Prakash N. Shrivastava

RTOG quality assurance guidelines for clinical trials using hyperthermia.

M. W. DEWHIRST, D.V.M., PH.D.,* T. L. PHILLIPS, M.D.,+ T. V. SAMULSKI, PH.D.,+ P. STAUFFER, MSEE,? P. SHRIVASTAVA, PH.D.,+ B. PALIWAL, PH.D.,+ T. PAJAK, PH.D.,+ M. GILLIM, PH.D.,+ M. SAPOZINK, M.D., PH.D.,+ R. MYERSON, M.D., PH.D.,+ F. M. WATERMAN, PH.D.,+ S. A. SAPARETO, PH.D.,+ P. CORRY, PH.D.,+ T. C. CETAS, PH.D.,+ D. B. LEEPER, PH.D.,+ P. FESSENDEN, PH.D.,+ D. KAPP, M.D., PH.D.,+ J. R. OLESON, M.D., PH.D.+ AND B. EMAMI, M.D.*

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.

RTOG quality assurance guidelines for interstitial hyperthermia

This document specifies the current recommendations for quality assurance for hyperthermia administration with interstitial techniques as specified by the Radiation Therapy Oncology Group (RTOG). The document begins by providing a brief description of the physical principles behind the use of the three most commonly used methods of interstitial hyperthermia: radiofrequency (RF-LCF), microwave antennas, and ferromagnetic seeds. Emphasis is placed on features that effect quality assurance. Specific recommendations are provided for: a) Pretreatment planning and equipment performance checks, b) Implant considerations and documentation, c) Thermometry, and d) Safety procedures. Specific details regarding quality assurance issues that are common to all local and regional hyperthermia methods are outlined in previous documents sponsored by the RTOG. It is anticipated that technological advances may lead to future modifications of this document.

RTOG quality assurance guidelines for clinical trials using hyperthermia for deep-seated malignancy

Quality assurance has been vague or lacking in many previous hyperthermia trials. Recent publications by the Hyperthermia Physics Center, the Center for Devices and Regulatory Health, and the Radiation Therapy Oncology Group have described general guidelines for quality assurance in equipment reliability and reproducibility, superficial applications, and microwave techniques. The present report details quality assurance factors that are believed to be important for hyperthermia of deep clinical sites, defined as extending at least 3 cm beyond the skin surface. This document will discuss patient and physician factors, as well as thermometric accuracy, assessment of specific absorption rates (SAR), assurance of adequate coverage of tumors by the energy deposition pattern of the treatment device, and recommended documentation of the location, quantity, and frequency of treatment, specifically oriented to deep hyperthermia. The recommendations are structured to facilitate compliance in multiinstitutional trials.

RTOG QUALITY ASSURANCE GUIDELINES FOR CLINICAL TRIALS USING HYPERTHERMIA ADMINISTERED BY ULTRASOUND

Clinical quality assurance guidelines are established for RTOG hyperthermia protocols in which unfocused planar ultrasound may be used to administer hyperthermia. Measurement of temperature at a few fixed points is no longer considered to be adequate. Thermal mapping is required to obtain profiles of the temperature across the tumor dimensions, including margins of normal tissue. The thermometry strategies established for microwaves are to be adhered to with oblique insertion of the probes recommended. Two types of errors arise which are generally not present with microwaves. A measurement error, commonly referred to as a temperature artifact, arises because of absorption and/or viscous heating of the probe. Another error arises when thermocouples are used due to the conduction of heat along the wire leads, especially the copper wire. Several thermometry systems are evaluated with regard to the expected artifact and conduction errors. Acceptable systems include: a) indexing a polyurethane sheathed single sensor thermocouple in a polyurethane catheter, b) indexing a fiberoptic probe in a steel needle, c) indexing a single sensor thermocouple in a steel needle, and d) use of manganin-constantan multisensor thermocouples. Unacceptable systems include: a) fixed or static probes that do not provide profiles of the temperature across the tumor dimensions, b) copper-constantan multisensor thermocouples, and c) teflon sheathed thermocouples inserted into a teflon catheter.

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.

