Detection of Docetaxel-induced Interstitial Pneumonitis on Ga-68 PSMA PET/CT Imaging.

Ga-68 labeled prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) is increasingly recognized as the best imaging modality for disease staging and detection of recurrent prostate cancer. Despite its name, PSMA expression has been reported in the neovasculature of several nonprostatic benign and malignant pathologies. Docetaxel, a taxane antineoplastic agent, is the mainstay of treatment in castration-resistant prostate cancer and high-volume hormone-sensitive prostate cancer. Although the occurrence of docetaxel-related interstitial lung disease is rare, it may lead to respiratory failure if treatment is delayed. We present a case of metastatic castration-resistant prostate cancer, wherein docetaxel-induced interstitial pneumonitis was detected on Ga-68 PSMA PET/CT after docetaxel administration.

Use of a radiology tool for the diagnosis of pulmonary fibrosis.

OBJECTIVE: The purpose of this paper was to perform an exploratory reader study to assess the utility of a web-based application in assisting non-chest radiologist in correctly diagnosing the radiographic pattern of pulmonary fibrosis. METHODS: Three non-chest radiologists with 5 to 20 years of experience individually reviewed 3 rounds of randomly chosen chest CT scans (round 1: 100 scans, round 2: 50 scans, round 3: 25 scans) from a list of patients with established diagnosis of pulmonary fibrosis. In round 1, radiologists were asked to directly record their diagnosis for the pattern of fibrosis. In round 2 and 3 they were asked to review for features provided in a web-based application and provide diagnosis based on the most likely predicted diagnosis from the application. There was an approximate 1-month interval and relevant tutorials were provided between each round. Diagnosis accuracy is reported by readers at each round. RESULTS: The overall accuracy increased from 63 % (n = 188/299) in round 1 to 74 % in round 3 (n = 52/70) (p = 0.0265). Difficulty in recognition of mosaic attenuation and homogeneous has led to misdiagnosis. Refining the definition for feature homogeneous increased the diagnosis accuracy of NSIP from 42 % (n = 20/48) in round 2 to 65 % (n = 24/37) in round 3(p = 0.0179). The Fleiss Kappa across readers varied from Round 1 to Round 3 with values 0.36 to 0.42. CONCLUSIONS: Using the web-based application with refined definition for feature homogeneous helps to improve the non-subspecialty radiologist's accuracy in diagnosing different types of fibrosis.

[Smoking-related interstitial lung disease : Radiological findings, histopathological correlations, and clinical observations]. / Raucherassoziierte interstitielle Lungenerkrankungen : Radiologisches Erscheinungsbild, histopathologische Korrelation und klinische Aspekte.

CLINICAL/METHODOLOGICAL ISSUE: Identifying smoking-related interstitial lung diseases (SRILD) in smokers is challenging, as clinical manifestations can be nonspecific, and there is a variety of SRILD entities that not only interconnect but can also overlap. RADIOLOGICAL STANDARD PROCEDURES: In diagnosing SRILD, imaging techniques such as high-resolution computed tomography (HRCT) allow the identification of characteristic features, serving as crucial pieces of the puzzle for definitive differentiation. PERFORMANCE: Studies have demonstrated that HRCT exhibits a sensitivity of approximately 80-90% in identifying SRILD, with a specificity around 70-80%. The conclusive diagnosis often requires a correlation between histopathological findings and clinical observations. PRACTICAL RECOMMENDATIONS: Regular monitoring of smokers, especially when experiencing symptoms like shortness of breath and cough, coupled with a comprehensive diagnosis of SRILD, is crucial for accurate identification and individualized therapy.

Canine Visceral Leishmaniasis: A Histological and Immunohistochemical Study of Fibropoiesis in Chronic Interstitial Pneumonitis.

