Biomedical subjects
Publications and source records attributed to Michelle S Ginsberg.
Lung cancer is the most frequently occurring cancer in the world, and in the United States it is the second most common cancer diagnosed. Accurate staging by imaging can have a significant impact on appropriate treatment and surgical options. Familiarity with the different histologic subtypes of lung cancer and the typical and atypical appearances of lung cancer is vital. Radiologists serve a critical role in the diagnosis, staging, and follow-up of patients with lung cancer.
A 65-year-old man with metastatic renal cell carcinoma developed progressive disease after treatment with interferon-alpha. He began treatment with sunitinib, a multitargeted tyrosine kinase inhibitor, on clinical trial. The patient achieved a partial response after two cycles of therapy, with a durable response continuing after 2 years of treatment. This case report illustrates the long-term response to sunitinib for patients with metastatic renal cell carcinoma.
CONTEXT: Current treatment options for metastatic renal cell carcinoma (RCC) are limited and there is a need to identify novel and effective therapies. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, which has shown activity in an initial study of cytokine-refractory metastatic RCC patients. OBJECTIVE: To confirm the antitumor efficacy of sunitinib as second-line treatment in patients with metastatic clear-cell RCC, the predominant cell type of this malignancy. DESIGN, SETTING, AND PATIENTS: Open-label, single-arm, multicenter clinical trial. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The reported data apply through August 2005. Patients (N = 106) had metastatic clear-cell RCC, which had progressed despite previous cytokine therapy. INTERVENTION: Repeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle. MAIN OUTCOME MEASURES: Assessment of clinical response, degree of tumor regression on imaging studies using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Primary end point was overall objective response rate (complete plus partial). Secondary end points were progression-free survival and safety. Response was evaluated by independent third-party core imaging laboratory and by treating physicians (investigator assessment). RESULTS: All 106 patients received sunitinib and were included in the intent-to-treat population for safety analyses. Of these, 105 patients were evaluable for efficacy analyses. The objective response rate according to an independent third-party assessment resulted in 36 patients with partial response (34%; 95% confidence interval, 25%-44%), and a median progression-free survival of 8.3 months (95% confidence interval, 7.8-14.5 months). The most common adverse events experienced by patients were fatigue in 30 (28%) and diarrhea 21 (20%). Neutropenia, elevation of lipase, and anemia were the most common laboratory abnormalities observed in 45 (42%), 30 (28%), and 27 (26%) patients, respectively. CONCLUSION: The results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00077974.
A pulmonary carcinoid tumorlet (PCT) is a nodular proliferation of neuroendocrine cells smaller than 0.5 cm. On computed tomographic (CT) imaging, these nodules are nonspecific in appearance and can mimic metastatic disease. Cases of multiple PCTs diagnosed between 1992 and 2003 in patients with history of breast cancer were identified through a search of the pathology files. The clinical information was abstracted from the medical records. We identified 12 women with a history of breast cancer and biopsy-proven PCTs, who were treated at our institution in a period of 12 years. Only 3 women were smokers. The mean age at diagnosis of the breast cancer was 62.8 years. The breast cancer was invasive carcinoma in 10 cases (9 ductal and 1 lobular) and ductal carcinoma in situ and malignant phyllodes tumor in 1 case each. Six women received radiotherapy; 5, chemotherapy; and 4, hormonal treatment, alone or in combination. Pulmonary carcinoid tumorlets were identified within 5 months from diagnosis of the breast malignancy in 7 patients and at follow-up (range, 57-162 months) in the remaining 5. In all cases, the PCTs consisted of multiple pulmonary nodules that were radiologically interpreted as suspicious for pulmonary metastases. Misdiagnosis of metastatic carcinoma was rendered intraoperatively by frozen section analysis in 3 cases. None of the patients had known metastatic disease at the time of diagnosis of PCTs. Three patients subsequently developed recurrent disease, including 2 with extramammary spread. Pulmonary carcinoid tumorlets are radiologic and histologic mimickers of pulmonary metastases in patients with a history of breast cancer. Consideration should be given to the possibility of PCTs in patients with breast cancer with pulmonary nodules, even if multiple.
