scholarly journals The Diagnostic Value of Chromogranin A in Neuroendocrine Neoplasms is Potentiated by Clinical Factors and Inflammatory Markers

Endocrines ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 1-12
Author(s):  
Olga Papalou ◽  
Melpomeni Peppa ◽  
Eleni Kandaraki ◽  
Evanthia Diamanti-Kandarakis ◽  
George Nikou
Keyword(s):  
Metastatic Disease ◽  
Chromogranin A ◽  
Clinical Laboratory ◽  
Probability Model ◽  
Diagnostic Value ◽  
Initial Diagnosis ◽  
Neuroendocrine Neoplasms ◽  
Special Focus ◽  
Accurate Identification ◽  
Increased Risk

Objective: Neuroendocrine neoplasms (NENs) are a heterogenous group of indolent tumors, with variable clinical behavior and steadily rising incidence. The aim of this study is to investigate the clinical and laboratory factors that contribute in predicting the aggressiveness and invasiveness of NENs. Special focus is given to clinical parameters that would enhance the diagnostic value of chromogranin A (CgA), via formalizing an integrated probability model, which would contribute to the timely and accurate identification of patients at high risk for metastatic disease at initial diagnosis. Designs and Methods: We identified a total of 93 patients with NENs, recruited at a specialized academic center in Athens, Greece. Anthropometric, clinical, laboratory, and pathological data were obtained from every patient before any therapeutic intervention. Results: Age over 50 years and male gender were accompanied by increased risk for metastases at the time of initial diagnosis. Additionally, when these parameters were combined with CgA levels, they were shown to enhance the predictive capacity of CgA. Different patient scenarios combining age, gender, and CgA levels are associated with different probabilities for metastatic disease, demonstrated schematically in a gradually escalating model, as age and CgA levels increase in both males and females. The lowest risk is observed in women aged <50 years old with CgA levels <200 ng/dl (6.5%), while the highest one is in males over 50 years old with CgA > 200 ng/dl (62.9%). Finally, it was shown that c-reactive protein (CRP) can predict disease extent at the time of diagnosis. Conclusions: CgA levels can not only be used as a direct predictor of tumor load in patients with NENs, but also, when interpolated with the effects of age and gender, cumulatively predict whether a NEN would be metastatic or not at the time of initial diagnosis, via a risk-escalating probability model.

scholarly journals Unique Metastatic Patterns in Neuroendocrine Neoplasms of Different Primary Origin

2020 ◽  
Author(s):  
B C. M. Hermans ◽  
J de Vos - Geelen ◽  
J L Derks ◽  
L Latten ◽  
I H Liem ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Metastatic Disease ◽  
Reference Network ◽  
Neuroendocrine Neoplasms ◽  
Screening Methods ◽  
Special Focus ◽  
Additional Information ◽  
Netherlands Cancer Registry ◽  
Metastatic Patterns ◽  
Primary Origin

Introduction Neuroendocrine neoplasms (NEN) can originate in different organs, e.g. the gastroenteral tract (GE), pancreas (Pan) or lung (L). Our aim was to examine metastatic patterns for patients with NEN of various primary origins with a special focus on brain metastases to indicate utility for screening. Methods All NEN patients except for small cell lung cancer registered in the Netherlands Cancer Registry from 2008-2018 were selected. Metastatic patterns at initial diagnosis for NEN with different primary origin were compared. In a subcohort of patients from two referral hospitals (2014-2019), additional information on for example development of metastases after initial presentation was available. Results In the nationwide cohort 4,768/11,120 (43%) patients had metastatic disease at diagnosis (GE 1,504/4,710 (32%), Pan 489/1,150 (43%), L 1,230/2,978 (41%)). For GE- and Pan-NEN, the most prevalent metastatic site was the liver (25% and 39%), followed by distant lymph nodes (8% and 8%), whereas only few patients with brain metastases were identified (0% in both). In contrast, for L-NEN, prevalence of metastases in liver (19%), brain (9%), lung (7%) and bone (14%) was more equal. In the reference network cohort, slightly more NEN patients had metastatic disease (260/539, 48%) and similar metastatic patterns were observed. Conclusion Almost half of NEN patients were diagnosed with synchronous metastatic disease. L-NEN have a unique metastatic pattern compared to GE- and Pan-NEN. Remarkably, an important part of L-NEN metastases were in the brain, whereas brain metastases were almost absent in GE- and Pan-NEN, indicating utility of screening in L-NEN.

