Biomedical subjects

S Vijayakumar

Publications and source records attributed to S Vijayakumar.

At least 91 records · Page 5Linked to original sources

PubMed1994

Can prostate-specific antigen levels predict bone scan evidence of metastases in newly diagnosed prostate cancer?

Staging in prostate cancer, as in any other cancer has significant ramifications in management. Currently, prostate-specific antigen (PSA) determination and the bone scan are two important procedures in the pretreatment staging workup of prostate cancer. PSA is a very useful serum tumor marker in the management of prostate cancer patients. We retrospectively evaluated 90 patients at the time of initial diagnosis of prostate cancer, all of whom had initial PSA levels measured, as well as bone scans obtained. In addition to the PSA level, we considered clinical stage and pathologic grade in the prediction of bone scan for metastases, at the time of initial diagnosis of prostate cancer. Negative predictive value for PSA values < 10 ng/ml (27 patients), clinical stage A (9 patients) and pathologic grade 1 (19 patients) was 100%. The number of patients with bone scan evidence of metastasis with < 10 ng/ml and > 10 ng/ml PSA levels were 0% (0/27 patients) and 27% (17/63 patients) (p = .0022 [Fisher's Exact test]; p = .003 [chi-square test]). In patients with higher stage (p = .688), grade (p = .039), or PSA levels (p = .0001), the incidence of bone metastases increased. However, none of these three parameters can predict reliably bone scan evidence of metastases (i.e., positive predictive value). The negative predictive values did not improve when a combination of the two or three of the above parameters were used.

Aged↗

PubMed1994

Craniospinal axis irradiation: an improved electron technique for irradiation of the spinal axis.

In this work we review the dosimetric features of craniospinal axis irradiation in the areas of matching cranial and spinal fields, with reference to the normal structures within the spinal field. The implications of the use of photon or electron modalities for the spinal port were evaluated. A novel method of matching the cranial photon and the spinal electron fields involving a computer-aided junction design is presented. The technique involves moving the photon beam in three steps to degrade its penumbra to match that of the electron field. Thermoluminescent dosimetry in a Rando phantom and computed tomography-based dose-volume histogram study for an illustrative paediatric case were used to compare the dose to normal structures within the spinal field. Our results show that the use of electrons for the spinal field leads to better sparing of deep seated normal structures. In the case of bone marrow, the use of a customized bolus for the spinal field results in an improved dose distribution, making electrons potentially superior to photons for radiobiological reasons.

Bone Marrow↗

PubMed1993

Online repositioning during treatment of the prostate: a study of potential limits and gains.

PURPOSE: With on-line portal imaging devices and image registration tools, the verification of radiation field position prior to each treatment becomes technically feasible. In this paper, we analyze the impact of pre-treatment verification and field position adjustment on target coverage and normal tissue sparing. METHODS AND MATERIALS: Port films were compared with corresponding simulation films to determine the magnitude of setup variations in patients treated for prostate cancer. From these data, an analytic function was determined between geometric coverage of the target and field margin size. A paradigm for on-line patient repositioning was employed to generate a new relationship between margin and target coverage. Margins were selected for the situations of normal treatment and on-line repositioning to ensure target coverage. Dose-volume histograms were generated for a typical prostate treatment using these margins. RESULTS: On-line repositioning, when setup errors exceed 1 cm, results in a 6 mm reduction in margin, suggesting that 10% of the volume of bladder and rectum may be spared of high dose. CONCLUSION: The use of on-line imaging and image registration to guide adjustment of patient setup may lead to a reduction in the volume of normal tissues irradiated, and possibly improve the probability of complication-free survival in future treatments.

Computer Simulation↗

PubMed1993

Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: preliminary results of a randomized, open-labeled, phase II trial.

