Congress of Neurological Surgeons Systematic Review and Evidence-based Guidelines Update on the Role of Neuropathology in the Management of Progressive Glioblastoma in Adults

Target population These recommendations apply to adult patients with progressive or recurrent glioblastoma (GBM).QuestionFor adult patients with progressive glioblastoma does testing for Isocitrate Dehydrogenase (IDH) 1 or 2 mutations provide new additional management or prognostic information beyond that derived from the tumor at initial presentation?RecommendationLevel III: Repeat IDH mutation testing is not necessary if the tumor is histologically similar to the primary tumor and the patient’s clinical course is as expected. Question For adult patients with progressive glioblastoma does repeat testing for MGMT promoter methylation provide new or additional management or prognostic information beyond that derived from the tumor at initial presentation and what methods of detection are optimal?Recommendation Level III: Repeat MGMT promoter methylation is not recommended. Question For adult patients with progressive glioblastoma does EGFR amplification or mutation testing provide management or prognostic information beyond that provided by histologic analysis and if performed on previous tissue samples, does it need to be repeated?RecommendationLevel III: In cases that are difficult to classify as glioblastoma on histologic features EGFR amplification testing may help in classification. If a previous EGFR amplification was detected, repeat testing is not necessary. Repeat EGFR amplification or mutational testing may be recommended in patients in which target therapy is being considered.Question For adult patients with progressive glioblastoma does whole genome or large panel sequencing provide management or prognostic information beyond that derived from histologic analysis?RecommendationLevel III: Primary or repeat whole genome or large panel sequencing may be considered in patients who are eligible or interested in molecularly guided therapy or clinical trials.QuestionFor adult patients with progressive glioblastoma should immune checkpoint biomarker testing be performed to provide management and prognostic information beyond that obtained from histologic analysis?RecommendationLevel III: The current evidence does not support making PD-L1 or mismatch repair (MMR) enzyme activity a component of standard testing.QuestionFor adult patients with progressive glioblastoma are there meaningful biomarkers for bevacizumab responsiveness and does their assessment provide additional information for tumor management and prognosis beyond that learned by standard histologic analysis?RecommendationLevel III: No established Bevacizumab biomarkers are currently available based upon the inclusion criteria of this guideline.

Coverage Criteria for State-Based Testing

State-based testing (SBT) is known as deriving test cases from state machines and examining the dynamic behaviour of the system. It helps to identify various types of state-based faults within a system under test (SUT). For SBT, test cases are generated from state chart diagrams based on various coverage criteria such as All Transition, Round Trip Path, All Transition Pair, All Transition Pair with length 2, All Transition Pair with length 3, All Transition Pair of length 4 and Full Predicate. This article discuses a number of coverage criteria at the design level to find out various types of state-based faults in SBT. First, the intermediate graph is generated from a state chart diagram using an XML parser. The graph is traversed based on the given coverage criteria to generate a sequence of test cases. Then, mutation testing and sneak-path testing are applied on the generated test cases to check the effectiveness of the generated test suite. These two are common methods for checking the effectiveness of test cases. Mutation testing helps in the number of seeded errors covered whereas sneak-path testing basically helps to examine the unspecified behavior of the system. In round trip path (RTP), it is not possible to cover all paths. All transition is not an adequate level of fault detection with more execution time compared to all transition pair (ATP) with length 4 (LN4). In the discussion, ATP with LN4 is the best among all coverage criteria. SBT can able to detect various state-based faults-incorrect transition, missing transition, missing or incorrect event, missing or incorrect action, extra missing or corrupt state, which are difficult to detect in code-based testing. Most of these state-based faults can be avoided, if the testing is conducted at the early phase of design.

Leptomeningeal Dissemination of Low-Grade Neuroepithelial Tumor with FGFR1_TACC1 Fusion with Clinical and Radiographic Response to Pazopanib and Topotecan

<b><i>Introduction:</i></b> Low-grade neuroepithelial tumors are a heterogeneous group of central nervous system tumors that are generally indolent in nature but in rare instances can progress to include leptomeningeal dissemination. <b><i>Case Presentation:</i></b> We present a case of a patient with a low-grade neuroepithelial tumor of indeterminate type with symptomatic leptomeningeal dissemination despite 3 chemotherapy regimens and radiotherapy. Somatic targetable mutation testing showed an FGFR1_TACC1 fusion. Therapy with pazopanib/topotecan was initiated, and disease stabilization was achieved. He received pazopanib/topotecan for a total of 2 years and is now &#x3e;2 years from completion of treatment and continues to do well with no evidence of disease. <b><i>Discussion:</i></b> This case highlights the utility of targetable mutation testing in therapeutic decision-making and the novel use of systemic pazopanib/topotecan therapy for refractory low-grade neuroepithelial tumor within the context of this clinical situation and specific mutation profile.

ImReMuDF: Redundant Mutants Identification Method Based on Definition and Reference of Variables

Mutation testing is an effective defect-based software testing method, but a large number of mutants lead to expensive testing costs, which hinders the application of variation testing in industrial engineering. To solve this problem and enable mutation testing to be applied in industrial engineering, this paper improves the method of identifying redundant mutants based on data flow analysis and proposes the inclusion relationship between redundant mutants, so that the redundancy rate of mutants is reduced. In turn, the cost of mutation testing can be reduced. The redundant mutants identification method based on definition and reference of variables (ImReMuDF) was validated and evaluated using 8 C programs. The minimum improvement in redundant mutant identification rate was 34.0%, and the maximum improvement was 71.3% in the 8 C programs tested, and the verification results showed that the method is feasible and effective and has been improved in reducing redundant mutants and effectively reducing the execution time of mutation testing.

Nationwide evaluation of mutation-tailored anti-EGFR therapy selection in patients with colorectal cancer in daily clinical practice

For a nationwide real-word data study on the application of predictive mutation testing of patients with colorectal cancer (CRC) for anti-epidermal growth factor receptor (EGFR) therapy stratification, pathology data were collected from the Dutch Pathology Registry from October 2017 until June 2019 (N=4060) and linked with the Netherlands Cancer Registry. Mutation testing rates increased from 24% at diagnosis of stage IV disease to 60% after 20–23 months of follow-up (p<0.001). Application of anti-EGFR therapy in KRAS/NRAS wild-type patients was mainly observed from the third treatment line onwards (65% vs 17% in first/second treatment line (p<0.001)). The national average KRAS/NRAS/BRAF mutation rate was 63.9%, being similar for next-generation sequencing (NGS)-based approaches and single gene tests (64.4% vs 61.2%, p=ns). NGS-based approaches detected more additional potential biomarkers, for example, ERBB2 amplifications (p<0.05). Therefore, single gene tests are suitable to stratify patients with mCRC for anti-EGFR therapy, but NGS is superior enabling upfront identification of therapy resistance or facilitate enrolment into clinical trials.