Inhaled corticosteroid use and risk of pneumonitis in patients treated with immune checkpoint inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3140-3140
Author(s):  
Mingjia Li ◽  
Daniel Spakowicz ◽  
Songzhu Zhao ◽  
Sandip H. Patel ◽  
Andrew Johns ◽  
...  

3140 Background: The identification of risk factors for immune-related adverse events (irAEs) is an important area of research. Among irAEs, pneumonitis carries one of the highest morbidities. There is a lack of strong predictors for pneumonitis in patients (pts) treated with ICI. We sought to identify predictors for the development of pneumonitis, and whether the use of inhaled corticosteroids (ICS) at time of ICI could be protective. Methods: Pts with advanced cancer treated with ICI from 2011 and 2018 were included in this retrospective study. Pneumonitis attribution to ICI was determined by treating physician at time of diagnosis. Time to pneumonitis was defined as days from the start of ICI to pneumonitis diagnosis. Pts who never had pneumonitis were censored at the time of last follow up or death. Predictors of pneumonitis were assessed by univariate Cox proportional hazard models at a significance threshold of alpha = 0.05. Results: A total of 837 pts were identified, and 30 (3.6%) pts developed any grade pneumonitis (12 grade 2, 14 grade 3, 1 grade 4, 3 grade 5) after receiving ICI (Table). Pts with age ≥65 years (y) had increased risk of developing pneumonitis over pts with age < 65y (HR 2.1, 95 CI: 1.02-4.4, p=0.041). 82 (9.7%) of the total cohort were on inhaled corticosteroid (ICS) at time of ICI, and 9 (11%) developed pneumonitis. Rather than being protective, pts on ICS had higher risk of pneumonitis (HR 4.2, 95 CI: 1.9-9.2, p=0.001). Pts with lung cancer had an increased risk for pneumonitis compared to pts with other cancers (HR 3.2, 95 CI: 1.5-6.4, p =0.003). Other risk factors included performance status, smoking history, line of therapy, or prior treatment including radiation were not statistically significant. Conclusions: Rather than a protective effect of ICS, our analysis found a higher risk of pneumonitis in pts treated with ICS. We confirmed an increased risk of pneumonitis for lung cancer pts compared to pts with other cancers, and higher risk of pneumonitis in pts age >65y. We hypothesize that the increased inflammatory status in chronic lung inflammation may predispose pts to pneumonitis that was not ameliorated by ICS. Future study is needed in prospective cohorts to further clarify the underlying inflammatory mechanism. [Table: see text]

Author(s):  
Alvin J. X. Lee ◽  
Karin Purshouse

AbstractThe SARS-Cov-2 pandemic in 2020 has caused oncology teams around the world to adapt their practice in the aim of protecting patients. Early evidence from China indicated that patients with cancer, and particularly those who had recently received chemotherapy or surgery, were at increased risk of adverse outcomes following SARS-Cov-2 infection. Many registries of cancer patients infected with SARS-Cov-2 emerged during the first wave. We collate the evidence from these national and international studies and focus on the risk factors for patients with solid cancers and the contribution of systemic anti-cancer treatments (SACT—chemotherapy, immunotherapy, targeted and hormone therapy) to outcomes following SARS-Cov-2 infection. Patients with cancer infected with SARS-Cov-2 have a higher probability of death compared with patients without cancer. Common risk factors for mortality following COVID-19 include age, male sex, smoking history, number of comorbidities and poor performance status. Oncological features that may predict for worse outcomes include tumour stage, disease trajectory and lung cancer. Most studies did not identify an association between SACT and adverse outcomes. Recent data suggest that the timing of receipt of SACT may be associated with risk of mortality. Ongoing recruitment to these registries will enable us to provide evidence-based care.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13166-e13166
Author(s):  
Misako Nagasaka ◽  
Dina Farhat ◽  
Kimberly Belzer ◽  
Seongho Kim ◽  
Hirva Mamdani ◽  
...  

