Search

Background: A key component in the management of chronic obstructive pulmonary disease (COPD) patients is pulmonary rehabilitation (PR), the corner stone of which is exercise training. Aim: This study aims to evaluate the effect of a two-months, home-based PR program with outpatient supervision every two weeks, on exercise tolerance and health-related quality of life (HRQL) using Arabic-translated standardized generic and specific questionnaires in COPD patients recently recovered from acute exacerbation, Design: Randomized clinical trial. Setting and Subjects: A total of 39 COPD patients who recovered from acute exacerbation were randomly allocated either a two-month home-based PR program in addition to standard medical therapy or standard medical therapy alone in the period between July 2008 and March 2009. Methods: Pulmonary function tests (PFTs), six-minute walk distance (6-MWD) test, Arabic-translated chronic respiratory disease questionnaire-self administered standardized format (CRQ-SAS) and quality of life scale Short Form (SF-36) were compared between 25 patients with moderate to severe COPD who underwent a two-month PR program (group 1) and 14 COPD patients who did not (group 2). Results: Group 1 showed significant improvement in the 6-MWD, and HRQL scores at two months compared with the usual care patients in group 2 (P less than 0.05). Improvement in both CRQ-SAS and SF-36 scores were statistically significant and comparable in group 1. Conclusion: The supervised, post discharge, two-month home-based PR program is an effective non pharmacological intervention in the management of stable patients with COPD. The 6-MWD is a simple, inexpensive and safe test to assess physical and functional capabilities among COPD patients. HRQL can be measured in patients with COPD either by disease-specific tools that have been specifically designed for use in patients with respiratory system disorders or by generic HRQL tools that can be used across populations with a variety of medical conditions. The Arabic-translated CRQ-SAS is a new tool for assessment of Arabic-speaking patients with chronic respiratory diseases.

The Staphylococcus aureus enterotoxin A (SEA) is the toxin mostly involved in Staphylococcus aureus (S. aureus) food poisoning. In this study, the effect of different lactic acid (LA) concentrations (LA 1% and 2%) and temperatures (4°C, 25°C, and 37 °C) on S. aureus growth and relative sea expression in fresh meat cuts were studied. Real-Time RT-PCR used to determine the relative sea expression. Fresh meat cuts were inoculated with 105 CFU/g of S. aureus producing enterotoxin A. S. aureus growth and relative sea expression were regularly tested for 48 hours. The growth of S. aureus was decreased by one log CFU/g than control sample using 1% LA and 2% LA 2% (5.32 ± 3.76 log CFU/g, 4.38 ± 3.00 log CFU/g and 4.54 ± 3.18 log CFU/g respectively) at zero time. Relative expression of the sea gene in both LA concentrations was lower than control. Moreover, both lactic acid concentrations had effect on relative sea gene expression at all examined hours, especially at 4°C compared to control samples. The higher the lactic acid concentration, the lower the S. aureus entero- toxin A relative expression was. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of septoplasty versus non-surgical management for patients experiencing nasal obstruction due to deviated nasal septum (DNS)., Methods: We conducted a comprehensive search of PubMed, Scopus, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov, ICTRP, and ISRCTN for relevant RCTs. The primary outcomes included the Nasal Obstruction Symptom Evaluation (NOSE) scale, Sino-Nasal Outcome Test (SNOT-22), Peak Nasal Inspiratory Flow (PNIF), surgical complications, and quality of life. Data were synthesized using RevMan 5.4 and STATA 18, with effect estimates presented as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). The study protocol was registered with PROSPERO (ID: CRD42024538373)., Results: Our search identified 537 studies, of which 3 RCTs involving 721 participants met the inclusion criteria. The meta-analysis revealed that septoplasty significantly improved NOSE and SNOT-22 scores compared to non-surgical interventions at 6 and 12 months of follow-up, despite no notable differences at 3 months post-treatment. No significant difference was observed regarding nasal flow assessed by PNIF. The rate of complications was low, ranging from 0.31% (revision rate) to 4.12% (bleeding and infection rates). Additionally, our qualitative synthesis showed an improvement in the