Principal component, Varimax rotation and cost analysis of volume effects in rectal bleeding in patients treated with 3D-CRT for prostate cancer.

We investigate the utility of principal component analysis as a tool for obtaining dose-volume combinations related to rectal bleeding after radiotherapy for prostate cancer. A direct implementation of principal component analysis reduces the number of degrees of freedom from the patient's dose-volume histograms that are associated with bleeding. However, when low-variance principal components are strongly correlated to outcome, their interpretation is problematic.

Intensity-modulated radiation treatment for head-and-neck squamous cell carcinoma--the University of Iowa experience.

Purpose: To review the University of Iowa experience with intensity-modulated radiotherapy (IMRT) in the treatment of head-and-neck squamous cell carcinoma.

Methods And Materials: From October 1999 to April 2004, 151 patients with head-and-neck squamous cell carcinoma were treated with IMRT for curative intent. One patient was lost to follow-up 2 months after treatment and therefore excluded from analysis.

Value of FDG PET in assessment of treatment response and surveillance in head-and-neck cancer patients after intensity modulated radiation treatment: a preliminary report.

Purpose: [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging has been shown to be valuable in early detection of persistent and recurrent head-and-neck cancer after treatment. Previous studies have reported its use in patients treated with conventional radiation. Many patients are now treated with intensity-modulated radiation treatment (IMRT).

The role of post-radiation therapy FDG PET in prediction of necessity for post-radiation therapy neck dissection in locally advanced head-and-neck squamous cell carcinoma.

Purpose: The role of neck dissection after radiation therapy ([RT] with or without chemotherapy) for regionally advanced head and neck cancer is controversial. As much as 50% of residual lymphadenopathy after radiation has no viable tumor cells present on histopathologic analysis. [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging can detect metabolically active cancer.

Does prone positioning reduce small bowel dose in pelvic radiation with intensity-modulated radiotherapy for gynecologic cancer?

Purpose: Intensity-modulated radiotherapy (IMRT) has been shown to reduce the radiation dose to small bowel in pelvic RT in gynecology patients. Prone positioning has also been used to decrease small bowel dose by displacement of small bowel from the RT field in these patients. The purpose of this study was to determine whether the combination of both IMRT and prone positioning on a belly board can reduce small bowel dose further in gynecologic cancer patients undergoing pelvic RT.

Disruption of DAG1 in differentiated skeletal muscle reveals a role for dystroglycan in muscle regeneration.

Striated muscle-specific disruption of the dystroglycan (DAG1) gene results in loss of the dystrophin-glycoprotein complex in differentiated muscle and a remarkably mild muscular dystrophy with hypertrophy and without tissue fibrosis. We find that satellite cells, expressing dystroglycan, support continued efficient regeneration of skeletal muscle along with transient expression of dystroglycan in regenerating muscle fibers. We demonstrate a similar phenomenon of reexpression of functional dystroglycan in regenerating muscle fibers in a mild form of human muscular dystrophy caused by disruption of posttranslational dystroglycan processing.

Intensity-modulated radiation therapy in the treatment of children.

Intensity-modulated radiation therapy (IMRT) is a relatively new method of conformal radiotherapy delivery that is rapidly being incorporated in clinical practice. Of all patients treated with conformal techniques, children are the most likely to benefit as normal, developing structures can be minimized in the radiation field. The advantages of IMRT, including increased conformality and possible dose escalation, are discussed in this review.

Risk group dependence of dose-response for biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer.

Background And Purpose: We fit phenomenological tumor control probability (TCP) models to biopsy outcome after three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer patients to quantify the local dose-response of prostate cancer.

Materials And Methods: We analyzed the outcome after photon beam 3D-CRT of 103 patients with stage T1c-T3 prostate cancer treated at Memorial Sloan-Kettering Cancer Center (MSKCC) (prescribed target doses between 64.8 and 81Gy) who had a prostate biopsy performed >or=2.

In vivo determination of extra-target doses received from serial tomotherapy.