We studied some fibrotic aspects of chronic interstitial pneumonitis in the lungs of dogs infected with Leishmania infantum. The lungs of eleven naturally infected dogs, twelve experimentally infected with two distinct strains of L. infantum (BH401 and BH46), and six uninfected (controls) dogs, were analyzed by histological, parasitological, and immunohistochemical studies. Conventional histology (HE), collagen deposition (Gomori's silver staining for reticulin collagen fibers), and immunohistochemistry for myofibroblast characterization were carried out based on the cellular expression of alpha-smooth muscle actin, vimentin, cytokeratin, E-cadherin, snail antigen homologue 1 (SNAI1) (Snail), and the cytokine expression of transforming growth factor-beta (TGF-ß). Parasitological screening was carried out using conventional polymerase chain reaction (PCR) and the immunohistochemical reaction of streptavidin-peroxidase for visualizing Leishmania amastigotes. Dogs naturally infected with L. infantum and experimentally infected with L. infantum BH401 strains showed intense interstitial pneumonitis characterized by thickening of the alveolar septa as a consequence of an intense diffuse and focal (plaques) chronic exudate of mononuclear cells associated with fibrogenesis. The expression of alpha-actin, vimentin, and TGF-ß was higher in the lung interstitium of all infected dogs than in the other two groups (BH46 strain and controls). Moreover, in both the naturally and experimentally infected dog (BH401 strain) groups, the expression of Snail was moderate to intense in contrast to the other groups. Based on these immunohistochemical results, we concluded that mesenchymal cells are active in promoting changes in the extracellular matrix in the lungs of dogs naturally and experimentally infected with L. infantum, but it depends on the virulence of the parasite.

Brentuximab-induced pneumonitis and organizing pneumonia: a case report with literiture review.

Introduction and importance: Brentuximab vedotin (BV) is an anti-CD30 antibody approved for various cancers, including refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL) among others. In general, BV has been found to be well-tolerated, with the most frequently reported side effects being peripheral neuropathy and neutropenia. BV-induced pneumonitis is extremely rare. To the best of our knowledge, this is the sixth reported instance of BV-induced lung toxicity. Case presentation: This case presents a female patient in her forties diagnosed with cutaneous T-cell lymphoma undergoing BV treatment. She developed acute hypoxic respiratory failure, ultimately, underwent a diagnostic evaluation including a computed tomography (CT) scan, which showed bilateral airspace consolidations and ground-glass opacities, suggestive of organizing pneumonia and diffuse alveolar damage. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy ruled out infection, and pulmonary lymphoma and confirmed the diagnosis of BV-induced pneumonitis. The patient had significant clinical improvement after stopping the offending agent, and starting steroids, with optimal clinical recovery at 8 weeks follow-up. Clinical discussion: Drug-related pneumonitis poses a significant concern in the management of cancer patients. Numerous chemotherapeutic agents, such as bleomycin, cyclophosphamide, methotrexate, thalidomide, and others, have been associated with pulmonary-related toxicities. These adverse effects primarily stem from direct toxicity or immunosuppression-related infections. Less commonly, immune-mediated injury may occur. Conclusion: Physicians must have a high index of suspicion for BV-induced pneumonitis, hence, early recognition with subsequent holding of the causative agent, initiation of immunosuppression with steroids, and occasionally steroid-sparing medications, prevent an otherwise fatal outcome.

MDA5-autoimmunity and interstitial pneumonitis contemporaneous with the COVID-19 pandemic (MIP-C).

BACKGROUND: Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5+-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 is an RNA sensor and a key pattern recognition receptor for the SARS-CoV-2 virus. METHODS: This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018 and December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5+-DM outbreak. FINDINGS: Sixty new anti-MDA5+, but not other MSAs surged between 2020 and 2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response. INTERPRETATION: A distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms. FUNDING: This work was supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC), and in part by the National Institutes of Health (NIH) grant R01-AI155696 and pilot awards from the UC Office of the President (UCOP)-RGPO (R00RG2628, R00RG2642 and R01RG3780) to P.G. S.S was supported in part by R01-AI141630 (to P.G) and in part through funds from the American Association of Immunologists (AAI) Intersect Fellowship Program for Computational Scientists and Immunologists.

Adult respiratory distress syndrome (ARDS) due to omeprazole-induced drug reaction with eosinophilia and systemic symptoms (DRESS): Case report and review of the literature.

Eosinophilia in not an uncommon findings in the intensive care unit (ICU); however, DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome, which is characterized by a hypersensitivity reaction to drugs and manifests as eosinophilia, systemic involvement and maculopapular erythematous rash 2-6 weeks after exposure to the offending drug, is an exceptional occurrence. We present the first case described in the literature of DRESS syndrome with pulmonary involvement in the form of interstitial pneumonitis and persistent adult respiratory distress syndrome (ARDS) secondary to proton pump inhibitors (PPI). The patient made a good recovery after withdrawal of the offending drug and long-term treatment with systemic corticosteroids. We also present a systematic review of all cases of DRESS with pulmonary involvement in the form of interstitial pneumonitis and cases of PPI-induced DRESS published to date; none of these describe pulmonary involvement.