quality of life at 6 and 12 months in the septoplasty group compared with the non-surgical group., Conclusions: This systematic review and meta-analysis of 721 patients revealed the efficacy of septoplasty, with or without turbinate surgery, in improving nasal obstruction symptoms at 6 and 12 months. Additionally, septoplasty consists of a relatively low rate of complications such as bleeding, infection, and septal perforation. Furthermore, a low revision rate was found. Septoplasty improved the quality of life, especially after 6 and 12 months. However, our findings should be interpreted with caution, and further research is needed to consolidate our results., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Genomic fusions are potent oncogenic drivers across cancer types and many are targetable. We demonstrate the clinical performance of DNA-based comprehensive genomic profiling (CGP) for detecting targetable fusions., Materials and Methods: We analyzed targetable fusion genes in >450 000 tissue specimens profiled using DNA CGP (FoundationOne CDx, FoundationOne). Using a de-identified nationwide (US-based) non-small cell lung cancer (NSCLC) clinico-genomic database, we assessed outcomes in patients with nonsquamous NSCLC (NonSqNSCLC) who received matched therapy based on a fusion identified using DNA CGP. Lastly, we modeled the added value of RNA CGP for fusion detection in NonSqNSCLC., Results: We observed a broad diversity of fusion partners detected with DNA CGP in conjunction with targetable fusion genes (ALK, BRAF, FGFR2, FGFR3, NTRK1/2/3, RET, and ROS1). In NonSqNSCLC with oncogenic ALK, NTRK, RET, and ROS1 fusions detected by DNA CGP, patients treated with a matched tyrosine kinase inhibitor had better real-world progression-free survival than those receiving alternative treatment regimens and benefit was observed regardless of the results of orthogonal fusion testing. An estimated 1.3% of patients with NonSqNSCLC were predicted to have an oncogenic driver fusion identified by RNA, but not DNA CGP, according to a model that accounts for multiple real-world factors., Conclusion: A well-designed DNA CGP assay is capable of robust fusion detection and these fusion calls are reliable for informing clinical decision-making. While DNA CGP detects most driver fusions, the clinical impact of fusion detection is substantial for individual patients and exhaustive efforts, inclusive of additional RNA-based testing, should be considered when an oncogenic driver is not clearly identified., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: Timely biomarker testing remains out of reach for many patients with advanced non-small-cell lung cancer (aNSCLC). Here, we studied the quality-of-care implications of closing the gap in timely receipt of comprehensive genomic profiling (CGP) to inform first-line (1L) decisions., Methods: Using a real-world clinicogenomic database, we studied testing and 1L treatment patterns in aNSCLC after the approval of pembrolizumab in combination with pemetrexed and carboplatin (May 10, 2017). To estimate the association of timely CGP results with therapy selection and patient outcomes, we identified patients with no previous genomic testing beyond PD-L1 immunohistochemistry and dichotomized patients by whether CGP results were available before or after 1L therapy initiation., Results: In total, 2,694 patients were included in the 1L therapy decision impact assessment. Timely CGP increased matched targeted therapy use by 14 percentage points (17% with CGP v 2.8% without) and precision immune checkpoint inhibitor (ICPI) use by 14 percentage points (18% with CGP v 3.9% without). Receipt of timely CGP resulted in an estimated 31 percentage point decrease in ICPI use among ALK/EGFR/RET/ROS1 -positive patients at an expected per-patient reduction in ineffective ICPI therapy cost of $13,659.37 with timely CGP to inform 1L treatment selection. Patient benefit of CGP extended to real-world time to therapy discontinuation (median time to therapy discontinuation: 3.9 v 10 months [hazard ratio, HR, 0.54 [95% CI, 0.42 to 0.70]; P = 1.9E-06; adjusted hazard ratio [aHR], 0.50 [95% CI, 0.38 to 0.67]; P = 2.0E-06) in 1L driver-positive patients. This effect was not significant for real-world overall survival (median overall survival: 32 v 29 months [HR, 1.2 [95% CI, 0.84 to 1.67]; P = .33; aHR, 1.4 [95% CI, 0.92 to 1.99]; P = .12)., Conclusion: Timely CGP is associated with the quality of patient care as measured by 1L matched targeted therapy use, time to therapy discontinuation, and avoidance of ineffective, costly ICPIs.

