Gamma Knife Radiosurgery (GKRS) for Patients with Prolactinomas: Long-Term Results From a Single-Center Experience.

BACKGROUND The aim of this study was to review outcomes of gamma knife radiosurgery (GKRS) for prolactinoma and report our experience with it. MATERIAL AND METHODS We reviewed the patient database in our center and identified 24 patients with prolactinoma who underwent GKRS from 1993 to 2016.  Complete endocrine, clinical, and radiological data were available on these individuals before and after GKRS. RESULTS Data from 5 males and 19 females with a median age of 30.5 years (range, 18.1 to 51.1) were reviewed. The median follow-up was 109.3 months (range, 23.2-269.3). The median margin dose of GKRS was 15 Gy (range, 10.5 to 23.6). In total, prolactin (PRL) normalization after GKRS was achieved in 66.7% of patients. Endocrine remission (normal PRL levels after discontinuation of dopamine agonists) was achieved in 10 patients (41.7%), and endocrine control (normal PRL levels while taking dopamine agonists) was achieved in 6 patients (25.0%). All of the patients showed tumor control. New-onset hypopituitarism post-GKRS occurred in 4 patients (16.7%). No new visual dysfunction or cranial nerve dysfunction were observed after GKRS. CONCLUSIONS For treatment of prolactinomas, GKRS may provide relatively high rates of endocrine remission and tumor control, as well as a low rate of new-onset hypopituitarism. GKRS may be an effective and safe treatment for prolactinomas.

Role of gamma knife radiosurgery in the treatment of prolactinomas.

PURPOSE: Stereotactic radiosurgery is one of the treatment options for prolactinomas, the most commonly used being Gamma Knife Radiosurgery (GKRS). GKRS is indicated mainly in the treatment of dopamine agonist (DA)-resistant prolactinomas. In our study, we report on our experience in treating prolactinoma patients by GKRS. METHODS: Twenty-eight patients were followed-up after GKRS for 26-195 months (median 140 months). Prior to GKRS, patients were treated with DAs and 9 of them (32.1%) underwent previous neurosurgery. Cavernous sinus invasion was present in 16 (57.1%) patients. Indications for GKRS were (i) resistance to DA treatment (17 patients), (ii) drug intolerance (5 patients), or (iii) attempts to reduce the dosage and/or shorten the length of DA treatment (6 patients). RESULTS: After GKRS, normoprolactinaemia was achieved in 82.1% of patients, out of which hormonal remission (normoprolactinaemia after discontinuation of DAs) was achieved in 13 (46.4%), and hormonal control (normoprolactinaemia while taking DAs) in 10 (35.7%) patients. GKRS arrested adenoma growth or decreased adenoma size in all cases. Two patients (8.3%) developed hypopituitarism after GKRS. Prolactinoma cystic transformation with expansive behaviour, manifested by bilateral hemianopsia, was observed in one patient. CONCLUSIONS: GKRS represents an effective treatment option, particularly for DA-resistant prolactinomas. Normoprolactinaemia was achieved in the majority of patients, either after discontinuation of, or while continuing to take, DAs. Tumour growth was arrested in all cases. The risk of the development of hypopituitarism can be limited if the safe dose to the pituitary and infundibulum is maintained.

Giant Prolactinoma in Men: Clinical Features and Therapeutic Outcomes.

