title: Outcomes of proton therapy for patients with functional pituitary adenomas.
abstract: OBJECTIVE
  This study evaluated the efficacy and toxicity of proton therapy for functional pituitary adenomas (FPAs).
  
  
  METHODS
  We analyzed 165 patients with FPAs who were treated at a single institution with proton therapy between 1992 and 2012 and had at least 6 months of follow-up. All but 3 patients underwent prior resection, and 14 received prior photon irradiation. Proton stereotactic radiosurgery was used for 92% of patients, with a median dose of 20 Gy(RBE). The remainder received fractionated stereotactic proton therapy. Time to biochemical complete response (CR, defined as ≥ 3 months of normal laboratory values with no medical treatment), local control, and adverse effects are reported.
  
  
  RESULTS
  With a median follow-up time of 4.3 years (range, 0.5-20.6 years) for 144 evaluable patients, the actuarial 3-year CR rate and the median time to CR were 54% and 32 months among 74 patients with Cushing disease (CD), 63% and 27 months among 8 patients with Nelson syndrome (NS), 26% and 62 months among 50 patients with acromegaly, and 22% and 60 months among 9 patients with prolactinomas, respectively. One of 3 patients with thyroid stimulating hormone-secreting tumors achieved CR. Actuarial time to CR was significantly shorter for corticotroph FPAs (CD/NS) compared with other subtypes (P=.001). At a median imaging follow-up time of 43 months, tumor control was 98% among 140 patients. The actuarial 3-year and 5-year rates of development of new hypopituitarism were 45% and 62%, and the median time to deficiency was 40 months. Larger radiosurgery target volume as a continuous variable was a significant predictor of hypopituitarism (adjusted hazard ratio 1.3, P=.004). Four patients had new-onset postradiosurgery seizures suspected to be related to generously defined target volumes. There were no radiation-induced tumors.
  
  
  CONCLUSIONS
  Proton irradiation is an effective treatment for FPAs, and hypopituitarism remains the primary adverse effect.
authors.affiliation: Harvard Radiation Oncology Program, Boston, Massachusetts.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Wattson
authors.affiliation: Harvard Radiation Oncology Program, Boston, Massachusetts.
authors.forename: Shyam K
authors.initials: SK
authors.lastname: Tanguturi
authors.affiliation: Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Daphna Y
authors.initials: DY
authors.lastname: Spiegel
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Niemierko
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Beverly M K
authors.initials: BM
authors.lastname: Biller
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Nachtigall
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Bussière
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Brooke
authors.initials: B
authors.lastname: Swearingen
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Chapman
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Loeffler
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: hshih@partners.org.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Shih
mesh_terms: D000172:Acromegaly / Q000652:urine; D000236:Adenoma / Q000378:metabolism / Q000601:surgery*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007018:Hypopituitarism / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000601:surgery*; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods*; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods; D012189:Retrospective Studies; D013972:Thyrotropin / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D013972:Thyrotropin