Citations

Object Carcinoid tumors are rare and have generally been regarded as indolent neoplasms. Systemic disease is often incurable; however, patients may live years with this disease. Furthermore, metastatic brain lesions are extremely uncommon. As such, few series have examined outcomes and prognostic factors in those with brain involvement. Methods The authors performed a retrospective review of patients who underwent primary treatment at Mayo Clinic in Rochester, Minnesota, for metastatic carcinoid tumors to the brain between 1986 and 2011. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier statistics. Cox proportional hazards were used to determine predictors of survival. Results Fifteen patients underwent primary treatment for metastatic carcinoid tumors to the brain between 1986 and 2011. Their mean age was 58 ± 12 years. Eighty percent (n = 12) of patients underwent surgery, whereas 2 received stereotactic radiosurgery and 1 had whole-brain radiation therapy (WBRT) as the primary treatment. The median follow-up duration was 19 months (maximum 124 months). Systemic disease progression occurred in 73% and was the leading cause of death in known cases, while intracranial disease recurred in 40%. The median PFS and OS were 21 and 19 months, respectively. The use of adjuvant WBRT correlated with improved PFS (HR 0.15, CI 0.0074–0.95, p = 0.044). Those who underwent surgery as primary modalities trended toward longer progression-free intervals (p = 0.095), although this did not reach significance. Conclusions Metastatic carcinoid disease to the brain appears to have a worse prognosis than that of other extracranial metastases. Although there was a trend toward a survival advantage in patients who underwent surgery and WBRT, further study is needed to establish definitive treatment recommendations.

RAS is an oncogene frequently mutated in human cancer. RAS mutations have been reported in 10–15% of cases of acute myeloid leukemia (AML) but they appear to be less frequent among patients with myelodysplastic syndrome (MDS). The impact of RAS mutations in patients with MDS is unclear. We conducted a retrospective study in 1,067 patients with newly diagnosed MDS for whom RAS mutational analysis was available. Overall, 4% of patients carried mutant RAS alleles. Notably, FLT3 mutations, which were found in 2% of patients, were mutually exclusive with RAS mutations. Patients with RAS mutations had a higher white blood cell count as well as bone marrow blasts compared with patients carrying wild‐type RAS. However, no differences were observed between both groups regarding the risk of AML transformation (9% vs. 7%) and overall survival (395 days vs. 500 days, P = 0.057). In summary, RAS mutations are infrequent in patients with MDS and do not appear to negatively impact their outcome. Am. J. Hematol. 88:365–369, 2013. © 2013 Wiley Periodicals, Inc.

Background— Homozygous or compound heterozygous mutations in KCNQ1 cause Jervell and Lange-Nielsen syndrome, a rare, autosomal-recessive form of long-QT syndrome characterized by deafness, marked QT prolongation, and a high risk of sudden death. However, it is not understood why some individuals with mutations on both KCNQ1 alleles present without deafness. In this study, we sought to determine the prevalence and genetic determinants of this phenomenon in a large referral population of patients with long-QT syndrome. Methods and Results— A retrospective analysis of all patients with long-QT syndrome evaluated from July 1998 to April 2012 was used to identify those with ≥1 KCNQ1 mutation. Of the 249 KCNQ1 -positive patients identified, 15 (6.0%) harbored a rare putative pathogenic mutation on both KCNQ1 alleles. Surprisingly, 11 of these patients (73%) presented without the sensorineural deafness associated with Jervell and Lange-Nielsen syndrome. The degree of QT-interval prolongation and the number of breakthrough cardiac events were similar between patients with and without deafness. Interestingly, truncating mutations were more prevalent in patients with Jervell and Lange-Nielsen syndrome (79%) than in nondeaf patients (36%; P <0.001) derived from this study and those in the literature. Conclusions— In this study, we provide evidence that the recessive inheritance of a severe long-QT syndrome type 1 phenotype in the absence of an auditory phenotype may represent a more common pattern of long-QT syndrome inheritance than previously anticipated and that these cases should be treated as a higher-risk long-QT syndrome subset similar to their Jervell and Lange-Nielsen syndrome counterparts. Furthermore, mutation type may serve as a genetic determinant of deafness, but not cardiac expressivity, in individuals harboring ≥1 KCNQ1 mutation on each allele.