Local/regional therapy of primary breast cancer: a contemporary multimodal approach.
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Biopsy↗
Biomedical subjects
D E Wazer
Publications and source records attributed to D E Wazer.
Prompt engraftment using autologous peripheral blood stem cells for double autologous bone marrow rescue.
A patient with Hodgkin's Disease, stage IIIA, was treated for recurrent disease with autologous peripheral blood stem cells after ablative chemotherapy. Bone marrow rescue occurred promptly and his disease was significantly reduced. Ablative chemotherapy was administered again and a second bone marrow rescue with peripheral blood stem cells was successful. Sequential peripheral blood stem cell bone marrow rescue, following high dose chemotherapy, may provide an alternative approach in selected patients.
Adult↗
Proliferative inhibition of human breast carcinoma cells by high concentration estradiol does not alter radiosensitivity.
The proliferation of ER+ malignant mammary epithelial cells (MMEC), MCF-7 and T-47D, was markedly inhibited by 10 microM 17 beta-estradiol (E2), while the ER- line, MDA-MB-231, was minimally affected. This concentration of E2 did not alter the proportion of non-viable cells or the plating efficiency. The decrease in proliferation was not associated with any consistent alteration in the cell kinetic profile between lines, though there was clearly no dominant cell cycle re-assortment after a two day incubation. Colony forming ability after exposure to ionizing irradiation was compared for proliferating and confluent MMEC to cells incubated in 10 microM E2 for two days. The presence of E2 resulted in no significant differences for any of the linear quadratic curve fitting parameters or for mean inactivation doses for both subconfluent and confluent cultures. Further, 10 microM E2 had no effect on the ability of cells to recover from split radiation fractions. There were no differences in the amount of DNA single strand break induction with E2, but there was a significant shortening in the repair halftime with E2 for the ER- MDA-MB-231 cells. Though high concentrations of E2 can markedly inhibit the proliferation of ER+ MMEC, this does not alter sensitivity to ionizing irradiation.
Breast Neoplasms↗
Accelerated superfractionated irradiation for advanced carcinoma of the head and neck: concomitant boost technique.
Between 1980 and 1988, 94 patients with AJCC Stage III and IV squamous cell carcinoma of all sites of the upper aero-digestive tract were treated with radiotherapy. We report here on 62 patients who are followed for a minimum of 2 years. Of these, 30 patients were treated with conventional once-a-day radiotherapy and 32 patients were irradiated using an accelerated superfractionation regimen during part of the treatment course. The altered fractionation schedule employed a concomitant boost technique with clinically demonstrable disease being irradiated twice-a-day during the first or second half of the treatment course. Daily radiation fractions were 1.8 Gy and the boost field was treated with 1.6 Gy after a 4- to 6-hr interval. No significant differences in acute treatment toxicity were observed in the two treatment groups. Patients treated with conventional and accelerated fractionation regimens experienced 36 months actuarial local tumor control rates of 40% and 67% (p = 0.03), respectively, which translated into an actuarial disease-free survival of 40% and 64% (p = 0.04). The increased locoregional control rates in patients treated with accelerated fractionation were associated with an adjusted and overall survival advantage at the p = 0.05 level. We conclude that our regimen of accelerated superfractionated irradiation with shortening of the treatment course resulted in improved control and survival rates at conventional doses of 68.4 to 73.8 Gy.
Adult↗
Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors.
Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces (with RBE weighting) a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction. With parallel-opposed lateral irradiation, the planar advantage depth contour for this beam (with the B-10 distribution defined above) encompasses nearly the whole brain. Experimental calibration techniques for the conversion of normalized to absolute treatment plans are described.
Boron↗
Clinical considerations for neutron capture therapy of brain tumors.
The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the United States in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should now be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam causes gamma rays to be generated when it interacts with tissue, we think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue. I look forward to the remainder of this Workshop, which will detail recent progress in the development of epithermal, as well as thermal, beams and new methods for tracking and measuring the uptake of boron in normal and tumor tissues.
Animals↗
A linear quadratic analysis of differing fractionation schemes for prophylactic cranial irradiation.
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Brain Neoplasms↗
In situ breast cancer: a multidisciplinary approach.
