Parathyroid Hormone Resistance: An Uncommon Cause of Hypocalcaemia in an Adult Ghanaian Female.

BACKGROUND AND OBJECTIVE: Parathyroid hormone (PTH) resistance, the main biochemical feature of a rare group of disorders known as Pseudohypoparathyroidism (PHP) is an uncommon cause of hypocalcaemia. In addition to the biochemical abnormalities, some individuals with PHP may have features of Albright Hereditary Osteodystrophy (AHO). Being a rare disorder with a significant level of variation and overlap in its clinical presentation, diagnosis of PHP may be challenging in some clinical settings. This case report highlights the diagnosis of this rare disorder. CASE REPORT: A 20-year-old Ghanaian female who had been involved in a road traffic accident (RTA) was referred to the endocrine clinic after a computer tomography (CT) scan of her head revealed an incidental finding of multiple basal ganglia calcifications. Investigations revealed hypocalcaemia, hyperphosphatemia, and elevated intact PTH in the presence of normal levels of 25-hydroxyvitamin D and magnesium, and a normal kidney function. She also had phenotypic features of AHO. Findings suggested a diagnosis of PHP, however, the type could not be identified due to the unavailability of further testing. CONCLUSION: This report of a Ghanaian female with PTH resistance and features of AHO diagnosed at the age of 20 years, is expected to add to the existing literature and assist in increasing the level of awareness and facilitate the diagnosis of this disorder in our setting.

CONTEXTE ET OBJECTIF: La résistance à l'hormone parathyroïdienne (PTH), principale caractéristique biochimique d'un groupe rare de troubles connus sous le nom de pseudohypoparathyroïdie (PHP), est une cause rare d'hypocalcémie. En plus des anomalies biochimiques, certaines personnes atteintes de PHP peuvent présenter des caractéristiques d'ostéodystrophie héréditaire d'Albright (AHO). Étant un trouble rare avec un niveau significatif de variation et de chevauchement dans sa présentation clinique, le diagnostic de PHP peut être difficile dans certains contextes cliniques. Ce rapport de cas met en lumière le diagnostic de cette maladie rare. RAPPORT DE CAS: Une femme ghanéenne de 20 ans qui avait été impliquée dans un accident de la circulation routière (RTA) a été référée à la clinique endocrinienne après qu'une tomodensitométrie (TDM) de sa tête a révélé la découverte fortuite de multiples calcifications des ganglions de la base. Les examens ont révélé une hypocalcémie, une hyperphosphatémie et une PTH intacte élevée en présence de taux normaux de 25 hydroxyvitamine D et de magnésium et d'une fonction rénale normale. Elle avait également des caractéristiques phénotypiques d'AHO. La découverte a suggéré un diagnostic de PHP, mais le type n'a pas pu être identifié en raison de l'indisponibilité de tests supplémentaires. CONCLUSION: Ce rapport d'une femme ghanéenne présentant une résistance à la PTH et des caractéristiques d'AHO diagnostiquée à l'âge de 20 ans, devrait s'ajouter à la littérature existante et aider à accroître le niveau de sensibilisation et à faciliter le diagnostic de ce trouble dans notre contexte. Mots-clés: Hypocalcémie, Hormone parathyroïdienne, Ghana.

High BMI: an important health risk factor among older adults in Ghana.

