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Advances for Sellar and Parasellar Tumours: Current Treatments and Future Directions

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 12187

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Special Issue Editor

Dr. Giuseppe Minniti

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Guest Editor

Radiation Oncology Unit, UPMC Hillman Cancer Center, San Pietro Hospital FBF, 00189 Rome, Italy
Interests: brain tumors; stereotactic radiosurgery; radiation therapy; gliomas; brain metastases; benign brain tumors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Parasellar tumors represent a wide group of intracranial lesions, both benign and malignant. The treatment of tumors located in these areas is challenging because of their complex anatomical location and heterogenous histology. It often requires a multimodal approach, including surgery, radiation therapy (RT), and medical therapy. Surgery remains the cornerstone for the treatment of skull-based tumors, and advances in technology mean that surgery is becoming safer and more precise. Conventional fractionated RT and modern radiation techniques, such as stereotactic radiosurgery and proton beam RT, have become a standard management option, particularly for cases with residual or recurrent tumors after surgery and for those cases where surgery is contraindicated. Recently, immunotherapy and targeted agents have shown a promising clinical activity in tumors harboring specific molecular mutations, and clinical trials are ongoing.

Dr. Giuseppe Minniti
Guest Editor

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Keywords

surgery
radiosurgery
radiotherapy
pituitary tumors
parasellar tumors
chordoma
craniopharyngioma
meningioma

Published Papers (7 papers)

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Research

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12 pages, 1846 KiB

Open AccessArticle

Machine Learning Analysis of Post-Operative Tumour Progression in Non-Functioning Pituitary Neuroendocrine Tumours: A Pilot Study

by Ziad Hussein, Robert W. Slack, Stephanie E. Baldeweg, Evangelos B. Mazomenos and Hani J. Marcus

Cancers 2024, 16(6), 1199; https://doi.org/10.3390/cancers16061199 - 19 Mar 2024

Viewed by 714

Abstract

Post-operative tumour progression in patients with non-functioning pituitary neuroendocrine tumours is variable. The aim of this study was to use machine learning (ML) models to improve the prediction of post-operative outcomes in patients with NF PitNET. We studied data from 383 patients who underwent surgery with or without radiotherapy, with a follow-up period between 6 months and 15 years. ML models, including k-nearest neighbour (KNN), support vector machine (SVM), and decision tree, showed superior performance in predicting tumour progression when compared with parametric statistical modelling using logistic regression, with SVM achieving the highest performance. The strongest predictor of tumour progression was the extent of surgical resection, with patient age, tumour volume, and the use of radiotherapy also showing influence. No features showed an association with tumour recurrence following a complete resection. In conclusion, this study demonstrates the potential of ML models in predicting post-operative outcomes for patients with NF PitNET. Future work should look to include additional, more granular, multicentre data, including incorporating imaging and operative video data. Full article

(This article belongs to the Special Issue Advances for Sellar and Parasellar Tumours: Current Treatments and Future Directions)

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13 pages, 2513 KiB

Open AccessArticle

A β-Arrestin 2-Biased Dopamine Receptor Type 2 (DRD2) Agonist Is More Efficacious Than Cabergoline in Reducing Cell Proliferation in PRL-Secreting but Not in Non-Functioning Pituitary Tumor Cells

by Genesio Di Muro, Federica Mangili, Emanuela Esposito, Anna Maria Barbieri, Rosa Catalano, Donatella Treppiedi, Giusy Marra, Emma Nozza, Andrea G. A. Lania, Emanuele Ferrante, Marco Locatelli, Maura Arosio, Erika Peverelli and Giovanna Mantovani

Cancers 2023, 15(12), 3218; https://doi.org/10.3390/cancers15123218 - 16 Jun 2023

Cited by 1 | Viewed by 1160

Abstract

The molecular events underlying the variable effectiveness of dopamine receptor type 2 (DRD2) agonists in pituitary neuroendocrine tumors (PitNETs) are not known. Besides the canonical pathway induced by DRD2 coupling with Gi proteins, the β-arrestin 2 pathway contributes to DRD2′s antimitotic effects in PRL- and NF-PitNETs. A promising pharmacological strategy is the use of DRD2-biased agonists that selectively activate only one of these two pathways. The aim of the present study was to compare the effects of two biased DRD2 ligands, selectively activating the G protein (MLS1547) or β-arrestin 2 (UNC9994) pathway, with unbiased DRD2 agonist cabergoline in PRL- and NF-PitNET cells. In rat tumoral pituitary PRL-secreting MMQ cells, UNC9994 reduced cell proliferation with a greater efficacy compared to cabergoline (−40.2 ± 20.4% vs. −21 ± 10.9%, p < 0.05), whereas the G-protein-biased agonist induced only a slight reduction. β-arrestin 2 silencing, but not pertussis toxin treatment, reverted UNC9994 and cabergoline’s antiproliferative effects. In a cabergoline-resistant PRL-PitNET primary culture, UNC9994 inhibited cell proliferation and PRL release. In contrast, in NF-PitNET primary cultures (n = 23), biased agonists did not show better antiproliferative effects than cabergoline. In conclusion, the preferential activation of the β-arrestin 2 pathway by UNC9994 improves DRD2-mediated antiproliferative effects in PRL-PitNETs, suggesting a new pharmacological approach for resistant or poorly responsive tumors. Full article

