Descriptive analysis of poisoning cases involving attention deficit hyperactivity disorder medications in Hong Kong.

INTRODUCTION: The number of poisoning cases involving attention deficit hyperactivity disorder (ADHD) medications has reportedly risen with their increased use. However, there is limited relevant evidence from Asia. We analysed the characteristics of poisoning events involving these medications in Hong Kong. METHODS: We retrieved data regarding ADHD medication-related poisoning cases from the Hong Kong Poison Information Centre and conducted a descriptive analysis of the demographic information and poisoning information including sources of cases, exposure reason, exposure location, and outcome. The HKPIC data were linked with the Hospital Authority Clinical Data Analysis and Reporting System (CDARS) via de-identified Accident and Emergency numbers of public hospitals to investigate clinical characteristics. We also retrieved ADHD medication prescription records from the CDARS, then compared trends between poisoning cases and ADHD medication use. RESULTS: We identified 72 poisoning cases involving ADHD medications between 2009 and 2019, of which approximately 70% occurred in the affected individual's residence; most were intentional poisoning events (65.3%). No statistically significant association was observed between ADHD medication prescription trends and poisoning events involving ADHD medications. Of the 66 cases (91.7%) successfully linked to CDARS, 40 (60.6%) occurred in individuals with ADHD (median age: 14 years); 26 (39.4%) occurred in individuals who lacked ADHD (median age: 33 years) but displayed higher rates of other mental disorders including depression and anxiety. CONCLUSION: No significant correlation was evident between ADHD medication prescriptions and poisoning events involving ADHD medications. However, medication management and caregiver education must be emphasised to prevent potential poisoning events.

Elevated risk of multimorbidity post-COVID-19 infection: protective effect of vaccination.

BACKGROUND: It is unclear how the coronavirus disease 2019 (Covid-19) pandemic has affected multimorbidity incidence among those with one pre-existing chronic condition, as well as how vaccination could modify this association. AIM: To examine the association of Covid-19 infection with multimorbidity incidence among people with one pre-existing chronic condition, including those with prior vaccination. DESIGN: Nested case-control study. METHODS: We conducted a territory-wide nested case-control study with incidence density sampling using Hong Kong electronic health records from public healthcare facilities and mandatory Covid-19 reports. People with one listed chronic condition (based on a list of 30) who developed multimorbidity during 1 January 2020-15 November 2022 were selected as case participants and randomly matched with up to 10 people of the same age, sex and with the same first chronic condition without having developed multimorbidity at that point. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) of multimorbidity. RESULTS: In total, 127 744 case participants were matched with 1 230 636 control participants. Adjusted analysis showed that there were 28%-increased odds of multimorbidity following Covid-19 [confidence interval (CI) 22% to 36%] but only 3% (non-significant) with prior full vaccination with BNT162b2 or CoronaVac (95% CI -2% to 7%). Similar associations were observed in men, women, older people aged 65 or more, and people aged 64 or younger. CONCLUSIONS: We found a significantly elevated risk of multimorbidity following a Covid-19 episode among people with one pre-existing chronic condition. Full vaccination significantly reduced this risk increase.

Antihypertensive Agents and Incident Alzheimer's Disease: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Hypertension is a recognized risk factor for dementia. However, evidence for using antihypertensive agents to reduce the risk of Alzheimer's disease in people with hypertension is inconclusive. OBJECTIVE: To examine the association between antihypertensive agents and the incidence of Alzheimer's disease in adults with hypertension and normal cognition. DESIGN: We conducted a systemic review and performed meta-analyses using Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, Web of science and Scopus, from inception to 18th February 2022. SETTING: Cohort and case-control studies. PARTICIPANTS: Adults ≥ 40 years with hypertension and normal cognition. INTERVENTION: Antihypertensive agents. MEASUREMENTS: We performed two separate meta-analyses, pooling the adjusted relative risk (RR) of non-antihypertensive comparator and antihypertensive comparator study design. RESULTS: We included nine studies, totalling 1,527,410 individuals. Meta-analysis of non-antihypertensive user comparator studies found that the use of antihypertensive agents is associated with a reduced risk of incident Alzheimer's disease (RR= 0.94, 95% CI 0.90-0.99; p=0.01). Meta-analysis of antihypertensive comparator studies found evidence that angiotensin II receptor blocker users are associated with a reduction in the risk of Alzheimer's disease compared to other antihypertensive agents (RR= 0.78, 95% CI 0.68-0.88; p< 0.001). CONCLUSION: Our review provides evidence that the use of antihypertensive agents is associated with a lower incidence of Alzheimer's disease. The use of angiotensin II receptor blockers may provide the most benefit among antihypertensive agents. Lowering raised blood pressure may not be the only mechanism for cognitive protection and further investigation of the effects of angiotensin II on cognition is indicated.