PURPOSE: To prospectively quantify tumor response or progression in patients with lung cancer by using thin-section computed tomography (CT) and a semiautomated algorithm to calculate tumor volume and other parameter values. MATERIALS AND METHODS: This HIPAA-compliant study was institutional review board approved; informed patient consent was waived. CT scans of 15 measurable non-small cell lung cancers (in five men and 10 women; mean age, 64 years; range, 38-78 years) before and after gefitinib treatment were analyzed. A semiautomated three-dimensional lung cancer segmentation algorithm was developed and applied to each tumor at baseline and follow-up. The computer calculated the greatest diameter (unidimensional measurement), the product of the greatest diameter and the greatest perpendicular diameter (bidimensional measurement), and the volume of each tumor. Exact McNemar tests were used to analyze differences in the percentage change calculated with different measurement techniques. RESULTS: The computer accurately segmented 14 of the 15 tumors. One paramediastinal tumor required manual separation from the mediastinum. Eleven (73%) of the 15 patients had an absolute change in tumor volume of at least 20%, compared with one (7%) and four (27%) patients who had similar changes in unscaled unidimensional (P < .01) and bidimensional (P = .04) tumor measurements, respectively. Seven (47%) patients had an absolute change in tumor volume of at least 30%. In contrast, at unscaled analysis, no patients at unidimensional measurement (P = .02) and two (13%) patients at bidimensional measurement (P = .06) had a change of at least 30%. CONCLUSION: Compared with the unidimensional and bidimensional techniques, semiautomated tumor segmentation enabled the identification of a larger number of patients with absolute changes in tumor volume of at least 20% and 30%.
PURPOSE: Renal cell carcinoma (RCC) is characterized by loss of von Hippel Lindau tumor suppressor gene activity, resulting in high expression of pro-angiogenic growth factors: vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). SU11248 (sunitinib malate), a small molecule inhibitor with high binding affinity for VEGF and PDGF receptors, was tested for clinical activity in patients with metastatic RCC. PATIENTS AND METHODS: Patients with metastatic RCC and progression on first-line cytokine therapy were enrolled onto a multicenter phase II trial. SU11248 monotherapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off. Overall response rate was the primary end point, and time to progression and safety were secondary end points. Results Twenty-five (40%) of 63 patients treated with SU11248 achieved partial responses; 17 additional patients (27%) demonstrated stable disease lasting > or = 3 months. Median time to progression in the 63 patients was 8.7 months. Dosing was generally tolerated with manageable toxicities. CONCLUSION: SU11248, a multitargeted receptor tyrosine kinase inhibitor of VEGF and PDGF receptors, demonstrates antitumor activity in metastatic RCC as second-line therapy, a setting where no effective systemic therapy is presently recognized. The genetics of RCC and these promising clinical results support the hypothesis that VEGF and PDGF receptor-mediated signaling is an effective therapeutic target in RCC.
PURPOSE: To assess the effect of commonly used computed tomographic (CT) section thicknesses on metastatic tumor measurements calculated with unidimensional, bidimensional, area, and volumetric methods. MATERIALS AND METHODS: Analysis and data collection were approved by the Institutional Review Board, with waived informed patient consent. Forty-two pulmonary metastases in 10 patients (three men and seven women; age range, 43-83 years; mean age, 65.4 years) were analyzed on CT scans obtained with 3.75-, 5.0-, and 7.5-mm section thicknesses. The lesions were automatically delineated by using a three-dimensional multicriteria segmentation algorithm. Unidimensional (the largest diameter), bidimensional (the product of the two maximal perpendicular diameters), maximal cross-sectional area, and volumetric measurements were automatically obtained for each pulmonary lesion on each section thickness. Means and variances were calculated, and the differences across the three section thicknesses for each of the four measurements were studied by using linear mixed-effects models. The Levene test was used to study the equality of variances. RESULTS: Differences in the means for unidimensional, bidimensional, and area measurements were significant between a section thickness of 3.75 and 5.0 mm (unidimensional, P=.05; bidimensional, P=.05; area, P=.01) and 3.75 and 7.5 mm (unidimensional, P=.06; bidimensional, P=.03; area, P=.02), but not 5.0 and 7.5 mm. There was a significant difference in volumetric measurement as section thickness decreased from 7.5 to 5.0 mm (P <.001) and from 7.5 to 3.75 mm (P <.001). Although there was a slight trend for differences in the variances across section thickness for each measurement, none of the differences were significant. CONCLUSION: Volumetric tumor measurements change with a reduction in section thickness from 7.5 to 5.0 and 3.75 mm. For unidimensional measurement, no change was found when thickness decreased from 7.5 to 5.0 mm.
