Opportunities for NanoTheranosis in Lung Cancer and Pulmonary Metastasis.

Malignancies of the lungs, both primary and metastatic, are the leading cause of death worldwide. Over 1.5 million new cases of primary lung cancer are diagnosed annually worldwide with a dismal five-year survival rate of approximately 15%, which remains unchanged despite major efforts and medical advances. As expected, survival for patients with lung metastases is even worse at about 5%. Early detection and staging are fundamental in improving survival rates and selecting the most effective treatment strategies. Recently, nanoparticles have been developed for imaging and treating various cancers, including pulmonary malignancies. In this work, three different examples of nanoparticle configurations for cancer theranosis are presented, namely conventional spherical polymeric nanoparticles with a diameter of ~ 150 nm; and discoidal mesoporous silicon nanoconstructs and discoidal polymeric nanoconstructs with a diameter of ~ 1,000 nm and a height of 400 and 500 nm, respectively. The spherical nanoparticles accumulate in tumors by means of the well-known enhanced permeation and retention effect, whereas sub-micrometer discoidal nanoconstructs are rationally designed to adhere firmly to the tortuous tumor vasculature. All three nanoparticles are characterized for their in vivo performance in terms of magnetic resonance, positron-emission tomography (PET), and optical imaging. Preliminary data on the in vivo and ex vivo PET/CT imaging of breast cancer metastasis in the lungs using discoidal nanoconstructs is presented. In conclusion, opportunities for nanoparticle-based theranosis in primary lung cancer and pulmonary metastasis are presented and discussed.

New era of radiotherapy: an update in radiation-induced lung disease.

Over the last few decades, advances in radiotherapy (RT) technology have improved delivery of radiation therapy dramatically. Advances in treatment planning with the development of image-guided radiotherapy and in techniques such as proton therapy, allows the radiation therapist to direct high doses of radiation to the tumour. These advancements result in improved local regional control while reducing potentially damaging dosage to surrounding normal tissues. It is important for radiologists to be aware of the radiological findings from these advances in order to differentiate expected radiation-induced lung injury (RILD) from recurrence, infection, and other lung diseases. In order to understand these changes and correlate them with imaging, the radiologist should have access to the radiation therapy treatment plans.

Radiographic imaging features of thoracic complications after pneumonectomy in oncologic patients.

PURPOSE: The morbidity and mortality for pneumonectomy in patients has been reported to be as high as 24%. To determine if a subset of patients undergoing pneumonectomy for a malignancy would have similar complication rates and appearances, we performed a review of the radiographic findings of patients at our institution. METHOD: A retrospective review of a thoracic surgery database was performed at our institution for patients who underwent pneumonectomy between January 2001 and April 2004. All images were reviewed on the institutional patient archive communication system, by two experienced, fellowship trained, thoracic radiologists. RESULTS: There were 144 patients (112 men and 32 women) with a mean age of 52 years (range 21-83 years). Of the 144 patients, thoracic complications were present in 52 (36%) patients consisting of pneumonia in 19 (13%), empyema/pleural space infection in 9 (6%), adult respiratory distress syndrome (ARDS) in 8 (6%), bronchopleural fistula in 7 (5%), gortex graft failure/organ herniation in 4 (3%), chylothorax/chyle leak in 2 (1%), pulmonary embolus in 2 (1%), pulmonary hemorrhage in 1 (<1%). CONCLUSION: In oncologic patients, post-pneumonectomy complications occur in over a third of patients and can be life threatening. The presentations are similar to other pneumonectomy patients and are often radiographically detectable. Therefore it is important for radiologist to be aware of the radiographic manifestations of these complications so that appropriate immediate treatment is instituted.

Radiotherapy patterns of care study in lung carcinoma.

