A team of researchers sought to learn whether some people with primary central nervous system lymphoma (PCNSL) might benefit from intensive treatments offered in clinical trials even if they technically don’t qualify for inclusion in a trial. Their results were published in the journal Cancers.

Eastern cooperative oncology group (ECOG <4 or ECOG <3) and Karnofsky performance status (KPS <40, KPS <60 independent of PCNSL, or KPS <30 because of PCNSL) are common measures used to determine eligibility for clinical trials. Other exclusion criteria include immunosuppression, inadequate renal function, and heart disease. Patients with psychiatric disorders that may compromise their ability to give informed consent, and potentially hamper compliance, also are generally excluded from participating in clinical trials.

The researchers analyzed treatment, outcome, and prognostic factors from 34 patients with PCNSL at a single medical center in Europe who didn’t meet the inclusion criteria for clinical trials. They then compared those results with results from patients in the German PCNSL Study Group 1 (G-PCNSL-SG-1) trial, the largest multicenter prospective study of PCNSL.

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Of the 34 patients who were seen at their medical center between 2005 and 2019, 27 patients received high-dose methotrexate (HDMTX)-based polychemotherapy (non-study group). Their results were compared with those of 526 patients in the G-PCNSL-SG-1 trial who had received HDMTX (study group). The median overall survival rate between the 2 groups was similar: 20 months in the non-study group compared with 21 months in the study group (P =.766).

Three factors were cited as important prognostic factors in overall survival: age of the patient, application of HDMTX despite the potential risk of toxicity, and an early complete response.

The authors noted some study limitations. It was a retrospective analysis of a relatively small number of patients from 1 center, which differed from the multicenter patient pool of the G-PCNSL-SG-1 trial.

The time period may have played a role in that the patients in the non-study group were treated at later dates than the patients in the study group. The researchers noted that the impact of era of treatment could not be analyzed from a statistical point of view in their population because PCNSL diagnosis occurred in only 5 patients in the non-study group between 2005 and 2009, whereas all the patients in the study group were recruited between 2000 and 2005.

 “Our data further suggest that intensive chemotherapy is feasible in patients of a particularly compromised clinical state (KPS <30) at first diagnosis or in the case of (mostly psychiatric) comorbidities influencing informed consent, as long as the general physical condition allows application of chemotherapy,” the researchers wrote.

Ultimately, the researchers concluded, their results were promising and showed that it may be worthwhile to offer intensive treatment with HDMTX to patients with PCNSL who don’t meet the inclusion criteria for a clinical trial.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Seidel S, Margold M, Kowalski T, et al. Patients with primary central nervous system lymphoma not eligible for clinical trials: prognostic factors, treatment and outcome. Cancers. 2021;13(12):2934. doi:10.3390/cancers13122934