This document is a revision of a previously published cardiothoracic curriculum for diagnostic radiology residency, and reflects interval changes in the clinical practice of cardiothoracic radiology and changes in the Accreditation Council for Graduate Medical Education (ACGME) requirements for diagnostic radiology training programs. The revised ACGME Program Requirements for Residency Education in Diagnostic Radiology went into effect December 2003.
OBJECTIVES: Adenocarcinoma has replaced squamous cell carcinoma as the most common cell type of lung cancer in the United States. It has been proposed that this shift is due to the increased use of filter and lower-tar cigarettes, resulting in increased delivery of smoke to peripheral regions of the lungs, where adenocarcinoma usually occurs. We reviewed radiologic data to evaluate the hypothesis that tumors in smokers of cigarettes with lower-tar yield are more likely to occur peripherally than tumors in smokers of higher-yield cigarettes. METHODS: At two urban academic medical centers, we reviewed computed tomographic scans, chest radiographs, and medical records to assign tumor location (peripheral or central) for 330 smokers diagnosed with carcinoma of the lung between 1993 and 1999. We compared the proportion of tumors in a peripheral versus central location by lifetime filter use and average lifetime tar rating (< 21 and > or = 21 mg). RESULTS: Tumor location (69% peripheral and 31% central) was unrelated to cigarette filter use. Smokers of cigarettes with lower-tar ratings were more likely than those with higher ratings to have peripheral rather than central tumors (odds ratio, 1.76; 95% confidence interval, 0.89-3.47). When restricted to subjects with adenocarcinoma or squamous cell carcinoma, the odds ratio (95% confidence interval) was 2.31 (1.05-5.08). CONCLUSIONS: Among cigarette smokers with lung cancer, use of cigarettes with lower-tar yield was associated with preferential occurrence of tumors in peripheral sites. Our findings support the hypothesis that changes in smoking associated with lower-tar cigarettes have led to a shift in the location of smoking-related lung cancer.
OBJECTIVE: Our objective was to evaluate interobserver variability in interpretations performed by on-call radiology fellows and subsequently by attending radiologists of CT angiograms obtained for clinically suspected pulmonary embolism and to evaluate factors contributing to discrepancies. MATERIALS AND METHODS: Written interpretations made by on-call fellows were compared with reports approved by attending radiologists for all CT angiograms obtained for suspected pulmonary embolism after work hours and on weekends in a recent 19-month period. Interpretations were stratified as positive, negative, or equivocal for pulmonary embolism. In cases of discordant interpretations, those CT angiograms were rereviewed by two thoracic radiologists; then patient medical records were reviewed for evidence of clinical effect. Technical and patient-related reasons for discordant interpretations of CT angiograms were recorded. RESULTS: Six hundred fifty-eight oncology patients were examined on CT angiography; five were examined twice. The fellows reported 137 CT angiograms (21%) as positive, 498 (75%) as negative, and 28 (4%) as equivocal for pulmonary embolism. Interpretations of the fellows and attending radiologists agreed in 93% (615/663) of CT angiograms (kappa = 0.80). The concordance rates for CT angiograms interpreted by fellows as positive (89%, 122/137), negative (96%, 479/498), and equivocal (50%, 14/28) were significantly different from each other (p < 0.001 for each). A significantly greater proportion of CT angiograms with discordant interpretations was reported to be technically limited (p < 0.01). No clear adverse clinical events were attributed to discordant interpretations of CT angiograms, although the death of one patient in that subgroup was of indeterminate cause. CONCLUSION: In the evaluation of CT angiograms obtained for suspected pulmonary embolism, on-call fellows showed good agreement with attending radiologists. CT angiograms with discordant interpretations often were limited by technical or patient-related factors.