Introduction: Tyrosine kinase inhibitors and immune checkpoint inhibitors (ICIs), each requiring testing for precision biomarkers, have recently been approved in the adjuvant setting. We assessed the potential value of multigene testing in early lung adenocarcinoma (LUAD)., Methods: Using a real-world clinicogenomic database linking deidentified electronic health record-derived clinical data to genomic data, we selected patients with LUAD who underwent tissue comprehensive genomic profiling (CGP). Using a probabilistic decision tree, we estimated the cost implications of the avoidance of adjuvant ICI in patients with programmed death-ligand 1-positive (PD-L1+) LUAD and an ALK, ROS1 or RET driver., Results: The CGP was performed on a specimen collected before advanced disease in 20% (1320 of 6697) of cases and ordered before advanced diagnosis for 12.6% (847 of 6697) of patients. The prevalence of driver alterations in early and advanced-stage specimens was similar, though KRAS mutations were enriched in early disease and drivers including ALK rearrangements in advanced disease. Patients who had CGP results obtained before versus after recurrence had less time between recurrence and the start of any first-line treatment (median 3.6 versus 6 wk, p < 0.001). Through avoidance of ICI in programmed death-ligand 1-positive early LUAD with an ALK, ROS1 or RET driver, we estimated that the universal CGP could reduce expected costs by $1597.23 per patient relative to EGFR single-gene testing., Conclusions: The CGP can identify driver alterations and accelerate the start of first-line therapy at recurrence. It may also represent a cost-effective approach for avoiding futile adjuvant ICI in patients with drivers that have historically lacked activity with ICI in metastatic disease., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

In this study, we report the clinicopathologic and genomic profiles of 891 patients with RET fusion driven advanced solid tumors. All patient samples were tested using a tissue-based DNA hybrid capture next generation sequencing (NGS) assay and a subset of the samples were liquid biopsies tested using a liquid-based hybrid capture NGS assay. RET fusions were found in 523 patients with NSCLC and in 368 patients with other solid tumors. The two tumor types with the highest number of RET fusion were lung adenocarcinoma and thyroid papillary carcinoma, and they had a prevalence rate 1.14% (455/39,922) and 9.09% (109/1199), respectively. A total of 61 novel fusions were discovered in this pan-tumor cohort. The concordance of RET fusion detection across tumor types among tissue and liquid-based NGS was 100% (8/8) in patients with greater than 1% composite tumor fraction (cTF). Herein, we present the clinicopathologic and genomic landscape of a large cohort of RET fusion positive tumors and we observed that liquid biopsy-based NGS is highly sensitive for RET fusions at cTF ≥1%., (© 2023. The Author(s).)

Background: For patients with advanced non-small cell lung carcinoma (NSCLC), immune checkpoint inhibitor (ICPI) and chemotherapy (chemo) ICPI represent two distinct first-line standard-of-care regimens without clear and established biomarkers to inform the optimal choice for individual patients. Here, we examined the complementary roles of tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) immunohistochemistry (IHC) to inform first-line therapy using a large real-world (rw) data set., Materials and Methods: The study included patients with NSCLC from an rw de-identified clinico-genomic database. All patients underwent genomic testing using Foundation Medicine's tissue comprehensive genomic profiling assay and PD-L1 IHC assay scored for tumor cell staining (TS)., Results: Of 2165 patients included in the analysis, 150 exhibited durable benefit from first-line ICPI regimens (these patients were enriched for PD-L1 TS ≥50, non-squamous histology, and TMB ≥20 mutations/megabase (muts/Mb)). Comparing low TMB (<10 muts/Mb), high TMB (10-19 muts/Mb), and very high TMB (≥20 muts/Mb) receiving ICPI alone, we observed a stepwise increase in median rwPFS (real world-progression free survival) (6.5, 7.5, 17.2 months) and rwOS (real world-overall survival) (10.1, 11.8, 26.9 months) as TMB increased. In the low PD-L1 (TS <50%) cohort, TMB <20 muts/Mb showed a more favorable rwPFS (HR: 0.56 (95% CI: 0.40 to 0.79)) and rwOS (HR 0.74 (95% CI: 0.58 to 0.96)) on chemoICPI when compared with ICPI alone while the point estimate in rwPFS favored monoICPI in the TMB ≥20 muts/Mb cohort, the CI is wide and does not reach statistical significance (HR: 1.68 (95% CI: 0.52 to 5.48))., Conclusion: This study provides evidence that higher TMB cut-offs, such as 20 muts/Mb, can identify patients with prolonged benefit from ICPI. TMB ≥20 muts/Mb is a potential biomarker that may identify patients in whom an ICPI without chemo could be considered, even in the setting of lower PD-L1 levels. Prospective validation of these findings could increase access to chemo-sparing regimens for the first-line treatment of advanced NSCLC., Competing Interests: Competing interests: RSPH, GL, AS, RG, LZ, KM, JSR, KT, and GRO are employees of Foundation Medicine, a wholly owned subsidiary of Roche and these employees have equity interest in Roche. DC is an employee/paid consultant for