Improved pulmonary function and exercise tolerance despite persistent pulmonary fibrosis over 1 year after severe COVID-19 infection.

We conducted a prospective single-centre cohort study of 104 multi-ethnic severe COVID-19 survivors from the first wave of the pandemic 15 months after hospitalisation. Of those who were assessed at 4 and 15 months, improvement of ground glass opacities correlated with worsened fibrotic reticulations. Despite a high prevalence of fibrotic patterns (64%), pulmonary function, grip strength, 6 min walk distance and frailty normalised. Overall, dyspnoea, cough and exhaustion did not improve and were not correlated with pulmonary function or radiographic fibrosis at 15 months, suggesting non-respiratory aetiologies. Monitoring persistent, and often subclinical, fibrotic interstitial abnormalities will be needed to determine their potential for future progression.

TGF-ß signaling: critical nexus of fibrogenesis and cancer.

The transforming growth factor-beta (TGF-ß) signaling pathway is a vital regulator of cell proliferation, differentiation, apoptosis, and extracellular matrix production. It functions through canonical SMAD-mediated processes and noncanonical pathways involving MAPK cascades, PI3K/AKT, Rho-like GTPases, and NF-κB signaling. This intricate signaling system is finely tuned by interactions between canonical and noncanonical pathways and plays key roles in both physiologic and pathologic conditions including tissue homeostasis, fibrosis, and cancer progression. TGF-ß signaling is known to have paradoxical actions. Under normal physiologic conditions, TGF-ß signaling promotes cell quiescence and apoptosis, acting as a tumor suppressor. In contrast, in pathological states such as inflammation and cancer, it triggers processes that facilitate cancer progression and tissue remodeling, thus promoting tumor development and fibrosis. Here, we detail the role that TGF-ß plays in cancer and fibrosis and highlight the potential for future theranostics targeting this pathway.

Lung nodule malignancy classification with associated pulmonary fibrosis using 3D attention-gated convolutional network with CT scans.

BACKGROUND: Chest Computed tomography (CT) scans detect lung nodules and assess pulmonary fibrosis. While pulmonary fibrosis indicates increased lung cancer risk, current clinical practice characterizes nodule risk of malignancy based on nodule size and smoking history; little consideration is given to the fibrotic microenvironment. PURPOSE: To evaluate the effect of incorporating fibrotic microenvironment into classifying malignancy of lung nodules in chest CT images using deep learning techniques. MATERIALS AND METHODS: We developed a visualizable 3D classification model trained with in-house CT dataset for the nodule malignancy classification task. Three slightly-modified datasets were created: (1) nodule alone (microenvironment removed); (2) nodule with surrounding lung microenvironment; and (3) nodule in microenvironment with semantic fibrosis metadata. For each of the models, tenfold cross-validation was performed. Results were evaluated using quantitative measures, such as accuracy, sensitivity, specificity, and area-under-curve (AUC), as well as qualitative assessments, such as attention maps and class activation maps (CAM). RESULTS: The classification model trained with nodule alone achieved 75.61% accuracy, 50.00% sensitivity, 88.46% specificity, and 0.78 AUC; the model trained with nodule and microenvironment achieved 79.03% accuracy, 65.46% sensitivity, 85.86% specificity, and 0.84 AUC. The model trained with additional semantic fibrosis metadata achieved 80.84% accuracy, 74.67% sensitivity, 84.95% specificity, and 0.89 AUC. Our visual evaluation of attention maps and CAM suggested that both the nodules and the microenvironment contributed to the task. CONCLUSION: The nodule malignancy classification performance was found to be improving with microenvironment data. Further improvement was found when incorporating semantic fibrosis information.

Comparison of lung cancer occurring in fibrotic versus non-fibrotic lung on chest CT.

