Evaluation of ultrasound airway assessment parameters in pregnant patients and their comparison with that of non-pregnant women: a prospective cohort study.

BACKGROUND: Clinical airway assessment parameters differ significantly between pregnant and non-pregnant patients, however literature comparing their ultrasound (US) airway parameters is limited. We planned a prospective cohort study to compare US-assessed airway parameters between pregnant and non-pregnant women. METHODS: We enrolled 82 pregnant females scheduled for elective cesarean section under neuraxial anesthesia and 80 age-matched non-pregnant females scheduled for elective surgery. Pre-operative clinical airway assessment was performed in both groups. The US airway assessment was done pre-operatively in non-pregnant and postoperatively in pregnant patients. Our primary objective was to compare US-assessed parameters, and secondary objectives included a comparison of clinical airway assessment parameters and investigating a relationship between a difficult airway (defined as a modified Mallampati grade (MMG) ≥ 3) and other airway assessment parameters. RESULTS: Among several US airway parameters, pregnant patients had significantly higher hyomental distance, anterior neck soft tissue thickness at the hyoid and vocal cord level, and oral cavity height, while the tongue thickness and mandibular condylar movements were significantly lower than in non-pregnant patients. Similarly, for the clinical airway assessment, pregnant patients had significantly higher MMG and upper lip bite test scores, mentohyoid distance, and neck circumference. Pregnancy, the ratio of pre-epiglottic space and epiglottis-to-vocal cords distance (Pre-E/E-VC), and hyoid bone visibility were independent predictors of a difficult airway. CONCLUSION: The US airway assessment parameters differ significantly between pregnant and non-pregnant patients. Pregnancy, hyoid bone visibility, and Pre-E/E-VC ratio were independent predictors of the difficult airway in female patients.

Heating patterns induced by a 13.56 MHz radiofrequency generator in large phantoms and pig abdomen and thorax.

Heating patterns generated by a commercially available 13.5 MHz radiofrequency generator and induction coil hyperthermia system in human size phantoms and a 230 pound pig were studied using a multichannel computer-monitored thermometry system that is noninteractive in electromagnetic fields. The phantom studies were composed of synthetic muscle equivalent material and fresh tissue. The pig was heated in the regions of the upper abdomen and the midthorax, both under anesthesia and dead. The temperature was measured along fine penetrating catheters at 1 cm intervals in all experiments. In a homogeneous cylindrical phantom, under our measurement conditions, the temperature profile across the diameter is parabolic with marked superficial heating and essentially no central heating. In nonhomogeneous phantoms and in the pig, the symmetry of this profile was distorted but the basic pattern of marked superficial heating and nearly absent deep central heating remained. Blood flow in the living animal produced some thermal smoothing. It is considered probable that substantial radial temperature gradients will exist within eccentrically located human tumors heated with this device and that certain deep central tumors will be difficult or impossible to heat. Determination of its ultimate value for investigational; clinical hyperthermia studies will require accurate temperature mapping of tumors and normal tissues in various anatomic sites in comparison with other approaches to deep heating.

Hyperthermia thermometry evaluation: criteria and guidelines.

Results of the evaluation of thermometry devices used during hyperthermia treatments at 14 different clinics in the USA are presented. Measurements were made by the Hyperthermia Physics Center (HPC, a national hyperthermia quality assurance program under NCI contract No. N01-CM-37512) according to a protocol. Our sample included thermocouples, fiberoptic thermometers, and high lead resistance thermistors. We found that only some but not all of the thermometers of each kind performed within the +/- 0.2 degrees C acceptability criteria of accuracy. The precision, stability, and response times achieved with each type of thermometer are presented. A summary of perturbations and artifacts typical for each system is presented together with suggested precautions to avoid them during clinical usage. We conclude that although the technology used with each thermometer system is capable of producing a temperature accuracy of 0.2 degrees C, this accuracy is clinically achievable only with a concerted effort and a constant alertness on the part of the investigator. Based on the combined experience of this survey, the clinical investigators we visited, and published reports, we present certain guidelines and procedures that can help to reduce the inaccuracies and improve the reliability of temperature data obtained in clinical hyperthermia trials.

