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A Jackson

Publications and source records attributed to A Jackson.

At least 37 records · Page 2Linked to original sources
PubMed2002

Predictors of outcome of mammography in the National Health Service Breast Screening Programme.

BACKGROUND: Little is known about the factors influencing the risk of recall for assessment, invasive diagnostic procedures, and early rescreening after screening mammography. METHODS: From June 1996 to March 1998 women attending screening at 10 National Health Service Breast Screening Programme (NHSBSP) centres completed a self administered questionnaire and were followed up for their screening outcome. RESULTS: 1969 (3.3%) out of 60 443 women aged 50-64 who had never used hormone replacement therapy (HRT) were recalled for assessment but were not diagnosed with breast cancer (defined here as false positive recall). After adjustment for the variation between centres, false positive recall was decreased significantly among women who were likely to have had a previous NHSBSP mammogram (odds ratio (OR) 0.49, 95% confidence interval (95% CI) 0.38 to 0.63 for likely versus unlikely), who were postmenopausal (OR 0.65, 95% CI 0.56 to 0.76 for postmenopausal v premenopausal) and increased significantly for women reporting previous breast surgery (OR 1.64, 95% CI 1.42 to 1.89). Although false positive recall decreased significantly with parity and increasing body mass index, these effects were not large and no significant variation was found with age, education, family history of breast cancer, oral contraceptive use, sterilisation, exercise, smoking, or alcohol consumption. Altogether 655 (1.1%) women had an invasive diagnostic procedure; no personal characteristics were predictive of this outcome, 286(0.5%) were referred for early rescreening, and this was increased significantly by nulliparity and a family history of breast cancer. INTERPRETATION: Premenopausal women, those without a previous NHSBSP mammogram, and women with previous breast surgery have an increased risk of false positive recall by the NHSBSP.

Age Factors↗
PubMed2002

Human microdialysis.

Microdialysis has been used extensively in animal studies for decades and in human pharmacokinetic studies for about 10 years. Microdialysis is based on the passive diffusion of a compound along its concentration gradient from the tissue through the membrane into the dialysate. Microdialysis samples from the interstitial space which is a defined, anatomical compartment; there is no net loss of body fluid; the sample is "purified" and no enzymatic degradation takes place because proteins do not pass through the probe membrane into the dialysate; microdialysis data relate to the intact molecule; time resolution is high compared to biopsy and skin blister techniques; radioabelling or induction of a magnetic response is not needed; microdialysis is also an alternative method to determine protein binding of a compound in vivo; microdialysis can readily be set up in clinical research units without expensive infrastructure. Microdialysis has been used to measure tissue concentrations of endogenous compounds and to investigate the tissue penetration of drugs in a variety of tissues in humans in vivo in both healthy volunteers and patients. Microdialysis data have also been used in PK-PD modelling and to obtain concentration-response relationships locally in tissues in vivo. There are also studies combining microdialysis with imaging techniques, e.g. PET. Microdialysis data may be used in early studies to select the appropriate compound, to optimise dosing regimens and to investigate the kinetic and dynamic consequences in the tissues of drug-drug and drug-disease interactions. Microdialysis can also be used in late phase studies to provide tissue concentration data in support of therapeutic efficacy trials or to create a niche for an already marketed drug. FDA and CPMP documents emphasise the value and importance of human tissue drug concentration data and support the use of microdialysis in humans to obtain such information. Microdialysis can satisfy regulatory requirements by providing data on drug concentrations in a well-defined anatomical tissue compartment at or close to the effect target site. Microdialysis is a versatile technique because of its multifaceted utility, low cost, ease of use, adaptability to different types of compounds and its feasibility for a number of organs and tissues. Equipment and probes for use in various organs have been commercially available for years.

Animals↗
PubMed2001

Inhibition of lordosis behavior by intrahypothalamic infusion of a protein kinase G antagonist.

Previous experiments demonstrated that intracerebroventricular infusion of the protein kinase G inhibitor KT5823 inhibits lordosis behavior in hormone-treated female rats. Present studies show that KT5823 attenuates lordosis in a dose-dependent manner when infused bilaterally into the ventromedial hypothalamus. Thus, activation of protein kinase G in the ventromedial hypothalamus is necessary for the expression of hormone-dependent lordosis behavior in female rats.