The effectiveness of exercises on fall and fracture prevention amongst community elderlies: A systematic review and meta-analysis.

OBJECTIVE: To analyze the effectiveness of exercise interventions on falls and fall-related fracture prevention among community-dwelling elderlies. METHODS: Literature search was conducted in Pubmed and Embase. Keywords used for literature search were "fracture" AND "fall" AND "exercise". Randomized controlled trials involving community-dwelling elderlies older than 60 years old with physical exercises as intervention were included. A systematic review and meta-analysis was performed. The primary outcomes were falls and fractures. RESULTS: Twelve studies were included and 4784 participants were involved with a mean age of 75.4. The most common exercise interventions were strength and balance exercises. The results of meta-analysis of 11 studies showed that exercise intervention had beneficial effect on fall prevention (RR = 0.71, 95% CI, 0.62-0.82; I2 = 24%, p < 0.0001). The effect was better when exercise intervention applied to women participants (RR = 0.64, 95% CI, 0.49-0.83; I2 = 28%, p = 0.00009) compared to men and women participants (RR = 0.75, 95% CI, 0.64-0.89; I2 = 24%, p = 0.001). The results of meta-analysis of seven studies showed that physical exercise had significant effect on fracture prevention (RR = 0.54, 95% CI, 0.35-0.83; I2 = 25%, p = 0.005). However, the effect was significant when exercise intervention applied to women participants only (RR = 0.37, 95% CI, 0.20-0.67; I2 = 0%, p = 0.001) but not significant when exercise intervention applied to both genders (RR = 0.80, 95% CI, 0.58-1.09; I2 = 0%, p = 0.15). CONCLUSION: Exercise interventions, especially the combination of strength and balance training, were effective in preventing falls. Resistance exercises and jumping exercises were effective for fracture prevention among community-dwelling older population. The effectiveness of exercise interventions on fracture prevention have more significant effect on women. Further studies are needed to test the effectiveness of exercise interventions in men. TRANSLATIONAL POTENTIAL: The use of effective exercises or biophysical interventions including vibration therapy can be incorporated into Fracture Liaison Services to prevent future fall and fracture.

Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.

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.

Total body irradiation with an arc and a gravity-oriented compensator.

PURPOSE: To deliver uniform dose distributions for total-body irradiation (TBI) with an arc field and a gravity-oriented compensator. This technique allows the patient to be treated lying on the floor in a small treatment room. METHODS AND MATERIALS: Through the sweeping motion of the gantry, a continuous arc field can deliver a large field to a patient lying on the floor. The dose profile, however, would not be uniform if no compensator were used, due to the effects of inverse square variation of beam intensity with distance as well as the slanted depth in patient. To solve this problem, a gravity-oriented compensator made of cerrobend alloy was designed. This compensator has a cross-section of an inverted isosceles triangle, with the apex always pointing downward, due to gravity. By properly selecting the thickness of the compensator, the width of the base, and the distance between the pivots to the base, the difference in the path length through the compensator can be made just right to compensate the effects of inverse-square and slanted depth, thus producing a uniform dose profile. RESULTS: Arc fields with a gravity-oriented compensator were used for 6, 10, 15, and 18 MV photon beams. The arc field can cover a patient with a height up to 180 cm. The field width was chosen from 32 to 40 cm at the machine isocenter. The optimal thickness of the compensator was found to be 2.5 cm, and its base was 25 cm wide. The distance from the pivot points to the flat surface of the compensator proximal to the beam ranges from 13 to 14 cm for different beam energies. The dose uniformity at a depth of 10 cm is within +/-5% for all beam energies used in this study. CONCLUSIONS: Highly uniform dose profiles for TBI treatments can be delivered with an arc and a gravity-oriented compensator. The proposed technique is simple and versatile. A single compensator can be used for all energies, because the amount of compensation can be adjusted by changing the distance to the pivot and/or the field size.