OBJECTIVE: We examined BMI as a health risk factor for self-reported diabetes mellitus, angina, strokes and arthritis among older Ghanaians aged 50 years and above. DESIGN: We analysed the individual-level data from the World Health Organization Study on global AGEing and adult health Ghana Wave 2 (2014/2015). The influence of BMI on self-reported chronic conditions including diabetes, angina, stroke and arthritis was examined. SETTING: Households from all the administrative regions of Ghana. PARTICIPANTS: Included 3350 adults aged 50 years and older. RESULTS: The prevalence of overweight and obesity among participants was 22·8 % (95 % CI 20·6, 25·2) and 13·2 %, respectively (95 % CI 11·5, 15·1). With respect to individual chronic conditions, arthritis emerged with the highest prevalence rate of 7·3 (95 % CI 5·3, 9·9), while the prevalence rate of diabetes, angina and stroke was 2·8 % (95 % CI 2·0, 3·9), 1·7 % (95 % CI 1·1, 2·6) and 1·3 % (95 % CI 1·0, 1·8), respectively. The risk of diabetes among overweight and obesity was over three and two times, respectively, higher compared with participants with normal weights. Overweight and obesity were significantly more than two and three times likely to experience angina, respectively, compared with participants with normal weight. Obesity significantly influences arthritis with approximately two times increased odds compared with normal weight participants. CONCLUSION: Prevalence of obesity and overweight in Ghana is high and increasing, which poses a health risk at the individual and population levels. Inter-sectorial and multidisciplinary measures in line with the national non-communicable disease policies aimed at curbing this trend are imperative.

Determinants of willingness to accept kidney transplantation among chronic kidney disease patients in Ghana.

BACKGROUND: The burden of chronic kidney disease in Africa is three to four times higher compared to high-income countries and the cost of treatment is beyond the reach of most affected persons. The best treatment for end stage renal disease is kidney transplantation which is not available in most African countries. As kidney transplantation surgery is emerging in Ghana, this study assessed factors which could influence the willingness of patients with chronic kidney disease to accept it as a mode of treatment. METHODS: This cross-sectional survey was carried out among patients with chronic kidney disease in Korle-Bu Teaching Hospital. A consecutive sampling method was used to recruit consenting patients. A structured questionnaire and standardized research instruments were used to obtain information on demographic, socio-economic characteristics, knowledge about transplantation, perception of transplantation, religiosity and spirituality. Logistic regression model was used to assess the determinants of willingness to accept a kidney transplant. RESULTS: 342 CKD patients participated in the study of which 56.7% (n = 194) were male. The mean age of the participants was 50.24 ± 17.08 years. The proportion of participants who were willing to accept a kidney transplant was 67.3% (95%CI: 62.0-72.2%). The factors which influenced participants' willingness to accept this treatment included; willingness to attend a class on kidney transplantation (p < 0.016), willingness to donate a kidney if they had the chance (p < 0.005), perception that a living person could donate a kidney (p < 0.001) and perceived improvement in quality of life after transplantation (p < 0.005). The barriers for accepting kidney transplantation were anticipated complications of transplant surgery and financial constraints. CONCLUSION: More than two-thirds of CKD patients were willing to accept a kidney transplant and this is influenced by multiple factors. Government health agencies must consider full or partial coverage of kidney transplantation through the existing national health insurance scheme. Further, efficient educational programmes are required to improve both patients' and physicians' knowledge on the importance of kidney transplantation in the management of end stage renal disease in Ghana.

Predictors and outcome of systemic lupus erythematosus (SLE) admission rates in a large teaching hospital in sub-Saharan Africa.

Although it was previously believed that systemic lupus erythematosus was uncommon among Africans, it has become increasingly apparent that the incidence is higher, and socioeconomic challenges such as physician shortages, poor medical facility access, and poor health literacy may worsen prognosis. This retrospective study examines characteristics and outcomes of hospitalized systemic lupus erythematosus patients over a two-year period and serves as a baseline for comparison for future studies to examine the outcomes with the provision of more dedicated care. There were 51 patient admissions over a two-year period, with a mean duration from start of illness to admission of approximately two years. Duration of admission ranged from one to 140 days with a mean period of 26.12 days (SD ± 26.6). There were 22 deaths (43.1% of admissions), which were mainly due to infections and renal complications. Factors associated with risk of death in regression analysis were: infections, fever, disease flare, musculoskeletal involvement, amenorrhea, depression, a clinical finding of hepatomegaly, and chest infection. Understanding the effect and outcome of systemic lupus erythematosus across different countries can elucidate the role of genetic, environmental, and other causative factors in the progression of the disease.

A study of respiration-correlated cone-beam CT scans to correct target positioning errors in radiotherapy of thoracic cancer.