PURPOSE: To determine the efficacy and safety of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) at a dose of 200 units/kg/day to cancer patients undergoing radiotherapy. METHODS AND MATERIALS: This is a randomized, open-labeled, Phase II study. Only patients receiving radiotherapy +/- chemotherapy are included. Eligibility is restricted to patients with lung cancer, carcinoma of the uterine cervix, prostatic adenocarcinoma, or adenocarcinoma of the breast. Patients in the control and treatment arms receive radiotherapy with similar policies, and their doses of radiotherapy and treatment volumes are determined by the site and stage of the disease. Patients in the "treatment arm" receive 200 units/kg/day of r-HuEPO, subcutaneously, five times a week with iron (Fe SO4, 325 mg. p.o., t.i.d.) supplements. Complete blood counts are obtained weekly. Quality of life is assessed weekly by the patients themselves by a few simple entries on an analog scale. RESULTS: Twenty-six patients have been entered in the study so far. Twelve patients were placed in the control arm and 14 in the treatment arm. Pre-randomization demographic and laboratory mean values in both arms were comparable, with none of 16 parameters compared reaching statistical significance. Our results can be summarized as follows: (a) Mean hemoglobin, hematocrit, and red blood cell values increased gradually in the treatment arm patients. Week-by-week comparison showed that mean values for these three parameters were significantly higher in the treatment arm than in the control arm. For example, the p values for the differences in hemoglobin mean values for weeks 1-6 were 0.015, 0.002, 0.003, 0.0002, 0.0006, and 0.007, respectively. Similar trends were observed for red blood cells and the hematocrit values. (b) No significant toxicity has been encountered. (c) No significant differences in the mean values of white blood cells and platelet counts were seen between the two arms. The values of these two parameters declined over the course of radiotherapy. (d) The mean weekly increase in hemoglobin levels in the treatment arm was 0.43 gm/dl. CONCLUSION: (a) The safety and efficacy of r-HuEPO, with 200 units/kg/day of subcutaneous administration, have been confirmed in our study group. (b) However, the rate of increase in hemoglobin levels is not very rapid with the doses used. (c) Dose escalation studies are needed for determination of the feasibility of improving hemoglobin levels by about 1 gm/dl/week. (d) The question whether improvement in hemoglobin with r-HuEPO therapy can improve outcome by improving tumor oxygenation needs to be studied in carcinoma of the uterine cervix and squamous cell carcinoma of the head and neck.

Adenocarcinoma↗

PubMed1993

Acute toxicity during external-beam radiotherapy for localized prostate cancer: comparison of different techniques.

PURPOSE: The chronic and acute toxicities associated with conventional radiotherapy of localized prostate cancer are well documented. However, the degree and incidence of toxicities with conformal techniques are not known. Studying side effects associated with modern radiotherapeutic techniques is more important now since there has been a general trend to use computerized tomography-based techniques in recent years; beam's eye view-based conformal techniques are also becoming more commonplace. It is possible that the local disease control can be improved with the delivery of higher doses than currently used. Conformation of the treatment volume to the target volume may facilitate such dose-escalation. However, prior to such dose-escalation, it is important to know the toxicities associated with such techniques with conventional doses. METHODS AND MATERIALS: We have compared week-by-week acute toxicities associated with conventional (Group A, 16 patients), computerized tomography-based, manual (Group B, 57 patients) and beam's eye view-based (Group C, 43 patients) techniques during 7 weeks of radiotherapy. Group B and C patients were treated contemporaneously (1988-1990). RESULTS: Acute side effects gradually increased from week 1 through weeks 4-5 and generally declined or plateaued after that. The incidence of acute toxicities was significantly less with the beam's eye view/based technique than with the other two methods. For instance, the percentages of Grade 2 acute genitourinary toxicities for Groups A, B, and C were as follows: Week 1-0, 0, 0; Week 2-6, 0, 0; Week 3-6, 9, 2; Week 4-12, 14, 9; Week 5-35, 14, 9; Week 6-31, 16, 7; Week 7-33, 8, 8, respectively. The p values associated with differences in acute genitourinary toxicities for Weeks 1-7 using chi-square test were 0.072, 0.627, 0.389, 0.538, 0.123, 0.06, and 0.012; the p values for acute gastrointestinal toxicities were 0.512, 0.09, 0.031, 0.031, 0.003, < 0.0001, and 0.004, respectively. Pairwise comparison (Wilcoxon rank-sum test) showed statistically significant lower acute toxicity in Group C than Group B (e.g., p values, Weeks 1-7 for gastrointestinal toxicity: 0.633, 0.056, 0.010, 0.014, < 0.0001, < 0.0001, and < 0.0001, respectively) in the latter part of the treatment course. No correlation was found between the extent of toxicity and the patient age or the overall treatment time. Also, no correlation was found between the degree of toxicity and the radiation dose and fraction size, within the narrow ranges used (65-70 Gy and 180-200 cGy, respectively). A trend suggesting increased severity of toxicity with increase in the volume of treatment was seen. CONCLUSION: The findings in this retrospective study need to be confirmed by other prospective studies.