e13166 Background: The risk for development of a SPLC after treatment of an IPLC is around 1% to 2% per pt per year. The aim of this study was to characterize the risk factors associated with the development of a SPLC. Methods: Pts registered in the Karmanos Cancer Institute Tumor Registry diagnosed with an IPLC between 2000 and 2017 were included in this study. Pts with an IPLC who later developed a SPLC were matched for age, histology and stage to pts with an IPLC who did not develop a SPLC. SPLC was defined as a second lung cancer with a different pathology or if the same pathology, anatomically, molecularly, or chronologically distinct. Six variables including: stage at IPLC, histology, family history, surgery as a primary treatment for IPLC, and smoking history (determined by pack years, and continued tobacco use after first diagnosis) were reviewed. Logistic and Cox regression analyses were performed to determine the relationship of these characteristics with the development of a SPLC, and their association with overall survival (OS). Results: 121 pts with IPLC who later developed an SPLC were identified and compared to 120 pts with IPLC who did not develop a SPLC. Logistic analyses did not show that stage at first diagnosis, histology, family history, smoking history, and continued tobacco use after first diagnosis to be relevant for increased risk of SPLC. Pts who were primarily treated with surgical resection had a significantly higher probability of developing a SPLC (Odds Ratio: 0.24, 95% CI: 0.12 to 0.48, p < 0.001). Pts who did not have surgical resection as their primary mode of treatment for IPLC had a significantly higher risk of death than those who received surgical resection (HR 3.02, 95% CI: 1.99 to 4.57; p < 0.001). Conclusions: Based on our findings, pts who had surgical resection for an IPLC were found to have improved OS and a higher possibility of developing a SPLC. Stage at first diagnosis of IPLC, histology, family history, smoking history and continued use of tobacco after first diagnosis did not correlate with increased risk for SPLC. These results warrant further investigation and if confirmed could have an impact on surveillance recommendations post resection of initial lung cancers.


2021 ◽  
Vol 9 (3) ◽  
pp. e001935
Author(s):  
Mark Kalinich ◽  
William Murphy ◽  
Shannon Wongvibulsin ◽  
Vartan Pahalyants ◽  
Kun-Hsing Yu ◽  
...  

BackgroundImmune-related adverse events (irAEs) are a serious side effect of immune checkpoint inhibitor (ICI) therapy for patients with advanced cancer. Currently, predisposing risk factors are undefined but understanding which patients are at increased risk for irAEs severe enough to require hospitalization would be beneficial to tailor treatment selection and monitoring.MethodsWe performed a retrospective review of patients with cancer treated with ICIs using unidentifiable claims data from an Aetna nationwide US health insurance database from January 3, 2011 to December 31, 2019, including patients with an identified primary cancer and at least one administration of an ICI. Regression analyses were performed. Main outcomes were incidence of and factors associated with irAE requiring hospitalization in ICI therapy.ResultsThere were 68.8 million patients identified in the national database, and 14 378 patients with cancer identified with at least 1 administration of ICI in the study period. Patients were followed over 19 117 patient years and 504 (3.5%) developed an irAE requiring hospitalization. The incidence of irAEs requiring hospitalization per patient ICI treatment year was 2.6%, rising from 0% (0/71) in 2011 to 3.7% (93/2486) in 2016. Combination immunotherapy (OR: 2.44, p<0.001) was associated with increased odds of developing irAEs requiring hospitalization, whereas older patients (OR 0.98 per additional year, p<0.001) and those with non-lung cancer were associated with decreased odds of irAEs requiring hospitalization (melanoma OR: 0.70, p=0.01, renal cell carcinoma OR: 0.71, p=0.03, other cancers OR: 0.50, p<0.001). Sex, region, zip-code-imputed income, and zip-code unemployment were not associated with incidence of irAE requiring hospitalization. Prednisone (72%) and methylprednisolone (25%) were the most common immunosuppressive treatments identified in irAE hospitalizations.ConclusionsWe found that 3.5% of patients initiating ICI therapy experienced irAEs requiring hospitalization and immunosuppression. The odds of irAEs requiring hospitalization were higher with younger age, treatment with combination ICI therapy (cytotoxic T lymphocyte-associated 4 and programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1)), and lower for other cancers compared with patients on PD-1 or PD-L1 inhibitors with lung cancer. This evidence from the first nationwide study of irAEs requiring hospitalization in the USA identified the real-world epidemiology, risk factors, and treatment patterns of these irAEs which may guide treatment and management decisions.


Author(s):  
Mahnaz Mozdourian ◽  
Rozita Khodashahi

: The incidence of nontuberculous mycobacterial (NTM) pulmonary disease has increased in recent years. It seems that patients with structural lung diseases treated with inhaled corticosteroids (ICS) are at risk of pulmonary NTM infection. This systematic review investigated the articles focused on the association between the use of ICS and pulmonary NTM infection. The current study assessed four categories, namely the association between the use of ICS therapy and NTM infections, bacterial factors involved in the incidence of NTM infection in patients undergoing ICS therapy, relationship between dosage and long-term use of ICS therapy in the incidence of NTM infection, and main risk factors of the incidence of NTM infection in patients undergoing ICS therapy. Based on the obtained results of the present study, there was an association between the use of ICS therapy and NTM infections. It seems that ICS increases the risk of NTM infection by 1.8 to 8 times. Accordingly, 40-90% of patients with NTM had a history of ICS usage. Mycobacterium avium complex was the most common bacterial factor in NTM patients undergoing ICS therapy. The relationship between a higher dosage of ICS therapy and increased risk of NTM was confirmed in the majority of the studies. Age, gender, smoking history, and underlying diseases are the main risk factors for the incidence of NTM in patients receiving ICS therapy.