Radiographic visualization of vaginal cylinders in gynecologic high dose rate brachytherapy.

PURPOSE: To develop a marker system allowing an accurate determination of vaginal applicator dimensions and geometry from a radiograph. METHODS AND MATERIALS: The markers consist of two sets of gold seeds embedded into each cylinder identifying the cylinder diameter, and a thin stainless steel disk interposed between adjacent cylinders identifying their interface. An evaluation of the dosimetric properties of the markers was undertaken. An applicator was assembled using four cylinders (4 cm diameter) surrounding a stainless steel uterine tandem with a stainless steel disk 0.05 mm thick and 3.6 cm in diameter interposed between each consecutive pair of cylinders. The assembly was placed on a film and an Ir-192 high dose rate source was programmed to a single dwell position within the applicator. The markers were removed and a second film was exposed with the same dwell position and time. This procedure was repeated with various dwell positions along the applicator. A scanning densitometer was used to measure the density profiles and isodensity distributions of each film. RESULTS: The optical density profiles and isodensity distributions with and without the markers in place were identical for all source dwell positions except when the source was centered in the plane of one of the stainless steel disks, where a maximum decrease of less than 2% in the dose rate was measured. The disks had no effect on the profiles measured along axes more than 2 cm from the projection of the applicator central axis on the film. CONCLUSION: The markers provide geometrical information about the position of the applicator relative to the anatomy necessary for optimized treatment planning. Slight dose perturbations resulting from the markers do occur, but only for dwell positions that center the source in the plane of a disk, and even then only at points very close to the disk. The markers can therefore be ignored from a dosimetric point of view.

A new approach to dose escalation in non-small-cell lung cancer.

PURPOSE: To describe the radiobiological rationale for dose-per-fraction escalation in non-small-cell lung cancer (NSCLC) and to devise a novel Phase I scheme to implement this strategy using advanced radiotherapy delivery technologies. METHODS AND MATERIALS: The data from previous dose escalation trials in NSCLC are reanalyzed to establish a dose-response relationship in this disease. We also use data relating prolongation in treatment time to survival to compute the potential doubling time for lung tumors. On the basis of these results, and using a Bayesian model to determine the probability of pneumonitis as a function of mean normalized lung dose, a dose-per-fraction escalation strategy is developed. RESULTS: Standard approaches to dose escalation using 2 Gy per fraction, five fractions per week, require doses in excess of 85 Gy to achieve 50% long-term control rate. This is partly because NSCLCs repopulate rapidly, with a 1.6% per day loss in survival from prolongation in overall treatment time beyond 6 weeks, and a cell doubling time of only 2.5 to 3.3 days. A dose-per-fraction escalation strategy, with a constant number of fractions, 25, and overall time, 5 weeks, is projected to produce tumor control rates predicted to be 10%-15% better than 2 Gy per fraction dose escalation, with equivalent late effects. This Phase I clinical study is divided into three parts. Step 1 examines the feasibility of the maximum breath-holding technique and junctioning of tomotherapy slices. Step 2 treats 10 patients with 30 fractions of 2 Gy over 6 weeks and then reduces duration to 5 weeks using fewer but larger fractions in 10 patients. Step 3 will consist of a dose-per-fraction escalation study on roughly 50 patients, maintaining 25 fractions in 5 weeks. Bayesian methodology (a modification of the Continual Reassessment Method) will be used in Step 3 to allow consistent and efficient escalation within five volume bins. CONCLUSION: A dose-per-fraction escalation approach in NSCLC should yield superior outcomes, compared to standard dose escalation approaches using a fixed dose per fraction, for a given level of pneumonitis and late toxicity. Highly conformal radiotherapy techniques, such as intensity modulated radiotherapy (IMRT) and helical tomotherapy with its adaptive capabilities, will be necessary to achieve significant dose-per-fraction escalation without unacceptable lung and esophageal morbidity.

Versatility of distributed focus ultrasound in treatment of superficial lesions.

