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Biomedical subjects

Reginald F Munden

Publications and source records attributed to Reginald F Munden.

6 recordsLinked to original sources

Interobserver and intraobserver variability in measurement of non-small-cell carcinoma lung lesions: implications for assessment of tumor response.

PURPOSE: Response of solid malignancies to therapy is usually determined by serial measurements of tumor size. The purpose of our study was to assess the consistency of measurements performed by readers evaluating lung tumors. MATERIALS AND METHODS: The study group was composed of 33 patients with lung tumors more than 1.5 cm. Bidimensional (BD) and unidimensional (UD) measurements were performed on computed tomography (CT) scans according to the World Health Organization (WHO) criteria and the Response Evaluation Criteria in Solid Tumors (RECIST), respectively. Measurements were performed independently by five thoracic radiologists using printed film and were repeated after 5 to 7 days. Inter- and intraobserver measurement variations were estimated through statistical modeling. RESULTS: There were 40 tumors with an average size of 1.8 to 8.0 cm (mean, 4.1 cm). Analysis of variance showed a significant difference (P <.05) among readers and among the measured nodules for UD and BD measurements. Interobserver misclassification rates were more than intraobserver misclassification rates using either progressive disease or response criteria. The probability of misclassifying a tumor with the WHO criteria or RECIST was greatest with interobserver measurements when criteria for progression (43% BD, 30% UD) were used and lowest with intraobserver measurements when criteria for response (2.5% BD, 3.0% UD) were used. In addition, interobserver misclassification rates were more than intraobserver misclassification rates for both regular and irregular tumors. CONCLUSION: Measurements of lung tumor size on CT scans are often inconsistent and can lead to an incorrect interpretation of tumor response. Consistency can be improved if the same reader performs serial measurements for any one patient.

Adult↗

Lung cancer screening.

Low-dose CT screening for lung cancer is a complex and controversial topic. This article reviews the history of lung cancer screening trials and addresses the principles and confounding biases associated with screening. Chest radiography was initially used for lung cancer screening in the 1970s. In the mid-1990s helical single-detector CT came into use, followed by helical multidetector CT, the current method of screening. Results from prevalence studies and a few single-arm incidence studies have raised concerns about overdiagnosis and the high rate of nodule detection. Follow-up studies and further investigation are needed. To this end, a randomized, controlled trial sponsored by the National Cancer Institute is underway to evaluate disease-specific mortality.

Clinical Trials as Topic↗

The novel and effective nonplatinum, nontaxane combination of gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma: potential for decreased toxicity and combination with biological therapy.

BACKGROUND: Gemcitabine and vinorelbine are two of the most active third-generation agents for the treatment of advanced nonsmall cell lung carcinoma (NSCLC). The authors conducted a formal Phase II trial to evaluate the efficacy of this combination in both untreated and previously treated patients with Stage IIIB (with pleural effusion) or Stage IV NSCLC. METHODS: A total of 78 patients were treated on the current Phase II trial of front-line or second/third-line therapy with gemcitabine and vinorelbine in NSCLC. Eligible patients manifested either untreated disease (n = 42) or had received at least one but not more than two prior chemotherapy regimens (n = 36). The median age was 57.5 years (range, 33-79) with 57 men (73%) and 21 women (27%). The median performance status was one (range, one to two). The initial eight patients (four untreated and four previously treated) were treated at a previously established maximum tolerated dose of vinorelbine (30 mg/m(2)) and gemcitabine (1000 mg/m(2)) on Days 1, 8, and 15, with significant myelosuppression seen in five out of eight patients requiring dose omission in the first cycle. The next 70 patients received a reduced dose of vinorelbine (25 mg/m(2)) followed by gemcitabine (900 mg/m(2)) on Days 1, 8, and 15. RESULTS: Seventy eight patients were treated. Fifteen (36%) of the 42 evaluable patients who received front-line therapy had objective responses and 14 (33%) had stable disease. In the patients with prior treatment, 6 (17%) of 36 patients had partial response and 18 patients (50%) had stable disease. Median survival time for the previously untreated patient group was 10.1 months, with a one year survival of 43% and a two year survival rate of 32%. For the previously treated patients, the median survival time was 8.5 months, with a one year survival rate of 30%. Toxic effects were notable for significant myelosuppression, with > or =Grade 3 granulocytopenia seen in 55% of the patients on the untreated arm and 67% of the patients on the previously treated arm. Additionally, 9.5% and 13.9% (untreated and previously treated), respectively, of these patients experienced Grades 3 and 4 thrombocytopenia at some point in their treatment. A full dose delivery analysis showed that this myelosuppression resulted in Course 1, Day 15 skipped doses (even at the reduced dose level) in 42% of previously untreated patients and 47% of pretreated patients. Other side effects seen at Grades 3 and 4 in previously untreated and treated patients included anemia (9.5% and 2.8%), asthenia (4.8% and 5.5%), infection (14.3% and 5.6%), pain (9.5% and 19.4%), and pulmonary complications (4.8% and 13.8%). CONCLUSIONS: Gemcitabine/vinorelbine is an active, well-tolerated combination in both front-line and second/third-line therapy for Stage IIIB/IV NSCLC. The response rate, median survival rate, and one year survival rate compare favorably with platinum-based regimens. The toxicity profile of the gemcitabine/vinorelbine combination was quite favorable, with minimal Grade 3 and 4 toxic effects aside from granulocytopenia, which resulted in numerous Day 15 skipped doses but no significant febrile neutropenia or infection. The combination of gemcitabine and vinorelbine could be a useful regimen in standard clinical practice and has the potential for efficient combination with biologic/targeted therapy. Multiple randomized trials of this combination versus platinum combinations are now ongoing [corrected].

