Search PubMed⌕ Search

Biomedical subjects

Jack Fowler

Publications and source records attributed to Jack Fowler.

10 recordsLinked to original sources
PubMed2006

Accreditation and quality assurance for Radiation Therapy Oncology Group: Multicenter clinical trials using Stereotactic Body Radiation Therapy in lung cancer.

Starting in 2002, the Radiation Therapy Oncology Group in North America began the process of developing multicenter prospective trials in lung cancer using Stereotactic Body Radiation Therapy (SBRT). Much of the work was based on the prospective single institution trials from Indiana University that had been presented and published. In late 2004, RTOG 0236 using SBRT for medically inoperable patients with clinical stage I non-small cell lung cancer (NSCLC) was activated for accrual. Prior to activation, representatives from the Lung, Image-Guided Therapy, Physics, and Radiobiology Committees met on regular occasions to design the multicenter study and quality assurance measures. SBRT is not a black box, and the essence of the therapy had to be distilled via guidelines. Issues related to patient selection, method of dosimetry construction, equipment requirements, motion assessments and control, site accreditation, data exchange, and follow-up policies were worked out by compromise and consensus. RTOG 0236 has nearly completed its accrual. The Lung Committee has initiated the development of several other trials, each building on the last, to investigate the therapy in central tumors, in combinations with systemic therapy, in operable patients, and in lung metastases patients. The guidelines developed for RTOG 0236 will be refined to take advantage of more modern innovations including heterogeneity corrections and intensity modulation when appropriate. The development of RTOG 0618 using SBRT in operable patients with early stage NSCLC is a testament to both the enthusiasm from already published works and prospective multicenter clinical testing using SBRT techniques.

Accreditation↗
PubMed2006

Clinical implementation of adaptive helical tomotherapy: a unique approach to image-guided intensity modulated radiotherapy.

Image-guided IMRT is a revolutionary concept whose clinical implementation is rapidly evolving. Methods of executing beam intensity modulation have included individually designed compensators, static multi-leaf collimators (MLC), dynamic MLC, and sequential (serial) tomotherapy. We have developed helical tomotherapy as an innovative solution to overcome some of the limitations of other IMRT systems. The unique physical design of helical tomotherapy allows the realization of the concepts of adaptive radiotherapy and conformal avoidance. In principle, these advances should improve normal tissue sparing and permit dose reconstruction and verification, thereby allowing significant biologically effective dose escalation. Recent radiobiological findings can be translated into altered fractionation schemes that aim to improve the local control and long-term survival. This strategy is being tested at the University of Wisconsin using helical tomotherapy with its highly precise delivery and verification system along with meticulous and practical forms of immobilization. Innovative techniques such optical guidance, respiratory gating, and ultrasound assessments are being designed and tailored for helical tomotherapy use. The intrinsic capability of helical tomotherapy for megavoltage CT (MVCT) imaging for IMRT image-guidance is being optimized. The unique features of helical tomotherapy might allow implementation of image-guided IMRT that was previously impossible or impractical. Here we review the technological, physical, and radiobiological rationale for the ongoing and upcoming clinical trials that will use image-guided IMRT in the form of helical tomotherapy; and we describe our plans for testing our hypotheses in a rigorous prospective fashion.

Humans↗
PubMed2005

Feasibility study of helical tomotherapy for total body or total marrow irradiation.

Total body radiation (TBI) has been used for many years as a preconditioning agent before bone marrow transplantation. Many side effects still plague its use. We investigated the planning and delivery of total body irradiation (TBI) and selective total marrow irradiation (TMI) and a reduced radiation dose to sensitive structures using image-guided helical tomotherapy. To assess the feasibility of using helical tomotherapy, (A) we studied variations in pitch, field width, and modulation factor on total body and total marrow helical tomotherapy treatments. We varied these parameters to provide a uniform dose along with a treatment times similar to conventional TBI (15-30 min). (B) We also investigated limited (head, chest, and pelvis) megavoltage CT (MVCT) scanning for the dimensional pretreatment setup verification rather than total body MVCT scanning to shorten the overall treatment time per treatment fraction. (C) We placed thermoluminescent detectors (TLDs) inside a Rando phantom to measure the dose at seven anatomical sites, including the lungs. A simulated TBI treatment showed homogeneous dose coverage (+/-10%) to the whole body. Doses to the sensitive organs were reduced by 35%-70% of the target dose. TLD measurements on Rando showed an accurate dose delivery (+/-7%) to the target and critical organs. In the TMI study, the dose was delivered conformally to the bone marrow only. The TBI and TMI treatment delivery time was reduced (by 50%) by increasing the field width from 2.5 to 5.0 cm in the inferior-superior direction. A limited MVCT reduced the target localization time 60% compared to whole body MVCT. MVCT image-guided helical tomotherapy offers a novel method to deliver a precise, homogeneous radiation dose to the whole body target while reducing the dose significantly to all critical organs. A judicious selection of pitch, modulation factor, and field size is required to produce a homogeneous dose distribution along with an acceptable treatment time. In addition, conformal radiation to the bone marrow appears feasible in an external radiation treatment using image-guided helical tomotherapy.

Bone Marrow↗
PubMed2005

Potential for radiation therapy technology innovations to permit dose escalation for non-small-cell lung cancer.