Background And Purpose: The purpose of this study was to perform in-vivo measurements of extracranial doses received by patients undergoing serial tomotherapy of the head and neck.

Material And Methods: Intensity modulated radiotherapy treatment (IMRT) plans were designed for nine patients using the CORVUS treatment planning system (NOMOS Corp.).

Fitting tumor control probability models to biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer: pitfalls in deducing radiobiologic parameters for tumors from clinical data.

Purpose: The goal of tumor control probability (TCP) models is to predict local control for inhomogeneous dose distributions. All existing fits of TCP models to clinical data have utilized summaries of dose distributions (e.g.

Late rectal bleeding after conformal radiotherapy of prostate cancer. II. Volume effects and dose-volume histograms.

Purpose And Objective: Late rectal bleeding is a potentially dose limiting complication of three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. The frequency of late rectal bleeding has been shown to increase as the prescription dose rises above 70 Gy. The purpose of this study is to identify features of the cumulative dose-volume histogram (DVH) for the rectal wall that correlate with late rectal bleeding after 3D-CRT for prostate cancer.

Analysis of biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer using dose-distribution variables and tumor control probability models.

Purpose: To investigate tumor control following three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer and to identify dose-distribution variables that correlate with local control assessed through posttreatment prostate biopsies.

Methods And Material: Data from 132 patients, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), who had a prostate biopsy 2.5 years or more after 3D-CRT for T1c-T3 prostate cancer with prescription doses of 64.

Clinical experience with intensity modulated radiation therapy (IMRT) in prostate cancer.

Purpose: To compare acute and late toxicities of high-dose radiation for prostate cancer delivered by either conventional three-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT).

Materials And Methods: Between September 1992 and February 1998, 61 patients with clinical stage T1c- T3 prostate cancer were treated with 3D-CRT and 171 with IMRT to a prescribed dose of 81 Gy. To quantitatively evaluate the differences between conventional 3D-CRT and IMRT, 20 randomly selected patients were planned concomitantly by both techniques and the resulting treatment plans were compared.

Late rectal toxicity after conformal radiotherapy of prostate cancer (I): multivariate analysis and dose-response.

Purpose: The purpose of this paper is to use the outcome of a dose escalation protocol for three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer to study the dose-response for late rectal toxicity and to identify anatomic, dosimetric, and clinical factors that correlate with late rectal bleeding in multivariate analysis.

Methods And Materials: Seven hundred forty-three patients with T1c-T3 prostate cancer were treated with 3D-CRT with prescribed doses of 64.8 to 81.

Changes in histology and fibrogenic cytokines in irradiated colorectum of two murine strains.

Purpose: A strain difference in the development of radiation-induced fibrosis of the colorectum was recently observed. C57B1/6 mice developed colorectal obstruction with significantly higher incidence compared to C3Hf/Kam mice after partial volume irradiation with 30 Gy. Previous reports have demonstrated differences in cytokine mRNA levels in fibrosis-prone and -resistant mice after lung irradiation.

Murine strain differences in the volume effect and incidence of radiation-induced colorectal obstruction.

Purpose: Interindividual variation in the level of normal tissue damage after radiotherapy has been clinically observed. Murine models have suggested that there may be a genetic component to the variation in susceptibility of different radiation-induced normal tissue complications. Currently, there are no experimental data available describing interstrain differences in the "volume effect" for irradiated normal tissues, such as the colorectum.

Volume effects and epithelial regeneration in irradiated mouse colorectum.

The use of three-dimensional treatment planning and volume-reduction techniques in radiotherapy has prompted the development of a number of mathematical models to describe the effect of changing treatment volume on the probability of associated complications in normal tissues. However, limited data are available to test or support these models. One prediction of the Probability model and analogous models, which describe the volume-effect relationship for late end points in tissues with a series-type arrangement of functional subunits, is that there is no threshold volume in the development of the end point.

High dose rate (HDR) and low dose rate (LDR) interstitial irradiation (IRT) of the rat spinal cord.

