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Donald Podoloff

Publications and source records attributed to Donald Podoloff.

9 recordsLinked to original sources

NCCN Task Force Report: Bone Health and Cancer Care.

Higher incidences of osteoporosis and osteopenia are found in cancer patients, particularly in women receiving aromatase inhibitors or with chemotherapy-induced ovarian failure, or in men with prostate cancer and androgen deprivation therapy. Therefore, management of long-term bone health is emerging as an important aspect of comprehensive cancer care. Patients with cancer typically have a number of additional risk factors for osteoporosis that should prompt screening, regardless of patient age or sex. Maintaining bone health requires a broad knowledge base, including understanding underlying bone metabolism and how it is affected by both cancer itself and the drugs used to treat cancer, the effect of chemotherapy-induced menopause on bone health, bone markers and imaging techniques used to assess bone health, therapeutic strategies to maintain bone health, and treatment of bone metastases, including surgery for pathologic fractures. Multiple members of the healthcare team may need to be involved in education and care of the patient. This report summarizes discussion of these and other issues regarding bone health and cancer care from the NCCN Bone Health and Cancer Care Task Force meeting in early 2006.

Advisory Committees↗

Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab.

PURPOSE: To determine overall response (OR) and complete response (CR) rates, response duration, progression-free (PFS) and overall survival and safety with the tositumomab and iodine-131 tositumomab ((131)I tositumomab) therapeutic regimen in patients with indolent, follicular large-cell, or transformed B-cell lymphoma, progressive after rituximab. PATIENTS AND METHODS: From July 1998 to November 1999, 40 patients (24 rituximab nonresponders: 11 with response < 6 months, and five with response > or = 6 months) received a therapeutic dose (0.65 to 0.75 Gy per platelet count) of (131)I tositumomab based on total-body dosimetry in this prospective phase II study. The median number of prior treatments was four; 59% of patients were chemotherapy-resistant. RESULTS: Confirmed OR (65%) and CR (38%) rates were not significantly associated with prior rituximab response. With a median follow-up of 3.3 years, the median PFS was 10.4 months, 24.5 months for responders, and not reached for CR patients. Among follicular grade 1 or 2 patients with tumors < or = 7 cm (n = 21), the OR and CR rates were 86% and 57%. Estimated 3-year PFS in this subgroup was 48%, compared with 11% for all others (P = .002). Transient grade 3 to 4 marrow toxicity was seen in 50% of patients. Two patients, one of whom received two subsequent chemotherapy regimens, developed secondary myelodysplasia. CONCLUSION: (131)I tositumomab is effective in CD20-positive lymphoma progressive after rituximab, with a 65% OR rate and median PFS of 24.5 months for responders. Patients with follicular grade 1 or 2 histology and tumors < or = 7 cm achieved very high OR and CR rates, with 48% PFS at 3 years.

Adult↗

Assessment of therapeutic tumor response using 99mtc-ethylenedicysteine-glucosamine.

PURPOSE: The aim of this study was to evaluate 99mTc-ethylenedicysteine-glucosamine (EC-DG) for the assessment of tumor growth. METHOD: To evaluate whether 99mTc-EC-DG is involved in cell nuclei activity, in vitro thymidine incorporation, and cell-cycle assays of EC-DG were conducted using lung and breast cancer cells. Biodistribution of 99mTc-EC-DG in lung tumor-bearing mice (0.5-4 hours, 1 Ci/mouse, i. v.) was used to estimate the radiation-absorbed dose. Autoradiograms of 99mTc-EC-DG and 18F-FDG were compared in nude mice bearing uterine sarcoma. Rabbits inoculated with VX-2 cells were imaged with 99mTc-EC-DG and 99mTc-EC. For therapeutic assessment studies, scintigraphic imaging studies with 99mTc-EC-DG in mammary tumor-bearing rats were conducted at various days after treatment with paclitaxel and cisplatin. The imaging findings were correlated immunohistochemical assays (mRNA expression, apoptosis, and cell-cycle changes in tumor), and flow cytometry analysis was performed. RESULTS: In vitro cellular uptake assays indicated that cell nuclei activity could be assessed by 99mTc-EC-DG. Scintigraphy and autoradiograms in animal models demonstrated that the tumor could be clearly visualized by 99mTc-EC-DG. The efficacy of paclitaxel and cisplatin treatment in rodent models could be assessed using tumor/muscle ratios. Immunohistochemical staining indicated a reduced expression of bFGF and an increased apoptosis and cell-cycle changes after paclitaxel and cisplatin treatment. CONCLUSION: 99mTc-EC-DG is involved in cell nuclei activity and could assess the therapeutic tumor response.

Animals↗

The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors.