PURPOSE: Evaluate the behavior of lung nodules occurring in areas of pulmonary fibrosis and compare them to pulmonary nodules occurring in the non-fibrotic lung parenchyma. METHODS: This retrospective review of chest CT scans and electronic medical records received expedited IRB approval and a waiver of informed consent. 4500 consecutive patients with a chest CT scan report containing the word fibrosis or a specific type of fibrosis were identified using the system M*Model Catalyst (Maplewood, Minnesota, U.S.). The largest nodule was measured in the longest dimension and re-evaluated, in the same way, on the follow-up exam if multiple time points were available. The nodule doubling time was calculated. If the patient developed cancer, the histologic diagnosis was documented. RESULTS: Six hundred and nine patients were found to have at least one pulmonary nodule on either the first or the second CT scan. 274 of the largest pulmonary nodules were in the fibrotic tissue and 335 were in the non-fibrotic lung parenchyma. Pathology proven cancer was more common in nodules occurring in areas of pulmonary fibrosis compared to nodules occurring in areas of non-fibrotic lung (34% vs 15%, p < 0.01). Adenocarcinoma was the most common cell type in both groups but more frequent in cancers occurring in non-fibrotic tissue. In the non-fibrotic lung, 1 of 126 (0.8%) of nodules measuring 1 to 6 mm were cancer. In contrast, 5 of 49 (10.2%) of nodules in fibrosis measuring 1 to 6 mm represented biopsy-proven cancer (p < 0.01). The doubling time for squamous cell cancer was shorter in the fibrotic lung compared to non-fibrotic lung, however, the difference was not statistically significant (p = 0.24). 15 incident lung nodules on second CT obtained ≤ 18 months after first CT scan was found in fibrotic lung and eight (53%) were diagnosed as cancer. CONCLUSIONS: Nodules occurring in fibrotic lung tissue are more likely to be cancer than nodules in the nonfibrotic lung. Incident pulmonary nodules in pulmonary fibrosis have a high likelihood of being cancer.

Incidence of Interstitial Lung Abnormalities: The MESA Lung Study.

The incidence of newly developed interstitial lung abnormalities (ILA) and fibrotic ILA have not been previously reported.Trained thoracic radiologists evaluated 13 944 cardiac CT scans for the presence of ILA in 6197 Multi-Ethnic Study of Atherosclerosis longitudinal cohort study participants >45 years of age from 2000 to 2012. 5% of the scans were re-read by the same or a different observer in a blinded fashion. After exclusion of participants with ILA at baseline, incidence rates and incidence rate ratios for ILA and fibrotic ILA were calculated.The intra-reader agreement of ILA was 92.0% (Gwet AC1=0.912, ICC=0.982) and the inter-reader agreement of ILA was 83.5% (Gwet AC1=0.814; ICC=0.969). Incidence of ILA and fibrotic ILA was estimated to be 13.1 cases/1000 person-years and 3.5/1000 person-years, respectively. In multivariable analyses, age (HR 1.06 (1.05, 1.08), p <0.001; HR 1.08 (1.06, 1.11), p <0.001), high attenuation area (HAA) at baseline (HR 1.05 (1.03, 1.07), p <0.001; HR 1.06 (1.02, 1.10), p=0.002), and the MUC5B promoter SNP (HR 1.73 (1.17, 2.56) p=0.01; HR 4.96 (2.68, 9.15), p <0.001) were associated with incident ILA and fibrotic ILA, respectively. Ever smoking (HR 2.31 (1.34, 3.96), p= 0.002) and an IPF polygenic risk score (HR 2.09 (1.61-2.71), p<0.001) were associated only with incident fibrotic ILA.Incident ILA and fibrotic ILA were estimated by review of cardiac imaging studies. These findings may lead to wider application of a screening tool for atherosclerosis to identify preclinical lung disease.

Fibrotic-Like Pulmonary Radiographic Patterns Are Not Associated With Adverse Outcomes in COVID-19 Chronic Critical Illness.

