# Radiation Oncology/Palliation/Brain Metastases/Surgery

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Brain Metastases: Surgery

## Overview

* AANS/CNS; 2010 PMID 19960230 -- "The role of surgical resection in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline." (Kalkanis SN, J Neurooncol. 2010 Jan;96(1):33-43. Epub 2009 Dec 4.)
** Recommendations apply to adults with newly diagnosed single brain metastasis amenable to surgical resection
** Surgical resection plus WBRT vs surgical resection alone
*** (Level 1): Surgical resection followed by WBRT superior for local control and overall brain control
** Surgical resection plus WBRT vs SRS +/- WBRT
*** (Level 2): Surgical resection plus WBRT and SRS plus WBRT both represent effective treatment strategies, resulting in relatively equal survival rates
*** (Level 3): SRS alone may provide equivalent function and survival, so long as detection of distant sites of failure and salvage SRS are possible
** Surgical resection plus WBRT vs WBRT alone
*** (Level 1): Surgical resection plus WBRT is superior to WBRT alone in patients with good performance status and limited extracranial disease. There is insufficient evidence for other patients

## WBRT +/- Surgery

* Several retrospective series showed benefit of adding surgery to WBRT for single brain metastases
* Three randomized trials were performed; 2 showed benefit, while 1 showed no difference.
* Overall, surgery + WBRT offers better local control, decreased recurrence, and probably improved survival over WBRT alone
* Survival outcomes are not improved with surgery for patients with active extra-cranial disease, or poor performance status
* Canada Multi-Institutional (1989-1993) -- WBRT 30/10 vs. Surgery + WBRT 30/10
** Randomized. 84 patients. Single brain metastasis, KPS >50, no lymphoma/SCLC. Dexamethasone per institutional policy. Arm 1) WBRT 30/10 vs. Arm 2) Surgery + WBRT 30/10. Treatment within 3 weeks of CT scan.
** 1996 PMID 8839553 — "A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis." (Mintz AH, Cancer. 1996 Oct 1;78(7):1470-6.)
*** Outcome: Median OS WBRT 6 months vs. surgery + WBRT 6 months (NS). No difference in QoL
*** Conclusion: No benefit from adding surgery to whole brain RT
** Comment: Worse baseline KPS than Kentucky and Netherlands studies.
* University Hospital Leiden (Netherlands)(1985-90) -- WBRT 40/20 BID vs. Surgery + WBRT 40/20 BID
** Randomized. 63/66 patients. Single brain metastasis. Arm 1) Pts randomized to resection + WBRT vs WBRT alone. XRT was to whole brain 2Gy BID for 40 Gy over 2 weeks. No MRI.
** 1993 PMID 8498838 — "Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery?" (Vecht CJ, Ann Neurol. 1993 Jun;33(6):583-90.)
*** Outcome: Stable extracranial disease: median OS 7 months vs. 12 months. Progressive extracranial disease: median OS 5 months both groups (NS).
*** Functional independence: Stable extracranial disease: 4 months vs. 9 months. Progressive extracranial disease: 2.5 months both groups (NS). More rapid and longer after surgery + RT
** 1994 PMID 8040016 — "The choice of treatment of single brain metastasis should be based on extracranial tumor activity and age." (Noordijk EM, Int J Radiat Oncol Biol Phys. 1994 Jul 1;29(4):711-7.)
*** Outcome: median OS WBRT 6 months vs. surgery + WBRT 10 months (SS). Stable extracranial disease (7 months vs 12 months), active extracranial disease (5 months both groups). Age independent predictor (60 years). Majority of deaths due to systemic progression
*** Conclusions: surgery and radiotherapy should be offered over radiotherapy alone. However, for patients with active extracranial disease, radiotherapy alone is sufficient.
* University of Kentucky / Patchell#1 (1985-1988) -- WBRT 36/12 vs. Surgery + WBRT 36/12
** Randomized. 48 patients. Suspected single brain metastasis. Dexamethasone 4mg Q6 hours. Arm 1) (biopsy) then WBRT vs. Arm 2) Surgery + WBRT. Surgery within 72 hours of randomization. WBRT within 14 days of surgery; within 48 hours of randomization or biopsy; dose 36/12
** 1990 PMID 2405271 - "A randomized trial of surgery in the treatment of single metastases to the brain." (Patchell RA, N Engl J Med. 1990 Feb 22;322(8):494-500.
*** Outcome: Local recurrence WBRT 52% vs surgery + WBRT 20% (SS); time-to-recurrence 5 months vs >14 months (SS). Distant brain recurrence 13% vs. 20% (NS). QoL (KPS >=70, functionally independent) 2 months vs. 9 months (SS)
*** Survival: Median OS 3 months vs. 9 months (SS), "neurologic death" 6 months vs. 14 months (SS). No difference in "systemic death".
*** Toxicity: operative mortality 4%, operative morbidity 8%
*** Conclusion: Patients with single metastasis treated with surgery + RT live longer, have fewer recurrences, and better quality of life than patients treated with RT alone
* SWOG/RTOG; 1990 (1983-1986) PMID 2220663 — "Solitary brain metastasis: Results of an RTOG/SWOG protocol evaluating surgery + RT vs RT alone." (Sause W, Am J Clin Oncol 3:427-432, 1990)
** Prospective, non-randomized. Originally a randomized trial, but due to poor accrual was changed to a registry study. 80/97 patients. RT alone (n=55) and surgery + RT (n=25).
** Outcome: Improved/stabilized function RT alone 59% vs. surgery + RT 79%. Recurrence 45% vs. 22%. Improved survival for surgery + RT when corrected for other factors
** Conclusion: Study suggests improvement in survival advantage for surgical resection