Neonatal-onset pulmonary alveolar proteinosis is a phenotype associated with poor outcomes in surfactant protein-C disorder.

BACKGROUND: Surfactant protein C (SP-C) disorder is a major component of hereditary interstitial lung disease (HILD) among Japanese. The correlation between clinical outcomes and the phenotype/genotype of SP-C disorder has not been evaluated comprehensively. The current study aimed to evaluate the phenotype/genotype correlated with poor outcomes in patients with SP-C disorder. METHODS: Sequencing analysis of SFTPC in 291 candidates with HILD was performed. The phenotype and genotype correlated with poor outcomes were examined. The log-rank test was used to compare the probability of good outcomes between two patient groups. RESULTS: Twenty patients were diagnosed with SP-C disorder. Of nine patients with neonatal-onset disease, four and five presented with pulmonary alveolar proteinosis (PAP) and interstitial pneumonitis (IP), respectively. The remaining 11 patients with late-onset disease had IP. In total, four and 16 patients had PAP and IP phenotypes, respectively. Four of nine patients with neonatal-onset disease died, and one survived after lung transplant. Further, 1 of 11 patients with late-onset disease died. Four patients with neonatal-onset PAP had a significantly lower probability of good outcomes than the remaining patients. Two patients with neonatal-onset PAP had the p.Leu45Arg variant, one died and the another survived after lung transplant. Of eight patients with variants in the BRICHOS domain, one with frame shift variant located in exon 4, one with variant located at the splicing acceptor site of exon 4, and one with variant located at the splicing donor site of exon 4 died. CONCLUSION: Neonatal-onset PAP was a phenotype predicting poor outcomes in patients with SP-C disorder. The p.Leu45Arg variant and splicing disorder of exon 4 might be genotypes predicting poor outcomes in patients with SP-C disorder.

Combination Therapy With Erlotinib and Ramucirumab in a Patient With Epidermal Growth Factor Receptor Mutation Positive Lung Adenocarcinoma and Interstitial Pneumonia: A Case Report.

Interstitial pneumonia often acts as a barrier to lung cancer treatment. We report the case of a 79-year-old man who was diagnosed with epidermal growth factor receptor (EGFR) mutation positive lung adenocarcinoma (T2aN0M0, stage ⅠB, EGFR exon 19 deletion), and was positive for anti-aminoacyl-tRNA synthetase antibodies with interstitial pneumonia. Metastasis in the right seventh rib was detected three months after surgical resection and radiation therapy was initiated. As recurrence was observed at both ends of the radiation field five months later, combination chemotherapy with erlotinib and ramucirumab was initiated. Approximately one year has passed since the start initiation of treatment, and acute exacerbation of interstitial pneumonia has not been observed during the follow-up period observation. The tumor has remained stable, indicating stable disease.

COVID-19? Let me see your hands.

During the first wave of the COVID�19 pandemic, a patient with anti-synthetase syndrome (ASS) was misdiagnosed as having bilateral severe acute respiratory syndrome coronavirus 2 pneumonia on admission. A comprehensive clinical evaluation would have led to the correct diagnosis earlier, as he had some data consistent with ASS on both physical examination and laboratory tests that were initially overlooked. In addition, a malignant lesion in the colon was found on screening for underlying malignancy. In this context, ASS has been considered a low-risk subgroup for cancer among idiopathic inflammatory myopathies. However, this should be interpreted cautiously and should not lead to neglect of adequate cancer screening adjusted for age, sex and other potential risk factors.

Trastuzumab-Induced Interstitial Pneumonitis.

Trastuzumab is a recombinant immunoglobulin G1 monoclonal antibody used to treat human epidermal growth factor receptor 2 (HER2) cancers. Trastuzumab-induced interstitial pneumonitis is a rare adverse effect reported in a few patients. Interstitial pneumonitis presents as symptoms of dyspnea, hypoxia, cough, and fever. If the patient is treated early, corticosteroids can slow or reverse the disease progression. A 41-year-old woman presented with dyspnea and a dry cough three weeks after her third cycle of trastuzumab therapy for breast cancer. A diagnosis of trastuzumab-induced interstitial pneumonitis was made after multiple other disease processes were ruled out. The patient was started on methylprednisolone while inpatient and transitioned to prednisone for outpatient therapy. The patient was maintained on 2-3L of oxygen throughout her hospital stay and was discharged on 3L of oxygen through nasal cannula. Trastuzumab was never restarted after discharge. There have been many trials evaluating the safety, efficacy, and optimal treatment regimen of trastuzumab, but there are only a few reports of interstitial pneumonitis adverse reaction. The lack of correlation and limited cases make this adverse effect very difficult to diagnose and monitor. New trials and case reports can bring an insight into contributing factors, symptoms at onset, and treatment for future patients. With the increase in use of trastuzumab therapy, physicians should be aware of how to diagnose and treat the rare adverse reaction of trastuzumab-induced interstitial pneumonitis.

