Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry.

Lung cancer is a leading cause of cancer deaths worldwide. Metabolic alterations in tumor cells coupled with systemic indicators of the host response to tumor development have the potential to yield blood profiles with clinical utility for diagnosis and monitoring of treatment. We report results from two separate studies using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) to profile metabolites in human blood samples that significantly differ from non-small cell lung cancer (NSCLC) adenocarcinoma and other lung cancer cases. Metabolomic analysis of blood samples from the two studies yielded a total of 437 metabolites, of which 148 were identified as known compounds and 289 identified as unknown compounds. Differential analysis identified 15 known metabolites in one study and 18 in a second study that were statistically different (p-values <0.05). Levels of maltose, palmitic acid, glycerol, ethanolamine, glutamic acid, and lactic acid were increased in cancer samples while amino acids tryptophan, lysine and histidine decreased. Many of the metabolites were found to be significantly different in both studies, suggesting that metabolomics appears to be robust enough to find systemic changes from lung cancer, thus showing the potential of this type of analysis for lung cancer detection

A Practical Guide of the Southwest Oncology Group to Measure Malignant Pleural Mesothelioma Tumors by RECIST and Modified RECIST Criteria

Abstract:Malignant pleural mesothelioma (MPM) is difficult to measure radiographically due to the nonradial and variable pattern of growth and response to therapy. Inaccurate and inconsistent tumor measurements often compromise results from clinical trials that are dependent on identifying response rate and progression-free survival. In this article, we sought to provide a practical guide through the Southwest Oncology Group on how to measure MPM by the updated RECIST version 1.1 and by modified RECIST. We hope that these steps will provide a simple means by which computed tomography measurements can be consistently performed, minimizing intra- and interobserver variability. With this consistency, we may be able to better estimate the prognosis and response to therapy. With greater utilization, we will be able to better understand the biology of MPM

Molecular Sieving Properties of Nanoporous Mixed-Linker ZIF-62: Associated Structural Changes upon Gas Adsorption Application

The evaluation of the flexibility in zeolitic imidazolate frameworks (ZIFs) has been very useful to understand their performance in gas adsorption and separation applications. Here, we have evaluated the adsorption properties of a nanoporous mixed-linker ZIF-62 using a combination of gas adsorption measurements, grand canonical Monte Carlo simulations, and synchrotron X-ray powder diffraction under operando conditions. While adsorption studies in nanoporous ZIF-62 at 77 K and atmospheric pressure predict a large O2/N2 separation ability, computational studies anticipate that the observed differences must be attributed to kinetic restrictions of N2 to access the internal porosity at cryogenic temperatures. Interestingly, upon a small increase in the adsorption temperature (90 K vs 77 K), both N2 and O2 are able to access the inner porous structure through the promotion of a phase transition (ca. 3.8% volume expansion) upon gas adsorption. This narrow phase (np) to expanded phase (ep) structural transition in ZIF-62 is completely suppressed above 150 K. Based on the excellent molecular sieve properties of nanoporous ZIF-62 for O2/N2 at cryogenic temperatures, we extended our study to the adsorption of linear and branched hydrocarbons. This study predicts the preferential adsorption of alkanes over alkenes in ZIF-62 for small hydrocarbons (C2), while in the case of C3 hydrocarbons and above, the adsorption process is mainly defined by kinetic restrictions.J.S.-A. acknowledges financial support from the MINECO (Projects MAT2016-80285-p and PID2019-108453GB-C21). The authors acknowledge ALBA for providing beamtime (Project No. 2019023264). Computational work was supported by the Cambridge High-Performance Computing Service, the Cambridge Service for Data-Driven Discovery (CSD3)

Resection of multifocal non–small cell lung cancer when the bronchioloalveolar subtype is involved