The approach to these lesions is being reexamined in light of results with conservative surgery for invasive breast cancers. According to available data, the invasive potential of in situ lesions varies. Mammographic and pathologic findings may differentiate patients who will benefit from lumpectomy (with or without radiotherapy) from those requiring mastectomy.
Breast Neoplasms↗
Tumor margin assessment as a guide to optimal conservation surgery and irradiation in early stage breast carcinoma.
Between 1982 and 1985, 108 women with AJC Stage I and II invasive mammary carcinoma were treated to 115 breasts with conservative surgery and irradiation. The irradiation dose was adjusted to the histopathological normal tissue margin around the carcinoma in the tumor excision specimens. Margins were arbitrarily determined negative, close, and positive with normal tissue margins in the inked tumor excision specimens of greater than 5 mm, 2-5 mm, and less than 2 mm, respectively. Negative, close, and positive tumor margin patients were treated to radiation doses of 60, 65, and 70 Gy, respectively. The boost in excess of 50 Gy was directed to the tumor bearing quadrant of the breast using interstitial Ir-192 implants for doses greater than or equal to 70 Gy. The draining lymphatics were irradiated to 50 Gy except in patients with tumor in the lateral half of the breast and no axillary lymph node metastases. Histopathological evaluation of re-excision specimens revealed the difficulty of obtaining negative margins for tumors greater than 2 cm. By our criteria, 54% of the patients had a positive resection margin. None of the patients experienced a local recurrence at 60 months median follow-up. Three patients failed regionally, two in un-irradiated lymph node areas, one in the skin of the contralateral breast; five patients failed systemically. Overall and disease-free survival for Stages T1/N0, T1/N1, T2/N0 was 100 and 95%, respectively, and for T2/N1, 90 and 80%, respectively. The cosmesis was excellent in 66% of the patients with minimal treatment related complications. Carefully planned standardized irradiation with assessment of resection margins yields both excellent local control rates and cosmetic results.
Axilla↗
Modulation in the radiosensitivity of MCF-7 human breast carcinoma cells by 17B-estradiol and tamoxifen.
Colony-forming ability after exposure to ionizing irradiation was compared for proliferating hormone response MCF-7 breast carcinoma cells and cells whose growth was inhibited by tamoxifen or 17B-estradiol. As compared with controls (Do = 1.20 Gy, n = 3.1), cells in 1 microM or 5 microM tamoxifen were less radiosensitive (Do = 1.20 Gy, n = 7.0; Do = 1.22 Gy, n = 7.0, respectively) with the predominant effect being a widened shoulder on the survival curve. This protective effect could be abolished by co-incubation of 5 microM tamoxifen with 100 nM 17B-estradiol (Do = 1.30 Gy, n = 2.6; Do = 1.20 Gy, n = 2.6, respectively). The decrease in radiosensitivity induced by tamoxifen was similar to that seen when replating of irradiated plateau-phase cultures was delayed for 24 h (Do = 1.30 Gy, n = 6.0). In contrast, when proliferation of MCF-7 cultures was inhibited by 10 microM 17B-estradiol, radiosensitivity was increased with a markedly diminished survival curve shoulder (Do = 1.40 Gy, n = 1.0). Different hormonal manipulations of cycling human breast carcinoma cells may have profound but disparate effects on radiosensitivity such that tamoxifen and estrogens may serve as useful agents with which to study the biochemical mechanisms of repair.
Breast Neoplasms↗
The role of combined composite resection and irradiation in the management of carcinoma of the oral cavity and oropharynx.
Squamous cell carcinoma of the oral cavity and oropharynx can invade the mandible requiring an "en bloc" or composite resection. With this procedure alone, reported local control rates for advanced stage tumors have been suboptimal suggesting the need for adjuvant therapy. The treatment records of 35 patients were reviewed who were treated with composite resection alone, composite resection plus radiotherapy, or composite resection as a salvage procedure for a primary treatment failure. Combined irradiation and composite resection resulted in a higher local control than patients receiving composite resection alone (72% vs. 43%). There was no difference in complication rates between these two treatment groups. Composite resection as a salvage procedure resulted in local control in 38% of patients through this was associated with a 64% rate of complications. This data and a review of the literature suggest that tumors of the oral cavity and oropharynx with extension to the mandible requiring composite resection probably represent a category of tumors with a high risk of local recurrence and may benefit from adjuvant irradiation.