Lying-on position of total skin electron therapy.

PURPOSE: A technique for whole-body electron therapy with the patient in a lying position has been developed. This technique allows Total Skin Electron Therapy (TSET) for those patients who were previously unable to be treated in a conventional standing position. METHODS AND MATERIALS: This study was carried out on a Varian 2100C linear accelerator with a 6 MeV high dose rate electron beam. The collimator was open to a width of 36 x 36 cm. There were two main procedures, with six dual-field techniques: 1) two static AP/PA vertical dual fields (VDF): the patient laid on the floor transversely under the collimator when the gantry was in a vertical position. A 0.6 cm acrylic board was placed 15 cm away from the patient, then the gantry was rotated 25 degrees clockwise and counterclockwise to treat the patient in the supine and prone positions, respectively. 2) Four oblique junction fields (OJF): the patient laid on the floor in a prone and supine position parallel to the wave guide at (227 - body thickness x tan 60 degrees) cm away from the vertical axis of the gantry, then the gantry was rotated 60 degrees toward the patient. A 0.6 cm acrylic board was placed 15 cm away from the patient perpendicular to the beam. The patient was move along the field central axis. It allowed the patient's body to be within the 160 cm effective treatment profile. When the patient's body axis move 5 degrees toward the lateral side of the field central axis, we could obtain a better dose distribution in the vertex of the scalp and the soles of the feet. The angle of the VDF was measured by chamber detectors to obtain the effective treatment profile. Likewise, the optimal profile for the OJF was determined by the same procedures. The Rando phantom was used to measure the superficial dose of the body. RESULTS: The dimension of effective treatment profile for the VDF was 188 x 72 cm at 87% dose level For the OJF, we had to move the patient along the field central axis to obtain the effective treatment profile in a 180 x 85 cm dimension at a 87% dose level. The vertex and sole dose measured in this setup was in the range of 80-88%. CONCLUSIONS: The empirical data showed that the lying-on position for TSET was technically feasible. The dose distribution in the body surface was also compatible with the Stanford standing technique. The nonambulatory skin malignancy patient can be treated in a comfortable and reproducible position.

Effect of ocular implants of different materials on the dosimetry of external beam radiation therapy.

PURPOSE: To study the attenuation and scattering effects of ocular implants, made from different materials, on the dose distributions of a 6 MV photon beam, and 6, 9, and 12 MeV electron beams used in orbital radiotherapy. METHODS AND MATERIALS: Central axis depth-dose measurements were performed in a polystyrene phantom with embedded spherical ocular implants using film dosimetry of a 6 MV photon beam and electron beams of 6, 9, and 12 MeV energy. The isodose distributions were also calculated by a computerized treatment planning system using computerized tomography (CT) scans of a polystyrene phantom that had silicone, acrylic, and hydroxyapatite ocular implants placed into it. RESULTS: Electron beam dose distributions display distortions both on the measured and calculated data. This effect is most accentuated for the hydroxyapatite implants, for which the transmissions through ocular implants are on the order of 93% for the 6 MV photon beam, and range from 60% for 6 MeV electrons to 90% for 12 MeV electrons. CONCLUSION: We studied the effect of ocular implants of various materials, embedded in a polystyrene phantom, on the dose distributions of a 6 MV photon beam, and 6, 9, and 12 MeV electron beams. Our investigations show that while 6 MV photons experience only a few percent attenuation, lower energy electron beam with 60% transmission is not a suitable choice of treating tumors behind the ocular implants.

The use of a multi-leaf collimator for conformal radiotherapy of carcinomas of the prostate and nasopharynx.

We investigate the use of a multi-leaf collimator for conformal radiation therapy of carcinomas of the prostate and of the nasopharynx. Following verification of dose calculation algorithms for multi-leaf collimated fields using film dosimetry, we compute dose distributions for multi-field conformal treatment using fields shaped with either the multi-leaf collimator or conventional cerrobend blocks. We compare the two sets of treatment plans using graphical isodose displays, tissue specific dose volume histograms, tumor control probabilities, and normal tissue complication probabilities. We also incorporate setup errors into the calculated dose distributions to assess the effect of treatment uncertainties on the various criteria. Based on these comparisons, we conclude that for multi-field conformal radiotherapy for these two disease sites, the use of multi-leaf collimation is equivalent to that of conventional cerrobend blocks.