scholarly journals SAT0306 SEMIQUANTITATIVE AND QUANTITATIVE ANALYSIS OF LUNG CT IN THE ASSESSMENT OF INTERSTITIAL LUNG DISEASE IN IDIOPATHIC INFLAMMATORY MYOPATHIES WITH A FOCUS ON ANTISYNTHETASE.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1098.2-1098
Author(s):  
S. Barsotti ◽  
C. Roncella ◽  
A. Valentini ◽  
L. Cavagna ◽  
R. Castellana ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Special Focus ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Increased Risk ◽  
Group 2 ◽  
Lung Ct ◽  
Group 1

Background:Interstitial lung disease (ILD), is common in patients with idiopathic inflammatory myopathies (IIM) and strongly impact on patients’ morbidity and mortality. Patients with anti-aminoacyl-transfer RNA-synthetases (anti-ARS) antibodies are associated with an increased risk of ILD.Objectives:Defining the radiological characteristics of IIM patients, with special focus on serological groups, through qualitative, semiquantitative and quantitative analysis of lung CT.Methods:This was a prospective study conducted from 2016 to 2019. Ninety-eight IIM patients (35 men, 63 women) were included. Myositis specific autoantibodies (MSA) were assessed with Myositis Prophyle III (Euroimmune, Lubeck).Each patient had a baseline CT; the total score of Warrick (WS) was obtained at semiquantitative analysis. The radiological scores ILD% (interstitial lung disease %) and PVRS% (pulmonary vascular related structure) were the result of quantitative analysis in 61 patients (CALIPER). Pulmonary function tests (PFTs) included TLC%, FVC% and DLCO% (65 patients). The analysis was conducted in the whole group and divided in subgroups based on their MSA pattern: in particular anti-ARS (Group 1) and patients negative to MSA (Group 2) were analysed.Results:Positive correlations between ILD% and PVRS% (Rho=0.916; ρ=0.000), WS and ILD% (Rho=0.663; ρ=0.000) and WS and PVRS% (Rho=0.637; ρ<0.001) were found.The most relevant inverse correlations were found between ILD% and DLCO% (Rho=-0.590; ρ=0.001), PVRS% and DLCO% (Rho=-0.549; ρ<0.001) and WS and DLCO% (Rho=-0.471; ρ<0.001).Statistically significant higher values of WS, ILD% and PVRS% were found in Group 1 (WS=15, ILD%=11 and PVRS%=3.5), compared to Group 2 (WS=2.5, ILD%=0.84 and PVRS%=2.2). NSIP pattern resulted dominant represented in the two groups (80% Group 1, 75% Group 2). No statistically significant differences of DLCO%, FVC% and TLCO% were found.Conclusion:The inverse correlations between the radiological scores and the functional data TLC% and DLCO% (ρ<0.001) confirm the role of lung CT in the clinical management of ILD in IIM patients, and may represent a promising tool for clinical trials. For the first time anti-ARS and serological negative patients were defined through qualitative, semiquantitative and quantitative analysis of lung CT. Further study should be conducted in order to define the prognostic value of the quantitative analysis of lung CT in the follow up of IIM patients.Disclosure of Interests:None declared

CAT SCRATCH SYNDROME

PEDIATRICS ◽  
1952 ◽  
Vol 10 (3) ◽  
pp. 311-318
Author(s):  
WILLIAM J. WATERS ◽  
SEYMOUR S. KALTER ◽  
JOHN T. PRIOR
Keyword(s):  
Skin Test ◽  
Laboratory Tests ◽  
Complement Fixation Test ◽  
Complement Fixation ◽  
Clinical Laboratory ◽  
Clinical Course ◽  
Diagnostic Value ◽  
Clinical Findings ◽  
Pathologic Findings ◽  
History Of

