Radiation Treatment Strategies for Acromegaly

In This Article

Abstract and Introduction
Methods
Results
Conclusions
References

Abstract and Introduction

Abstract

The high morbidity and mortality associated with acromegaly can be addressed with multiple treatment modalities, including surgery, medicines, and radiation therapy. Radiation was initially delivered through conventional fractionated radiotherapy, which targets a wide area over many treatment sessions and has been shown to induce remission in 50%–60% of patients with acromegaly. However, conventional fractionated radiotherapy takes several years to achieve remission in patients with acromegaly and carries a risk of hypopituitarism that may limit its use. Stereotactic radiosurgery, of which there are several forms, including Gamma Knife surgery, CyberKnife therapy, and proton beam therapy, offers slightly attenuated efficacy but achieves remission in less time and provides more precise targeting of the adenoma with better control of the dose of radiation received by adjacent structures such as the pituitary stalk, pituitary gland, optic chiasm, and cranial nerves in the cavernous sinus. Of the forms of stereotactic radiosurgery, Gamma Knife surgery is the most widely used and, because of its long-term follow-up in clinical studies, is the most likely to compete with medical therapy for first-line adjuvant use after resection. In this review, the authors outline the major modes of radiation therapies in clinical use today, and they critically assess the feasibility of these modalities for acromegaly treatment. Acromegaly is a multisystem disorder that demands highly specialized treatment protocols including neurosurgical and endocrinological intervention. As more efficient forms of pituitary radiation develop, acromegaly treatment options may continue to change with radiation therapies playing a more prominent role.

Introduction

Transsphenoidal microsurgery to resect the causative GH-secreting pituitary adenoma remains the initial treatment of choice in the majority of patients with acromegaly.^{[10,25,48,52,53,74,90]} However, the optimal management of the 10%–50% of patients who do not enter remission after transsphenoidal surgery^[13,52] and the 20% of patients who experience recurrence of acromegaly after transsphenoidal surgery^[13] remains less clear. Radiation represents an evolving treatment modality for acromegaly that warrants consideration as an alternative to medical therapy for tumors refractory to transsphenoidal surgery.

The conceptual groundwork for focused irradiation of GH-secreting pituitary adenomas while avoiding damage to surrounding neural structures was established more than 50 years ago.^[2,56,97] Since that time, substantial advances in radiation technology have yielded increasingly precise pituitary adenoma–targeting capability and consequently an expanded set of treatment options for acromegaly to supplement resection and hormonal suppression with medical management. A complex array of factors dictate treatment decisions for acromegaly in the modern era, including adenoma size, degree of secretory hyperactivity, invasion of surrounding structures, and therapeutic side effects and their particular impact in the patient in question. For these reasons, contemporary treatment of patients with acromegaly now routinely involves multiple disciplines, including neurosurgery, endocrinology, and radiation oncology.^{[1,3,27,34,47,62,64,65,76,78]} Indeed, in cases of acromegaly, all 3 approaches (surgery, medication, and radiation) can be beneficial and can play a role in management. Thus, an expert panel, the Acromegaly Consensus Group, formed in 2000, publishes guidelines for acromegaly management, most recently in 2009. The recommendations are that tumors deemed completely resectable undergo surgery, with somatostatin analogs used in cases in which remission after surgery is not achieved. Tumors deemed incompletely resectable are treated with somatostatin analogs. Cases in which remission is not achieved with the use of somatostatin analogs are treated with pegvisomant if there is no mass effect on MR imaging, because the tumor growth that can occur with pegvisomant would be tolerated, or with radiation if there is mass effect on MR imaging.^[63] However, because these recommendations are not based on randomized clinical trials, further studies will likely be needed to definitively determine the role of radiation therapy in achieving the best long-term outcome for patients with acromegaly. Here, we review the results to date with radiation as a treatment modality for acromegaly, and we outline future directions that might get us closer to a definitive understanding of the role of radiation in acromegaly management.

Cite this: Radiation Treatment Strategies for Acromegaly - Medscape - Oct 01, 2010.

