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Surgery may benefit certain patients with primary central nervous system lymphoma
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Cytoreductive surgery may be an effective treatment option for specific subgroups of patients with primary central nervous system lymphoma, according to results of a systematic review.
“What our study showed us is that we really should be thinking about primary CNS lymphoma as two types of tumors with different methods of treatment for each,” Debraj Mukherjee, MD, MPH, assistant professor of neurosurgery and director of neurosurgical oncology at Johns Hopkins Bayview Medical Center, said in a press release. “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, [whereas] the larger, deeper tumors are not suited for surgery because of their location near the ventricle system in the brain.”
Mukherjee and colleagues pooled data from studies published between Jan. 1, 1968, and May 2, 2018, of patients with primary CNS lymphoma who underwent biopsy or resection. They assessed findings on morbidity, PFS and OS.
Researchers found that of the 15 studies that failed to show a benefit of cytoreductive surgery, most included somewhat small cohorts and predated standardization of high-dose systemic methotrexate treatment. Conversely, nine more recent, larger cohort studies showed potential benefits of cytoreductive surgery.
Factors associated with improved survival included age, functional status, and treatment with chemotherapy and/or radiation.
HemOnc Today spoke with Mukherjee about the study findings and their potential clinical implications.
Question: What prompted this research?
Answer: Interest in primary CNS lymphoma has increased within the past decade. In 2012, researchers in Germany conducted a post-hoc analysis of a randomized clinical trial of patients treated with different versions of methotrexate and other chemotherapy for primary CNS lymphoma. They found some benefit to surgery over biopsy. Since that time, investigators have looked at different data sources, including national databases and some small institutional series, to answer to the question of whether it is appropriate to perform cytoreductive surgery on some of these lymphomas or whether it is better to stick with the traditional approach — biopsy and chemotherapy, which has been mediated primarily by methotrexate dating to 1990. At Johns Hopkins Bayview Medical Center, we see a lot of these tumors. A lot of patients who have confusing diagnoses or questionable imaging and want a second opinion come to us. Because of this large referral base, we wanted to thoughtfully look at this question in a way that other groups had not.
Q: How did you conduct the study?
A: We sought initially to perform a systematic review and meta-analysis of data from the past 50 years. We looked at close to 1,300 articles published during that period, but the rigor of that data did not seem strong enough to warrant a meta-analysis. However, we did conduct a thoughtful systematic review noting trends over time and focused on 24 articles that assessed the value of biopsy vs. resection for primary CNS lymphoma.
Q: What did you find ?
A: There appear to be two clinical types of primary CNS lymphoma. The first type, superficial solitary lesions, can be operated upon safely these days, especially with the use of newer intraoperative techniques including intraoperative MRI, ultrasound and neuro-monitoring. For the other type of lymphoma, which consists of more diffuse and deeper lesions, the data seem to still support the use of biopsy, given perioperative risks for surgical resection. We should catalog the type of primary CNS lymphoma, superficial or deep, afflicting our patients. Such a clinical distinction may represent a paradigm shift in how we treat these tumors.
Q: Did any of your findings surprise you?
A: What was most surprising was that only in the past few years have people tried to think about these tumors in these different anatomic terms. If researchers historically had thought about this tumor as two different anatomic subsets of disease, we would probably have better data, potentially allowing us to perform a robust meta-analysis. Increasingly, neurosurgeons are becoming involved in the workup and management of these lesions. Surgeons will instinctively look at lesions based on their anatomical location and what we can safely biopsy vs. resect. I believe the recent interest in this topic among neurosurgeons has improved the anatomic details associated with these cases, which has secondarily expanded the quality of available data.
Q: What is next for research?
A: We are planning a prospective registry study to track these two categories of primary CNS lymphoma, allowing our analysis and understanding to guide how we treat these patients. Well-done, multi-institutional registries will be looking not just at PFS and OS, but also at quality of life. Studying the impact of these treatments on quality of life would significantly add to the scientific literature and give patients a sense of what to expect after biopsy or resection. Depending upon registry findings, we may conduct randomized clinical trials that focus on prognostic and outcome differences between the subsets of primary CNS lymphoma. – by Jennifer Southall
References:
Labak CM, et al. World Neurosurg. 2019;doi:10.1016/j.wneu.2019.02.252.
Weller M, et al. Neuro Oncol. 2012;doi:10.1093/neuonc/nos159.
For more information:
Debraj Mukherjee, MD, MPH , can be reached at Johns Hopkins Bayview Medical Center, 4940 Eastern Ave., Baltimore, MD 21224; email: dmukher1@jhmi.edu.
Disclosure: Mukherjee reports no relevant financial disclosures.