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Biomedical subjects

C C Ling

Publications and source records attributed to C C Ling.

At least 73 records · Page 4Linked to original sources
PubMed1996

Treatment planning for carcinoma of the cervix: a patterns of care study report.

PURPOSE: The Patterns of Care Study (PCS) of patients treated in 1988-89 included "patterns of treatment planning" for radiotherapy of carcinoma of the uterine cervix. A Consensus Committee of radiation physicists and oncologists established current guidelines and developed questionnaires to assess the treatment planning process (i.e., the general structure, methodology, and tools) of institutions involved in the Patterns of Care Study. This paper reports the findings of the assessment. METHODS AND MATERIALS: The PCS surveyed 73 radiotherapy facilities, of which 21 are academic institutions (AC), 26 hospital-based facilities (HB), and 26 free-standing centers (FS). In total, 242 cases were assessed with 39% from academic centers, 33% from hospital-based centers, and 28% from free-standing centers. The survey collected treatment planning information such as the use of computed tomography (CT), simulation procedure, contouring of patient outline, tumor or target delineation, identification of critical structures, method of dose prescription (point or isodose), etc. Data was also obtained concerning implant boosts, e.g., radioisotope used, use of midline block for external beam treatment, availability of remote afterloader, practice of interstitial implants, combination with hyperthermia, etc. RESULTS: There is a high degree of compliance relative to the basic treatment planning standards. For example, 171 cases (out of 173) from AC and HB institutions included simulation and 169 used port film; for cases from FS centers, 61 out of 69 involved simulation and 66 out of 69 included port film. Most institutions used linacs (231 out of 242); in five cases, Co-60 units and in six cases betatron was used. In terms of treatment planning, 53% used skin contours, but only 14% had target volume delineation, with AC and HB being slightly more conscientious in these efforts. Critical organs did not appear to be explicitly considered in external beam treatment planning, with only 3% outlining the bladder, 5% the rectum, and less than 1% the small bowel. Only 11% of the centers used CT in treatment planning, and none reported the use of magnetic resonance imaging (MRI). For patients receiving implants, about 40% had midline blocking during external beam treatment, of which one out of three were shielded by standard blocks and two out of three with customized ones. About 11% of the patients receiving implants were treated with remote afterloading devices, 5% received interstitial implants, and none were treated in combination with hyperthermia. CONCLUSION: The treatment planning aspects of radiotherapy of carcinoma of the cervix have been established by this Patterns of Care Study Survey. There is a high level of uniformity in the approach. Some variations exist among centers in the different strata.

Brachytherapy↗
PubMed1996

Analysis of factors affecting the therapeutic gain in high dose rate gynecological implants relative to low dose rate implants.

The radiobiological efficacy of high dose rate (HDR) intracavitary implant relative to that of low dose rate (LDR) implants has been represented quantitatively by the therapeutic factor lamba defined as [EDRtum/ERDorgan]HDR/[ERDtum/ERDorgan]LDR where ERD is the extrapolated response dose. The ERDs for the tumor and a critical organ are calculated using the linear-quadratic model and depend on the values of alpha/beta ratio, the tumor and normal tissue repair time constants (mu 1 and mu 1), number (N) of HDR fractions, the dose per fraction (d), and the fractional tumor and organ dose (ft and fl) relative to the dose at the reference point. We have studied the variation of gamma with d, mu t, mu l, ft, and ft and have derived specific conditions for which lamba can have a value equal to or greater than unity leading to a therapeutic gain in HDR. It is found that lamba is less than unity for commonly used parameter values, specifically when mu t is assumed to be equal to mu l. However, if mu t is greater than mu l, lamba can have a value greater than unity for many possible values of ft and fl.

Biophysical Phenomena↗
PubMed1996

Apoptosis in heat-induced cell killing: the protective role of hsp-70 and the sensitization effect of the c-myc gene.

