Biomedical subjects

Kenneth Forster

Publications and source records attributed to Kenneth Forster.

13 recordsLinked to original sources

PubMed2006

Efficacy of ablative high-dose-per-fraction radiation for implanted human renal cell cancer in a nude mouse model.

OBJECTIVES: Stereotactic body radiation therapy (SBRT) is a new therapeutic paradigm that uses a very large dose per fraction treatments (ablative hypofractionation). We investigated the use of ablative hypofractionation in treating human renal cell carcinoma using a nude mouse model. METHODS: Nude mice were injected subcutaneously with A498 human renal carcinoma cells. Tumour-bearing animals were radiated with three fractions (one per week) for a total dose of 48 Gy (n = 12), while untreated animals served as controls (n = 7). The mice were weighed, and tumour volumes were measured at baseline and weekly until 7 weeks post-treatment. RESULTS: Control animals demonstrated progressive tumour growth and were sacrificed because of either tumour size or ulceration. Tumours in the treatment group grew to three times their initial size over the 3 weeks of treatment but subsequently decreased progressively to less than 30% of their initial volume. All treated tumours exhibited marked cytologic changes. Tumours from mice sacrificed before post-treatment week 4 had a mitotic count of 1-4/10 hpf. Tumours from mice sacrificed more than 4 weeks post-treatment (n = 4) demonstrated no mitoses. CONCLUSIONS: Treatment with high-dose-per-fraction radiation to 48 Gy resulted in a sustained decrease in tumour volume and marked cytologic changes. These results are preliminary--but promising--and encourage further research into this application of ablative hypofractionated radiation for kidney cancer.

Animals↗

PubMed2006

Efficacy of high dose per fraction radiation for implanted human prostate cancer in a nude mouse model.

PURPOSE: SBRT is a new therapeutic paradigm using large dose per fraction treatments (aggressive hypofractionation). While SBRT has shown efficacy for treating patients with lung, liver and spine tumors, to our knowledge there have been no preclinical studies evaluating the efficacy of this treatment for prostate cancer. We investigated the dose-response characteristics of SBRT for treating human prostate cancer in a nude mouse model. MATERIALS AND METHODS: Nude mice were injected subcutaneously into the right flank with C4-2 prostate cancer cells grown in culture. A dose escalation trial was performed to assess toxicity and response. Tumor bearing animals were radiated with 3 fractions (1 per week) for a total dose of 15 Gy in 11, 22.5 Gy in 9 and 45 Gy in 10, while 8 untreated animals served as controls. The mice were weighed, and tumor volume and PSA measurements were performed at baseline and weekly until 4 weeks after treatment. RESULTS: There was no treatment related toxicity. There was a significant difference in the tumor response to higher radiation doses. In the 15 and 22.5 Gy groups mean tumor volume decreased to 58% and 90% of the original volume, respectively, but the rats experienced progressive tumor regrowth within 1 week after the completion of therapy. The 45 Gy group had a mean tumor volume and PSA decrease of greater than 90%, which was sustained 1 month after treatment in all except 2 mice. CONCLUSIONS: SBRT dose level treatments were able to significantly decrease tumor volume and PSA. However, using 15 and 22.5 Gy durable responses were not achieved except in a few mice. The 45 Gy group demonstrated sustained PSA and tumor volume decreases in most mice. These results clearly show an increasing dose-response relationship for a range of hypofractionated dose levels, as used in SBRT.

Animals↗

PubMed2005

Intensity-modulated radiation therapy for mesothelioma: impact of multileaf collimator leaf width and pencil beam size on planning quality and delivery efficiency.

PURPOSE: To compare treatment plans for multileaf collimators (MLCs) with different leaf widths and different finite pencil beam (FPB) sizes, to determine the planning quality and delivery efficiency of segmented MLC (SMLC) delivery of intensity-modulated radiation therapy (IMRT) for malignant pleural mesothelioma (MPM). METHODS AND MATERIALS: Computerized tomography images of 10 right-side MPM patients were used for this planning study on a CORVUS treatment-planning system (NOMOS Corporation, Sewickley, PA) for a Varian Millennium 120-MLC (Varian Medical Systems, Palo Alto, CA). Three beam models were used. The first model forced two 0.5-cm MLC leaves to move in tandem to simulate a 1-cm leaf-width MLC and a FPB size of 1 x 1 cm2. The second model used 0.5-cm leaves with a FPB size of 0.5 x 1 cm2 (1 cm in the direction of leaf movement). The third model used 0.5-cm leaves, with a FPB size of 0.5 x 0.5 cm2. For optimization, the same dose constraints and beam parameters were used for each data set. Tissue heterogeneity corrections were used during optimization and dose calculation. Plans were optimized such that the clinical target volume received 50 Gy in 25 fractions. Dose distributions to the target and normal structures were evaluated. The number of monitor units, the number of segments, and delivery times were used to evaluate delivery efficiency. RESULTS: All three beam models could be used for IMRT planning for MPM. The doses to clinical target volume, spinal cord, lung, liver, heart, and contralateral kidney were acceptable with all three beam models. The 0.5 x 0.5-cm2 beam model used the most monitor units (6883 +/- 974 vs. 3332 +/- 406 and 3407 +/- 443 for the 1 x 1-cm2 and 0.5 x 1-cm2 models, respectively) and treated the most segments (4297 +/- 802 vs. 1357 +/- 156 and 1767 +/- 212 for the 1 x 1-cm2 and 0.5 x 1-cm2 models, respectively). The plan generated with the 1 x 1-cm2 model required the least amount of time to deliver. CONCLUSIONS: The quality of the MPM IMRT plans generated with the three beam models presented here was similar; however, the 1 x 1-cm2 model provided the most efficient delivery of MPM IMRT with the CORVUS planning system.

