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Biomedical subjects

W D Kaplan

Publications and source records attributed to W D Kaplan.

At least 37 records · Page 2Linked to original sources

Bone scans with one or two new abnormalities in cancer patients with no known metastases: reliability of interpretation of initial correlative radiographs.

To determine the reliability of radiographs obtained for correlation with bone scans showing one or two new abnormalities in cancer patients without known metastases, a retrospective study of 306 scans showing such lesions was performed. Overall, 14% of the lesions proved to be malignant. The initial radiographic interpretation was normal for 43% of the new bone scan lesions; 17% of these lesions were metastases. A benign process was identified on radiographs for 38% of the abnormalities; only one (1%) was a metastasis. Twelve percent of new bone scan lesions correlated with radiographic abnormalities considered either suggestive of or consistent with metastasis, of which 24% and 71%, respectively, proved to be metastases. In cancer patients with one or two new bone scan abnormalities, correlative radiographs showing a benign abnormality are reliable. However, if the radiographs are either normal or show findings considered suggestive of or consistent with metastasis, further evaluation or follow-up is warranted.

Bone Diseases↗

Bone scans with one or two new abnormalities in cancer patients with no known metastases: frequency and serial scintigraphic behavior of benign and malignant lesions.

Scintigraphic, radiologic, and clinical follow-up findings were reviewed in cases in which bone scans (n = 301) showed one or two new abnormalities in patients with malignancy but no known metastases. Metastatic disease was confirmed for 25 of 231 scans (11%) with one new abnormality and for 17 of 70 scans (24%) with two new abnormalities. The prevalence of metastases was 0.06 to 0.13 for lesions in all regions of the skeleton, except the sternum (three of six) and the pelvis (10 of 32). On follow-up scans, in the absence of an interval change in therapy, 19 of 21 metastases became more intense, whereas most benign abnormalities either remained unchanged (47%) or resolved (41%). Benign lesions in the ribs, extremities, and pelvis generally resolved within 12-24 months, while most benign skull and spine abnormalities were still apparent after 35-58 months of follow-up.

Bone Neoplasms↗

Gallium-67 imaging: a predictor of residual tumor viability and clinical outcome in patients with diffuse large-cell lymphoma.

Durable complete remissions (CRs) can be achieved in patients with diffuse large-cell lymphoma (DLCL) with multidrug chemotherapy. The length of time to reach CR may be predictive of treatment outcome. However, defining CR by chest radiograph or computed tomography (CT) is often difficult since residual abnormalities do not always indicate residual disease. We have prospectively evaluated the ability of gallium-67 citrate (Ga-67) imaging to define residual disease and predict outcome in 37 consecutive patients with DLCL. Patients received 296 to 370 megabecquerels (MBq) Ga-67 and were imaged prior to, following cycles 4 to 6, and at completion of intensive chemotherapy. Ga-67 scan results were correlated with radiographic studies. Seventeen of 37 patients (46%) showed persistent, abnormal Ga-67 uptake halfway through chemotherapy. Of these, four were in CR, 11 were in partial remission (PR), and two showed no change in tumor size. At follow-up, 10 (59%) have died (three who were scored as CR and seven who were in PR halfway through therapy), two are alive with active tumor, one relapsed and survives following bone marrow transplant, and four (three in PR and one in CR at the therapeutic halfway point) are without disease at a median of 28 months from presentation. Of the 20 patients who were Ga-67-negative halfway through therapy, 11 were in CR and nine were in PR. Five of 20 patients (25%) have died. Three, in radiographic CR died at 11, 26, and 28 months, and two in radiographic PR died at 15 and 17 months. One patient is alive with active tumor, and 14 patients (70%) are alive without disease at a median of 34 months from presentation. Ga-67 imaging proved to be an excellent indicator of residual viable tumor; a positive scan halfway through therapy predicted for a poor outcome and may well justify a change in treatment.

Adult↗

Increased lung uptake on technetium-99m-sulfur colloid liver-spleen scans in patients with hepatic venoocclusive disease following bone marrow transplantation.

