Radioterapia degli adenomi ipofisari G Minniti Radiation Oncology, Sant Andrea Hospital, University of Rome Sapienza, and IRCCS Neuromed, Pozzilli (IS) Roma 6-9 Novembre 14
! Outline " Radiation techniques " FSRT and SRS results for pituitary adenomas " FSRT vs SRS (indications) " Nonfunctioning pituitary adenomas: early vs delayed treatment " Secreting adenomas
! Stereotactic techniques " Radiosurgery (SRS) either Gamma Knife (GK), Cyberknife, or a l i n e a r a c c e l e r a t o r (LINAC), delivered as a single treatment; " Stereotactic fractionated radiotherapy (FSRT) delivered as a fractionated treatment.
" Target delineation AIRO; Genova, 21-11-2011
" Treatment planning AIRO; Genova, 21-11-2011
! Treatment delivery
" Immobilization Technique Immobilization system Fractionation Accuracy Conventional RT mask conventional (25-30) 5-7 mm IMRT mask conventional (25-30) 3-5 mm Radiosurgery LINAC system stereotactic fixed frame single session < 1mm GammaKnife system stereotactic fixed frame single session < 1mm Proton RS stereotactic fixed frame single session < 1mm CyberKnife system stereotactic mask single session/ hypofractionation (3-5) < 1mm Proton therapy stereotactic relocatable conventional (25-30) 1-2 mm FSRT frame/mask stereotactic relocatable frame/mask conventional (25-30) 1-2 mm Minniti et al, Rad Oncol 2010
" Clinical results of RT for pituitary adenoma Efficacy Tumor control Endocrine control Toxicity
" FSRT for NF pituitary adenoma authors patients follow-up control rate late toxicity (%) median (months) % visual Hypopituitarism Coke 1997 19* 9 100 0 0 Mitsumori 1998 30* 33 86 at 3 years 0 20 Milker-Zabel 2001 68* 38 93 at 5 years 4 5 Paek 2005 68 30 98 at 5 years 3 6 Colin 2005 110* 48 99 at 5 years 2 29 at 5 years Minniti 2006 92* 32 98 at 5 years 1 22 Selch 2006 39* 60 100 0 15 Kong 2007 64* 37 97 at 4 years 0 11 *series include secreting pituitary adenomas Minniti et al, Neurosurgical reviews 2008
! FSRT for secreting pituitary adenomas 5-year control 97% 50% at 5 years Minniti et al, Clin Endocrinol 2006
! Radiosurgery for pituitary adenomas " NF adenomas " Secreting adenomas
! Radiosurgery for NFAs Author Number follow-up tumor control patients (months) % Losa 04 56 41 88 at 5 yrs Liscak 07 140 60 100 at 5 yrs Pollock 08 62 64 95 at 5 yrs Park 11 125 62 94 at 5 yrs Starke 12 140 50 97 at 5 yrs Losa 08 83 69 85 at 10 yrs wilson 12 51 50 100 at 5 yrs Sheehan 13 512 36 95 at 5 yrs Lee 14 41 48 85 at 5 yrs Total 1210 48 95 at 5 years
! Radiosurgery for acromegaly Author Number follow-up normal GH patients (months) % Attanasio 03 30 46 30 at 5 yrs Jezkova 06 96 32 44 at 5 yrs Voges 06 64 54 33 at yrs Total Pollock 07 675 46 55 63 4660 at at 5 yrs years Vik-mo 07 53 67 86 at 10 yrs Losa 08 83 69 85 at 10 yrs Ronchi 09 35 114 46 at 10 yrs Iwai 10 26 84 17 at 5 yrs Sheehan 11 130 31 38 at 5 yrs Franzin 12 112 71 58 at 5 yrs
! Radiosurgery for Cushing Author Number follow-up normal patients months ACTH % Degerblad 1998 29 72 48 Sheehan 2000 43 44 63 Hoybye 2001 18 180 83 Kobayashi 2002 20 60 35 Devin 2004 35 35 49 Jane 2007 45 >18 63 Castinetti 2007 40 54 42 Jagannathan 2007 90 45 54 Pollock 2008 11 36 35 Sheehan 2013 96 48 70 Wilson 2014 36 66 25 Total 463 54 54
! Radiosurgery for prolactinomas Author Number follow-up normal patients (months) PRL % Pan et al 27 29 30 Lim et a 19 26 50 Mokry et al 21 31 57 Landolt et al 20 29 25 Pan et al 128 33 41 Choi et al 21 43 23 Jane et al 19 >18 11 Pouratian et al 23 55 26 Jezkova et al 35 75 37 Sheehan et al 32 31 26 Total 345 38 37
" Open issues! FSRT vs SRS
" Results of SRS/FSRT in pituitary tumors " NF adenomas 90-95% at 5 years / 90-100% at 5 years " GH-secreting adenomas 40-55% at 5 years / 30-55% at 5 years " ACTH-secreting adenomas 40-60% at 5 years / 70-80% at 5 years " PRL-secreting adenomas 30-50% at 5 years / 30-50% at 5 years Minniti et al, Rev Endocr Metab Disord. 2009
" Limitation of SRS Size of adenoma (more than 2.5-3.0 cm) Proximity to the optic chiasm (< 2-3 mm)
! Radiation tolerance to SRS " Radiation induced optic neuropathy (RON) dose to optic apparatus incidence of RON < 10 Gy 0-3% 10-12 Gy 2-5% > 12 Gy >10%
NF pituitary adenoma A B C D E F G H
Surgery followed by SRS for an ACTH-secreting pituitary adenoma Pre-surgery Post-surgery
Hypofractionated SRT
" Median radiation doses to cavernous sinus, optic nerves and chiasm in patients treated with multi-fraction SRS (5 5 Gy) Minniti et al, Rad Oncol 2014
" Open issues! Which nonfunctioning adenomas need treatment?! Immediate versus delayed treatment
IMRS for residual pituitary adenoma
NF pituitary adenoma Pre-surgery Intraoperative MRI 2 years post-srt
" Open issues! Indications for secreting pituitary adenomas: hormone normalization
! Hormone control in acromegaly after RT 100 80 GH ng/ml 100 80 IGF-I ng/ml 60 60 40 40 20 20 0 0 0 2 5 10 0 2 5 10 years years Minniti et al, Clin Endocrinol 2005
! SRS for acromegaly retrospective comparison SRS 25 Gy in one fraction 16 patients (1994-96) vs FSRT 40 Gy in 20 fractions 50 patients (1973-92) SRS FSRT mean time to normalization of GH & IGF-1 (years) 1.4 7.1 pretreatment GH (miu/l) mean 18.0* 29.7 range 2.9-35 4-135 Landolt et al 1998
! GH after SRS " median decrease in GH and IGF-I after GK SRS Attanasio et al 2003
! Results of SRS/FSRT for secreting pituitary tumors " GH-secreting adenomas 40-55% vs 30-55% at 5 years " ACTH-secreting adenomas 40-60% vs 70-80% at 5 years " PRL-secreting adenomas 30-50% vs 30-50% at 5 years Minniti et al, Rev Endocr Metab Disord. 2009
! Conclusions " Stereotactic radiation techniques are effective and may reduce the potential long-term toxicity of radiation; " Both FSRT and SRS are feasible options for patients with otherwise uncontrolled pituitary adenomas; " SRS should be employed for small- to moderatesized (< 2.5-3 cm) adenomas 3-5 mm away from the optic chiasm.
.Grazie per l attenzione...