The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Mizuki Nishino - One of the best experts on this subject based on the ideXlab platform.
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Imaging of Oncologic Treatment-Related Pneumonitis: A Focused Review on Emerging Issues of Immune-Checkpoint Inhibitor Pneumonitis, From the AJR Special Series on Inflammation.
AJR. American journal of roentgenology, 2021Co-Authors: Mizuki NishinoAbstract:Treatment-related Pneumonitis represents a major challenge in oncology patients undergoing therapy, and imaging plays an essential role in detection, diagnosis, and monitoring of Pneumonitis in these patients. Among various types of Pneumonitis from different kinds of cancer treatments, immune-checkpoint inhibitor-related Pneumonitis (ICI Pneumonitis) has been recognized as an important topic in the radiology and oncology communities in the past few years, given increasing clinical indications for ICI therapy in patients with cancer. Moreover, clinical applications of ICI continue to advance rapidly with novel combination approaches, leading to further emerging challenges. This focused review describes the current knowledge of ICI Pneumonitis and discusses several newly emerging issues involving recurrence and flare of ICI Pneumonitis, as well as involving Pneumonitis from new combination approaches including ICI with EGFR inhibitors and ICI with radiotherapy. The article concludes with a summary of unmet needs in the care of patients with ICI Pneumonitis, as well as of future directions in the advancement of knowledge and patient care for ICI Pneumonitis. Given the demonstrated multifaceted value of imaging in ICI Pneumonitis, radiologists will remain central in the ongoing multidisciplinary journey to further understand and overcome this challenging toxicity for patients with cancer.
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immune related ir Pneumonitis during the covid 19 pandemic multidisciplinary recommendations for diagnosis and management
Journal for ImmunoTherapy of Cancer, 2020Co-Authors: Jarushka Naidoo, Mizuki Nishino, Patrick M. Forde, Joshua E Reuss, Karthik Suresh, David Fellerkopman, Seema Mehta Steinke, Clare Rock, Douglas B Johnson, Julie R BrahmerAbstract:Immune-related (IR)-Pneumonitis is a rare and potentially fatal toxicity of anti-PD(L)1 immunotherapy. Expert guidelines for the diagnosis and management of IR-Pneumonitis include multidisciplinary input from medical oncology, pulmonary medicine, infectious disease, and radiology specialists. Severe acute respiratory syndrome coronavirus 2 is a recently recognized respiratory virus that is responsible for causing the COVID-19 global pandemic. Symptoms and imaging findings from IR-Pneumonitis and COVID-19 pneumonia can be similar, and early COVID-19 viral testing may yield false negative results, complicating the diagnosis and management of both entities. Herein, we present a set of multidisciplinary consensus recommendations for the diagnosis and management of IR-Pneumonitis in the setting of COVID-19 including: (1) isolation procedures, (2) recommended imaging and interpretation, (3) adaptations to invasive testing, (4) adaptations to the management of IR-Pneumonitis, (5) immunosuppression for steroid-refractory IR-Pneumonitis, and (6) management of suspected concurrent IR-Pneumonitis and COVID-19 infection. There is an emerging need for the adaptation of expert guidelines for IR-Pneumonitis in the setting of the global COVID-19 pandemic. We propose a multidisciplinary consensus on this topic, in this position paper.