Case report: Interstitial pneumonitis after initiation of lamotrigine.

The second-generation anticonvulsant lamotrigine is widely used in the psychiatric field as a mood stabilizer or antidepressant augmentation therapy. Although particularly older anticonvulsants are known for their potential to cause hypersensitivity syndromes, newer antiepileptic drugs do hold a certain risk as well. Presenting a case of a 32-year-old male inpatient of African ethnicity suffering from a primary severe depressive episode in the course of a recurrent major depressive disorder, we report the occurrence of a rapid-onset drug-induced pneumonitis. Herewith, the interstitial pneumonitis occurred after the initiation of 25 mg lamotrigine as an augmentation therapy. Except for the clear temporal correlation between the administration of lamotrigine and the onset of pneumonitis, we did not reveal any further potentially causal diagnostic hints. Importantly, no relevant genetic variations of metabolizing enzymes or drug interactions resulting in lamotrigine overdosage as a potential cause of toxicity were identified. Our experience with a potentially life-threatening adverse drug reaction shortly after the initiation of the largely well-tolerated lamotrigine suggests a potential side effect under the second-generation anticonvulsant although similar adverse events are deemed to be very rare.

Infliximab-Induced Interstitial Pneumonitis: A Case Report.

Anti-tumor necrosis factor inhibitors are increasingly being recommended to treat and control a wide range of diseases, including Crohn's disease, ulcerative colitis, rheumatoid, and psoriatic arthritis. Serious pulmonary consequences, ranging from infectious disease to pulmonary edema, airway involvement, and even interstitial lung disease, are well-known multisystemic side effects. Interstitial lung disease is a well-known but uncommon condition. This report presents a case of a 49-year-old man with ulcerative colitis who developed interstitial pneumonitis following three infusions of infliximab therapy based on clinical, radiologic, and pathology data that are consistent with drug-induced interstitial pneumonitis. After stopping infliximab and starting steroid therapy, we noticed complete symptom resolution and improvement in respiratory symptoms and imaging.

Trimethoprim-sulfamethoxazole prevents interstitial pneumonitis in B-cell lymphoma patients receiving chemotherapy: a propensity score matching analysis.

B-cell lymphoma is the most prevalent type of non-Hodgkin lymphoma, for which the standard treatment regimen includes rituximab combined with CHOP. However, some patients may develop interstitial pneumonitis (IP), which can be caused by various factors; one of the most important factors is Pneumocystis jirovecii. It is crucial to investigate the pathophysiology of IP and implement preventive measures since IP can be fatal for some people. The data were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, where patients with B-cell lymphoma received the R-CHOP/R-CDOP regimen with or without prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX). Multivariable logistic regression and propensity score matching (PSM) were used to investigate any potential association. Eight hundred thirty-one patients with B-cell lymphoma were classified into two groups: the non-prophylaxis group without TMP-SMX (n=699) and the prophylaxis group with TMP-SMX (n = 132). IP occurred in 66 patients (9.4%, all in the non-prophylaxis group), with an onset median of three cycles of chemotherapy. Multiple logistic regression analysis demonstrated that IP incidence was associated with pegylated liposome doxorubicin (OR=3.29, 95% CI 1.84-5.90, P<0.001). After utilizing a 1:1 matching algorithm for PSM, 90 patients from each group were obtained. There was a statistical difference between the two cohorts in the IP incidence (non-prophylaxis 12.2% vs prophylaxis 0.0%, P <0.001). The prophylactic use of TMP-SMX could prevent the occurrence of IP whose risk factor was pegylated liposome doxorubicin after chemotherapy for B-cell lymphoma.

Nivolumab-Induced Pneumonitis in a Patient With Urothelial Cancer.