The aim of the study was to evaluate the clinical features and long-term therapeutic outcome of giant prolactinoma (gPRLoma) in men and to compare them with those of a group of male patients with non-gPRL macroprolactinomas (non-gPRLomas). A retrospective and multicenter study of gPRLomas in men diagnosed in a 20-year period was performed. Clinical data and treatment outcome were registered. The diagnosis of gPRLoma was established when the maximal tumor diameter was ≥40 mm or the tumor had ≥20 mm of suprasellar extension associated to hyperprolactinemia (PRL>1000 ng/ml). Non-gPRLoma was considered when tumor diameter was ≥ 10 mm and<40 mm associated to hyperprolactinemia (PRL≥200 ng/ml). Twenty-three patients with gPRLoma (age 38.3±13.5 years) followed for at least 3 months (follow-up 87.1±60.5 months, range 3-211 months) were evaluated. A group of 42 patients with non-gPRLoma (age 42±16.6 years; NS; follow-up 89±65.9 months, range 3-222 months; NS) served as a control group. More than half (56.5%) of the gPRLoma patients were younger than 40 years at diagnosis. Visual disturbances were significantly more common in gPRLoma than in non-gPRLoma patients (65.2 vs. 25.6%; p=0.004). Prevalence of hypopituitarism was similar in both groups of patients (73.9% vs. 80.9%; gPRLoma vs non-gPRLoma; NS). Serum PRL concentrations were significantly higher in gPRLoma than in non-gPRLoma patients [median (IR), 3978 ng/ml (1179-9012) vs. 907 ng/ml (428-3119); p<0.001]. Maximum tumor diameter in gPRLomas was 4.8±0.8 cm and 2.4±0.7 cm in non-gPRLoma (p<0.001). All patients were treated with dopamine agonists (DA). Twelve (52.2%) gPRLoma patients and 32 (73.8%) non-gPRLoma patients were treated with DA as monotherapy (p=0.045). Surgery was used in 12 (52.2%) gPRLoma patients and in 12 (28.6%) non-gPRLoma patients (p=0.054). Lastly, radiotherapy was used in 5 (21.7%) gPRLoma patients and in 6 (14.2%) non-gPRLoma patients (NS). At last visit, PRL was similar in both groups of patients [16 ng/ml (4-30) vs. 11 ng/ml (4-25); gPRLomas vs. non-gPRLomas; ns] and tumor size decreased significantly (p<0.001) in both groups of patients. Clinical cure (maintained normoprolactinemia without therapy for>1 year and no radiological evidence of pituitary tumor) was achieved in 2 (8.7%) gPRLoma patients and in 2 (4.8%) non-gPRLoma patients (NS). gPRLomas in men are usually diagnosed at a mean age of 40 years, an age similar to that of non-gPRLomas. The only clinical difference with non-gPRLomas is their greater prevalence of visual disturbances. The therapeutic approaches and tumor outcomes were similar to those obtained in patients with non-gPRLomas. Complete cure in gPRLoma is rare, but similar to that achieved in non-gPRLomas, reached in less than 10% of patients.

Peptide receptor radionuclide therapy for aggressive atypical pituitary adenoma/carcinoma: variable clinical response in preliminary evaluation.

PURPOSE: There are limited treatment options for progressive atypical pituitary adenomas and carcinomas. Peptide receptor radionuclide therapy that targets somatostatin receptors has recently been proposed as a potential treatment option. The theoretical rationale for efficacy is elegant but evaluation of outcomes in the first patients treated for this indication is required to assess whether further study is warranted. METHODS: We performed a case review of the three pituitary patients we have treated with (177)Lutetium DOTATATE in our institution (two atypical adenomas, one carcinoma) and dosimetric analysis of the radiation uptake in one patient. RESULTS: Treatment was well tolerated. One patient with slowly progressive pituitary carcinoma has stable disease 40 months after completing the planned 4 cycles of treatment. Two patients with rapidly progressive atypical adenomas terminated treatment early due to continued disease progression. Dosimetric evaluation revealed inhomogenous uptake across the tumour (1.3-11.9 Gy with one cycle). CONCLUSION: We have found mixed results in our first 3 patients with stable disease achieved only in the patient with the more slowly progressive tumour. As only a limited number of centres offer Peptide receptor radionuclide therapy, a formal study with prospective data collection may be feasible and if carried out should include dosimetric evaluation of absorbed dose.

Gamma knife stereotactic radiosurgery for drug resistant or intolerant invasive prolactinomas.