AbbVie, Adaptimmune, Agenus, Amgen, Ariad, AstraZeneca, Biocept, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, EMD Serono, Foundation Medicine, Genentech/Roche, Gritstone, Guardant Health, Inovio, Merck, MSD, Novartis, Palobiofarma, Pfizer, prIME Oncology, and Takeda, and reports receiving commercial research grants from Bristol Myers Squibb. JSR has consulting/advisory board AstraZeneca, Curadev, Daiichi-Sankyo, Jazz Pharmaceuticals, Medtronic, Pharma Mar. DS reports receiving research funding from AstraZeneca, Genentech/Roche, Novartis, Celgene, Bristol Myers Squibb, Pfizer, Boehringer Ingelheim, AbbVie, Foundation Medicine, GlaxoSmithKline, Eli Lilly, Merck, Nektar, Takeda, Amgen, University of Texas Southwestern Medical Center–Simmons Cancer Center, G1 Therapeutics, Neon Therapeutics, Celldex, Clovis Oncology, Daiichi Sankyo, EMD Serono, Astellas Pharma, GRAIL, Transgene, Aeglea Therapeutics, Tesaro, Ipsen, Janssen, BIND Therapeutics, Eisai, and ImClone Systems; and consulting, advisory, and/or speakers’ bureau fees from AstraZeneca, Genentech/Roche, Novartis, Celgene, Bristol Myers Squibb, Pfizer, Boehringer Ingelheim, AbbVie, Foundation Medicine, GlaxoSmithKline, Eli Lilly, Merck, Moderna, Nektar, Takeda, Amgen, TRM Oncology, Precision Oncology, Evelo Therapeutics, Illumina, Pharmamar, EMD Serono, Aptitude Health, Dracen Pharmaceuticals, Iksuda Therapeutics, Molecular Templates, Seattle Genetics, TRIPTYCH Health Partners, and Intellisphere., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In patients with non-small cell lung cancer (NSCLC), 10%-40% will eventually develop brain metastases. We present the clinicopathologic, genomic, and biomarker landscape of a large cohort of NSCLC brain metastases (NSCLC-BM) samples., Materials and Methods: We retrospectively analyzed 3035 NSCLC-BM tested with comprehensive genomic profiling (CGP) during routine clinical care. In addition, we compared the NSCLC-BM to a separate cohort of 7277 primary NSCLC (pNSCLC) specimens. Finally, we present data on 67 paired patients with NSCLC-BM and pNSCLC., Results: Comprehensive genomic profiling analysis of the 3035 NSCLC-BMs found that the most frequent genomic alterations (GAs) were in the TP53, KRAS, CDKN2A, STK11, CDKN2B, EGFR, NKX2-1, RB1, MYC, and KEAP1 genes. In the NSCLC-BM cohort, there were significantly higher rates of several targetable GAs compared with pNSCLC, including ALK fusions, KRAS G12C mutations, and MET amplifications; and decreased frequency of MET exon14 skipping mutations (all P < .05). In the subset of NSCLC-BM (n = 1063) where concurrent PD-L1 immunohistochemistry (IHC) was performed, 54.7% of the patients with NSCLC-BM were eligible for pembrolizumab based on PD-L1 IHC (TPS ≥ 1), and 56.9% were eligible for pembrolizumab based on TMB-High status. In addition, in a series 67 paired pNSCLC and NSCLC-BM samples, 85.1% (57/67) had at least one additional GA discovered in the NSCLC-BM sample when compared with the pNSCLC sample., Conclusions: Herein, we defined the clinicopathologic, genomic, and biomarker landscape of a large cohort of patients with NSCLC-BM which can help inform study design of future clinical studies for patients with NSCLC with BM. In certain clinical situations, metastatic NSCLC brain tissue or cerebral spinal fluid specimens may be needed to fully optimize personalized treatment., (© The Author(s) 2022. Published by Oxford University Press.)

Introduction: Whereas tumor biopsy is the reference standard for genomic profiling of advanced NSCLC, there are now multiple assays approved by the Food and Drug Administration for liquid biopsy testing of circulating tumor DNA. Here, we study the incremental value that liquid biopsy comprehensive genomic profiling (CGP) adds to tissue molecular testing., Methods: Patients with metastatic NSCLC were enrolled in a prospective diagnostic study to receive circulating tumor DNA CGP; tissue CGP was optional in addition to their standard tissue testing. Focusing on nine genes listed per the National Comprehensive Cancer Network (NCCN) guidelines, liquid CGP was compared with available tissue testing results across three subcohorts: tissue CGP, standard-of-care testing of up to five biomarkers, or no tissue testing., Results: A total of 515 patients with advanced nonsquamous NSCLC received liquid CGP. Among 131 with tissue CGP results, NCCN biomarkers were detected in 86 (66%) with tissue CGP and 56 (43%) with liquid CGP ( p < 0.001). Adding liquid CGP to tissue CGP detected no additional patients with NCCN biomarkers, whereas tissue CGP detected NCCN biomarkers in 30 patients (23%) missed by liquid CGP. Studying 264 patients receiving tissue testing of up to five genes, 102 (39%) had NCCN biomarkers detected in tissue, with an additional 48 (18%) detected using liquid CGP, including 18 with RET , MET , or ERBB2 drivers not studied in tissue., Conclusions: For the detection of patients with advanced nonsquamous NSCLC harboring 9 NCCN biomarkers, liquid CGP increases detection in patients with limited tissue results, but does not increase detection in patients with tissue CGP results available. In contrast, tissue CGP can add meaningfully to liquid CGP for detection of NCCN biomarkers and should be considered as a follow-up when an oncogenic driver is not identified by liquid biopsy., (© 2022 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.)