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Pneumonitis resulting from radiation and immune checkpoint blockade illustrates characteristic clinical radiologic and circulating biomarker features
Journal for ImmunoTherapy of Cancer, 2019Co-Authors: Jonathan D Schoenfeld, Mizuki Nishino, Mariano Severgnini, Michael Manos, Raymond H Mak, Stephen F HodiAbstract:Pneumonitis is a potential consequence of both lung-directed radiation and immune checkpoint blockade (ICB), particularly treatment with PD-1/PD-L1 inhibitors. Significant morbidity and mortality can result, and severe Pneumonitis attributed to ICB precludes continued therapy. Thus, discriminating between radiation- and ICB- related Pneumonitis is of importance for the increasing number of patients receiving both treatments. Furthermore, data are limited regarding the interplay between radiation- and ICB-induced lung injury, and which biomarkers might be associated with toxicity. We report longitudinal clinical and radiologic data, and circulating biomarkers in a melanoma patient treated with axillary radiation followed by ICB who developed consolidation and ground glass opacities (GGO) within the radiation field suggestive of radiation-Pneumonitis followed by consolidation outside of the radiation field suggestive of ICB-related Pneumonitis. Of note, symptomatic radiation-Pneumonitis developed despite a low radiation dose to the lung (V20 < 8%), and ICB-related Pneumonitis was limited to the ipsilateral lung, suggesting additive effect of radiation and ICB in the development of lung injury. Circulating biomarker analyses demonstrated increases in CXCR2, IL1ra and IL2ra that coincided with the development of symptomatic Pneumonitis. These data highlight the imaging findings associated with radiation and ICB-related lung toxicity, and anecdotally describe a clinical course with circulating biomarker correlates. This information can help guide clinical evaluation and future research investigations into the toxicity of combined radiation immunotherapy approaches.
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Pneumonitis in advanced non small cell lung cancer nsclc patients pts treated with epidermal growth factor receptor egfr tyrosine kinase inhibitor tki meta analysis of 153 trial cohorts with 15 713 pts
Journal of Clinical Oncology, 2018Co-Authors: Chong Hyun Suh, Hiroto Hatabu, Hyesun Park, Kyung Won Kim, Junhee Pyo, Mizuki NishinoAbstract:e21223Background: Pneumonitis is a significant toxicity of EGFR-TKI in NSCLC pts. We studied the incidence of EGFR-TKI Pneumonitis in clinical trials published in 2003-2017, and performed subgroups...
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pd 1 inhibitor related Pneumonitis in advanced cancer patients radiographic patterns and clinical course
Clinical Cancer Research, 2016Co-Authors: Mizuki Nishino, Hiroto Hatabu, Nikhil H Ramaiya, Mark M Awad, Lynette M Sholl, Jennifer A Maattala, Myriam Taibi, Patrick A Ott, Philippe Armand, Stephen F HodiAbstract:Purpose: Investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor–related Pneumonitis in advanced cancer patients. Experimental Design: Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed Pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of Pneumonitis. Results: Among 170 patients treated in 10 different trials of nivolumab, 20 patients (10 melanoma, 6 lymphoma, and 4 lung cancer) developed Pneumonitis. Five patients received nivolumab monotherapy, and 15 received combination therapy. The median time from therapy initiation to Pneumonitis was 2.6 months. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 13, nonspecific interstitial pneumonia (NSIP) in 3, hypersensitivity Pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. The AIP/ARDS pattern had the highest grade, followed by COP, whereas NSIP and HP had lower grade (median grade: 3, 2, 1, 1, respectively; P = 0.006). The COP pattern was most common in all tumors and treatment regimens. Most patients (17/20; 85%) received corticosteroids, and 3 (15%) also required infliximab. Seven patients restarted nivolumab therapy; 2 of them developed recurrent Pneumonitis and were successfully retreated with corticosteroids. One of the patients experienced a Pneumonitis flare after completion of corticosteroid taper without nivolumab retreatment. Conclusions: PD-1 inhibitor–related Pneumonitis showed a spectrum of radiographic patterns, reflecting Pneumonitis grades. COP was the most common pattern across tumor types and therapeutic regimens. Most patients were successfully treated with corticosteroids. Recurrent Pneumonitis and Pneumonitis flare were noted in a few patients. Clin Cancer Res; 22(24); 6051–60. ©2016 AACR. See related commentary by Castanon, p. 5956
Stephen F Hodi - One of the best experts on this subject based on the ideXlab platform.
