Certain patients with primary central nervous system (PCNS) lymphoma, a rare type of brain cancer, may benefit more from having surgery to remove their tumor than following the current standard of care, which does not include surgery, a review of studies concludes.
Until now, surgical resection has not been an option due to the often diffuse and deep-rooted nature of these lymphomas. That increases the risk of damaging healthy parts of the brain.
But in their study, “Surgical Resection for Primary Central Nervous System Lymphoma: A Systematic Review,” researchers from the Johns Hopkins University School of Medicine and Johns Hopkins Kimmel Cancer Center found that a type of PCNS lymphoma — one easily distinguishable on magnetic resonance imaging (MRI) scans — may benefit from surgery. The report was published in the journal World Neurosurgery.
PCNS lymphoma is a rare but aggressive type of lymphoma primarily affecting the brain, the spinal cord, or the meninges, the outer layers covering the brain. It also, in some cases, can affect the eyes.
The current standard of care for the condition includes biopsy, radiotherapy, and high-dose chemotherapy with methotrexate. However, with the recent standardization of adjuvant chemo and radiation therapy, and improvements in neuroimaging and surgical techniques, “there has been renewed interest in a potential role for cytoreductive surgery in the treatment of PCNSL,” the researchers said.
Building on that, the scientists were interested in better understanding the risks and benefits of having surgery for this type of cancer.
The researchers performed a systematic review of studies published during the 50-year period between January 1968 and May 2018. The review assessed patients who had biopsies or surgeries to remove their brain tumors.
They used this comprehensive data to compare the outcomes of patients who had biopsies with those who had surgical resections — including post-operative complications, overall survival, and survival without disease progression.
Taken together, information from the 24 studies selected included data on 15,280 patients.
Among these articles, 15 failed to show a benefit from surgery to remove some or all of the tumor. But most of those reports were on small studies done at a single institution, and conducted before therapy with methotrexate was a standard.
The most prominent of these studies was carried out in 1990 and confirmed the benefits of methotrexate. However, it reported post-operative complications in four of 10 patients undergoing surgery. At the time, researchers concluded that surgical treatment was not recommended.
The other articles reviewed consisted of nine studies that were larger and more recent.
One report, referring to a 2012 randomized clinical trial that enrolled 526 patients, found surgery was beneficial for certain patients — namely, those who were younger and whose tumors were well-defined, and located in more superficial regions of the brain.
The other studies also supported a benefit of surgery when compared with biopsy, noting either improvements in patient survival, or fewer complications. Five of them also revealed the existence of two types of PCNS lymphoma types that are detectable on MRI scans.
One is superficial and localized, and thus may be suitable for surgery. The other is located deep in the tissue and spread, or diffuse, and thus not recommended for surgery.
Researchers estimate that nearly 20% of people with PCNS lymphoma have a superficial type of tumor, and thus “hold the potential for cure with surgery followed by treatment with methotrexate,” according to a press release from Johns Hopkins Medicine.
“What our study showed us is that we really should be thinking about PCNS lymphoma as two types of tumors with different methods of treatment for each,” said Debraj Mukherjee, MD, MPH, a professor at Johns Hopkins Bayview Medical Center, and a study leader.
“Surgery to remove the superficial, localized types of tumors does not seem to put patients at greater risk and also improves outcomes for these patients, while the larger, deeper tumors are not suited for surgery because of their location near the ventricle system in the brain,” he added.
According to researchers, the two different types of PCNS lymphoma detected may explain the disparities between older studies — which found no overall benefit to surgery — and more recent research.
Older studies were done at a time when MRI, intraoperative neuromonitoring, neuronavigation, and fluorescent tumor visualization were not routinely used.
“The older trials never delved into this question of size, type and location of tumor,” Mukherjee said. “It was thought that these tumors were all diffuse and multifocal, and too difficult to remove with surgery without increased risk to patients.”
The new and improved technologies now available warrant updated reviews, the researchers said.
“Given these data, neurosurgeons and neuro-oncologists may consider cytoreductive surgery as a reasonable upfront treatment strategy for select patients with PCNSL,” they said.
Future studies are warranted to help determine the risks and benefits of surgery, including well-designed prospective studies conducted specifically with that goal, according to the investigators.
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