Author(s):  
Michael P. Hagerty ◽  
Rafael Walker-Santiago ◽  
Jason D. Tegethoff ◽  
Benjamin M. Stronach ◽  
James A. Keeney

AbstractThe association of morbid obesity with increased revision total knee arthroplasty (rTKA) complications is potentially confounded by concurrent risk factors. This study was performed to evaluate whether morbid obesity was more strongly associated with adverse aseptic rTKA outcomes than diabetes or tobacco use history—when present as a solitary major risk factor. Demographic characteristics, surgical indications, and adverse outcomes (reoperation, revision, infection, and amputation) were compared between 270 index aseptic rTKA performed for patients with morbid obesity (n = 73), diabetes (n = 72), or tobacco use (n = 125) and 239 “healthy” controls without these risk factors at a mean 75.7 (range: 24–111) months. There was no difference in 2-year reoperation rate (17.8 vs. 17.6%, p = 1.0) or component revision rate (8.2 vs. 8.4%) between morbidly obese and healthy patients. However, higher reoperation rates were noted in patients with diabetes (p = 0.02) and tobacco use history (p < 0.01), including higher infection (p < 0.05) and above knee amputation (p < 0.01) rates in patients with tobacco use history. Multivariate analysis retained an independent association between smoking history and amputation risk (odds ratio: 7.4, 95% confidence interval: 1.7–55.2, p < 0.01). Morbid obesity was not associated with an increased risk of reoperation or component revision compared with healthy patients undergoing aseptic revision. Tobacco use was associated with increased reoperation and above knee amputation. Additional study will be beneficial to determine whether risk reduction efforts are effective in mitigating postoperative complication risks.


Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 384 ◽  
Author(s):  
Ashley Hopkins ◽  
Anh-Minh Nguyen ◽  
Christos Karapetis ◽  
Andrew Rowland ◽  
Michael Sorich

Afatinib is an effective therapy for metastatic non-small cell lung cancer (NSCLC) but it is associated with a relatively high incidence of severe diarrhea. The association between pre-treatment candidate predictors (age, sex, race, performance status, renal function, hemoglobin, and measures of body mass) and severe (grade ≥ 3) diarrhea was evaluated using logistic regression with pooled individual participant data from seven clinical studies. A risk score was developed based on the count of major risk factors. Overall, 184 of 1151 participants (16%) experienced severe diarrhea with use of afatinib. Body weight, body mass index, and body surface area all exhibited a prominent non-linear association where risk increased markedly at the lower range (p < 0.005). Low weight (<45 kg), female sex, and older age (≥60 years) were identified as major independent risk factors (p < 0.01). Each risk factor was associated with a two-fold increase in the odds of severe diarrhea, and this was consistent between individuals commenced on 40 mg or 50 mg afatinib. A simple risk score based on the count of these risk factors identifies individuals at lowest and highest risk (C-statistic of 0.65). Risk of severe diarrhea for individuals commenced on 40 mg afatinib ranged from 6% for individuals with no risk factors to 33% for individuals with all three risk factors.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi148-vi148
Author(s):  
Alexander Ou ◽  
Heather Lin ◽  
Ying Yuan ◽  
Charles Bornstein ◽  
Kristin Alfaro-Munoz ◽  
...  

