Peripheral Lung Involvement Research Articles

Trastuzumab Deruxtecan‒Related Interstitial Lung Disease/Pneumonitis: Computed Tomography Imaging Patterns to Guide Diagnosis and Management

PURPOSE Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate approved for the treatment of several advanced cancers; however, severe or fatal interstitial lung disease/pneumonitis can occur. We characterized the computed tomography (CT) patterns of T-DXd‒related pneumonitis as a marker for its clinical severity. MATERIALS AND METHODS Ninety patients with advanced cancers who developed T-DXd‒related pneumonitis in two completed single-arm clinical trials were included. Three radiologists independently characterized the CT patterns of pneumonitis at diagnosis, for analyses of those patterns' relationships with clinical severity and pneumonitis outcome. RESULTS T-DXd‒related pneumonitis most commonly presented with cryptogenic organizing pneumonia (COP) pattern, observed in 65 patients (72%), followed by a newly identified COP/hypersensitivity pneumonitis (HP) pattern (13%), acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) pattern (11%), and HP pattern (3%). A subset of cases with COP pattern demonstrated an atypical distribution with upper and peripheral lung involvement (6/65; 9%). CT patterns were associated with Common Terminology Criteria for Adverse Events severity grades of pneumonitis, with the AIP/ARDS pattern having higher grades compared with others ( P < .0001). Fatal pneumonitis was more common in the AIP/ARDS pattern than in others ( P = .005). The onset of pneumonitis was earlier in the AIP/ARDS pattern compared with others (median time to onset: at 17.9 v 32.7 weeks of therapy; P = .019). Pneumonitis was treated by withholding T-DXd with or without corticosteroids in most patients (78/90; 87%). CONCLUSION T-DXd‒related pneumonitis most commonly demonstrated a COP pattern, with a subset having an atypical distribution. The AIP/ARDS pattern was indicative of severe, potentially fatal pneumonitis, and requires immediate clinical attention to mitigate serious adverse events.

Chest X-ray findings in COVID-19 patients: a descriptive study

Background: Early suspicion and diagnosis remains the cornerstone for the better outcome of patients and to decrease cross infection in cases of COVID-19 pneumonia. In a country like Nepal X-ray facilities are readily available radiological tool in most of the centers and can be important screening tool. There is a lack of studies detailing the chest XR (C-XR) findings in these patients when compared to that dedicated to the CT features. Study aims to describe the patterns of the lung opacities in CXR in these patients.Methods: This is retrospective descriptive study conducted at NMCTH in COVID-19 patients from 12 September to 17 October 2020. Demographic characteristics, symptoms, co-morbidities and C-XR findings were studied. CXR findings were categorized according to BSTI classification.Results: Among 111 COVID-19 RT-PCR positive cases admitted 102 (91.9%) belonged to age group 18-65 years, 89 (80.2%) were males. Cough and fever were the commonest symptoms present in 109 (98.2%) patients. Ischemic heart disease and hypertension in 32 (28.8%) patients were the commonest co morbidities. According to British society of thoracic imaging (BSTI) COVID-19 CXR classification, six patients (5.4%) had normal chest X-rays. Classic/probable COVID-19 picture was present in 79 (71.17%) patients while (7.2%) had intermediate for COVID-19 X-ray findings. Among 79 patients with classic/probable COVID-19 CXR findings 71 (89.8%) had bilateral consolidation/ground glass haze, 72 (91.1%) had peripheral lung involvement while 66 (83.5%) had middle and lower zone involvement.Conclusions: Ground glass opacities/consolidations with bilateral location, peripheral distribution and middle- lower zone predominance were the commonest X-ray findings in our study.

Determining the diagnostic accuracy of non contrast HRCT Chest study in COVID-19 Pneumonia Keeping PCR assay as gold standard

