Demetris Patsios

Tumor Cavitation: Impact on Objective Response Evaluation in Trials of Angiogenesis Inhibitors in Non-Small-Cell Lung Cancer

PURPOSE We have observed cavitation of lesions in clinical trials of an angiogenesis inhibitor combined with chemotherapy for non-small-cell lung cancer (NSCLC). We hypothesized that cavitation might alter response assessment in such clinical trials. PATIENTS AND METHODS We performed a retrospective radiologic review of patients with NSCLC enrolled onto three National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trials of platinum-based chemotherapy with or without a small-molecule angiogenesis inhibitor (vascular endothelial growth factor receptor inhibitor [VEGFRI]). Response was assessed both by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and a novel alternate method in which the longest diameter of any cavity was subtracted from the overall longest diameter of that lesion to measure target lesions. Rates of cavitation were documented. RESULTS Marked cavitation of pulmonary lesions was seen in 24% of 33 patients treated with VEGFRI combined with platinum-based chemotherapy but in none of 18 patients treated with platinum-based chemotherapy alone. Use of the alternate method for response assessment resulted in an alteration of response assessment, time to best response, duration of response, and time of disease progression in a minority of patients compared with RECIST. CONCLUSION Cavitation of target and nontarget lesions is common in NSCLC patients treated with VEGFRIs and platinum-based chemotherapy. Impact on response and time to event outcomes occurred but seems to be less common. Response assessment might be improved by incorporating cavitation into volume assessment for target lesions, potentially altering outcomes of key efficacy parameters in clinical trials. This should be prospectively assessed in clinical trials of angiogenesis inhibitors.

Lung cancer screening using low-dose computed tomography in at-risk individuals: The Toronto experience

OBJECTIVE The Department of Medical Imaging at the University Health Network in Toronto is performing a lung cancer screening study, utilizing low-dose computed tomography (LDCT) as the modality. Baseline and annual repeat results are reported on the first 3352 participants, enrolled between June 2003 and May 2007. METHODS Enrollment was limited to those aged 50 years or older, with a smoking history of at least 10 pack-years, no previous cancer and general good health. A helical low-dose CT (LDCT) of the chest was performed using 120kVp, 40-60mA, images were reconstructed with 1-1.25mm overlapping slices. The primary objectives were the detection of parenchymal nodules and diagnosis of early stage lung cancer. Baseline LDCTs were termed positive if at least one indeterminate non-calcified nodule 5mm or larger in size, or non-solid nodule 8mm or larger in size was identified. Follow up periods for individuals with a positive baseline LDCT were determined by nodule characteristics. RESULTS The median age at baseline was 60 years (range 50-83), with a median of 30 pack-years of cigarette smoking (range 10-189). Baseline CT evaluations were positive in 600 (18%) participants. To date, 2686 (80%) of the participants have returned for at least one annual repeat screening LDCT. Biopsies have been recommended for 82 participants since the study began, and 64 have been diagnosed with screen-detected cancer (62 lung, two plasmacytoma of the rib). A total of 65 lung cancers have been diagnosed (62 screen-detected, 3 interim), 57 are NSCLC (82% with known stage are stage I or II) and the rate of surgical resection was 80%. Sensitivity and specificity of the protocol in successfully diagnosing early stage lung cancers were 87.7% and 99.3%, respectively. CONCLUSIONS Data indicate that LDCT can identify small lung cancers in an at-risk population. The diagnostic algorithm results in few false-positive invasive procedures. Most cancers are detected at an early stage, where the cancer is resectable with a greater potential for cure. Long-term follow up of lung cancer cases will be carried out to determine survival.