We evaluated the efficacy of Gamma knife stereotactic radiosurgery (GKSR) as an adjunctive management modality for patients with drug resistant or intolerant cavernous sinus invasive prolactinomas. Twenty-two patients with cavernous sinus invasive prolactinoma underwent GKSR between 1994 and 2009. Thirteen patients were dopamine agonist (DA) resistant. Six patients were intolerant to DA. Three patients chose GKSR as their initial treatment modality in hopes they might avoid life long suppression medication. The median tumor volume was 3.0 cm3 (range 0.3­11.6). The marginal tumor dose (median= 15 Gy, range 12­25 Gy) prescribed was based on the dose delivered to the optic apparatus. The median follow-up interval was 36 months (range, 12­185). Endocrine normalization was defined as a normal serum prolactin level off DA (cure) or on DA. Endocrine improvement was defined asa decreased but still elevated serum prolactin level. Endocrine deterioration was defined as an increased serum prolactin level. Endocrine normalization was achieved in six(27.3%) patients. Twelve (54.5%) patients had endocrine improvement. Four patients (18.2%) developed delayed increased prolactin. Imaging-defined local tumor control was achieved in 19 (86.4%) patients, 12 of whom had tumor regression. Three patients had a delayed tumor progression and required additional management. One patient developed a new pituitary axis deficiency after GKSR. Invasive prolactinomas continue to pose management challenges. GKSR is a non invasive adjunctive option that may reduce prolactin levels in patients who are resistant to or intolerant of suppression medication. In a minority of cases, patients may no longer require long term suppression therapy.

Radiotherapy for prolactin-secreting pituitary tumors.

Review the medical and surgical management of patients with prolactinomas and provide an in-depth appraisal of the role of radiotherapy in the treatment of prolactinomas. A thorough review of the pertinent literature was carried out and relevant topics were identified. Topics covered in this comprehensive review include: indications for the use of radiotherapy, choice between conventional radiotherapy and stereotactic radiosurgery, as well as the benefits and potential complications associated with each modality. Due to the excellent response rates with medical management, and rapid symptom relief afforded by resection or debulking surgery in patients who do not respond or tolerate medical therapy, radiotherapy is reserved for patients who do not respond to dopamine agonists and surgery. Both external beam radiotherapy and stereotactic radiosurgery retain important roles in the treatment of refractory or recurrent prolactinomas. Choosing the optimal approach is crucial in maximizing tumor control outcomes and minimizing the risks associated with treatment. The primary determinants of optimal radiation approach are proximity of the tumor to the optic apparatus and tumor size, with radiosurgery being our recommended treatment of choice unless the tumor is larger than 3-4 cm or within 3 mm of the optic nerves, chiasm or tracts. Optimal multidisciplinary management requires the identification of appropriate candidates for radiotherapy in order to take full advantage of treatment options available for each patient.

Stereotactic radiosurgery for secretory pituitary adenomas: systematic review and International Stereotactic Radiosurgery Society practice recommendations.

OBJECTIVE: A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and develop consensus recommendations. METHODS: The authors performed a systematic review of the English-language literature up until June 2018 using the PRISMA guidelines. The PubMed (Medline), Embase, and Cochrane databases were searched. A total of 45 articles reporting single-institution outcomes of SRS for acromegaly, Cushing's disease, and prolactinomas were selected and included in the analysis. RESULTS: For acromegaly, random effects meta-analysis estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rates were 97.0% (95% CI 96.0%-98.0%), 44.0% (95% CI 35.0%-53.0%), and 17.0% (95% CI 13.0%-23.0%), respectively. For Cushing's disease, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 92.0% (95% CI 87.0%-95.0%), 48.0% (95% CI 35.0%-61.0%), and 21.0% (95% CI 13.0%-31.0%), respectively. For prolactinomas, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 93.0% (95% CI 90.0%-95.0%), 28.0% (95% CI 19.0%-39.0%), and 12.0% (95% CI 6.0%-24.0%), respectively. Meta-regression analysis did not show a statistically significant association between mean margin dose with crude endocrine remission rate or mean margin dose with development of any new hypopituitarism rate for any of the secretory subtypes. CONCLUSIONS: SRS offers effective tumor control of hormone-producing pituitary adenomas in the majority of patients but a lower rate of endocrine improvement or remission.

