Pediatric Normal Tissue Effects in the Clinic (PENTEC): An International Collaboration to Analyse Normal Tissue Radiation Dose-Volume Response Relationships for Paediatric Cancer Patients.

With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy can cause debilitating or even fatal late adverse events that are critical to understand, mitigate or prevent. QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) identified radiation dose constraints for normal tissues in adults and pointed out the uncertainties in those constraints. The range of adverse events seen in children is different from that in adults, in part due to the vulnerability/characteristics of radiation damage to developing tissues, and in part due to the typical body sites affected by childhood cancer that lead to collateral irradiation of somewhat different normal tissues and organs compared with adults. Many childhood cancer survivors have a long life expectancy and may develop treatment-induced secondary cancers and severe organ/tissue injury 10, 20 or more years after treatment. Collaborative long-term observational studies and clinical research programmes for survivors of paediatric and adolescent cancer provide adverse event data for follow-up periods exceeding 40 years. Data analysis is challenging due to the interaction between therapeutic and developmental variables, the lack of radiation dose-volume data and the fact that most childhood malignancies are managed with combined modality therapy. PENTEC (Pediatric Normal Tissue Effects in the Clinic) is a volunteer research collaboration of more than 150 physicians, medical physicists, mathematical modellers and epidemiologists organised into 18 organ-specific working groups conducting a critical review and synthesis of quantitative data from existing studies aiming to: (1) establish quantitative, evidence-based dose/volume/risk guidelines to inform radiation treatment planning and, in turn, improve outcomes after radiation therapy for childhood cancers; (2) explore the most relevant risk factors for toxicity, including developmental status; (3) describe specific physics and dosimetric issues relevant to paediatric radiotherapy; and (4) propose dose-volume outcome reporting standards for publications on childhood cancer therapy outcomes. The impact of other critical modifiers of normal tissue radiation damage, including chemotherapy, surgery, stem cell transplantation and underlying genetic predispositions are also considered. The aims of the PENTEC reports are to provide clinicians with an analysis of the best available data to make informed decisions regarding radiation therapy normal organ dose constraints for planning childhood cancer treatment, and to define future research priorities.

TU-F-BRCD-01: Tolerance Levels and Methodologies for IMRT Verification QA.

Intensity modulated radiation therapy (IMRT) is a technology intensive treatment modality involving the delivery of highly conformal dose distributions to patients. IMRT is becoming a standard of care for many disease sites and approximately 30%-60% of cancer patients in the United States receive IMRT treatments. Given the complexity of the IMRT treatment planning and delivery processes, a number of AAPM reports and guidance documents addressed the technical aspects of IMRT, including the need for comprehensive acceptance testing, commissioning, and QA programs for IMRT planning and delivery equipment. The implementation of these verification programs is essential to ensure the accuracy of IMRT delivery. Despite the critical role of patient-specific IMRT verification QA to ensure the safe delivery of IMRT treatments to patients as planned, there is little systematic guidance on the type of methodologies, tools, and acceptable tolerance levels that are needed in clinical practice. Furthermore, there are limited discussion on the pros and cons of the different delivery methods for QA measurements, and no recommendations on how to assess the clinical relevance of failed IMRT plans. LEARNING OBJECTIVES: 1. To discuss commonly employed IMRT measurement methods and discuss the pros and cons of each method. 2. To review methodologies for absolute dose verification (single small-volume, 1D, 2D methods), and review dose-difference, DTA, and Gamma analysis techniques including the variability of vendors implementation 3. To review IMRT QA passing rates for given tolerances and action levels, and discuss the clinical relevance of failed IMRT QA.

Potential therapeutic misadministration due to inappropriate electron beam field shaping.

Lead or cerrobend blocking strips are used to shape electron treatment fields when an appropriate custom insert is not available. For the Varian 2100C accelerator, the structural supports of the electron applicators impede the free placement of these field-shaping strips on the open custom insert frame while placement at the top of the applicator is unimpeded. We have investigated the dosimetric ramifications of placing field shaping strips at the top level of the 15x15 applicator for 6, 9, and 16 MeV electrons. Our results demonstrate as much as a 30% dose decrease and 2 cm penumbral increase when this is done compared to field shaping at the insert level. The magnitude of this dosimetric error qualifies as a therapeutic misadministration in many states depending on how many treatments are delivered in this manner. Based on this finding, we recommend that routine use of lead strip blocking be discouraged in favor of custom inserts due to the potential for inappropriate placement on some linear accelerators.

Range spectra in electron penetration problems.