AbstractObjectiveBronchioloalveolar lung cancer is commonly multifocal and can also present with other non–small cell types. The staging and treatment of multifocal non–small cell cancer are controversial. We evaluated the current staging of multifocal bronchioloalveolar carcinoma and the therapeutic effectiveness of resection when this tumor type is involved.MethodsWe reviewed our experience between 1992 and 2000 with complete pulmonary resections for bronchioloalveolar carcinoma. Kaplan-Meier survival curves were calculated from the dates of pulmonary resection.ResultsAmong 73 patients with bronchioloalveolar carcinoma, 14 patients, 7 male and 7 female with a mean age of 65 years (51-87 years), had multifocal lesions without lymph node metastases. Follow-up was 100% for a median of 5 years (range 2.6-8.5 years). Tumor distribution was unilateral in 9 patients and bilateral in 5 patients. The multifocal nature of the disease was discovered intraoperatively in 4 patients. Nine patients had 2 lesions, 4 patients had 3 lesions, and 1 patient had innumerable discrete foci in a single lobe. Operative mortality was 0. Postoperatively, 10 patients were staged pIIIB or pIV on the basis of multiple foci of similar morphology; 4 patients had some differences in histology (implying multiple stage 1 primaries). The median survival time to death from cancer was 14 months (141 days–5.6 years). The overall 5-year survival after resection of multifocal bronchioloalveolar carcinoma was 64%. Unilateral or bilateral distribution had no impact on survival.ConclusionsThe current staging system is not prognostic for multifocal bronchioloalveolar carcinoma without lymph node metastases. Complete resection of multifocal non–small cell lung cancer when bronchioloalveolar carcinoma is a component may achieve survivals similar to that of stage I and II unifocal non–small cell lung cancer. When bronchioloalveolar carcinoma is believed to be one of the cell types in multifocal disease without lymph node metastases, consideration should be given to surgical resection

MRSA Causing Infections in Hospitals in Greater Metropolitan New York: Major Shift in the Dominant Clonal Type Between 1996 and 2014

A surveillance study in 1996 identified the USA100 clone (ST5/SCCmecII)-also known as the New York/Japan clone-as the most prevalent MRSA causing infections in 12 New York City hospitals. Here we update the epidemiology of MRSA in seven of the same hospitals eighteen years later in 2013/14. Most of the current MRSA isolates (78 of 121) belonged to the MRSA clone USA300 (CC8/SCCmecIV) but the USA100 clone-dominant in the 1996 survey-still remained the second most frequent MRSA (25 of the 121 isolates) causing 32% of blood stream infections. The USA300 clone was most common in skin and soft tissue infections (SSTIs) and was associated with 84.5% of SSTIs compared to 5% caused by the USA100 clone. Our data indicate that by 2013/14, the USA300 clone replaced the New York/Japan clone as the most frequent cause of MRSA infections in hospitals in Metropolitan New York. In parallel with this shift in the clonal type of MRSA, there was also a striking change in the types of MRSA infections from 1996 to 2014

An efficient analog circuit sizing method based on machine learning assisted global optimization

Machine learning-assisted global optimization methods for speeding up analog integrated circuit sizing is attracting much attention. However, often a few typical analog IC design specifications are considered in most relevant research. When considering the complete set of specifications, two main challenges are yet to be addressed: (1) The prediction error for some performances may be large and the prediction error is accumulated by many performances. This may mislead the optimization and fail the sizing, especially when the specifications are stringent. (2) The machine learning cost could be high considering the number of specifications, considerably canceling out the time saved. A new method, called Efficient Surrogate Model-assisted Sizing Method for High-performance Analog Building Blocks (ESSAB), is proposed in this paper to address the above challenges. The key innovations include a new candidate design ranking method and a new artificial neural network model construction method for analog circuit performances. Experiments using two amplifiers and a comparator with a complete set of stringent design specifications show the advantages of ESSAB

Gemcitabine and Irinotecan for Patients with Untreated Extensive Stage Small Cell Lung Cancer: SWOG 0119

IntroductionTo evaluate the activity of a nonplatinum-, nonetoposide-containing regimen for patients with extensive stage small cell lung cancer.MethodsPatients with untreated extensive stage small cell lung cancer were treated with gemcitabine 1000 mg/m2 and irinotecan 100 mg/m2 on days 1 and 8 of a 21-day cycle for a maximum of six cycles. Patients with brain metastases were eligible if asymptomatic or controlled after radiation.ResultsEighty-four eligible patients with untreated extensive stage small cell lung cancer with adequate organ function and a performance status of 0–2 were accrued. The median age was 64 years (range, 42–85) and 45 (54%) were women. Six cycles were completed by 28 (33%) patients. Some degree of diarrhea occurred in 57% (grade 3/4, 18%). Other grade 3/4 toxicities were neutropenia (26%), anemia (10%), thrombocytopenia (8%), febrile neutropenia (5%), fatigue (11%), nausea (10%), and vomiting (8%). The response rate was 32% (95% confidence interval: 22%–43%) among the 81 patients with measurable disease. The median survival was 8.5 months (95% confidence interval: 7.0–9.8) with 1- and 2-year survival rates of 26% and 7%, respectively. Salvage therapy data were captured by prospective collection, and only 50% of patients were treated secondarily.ConclusionThe overall response rate with the combination of gemcitabine and irinotecan was disappointing, and the median survival rate was lower than expected. Further development of this combination in small cell lung cancer is not recommended