PURPOSE: For the first time, a lung Patterns of Care Study was conducted to determine the national patterns of radiation (RT) practice in patients treated for nonmetastatic lung cancer in 1998 to 1999. MATERIALS AND METHODS: A national survey of randomly selected RT institutions in the United States was conducted using two-stage cluster sampling, stratified by practice type. Patients with nonmetastatic lung cancer (Karnofsky performance score [KPS] > or = 60), who received RT as definitive or adjuvant therapy, were randomly selected. To determine national estimates, sample size was weighted by the relative number of institutions per strata and the number of patient records reviewed per the number of patients eligible. Accordingly, 42,335 patient records from 58 institutions were reviewed by trained research associates. The unweighted sample size (or number of patients) was 541. RESULTS: The histologies were small-cell lung cancer (SCLC) in 14.5% of patients versus non-small-cell lung cancer (NSCLC) in 85.5% of patients. The median age was 67 years (range, 29 to 92 years); 61% of patients were male, and 38% were current smokers. Bone scans and brain imaging were not obtained in 34% and 52% of clinical stage (CS) III NSCLC patients, respectively. Regarding treatment strategies, for SCLC and CS III NSCLC, chemotherapy plus RT was used significantly more than RT alone (P <.05); in CS I NSCLC, RT alone was the primary treatment (P <.05). Overall, 58% of patients received systemic therapy. On multivariate analysis, factors correlating with increased use of chemotherapy included younger age, histology (SCLC > NSCLC), increasing CS, increasing KPS, and lack of comorbidities. Only 3% of all patients were treated on prospective clinical trials. CONCLUSION: This study establishes the general patterns of care for lung carcinoma in RT facilities within the United States. As supported by clinical trials, patients with limited-stage SCLC and CS III NSCLC received chemotherapy plus RT more than they received RT alone. Further improvements in staging, smoking cessation, and increased accrual to clinical trials must be encouraged.

Respiratory-driven lung tumor motion is independent of tumor size, tumor location, and pulmonary function.

PURPOSE: To determine whether superior-inferior lung tumor motion is predictable by tumor size or location, or pulmonary function test results. METHODS AND MATERIALS: Superior-inferior tumor motion was measured on orthogonal radiographs taken during simulation of 22 patients with inoperable lung cancer diagnosed by orthogonal radiographs. RESULTS: The tumor size averaged 5.5 +/- 3.1 cm (range 1.5-12 cm). Seven of 11 central tumors demonstrated some motion compared with 5 of 11 peripheral tumors. Four of 5 upper lobe tumors moved compared with 8 of 17 tumors that were either middle or lower lobe lesions. The mean fourth rib motion was 7.3 +/- 3.2 mm (range 2-15). The mean FeV(1) was 1.8 +/- 1.2 (range 0.55-5.33. The mean diffusing capacity of the lung for carbon monoxide was 14.0 +/- 6.5 (range 7.8-21.9). The mean total lung capacity was 6.5 +/- 1.2 (range 3.3-8.4). None of these parameters correlated with tumor motion. Although lateral tumor motion could not be consistently determined, 1 tumor moved 10 mm anterior-posteriorly. CONCLUSIONS: Lung tumors often move significantly during respiration. Tumor motion is not predictable by tumor size or location, or pulmonary function test results. Therefore, tumor motion must be measured in all patients. Measurement in three dimensions will likely be necessary to maximize the irradiated lung volumes or choose beam arrangements parallel to the major axis of motion.

Multi-institutional phase I/II trial of oral bexarotene in combination with cisplatin and vinorelbine in previously untreated patients with advanced non-small-cell lung cancer.

