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R M Macklis

Publications and source records attributed to R M Macklis.

At least 19 recordsLinked to original sources
PubMed2001

Ionizing radiation induces CD20 surface expression on human B cells.

The CD20 surface antigen is expressed on the great majority of B-cell lymphoma cases. The expression of this antigen ranges from moderate to bright, and it is neither internalized nor shed. These characteristics make CD20 a common target for antibody directed lymphoma therapy. The development of strategies to significantly increase CD20 expression on lymphoma cells is therefore of great interest as a means of increasing specific targeting and cell kill in antibody therapy and radio-immunotherapy. We present here data demonstrating that relatively low doses of external beam radiotherapy are capable of significant and consistent increases in CD20 surface expression in vitro. The effect is dose related up to approximately 10 Gy and is maximal in the first day after radiotherapy. We believe that these data may suggest a potent way to combine a short pretreatment course of external beam radiotherapy with a subsequent course of immunotherapy using either an unlabeled antibody or a radio-immunotoxin.

Antigens, CD20↗
PubMed2001

Contralateral breast cancer risk.

The use of breast-conserving treatment approaches for breast cancer has now become a standard option for early stage disease. Numerous randomized studies have shown medical equivalence when mastectomy is compared to lumpectomy followed by radiotherapy for the local management of this common problem. With an increased emphasis on patient involvement in the therapeutic decision making process, it is important to identify and quantify any unforeseen risks of the conservation approach. One concern that has been raised is the question of radiation- related contralateral breast cancer after breast radiotherapy. Although most studies do not show statistically significant evidence that patients treated with breast radiotherapy are at increased risk of developing contralateral breast cancer when compared to control groups treated with mastectomy alone, there are clear data showing the amount of scattered radiation absorbed by the contralateral breast during a routine course of breast radiotherapy is considerable (several Gy) and is therefore within the range where one might be concerned about radiogenic contralateral tumors. While radiation related risks of contralateral breast cancer appear to be small enough to be statistically insignificant for the majority of patients, there may exist a smaller subset which, for genetic or environmental reasons, is at special risk for scatter related second tumors. If such a group could be predicted, it would seem appropriate to offer either special counseling or special prevention procedures aimed at mitigating this second tumor risk. The use of genetic testing, detailed analysis of breast cancer family history, and the identification of patients who acquired their first breast cancer at a very early age may all be candidate screening procedures useful in identifying such at- risk groups. Since some risk mitigation strategies are convenient and easy to utilize, it makes sense to follow the classic 'ALARA' (as low as reasonably achievable) principles and to minimize scattered radiation for these special risk groups and perhaps for all patients undergoing breast radiotherapy. This paper reviews the literature on the risk of radiation- related second contralateral breast cancers.

Breast Neoplasms↗
PubMed2001

Stability of biodegradable radioactive rhenium (Re-186 and Re-188) microspheres after neutron-activation.

Our objective was to determine if microspheres made from the biodegradable polymer poly(lactic acid) that contained rhenium could withstand the conditions of direct neutron activation necessary to produce therapeutic amounts of radioactive rhenium. The radiation damage of the polymer produced by gamma-doses of up to 1.05 MGy from Re-186 and Re-188 was examined by scanning electron microscopy and size exclusion chromatography. At a thermal neutron flux of 1.5 x 10(13)n/cm2/s the microspheres melted after 3 h in the nuclear reactor, but suffered little damage after 1 h of radiation and released less than 5% of the radioactivity during incubation in buffer at 37 degrees C. The radioactive microspheres produced in this manner have a specific activity too low for radioembolization for treatment of liver tumors, but could be injected directly into tumors or applied topically to the wound bed of partially resected tumors.

Biodegradation, Environmental↗
PubMed2001

Promoting patient safety: is technology the solution?

