Protocolos de consenso: MTS Cerebrales Resumen ASTRO. Javier Aristu y Germán Valtueña Servicio Oncología Rad. Depart.

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1 Protocolos de consenso: MTS Cerebrales Resumen ASTRO Javier Aristu y Germán Valtueña Servicio Oncología Rad. Depart.

2 ASTRO 2013 Brain met SRS Abstracts

3 97. Comparative Effectiveness of SRS versus WBRT for Patients with BM From NSCLC L.M. Halasz et al.; NCCN database 413 patients SRS 118 (29%) WBRT 295 (71%) Both 13 (3%) Factors signif associated with SRS 1-3 BM smaller size 0-1 extracraneal sites SRS was independently associated with longer OS < 4 MET (235p) MS SRS (109p) 9m WBRT (126p) 3.9m

4 118. When Should Whole Brain Radiation Therapy Be Utilized With SRS to Reduce Regional Failure in the treatment of Oligometastatic Brain Disease?: Clinical Nomogram and Recursive Partitioning Analysis G. Rodrigueset al.; London Regional Cancer Program, London, ON, Canada. RPA classifications A retrospective 361 pats SRS database 1-year RF Low-risk <20% Solitary lesion and age >55y High-risk >40% WHO=0 and 2-3 lesions Intermediate-risk 20-40% All other patient combinations A clinical nomogram for the prediction of 1-year cumulative RF

5 Rodrigues G, et al. Radiother Oncol 2014

6 121. Lesion Location as a Predictor of Adverse Radiation Effect After SRS for Brain Metastasis C.L. Tinkle, et al.; University of California San Francisco Retrospective. ARE was determined by serial MRI and/or surgical pathology A BM location grading system relative to the ventricular system was developed based on isotropic expansion of this structure, including 0.5 cm, 1 cm, and 2 cm. 435 patients and 2,200 brain metastases Variables UV ARE MV ARE MV symp ARE BM maximum diameter V10 V12 Prior or concurrent RT BM distance from ventricle Lesion location, namely distance from the ventricle is significantly predictive of ARE. Dose-volume analyses of the peri-ventricular region, including the subventricular zone, are ongoing.

7 123. Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of WBRT Versus WBRT Plus SRS in Patients With 1-3 BM; Poststratified by the Graded Prognostic Assessment (GPA) P.W. Sperduto et al.; RTOG If the data from RTOG 9508 were post-stratified by the GPA, the conclusions may vary - Conclusions vary from the original analysis: there is a survival advantage for patients with GPA treated with WBRT + SRS regardless of whether they have 1, 2 or 3 BM - No such benefit was seen among lower GPA pat. - Prospective validation of this effort in a larger cohort of high GPA patients is warranted.

8 1033. Time to Intracranial Failure Following Postresection Cavity Radiosurgery for Patients With a Single BM K. Kalakota wet al.; Chicago, and Baltimore , 76 pats SRS 17 Gy (12-20 Gy) MFU15 months. 35 pats (46%) developed an intracranial recurrence 9 (12%) LBF 28 (37%) DBF. MTLBF 6 months (range, 2-14 mo) MTDBF 6 months (range, 1-28 mo) The highest rates LBF 6-12 mo after SRS. The highest rates of DBF 4-12 mo after SRS Surveillance imaging should be most frequent, possibly every 2 months, during the first year post-treatment and the frequency could be decreased thereafter.

9 1034. Brain Metastases and Resection Cavities From Colorectal Carcinoma Treated With Stereotactic Radiosurgery Have Poor Local Control Compared to Noncolorectal Histology J. Pai et al.; Stanford University Medical Center Intact mets Resection cavities CRC 1-y LC Factors predictive of LC Non-CRC CRC histology PTV size (1.7 cc) PTV size Single session Eq dose

10 1035. Factors Influencing Local Control and Survival in Patients Treated With Radiosurgery Following Surgical Resection of CNS Metastases J.C. Rosenberg et al.; Tufts University Affiliated Hospitals, Boston and Rhode Island Hospital, Providence , 87 pats, 18Gy (14-22 Gy) MFU 14 m (2-257) 1-y and 2-y LC 75% Local failure Tumor size (>3 cm) (p=0.02) Resection cavity volume (>14cc) (p=0.04). 89% vs 65%

11 2038. Breast Cancer Luminal Status Predicts Survival Following Stereotactic Radiosurgery of BM R.Kalash; University of Pittsburg, Pittsburg, PA 111 patients (391 BM) Median age 55 y; size 0.55 cc; Dose 24Gy; 1 fx 6m/1y MFU: 7 m (1-73 m) Local control (LC) 90%/77% Distant-brain control (DBC) 76%/54% Overall Survival (OS) 74%/50% Luminal status (p=0.025), prior WBRT (p=0.008) significant predictors for OS following SRS