Purpose: To describe a newly developed technique to study radiation tolerance of rat spinal cord to continuous interstitial irradiation (IRT) at different dose rates.

Material And Methods: Two parallel catheters are inserted just laterally on each side of the vertebral bodies from the level of Th10 to L4. These catheters are afterloaded with two 192Ir wires of 4 cm length each (activity 1-2.

Substructure in the radiation survival response at low dose in cells of human tumor cell lines.

In earlier studies using asynchronously growing Chinese hamster cells, we observed substructure in the survival response at low doses. The substructure appeared to result from subpopulations of cells having different, cell cycle phase-dependent radiosensitivity. We have now applied the same flow cytometry and cell sorting technique to accurately measure the responses of cells of eight different asynchronously growing human tumor cell lines, representing a wide range in radiosensitivity.

The use of radiochromic film to measure dose distributions resulting from high dose rate 192Iridium single catheter treatments.

Purpose: Radiochromic film was used to measure and compare the dose distributions parallel to a high dose rate (HDR) 192Iridium (192Ir) brachytherapy afterloading catheter that resulted from optimized treatment plans using various combinations of prescribed dose magnitude and location as well as source spacing.

Methods And Materials: Differences exist among clinical investigators for specification of the magnitude and location of prescribed treatment dose for brachytherapy irradiations using HDR 192Ir afterloading. Typical prescriptions for endobronchial irradiation include 5 to 10 Gy at 10 mm or 15 Gy at 6 mm measured from the center of the afterloading catheter.

The cytotoxicity of melphalan and its relationship to pH, hypoxia and drug uptake.

In the present in vitro studies we examined the effect of hypoxia and acidic pH, two important consequences of reduced blood flow in vivo, on the cytotoxicity of melphalan treatment in Chinese hamster V79-WNRE and SiHa human tumor cells. Cells were exposed to various concentrations of melphalan for 1 hr at 37 degrees C under oxic or hypoxic conditions; pH 6.6 or 7.

The effect of low pH and hypoxia on the cytotoxic effects of SR4233 and mitomycin C in vitro.

Purpose: We examined the effect of acidic pH and hypoxia on the cytotoxicity of SR4233 and mitomycin C in vitro.

Methods And Materials: The importance of tumor microenvironment to the response of solid tumors to cytotoxic treatment is well established. The bioreductive drug SR4233 has a very substantial selective toxicity for hypoxic cells.

The survival of asynchronous V79 cells at low radiation doses: modeling the response of mixed cell populations.

We have observed that when a single linear-quadratic (LQ) function is used to fit the radiation survival response of an asynchronously dividing population of V79 cells, a consistent misfit occurs at low doses. The data can be better described by fitting the low-dose and high-dose ranges separately, and there is evidence of a two-component response. The most obvious explanation is that we may simply be seeing the response of subpopulations of cells of different radiosensitivity: sensitive G1-, G2- and M-phase cells and resistant S-phase cells.

Substructure in the radiation survival response at low dose: asynchronous and partially synchronized V79-WNRE cells.

The radiation survival response of asynchronously-dividing populations of the cell line V79-WNRE indicates substructure in the low dose region that can be better characterized by separately fitting the data within the low and high dose regions to the linear-quadratic (LQ) equation. Flow cytometry and cell sorting techniques have been used to determine the response of both asynchronous populations and synchronous populations obtained by mitotic selection with or without an additional drug block. The statistically significant substructure which is present in the radiation response of asynchronous cells is absent in G1/S cells synchronized by mitotic selection followed by hydroxyurea (or aphidicolin) accumulation at the G1/S boundary.

The effect of pH on the aerobic and hypoxic cytotoxicity of SR4233 in HT-29 cells.

We have observed that low pH can substantially potentiate the cytotoxic effect of the bioreductive drug SR4233 in aerobic HT-29 human tumour cells. No such potentiation was observed under hypoxic conditions. This pH effect might be relevant both to the therapeutic effectiveness and to the normal tissue toxicity of this new agent.