PURPOSE: There is increasingly widespread usage of cone-beam CT (CBCT) for guiding radiation treatment in advanced-stage lung tumors, but difficulties associated with daily CBCT in conventionally fractionated treatments include imaging dose to the patient, increased workload and longer treatment times. Respiration-correlated cone-beam CT (RC-CBCT) can improve localization accuracy in mobile lung tumors, but further increases the time and workload for conventionally fractionated treatments. This study investigates whether RC-CBCT-guided correction of systematic tumor deviations in standard fractionated lung tumor radiation treatments is more effective than 2D image-based correction of skeletal deviations alone. A second study goal compares respiration-correlated vs respiration-averaged images for determining tumor deviations. METHODS: Eleven stage II-IV nonsmall cell lung cancer patients are enrolled in an IRB-approved prospective off-line protocol using RC-CBCT guidance to correct for systematic errors in GTV position. Patients receive a respiration-correlated planning CT (RCCT) at simulation, daily kilovoltage RC-CBCT scans during the first week of treatment and weekly scans thereafter. Four types of correction methods are compared: (1) systematic error in gross tumor volume (GTV) position, (2) systematic error in skeletal anatomy, (3) daily skeletal corrections, and (4) weekly skeletal corrections. The comparison is in terms of weighted average of the residual GTV deviations measured from the RC-CBCT scans and representing the estimated residual deviation over the treatment course. In the second study goal, GTV deviations computed from matching RCCT and RC-CBCT are compared to deviations computed from matching respiration-averaged images consisting of a CBCT reconstructed using all projections and an average-intensity-projection CT computed from the RCCT. RESULTS: Of the eleven patients in the GTV-based systematic correction protocol, two required no correction, seven required a single correction, one required two corrections, and one required three corrections. Mean residual GTV deviation (3D distance) following GTV-based systematic correction (mean ± 1 standard deviation 4.8 ± 1.5 mm) is significantly lower than for systematic skeletal-based (6.5 ± 2.9 mm, p = 0.015), and weekly skeletal-based correction (7.2 ± 3.0 mm, p = 0.001), but is not significantly lower than daily skeletal-based correction (5.4 ± 2.6 mm, p = 0.34). In two cases, first-day CBCT images reveal tumor changes-one showing tumor growth, the other showing large tumor displacement-that are not readily observed in radiographs. Differences in computed GTV deviations between respiration-correlated and respiration-averaged images are 0.2 ± 1.8 mm in the superior-inferior direction and are of similar magnitude in the other directions. CONCLUSIONS: An off-line protocol to correct GTV-based systematic error in locally advanced lung tumor cases can be effective at reducing tumor deviations, although the findings need confirmation with larger patient statistics. In some cases, a single cone-beam CT can be useful for assessing tumor changes early in treatment, if more than a few days elapse between simulation and the start of treatment. Tumor deviations measured with respiration-averaged CT and CBCT images are consistent with those measured with respiration-correlated images; the respiration-averaged method is more easily implemented in the clinic.

Willingness to pay for kidney transplantation among chronic kidney disease patients in Ghana.