(This article belongs to the Special Issue Advances for Sellar and Parasellar Tumours: Current Treatments and Future Directions)

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Graphical abstract

11 pages, 1101 KiB

Open AccessArticle

Post-Operative Medium- and Long-Term Endocrine Outcomes in Patients with Non-Functioning Pituitary Adenomas—Machine Learning Analysis

by Ziad Hussein, Robert W. Slack, Hani J. Marcus, Evangelos B. Mazomenos and Stephanie E. Baldeweg

Cancers 2023, 15(10), 2771; https://doi.org/10.3390/cancers15102771 - 16 May 2023

Cited by 3 | Viewed by 1247

Abstract

Post-operative endocrine outcomes in patients with non-functioning pituitary adenoma (NFPA) are variable. The aim of this study was to use machine learning (ML) models to better predict medium- and long-term post-operative hypopituitarism in patients with NFPAs. We included data from 383 patients who underwent surgery with or without radiotherapy for NFPAs, with a follow-up period between 6 months and 15 years. ML models, including k-nearest neighbour (KNN), support vector machine (SVM), and decision tree models, showed a superior ability to predict panhypopituitarism compared with non-parametric statistical modelling (mean accuracy: 0.89; mean AUC-ROC: 0.79), with SVM achieving the highest performance (mean accuracy: 0.94; mean AUC-ROC: 0.88). Pre-operative endocrine function was the strongest feature for predicting panhypopituitarism within 1 year post-operatively, while endocrine outcomes at 1 year post-operatively supported strong predictions of panhypopituitarism at 5 and 10 years post-operatively. Other features found to contribute to panhypopituitarism prediction were age, volume of tumour, and the use of radiotherapy. In conclusion, our study demonstrates that ML models show potential in predicting post-operative panhypopituitarism in the medium and long term in patients with NFPM. Future work will include incorporating additional, more granular data, including imaging and operative video data, across multiple centres. Full article

(This article belongs to the Special Issue Advances for Sellar and Parasellar Tumours: Current Treatments and Future Directions)

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14 pages, 2776 KiB

Open AccessArticle

Efficacy of a Novel Augmented Reality Navigation System Using 3D Computer Graphic Modeling in Endoscopic Transsphenoidal Surgery for Sellar and Parasellar Tumors

by Yoshiaki Goto, Ai Kawaguchi, Yuki Inoue, Yuki Nakamura, Yuta Oyama, Arisa Tomioka, Fumi Higuchi, Takeshi Uno, Masaaki Shojima, Taichi Kin and Masahiro Shin

Cancers 2023, 15(7), 2148; https://doi.org/10.3390/cancers15072148 - 4 Apr 2023

Cited by 5 | Viewed by 1754

Abstract

In endoscopic transsphenoidal skull base surgery, knowledge of tumor location on imaging and the anatomic structures is required simultaneously. However, it is often difficult to accurately reconstruct the endoscopic vision of the surgical field from the pre-surgical radiographic images because the lesion remarkably displaces the geography of normal anatomic structures. We created a precise three-dimensional computer graphic model from preoperative radiographic data that was then superimposed on a visual image of the actual surgical field and displayed on a video monitor during endoscopic transsphenoidal surgery. We evaluated the efficacy of this augmented reality (AR) navigation system in 15 consecutive patients with sellar and parasellar tumors. The average score overall was 4.7 [95% confidence interval: 4.58–4.82], which indicates that the AR navigation system was as useful as or more useful than conventional navigation in certain patients. In two patients, AR navigation was assessed as less useful than conventional navigation because perception of the depth of the lesion was more difficult. The developed system was more useful than conventional navigation for facilitating an immediate three-dimensional understanding of the lesion and surrounding structures. Full article

(This article belongs to the Special Issue Advances for Sellar and Parasellar Tumours: Current Treatments and Future Directions)

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Review

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13 pages, 5051 KiB

Open AccessReview

History, Current Techniques, and Future Prospects of Surgery to the Sellar and Parasellar Region

by Cameron A. Rawanduzy and William T. Couldwell

Cancers 2023, 15(11), 2896; https://doi.org/10.3390/cancers15112896 - 24 May 2023