BACKGROUND: On April 30, 2001, the Cleveland Clinic Foundation and Cleveland Clinic Health System Quality Institute sponsored a 1-day conference focused on technology in patient safety. PATIENT SAFETY-A CALL TO ACTION: Kenneth W. Kizer focused on ten high-priority patient safety strategies identified by the National Quality Forum-including implementing recognized "safe practices", recognizing and dealing with professional misconduct, and supporting efforts to create a nonpunitive environment for health care error reporting. CULTURAL IMPLICATIONS OF INTRODUCING NEW TECHNOLOGY: Randolph A. Miller described a computerized clinician order-entry system used to provide decision support, reduce excess test ordering, introduce cost savings, and meet regulations for inpatient radiology and cardiology tests. USING BAR CODES TO ELIMINATE MEDICATION ERRORS: Jeff Ramirez reported on the Veterans Health Administration's use of bar coding technology for point-of-care validation of medication administration, which has resulted in improvements in response time; the efficiency of the dispensing, delivery, and administration process; and patient care. HOW TO MAKE COMPUTERS TEAM PLAYERS: The knowledge base exists to design computers as team players that expand human expertise and help health care practitioners better create safety. Yet David D. Woods challenged the audience to anticipate the changing shape of iatrogenic risk as a result of increasing dependence on automation in health care. TECHNOLOGY AND MEDICATION SYSTEMS: Mark Neuenschwander spoke about automating various steps within the medication use system, through computerized prescriber order entry and bedside scanning. FUTURE TECHNOLOGICAL POSSIBILITIES: Charles Denham suggested how technology may aid health care professionals in their care of patients, such as in using predictive modeling to identify the risks of therapeutic intervention.

Equipment Safety↗
PubMed2000

Radiotherapy for pediatric genitourinary tumors. Its role and long-term consequences.

Radiation therapy has traditionally played a major role in the treatment of pediatric genitourinary malignancies. In particular, Wilms' tumor, rhabdomyosarcoma, and neuroblastoma often include radiotherapy in the local control phase of treatment. Recently, clinical trials have focused on decreasing the toxicity of radiotherapy through dose modifications and conformal field arrangements. Radiotherapy will continue to be a major treatment modality for this patient group if technologic advances in radiation delivery continue to increase efficacy without comorbidities.

Child↗
PubMed2000

Treatment of prognosis of primary breast lymphoma: a review of 13 cases.

Primary non-Hodgkin's lymphoma (NHL) of the breast is a rare entity that does not have a well-defined treatment strategy. At presentation, most patients are clinically thought to have a primary breast carcinoma, and the diagnosis of lymphoma is made at biopsy. Once the diagnosis of lymphoma is made, patients are treated with some combination of chemotherapy, radiation therapy, and surgery. We review The Cleveland Clinic Foundation experience with primary breast lymphoma. Between 1980 and 1996, 17 patients with primary breast lymphoma were seen at The Cleveland Clinic Foundation, and 13 had follow-up information available. All patients underwent a staging workup including computed tomography (CT) scan of the chest, abdomen, and pelvis, as well as bilateral bone marrow biopsies; all patients staged IE (breast involvement only) or IIE (limited to the breast and ipsilateral axilla) were included. We did not include patients with more extensive supradiaphragmatic nodal involvement who were stage IIE. Patients received some combination of surgery, radiation, and chemotherapy. The median follow-up was 34 months, with a range of 7 to 138 months. There was an equal incidence of right- versus left-sided lesions. Five patients survived at least 5 years from the time of diagnosis. Long-term survival in patients with primary NHL of the breast is possible. We recommend treating patients with aggressive NHL of the breast with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, followed by involved field radiation and treating those patients with indolent lymphoma with involved field radiation alone.

Aged↗
PubMed2000

Palliative radiotherapy.

Radiotherapy is often used for the palliative treatment of advanced cancer. Although each cancer is unique in its histology and natural history, there are several scenarios that repeatedly challenge physicians. Specifically, skeletal metastases, spinal cord compression, brain metastasis, bronchial obstruction, and vena cava obstruction are regularly encountered. This review will discuss the diagnosis and treatment of these common important situations.

Bone Neoplasms↗
PubMed2000

Radiation therapy in pregnancy: risk calculation and risk minimization.