BACKGROUND: Innovations in radiation therapy (RT) technology could have the potential to allow for radiation dose escalation by evaluating tumor motion, minimizing and compensating for motion, and evaluating delivery technologies such as 3-dimensional (3D) conformal radiation therapy (CRT) and intensity-modulated RT (IMRT) using tomotherapy. MATERIALS AND METHODS: Ninety different RT plans were generated using 3 different treatment techniques for 10 patients. These were evaluated using dosimetric tools such as dose-volume histogram (DVH) analysis, tumor equivalent uniform dose (EUD), and dosimetric parameters predictive for lung toxicity, such as the volume of lung receiving > 20 Gy of radiation (V20) and the normalized mean total radiation dose to the lung (NTDmean). The 3 techniques studied included free breathing using 3D CRT, 3D CRT with maximum-inspiration breath-hold (MIBH) to minimize tumor motion, and IMRT delivery with MIBH; the combination of 3 separate planning treatment-volume sets resulted in the generation of 90 different treatment plans. To plan these, patients underwent treatment-planning computed tomography in MIBH and free breathing followed by simulation with measurement of tumor motion and generation/evaluation of DVHs, EUDs, V20, and NTDmean. RESULTS: Average tumor motion was 1.54 cm in the cephalocaudad directions, 1.26 cm in the anteroposterior directions, and 0.56 cm in the lateral directions between maximum inspiration and expiration. Maximum-inspiration breath-hold produced superior lung sparing evidenced by lower V20 and NTDmean values, and these parameters predicted lower modeled pneumonitis rates. Tomotherapy-based IMRT provided further lung sparing. CONCLUSION: Treatment in MIBH results in lower V20 and NTDmean values and lower modeled pneumonitis rates. This effect is enhanced by the use of IMRT. The use of MIBH with IMRT may therefore aid in escalating the dose in RT.

Adenocarcinoma↗
PubMed2003

Image guidance for precise conformal radiotherapy.

PURPOSE: To review the state of the art in image-guided precision conformal radiotherapy and to describe how helical tomotherapy compares with the image-guided practices being developed for conventional radiotherapy. MATERIALS AND METHODS: Image guidance is beginning to be the fundamental basis for radiotherapy planning, delivery, and verification. Radiotherapy planning requires more precision in the extension and localization of disease. When greater precision is not possible, conformal avoidance methodology may be indicated whereby the margin of disease extension is generous, except where sensitive normal tissues exist. Radiotherapy delivery requires better precision in the definition of treatment volume, on a daily basis if necessary. Helical tomotherapy has been designed to use CT imaging technology to plan, deliver, and verify that the delivery has been carried out as planned. The image-guided processes of helical tomotherapy that enable this goal are described. RESULTS: Examples of the results of helical tomotherapy processes for image-guided intensity-modulated radiotherapy are presented. These processes include megavoltage CT acquisition, automated segmentation of CT images, dose reconstruction using the CT image set, deformable registration of CT images, and reoptimization. CONCLUSIONS: Image-guided precision conformal radiotherapy can be used as a tool to treat the tumor yet spare critical structures. Helical tomotherapy has been designed from the ground up as an integrated image-guided intensity-modulated radiotherapy system and allows new verification processes based on megavoltage CT images to be implemented.

Animals↗
PubMed2002

How fast is repopulation of tumor cells during the treatment gap?

PURPOSE/OBJECTIVE: Our goal was to analyze the repopulation of surviving tumor cells during a treatment gap in radiotherapy for head-and-neck cancer. METHODS AND MATERIALS: Clinical material is based on the records of 1502 patients treated by radiotherapy alone in Maria Sklodowska-Curie Memorial Institute in Gliwice during the period between1980 and 1989. All patients had histologically confirmed squamous cell carcinoma of the larynx or pharynx. The mean gap duration was 9 days. Only 10% of patients were treated without gaps. The dose per fraction was in the range of 1.5 to 2.5 Gy. Patient data were fitted directly to the mixed linear-quadratic model using maximum-likelihood estimation. Tumor stage or tumor localization was introduced into the equation as a categorical variable. Tumor proliferation was estimated by dividing the treatment gaps into three groups: the first 2 weeks, second 2 weeks, and the period after 4 weeks of irradiation. RESULTS: Tumor control probability was significantly correlated with radiation dose, tumor progression (according to TNM), overall treatment time, and gap duration. Laryngeal cancers had a better prognosis than cancers of the oro- and nasopharynx. Significant tumor repopulation was found after the first 2 weeks of radiotherapy. During the treatment gap, the proliferation rate was equal to 0.75 Gy/day. During the days with irradiation, repopulation was slower and equal to 0.2 Gy/day. CONCLUSION: The repopulation of tumor cells is faster during a gap than during the normal days of irradiation. Accelerated repopulation probably starts soon after 2 weeks of irradiation.

Cell Division↗
PubMed2002

An experimental evaluation of three preoperative radiation regimens for resectable rectal cancer.

BACKGROUND: We investigated the degree of tumor cell killing after radiotherapy regimens commonly used in clinical practice in comparison with an accelerated schedule. METHODS: Mtln3 mammary adenocarcinoma tumor cells were inoculated subcutaneously in the hind leg of syngeneic Fischer 344 rats. Tumors were irradiated with 5 x 5 Gy in 5 days, 10 x 3 Gy over 10 days, or 5 x (2 x 3) Gy in 5 days. After excision of the irradiated tumors, the dye exclusion, a tetrazolium-based colorimetric and the clonogenic assays were used to determine tumor cell viability and surviving fractions. RESULTS: Estimated potential doubling time values indicate a rapid proliferation capacity, comparable with potential doubling time values in human rectal cancer. The dye exclusion and clonogenic assays revealed a significantly higher degree of cell killing after the hypofractionated and the accelerated regimens of, respectively, 5 x 5 Gy and 5 x (2 x 3) Gy over 5 days compared with 10 x 3 Gy over 10 days. CONCLUSIONS: A shorter treatment time offered the best therapeutic efficacy. The schedule involving two daily fractions of 3 Gy over 5 days should be less toxic than 5 x 5 Gy and may therefore provide a therapeutic advantage.

Adenocarcinoma↗