The optimal margin size in postoperative stereotactic radiosurgery (SRS) for brain metastases is unknown. Herein, the authors investigated the effect of SRS planning target volume (PTV) margin on local recurrence and symptomatic radiation necrosis postoperatively.
Records of patients who received postoperative LINAC-based SRS for brain metastases between 2006 and 2016 were reviewed and stratified based on PTV margin size (1.0 or > 1.0 mm). Patients were treated using frameless and framed SRS techniques, and both single-fraction and hypofractionated dosing were used based on lesion size. Kaplan-Meier and cumulative incidence models were used to estimate survival and intracranial outcomes, respectively. Multivariate analyses were also performed.
A total of 133 patients with 139 cavities were identified; 36 patients (27.1%) and 35 lesions (25.2%) were in the 1.0-mm group, and 97 patients (72.9%) and 104 lesions (74.8%) were in the > 1.0–mm group. Patient characteristics were balanced, except the 1.0-mm cohort had a better Eastern Cooperative Group Performance Status (grade 0: 36.1% vs 19.6%), higher mean number of brain metastases (1.75 vs 1.31), lower prescription isodose line (80% vs 95%), and lower median single fraction–equivalent dose (15.0 vs 17.5 Gy) (all p < 0.05). The median survival and follow-up for all patients were 15.6 months and 17.7 months, respectively. No significant difference in local recurrence was noted between the cohorts. An increased 1-year rate of symptomatic radionecrosis was seen in the larger margin group (20.9% vs 6.0%, p = 0.028). On multivariate analyses, margin size > 1.0 mm was associated with an increased risk for symptomatic radionecrosis (HR 3.07, 95% CI 1.13–8.34; p = 0.028), while multifraction SRS emerged as a protective factor for symptomatic radionecrosis (HR 0.13, 95% CI 0.02–0.76; p = 0.023).
Expanding the PTV margin beyond 1.0 mm is not associated with improved local recurrence but appears to increase the risk of symptomatic radionecrosis after postoperative SRS.
AsherALBurriSHWigginsWFKellyRPBoltesMOMehrlichM: A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence. Int J Radiat Oncol Biol Phys88:899–9062014
BlonigenBJSteinmetzRDLevinLLambaMAWarnickREBrenemanJC: Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys77:996–10012010
BrownPDAsherALBallmanKVFaraceECerhanJHAndersonSK: NCCTG N0574 (Alliance): A phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases. J Clin Oncol33 (18 Suppl):LBA4 2015 (Abstract)
BrownPDBallmanKVCerhanJAndersonSKCarreroXWWhittonA: N107C/CEC.3: A Phase III trial of post-operative stereotactic radiosurgery (SRS) compared with whole brain radiotherapy (WBRT) for resected metastatic brain disease. Int J Radiat Oncol Biol Phys96:9372016 (Abstract)
ChangELWefelJSHessKRAllenPKLangFFKornguthDG: Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol10:1037–10442009
ChoiCYChangSDGibbsICAdlerJRHarshGR IVLiebersonRE: Stereotactic radiosurgery of the postoperative resection cavity for brain metastases: prospective evaluation of target margin on tumor control. Int J Radiat Oncol Biol Phys84:336–3422012
EatonBRLaRiviereMJKimSPrabhuRSPatelKKandulaS: Hypofractionated radiosurgery has a better safety profile than single fraction radiosurgery for large resected brain metastases. J Neurooncol123:103–1112015 (Erratum in J Neurooncol 123:113 2015)
FokasEHenzelMSurberGKleinertGHammKEngenhart-CabillicR: Stereotactic radiosurgery and fractionated stereotactic radiotherapy: comparison of efficacy and toxicity in 260 patients with brain metastases. J Neurooncol109:91–982012
KirkpatrickJPWangZSampsonJHMcSherryFHerndonJEIIAllenKJ: Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: results of a randomized trial. Int J Radiat Oncol Biol Phys91:100–1082015
KocherMSoffiettiRAbaciogluUVillàSFauchonFBaumertBG: Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol29:134–1412011
MinnitiGPaoliniSD’AndreaGLanzettaGCiconeFConfaloniV: Outcomes of postoperative stereotactic radiosurgery to the resection cavity versus stereotactic radiosurgery alone for melanoma brain metastases. J Neurooncol132:455–4622017
MinnitiGScaringiCPaoliniSLanzettaGRomanoACiconeF: Single-fraction versus multifraction (3 × 9 Gy) stereotactic radiosurgery for large (>2 cm) brain metastases: a comparative analysis of local control and risk of radiation-induced brain necrosis. Int J Radiat Oncol Biol Phys95:1142–11482016
PatelKRBurriSHAsherALCrockerIRFraserRWZhangC: Comparing preoperative with postoperative stereotactic radiosurgery for resectable brain metastases: a multi-institutional analysis. Neurosurgery79:279–2852016
PatelKRPrabhuRSKandulaSOliverDEKimSHadjipanayisC: Intracranial control and radiographic changes with adjuvant radiation therapy for resected brain metastases: whole brain radiotherapy versus stereotactic radiosurgery alone. J Neurooncol120:657–6632014
ShawEScottCSouhamiLDinapoliRBaharyJPKlineR: Radiosurgery for the treatment of previously irradiated recurrent primary brain tumors and brain metastases: initial report of Radiation Therapy Oncology Group protocol (90-05). Int J Radiat Oncol Biol Phys34:647–6541996