Brain Metastases Resection Linked to Pachymeningeal Tumour Seeding

A unique pattern of intracranial progression has been detected in patients who undergo neurosurgery and cavity radiation for brain metastases

medwireNews: Patients with brain metastases treated with neurosurgical resection and adjuvant stereotactic radiotherapy may have a different pattern of recurrence to those given whole-brain radiation, research suggests. 

The review of 1188 patients with a new diagnosis of brain metastases showed that pachymeningeal seeding was significantly linked to treatment mode, affecting 36 of 318 patients treated with surgery and stereotactic radiation between 2001 and 2015, but none of the 870 patients treated with whole-brain radiation during the same period. 

By contrast, the incidence of leptomeningeal disease was comparable between the treatment groups, report Daniel Cagney, from Dana-Farber Cancer Center in Boston, Massachusetts, USA, and colleagues. 

The investigators note that patients who underwent neurosurgery had a better prognosis than those who received whole-brain radiation, with fewer brain metastases and fewer prior chemotherapy regimens, as well as less extracranial disease and a lower incidence of presentation with seizure at time of brain disease diagnosis. 

In addition, pachymeningeal seeding after resection was more common in patients with controlled extracranial disease at the time of metastases diagnosis – “those who have an otherwise favorable prognosis”, the researchers explain – than in those with uncontrolled or newly diagnosed extracranial tumours, affecting 13.7% of 205 patients versus 3.6% of 223 patients. 

This trend may be “likely owing to the lower competing risk of systemic progression or death, and therefore represents a marked prognostic turn with significant clinical consequences for such patients”, caution Daniel Cagney and team. 

“In patients who develop pachymeningeal failure, neurologic death represents a key cause of patient mortality”, they continue, noting that 72% of the pachymeningeal cohort died after neurological disease progression.

Nevertheless, the authors note that salvage stereotactic radiation was associated with an improvement in all-cause mortality in this patient group compared with whole-brain radiation, with a hazard ratio of 0.49. 

And overall survival  in those receiving pachymeningeal seeding and salvage radiation was comparable regardless of whether they had controlled extracranial disease or uncontrolled or newly diagnosed extracranial tumours. 

Multivariable analysis on a per metastasis level revealed that patients who had previously received  radiation were a significant 2.39 times more likely to experience pachymeningeal seeding after resection than those who had not previously received radiotherapy. 

“Given that the standard practice in many institutions is stereotactic radiation of the cavity after surgical resection, further investigation into mechanisms to prevent pachymeningeal seeding are warranted”, the investigators conclude.

“In addition, delineation of optimal radiotherapeutic management of patients who develop pachymeningeal seeding would be prudent”, they advise. 



Cagney DN, Lamba N, Sinha S, et al. Association of neurosurgical resection with development of pachyme n ingeal seeding in patients with brain metastases . JAMA Oncol; Advance online publication 7 March 2019. doi:10.1001/jamaoncol.2018.7204

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