12 2202. Predictive Factors for Local Control of BM After SRS T.R. Santos; Hospital A.C. Camargo, Sao Paulo, Brazil 165 BM (75 patients) 55% of BM treated previously with WBRT (<SRS dose 10-30%) 3 Groups: 15 Gy (22%); Gy (53%); and 19 Gy (25%) Max Diameter: 10 mm (53%), 10 mm (49%) Median: Follow up (7m), Dose (18Gy), Size (10 mm). Univariable analisys: 1-y LC p Max diameter ( 10 mm/ 10 mm) 76%/55% 0.02 Dose ( 15 Gy/16-18 Gy/ 19 Gy) 38%/68%/87% Prior WBRT (yes/no) 57%/75% 0.02 Multivariable analisys: Dose remained the most powerful predictor of LC (p<0.0001)

13 2203. Local Control after SRS for BM in Melanoma Patients With and without BRAF Mutation and Treatment D.Ly; University of Utah, S. Lake City 51 pat, 166 BM and 13 BM resection beds Dose: 20 Gy 31 LF /1-year LC 73.3% BRAF+: 30 pat (16 BRAF inhibitor) BRAF-: 21 pat BRAF- vs BRAF + (± inhib) = 1-yLC, DBM, FFWBRT, TTHemorrhage BRAF+/+ttoINHIB BRAF+/-ttoINHIB 1-y LC 86,8% 60% P=0.068

14 ASTRO 2014 Brain met SRS Abstracts

15 273. Whole Brain Radiation Therapy With Simultaneous Integrated Boost Using Volumetric Modulated Arc Therapy: A Phase II Study for 1 to 10 Brain Metastases A Nichol. BC Cancer Agency. Canada Clinical trial NCT pac; 20 Gy WBRT and 50 Gy SIB in 5 fx Ineligible if the total volume of BM >30 cm 3 To compare 3y-PFS with that of the WBRT (37.5 Gy/15) and SRS: Gy/1 arm of the RTOG study OS for subgroups 1-3 vs 4-10 metastases were compared MFU 9 m 3-mRESPONSE: 10% CR, 48% PR; 33% SD, 10% PD Radionecrosis 12% ( 2G4, 2G3 and 3G2) Multivariable analysis OS: KPS (HR = 3.2, p < 0.004), extracranial disease (HR = 2.9, p = 0.04) and not using anti-her2/egfr systemic therapy (HR = 7.5, p = ) were associated with worse survival, but age (HR = 0.98, p = 0.1) and number of metastases 1-3 vs (HR = 1.1, p = 0.8) were not.

16 274. Brain Metastasis: It's Not a Numbers Game C Hadziheodorou. New Brunswick, NJ To determine whether number of lesions, total tumor volume, or a combination of the two best predicts for OS and local tumor control 157 patients -There was a significant difference in tumor recurrence in patients with higher number of lesions -They did not find a significant difference in tumor recurrence based on tumor volume alone - 4 BM + 2 cm 3 had reduced survival The combination of volume and number of lesions may be more predictive of death than either parameter alone

17 275. A Multi-institutional Predictive Nomogram for Distant Brain Failure in Patients Treated with Upfront Stereotactic Radiosurgery Without Whole Brain Radiation Therapy DN Ayala-Peacock. Winston Salem, Nashville, Providence, Alabama, Toronto To determine the likelihood of DBF after SRS Retrospective cohort of 1098 patients Dominant factors predicting for early DBF in our model were > 4 metastases vs 1-3 (HR = 1.37, p value = ), squamous cell lung cancer vs adenocarcinoma (HR = 2.23, p < ), and melanoma (1.33, p = ) histologies

18 275. A Multi-institutional Predictive Nomogram for Distant Brain Failure in Patients Treated with Upfront Stereotactic Radiosurgery Without Whole Brain Radiation Therapy DN Ayala-Peacock. Winston Salem, Nashville, Providence, Alabama, Toronto

19 276. Toward Knowledge-Based Radiosurgery Planning for BM O. Bohoudi. VUMC, Amsterdam, Netherlands SRS alone from RN in a subset of 96 patients V10-17 Gy for each given lesion volume treated with RS Gy RN was 22% None of V10-V17 Gy correlated with the risk of RN Mean V12 Gy in patients with RN was 10.4 cm 3 V12 Gy < 10 cm 3 has been adapted as toxicity parameter, The individualized RS dose can be calculated for any given GTV size based on a linear relationship between V 12Gy and GTV size.

20 1021. Factors Predicting for Increase in Peritumoral Edema Following SRS of BM A Hanna. Baltimore Volumetric analysis Pre-SRS and Post-SRS related edema 114 BM (55 pats) Predictors of baseline edema Non melanoma/renal histology Male gender Prior WBRT More smoking pack years (0.21 cc per pack year) Larger Pre-SRS tumor volume (4.55 cc per tumor cc) Predictor of post-srs edema Melanoma/renal histology (vs other histologies) RPA class III (vs I and II) Prior WBRT (vs not) Pretreatment edema/tumor ratio (0.4% risk of increased edema per unit increase in ratio) Steroid dose at time of SRS (2% decreased risk per mg)

21 Muchas gracias!!!