OBJECTIVES: Pulmonary fibrosis is a feared complication of COVID-19. To characterize the risks and outcomes associated with fibrotic-like radiographic abnormalities in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and chronic critical illness. DESIGN: Single-center prospective cohort study. SETTING: We examined chest CT scans performed between ICU discharge and 30 days after hospital discharge using established methods to quantify nonfibrotic and fibrotic-like patterns. PATIENTS: Adults hospitalized with COVID-19-related ARDS and chronic critical illness (> 21 d of mechanical ventilation, tracheostomy, and survival to ICU discharge) between March 2020 and May 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We tested associations of fibrotic-like patterns with clinical characteristics and biomarkers, and with time to mechanical ventilator liberation and 6-month survival, controlling for demographics, comorbidities, and COVID-19 therapies. A total of 141 of 616 adults (23%) with COVID-19-related ARDS developed chronic critical illness, and 64 of 141 (46%) had a chest CT a median (interquartile range) 66 days (42-82 d) after intubation. Fifty-five percent had fibrotic-like patterns characterized by reticulations and/or traction bronchiectasis. In adjusted analyses, interleukin-6 level on the day of intubation was associated with fibrotic-like patterns (odds ratio, 4.40 per quartile change; 95% CI, 1.90-10.1 per quartile change). Other inflammatory biomarkers, Sequential Organ Failure Assessment score, age, tidal volume, driving pressure, and ventilator days were not. Fibrotic-like patterns were not associated with longer time to mechanical ventilator liberation or worse 6-month survival. CONCLUSIONS: Approximately half of adults with COVID-19-associated chronic critical illness have fibrotic-like patterns that are associated with higher interleukin-6 levels at intubation. Fibrotic-like patterns are not associated with longer time to liberation from mechanical ventilation or worse 6-month survival.

Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length.

The risk factors for development of fibrotic-like radiographic abnormalities after severe COVID-19 are incompletely described and the extent to which CT findings correlate with symptoms and physical function after hospitalisation remains unclear. At 4 months after hospitalisation, fibrotic-like patterns were more common in those who underwent mechanical ventilation (72%) than in those who did not (20%). We demonstrate that severity of initial illness, duration of mechanical ventilation, lactate dehydrogenase on admission and leucocyte telomere length are independent risk factors for fibrotic-like radiographic abnormalities. These fibrotic-like changes correlate with lung function, cough and measures of frailty, but not with dyspnoea.

CT Screening for Lung Cancer: Part-Solid Nodules in Baseline and Annual Repeat Rounds.

OBJECTIVE: The purpose of this study was to assess the frequencies of identifying participants with part-solid nodules, of diagnostic pursuit, of diagnoses of lung cancer, and long-term lung cancer survival in baseline and annual repeat rounds of CT screening in the International Early Lung Cancer Action Project. MATERIALS AND METHODS: Screenings were performed under a common protocol. Participants with solid, nonsolid, and part-solid nodules and the diagnoses of lung cancer were documented. RESULTS: Part-solid nodules were identified in 2892 of 57,496 (5.0%) baseline screening studies; 567 (19.6%) of these nodules resolved or decreased in size. Diagnostic pursuit led to the diagnosis of adenocarcinoma in 79 cases, all clinical stage I. At resection, one nodule (12-mm solid component) had a single N2 metastasis. A new part-solid nodule was identified in 541 of 64,677 (0.8%) annual repeat screenings; 377 (69.7%) of these nodules resolved or decreased in size. In eight cases among the 541, the diagnosis of adenocarcinoma manifesting as a part solid nodule was made; on retrospective review the nodule originally had been a nonsolid nodule. In another 20 cases, the cancer originally had manifested as a nonsolid nodule but had progressed to become part-solid at annual repeat screening before any diagnosis was pursued. These 28 annual repeat cases of lung cancer were all pathologic stage IA. Of the 107 cases of lung cancer (79 baseline cases and 28 annual repeat cases), 106 were surgically resected, and one baseline case was followed up with imaging for 4 years. The lung cancer survival rate was 100% with a median follow-up period from diagnosis of 89 months (interquartile range, 52-134 months). CONCLUSION: Lung cancers manifesting as part-solid nodules at repeat screening studies all started as nonsolid nodules. Among 107 cases of adenocarcinoma manifesting as a part-solid nodule, a single lymph node metastasis was found in a single case (solid component, 12 mm).

