Biomedical subjects

S Vijayakumar

Publications and source records attributed to S Vijayakumar.

At least 19 recordsLinked to original sources

PubMed1992

Molecular modeling of the 3-D structure of cytochrome P-450scc.

Sequence-alignment studies of the bovine mitochondrial cholesterol side-chain cleavage enzyme cytochrome P-450scc with the bacterial cytochrome P-450cam (camphor hydroxylating enzyme) have been undertaken. Our novel alignment of the sequences revealed 69 identical residues and many highly conserved regions. The results of the sequence alignment studies were used to model the 3-D structure of P-450scc based on the available crystal structure of P-450cam. The major insertions in the sequence are found mainly on four external-loop regions of the molecule, while the core structure of P-450cam is retained with subtle internal modifications. The most hydrophobic of these four external loops is proposed as a candidate for membrane attachment.

Amino Acid Sequence↗

PubMed1992

Phosphorous metabolite and cell cycle kinetic response of two human squamous cell carcinomas to radiation.

Phosphorous metabolism and cell cycle phase kinetics in response to radiation of two perfused human squamous cell carcinoma cell lines, SQ20B (radioresistant) and SQ38 (relatively radiosensitive), embedded in both basement membrane (Matrigel) and agarose gel threads were studied. The findings for these human cancer cells in response to 2- and 50-Gy irradiation are as follows. (a) Well perfused pure cancer cells (both SQ20B and SQ38) in both proliferative (cells embedded in Matrigel) and static (cells embedded in agarose threads) states did not show significant alteration in either phosphorous bioenergetics or membrane metabolites at 24 and 48 h after irradiation, although a large fraction of the population was clonogenically impaired. Previously reported, sensitively detected, metabolite alterations in response to radiation in rodent and human tumors in situ were not seen in these homogeneous cancer cell populations. (b) The radiosensitive squamous cell carcinoma cell lines SQ38 exhibited G1 block (from 54.38 +/- 1.40% in control to 73.93 +/- 1.01% after irradiation; mean +/ SD) in response to low-dose 2-Gy irradiation and G2 block (from 12.98 +/- 2.15% in control to 25.6 +/- 3.15% after irradiation) in response to high-dose 50-Gy irradiation, while the radioresistant cell line SQ20B showed only conventional G2 block in response to both doses. The differential cell cycle phase response may indicate the difference in radioresistance. (c) The membrane metabolites (including phosphomonoesters and phosphodiesters) and phosphocreatine gradually increased from the early passages to late passages, suggesting that cell proliferation rates were increasing as the cells adapted to tissue culture. The results suggest that the radiation-induced metabolite changes observed in solid tumors in situ may not be a direct response to interim changes within the cancer cells but, rather, a consequence of radiation damage either to the vasculature or to other host-mediated factors.

Animals↗

PubMed1992

Prognostic indicators in node-negative early stage breast cancer.

With the increasing availability of screening mammography, more women are diagnosed as having breast cancers at an early, node-negative stage. The majority of these patients would be cured with total mastectomy or breast conservation treatment. However, about 30% of the patients would have recurrence of disease in distant sites. In recent randomized clinical trials, adjuvant systemic therapy has been shown to reduce the rate of recurrence in these patients. Proper selection of patients for adjuvant therapy is necessary to avoid exposing many patients with low risk of recurrence to treatments for whom the benefit is not justified by the toxicity and the cost. In this article, we review the clinical and pathologic prognostic factors in early stage, node-negative breast cancer patients, including tumor size, nuclear and histologic grades, estrogen and progesterone receptors, menopausal status, proliferative rate, HER-2/neu oncogene amplification, and cathepsin D level. Favorable prognostic factors include tumor size less than or equal to 2 cm, low nuclear and histologic grades, low S-phase fraction, diploid state, low cathepsin-D level, and positive estrogen and progesterone receptor status. The value of HER-2/neu oncogene overexpression is controversial, and further studies are needed to define its role as a prognostic factor in patients with node-negative breast cancer. Based on these prognostic factors, it is possible to identify subsets of patients who have a low risk of recurrence and would not benefit significantly from adjuvant systemic therapy.

Breast Neoplasms↗

PubMed1992

An updated dose-response analysis in Hodgkin's disease.