Objective: To determine the diagnostic accuracy of high-resolution computed tomography (HRCT) chest in determination of corona virus disease (COVID-19) taking polymerase chain reaction (PCR) as gold standard. Methods: This diagnostic cross-sectional study was conducted at Shifa International Hospital Islamabad (SIH) from February 2020 to April 2020. All patients suspected for COVID 19 pneumonia were consecutively enrolled. Diagnosis was done via both HRCT chest and PCR assay. Patient s demographic characteristics and PCR results were retrieved from hospital database. Diagnostic accuracy was explored by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall diagnostic accuracy. Results: Of 250 patients, the mean age was 58.5 years +- 14.7 years. HRCT findings in positive scans showed that of 181 patients, majority of the patients presented with multifocal peripheral rounded ground glass opacities (GGOs) with crazy paving observed in 77 (42.5%), multifocal peripheral rounded in GGOs 51 (28.1%), and multifocal peripheral rounded GGOs with crazy paving and consolidations 45 (24.8%). Furthermore, bilateral lungs and multifocal multilobar involvement of lungs was observed in 179 (98.8%) each. While peripheral lung involvement was observed in 176 (97.2%) patients. The sensitivity, specificity, PPV, NPV, and overall diagnostic accuracy of HRCT chest in diagnosing COVID-19 pneumonia was 93.4%, 53.5%, 71.2%, 86.9%, and 75.6% respectively. Conclusion: HRCT chest has a higher sensitivity and comparable diagnostic accuracy to PCR testing in diagnosing COVID 19 pneumonia and thus in the epidemic areas, it can be used as an important adjunct to PCR testing.

Chest X-rays findings in COVID 19 patients at a University Teaching Hospital - A descriptive study.

Objective:To analyze Chest X-ray findings in COVID 19 positive patients, presented at corona filtration center, Benazir Bhutto Hospital Rawalpindi, based on CXR classification of British Society of Thoracic Imaging (BSTI).Methods:In this study, all RT-PCR COVID-19 positive patients screened at corona filtration center, Benazir Bhutto hospital Rawalpindi from 20th March 2020 to 10th April 2020 were included. Mean age of the cohort with age range was calculated. Presenting complaints & Co-morbid were analyzed and tabulated in frequencies and percentages. Portable CXR findings were classified according to BSTI classification and documented in frequencies and percentages.Results:Mean age of the patients was 44 years. Presenting complaints were cough 20 (67%), fever 18 (60%), shortness of breath 11 (37%), sore throat six (20%), loss of sense of taste and smell four(13%). Main co-morbid was hypertension six (20%). Two (7%) patients had normal and seven (23%) had classical COVID CXRs. 21 (70%) patients were in indeterminate group with only one (3%) having unilateral lung disease. Three (10%) patients had diffuse lung involvement and 18(60%) had peripheral lung involvement. Majority of patients 19 (63%), had bilateral middle and lower zonal involvement.Conclusions:In this study, COVID-19 CXRs generally manifested a spectrum of pure ground glass, mixed ground glass opacities to consolidation in bilateral peripheral middle and lower lung zones. BSTI CXR reporting classification of COVID-19 is valid in our patients with addition of middle zonal involvement in classical COVID-19 criteria as opposed to just lower zone involvement.

Abstract IA09: Squamous cell carcinoma pathology, etiology, and molecular drivers.