Alkaloids↗
PubMed2001

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., prescription dose). Ideally, model fits should be based on dose distributions in the tumor, but usually only dose-volume histograms (DVH) of the planning target volume (PTV) are available. We fit TCP models to biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer using either a dose distribution summary or the full DVH in the PTV. We discuss differences in the radiobiologic parameters and dose-response curves and demonstrate pitfalls in interpreting the results. METHODS AND MATERIAL: Two mechanistic TCP models were fit with a maximum likelihood technique to biopsy outcome from 103 prostate patients treated at Memorial Sloan-Kettering Cancer Center. Fits were performed separately for different patient subgroups defined by tumor-related prognostic factors. Fits were based both on full DVHs, denoted TCP(DVH(calc)), and, alternatively, assuming a homogeneous PTV dose given by the mean dose (Dmean) of each DVH, denoted TCP(Dmean(calc)). Dose distributions for these patients were very homogeneous with any cold spots located on the periphery of the PTV. These cold spots were uncorrelated with biopsy outcome, likely because the low-dose regions may not contain tumor cells. Therefore, fits of TCP models that are potentially sensitive to cold spots (e.g., TCP(DVH(calc))) likely give biologic parameters that diminish this sensitivity. In light of this, we examined differences in fitted clonogenic cell number, N(C), or density, rho(C), surviving fraction after 2 Gy, SF(2), or radiosensitivity, alpha, and their standard deviations in the population, sigma(SF(2)) and sigma(alpha), resulting from fits based on TCP(DVH(calc)) and TCP(Dmean(calc)). Dose-response curves for homogeneous irradiation (characterized by TCD(50), the dose for a TCP of 50%) and differences in TCP predictions calculated from the DVH using alternatively derived parameters were evaluated. RESULTS: Fits of TCP(Dmean(calc)) are better (i.e., have larger likelihood) than fits of TCP(DVH(calc)). For TCP(Dmean(calc)) fits, matching values of SF(2) and sigma(SF(2)) (or alpha and sigma(alpha)) exist for all N(C) (rho(C)) above a threshold that give fits of equal quality, with no maximum in likelihood. In contrast, TCP(DVH(calc)) fits have maximum likelihood for high SF(2) (low alpha) values that minimize effects of cold spots. Consequently, small N(C) (rho(C)) values are obtained to match the observed control rate. For example, for patients in low-, intermediate-, and high-risk groups, optimum values of SF(2) and N(C) are 0.771 and 3.3 x 10(3), 0.736 and 2.2 x 10(4), and 0.776 and 1.0 x 10(4), respectively. The TCD(50) of dose-response curves for intermediate-risk patients is 2.6 Gy lower using TCP(DVH(calc)) parameters (TCD(50) = 67.8 Gy) than for TCP(Dmean(calc)) parameters (TCD(50) = 70.4 Gy). TCP predictions calculated from the DVH using risk group-dependent TCP(Dmean(calc)) parameters are up to 53% lower than corresponding calculations with TCP(DVH(calc)) parameters. CONCLUSION: For our data, TCP parameters derived from DVHs likely do not reflect true radiobiologic parameters in the tumor, but are a consequence of the reduced importance of low-dose regions at the periphery of the PTV. Deriving radiobiologic parameters from TCP(Dmean(calc)) fits is not possible unless one parameter is already known. TCP predictions using TCP(DVH(calc)) and TCP(Dmean(calc)) parameters may differ substantially, requiring consistency in the derivation and application of model parameters. The proper derivation of radiobiologic parameters from clinical data requires both substantial dose inhomogeneities and understanding of how these coincide with tumor location.

Adenocarcinoma↗
PubMed2001

Temporal and spatial profiling of the modification of an electroactive polymeric interface using neutron reflectivity.