Although radiotherapy cures a very high percentage of early stage patients with Hodgkin's disease (HD), there is a controversial dichotomy in the dose recommendations believed necessary to achieve greater than 95% local control: Whereas one school of thought is to administer 40-44 Gy, other reports claim equal results with about 36 Gy. It is also not clear what doses are required for various tumor cell burdens. The original recommendation of 40-44 Gy was derived from a retrospective analysis of in-field control of disease from mostly kilovoltage data three decades ago. However, there have been many advances in the evaluation of the extent of the disease and in the practice of radiotherapy since the 1960s. Many more dose-control studies have been published in recent years, necessitating a revisit to the dose-response question in HD. Here we have compiled the dose-control data from the 60s to the 90s and analyzed the original and the updated data with the same statistical method to see any differences. We also have performed similar analysis of dose-control information for subclinical disease, less than 6 cm and greater than 6 cm disease. Whereas original analysis (1040 sites at risk) suggested 98% in-field control with 44 Gy, our re-analysis including modern megavoltage data (4117 sites at risk) shows that similar in-field control rates could be achieved with 37.5 Gy. With megavoltage radiotherapy, the doses required for 98% in-field control for subclinical disease and disease of less than 6 cm and greater than 6 cm are, 32.4 Gy (1426 sites at risk), 36.9 Gy (1005 sites at risk) and 37.4 Gy (98 sites at risk), respectively. The results of current updated analysis will provide in-field disease control probabilities for different disease burdens and can serve as a guide in deciding dose prescriptions for practicing radiation oncologists.

Dose-Response Relationship, Radiation↗

PubMed1992

Therapeutic gain with hyperfractionation in prophylactic cranial irradiation of children with acute lymphoblastic leukemia.

IQ deterioration after prophylactic cranial irradiation is a dreaded complication for children with acute lymphoblastic leukemia. Alternate treatment schemes are needed that achieve comparable tumor control, but avoid such long-term complication. To this end, a hyperfractionated treatment scheme is proposed. Using two different radiobiological models, we analyze the doses required to achieve equivalent disease control while reducing the severity of late sequelae. Analysis based on the linear-quadratic and surviving fractions models clearly indicates a therapeutic gain with hyperfractionation.

Brain Neoplasms↗

PubMed1992

Hyperfractionated, twice-a-day, radiotherapy may decrease IQ deterioration due to prophylactic cranial irradiation in childhood acute lymphoblastic leukemia: a radiobiological analysis.

High cure rates in childhood acute lymphoblastic leukemia (ALL) are being achieved with aggressive systemic chemotherapy and treatment to sanctuary sites including prophylactic cranial irradiation. However, IQ deterioration is a dreaded complication of prophylactic cranial irradiation. IQ deterioration is a late sequela. Since there is evidence--both radiobiological and clinical--to suggest that acute tissue (including tumor) response and late tissue response can be separated by hyper-fractionation, we propose a twice-a-day radiotherapy in prophylactic cranial irradiation of childhood ALL to decrease delayed toxicity. Analysis based on current radiobiological models favors such a treatment scheme. However, only a prospective clinical trial can confirm whether IQ deterioration can be prevented or decreased with hyper-fractionated radiotherapy.

Brain Neoplasms↗

PubMed1992

The use of beam's eye view volumetrics in the selection of non-coplanar radiation portals.

In 3-dimensional treatment planning, beam's eye view (BEV) is used as an interactive tool to define portal entry angles that exclude critical structures while fully encompassing the target volume. With beam's eye view volumetrics (BEV volumetrics), the volume of intersected normal tissues is also calculated and is used as a quantitative tool to choose portal orientations that minimize normal tissue volumes irradiated. The axial beam entry angle and a polar angle (relative to the patient longitudinal axis) are specified to define the central axis orientation. Using BEV volumetrics, we have studied the quantities of normal tissues irradiated when treating tumors in the abdomen, thorax, and pelvis. The reduction of normal tissue irradiated is a strong function of site and patient-specific tumor size and location. Volumetrics combined with BEV is found to be useful in treatment planning because it (a) provides quantitative information needed in rationally choosing portal entry angles, (b) provides a near interactive speed approach to understanding the relative merits of different multiple field plans, and (c) compliments the information provided by the more time-consuming generation of dose volume histograms.

Humans↗

PubMed1992

Beam's eye view volumetrics: an aid in rapid treatment plan development and evaluation.

