Radiotherapy for Pituitary Adenomas: What You Need to Know - PDF document

Radiotherapy for Pituitary Adenomas: What You Need to Know Pituitary Disorders: Advances in Diagnosis and Management Steve Braunstein, MD, PhD Assistant Professor and Vice Chair SRS Program Co-Director UCSF Department of Radiation Oncology 1/25/20 1 Disclosures I have no relevant disclosures 2 Radiotherapy approaches to pituitary adenomas 1/25/20 2 1 1/25/20 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Outline Overview of radiotherapy in management of pituitary tumors § Indication/decision algorithm § Conventional/fractionated external beam radiotherapy (EBRT) § Stereotactic radiosurgery (SRS) § Fractionated stereotactic radiotherapy (FSRT/SBRT) § Disease outcomes § Follow up protocol § Toxicity § Future directions 3 Radiotherapy approaches to pituitary adenomas 1/25/20 3 Incidence Tumors of the pituitary (rare?) § 10-20% of intracranial tumors § Pituitary incidentaloma ~10-20% Orija et al. BPRCEM 2012 4 Radiotherapy approaches to pituitary adenomas 1/25/20 4 2 1/25/20 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

GK Radiosurgery at UCSF Other Other Pit AVMs Fn Schw Fn Pit Mening 10% Schw 8% AVMs 9% 36% Gliomas Mets Mening 22% 47% 16% Mets 25% Sept 1991-1993 2012-2016 n = 328 n = 1627 5 Radiotherapy approaches to pituitary adenomas 1/25/20 5 Classification Tumors of the pituitary mone, LH luteinizing hormone, SF steroidogenic factor) Tumor type Transcription factors Hormones, others The Pit-1 family Somatotroph adenoma Densely granulated somatotroph adenoma Pit-1 GH, a -subunit Sparsely granulated somatotroph adenoma Pit-1 GH, keratin whorls (fibrous bodies) Mammosomatotroph/mixed adenoma Pit-1, ER GH, PRL, a -subunit Lactotroph adenoma Sparsely granulated lactotroph adenoma Pit-1, ER, ?GH-repressor PRL, Golgi pattern Densely granulated lactotroph adenoma Pit-1, ER, ?GH-repressor PRL di ff use cytoplasmic Acidophil stem cell adenoma Pit-1, ER PRL, (GH), keratin whorls (fibrous bodies) Thyrotroph adenoma Pit-1, TEF, GATA-2 b -TSH, a -subunit Plurihormonal adenoma Pit-1, ER, TEF, GATA-2 GH, PRL, b -TSH, a -subunit ACTH family Corticotroph adenoma Tpit ACTH, keratins Gonadotropin family Gonadotroph adenoma SF-1, ER, GATA-2 b -FSH, b -LH, a -subunit Unclassified adenoma Hormone-negative/ null cell adenoma None None Unusual plurihormonal adenoma ?multiple Multiple Al-Shraim et al. Acta Neuropath 2006 6 Radiotherapy approaches to pituitary adenomas 1/25/20 6 3 1/25/20 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Classification Tumors of the pituitary § Pituitary adenoma • Microadenoma (<1cm) • Macroadenoma (≥1cm) • Functioning • Non-functioning § Pituitary carcinoma § Metastases (breast and lung) 7 Radiotherapy approaches to pituitary adenomas 1/25/20 7 Treatment Approach 8 Radiotherapy approaches to pituitary adenomas 1/25/20 of serum IGF-1 as the remission criterion, the effjcacy of 8 4 1/25/20 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS] m analysis refmect 2010 US dollars. However, other data have shown no signifjcant improve so the overall effjcacy of this specifjcally to assess QOL in patients suffering from ac ly a fjrst-line modality and is usually reserved for treat to rely on nonspecifjc QOL questionnaires. Data obtained either source were quantifjed whenever possible to make attributable to variability in the defjnition of “remission” cifjc treatments on QOL. Results Effjcacy

