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Biomedical subjects

S Vijayakumar

Publications and source records attributed to S Vijayakumar.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Estimation of doses to heart, coronary arteries, and spinal cord in mediastinal irradiation for Hodgkin's disease.

Early-stage Hodgkin's disease is highly curable with radiotherapy. However, radiotherapy for Hodgkin's disease is not without complications, particularly those related to irradiation of the mediastinum. In attempts to decrease complications, it is important not to compromise the results. To plan such a strategy, one needs to know the doses delivered to various volumes of normal tissues with present techniques. However, such dose-volume data do not exist. Here we demonstrate, with computerized tomography-based dosimetric techniques, such a dose-volume relationship for the heart, coronary arteries, and spinal cord. The doses were determined retrospectively in eight patients. With a prescribed dose of 44 Gy, the volumes of the heart receiving at least 22, 26, 31, 35, 40, or 44 Gy were: 77%, 75%, 70%, 57%, 33%, and 2%, respectively. The average modal doses to the coronary arteries were: anterior interventricular artery, 18.48 Gy; circumflex arterial branch, 37.84 Gy; left coronary artery, 34.76 Gy; and right coronary artery, 36.96 Gy. The average maximum spinal cord dose was 37.25 Gy. A similar prospective documentation of dose-volume relationships and correlation with (functional) long-term complications may be helpful in the development of new strategies for decreasing complications.

Coronary Vessels↗

Equivalent total doses for different fractionation schemes, based on the linear quadratic model.

A majority of patients receiving radical radiation therapy are treated with 1.8-2.0-Gy fractions, a dose that has evolved from clinical experience. However, other fractionation schemes can be advantageous. When fractionation is altered, the total dose prescribed should lead to equivalent or higher tumor control with the same or less tissue toxicity. To facilitate the use of different fractionation schemes, the authors compiled tables for equivalent biologic doses for late toxicity in normal tissues and tumoricidal doses for epithelial tumors, for various fraction sizes. The linear quadratic model according to Fowler was used. It is shown how these tables should be modified for proliferation of tumors during the course of radiation therapy. The tables make the use of different fractionation schemes easy. They also allow adjustment of total dose if fractionation needs to be changed during the course of treatment.

Cell Survival↗

5-Fluorouracil with oral leucovorin and hydroxyurea and concomitant radiotherapy for stage III non-small cell lung cancer.

Twenty-three patients with regionally advanced non-small cell lung cancer (NSCLC) (Stage III) were treated with continuous infusion 5-fluorouracil (5-FU) augmented by high-dose oral leucovorin and hydroxyurea and concomitant radiotherapy. This chemoradiotherapy regimen was administered during 5 days of every other week for six cycles (total radiation dose, 6000 cGy). Three patients (13%) had stable disease, 13 patients (57%) had a partial response (PR), and 1 patient (4%) had a complete response (CR). The overall response rate was 61% (95% confidence interval, 41% to 81%). At a median follow-up time of 19 months, the median survival time for all 23 patients was 12 months. The median time to disease progression was 6 months. Twelve patients have had disease progression outside of the chest, and only 3 patients have had intrathoracic disease progression as the site of first failure. The toxicities of this regimen consisted of mild to moderate myelosuppression and moderate degree dermatitis and mucositis. It was concluded that concomitant chemoradiotherapy with this regimen results in high local activity at acceptable toxicity. However, the systemic activity of this regimen was low, resulting in a high distant recurrence rate and a median survival time that was not different from that achieved with standard therapy. Therefore, its use, as defined in this study, cannot be recommended.

Administration, Oral↗

Role of systemic therapy in advanced non-small-cell lung cancer.

Increasing evidence supports the investigation of chemotherapy in patients with non-small-cell lung cancer (NSCLC). Randomized studies in patients with stage IV disease have shown increased survival in chemotherapy-treated patients compared to best supportive care and indicate the ability of chemotherapy to alter the natural history of this disease. Randomized studies involving adjuvant and neoadjuvant chemotherapy have also shown encouraging results. These studies and results of recent pilot studies utilizing neoadjuvant chemotherapy and concomitant chemoradiotherapy indicate a potential benefit from the use of chemotherapy in patients with NSCLC and call for its continued intensive investigation in clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗

Beam's eye view based prostate treatment planning: is it useful?