Radiation-induced ocular motor cranial nerve palsies in patients with pituitary tumor.

BACKGROUND: Radiation therapy is often used in the treatment of pituitary tumor. Diplopia due to radiation damage to the ocular motor cranial nerves has been infrequently reported as a complication in this clinical setting. METHODS: Retrospective case series of 6 patients (3 men and 3 women) with pituitary adenoma, all of whom developed diplopia following transsphenoidal resection of pituitary adenoma with subsequent radiation therapy. None had evidence of tumor involvement of the cavernous sinus. RESULTS: Five patients developed sixth nerve palsies, 3 unilateral and 2 bilateral, and in 1 patient, a sixth nerve palsy was preceded by a fourth cranial nerve palsy. One patient developed third nerve palsy. Five of the 6 patients had a growth hormone-secreting pituitary tumor with acromegaly. Following transsphenoidal surgery in all 6 patients (2 had 2 surgeries), 4 had 2 radiation treatments consisting of either radiosurgery (2 patients) or external beam radiation followed by radiosurgery (2 patients). CONCLUSIONS: Patients with pituitary tumors treated multiple times with various forms of radiation therapy are at risk to sustain ocular motor cranial nerve injury. The prevalence of acromegalic patients in this study reflects an aggressive attempt to salvage patients with recalcitrant growth hormone elevation and may place the patient at a greater risk for ocular motor cranial nerve damage.

Outcome of fractionated stereotactic radiotherapy in patients with pituitary adenomas resistant to conventional treatments: a 5.25-year follow-up study.

OBJECTIVE: To investigate the long-term outcome of fractionated stereotactic radiotherapy (FSRT) [45 Gy (range 45-54) in 25 fractions] in patients with pituitary adenomas characterized by tumour progression or hormonally active disease despite surgery and/or medical therapy. DESIGN: This was an observational follow-up study of 5.25 years (median; range 1.7-10.4). PATIENTS AND MEASUREMENTS: Pituitary tumour volume, visual acuity/fields, hypersecretion, hypopituitarism, cerebrovascular disease, second brain tumours and mortality were examined at regular intervals after FSRT in 30 patients with pituitary adenomas (20 nonfunctioning macroadenomas, 10 functioning). Prior to FSRT, 83% had been operated 1-3 times, 47% had visual field deficits/impaired vision and 50% pituitary dysfunction. Progressive disease, stable disease, partial and complete tumour response were defined by MRI. RESULTS: Tumour growth control was 100%. At the end of follow-up, 30% had stable disease, 60% partial and 10% complete tumour response. Visual function was preserved and 36% of patients with prior field deficits improved. GH decreased from 4.2 (range, 2.3-6.5) to 1.1 (range, 0.5-1.5) microg/l (P < 0.001) in patients with acromegaly, and medical therapy could be reduced. In large prolactinomas, partial response or complete tumour response was achieved. FSRT was well tolerated. Pituitary function remained normal in 27%, 33% of patients had stable dysfunction, 17% deteriorated further and 23% developed new dysfunction. There were no cerebrovascular events, second brain tumours or FSRT-related deaths. CONCLUSION: According to this long-term follow-up study, FSRT is an efficient and safe adjuvant therapy for pituitary adenomas refractory to conventional treatments.

Clinical profile and long term follow up of children and adolescents with prolactinomas.

