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Biomedical subjects

Roger M Macklis

Publications and source records attributed to Roger M Macklis.

8 recordsLinked to original sources
PubMed2006

Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study.

PURPOSE: An objective of the fifth National Wilms' Tumor Study (NWTS-5) was to evaluate the efficacy of treatment regimens for anaplastic histology Wilms' tumor (AH). PATIENTS AND METHODS: Prospective single-arm studies were conducted. Patients with stage I AH were treated with vincristine and dactinomycin for 18 weeks. Patients with stages II to IV diffuse AH were treated with vincristine, doxorubicin, cyclophosphamide, and etoposide for 24 weeks plus flank/abdominal radiation. RESULTS: A total of 2,596 patients with Wilms' tumor were enrolled onto NWTS-5, of whom 281 (10.8%) had AH. Four-year event-free survival (EFS) and overall survival (OS) estimates for assessable patients with stage I AH (n = 29) were 69.5% (95% CI, 46.9 to 84.0) and 82.6% (95% CI, 63.1 to 92.4). In comparison, 4-year EFS and OS estimates for patients with stage I favorable histology (FH; n = 473) were 92.4% (95% CI, 89.5 to 94.5) and 98.3% (95% CI, 96.4 to 99.2). Four-year EFS estimates for patients who underwent immediate nephrectomy with stages II (n = 23), III (n = 43), and IV (n = 15) diffuse AH were 82.6% (95% CI, 60.1 to 93.1), 64.7% (95% CI, 48.3 to 77.7), and 33.3% (95% CI, 12.2 to 56.4), respectively. OS was similar to EFS for these groups. There were no local recurrences among patients with stage II AH. Four-year EFS and OS estimates for patients with bilateral AH (n = 29) were 43.8% (95% CI, 24.2 to 61.8) and 55.2% (95% CI, 34.8 to 71.7), respectively. CONCLUSION: The prognosis for patients with stage I AH is worse than that for patients with stage I FH. Novel treatment strategies are needed to improve outcomes for patients with AH, especially those with stage III to V disease.

Adolescent↗
PubMed2006

Review of clinical radioimmunotherapy.

Radioimmunotherapy involves a form of biologically targeted radiopharmaceutical treatment in which a radioactive isotope (typically a short-range, high-energy beta-emitter) is chemically bound to a target-specific monoclonal antibody or fragment. Thus, these radioimmunoconjugates combine the exquisite targeting specificity of the humoral immune system with the known cancer-killing power of high-energy radiotherapy. To date, two radioimmunotherapy agents have been fully approved for commercial use: 90Yttrium ibritumomab tiuxetan and (131)Iodine tositumomab. Both compounds target the CD20 surface molecule found on normal and malignant B cells, and both are medically indicated for the treatment of indolent B-cell lymphoma and related conditions. Clinical results are excellent (20-40% complete response rates and 60-80% overall response rates) and toxicity is typically quite mild. Current research is now attempting to both explore the biology of these compounds and to expand the spectrum of CD20+ diseases that could be treated using either or both of these active agents. Concurrently, work is in progress to achieve the same excellent clinical results using antibodies specific for other, more common epithelial tumors. This work is at an earlier stage than the lymphoma work, partly due to the high innate radiosensitivity of the lymphoid system. Thus, various enhancement methodologies are being explored to increase clinical response rates for these solid tumors, and a number of solid tumor RIT agents are now in early-stage clinical trials. The most likely pattern of use for this field in the next 5 years will probably involve combination or sequential regimens incorporating both radioimmunotherapy and more conventional chemotherapy or external radiotherapy.

Antibodies, Monoclonal↗
PubMed2005

Gamma camera scans and pretreatment tumor volumes as predictors of response and progression after Y-90 anti-CD20 radioimmunotherapy.

