Citations

Abstract Introduction. For patients with non-small cell lung cancer (NSCLC) to benefit from ALK inhibitors, sensitive and specific detection of ALK genomic rearrangements is needed. ALK break-apart fluorescence in situ hybridization (FISH) is the U.S. Food and Drug Administration approved and standard-of-care diagnostic assay, but identification of ALK rearrangements by other methods reported in NSCLC cases that tested negative for ALK rearrangements by FISH suggests a significant false-negative rate. We report here a large series of NSCLC cases assayed by hybrid-capture-based comprehensive genomic profiling (CGP) in the course of clinical care. Materials and Methods. Hybrid-capture-based CGP using next-generation sequencing was performed in the course of clinical care of 1,070 patients with advanced lung cancer. Each tumor sample was evaluated for all classes of genomic alterations, including base-pair substitutions, insertions/deletions, copy number alterations and rearrangements, as well as fusions/rearrangements. Results. A total of 47 patients (4.4%) were found to harbor ALK rearrangements, of whom 41 had an EML4-ALK fusion, and 6 had other fusion partners, including 3 previously unreported rearrangement events: EIF2AK-ALK, PPM1B-ALK, and PRKAR1A-ALK. Of 41 patients harboring ALK rearrangements, 31 had prior FISH testing results available. Of these, 20 were ALK FISH positive, and 11 (35%) were ALK FISH negative. Of the latter 11 patients, 9 received crizotinib based on the CGP results, and 7 achieved a response with median duration of 17 months. Conclusion. Comprehensive genomic profiling detected canonical ALK rearrangements and ALK rearrangements with noncanonical fusion partners in a subset of patients with NSCLC with previously negative ALK FISH results. In this series, such patients had durable responses to ALK inhibitors, comparable to historical response rates for ALK FISH-positive cases.

PurposeThe purpose of this study is to evaluate the impact of perioperative fluid administration on the rates of postoperative complications following head and neck reconstruction with fibular free flaps (FFF).MethodsA retrospective cohort study of subjects undergoing head and neck reconstruction with FFF was completed. The primary predictor variable was the total volume of perioperative fluids administered on the day of surgery. The primary outcome variable was the presence of medical and surgical complications occurring within 30 days of surgery. Medical and surgical complications were stratified as major or minor based on severity level. Basic demographic information, comorbidity indices, and intraoperative parameters were abstracted as covariates. Univariable and multivariable models were developed to assess for associations between total fluid volume administered on the day of surgery and postoperative medical/surgical complications occurring within 30 days of surgery.ResultsIn 154 subjects, the partial flap failure rate was 3% and there were no complete flap failures. Total fluid volume was significantly associated with the presence of postoperative medical/surgical complications (OR = 1.21; 95% CI: 1.02–1.44; p = 0.032). A cutpoint for total fluid volume predicting any severity level of postoperative complication was identified at 5,500 mL. A cutpoint for total fluid volume predicting major postoperative complications was identified at 7,000 mL.ConclusionsThe results of this study suggest that liberal fluid administration is associated with increased rates of medical/surgical complications following head and neck reconstruction with FFF. © 2016 Wiley Periodicals, Inc. Microsurgery 37:128–136, 2017.

AbstractThe International Myeloma Working Group consensus updates the definition for high-risk (HR) multiple myeloma based on cytogenetics Several cytogenetic abnormalities such as t(4;14), del(17/17p), t(14;16), t(14;20), nonhyperdiploidy, and gain(1q) were identified that confer poor prognosis. The prognosis of patients showing these abnormalities may vary with the choice of therapy. Treatment strategies have shown promise for HR cytogenetic diseases, such as proteasome inhibition in combination with lenalidomide/pomalidomide, double autologous stem cell transplant plus bortezomib, or combination of immunotherapy with lenalidomide or pomalidomide. Careful analysis of cytogenetic subgroups in trials comparing different treatments remains an important goal. Cross-trial comparisons may provide insight into the effect of new drugs in patients with cytogenetic abnormalities. However, to achieve this, consensus on definitions of analytical techniques, proportion of abnormal cells, and treatment regimens is needed. Based on data available today, bortezomib and carfilzomib treatment appear to improve complete response, progression-free survival, and overall survival in t(4;14) and del(17/17p), whereas lenalidomide may be associated with improved progression-free survival in t(4;14) and del(17/17p). Patients with multiple adverse cytogenetic abnormalities do not benefit from these agents. FISH data are implemented in the revised International Staging System for risk stratification.

Over the past decade, a number of changes have occurred in the diagnostic evaluation, management, and long‐term follow‐up of patients with POEMS syndrome at our institution. This study included 291 patients with POEMS syndrome diagnosed at the Mayo Clinic between 1974 and 2014. Patients diagnosed after 2003 had more features of the syndrome identified at diagnosis and were more likely to receive an autologous transplant (49% versus 8%, P < 0.0001) and to have achieved a hematologic complete response (CR) to treatment (41% vs 25%, P < 0.0001). With 2273 person‐years of follow‐up, 10‐year overall survival (OS) was 62% (95% C.I., 56%, 67%). On multivariate analysis, the three factors associated with superior OS were younger age (RR 0.98 [0.96–1.00]), albumin greater‐than 3.2 g/dL (RR 0.5 [0.32–0.89]) and attainment of complete hematologic response (RR 0.4 [0.2, 0.9]). This study confirms the very good long‐term outcomes of patients with POEMS syndrome and identifies two new prognostic risk factors: albumin at diagnosis and attainment of complete hematologic response. Am. J. Hematol. 91:585–589, 2016. © 2016 Wiley Periodicals, Inc.