In order to study the efficacy of hyperthermia as a cancer treatment modality, it is important to be able to define the specific volume being raised to hyperthermic temperatures corresponding to the selected method of heating. Measurements have been made of temperature distributions in rat mammary tumors during steady state heating with annular focused ultrasound (2.0 MHz). Biological response in terms of growth inhibition is compared with uniformity of induced temperature throughout the tumors as a function of annular focusing dimensions.

Monte Carlo and convolution dosimetry for stereotactic radiosurgery.

The dosimetry of small photon beams used for stereotactic radiosurgery was investigated using Monte Carlo simulation, convolution calculations, and measurements. A Monte Carlo code was used to simulate radiation transport through a linear accelerator to produce and score energy spectrum and angular distribution of 6 MV bremsstrahlung photons exiting from the accelerator treatment head. These photons were then transported through a stereotactic collimator system and into a water phantom placed at isocenter. The energy spectrum was also used as input for the convolution method of photon dose calculation. Monte Carlo and convolution results were compared with the measured data obtained using an ionization chamber, a diode, and film.

A three-dimensional volume visualization package applied to stereotactic radiosurgery treatment planning.

A comprehensive software package has been developed for visualization and analysis of 3-dimensional data sets. The system offers a variety of 2- and 3-dimensional display facilities including highly realistic volume rendered images generated directly from the data set. The package has been specifically modified and successfully used for stereotactic radiosurgery treatment planning. The stereotactic coordinate transformation is determined by finding the localization frame automatically in the CT volume. Treatment arcs are specified interactively and displayed as paths on 3-dimensional anatomical surfaces. The resulting dose distribution is displayed using traditional 2-dimensional displays or as an isodose surface composited with underlying anatomy and the target volume. Dose volume histogram analysis is an integral part of the system. This paper gives an overview of volume rendering methods and describes the application of these tools to stereotactic radiosurgery treatment planning.

The use of generalized cell-survival data in a physiologically based objective function for hyperthermia treatment planning: a sensitivity study with a simple tissue model implanted with an array of ferromagnetic thermoseeds.

PURPOSE: A physiologically based objective function for identifying a combination of ferromagnetic seed temperatures and locations that maximizes the fraction of tumor cells killed in pretreatment planning of local hyperthermia. METHODS AND MATERIALS: An objective-function is developed and coupled to finite element software that solves the bioheat transfer equation. The sensitivity of the objective function is studied in the optimization of a ferromagnetic hyperthermia treatment. The objective function has several salient features including (a) a physiological basis that considers increasing the fraction of cells killed with increasing temperatures above a minimum therapeutic temperature (Tmin,thera), (b) a term to penalize for heating of normal tissues above Tmin,thera, and (c) a scalar weighting factor (gamma) that has treatment implications. Reasonable estimates for gamma are provided and their influence on the objective function is demonstrated. The cell-kill algorithm formulated in the objective function is based empirically upon the behavior of published hyperthermic cell-survival data. The objective function is shown to be independent of normal tissue size and shape when subjected to a known outer-surface, thermal boundary condition. Therefore, fractions of cells killed in tumors of different shapes and sizes can be compared to determine the relative performance of thermoseed arrays to heat different tumors. RESULTS: In simulations with an idealized tissue model perfused by blood at various rates, maxima of the objective function are unique and identify seed spacings and Curie-point temperatures that maximize the fraction of tumor cells killed. In ferromagnetic hyperthermia treatment planning, seed spacing can be based on maximizing the minimum tumor temperature and minimizing the maximum normal tissue temperature. It is shown that this treatment plan is less effective than a plan based on seed spacings that maximize the objective function. CONCLUSIONS: It is shown that under the assumptions of the model and based on a desired therapeutic goal, the objective function identifies a combination of thermoseed temperatures and locations that maximizes the fraction of tumor cells killed.

High dose rate intracavitary brachytherapy for carcinoma of the cervix: the Madison system: II. Procedural and physical considerations.

