Kenneth G. Evans

Probability of Cancer in Pulmonary Nodules Detected on First Screening CT

BACKGROUND Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up. METHODS We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer. RESULTS In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set. CONCLUSIONS Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; ClinicalTrials.gov number, NCT00751660.).

Glandular neoplasia of the lung. A proposed analogy to colonic tumors

In 62 consecutive resections for adenocarcinoma of the lung, 50 cases (81%) had single adenocarcinomas and 12 (19%) had multiple adenocarcinomas. In seven of these 12 patients, two adenocarcinomas were found. In the other five patients, the specimen contained a dominant adenocarcinoma and several 0.1‐ to 1‐cm nodules of similar histologic appearance. In four of the 50 single tumor patients and one of seven double tumor patients, 1‐ to 2‐mm nodules were found along with adenocarcinomas that we interpreted as being bronchioloalveolar tumors of uncertain malignant potential. An analogy is drawn between these four types of findings and single tumors of the colon, double tumors of the colon, polyposis syndromes, and tubular adenomas of the colon, respectively.

Lung Nodules: CT-guided Placement of Microcoils to Direct Video-assisted Thoracoscopic Surgical Resection

PURPOSE To prospectively assess the safety and effectiveness of computed tomography (CT)-guided placement of fiber-coated microcoils used to guide video-assisted thoracoscopic surgical (VATS) excision of small peripheral lung nodules, with successful excision as the primary outcome and successful CT-guided microcoil placement and procedural complications as secondary outcomes. MATERIALS AND METHODS The institutional review board approved the study protocol. Informed consent was obtained from all 69 enrolled patients (30 men, 39 women; mean age, 60.7 years +/- 10.1 [standard deviation]) with 75 nodules. At CT, one end of an 80-mm long, 0.018-inch-diameter fiber-coated microcoil was placed deep to the small peripheral lung nodule, and the other end was coiled in the pleural space. VATS excision of lung tissue, nodules, and the microcoil was performed with fluoroscopic guidance. RESULTS Seventy-three (97%) 4-24-mm nodules were successfully removed at fluoroscopically guided VATS excision; two nodules could not be removed. CT-guided microcoil placement was successful in all cases; however, two (3%) of 75 coils were displaced at VATS excision. Pneumothorax requiring chest tube placement occurred in two (3%) patients, and asymptomatic hemothorax occurred in one (1%) patient. The microcoil did not impede intraoperative frozen-section histopathologic analysis, which facilitated accurate clinical management in all patients. For 19 (28%) patients, the preoperative treatment plan based on bronchoscopy, needle biopsy, and positron emission tomography findings changed after VATS excision. CONCLUSION Microcoil localization of small peripheral lung nodules enabled fluoroscopically guided VATS resection of 97% of the nodules, with a low rate of intervention (3%) for procedural complications.

Peripheral Lung Nodules: Fluoroscopically Guided Video-Assisted Thoracoscopic Resection After Computed Tomography-Guided Localization Using Platinum Microcoils

Objectives:We sought to test the safety and efficacy of fluoroscopically guided, video-assisted, thoracoscopic resection after computed tomography (CT)-guided localization using platinum microcoils. Summary Background Data:Video-assisted thoracoscopic (VATS) resection of small pulmonary nodules >5 mm deep to the visceral pleura fails to locate the nodule and requires conversion to open thoracotomy in two thirds of cases. Therefore, we developed a new technique for intraoperative localization of these nodules using CT-guided placement of platinum microcoils. This study tests the safety and efficacy of this technique in a Phase I human study. Methods:Twelve patients with undiagnosed growing pulmonary nodules <20 mm were marked preoperatively using percutaneously placed CT-guided platinum microcoils. The coil was deployed adjacent to the nodule with the distal end of the coil placed deep to the nodule and the superficial end coiled on the pleural surface. The nodule and coil were excised using endostaplers guided by VATS and fluoroscopy. Histopathologic diagnosis was performed immediately after resection. Results:CT-guided microcoil localization was successful in all patients. A small hemothorax and a pneumothorax requiring a chest tube occurred in 2 patients. Mean distance from visceral pleura to the deep edge of the nodule was 30.9 ± 15.4 mm. VATS resection of the nodules (size = 11.8 ± 3.2mm) was successful in all patients. Mean microcoil localization, fluoroscopy, and operative times were 42 ± 14, 3.1 ± 2.0, and 67 ± 27 minutes. A diagnosis of primary nonsmall cell bronchogenic carcinoma was made in 6 patients who then received a completion lobectomy. Six patients (hamartoma: 2, reactive lymph node: 1, bronchoalveolar cell carcinoma: 2, metastatic sarcoma: 1) did not receive further resections. Conclusions:Preoperative localization of pulmonary nodules using percutaneous CT-guided platinum microcoil insertion combined with operative fluoroscopic visualization is a safe, effective technique that increases the success rate of VATS excision.