Aged↗
Clinical considerations in palliative treatment of metastatic prostate carcinoma.
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Humans↗
Murine lymphocytes lack clearly defined receptors for muscarinic and dopaminergic ligands.
[3H]Quinuclidinyl benzilate and [3H]spiperone binding to murine lymphocytes is displaceable but differs from binding to brain receptor sites for these ligands: (1) binding to intact lymphocyte preparations was not saturable; (2) disruption of intact lymphocytes was associated with a marked loss of displaceable ligand binding; (3) drugs differentially displace these ligands in lymphocytes compared to brain. Displaceable binding was increased following incubation of lymphocytes under phospholipid methylating conditions; however, marked effects on cell viability and cell recovery make it difficult to interpret these binding changes. If dopaminergic and cholinergic receptors do exist on lymphocytes, their binding characteristics are profoundly different from comparable cns receptors.
Animals↗
Norepinephrine stimulation of phospholipid methylation in rat cortical synaptosomes: fact or artifact?
Synaptosomes from rat cerebral cortex incubated with 3H-S-adenosyl-L-methionine (3H-SAM) displayed an increase in chloroform- extractable tritium when norepinephrine was added to the reaction mixture. The products of this mixture were maximally generated from intact synaptosomes, only partially inhibited by propranolol, and not enhanced by exogenous phospholipids. Thin layer chromatographic analysis of these chloroform extracts in three solvent systems yielded large norepinephrine- stimulated peaks of radioactivity that did not consistently co-chromatograph with authentic methylated phospholipid standards: phosphatidylmonomethylethanolamine (PME), phosphatidyldimethylethanolamine (PDE), and phosphatidylcholine (PC). Further, attempts to identify these peaks of radioactivity using as standards several putative methylated products of varied chemical classes, failed to elucidate likely candidates. It appears that while norepinephrine markedly stimulates the amount of tritium extracted into the chloroform phase, careful and positive structural elucidation of formed products is required before it can be concluded that these are indeed methylated phospholipids.
Animals↗
The benzamides: evidence for action at dopamine receptors--shortcomings of current models.
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Animals↗
High-dose boost irradiation techniques for carcinoma of the nasopharynx.
Irregularly shaped tumors of the nasopharynx require the capacity to design flexible and reproducible treatment plans for high-dose boost irradiation. We use a variety of external beam techniques which may be combined with an afterloading intracavitary implant. Careful planning of such treatment is crucial and requires an accurate assessment of tumor volume and regional anatomy as defined by lateral simulator films, computed tomography, and magnetic resonance imaging scans. External beam irradiation is performed using a variety of arc rotations or fixed-beam cross-fire techniques in order to maximize the dose to an irregular tumor volume while minimizing irradiation of sensitive neighboring structures. Intracavitary implantation is achieved by constructing a mold of the nasopharynx with a silastic polymer and fitting it with hollow plastic catheters for afterloading with iridium-192.
Brachytherapy↗
Development of a colorimetric dosimeter for quality control of blood units and irradiators.
The development is reported of a reproducible colorimetric irradiation dosimeter that is easy to prepare as well as to interpret. Optimal chloroform, dithizone, and paraffin concentrations to produce a distinctive color change at > 1500 cGy (optimized for 3000 cGy) were determined by combining various concentrations of each component at 65 degrees C. The melted dosimetric material was poured into molds, allowed to solidify, and irradiated with doses ranging from 0 to 3000 cGy. Color change was evaluated visually and spectrophotometrically to determine reproducibility. Twenty-percent chloroform (wt/wt) and a dithizone concentration of 5.0 x 10(-5) M combined in paraffin (TP-2) produced optimal color change from pink to green after > 1500 cGy. The change was reproducible, and 50 individuals were able to distinguish between irradiated and nonirradiated dosimeters. Additionally, five of five of these individuals correctly ranked five dosimeters in order of increasing irradiation from 0 to 3000 cGy, in increments of 750 cGy. This dosimeter is easy to make and easy to read and may allow blood banks to show unit-by-unit quality assurance for irradiated blood components and quality control of the irradiator itself.
Blood Component Transfusion↗