Surgical debulking of pituitary adenomas improves responsiveness to octreotide lar in the treatment of acromegaly

Fahlbusch, Rudolf; Kleinberg, David L.; Bonert, Vivien; Buchfelder, Michael; Cappabianca, Paolo; Carmichael, John D.; Chandler, William F.; Colao, Annamaria; George, Ajax E.; Klibanski, Anne; Knopp, Edmond A.; Kreutzer, J.; Kundurti, Neehar; Lesser, Martin; Mamelak, Adam N.; Pivonello, Rosario; Post, Kalmon D.; Swearingen, Brooke; Vance, Mary Lee; Barkan, Ariel L.

doi:10.1007/s11102-017-0832-8

Cited by 26 publications

(11 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is the first study that evaluates molecular predictors of response to SRLs after debulking surgery of invasive GH‐secreting pituitary tumours. Our data are in the line of other studies showing that surgical debulking improve biochemical response to first‐generation SRLs in patients with large GH‐producing adenomas 9‐13 . In addition, we have identified two molecular markers: Ki‐67 and RORC linked to the odds of response to SRLs after debulking surgery that could be useful in clinical prediction algorithms.…”

Section: Discussionsupporting

confidence: 89%

“…Therefore, enhancing SRLs response could be very useful. Several studies have proved that surgical debulking of these tumours improves SRLs response 9‐13 . Consequently, the current general consensus is to perform surgical debulking even if surgical cure is unlikely, both to alleviate mass effect and to improve SRLs treatment response 14‐16 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH‐producing adenomas

Gil

Marqués‐Pamies

Jordá

et al. 2021

Clinical Endocrinology

View full text Add to dashboard Cite

Objective Large somatotrophic adenomas depict poor response to somatostatin receptor ligands (SRLs). Debulking has shown to enhance SRLs effect in some but not all cases and tumour volume reduction has been proposed as the main predictor of response. No biological studies have been performed so far in this matter. We aimed to identify molecular markers of response to SRLs after surgical debulking in GH‐secreting adenomas. Design We performed a multicenter retrospective study. Patients 24 patients bearing large GH‐producing tumours. Measurements Clinical data and SRLs response both before and after surgical debulking were collected, and 21 molecular biomarkers of SRLs response were studied in tumour samples by gene expression. Results From the 21 molecular markers studied, only two of them predicted enhanced SRLs response after surgery. Tumours with improved response to SRLs after surgical debulking showed lower levels of Ki‐67 (MKI67, FC = 0.17 and P = .008) and higher levels of RAR‐related orphan receptor C (RORC) (FC = 3.1 and P ˂ .001). When a cut‐off of no detectable expression was used for Ki‐67, the model provided a sensitivity of 100% and a specificity of 52.6% with an area under the curve of 65.8%. Using a cut‐off of 2 units of relative expression of RORC, the prediction model showed 100% of sensitivity and specificity. Conclusions High levels of RORC and low levels of Ki‐67 identify improved SRLs response after surgical debulking in large somatotropic adenomas. To determine their expression would facilitate medical treatment decision‐making after surgery.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH‐producing adenomas

Gil

Marqués‐Pamies

Jordá

et al. 2021

Clinical Endocrinology

View full text Add to dashboard Cite

show abstract

“…One of two patients who were not controlled before surgery became controlled when lanreotide was re-introduced following the operation (36). Similar results were obtained by a recent observational study (35).…”

Section: Surgical Debulking and Responsiveness To Srlssupporting

confidence: 72%

“…In addition to a decrease of tumour burden, the goal of surgery for large tumours is to decompress the optic apparatus and the pituitary gland, thereby optimising a potential radiosurgery target. Moreover, surgical debulking of GH-secreting pituitary adenomas improves the postoperative control by SRLs (34,35,36,37). The first study that assessed if debulking surgery improved the post-surgical outcome of SRLs given postoperatively showed that GH normalisation was achieved in 29% patients preoperatively and rose to 54% after debulking, whereas the effect on IGF-I was more impressive, rising from 46 to 78% with postoperative medical therapy (37).…”

Section: Surgical Debulking and Responsiveness To Srlsmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Individualised management of acromegaly