The theory of electron penetration as predicted by the Fokker-Planck equation is first reviewed within a restricted context that considers the multiple scattering and transport of charged particles. We then broaden the context and show that range straggling effects also fit successfully into this framework, which completes an electron model initiated by Yang. We introduce those effects with a superposition of Fokker-Planck solutions, i.e., by using an incident beam that contains a spectrum of initial energies, or equivalently, a set of csda ranges. Straggling effects appear to be a beam property in this approach but are returned to the material when we use it. All the information needed to construct the spectrum is obtained from a measurement of the electron rest charge distribution in polystyrene. To illustrate the correctness of this procedure, we consider the case of a 20 MeV electron beam incident on water. We predict the absorbed dose distribution as a function of depth and also measure it with an ionization chamber in a water tank. We find nearly perfect agreement between calculation and experiment in this case where all the results derive and apply to a clinically operational machine.

Code of practice for brachytherapy physics: report of the AAPM Radiation Therapy Committee Task Group No. 56. American Association of Physicists in Medicine.

Recommendations of the American Association of Physicists in Medicine (AAPM) for the practice of brachytherapy physics are presented. These guidelines were prepared by a task group of the AAPM Radiation Therapy Committee and have been reviewed and approved by the AAPM Science Council.

The need for individualized dosimetry for tangential breast treatment.

We have examined the isodose distributions of 119 intact breast patients treated on a 6 MV linac to determine if a library of treatment plans could be used instead of individualized computer plans for patient treatments without compromising the quality of those treatments. The parameters studied were: field width, baseline separation, central axis separation, wedge angle, and isodose coverage. At least two wedges were used in the computer plans for each patient and the best plan was then chosen. In order to construct a library of plans, the choice of wedge, treatment isodose, and dose uniformity should be predictable. Our results show that for 90 out of 119 plans (76%), the 30 degrees wedge was best. In the other 29 cases, either the 15 degrees or the 45 degrees wedge yielded better plans. On average, the improvement in dose homogeneity due to choice of wedge was about 2% (range 0-7%) for these cases. Although grouping like-patient parameters generally restricted the isodose variation to +/- 2.5%, there were five patients for which up to a 7% underdosage would not have been predicted. For the set of plans using a 30 degrees wedge, a significant correlation was found for the ratio of the baseline to central axis separation vs. treatment isodose. The average isodose which covered the target area was 97% (range 90-100%) and 102 out of 107 patient plans using the 30 degrees wedge fell between 94 and 100%. We conclude from these results that the variation in dose distribution found with seemingly similar sized breasts is due to the variation in breast shape and symmetry. The use of a library plan with a single wedge and a standardized isodose line for tangential field treatment of intact breast could cause up to a 7% dose difference compared to the actual dosimetry for that patient.

Application of the ICRU Report 38 reference volume concept to the radiotherapeutic management of recurrent endometrial and cervical carcinoma.

Radiation therapy was given to 25 patients presenting with pelvic recurrence of endometrial (14) and cervical (11) cancer. Of these patients, all but one had undergone hysterectomy following their original diagnosis. Two endometrial patients received preoperative intracavitary irradiation. The recurrence-free interval ranged from 5 to 71 months (mean = 21 months). External beam radiation therapy for pelvic recurrence ranged from 3000 to 5000 cGy. Additional central radiation was given to 18 patients with either external beam, intracavitary, interstitial, or transvaginal technique. Dose and dose rates from brachytherapy are documented with maximum values, along with the location of these dose points. Such specification is essential in obtaining a more accurate impression of the total dose delivered to the patient, especially when different techniques are employed to increase the dose to the center of the pelvis. Reference volume dimensions, similar to those specified by ICRU Report 38 for intracavitary treatments, are presented. Mean follow-up from completion to radiotherapy is 22 months; 16 patients are dead, 2 are alive with disease, and 7 are alive with no evidence of disease.

Conversion from Cs-137 to Ir-192 for high dose rate remote afterloading: practical considerations.

High dose rate (HDR) remote afterloading is increasingly being used to replace many conventional low dose rate (LDR) brachytherapy procedures. Implementation of the microSelectron-HDR with Ir-192 at our facility necessitated this study to obtain equivalent dosimetric distributions with those of our LDR Cs-137 techniques using our current treatment planning system. Three anatomical sites are presented: nasopharynx, esophagus, and uterine cervix. Attention must be given to the anisotropy of Cs-137 tubes when converting to Ir-192; for linear geometries, total equivalent activity may be preserved but the shapes of the resulting isodose curves for Ir-192 are longer than those of Cs-137. In the case of Fletcher-Suit intracavitary treatments of the uterine cervix, the longer contours for Ir-192 in the vaginal ovoids results in higher isodose levels reaching the bladder and rectum. Maintaining the traditional dose levels to these organs is accomplished by modifying the loading of the ovoids to approximately 85% of the corresponding Cs-137 activity. Computerized dosimetry is presented, along with a chart we have devised to easily convert a standard LDR treatment to HDR dwell times. Our results are especially suitable to those users who will continue to make use of their present computer treatment planning system.

The CT scanner as a therapy machine.