The benefits of radiation therapy (RT) as part of a treatment regimen for cancer must be weighed against the potential risk of harm to the patient and in the pregnant patient, the risk to the developing fetus. Information necessary for determining the potential effects of RT on the developing fetus include the gestational age, absorbed fetal dose-equivalent, and dose-rate. The risk periods in humans for RT-induced prenatal or neonatal death, congenital anomalies, severe mental retardation (SMR), temporary (TGR) or permanent growth retardation (PGR), carcinogenesis, sterility, and germ cell mutations have been elicited directly from the study of Japanese victims of the atomic bombs and unintentional medical exposures, and indirectly from animal experiments. The wide range of congenital anomalies elicited from animal studies have not occurred in the Japanese atomic bomb victims exposed in utero. The major congenital anomaly observed in the Japanese cohort has been microcephaly. The highest risk period for SMR correlates with the proliferation, differentiation, and, most importantly, migration of neurons from their proliferative zones. PGR was apparent 17 years after ionizing radiation (IR) exposure at Hiroshima in children who were within 1,500 meters of the hypocenter. Children were on average 2.25 cm shorter, 3 kg lighter, and had head diameters 1.1 cm smaller than age-matched children. The projected lifetime risk of cancer mortality in the Japanese cohort is 14% per gray. The risk of a radiation-induced hereditary disorder is reported to be approximately 1% per gray. RT plays a major role in the definitive treatment of cervical and breast carcinomas, Hodgkin's disease, and non-Hodgkin's lymphoma. With appropriate abdominal shielding in place, the estimated fetal dose can be reduced by 50% or greater in most cases. In certain clinical situations, RT may be administered during pregnancy.

Female↗
PubMed2000

Lymphoma and pregnancy.

Coincident lymphoma and pregnancy is rare, occurring in only one of 1,000 or fewer deliveries. Patients with Hodgkin's disease usually present with typical manifestations, and most studies suggest that the disease probably has little or no effect on the pregnancy and vise versa. In contrast, patients with non-Hodgkin's lymphoma often have unusual manifestations and their diagnosis is frequently delayed. These patients usually have aggressive, advanced-stage disease and a poor outcome. The optimal management of these women requires special considerations. Treatment during the first trimester is associated with significant risk to the developing fetus and should be avoided. Women requiring treatment at this time should have a therapeutic abortion. Beyond the first trimester, the management options for women with Hodgkin's disease include observation until disease progression or delivery, single-agent vinblastine, modified or standard combination chemotherapy, and radiation therapy (with appropriate shielding). Because of their poor prognosis, women with non-Hodgkin's lymphoma should receive standard chemotherapy (despite the potential risk to the developing fetus).

Female↗
PubMed1999

Reducing scatter radiation to the contralateral breast with a mobile, conformal shield during breast cancer radiotherapy.

During a standard course of breast radiotherapy, the contralateral breast generally receives approximately 2.5 to 6.0 Gy of scattered radiation. Although most studies have not found an overall increase in metachronous contralateral breast cancers in patients undergoing radiotherapy, a cohort of younger women may be genetically more susceptible to radiation-induced breast cancers and may thus be adversely affected by the scattered radiation. We are attempting to develop a simple, convenient, effective mechanism for minimizing the scattered radiation to the contralateral breast during the process of clinical breast radiotherapy. We therefore designed a conformal, platform-based breast shield consisting of 2.5 cm of molded lead in a mobile counterweighted polystyrene casing. This shield was intended to serve as a physical barrier to prevent both low and high energy scattered photons from the medial and lateral tangential fields. We conducted a prospective trial of 20 women, each woman serving as her own control. Each woman received breast radiotherapy with and without shield, and an array of thermoluminescent dosimeters was positioned across the contralateral breast to evaluate the in vivo dosimetry and the impact of the breast shield on surface absorption of scattered radiation. We found that the use of the breast shield reduced the median dose of scattered radiation by approximately 60% (p < 0.0001). This represented a median dose reduction of approximately 300 cGy at the nipple. The shield was easily positioned and added < 1 min to daily setup time. We conclude that the use of this sort of surface barrier shielding technique was feasible, effective, and practical for clinical use. The degree of scatter reduction accomplished through the use of this breast shield may be biologically significant, especially for those patients with biologic or epidemiologic risk factors that may predispose them to the development of radiogenic breast cancers.