Electropolymerized films of the functionalized pyrrole, pentafluorophenyl-3-(pyrrol-1-yl)propionate (PFP), were reacted with a solution-phase nucleophile, ferrocene ethylamine. This reaction was chosen as a model representative of a postdeposition modification of the polymer membrane's properties. For the first time, a nondestructive method for direct chemical analysis of the reaction profile within the electrodeposited polymer membrane after nucleophilic substitution is presented. This was achieved through the application of in situ neutron reflectivity with supplementary analytical information concerning the film's chemical composition obtained from XPS, FT-IR, and electrochemical measurements. The results presented illustrate how, for a partially reacted film resulting from a short reaction time, the extent of reaction with ferrocene ethylamine is not homogeneous throughout the thickness of the film, but occurs predominantly at the polymer/solution interface. We show that the progress of the reaction within the polymer film is limited by the transport of reacting species in the dense regions of the membrane that are furthest from the solution interface. The data do not fit an alternative model in which there is spatially homogeneous progression of the reaction front throughout the bulk of the thin film polymer. Guided by the neutron reflectivity measurements, suitable modifications were made to the electrodeposition method to prepare films whose architecture resulted in faster rates of reaction.

Journal Article↗
PubMed2001

Motor control: forcing neurons to change.

New research shows that the properties of cells in motor cortex change during learning of new tasks, shedding new light on the neural basis of motor adaptation.

Adaptation, Physiological↗
PubMed2001

Estrogen-derived steroidal metal complexes: agents for cellular delivery of metal centers to estrogen receptor-positive cells.

Targeted cellular delivery of drugs to specific tissues is an important goal in biomedical chemistry. Achieving this requires harnessing and applying molecular-level recognition events prevalent in (or specific to) the desired tissue type. Tissues rich in estrogen receptors (ERs), which include many types of breast cancer, accumulate molecules that have high binding affinities for these receptors. Therefore, molecules that (i) bind to the ER, (ii) have favorable cellular transport properties, and (iii) contain a second functionality (such as a center that may be used for diagnostic imaging or medical therapy) are exciting synthetic targets in the field of drug delivery. To this end, we have prepared a range of metallo-estrogens based on 17alpha-ethynylestradiol and examined their binding to the ER both as isolated receptor and in whole cell assays (ER positive MCF-7 cells). Estrogens functionalized with metal binding units are prepared by palladium-catalyzed cross-coupling reactions and a wide range of metal centers introduced readily. All the compounds prepared and tested exhibit effective binding to the estrogen receptor and are delivered across the cell membrane into MCF-7 cells. In the whole cell assays, despite their monocationic nature, the palladium and platinum complexes prepared exhibit similar (and even enhanced) receptor binding affinities compared to their corresponding neutral free ligands. It is unprecedented for a higher ER binding affinity to be observed for a cationic complex than for its metal-free ligand.

Biological Transport↗
PubMed2001

Ammonium extraction method for ion chromatographic measurements of disc drive components.

The analysis of ionic micro-contamination is of growing importance in the disc drive industry. Through the use of ion chromatography, cleanliness of drive components can be assessed. An objective to improve quantification of highly reactive inorganic ions that exist within the drive environment was implemented. This paper presents a new extraction technique used to determine low levels of ammonium, by microbore ion chromatography. Various chemical compounds within adhesive formulations can be a source of extractable ammonium. By combining this new extraction method with ion chromatography, the percentage of different chemical compounds within adhesive formulations was correlated to the level of extractable ammonium observed.

