Checkpoint inhibition in meningiomas.

Meningiomas are increasingly appreciated to share similar features with other intra-axial central nervous system neoplasms as well as systemic cancers. Immune checkpoint inhibition has emerged as a promising therapy in a number of cancers, with durable responses of years in a subset of patients. Several lines of evidence support a role for immune-based therapeutic strategies in the management of meningiomas, especially high-grade subtypes. Meningiomas frequently originate juxtaposed to venous sinuses, where an anatomic conduit for lymphatic drainage resides. Multiple populations of immune cells have been observed in meningiomas. PD-1/PD-L1 mediated immunosuppression has been implicated in high-grade meningiomas, with association between PD-L1 expression with negative prognostic outcome. These data point to the promise of future combinatorial therapeutic strategies in meningioma.

The management of primary central nervous system lymphoma related to AIDS in the HAART era.

PURPOSE OF REVIEW: The review highlights the recent advances in the pathogenesis, diagnosis and treatment of AIDS-related primary CNS lymphoma (AIDS-PCNSL). RECENT FINDINGS: The incidence of AIDS-PCNSL has decreased in the era of highly active antiretroviral therapy (HAART). The prognosis has improved and this most probably in relation both with the HAART-induced immunologic status recovery and subsequently the possibility to use more aggressive treatment strategies. Immunomodulatory effect of HAART seems also to have an indirect antitumor activity on the disease. SUMMARY: The treatment strategy for AIDS-PCNSL in the HAART era tends to become similar to that of the immunocompetent population. In the absence of randomized trials devoted to AIDS-PCNSL, most current national comprehensive cancer network guidelines recommend the use of high-dose methotrexate-based chemotherapy combined or not with whole-brain radiotherapy as initial treatment in addition to HAART. The objective for the future would be that prognosis of AIDS-PCNSL catch up with that of the immunocompetent patients with special attention to systemic and neurocognitive tolerance of the treatments.

Enhanced survival associated with vitiligo expression during maintenance biotherapy for metastatic melanoma.

Vitiligo, an autoimmune skin disorder, was evaluated in 49 metastatic melanoma patients treated with an immunotherapy regimen of maintenance biotherapy (mBT) following induction concurrent biochemotherapy (cBCT). Patients receiving mBT demonstrated a stable or better response to cBCT. The mBT regimen consisted of outpatient subcutaneous injections of low-dose IL-2 (1 MIU/m(2)) 5/7 days weekly, GM-CSF (125 mcg/m(2)) 14 days monthly, and high-dose pulses of in-patient continuous infusion decrescendo IL-2 (54 MIU/m(2)) over 48 hours monthly for the first 6 months and every 2 months thereafter. The majority of patients had poor prognostic features. Forty-nine patients were without evidence of vitiligo at the start of mBT. Of these, 21 patients (43%) developed vitiligo during mBT and had a median overall survival from the start of mBT of 18.2 months (95% CI, 12.3-N/A) compared to 8.5 months (95%CI <6.7-12.7) for 28 non-vitiligo patients (P=0.027). Six of 21 vitiligo patients (29%) expressed IgG antibody titers to tyrosinase-related protein-2 compared to four of 28 non-vitiligo patients (14%) (P=NS). The development of vitiligo in metastatic melanoma patients on cBCT/mBT immunotherapy correlates with a better therapeutic outcome.

Proton magnetic resonance spectroscopy in immunocompetent patients with primary central nervous system lymphoma.

BACKGROUND: Magnetic resonance spectroscopy imaging (MRSI) non-invasively evaluates the metabolic profile of normal and abnormal brain tissue. Primary central nervous system lymphoma (PCNSL) is a highly aggressive tumor responsive to high-dose methotrexate based regimens. Patients often have complete responses but relapses are common. We characterized the MR spectra of PCNSL patients, correlated MRSI with MRI and evaluated whether early recurrence could be detected by MRSI. METHODS: Patients with PCNSL had multi-voxel MRSI before, during, and after treatment. The region of interest was defined using axial FLAIR images. Metabolites assessed were N-acetyl-aspartate (NAA), choline (Cho), creatine (Cr), lipid, and lactate. Ratios of Cho/Cr, NAA/Cho, and NAA/Cr were calculated and correlated with MRI. Overall survival (OS), progression free survival (PFS), and relative risks of each of the ratios were determined. RESULTS: MRSI was performed on 11 men and seven women; median age of 59. Sixty-seven MRSI studies were performed, 17 baseline and 48 follow-up studies. Median ratios in 16 pretreated patients were Cho/Cr-1.90, NAA/Cho-0.39, and NAA/Cr-1.27. Two patients had lipid at baseline, five had lactate and two had both. MRSI correlated with tumor response or progression on MRI; in three patients MRSI suggested disease progression prior to changes on MRI. Univariate analysis of metabolite ratios, lipid, and lactate revealed that none significantly affected PFS or OS. Kaplan-Meier analysis of the presence or absence of lipid, lactate or both revealed a trend for increased PFS. CONCLUSION: MRSI and MRI correlate with tumor response or progression and may allow early detection of disease recurrence. The presence or absence of lipid and/or lactate may have prognostic significance. Further research using MRSI needs to be done to validate our findings and determine the role of MRSI in PCNSL.

Risks of cancer associated with long-term exposure to PUVA in humans: current status--1991.

Since 1975 oral 8-methoxypsoralen administered in association with ultraviolet-A radiation (UVA), (PUVA) has been widely used to treat psoriasis and other cutaneous diseases. PUVA is mutagenic, and in animals carcinogenic. Prospective study of a cohort of patients with psoriasis who were first treated with PUVA in 1975-1976 has provided data on the carcinogenic risk of this treatment. There is a dose-dependent increase in the risk of squamous cell cancer of the skin associated with exposure to PUVA. A recent large-scale Swedish study confirmed this association. The risk of squamous cell cancer of the genitals of males exposed to high doses of PUVA is especially high. A consistent, confirmed, and significant relationship of exposure to PUVA to other types of malignancies in man has not been established. Although highly effective in the treatment of psoriasis, the risk of squamous cell cancer associated with long-term therapy with PUVA must be considered in determining when this therapy is appropriate for an individual patient. Additional study of PUVA-treated patients will better define the full spectrum of the carcinogenic risk of PUVA therapy and the clinical behavior of tumors that arise in association with this treatment.