PURPOSE: Bexarotene (Targretin; Ligand Pharmaceuticals, Inc, San Diego, CA) is a retinoid-X-receptor (RXR)-selective retinoid with preclinical antitumor activity in squamous cell cancers. In this phase I/II trial, we combined bexarotene with cisplatin and vinorelbine in the treatment of patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-three patients who had stage IIIB NSCLC with pleural effusion or stage IV NSCLC and had received no prior therapy received bexarotene in combination with cisplatin (100 mg/m2) and vinorelbine (alternating doses of 30 mg/m2 and 15 mg/m2). In the phase I portion, the daily dose of bexarotene was escalated in cohorts of three patients from 150 mg/m2 to 600 mg/m2, beginning 1 week before the start of the cisplatin-vinorelbine regimen. Once the maximum-tolerated dose (MTD) of bexarotene was determined, the study entered the phase II portion. Response rate was the primary end point; median survival time and 1-year survival rate were secondary end points. RESULTS: In the phase I portion, the daily MTD of bexarotene was determined to be 400 mg/m2. Eight of 43 patients exhibited major responses. Seven (25%) of the 28 patients in the phase II portion responded to treatment. The median survival time in the phase II portion was 14 months; nine (32%) of the 28 patients were still alive at a minimum follow-up of 2 years. One-year and projected 3-year survival rates were 61% and 30%, respectively. The most common grade 3 and 4 adverse events were hyperlipemia, leukopenia, nausea, vomiting, pneumonia, dyspnea, anemia, and asthenia. Grade 3 and 4 laboratory abnormalities with incidences greater than 5% were decreased hemoglobin levels and WBC, absolute neutrophil, and absolute lymphocyte counts and increased prothrombin time and creatinine and amylase levels. Of the two cases of pancreatitis, one required hospitalization and both were associated with increased triglyceride levels. There was one death secondary to renal insufficiency unrelated to bexarotene treatment. CONCLUSION: In patients with advanced NSCLC, bexarotene with cisplatin and vinorelbine yielded acceptable phase II response rates (25%) and was associated with better-than-expected survival (14-month median survival time; 61% 1-year, 32% 2-year, and 30% projected 3-year survival rates). The regimen should be studied in larger clinical trials.

"Ditzels" on chest CT: survey of members of the Society of Thoracic Radiology.

OBJECTIVE: We surveyed the members of the Society of Thoracic Radiology regarding their interpretation of and management decisions for very small (3-5 mm) pulmonary nodules-"ditzels"-noted on CT. SUBJECTS AND METHODS: A survey consisting of 13 case scenarios in which ditzels were encountered on CT examinations was mailed to the 406 members of the Society of Thoracic Radiology. Statistical analysis was performed to determine associations between responses, years of experience, location in an endemic region of granulomatous disease, and location at a lung or a general cancer center. RESULTS: One hundred fifty-one surveys (37%) could be included in the analysis. The most common response was "short-term follow-up." As the likelihood of malignancy increased, the response of "recommend biopsy" or "considered malignant or metastatic" increased. Those radiologists located in an area considered endemic for granulomatous disease were more likely to consider an incidental ditzel benign and to recommend follow-up, whereas those in a nonendemic area were more likely to recommend biopsy. In the cases in which years of experience had an influence, the less experienced respondents were more likely to choose "nothing, considered benign" or short-term follow-up than biopsy. CONCLUSION: The most common response was short-term follow-up, with less aggressive recommendations in cases with a lower likelihood of malignancy and more aggressive recommendations in cases with a higher likelihood of malignancy. Location in an area considered endemic for granulomatous disease and years of experience influenced decisions.

Coronary artery dosimetry in intact left breast irradiation.

PURPOSE: The purpose of this article is to report dose-volume histograms of coronary vessels from irradiation of the intact left breast. PATIENTS AND METHODS: Fifteen women with cancer of the left breast underwent computed tomographic treatment planning for radiation treatments of an intact left breast. Images through the heart were reconstructed at 1-mm increments to permit contouring of the coronary vessels. Five treatment plans were created for each patient; one plan from the simulated treatment fields and four additional plans that were generated from virtual treatment fields created by shifting the isocenter 5 mm and 10 mm both superficially and deep. The radiation dose was calculated using a three-dimensional treatment planning system that incorporated heterogeneity correction factors. RESULTS: With no adjustment to the perpendicular lung distance, a mean volume of 12% of the left anterior descending coronary artery received 20 Gy, 6% received 30 Gy, and 3% received 40 Gy. The dose to the left anterior descending coronary artery varied significantly with changes in the perpendicular lung distance. From the mean perpendicular lung distance of 1.87 for the simulated fields, a 5-mm increase in the perpendicular lung distance resulted in an increase of 20%, 15%, and 12% in the percentage of the left anterior descending coronary artery treated to 20 Gy, 30 Gy, and 40 Gy, respectively. With a 10-mm increase, the respective volumes were increased to 49%, 41%, and 34%, respectively. A 5-mm reduction of lung distance in the original plan resulted in a decrease of 10%, 5%, and 3% in the percentage treated to 20 Gy, 30 Gy, and 40 Gy, respectively. The dose to the left main coronary artery, the right main coronary artery, and the left circumflex coronary artery was limited to scatter and was less than 7 Gy. Changes in the perpendicular lung distance did not significantly affect the dose administered to these vessels. DISCUSSION: The left anterior descending coronary artery is anatomically located at the edge of the cardiac silhouette on traditional treatment films. Small changes in the perpendicular lung distance can significantly change the dose delivered to this vessel. A fundamental change in the shape of the dose-volume histogram occurs at a perpendicular lung distance of 2.3 cm, whereas the dose is very low when the perpendicular lung distance is less than 1.3 cm. These points may serve as clinically important values in the treatment planning for cancer of an intact breast.