Chromatography, Liquid↗
PubMed2001

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. METHODS AND MATERIALS: Follow-up information on rectal bleeding is available for 261 and 315 patients treated using 3D-CRT at Memorial Sloan-Kettering Cancer Center for Stage T1c-T3 prostate cancer with minimum target doses of 70.2 and 75.6 Gy, respectively. All patients in this study were treated with a coplanar 6-field technique (2 lateral and 4 oblique fields). Patients were classified as having rectal bleeding if they bled (> or = Grade 2) before 30 months, and nonbleeding (< or = Grade 1) if they were without bleeding at 30 months, using the RTOG morbidity scale. Rectal bleeding was observed in 13 and 38 of the patients treated at 70.2 and 75.6 Gy, respectively. Treatment plans were analyzed for 39 nonbleeding and 13 bleeding patients receiving 70.2 Gy, and 83 nonbleeding and 36 bleeding patients receiving 75.6 Gy. Dose-volume histograms (DVHs) for the anatomic rectal wall were calculated. Average DVHs of the bleeding and nonbleeding patients were generated, and a permutation test was used to assess the significance of differences between them, for each dose group. The confounding effect of total rectal wall volume (V(RW)) was removed by calculating the average differences in DVHs between all combinations of bleeding and nonbleeding patients with similar V(RW)s. Finally, multivariate analysis using logistic regression was performed to test the significance of the DVH variables in the presence of anatomic, geometric, and medical variables previously found to correlate with rectal bleeding in a companion analysis of the same patients. RESULTS: The area under the average percent volume DVH for the rectal wall of patients with bleeding was significantly higher than those of patients without bleeding in both dose groups (p = 0.02, 70.2 Gy; p < 0.0001, 75.6 Gy). However, small V(RW)s were associated with rectal bleeding (p = 0.06, 70.2 Gy; p < 0.01, 75.6 Gy), resulting in an increase in average percent volumes exposed to all doses for patients with rectal bleeding. For patients with similar V(RW)s, rectal bleeding was significantly correlated with the volumes exposed to 46 Gy in both dose groups (p = 0.02, 70.2 Gy; p = 0.005, 75.6 Gy, tolerance in V(RW): 5 ccs). For the 75.6 Gy dose group, the percent volume receiving 77 Gy was significantly correlated with rectal bleeding (p < 0.005). Bivariate analysis using logistic regression, including V(RW) together with a single DVH variable, showed good agreement with the above analysis. Multivariate analysis revealed a borderline significant correlation of the percent volume receiving 71 Gy in the 70.2 Gy dose group. It also showed that the DVH variables were highly correlated with geometric and dosimetric variables previously found to correlate with rectal bleeding in multivariate analysis. CONCLUSION: Significant volume effects were found in the probability of late rectal bleeding for patients undergoing 3D-CRT for prostate cancer with prescription doses of 70.2 and 75.6 Gy. The percent volumes exposed to 71 and 77 Gy in the 70.2 and 75.6 Gy dose groups respectively were significantly correlated with rectal bleeding. The independent correlation of small V(RW) with rectal bleeding may indicate the existence of a functional reserve for the rectum. The independent association with larger percent volumes exposed to intermediate doses ( approximately 46 Gy) seen in both dose groups may indicate that a large surrounding region of intermediate dose may interfere with the ability to repair the effects of a central high dose region.

Algorithms↗
PubMed2001

The problem of uniqueness of fit for viscoelastic films on thickness-shear mode resonator surfaces.

We describe a new strategy for interpreting frequency responses of thickness shear mode resonators loaded with spatially uniform viscoelastic films. This procedure leads to unambiguous extraction of the four parameters that characterize such a film: its thickness, density and shear modulus components (storage and loss moduli). The interpretational difficulty is that the experimental frequency response (impedance spectrum) can only provide two parameters; thus, the problem is underdetermined. Previous interpretations employed various approximations and assumptions for two (or more) film parameters to effectively reduce the problem to a two-parameter fit. Such approaches are clearly imperfect. Our new strategy splits the problem into two separate two-parameter sub-problems, each of which is solved by the measurement of two different experimental responses. The result is a unique fit to the data without the need to make approximations or assumptions for film parameters. First, in the acoustically thin regime, measured frequency shift and film charge are combined to provide a unique solution for film thickness and density; shear moduli components do not affect the response in this regime. Second, film density is carried forward directly, and the film thickness-charge relationship is extrapolated into the acoustically thick regime. Third, with film density and thickness held fixed, crystal impedance data in the acoustically thick regime provide unambiguous shear modulus components. The method is generalized to any other (nonelectrochemical) probe that provides film thickness data and validated using crystal impedance data for poly(3-methylthiophene) films exposed to propylene carbonate.

Journal Article↗
PubMed2001

Regional cerebral volume measurements in late-life depression: relationship to clinical correlates, neuropsychological impairment and response to treatment.

BACKGROUND: Elderly people who develop depression have demonstrable changes in cerebral structure but little is known of the relationship between regional cerebral volumes, treatment response and cognitive impairment. METHOD: Forty-four patients with major depression diagnosed according to DSM-IIIR criteria underwent magnetic resonance imaging and regional cerebral volumes were quantified using multispectral analysis. Response to antidepressant treatment was assessed prospectively and a neuropsychological test battery was administered. RESULTS: There was a trend for smaller fronto-temporal volumes in the treatment-resistant patients. Impaired immediate working memory was linked with reduced frontal and parietal lobe volume and impaired short-term memory functioning was associated with reduced temporal lobe volume. Ventricular enlargement was associated with prior administration of electro-convulsive therapy, poor physical health and later age at onset of first episode of depression. CONCLUSION: In late-life depression, brain changes should not preclude vigorous antidepressant treatment. Regional cerebral volume changes may be a complication of poor physical health and are associated with memory dysfunction even upon recovery from depression.