Relative profile and dose verification of intensity-modulated radiation therapy.

PURPOSE: To develop a quality assurance (QA) procedure to assess the intensity profile and dosimetry for intensity-modulated (IM) treatment fields using electronic portal imaging devices (EPIDs). METHODS AND MATERIALS: A series of rapidly acquired (approximately 1/sec) portal images are summed and converted to dose. For relative intensity QA, the intended profile is subtracted point-by-point from the measured profile forming a series of error values. The standard deviation, sigma, of the errors, a measure of the goodness of the match, is minimized by applying a normalization and uniform scatter subtraction from the measured profile. For dose verification (dose to isocenter), an empirically determined phantom-correction factor is added to incorporate the effect of patient presence on EPID readings. Seventy prostate treatment fields were used in a phantom study to verify these approaches. Sensitivity was studied by creating artificial mismatches. RESULTS: The average sigma for relative profile verification is 3.3% (percentage of average intended intensity) whereas artificial mismatches resulted in sigma values from 5% to 27%. The average isocentric dose calculated from EPID readings is 1.001 relative to the planned dose with a standard deviation of 0.018. CONCLUSIONS: An EPID can be used for profile verification and absolute isocentric dose measurement for IM fields.

Arbitrary oblique image sections for 3-D radiation treatment planning.

Methods for selecting and computing arbitrary image sections for displaying anatomic and isodose information for three-dimensional treatment planning are investigated. Selection of the desired plane may be made by defining a plane that is perpendicular to an existing image section (called the base image) and passing through a line on the base image. Alternatively, the anatomic structures displayed perspectively in three dimensions as a series of contours that can be rotated and translated may be used to define an arbitrary plane for image reconstruction. The viewing screen is considered to be the plane of interest. As a typical three-dimensional image of 30 to 60 sections requires considerable computer storage (on the order of 25 megabytes), a reconstruction algorithm may need extensive memory space or CPU and disk I/O time. Of the schemes examined, we believe the following is the most efficient. One pair of images is read from the disk at a time in sequence and intersections of the rows of the cutting plane with the box formed by the consecutive images are computed. Pixel values of all points between the given images are computed by interpolation. Special cases, such as the cutting plane being parallel to or coincident with an existing image, must be considered separately.

A comprehensive three-dimensional radiation treatment planning system.

A comprehensive software system has been developed to allow 3-dimensional planning of radiation therapy treatments using the extensive anatomical information made available by imaging modalities such as CT and MR. Biological structures of interest and tumor volumes are defined by outlines drawn on a sequence of CT slices. Beam set-ups may then be determined in three dimensions by displaying the structure contours in a beam's eye view, or in two dimensions using a single CT cut. Each beam defined may be shaped by the specification of block aperture contours, and its intensity may be modified with the use of planar compensators. 3D dose calculation algorithms are discussed. To evaluate the calculation results, dose volume histograms are provided, as well as various types of displays in two and three dimensions, including dose on arbitrarily oriented planes, dose on the surface of anatomical objects, and isodose surfaces. Computer generated beam films are also available as an aid in patient set-up verification. These tools, and others, provide the basis for a comprehensive 3D system that can be used throughout the treatment planning process.

Planning, delivery, and quality assurance of intensity-modulated radiotherapy using dynamic multileaf collimator: a strategy for large-scale implementation for the treatment of carcinoma of the prostate.