Abstract BACKGROUND Patients with high-grade gliomas (HGG) often receive anti-angiogenic therapy with bevacizumab to slow disease progression and/or palliate neurological symptoms. Bevacizumab has been associated with an increased risk of two major vascular complications: venous thromboembolism (VTE) and intracranial hemorrhage (ICH). We sought to identify clinical, pathologic, and radiographic variables correlated with risk of either event occurring in patients with HGG receiving bevacizumab. METHODS We retrospectively identified 94 patients with HGG who received bevacizumab at our center from 2015-2021. Variables included demographics, performance status, IDH, MGMT, vascular risk factors, baseline anti-coagulant/anti-platelet use, concurrent chemotherapy, and presence of macrobleeds on MRI (&gt;1 cm3 susceptibility) at the time of bevacizumab initiation. We conducted competing risk analysis using subdistribution hazard models with death as competing risk for ICH or VTE. The effects of covariates on the incidence of hemorrhage or VTE were evaluated in univariate and multivariate settings. RESULTS Of 94 patients, 36 (38.3%) and 27 (28.7%) developed VTE and ICH, respectively. 31 (33%) did not develop either. ICH and VTE events occurred after a mean of 4.46 and 5.94 cycles of bevacizumab, respectively. 20 had baseline anti-platelet/anticoagulant use, and 16 had prior VTEs. Patients with macrobleeds on MRI had a larger HR of developing acute hemorrhage [HR=2.368 (1.112, 5.043), p=0.0254]. Patients older than 50 trended toward larger HR of developing VTE in univariate analysis that approached significance [HR=1.799 (0.889, 3.637), p=0.1023]. Sex, performance status, IDH, MGMT, vascular risk factors, baseline anticoagulant/anti-platelet use and concurrent chemotherapy were not significantly associated with occurrence of VTE. CONCLUSIONS The presence of macrobleeds on MRI is associated with increased risk of developing acute ICH while on bevacizumab. Older age at diagnosis of HGG may be associated with an increased risk of VTE in patients receiving bevacizumab. Larger studies are needed to confirm these findings.


2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Chengyan Zhang ◽  
Guanchao Pang ◽  
Chengxi Ma ◽  
Jingni Wu ◽  
Pingli Wang ◽  
...  

Background. Lymph node status of clinical T1 (diameter≤3 cm) lung cancer largely affects the treatment strategies in the clinic. In order to assess lymph node status before operation, we aim to develop a noninvasive predictive model using preoperative clinical information. Methods. We retrospectively reviewed 924 patients (development group) and 380 patients (validation group) of clinical T1 lung cancer. Univariate analysis followed by polytomous logistic regression was performed to estimate different risk factors of lymph node metastasis between N1 and N2 diseases. A predictive model of N2 metastasis was established with dichotomous logistic regression, externally validated and compared with previous models. Results. Consolidation size and clinical N stage based on CT were two common independent risk factors for both N1 and N2 metastases, with different odds ratios. For N2 metastasis, we identified five independent predictors by dichotomous logistic regression: peripheral location, larger consolidation size, lymph node enlargement on CT, no smoking history, and higher levels of serum CEA. The model showed good calibration and discrimination ability in the development data, with the reasonable Hosmer-Lemeshow test (p=0.839) and the area under the ROC being 0.931 (95% CI: 0.906-0.955). When externally validated, the model showed a great negative predictive value of 97.6% and the AUC of our model was better than other models. Conclusion. In this study, we analyzed risk factors for both N1 and N2 metastases and built a predictive model to evaluate possibilities of N2 metastasis of clinical T1 lung cancers before the surgery. Our model will help to select patients with low probability of N2 metastasis and assist in clinical decision to further management.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10594-10594
Author(s):  
S. Carrera ◽  
G. López-Vivanco ◽  
B. Calvo ◽  
U. Aresti ◽  
M. S. Jangi ◽  
...  

10594 Background: Telomerase adds hexameric TTAGGG nucleotide repeats onto the ends of chromosomal DNAs to compensate for losses of each cell replication. In several tumors, telomerase is expressed in a way that tumoral cell proliferates indefinitely. Correlation between telomerase level expression, clinico-pathological characteristics and survival of lung cancer is not well established in NSCLC. Methods: We studied 149 consecutive patients (140 men/9 women) with resected NSCLC: 37.6% adenocarcinoma, 59 % squamous cell, and 3.4% large cell carcinoma. Pathological stage: I (36.9%), II (32.3%) and III (30.8%). Reverse transcription-polymerase chain reaction (RT-PCR) analysis was used for the detection hTERT expression in lung cancer tissues immediately snap-frozen in liquid nitrogen at -80 °C. Results: Median and mean values of hTERT mRNA were 18.27 and 475.29 (SE 309.76). There were no significant differences on expression according to sex, histology, smoking history and pathological stage (ANOVA). Patients with highest values of hTERT mRNA expression (percentile 95, cut-off value >353) had worse median progression free survival (PFS) (p=0.024) and overall survival (OS) (p=0.020), using Kaplan-Meier method. Multivariate analysis by Cox regression yielded that hTERT level > 353 independently predicted a worse PFS (HR=0.39; 95% CI 0.17–0.93, p=0.034) and OS (HR=0.32; 95% CI 0.12–0.82, p=0.017). Conclusions: A high level of telomerase expression in tumoral tissue is strongly associated with increased risk of recurrence and mortality in resected NSCLC. The level of hTERT mRNA would predict the prognosis of lung cancer patients. No significant financial relationships to disclose.


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