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Pneumonitis resulting from radiation and immune checkpoint blockade illustrates characteristic clinical radiologic and circulating biomarker features
Journal for ImmunoTherapy of Cancer, 2019Co-Authors: Jonathan D Schoenfeld, Mizuki Nishino, Mariano Severgnini, Michael Manos, Raymond H Mak, Stephen F HodiAbstract:Pneumonitis is a potential consequence of both lung-directed radiation and immune checkpoint blockade (ICB), particularly treatment with PD-1/PD-L1 inhibitors. Significant morbidity and mortality can result, and severe Pneumonitis attributed to ICB precludes continued therapy. Thus, discriminating between radiation- and ICB- related Pneumonitis is of importance for the increasing number of patients receiving both treatments. Furthermore, data are limited regarding the interplay between radiation- and ICB-induced lung injury, and which biomarkers might be associated with toxicity. We report longitudinal clinical and radiologic data, and circulating biomarkers in a melanoma patient treated with axillary radiation followed by ICB who developed consolidation and ground glass opacities (GGO) within the radiation field suggestive of radiation-Pneumonitis followed by consolidation outside of the radiation field suggestive of ICB-related Pneumonitis. Of note, symptomatic radiation-Pneumonitis developed despite a low radiation dose to the lung (V20 < 8%), and ICB-related Pneumonitis was limited to the ipsilateral lung, suggesting additive effect of radiation and ICB in the development of lung injury. Circulating biomarker analyses demonstrated increases in CXCR2, IL1ra and IL2ra that coincided with the development of symptomatic Pneumonitis. These data highlight the imaging findings associated with radiation and ICB-related lung toxicity, and anecdotally describe a clinical course with circulating biomarker correlates. This information can help guide clinical evaluation and future research investigations into the toxicity of combined radiation immunotherapy approaches.
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pd 1 inhibitor related Pneumonitis in advanced cancer patients radiographic patterns and clinical course
Clinical Cancer Research, 2016Co-Authors: Mizuki Nishino, Hiroto Hatabu, Nikhil H Ramaiya, Mark M Awad, Lynette M Sholl, Jennifer A Maattala, Myriam Taibi, Patrick A Ott, Philippe Armand, Stephen F HodiAbstract:Purpose: Investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor–related Pneumonitis in advanced cancer patients. Experimental Design: Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed Pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of Pneumonitis. Results: Among 170 patients treated in 10 different trials of nivolumab, 20 patients (10 melanoma, 6 lymphoma, and 4 lung cancer) developed Pneumonitis. Five patients received nivolumab monotherapy, and 15 received combination therapy. The median time from therapy initiation to Pneumonitis was 2.6 months. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 13, nonspecific interstitial pneumonia (NSIP) in 3, hypersensitivity Pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. The AIP/ARDS pattern had the highest grade, followed by COP, whereas NSIP and HP had lower grade (median grade: 3, 2, 1, 1, respectively; P = 0.006). The COP pattern was most common in all tumors and treatment regimens. Most patients (17/20; 85%) received corticosteroids, and 3 (15%) also required infliximab. Seven patients restarted nivolumab therapy; 2 of them developed recurrent Pneumonitis and were successfully retreated with corticosteroids. One of the patients experienced a Pneumonitis flare after completion of corticosteroid taper without nivolumab retreatment. Conclusions: PD-1 inhibitor–related Pneumonitis showed a spectrum of radiographic patterns, reflecting Pneumonitis grades. COP was the most common pattern across tumor types and therapeutic regimens. Most patients were successfully treated with corticosteroids. Recurrent Pneumonitis and Pneumonitis flare were noted in a few patients. Clin Cancer Res; 22(24); 6051–60. ©2016 AACR. See related commentary by Castanon, p. 5956
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incidence of programmed cell death 1 inhibitor related Pneumonitis in patients with advanced cancer a systematic review and meta analysis