Soluble Mesothelin-Related Peptide and Osteopontin As Markers of Response in Malignant Mesothelioma

PURPOSE In malignant mesothelioma (MM), radiologic assessment of disease status is difficult. Both soluble mesothelin-related peptide (SMRP) and osteopontin (OP) have utility in distinguishing MM from benign pleural disease. We evaluated whether SMRP and OP also correlated with the disease course of MM. PATIENTS AND METHODS Serial plasma samples from patients with MM were prospectively collected, and SMRP and OP levels were measured. Radiologic tests across time periods showing disease progression, stability, or shrinkage were compared with corresponding changes in SMRP/OP levels. RESULTS From 41 patients, 165 samples were collected (range, 2 to 10; median 4). At study entry, 37 of 41 patients had measurable disease, of whom 92% (34 of 37) had elevated baseline SMRP levels; four of 41 patients had no evidence of recurrence and each had normal baseline SMRP levels. In 21 patients receiving systemic therapy, percentage change in SMRP more than 10% correlated with the radiologic assessment by a trained thoracic radiologist (P < .001), by formal Response Evaluation Criteria in Solid Tumors (RECIST; P = .008), or by modified RECIST (P < .001). All seven patients who underwent surgical resection with negative margins had elevated preoperative SMRP levels that fell to normal postoperatively. Rising SMRP was observed in all patients with radiologic disease progression. No associations were found with OP. CONCLUSION Percentage changes in SMRP levels, but not changes in OP levels, are a potentially useful marker of disease course. These findings should be validated prospectively for a role as an objective adjunctive measure of disease course in both clinical trials and clinical practice.

CT-guided percutaneous fine-needle aspiration biopsy of pulmonary nodules measuring 10 mm or less

AIM To determine the value of computed tomography (CT)-guided fine-needle aspiration biopsy (FNAB) of small pulmonary nodules measuring 10 mm or less. MATERIAL AND METHODS CT-guided FNABs of 55 nodules, measuring 10mm or less, were performed between January 2003 and February 2006. A coaxial technique was used, with an outer 19 G Bard Truguide needle and inner 22 G disposable Greene biopsy needle. Adequacy of specimens was assessed on-site by a cytotechnologist. The sizes of the nodules, distance from pleura, number of pleural punctures and aspirates, complications encountered, cytological diagnosis, and outcome were recorded. RESULTS The mean nodule diameter was 9 mm (range 5-10 mm). The average distance from the costal pleura was 31 mm (range 0-88 mm). In 50 of the 55 FNABs, the pleura was crossed once. An average of four aspirates was performed per case. Twenty-five FNABs (45.5%) were adequate for diagnosis (24 malignant and one tuberculosis). In 11 cases, where no definite diagnosis was made following FNAB, the outcome was not affected. In 10 cases, samples were insufficient for diagnosis and the nodules were subsequently diagnosed as malignant. Eight cases were excluded in the final analysis as follow-up details were unavailable. The sensitivity for malignancy and overall accuracy were 67.7 and 78.8%, respectively. Pneumothorax occurred in 29 (52.7%) patients, with five (9.1%) requiring thoracostomy tubes. CONCLUSION CT-guided FNAB is a useful tool in the diagnosis and management of small pulmonary nodules, despite the lower diagnostic accuracy and higher complication rate than those of larger pulmonary lesions.

Screening for Malignant Pleural Mesothelioma and Lung Cancer in Individuals with a History of Asbestos Exposure

Purpose: We established a screening program for prior asbestos workers using low-dose computed tomography (LDCT). Methods: Between March 2005 and October 2007 we performed LDCT (50–60 mA, 120 kV, 1.25 mm) in 516 asbestos-exposed individuals. Parenchymal nodules were followed according to lung cancer screening recommendations, morphology and location of pleural plaques was noted in detail. Results: We included 507 men and 9 women (median 60.0 years), 395 (76.6%) were smokers. Annual repeat has been performed in 356 participants. We found plaques in 357 subjects (69.2%), commonly calcified (79.6%), flat (86.6%), and symmetric (86.8%), and mostly involving the costal (96.4%) and diaphragmatic (81.8%) pleura. Uncommon plaques were lobulated (13.2%), right-dominant asymmetric (4.5%), or with effusions (0.1%). We found pulmonary nodules in 371 subjects (71.9%), 91 (17.6%) had at least one nodule ≥5 mm; 10 growing nodules were found on annual repeat LDCT. In 41 individuals, plaques were regarded as atypical; three had new pleural/peritoneal abnormalities on annual repeat LDCT. An interim limited computed tomography of the observed abnormality prompted 10 diagnostic biopsies, resulting in a diagnosis of six lung cancers, two pleural mesothelioma and two peritoneal mesothelioma; overall rate of screen-detected malignancies is 2.1%. There were four interval cancers, diagnosed after baseline (n = 1) or after the annual repeat (n = 3): two pleural and one peritoneal mesothelioma, and one mixed squamous/small cell carcinoma. Conclusion: Screening prior asbestos workers detects advanced malignant pleural mesothelioma and early as well as late stage lung cancer. We expect to learn more about the appearance of “early mesothelioma” with continued screening.

