Stephen A. Sapareto

Hyperthermic Radiosensitization of Synchronous Chinese Hamster Cells: Relationship between Lethality and Chromosomal Aberrations

Synchronous Chinese hamster cells in vitro were obtained by mitotic selection. The cells were heated at 45.5°C for 4 min in mitosis, 11 min in G1, or 7 min in S sphase and then X-irradiated immediately thereafter. Colony survival from heat alone was 0.30 to 0.45, and the frequency of chromosomal aberrations induced by heat was 0.00, 0.14, or 0.97 for heat treatments during M, G1, or S, respectively. As shown previously, lethality from hyperthermia alone is due to chromosomal aberrations only when the cells are heated during S phase. The log survival

RTOG quality assurance guidelines for clinical trials using hyperthermia.

(D_{0}^{\sim}=80\ \text{rad})

Correlations between 31P NMR spectroscopy and 15O perfusion measurements in the RIF-1 murine tumor in vivo.

and aberration frequency curves for cells irradiated during mitosis were linear, and the only effect of hyperthermia was to shift the curves in accord with the effect from heat alone. Thus, hyperthermia did not radiosensitize the mitotic cells. The cells irradiated in G1 were more resistant

Hyperthermia quality assurance guidelines

(D_{0}^{\sim}=100\ \text{rad})

RTOG quality assurance guidelines for interstitial hyperthermia

than those irradiated in mitosis, and the survival and aberration...

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

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.*

Thermal isoeffect dose: addressing the problem of thermotolerance.

The tumor physiological environment is one of the least understood and most important factors in determining the response of solid tumors to cancer therapy. To examine several important characteristics of the tumor physiological environment we have used in situ photon activation-15O decay measurements (perfusion characteristics) and 31P surface coil-NMR spectroscopy (metabolic characteristics) to observe in vivo subcutaneous RIF-1 tumors grown in female C3H/Anf mice. The following correlations between the 15O perfusion characteristics and the 31P NMR metabolic characteristics in individual tumors were observed: a negative correlation between pH, as measured by NMR (pHNMR), and the inorganic phosphate to nucleosides triphosphate peak height ratio (Pi:NTP); for the well-perfused fraction of the tumor there is a positive correlation with both pHNMR and the phosphocreatine to nucleosides triphosphate peak height ratio (PCr:NTP), and a negative correlation with Pi:NTP. These correlations are interpreted as evidence for a direct relationship between the distribution of cellular physiological environments and the tumor metabolic state. Because these physiological characteristics affect tumor response to various therapeutic modalities and both measurements can be made on humans, it is suggested that these techniques may be of prognostic value in the clinical management of human cancer.

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

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.

A proposed standard data file format for hyperthermia treatments

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.

Analysis of Mopc-315 Plasmacytoma By Elutriation and Flow Cytometry

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.