Case Report: A Case of Pituitary Carcinoma Treated With Sequential Dual Immunotherapy and Vascular Endothelial Growth Factor Inhibition Therapy

Lamb, Lydia S; Sim, Hao‐Wen; McCormack, Ann

doi:10.3389/fendo.2020.576027

Cited by 26 publications

(31 citation statements)

References 87 publications

(123 reference statements)

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“…Angiogenesis, a widely studied process by us and by other authors in pituitary pathogenesis ( 17 , 43 – 48 ), can affect tumor promotion and therapy responses. Markers of angiogenesis as VEGF and vascular density were reported to increase in aggressive pituitary tumors, although their significance related to response to anti-angiogenic therapy is uncertain ( 49 ). In our present study, the evaluation of angiogenic parameters showed that the lesion evolved from a highly vascularized and less proliferative to an aggressive and less vascularized tumor, denoting that aggressiveness was driving tumor growth despite less vascularization.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Progression of a Silent Corticotroph Tumor to an Aggressive Secreting Corticotroph Tumor, Treated by Temozolomide. Changes in the Clinic, the Pathology, and the β-Catenin and α-SMA Expression

Demarchi

Perrone²,

Romero³

et al. 2022

Front. Endocrinol.

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Clinically silent corticotroph tumors are usually macroadenomas that comprise 20% of ACTH tumors. They frequently progress to aggressive tumors with high recurrence, invasiveness, and on rare occasions, they may become hormonally active causing Cushing’s disease. Trustable biomarkers that can predict their aggressive course, as well as their response to traditional or new therapies, are paramount. Aberrant β-Catenin expression and localization have been proposed as responsible for several malignancies including pituitary tumors. Nevertheless, the role of β-Catenin in the aggressive transformation of silent corticotropinomas and their response to Temozolomide salvage treatment have not been explored yet. In this work, we present a case of a silent corticotroph tumor that invaded cavernous sinus and compressed optic chiasm and, after a first total resection and tumor remission it recurred six years later as an aggressive ACTH-secreting tumor. This lesion grew with carotid compromise and caused Cushing’s signs. It required multiple medical treatments including Cabergoline, Ketoconazole, TMZ, and radiotherapy. Besides, other two surgeries were needed until it could be controlled. Interestingly, we found α-SMA vascular area reduction and differential β-Catenin cell localization in the more aggressive tumor stages characterized by high Ki-67 indexes and p53 expression. Our results may indicate a role of angiogenesis and β-Catenin trigged events in the pituitary tumor progression, which could in turn affect the response to TMZ and/or conventional treatments. These molecular findings in this unusual case could be useful for future management of aggressive pituitary tumors.

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Section: Discussionmentioning

confidence: 99%

Case Report: Progression of a Silent Corticotroph Tumor to an Aggressive Secreting Corticotroph Tumor, Treated by Temozolomide. Changes in the Clinic, the Pathology, and the β-Catenin and α-SMA Expression

Demarchi

Perrone²,

Romero³

et al. 2022

Front. Endocrinol.

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“…In contrast, progressive disease (PD) was reported in 7 patients [ 15 , 16 , 17 , 18 , 19 , 22 ]. These included 3 cases of uncontrolled progression despite treatment at first evaluation (within 4 months) (1 aggressive corticotroph with CD, 1 aggressive prolactinoma, 1 metastatic prolactinoma) (cases 2, 4, 9).…”

Section: Analysis Of Pitnets Response To Icis According To Their Func...mentioning

confidence: 99%

“…In other patients started on dual ICIs, the treatment was withdrawn for rapid PD and severe immune-related adverse effects (irAEs) in one case (case 4) or shifted to Nivo alone due to irAEs in 2 cases (cases 1 and 5). Of note, in these latter cases, a secondary escape occurred and re-challenge with dual ICIs alone failed, requiring additional local and systemic treatments [ 15 , 19 , 22 ]. In Case 1, pseudoprogression of liver metastasis was observed during 2 separate courses of dual ICIs [ 15 , 22 ].…”

Section: Analysis Of Pitnets Response To Icis According To Their Func...mentioning

confidence: 99%

“…Based on their potential clinical efficacy and acceptable tolerance, ICIs are currently under active evaluation in patients with neuroendocrine tumors (NETs) of different origin, based on either single or combined therapeutic protocols [ 9 , 10 , 11 , 12 , 13 , 14 ]. In PitNETs, the experience is yet limited to case reports or small case series reported since 2018 [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ], including aggressive and metastatic tumors—which will be respectively designed as ag-PitNETs and met-PitNETs. All patients had previously received TMZ and the outcome of ICIs was variable despite very encouraging reports.…”

Section: Introductionmentioning

confidence: 99%

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

Feola

Carbonara

Verrico

et al. 2022

Cancers

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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.

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“…Caccese et al also reported about a patient with a MMRd pituitary adrenocorticotropic hormone- (ACTH-) secreting adenoma treated with the checkpoint inhibitor pembrolizumab [ 38 ]. Similarly, Lamb et al treated a case of prolactin pituitary cancer using ipilimumab and nivolumab in combination with vascular endothelial growth factor inhibition therapy [ 39 ]. In conclusion, the exploration of immunotherapy in pituitary tumors or pituitary carcinomas with high PD-L1 expression is a promising work.…”

Section: Pd-1/pd-l1mentioning

confidence: 99%

Immune Checkpoints: Therapeutic Targets for Pituitary Tumors

et al. 2021

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Pituitary tumors are the third most common intracranial tumors in adults. Treatment of refractory pituitary tumors is known to be difficult due to limited treatment options. As a promising therapeutic method, tumor immunotherapy has been applied in the treatment of many tumors, including pituitary tumors. Immune checkpoint blocking is one of the effective strategies to activate antitumor immunity. Immune checkpoints prevent tissue damage by regulating the immune response of peripheral tissues and participate in the maintenance of a normal immune environment. In the presence of a tumor, inhibition of T cell activity by tumor cells binding to immune checkpoints and their ligands is an important mechanism for tumor cells to escape immune injury. In this review, we summarize the latest findings of immune checkpoints and their potential as immunotherapeutic targets for pituitary tumors.

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Case Report: A Case of Pituitary Carcinoma Treated With Sequential Dual Immunotherapy and Vascular Endothelial Growth Factor Inhibition Therapy

Cited by 26 publications

References 87 publications

Case Report: Progression of a Silent Corticotroph Tumor to an Aggressive Secreting Corticotroph Tumor, Treated by Temozolomide. Changes in the Clinic, the Pathology, and the β-Catenin and α-SMA Expression

Case Report: Progression of a Silent Corticotroph Tumor to an Aggressive Secreting Corticotroph Tumor, Treated by Temozolomide. Changes in the Clinic, the Pathology, and the β-Catenin and α-SMA Expression

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

Immune Checkpoints: Therapeutic Targets for Pituitary Tumors

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