UNLABELLED: Gastrointestinal stromal tumors (GISTs) are gaining the interest of researchers because of impressive metabolic response to the targeted molecular therapeutic drug imatinib mesylate. Initial reports suggest an impressive role for (18)F-FDG PET in follow-up of therapy for these tumors. However, the role of (18)F-FDG PET versus that of CT has not been established. Therefore, we compared the roles of (18)F-FDG PET and CT in staging and evaluation of early response to imatinib mesylate therapy in recurrent or metastatic GIST. METHODS: The study included 54 patients who underwent (18)F-FDG PET and CT scans within 3 wk before initiation of imatinib mesylate therapy. Forty-nine of these patients underwent repeat scans 2 mo after therapy. The numbers of sites or organs containing lesions on (18)F-FDG PET and CT scans were compared. Corresponding lesions on (18)F-FDG PET and CT scans or those confirmed to be malignant in appearance by other imaging modalities or on follow-up were considered true positives. Lesions seen on (18)F-FDG PET or CT scans but not seen or confirmed to be of benign appearance with other imaging modalities or on follow-up were considered false positives. Measurements of the maximum standard uptake value (SUV) on (18)F-FDG PET scans and tumor size on CT scans were used for quantitative evaluation of early tumor response to therapy. RESULTS: A total of 122 and 114 sites and/or organs were involved on pretherapy (18)F-FDG PET and CT scans, respectively. The sensitivity and positive predictive values (PPVs) for CT were 93% and 100%; whereas these values for (18)F-FDG PET were 86% and 98%. However, the differences between these values for CT and (18)F-FDG PET were not statistically significant (P = 0.27 for sensitivity and 0.25 for PPV). This suggests comparable performance of (18)F-FDG PET and CT in staging GISTs. Repeat scans at 2 mo after therapy showed agreement between (18)F-FDG PET and CT scans in 71.4% of patients (57.1% having a good response to therapy and 14.3% lacking a response). Discrepant results between (18)F-FDG PET and CT were recorded for 28.6% of the patients. (18)F-FDG PET predicted response to therapy earlier than did CT in 22.5% of patients during a longer follow-up interval (4-16 mo), whereas CT predicted lack of response to therapy earlier than (18)F-FDG PET in 4.1%. One patient did not undergo long-term follow-up. These findings suggest that (18)F-FDG PET is superior to CT in predicting early response to therapy in recurrent or metastatic GIST patients. CONCLUSION: The performances of (18)F-FDG PET and CT are comparable in staging GISTs before initiation of imatinib mesylate therapy. However, (18)F-FDG PET is superior to CT in predicting early response to therapy. Thus, (18)F-FDG PET is a better guide for imatinib mesylate therapy.

Adult↗

166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials.

Holmium-166 1, 4, 7, 10-tetraazcyclododecane-1, 4, 7, 10-tetramethylenephosphonate (166Ho-DOTMP) is a radiotherapeutic that localizes specifically to the skeleton and can deliver high-dose radiation to the bone and bone marrow. In patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation two phase 1/2 dose-escalation studies of high-dose 166Ho-DOTMP plus melphalan were conducted. Patients received a 30 mCi (1.110 Gbq) tracer dose of 166Ho-DOTMP to assess skeletal uptake and to calculate a patient-specific therapeutic dose to deliver a nominal radiation dose of 20, 30, or 40 Gy to the bone marrow. A total of 83 patients received a therapeutic dose of 166Ho-DOTMP followed by autologous hematopoietic stem cell transplantation 6 to 10 days later. Of the patients, 81 had rapid and sustained hematologic recovery, and 2 died from infection before day 60. No grades 3 to 4 nonhematologic toxicities were reported within the first 60 days. There were 27 patients who experienced grades 2 to 3 hemorrhagic cystitis, only 1 of whom had received continuous bladder irrigation. There were 7 patients who experienced complications considered to be caused by severe thrombotic microangiopathy (TMA). No cases of severe TMA were reported in patients receiving in 166Ho-DOMTP doses lower than 30 Gy. Approximately 30% of patients experienced grades 2 to 4 renal toxicity, usually at doses targeting more than 40 Gy to the bone marrow. Complete remission was achieved in 29 (35%) of evaluable patients. With a minimum follow-up of 23 months, the median survival had not been reached and the median event-free survival was 22 months. 166Ho-DOTMP is a promising therapy for patients with multiple myeloma and merits further evaluation.

Adult↗

Factors affecting left ventricular ejection fraction using automated quantitative gated SPECT.