BACKGROUND: Kidney transplantation is the preferred treatment for patients with end stage renal disease. However, it is largely unavailable in many sub-Sahara African countries including Ghana. In Ghana, treatment for end stage renal disease including transplantation, is usually financed out-of-pocket. As efforts continue to be made to expand the kidney transplantation programme in Ghana, it remains unclear whether patients with Chronic Kidney Disease (CKD) would be willing to pay for a kidney transplant. AIM: The aim of the study was to assess CKD patients' willingness to pay for kidney transplantation as a treatment option for end stage renal disease in Ghana. METHODS: A facility based cross-sectional study conducted at the Renal Outpatient clinic and Dialysis Unit of Korle-Bu Teaching Hospital among 342 CKD patients 18 years and above including those receiving haemodialysis. A consecutive sampling approach was used to recruit patients. Structured questionnaires were administered to obtain information on demographic, socio-economic, knowledge about transplant, perception of transplantation and willingness to pay for transplant. In addition, the INSPIRIT questionnaire was used to assess patients' level of religiosity and spirituality. Contingent valuation method (CVM) method was used to assess willingness to pay (WTP) for kidney transplantation. Logistic regression model was used to determine the significant predictors of WTP. RESULTS: The average age of respondents was 50.2 ± 17.1 years with most (56.7% (194/342) being male. Overall, 90 out of the 342 study participants (26.3%, 95%CI: 21.7-31.3%) were willing to pay for a kidney transplant at the current going price (≥ $ 17,550) or more. The median amount participants were willing to pay below the current price was $986 (IQR: $197 -$1972). Among those willing to accept (67.3%, 230/342), 29.1% (67/230) were willing to pay for kidney transplant at the prevailing price. Wealth quintile, social support in terms of number of family friends one could talk to about personal issues and number of family members one can call on for help were the only factors identified to be significantly predictive of willingness to pay (p-value < 0.05). CONCLUSION: The overall willingness to pay for kidney transplant is low among chronic kidney disease patients attending Korle-Bu Teaching Hospital. Patients with higher socio-economic status and those with more family members one can call on for help were more likely to pay for kidney transplantation. The study's findings give policy makers an understanding of CKD patients circumstances regarding affordability of the medical management of CKD including kidney transplantation. This can help develop pricing models to attain an ideal poise between a cost effective but sustainable kidney transplant programme and improve patient access to this ultimate treatment option.

Knowledge and Willingness to Donate Kidneys for Transplantation in Ghana: A Cross-Sectional Survey.

BACKGROUND: The main treatment modalities for chronic kidney disease (CKD) are dialysis and kidney transplantation. While kidney transplantation provides better survival and quality of life outcomes, it is a new treatment option in Ghana. Finding kidney donors for transplant may be a major challenge due to varied views of the public. METHODS: This cross-sectional study was carried out in 5 purposively selected communities in the Greater Accra region in Ghana. Structured questionnaires and standardized instruments were used to assess sociodemographic characteristics, spirituality, and perception of kidney transplantation. RESULTS: The mean age of the 480 participants was 29.60 ± 10.65 years. The proportion of men was 51%. The average score for knowledge of participants on kidney donation was 4.8 ± 2.6. The level of spirituality score was 25.4 ± 3.89. Approximately 48% (231/480) of participants were willing to donate a kidney while still alive. Willingness to donate when dead was 72% (344/480). Willingness to donate a kidney when dead was significantly lower among the participants in the older age groups. High level of knowledge about kidney transplantation, being employed, basic formal education, and never married were associated with willingness to donate kidney (P < .05). CONCLUSION: Our results suggest that participants have a low level of knowledge regarding kidney transplantation, while about two-thirds are willing to donate only after death. Continuous public education is key to raise public awareness of the need for kidney transplants. This will support the Ministry of Health in their efforts to institute a kidney transplant program in Ghana.

Toward personalized dose-prescription in locally advanced non-small cell lung cancer: Validation of published normal tissue complication probability models.

PURPOSE: To identify published normal tissue complication probability (NTCP) models suitable for patient-specific dose-prescription in locally advanced non-small cell lung cancer (LA-NSCLC) through in-house validation. MATERIAL AND METHODS: From eight previously published candidate NTCP models (≥grade 2 acute esophagitis and radiation pneumonitis; AE2, RP2), patient-specific dose-responses were calculated using model variables and fractionation-corrected doses for 241 LA-NSCLC patients treated with chemo-IMRT to 50-80 Gy@1.8-2.0 Gy between 2004 and 2014 (AE2/RP2 rate: 50%/12%). A model was judged final if it significantly predicted AE2 or RP2 (p ≤ 0.05), was discriminative and well calibrated (AUC > 0.60; Hosmer-Lemeshow test pHL > 0.05), which were assessed as the median over 1000 bootstrap samples. RESULTS: Models for AE2 had superior discrimination to RP2 models (AUC = 0.63-0.65 vs. 0.51-0.65). The final AE2 model included mean esophageal dose and concurrent chemotherapy (AUC = 0.65; p < 0.0001). The final RP2 model was a slightly adjusted version of the RP2 model with the best discrimination, and included age, mean lung dose, and pulmonary comorbidity (AUC = 0.73; p < 0.0001). CONCLUSION: Of the eight investigated and published NTCP models, one model successfully described AE2 and one slightly adjusted model successfully described RP2 in the independent cohort. Estimates from these two NTCP models will, therefore, be considered internally when prescribing patient-specific doses in LA-NSCLC patients.

