Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations

Patients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR-mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients’ reported outcomes. For patients with NSCLC harboring EGFR-activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

Eribulin Provides a Remarkable Effect in Trabectedin-Resistant Myxoid Liposarcoma

Adriamycin-based chemotherapy is commonly used for malignant soft tissue sarcoma including myxoid liposarcoma. However, in the case of unavailability or failure of the adriamycin-based regimen, trabectedin or eribulin can produce a good antitumor effect for myxoid liposarcoma. We relate the experience of a 64-year-old female with myxoid liposarcoma, who noticed a nodule on her left thigh and visited our institute. At initial presentation, the tumor was 18.7 cm in diameter, and the magnetic resonance imaging (MRI) showed a malignant lipomatous tumor with a myxoid component. We recommended that she undergo treatment; however, she refused. Three years later, the tumor had grown larger, so she finally decided to undergo treatment. A needle biopsy revealed a myxoid liposarcoma. The tumor massively involved the neurovascular structures; we thus determined that hip disarticulation was inevitable. Two years later, metastases in the right thigh, left lung, right ileum, and abdominal space were pointed out and chemotherapy was initiated. Adriamycin was unusable due to cardiac dysfunction, so trabectedin was administered; however, the tumors progressed. Eribulin was subsequently started and has been considerably effective for more than 2 years without severe adverse effects. In conclusion, we experienced a case showing the remarkable and long-lasting effect of eribulin against trabectedin-resistant myxoid liposarcoma

Self-Calibration of a Large-Scale Variable-Line-Spacing Grating for an Absolute Optical Encoder by Differencing Spatially Shifted Phase Maps from a Fizeau Interferometer

A new method based on the interferometric pseudo-lateral-shearing method is proposed to evaluate the pitch variation of a large-scale planar variable-line-spacing (VLS) grating. In the method, wavefronts of the first-order diffracted beams from a planar VLS grating are measured by a commercial Fizeau form interferometer. By utilizing the differential wavefront of the first-order diffracted beam before and after the small lateral shift of the VLS grating, the pitch variation of the VLS grating can be evaluated. Meanwhile, additional positioning errors of the grating in the lateral shifting process could degrade the measurement accuracy of the pitch variation. To address the issue, the technique referred to as the reference plane technique is also introduced, where the least squares planes in the wavefronts of the first-order diffracted beams are employed to reduce the influences of the additional positioning errors of the VLS grating. The proposed method can also reduce the influence of the out-of-flatness of the reference flat in the Fizeau interferometer by taking the difference between the measured positive and negative diffracted wavefronts; namely, self-calibration can be accomplished. After the theoretical analysis and simulations, experiments are carried out with a large-scale VLS grating to verify the feasibility of the proposed methods. Furthermore, the evaluated VLS parameters are verified by comparing them with the readout signal of an absolute surface encoder employing the evaluated VLS grating as the scale for measurement

Design, Implementation, and Evaluation of Optimizations in a Just-In-Time Compiler

The Java language incurs a runtime overhead for exception checks and object accesses without an interior pointer in order to ensure safety. It also requires type inclusion test, dynamic class loading, and dynamic method calls in order to ensure flexibility. A "JustIn -Time" (JIT) compiler generates native code from Java byte code at runtime. It must improve the runtime performance without compromising the safety and flexibility of the Java language. We designed and implemented effective optimizations for the JIT compiler, such as exception check elimination, common subexpression elimination, simple type inclusion test, method inlining, and resolution of dynamic method call. We evaluate the performance benefits of these optimizations based on various statistics collected using SPECjvm98 and two JavaSoft applications with byte code sizes ranging from 20000 to 280000 bytes. Each optimization contributes to an improvement in the performance of the programs. 1. Introduction Java [1] is a ..

Design, Implementation, and Evaluation of Optimizations in a Java ™ Just-In-Time Compiler

The Java language incurs a runtime overhead for exception checks and object accesses, which are executed without an interior pointer in order to ensure safety. It also requires type inclusion test, dynamic class loading, and dynamic method calls in order to ensure flexibility. A “Just-In-Time ” (JIT) compiler generates native code from Java byte code at runtime. It must improve the run-time performance without compromising the safety and flexibility of the Java language. We designed and implemented effective optimizations for a JIT compiler, such as exception check elimination, common subexpression elimination, simple type inclusion test, method inlining, and devirtualization of dynamic method call. We evaluate the performance benefits of these optimizations based on various statistics collected using SPECjvm98, its candidates, and two JavaSoft applications with byte code sizes ranging from 23000 to 280000 bytes. Each optimization contributes to an improvement in the performance of the programs. 1