OBJECTIVE: Pulmonary tumorlets are defined in pathologic terms as benign localized neuroendocrine cell proliferations a few millimeters in size that are usually associated with damaged and ectatic small airways. The purpose of this study was to determine the frequency with which pulmonary tumorlets can be seen on CT and to describe their CT appearance. CONCLUSION: In 33 patients with proven tumorlets, a nodule was visible on CT in the same region as that of the resected specimen. Despite its ominous-sounding name, a pulmonary tumorlet represents benign tissue that may manifest as a subcentimeter pulmonary nodule and should be considered in the differential diagnosis of small pulmonary nodules visible on CT.
RATIONALE AND OBJECTIVES: The authors performed this study to determine the effect of routine editing on the style quality of trainee-generated radiology reports. MATERIALS AND METHODS: Trainee-generated reports of 50 body computed tomographic scans obtained at a tertiary care cancer center were edited in a routine fashion by one of two attending radiologists. Three physicians and four radiologists each independently evaluated the randomized unedited and edited reports (n = 100) and rated each report for clarity, brevity, readability, and quality of the impression by using a five-point scale. RESULTS: Editing significantly improved mean ratings for clarity (4.6 after editing vs 4.2 before editing, P < .007), brevity (4.6 vs 4.2, P < .007), readability (4.4 vs 4.1, P < .007), and quality of the impression (4.5 vs 4.3, P < .007). CONCLUSION: Routine editing of trainee-generated reports significantly improves the perceived report quality. This finding suggests that greater emphasis should be placed on stylistic aspects of reporting during training to improve report style quality at dictation.
Fifty-five patients with metastatic renal cell carcinoma (RCC) were treated on a multicenter, single-arm Phase II trial. Patients received single-agent Cetuximab (C225) administered by intravenous infusion at a loading dose of 400 or 500 mg/m2 followed by weekly maintenance doses at 250 mg/m2. None of the patients treated with C225 achieved either a complete or partial response. The median time to progression was 57 days. The most frequently reported grade 3 or 4 toxicity treatment-related adverse events were acne (17%) and rash or dry skin (4%). The lack of clinical response or suggestion of prolonging time to progression compared to historical data with interferon-alfa supports no further study of single-agent C225 in patients with metastatic RCC.
Increasingly, computed tomography (CT) offers higher resolution and faster acquisition times. This has resulted in the opportunity to detect small lung nodules, which may represent lung cancers at earlier and potentially more curable stages. However, in the current clinical practice, hundreds of such thin-sectional CT images are generated for each patient and are evaluated by a radiologist in the traditional sense of looking at each image in the axial mode. This results in the potential to miss small nodules and thus potentially miss a cancer. In this paper, we present a computerized method for automated identification of small lung nodules on multislice CT (MSCT) images. The method consists of three steps: (i) separation of the lungs from the other anatomic structures, (ii) detection of nodule candidates in the extracted lungs, and (iii) reduction of false-positives among the detected nodule candidates. A three-dimensional lung mask can be extracted by analyzing density histogram of volumetric chest images followed by a morphological operation. Higher density structures including nodules scattered throughout the lungs can be identified by using a local density maximum algorithm. Information about nodules such as size and compact shape are then incorporated into the algorithm to reduce the detected nodule candidates which are not likely to be nodules. The method was applied to the detection of computer simulated small lung nodules (2 to 7 mm in diameter) and achieved a sensitivity of 84.2% with, on average, five false-positive results per scan. The preliminary results demonstrate the potential of this technique for assisting the detection of small nodules from chest MSCT images.