The loss in therapeutic ratio accompanying a conversion from low dose-rate (LDR) to high dose-rate (HDR) intracavitary brachytherapy (ICR) requires increased attention to the precision and accuracy of dose distribution calculations and treatment delivery. While the HDR-ICR treatment unit allows better custom-tailored dose distributions compared to LDR, it also requires more attention to detail to achieve the distribution desired. Because the relative biological effectiveness of different isodose levels in a dose distribution varies with the absolute dose (as described in Part 1 of this article), the relative dose distribution used with LDR must be modified for HDR to produce the same expected biological effect. Because of the difference in the radiobiology and physical positioning, simply duplicating applications as performed with LDR misses opportunities for dose distribution improvement as well as opens possibilities for significant complications. Due to differences in positioning the applicator (e.g., retraction of the cervix low in the pelvis instead of packing the applicator high), traditional definitions of points of interest (such as point A) apply poorly with HDR-ICR, compelling new systems of dose specification. With HDR-ICR, irreparable mistakes can happen very quickly, and quality assurance for the treatment plan and calculated dwell times prove much more important than with LDR. Key features of the dose distribution and constant relationships involving doses and dwell times help screen planned treatments for mistakes. This paper details the procedural and physical consideration of the Madison system for HDR-ICR brachytherapy for carcinoma of the cervix.

High dose rate intracavitary brachytherapy for carcinoma of the cervix: the Madison system: I. Clinical and radiobiological considerations.

The decision to use five high dose rate intracavitary (HDR-ICR) insertions at weekly intervals for invasive carcinoma of the cervix treated at the University of Wisconsin Comprehensive Cancer Center (UWCCC) was made clinically. It was based on practical considerations and on previous clinical experience worldwide which showed that between 2 and 16 insertions have been used with apparently acceptable results. Although radiobiological considerations favor a large number of small doses, such a large number of HDR-ICR insertions is not clinically practical. Our strategy was to keep the biological effects of external beam and intracavitary insertions in the same ratio as used on a large series of patients treated here with low dose rate (LDR) therapy. This means keeping the same external beam treatment scheme and finding high dose rate (HDR) doses that are biologically equivalent to the previous LDR therapy, as far as possible. External beam and HDR intracavitary dose schedules for the Madison System of treating cervical carcinoma are described in detail. Because there is more repairable damage in late-reacting normal tissues, there is a bigger loss of sparing in these tissues than in tumors when changing from LDR to HDR, so total doses should be reduced more for equal late complications than for equal tumor control. The clinical decision was made to aim at equal tumor control. The possible increase in late complications has to be avoided by reducing the doses to critical normal tissues using extremely careful anatomic positioning of the HDR sources. Critical normal tissues must be kept further away from the radiation sources so that their doses are about 20% lower than with LDR geometry. This requires an extra separation of some millimeters depending on the anatomy and geometry of the individual insertion. The strategy is that the unfavourable radiobiological effects of a few large fractions must be counteracted by better physical dose distributions with HDR-ICR than with the previous LDR insertions. These good distributions are obtainable with the short exposures at HDR.

Hyperthermia quality assurance guidelines.

These Hyperthermia Quality Assurance guidelines are a result of a joint workshop of the Hyperthermia Committee of the American College of Radiology and the Hyperthermia Physics Center, which is the national quality assurance program under Contract No. N01-CM-37512 with the National Cancer Institute. Hyperthermia technology presently lacks the kind of standardization in equipment, treatment procedures, patient monitoring, and treatment documentation available in radiotherapy. Therefore, preventing unacceptable variability in treatment data demands a strong commitment to in-house quality control procedures and to centralized quality assurance reviews in cooperative multi-institutional trials. This paper presents a set of test procedures necessary to ensure proper operation of equipment, suggests a frequency for such tests, and also includes guidelines on quality control procedures to be used during treatment to improve the safety, effectiveness, and reproducibility of hyperthermia treatments. A set of forms are presented to indicate the minimum data, albeit incomplete, that must be collected for acceptable documentation of treatment. These guidelines should be valuable not only to the new entrants in the field but also to those participating in multi-institutional cooperative hyperthermia trials. They have been approved by the Hyperthermia Committees of American College of Radiology, American Society for Therapeutic Radiology and Oncology, Radiation Therapy Oncology Group and the American Association of Physicists in Medicine.

Thermoradiotherapy of intraocular tumors in an animal model: concurrent vs. sequential brachytherapy and ferromagnetic hyperthermia.

