). Conclusion: We found ETS resection to be an effective and safe procedure for majority of the ACTH-secreting adenomas, with remission rates >70%. Additionally, patients with microadenomas, negative preoperative MR, and cavernous sinus adjacency were less likely to achieve remission.

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Electronic Medical Records as Input to Predict Postoperative Immediate Remission of Cushing’s Disease: Application of Word Embedding

Frontiers in Oncology ◽

10.3389/fonc.2021.754882 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wentai Zhang ◽

Dongfang Li ◽

Ming Feng ◽

Baotian Hu ◽

Yanghua Fan ◽

...

Keyword(s):

Electronic Medical Records ◽

Cushing’S Disease ◽

Medical Records ◽

Transsphenoidal Surgery ◽

Remission Rate ◽

Area Under The Curve ◽

Word Embedding ◽

Cushing's Disease ◽

Free Text ◽

College Hospital

BackgroundNo existing machine learning (ML)-based models use free text from electronic medical records (EMR) as input to predict immediate remission (IR) of Cushing’s disease (CD) after transsphenoidal surgery.PurposeThe aim of the present study is to develop an ML-based model that uses EMR that include both structured features and free text as input to preoperatively predict IR after transsphenoidal surgery.MethodsA total of 419 patients with CD from Peking Union Medical College Hospital were enrolled between January 2014 and August 2020. The EMR of the patients were embedded and transformed into low-dimensional dense vectors that can be included in four ML-based models together with structured features. The area under the curve (AUC) of receiver operating characteristic curves was used to evaluate the performance of the models.ResultsThe overall remission rate of the 419 patients was 75.7%. From the results of logistic multivariate analysis, operation (p < 0.001), invasion of cavernous sinus from MRI (p = 0.046), and ACTH (p = 0.024) were strongly correlated with IR. The AUC values for the four ML-based models ranged from 0.686 to 0.793. The highest AUC value (0.793) was for logistic regression when 11 structured features and “individual conclusions of the case by doctor” were included.ConclusionAn ML-based model was developed using both structured and unstructured features (after being processed using a word embedding method) as input to preoperatively predict postoperative IR.

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Racial disparities in acromegaly and Cushing’s disease: a referral center study in 241 patients

Journal of the Endocrine Society ◽

10.1210/jendso/bvab176 ◽

2021 ◽

Author(s):

Adriana G Ioachimescu ◽

Neevedita Goswami ◽

Talin Handa ◽

Adlai Pappy ◽

Emir Veledar ◽

...

Keyword(s):

Cushing’S Disease ◽

Census Data ◽

Remission Rate ◽

Black Population ◽

Postoperative Outcomes ◽

Cushing's Disease ◽

Tumor Diameter ◽

Cavernous Sinus Invasion ◽

Black Patients ◽

The Impact

Abstract Purpose The impact of race on presentation and postoperative outcomes in adults with acromegaly (ACM) and Cushing’s disease (CD) has not been evaluated. Methods This is a retrospective study of consecutive patients operated at a large-volume pituitary center. We evaluated: 1) racial distribution of patients residing in the metropolitan area (Metro, N=124) versus 2010 U.S. Census data, 2) presentation and postoperative outcomes in Black versus White for patients from the entire catchment area (N=241). Results For Metro area (32.4% Black population), Black patients represented 16.75% ACM (p=0.006) and 29.2% CD (p=0.56).Among 112 total ACM patients, presentations with headaches or incidentaloma were more common in Black patients (76.9% versus 31% White, p=0.01). Black patients had a higher prevalence of diabetes (54% versus 16% White, p=0.005), significantly lower IGF-1 deviation from normal (p=0.03) and borderline lower median GH levels (p=0.09). Mean tumor diameter and proportion of tumors with cavernous sinus invasion were similar. Three-month biochemical remission (46% Black, 55% White, p=0.76) and long-term IGF-1 control by multimodality therapy (92.3% Black, 80.5% White, p=0.45) were similar. Among 129 total CD patients, Black patients had more hypopituitarism (69% vs 45% White, p=0.04) and macroadenomas (33% vs 15% White, p=0.05). At 3 months, remission rate was borderline higher in White (92% vs 78% Black, p=0.08) which was attributed to macroadenomas by logistic regression. Conclusion We identified disparities regarding racial distribution, clinical and biochemical characteristics in ACM, suggesting late or missed diagnosis in Black patients. Large nationwide studies are necessary to confirm our findings.