Radiotherapeutic implications of the updated ICRP thresholds for tissue reactions related to cataracts and circulatory diseases.

Radiation therapy of cancer patients involves a trade-off between a sufficient tumour dose for a high probability of local control and dose to organs at risk that is low enough to lead to a clinically acceptable probability of toxicity. The International Commission on Radiological Protection (ICRP) reviewed epidemiological evidence and provided updated estimates of 'practical' threshold doses for tissue injury, as defined at the level of 1% incidence, in ICRP Publication 118. Particular attention was paid to cataracts and circulatory diseases. ICRP recommended nominal absorbed dose threshold for these outcomes as low as 0.5 Gy. Threshold doses for tissue reactions can be reached in some patients during radiation therapy. Modern treatment planning systems do not account for such low doses accurately, and doses to therapy patients from associated imaging procedures are not generally accounted for. While local control is paramount, the observations of ICRP Publication 118 suggest that radiation therapy plans and processes should be examined with particular care. The research needs are discussed in this paper.

Phase and amplitude binning for 4D-CT imaging.

We compare the consistency and accuracy of two image binning approaches used in 4D-CT imaging. One approach, phase binning (PB), assigns each breathing cycle 2pi rad, within which the images are grouped. In amplitude binning (AB), the images are assigned bins according to the breathing signal's full amplitude. To quantitate both approaches we used a NEMA NU2-2001 IEC phantom oscillating in the axial direction and at random frequencies and amplitudes, approximately simulating a patient's breathing. 4D-CT images were obtained using a four-slice GE Lightspeed CT scanner operating in cine mode. We define consistency error as a measure of ability to correctly bin over repeated cycles in the same field of view. Average consistency error mue+/-sigmae in PB ranged from 18%+/-20% to 30%+/-35%, while in AB the error ranged from 11%+/-14% to 20%+/-24%. In PB nearly all bins contained sphere slices. AB was more accurate, revealing empty bins where no sphere slices existed. As a proof of principle, we present examples of two non-small cell lung carcinoma patients' 4D-CT lung images binned by both approaches. While AB can lead to gaps in the coronal images, depending on the patient's breathing pattern, PB exhibits no gaps but suffers visible artifacts due to misbinning, yielding images that cover a relatively large amplitude range. AB was more consistent, though often resulted in gaps when no data existed due to patients' breathing pattern. We conclude AB is more accurate than PB. This has important consequences to treatment planning and diagnosis.

Evaluation of an automated deformable image matching method for quantifying lung motion in respiration-correlated CT images.

We have evaluated an automated registration procedure for predicting tumor and lung deformation based on CT images of the thorax obtained at different respiration phases. The method uses a viscous fluid model of tissue deformation to map voxels from one CT dataset to another. To validate the deformable matching algorithm we used a respiration-correlated CT protocol to acquire images at different phases of the respiratory cycle for six patients with nonsmall cell lung carcinoma. The position and shape of the deformable gross tumor volumes (GTV) at the end-inhale (EI) phase predicted by the algorithm was compared to those drawn by four observers. To minimize interobserver differences, all observers used the contours drawn by a single observer at end-exhale (EE) phase as a guideline to outline GTV contours at EI. The differences between model-predicted and observer-drawn GTV surfaces at EI, as well as differences between structures delineated by observers at EI (interobserver variations) were evaluated using a contour comparison algorithm written for this purpose, which determined the distance between the two surfaces along different directions. The mean and 90% confidence interval for model-predicted versus observer-drawn GTV surface differences over all patients and all directions were 2.6 and 5.1 mm, respectively, whereas the mean and 90% confidence interval for interobserver differences were 2.1 and 3.7 mm. We have also evaluated the algorithm's ability to predict normal tissue deformations by examining the three-dimensional (3-D) vector displacement of 41 landmarks placed by each observer at bronchial and vascular branch points in the lung between the EE and EI image sets (mean and 90% confidence interval displacements of 11.7 and 25.1 mm, respectively). The mean and 90% confidence interval discrepancy between model-predicted and observer-determined landmark displacements over all patients were 2.9 and 7.3 mm, whereas interobserver discrepancies were 2.8 and 6.0 mm. Paired t tests indicate no significant statistical differences between model predicted and observer drawn structures. We conclude that the accuracy of the algorithm to map lung anatomy in CT images at different respiratory phases is comparable to the variability in manual delineation. This method has therefore the potential for predicting and quantifying respiration-induced tumor motion in the lung.

