Focal Spot, Spring 2004

https://digitalcommons.wustl.edu/focal_spot_archives/1096/thumbnail.jp

The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer.

The advances in targeted therapies for lung cancer are based on the evaluation of specific gene mutations especially the epidermal growth factor receptor (EGFR). The assays largely depend on the acquisition of tumor tissue via biopsy before the initiation of therapy or after the onset of acquired resistance. However, the limitations of tissue biopsy including tumor heterogeneity and insufficient tissues for molecular testing are impotent clinical obstacles for mutation analysis and lung cancer treatment. Due to the invasive procedure of tissue biopsy and the progressive development of drug-resistant EGFR mutations, the effective initial detection and continuous monitoring of EGFR mutations are still unmet requirements. Circulating tumor DNA (ctDNA) detection is a promising biomarker for noninvasive assessment of cancer burden. Recent advancement of sensitive techniques in detecting EGFR mutations using ctDNA enables a broad range of clinical applications, including early detection of disease, prediction of treatment responses, and disease progression. This review not only introduces the biology and clinical implementations of ctDNA but also includes the updating information of recent advancement of techniques for detecting EGFR mutation using ctDNA in lung cancer

CHRONIC COUGH IN A 10- YEAR OLD BOY AS A FIRST PRESENTATION OF INFLAMMATORY MYOFIBROBLASTIC TUMOR (IMT): A CASE REPORT

An inflammatory myofibroblastic tumor (IMT) is a rare benign tumor with an unknown origin. Its clinical and radiological manifestations are variable and nonspecific, also half of them are asymptomatic while cough, hemoptysis, dyspnea are possible to see. Therefore the diagnosis is too hard to establish unless an exact evaluation by an expert pathologist on a biopsy from surgical resection. The standard treatment for diagnostic and therapeutic reasons is a complete resection whereas incomplete resection increases the risk of recurrence. Here we report a 10-year old boy with prolonged cough and collapse-consolidation in his chest x-ray who referred to our pediatric center in the northeast of Iran. Keywords: Inflammatory myofibroblastic tumor, cough, collapse, pediatric

Quantitative Evaluation of Pulmonary Emphysema Using Magnetic Resonance Imaging and x-ray Computed Tomography

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality affecting at least 600 million people worldwide. The most widely used clinical measurements of lung function such as spirometry and plethysmography are generally accepted for diagnosis and monitoring of the disease. However, these tests provide only global measures of lung function and they are insensitive to early disease changes. Imaging tools that are currently available have the potential to provide regional information about lung structure and function but at present are mainly used for qualitative assessment of disease and disease progression. In this thesis, we focused on the application of quantitative measurements of lung structure derived from 1H magnetic resonance imaging (MRI) and high resolution computed tomography (CT) in subjects diagnosed with COPD by a physician. Our results showed that significant and moderately strong relationship exists between 1H signal intensity (SI) and 3He apparent diffusion coefficient (ADC), as well as between 1H SI and CT measurements of emphysema. This suggests that these imaging methods may be quantifying the same tissue changes in COPD, and that pulmonary 1H SI may be used effectively to monitor emphysema as a complement to CT and noble gas MRI. Additionally, our results showed that objective multi-threshold analysis of CT images for emphysema scoring that takes into account the frequency distribution of each Hounsfield unit (HU) threshold was effective in correctly classifying the patient into COPD and healthy subgroups. Finally, we found a significant correlation between whole lung average subjective and objective emphysema scores with high inter-observer agreement. It is concluded that 1H MRI and high resolution CT can be used to quantitatively evaluate lung tissue alterations in COPD subjects

Serum protein markers for the early detection of lung cancer:a focus on autoantibodies

Lung cancer has the highest mortality rate among cancer patients in the world, in particular because most patients are only diagnosed at an advanced and non-curable stage. Computed tomography (CT) screening on high-risk individuals has shown that early detection could reduce the mortality rate. However, the still high false-positive rate of CT screening may harm healthy individuals because of unnecessary follow-up scans and invasive follow-up procedures. Alternatively, false-negative and indeterminate results may harm patients due to the delayed diagnosis and treatment of lung cancer. Non-invasive biomarkers, complementary to CT screening, could lower the false-positive and false-negative rate of CT screening at baseline and thereby reduce the number of patients that need follow-up and diagnose patients at an earlier stage of lung cancer. Lung cancer tissue generates lung cancer-associated proteins to which the immune system might produce high-affinity autoantibodies. This autoantibody response to tumor-associated antigens starts during early-stage lung cancer and may endure over years. Identification of tumor-associated antigens or the corresponding autoantibodies in body fluids as potential non-invasive biomarkers could thus be an effective approach for early detection and monitoring of lung cancer. In this review we provide an overview of differentially expressed protein, antigen and autoantibody biomarkers that combined with CT imaging might be of clinical use for early detection of lung cancer.</p

TTF-1/p63-positive poorly differentiated NSCLC: A histogenetic hypothesis from the basal reserve cell of the terminal respiratory unit

TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majority of non-small-cell lung cancers, with TTF and CK7 being typically expressed in adenocarcinomas and the latter three being expressed in squamous cell carcinoma. As tumors with coexpression of both TTF-1 and p63 in the same cells are rare, we describe different cases that coexpress them, suggesting a histogenetic hypothesis of their origin. We report 10 cases of poorly differentiated non-small-cell lung carcinoma (PD-NSCLC). Immunohistochemistry was performed by using TTF-1, p63, p40 (∆Np63), CK5/6 and CK7. EGFR and BRAF gene mutational analysis was performed by using real-time PCR. All the cases showed coexpression of p63 and TTF-1. Six of them showing CK7+ and CK5/6− immunostaining were diagnosed as “TTF-1+ p63+ adenocarcinoma”. The other cases of PD-NSCLC, despite the positivity for CK5/6, were diagnosed as “adenocarcinoma, solid variant”, in keeping with the presence of TTF-1 expression and p40 negativity. A “wild type” genotype of EGFR was evidenced in all cases. TTF1 stained positively the alveolar epithelium and the basal reserve cells of TRU, with the latter also being positive for p63. The coexpression of p63 and TTF-1 could suggest the origin from the basal reserve cells of TRU and represent the capability to differentiate towards different histogenetic lines. More aggressive clinical and morphological features could characterize these “basal-type tumors” like those in the better known “basal-like” cancer of the breast

Assessment of recurrence of non-small cell lung cancer after therapy using CT and Integrated PET/CT

WSTĘP: Niedrobnokomórkowy rak płuca (NDRP) jest wiodącą przyczyną zgonów spowodowanych chorobami nowotworowymi w Polsce. Kontrola pacjentów po leczeniu raka płuca ma na celu wczesne wykrycie wznowy miejscowej, rozsiewu procesu nowotworowego, powikłań po leczeniu. Istotne jest też wczesne wykrycie kolejnego nowotworu.W pracy badano przydatność metody PET-CT w ocenie nawrotu NDRP po leczeniu.MATERIAŁ I METODY: Do badania włączono retrospektywnie 72 pacjentów (19 kobiet, 56 mężczyzn) z NDRP w stopniu zaawansowania I–IV poddanych leczeniu operacyjnemu i/lub radioterapii. Niektórzy z nich byli poddani chemioterapii. Radiogram klatki piersiowej i/lub badanie TK lokalizowały zmiany podejrzane o wznowę przed badaniem PET-CT. Wszyscy pacjenci mieli wykonane badanie TK i PET-CT pomiędzy styczniem 2008 roku a styczniem 2012 roku. Badania PET-CT interpretowano w zestawieniu z badaniami TK. Następnie wyniki zestawiono z badaniem histopatologicznym.WYNIKI: Wśród badanych pacjentów u 45 potwierdzono nawrót raka płuca, u 3 obecność drugiego raka płuca. Wznowa występowała częściej u mężczyzn niż u kobiet oraz u chorych, u których stwierdzono zatory z komórek nowotworowych w naczyniach guza. U 4 chorych rozpoznanie wznowy na podstawie PET-CT nie zostało potwierdzone podczas dalszej diagnostyki. Dotyczyło to przede wszystkim chorych, u których ostatecznie rozpoznano zmiany o etiologii zapalnej. Dokładność badania PET-CT u pacjentów badanych pod kątem nawrotu raka płuca wyniosła 94,4% (95% CI 91; 100).WNIOSKI: FDG PET-CT pozwoliło u większości pacjentów odróżnić zmiany nowotworowe od zmian zapalnych po przebytym leczeniu. W pracy wykazano, że PET-CT jest bardziej dokładne od metody TK w ocenie nawrotu raka płuca. Badanie PET-CT ma istotne znaczenie w postępowaniu klinicznym i planowaniu leczenia.INTRODUCTION: Non-small cell lung cancer (NSCLC) has become the leading cause of cancer-related deaths in Poland. Follow-up of patients with NSCLC is aimed at early detection of local recurrence, metastatic process, treatment-related complications or second primary lung cancer. We investigated the diagnostic accuracy of FDG-PET-CT in the detection of recurrence of NSCLC after treatment.MATERIAL AND METHODS: Seventy-two NSCLC patients (19 females, 56 males), stage I to IV, who had undergone surgery and/ /or radiation therapy, occasionally associated with chemotherapy, were retrospectively included in our study. Chest radiographs and thoracic computed tomography (CT) were performed to localize the abnormality prior to PET-CT. All the patients underwent CT and PET-CT in the period from January 2008 until January 2012. All PET images were interpreted in conjunction with thoracic CT. PET-CT and CT diagnoses were correlated with pathological diagnoses.RESULTS: Forty-five patients had recurrent tumour. Tumour recurrence was observed more often in men than in women and also in case of neoplastic cell emboli in lymphatic or blood vessels. In three patients second primary lung cancer was diagnosed. False positive diagnosis of relapse based on PET-CT was obtained in 4 patients, mainly due to inflammatory lesions. The accuracy of PET-CT for diagnosis of recurrence was 94.4% (95% CI 91; 100).CONCLUSIONS: FDG PET-CT was the best method to differentiate recurrent bronchogenic carcinoma from inflammatory lesions, especially at post-therapeutic sites. It has been shown that PET-CT is more accurate method than CT in recurrent NSCLC. PET-CT results had a further impact on the clinical management and treatment planning