Adult↗

Radiation injury of the lung after three-dimensional conformal radiation therapy.

OBJECTIVE: The objective of this study is to describe the CT patterns of radiation injury in the lungs of patients who have undergone three-dimensional (3D) conformal radiation therapy (CRT). MATERIALS AND METHODS: Over a 36-month period, the chest CT scans of 19 patients with non-small cell lung cancer who were treated with 3D CRT were reviewed. CT scans were evaluated for findings of radiation injury (ground-glass opacities, consolidation, bronchiectasis, and volume loss). The presence, extent, and distribution of these findings were reached by consensus. RESULTS: Radiation pneumonitis limited to a small area immediately around the tumor was present in all patients who were imaged within 3 months after completion of the treatment (n = 7). Radiation-induced fibrosis occurred in all patients (n = 19). Three distinct patterns of fibrosis were consistently present, and these were classified as modified conventional, masslike, and scarlike. Modified conventional fibrosis (consolidation, volume loss, and bronchiectasis similar to, but less extensive than, conventional radiation fibrosis) was seen in five patients. Masslike fibrosis (focal consolidation with traction bronchiectasis limited to the site of the original tumor) was seen in eight patients. Scarlike fibrosis (linear opacity in the region of the original tumor associated with moderate to severe volume loss) was seen in six patients. CONCLUSION: Three-dimensional conformal radiation therapy results in three patterns of radiation fibrosis that differ from the conventional radiation-induced lung injury. Knowledge of the full spectrum of these manifestations is useful in the correct interpretation of CT scans after 3D CRT.

Adult↗

Primary thoracic sarcomas.

Primary sarcomas of the thorax are rare. The diagnosis is established only after sarcomalike primary lung malignancies and metastatic disease have been excluded. Primary sarcomas of the thorax are classified according to their histologic features and constitute a large group of tumors that occur in the lung, mediastinum, pleura, and chest wall. Angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, and mesothelioma (sarcomatoid variant) are the most common primary intrathoracic sarcomas. Ewing sarcoma, primitive neuroectodermal tumor, chondrosarcoma, malignant fibrous histiocytoma, osteosarcoma, synovial sarcoma, and fibrosarcoma usually arise in the chest wall. Although primary thoracic sarcomas commonly manifest as large, heterogeneous masses, they have a wide spectrum of radiologic manifestations, including solitary pulmonary nodules, central endobronchial tumors, and intraluminal masses within the pulmonary arteries. The different histologic types of sarcomas are frequently indistinguishable at radiologic analysis. However, differences in clinical presentation and the location of the tumor, as well as morphologic features such as calcification within the mass and rib involvement, can be useful in suggesting the appropriate diagnosis. For example, a large rib mass in a child with fever and malaise indicates a Ewing sarcoma, a mass with a calcified matrix is likely a chondrosarcoma or osteosarcoma, and a pulmonary artery mass is likely a leiomyosarcoma.

Adult↗