Prostate cancer is a common malignancy often treated with radiation therapy. Treatment optimization may improve local control while reducing acute and long-term complications. We routinely obtained CT scans on prostate cancer patients in treatment position after simulation. We analyzed the impact and implications of using our 3-D Beam's Eye View (BEV) capability on field definition and blocking for 12 consecutive patients. Conclusions include: (a) it is necessary to use multiple bony landmarks to align BEV images with simulator films; (b) it is difficult to enter volumes precisely, that is, the exact inferior extent of prostate; (c) Beam's Eye View-based plans show more individual variability in field size and position than are allowed for by recommendations in the literature; and (d) in this small series we found no significant correlation between prostate volume and clinical staging. In addition, computerized Beam's Eye View capability enables us to do normal tissue dosimetry. We have used Dose Volume Histograms (DVH) to study the impact of Beam's Eye View on optimization of dose to the bladder and rectum while adequately treating the prostate, with or without the seminal vesicles. Dose Volume Histograms using Beam's Eye View are compared with Dose Volume Histograms using target volumes from the literature. The results will be discussed, as well as the relative advantages of using Beam's Eye View for prostate cancer on a routine basis.

Evaluation Studies as Topic↗

Radiobiological characterization of head and neck and sarcoma cells derived from patients prior to radiotherapy.

The radiobiological parameters of 33 tumor cell lines were studied in biopsy samples obtained from patients prior to radiotherapy. Epithelial tumor cells derived from head and neck cancer patients were more radioresistant than tumor cell lines derived from patients with sarcoma regardless of method of analysis. The presence of radioresistant tumor cell lines was associated with local failure in some patients. However, the presence of radiosensitive tumor cells did not necessarily predict local control. Our data suggest radiocurability is complex and inherent radiobiological parameters of tumor cells may be only one factor in radiotherapy outcome.

Carcinoma, Squamous Cell↗

Mean inactivation dose (D). A critical analysis of a neglected parameter in radiotherapy.

By predicting treatment outcome to radiotherapy from in vitro radiobiological parameters, not only individual patient treatments can be tailored, but also new promising treatment protocols can be tried in patients in whom unfavorable outcome is predicted. In this respect, choosing the right parameter can be very important. Unlike D0 and N which provide information of the distal part of the survival curve, mean inactivation dose (D) estimates overall radiosensitivity. However, the parameters reflecting the response at the clinically relevant low-dose region are neglected in the literature. In a literature survey of 98 papers in which survival curves or D0/N were used, only in 2D was used. In 21 papers the D0/N values were important in drawing conclusions. By calculating D in 3 of these 21 papers, we show that the conclusion drawn may be altered with the use of D. The importance of 'low-dose-region-parameters' is reviewed.

Animals↗

Metastases to pineal gland.

Metastases to the pineal gland is an uncommon event. Bronchogenic carcinomas are the most frequent source of the primary lesion. A case of small cell carcinoma of the lung with solitary metastases to the pineal gland is reported; the literature is reviewed.

Brain Neoplasms↗

Therapeutic response of breast carcinoma monitored by 31P MRS in situ.

In situ phosphorous MRS was employed to study the metabolites of normal and cancerous breasts, and the alterations of tumor response to therapy. In a group of 7 normal volunteers and 12 patients, the total mobile phosphate content of breast carcinomas was found to be at least two to three times higher than that of the normal breast measured off menstruation. The metabolite profiles of normal and tumorous breasts are coarsely similar. In both cases the intracellular pH (pHi) was either neutral or slightly alkaline (pH greater than 7.0). Prior to treatments, the metabolite levels of phosphoryl monoester-to-ATP ratio of breast neoplasms were higher than those of the controls and decreased after the patients received a few treatments while the pHi fluctuated at a value greater than 7.0. The phosphoryl diester-to-ATP ratio also demonstrated to a lesser extent a decreasing trend in response to therapy.

Breast↗