CT Screening for Lung Cancer: Nonsolid Nodules in Baseline and Annual Repeat Rounds.

PURPOSE: To address the frequency of identifying nonsolid nodules, diagnosing lung cancer manifesting as such nodules, and the long-term outcome after treatment in a prospective cohort, the International Early Lung Cancer Action Program. MATERIALS AND METHODS: A total of 57,496 participants underwent baseline and subsequent annual repeat computed tomographic (CT) screenings according to an institutional review board, HIPAA-compliant protocol. Informed consent was obtained. The frequency of participants with nonsolid nodules, the course of the nodule at follow-up, and the resulting diagnoses of lung cancer, treatment, and outcome are given separately for baseline and annual repeat rounds of screening. The χ(2) statistic was used to compare percentages. RESULTS: A nonsolid nodule was identified in 2392 (4.2%) of 57,496 baseline screenings, and pathologic pursuit led to the diagnosis of 73 cases of adenocarcinoma. A new nonsolid nodule was identified in 485 (0.7%) of 64,677 annual repeat screenings, and 11 had a diagnosis of stage I adenocarcinoma; none were in nodules 15 mm or larger in diameter. Nonsolid nodules resolved or decreased more frequently in annual repeat than in baseline rounds (322 [66%] of 485 vs 628 [26%] of 2392, P < .0001). Treatment of the cases of lung cancer was with lobectomy in 55, bilobectomy in two, sublobar resection in 26, and radiation therapy in one. Median time to treatment was 19 months (interquartile range [IQR], 6-41 months). A solid component had developed in 22 cases prior to treatment (median transition time from nonsolid to part-solid, 25 months). The lung cancer-survival rate was 100% with median follow-up since diagnosis of 78 months (IQR, 45-122 months). CONCLUSION: Nonsolid nodules of any size can be safely followed with CT at 12-month intervals to assess transition to part-solid. Surgery was 100% curative in all cases, regardless of the time to treatment.

Radiographic grading system for usual interstitial pneumonia correlates with mortality and may serve as a surrogate endpoint in clinical trials.

PURPOSE: Usual interstitial pneumonia (UIP)/ idiopathic pulmonary fibrosis (IFP) is a relentlessly progressive lung disease with outcomes similar to cancer. We have previously established a radiologic grading system for UIP and demonstrated that it correlates with pulmonary function tests; here we test the hypothesis that it correlates with mortality. Validating a correlation with mortality will demonstrate the utility of this system for monitoring progression over time clinically and in trials of anti-fibrotic agents. METHODS: We searched the radiology record system "Catalyst" to identify cases and reviewed each case to confirm the diagnosis. 94 patients met the inclusion criteria for further assessment. Chest CT grade was determined by consensus of two cardiothoracic radiologists. Data was analyzed to identify the interval between chest CT and death. This interval was correlated with CT grade using Spearman correlation analysis. RESULTS: For all cases, chest CT grade and mortality demonstrated a positive correlation of rs = 0.37732, 2-tailed p = 0.00018. We also employed subgroup analysis; for the subgroup with intervals less than or equal to 100 days, there was a positive correlation, rs = 0.48339, 2-tailed p = 0.03602; for the subgroup with an interval greater than 100 days between imaging and death there was a positive correlation, rs = 0.302, 2-tailed p = 0.00846. CONCLUSION: These data support use of this system for monitoring clinical progression and as a surrogate endpoint for clinical trials. Future work building upon the data presented here will evaluate its utility in clinical trials and develop automated grading.

CT predictors of outcomes in patients with connective tissue disease and progressive lung fibrosis.