The clinical, laboratory and pathologic findings of a series of cases of cat scratch syndrome have been reviewed. In spite of a variable clinical course, certain features associated with a selected group of laboratory tests appear to be constant enough to be of diagnostic value. A history of contact with a cat and/or scratch which is usually associated with a peripheral skin lesion, lack of lymphangitis, presence of regional lymphadenopathy with tenderness to palpation are the most constant clinical findings. Fever, so frequently emphasized as a characteristic clinical sign, may be extremely variable in type and duration or entirely absent. A skin test with cat scratch antigen has been positive in all cases. Lacking this antigen, a negative Frei skin test in conjunction with a positive complement fixation test (Lygranum C. F.) is suggestive evidence for the diagnosis. With positive evidence from the above data, biopsy of an affected gland with its relatively nonspecific pathologic picture is not considered essential for the establishment of the diagnosis of cat scratch syndrome.

Diagnostic value of assessment of coronary calcification in dysplastic heart

2021 ◽  
Vol 19 (1) ◽  
pp. 75-77
Author(s):  
L. T. Pimenov ◽  
◽  
V. V. Remnyakov ◽  
M. Yu. Smetanin ◽  
E. N. Avdeev ◽  
...  
Keyword(s):  
Connective Tissue ◽  
System Development ◽  
Heart Diseases ◽  
Coronary Calcification ◽  
Diagnostic Value ◽  
Conduction Disorders ◽  
Increased Risk ◽  
Structural Heart Diseases ◽  
Connective Tissue Dysplasia ◽  
Functional Features

The problem of heart connective tissue dysplasia syndrome is extremely relevant due to the increased risk of rhythm and conduction disorders, infectious endocarditis, thromboembolism and sudden cardiac death (SCD). Structural heart diseases (SHD) are manifestations of minor anomalies of the cardiovascular system development. Dysplastic heart refers to the combination of constitutional, topographical, anatomical, and functional features of the heart in a patient with connective tissue dysplasia (CTD). The standard for the diagnosis of coronary calcification (CC), one of the known predictors of coronary heart disease (CHD) and complications of cardiovascular diseases (CVD), is multispiral computed tomography (MSCT).

Incidence, timing, and predictors of CNS metastasis in patients (Pts) with clinically localized cutaneous melanoma (CM).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9580-9580
Author(s):  
Merve Hasanov ◽  
Denai R. Milton ◽  
Sapna Pradyuman Patel ◽  
Hussein Abdul-Hassan Tawbi ◽  
Isabella Claudia Glitza ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Cumulative Incidence ◽  
Tumor Location ◽  
Initial Diagnosis ◽  
Stage I ◽  
Acral Lentiginous Melanoma ◽  
Primary Tumor Location ◽  
Cns Metastasis ◽  
Increased Risk

9580 Background: Surveillance for CNS metastasis (mets) is not routinely performed in pts with clinically localized CM. Improved understanding of the incidence, timing and risk factors for the development of CNS metastasis in these pts may inform surveillance strategies. Methods: Under an IRB-approved protocol, demographics, tumor characteristics, and clinical events were collected for pts diagnosed from 1998 to 2019 with AJCC 8th edition stage I or II CM at MD Anderson Cancer Center. Dates of initial diagnosis, regional, distant non-CNS, and CNS mets were recorded. Symptoms and the extent of disease (brain, LMD, both) were recorded for pts with CNS mets. Cumulative incidence of distant mets (CNS and non-CNS) was determined using the competing risks method, including death; pts without CNS mets and alive at last follow-up were censored. Differences in cumulative incidence between groups were assessed using Gray’s test. Associations between measures of interest and cumulative incidence were determined using proportional subdistribution hazards regression models. All statistical tests used a significance level of 5%. Results: 5,179 Stage I-II CM pts were identified. At a median follow up of 82 (0.0-268.8) months, 703 (13.6%) pts were diagnosed with distant mets, including 355 (6.9%) with CNS mets. Cumulative incidence of CNS mets was 0%, 2%, and 5% at 1, 2, and 5 years, respectively. Among pts with distant mets, the first site of distant mets was CNS only for 29 (4%), non-CNS only for 557 (79%), and both for 116 (17%) pts. At initial diagnosis of CNS mets, 195 (55%) pts were asymptomatic, and 46 (13%) had no active extracranial disease. Median time to any distant met was longer for pts who were diagnosed with CNS mets [40.0 (1.9-238.0) months] vs pts diagnosed with non-CNS mets only [31.4 (1.1-185.7) months, p < 0.001]. On multivariable analysis, risk of CNS mets was significantly associated with primary tumor location of scalp [Hazard Ratio (HR) 3.4, 95% Confidence interval (CI) 1.9-5.9], head/neck (HR 3.3, 95% CI 2.0-5.3), or trunk (HR 2.3, 95% CI 1.5-3.5) (vs upper extremity); acral lentiginous melanoma subtype (HR 2.0, 95% CI 1.2-3.6) (vs superficial spreading); increased T category (T2 HR 1.5, 95% CI 1.1-2.2; T3 HR 1.9, 95% CI 1.2-3.0; T4 HR 2.1, 95% CI 1.1-3.8; vs T1), Clark level (CL) (CL4 HR 2.1, 95% CI 1.2-3.7 vs CL2), and mitotic rate (MR) (MR 5-9/mm2 HR 2.1, 95% CI 1.5-3.0; MR > 9/mm2 HR 2.0, 95% CI 1.3-3.0; vs MR 0-4/mm2). While high ( > 9/mm2) MR was associated with increased risk of CNS and non-CNS mets, intermediate (5-9/mm2) was associated with CNS mets only. Conclusions: Primary tumor location, tumor thickness, and MR were strongly associated with risk of CNS mets. MR rate was more strongly associated with risk of CNS than non-CNS mets. Validation in independent cohorts may provide evidence to support CNS surveillance strategies in select pts with stage I-II CM who are deemed high risk for CNS mets.