Three patients who developed signs and symptoms of liver dysfunction following autologous bone marrow transplantation showed varying degrees of increased lung uptake on technetium-99m-sulfur colloid (99mTc-SC) liver-spleen-scans and were subsequently demonstrated to have hepatic venoocclusive disease (VOD) at autopsy. Although increased lung uptake of labeled colloid has been noted in solid organ and bone marrow transplant patients, an association between this phenomenon and VOD has not been previously reported.

Adult↗

Association between number and sites of new bone scan abnormalities and presence of skeletal metastases in patients with breast cancer.

Review of 1,441 bone scans performed on 242 breast cancer patients without known skeletal metastases identified 239 scans with new abnormalities. Findings on 54 of these 239 scans (23%) represented bone metastases. The proportion of scans reflecting metastases, grouped by the number of new abnormalities, was: (1) 20/182 (11%); (2) 9/26 (35%); (3) 4/9 (45%); (4) 1/2 (50%); greater than or equal to 5-20/20 (100%). When metastatic disease presented as a bone scan with 1-4 new abnormalities, the spine was the most common site of involvement (18 of 34 (53%)), followed by the skull (5/34; 15%), extremities and sternum (each 4/34; 12%). Rib lesions were the most common new findings on scans with less than 5 new abnormalities (seen on 76 of 219 scans (35%)) but only infrequently represented metastases (n = 2). Considering as indicative of malignancy only, those bone scans which demonstrated either (a) greater than or equal to 5 new abnormalities, (b) initial radiographic correlation suggestive of metastases, or (c) thoracic spine lesions with normal correlative radiographs, the presence of skeletal metastatic disease could be predicted with a sensitivity of 0.80 and a specificity of 0.94.

Bone Neoplasms↗

Alpha particle radio-immunotherapy: animal models and clinical prospects.

Short-lived isotopes that emit alpha particles have a number of physical characteristics which make them attractive candidates for radioimmunotherapy. Among these characteristics are high linear energy transfer and correspondingly high cytotoxicity; particle range limited to several cell diameters from the parent atom; low potential for repair of alpha-induced DNA damage; and low dependence on dose rate and oxygen enhancement effects. This report reviews the synthesis, testing and use in animal models of an alpha particle emitting radioimmunoconjugate constructed via the noncovalent chelation of Bismuth-212 to a monoclonal IgM antibody specific for the murine T cells/neuroectodermal surface antigen, Thy 1.2. These 212Bi-anti-Thy 1.2 immunoconjugates are capable of extraordinary cytotoxicity in vitro, requiring approximately three 212Bi-labeled conjugates per target cell to suppress 3H-thymidine incorporation to background levels. The antigen specificity afforded by the monoclonal antibody contributes a factor of approximately 40 to the radiotoxicity of the immunoconjugate. Animals inoculated with a Thy 1.2+ malignant ascites were cured of their tumor in an antigen-specific fashion by intraperitoneal doses of approximately 200 microCi per mouse. Alpha particle emitting radioimmunoconjugates show great potential for regional and intracavitary molecular radiotherapy.

Alpha Particles↗

Breast carcinoma metastatic to a meningioma. Case report and review of the literature.

We describe a patient who developed an intracranial mass that consisted of a meningioma and metastatic breast cancer. A literature review revealed 12 similar cases. In epidemiologic studies, the incidence of meningioma in patients with breast cancer is higher than expected. Both tumors are more common in women, have been reported to flare during pregnancy, and express hormone receptors. In a patient with breast cancer, an intracranial mass with radiographic features suggestive, but atypical, of a meningioma should be evaluated surgically. The lesion may represent a metastasis, a meningioma, or both.

Bone Neoplasms↗

Increased iofetamine I 123 brain uptake in metastatic melanoma.

Four of five patients with brain metastases from melanoma had increased lofetamine I 123 uptake in the region of the tumor deposits. A comparison group of five patients with melanoma with no clinical or radiologic evidence of brain involvement and 46 of 47 patients without malignant melanoma but with known brain tumors of other histologic types had normal or decreased iofetamine I 123 brain uptake in the region of the tumor. An exception was one patient whose metastatic small cell lung cancer to the brain showed focally increased uptake. These findings suggest that certain brain tumors such as melanoma are capable of selectively binding iofetamine I 123 because of specific chemical properties of the radiopharmaceutical. Increased uptake of iofetamine I 123 in brain lesions in a patient at risk for metastatic melanoma may be a useful aid to differential diagnosis.