Imaging of Lung Transplantation: Review

OBJECTIVE Lung transplantation is an established treatment for end-stage pulmonary disease. Complications of lung transplantation include airway stenosis and dehiscence, reimplantation response, acute rejection, infection, posttransplantation lymphoproliferative disorder, and bronchiolitis obliterans syndrome. The incidence of graft rejection and airway anastomosis experienced in the early years of lung transplantation have been significantly reduced by advances in immunosuppression and surgical techniques. Infection is currently the most common cause of mortality during the first 6 months after transplantation, whereas chronic rejection or obliterative bronchiolitis is the most common cause of mortality thereafter. This article reviews the radiologic findings of different surgical techniques as well as the common early and late complications of lung transplantation. CONCLUSION Radiology plays a pivotal role in the diagnosis and management of complications of lung transplantation. Advancements in surgical technique and medical therapy influence the spectrum of expected radiologic findings. Familiarity with the radiologic appearances of common surgical techniques and complications of lung transplantation is important.

Neoadjuvant chemoradiation and surgery improves survival outcomes compared with definitive chemoradiation in the treatment of stage IIIA N2 non-small-cell lung cancer

OBJECTIVES The objective of this study was to compare survival in patients with stage IIIA (N2) non-small-cell lung cancer (NSCLC) treated with definitive chemoradiation (CRT) or surgery plus neoadjuvant chemoradiation or chemotherapy (CRTS). METHODS A retrospective analysis of 242 patients with stage IIIA (N2) NSCLC treated with curative intent between 1997 and 2007, identified 215 patients with surgically resectable disease. Overall survival outcomes were analysed using the Kaplan-Meier plots, log-rank tests and Cox proportional hazards models adjusting for age, gender, histology, smoking history and performance status. Recurrences were compared using competing risks methods, including the proportional subdistribution hazards regression model. RESULTS CRTS was used to treat 104 patients and CRT in 111. Comparing CRTS with CRT patients, median age was 60 vs 62, 50 (48%) vs 69 (62%) were male and 65 (62.5%) vs 60 (54%) had adenocarcinoma. Of CRTS patients, 83 (80%) had a lobectomy. CRTS patients compared with CRT patients had decreased risk of recurrence at any site [hazard ratio (HR) = 0. 46, 95% confidence interval (CI): 0.32-0.64 P < 0.0001], local recurrence (HR = 0.50, 95% CI: 0.29-0.87, P = 0.013), loco--regional recurrence (HR = 0.51, 95% CI: 0.33-0.78, P = 0.002) and death (HR: 0.45, 95% CI: 0.33-0.62, P < 0.0001) with a median survival of 4.2 years vs 1.7 years). Risk of distant recurrence was also reduced in the surgical group (HR: 0.57; 95% CI: 0.38-0.87, P = 0.017). Treatment-related mortality was low in both cohorts. CONCLUSION For patients with surgically resectable stage IIIA (N2) NSCLC, neoadjuvant therapy plus surgery reduces loco-regional and distant recurrence and improves survival. Treatment-related mortality was not significantly increased compared with the patients treated with CRT alone.