JAMA Oncology, 2016Co-Authors: Mizuki Nishino, Hiroto Hatabu, Nikhil H Ramaiya, Anita Giobbiehurder, Stephen F HodiAbstract:Importance Programmed cell death 1 (PD-1) inhibitor–related Pneumonitis is a rare but clinically serious and potentially life-threatening adverse event. Little is known about its incidence across different tumor types and treatment regimens. Objective To compare the incidence of PD-1 inhibitor–related Pneumonitis among different tumor types and therapeutic regimens. Data Sources A PubMed search through November 10, 2015, and a review of references from relevant articles. For the PubMed search, the following keywords or corresponding Medical Subject Heading terms were used: nivolumab , pembrolizumab , and PD-1 inhibitor . Study Selection Twenty-six original articles of PD-1 inhibitor trial results were identified. Among them, 20 studies of melanoma, non–small cell lung cancer (NSCLC), or renal cell carcinoma (RCC) were eligible for a meta-analysis. Data Extraction and Synthesis The data were extracted by 1 primary reviewer and then independently reviewed by 2 secondary reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comparisons of the incidence were based on marginal, exact generalized linear models with generalized estimating equations. Main Outcomes and Measures Incidence of all-grade and grade 3 or higher Pneumonitis and Pneumonitis-related deaths. Results Twenty studies of single-tumor-type trials of PD-1 inhibitor (12 melanoma studies, 5 NSCLC studies, and 3 RCC studies) (a total of 4496 unique patients) were included in the meta-analysis. The overall incidence of Pneumonitis during PD-1 inhibitor monotherapy was 2.7% (95% CI, 1.9%-3.6%) for all-grade and 0.8% (95% CI, 0.4%-1.2%) for grade 3 or higher Pneumonitis. The incidence was higher in NSCLC for all-grade (4.1% vs 1.6%; P = .002) and grade 3 or higher Pneumonitis (1.8% vs 0.2%; P P P P = .001) in melanoma, with 1 Pneumonitis-related death during combination therapy. Multivariable analyses demonstrated higher odds of Pneumonitis in NSCLC for all-grade (odds ratio [OR], 1.43; 95% CI, 1.08-1.89; P = .005) and grade 3 or higher Pneumonitis (OR, 2.85; 95% CI, 1.60-5.08; P P P P Conclusions and Relevance The incidence of PD-1 inhibitor–related Pneumonitis was higher in NSCLC and RCC and during combination therapy. These findings contribute to enhance awareness among clinicians and support further investigations to meet the clinical needs.
Yvon Cormier - One of the best experts on this subject based on the ideXlab platform.
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farmer s lung induced hypersensitivity Pneumonitis complicated by shock
Respiratory Care, 2011Co-Authors: Dominique Deschenes, Steeve Provencher, Yvon CormierAbstract:Hypersensitivity Pneumonitis is an immunologic reaction to an inhaled antigen, with a wide spectrum of clinical presentations. The most common manifestations are fever, cough, and dyspnea. We describe a case of hypersensitivity Pneumonitis with marked alveolar lymphocytosis; the patient presented with respiratory failure and shock requiring mechanical ventilation and vasopressive agents. We hypothesized that immune mediators implicated in the pathogenesis of hypersensitivity Pneumonitis were responsible for the transient shock observed in this patient.
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Hypersensitivity Pneumonitis.
Current opinion in allergy and clinical immunology, 2010Co-Authors: Mélissa Girard, Yvon CormierAbstract:To bring readers up to date on recent reports, both clinical and basic understanding, on hypersensitivity Pneumonitis. Although many antigens and environmental settings have already been described as sources of this hyperimmune pulmonary disease, the literature continues to bring forth other conditions that can cause hypersensitivity Pneumonitis. We also highlight new findings in the diagnosis of hypersensitivity Pneumonitis, its histopathology, insight into its potential outcomes, and understanding of its immune mechanisms that could lead to new treatments. The review will help clinicians in their diagnostic approach to hypersensitivity Pneumonitis and lead them to look for other potential sources of the disease. The findings described will help guide further research on the pathophysiology and seek new treatments for this worldwide orphan disease.