Amphetamines↗

Three-dimensional internal mammary lymphoscintigraphy: implications for radiation therapy treatment planning for breast carcinoma.

Conservative surgery combined with radiation therapy for the treatment of early breast carcinoma has been shown to achieve both a high rate of local tumor control and good cosmetic results with a minimum of complications. Whether the internal mammary lymph nodes (IMNs) should be included in the treatment volume is a topic of considerable controversy. Radionuclide internal mammary node lymphoscintigraphy (IMN-LS) can locate these nodes in three dimensions. We have analyzed the results of IMN-LS in 167 patients imaged at the Dana-Farber Cancer Institute and treated at the Joint Center for Radiation Therapy between 1977 and 1980. The location of the IMNs was found variable from patient to patient. At least one IMN was not included within tangential fields arbitrarily arranged to have a medial entrance point 3.0 cm across the midline in 17% of evaluable patients. However, 48% and 66% of patients had IMNs that could be adequately treated with fields positioned only 1.0 cm or 2.0 cm across midline, respectively. We conclude that when treatment of the IMNs is warranted, IMN-LS not only assures their complete coverage in the majority of patients but also may help reduce the amount of heart and lung irradiated.

Breast↗

Biodistribution studies of anti-Thy 1.2 IgM immunoconjugates: implications for radioimmunotherapy.

We have prepared 111In radioimmunoconjugates (RICs) of the IgM isotype with specificity for the murine T cell/neuroectodermal surface antigen, Thy 1.2. Using gamma camera immunoscintigraphy, we have analyzed the biodistribution patterns of the RICs after intravenous and intraperitoneal injection into normal Thy 1.2+ and Thy 1.2- mice. Both routes of administration show antigen-specific uptake by the splenic T lymphocyte population. A high degree of nonspecific uptake by the reticuloendothelial system is also observed. Analysis of the specific activity of various segments of spleens from RIC-injected animals shows inhomogeneous uptake of the RIC not readily apparent by immunoscintigraphy. Animals injected with the RIC and then given high dose total body irradiation showed rapid shifts in radionuclide distribution away from the target cell population and into the general reticuloendothelial system, suggesting that death of the target cell can alter RIC biodistribution. Analyses of RIC biodistribution patterns will contribute to optimization of treatment by radioimmunotherapy.

Animals↗

Detection of hepatic metastases in diffuse fatty infiltration by CT: the complementary role of imaging.

Six patients undergoing computed tomographic (CT) evaluation for possible abdominal and pelvic metastases were shown to have diffuse fatty infiltration of the liver and findings indeterminate for hepatic metastases. In two patients with diffuse fatty infiltration and no focal hepatic lesions on CT, technetium-99m sulfur colloid imaging demonstrated focal hepatic defects confirmed to represent metastases. In four patients with diffuse fatty infiltration and hyperdense liver foci on CT, radionuclide imaging demonstrated normal uptake in the hyperdense foci confirmed to represent areas of normal liver spared by fatty infiltration. In each of the six patients, clinical management was altered by the radionuclide findings.

Fatty Liver↗

Failure patterns of nonseminomatous testicular germ cell tumors: radiographic analysis of 51 cases.

A retrospective analysis was performed of 51 consecutive cases of treatment failure (tumor recurrence) of nonseminomatous germ cell tumors. Twelve patients with clinical stage I disease relapsed after lymph node dissection; 39 with stage II or III disease relapsed after chemotherapy. Routine follow-up consisted of monthly chest radiography and determination of serum tumor marker levels (alpha-fetoprotein and human chorionic gonadotropin), as well as abdominal computed tomography every 6 months. The median recurrence interval was 3 months; 96% of the relapses occurred within 2 years. In 61% of patients, recurrence was in the initial disease site only, in 26% it was in both new and initial sites, and in 13% it was in new sites only. At the time of treatment failure, 47 (92%) of the patients had positive radiologic studies and 44 (86%) had positive serum marker levels. Nine (18%) had positive radiologic studies only, and four (8%) had positive serum marker levels only. The analysis demonstrated the complementary role of radiologic studies and serum tumor-marker assays in detecting treatment failure.