A Pilot Study (SWOG S0429) of Weekly Cetuximab and Chest Radiotherapy for Poor-Risk Stage III Non-Small Cell Lung Cancer

PURPOSE: Stage III non-small cell lung cancer (NSCLC) patients with poor performance status (PS) or co-morbidities are often not candidates for standard chemoradiotherapy (chemoRT) due to poor tolerance to treatments. A pilot study for poor-risk stage III NSCLC patients was conducted combining cetuximab, a chimeric monoclonal antibody targeting epidermal growth factor receptor (EGFR), with chest radiation (RT). METHODS: Stage III NSCLC patients with Zubrod PS 2, or Zubrod PS 0-1 with poor pulmonary function and co-morbidities prohibiting chemoRT were eligible. A loading dose of cetuximab (400 mg/m(2)) was delivered week 1, followed by weekly cetuximab (250 mg/m(2))/RT to 64.8 Gy in 1.8 Gy daily fractions, and maintenance weekly cetuximab (250 mg/m(2)) for 2 years or until disease progression. H-score for EGFR protein expression was conducted in available tumors. RESULTS: Twenty-four patients were enrolled. Twenty-two were assessed for outcome and toxicity. Median survival was 14 months and median progression-free survival was 8 months. The response rate was 47% and disease control rate was 74%. Toxicity assessment revealed 22.7% overall \u3e /=Grade 3 non-hematologic toxicities. Grade 3 esophagitis was observed in one patient (5%). The skin reactions were mostly Grade 1 or 2 except two of 22 (9%) had Grade 3 acne and one of 22 (5%) had Grade 3 radiation skin burn. Grade 3-4 hypomagnesemia was seen in four (18%) patients. One patient (5%) had elevated cardiac troponin and pulmonary emboli. H-score did not reveal prognostic significance. An initially planned second cohort of the study did not commence due to slow accrual, which would have added weekly docetaxel to cetuximab/RT after completion of the first cohort of patients. CONCLUSION: Concurrent weekly cetuximab/chest RT followed by maintenance cetuximab for poor-risk stage III NSCLC was well tolerated. Further studies with larger sample sizes will be useful to establish the optimal therapeutic ratio of this regimen

Atezolizumab Versus Docetaxel in Pretreated Patients With NSCLC: Final Results From the Randomized Phase 2 POPLAR and Phase 3 OAK Clinical Trials

INTRODUCTION: The phase 2 POPLAR and phase 3 OAK studies of the anti-programmed death-ligand 1 (PD-L1) immunotherapy atezolizumab in patients with previously treated advanced NSCLC revealed significant improvements in survival versus docetaxel (p = 0.04 and 0.0003, respectively). Longer follow-up permits evaluation of continued benefit of atezolizumab. This study reports the final overall survival (OS) and safety findings from both trials. METHODS: POPLAR randomized 287 (atezolizumab,144; docetaxel,143) and OAK randomized 1225 (atezolizumab, 613; docetaxel, 612) patients. Patients received atezolizumab (1200-mg fixed dose) or docetaxel (75 mg/m(2)) every 3 weeks. Efficacy and safety outcomes were evaluated. RESULTS: A longer OS was observed in patients receiving atezolizumab versus docetaxel in POPLAR (median OS = 12.6 mo versus 9.7 mo; hazard ratio = 0.76, 95% confidence interval [CI]: 0.58-1.00) and OAK (median OS = 13.3 versus 9.8 mo; hazard ratio = 0.78, 95% CI: 0.68-0.89). The 4-year OS rates in POPLAR were 14.8% (8.7-20.8) and 8.1% (3.2-13.0) and those in OAK were 15.5% (12.4-18.7) and 8.7% (6.2-11.3) for atezolizumab and docetaxel, respectively. Atezolizumab had improved OS benefit compared with docetaxel across all PD-L1 expression and histology groups. Most 4-year survivors in the docetaxel arms received subsequent immunotherapy (POPLAR, 50%; OAK, 65%). Of the 4-year survivors, most had Eastern Cooperative Oncology Group performance status of 0 and nonsquamous histological classification and approximately half were responders (POPLAR: atezolizumab, seven of 15; docetaxel, three of four; OAK: atezolizumab, 24 of 43; docetaxel, 11 of 26). Treatment-related grade 3/4 adverse events occurred in 27% and 16% of atezolizumab 4-year survivors in POPLAR and OAK, respectively. CONCLUSIONS: Long-term follow-up suggests a consistent survival benefit with atezolizumab versus docetaxel in patients with previously treated NSCLC regardless of PD-L1 expression, histology, or subsequent immunotherapy. Atezolizumab had no new safety signals, and the safety profile was similar to that in previous studies