PURPOSE: To improve the local control of patients with adenocarcinoma of the prostate we have implemented intensity modulated radiation therapy (IMRT) to deliver a prescribed dose of 81 Gy. This method is based on inverse planning and the use of dynamic multileaf collimators (DMLC). Because IMRT is a new modality, a major emphasis was on the quality assurance of each component of the process and on patient safety. In this article we describe in detail our procedures and quality assurance program. METHODS AND MATERIALS: Using an inverse algorithm, we have developed a treatment plan consisting five intensity-modulated (IM) photon fields that are delivered with DMLC. In the planning stage, the planner specifies the number of beams and their directions, and the desired doses for the target, the normal organs and the "overlap" regions. Then, the inverse algorithm designs intensity profiles that best meet the specified criteria. A second algorithm determines the leaf motion that would produce the designed intensity pattern and produces a DMLC file as input to the MLC control computer. Our quality assurance program for the planning and treatment delivery process includes the following components: 1) verification of the DMLC field boundary on localization port film, 2) verification that the leaf motion of the DMLC file produces the planned dose distribution (with an independent calculation), 3) comparison of dose distribution produced by DMLC in a flat phantom with that calculated by the treatment planning computer for the same experimental condition, 4) comparison of the planned leaf motions with that implemented for the treatment (as recorded on the MLC log files), 5) confirmation of the initial and final positions of the MLC for each field by a record-and-verify system, and 6) in vivo dose measurements. RESULTS: Using a five-field IMRT plan we have customized dose distribution to conform to and deliver 81 Gy to the PTV. In addition, in the overlap regions between the PTV and the rectum, and between the PTV and the bladder, the dose is kept within the tolerance of the respective organs. Our QA checks show acceptable agreement between the planned and the implemented leaf motions. Correspondingly, film and TLD dosimetry indicates that doses delivered agrees with the planned dose to within 2%. As of September 15, 1996, we have treated eight patients to 81 Gy with IMRT. CONCLUSION: For complex planning problems where the surrounding normal tissues place severe constraints on the prescription dose, IMRT provides a powerful and efficient solution. Given a comprehensive and rigorous quality-assurance program, the intensity-modulated fields can be efficaciously and accurately delivered using DMLC. IMRT treatment is now ready for routine implementation on a large scale in our clinic.

Interinstitutional experience in verification of external photon dose calculations.

Under the auspices of NCI contracts, four institutions have collaborated to assess the accuracy of the pixel-based dose calculation methods they employ for external photon treatment planning. The approach relied on comparing calculations using each group's algorithm with measurements in phantoms of increasing complexity. The first set of measurements consisted of ionization chamber measurements in water phantoms in normally incident square fields, an elongated field, a wedged field, a blocked field, and an obliquely incident beam. The second group of measurements was carried out using thermoluminescent dosimeters in phantoms designed to investigate the effects of surface curvature, high density heterogeneities, and low density heterogeneities. The final study tested the entire treatment planning system, including CT data conversion, in an anthropomorphic phantom. Overall, good agreement between calculation and measurements was found for all algorithms. Regions in which discrepancies were observed are pointed out, areas for algorithm improvement are identified and the clinical import of algorithm accuracy is discussed.

Initial clinical experience with computer-controlled conformal radiotherapy of the prostate using a 50-MeV medical microtron.

PURPOSE: We have described previously a model for delivering computer-controlled radiation treatments. We report here on the implementation and first year's clinical experience with such treatments using a 50 MeV medical microtron. METHODS AND MATERIALS: The microtron is equipped with a multileaf collimator and is capable of setting up and treating a sequence of fixed fields called segments, under computer control. An external computer derives machine parameters for the segments from a three-dimensional treatment planning system, transfers them to the microtron control computer, checks the machine settings before allowing dose delivery to begin, and records the treatment. We describe the patient treatment methodology, portal film acquisition, electronic portal imaging, and quality assurance. RESULTS: Patient treatments began in July 1992, comprising six-segment conformal treatments of the prostate. Using the recorded treatment data, the system performance has been examined and compared to other treatment machines. The average treatment time is 10 min, of which 4 min is for computer-controlled setup and irradiation; the remaining time is for patient positioning and checking of clearances. Long-term reproducibility of computer-controlled setup of the gantry and multileaf position is better than 0.5 degrees and 1 mm, respectively. Termination due to a machine fault has occurred in 5.5% of treatments, improving to 2.5% in recent months. CONCLUSION: Our initial experience indicates that computer-controlled segmental therapy can be performed reliably on a routine basis. Treatment times with the microtron are significantly shorter than with conventional linacs, and setup accuracy is consistent with that needed for conformal therapy. We believe that treatment times can be further improved through software upgrades and integration of electronic portal imaging.

Conformal radiation treatment of prostate cancer using inversely-planned intensity-modulated photon beams produced with dynamic multileaf collimation.