We studied heat-induced apoptosis and loss of clonogenicity in Rat-1 fibroblasts, thermotolerant Rat-1 (TT Rat-1), Rat-1 transfected with the human hsp-70 gene (M21) and Rat-1 transfected with the human c-myc proto-oncogene (Rat-1:myc). Relative to Rat-1, TT Rat-1 and M21 cells are heat-resistant, but Rat-1:myc cells are heat-sensitive, in terms of both apoptosis and clonogenic survival. The apoptotic fractions assayed 24 h after a heat treatment of 60 min at 44 degrees C, are about 20% for Rat-1, 7% for TT Rat-1, 10% for M21 and 70% for Rat-1:myc cells, respectively. Most of the apoptotic cells detach from substratum within 1 day of heat treatment and exhibit morphological changes, chromatin condensation and DNA fragmentation. The results of this study suggest that (1) apoptosis is an important mechanism of heat-induced cell killing in some cell lines, (2) apoptosis-mediated cell killing manifests rapidly (relative to clonogenic assay) after a heat treatment, and (3) overexpression of the human hsp-70 gene reduces, whereas expression of the human c-myc proto-oncogene enhances, heat-induced apoptosis. Lastly, the effects of the hsp-70 and c-myc genes on the thermosensitivity of cells are correlated with their modulation of apoptosis.

Animals↗
PubMed1995

Radiation-induced apoptosis: effects of cell age and dose fractionation.

The cell cycle dependence of radiation-induced apoptosis was measured using mitotically synchronized REC:myc(ch1) and Rat1:mycb cells. Cells in S and G2 phases were more susceptible; the apoptotic fraction was about 0.7-0.8 as compared to about 0.4 for G1 cells at a dose of 10 Gy. Two-dimensional cytofluorimetric analysis of cells, pulsed-labeled with bromodeoxyuridine and then irradiated with 10 Gy, showed both G1 and G2 blocks (6-8 h) for REC:myc(ch1) cells but only G2 block for Rat1:mycb cells. Consistent with these results, wild-type p53 and WAF1 (or p21), known to play a role in G1 delay, was induced by radiation in REC:myc(ch1) but not in Rat1:mycb cells. The cell cycle dependence of radiation-induced apoptosis and the absence of a G1 block for Rat1:mycb cells led to the prediction and observation of the novel "inverse split-dose effect," i.e., a radiation dose given in two equal halves separated by a few hours yielded a higher level of apoptosis relative to that resulting from the same total dose given all at once. This effect is due to cell cycle progression from G1 to the more sensitive S-G2 phase during the interval between the split doses. In contrast, the inverse split-dose effect for apoptosis is absent for REC:myc(ch1), due presumably to the radiation-induced G1 delay. Parallel split-dose experiments, but using clonogenic survival as end points, show recovery for REC:myc(ch1) cells but not for Rat1:mycb cells, reflecting the influence of split-dose, radiation-induced apoptosis.

Animals↗
PubMed1995

Radiation-induced apoptosis: relevance to radiotherapy.

Radiation-induced apoptosis is reviewed in terms of: (a) the identification of apoptotic and necrotic cells, (b) observations in vitro and in vivo of radiation-induced apoptosis, (c) genes controlling apoptosis, (d) evidence that the target may be the plasma membrane or nuclear DNA, (e) quantitative comparisons of apoptotic death and reproductive (clonogenic) death, (f) the importance of radiation-induced apoptosis in radiotherapy, and (g) studies of radiation-induced apoptosis that are needed. High priority should be placed on determining the molecular pathways that are important in the expression and modulation of radiation-induced apoptosis. Specifically, the events that modulate the apoptosis that occurs in interphase before the cell can divide should be distinguished from the events before division that modulate the misrepair of DNA damage, that results in chromosomal aberrations observed in mitotic cells, which in turn cause the progeny of the dividing cell with aberrations to die by either apoptosis or necrosis. Then, molecular events that determine whether a cell that divides with or without a chromosomal aberration will produce progeny that apoptose or necrose need to be identified. These considerations are important for determining how modulation of radiation-induced apoptosis will affect the ultimate clonogenic survival, and possibly genomic instability in the surviving progeny.

Animals↗
PubMed1995

Carcinoma of the cervix: patterns of care studies: review of 1978, 1983, and 1988-1989 surveys.