Abstract Squamous cell carcinoma (SCC) accounts for approximately 20% of all lung cancers in the United States and 30% in Europe [1-3]. It is a model of smokers related tumors with SCLC. The frequency of peripheral lung involvement has increased as compared to central squamous cell carcinoma. Morphologically, squamous differentiation is identified by inter-cellular bridging, squamous pearl formation and individual cell keratinisation. The intensity of these features characterizes well differentiated squamous cell carcinoma, versus poorly differentiated tumors that lack clear squamous morphology, are more difficult to differentiate from large cell carcinoma or from non cell lung carcinoma on small biopsies. In this cases the molecular marker P63 and/or P40 (the delta-N deleted P63 isoform) and negativity of TTF1 allows for a tumor to be classified as SCC. With high concordance q with the genomic prediction from exome sequencing (D.Seidel et al,Science Translational Medicine 2013 in press ) In addition to keratinized (well differentiated) and non keratinized (poorly differentiated) squamous cell carcinoma, basaloid carcinoma represent a third class recently identified as a specific molecular entity among SCC on gene expression profiling (WHO 2004 Travis , E. Brambilla, submitted 2013), with a significantly dismal prognosis among SCC. Basaloid carcinoma carries 95 % P53 mutation (G-T transversion). Supervised analyses reveal that basaloïd SCC significantly display a specific mRNA profile. Genes related to cell cycle, transcription factors, germ cells specific signatures, mRNA spliceosome, chromatin modification, and stemness are shown to be overexpressed in pure basaloid tumors, while genes related to squamous differentiation are shown to be underexpressed. This is highly coherent with the poorly differentiated status fast growth and aggressiveness of these tumors. Moreover, unsupervised analyses identify a molecular subgroup corresponding to pure basaloïd tumors. The transcription factor SOX4 showed 100% specificity and 50% sensitivity to discriminate basaloïd tumors in our cohort confirmed by immunohistochemical analysis. Using a centroid-based predictor, this molecular subtype was found in 8 independent public datasets (n=58/533), and was shown associated to a very poor survival as compared to other SCC (adjusted HR =2.45, p =0.00001 SCC. In addition to gene copy number alterations common to all SCC at the single gene level, gains of MYB, JUN, FGFR1, PIK3C3, DSC/DSG genes were found more frequent in pure basaloïd tumors. First identification of genomic druggable oncogene target were FGFR1 amplification [4] sensitive to a specific FGFR inhibitor [5] and DDR2 (Discoidin domain receptor) mutation [6] sensitive to dasatinib. Recently significant knowledge of genomics of SCC has been provided by comprehensive analysis of genetic alteration as part of the cancer gene genome atlas (TGA) [7] which transformed the landscape of genomic and epigenomic alterations. Among specific genetic alterations discovered as driver oncogenes targetable by specific therapies, FGFR1 amplification to 25 % of SCC even smokers restricted to those cases exposed to tobacco carcinogens (upper and lower airways) exclusively, DDR2 mutation accounting for 3 % of SCCand PIK3 amplication (PIK3CA inhibitors). The PIK3CA is amplified in 20-30 % of SCC. In addition, frequent mutation has been discovered on CDKN2/P16 gene, PTEN, PIK3CA, KEAP1 and other NRF2 complex (NRF2, Cul3) and MLL2, as well as significant copy number alterations including amplifications on SOX2, confirming previous description of a 3q 26 amplicon in all subtypes triggering high expression of SOX2 ,TP63 and PIK3CA [8, 9] and deletion of CDKN2/P16. Many of the somatic alterations identified in SCC were drivers of pathway important for initiation and tumor progression even those not yet but potentially targetable like SOX2. Therapeutic targets are ready for DDR2 mutation (dasatinib) and FRGR1 amplification (FGFR TKI) with anticipated approval for a target for PIK3CA. All together about 60 % of squamous cell carcinoma are potentially targetable with specific therapies [7,10]. Citation Format: Elisabeth Brambilla. Squamous cell carcinoma pathology, etiology, and molecular drivers. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA09.

Severe acute respiratory syndrome: radiographic appearances and pattern of progression in 138 patients.

To retrospectively evaluate the radiographic appearances and pattern of progression of severe acute respiratory syndrome (SARS). Chest radiographs obtained at clinical presentation and during treatment in 138 patients with confirmed SARS (66 men, 72 women; mean age, 39 years; age range, 20-83 years) were assessed. Radiographic appearances of pulmonary parenchymal abnormality, distribution, and extent of involvement on initial chest radiographs were documented. Recognizable patterns of radiographic progression were determined by comparing the overall mean percentage of lung involvement for each patient on serial radiographs. Initial chest radiographs were abnormal in 108 of 138 (78.3%) patients and showed air-space opacity. Lower lung zone (70 of 108, 64.8%) and right lung (82 of 108, 75.9%) were more commonly involved. In most patients, peripheral lung involvement was more common (81 of 108, 75.0%). Unifocal involvement (59 of 108, 54.6%) was more common than multifocal or bilateral involvement. No cavitation, lymphadenopathy, or pleural effusion was demonstrated. Four patterns of radiographic progression were recognized: type 1 (initial radiographic deterioration to peak level followed by radiographic improvement) in 97 of 138 patients (70.3%), type 2 (fluctuating radiographic changes) in 24 patients (17.4%), type 3 (static radiographic appearance) in 10 patients (7.3%), and type 4 (progressive radiographic deterioration) in seven patients (5.1%). Initial focal air-space opacity in 44 of 59 patients (74.6%) progressed to unilateral multifocal or bilateral involvement during treatment. Predominant peripheral location; common progression pattern from unilateral focal air-space opacity to unilateral multifocal or bilateral involvement during treatment; and lack of cavitation, lymphadenopathy, and pleural effusion are the more distinctive radiographic findings of SARS.

Roentgenographic findings in pulmonary mucormycosis.

ROENTGENOGRAPHIC FINDINGS IN PULMONARY MUCORMYCOSISROYAL J. BARTRUM, JR., M.D., MURRAY WATNICK, M.D. and PETER G. HERMAN, M.D.Audio Available | Share