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Pathogenesis of hypersensitivity Pneumonitis.
Current opinion in allergy and clinical immunology, 2004Co-Authors: Mélissa Girard, Evelyne Israël-assayag, Yvon CormierAbstract:PURPOSE OF REVIEW Hypersensitivity Pneumonitis is a group of immunologically mediated diseases caused by an abnormal response to a wide variety of inhaled antigens. Its pathogenesis is complex and involves many immunological concepts. This review discusses recent advances in our understanding of the pathogenesis of hypersensitivity Pneumonitis. RECENT FINDINGS Over the last 3 years, several studies on the pathogenesis of hypersensitivity Pneumonitis have been published. New antigens have been identified. We now have a better understanding of the role of inflammatory cells and mediators, and promoting and protective factors have been suggested. SUMMARY Most of the mechanisms involved in the pathogenesis of hypersensitivity Pneumonitis remain incompletely understood. Current and future findings will not only help our understanding of the disease and its prevention, but also improve its treatment.
Nevin W. Wilson - One of the best experts on this subject based on the ideXlab platform.
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Basement shower hypersensitivity Pneumonitis secondary to epicoccum nigrum
Chest, 1996Co-Authors: Mary Beth Hogan, W. Thomas Corder, Robert S. Pore, Roy Patterson, Nevin W. WilsonAbstract:Two children developed hypersensitivity Pneumonitis after extensive exposure to an unventilated basement shower. Commercial precipitin panels were negative. After home inspection, individual mold species were isolated from the household and extracted. Precipitating antibodies to Epicoccum nigrum were found in both children. Resolution of the hypersensitivity Pneumonitis occurred with avoidance and glucocorticosteroid therapy. E nigrum is a newly identified etiologie agent for hypersensitivity Pneumonitis found in a mold-contaminated home.
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Basement shower hypersensitivity Pneumonitis secondary to Epicoccum nigrum
Chest, 1996Co-Authors: Mary Beth Hogan, W. Thomas Corder, Robert S. Pore, Roy Patterson, Nevin W. WilsonAbstract:Two children developed hypersensitivity Pneumonitis after extensive exposure to an unventilated basement shower. Commercial precipitin panels were negative. After home inspection, individual mold species were isolated from the household and extracted. Precipitating antibodies to Epicoccum nigrum were found in both children. Resolution of the hypersensitivity Pneumonitis occurred with avoidance and glucocorticosteroid therapy. E nigrum is a newly identified etiologic agent for hypersensitivity Pneumonitis found in a mold-contaminated home.
Nikhil H Ramaiya - One of the best experts on this subject based on the ideXlab platform.