PURPOSE: A review of the Patterns of Care Studies Process Survey data on carcinoma of the cervix conducted on patients in 1978, 1983, and 1988-89 was carried out to identify changes or trends in the demographics, evaluation, and treatment that might have occurred over this time period. METHODS AND MATERIALS: Patterns of Care Studies conducted surveys on patients treated by radiation therapy for cervical carcinoma in 1978, 1983, and 1988-89. These surveys have compiled demographic and treatment data on a total of 993 patients. There is outcome data for the 1978 and 1983 surveys, but not for the 1988-89 survey because follow-up has not been collected yet. The demographic and treatment delivery data on all three surveys has been reviewed and analyzed and is the subject of this study. RESULTS: There was no difference in the age distribution at the time of diagnosis of the patients in these surveys. The percentage of black patients remained constant in the three surveys, 19%, 17%, and 21%, respectively. The percentage of white patients was 76%, 78%, and 67%, but that of nonwhite/nonblack patients was 3%, 4%, and 12% (p < 0.001). The distribution of patients by stage was similar in the first two surveys. In the third survey, there was a decrease in the percentage of patients with Stage IA and IB (first = 35%; second = 38%; third = 29%) with a concurrent increase in Stage IIIA and IIIB patients (first = 20%; second = 18%; third = 26%). The surveys showed a major change in the pretreatment evaluation tests used. There was a progressive decrease in the use of intravenous pyelogram (IVP) (86 to 42%), barium enema (58 to 32%), cystoscopy for patients Stage IIB and higher (64 to 52%), and lymphangiography (18 to 14%). The use of abdominal or pelvic computed tomography dramatically increased from 6 to 70% between the first and third surveys. The use of 60Co units decreased from 35 to 2% from the first to the third survey [6 to 0% for short source-surface distance (SSD) 60Co units]. Point dose calculations for the intracavitary therapy increased from 78% in the 1978 survey to 95% in the third survey. As determined by the total dose delivered to the paracentral points, more patients (75.1%) were treated according to the Patterns of Care recommended guidelines in the 1988-89 survey than in the 1983 survey (63.6%). Chemotherapy was given to 12% of the patients undergoing radiation therapy during the period of the third survey, but these data are not available for the first and second surveys. CONCLUSION: Review of the Carcinoma of the Cervix Patterns of Care studies discloses significant changes in the demographics, patient evaluation, and radiation therapy techniques during the period of the studies. The potential impact of these changes on treatment outcome cannot be determined at this time until longterm follow-up for the 1988-89 survey is available, but improvements in the processes of care should lead to improvements in outcome.

Adult↗
PubMed1995

The relative biological effectiveness of I-125 and Pd-103.

PURPOSE: To determine the relative biological effectiveness (RBE) of I-125 and Pd-103 relative to Co-60. METHODS AND MATERIALS: A cell line REC:ras, derived from rat embryo cells, was used. Cells in exponential or plateau phase were irradiated at dose rates of about 0.07 Gy/h and 0.14 Gy/h. To circumvent the interface effect, cells were grown and irradiated on membranes made of cellulose acetate, which has an effective Z of 7.5. I-125 and Pd-103 seeds were placed in a custom designed template that yielded a homogeneous dose distribution in the plane of the cell culture. The dose rates of irradiation were measured by calibrated thermoluminescence dosimetry (TLD) chips. RESULTS AND CONCLUSIONS: Our measurements yielded an RBE of about 1.4 for I-125 at dose rates of about 0.07 Gy/h, and an RBE of about 1.9 for Pd-103 at dose rates of about 0.07 Gy/h and 0.14 Gy/h. The RBE of I-125 is similar to those measured by other investigators, the RBE for Pd-103 is being reported for the first time.

Animals↗
PubMed1995

Optimization of intensity-modulated 3D conformal treatment plans based on biological indices.

To overcome the limitations of the intensity modulation optimization techniques based on dose criteria, we introduce a method for optimizing intensity distributions in which we employ an objective function based on biological indices. The objective function also includes constraints on dose and dose-volume combinations to ensure that the results are consistent with the physician's judgement. We apply a variant of the steepest-descent method to optimize the objective function. The method is three-dimensional and incorporates scattered radiation in the optimization process using an iterative scheme employing the pencil beam convolution method. Previously we had shown that the inverse technique of obtaining optimum intensity distributions, for which the objectives are defined in terms of a desired uniform dose to the target volume and desired upper limits of dose to normal organs, produces satisfactory approximations of the desired dose distributions for prostate plans. However, for lung, the performance of this technique was considerably inferior. Our conclusion was that, in general, it is not sufficient to specify the objectives of optimization purely in terms of a desired pattern of dose and that the objectives should also incorporate biology, perhaps in the form of biological indices. We demonstrate that the biology-based approach produces lung plans that are superior to those produced when only dose-based objectives are used. For the treatment of prostate, the two methods produce comparable dose distributions.

