Retrospective analysis of salvage surgery for local progression of brain metastasis previously treated with stereotactic irradiation: diagnostic contribution, functional outcome, and prognostic factors

Abstract

Background: Stereotactic irradiation (STI) is a primary treatment for patients with newly diagnosed brain metastases. Some of these patients experience local progression, which is difficult to differentiate from radiation necrosis, and difficult to treat. So far, just a few studies have clarified the prognosis and effectiveness of salvage surgery after STI. We evaluated the diagnostic value and improvement of functional outcomes after salvage surgery. Based on these results, we reconsidered surgical indication for patients with local progression after STI. Methods: We evaluated patients with brain metastases treated with salvage surgery for local progression from October 2002 to July 2019. These patients had undergone salvage surgery based on magnetic resonance imaging findings and/or clinical evidence of post-STI local progression and stable systemic disease. We employed two prospective strategies according to the eloquency of the lesions. Lesions in non-eloquent areas had been resected completely with a safety margin, utilizing a fence-post method; while lesions in eloquent areas had been treated with minimal resection and postoperative STI. Kaplan-Meier curves were used for the assessment of overall survival. Prognostic factors for survival were analyzed. Results: Fifty-four salvage surgeries had been performed on 48 patients. The median age of patients was 63.5 years (range 36-79). The median interval from STI to surgery was 12 months. The median overall survival was 20.2 months from salvage surgery and 37.5 months from initial STI. Primary cancers were lung 31, breast 9, and others 8. Local recurrence developed in 13 of 54 lesions (24%). Leptomeningeal dissemination occurred after surgery in 3 patients (5.6%). Primary breast cancer (breast vs. lung: HR: 0.17), (breast vs. others: HR: 0.08) and RPA class 1-2 (RPA 1 vs. 3, HR:0.13), (RPA 2 vs 3, HR:0.4) were identified as good prognostic factors for overall survival (OS) in multivariate analyses. The peripheral neutrophil-to-lymphocyte ratio (NLR) of ≤3.65 predicted significantly longer OS (median 25.5 months) than an NLR > 3.65 (median 8 months).

The Management of Brain Metastases—Systematic Review of Neurosurgical Aspects

“…Careful histological studies have revised this assumption [ 103 , 104 ], which is corroborated by a significant local recurrence rate after both surgical resection [ 47 ] and focal radiotherapy [ 105 ]. The improved systemic disease control rates due to modern treatment strategies [ 8 ] lead to an increased number of cases with recurrent BM requiring salvage therapy [ 106 ]. Surgical re-resection is a valid option in selected patients with recurrent BM, according to a recent review [ 107 ].…”

“…Unfortunately, there are only retrospective case-series available to establish the beneficial impact of surgery in this setting [ 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 ]. An indication for re-operation was reported in several studies if patients show a rapidly progressing, symptomatic mass lesion that was surgically accessible and at the same time display controlled systemic disease and a good functional condition reflected by a KPI score of >60 [ 106 , 112 , 114 , 116 , 117 , 118 ]. The median OS after salvage operation ranged between 7.5 months [ 114 ] and 20.2 months [ 106 ], and depended on presurgical performance status [ 113 ], time between initial and salvage BM surgery [ 109 ], as well as extent of resection during re-operation [ 114 ].…”

“…An indication for re-operation was reported in several studies if patients show a rapidly progressing, symptomatic mass lesion that was surgically accessible and at the same time display controlled systemic disease and a good functional condition reflected by a KPI score of >60 [ 106 , 112 , 114 , 116 , 117 , 118 ]. The median OS after salvage operation ranged between 7.5 months [ 114 ] and 20.2 months [ 106 ], and depended on presurgical performance status [ 113 ], time between initial and salvage BM surgery [ 109 ], as well as extent of resection during re-operation [ 114 ]. Bindal et al have summarized all of the potential prognostic factors in a grading system to predict outcome after salvage surgery, including the status of systemic disease, preoperative KPI score, time to recurrence, age, and primary tumor [ 111 ].…”

“…Consequently, the median survival rates after re-resection of recurrent BM ranged from 13.4 to 3.4 months, depending on the grading score [ 111 ]. Interestingly, five retrospective studies reported functional improvement rates in patients with symptomatic BM recurrence between 62–90% after surgical resection [ 106 , 109 , 111 , 115 , 117 ], highlighting the beneficial impact of surgery on symptom burden and functional independency. However, the management of recurrent cerebral metastases is challenging, as the majority has already been treated with radio- and chemotherapy, potentially rendering any cranial re-operation difficult in terms of an increased risk of wound healing disorders, infections, hemorrhages, and CSF-fistulas due to scarring, arachnoiditis, and pathological dural adherences of edematous brain tissue [ 106 , 117 , 119 ].…”

“…Interestingly, five retrospective studies reported functional improvement rates in patients with symptomatic BM recurrence between 62–90% after surgical resection [ 106 , 109 , 111 , 115 , 117 ], highlighting the beneficial impact of surgery on symptom burden and functional independency. However, the management of recurrent cerebral metastases is challenging, as the majority has already been treated with radio- and chemotherapy, potentially rendering any cranial re-operation difficult in terms of an increased risk of wound healing disorders, infections, hemorrhages, and CSF-fistulas due to scarring, arachnoiditis, and pathological dural adherences of edematous brain tissue [ 106 , 117 , 119 ]. The morbidity rates reported in the available studies range from 31% [ 110 ] to 0% [ 106 , 109 , 112 ], and they may depend on the specific status of the patients recruited for the individual studies.…”