Viewed by 2628

Abstract

The sellar and parasellar region can be affected by diverse pathologies. The deep-seated location and surrounding critical neurovascular structures make treatment challenging; there is no singular, optimal approach for management. The history and development of transcranial and transsphenoidal approaches by pioneers in skull base surgery were largely aimed at treating pituitary adenomas, which are the most common lesions of the sella. This review explores the history of sellar surgery, the most commonly used approaches today, and future considerations for surgery of the sellar/parasellar region. Full article

(This article belongs to the Special Issue Advances for Sellar and Parasellar Tumours: Current Treatments and Future Directions)

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31 pages, 17240 KiB

Open AccessReview

The Party Wall: Redefining the Indications of Transcranial Approaches for Giant Pituitary Adenomas in Endoscopic Era

by Sabino Luzzi, Alice Giotta Lucifero, Jessica Rabski, Paulo A. S. Kadri and Ossama Al-Mefty

Cancers 2023, 15(8), 2235; https://doi.org/10.3390/cancers15082235 - 10 Apr 2023

Cited by 2 | Viewed by 1918

Abstract

The evolution of endoscopic trans-sphenoidal surgery raises the question of the role of transcranial surgery for pituitary tumors, particularly with the effectiveness of adjunct irradiation. This narrative review aims to redefine the current indications for the transcranial approaches for giant pituitary adenomas in the endoscopic era. A critical appraisal of the personal series of the senior author (O.A.-M.) was performed to characterize the patient factors and the tumor’s pathological anatomy features that endorse a cranial approach. Traditional indications for transcranial approaches include the absent pneumatization of the sphenoid sinus; kissing/ectatic internal carotid arteries; reduced dimensions of the sella; lateral invasion of the cavernous sinus lateral to the carotid artery; dumbbell-shaped tumors caused by severe diaphragm constriction; fibrous/calcified tumor consistency; wide supra-, para-, and retrosellar extension; arterial encasement; brain invasion; coexisting cerebral aneurysms; and separate coexisting pathologies of the sphenoid sinus, especially infections. Residual/recurrent tumors and postoperative pituitary apoplexy after trans-sphenoidal surgery require individualized considerations. Transcranial approaches still have a critical role in giant and complex pituitary adenomas with wide intracranial extension, brain parenchymal involvement, and the encasement of neurovascular structures. Full article

(This article belongs to the Special Issue Advances for Sellar and Parasellar Tumours: Current Treatments and Future Directions)

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16 pages, 12579 KiB

Open AccessReview

Immunotherapy for Aggressive and Metastatic Pituitary Neuroendocrine Tumors (PitNETs): State-of-the Art

by Tiziana Feola, Francesca Carbonara, Monica Verrico, Rosa Maria Di Crescenzo, Francesca Gianno, Claudio Colonnese, Antonietta Arcella, Dario de Alcubierre, Silverio Tomao, Vincenzo Esposito, Felice Giangaspero, Giuseppe Minniti and Marie-Lise Jaffrain-Rea

Cancers 2022, 14(17), 4093; https://doi.org/10.3390/cancers14174093 - 24 Aug 2022

Cited by 8 | Viewed by 2006

Abstract

Background: Aggressive and metastatic PitNETs are challenging conditions. Immune checkpoint inhibitors (ICIs) are currently considered in cases resistant to temozolomide (TMZ). However, clinical experience is essentially limited to case reports, with variable outcomes. Material and Methods: The effects of ICIs on 12 aggressive/metastatic PitNETs from the literature were reviewed and analyzed according to tumor characteristics, with the additional description of a silent-Pit1 metastatic tumor responding to pembrolizumab. Results: Most cases were metastatic (10/13: 6 corticotroph, 3 lactotroph, 1 silent Pit1); 3 were aggressive (2 corticotroph, 1 lactotroph). ICIS was used either as monotherapy or in combination. At last follow-up on ICI, a complete response (CR) was present in 3 cases and a partial response (PR) in 2 cases (4/5 metastatic). One sustained stable disease (SD) was reported. Progressive disease (PD) was observed in 7 cases, 3 of them after initial SD (n = 1) or PR (n = 3), with 2 reported deaths. PDL1 expression was studied in 10 cases and was high (>95%) in 2 Pit1-derived metastatic PitNETs (1 CR and 1 remarkable PR) but absent/low (<1%) in the remaining cases (including 1 CP and 2 PR). Elevated tumor mutation burden could be informative in corticotroph PitNETs, especially in mismatch repair-deficient tumors. Conclusion: Significant benefits from ICIs were documented in about half of TMZ-resistant PitNETS. High PDL1 expression was associated with remarkable responses but may be dispensable. Based on their acceptable tolerance and awaiting recognized predictors of response, ICIs may be considered a valuable option for such patients. Full article

(This article belongs to the Special Issue Advances for Sellar and Parasellar Tumours: Current Treatments and Future Directions)

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