PURPOSE: Progressive fibrosing interstitial lung disease (PF-ILD) is a phenotype defined by rapid clinical progression towards respiratory failure. While idiopathic pulmonary fibrosis is the archetype of PF-ILD, connective tissue disease associated interstitial lung disease (CTD-ILD) can also manifest as PF-ILD. Few studies have described the value of serial computed tomography (CT) in predicting clinical progression of ILD. We explore which single and serial clinical and radiographic variables, in particular serial CT variables and a novel variable, the right lower lobe anterior bronchial angle (RLL-ABA), best predict mortality, oxygen requirement, hospital admissions, and lung transplant in CTD-ILD. METHODS: This is a single-center retrospective study of 84 patients with a history of CTD-ILD. Cox survival analysis was used to predict two endpoints, all-cause mortality and composite negative outcomes (CNO): new oxygen requirement, respiratory admission, lung transplant, and death. RESULTS: On serial CT, change in pulmonary artery (PA) size and RLL-ABA were predictive of mortality and CNO, and change in fibrosis was predictive of mortality alone. On single CT, the extent of fibrosis, PA size, and PA to aorta ratio were predictive of mortality and CNO. Among clinical variables, oxygen requirement, forced vital capacity (FVC), change in FVC, and worsening shortness of breath were predictive of mortality and CNO, and diffusing capacity for carbon monoxide was predictive of mortality alone. CONCLUSIONS: In addition to clinical and single CT variables, serial CT measurements such as change in extent of fibrosis, PA size, PA to aorta ratio, and RLL-ABA were predictive of mortality and CNO.

Establishing quantitative radiographic criteria for the diagnosis of pleuroparenchymal fibroelastosis.

PURPOSE: Pleuroparenchymal Fibroelastosis (PPFE) is a type of pulmonary fibrosis most commonly occurring at the apices. Patients with PPFE have an increased risk of adverse effects from lung biopsy and in the post-surgical setting. Here, we investigated simple and reproducible measurements on chest CT to evaluate their predictive value in diagnosing PPFE. METHODS: We analyzed a cohort of patients with histologically-proven PPFE and compared them to a cohort of patients diagnosed with "biapical scarring" (BAS) on chest CT. We measured plueuroparenchymal thickness using several independent parameters on chest CT. We also assessed other radiologic and clinical characteristics to identify if any were predictive of PPFF. RESULTS: Our analysis demonstrated the average greatest apical thickness with a cut off of 4.5 mm yielded a sensitivity of 94.4% and a specificity of 88.9%, and an area under the curve of 97.2%. Single greatest apical thickness with a cut off of 7.5 mm had a sensitivity of 100% and a specificity of 88.9%, with the area under the curve of 97.8%. Average greatest upper lobe thickness with a cut off of 8.0 mm had a sensitivity of 88.9% and a specificity of 100%, with an area under the curve of 98.2%. Single greatest upper lobe thickness with a cut off of 8.5 yielded both a sensitivity and specificity of 94.4% and an area under the curve of 94.3%. CONCLUSION: Measurements described above are highly sensitive and specific for the diagnosis of PPFE and warrant investigation with a larger cohort of patients.

Reporting breast density on chest computed tomography.

Women are encouraged to have a yearly mammogram and in addition to screening for breast cancer, the radiologist reports the patient's breast density. High breast density increases a woman's risk of developing breast cancer. The number of chest computed tomography (CT) scans performed each year is increasing. Chest CT scans for lung cancer screening in high-risk patients are the standard of care. Important additional findings can be identified on these exams including coronary artery calcifications, thyroid nodules, and breast density. Our previous research has shown that breast density can be reliably graded on chest CT and is comparable to mammographic grading. However, the inter-reader agreement was higher for chest CT. It is important that thoracic radiologists include the grading of breast density in their chest CT reports. According to mammography literature, this information has proven to be helpful for early detection of breast cancer. Federal legislation recommends notifying both providers and patients about breast density on mammography and so it follows that if we see the same information on chest CT, we should report it so that at the very least the clinician can encourage their patient to have a routine mammogram.

Radiographic features of pneumonitis in patients treated with immunotherapy compared to traditional chemotherapy for non-small cell lung cancer.