Reduction of organ motion effects in IMRT and conformal 3D radiation delivery by using gating and tracking techniques.

Respiration-gated radiotherapy offers a significant potential for improvement in the irradiation of tumour sites affected by respiratory motion such as lung, breast and liver tumours. An increased conformality of irradiation fields leading to decreased complications rates of organs at risk (lung, heart) is expected. Four main strategies are used to reduce respiratory motion effects: integration of respiratory movements into treatment planning, breath-hold techniques, respiratory gating techniques, and tracking techniques. Measurements of respiratory movements can be performed either in a representative sample of the general population, or directly on the patient before irradiation. The measured amplitude could be applied to a geometrical margin or integrated into dosimetry. However, these strategies remain limited for very mobile tumours, in which this approach results in larger irradiated volumes. Reduction of breathing motion can be achieved by using either breath-hold techniques or respiration synchronized gating techniques. Breath-hold can be achieved with active techniques, in which a valve temporarily blocks airflow of the patient, or passive techniques, in which the patient voluntarily breath-holds. Synchronized gating techniques use external devices to predict the phase of the respiration cycle while the patient breaths freely. Another category is tumour tracking, which consists of two major aspects: real-time localization of, and real-time beam adaptation to, a constantly moving tumour. These techniques are presently being investigated in several medical centres worldwide. Although promising, the first results obtained in lung and liver cancer patients require confirmation. This paper describes the most frequently used gating and tracking techniques and the main published clinical reports.

Modeling the development of metastases from primary and locally recurrent tumors: comparison with a clinical data base for prostatic cancer.

For many types of cancer, patients who relapse locally following localized treatment such as surgery or radiation therapy are found to have a higher incidence of distant metastases than those who are locally controlled. In this study we developed a mathematical model to investigate whether the excess distant metastases arise mainly from the local recurrence or whether the primary tumors in this group of patients have an intrinsically higher metastatic potential than those of locally controlled patients of the same clinical stage. The parameters of the model were chosen to be representative of prostate cancer and the calculated results were compared with published clinical data for carcinoma of the prostate. The best agreement with the data was seen for parameters which imply somewhat more "aggressive" primary tumors for locally relapsing patients, yielding relatively high rates of micrometastatic dissemination prior to initial diagnosis. However, the model calculations indicate that more than half of the metastases in such patients originated in association with the development of a local recurrence. Therefore, achieving local control in this group of patients would be beneficial in improving long term survival.

Can current models explain the lack of liver complications in Y-90 microsphere therapy?

Normal liver complications have not been observed in Y-90 microsphere therapy of hepatic tumors [selective internal radiation (SIR)], despite clinical studies reporting estimated absorbed doses to normal liver between 100 and 150 Gy. The purpose of the study was to see whether predictions of normal tissue complication probability (NTCP) models for liver based on clinical data from external beam therapy are consistent with clinical results of SIR. Liver NTCP was calculated using a parallel architecture model and normal liver dose-volume histograms that have been proposed for SIR. A parallel model including internal functional subunit structure is also proposed. Dose rate effects are incorporated. A criterion for comparing model calculations with clinical data is presented. For the parallel architecture model, the predicted NTCP is sensitive to the dose distribution in normal liver and to the model parameters, particularly the repair time. With reasonable assumptions about the microsphere distribution, the parallel model with parameters deduced from external beam therapy outcome analysis is consistent with the observed lack of liver complications. Inclusion of FSU structure widens the range of assumptions under which consistency is found. The parallel model can be consistent with the clinically observed lack of liver complications in SIR. More information about the activity distribution and the radiobiology of normal liver under conditions typical of microsphere therapy should be sought.