Abdomino-pelvic hypertherma and intraperitoneal carboplatin in epithelial ovarian cancer: Feasibility, tolerance and pharmacology☆

PURPOSE To investigate the feasibility, toxicity, and pharmacokinetics of intraperitoneal (i.p.) carboplatin (CB) with concomitant abdomino-pelvic hyperthermia (HT) in advanced ovarian cancer patients. METHODS AND MATERIALS Patients with residual disease mainly confined to the peritoneal cavity after platinum based chemotherapy received an initial course of i.p. CB for baseline pharmacokinetics followed by three cycles of i.p. CB with concomitant regional hyperthermia. The goal of HT was to achieve at least 45 min of intraperitoneal temperature > 42 degrees but < 50 degrees C while maintaining normal tissue temperatures < 43 degrees C and systemic body temperatures < 38 degrees C. No analgesic premedication was used. Thermometry was recorded by multisensor fiberoptic probes placed within the peritoneal cavity, bladder, vagina, and oral cavity. RESULTS Thirteen patients received a total of 31 sessions. Our intraperitoneal temperature goal could not be achieved because of patient intolerance. At best, we could maintain intraperitoneal temperatures > 40 degrees C, for more than 40 min in 7 of 31 sessions. The average values of thermal variables were T90 = 40 degrees C, TAVE = 41 degrees C, TMIN = 38.2 degrees C, and TMAX = 42.9 degrees C. The mean maximum systemic temperature was 38 degrees C. Acute thermal toxicities requiring early interruption of hyperthermia were systemic temperature exceeding 38 degrees C (11 of 31), abdominal pain or generalized distress (20 of 31), and vomiting (2 of 31). Hematological toxicities were not increased by hyperthermia. Pharmacokinetics were consistent with enhanced clearance of CB by HT. Lower radio frequencies (< 75 MHz) achieved better heat deposition in the peritoneal cavity than higher frequencies (> 75 MHz). Two of the 13 patients (a Stage III and a Stage IV patient) are alive with no evidence of disease at 40 and 43 months from treatment. CONCLUSIONS Intraperitoneal temperatures in the range of 40 degrees C maintained for approximately 40 min can be achieved within the described setting. The probability of successful induction of therapeutic intraperitoneal temperatures appears to be higher when frequencies below 75 MHz are used. Patients who are potentially platinum sensitive and have minimal residual disease could potentially benefit from the combined treatment under the conditions studied. However, this temperature-time range appears inadequate against platinum resistant disease, and/or bulky residual pelvic disease. Alternative approaches such as whole body hyperthermia and carboplatin are warranted to overcome some of the obstacles observed.

An approach to summarizing interrelations between functions used in radiotherapy dose calculations

An approach to summarizing interrelations between functions used in radiotherapydose calculations is suggested. A mnemonic diagram is proposed which should be useful for radiationphysicists in radiotherapy to obtain at a quick glance the definitions and interrelations between the commonly used functions like back‐scatter factor, percent depth dose, tissue–air ratio, scatter–air ratio, and scatter function. The conditions under which the measurements must be made for these functions and interrelations to be valid are described. Rules for application of the diagram and some practical examples are included. The diagram also serves as a very effective teaching aid.

Hyperthermia: Principles and quality assurance

The methods of energy deposition, the power absorbtion properties of biological tissues and the basic components of a typical hyperthermia system are described. In addition, the clinical requirements of hyperthermia treatment are discussed. A perspective on treatment planning and quality control is presented.

Concept of depth dose functions for radiotherapy beams: definition and values for different energy beams

Abstract Depth dose functions are defined and based on empirically observed interrelation of percent depth doses for different energy beams. By using this function, if the depth dose for a given source-surface distance (SSD), field size and depth are known for a standard beam energy, the corresponding depth dose for another beam energy can be derived. The results obtained are accurate to within ±1% in a considerable range of SSD, field size and depths used in routine radiotherapy. The formulation can be extended to hold at depths between the surface and depth of maximum but is somewhat less accurate than ±1% for depths up to two times the depth of maximum. This method is of considerable usefulness in computer dosimetry algorithms to save memory space and/or to increase speed by avoiding multiple table look up procedures. It is the particular importance in irregular field dose calculations for high energy beams where specific measured data for separation of primary and scatter components of dose are not available.