PAX3-FKHR and PAX7-FKHR Gene Fusions Are Prognostic Indicators in Alveolar Rhabdomyosarcoma: A Report From the Children’s Oncology Group

2002 ◽  
Vol 20 (11) ◽  
pp. 2672-2679 ◽  
Author(s):  
Poul H.B. Sorensen ◽  
James C. Lynch ◽  
Stephen J. Qualman ◽  
Roberto Tirabosco ◽  
Jerian F. Lim ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Metastatic Disease ◽  
Gene Fusion ◽  
Bone Marrow Involvement ◽  
Alveolar Rhabdomyosarcoma ◽  
Outcome Analysis ◽  
Striking Difference ◽  
Gene Fusions ◽  
Fusion Transcripts ◽  
Increased Risk

PURPOSE: Alveolar rhabdomyosarcoma (ARMS) is an aggressive soft tissue malignancy of children and adolescents. Most ARMS patients express PAX3-FKHR or PAX7-FKHR gene fusions resulting from t(2;13) or t(1;13) translocations, respectively. We wished to confirm the diagnostic specificity of gene fusion detection in a large cohort of RMS patients and to evaluate whether these alterations influence clinical outcome in ARMS. PATIENTS AND METHODS: We determined PAX3-FKHR or PAX7-FKHR fusion status in 171 childhood rhabdomyosarcoma (RMS) patients entered onto the Intergroup Rhabdomyosarcoma Study IV, including 78 ARMS patients, using established reverse transcriptase polymerase chain reaction assays. All patients received central pathologic review and were treated using uniform protocols, allowing for meaningful outcome analysis. We examined the relationship between gene fusion status and clinical outcome in the ARMS cohort. RESULTS: PAX3-FKHR and PAX7-FKHR fusion transcripts were detected in 55% and 22% of ARMS patients, respectively; 23% were fusion-negative. All other RMS patients lacked transcripts, confirming the specificity of these alterations for ARMS. Fusion status was not associated with outcome differences in patients with locoregional ARMS. However, in patients presenting with metastatic disease, there was a striking difference in outcome between PAX7-FKHR and PAX3-FKHR patient groups (estimated 4-year overall survival rate of 75% for PAX7-FKHR v 8% for PAX3-FKHR; P = .0015). Multivariate analysis demonstrated a significantly increased risk of failure (P = .025) and death (P = .019) in patients with metastatic disease if their tumors expressed PAX3-FKHR. Among metastatic ARMS, bone marrow involvement was significantly higher in PAX3-FKHR–positive patients. CONCLUSION: Not only are PAX-FKHR fusion transcripts specific for ARMS, but expression of PAX3-FKHR and PAX7-FKHR identifies a very high-risk subgroup and a favorable outcome subgroup, respectively, among patients presenting with metastatic ARMS.