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pd 1 inhibitor related Pneumonitis in advanced cancer patients radiographic patterns and clinical course
Clinical Cancer Research, 2016Co-Authors: Mizuki Nishino, Hiroto Hatabu, Nikhil H Ramaiya, Mark M Awad, Lynette M Sholl, Jennifer A Maattala, Myriam Taibi, Patrick A Ott, Philippe Armand, Stephen F HodiAbstract:Purpose: Investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor–related Pneumonitis in advanced cancer patients. Experimental Design: Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed Pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of Pneumonitis. Results: Among 170 patients treated in 10 different trials of nivolumab, 20 patients (10 melanoma, 6 lymphoma, and 4 lung cancer) developed Pneumonitis. Five patients received nivolumab monotherapy, and 15 received combination therapy. The median time from therapy initiation to Pneumonitis was 2.6 months. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 13, nonspecific interstitial pneumonia (NSIP) in 3, hypersensitivity Pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. The AIP/ARDS pattern had the highest grade, followed by COP, whereas NSIP and HP had lower grade (median grade: 3, 2, 1, 1, respectively; P = 0.006). The COP pattern was most common in all tumors and treatment regimens. Most patients (17/20; 85%) received corticosteroids, and 3 (15%) also required infliximab. Seven patients restarted nivolumab therapy; 2 of them developed recurrent Pneumonitis and were successfully retreated with corticosteroids. One of the patients experienced a Pneumonitis flare after completion of corticosteroid taper without nivolumab retreatment. Conclusions: PD-1 inhibitor–related Pneumonitis showed a spectrum of radiographic patterns, reflecting Pneumonitis grades. COP was the most common pattern across tumor types and therapeutic regimens. Most patients were successfully treated with corticosteroids. Recurrent Pneumonitis and Pneumonitis flare were noted in a few patients. Clin Cancer Res; 22(24); 6051–60. ©2016 AACR. See related commentary by Castanon, p. 5956
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incidence of programmed cell death 1 inhibitor related Pneumonitis in patients with advanced cancer a systematic review and meta analysis
JAMA Oncology, 2016Co-Authors: Mizuki Nishino, Hiroto Hatabu, Nikhil H Ramaiya, Anita Giobbiehurder, Stephen F HodiAbstract:Importance Programmed cell death 1 (PD-1) inhibitor–related Pneumonitis is a rare but clinically serious and potentially life-threatening adverse event. Little is known about its incidence across different tumor types and treatment regimens. Objective To compare the incidence of PD-1 inhibitor–related Pneumonitis among different tumor types and therapeutic regimens. Data Sources A PubMed search through November 10, 2015, and a review of references from relevant articles. For the PubMed search, the following keywords or corresponding Medical Subject Heading terms were used: nivolumab , pembrolizumab , and PD-1 inhibitor . Study Selection Twenty-six original articles of PD-1 inhibitor trial results were identified. Among them, 20 studies of melanoma, non–small cell lung cancer (NSCLC), or renal cell carcinoma (RCC) were eligible for a meta-analysis. Data Extraction and Synthesis The data were extracted by 1 primary reviewer and then independently reviewed by 2 secondary reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comparisons of the incidence were based on marginal, exact generalized linear models with generalized estimating equations. Main Outcomes and Measures Incidence of all-grade and grade 3 or higher Pneumonitis and Pneumonitis-related deaths. Results Twenty studies of single-tumor-type trials of PD-1 inhibitor (12 melanoma studies, 5 NSCLC studies, and 3 RCC studies) (a total of 4496 unique patients) were included in the meta-analysis. The overall incidence of Pneumonitis during PD-1 inhibitor monotherapy was 2.7% (95% CI, 1.9%-3.6%) for all-grade and 0.8% (95% CI, 0.4%-1.2%) for grade 3 or higher Pneumonitis. The incidence was higher in NSCLC for all-grade (4.1% vs 1.6%; P = .002) and grade 3 or higher Pneumonitis (1.8% vs 0.2%; P P P P = .001) in melanoma, with 1 Pneumonitis-related death during combination therapy. Multivariable analyses demonstrated higher odds of Pneumonitis in NSCLC for all-grade (odds ratio [OR], 1.43; 95% CI, 1.08-1.89; P = .005) and grade 3 or higher Pneumonitis (OR, 2.85; 95% CI, 1.60-5.08; P P P P Conclusions and Relevance The incidence of PD-1 inhibitor–related Pneumonitis was higher in NSCLC and RCC and during combination therapy. These findings contribute to enhance awareness among clinicians and support further investigations to meet the clinical needs.