We report clinical presentation, response to medical treatment, and long-term follow-up of 39 children and adolescents with prolactinoma (F:M; 30:9) (30 macro and 9 microadenoma) diagnosed at the age of 9-20 years. Mean duration of follow up was 56 months. All patients were treated with bromocriptine (BC) at doses ranging from 2.5 to 20 mg/day or by cabergoline at doses ranging from 0.5 to 2 mg/week orally. Two patients received external conventional radiotherapy after surgery. In patients with macroprolactinoma (F:M; 21:9), headache and/or visual defects were the first symptoms. All females had primary or secondary amenorrhea. Growth arrest was not observed in any patient and pubertal development was appropriate for their age. Spontaneous or provocative galactorrhea was observed in 23 patients (all females) and none of male patient had gynecomastia. Mean serum prolactin (PRL) concentration at the time of diagnosis was 322.50 ng/ml in patients with microadenoma, 522.38 ng/ml in patients with macroadenoma and 2,294.86 ng/ml in patients with macroadenoma with suprasellar extension. In 25 patients, BC normalized PRL levels and caused variable, but significant, tumor shrinkage. Cabergoline normalized PRL concentrations in 14 patients. Pregnancy occurred in 6 patients while on treatment. Pregnancies were uncomplicated, and the patients delivered normal newborns at term. Impairment of other pituitary hormone secretion was documented at the time of diagnosis in only one patient. Postoperatively six patients had other pituitary hormone deficiencies. In conclusion, the medical treatment with dopaminergic compounds is effective and safe in patients with prolactinoma with onset in childhood, allowing preservation of the anterior pituitary function.

Initial clinical experience with frameless optically guided stereotactic radiosurgery/radiotherapy in pediatric patients.

OBJECTIVE: The objective of this study is to report our initial experience treating pediatric patients with central nervous system tumors using a frameless, optically guided linear accelerator. MATERIALS AND METHODS: Pediatric patients were selected for treatment after evaluation by a multidisciplinary neuro-oncology team including neurosurgery, neurology, pathology, oncology, and radiation oncology. Prior to treatment, all patients underwent treatment planning using magnetic resonance imaging (MRI) and treatment simulation on a standard computed tomography scanner (CT). For CT simulation, patients were fitted with a customized plastic face mask with a bite block attached to an optical array with four reflective markers. After ensuring adequate reproducibility, these markers were tracked during treatment by an infra-red camera. All treatments were delivered on a Varian Trilogy linear accelerator. The follow-up period ranges from 1-18 months, with a median follow-up of 6 months. RESULTS: Nine patients, ages ranging from 12 to 19 years old (median age 15 years old), with a variety of tumors have been treated. Patients were treated for juvenile pilocytic astrocytoma (JPA; n = 2), pontine low-grade astrocytoma (n = 1), pituitary adenoma (n = 3), metastatic medulloblastoma (n = 1), acoustic neuroma (n = 1), and pineocytoma (n = 1). We followed patients for a median of 12 months (range 3-18 months) with no in-field failures and were able to obtain encouraging toxicity profiles. CONCLUSION: Frameless stereotactic optically guided radiosurgery and radiotherapy provides a feasible and accurate tool to treat a number of benign and malignant tumors in children with minimal treatment-related morbidity.

Prospective study of high-dose cabergoline treatment of prolactinomas in 150 patients.