A well-designed treatment plan fully irradiates the target to the prescribed dose while minimizing radiation to adjacent critical structures. Beam's eye view is an important component of treatment planning systems because it provides the operator with tools needed to achieve this goal. Through interactive manipulation of displays, the planner uses beam's eye view to adequately cover the target volume while geometrically avoiding certain critical, normal structures. A factor not considered in current beam's eye view programs is the fractional volume of each structure irradiated given a specified beam direction. We have incorporated a rapid volume calculation capability in our beam's eye view program, and have applied it to provide a quantitative aid to treatment planning development and evaluation. Treatment planning of lung tumors has been studied using this tool. Volumes of lung and spinal cord treated as a function of portal angle may be calculated much more rapidly than dose volume histograms and yet provide quantitative indices which follow the trends of dose volume histograms as a function of field angle. Plots of normal tissue volume irradiated as a function of field angle identify the optimal angle to minimize irradiated volume of a structure at a glance. For multiple field plans, a bitmap approach identifies areas treated by various combinations of beams. Volumetrics combined with beam's eye view are useful in treatment planning because they (a) provide quantitative information needed in choosing and optimizing portal entry angle (b) provide an interactive approach to understanding the relative merits of different multiple field plans and (c) complement the information provided by the more time consuming generation of dose volume histograms. The clinical application of this tool in treatment planning is presented.

Computer Graphics↗

PubMed1992

Practical applications of Beam's Eye View-based treatment planning to head and neck sites.

Because of the complex anatomy of the structures involved by tumor as well as of the critical normal structures, treatment planning for advanced or spatially irregular cancers of head and neck sites is often extremely challenging. Computerized axial tomographic scanning is frequently invaluable in delineating tumor extension into areas inaccessible to physical examination. Our Beam's Eye View Planning (BEVP) capability allows us to incorporate this radiographic information accurately into actual plans used in the clinic. Over the past 2 1/2 years, we have applied this technique to 31 selected head and neck cancer patients at Michael Reese/University of Chicago Center for Radiation Therapy. Tumors were chosen on the basis of anatomical complexity: most involved multiple head and neck sites including orbit, skull base, paranasal sinuses and cavernous sinus. In all cases, radiation tolerance of critical normal structures including spinal cord, brain stem, optic chiasm, and eye had to be considered. With careful use of rigid immobilization devices and the outlining of several normal structures for purposes of alignment, we had no difficulty applying our BEVP technique to clinical simulations. Oblique field blocking was especially facilitated by BEVP. We found the BEVP technique very useful to assure that tumor coverage was adequate and tolerance of normal tissues not exceeded.

Computer Simulation↗

PubMed1992

Quantitation of treatment volumes from CT and MRI in high-grade gliomas: implications for radiotherapy.

Long-term survival of patients with high-grade gliomas remains extremely poor. The main reason for such an outcome is local failure, or recurrence, after surgery and/or radiotherapy. Higher doses of radiation may result in decreased local failure rates provided that the location (and extent) of gross tumor and microscopic disease can be defined accurately. The abnormalities appearing in images from diagnostic modalities, such as CT and MRI, are being used as a starting point and as a guide for the clinical definition of tumor and its extensions. However, some recent studies on two-dimensional specimens, correlating histopathological findings to CT and MRI images, showed that the resulting definition of tumor cell extensions was unsatisfactory, different, and in need of ample margins. We carried out a retrospective analysis to compare the target volumes that would have been defined by CT, T2-weighted MRI, and T1-weighted postgadolinium MRI images of the same individual and to explore the implications of the resulting volume definitions for radiotherapy. The results of our limited study, based on the margins used, indicate that the CT-defined target volume is consistently larger than that from either of the two MRI modalities and suggest that noncoplanar approaches for its treatment and other local approaches for tumor boost should be considered. We conclude that until more definitive histopathological guidelines correlated to image features have been formulated and agreed upon, one should try to make full use of all available diagnostic information in order to minimize the possibility of geographical miss of target extensions.

Adult↗

PubMed1992

Quantification of doses to mediastinal lymph nodes in Hodgkin's disease.

