Predictive molecular markers in metastases to the central nervous system: recent advances and future avenues.

Metastases to the central nervous system (CNS) are common in several cancer types. For most primary tumors that commonly metastasize to the CNS, molecular biomarker analyses are recommended in the clinical setting for selection of appropriate targeted therapies. Therapeutic efficacy of some of these agents has been documented in patients with brain metastases, and molecular testing of CNS metastases should be considered in the clinical setting. Here, we summarize the clinically relevant biomarker tests that should be considered in neurosurgical specimens based on the current recommendations of the European Society of Medical Oncology (ESMO) or the National Comprehensive Cancer Network (NCCN) for the most relevant primary tumor types: lung cancer (EGFR mutations, ALK rearrangement, BRAF mutations), breast cancer (HER2 amplification, steroid receptor overexpression), melanoma (BRAF mutations), and colorectal cancer (RAS mutations). Furthermore, we discuss emerging therapeutic targets including novel oncogenic alterations (ROS1 rearrangements, FGFR1 amplifications, CMET amplifications, and others) and molecular features of the tumor microenvironment (including immune-checkpoint molecules such as CTLA4 and PD-1/PD-L1). We also discuss the potential role of advanced biomarker tests such as next-generation sequencing and "liquid biopsies" for patients with CNS metastases.

Clinical features, treatment and outcome of mucosa-associated lymphoid tissue (MALT) lymphoma of the ocular adnexa: single center experience of 60 patients.

BACKGROUND: Orbital marginal zone B-cell lymphoma (OAML) constitutes for the most frequent diagnosis in orbital lymphoma. Relatively little data, however, have been reported in larger cohorts of patients staged in a uniform way and no therapy standard exists to date. MATERIAL AND METHODS: We have retrospectively analyzed 60 patients diagnosed and treated at our institution 1999-2012. Median age at diagnosis was 64 years (IQR 51-75) and follow-up time 43 months (IQR 16-92). All patients had undergone uniform extensive staging and histological diagnosis was made by a reference pathologist according to the WHO classification. RESULTS: The majority of patients presented with stage IE (n = 40/60, 67%), three had IIE/IIIE and the remaining 17 stage IVE. Seven patients with IVE had bilateral orbital disease whereas the others showed involvement of further organs. Treatment data were available in 58 patients. Local treatment with radiotherapy (14/58, 24%) or surgery (3/58, 5%) resulted in response in 82% of patients. A total of 26 patients (45%) received systemic treatment with a response rate of 85%. Nine patients received antibiotics as initial therapy; response rate was 38%. Watchful-waiting was the initial approach in 6/58 patients. In total 28/58 patients (48%) progressed and were given further therapy. Median time-to-progression in this cohort was 20 months (IQR 9-39). There was no difference in time-to-progression after first-line therapy between the different therapy arms (p = 0.14). Elevated beta-2-microglobulin, plasmacytic differentiation, autoimmune disorder and site of lymphoma were not associated with a higher risk for progress. CONCLUSION: Our data underscore the excellent prognosis of OAML irrespective of initial therapy, as there was no significant difference in time-to-progression and response between local or systemic therapy. In the absence of randomized trials, the least toxic individual approach should be chosen for OAML.

Does MALT lymphoma of the lung require immediate treatment? An analysis of 11 untreated cases with long-term follow-up.

BACKGROUND: Mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the lung is a relatively rare disease. As little is known about the natural clinical course if left untreated, all patients undergoing a watch-and-wait policy at our institution were investigated. PATIENTS AND METHODS: A retrospective analysis identified a total of 11 patients with MALT lymphoma of the lung who did not undergo treatment following initial diagnosis. All patients had undergone extensive staging and were closely observed with restaging every three months. Histological assessment included immunhistochemistry for demonstration of the immunphenotype CD20+/CD5-/ CD10-/cyclinD1-/CD23-. Genetic aberrations were assessed, using RT-PCR for t(11;18) (q21;21) and fluorescence in situ hybridisation for the evaluation of t(14;18)(q32;q21), t(1;14) (p22;q32), trisomies 3 and 18. RESULTS: Five patients had MALT lymphoma restricted to the lung, while the remaining six had additional extrapulmonary sites detected during staging. The median time of observation without therapy was 28.1 months (inter-quartile range: 5 to 60 months); within this time, all 11 patients showed at least stable disease. Six of these 11 patients, however, had spontaneous regressions and wax-and-wane phenomena of the pulmonary lesions, but not of extrapulmonary manifestations. Three of these patients had evidence of t(11;18)(q21;q21), while the remaining three had no evidence of genetic aberrations. One patient was referred for treatment after progression in the lung, while two patients experienced progression outside the lung. Currently, all patients are alive, with 8 patients still only being watched. CONCLUSION: Our findings suggest that MALT lymphoma of the lung is a very indolent disease with the potential for spontaneous regression. In view of this, patients diagnosed with pulmonary MALT lymphoma might not require immediate treatment in the absence of symptoms and a watch-and-wait policy could be adopted.