A new method of body habitus correction for total body potassium measurements.

This paper describes an accurate and time-efficient method for the determination of total body potassium via a combination of measurements in the Birmingham whole body counter and the use of the Monte Carlo n-particle (MCNP) simulation code. In developing this method, MCNP has also been used to derive values for some components of the total measurement uncertainty which are difficult to quantify experimentally. A method is proposed for MCNP-assessed body habitus corrections based on a simple generic anthropomorphic model, scaled for individual height and weight. The use of this model increases patient comfort by reducing the need for comprehensive anthropomorphic measurements. The analysis shows that the total uncertainty in potassium weight determination by this whole body counting methodology for water-filled phantoms with a known amount of potassium is 2.7% (SD). The uncertainty in the method of body habitus correction (applicable also to phantom-based methods) is 1.5% (SD). It is concluded that this new strategy provides a sufficiently accurate model for routine clinical use.

Response corrections for solid-state detectors in megavoltage photon dosimetry.

Solid-state detectors offer high sensitivity, stability and resolution and are frequently the dosimeter of choice for on-line dosimetry and small field therapies such as stereotactic radiosurgery. The departure from tissue equivalence of many solid-state devices, including diodes and MOSFETs, has to be carefully considered at lower energies and for Compton scattered radiation where the strongly Z-dependent photoelectric effect is significant. A modification of Burlin cavity theory is proposed that treats primary and scatter photon spectra separately and this has been applied to determine the correction factors for diode detector measurements of 6 and 15 MV linear accelerator beams. Uncorrected, an unshielded diode overestimates the dose at depth by as much as 15% for the 6 MV beam. The model predicts the effect to within 1% for both energies offering a basis for the correction of diodes for use in routine dosimetry.

Prompt-gamma neutron activation analysis facility for in vivo body composition studies in small animals.

The design, calibration, dosimetry and performance evaluation of a prompt-gamma neutron activation analysis facility for in vivo body composition studies in small animals (i.e. rats or rabbits) is discussed. The system design was guided by Monte Carlo transport calculations using MCNP-4C code. A system was built and performance evaluation was made using a 185-GBq Pu-Be neutron source. Prompt-gamma rays produced by neutron capture reactions were detected by a combination of a NaI(Tl) scintillation and a HPGe semiconductor detectors. Nitrogen and chlorine were quantified by analysis of the 10.83-MeV and 6.11-MeV peaks, respectively. Appropriate corrections for the animal body size were determined. The facility described allows the in vivo determination of protein and extracellular space in sets of experimental animals.

The effects of delays in radiotherapy treatment on tumour control.

There is often a considerable delay from initial tumour diagnosis to the start of radiotherapy treatment, which may be due to factors such as waiting lists and referral delays. This paper uses widely published models and clinical parameters to calculate the effect of delays in treatment on local tumour control for four different types of tumour-squamous cell carcinoma (head and neck), breast, cervix and prostate. The Poisson model for tumour control probability (TCP), an exponential function for tumour growth and the linear quadratic model of cell kill are used to calculate the change in TCP for delays between diagnosis and treatment of up to 100 days. Typical values of the clinical parameters have been taken from the literature; these include alpha and beta, sigma(alpha), tumour size at diagnosis, pre-treatment doubling time, delay in onset of accelerated repopulation and doubling time during treatment. It is acknowledged that there are limitations in the reliability of these data for predicting absolute values of tumour control, but models are still useful for predicting how changes in treatment parameters are likely to affect the outcome. It is shown that for fast-growing tumours a delay of 1-2 months can have a significant adverse effect on the outcome, whereas for slow-growing tumours such as Ca prostate a delay of a few months does not significantly reduce the probability of tumour control. These calculations show the importance of ensuring that delays from diagnosis through to treatment are minimized, especially for patients with rapidly proliferating tumours.

Response of silicon diode dosemeters to scattered radiation from megavoltage photon beams.