PURPOSE: To compare concurrent vs. sequential ferromagnetic thermoradiotherapy in vivo. METHODS AND MATERIALS: Greene melanomas were implanted subretinally in rabbits and observed until they were 3-5 mm in diameter. Episcleral plaques were assembled with 125I seeds for radiation therapy, or with ferromagnetic (FM) thermoseeds and nonradioactive I seeds for hyperthermia. Rabbits were implanted by centering a plaque over the intraocular melanoma. After a given dose of radiation had been delivered, the plaque was removed and a nonradioactive plaque containing FM thermoseeds was inserted into the same extrascleral space. One hour later, hyperthermia (46-47 degrees C at the plaque-scleral interface) was initiated and continued for a period of 1 h by placing the rabbits in a magnetic induction coil powered to 1200 W. Tumor size was determined at 1- to 2-week intervals by indirect ophthalmoscopy and by ultrasound. RESULTS: Dose-response analysis of 27 treated eye melanomas showed 50% local tumor control at 43 Gy for 125I alone and 29.4 Gy for 125I followed by FM hyperthermia. The thermal enhancement ratio was 1.4. CONCLUSION: Comparison with a previously published thermal enhancement ratio of 4.4 (for concurrent 125I and FM hyperthermia) leads us to conclude that thermal enhancement of 125I brachytherapy is more efficient in this tumor model system when hyperthermia is delivered during, rather than after, the irradiation process.

A solid water pelvic and prostate phantom for imaging, volume rendering, treatment planning, and dosimetry for an RTOG multi-institutional, 3-D dose escalation study. Radiation Therapy Oncology Group.

PURPOSE: With increased interest in 3-D conformal radiation therapy and dose escalation, it is necessary to provide advanced techniques to assure quality in treatment delivery. Multi-institutional trials for these newer treatment techniques require methods of verifying the consistency of treatments between the participating institutions. For this reason, a phantom was designed to address the quality and consistency of Radiation Therapy Oncology Group (RTOG) 3-D prostate treatment protocol. METHODS AND MATERIALS: A solid water pelvic and prostate phantom for imaging, volume rendering, treatment planning, and dosimetry applications for performing comprehensive quality assurance has been designed and fabricated. Its configuration was based upon CT slices obtained from a patient study. Individual slices were machined with corresponding contours of the prostate, bladder, rectum, and the left and right femurs. Most of the phantom is made of solid water (Gammex/RMI, Middleton, WI), while the femurs are made of bone-equivalent material. The CT numbers from patient images were used to adjust the solid water composition within the organ volumes, providing image contrast from the remainder of the phantom. Cylindrical insertion grooves are machined in the phantom to allow placement of ionization chambers and thermal luminal dosimeters (TLDs) for dosimetry applications. During imaging, the cavities are filled with rods fabricated from solid water material. RESULTS: The phantom is being used to evaluate the consistency of a range of processes in radiation therapy simulation, planning, and delivery of 3-D-based treatments for prostate cancer. CONCLUSION: The ultimate study objective is to use the phantom to evaluate the accuracy and consistency of treatments delivered by institutions participating in national collaborative clinical trials involving 3-D conformal dose escalation.

Effect of field irregularities on the dose distribution of 4 MV photon beam.

Complex irregular fields are often used for the treatment of tumors in radiation therapy. The dose distribution of irregularly shaped fields depend strongly on the shape of field irregularities. The effect of field irregularities on the uniformity of the dose distribution of a 4 MV photon beam has been studied. The uniformity index of the blocked field which is a measure of the dose uniformity of the field has been compared to its corresponding unblocked field. The measured and computer calculated dose are compared for points within 1 and 2 cm from the edge of the field irregularities at the depth of 10 cm. The discrepancies between the computer calculated dose and the measured dose are discussed. Some suggestions are made to improve the dose uniformity of the irregularly shaped blocked fields.

Improving dose homogeneity in routine head and neck radiotherapy with custom 3-D compensation.