Modeling the effects of inhomogeneous dose distributions in normal tissues.

Conformal radiation therapy frequently produces inhomogeneous dose distributions in normal tissues near the target. Most mathematical models of normal tissue complication probabilities (NTCP) are based on uniform whole or partial organ irradiation, and the model parameters are chosen to obtain agreement with clinical outcomes in these simple situations. Frequently used NTCP models and methods for including inhomogeneous dose distributions in model calculations are outlined in this report. It has been found that the model adopted may qualitatively affect prediction of complications. Limitations placed on current models by the scarcity of reliable complications data and other approaches to using the calculated dose distribution to predict NTCP are discussed.

Monte Carlo evaluation of tissue inhomogeneity effects in the treatment of the head and neck.

PURPOSE: To use Monte Carlo dose calculation to assess the degree to which tissue inhomogeneities in the head and neck affect static field conformal, computed tomography (CT)-based 6-MV photon treatment plans. METHODS AND MATERIALS: We retrospectively studied the three-dimensional treatment plans that had been used for the treatment of 5 patients with tumors in the nasopharyngeal or paranasal sinus regions. Two patients had large surgical cavities. The plans were designed with a clinical treatment planning system that uses a measurement-based pencil-beam dose-calculation algorithm with an equivalent path-length inhomogeneity correction. Each plan employs conformally-shaped 6-MV photon beams. Patient anatomy and electron densities were obtained from the treatment planning CT images. For each plan, the dose distribution was recalculated with the Monte Carlo method, utilizing the same beam geometry and CT images. The Monte Carlo method accurately accounts for the perturbation effects of local tissue heterogeneities. The Monte Carlo calculated dose distributions were compared with those from the clinical treatment planning system. RESULTS: The degree to which tissue inhomogeneity affects the dose distributions of individual fields varies with the specific anatomic geometry, especially the size and location of air cavities in relation to the beam orientation and field size. Most of the beam apertures completely enclose the air cavities within or adjacent to the gross tumor volume (GTV). Equivalent squares (including blocking) ranged from approximately 5 to 9.5 cm. A common feature observed for individual fields is that the Monte Carlo calculated doses to tissue directly behind and within an air cavity are lower. However, after combining the fields employed in each treatment plan, the overall dose distribution shows only small differences between the two methods. For all 5 patients, the Monte Carlo calculated treatment plans showed a slightly lower dose received by the 95% of target volume (D(95)) than the plans calculated with the pencil-beam algorithm. The average difference in the target volume encompassed by the prescription isodose line was less than 2.2%. The difference between the dose-volume histograms (DVHs) of the GTV was generally small. For the brainstem and chiasm, the DVHs of the two plans were similar. For the spinal cord, differences in the details of the DHV and the dose to 1 cc (D(1cc)) of the structure were observed, with Monte Carlo calculation generally predicting increased dose indices to the spinal cord. However, these changes are not expected to be clinically significant. CONCLUSION: For 6-MV photons, the effects of both normal tissue inhomogeneities and surgical air cavities on the target coverage were adequately accounted for by conventional pencil beam methods for all of the cases studied. Although differences in details of the DVHs of the normal structures were observed, depending on whether Monte Carlo or pencil-beam algorithm was used for calculation, these differences are not expected to be clinically significant. In general, the pencil-beam calculation corrected for primary attenuation by the equivalent pathlength is a sufficiently accurate method for head-and-neck treatment planning using 6-MV photons.

Dosimetric considerations in radiation therapy of coin lesions of the lung.