scholarly journals The Expression of Chromogranin A, Syanptophysin and Ki67 in Detecting Neuroendocrine Neoplasma at High Grade Colorectal Adenocarcinoma

2021 ◽  
Vol 9 (A) ◽  
pp. 1142-1147
Author(s):  
W. A. Gusti Deasy ◽  
M. Husni Cangara ◽  
Andi Alfian Zainuddin ◽  
Djumadi Achmad ◽  
Syarifuddin Wahid ◽  
...  
Keyword(s):  
Chromogranin A ◽  
Colorectal Adenocarcinoma ◽  
Final Diagnosis ◽  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
High Grade ◽  
Neuroendocrine Markers ◽  
Study Results ◽  
Cell Neoplasm ◽  
Sample Characteristics

BACKGROUND: Neuroendocrine neoplasm (NEN) is an epithelial cell neoplasm that can give a histopathological appearance resembling high-grade colorectal adenocarcinoma. Immunohistochemical assays with specific neuroendocrine markers of chromogranin A and synaptophysin are required to establish a definite diagnosis of NEN. AIM: This study aimed to determine whether there was an expression of chromogranin A, synaptophysin and Ki67 which indicated the presence of neuroendocrine neoplasms in samples that have been diagnosed as high-grade colorectal adenocarcinoma. MATERIALS AND METHODS: A study of the expression of chromogranin A, synaptophysin and Ki67 in paraffin blocks was carried out as a result of biopsy and tissue surgery of 70 samples of colorectal tumor specimens diagnosed with colorectal adenocarcinoma. Descriptive analyses were used to assess the study results of the amount of chromogranin A, synaptophysin, and sample characteristics. RESULTS: We discovered that eight (8) samples (11.4%) were NEN from 70 previously diagnosed samples as high-grade colorectal adenocarcinoma using immunohistochemical assay with neuroendocrine markers, namely chromogranin A and synaptophysin. CONCLUSION: The final diagnosis obtained from 8 samples diagnosed as NEN were Neuroendocrine tumor (NET) G1, G2, and G3, respectively 1.4% and LCNEC 7.1% based on the specific neuroendocrine markers of chromogranin A, synaptophysin and Ki67.

scholarly journals PEMERIKSAAN TINGKAT sdLDL SERUM SEBAGAI PETANDA DIAGNOSTIK STENOSIS KORONER (Serum sdLDL Level as A Diagnostic Marker of Coronary Stenosis)

2018 ◽  
Vol 22 (1) ◽  
pp. 9
Author(s):  
Indranila K Samsuria ◽  
Laily Adninta
Keyword(s):  
Predictive Value ◽  
Coronary Stenosis ◽  
Area Under The Curve ◽  
Clinical Pathology ◽  
Diagnostic Value ◽  
T Test ◽  
Cross Sectional ◽  
Increased Risk ◽  
Test Kit ◽  
Vascular Stenosis

Small dense LDL (sdLDL) is the LDL which particles are small and dense, it is pro-atherogenic. Increased levels of serum sdLDL areassociated with an increased risk of coronary stenosis. The aim of this study was to examine the diagnostic value of sd LDL in coronarystenosis. An analytical observational study with cross sectional approach was conducted at the Department of Clinical Pathology, MedicalFaculty of Diponegoro University/Dr. Kariadi Hospital and the Unit of Cardiac diseases during the period of March-October 2013. Thesubjects were 39 patients suspected of suffering a coronary stenosis. The diagnosis of coronary stenosis, degree of stenosis and numberof vascular stenosis was established at the time of cardiac catheterization. SdLDL assessment used a test kit. The statistical analysis usedwere unpaired t-test, Spearman correlation test, ROC analysis and diagnostic test. LDL levels in stenosis subjects, 35.4±9.01 mg/dL weresignificantly higher compared to levels in subjects that had no stenosis, 20.7±7.10 mg/dL (p<0.001; unpaired t-test). Correlation testresults showed a correlation between levels of serum sdLDL with severe degree of stenosis (correlation coefficient -0.64, p <0.001) and amoderate positive correlation between the number of vascular stenosis (Coefficient correlation 0.46; p=0.003; Spearman Correlation’sTest). The area under the curve of ROC was 0.9 (p <0.001). The cut off levels sdLDL were used to detect stenosis. The results showeda sensitivity of 85.2%, specificity of 75%, positive predictive value of 88.5%, negative predictive value of 69.2% and accuracy of 82%.Levels of serum sdLDL were associated with severe to extensive stenosis degree, and showed a good diagnostic value, thus, it can beused for screening to determine the presence of coronary stenosis.