Breast Neoplasms↗
PubMed1999

Successful conversion from a linear accelerator-based program to a Gamma Knife radiosurgery program: the Cleveland Clinic experience.

From August 1989 to January 1997, 307 treatments in 293 patients were performed with a linear accelerator-based (LINAC) stereotactic radiosurgery system. Because of the program s success, the need for a dedicated radiosurgery unit in Ohio and the desire to treat functional disorders, the Cleveland Clinic Health System (CCHS) obtained the first Gamma Knife in the state of Ohio. Based on the previous volume of patients for radiosurgery, it was estimated that 75-100 patients would be treated during the first year of operation. However, during the first calendar year, 214 treatments were performed on 205 patients, which far exceeded expectations. The success of the CCHS Gamma Knife Center can be attributed to an increase in a number of factors. These included marketing efforts, patient awareness, increased use for functional disorders, physician understanding of radiosurgery, use by qualified nonaffiliated radiation oncologists and neurosurgeons, and outpatient delivery (95% with the Gamma Knife vs <5% with the LINAC). With proper planning, education, and awareness, the opening of a Gamma Knife Center can greatly increase the volume of radiosurgery performed when compared with a LINAC-based program.

Brain Neoplasms↗
PubMed1999

The role of radiation therapy in the management of Wilms' tumor.

Since the early decades of this century, radiation therapy has played an important role in the management of Wilms' tumor. Although in prior years the high radiation doses and eccentric field arrangements used in treatment were responsible for significant late toxicity, examination of long-term survivors and the important information obtained from the National Wilms' Tumor Studies (NWTS) and Societe Internationale d'Oncologie Pediatrique studies have now allowed us to tailor radiation fields and doses to provide high levels of local tumor control with minimal late effects. At present, most patients with NWTS stage III and stage IV tumors are offered radiotherapy as an integral component of their cancer management. Attempts to further refine selection criteria defining those patient groups who will benefit from radiation therapy are ongoing.

Child↗
PubMed1998

Brief courses of palliative radiotherapy for metastatic bone pain: a pilot cost-minimization comparison with narcotic analgesics.

The use of radiotherapy to treat metastatic bone pain is being challenged by claims of high cost and by more readily available, noninvasive treatment approaches. The authors assessed the effectiveness of brief courses of radiotherapy in reducing pain and estimated cost data for a pilot comparison between radiotherapy and narcotic analgesics in patients with cancer. A representative group of outpatients undergoing brief courses of radiotherapy with Karnofsky scores above 70 and without serious comorbidities were recruited from 1995 through 1996. Patients indicated their pain at rest and with movement on a scale of from 1 to 10 both before and up to 12 months after radiotherapy. Radiotherapy costs were estimated from Medicare-allowable charges. Narcotic analgesia costs were estimated from published values. In 66 patients with 131 individually treated sites, median at rest pain score decreased by about 4 points after treatment (5.58 [-/+3.28] before treatment vs. 1.55 [-/+1.8] after treatment; p < 0.05). Median with movement pain score was about 5 points lower after treatment (7.32 [-/+2.72] before treatment vs. 1.94 [-/+2.07] after treatment; p < 0.05). No differences were found when stratifying by type of pain, tumor histologic type, or skeletal site. The estimated cost per patient ranged from $1,200 to $2,500 for radiotherapy. This compares with an estimated cost of $9,000 to $36,000 for 9 months of narcotics. In this pilot study, a brief course of radiotherapy significantly reduced pain and appeared to be cost effective when compared with narcotic analgesia. A full economic evaluation is warranted.

Aged↗
PubMed1998

Error rates in clinical radiotherapy.