Adolescent↗

Planning mantle radiation therapy in patients with Hodgkin disease: role of gallium-67 scintigraphy.

Detection of all sites of lymphoma is imperative for accurate planning of radiation therapy. In patients with Hodgkin disease, mantle radiation is used to treat the thoracic lymph nodes; in those with early-stage or nonbulky disease, mantle and paraaortic radiation may be the only treatment given. CT scanning of the chest adds important information to that obtained from chest radiographs. Gallium-67 scintigraphy has also been used to provide additional information on sites of active tumor. To determine the usefulness of 67Ga-citrate scintigraphy in planning the portals for radiation therapy, we analyzed the radiation treatment plans in 26 consecutive patients with Hodgkin disease; in all 26 patients, the disease had been staged by chest radiographs, chest CT scans, and gallium-67 images. Gallium-67 imaging alone provided unique information that affected the treatment plans in three patients (12%). The combined results of gallium-67 imaging and CT scans influenced the planning of radiation therapy in eight patients (31%). Gallium-67 imaging was found to be an important adjunctive study for optimal planning of radiation therapy in patients with Hodgkin disease.

Gallium Radioisotopes↗

Clinical significance of isolated scintigraphic sternal lesions in patients with breast cancer.

Isolated scintigraphic sternal lesions are rare. In a retrospective review of the bone scan results of 1,104 patients with breast cancer, 34 individuals (3.1%) presented with this abnormality. Of these foci, 26 (76%) were found to represent metastatic disease. There did not appear to be a relationship with axillary lymph node metastasis, the quadrant involved by primary breast tumor, or selected serum chemistries. These sternal lesions may be associated with regional lymphatic tumor spread rather than hematogenous seeding and therefore could be considered a local recurrence.

Bone Neoplasms↗

The three-dimensional localization of internal mammary lymph nodes by radionuclide lymphoscintigraphy.

In breast cancer patients, radiation therapy planning must account for individual anatomy to ensure optimal coverage of tumor and internal mammary nodes. To achieve this, three-dimensional radionuclide lymphoscintigraphy (RNLS) was performed in 167 patients by obtaining two images of the nodes using a 30-degree slant hole collimator rotated 180 degrees between images. Analysis of 768 nodes (mean 4.6/patient) visualized from the level of rib 1 through interspace 5 was performed. The number of nodes seen was not a function of patient age. Cross-communication to the contralateral node chain occurred in 13.8% of cases. Eighty-two percent of nodes were located near the first three ribs and interspaces; 23% were located beyond 3.0 cm from the mid-sternal line. At the level of the radiation beam match line (second rib or interspace), 4.5% of nodes were deeper than 3.0 cm. From rib 3 through interspace 5, 3.9% were deeper than 3.0 cm. Using an idealized tangential field, at least one node would have been missed in 16.2% of patients. Three-dimensional RNLS allows definition and localization of normal sized nodes and ensures that radiation therapy portals can be tailored for each individual under treatment.

Adult↗

Lymphoma: evaluation with Ga-67 SPECT.

To determine the value of gallium-67 single photon emission computed tomography (SPECT) in imaging patients with lymphoma, the authors compared Ga-67 planar images and SPECT images in 40 consecutive patients, using radiologic examinations and/or medical records to confirm the presence or absence of disease. Thirty-three patients had Hodgkin disease, and seven had non-Hodgkin lymphoma. Fifty-four examinations were performed. Of 57 sites of lymphoma in the chest, planar imaging depicted 38, while SPECT depicted 55, resulting in sensitivities of 0.66 and 0.96 for planar and SPECT imaging, respectively. In eight sites, both modalities were truly negative, but SPECT was negative in four additional sites that were equivocal on planar imaging, resulting in specificities of 0.66 and 1.00 for planar and SPECT imaging, respectively. In the abdomen, the sensitivities of planar and SPECT imaging were 0.69 and 0.85, and the specificities 0.87 and 1.00, respectively. SPECT was more accurate in depicting foci of gallium-avid lymphoma in the chest and abdomen and in excluding disease when planar imaging was equivocal.

Adolescent↗