PURPOSE: To evaluate two potential approaches to predicting site-specific patterns of recurrence after yttrium-90 ibritumomab tiuxetan radioimmunotherapy (RIT) for CD20+ B-cell Non-Hodgkin's lymphoma. These predictive methods may be useful in evaluating the utility of local intensification of individual nodal or extranodal sites using external beam radiotherapy. METHODS AND MATERIALS: Records and images were evaluated for 20 patients previously treated with yttrium-90 ibritumomab RIT. Intensity of isotope uptake on the pretreatment two-dimensional antibody scans and maximal extent of tumor deposits found on computed tomography images of each anatomic site were correlated with response and subsequent patterns of recurrence or progression. RESULTS: Our data failed to suggest a significant correlation between the site-by-site two-dimensional image intensity on the pre-RIT scan and the likelihood of response at those sites. In contrast, an analysis of pretreatment target volumes did correlate significantly with progression. A collective analysis of disease sites from all 20 patients found that 83% (10/12) sites of "bulky" (maximal diameter > or = 5 cm) disease displayed evidence of progression vs. 28% (26/93) of "nonbulky" disease sites containing gross disease but no area measuring >5 cm (p < 0.001). All patients with at least one site of bulky disease had initial disease progression occur at a bulky site, with a bulky site being the sole first site of progression in approximately 50%. In patients with only nonbulky disease sites, approximately one third progressed initially at an entirely new site of disease. CONCLUSION: We conclude that we can use tumor bulk to establish a statistical hierarchy of likely tumor progression sites and use this pattern to direct the use of additional external beam radiotherapy to augment treatment.

Adult↗
PubMed2005

Synergistic cytotoxic effects of zoledronic acid and radiation in human prostate cancer and myeloma cell lines.

PURPOSE: The clinical use of the potent bisphosphonate zoledronic acid has increased recently, especially for the treatment of bone metastases. Synergistic effects with chemotherapeutic agents (e.g., doxorubicin, paclitaxel) have been shown. It is not known whether similar synergistic effects exist with radiation. METHODS AND MATERIALS: IM-9 myeloma cells and C4-2 prostate cancer cells were treated with up to 200 microM concentrations of zoledronic acid, irradiated with single doses of up to 1,000 cGy, or exposed to combinations of both treatments. Cell viability was then determined via yellow dye 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay and the affected fractions analyzed using the median effect principal, a method developed and validated by Chou and Talalay. RESULTS: A statistically significant synergistic cytotoxic effect of the combination of zoledronic acid and radiation was documented. The extent of the effect was cell type-dependent, with the C4-2 cells showing a greater synergistic effect than the IM-9 cells. CONCLUSIONS: The combined use of zoledronic acid and radiotherapy shows enhanced in vitro cytotoxicity for two human prostate and myeloma cancer cell lines over that expected for a simple additive effect from each treatment alone. A clinical trial is under way to test this combination therapy.

Animals↗
PubMed2004

TRAIL induction by radiation in lymphoma patients.

TRAIL/Apo-2 L, a member of the Tumor Necrosis Factor cytokine family, induces apoptosis specifically in malignant cells. A combination of TRAIL and radiation is highly synergistic in in vitro experiments. In addition to this additive effect, we observed that TRAIL is induced by irradiation of certain cell lines. The induction begins approximately 2 hours after irradiation. This might even enhance the antineoplastic effect of ionizing radiation and partially explain the abscopal effect observed in hematopoietic malignancies. TRAIL levels were evaluated in 17 patients treated with radiation for Hodgkin's and non-Hodgkin's lymphoma. We did not observe a specific TRAIL expression pattern that could be correlated with histology, disease status, volume of disease, radiation dose, and other antineoplastic therapies, but a definite pattern observed in a single patient remained constant over time. TRAIL and interferons display a common pattern of gene expression at certain nodal points of interaction between the two physiologic pathways. Our hypothesis is that the radiation-induced changes in TRAIL expression observed in patients undergoing therapeutic radiation may be emblematic of the various physiologic pathways induced or inhibited by ionizing radiation and may even be partially responsible for the "bystander effect" observed in unirradiated cells in close proximity to irradiated cells.

Adult↗
PubMed2002

Portrait of Science. Scientist, technologist, proto-feminist, superstar.

Although Marie Curie is known primarily for her discovery of radium, her true gift to science was her realization that radioactivity is an intrinsic atomic property of matter rather than the result of chemical processes. She was one of the few Nobel laureates to win the prize twice (physics and chemistry). During her career and as one of the first prominent women scientists, she became increasingly aware of the need for funding for research and of the scientific freedom that money can bring. By nature shy and reserved, Marie's fame, as both a scientist and as an exemplar of a liberated professional woman of the roaring twenties, grew to superstar proportions.

Academies and Institutes↗