Aged↗

PubMed2005

[18F]fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non-small-cell lung cancer.

PURPOSE: To determine whether the standardized uptake value (SUV) of [(18)F]fluorodeoxyglucose uptake by positron emission tomography could be a prognostic factor for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred sixty-two patients with stage I to IIIb NSCLC were analyzed. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional control (LRC) were calculated by the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed by univariate and multivariate analyses. RESULTS: There were 93 patients treated with surgery and 69 patients treated with radiotherapy. A cutoff of 5 for the SUV for the primary tumor showed the best discriminative value. The SUV for the primary tumor was a significant predictor of OS (P = .02) in both groups. Low SUVs (</= 5.0) showed significantly better DFS rates than those with high SUVs (> 5.0; surgery group, P = .02; radiotherapy group, P = .0005). Low SUVs (</= 5.0) indicated a significantly better DFS than those with high SUVs (> 5.0; stage I or II, P = .02; stage IIIa or IIIb, P = .004). However, using the same cutoff point of 5, the SUV for regional lymph nodes was not a significant indicator for DFS (P = .19), LRC (P = .97), or DMFS (P = .17). The multivariate analysis showed that the SUV for the primary tumor was a significant prognostic factor for OS (P = .03) and DFS (P = .001). CONCLUSION: The SUV of the primary tumor was the strongest prognostic factor among the patients treated by curative surgery or radiotherapy.

Adult↗

PubMed2005

Treatment planning system evaluation for mesothelioma IMRT.

BACKGROUND AND PURPOSE: Malignant pleural mesothelioma (MPM) has been treated with extrapleural pneumonectomy (EPP) followed by IMRT. IMRT improved radiation dose distributions to the complex operative bed, and preliminary results suggested improved local control compared with conventional treatment planning. IMRT was initially developed on the Corvus treatment planning system. Other treatment planning systems are also IMRT-capable. Treatment plans from several systems were compared to determine the feasibility of using IMRT in a multi-institution trial. PATIENTS AND METHODS: Treatment plans were generated on Corvus, Eclipse, and Pinnacle for a right-sided MPM after EPP using 6 MV X-rays. Tissue heterogeneity corrections were used in dose calculation. Plans were optimized such that the clinical target volume received 50 Gy in 25 fractions. Dose distributions to the target and normal structures were evaluated. The treatment time and delivery efficiency were estimated. RESULTS: Treatment plans could be calculated by all three planning systems without system failure. Larger volumes received 60Gy in Corvus plans (40%, 17% and 8% for Corvus, Pinnacle and Eclipse, respectively). Corvus used the most monitor units (2786 versus 1451 and 1813 for Pinnacle and Eclipse), and treated the most segments (1050 versus 267 and 173 for Pinnacle and Eclipse). Doses to spinal cord, lung, heart, liver, and contralateral kidney were acceptable for all planning systems. CONCLUSIONS: IMRT plans can be calculated for MPM targets by at least three commonly available treatment planning systems. Pinnacle- and Eclipse-based plans seem more efficient, and may be delivered in a shorter time than Corvus-based plans.

Aged↗

PubMed2005

Elastic image mapping for 4-D dose estimation in thoracic radiotherapy.

PURPOSE: Demonstrate the path integration of a four-dimensional (4-D) dose distribution onto the 3-D anatomy. MATERIALS AND METHODS: A computer-generated 4-D thoracic phantom with a lung tumour was constructed. Eight respiratory phases were generated. A radiotherapy treatment plan was applied to all the phases resulting in a 4-D dose distribution. An elastic image registration algorithm was used to find the vector displacement between all the image elements and the end expiration phase. The path-integrated tissue dose distribution and each component dose distribution were compared with the planned dose distribution. RESULTS: Numerical path integration was performed to calculate the tissue dose distribution. Loss of tumour coverage was the predominant effect observed with tumour motion in this study. The loss was asymmetric and dependent on the tumour trajectory. CONCLUSION: The elastic image registration allowed an accurate path integration through a 4-D data set to produce an accurate 3-D tissue dose estimate.