Dose response effects of diodes due to the high atomic number of silicon relative to water are investigated. While quality chances in the primary component of a megavoltage beam with depth are minimal. Compton scattered photons are shown to have a substantial effect on the quality leading to their enhanced absorption in silicon via the photoelectric effect. Monte Carlo methods were used to study and model this phenomenon. Measurements of dose rate, depth and field size dependence are examined for commercially available diode detectors and ionisation chambers.

Investigation into the relationship between body surface area and total body potassium using Monte Carlo and measurement.

The use of body surface area (BSA) as a means of indexing chemotherapy doses is widespread even though the value of this practice is uncertain. In principle, the body cell mass (BCM) more closely represents the body's metabolic size and this is investigated here as an alternative to BSA; since 98% of body potassium is intracellular the derivation of total body potassium (TBK) via the measurement of 40K in a whole body counter (WBC) will provide a useful normalizing index for metabolic size, potentially avoiding toxicity and underdosing. The Queen Elizabeth Hospital WBC has been used in this study, initially involving single geometrical phantoms and then combinations of these to simulate human body habitus. Monte Carlo N-particle (MCNP) codes were constructed to model the phantoms and simulate the measurements made in the WBC. Efficiency corrections were derived by comparing measurement and modelled data for each detector separately. A method of modelling a person in the WBC as a series of ellipsoids was developed. Twenty-four normal males and 24 females were measured for their 40K emissions. Individual MCNP codes were constructed for each volunteer and the results used in conjunction with the measurements to derive TBK, correcting for body habitus effects and detector efficiencies. An estimate of the component of error arising from sources other than counting statistics was included by analysing data from the measurement of phantoms. The total residual errors (expressed as coefficients of variation) for males and females were 10.1% and 8.5% respectively. The measurement components were determined to be 2.4% and 2.5%, implying that the biological components were 9.8% and 8.1% respectively. These results suggest that the use of BSA for indexing chemotherapy doses is likely to give rise to clinically significant under- or overdosing.

Application of diamond detectors to the dosimetry of 45 and 100 kvp therapy beams: comparison with a parallel-plate ionization chamber and Monte Carlo.

Diamond detectors have become an increasingly popular dosimetric method where either high spatial resolution is required or where photon or electron spectra are likely to change with depth or field size. However, little work has been previously reported for superficial energies. This paper reports the response of a commercially available diamond detector (PTW Freiburg/IPTB Dubna) at 45 kVp (0.55 mm Al first HVL) and 100 kVp (2.3 mm Al first HVL) including dose and dose-rate linearity, percentage depth-dose and output factors as a function of applicator size. Comparisons are made with Br J. Radiol. supplement 25 data, measurements using a PTW parallel-plate chamber and Monte Carlo simulations based on spectra determined from transmission measurements in aluminium. Excellent agreement was obtained for percentage depth-dose curves between Monte Carlo and diamond after correcting for sublinearity of the dose-rate response and energy dependence of the diamond detector. However, significant differences were noted between diamond/Monte Carlo and the parallel-plate chamber, which is attributed to the perturbation caused by the polyethylene base of the chamber

Experimental simulation of A-bomb gamma ray spectra for radiobiology studies.

Improved radiation protection of humans requires a better understanding of the mechanisms of radiation action and accurate estimates of radiation risk for both internal and external radiations. The Japanese atomic bomb survivors represent one of the most important sources of human data on the late carcinogenic effects of ionising radiations. The present study was undertaken to investigate whether it would be possible to use hospital radiotherapy/radiobiology equipment to mimic the spectra encountered in Hiroshima and Nagasaki. The estimated total gamma ray fluence spectra (including both prompt and delayed photons) at both Hiroshima and Nagasaki, for distances of 500, 1000, 1500 and 2000 m have been evaluated using DS86 data and previously unpublished information for delayed gamma radiations which constitute the major contribution to survivor doses. Monte Carlo (EGS4) simulations were performed to transport these photons through the body in order to investigate the variation in electron spectra for various body organs. The electron spectra obtained for these fluences at, for example, the colon, have been matched with combinations of electron spectra produced by linear accelerators to within 5% SD. These will, for the first time, enable a direct link to be made between radiobiological studies (for example, on mammography spectra) and the epidemiological data from Japan, which currently underpin radiation risk estimates.