Table 1. Results of published series studying conventional fractionated radiotherapy in the treatment of acromegaly^*
Authors & Year	No. of Patients	FU Time (yrs)	Mean Total Dose in Gy (range)	Mean No. of Fractions (range)	Remission Criteria	Remission Rate (%)	Mean Time to Remission (yrs)	New Posttreatment Hormone Deficiency		Induced Tumors
Authors & Year	No. of Patients	FU Time (yrs)	Mean Total Dose in Gy (range)	Mean No. of Fractions (range)	Remission Criteria	Remission Rate (%)	Mean Time to Remission (yrs)	% Patients	Mean Time to Deficit (yrs)	Induced Tumors
Barkan et al., 1997	38	mean 6.8	46 (45–50)	24	normal IGF-I	5	5	NE	NE	NE
Powell et al., 2000	47	mean 5.2	47 (45–54)	26 (25–30)	normal IGF-I	60	10	32	NE	0
Biermasz et al., 2000	0	mean 11.3	40 (25–50)	19	normal IGF-I	74	10	50	10	0
Epaminonda et al., 2001	67	median 10	54 (40–75)	33 (30–35)	GH <2.5 ng/ml & normal IGF-I	65	15	60	NE	2 meningiomas, 1 pinealoma 9–22 yrs after CFR
Barrande et al., 2000	128	mean 11.5	52	29	GH <2.5 ng/ml & normal IGF-I	53	10	80	10	0
Cozzi et al., 2001	49	median 14	45	22	GH <2.5 ng/ml & normal IGF-I	10	10	8	10	2 meningiomas 27–30 yrs after CFR
Minniti et al., 2005	74	median 12	45	25	GH <1.0 ng/ml & normal IGF-I	47	10	80	10	0
Jenkins et al., 2006	884	median 7	45 (10–55)	25	GH <2.5 ng/ml or normal IGF-I	60	10	60	10	0
Jallad et al., 2007	89	mean 5.9	50 (32.4–60)

* NE = not evaluated.

Table 2. Results of series reported in 2007–2009 studying radiosurgery for the treatment of acromegaly^*
Authors & Year	No. of Patients	FU Time (yrs)	Modality (targeted field of treatment)	Dose	Remission Criteria	Remission Rate (%)	Mean Time to Remission (mos)	New Posttreatment Hormone Deficiency
Authors & Year	No. of Patients	FU Time (yrs)	Modality (targeted field of treatment)	Dose	Remission Criteria	Remission Rate (%)	Mean Time to Remission (mos)	% Patients	Time to Deficit (yrs)
Roberts et al., 2007	9	mean 2.1†	CyberKnife therapy (NR)	21 Gy‡	normal IGF-I	44	12	33	NR
Petit et al., 2007	22	median 6.3	PBRS (sella)	median 20 CGE	normal IGF-I	59	42	38	median 3–4.7†,§
Pollock et al., 2007	48	median 5.3†	GKS (tumor margins)	20 Gy¶	normal IGF-I & GH <2 ng/ml	50	36	33	median 2.7†
Vik-Mo et al., 2007	53	mean 5.5	GKS (tumor margins)	25 Gy‡	normal IGF-I	17	not stated	13	NR
Jagannathan et al., 2008	95	mean 4.8†	GKS (various)	22 Gy‡	normal IGF-I	53	29.8	34 (1.6)	mean 1.6†
Losa et al., 2008	83	median 5.8†	GKS (tumor margins)	25 Gy‡	normal IGF-I & GH <2.5 ng/ml	60	60	10	3.3%–4.9% cumulative risk at 5 yrs
Imran et al., 2009	12	median 2.4†	LINAC-based (tumor margins)	NE	normal IGF-I	33	NR	8	2 (in 1 patient)†
Swords et al., 2009	10	median 3.0†,**	GKS (tumor margins)	NE	normal IGF-I	80	NR	NR	NR
Cho et al., 2009	6	median 3.0†,**	CyberKnife therapy (tumor margins)	1983 cGy††	GH <5 mIU/L	33	15	0
Ronchi et al., 2009	35	median 9.5†	GKS (tumor margins)	20 Gy¶	GH <2.5 ng/ml, normal IGF-I, & postglucose GH nadir <1 ng/ml	46	120	50	median 8.3†
Castinetti et al., 2009	43	mean 8.5 remission†; mean 8.2 uncured†	GKS (tumor margins)	24 Gy‡‡	GH <2 ng/ml &/or postglucose GH <1 ng/ml & normal IGF-I	42	50	NR for acro cohort	NR for acro cohort
Kobayashi, 2009	71	mean 5.3†	GKS (NR)	18.9 Gy‡	GH <1 ng/ml	4.8	NR	14.6	NR

* acro = acromegaly; CGE = cobalt Gray equivalents; NR = not reported; PBRS = proton-beam radiosurgery.
† Conversion from months.
‡ Mean margin dose.
§ Depending on the hormone deficit.
¶ Median margin dose.
** Calculated median from raw data to nearest tenth.
†† Mean total dose.
‡‡ Mean isodose 50.

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

My Alerts

Add to Email Alerts

Radiation Treatment Strategies for Acromegaly

Abstract and Introduction

Abstract

Introduction

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

Comments

Email This

Feedback