Kaposi sarcoma in a renal transplant patient.

The radiographic abnormalities of primary Kaposi's sarcoma of the lung in a patient with a renal transplant are reported. The findings are similar to other malignancies and infections that are well recognized in the renal transplant population. In the appropriate clinical setting, the radiologist should consider the diagnosis of Kaposi's sarcoma even in the absence of cutaneous lesions as reducing immunosuppression can be curative therapy.

A multidisciplinary surgical approach to superior sulcus tumors with vertebral invasion.

BACKGROUND: Vertebral body invasion by superior sulcus tumor has traditionally been considered a contraindication to surgical resection. Attempts at definitive radiation or chemoradiation have not been successful. Recent advances in spinal instrumentation have allowed more complete resection of vertebral body tumors. We, therefore, reviewed our recent experience with vertebral resection of superior sulcus tumors. METHODS: All patients (n = 17) undergoing resection of superior sulcus tumors with T4 involvement of the vertebrae from October 18, 1990 to September 21, 1998 at the University of Texas M.D. Anderson Cancer Center (MDACC) were evaluated. Their clinical and pathologic data were reviewed and analyzed for short- and long-term outcomes. RESULTS: Total vertebrectomy was performed in 7 patients (42%), partial vertebrectomy in 7 (42%), and 3 (18%) underwent neural foramina or transverse process resection. The median hospital stay was 11 days. Postoperative complications occurred in 7 patients (42%) and included pneumonia (6, 36%), arrhythmia (2, 12%), cerebrospinal fluid leak (2, 12%), wound breakdown (1, 6%), and reoperation for bleeding (1, 6%). Sixteen out of 17 patients received preoperative or postoperative radiation therapy. No perioperative mortality occurred. All patients remained ambulatory after spinal reconstruction. Overall actuarial survival at 2 years was 54%, with 11 patients still alive 2 to 50 months after resection. Locoregional tumor recurrence was noted in all 6 patients who had positive surgical margins, as opposed to 1 out of 11 patients (9%) with negative margins (p < 0.006). Additionally, the 2-year actuarial survival of patients with negative microscopic margins was 80% versus 0% for positive margins (p < 0.0006). CONCLUSIONS: An aggressive multidisciplinary approach to superior sulcus tumors with vertebral invasion can lead to long-term survival with acceptable morbidity if negative margins can be obtained. Vertebral body invasion should no longer be considered a contraindication for resection of superior sulcus tumors.

Malignant pleural mesothelioma: the spectrum of manifestations on CT in 70 cases.