Artifacts↗

PubMed2004

Evaluation of internal lung motion for respiratory-gated radiotherapy using MRI: Part II-margin reduction of internal target volume.

PURPOSE: To analyze the relationship between lung motion and skin surface motion during respiration, determine the uncertainties and variability of such a relationship, and assess the potential of reducing internal target margin for gated radiotherapy. METHODS AND MATERIALS: Three healthy volunteers and four lung cancer patients were recruited in a prospective imaging study using MRI to track the internal lung and external skin motion during breathing. The relationship between the lung and skin motion was modeled using linear regression analysis. The slope of the linear fit and its confidence interval were analyzed for different lung locations, skin surface locations, and breathing patterns from separate imaging sessions. The margins of the internal target volume were calculated based on the residual lung motion during gating and its uncertainties from multiple treatment fractions for the gated treatment. RESULTS: The slope and confidence interval of the linear regression from the motion analysis were uniquely defined by the locations of the lung, skin surface, and breathing patterns. Statistically significant differences were observed among individuals and between different times of measurement. The normal free-breathing motion averaged from all volunteer and patient data was 13.4 +/- 7.4 mm along the superior-inferior (SI) direction and 6.9 +/- 2.6 mm along the anterior-posterior (AP) direction. With simulated respiratory gating, the average margin reduction was 5.5 +/- 4.8 mm and 1.6 +/- 1.0 mm, respectively, along the SI and AP directions (or 36% +/- 15% and 25% +/- 14%, respectively, relative to free-breathing motion). CONCLUSION: Because respiratory movement is rather complex, the relationship between the lung and skin surface motion is affected by many anatomic and physiologic factors. The reduction of internal target margin and efficacy of the free-breathing gating technique should be assessed for individual cases.

Adult↗

PubMed2004

Evaluation of internal lung motion for respiratory-gated radiotherapy using MRI: Part I--correlating internal lung motion with skin fiducial motion.

PURPOSE: To measure the internal lung motion due to respiration using magnetic resonance images (MRIs); to evaluate the correlation between lung motion and skin surface motion and the reliability of tracking lung motion with external fiducials. METHODS AND MATERIALS: An MRI protocol using fast gradient-echo sequences was developed to acquire dynamic cine images of the thoracoabdominal region along the axial, sagittal, and coronal planes. The subjects (3 healthy volunteers and 4 lung cancer patients) were instructed to perform normal or altered breathing during MRI. Lung vessels identified on MRI were used as anatomic landmarks for internal lung structures. From sagittal cine MRI scans, the positions of the lung vessels and skin surface were tracked and their movements measured. Correlation between the movements of the external markers and internal structures was then calculated and analyzed. RESULTS: Lung vessel motion in the superior-inferior (SI) direction correlated best with mid-upper abdominal skin surface movement (correlation coefficient, 0.89 +/- 0.09 and 0.87 +/- 0.23 for volunteers and patients, respectively). The anterior-posterior (AP) vessel motion generally correlated poorly with the skin surface movement, with marker placement on the upper chest yielding the strongest results (correlation coefficient, 0.72 +/- 0.23 and 0.44 +/- 0.27 for volunteers and patients, respectively). The strength of the correlation depended on the locations of the tracked vessels, locations of the skin surface, and subjects' breathing patterns. The best correlation was seen between the motion of an abdominal fiducial and SI lung motion. Significant intersubject variability was also observed. CONCLUSION: Movement of an external fiducial may not correlate fully with, or predict, internal lung motion. Effective monitoring of respiration may have to rely on a combination of multiple fiducials and other physiologic parameters, such as lung volume and/or air flow.

Adult↗

PubMed2004

Heterogeneous planning for homogeneous protocols.

Clinical trials often require homogeneous treatment plans. Many institutions, however, have begun using heterogeneous plans. Is it possible to satisfy the requirements of such a protocol while achieving the superior accuracy of heterogeneous treatment planning? At the University of Texas M. D. Anderson Cancer Center, we currently use conformal treatment planning with heterogeneities for thoracic cancers. This paper describes a procedure that has been developed to satisfy the requirements of a homogeneous protocol, such as RTOG 98-01 (A Phase III Study of Amifostine mucosal protection), while maintaining accuracy in treatment planning.

Amifostine↗

PubMed2003

Patient-specific point dose measurement for IMRT monitor unit verification.