BACKGROUND: Pneumonitis has been described as a side effect of immunotherapy as well as traditional chemotherapy. Although immune-related adverse event (IRAE) pneumonitis has been extensively characterized, the relationship between IRAE pneumonitis and pneumonitis secondary to chemotherapy is less clear. Here, we present the first analysis of radiographic features of pneumonitis secondary to immunotherapy compared to chemotherapy. METHODS: Using our radiology records system, we searched chest computed tomography (CT) reports for the term "pneumonitis". We evaluated medical records to establish chronicity of pneumonitis occurring after medication administration and excluded cases where radiation therapy appeared to be the cause of pneumonitis. We also obtained information regarding demographic, clinical, and treatment characteristics for comparison. RESULTS: Patients treated with immunotherapy demonstrated more specific features of pneumonitis including consolidation, ground glass opacities, septal thickening, traction bronchiectasis, and pulmonary nodules compared to those treated with chemotherapy. Immunotherapy treatment correlated with the development of pulmonary nodules (p = 0.048), and administration of more than one immunotherapy agent correlated with a greater incidence of development of nodules (p = 0.050). Radiographic features in patients treated with immunotherapy all decreased over time. Conversely, in patients treated with chemotherapy the incidence of ground glass opacities, traction bronchiectasis, pulmonary nodules, and mediastinal/hilar adenopathy increased over time. CONCLUSIONS: IRAE-pneumonitis has distinct features and a distinct clinical course compared to pneumonitis secondary to chemotherapy. Importantly, IRAE-pneumonitis features decreased over time, suggesting that careful consideration of the benefit-risk ratio may allow for continuation of immunotherapy in some patients who develop pneumonitis.

The Macklin effect closely correlates with pneumomediastinum in acutely ill intubated patients with COVID-19 infection.

PURPOSE: Patients with COVID-19 infection are frequently found to have pulmonary barotrauma. Recent work has identified the Macklin effect as a radiographic sign that often occurs in patients with COVID-19 and may correlate with barotrauma. METHODS: We evaluated chest CT scans in COVID-19 positive mechanically ventilated patients for the Macklin effect and any type of pulmonary barotrauma. Patient charts were reviewed to identify demographic and clinical characteristics. RESULTS: The Macklin effect on chest CT scan was identified in a total of 10/75 (13.3%) COVID-19 positive mechanically ventilated patients; 9 developed barotrauma. Patients with the Macklin effect on chest CT scan had a 90% rate of pneumomediastinum (p < 0.001) and a trend toward a higher rate of pneumothorax (60%, p = 0.09). Pneumothorax was most frequently omolateral to the site of the Macklin effect (83.3%). CONCLUSION: The Macklin effect may be a strong radiographic biomarker for pulmonary barotrauma, most strongly correlating with pneumomediastinum. Studies in ARDS patients without COVID-19 are needed to validate this sign in a broader population. If validated in a broad population, future critical care treatment algorithms may include the Macklin sign for clinical decision making and prognostication.

Integrating [18F]-Fluorodeoxyglucose Positron Emission Tomography with Computed Tomography with Radiation Therapy and Immunomodulation in Precision Therapy for Solid Tumors.

[18F]-FDG positron emission tomography with computed tomography (PET/CT) imaging is widely used to enhance the quality of care in patients diagnosed with cancer. Furthermore, it holds the potential to offer insight into the synergic effect of combining radiation therapy (RT) with immuno-oncological (IO) agents. This is achieved by evaluating treatment responses both at the RT and distant tumor sites, thereby encompassing the phenomenon known as the abscopal effect. In this context, PET/CT can play an important role in establishing timelines for RT/IO administration and monitoring responses, including novel patterns such as hyperprogression, oligoprogression, and pseudoprogression, as well as immune-related adverse events. In this commentary, we explore the incremental value of PET/CT to enhance the combination of RT with IO in precision therapy for solid tumors, by offering supplementary insights to recently released joint guidelines.

Defining the pathway to timely diagnosis and treatment of interstitial lung disease: a US Delphi survey.

