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Poor OS observed in men with brain metastases from germ cell tumors
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Brain metastases in men with germ cell tumors appeared associated with poor OS, especially when combined with other risk factors, according to results of an analysis from the Global Germ Cell Cancer Group.
Men with brain metastases at relapse may experience a survival benefit from high-dose chemotherapy and multimodality treatment, results also showed.
Jörg Beyer, MD, of the department of oncology at University Hospital Zurich, and colleagues analyzed retrospective data culled from 43 participating centers in the Global Germ Cell Cancer Group to define characteristics, treatment response and outcomes of men with brain metastases from germ cell tumors.
OS served the primary endpoint and PFS served as a secondary endpoint.
The analysis included data from 523 men aged 15 years or older (51% aged younger than 30 years). Researchers divided the patients into two groups: Patients in group A (n = 228) had brain metastases at the time of initial germ cell tumor diagnosis and patients in group B (n = 295) presented with brain metastases at recurrence.
Multiple brain metastases occurred more frequently among patients who presented with brain metastases at initial diagnosis than among patients with brain metastases at recurrence (67% vs. 56%; P < .05). Group A also had a higher prevalence of coexisting systemic disease (99% vs. 72%; P < .05).This difference was particularly pronounced in terms of liver and/or bone metastases, which were significantly more prevalent in group A vs. group B (46% vs. 25%; P < .001).
At 2 years, significantly more men in group A achieved PFS than men in group B (29%; 95% CI, 23-35 vs. 21%; 95% CI, 16-26; P < .05). Relapse after 2 years appeared uncommon in both groups.
Among patients with documented progression, 54% (86 of 158) in group A experienced progression in the brain after treatment vs. 49% (113 of 230) in group B.
In group A, the 3-year rate for OS was 48% (95% CI, 42-55) and median OS was 29.5 months. Twenty-seven percent (95% CI, 22-32) of patients in group B achieved 3-year OS and median OS in this cohort was 8 months. Mortality appeared uncommon after 3 years.
Death due to germ cell tumors with brain metastases progression occurred in 52% (66 of 128 deaths) of patients in group A and 45% (102 of 225 deaths) of patients in group B.
In group A, multivariable analysis revealed three factors significantly associated with poor OS:
• Mediastinal primary site in patients without nonseminoma (HR = 1.66; 95% CI, 0.98-2.82);
• Concurrent liver and/or bone metastases (HR = 2.11; 95% CI, 1.47-3.03); and
• Presence of multiple brain metastases (HR = 1.88; 95% CI, 1.24-2.85).
In group B, the following variables were identified as associated with poor OS in multivariable analysis:
• Multiple brain metastases (HR = 2; 95% CI, 1.4-2.87);
• Liver and/or bone metastases (HR = 1.92; 95% CI. 1.29-2.84); and
• Elevated levels of at least one tumor marker (α-fetoprotein of 100 ng/mL or greater or an HCG of 5,000 U/L or greater; HR = 2.11; 95% CI, 1.48-3.02).
Ninety-nine percent of patients in group A underwent chemotherapy. However, in these patients, multivariable analysis did not reveal a statistically significant improvement in survival in association with multimodality treatment or high-dose chemotherapy.
Fifty-four percent of patients in group B underwent chemotherapy, and multivariable analysis indicated survival improved with multimodality treatment vs. single-modality chemotherapy (HR = 0.51; 95% CI, 0.36-0.73) and high-dose chemotherapy vs. standard-dose chemotherapy (HR = 0.41; 95% CI, 0.24-0.7).
“We demonstrated that greater than 50% of patients with either synchronous brain metastases at the time of initial diagnosis or metachronous brain metastases at relapse experience disease progression and die within 1 year after the diagnosis of brain metastases and that approximately half of those patients died as a result of systemic progression rather than uncontrolled brain metastases,” Beyer and colleagues wrote. “Patients who present with adverse prognostic factors in addition to brain metastases, and particularly those who experience relapse with metachronous brain metastases, have worse outcomes.” – by Jennifer Byrne
Disclosures: Beyer reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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