NCCN guidelines for first-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC) patients without targetable driver alterations includes either immunotherapy alone or in combination with chemotherapy. In this study, we investigated genomic predictors of survival after immunotherapy to guide this treatment decision. Cox proportional hazards regression was used to identify genomic correlates of survival in a cohort of EGFR/ALK-, non-squamous NSCLC patients treated with first-line pembrolizumab monotherapy (mono-IO) or pembrolizumab in combination with carboplatin/cisplatin and pemetrexed (chemo-IO) within a real-world clinico-genomic database. The effect of deletions on 9p21 was further evaluated in five additional tumor types. Among mono-IO treated non-squamous NSCLC patients, tumors with 9p21.3 gene deletions (CDKN2A, CDKN2B, MTAP) were associated with worse survival compared to the corresponding deletion-negative tumors (CDKN2A deletion HR = 1.8, P = 0.001). However, this association was not observed among chemo-IO treated patients (CDKN2A deletion HR = 1.1, P = 0.4). This finding remained after adjusting for clinical and genomic features including TMB and PD-L1. Deletions at 9p21.3 were not associated with differences in TMB, PD-L1, or tumor inflammation. Due to the high incidence of 9p21.3 deletions across tumor types, we performed a pan-cancer analysis and found CDKN2A deletion-positive tumors had worse survival following first-line immunotherapy treatment in multiple tumor types (HR = 1.4, P < 0.001). These results indicate deletions at 9p21.3 are a putative negative predictor of clinical benefit from first-line immune checkpoint inhibitors and may have utility in choosing between mono-IO vs chemo-IO regimens in NSCLC., (© 2022. The Author(s).)

Background: Neuregulin 1 (NRG1) fusions, which activate ErbB signaling, are rare oncogenic drivers in multiple tumor types. Afatinib is a pan-ErbB family inhibitor that may be an effective treatment for NRG1 fusion-driven tumors., Patients and Methods: This report summarizes pertinent details, including best tumor response to treatment, for six patients with metastatic NRG1 fusion-positive tumors treated with afatinib., Results: The six cases include four female and two male patients who ranged in age from 34 to 69 years. Five of the cases are patients with lung cancer, including two patients with invasive mucinous adenocarcinoma and three patients with nonmucinous adenocarcinoma. The sixth case is a patient with colorectal cancer. NRG1 fusion partners for the patients with lung cancer were either CD74 or SDC4. The patient with colorectal cancer harbored a novel POMK-NRG1 fusion and a KRAS mutation. Two patients received afatinib as first- or second-line therapy, three patients received the drug as third- to fifth-line therapy, and one patient received afatinib as fifteenth-line therapy. Best response with afatinib was stable disease in two patients (duration up to 16 months when combined with local therapies) and partial response (PR) of >18 months in three patients, including one with ongoing PR after 27 months. The remaining patient had a PR of 5 months with afatinib 40 mg/day, then another 6 months after an increase to 50 mg/day., Conclusion: This report reviews previously published metastatic NRG1 fusion-positive tumors treated with afatinib and summarizes six previously unpublished cases. The latter include several with a prolonged response to treatment (>18 months), as well as the first report of efficacy in NRG1 fusion-positive colorectal cancer. This adds to the growing body of evidence suggesting that afatinib can be effective in patients with NRG1 fusion-positive tumors., Key Points: NRG1 fusions activate ErbB signaling and have been identified as oncogenic drivers in multiple solid tumor types. Afatinib is a pan-ErbB family inhibitor authorized for the treatment of advanced non-small cell lung cancer that may be effective in NRG1 fusion-driven tumors. This report summarizes six previously unpublished cases of NRG1 fusion-driven cancers treated with afatinib, including five with metastatic lung cancer and one with metastatic colorectal cancer. Several patients showed a prolonged response of >18 months with afatinib treatment. This case series adds to the evidence suggesting a potential role for afatinib in this area of unmet medical need., (© AlphaMed Press 2020.)