PURPOSE: To implement radiotherapy with intensity-modulated beams, based on the inverse method of treatment design and using a multileaf collimation system operating in the dynamic mode. METHODS AND MATERIALS: An algorithm, based on the inverse technique, has been integrated into the radiotherapy treatment-planning computer system in our Center. This method of computer-assisted treatment design was used to derive intensity-modulated beams to optimize the boost portion of the treatment plan for a patient with a T1c cancer of the prostate. A dose of 72 Gy (in 40 fractions) was given with a six-field plan, and an additional 9 Gy (in five fractions) with six intensity-modulated beams. The intensity-modulated fields were delivered using dynamic multileaf collimation, that is, individual leaves were in motion during radiation delivery, with the treatment machine operating in the clinical mode. Exhaustive quality assurance measurement and monitoring were carried out to ensure safe and accurate implementation. RESULTS: Dose distribution and dose-volume histogram of the "inverse method" boost plan and of the composite (72 Gy primary + 9 Gy boost) plan were judged clinically acceptable. Compared to a manually designed boost plan, the inverse treatment design gave improved conformality and increased dose homogeneity in the planning target volume. Film and ion chamber dosimetry, performed prior to the first treatment, indicated that each of the six intensity-modulated fields was accurately produced. Thermoluminescent dosimeter (TLD) measurements performed on the patient confirmed that the intended dose was delivered in the treatment. In addition, computer-aided treatment-monitoring programs assured that the multileaf collimator (MLC) position file was executed to the specified precision. In terms of the overall radiation treatment process, there will likely be labor savings in the planning and the treatment phases. CONCLUSIONS: We have placed into clinical use an integrated system of conformal radiation treatment that incorporated the inverse method of treatment design and the use of dynamic multileaf collimation to deliver intensity-modulated beams. The system can provide better treatment design, which can be implemented reliably and safely. We are hopeful that improved treatment efficacy will result.

Treatment planning and delivery of intensity-modulated radiation therapy for primary nasopharynx cancer.

PURPOSE: To implement intensity-modulated radiation therapy (IMRT) for primary nasopharynx cancer and to compare this technique with conventional treatment methods. METHODS AND MATERIALS: Between May 1998 and June 2000, 23 patients with primary nasopharynx cancer were treated with IMRT delivered with dynamic multileaf collimation. Treatments were designed using an inverse planning algorithm, which accepts dose and dose-volume constraints for targets and normal structures. The IMRT plan was compared with a traditional plan consisting of phased lateral fields and a three-dimensional (3D) plan consisting of a combination of lateral fields and a 3D conformal plan. RESULTS: Mean planning target volume (PTV) dose increased from 67.9 Gy with the traditional plan, to 74.6 Gy and 77.3 Gy with the 3D and IMRT plans, respectively. PTV coverage improved in the parapharyngeal region, the skull base, and the medial aspects of the nodal volumes using IMRT and doses to all normal structures decreased compared to the other treatment approaches. Average maximum cord dose decreased from 49 Gy with the traditional plan, to 44 Gy with the 3D plan and 34.5 Gy with IMRT. With the IMRT plan, the volume of mandible and temporal lobes receiving more than 60 Gy decreased by 10-15% compared to the traditional and 3D plans. The mean parotid gland dose decreased with IMRT, although it was not low enough to preserve salivary function. CONCLUSION: Lower normal tissue doses and improved target coverage, primarily in the retropharynx, skull base, and nodal regions, were achieved using IMRT. IMRT could potentially improve locoregional control and toxicity at current dose levels or facilitate dose escalation to further enhance locoregional control.

Stereotactic treatment of brain tumors with radioactive implants or external photon beams: radiobiophysical aspects.

We perform calculations, based on the linear-quadratic model, to assess the biologically effective doses (BED) of tumor and normal tissue in the stereotactic irradiation of brain tumors with either radioactive implants or radiosurgery techniques. Treatment protocols for radiosurgery and radioactive implants, as obtained from the literature, are reviewed and compared. A figure of merit is defined to be the ratio of tumor to normal tissue BED, expressed in units of Gy10/Gy3. These comparisons indicate a clear radiobiological advantage for brachytherapy, unless the radiosurgery is to be delivered in a large number of fractions. The differences in dose uniformity, and in the volume of normal tissue encompassed by the high dose regions, are factors that may also influence clinical results.

Perspectives of multidimensional conformal radiation treatment.

We consider the present technological advancement that underlies the implementation of computer-controlled conformal radiotherapy. We also consider the developments in modern biology that may provide input to therapy planning. The concept of multidimensional conformal radiotherapy is advanced, which integrates geometrical precision and biological conformality, to optimize the treatment planning for individual patients, with a view to improve the overall success of radiotherapy.