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Prediction of cavernous sinus invasion in patients with Cushing’s disease by magnetic resonance imaging

Journal of Neurosurgery ◽

10.3171/2018.2.jns172704 ◽

2019 ◽

Vol 130 (5) ◽

pp. 1593-1598 ◽

Cited By ~ 1

Author(s):

Panagiotis Mastorakos ◽

Davis G. Taylor ◽

Ching-Jen Chen ◽

Thomas Buell ◽

Joseph H. Donahue ◽

...

Keyword(s):

Cavernous Sinus ◽

Cushing’S Disease ◽

Predictive Value ◽

Radiographic Finding ◽

Positive Likelihood Ratio ◽

Cushing's Disease ◽

Preoperative Imaging ◽

Mri Findings ◽

Cavernous Sinus Invasion ◽

Pituitary Lesion

OBJECTIVECavernous sinus invasion (CSI) in Cushing’s disease (CD) negatively affects the probability of complete resection, biochemical cure, and need for adjuvant therapy. However, the prediction of CSI based on MRI findings has been inconsistent and variable. Among macroadenomas, the Knosp classification is the most widely utilized radiographic predictor of CSI, but its accuracy in predicting CSI and the probability of gross-total resection is limited in the setting of microadenomas or Knosp grade 0–2 macroadenomas. The authors noticed that the presence of a triangular shape of adenomas adjacent to the cavernous sinus on coronal MR images is frequently associated with CSI. The authors aimed to determine the correlation of this radiographic finding (“sail sign” [SS]) with CSI.METHODSThe authors performed a retrospective review of all patients with a pituitary lesion < 20 mm and a biochemical diagnosis of CD treated with endoscopic or microscopic transsphenoidal resection from November 2007 to May 2017. Overall 185 patients with CD were identified: 27 were excluded for negative preoperative imaging, 32 for lacking tumors adjacent to the sinus, 7 for Knosp grade 3 or higher, and 4 for inadequate intraoperative assessment of the CSI. Following application of inclusion and exclusion criteria, 115 cases were available for statistical analysis. Intraoperative CSI was prospectively evaluated at the time of surgery by one of two neurosurgical attending surgeons, and MRI data were evaluated retrospectively by a neurosurgical resident and attending neuroradiologist blinded to the intraoperative results.RESULTSA positive SS was identified in 23 patients (20%). Among patients with positive SS, 91% demonstrated CSI compared to 10% without an SS (p < 0.001). Using the SS as a predictor of CSI provided a sensitivity of 0.7 and a specificity of 0.98, with a positive predictive value (PPV) of 0.91 and a negative predictive value of 0.9. Among patients with positive SS, 30% did not achieve immediate postoperative remission, compared to 3.3% of patients without an SS (p < 0.001).CONCLUSIONSThe presence of a positive SS among Cushing’s adenomas adjacent to the CS provides strong PPV, specificity, and positive likelihood ratio for the prediction of CSI. This can be a useful tool for preoperative planning and for predicting the likelihood of long-term biochemical remission and the need for adjuvant radiosurgery.

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Outcomes of endoscopic transsphenoidal surgery for Cushing's disease

BMC Endocrine Disorders ◽

10.1186/s12902-021-00679-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zarina Brady ◽

Aoife Garrahy ◽

Claire Carthy ◽

Michael W. O’Reilly ◽

Christopher J. Thompson ◽

...

Keyword(s):