## Surgery +/- WBRT

* Patchell study #2, 1998 (1989-97) - PMID 9809728 — "Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial." Patchell RA. JAMA. 1998 Nov 4;280(17):1485-9.
** 95 pts. Randomized. Single brain met. Pts with complete resection (verified by MRI) randomized to postoperative whole brain RT or observation. Dose was 50.4 Gy over 5.5 weeks. Allowed to have other sites of metastases, but KPS >= 70%.
** Median f/u 43-48 wks. Postop RT was associated with less recurrence anywhere in the brain (18% vs 70%), at the site of resection (10% vs 46%), as well as other areas in the brain (14% vs 37%). Decreased neurologic death (6 of 43 pts, 14%; vs 17 of 39, 44%). No difference in overall survival (unlike Patchell #1) or length of time patient remained independent.
** Criticism: non-standard whole brain RT dose
* EORTC 22952-26001 -- Randomized, Surgery/SRS +/- WBRT
** See page at Radiosurgery +/- WBRT

## Surgery + SRS

* Randomized Trials published in 2017 by RTOG and MDACC
* Henry Ford; 2012 (2000-2011) PMID 22806080 -- "Radiosurgery to the surgical cavity as adjuvant therapy for resected brain metastasis." (Robbins JR, Neurosurgery. 2012 Nov;71(5):937-43)
** Retrospective. 85 patients, surgery + postop SRS without adjuvant WBRT. The median marginal radiosurgery dose was 16 Gy, and median target volume was 13.96 cm.
** Outcome: Median follow-up time was 11.2 months. Overall local control was 81.2%. The 6-month, 1-year, and 2-year rates of local control were 88.7%, 81.4%, and 75.7%, respectively. Median overall survival time was 12.1 months. From initial treatment until death or last follow-up, only 30 patients (35%) received WBRT as salvage treatment.
** Conclusion: Radiosurgery to the surgical cavity without WBRT achieved excellent local control of resected brain metastasis. Close imaging follow-up allows early intervention for any new metastasis.
* UC Irvine; 2009 (1999-2007) PMID 18922650 -- "Resection followed by stereotactic radiosurgery to resection cavity for intracranial metastases." (Do L, Int J Radiat Oncol Biol Phys. 2009 Feb 1;73(2):486-91. Epub 2008 Oct 14.)
** Retrospective. 30 patients, surgery + postop SRS/SRT. Dose SRS 15-18 Gy, SRT 22-27.5 Gy in 4-6 fractions.
** Outcome: LR 13%, regional recurrence 63%. 1-year LRFS 82%, neurologic deficit-free survival 67%, OS 51%. Salvage WBRT in 47%
** Conclusion: Postop SRS/SRT to resection cavity is feasible
* Allegheny General; 2008 (2000-2006) PMID 18183353 -- "Single session stereotactic radiosurgery boost to the post-operative site in lieu of whole brain radiation in metastatic brain disease." (Quigley MR, J Neurooncol. 2008 May;87(3):327-32. Epub 2008 Jan 9.)
** Retrospective. 32 patients, surgery for single met + postop linac SRS. 21 solitary, 11 multiple mets. Median cavity dose 14 Gy to 80% isodose, median met dose 15.5 Gy. Median F/U 14 months
** Outcome: Median OS 16 months. Local recurrence 6%. Distant brain recurrence 28%, treated with WBRT
** Conclusion: Use of SRS after surgery results in recurrence comparable to WBRT
* Pittsburgh; 2008 PMID 18414136 -- "TUMOR BED RADIOSURGERY AFTER RESECTION OF CEREBRAL METASTASES." (Mathieu D, Neurosurgery. 2008 Apr 9 [Epub ahead of print])