BACKGROUND: Factors affecting the accuracy of left ventricular ejection fraction (LVEF) quantification using automated quantitative gated SPECT have not been adequately investigated in patients in the clinical setting. Therefore, the authors studied the effect of defect size and Tc-99m tetrofosmin dose on the accuracy of LVEF calculation using the automated QGS program. MATERIALS AND METHODS: Thirty-two consecutive patients underwent gated rest and stress myocardial perfusion SPECT after administration of 8 and 27 mCi Tc-99m tetrofosmin, respectively. The LVEF was obtained for both the rest and stress studies using the QGS program and compared with the LVEF obtained using quantitative echocardiography performed within 2 weeks. Myocardial perfusion defects were recorded as scarring, ischemia, or mixed scarring and ischemia in 12 left ventricular segments. The defect size was evaluated by adding the number of affected segments. RESULTS: The mean LVEF calculated using high-dose stress QGS, low-dose rest QGS, and echocardiography was 49.2% +/- 15%, 46.2% +/- 17% and 48.7% +/- 16.9% respectively, with no statistically significant differences. The LVEF obtained using high-dose stress QGS correlated better with echocardiography than did that obtained using low-dose rest QGS (r = 0.86 versus 0.76). In addition, when the high-dose stress LVEF in the 14 patients with normal myocardial perfusion was compared with that in 11 patients who had one- or two-segment perfusion defects, and 7 patients who had perfusion defects in > or = three segments, there was good correlation with echocardiography in the three patient groups (r = 0.85, 0.88, and 0.91, respectively). CONCLUSIONS: Myocardial perfusion defects do not affect the accuracy of LVEF calculation using automated QGS. High-dose gated myocardial SPECT demonstrated better correlation with quantitative echocardiography LVEF results.

Adult↗

New method for calculating right ventricular ejection fraction using gated myocardial perfusion studies.

BACKGROUND: Quantification of right ventricular ejection fraction (RVEF) is important in patients who have right heart failure or cor pulmonale. When Tl-201 was the primary radiotracer used to evaluate myocardial perfusion, the outline of the right ventricle could vary and was not visualized in most patients. However, visualization of the right ventricle has become easier with the use of Tc-99m-labeled myocardial perfusion agents. PURPOSE: This study describes a new method for quantifying RVEF using gated stress myocardial perfusion (GMP) slices. The results are compared with those of first-pass radionuclide ventriculography (FPRNA) in the same patients. METHODS: Fifty-two consecutive patients referred for routine GMP imaging were included. After administration of Tc-99m tetrofosmin, all patients underwent FPRNA using a single crystal gamma camera and a GMP study. Regions of interest (ROI) were drawn to outline the right ventricular cavity at end diastole and end systole from three pairs of GMP slices. The RVEF was calculated from the number of pixels within the ROIs. The mean RVEF obtained using FPRNA and GMP imaging was 51.8 +/- 10.8% and 51.9 +/- 12.3%, respectively. The two methods showed good correlation with r = 0.81. In addition, there was no significant difference in the RVEFs calculated using these methods (P = 0.85). Bland-Altman analysis also showed good agreement between the two methods (limits of agreement +14.4% to -14.0%, slope = 0.19). Intraobserver and interobserver correlation were evaluated by reanalyzing 12 patients using the new RVEF quantification method and were good at r = 0.87 and 0.82, respectively. Therefore, this is a new convenient method for evaluating RVEF as part of a routine tomographic gated myocardial perfusion study.

Adult↗

Comparison of bone and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography in the evaluation of bony metastases in lung cancer.

UNLABELLED: Positron emission tomography (PET) is a proven accurate modality used for the detection of active malignant tumors. The performance of PET in detecting bony metastases, however, has not been adequately investigated. PURPOSE: The aim of this study was to compare the performance of bone and 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET scans in evaluating bony metastases from lung cancer. PROCEDURE: This retrospective study evaluated 85 patients with lung cancer who underwent both FDG-PET and bone scans within three weeks of each other for initial staging or restaging. The number and sites of bony lesions on FDG-PET and bone scans were correlated. Concordant lesions between the two modalities were considered to be positive for malignancy; discordant lesions were compared with X-rays, computed tomography (CT), magnetic resonance imaging (MRI), and/or follow-up findings. The mean follow-up interval was 7.9 months. RESULTS: Bone scans were positive for lesions in 24 patients and negative in 61 patients while FDG-PET was positive for bony lesions in 17 patients and negative in 65 patients. FDG-PET was indeterminate for rib involvement in three patients having an underlying lung cancer, whom were evaluated separately. A total of 88 and 41 bony lesions were identified on bone scans and FDG-PET, respectively. Correlation of bone scans with other imaging modalities and clinical follow-up findings revealed a sensitivity, specificity, positive and negative predictive value of 81%, 78%, 34%, and 93%, respectively and for FDG-PET 73% (P=0.81), 88% (P=0.03), 46% (P=0.5,) and 97% (P=0.04), respectively. Using bone scans, 10 patients were correctly diagnosed with bony metastases, 54 were correctly diagnosed free of bony metastases, 17 patients were falsely diagnosed with metastases, and metastases were missed in one patient. Using FDG-PET scans, eight patients were correctly diagnosed with bony metastases, 66 were correctly diagnosed free of bony metastases, seven patients were falsely diagnosed with metastases, and one patient had metastases which were missed. Of the three patients with lung cancer close to the chest wall in whom FDG-PET was indeterminate for rib involvement, the bone scans were truly positive for rib involvement in two of them, and truly negative in the remaining patient. CONCLUSIONS: FDG-PET scans demonstrated significantly higher specificity and negative predictive values than bone scans for evaluating bony metastases from lung cancer. On the other hand, bone scans are more sensitive with higher positive predictive values than FDG-PET scans, but the differences were not statistically significant.

Aged↗