CONTEXT: Cabergoline fails to normalize hyperprolactinemia in a considerable proportion of prolactinomas, especially macroadenomas. OBJECTIVE: We examined the effect of individualized high-dose cabergoline treatment on hyperprolactinemia in prolactinomas. PATIENTS: The study included 122 women and 28 men (93 microadenomas and 57 macroadenomas). Forty-seven had undergone transsphenoidal surgery. According to the preceding medical treatment, the participants were separated into untreated (group U; n = 60), intolerant (group I; n = 64), and resistant (group R; n = 26) groups. INTERVENTIONS: We promptly increased cabergoline dose on the basis of individual prolactin levels. Length of treatment was 1 yr. RESULTS: Cabergoline normalized hyperprolactinemia in all patients except one. The proportion of prolactin normalization in both groups U and I was 83% at 3 months and 95% at 6 months. By contrast, that in group R was 35% at 3 months and 58% at 6 months. Mean cabergoline dose in milligrams per week at the time of prolactin normalization was 2.0 +/- 0.3 in group U, 0.9 +/- 0.1 in group I, and 5.2 +/- 0.6 in group R. Prolactin normalization rate at the 3 mg/wk dose was 84% overall but only 35% in group R. Serum progesterone or testosterone levels, diminished in 122 women or 16 men, respectively, were recovered in all except one resistant and four postmenopausal or panhypopituitary patients. CONCLUSION: Individualized high-dose cabergoline treatment can normalize hyperprolactinemia and hypogonadism in nearly all prolactinomas irrespective of tumor size or preceding treatments. Hyperprolactinemia could be controlled in poor responders within 1 yr with doses higher than 3 mg/wk.

Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: a case report.

Pituitary carcinomas are very rare tumors, nearly always presenting as widely invasive masses, although the hallmark of these lesions is the finding of distant metastases. One third of reported cases are prolactin (PRL)-secreting tumors. We report the case of a fatal pituitary carcinoma evolving within 4 years from a PRL-secreting microadenoma. A 22-year-old woman presented because of galactorrhea. Evaluation of the patient disclosed slight hyperprolactinemia and magnetic resonance imaging (MRI) showed a 7-mm intrapituitary lesion, which responded to treatment with cabergoline. About 4 years after the first evaluation she developed sudden headache, ptosis, and diplopia in the right eye. MRI disclosed the growth of a large pituitary mass, invading the right cavernous sinus. Despite two trans-sphenoidal surgical procedures followed by gamma-knife radiosurgery, the patient showed rapid local progression of the tumor and the occurrence of new lung lesions, probably of metastatic nature. The patient died 7 months after the development of her first neurological symptoms because of tumor apoplexy and subsequent subarachnoid hemorrhage. This case represents the first documented rapid evolution from a microprolactinoma initially responding to dopamine agonists to a fatal pituitary carcinoma.

Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas.

OBJECTIVES: Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival. DESIGN: Multicenter retrospective study by members of the French Society of Endocrinology. METHODS: Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included. Most tumors were corticotroph (n = 23) or lactotroph (n = 13), and 14 were carcinomas. Clinical/pathological characteristics of PT, as well as data from treatment evaluation and from the last follow-up were recorded. A partial response was considered as a decrease in the maximal tumor diameter by more than 30% and/or in the hormonal rate by more than 50% at the end of treatment. RESULTS: The median treatment duration was 6.5 cycles (range 2-24), using a standard regimen for most and combined radiotherapy for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor at diagnosis was associated with a poor response. The median follow-up after the end of treatment was 16 months (0-72). Overall survival was significantly higher among responders (P = 0.002); however, ten patients relapsed 5 months (0-57) after the end of TMZ treatment, five in whom TMZ was reinitiated without success. DISCUSSION: Patients in our series showed a 51.2% response rate to TMZ, with an improved survival among responders despite frequent relapses. Our study highlights the high variability and lack of standardization of treatment protocols.

Long-term response of pituitary carcinoma to temozolomide. Report of two cases.