INTRODUCTION: Timely diagnosis of interstitial lung disease (ILD) is limited by obstacles in the current patient pathway. Misdiagnosis and delays are common and may lead to a significant burden of diagnostic procedures and worse outcomes. This Delphi survey aimed to identify consensus on the key steps that facilitate the patient journey to an accurate ILD diagnosis and appropriate management in the US. METHODS: A modified Delphi analysis was conducted, comprising three online surveys based on a comprehensive literature search. The surveys spanned five domains (guidelines, community screening, diagnosis, management and specialist referral) and were completed by a panel of US physicians, including primary care physicians and pulmonologists practising in community or academic settings. A priori definitions of consensus agreement were median scores of 2-3 (agree strongly/agree), with an IQR of 0-1 for questions on a 7-point Likert scale from -3 to 3, or ≥80% agreement for binary questions. RESULTS: Forty-nine panellists completed the surveys and 62 statements reached consensus agreement. There was consensus agreement on what should be included in the primary care evaluation of patients with suspected ILD and the next steps following workup. Regarding diagnosis in community pulmonology care, consensus agreement was reached on the requisition and reporting of high-resolution CT scans and the appropriate circumstances for holding multidisciplinary discussions. Additionally, there was consensus agreement on which symptoms and comorbidities should be monitored, the frequency of consultations and the assessment of disease progression. Regarding specialist referral, consensus agreement was reached on which patients should receive priority access to ILD centres and the contents of the referral package. CONCLUSIONS: These findings clarify the most common issues that should merit further evaluation for ILD and help define the steps for timely, accurate diagnosis and appropriate collaborative specialty management of patients with ILD.

Novel Targets, Novel Treatments: The Changing Landscape of Non-Small Cell Lung Cancer.

Treatment of non-small cell lung cancer (NSCLC) has undergone a paradigm shift. Once a disease with limited potential therapies, treatment options for patients have exploded with the availability of molecular testing to direct management and targeted therapies to treat tumors with specific driver mutations. New in vitro diagnostics allow for the early and non-invasive detection of disease, and emerging in vivo imaging techniques allow for better detection and monitoring. The development of checkpoint inhibitor immunotherapy has arguably been the biggest advance in lung cancer treatment, given that the vast majority of NSCLC tumors can be treated with these therapies. Specific targeted therapies, including those against KRAS, EGFR, RTK, and others have also improved the outcomes for those individuals bearing an actionable mutation. New and emerging therapies, such as bispecific antibodies, CAR T cell therapy, and molecular targeted radiotherapy, offer promise to patients for whom none of the existing therapies have proved effective. In this review, we provide the most up-to-date survey to our knowledge regarding emerging diagnostic and therapeutic strategies for lung cancer to provide clinicians with a comprehensive reference of the options for treatment available now and those which are soon to come.

Single-cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors.

PD-1 is an inhibitory receptor in T cells, and antibodies that block its interaction with ligands augment anti-tumor immune responses. The clinical potential of these agents is limited by the fact that half of all patients develop immune-related adverse events (irAEs). To generate insights into the cellular changes that occur during anti-PD-1 treatment, we performed single-cell RNA sequencing of circulating T cells collected from patients with cancer. Using the K-nearest-neighbor-based network graph-drawing layout, we show the involvement of distinctive genes and subpopulations of T cells. We identify that at baseline, patients with arthritis have fewer CD8 TCM cells, patients with pneumonitis have more CD4 TH2 cells, and patients with thyroiditis have more CD4 TH17 cells when compared with patients who do not develop irAEs. These data support the hypothesis that different populations of T cells are associated with different irAEs and that characterization of these cells' pre-treatment has the potential to serve as a toxicity-specific predictive biomarker.

Advances in PET/CT Imaging for Breast Cancer.

One out of eight women will be affected by breast cancer during her lifetime. Imaging plays a key role in breast cancer detection and management, providing physicians with information about tumor location, heterogeneity, and dissemination. In this review, we describe the latest advances in PET/CT imaging of breast cancer, including novel applications of 18F-FDG PET/CT and the development and testing of new agents for primary and metastatic breast tumor imaging and therapy. Ultimately, these radiopharmaceuticals may guide personalized approaches to optimize treatment based on the patient's specific tumor profile, and may become a new standard of care. In addition, they may enhance the assessment of treatment efficacy and lead to improved outcomes for patients with a breast cancer diagnosis.