The introduction of immune checkpoint inhibitors has revolutionized cancer treatment. These drugs function by inhibiting the binding of programmed death-1 (PD-1) and its ligand, PD-L1, which inhibits the immune response against cancer cells. Nivolumab is a PD-1 inhibitor that specifically targets the PD-1 pathway. The main side effects of these drugs are unpredictable immune-related toxicities that occur when self-reactive T cells are abnormally activated and cause inflammation in various organs. The organs most often affected are the endocrine glands, lungs, skin, and gut. Recognizing and addressing lung inflammation is crucial, particularly in individuals with lung cancer. However, it can be challenging to diagnose due to the distinctive features of their disease and treatment regimen. This case report presents a 66-year-old man with a medical history of hypertension, chronic kidney disease (stage 3A), hypothyroidism, type 2 diabetes mellitus (DM), and transitional cell carcinoma of the bladder with interstitial pneumonitis secondary to nivolumab. The patient presented to the Eisenhower Medical Center, Rancho Mirage, CA, with dyspnea and cough for two weeks. He received methylprednisolone (Solu-Medrol) at 1.0 mg/kg for immune checkpoint inhibitor-induced pneumonitis and was discharged on 1 liter (L)/min home-oxygen therapy along with prednisone 50 mg twice daily (BD) for six weeks, trimethoprim-sulfamethoxazole (Bactrim) DS BD, and pantoprazole (Protonix) 40 mg once daily. Subsequently, nivolumab therapy was discontinued. At his follow-up visit two weeks later, he felt well and did not need oxygen therapy at rest.

Interstitial Lung Disease in Neonates: A Long Road Is Being Paved.

Background: Interstitial lung disease (ILD) is one of the most difficult conditions in pulmonology due to difficulties in diagnosing, classifying, and treating this condition. They require invasive approaches to diagnose (e.g., lung biopsy), non-applicable methods (e.g., lung function tests in newborns), or potentially non-accessible methods (e.g., genetic testing in not-well-equipped facilities, and several weeks are required for results to be announced). They represent a heterogeneous group of diseases in which the alveolar epithelium, parenchyma, and capillaries of the lungs are damaged, which leads to changes in the pulmonary interstitium, proliferation of connective tissue, and thickening of the alveolar-capillary membranes and alveolar septa. These changes are accompanied by impaired oxygen diffusion, progressive respiratory failure, and radiographic signs of bilateral dissemination. Although adult and child classifications for ILD have evolved over the years, classification for ILD in neonates remains a challenge. Case presentation: Here we discuss ILD in neonates briefly, and report two rare cases of ILD (a male white neonate, two-day-old with fibrosing alveolitis, and another male white neonate, one-day old with desquamative interstitial pneumonitis), with these diagnoses initially thought to be presented only in adulthood. Lung biopsy and histopathological findings of the two neonates have shown mononuclear cells in the alveolar spaces, and thickening of the alveolar walls confirmed the diagnosis of fibrosing alveolitis in one neonate, and desquamation of the large mononuclear cells in the intra-alveolar space in the other neonate, with the diagnosis of desquamative interstitial pneumonitis being confirmed. Interstitial lung disease lacks a consensus guideline on classification and diagnosis in neonates, rendering it one of the greatest challenges to pediatricians and neonatologists with remarkable morbidity and mortality rates. Conclusions: Fibrosing alveolitis and desquamative interstitial pneumonitis (DIP) are not adult-only conditions, although rare in neonates, histopathological examination and clinical practice can confirm the diagnosis. Based on our clinical practice, prenatal and maternal conditions may serve as potential risk factors for developing IDL in neonates, and further studies are needed to prove this hypothesis.

Clinical results of carbon-ion radiotherapy for stage I non-small cell lung cancer with concomitant interstitial lung disease: a Japanese national registry study (J-CROS-LUNG).

Anti-cancer treatments for lung cancer patients with interstitial lung disease (ILD) are challenging. The treatment options for ILD are often limited because of concerns that treatments can cause acute exacerbation (AE) of ILD. This study aimed to analyze the outcomes of carbon-ion radiotherapy (CIRT) for stage I non-small cell lung cancer (NSCLC) with ILD, using a multi-institutional registry. Patients with ILD who received CIRT for stage I NSCLC in CIRT institutions in Japan were enrolled. The indication for CIRT was determined by an institutional multidisciplinary tumor board, and CIRT was performed in accordance with institutional protocols. Thirty patients were eligible. The median follow-up duration was 30.3 months (range, 2.5-58 months), and the total dose ranged from 50 Gy (relative biological effectiveness [RBE]) to 69.6 Gy (RBE), and five different patterns of fractionation were used. The beam delivery method was passive beam in 19 patients and scanning beam in 11 patients. The 3-year overall survival (OS), cause-specific survival, disease-free survival (DFS) and local control (LC) rates were 48.2%, 62.2%, 41.2% and 88.1%, respectively. Grade > 2 radiation pneumonitis occurred in one patient (3.3%). In conclusion, CIRT is a safe treatment modality for stage I NSCLC with concomitant ILD. CIRT is a safe and feasible treatment option for early lung cancer in ILD patients.