PURPOSE: The dose distribution in small lung lesions (coin lesions) is determined by the combined effects of reduced attenuation and electronic disequilibrium. The magnitude of the dose delivered also depends on the algorithm used to correct for reduced lung density. These effects are investigated experimentally and computationally for 10 MV photons. METHODS AND MATERIALS: Using a polystyrene miniphantom embedded in cork or cedar, thermoluminescent dosimetry and film dosimetry was performed to investigate interface effects and the central dose per monitor unit (MU). Three frequently applied calculation techniques--no density correction, ratio of tissue maximum ratios (TMRs), and the Batho correction--were also used to calculate the dose per MU. The measurements and calculations were compared with a one-dimensional phenomenological theory with parameters taken from the literature. RESULTS: The measurements at the entrance surface and center of the miniphantom agreed well with the predictions of the phenomenological theory. The interface regions are usually thin enough (2-3 mm) to be clinically unimportant for 10 MV. Depending on the algorithm used to correct for decreased lung density, the lesion dose may be larger or smaller than the prescribed dose by as much as 20% in extreme cases. A clinical example is presented. CONCLUSIONS: In comparing clinical results of treatments of small lung lesions, it is important to be aware of the density correction used.

Clinical implications of I-125 dosimetry of bone and bone-soft tissue interfaces.

The dose to bone from I-125 photon interactions is expected to be approximately five times greater than the dose to soft tissue for the same photon fluence because of the dominance of the photoelectric effect. However, adverse clinical effects are not observed for I-125 implants near bone. Both the strong absorption of I-125 photons in bone and the narrowness (about 10 mu) of the high dose transition zone at a bone-soft tissue interface act to limit the volume of radiation sensitive tissue in the high dose region. Examples of calculated implant dose distributions in bone and in soft tissue cavities in bone are presented. Radiobiological measurements are consistent with the theoretical interface calculations. Calculation of the macroscopic dose distribution uses a recently measured radial dose function, while at the bone-soft tissue interface an analytic theory of the transition zone that is applicable to regular shaped cavities is used. Radiobiological experiments comparing cell survival for cells irradiated with 70 kvP X rays at Al-water and polystyrene-water interfaces are consistent with the transition zone calculations.

Evaluation of respiratory movement during gated radiotherapy using film and electronic portal imaging.

PURPOSE: To evaluate the effectiveness of a commercial system(1) in reducing respiration-induced treatment uncertainty by gating the radiation delivery. METHODS AND MATERIALS: The gating system considered here measures respiration from the position of a reflective marker on the patient's chest. Respiration-triggered planning CT scans were obtained for 8 patients (4 lung, 4 liver) at the intended phase of respiration (6 at end expiration and 2 at end inspiration). In addition, fluoroscopic movies were recorded simultaneously with the respiratory waveform. During the treatment sessions, gated localization films were used to measure the position of the diaphragm relative to the vertebral bodies, which was compared to the reference digitally reconstructed radiograph derived from the respiration-triggered planning CT. Variability was quantified by the standard deviation about the mean position. We also assessed the interfraction variability of soft tissue structures during gated treatment in 2 patients using an amorphous silicon electronic portal imaging device. RESULTS: The gated localization films revealed an interfraction patient-averaged diaphragm variability of 2.8 +/- 1.0 mm (error bars indicate standard deviation in the patient population). The fluoroscopic data yielded a patient-averaged intrafraction diaphragm variability of 2.6 +/- 1.7 mm. With no gating, this intrafraction excursion became 6.9 +/- 2.1 mm. In gated localization films, the patient-averaged mean displacement of the diaphragm from the planning position was 0.0 +/- 3.9 mm. However, in 4 of the 8 patients, the mean (over localization films) displacement was >4 mm, indicating a systematic displacement in treatment position from the planned one. The position of soft tissue features observed in portal images during gated treatments over several fractions showed a mean variability between 2.6 and 5.7 mm. The intrafraction variability, however, was between 0.6 and 1.4 mm, indicating that most of the variability was due to patient setup errors rather than to respiratory motion. CONCLUSIONS: The gating system evaluated here reduces the intra- and interfraction variability of anatomy due to respiratory motion. However, systematic displacements were observed in some cases between the location of an anatomic feature at simulation and its location during treatment. Frequent monitoring is advisable with film or portal imaging.