scholarly journals Pulmonary cavitation in patients with thyroid cancer receiving antiangiogenic agents

2020 ◽  
Author(s):  
Saumil Datar ◽  
Maria Cabanillas ◽  
Ramona Dadu ◽  
David Ost ◽  
Horiana Grosu
Keyword(s):  
Thyroid Cancer ◽  
Metastatic Disease ◽  
Kinase Inhibitors ◽  
Pulmonary Nodules ◽  
Primary Objective ◽  
Small Sample ◽  
Attractive Potential ◽  
Antiangiogenic Agents ◽  
Increased Risk ◽  
Clinical Consequences

Abstract Background: Thyroid malignancies are among the most common endocrine cancers worldwide. Owing to the angiogenic nature of these malignancies, tyrosine kinase inhibitors (TKIs) are an attractive potential treatment. However, TKIs have been associated with an increased risk of tumor cavitation, in turn linked to poor outcomes, in patients with malignancies in the lungs, where thyroid cancer commonly metastasizes. Method: We performed a retrospective cohort study of patients with thyroid cancer and evidence of metastatic disease to the lung that were treated with multi-targeted antiangiogenic TKIs. The primary objective of this study was to determine the incidence of pulmonary cavitation. The secondary objective was to evaluate the effect of pulmonary cavitation on survival. Results: Of the 83 patients with pulmonary nodules,10 developed cavitation during treatment. Of these 83 patients, two patients had to stop the treatment due to pneumothorax. Additionally, cavitation did not demonstrate any significant effect on survival. Conclusion: In patients with thyroid cancer and evidence of metastatic disease to the chest, the use of multi-targeted TKIs led to cavitations that were not uncommon but clinical consequences were marginal. Treatment was stopped only in two patients that developed pneumothorax, however the small sample is a strong limitation of our study.

scholarly journals Pulmonary cavitation in patients with thyroid cancer receiving antiangiogenic agents

2020 ◽  
Author(s):  
Saumil Datar ◽  
Maria Cabanillas ◽  
Ramona Dadu ◽  
David Ost ◽  
Horiana Grosu
Keyword(s):  
Thyroid Cancer ◽  
Metastatic Disease ◽  
Kinase Inhibitors ◽  
Pulmonary Nodules ◽  
Primary Objective ◽  
Small Sample ◽  
Attractive Potential ◽  
Antiangiogenic Agents ◽  
Increased Risk ◽  
Clinical Consequences

Abstract Background:Thyroid malignancies are among the most common endocrine cancers worldwide. Owing to the angiogenic nature of these malignancies, tyrosine kinase inhibitors (TKIs) are an attractive potential treatment. However, TKIs have been associated with an increased risk of tumor cavitation, in turn linked to poor outcomes, in patients with malignancies in the lungs, where thyroid cancer commonly metastasizes. Method:We performed a retrospective cohort study of patients with thyroid cancer and evidence of metastatic disease to the lung that were treated with multi-targeted antiangiogenic TKIs. The primary objective of this study was to determine the incidence of pulmonary cavitation. The secondary objective was to evaluate the effect of pulmonary cavitation on survival. Results: Of the 83 patients with pulmonary nodules,10 developed cavitation during treatment. Of these 83 patients, two patients had to stop the treatment due to pneumothorax. Additionally, cavitation did not demonstrate any significant effect on survival. Conclusion:In patients with thyroid cancer and evidence of metastatic disease to the chest, the use of multi-targeted TKIs led to cavitations that were not uncommon but clinical consequences were marginal. Treatment was stopped only in two patients that developed pneumothorax, however the small sample is a strong limitation of our study.

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