Interstitial pneumonitis associated with combined regimen of immunotherapy and conventional therapies-pharmacovigilance database analysis with real-world data validation.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized. METHODS: A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation. RESULTS: Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05-8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60-184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78-1.04; P = 0.160) and 1.49 (95% CI, 0.95-2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34-50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89-7.92; P = 0.12) and 0.66 (95% CI, 0.03-4.55; P = 0.71), respectively, using ICI monotherapy as reference. CONCLUSIONS: Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP.

Interstitial pneumonitis associated with EGFR/ ALK tyrosine kinase inhibitors used in non-small cell lung cancer: an observational, retrospective, pharmacovigilance study.

BACKGROUND: Epidermal Growth Factor Receptor/ Anaplastic Lymphoma Kinase Tyrosine kinase inhibitors (EGFR/ALK TKIs) may provoke fatal interstitial pneumonitis (IP). The study was conducted to characterize the main characteristics of EGFR/ALK TKI-induced IP and identify factors associated with death. RESEARCH DESIGN AND METHODS: A disproportionality analysis was conducted using Vigibase, the World Health Organization pharmacovigilance database. Clinical features of patients with EGFR/ALK-TKI-related IP were compared between the fatal and non-fatal groups. RESULTS: A total of 3355 EGFR/ALK-TKI-IP events were identified, over half of them from Asia (57.47%) and mostly the aged (63.21%). Osimertinib appeared the strongest IP association. The median time to onset (TTO) was 40 (interquartile range [IQR] 16-84) days. There were significant differences between the fatal and non-fatal groups in terms of reporting year and TKI regimens (P < 0.05). The fatality rate of erlotinib-induced IP was the highest (35.54%). CONCLUSION: Our study showed that EGFR/ALK TKIs were associated with IP that had a high fatality rate and tended to occur earlier in fatal cases. It is necessary to raise awareness of IP surveillance when EGFR/ALK TKIs were administered.

Clinical and pathological observation of conversion therapy for malignant peritoneal mesothelioma: a case report and literature review.

Background: Malignant mesothelioma (MM) is a tumor originating from the pleura, peritoneum, or pericardial cavity. It is divided into diffuse and localized malignant mesothelioma, with four subtypes in diffuse MM: epithelioid, sarcomatoid, desmoplastic, and biphasic, with biphasic being less common. The onset of this tumor is insidious, and the prognosis is extremely poor in some cases, with a median survival of 6-18 months and no standard treatment options in the past. Aims: We report a case of peritoneal malignant mesothelioma that was successfully treated with transformative therapy. We also review the literature in the hope of providing reference for the treatment and pathological diagnosis of such patients. Methods: The case of the peritoneal malignant mesothelioma was processed and reported in the routine manner for biopsy specimens at different stages. Results and conclusion: We report a case of a malignant tumor originating in the hepatorenal recess, which was diagnosed as biphasic malignant mesothelioma through a biopsy. Immunohistochemical testing showed PD-L1 expression. After multidisciplinary discussion, the patient received transformative treatment, including a trial of combined immunotherapy. The tumor significantly shrank, and the patient obtained a chance for curative surgical resection. Microscopic examination showed significant collagenization in the lesion area, with almost no residual tumor. After 19 months of comprehensive treatment, the patient developed multiple fluffy opacities under the pleura of both lungs. Transthoracic core needle biopsy under CT guidance, the pathology showed organizing pneumonia, considering it as delayed interstitial pneumonitis due to immunotherapy based on previous treatment history. Successful comprehensive treatment was achieved for this case of peritoneal malignant mesothelioma, and the patient has been alive without evidence of disease for 33 months, with long-term follow-up. In this process, the pathologist had three opportunities for pathological diagnosis, which required understanding the patient's medical history, being attentive to the clinical purpose of the specimen, and providing accurate responses to morphological changes at different stages, along with corresponding descriptions and diagnoses to provide effective information for clinical treatment.