Diabetes Insipidus ◽

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Remission Rate ◽

Cushing's Disease ◽

Endoscopic Transsphenoidal Surgery ◽

Endocrine Society ◽

Csf Leakage ◽

Remission Rates

Abstract Background Transsphenoidal surgery (TSS) to resect an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment for Cushing’s disease (CD), with increasing usage of endoscopic transsphenoidal (ETSS) technique. The aim of this study was to assess remission rates and postoperative complications following ETSS for CD. Methods A retrospective analysis of a prospective single-surgeon database of consecutive patients with CD who underwent ETSS between January 2012–February 2020. Post-operative remission was defined, according to Endocrine Society Guidelines, as a morning serum cortisol < 138 nmol/L within 7 days of surgery, with improvement in clinical features of hypercortisolism. A strict cut-off of < 50 nmol/L at day 3 post-op was also applied, to allow early identification of remission. Results A single surgeon (MJ) performed 43 ETSS in 39 patients. Pre-operative MRI localised an adenoma in 22 (56%) patients; 18 microadenoma and 4 macroadenoma (2 with cavernous sinus invasion). IPSS was carried out in 33 (85%) patients. The remission rates for initial surgery were 87% using standard criteria, 58% using the strict criteria (day 3 cortisol < 50 nmol/L). Three patients had an early repeat ETSS for persistent disease (day 3 cortisol 306-555 nmol/L). When the outcome of repeat early ETSS was included, the remission rate was 92% (36/39) overall. Remission rate was 94% (33/35) when patients with macroadenomas were excluded. There were no cases of CSF leakage, meningitis, vascular injury or visual deterioration. Transient and permanent diabetes insipidus occurred in 33 and 23% following first ETSS, respectively. There was one case of recurrence of CD during the follow-up period of 24 (4–79) months. Conclusion Endoscopic transsphenoidal surgery produces satisfactory remission rates for the primary treatment of CD, with higher remission rates for microadenomas. A longer follow-up period is required to assess recurrence rates. Patients should be counselled regarding risk of postoperative diabetes insipidus.

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Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing's disease, even in case of macroadenomas or invasive adenomas

Acta Endocrinologica ◽

10.1530/eje-13-0325 ◽

2013 ◽

Vol 169 (3) ◽

pp. 329-337 ◽

Cited By ~ 48

Author(s):

M A E M Wagenmakers ◽

H D Boogaarts ◽

S H P P Roerink ◽

H J L M Timmers ◽

N M M L Stikkelbroeck ◽

...

Keyword(s):

Treatment Option ◽

Cushing’S Disease ◽

Remission Rate ◽

Pituitary Surgery ◽

Primary Treatment ◽

Endoscopic Technique ◽

Cushing's Disease ◽

Recurrence Rates ◽

Transsphenoidal Pituitary Surgery

ContextAlthough the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing's disease (CD) are still scarce and no studies have investigated long-term recurrence rates. This is the largest endoscopic series published till now.ObjectiveTo gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas.DesignRetrospective cohort study.Patients and methodsThe medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow-up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level ≤50 nmol/l either basal or after 1 mg dexamethasone.ResultsThe remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (n=20), 83% in microadenomas (n=35), 94% in noninvasive macroadenomas (n=16), and 40% in macroadenomas that invaded the cavernous sinus (n=15). The recurrence rate was 16% after 71±39 months of follow-up (mean±s.d., range 10–165 months).ConclusionsEndoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed.

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Association of different pathologic subtypes of growth hormone producing pituitary adenoma and remission in acromegaly patients: a retrospective cohort study

BMC Endocrine Disorders ◽

10.1186/s12902-021-00850-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Maryam Dehghani ◽

Zahra Davoodi ◽

Farahnaz Bidari ◽

Amin Momeni Moghaddam ◽

Davood Khalili ◽

...

Keyword(s):

Growth Hormone ◽

Cohort Study ◽

Cavernous Sinus ◽

Retrospective Cohort Study ◽

Pituitary Adenomas ◽

Retrospective Cohort ◽

Remission Rate ◽

Cavernous Sinus Invasion ◽

Dual Staining

Abstract Background Regarding the inconclusive results of previous investigations, this study aimed to determine the association between pathology, as a possible predictor, with remission outcomes, to know the role of pathology in the personalized decision making in acromegaly patients. Methods A retrospective cohort study was performed on the consecutive surgeries for growth hormone (GH) producing pituitary adenomas from February 2015 to January 2021. Seventy-one patients were assessed for granulation patterns and prolactin co-expression as dual staining adenomas. The role of pathology and some other predictors on surgical remission was evaluated using logistic regression models. Results Among 71 included patients, 34 (47.9%) patients had densely granulated (DG), 14 (19.7%) had sparsely granulated (SG), 23 (32.4%) had dual staining pituitary adenomas. The remission rate was about 62.5% in the patients with SG and DG adenomas named single staining and 52.2% in dual staining groups. Postoperative remission was 1.53-folds higher in the single staining adenomas than dual staining-one (non-significant). The remission rate was doubled in DG group compared to two other groups (non-significant). By adjusting different predictors, cavernous sinus invasion and one-day postoperative GH levels decreased remission rate by 91% (95% CI: 0.01–0.67; p = 0.015) and 64% (95% CI: 0.19–0.69; p < 0.001), respectively. Responses to the medications were not significantly different among three groups. Conclusion Various pathological subtypes of pituitary adenomas do not appear to have a predictive role in estimating remission outcomes. Cavernous sinus invasion followed by one-day postoperative GH is the strongest parameter to predict biochemical remission.

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