Hodgkin's disease is highly curable today. Radiotherapy (RT) is the treatment of choice in the early stages. A mantle field is often used in the RT of Hodgkin's disease, and the technique and dosimetry are quite complex. We used computerized tomography (CT)-based dosimetry to determine doses delivered to different mediastinal nodes with the commonly used technique in Hodgkin's disease that was originally described by Kaplan. We used dose-volume histograms to determine doses to various groups of nodes in nine patients. Significant inhomogeneity (30%, 30%, 35%, 35%, 30%, 40%, 35%, 35%, and 30% in the nine patients) in dose distribution was found within the mediastinum. With the advent of 3-dimensional CT-based treatment planning, we are able to quantify such inhomogeneities. The question arises whether a homogeneous, lesser dose can achieve equal results. Average doses and "effective doses" were also calculated. The "effective doses" in eight patients (for a prescribed dose of 44 Gy) with a midline posterior spinal cord block added at 20 Gy were 37.3 Gy, 34.3 Gy, 36.0 Gy, 38.4 Gy, 35.8 Gy, 38.1 Gy, 36.7 Gy, and 36.7 Gy, respectively. A homogeneous dose equivalent to effective dose may achieve the same control as an inhomogeneous dose delivery. Prospective 3-D dosimetric studies are required to confirm this concept.

Hodgkin Disease↗

PubMed1992

Treatment and prognosis of orbital non-Hodgkin's lymphomas.

Twenty patients with orbital lymphomas were treated and followed over a 14-year period. Ten of these patients had well-differentiated lymphocytic lymphoma (WDL), and all of them were clinical stage IE. Five patients had nodular poorly differentiated lymphocytic lymphomas (NPDL), three patients had diffuse histiocytic lymphomas (DHL), one had nodular mixed-cell lymphoma, and one had diffused mixed-cell lymphoma. The patients with WDL received local radiation therapy, and all of them entered completed remissions. The projected survival at 10 years was 100% for these patients. The patients with low-grade lymphomas with advanced disease were treated with chlorambucil and prednisone or cytoxan and vincristine. The patients with high-grade lymphomas received treatment with methotrexate, cyclophosphamide, doxorubicin, vincristine, bleomycin, dexamethasone (mBACOD) or cyclophosphamide, vincristine, methotrexate, cytosine arabinoside, leucovorin (COMLA). The overall survival estimate for all patients was 63% at 10 years. The disease-free survival was 49% at 10 years. The patients with high-grade lymphomas had a poor prognosis, with no survivors after 4 years. This study suggests that patients with WDL usually present with localized disease to the involved orbit, and have an excellent prognosis with radiation therapy alone. Patients with high-grade orbital non-Hodgkin's lymphomas have a poor outcome despite use of aggressive combination chemotherapy regimens.

Aged↗

PubMed1992

Beam's eye view--based radiation therapy: description of methods.

Improving three-dimensional target definitions and dose delivery may improve local control rates in radiation therapy. Computed tomography (CT)-based treatment planning is one step toward achieving this goal, but further progress is possible with beam's eye view (BEV)-based planning. Initially, CT is performed with the patient in the treatment position, and data are transferred to a computerized treatment planning system. Target volumes and vital structures are outlined on CT sections and digitized, and a treatment plan is produced. BEV display is used to calculate the angles needed for oblique fields that would avoid irradiation of vital structures. A BEV printout is obtained along with simulation radiographs. The radiograph is overlaid on the printout, all identified structures are matched, and the target volumes are transferred from the printout to the radiograph. BEV-based planning can improve three-dimensional coverage of a tumor, irradiation techniques, and the therapeutic ratio by decreasing the irradiation of normal tissue. The extra time required for BEV planning is acceptable, but further studies of long-term outcomes and cost-benefit analyses are needed.

Humans↗

PubMed1992

Localized prostate cancer: use of serial prostate-specific antigen measurements during radiation therapy.

The serum half-life of prostate-specific antigen (PSA) after radical prostatectomy is about 3 days; to the authors' knowledge, the PSA half-life during radiation therapy (RT) has not been investigated with weekly serial measurements. To determine the rate of decline and the half-life of PSA, serial measurements were obtained during 6-8 weeks of external-beam RT for localized prostate cancer. PSA values were determined immediately before and approximately 24 hours after the first dose of RT; thereafter, weekly measurements were made. There was a downward trend in PSA levels in 19 patients, with a median half-life of 58.5 days; the mean decline was 1.6% per day. However, in four patients, PSA levels either rose and fell to pre-RT values or increased steadily. The effect of digital rectal examination (DRE) on PSA levels was also analyzed. When the dates of DRE and subsequent PSA levels were inspected, no increase in PSA levels subsequent to DRE was found, although three of the four patients in whom PSA levels did not decrease underwent multiple DREs. The authors found a statistically significant (P = .023) transient elevation in the mean PSA values after the first fraction of RT (2 Gy) was administered; the mechanism and importance of which are not known.