Acute Disease↗

PubMed1993

Comparison of CT-based treatment planning and retrograde urethrography in determining the prostatic apex at simulation.

In 20 consecutive patients who underwent treatment planning, localization of the prostatic apex with CT-based techniques at simulation was compared to location of the apex as defined by retrograde urethrography. In addition, the location of the urethrogram-defined prostatic apex was compared with the bottom of the ischial tuberosities, which is often recommended as the inferior margin of the field. In 15% of the patients there was agreement between the CT-defined apex and the urethrogram-defined apex; in 85% there was discordance. In a majority of patients with discordance, the urethrogram apex was located caudad to the CT-defined apex (71%) with a median difference of .65 cm. In 29% of the patients the urethrogram apex was located superior to the CT-defined apex. Overall, 75% of the patients had discordance between the urethrogram apex and the CT apex of 0.5 cm or greater; 30% had an absolute difference of 1.0 cm or greater. Comparing the location of the prostatic apex with the bottom of the ischial tuberosities revealed that in 15% of the patients the apex was 1.0 cm or less from the bottom of the tuberosities and in 45% it was less than 1.5 cm. This would place the apex of the prostate in the penumbra region of the field and risk undertreatment of the prostate if the bottom of the ischial tuberosities was the inferior margin of the field. Measuring the location of the prostatic apex from the top of the symphysis pubis revealed that a distance of 4.9 cm encompassed the apex in all 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1993

Differential stability of beta-sheets and alpha-helices in beta-lactamase: a high temperature molecular dynamics study of unfolding intermediates.

beta-Lactamase, which catalyzes beta-lactam antibiotics, is prototypical of large alpha/beta proteins with a scaffolding formed by strong noncovalent interactions. Experimentally, the enzyme is well characterized, and intermediates that are slightly less compact and having nearly the same content of secondary structure have been identified in the folding pathway. In the present study, high temperature molecular dynamics simulations have been carried out on the native enzyme in solution. Analysis of these results in terms of root mean square fluctuations in cartesian and [phi, psi] space, backbone dihedral angles and secondary structural hydrogen bonds forms the basis for an investigation of the topology of partially unfolded states of beta-lactamase. A differential stability has been observed for alpha-helices and beta-sheets upon thermal denaturation to putative unfolding intermediates. These observations contribute to an understanding of the folding/unfolding processes of beta-lactamases in particular, and other alpha/beta proteins in general.

Enzyme Stability↗

PubMed1993

Fractionated total body irradiation: some radiobiological considerations.

Fractionated total body irradiation (TBI), as conditioning regimen for bone marrow transplantation in the treatment of non-lymphocytic leukaemia, has proved to be less toxic than single fraction TBI. However, higher relapse rates are reported. The linear quadratic (LQ) model has been applied to calculate equivalent total therapeutic doses as well as equivalent tolerance doses for fractionated TBI. The LQ model predicted that escalating total doses for fractionated TBI will still result in acceptable toxicity to lung while achieving better disease control. There is published clinical data supporting our conclusion from this radiobiological analysis.

Bone Marrow Transplantation↗

PubMed1993

Computer-aided treatment design of a distal upper extremity soft tissue tumor with electron beam radiotherapy.

We present here a novel approach for the planning and treatment of a distal upper extremity soft tissue tumor. Utilizing computed tomography (CT) based electron dose calculations, a customized compensating wax bolus was designed in order to deliver sufficient dose coverage to the tumor volume while sparing the draining lymphatics of the patient's hand and digits. A clinical case is presented as well as the design and construction of the compensator. Outcome and clinical implications are discussed.

Adult↗

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↗