PURPOSE: 10-propargyl-10-deazaaminopterin (PDX) has superior antitumor efficacy in mouse xenograft models, likely attributable to increased uptake by the RFC-1 folate transporter and greater intracellular polyglutamylation. In a previous Phase I trial, stomatitis was the dose-limiting (and only clinically significant) toxicity of PDX. The recommended Phase II dose was 150 mg/m(2) i.v. every 2 weeks. Responses observed in patients with non-small cell lung cancer (NSCLC) in the Phase I trial prompted this Phase II trial. EXPERIMENTAL DESIGN: Patients had stage IIIB or IV NSCLC and either no previous chemotherapy or progression after initial response or stable disease to one previous chemotherapy regimen. Initially, PDX was administered at a dose of 150 mg/m(2) every 2 weeks. However, to decrease the frequency of stomatitis, the last 10 patients were treated at a dose of 135 mg/m(2). We planned to correlate PDX effects with folate and homocysteine levels and the expression of genes associated with folate transport and polyglutamylation. RESULTS: Thirty-nine patients were enrolled, 38 of whom were evaluable for response. Four patients had confirmed, major objective responses (10% based on intent to treat, 95% confidence interval 3-25) lasting 4, 9, 12, and 15 months. Twelve patients (31%) had stable disease. The median survival was 13.5 months. The predicted 1- and 2-year survival rates were 56 and 36%, respectively. Two patients (5%) suffered grade 4 stomatitis, and 6 (15%) had grade 3. No clinically significant myelosuppression occurred. No correlation between homocysteine or serum folate levels and severity of stomatitis was observed. Area under the curve (calculated using a limited sampling model) correlated with mucositis grade. A trend was noted between folate transporter expression and treatment effect. CONCLUSIONS: The broad applicability of this new antifolate with limited toxicity and proven efficacy in NSCLC encourage further development of this compound. Several trials are now underway combining PDX with other chemotherapeutic agents and testing its efficacy in other cancers.
BACKGROUND: The 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) imaging is an advance over computed tomography alone in the staging of untreated nonsmall cell lung cancer (NSCLC). Aside from one 9-patient study, there are no data comparing FDG-PET imaging with surgical staging of NSCLC after induction therapy. METHODS: We reviewed our institutional experience with FDG-PET imaging followed by surgical staging of nonsmall cell lung cancer after induction therapy. A nuclear physician blinded to surgical findings reviewed the FDG-PET scans and assigned a clinical TNM stage. A thoracic surgeon assigned a pathologic TNM stage. Then the clinical TNM stage and the pathologic TNM stage were compared. RESULTS: Fifty-six patients (30 males and 26 females; median, age 60) with nonsmall cell lung cancer underwent chemotherapy (40 patients), chemoradiation (11 patients), or radiation alone (5 patients) followed by PET and operations. PET had a positive predictive value of 98% for detecting residual viable disease in the primary tumor. PET over-staged nodal status in 33% of patients, under staged nodal status in 15%, and was correct in 52%. PET correctly classified all patients with M1 disease. CONCLUSIONS: Positron emission tomography after induction therapy accurately detects residual viable primary tumor, but not the involvement of mediastinal lymph nodes.
OBJECTIVE: In patients who have a history of abdominopelvic radiation, surgery, or both, conventional colonoscopy may fail to examine the entire colon. The purpose of this study is to assess whether high-quality virtual colonoscopy can be achieved in this patient population. MATERIALS AND METHODS: After colonic cleansing, 61 patients (16 men and 45 women; mean age, 64 years; age range, 27-81 years) underwent 63 virtual colonoscopy examinations after using either single- or multidetector CT (slice thickness, 3.75-5.0 mm; table speed, 1.7-11.25 cm/sec; pitch, 1.5-3.0; and overlapped reconstructions, 1.95-2.5 cm) in supine and prone positions after IV administration of 1 mg of glucagon and rectal air insufflation. Conventional two-dimensional axial images were analyzed on a PACS (picture archiving and communication system) workstation. Two radiologists, who were unaware of patient history, independently evaluated the colonic distention on a 4-point scale (4 = optimal distention) and fluid retention on a 3-point scale (3 = no fluid) for all segments of the colon in patients who were imaged in both the supine and prone positions. Segmental and total average colon scores were calculated. RESULTS: Forty-one patients (65%; 43 examinations, 67%) underwent prior surgery, radiation, or both (surgery, n = 29; radiation, n = 3; both, n = 11). The average overall colonic distention and fluid retention for this group was 3.13 and 2.38, respectively, versus 3.24 and 2.3 in the control group (p = not significant). CONCLUSION: High-quality examinations were achieved in patients who had previously undergone radiation, surgery, or both with no clinically significant difference in distention or fluid retention compared with the controls.