Post surgical outcomes Non-functioning pituitary adenoma progression-free survival Tumor recurrence and tumor growth-free survival rates in 15 studies before 2011 Study reference Num- Follow-up Rate of tumor recurrence Tumor growth-free survival rate Tumor growth-free survival ber of time at 5 years rate at 10 years cases months total residual nonresidual total residual nonresidual total residual nonresidual Brochier S. [44] 142 83 56/142 10/42 47/100 75% 82 70 57% 68% 52% 85 or 49% § 100% 58 or 23% † 100% O’Sullivan E.P. [41] 126 68 53/126 53/100 0/26 76% 49% Losa M. [59] 355 53 NA/355 NA/76 NA/279 NA 39% 87% NA 17% 62% van den Bergh A.C. [57] 43 71 17/43 16/28 1/15 NA 49% 100% NA 22% 67% Dekkers O.M. [39] 91 72 9/91 9/70 0/21 94% 92% 100% 81% 74% 100% Ferrante E. [40] 150 112 59/150 45/77 14/73 NA 55% 93% NA 36% 62% Picozzi P. [60] 68 42 32/68 32/68 NA 51% 51% NA 51% 51% NA Park P. [5] 132 45 26/132 NA NA 85% NA NA 50% NA NA Greenman Y. [11] 108 51 47/108 41/78 6/30 48% 30% 84% NA 29% 63% Soto-Ares G. [58] 51 68 13/51 13/34 0/17 74% 61% 100% NA NA 100% Woollons A.C. [6] 22 58 10/22 8/11 2/11 34% 22% NA 34% 22% NA Turner H.E. [42] 65 76 21/65 12/34 9/31 82% NA NA 56% NA NA Lillehei K.O. [56] 32 66 2/32 NA 2/32 NA NA NA NA NA NA Gittoes N.J. [9] 53 97 14/53 NA NA 82% NA NA 59% NA NA Bradley K.M. [38] 73 NA 8/73 NA 8/73 NA NA NA 90% NA 70% § † Chen et al. Neuro-endocrinology 2012 9 Radiotherapy approaches to pituitary adenomas 1/25/20 9 Post surgical outcomes Non-functioning pituitary adenoma progression-free survival Tumor recurrence and tumor growth-free survival rates in 15 studies before 2011 Study reference Num- Follow-up Rate of tumor recurrence Tumor growth-free survival rate Tumor growth-free survival ber of time at 5 years rate at 10 years cases months total residual nonresidual total residual nonresidual total residual nonresidual Brochier S. [44] 142 83 56/142 10/42 47/100 75% 82 70 57% 68% 52% 85 or 49% § 100% 58 or 23% † 100% O’Sullivan E.P. [41] 126 68 53/126 53/100 0/26 76% 49% Losa M. [59] 355 53 NA/355 NA/76 NA/279 NA 39% 87% NA 17% 62% van den Bergh A.C. [57] 43 71 17/43 16/28 1/15 NA 49% 100% NA 22% 67% Dekkers O.M. [39] 91 72 9/91 9/70 0/21 94% 92% 100% 81% 74% 100% Ferrante E. [40] 150 112 59/150 45/77 14/73 NA 55% 93% NA 36% 62% Picozzi P. [60] 68 42 32/68 32/68 NA 51% 51% NA 51% 51% NA Park P. [5] 132 45 26/132 NA NA 85% NA NA 50% NA NA Greenman Y. [11] 108 51 47/108 41/78 6/30 48% 30% 84% NA 29% 63% Soto-Ares G. [58] 51 68 13/51 13/34 0/17 74% 61% 100% NA NA 100% Woollons A.C. [6] 22 58 10/22 8/11 2/11 34% 22% NA 34% 22% NA Turner H.E. [42] 65 76 21/65 12/34 9/31 82% NA NA 56% NA NA Lillehei K.O. [56] 32 66 2/32 NA 2/32 NA NA NA NA NA NA Gittoes N.J. [9] 53 97 14/53 NA NA 82% NA NA 59% NA NA Bradley K.M. [38] 73 NA 8/73 NA 8/73 NA NA NA 90% NA 70% § † Chen et al. Neuro-endocrinology 2012 10 Radiotherapy approaches to pituitary adenomas 1/25/20 10 5 1/25/20 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Post surgical outcomes Residual Tumor Volume Doubling Time (~3-4 years) Study reference TVDT P-TVDT 95% CI Hsu C.Y., 2010 [65] 3.0 3.00 [2.10; 4.00] Honegger J., 2008 [66] 3.0 3.00 [2.10; 4.00] Tanaka Y., 2003 [61] 5.0 5.00 [4.00; 6.00] Ekramullah S.M., 1996 [62] 2.5 2.50 [1.70; 3.50] Summary 3.4 3.40 [2.40; 4.50] 0 2 4 6 8 10 Chen et al. Neuro-endocrinology 2012 11 Radiotherapy approaches to pituitary adenomas 1/25/20 11 Post surgical outcomes Overall local control is 50-80% following resection Recurrence Risk for non-functioning tumors: Post-op MRI 5 yr 10 yr GTR 10-20% 30% STR 25-40% >50% Cortet-Rudelli et al. Annales d’Endocrinologie 2015 12 Radiotherapy approaches to pituitary adenomas 1/25/20 12 6 1/25/20 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Radiotherapy indications Surgical local control 50-80% § Medically inoperable (panhypopituitarism) § Subtotal resection (persistent hypersecretion) § Large tumor with extrasellar extension § Recurrence § Pituitary carcinoma (high mitotic index, invasive features) 13 Radiotherapy approaches to pituitary adenomas 1/25/20 13 Radiotherapy approach Pre-treatment workup § Complete endocrine evaluation § Visual field testing Cessation of suppressive medications § Non-randomized data 14 Radiotherapy approaches to pituitary adenomas 1/25/20 14 7 1/25/20 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]