Bollerslev

Heck

Olarescu

2019

European Journal of Endocrinology

View full text Add to dashboard Cite

Acromegaly is a rare and challenging disease calling for management in highly specialised multidisciplinary teams (MDTs). Untreated disease has severe morbidity and a clearly increased mortality. Major attainments have been gained over the latest decades, and therefore, the aim of this review is to discuss recent achievements in modern multimodal therapy of acromegaly performed by MDTs, with an emphasis on an individualised, proactive management from the time of diagnosis to long-term outcome. Treatment by surgery is the only potential curative treatment, however, even with modern techniques still with modest cure rates, leaving the patients to often long-term medical treatment. Treatment strategies have changed dramatically in the Western world over recent years, implying a more proactive treatment algorithm often with a shorter or longer pre-surgical treatment period with somatostatin receptor ligands (SRLs). Not all patients will however respond to primary treatment with conventional SRLs and there has recently been a development of potential biomarkers for response that has been implemented in the clinical routine. By today, multimodal treatment can bring every patient in remission, but still almost a third of all patients are undertreated according to large, international registries. On the other hand, it might be a challenge not to over treat thereby bringing the patient into a state of relative or absolute growth hormone deficiency. Clinical series published during the last decade on treatment of patients with acromegaly have indicated a normalisation of mortality, most probably reflecting the proactive and individualised modern treatment. In conclusion, modern, multimodal treatment seems to have normalised mortality, but still the patients suffer from a high multi-organ morbidity and often multipharmacy. Every patient should receive an individualised, proactive treatment in order to improve long-term outcome and to reduce costs for the society.Correspondence should be addressed to J Bollerslev . His special interest is within clinical and translational endocrinology, and in particular, in classical endocrine diseases, such as acromegaly and Cushing's, often studying bone as target tissues for clinical activity. A major topic has been clinical management of acromegaly, and especially searching for biomarkers for responsiveness to medical therapy. Prospectively collected data of newly diagnosed patients with acromegaly has been the background for current studies of individualised, multimodal and transdisciplinary treatment. European Journal of Endocrinology 181:2 R60 Review J Bollerslev and others Managing acromegaly https://eje.bioscientifica.com European Journal of Endocrinology 181:2 R61 Review J Bollerslev and others Managing acromegaly https://eje.bioscientifica.com European Journal of Endocrinology 181:2 R63 Review J Bollerslev and others Managing acromegaly https://eje.bioscientifica.com European Journal of Endocrinology 181:2 R64 Review J Bollerslev and others Managing acromegaly https://eje.bioscie...

show abstract

“…Moreover, with better surgery coverage, a greater possibility of pharmacological control in cases with no curative perspective can also be expected, which would also result in savings. Even when it is not possible to completely remove a tumour due to anatomical reasons, the resection of all possible tumour tissue (debulking) promotes a better response to drug treatment, which could lead to the use of lower doses of somatostatin analogues and a reduction in costs of treatment [ 4 , 32 – 34 ].…”

Section: Discussionmentioning

confidence: 99%

Economics of Acromegaly Treatment in Brazil: A Budget Impact Analysis of Pituitary Surgery Compared with Long-Term Octreotide LAR

Porto

Zimmermann

Naves

2018

PharmacoEconomics Open

View full text Add to dashboard Cite

Background Acromegaly is a rare, chronic and debilitating disease whose treatment places a high burden on health systems. In the reality of the Brazilian public health network, many patients are kept on drug treatment because of barriers to access to surgery. Objective The aim of this study was to estimate the costs and budget impact of routine transsphenoidal endoscopic surgery in relation to those of long-term drug treatment with octreotide long-acting release (LAR) from a cohort of patients followed at the referral medical centre for acromegaly treatment in the Federal District, Brazil. Methods Based on micro-costing data collected using mixed methods from a local perspective of the public health system, we performed a budget impact analysis (BIA) on a 3-year time horizon. Uncertainty was handled with deterministic (tornado and scenario) and probabilistic (Monte Carlo simulations) sensitivity analyses. Results Compared with the continued use of octreotide LAR at a dose of 30 mg every 28 days, the incremental budget impact of conducting two surgeries per month, considering a cure rate of 55%, could bring savings of approximately US$879,362.18 (95% CI 860,176.29–898,548.08) over 3 years. Depending on the key variable values, the savings amplitude ranged from US$431,836.39 to US$1,519,132.04. Conclusions Improving access to surgery could result in significant cost reductions in acromegaly treatment. The present study stands out for being the first to estimate the costs of transsphenoidal surgery in the context of the public health system in Brazil. Electronic supplementary material The online version of this article (10.1007/s41669-018-0103-2) contains supplementary material, which is available to authorized users.

show abstract

Surgical debulking of pituitary adenomas improves responsiveness to octreotide lar in the treatment of acromegaly

Cited by 26 publications

References 33 publications

Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH‐producing adenomas

Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH‐producing adenomas

MANAGEMENT OF ENDOCRINE DISEASE: Individualised management of acromegaly

Economics of Acromegaly Treatment in Brazil: A Budget Impact Analysis of Pituitary Surgery Compared with Long-Term Octreotide LAR

Contact Info

Product

Resources

About