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drug related Pneumonitis during mammalian target of rapamycin inhibitor therapy in patients with neuroendocrine tumors a radiographic pattern based approach
European Journal of Cancer, 2016Co-Authors: Mizuki Nishino, Lauren K Brais, Nichole V Brooks, Hiroto Hatabu, Matthew H Kulke, Nikhil H RamaiyaAbstract:Abstract Purpose The purpose of this study was to investigate the incidence of drug-related Pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in patients with neuroendocrine tumours (NET) and characterise radiographic patterns of Pneumonitis. Methods Sixty-six patients (39 males, 27 females, age: 22–79 years) with advanced NET treated with mTOR inhibitor, everolimus, were retrospectively studied. Chest computed tomography scans during therapy were reviewed for abnormalities suspicious for drug-related Pneumonitis by an independent review of two radiologists. Extent, distributions, and specific findings were evaluated in cases positive for Pneumonitis. Radiographic patterns of Pneumonitis were classified using the American Thoracic Society/European Respiratory Society classification of interstitial pneumonia. Results Drug-related Pneumonitis was radiographically detected in 14 patients (21%). Time from the initiation of therapy to Pneumonitis was within 6 months of therapy in 10 patients (71%), while it ranged from 1.0 to 27.7 months. Pneumonitis was more common in patients who had never smoked (p = 0.03). Lower lungs were more extensively involved than upper and middle lungs. Peripheral and lower distributions were most common (n = 8), followed by peripheral and multifocal distributions (n = 3). Ground glass and reticular opacities were present in all cases, with consolidation in eight cases. The radiographic pattern of Pneumonitis was classified as cryptogenic organising pneumonia (COP) pattern in eight patients, non-specific interstitial pneumonia (NSIP) pattern in five, and hypersensitivity Pneumonitis pattern in one patient. Conclusion Drug-related Pneumonitis was noted in 21% of the advanced NET patients treated with everolimus. Radiographic pattern of Pneumonitis was most commonly COP pattern, followed by NSIP pattern.
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Pneumonitis associated with mtor inhibitors therapy in patients with metastatic renal cell carcinoma incidence radiographic findings and correlation with clinical outcome
European Journal of Cancer, 2012Co-Authors: Donnette Dabydeen, Nikhil H Ramaiya, Jyothi P Jagannathan, Katherine M Krajewski, Fabio A B Schutz, Daniel C Cho, Ivan Pedrosa, Toni K ChoueiriAbstract:Abstract Background Mammalian target of rapamycin (mTOR) inhibitors are approved for use in patients with metastatic renal cell carcinoma (mRCC) and are under investigation in several other malignancies. We assessed the incidence, clinical presentation and computed tomography (CT) findings of Pneumonitis associated with mTOR inhibitors in mRCC. Correlation between radiological findings of Pneumonitis and clinical outcome was also determined. Methods We retrospectively reviewed the clinical data and serial CT scans from patients with mRCC treated with either temsirolimus or everolimus. Serial chest CT scans were reviewed in consensus, read by two independent radiologists for the presence of Pneumonitis, and corresponding clinical data were reviewed for symptoms and clinical outcome. The baseline and follow up CTs were reviewed to assess outcome to therapy. Results The study population consisted of 46pts, 21 treated with temsirolimus and 25 with everolimus (M:F 2.5:1; median 63years, range 31–79years). CT evidence of Pneumonitis was seen in 14/46pts (30%), at a median of 56days on mTOR inhibitor treatment (range 31–214days). Respiratory symptoms at the time of radiographically detected Pneumonitis, were observed in 7pts. Stable disease (SD) by Response Evaluation Criteria in Solid Tumours (RECIST) was achieved in 12/14pts (86%) who developed radiographic Pneumonitis compared to 14/32 (44%) without Pneumonitis ( p =0.01) The mean change of tumour long axis size for target lesions by RECIST, normalised for 30days on therapy was –2.9% in the Pneumonitis group and +4.3% in the non-Pneumonitis group ( p =.002). Conclusions Preliminary data suggest that Pneumonitis may be a marker of stable disease by RECIST and therefore, of therapeutic benefit. Careful patient assessment should be undertaken before the drug is discontinued.