BACKGROUND AND PURPOSE: Anatomic contour irregularity and tissue inhomogeneity can lead to significant radiation dose variation across the complex treatment volumes found in the head and neck (H&N) region. This dose inhomogeneity can routinely create focal hot or cold spots of 10-20% despite beam shaping with blocks or beam modification with wedges. Since 1992, we have implemented the routine use of 3-D custom tissue compensators fabricated directly from CT scan contour data obtained in the treatment position in order to improve dose uniformity in patients with tumors of the H&N. MATERIALS AND METHODS: Between July 1992 and January 1997, 160 patients receiving comprehensive H&N radiotherapy had 3-D custom compensators fabricated for their treatment course. Detailed dosimetric records have been analyzed for 30 cases. Dose uniformity across the treatment volume and clinically relevant maximum doses to selected anatomic sub-sites were examined with custom-compensated, uncompensated and optimally-wedged plans. RESULTS: The use of 3-D custom compensators resulted in an average reduction of dose variance across the treatment volume from 19+/-4% for the uncompensated plans to 5+/-2% with the use of 3-D compensators. Optimally-wedged plans were variable, but on average a 10+/-3% dose variance was noted. For comprehensive H&N treatment which encompassed the larynx within the primary field design, the peak doses delivered were reduced by 5-15% with 3-D custom compensation as compared to optimal wedging. CONCLUSIONS: The use of 3-D custom tissue compensation can improve dose homogeneity within the treatment volume for H&N cancer patients. Maximum doses to clinically important structures which often receive greater than 105-110% of the prescribed dose are routinely reduced with the use of 3-D custom compensators. Improved dose uniformity across the treatment volume can reduce normal tissue complication profiles and potentially allow for delivery of higher total doses in an attempt to enhance locoregional tumor control.

Chronic response of normal porcine fat and muscle to focused ultrasound hyperthermia.

Annular focused ultrasound (1.13 MHz) hyperthermia was used to evaluate chronic histologic effects of a range of high thermal dosages on normal porcine tissues. The effects of three peak temperatures (45, 47, and 49 degrees C) at a focal depth of 2 cm in thirty 4-cm-diameter sites were studied as a function of exposure time (10-60 min). Relative fat and muscle damage were histologically graded 1 month post-treatment. Unlike reports of radiofrequency hyperthermia, no necrosis or abscess formation was observed, even at 49 degrees C for 40 min. Fat sustained a greater percentage maximal tissue damage than muscle, although less than 4% of sections evaluated had histologic evidence of severe injury. Focused ultrasound provides a relatively uniform heat distribution in normal tissues. It should therefore be possible to raise normal tissues surrounding tumors to high temperatures using focused ultrasound, potentiating tumoricidal effects with minimal associated complications.

A study of the effect of cone shielding in intraoperative radiotherapy.

The primary goal of intraoperative radiation therapy is to irradiate the intraoperatively determined tumor target volume with a single fraction of tumoroidal dose while minimizing the dose to all adjacent healthy tissues. To reduce dose outside the treatment volume, lead sheets are often used to cover the external surface of the cone tip thus providing a shielding for the tissues outside the field. In this paper, the effect of the shielding on the depth dose distributions and dose profiles at different depths is studied based on experimental data. The results were also compared against an EGS4 Monte Carlo code for the same geometry as the measurements. The cones varied in size having diameters of 5 cm, 7 cm, and 9 cm, and the electron energies ranged from 6 MeV to 22 MeV. The depth dose curves and dose profiles (at two different depths in the phantom) were measured and computed with and without the lead shielding for the various combinations of cone sizes and electron energies using a water phantom to simulate the patient. It was found that the presence of lead increases on average across the treatment area the dose to the tumor from 2% up to 5%, while the dose outside the cone was reduced by as much as 75%. Both measurements and calculations were found to be in agreement.

Stopping-power and mass energy-absorption coefficient ratios for Solid Water.

The AAPM Task Group 21 protocol provides tables of ratios of average restricted stopping powers and ratios of mean energy-absorption coefficients for different materials. These values were based on the work of Cunningham and Schulz. We have calculated these quantities for Solid Water (manufactured by RMI), using the same x-ray spectra and method as that used by Cunningham and Schulz. These values should be useful to people who are using Solid Water for high-energy photon calibration.