** Retrospective. 40 patients, surgery + tumor bed boost with GKS. Single met 67%. Median cavity 9.1 ml, Median margin dose 16 Gy. Median F/U 13 months
** Outcome: Local control 73%; new remote brain mets in 54%. Symptomatic RT effects in 5%
** Conclusion: Tumor bed SRS effective local control
* Stanford; 2008 (1998-2006) PMID 17881139 -- "Stereotactic radiosurgery of the postoperative resection cavity for brain metastases." (Soltys SG, Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):187-93. Epub 2007 Sep 19.)
** Retrospective. 72 patients with 76 cavities, resected, SRS (Cyberknife) to resection cavity. Median marginal dose 18.6 Gy (15-30 Gy). Average tumor volume 9.8 cm3. Median F/U 8.1 months
** Outcome: 6-month LC 88%, 12-month LC 79%. Only predictor of LC was increasing conformality indices
** Conclusion: SRS to resection cavity is favorable to historical controls. Recommend 2mm margin
* MSKCC, 2006 ASCO Abstract -- "A phase II trial of stereotactic radiosurgery boost following surgical resection for solitary brain metastases." (Narayana A, Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 1552)
** Phase II. 25 patients accrued out of 50 total. Solitary brain met, KPS>70. SRS with BrainLab to 15-22 Gy single fraction.
** Outcome: 4 local failures (mean time to failure 9.5 months). 1-year LC 35%. 24% additional brain mets. 24% additional WBRT, 8% additional SRS, 4% additional surgery
** Toxicity: 1 patient radiation necrosis requiring surgery at 6 months
** Conclusion: preliminary - surgery-SRS appears inferior to surgery-WBRT data for local control, good salvage with WBRT
* UCSD, 2006 PMID 17018888 -- "Focal radiation therapy of brain metastases after complete surgical resection." (Bahl G, Med Oncol. 2006;23(3):317-24.)
** Retrospective. 7 patients. SRS or fractionated RT (54/27)
** Outcome: 4/7 local recurrence; time-to-recurrence 3.8 months. Out-of-field recurrence 1/7
** Conclusion: Further studies necessary given small number of patients

## Brachytherapy

GliaSite
* Multi-institutional; 2006 PMID 16961129 -- "Results of a phase II trial of the GliaSite radiation therapy system for the treatment of newly diagnosed, resected single brain metastases." (Rogers LR, J Neurosurg. 2006 Sep;105(3):375-84.)
** Phase II. Single met only. 62 patients implanted GliaSite, 54 received BT. 60 Gy prescribed at 1 cm. No WBRT. 43% had extracranial mets.
** Outcome: MRI-based LR 82-87%; median OS 10 months; cause of death neurological in 11%
** Reoperation in 13/62 patients: 9 radiation necrosis, 2 mix, 2 tumor recurrence
** Predictors of survival: extracranial mets, tumor size, radionecrosis
** Conclusion: GliaSite has similar outcome (LR, OS, functional independence) as WBRT

## Guidelines

* Please see the Brain Metastases Official Guidelines page