Citations

Purpose The addition of PCV (procarbazine, lomustine, and vincristine) chemotherapy to radiotherapy (RT) for patients with WHO grade 2 glioma improves progression-free survival (PFS). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long-term survival. Patients and Methods A total of 251 patients with WHO grade 2 glioma age ≥ 40 years with any extent of resection or age < 40 years with subtotal resection/biopsy were randomly assigned to RT (54 Gy) or RT plus PCV. We observed 111 patients age < 40 years with gross total resection. CF was assessed by Mini–Mental State Examination (MMSE) at baseline and years 1, 2, 3, and 5. Results Overall, few patients experienced significant decline in MMSE score. There were no significant differences in the proportion of patients experiencing MMSE score decline between the randomized study arms at any time point. Both study arms experienced a significant gain in average MMSE score longitudinally over time, with no difference between arms. Conclusion The MMSE is a relatively insensitive tool, and subtle changes in CF may have been missed. However, the addition of PCV to RT did not result in significantly higher rates of MMSE score decline than RT alone through 5 years of follow-up. Patients in both randomly assigned arms experienced a statistically significant average MMSE score increase over time, with no difference between arms. The addition of PCV chemotherapy to RT improves PFS without excessive CF detriment over RT alone for patients with low-grade glioma.

Richter syndrome (RS) is defined as the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). RS occurs in approximately 2% to 10% of CLL patients during the course of their disease, with a transformation rate of 0.5% to 1% per year. A combination of germline genetic characteristics, clinical features (eg, advanced Rai stage), biologic (ζ-associated protein-70+, CD38+, CD49d+) and somatic genetic (del17p13.1 or del11q23.1) characteristics of CLL B cells, and certain CLL therapies are associated with higher risk of RS. Recent studies have also identified the crucial role of CDKN2A loss, TP53 disruption, C-MYC activation, and NOTCH1 mutations in the transformation from CLL to RS. An excisional lymph node biopsy is considered the gold standard for diagnosis of RS; a 18F-fluorodeoxyglucose positron emission tomography scan can help inform the optimal site for biopsy. Approximately 80% of DLBCL cases in patients with CLL are clonally related to the underlying CLL, and the median survival for these patients is approximately 1 year. In contrast, the remaining 20% of patients have a clonally unrelated DLBCL and have a prognosis similar to that of de novo DLBCL. For patients with clonally related DLBCL, induction therapy with either an anthracycline- or platinum-based regimen is the standard approach. Postremission stem cell transplantation should be considered for appropriate patients. This article summarizes our approach to the clinical management of CLL patients who develop RS.

AbstractPurposeThe goals of part 2 of the study presented here were 1) to assess whether there is a difference in failure mode of different thicknesses (2.0, 1.5, 1.0, and 0.5 mm) of anatomically standardized full contour monolithic lithium disilicate restorations for posterior teeth, and 2) to assess if there is a difference among various crown thicknesses when these restorations are subjected to dynamic load forces common for posterior teeth.Materials and MethodsFour groups (n = 10), each with a different thickness of anatomically appropriate all‐ceramic crowns, were to be tested as established from the statistical analysis of the preliminary phase. Group 1: 2.0 mm; group 2: 1.5 mm; group 3: 1.0 mm; group 4: 0.5 mm. The specimens were adhesively luted to the corresponding die, and underwent dynamic cyclic loading (380 to 390 N) completely submerged in an aqueous environment until a failure was noted by graphic recording and continuous monitoring.ResultsThere was a statistically significant difference of the fatigue cycles to failure among four groups (p < 0.001; Kruskal‐Wallis test). The mean number of cycles to fail for 2.0 mm specimens was 17 times more than the mean number of cycles to fail for 1.0 mm specimens and 1.5 times more than the mean number of cycles to fail for 1.5 mm specimens. The 0.5 mm specimens failed with one cycle of loading. A qualitative characteristic noted among the 2.0 mm specimens was wear of the area of indenter contact followed by shearing of the material and/or crack propagation.ConclusionBased on the findings of this study, it may be reasonable to consider a crown thickness of 1.5 mm or greater for clinical applications of milled monolithic lithium disilicate crowns for posterior single teeth.

Significance Cancer cells reprogram their metabolism for optimal growth and survival. AMPK-activated protein kinase (AMPK) is a key energy sensor that controls many metabolic pathways including metabolic reprogramming. However, its role in cancer is poorly understood. Some studies claim that it has a tumor suppressor role while others show its protumor role. Two AMPK-activating compounds (including metformin, now in many clinical trials) are widely used to suppress cancer cell proliferation. We found that AMPK is abundantly expressed in high-grade gliomas and, in contrast to popular belief, these two AMPK activators suppressed glioma cell proliferation through unique AMPK-independent mechanisms.

Purpose To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation. Methods A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized. Results Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment. The International Staging System and chromosomal abnormalities identify high- and standard-risk patients. Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are the most active agents. The presence of concomitant diseases, frailty, or disability should be assessed and, if present, treated with reduced-dose approaches. Bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy are the most frequent disabling events requiring prompt and active supportive care. Conclusion These recommendations will help clinicians ensure the most appropriate care for patients with myeloma in everyday clinical practice.

Key Points Pomalidomide plus low-dose dexamethasone significantly improved PFS vs pomalidomide alone in relapsed and refractory multiple myeloma. Pomalidomide plus low-dose dexamethasone is an important new treatment option for RRMM patients who have received multiple prior therapies.