PURPOSE: Error rates in clinical oncology are undergoing increasing scrutiny. The purpose of this study was to understand error frequency, error patterns, underlying causal links, consequences, and possible prevention strategies in clinical radiotherapy. PATIENTS AND METHODS: Treatment information, self-reported error documentation, and retrospective analyses of electronic treatment verification transcripts for 1,925 consecutive patients treated with a total of 93,332 individual radiotherapy fields were reviewed and analyzed. RESULTS: A total of 59 separate errors that affected 168 individual treatment fields were detected, which yielded a crude radiation delivery error rate of 0.18%. All 59 errors were judged to be level I (negligible chance of adverse medical outcome) with the most common error category being a minor treatment field block misplacement. A comprehensive quality assurance program and an electronic record-and-verify linear accelerator interlock system seem to have prevented the occurrence of many additional errors. However, nine of the 59 errors were directly related to the use of this system and generally involved the transposition of similar numbers within series of treatment coordinate data-sets. Overall, radiotherapy error rates favorably compare with reported error rates for pharmaceutical administration in large tertiary care hospitals. CONCLUSION: When modern automated error-minimization methods are used along with nonpunitive error reporting systems, clinical radiotherapy seems to be highly safe. Formal error analysis studies may allow the rational design of prevention strategies that are attuned to the frequency, seriousness, and antecedent causes of many classes of potential radiotherapy errors.

Humans↗
PubMed1995

Effective targeting of magnetic radioactive 90Y-microspheres to tumor cells by an externally applied magnetic field. Preliminary in vitro and in vivo results.

Magnetic biodegradable poly(lactic acid) microspheres that incorporate both magnetite and the beta-emitter 90Y were prepared. By applying a directional external magnetic field gradient in excess of 0.02 Tesla/cm across a 96-well plate containing neuroblastoma cells incubated with the 90Y magnetite loaded microspheres, the radiation dose to the cells could be enhanced or reduced relative to the dose from a uniform loading of the well with 90Y-DTPA. Using the MTT assay, cell survival was measured for the magnetic field directed from above (cell sparing) and from below (cell targeting) the well plate, resulting in 65 +/- 8% or 18 +/- 5% survival respectively. This method was then applied to an in vivo murine tumor model. The biodistribution of intraperitoneally injected magnetic radioactive microspheres, after 24 h in mice, showed that 73 +/- 32% of the radioactivity was found on the subcutaneous tumor that had a rare earth magnet fixed above it. In contrast, the tumor radioactivity with no attached magnet was 6 +/- 4%. Magnetically targeted radiopolymers such as 90Y-microspheres show great promise for regional or intracavitary radiotherapy.

Animals↗
PubMed1995

The spatial accuracy of cellular dose estimates obtained from 3D reconstructed serial tissue autoradiographs.

In order to better predict and understand the effects of radiopharmaceuticals used for therapy, it is necessary to determine more accurately the radiation absorbed dose to cells in tissue. Using thin-section autoradiography, the spatial distribution of sources relative to the cells can be obtained from a single section with micrometre resolution. By collecting and analysing serial sections, the 3D microscopic distribution of radionuclide relative to the cellular histology, and therefore the dose rate distribution, can be established. In this paper, a method of 3D reconstruction of serial sections is proposed, and measurements are reported of (i) the accuracy and reproducibility of quantitative autoradiography and (ii) the spatial precision with which tissue features from one section can be related to adjacent sections. Uncertainties in the activity determination for the specimen result from activity losses during tissue processing (4-11%), and the variation of grain count per unit activity between batches of serial sections (6-25%). Correlation of the section activity to grain count densities showed deviations ranging from 6-34%. The spatial alignment uncertainties were assessed using nylon fibre fiduciary markers incorporated into the tissue block, and compared to those for alignment based on internal tissue landmarks. The standard deviation for the variation in nylon fibre fiduciary alignment was measured to be 41 microns cm-1, compared to 69 microns cm-1 when internal tissue histology landmarks were used. In addition, tissue shrinkage during histological processing of up to 10% was observed. The implications of these measured activity and spatial distribution uncertainties upon the estimate of cellular dose rate distribution depends upon the range of the radiation emissions. For long-range beta particles, uncertainties in both the activity and spatial distribution translate linearly to the uncertainty in dose rate of < 15%. For short-range emitters (< 100 microns), such as alpha particle sources, the magnitude of the uncertainty in serial section alignment is comparable with the particle track length. Under these circumstances, dosimetric errors are introduced in proportion to the serial section alignment inaccuracy.

Animals↗