Impact of new radiotherapy modalities on the surgical management of cancer of the esophagus and cardia.

At the Cancer Control Agency of British Columbia, 483 patients with cancer of the esophagus and cardia were seen from 1970-1980. Four hundred and one out of 483 (83%) had tumors larger than 5 cm (T2) and in 288/483 (60%) the disease had extended beyond the esophageal wall (T3). The overall 5-year survival rate was only 9% for all patients treated by external irradiation. The 5-year survival for a selected group having esophagectomy was 20%. Most patients died of persistent cancer at the primary site (83%); the cause of death was aspiration pneumonia (82%) due to obstruction caused by the persistent cancer. Our most recent experience using intracavitary irradiation either prior to or after external irradiation in 211 patients has been safe and simple and preliminary analysis of treatment results suggests that it has improved the therapeutic ratio. The analysis of quality of life at 6 months following therapy as it relates to performance status, swallowing ability, weight, and pain indicated significant improvement in all of these parameters. Of 171 patients, 33% were still alive at 1 year, 26% at 2 years, and 19% at 3 years following treatment. Of 43 patients suitable for preoperative irradiation, only 26 patients were actually resected and 19 of them are still alive with no evidence of disease, 8 to 30 months. The rationale and technical aspects of the combined treatment are described in detail. Treatment results, complications and an outline for future programs based on this experience are also described.

Disruption of the Non-Canonical WNT Pathway in Lung Squamous Cell Carcinoma

Disruptions of beta-catenin and the canonical Wnt pathway are well documented in cancer. However, little is known of the non-canonical branch of the Wnt pathway. In this study, we investigate the transcript level patterns of genes in the Wnt pathway in squamous cell lung cancer using reverse-transcriptase (RT)-PCR. It was found that over half of the samples examined exhibited dysregulated gene expression of multiple components of the non-canonical branch of the WNT pathway. In the cases where beta catenin (CTNNB1) was not over-expressed, we identified strong relationships of expression between wingless-type MMTV integration site family member 5A (WNT5A)/frizzled homolog 2 (FZD2), frizzled homolog 3 (FZD3)/dishevelled 2 (DVL2), and low density lipoprotein receptor-related protein 5 (LRP5)/secreted frizzled-related protein 4 (SFRP4). This is one of the first studies to demonstrate expression of genes in the non-canonical pathway in normal lung tissue and its disruption in lung squamous cell carcinoma. These findings suggest that the non-canonical pathway may have a more prominent role in lung cancer than previously reported.

Thymoma: A Population-Based Study of the Management and Outcomes for the Province of British Columbia

Introduction: Thymomas are rare neoplasms with variable clinical behavior. Our primary study aim was to analyze treatment practices and outcomes in a population-based cohort of thymoma patients. We hypothesized that stage I and II thymomas would have high cure rates with resection and adjuvant radiation, whereas locally advanced cases would benefit from multimodality therapy. Methods: All patients, diagnosed with thymoma or thymic carcinoma in British Columbia between 1994 and 2009, were identified using the British Columbia Cancer Agency Registry. Chart review was used to collect demographic and treatment data. Detailed pathology review was performed using the World Health Organization classification. Results: One hundred and seventy-one patients were identified for analysis. The 5-year overall survival was 93.3%, 88.7%, 74.6%, 43.4% for stages I, II, III, and IV, respectively. Survival varied significantly among patients with thymoma compared with thymic carcinoma. In patients with stage II disease, adjuvant radiation did not confer an overall survival or recurrence-free survival benefit. Seventy-five patients had locally advanced disease. There was practice variation in treatment of these patients. Patients with thymoma undergoing trimodality treatment had a 5-year median overall survival of 80%, whereas patients with thymic carcinoma had poor outcomes despite aggressive treatment. Conclusions: Survival rates in this population-based series were comparable to those in previously published reports. The ideal management of thymic tumors involves a multidisciplinary approach, particularly in locally advanced disease and selection of patients for adjuvant radiation therapy.