Dynamic Airway Evaluation with Volume CT: Initial Experience

Purpose The purpose of the study was to prospectively establish the use of a novel multidetector computed tomography unit (MDCT) with 320 × 0.5 detector rows for the evaluation of tracheomalacia by using a dynamic expiratory low-dose technique. Methods Six adult patients (5 men, 1 woman; mean age, 53.7 years [37–70 years]) referred for a clinical suspicion of tracheomalacia were studied on a 320-row MDCT unit by using the following parameters: 120 kVp, 40–50 mA, 0.5-second gantry rotation, and z-axis coverage of 160 mm sufficient to cover the thoracic trachea to the proximal bronchi. Image acquisition occurred during a forceful exhalation. The image data set was subject to the following analyses: cross-sectional area of airway lumen at 4 predefined locations (thoracic inlet, aortic arch, carina, and bronchus intermedius) and measurement of airway volume. Results All 6 patients had evidence of tracheomalacia, the proximal trachea collapsed at a later phase of expiration (3–4 seconds) than the distal trachea (2–3 seconds). The most common region of airway collapse occurred at the level of the aortic arch (5/6 [83%]), Three patients (50%) had diffuse segmental luminal narrowing that involved the tracheobronchial tree. The radiation dose (estimated dose length product, computed tomography console) measured 293.9 mGy in 1 subject and 483.5 mGy in 5 patients. Conclusions Four-dimensional true isophasic and isovolumetric imaging of the central airways by using 320-row MDCT is a viable technique for the diagnosis of tracheomalacia; it provides a comprehensive assessment of airways dynamic.

Comparison of the Spectrum of Radiologic and Clinical Manifestations of Pulmonary Disease Caused by Mycobacterium avium Complex and Mycobacterium xenopi

Aim Mycobacterium xenopi is described with upper lobe cavitation (“fibrocavitary” pattern), whereas the Mycobacterium avium complex (MAC) is described with bronchiectasis and centrilobular nodules (“nodular bronchiectasis”). We retrospectively described and compared computed tomography (CT) chest manifestations of disease caused by MAC and M xenopi. Materials and Methods We reviewed patients who had either MAC or M xenopi lung disease and who had CTs between January 2002 and December 2003. Clinical data were recorded, and the patterns on chest CTs were categorized as “fibrocavitary,” “nodular bronchiectatic,” and “unclassified.” Results There were 74 patients; 50 with MAC and 24 with M xenopi. The patients with MAC were older (mean 69 vs 58 years; P = .007). Patients with M xenopi more often had emphysema (50% vs 20%; P = .02), cavities (46% vs 16%; P = .01), and nodules ≤5 mm (88% vs 58%; P = .02). M xenopi cases more commonly had a fibrocavitary radiologic pattern (33% vs 18%), with no statistically significant difference (P = .24). MAC was more often associated with a nodular bronchiectatic pattern (68% MAC vs 4% M xenopi; P < .0001). Sixty-three percent of patients with M xenopi had a pattern that was predominantly randomly distributed nodules (11/15 [73%]) or consolidation and/or ground-glass opacities (4/15 [27%]). Conclusion Compared with MAC, patients with M xenopi infection develop more cavities and more nodules, and they less often have a predominant nodular bronchiectatic pattern. Although a predominantly cavitary pattern appears to be more common with M xenopi, the majority of patients with M xenopi had CT patterns of random nodules or consolidation and/or ground-glass opacities rather than classically described findings.

Radiologic Outcomes at 5 Years After Severe ARDS

OBJECTIVE Few studies have systematically evaluated high-resolution CT (HRCT) imaging of the thorax 5 years after severe ARDS to determine the association between radiologic fi ndings and functional disability. The primary aim of this study was to determine chest radiologic abnormalities at 5 years in survivors of severe ARDS from the University of Toronto ARDS cohort. The secondary aim was to determine the relationship between the observed radiologic abnormalities on HRCT scan and pulmonary symptoms, pulmonary function test abnormalities, and healthrelated quality of life at 5-year follow-up. METHODS HRCT scans were obtained in 24 of 64 eligible patients. Three anatomically comparable levels were selected for scoring, and each level was divided into four quadrants. The extent and distribution of individual CT image patterns (ground glass opacifi cation, intense parenchymal opacifi cation, reticular pattern, and decreased attenuation) were also reported. RESULTS Eighteen patients (75%) had abnormal fi ndings on HRCT imaging. These findings were minor and in the nondependent lung zones. No correlation was found between radiologic findings and patient symptoms, pulmonary function tests, 6-min walk distances, or heath-related quality of life measures. CONCLUSIONS Exercise and functional limitations experienced by survivors of severe ARDS are unlikely to be related to structural lung disease and may be more consistent with extrapulmonary muscle weakness.