Adenocarcinoma↗
PubMed1995

Conformal radiation treatment: a critical appraisal.

Significant technical advances have improved the precision of radiation treatment of human malignancies and permitted dose-escalation studies. However, a number of challenges remain, particularly in the clinical and radiobiological aspects of radiotherapy. Even with these deficiencies, it is likely that improved overall treatment results will be forthcoming with 3DCRT. Nevertheless, the cost-effectiveness of this approach needs to be assessed, based on the magnitude of the improvement in the treatment of various disease sites.

Clinical Trials as Topic↗
PubMed1995

Beam characteristics of a new generation 50 MeV racetrack microtron.

The first of a new generation of microtron accelerators has been installed and tested. It is currently in use for multisegment conformal radiotherapy at our institution. The unit produces x rays and electrons from 10 to 50 MeV in 5 MeV increments. It incorporates a 64 leaf, doubly focused multileaf collimator (MLC), which can be used to shape x-ray and electron beams. Both x-ray and electron beams are produced by magnetically scanning the electron beams from the accelerator. The new generation unit incorporates a purging magnet to sweep away any primary or secondary electrons that pass through the target(s). In this paper, the beam characteristics of the accelerator that were studied during acceptance testing are described. Representative examples of depth doses, beam profiles, output factors, and elementary beam distributions are presented and discussed, in comparison with the earlier generation of microtron accelerators and with other radiotherapy machines.

Humans↗
PubMed1994

Initial clinical experience with computer-controlled conformal radiotherapy of the prostate using a 50-MeV medical microtron.

PURPOSE: We have described previously a model for delivering computer-controlled radiation treatments. We report here on the implementation and first year's clinical experience with such treatments using a 50 MeV medical microtron. METHODS AND MATERIALS: The microtron is equipped with a multileaf collimator and is capable of setting up and treating a sequence of fixed fields called segments, under computer control. An external computer derives machine parameters for the segments from a three-dimensional treatment planning system, transfers them to the microtron control computer, checks the machine settings before allowing dose delivery to begin, and records the treatment. We describe the patient treatment methodology, portal film acquisition, electronic portal imaging, and quality assurance. RESULTS: Patient treatments began in July 1992, comprising six-segment conformal treatments of the prostate. Using the recorded treatment data, the system performance has been examined and compared to other treatment machines. The average treatment time is 10 min, of which 4 min is for computer-controlled setup and irradiation; the remaining time is for patient positioning and checking of clearances. Long-term reproducibility of computer-controlled setup of the gantry and multileaf position is better than 0.5 degrees and 1 mm, respectively. Termination due to a machine fault has occurred in 5.5% of treatments, improving to 2.5% in recent months. CONCLUSION: Our initial experience indicates that computer-controlled segmental therapy can be performed reliably on a routine basis. Treatment times with the microtron are significantly shorter than with conventional linacs, and setup accuracy is consistent with that needed for conformal therapy. We believe that treatment times can be further improved through software upgrades and integration of electronic portal imaging.

Humans↗
PubMed1994

Preclinical evaluation of the reliability of a 50 MeV racetrack microtron.

PURPOSE: A 50 MeV racetrack microtron has been installed and tested at Memorial Sloan-Kettering Cancer Center. It is designed to execute multi-segment conformal therapy automatically under computer control using scanned X ray and electron beams from 10 to 50 MeV. Prior to acceptance of the machine from the manufacturer, formal reliability testing was carried out. Only in this way could confidence be gained in its usefulness for routine 3D computer-controlled conformal therapy. MATERIALS AND METHODS: To assess reliability, a set of 25 multi-segment test cases, each consisting of 10 to 17 fixed segments, was developed. The field arrangements and modalities for some of the test cases were identical to 3D conformal treatments that were being delivered with multiple static fields on conventional linear accelerators at our institution. Other cases were designed to explore reliability under more complex sets of conditions. These cases were "treated" repeatedly during a total period of 45 hours, over 5 days. During the treatments, ion chambers attached to the head of the machine provided dosimetric data for each field. Data from sensors connected to every set-up parameter (for example, couch positions, gantry angle, collimator leaf positions, etc.) were recorded and verified by an external computer. RESULTS: While preliminary tests indicated an interlock rate of 5%, final reliability test results demonstrated an interlock fault rate of approximately 0.5%. The reproducibility of dosimetric data and geometric setup parameters was within specifications. As an example, leaf position reproducibility in the patient plane was within 0.5 mm for 97% of the setups. The times required to carry out treatments were recorded and compared with the times to carry out identical treatments on a conventional linear accelerator with cerrobend blocks. Areas where additional time savings can be achieved were identified. CONCLUSIONS: As an integral part of acceptance testing, the Scanditronix MM50 was rigorously tested for reliability. The machine successfully passed these tests, providing increased confidence in its usefulness for routine 3D conformal therapy.