The measurement of thermal neutron flux depression for determining the concentration of boron in blood.

Boron neutron capture therapy (BNCT) is a form of targeted radiotherapy that relies on the uptake of the capture element boron by the volume to be treated. The treatment procedure requires the measurement of boron in the patient's blood. The investigation of a simple and inexpensive method for determining the concentration of the capture element 10B in blood is described here. This method, neutron flux depression measurement, involves the determination of the flux depression of thermal neutrons as they pass through a boron-containing sample. It is shown via Monte Carlo calculations and experimental verification that, for a maximum count rate of 1 x 10(4) counts/s measured by the detector, a 10 ppm 10B sample of volume 20 ml can be measured with a statistical precision of 10% in 32 +/- 2 min. For a source activity of less than 1.11 x 10(11) Bq and a maximum count rate of less than 1 x 10(4) counts/s, a 10 ppm 10B sample of volume 20 ml can be measured with a statistical precision of 10% in 58 +/- 3 min. It has also been shown that this technique can be applied to the measurement of the concentration of any element with a high thermal neutron cross section such as 157Gd.

Laparoscopic lymphadenectomy for gynecologic malignancies.

OBJECTIVE: The purpose of our study was to detail our 5-year experience with laparoscopic lymphadenectomy for gynecologic malignancies. METHODS: From 11/5/92 to 3/9/98, we performed laparoscopic lymphadenectomies on 94 patients with various gynecologic malignancies. Pelvic, paraaortic, and combinations of both pelvic and paraaortic lymphadenectomies were performed depending on the primary site of disease and indication for lymph node dissection. Data were prospectively collected on all patients. RESULTS: From 11/5/92 to 3/9/98 we performed 94 laparoscopic lymphadenectomies for gynecologic malignancies. The distribution included 64 patients with cervical cancer, 14 with ovarian cancer, 12 with endometrial cancer, 2 with fallopian tube cancer, 1 with a uterine malignant mixed mesodermal tumor, and 1 with a metastatic neuroendocrine tumor. Fifty-five patients had only pelvic lymph node dissections, 9 patients had paraaortic dissections only, and 30 had both pelvic and paraaortic dissections performed. Among 30 patients having laparoscopic lymphadenectomy only, the mean hospital stay was 3.6 days. Included in this group were 19 patients who received postoperative neoadjuvant chemotherapy for cervical cancer as inpatients prior to ambulatory radiation therapy. The mean length of stay for this group was 4.6 days versus 1.7 days for the 11 patients who did not receive postoperative chemotherapy (P = 0.0025). The mean number of pelvic nodes was 11.9 (range 0-57), with a mean of 4. 5 between 11/5/92 and 12/31/95 and a mean of 19.1 from 1/1/96 to 3/9/98. The mean number of paraaortic nodes obtained was 3.7 (range 0-14), with a mean of 3.4 from 11/5/92 to 12/31/95 and a mean of 4.1 from 1/1/96 to 3/9/98. A total of 3 patients required conversions to laparotomy. One was for a vascular injury to the vena cava, 1 for a large tumor extending to both sidewalls, and the third for removal of densely matted lymph nodes. CONCLUSIONS: Laparoscopic lymphadenectomy is a technically feasible procedure for patients with gynecologic malignancies requiring lymph node dissections, with an acceptable safety profile and nodal yield. The number of nodes obtained increased in direct proportion to operator experience. In addition, patients may benefit from a decrease in hospital stay compared to conventional lymphadenectomy via laparotomy.

Body fat prediction from skinfold anthropometry referenced to a new gold standard: in vivo neutron activation analysis and tritium dilution.

Skinfold anthropometry is a widely practiced technique often with little appreciation of its limitations. The large residual error appearing in any regressions of body density versus sums of skinfolds is primarily due to biological causes, in particular the non-constancy of the ratio of subcutaneous to total body fat. Nevertheless this preliminary study shows that the residual error can be reduced by referencing to a gold standard other than body density. Using a difference technique involving in vivo neutron activation analysis and tritiated water dilution, this paper shows that at least in 20-29 year old normal subjects the residual error (expressed as a percentage of mean total body fat in the respective groups) can be reduced from 22% to 16% (p < 0.001) in males and from 17% to 9% in females (p < 0.0001). It is suggested that a large scale study could be initiated with this new gold standard to obtain accurate predictor relationships throughout the whole age range for both sexes.

