Circulating tumor DNA clearance predicts prognosis across treatment regimen in a large real-world longitudinally monitored advanced non-small cell lung cancer cohort

Background: Although growth advantage of certain clones would ultimately translate into a clinically visible disease progression, radiological imaging does not reflect clonal evolution at molecular level. Circulating tumor DNA (ctDNA), validated as a tool for mutation detection in lung cancer, could reflect dynamic molecular changes. We evaluated the utility of ctDNA as a predictive and a prognostic marker in disease monitoring of advanced non-small cell lung cancer (NSCLC) patients.Methods: This is a multicenter prospective cohort study. We performed capture-based ultra-deep sequencing on longitudinal plasma samples utilizing a panel consisting of 168 NSCLC-related genes on 949 advanced NSCLC patients with driver mutations to monitor treatment responses and disease progression. The correlations between ctDNA and progression-free survival (PFS)/overall survival (OS) were performed on 248 patients undergoing various treatments with the minimum of 2 ctDNA tests.Results: The results of this study revealed that higher ctDNA abundance (P=0.012) and mutation count (P=8.5x10(-4)) at baseline are associated with shorter OS. We also found that patients with ctDNA clearance, not just driver mutation clearance, at any point during the course of treatment were associated with longer PFS (P=2.2x10(-1)6, HR 0.28) and OS (P=4.5x10(-6), HR 0.19) regardless of type of treatment and evaluation schedule.Conclusions: This prospective real-world study shows that ctDNA clearance during treatment may serve as predictive and prognostic marker across a wide spectrum of treatment regimens

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis

BackgroundCheckpoint inhibitor–related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined.MethodsWe conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase’s characteristics.ResultsThere were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005).ConclusionsThe general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised

Dynamic monitoring of desertification in response to climatic factors: a case study from the Gelintan Oasis on the southeastern edge of the Tengger Desert, China

This study used GIS and remote sensing to establish DDI model based on vegetation cover Index (NDVI) and Surface Albedo (Albedo) normalization to evaluate in the Gelintan Oasis of Inner Mongolia past 30 years. Use Jenks Natural Breaks Method classified as undesertified land, slightly desertified land, moderately desertified land and severely desertified land. Used the Mann-Kendall test, the impact of climate change on land desertification in the study area was discussed. The results showed that, the Gelintan Oasis consisted primarily of moderately desertified land but the dominant land type shifted to severely desertified land from 2006 to 2016; Moderately desertified land occurs in the desert-oasis ecotone; Moderately desertified land showed pronounced expansions and contractions in area. In the future, we hope to provide more perfect data support for desertification control by using longer time series data to explore the relationship between desertification and climatic or human factors

Preserving Perspectives

This project, completed virtually, developed an online archive containing the stories of people working during the COVID-19 pandemic. In our research, we found that few records of the experiences of average people living during past pandemics exist today. In order to preserve the experiences of people living through the current pandemic, we interviewed twelve non-medical essential workers. In an effort to find themes in their experiences, our team coded the stories told in the transcripts. While each interviewee had a unique experience, common threads emerged around selflessness, social strain, and fear. A deeper analysis can be found at wp.wpi.edu/perspectives

Malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profiling

Background The clinical utility of malignant pleural effusion (MPE) to detect mutation has been well documented; however, routine practice of the use of MPE involves collection of the cell pellet to detect mutation, and limited studies have interrogated the MPE supernatant as an alternative source of tumor‐derived DNA for mutation profiling. In this study, we investigated the potential of MPE supernatant as a liquid biopsy specimen by comparing its mutation profile with that of matched MPE cell pellets, tissue, and plasma samples. Methods Sequencing data from 17 patients with matched lung tissue, plasma, and MPE samples were retrospectively analyzed. Capture‐based targeted sequencing was performed on matched plasma and MPE supernatant samples obtained from 154 patients with advanced lung adenocarcinoma. Results MPE supernatants had significantly higher median maximum allelic fractions (maxAFs) than their corresponding cell pellets (P = 0.008) and plasma samples (P = 0.036), and a comparable maxAF value to that of tissue samples (P = 0.675). Comparison of MPE supernatant and matched plasma samples from the larger cohort (n = 154) revealed a comparable mutation detection rate; however, MPE supernatant had a significantly higher median maxAF than plasma (20.3% vs. 1.13%; P < 0.001). Furthermore, the concordance rates between MPE supernatant and plasma for single‐nucleotide and copy number variations were 56% and 18%, respectively, suggesting that MPE supernatant reveals a more comprehensive mutation spectrum, particularly for copy number variations. Conclusion Overall, our study shows that MPE supernatant is an optimal alternative source of tumor‐derived DNA for comprehensive mutation profiling