Many tumors in the brain and in other tissues can be delineated precisely in images obtained with a CT scanner. After the scan is obtained the patient is taken to another room for radiation therapy and is positioned in the beam with the aid of external markers, simulators or stereotactic devices. This procedure is time consuming and subject to error when precise localization of the beam is desired. The CT scanner itself, with the addition of a collimator, is capable of delivering radiation therapy with great precision without the need for external markers. The patient can be scanned and treated on the same table, the isocenter of the beam can be placed precisely in the center of the lesion, the beam can be restricted to just those planes in which the lesion appears several arcs can be obtained by simply tilting the gantry, and the position of the patient in the beam can be monitored continuously during therapy. We describe here the properties of the CTX, the CT scanner modified for therapy.

Optimization of arc angles in rotational therapy.

Data is presented that will aid in optimizing the arc angles used for rotational therapy for a 6 Mv x-ray beam. Computer calculations of isodose distributions were carried out and the Ap and Lateral dimensions of the 95 and 100% isodose line were tabularized as a function of the field width (6-14 cm), distance between isocenter and patient midline (0-3 cm), and bilateral 120 or 100 degrees arc angle. The 300 degrees rotation cases we studied were generally found to be inferior to 120 degrees or 100 degrees bilateral arc rotations. 120 degrees arcs are best when the target center is within 2 cm of the patient's Ap center. As that separation increases, the bilateral arc angle should be decreased or wedges should be rotated through 300 degrees to avoid maximum doses greater than 105%. The data tables can be used as a starting point for computer calculations to select the field width and the arc angle for a particular target location and size. Of note is the degree to which the dimensions of the 100% isodose line decreases for small field widths and large isocenter to patient midline distances.

Radiotherapy planning for simulation of prostate cancer: computerized tomographic scanning vs. conventional radiographic localization.

A computerized tomographic localization protocol for prostate cancer treatment planning is described. In 23 patients, this new method is compared to localization using conventional orthogonal radiographic simulation with contrast media in the rectum, bladder, and urethra. Advantages of the CT localization protocol include enhanced ability to delineate the tumor extension, particularly for superior, lateral, anterior, and posterior spread. Accurate CT localization of the inferior border of the target volume has also been demonstrated to be feasible, thereby avoiding the need for invasive urethral, bladder, and rectal manipulations.

Variability of heating patterns in animals by magnetic induction hyperthermia.

In a test of electromagnetic induction hyperthermia to deep viscera of a live dog model, we found that heating was not uniform to any depth, but was quite variable. In general, there was a thermal gradient between peripheral and central portions of the transposed spleen of about 1 degree C. Though heat generation within the abdomen was not uniform, its temperature pattern in the alive animal resulted in significant heating of that part of the organ that had been surgically placed at the center of the animal. This heating could not be explained by perfusion with regionally heated core blood. Our results indicate that extensive investigations in living systems and complex dynamic phantoms will be necessary before individual patient response can be predicted.

The pharmacologic manipulation of blood flow in hyperthermia therapy.

Many human tumors treated by hyperthermia do not reach therapeutic temperatures (42 degrees C). The explanation for this difference may be that some tumors react to thermal stress in a manner similar to normal tissues; ie, they increase blood flow during hyperthermia in order to dissipate the heat. Higher temperatures might be achieved in these heat-resistant tumors by administering vasoconstrictive agents in an effort to reduce blood flow. In this preliminary study, we determined the extent to which pharmacologic inhibition of local blood flow might allow higher temperatures to develop in normal muscles exposed to localized radiofrequency hyperthermia. We found that the local muscle temperature rise could be increased by at least 90% in two dogs and six rabbits with the use of a local vasoconstrictive drug.

Single- and double-plane iridium-192 interstitial implants: implantation guidelines and dosimetry.

Computerized dosimetric studies of single- and double-plane iridium-192 (Ir-192) planar implants were performed. With respect to dose homogeneity, we found that the optimal source and ribbon separation for single-plane implants was 1.0 cm. For double-plane implants, the preferred ribbon and plane separation was 1.5 cm, maintaining a 1-cm separation for the sources. Using these separations, standard dose rate curves for single- and double-plane Ir-192 implants were generated by computer calculations. These standard curves are useful for quickly and fairly accurately estimating the dose from any size planar implant, without requiring more time-consuming individual computer dosimetry. We believe that the curves will prove to be of practical clinical value to physicists and radiotherapists.

Blood flow in human tumors during hyperthermia therapy: demonstration of vasoregulation and an applicable physiological model.

A quantitative assessment of the effect of localized magnetic-loop hyperthermia on blood flow was performed in 12 human tumors using the 133Xe clearance method. Because blood flow in these tumors changed in response to needle injection, a physiologically based, one-compartment model was developed that included both a hyperemic and a steady-state component. In six tumors, changes in blood flow induced by heat were also observed. The ability of tumor vessels to respond dynamically to stress and the degree of response may be predictive of tumor heating capacity and subsequent therapeutic response.