Age Factors↗
PubMed2001

Reproducibility of T2* blood volume and vascular tortuosity maps in cerebral gliomas.

The development of anti-angiogenic therapies for tumors has led to a demand for imaging-based surrogate markers of the angiogenic process. The utility of such markers is highly dependent on their test-retest reproducibility. This paper presents a formal assessment of the reproducibility of measurements of relative blood volume (rBV), normalized rBV (rBVnorm), and vascular tortuosity as estimated by measurement of relative recirculation (rR). The study was conducted in 11 patients with glioma who were scanned on two occasions 36-56 hours apart. The observed reliability estimates were used to calculate 95% confidence limits for detection of differences between groups and for changes in individual cases. The results show that measurement of rBV or rBVnorm in consecutive studies is statistically capable of reliably detecting changes in excess of 15% in between group studies and 25% in individual patients. Measurement of vascular tortuosity using is less reproducible but is able to confidently identify changes in excess of 30% in group studies and 35% in individuals.

Blood Volume↗
PubMed2001

Improved high resolution MR imaging for surface coils using automated intensity non-uniformity correction: feasibility study in the orbit.

This study examined the effects of a recently developed automated intensity non-uniformity correction on surface coil images using the orbit as an exemplar. Images were obtained using a standard head coil and a range of surface coils. Slices through the optic nerve head and cavernous sinus were subjected to the correction algorithm. Blind forced-choice rankings of the subjective image quality were performed. Quantitative measurements were taken of the similarity between vitreous humor at two depths from the coil, and of the conspicuity between orbital fat and temporalis muscle intensities. The combined qualitative ranks for corrected surface coil images were higher than for the equivalent uncorrected images in all cases. Intensity non-uniformity correction produced statistically significant improvements in orbital surface coil images, bringing their intensity uniformity in homogeneous tissue to the level of head coil images. The subjective quality of the corrected surface coil images was superior to head coil images, due to increased spatial resolution combined with improved signal to noise ratio across the image.

Algorithms↗
PubMed2001

A low dose alcohol drug discrimination in social drinkers: relationship with subjective effects.

RATIONALE: Although well characterised in animals, relatively little is known about alcohol discriminative stimulus effects in humans. OBJECTIVE: The study was carried out to investigate the correspondence of subjective effects and the discriminative response during the acquisition of a low dose alcohol discrimination in humans. METHODS: Healthy volunteers completed an Alcohol Use Questionnaire and were then trained to discriminate a dose of 0.2 g/kg alcohol from placebo using a money reinforced technique. Subjects sampled drinks during training, but also completed rating scales measuring Taste, Like/Dislike and Subjective Effects for each drink. RESULTS: Thirty-two subjects learned the discrimination (discriminators; Ds). In these subjects, differences between placebo scores and alcohol scores for Lightheadedness, Relaxed, Arousal and Fatigue were greater following acquisition of the discrimination, compared with differences at the start of training. Differences in other measures remained consistent. Twenty-six of the volunteers failed to learn the discrimination (non-discriminators; NDs). These subjects reported drinking approximately twice as much alcohol during the preceding 6 months, as the Ds (4.35+/-0.53 g/kg per week versus 2.08+/-0.19 g/kg per week, respectively, P<0.001). There were no alcohol specific differences in ratings for Lightheadedness, Relaxed, Arousal or Fatigue between the Ds and the NDs. However, Dislike scores did differentiate between the Ds and the NDs in that the NDs had reduced ratings for the alcohol drink only compared with the Ds (P<0.02). CONCLUSIONS: These results support the suggestion from animal studies, that the alcohol stimulus is a compound, and characterise the subjective effects which contribute to a low dose cue in humans. In addition, the data suggest that previous drinking experience may selectively alter aversive responses to alcohol and that this, in addition to differences in general arousal levels, may have affected subjects' ability to learn the discrimination.

Adolescent↗
PubMed2001

Estrogen modulates 5-HT(1A) agonist inhibition of lordosis behavior but not binding of [(3)H]-8-OH-DPAT.