Body fat: estimation or guesstimation?

Skinfold anthropometry is performed world-wide with little appreciation of its limitations. This paper shows that it is important to appreciate the magnitude of the biological component of the residual error in any regression of body density against sums of skinfolds; for example, for young adult males a biological error of around 21% (s.d.) is observed. Such 'errors' simply express nature's refusal to conform to imposed regression relationships, reflecting the inherent variability in the ratio of subcutaneous to total body fat.

Measurement and prediction of total body fat.

Though it has been established that skinfold anthropometry has severe limitations as a method of deriving total body fat (TBF), the possibility that the problem might be related more to the assumptions implicit in densitometry has to be addressed. This paper suggests that smaller residual errors might be obtained if sums of skinfolds are regressed against TBF measured by a difference technique (IVNAA + 3H2O dilution), suggesting that the latter may perhaps be a better standard than densitometry.

The 40K activity of one gram of potassium.

The activity of 40K in natural potassium as derived from the recent literature varies between 27.33 to 31.31 Bq g-1 of potassium. This paper reports measurements by gamma-ray spectrometry and compares these with independent calculations, yielding values of 30.18 +/- 0.72 Bq g-1 and 31.00 +/- 0.33 Bq g-1 respectively.

Absorbed dose measurements in dual energy X-ray absorptiometry (DXA).

In this study a predominantly film dosimetric method was used to measure the effective dose from posteroanterior (PA) lumbar spine and proximal femur scans performed on a Lunar DPX-L machine. Because of the very low dose rate in scanning mode, the depth dose data were determined using a stationary detector configuration. The characteristic curve for the film (Kodak TMAT-H) was obtained and depth dose measurements were made using slabs of "solid water". The film was calibrated using a superficial X-ray unit (calibrated against a standard traceable to a national standard). To assess the change in film response with beam hardening at depth, the film was exposed to calibration beams of different half value layer (HVL). The HVL of the DXA beam was determined for surface and depth doses using aluminium filters and a diamond detector (an energy independent device). All measurements were performed three times. Beam size was measured using film, and the scan areas and times were determined by scanning phantoms. The dose from a scan was calculated using Dsc = DTscAb/Asc, where D = dose rate (stationary), Tsc = scan time, Ab = beam area, and Asc = scan area. Organ doses were determined using an anatomical atlas and ICRP 23 female reference. All film measurements had good precision (coefficient of variation < 4%). There was little variation in film sensitivity with change in HVL (< 1% change for the first three HVLs) and consequently no corrections were applied to the depth dose data. Skin entrance dose was 11.5 microGy. Effective dose in females was 0.19 microSv for the PA lumbar spine. For the proximal femur scan, the effective dose was 0.14 microSv (ovaries included) and 0.023 microSv (ovaries excluded) for pre-menopausal and pos-menopausal women, respectively.

Enhanced radiosensitization with interferon-alpha-2b and cisplatin in the treatment of locally advanced cervical carcinoma.