AIM: The aim of this pictorial review is to illustrate the spectrum of manifestations on computed tomography (CT) of malignant pleural mesothelioma. Malignant pleural mesothelioma is the most common primary neoplasm of the pleura, but nevertheless is a rare tumour. It has a strong association with previous occupational exposure to asbestos and has a bleak prognosis. MATERIALS AND METHODS: The pre-treatment CT findings of 70 patients at our institution, and the subsequent findings of the 35 patients who had follow-up CT, have been reviewed by three observers by consensus. 16 patients had surgical resections. RESULTS: The most common pre-treatment findings were pleural thickening (94%) and pleural effusions (76%). Both contraction (27%) and enlargement (10%) of the ipsilateral hemithorax were identified. Extension of disease to the chest wall, mediastinum, thoracic lymph nodes, and below the diaphragm were identified. Concurrent bilateral pleural calcification and plaques indicative of previous asbestos exposure were identified in 16% of patients. CT failed to identify chest wall and mediastinal invasion in a number of patients who underwent surgical resections. CONCLUSION: CT plays an important role in the diagnosis, assessment, and evaluation of treatment response of this tumour, although it has some limitations in specific areas in evaluating patients for surgical resection.

The radiology of the thoracic manifestations of AIDS.

The thoracic manifestations of AIDS have undergone a gradual metamorphosis, partly due to more awareness about the disease leading to earlier diagnoses and partly due to the fact that research has produced more effective prophylaxis as well as treatment for these patients. Many patients now demonstrate partial or complete clinical response which prolongs the length and quality of life of individuals positive for the Human Immunodeficiency Virus (HIV+). Also, with the large number of infected individuals coming to medical attention, and the years of experience in diagnosing and treating these AIDS patients, we now recognize not only the usual but also less usual manifestations of thoracic illnesses in AIDS, including infections, non-infectious diseases such as HIV associated Lymphocytic Interstitial Pneumonia and the neoplasms associated with AIDS. A section will be devoted to HIV infection in children. We will finish the article with a discussion of the current role of Nuclear Medicine in the diagnosis of HIV associated thoracic diseases. These topics are the subject of this article.

Rounded atelectasis and mesothelioma.

OBJECTIVE: The purpose of this article is to report the coexistence of rounded atelectasis with malignant pleural mesothelioma as revealed by radiography and CT. CONCLUSION: Our five cases show the coexistence of rounded atelectasis and malignant mesothelioma. If rounded atelectasis is associated with a pleural effusion, a pleural mass with or without chest-wall invasion, or thickened pleura not adjacent to the rounded atelectasis, malignant mesothelioma should be strongly considered.

Value of spiral CT in hemodynamically stable patients following blunt chest trauma.

INTRODUCTION: Features of spiral CT (SCT)-fast scanning, dynamic injection of contrast allowing optimal vessel opacification, and supplemental multiplanar imaging-promises to provide increased accuracy in the diagnosis of acute and non acute thoracic vascular disease. Recent work demonstrating the cost effective triage of hemodynamically stable patients after blunt chest trauma for angiography based on dynamic CT findings has prompted an investigation into the accuracy of SCT in this clinical setting. METHODS: A retrospective review of all patients seen in the emergency department over the period of one year for aortic, thoracic, or blunt chest trauma evaluation was performed (74 patients) and all SCT scans available were reviewed and data reformatted for optimal delineation of pathology using maximum intensity projection and multiplanar reformation. The accuracy and predictive positive and negative values of SCT were calculated with respect to angiography, surgical, and/or clinical follow up evaluation. RESULTS: Twenty three (31%) patients went directly to angiography owing to mediastinal widening on chest film and hemodynamic instability, of which four were positive and required emergent surgery. Seven hemodynamically stable patients (9%) had noncontrast SCT owing to mediastinal widening on chest film, all of which had angiography with none having great vessel trauma. Fourty four hemodynamically stable patients (60%) had contrast enhanced SCT (ceSCT), of which five (11%) were abnormal and underwent angiography, four of these were positive for aortic damage, one for a subclavian artery laceration. Of the remaining 39 patients who had normal ceSCT; five had angiography, all of which were normal. Of the remaining 34 patients that had normal ceSCT none had adverse outcome on clinical follow-up, minimum of 12 months. CONCLUSION: The predictive positive value for aortic trauma of ceSCT in blunt trauma is 80%, with a predictive negative value of 100%, indicating that it is feasible for SCT to be a first line exam in blunt chest trauma in the future.