Previous studies showed that repeated estrogen treatment reduces the ability of the 5-HT(1A) receptor agonist, 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT), to inhibit lordosis behavior of female rats. The present study evaluated the effects of repeated estrogen treatment on lordosis behavior and 5-HT(1A) receptor binding and coupling to G protein in the hypothalamus-preoptic area using the agonist ligand [3H]-8-OH-DPAT, which binds selectively to G-protein-coupled 5-HT(1A) receptors. Rats were injected twice with 25 or 50 microg of estradiol benzoate (EB) 7 days apart followed by 500 microg of progesterone (P) 48 h after the second EB injection. Controls received a single injection of 25 or 50 microg EB followed 48 h later by 500 microg of P. Four hours after P, 0.15 mg/kg 8-OH-DPAT was injected, and lordosis behavior examined for 30 min. Rats treated twice with EB showed significantly less 8-OH-DPAT inhibition of lordosis behavior than rats receiving a single EB injection. For receptor binding, rats received EB without P treatment. None of the estrogen treatments reduced [3H]-8-OH-DPAT binding density or affinity in the hypothalamus-preoptic area or hippocampus. These studies suggest that estrogen modulates 5-HT(1A) agonist potency without a measurable change in 5-HT(1A) receptor density or coupling to G protein.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

The cytoplasmic tail of the D1A receptor subtype: identification of specific domains controlling dopamine cellular responsiveness.

In this study the rat D1A receptor (wild-type, WT) and truncation mutants thereof, are utilized to delineate specific cytoplasmic tail (CT) domains responsible for regulating ligand binding and receptor-mediated adenylyl cyclase activation. In human embryonic kidney (HEK) cells, all truncation mutants of the D1A receptor (Delta425, Delta379, Delta351) display cell surface localization and express at high but different receptor numbers. Binding studies suggest that residues located between Cys(351) and Asp(425) may serve to restrain the agonist binding conformation of the D1A receptor. This contention is supported by the observation that the constitutive activation of Delta351 is significantly increased in comparison with WT, Delta425 and Delta379. Furthermore, we demonstrate that the extent of dopamine-mediated maximal activation of adenylyl cyclase is significantly augmented in cells expressing Delta351 when compared with WT or mutants harboring shorter truncations. These results suggest that in addition to restraining receptor conformation, determinants located downstream of Cys(351) may act as negative regulators of the G protein coupling efficiency and adenylyl cyclase activation. Interestingly, all truncated receptors used in the present study display a decrease in dopamine potency when compared with WT. We show that inhibition of protein kinase A (PKA) activity leads also to a reduction in dopamine potency in cells expressing WT but not Delta351 receptors. These results hint at a potential previously unanticipated role for PKA in facilitating D1A receptor coupling efficiency in HEK cells. Overall, the present study has uncovered specific CT domains involved in regulating discrete aspects of the D1A receptor signaling.

Adenylyl Cyclases↗
PubMed2001

Partial irradiation of the rectum.

Data gathered from dose escalation protocols for the treatment of prostate cancers conducted in the past 10 years have shown that rectal toxicity can be controlled by the use of careful conformal techniques. The most severe complications of rectal irradiation (obstruction and fistula requiring colostomy) have been essentially eliminated. The most frequent gastrointestinal complications of conformal radiotherapy of prostate cancer are now rectal bleeding associated with telangiectatic changes to the vasculature of the submucosa, and in severe cases, ulceration requiring cautery procedures and or transfusion. The benefits of 3-dimensional conformal radiotherapy (3D-CRT) are strongly technique dependent, with a strong dose response for single techniques for prescription doses over 70 Gy. Studies of rectal motion show that the anterior wall can move approximately 1 cm during treatment, so portions of the anterior rectal wall will regularly receive the full prescription dose if posterior margin sizes >/= 1 cm are used in designing the planning target volume (PTV). There is strong evidence that increased rectal shielding and posterior PTV margin sizes approximately 0.6 cm reduce rectal complication rates. Despite uncertainties due to rectal motion, studies of dose-volume histograms (DVHs) show that rectal toxicity is strongly influenced by the percent volumes of rectal wall exposed to doses approximately 70 Gy and higher. Recent data suggests that percent volumes of rectal wall exposed doses between 40 to 50 Gy, and the existence of a reserve of unexposed tissue may also play a role in determining rectal bleeding rates.

Dose-Response Relationship, Radiation↗