PURPOSE: To evaluate the efficacy and toxicity of interferon-alpha-2b (IFN-alpha) and cisplatin given concomitantly with radiation therapy (RT) in the treatment of locally advanced cervical carcinoma. MATERIALS AND METHODS: Twenty-one patients with stage bulky Ib-IIIb (Ib, 2; IIa, 2; IIb, 8; IIIb, 9) cervical carcinoma were treated with combined IFN-alpha (5 million IU) subcutaneously three times per week and cisplatin (25 mg/m2) i.v. infusion over 2 h weekly for 7 weeks, given concomitantly with RT (4500 cGy of external beam plus 2 brachytherapy procedures). Total radiation doses delivered ranged from 7500 to 9960 cGy (median, 9300 cGy). Follow-up ranged from 16 to 33 months (median, 25 months). RESULTS: The 2-year local control rate was 100%. The only sites of disease recurrence were distant. Freedom from distant metastases, disease-free survival, and overall survival at 2 years was 76%. Late complication rates were high. Grade 4 rectosigmoid, bladder, and small bowel complication rates were 49, 18, and 23% at 2 years. Late toxicity was seen earlier than expected with rectosigmoid complications observed 5 to 11.5 months (median, 8 months) after completion of treatment. CONCLUSION: Combination IFN-alpha and cisplatin produced a marked effect of enhanced radiosensitization as evidenced by 100% local tumor control and high late normal tissue complication rates. Due to the unacceptable late toxicity, its routine clinical use cannot be recommended. Further investigation is needed to determine whether a therapeutic window exists such that the use of lower doses of IFN-alpha, cisplatin, or RT can increase tumor control with more acceptable normal tissue toxicity.

Microdosimetry of haemopoietic stem cells irradiated by alpha particles from the short-lived products of 222Rn decays in fat cells and haemopoietic tissue.

The Monte Carlo method is used to model fat cells and the nuclei of stem cells in haemopoietic tissue where 222Rn is dissolved in different amounts in the fat and tissue. Calculations are performed for fat cells of diameters 50 and 100 microns and for stem cell nuclei of 8 and 16 microns diameters for various fractions of fat filling the volume. Average doses (and their distributions) to stem cell nuclei from single passages of alpha particles are presented. In addition to dose, the relationship between LET and dose is obtained, illustrating the importance of 'stoppers' in the calculations. The annual average dose equivalent for a concentration of 1 Bq/m3 in air agrees well with other authors at 12 mu Sv/year. The method also allows the calculation of the fraction of stem cell nuclei hit annually. Here for 1 Bq/m3, stem cell nuclei of diameter 8 microns and 100% fat filing 15 x 10(-7) of the stem cell nuclei are hit.

Screening for human immunodeficiency virus in inner city females with abnormal cervical cytology.

OBJECTIVE: This report evaluates the acceptance, results, and predictors of human immunodeficiency virus (HIV) infection in inner city women referred to a colposcopy clinic for abnormal cervical cytology. METHODS: HIV testing results of 1,908 inner city women referred for abnormal cervical cytology were analyzed retrospectively with respect to acceptance, race, ethnicity, Pap smear results, sexually transmitted diseases (STDs), HIV exposures, and final histologic findings. RESULTS: HIV testing was accepted by 50.4% of patients. Women who agreed to screening were significantly more likely to admit exposure to HIV or to be Hispanic, foreign-born, or have a history of multiple STDs. Of those screened, 3.3% were found to be HIV seropositive. Although higher grades of referral Pap smears were noted in the women found to be HIV seropositive, final histologic findings were not different. The only predictors of unknown HIV seropositivity were admitted HIV exposure and external condyloma. CONCLUSIONS: Fifty percent of inner city women of unknown HIV status referred for abnormal cervical cytology will accept HIV serotesting and 3.3% are found to be positive. Most HIV-seropositive women can be detected based on either a history of exposure to HIV or the presence of external condyloma.

A comparison of dosimetry techniques in stereotactic radiosurgery.

Accurate dosimetry of small-field photon beams used in stereotactic radiosurgery (SRS) can be made difficult because of the presence of lateral electronic disequilibrium and steep dose gradients. In the published literature, data acquisition for radiosurgery is mainly based on diode and film dosimetry, and sometimes on small ionization chamber or thermolominescence dosimetry. These techniques generally do not provide the required precision because of their energy dependence and/or poor resolution. In this work PTW diamond detectors and Monte Carlo (EGS4) techniques have been added to the above tools to measure and calculate SRS treatment planning requirements. The validity of the EGS4 generated data has been confirmed by comparing results to those obtained with an ionization chamber, where the field size is large enough for electronic equilibrium to be established at the central axis. Using EGS4 calculations, the beam characteristics under the experimental conditions have also been quantified. It was shown that diamond detectors are potentially ideal for SRS and yield more accurate results than the above traditional modes of dosimetry.