Adenocarcinoma↗

PubMed1991

Beams eye view-based photon radiotherapy I.

Geographic miss, dosimetric miss (underdosing), and proximity of the tumor to sensitive normal tissues are some of the causes of inadequate radiation dose delivery; this is one of many causes of failure after radiotherapy. In the past decade, computerized tomography (CT)-based treatment planning has helped to overcome some of these problems. Beam's eye view (BEV)-based radiotherapy planning is an improvement over CT-based treatment planning that may further increase the therapeutic ratio. Since January 1988, we have treated 198 patients with BEV-based photon radiotherapy. About 40% of our patients treated with radical radiotherapy undergo BEV-based treatment, and about 70% of patients who undergo planning CT in the treatment position receive BEV-based radiotherapy. Our findings are as follows: (a) routine use of BEV-based RT (BEVRT) is possible in a busy radiation oncology department; (b) BEVRT improves geometric coverage of tumors; (c) BEVRT is extremely useful in the design of oblique portals; (d) time commitments for various members of the RT treatment-planning team are reasonable; (e) BEVRT helps individualize RT technique; (f) preliminary data suggest decreased acute toxicity with the use of BEVRT for prostate cancer patients. Whether these advantages will help to improve the outcome (i.e., improve local control and survival) and/or decrease the long-term toxicity is not yet known.

Breast Neoplasms↗

PubMed1991

Optimization of radical radiotherapy with beam's eye view techniques for non-small cell lung cancer.

The presence of vital and sensitive organs such as the spinal cord, heart, and lungs makes curative radiotherapy of non-small cell lung cancer difficult to implement and necessitates use of oblique portals. Defining the target volumes in oblique portals is very difficult. We now show, for non-small cell lung cancer, how beam's eye view-based radiotherapy can be used for accurate delineation of treatment volumes and for avoidance of real or dosimetric geographic misses. Furthermore, the beam's eye view-based method enables one to project accurately a 2-dimensional image of 3-dimensional disease extension, especially in oblique fields, thus facilitating the design of accurate customized blocking and avoiding inadvertent blocking of the tumor or unnecessary irradiation of normal tissues. Beam's eye view volumetric analysis is helpful for devising a customized treatment plan for each patient. Such customization may minimize local failure, which is one cause of poor results of radiotherapy in this site. Beam's eye view-based radiotherapy has the potential of improving local control and hence may improve the survival of patients with non-small-cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗

PubMed1991

An anterior appositional electron field technique with a hanging lens block in orbital radiotherapy: a dosimetric study.

A technique for orbital radiotherapy is presented consisting of an anterior, appositional electron beam with a hanging lens block. The beam was modified by introducing two 1.6 mm thick plastic spoilers, at about 3 cm and 15 cm from the lens, to boost in-scattering of electrons under the block. The 9 mm diameter, 2 cm long stainless steel cylindrical block was suspended 0.5-1.0 cm above the eye. We performed film, TLD (Thermo Luminescent Dosimetry), and diode dosimetry to determine the dose fill-in behind the lens. The introduction of the spoilers dramatically changed the dose distribution. The maximum dose under the block increased from 66% to 85% of the open field dose. Moreover, the dose to the posterior surface of the globe directly underneath the block, at a depth of 3 cm, increased from 48% to 76% of maximum dose, while the dose to the lens was still below 20%. This is a simple and easily reproducible treatment and is an improvement on a previously described technique. The dose distribution is adequate for cases where the target volume surrounds and is posterior to the globe.

Electrons↗

PubMed1991

The use of a negative beam to simulate a midline block.

The physics behind the use of a negatively weighted beam to calculate the dose distribution under a midline block in computerized treatment planning systems is reviewed. To correctly reproduce the dose under the block, it is necessary and sufficient to know the relative dose at one reference depth on the central axis under the block. If the relative weight of the negative beam is then adjusted to produce agreement at that depth, good agreement can be obtained throughout. Comparisons between calculated and measured dose distributions under a midline block are presented for two therapy beams with 4MV and 6MV nominal energies.

Computer Simulation↗