Humans↗
PubMed1994

Quantifying the effect of dose inhomogeneity in brachytherapy: application to permanent prostatic implant with 125I seeds.

PURPOSE: To quantitate the influence of dose inhomogeneity on brachytherapy efficacy. METHODS AND MATERIALS: A computed tomography-based system of planning, implementation and evaluation was used to generate tumor-specific dose-volume histograms of eight permanent 125I implants of prostate cancers. The radiobiological effect was then assessed, voxel by voxel, in terms of the biologically effective dose and the associated cell inactivation. The overall cell survival of the entire target volume was then computed. To evaluate the influence of inhomogeneity, the dose-volume histogram was modified in an iterative fashion, with the corresponding surviving fraction calculated after each step. Specifically, the volume in the highest dose bin was combined with that in the next bin to give a new frequency distribution from which cell survival was generated. Tumor control probability (TCP) was also used as an endpoint, using the same iterative procedure. RESULTS: Doses 20-30% higher than D99 (the dose that covered 99% of the target volume) contributed to additional cell inactivation, but still higher doses did not further increase cell kill. With homogeneous irradiation at D99 as a reference, we defined the inhomogeneity enhancement factor as the ratio of the biologic effective dose of the actual implant to that of the reference dose distribution. The calculated enhancement factors were inversely dependent on tumor potential doubling time (Tp), about 1.2-1.3 for a Tp of 30 days, and between 1.3 and 1.7 if Tp = 10 days, with higher values for implants with low D99. Dose inhomogeneity enhanced TCP. For implants with high control probabilities does significantly higher (> 20%) than the D99 value did not further enhance the tumor control probabilities. In contrast, for implants with relatively low tumor control and D99 values, the control probability continued to increase with doses significantly higher than D99, up to a dose of 2 x D99. The underlying reasons were the incorporation of patient "population averaging" in the calculation and the saturation of tumor control dose response at about 120 Gy. CONCLUSION: Dose heterogeneity in implants increased tumor cell kill and local control probability, although doses > 20% higher than the prescription dose is wasted. The increase the beneficial effect of dose inhomogeneity may be greatest when most needed.

Brachytherapy↗
PubMed1994

The potential and limitations of the inverse radiotherapy technique.

The objective of the work presented in this paper is to explore the scope of the applicability of the inverse radiotherapy technique for designing optimized intensity distributions to achieve a desired dose distribution. A specified desired uniform dose to the target volume is inverted, subject to constraints on the surrounding normal tissue dose, to produce optimum intensity distributions in a set of beams arranged around the target volume. We employed the inverse technique and software developed by Bortfeld and evaluated results both qualitatively and quantitatively using dose distribution displays, dose-volume histograms and biological indices including tumor control probability and normal tissue complication probabilities. So far we have applied this methodology to prostate and lung treatment plans. For prostate the inverse technique produces satisfactory approximations of the desired dose distributions. However, for lung its performance is considerably inferior. Our investigations point to a number of factors for this difference, the primary ones being differences in the tolerance doses of neighboring normal tissues, magnitudes of volume effect, tissue architectures, and the achievability of the specified desired dose distributions. We conclude that, for certain clinical situations, it is not sufficient to specify the objectives of optimization purely in terms of the desired pattern of the dose. The objectives must also include dose-volume effects and biological indices. Furthermore, the mathematics of optimization must be able to incorporate these factors into the process. We find that the inverse technique is not suitable for situations where dose-volume considerations and biological indices are important and that other methods of optimization of intensity distributions should be explored.

Adenocarcinoma↗