PURPOSE: To review intensity-modulated radiation therapy (IMRT) monitor unit verification in a phantom for 751 clinical cases. METHODS AND MATERIALS: A custom water-filled phantom was used to measure the integral dose with an ion chamber for patient-specific quality assurance. The Corvus IMRT planning system was used for all cases reviewed. The 751 clinical cases were classified into 9 treatment sites: central nervous system (27 cases), gastrointestinal (24 cases), genitourinary (447 cases), gynecologic (18 cases), head and neck (200 cases), hematology (12 cases), pediatric (3 cases), sarcoma (8 cases), and thoracic (12 cases). Between December 1998 and January 2002, 1591 measurements were made for these 751 IMRT quality assurance plans. RESULTS: The mean difference (MD) in percent between the measurements and the calculations was +0.37% (with the measurement being slightly higher). The standard deviation (SD) was 1.7%, and the range of error was from -4.5% to 9.5%. The MD and SD were +0.49% and 1.4% for MIMiC treatments delivered in 2-cm mode (261 cases) and -0.33% and 2.7% for those delivered in 1-cm mode (36 cases). Most treatments (420) were delivered using the step-and-shoot multileaf collimator with a 6-MV photon beam; the MD and SD were +0.31% and 1.8%, respectively. Among the 9 treatment sites, the prostate IMRT (in genitourinary site) was most consistent with the smallest SD (1.5%). There were 23 cases (3.1% of all cases) in which the measurement difference was greater than 3.5%; of those, 6 cases used the MIMiC in 1-cm mode, and 14 of the cases were from the head-and-neck treatment site. CONCLUSION: IMRT monitor unit calculations from the Corvus planning system agreed within 3.5% with the point-dose ion chamber measurement in 97% of 751 cases representing 9 different treatment sites. A good consistency was observed across sites.

Algorithms↗

PubMed2002

Masked word repetition results in increased fMRI signal: a framework for understanding signal changes in priming.

Evidence from multiple paradigms has converged on the finding that stimulus repetition most often results in decreases in neural activity. The mechanisms of these decreases, however, are not yet well understood. The current study attempted to determine, through the use of masked word repetition priming, whether decreases in activity levels occur in response to pre- or post-prime identification processes. fMRI was performed while participants engaged in a lexical decision task where words were primed with a briefly presented and masked word. Masked word priming resulted in increased fMRI signal in regions of cortex associated with the perceptual identification of the target words. This finding provides evidence suggesting that the impact of repetition priming on the fMRI signal may depend upon whether or not the prime is identified.

Adolescent↗

PubMedDate not supplied

Uncertainties in physical and biological targeting with radiation therapy.

Advances in radiation therapy over the past decade have resulted from increased accuracy of imaging and highly conformal three dimensional treatment planning and delivery of radiation therapy. Three-dimensional conformal radiation therapy (3D CRT) with higher doses than previously considered tolerable is now standard for many types of cancer. Intensity modulated radiation therapy (IMRT) with x-rays, proton beam treatments and intensity modulated proton therapy (IMPT) are major areas of research. Tumor motion between and even during radiation treatments represents a major uncertainty. Tumor heterogeneity results in additional uncertainties affecting tumor control with radiation therapy. Imaging the heterogeneous targets within tumors offers new opportunities for tumor delineation. Molecular therapeutic agents enhance the effects of ionizing radiations in murine systems. Clinical trials combining molecular targeting agents with conformal radiation therapy are being initiated.

Animals↗

PubMedDate not supplied

Target definition and contouring in carcinoma of the lung and esophagus.

The optimal treatment for intrathoracic tumors such as lung and esophageal cancer requires an improvement of therapeutic ratio to increase efficacy of the cancer-cell kill and decrease the normal-cell kill. This is not an easy task because sensitive normal cells such as alveoli and epithelial cells in the esophagus and bronchus surround these tumors. How to minimize the damage of such sensitive normal cells within irradiated fields without sparing cancer cells is a major issue for radiation oncologists, especially as concurrent chemoradiotherapy has become more standard treatment. One way to achieve this task is accurate delineation of the target volume, which will be emphasized here. Some other ways to achieve it are biological protection by ethyol, keratinocyte growth factors, biologically targeted treatments such as C225 and celecoxib, and anti-angiogenesis, which have been briefly addressed in Dr. Cox's article in this Journal. Molecular imaging is a new diagnostic and therapeutic modality that offers great potential for accuracy of target definition, although it is not quite ready for routine clinical use at the present time. Accurate target definition and contouring in cases of carcinoma of the lung and esophagus depend on expertise of diagnostic and therapeutic medical teams. There we review the normal anatomy, diagnostic methods, and tumor delineation of cancer of the lung and esophagus.

Carcinoma, Non-Small-Cell Lung↗