Pituitary carcinoma is a rare tumor characterized by poor responsiveness to therapy, leading to early death. Reported responses to standard chemotherapy have only been anecdotal, with no single agent or combination demonstrating consistent efficacy in the treatment of patients with this disease. The authors report rare examples of a persistent response to cytotoxic chemotherapy in two patients with pituitary carcinoma. One patient was a 38-year-old man with visual field loss caused by a luteinizing hormone-secreting pituitary carcinoma that had recurred despite multiple surgeries and radiation therapy. Intradural metastases to the spine that had failed to respond to radiation therapy were pathologically confirmed. The second patient was a 26-year-old man with hyperprolactinemia from a prolactin-secreting pituitary tumor. Spine magnetic resonance images obtained to search for causes of neck pain showed a vertebral tumor, which was later confirmed through pathological analysis to be a metastatic pituitary carcinoma. His disease progressed despite radiation therapy, high-dose bromocriptine, and chemotherapy. Both patients were treated monthly with temozolomide, which was administered orally on the first 5 days of a 28-day cycle. The patient in the first case underwent all 12 treatment cycles without serious side effects, and his visual field deficits improved. The patient in the second case had undergone only 10 cycles when the drug was stopped because of his severe fatigue. Nonetheless, his pain disappeared and his serum prolactin concentration decreased. Both patients continue to have partial responses and have been employed full-time for more than 1 year after discontinuing temozolomide therapy. These two examples demonstrate that temozolomide may be effective in treating pituitary carcinomas and thus should be considered in the treatment algorithm for these difficult cases.

[Radiotherapy of pituitary tumours]. / A hypophysisdaganatok radioteráipiáija.

In this article, the role of conventional radiotherapy and radiosurgery in the management of pituitary tumors is discussed. After a brief review about the mechanism of action and different techniques of irradiation therapy, the therapeutic effectiveness and side effects are analysed in the various types of pituitary tumors. Conventional fractionated radiotherapy has long been used to control growth and/or hormonal secretion of residual or recurrent pituitary tumors. Nevertheless, there is still a controversy concerning patient selection for radiotherapy, because several potentially significant side effects including hypopituitarism may develop. Stereotactic radiosurgical methods may have several advantages over conventional radiotherapy; they can be applied, for example, in patients with residual or recurrent pituitary tumors who had previously received conventional radiotherapy. However, long-term follow-up data with these relatively new techniques are still limited.

Long-term Outcome After Fractionated Radiotherapy for Pituitary Adenoma: The Curse of the Secretory Tumor.

OBJECTIVES: To determine the influence of secretory status on long-term outcome after fractionated radiotherapy (RT) for gross residual pituitary adenoma. MATERIALS AND METHODS: This is a retrospective study of 116 consecutively treated patients who met the following inclusion criteria: tissue diagnosis of pituitary adenoma, visible tumor at the time of RT, treatment with fractionated RT, and imaging follow-up of ≥2 years. Hypersecretion of growth hormone, adrenocorticotrophic hormone, prolactin, or thyroid-stimulating hormone was documented in 30 patients (26%). The RT dose in most (78%) patients was 45 Gy at 1.8 Gy per fraction. The major outcome endpoint is clinical and biochemical control, meaning no growth on follow-up scans and normalization of hypersecretion, if present before RT. RESULTS: Long-term tumor control was outstanding for nonsecretory tumors: 96% at 10 years. There was a major drop in the control rate of secretory tumors: 10-year clinical and biochemical control was 62% (P<0.0001 vs. 96%). Multivariate analysis confirmed secretory status as the only independent prognostic factor (variables analyzed were sex, age, tumor size, RT dose, and secretory status). CONCLUSIONS: Secretory pituitary adenomas have a worse prognosis than nonsecretory tumors after 45 to 50 Gy of conventionally fractionated RT. As a result of this finding, our plan is to increase the intensity of RT in secretory tumors, but our data did not evaluate this approach. The treatment guidelines that we currently use in pituitary adenoma are as follows. Radiosurgery (20 to 30 Gy) is our first-choice treatment of a secretory tumor that cannot be completely resected. When treating gross residual pituitary adenoma with fractionated RT, we use the following dose schedules: Nonsecretory: 45 Gy at 1.8 Gy/fraction, once-daily fractionation. Secretory: 54 Gy at 1.8 Gy/fraction once daily or 55.2 Gy at 1.2 Gy/fraction with twice-daily treatment.