Gilbert H. Nussbaum

Validation of a precision radiochromic film dosimetry system for quantitative two‐dimensional imaging of acute exposure dose distributions

We present an evaluation of the precision and accuracy of image-based radiochromic film (RCF) dosimetry performed using a commercial RCF product (Gafchromic MD-55-2, Nuclear Associates, Inc.) and a commercial high-spatial resolution (100 microm pixel size) He-Ne scanning-laser film-digitizer (Personal Densitometer, Molecular Dynamics, Inc.) as an optical density (OD) imaging system. The precision and accuracy of this dosimetry system are evaluated by performing RCF imaging dosimetry in well characterized conformal external beam and brachytherapy high dose-rate (HDR) radiation fields. Benchmarking of image-based RCF dosimetry is necessary due to many potential errors inherent to RCF dosimetry including: a temperature-dependent time evolution of RCF dose response; nonuniform response of RCF; and optical-polarization artifacts. In addition, laser-densitometer imaging artifacts can produce systematic OD measurement errors as large as 35% in the presence of high OD gradients. We present a RCF exposure and readout protocol that was developed for the accurate dosimetry of high dose rate (HDR) radiation sources. This protocol follows and expands upon the guidelines set forth by the American Association of Physicists in Medicine (AAPM) Task Group 55 report. Particular attention is focused on the OD imaging system, a scanning-laser film digitizer, modified to eliminate OD artifacts that were not addressed in the AAPM Task Group 55 report. RCF precision using this technique was evaluated with films given uniform 6 MV x-ray doses between 1 and 200 Gy. RCF absolute dose accuracy using this technique was evaluated by comparing RCF measurements to small volume ionization chamber measurements for conformal external-beam sources and an experimentally validated Monte Carlo photon-transport simulation code for a 192Ir brachytherapy source. Pixel-to-pixel standard deviations of uniformly irradiated films were less than 1% for doses between 10 and 150 Gy; between 1% and 5% for lower doses down to 1 Gy and 1% and 1.5% for higher doses up to 200 Gy. Pixel averaging to form 200-800 microm pixels reduces these standard deviations by a factor of 2 to 5. Comparisons of absolute dose show agreement within 1.5%-4% of dose benchmarks, consistent with a highly accurate dosimeter limited by its observed precision and the precision of the dose standards to which it is compared. These results provide a comprehensive benchmarking of RCF, enabling its use in the commissioning of novel HDR therapy sources.

Clinical results of irradiation combined with local hyperthermia

This report updates a previous publication describing the experience at the Mallinckrodt Institute of Radiology with irradiation and hyperthermia in the treatment of superficial metastatic and recurrent malignant tumors. In a dose‐seeking Phase I‐II clinical study, a total of 101 lesions have been treated. Twenty‐two tumors were treated with doses of irradiation ranging from 1000 to 3000 rad and the rest with doses between 3000 and 4000 rad. Irradiation was delivered twice weekly (every 72 hours) in tumor doses of 400 rad, usually with electrons (9–16 MeV). Hyperthermia was initiated within 30 minutes following irradiation, most of the patients being treated with 915 MHz microwaves, 41–43°C, for 60–90 minutes every 72 hours. Adequate temperatures were reached in most lesions measuring less than 2 cm in thickness, 70% of those 2–4 cm and only in 30% of those thicker than 4 cm. Of 36 measurable lesions in the head and neck, 20 had a complete response and 12 a partial response. In 16 of the 20 patients (80%) showing a complete response the tumor was controlled from three to 36 months. Of 30 adenocarcinoma of the breast lesions, recurrent in the chest wall, 16 showed a complete response and 9 a partial regression. Twelve of the 16 lesions that regressed completely (71.4%) showed long‐lasting tumor control. Of 22 metastatic or recurrent melanoma lesions, 16 had a complete regression and six a partial response. Of the 16 patients with complete response, 13 (81%) had no evidence of recurrence lasting from three to 36 months. Three sarcoma lesions responded well to the combination of irradiation and heat and did not recur after treatment. Patients treated with doses larger than 3000 rad in the head and neck or in the chest wall (epidermoid carcinoma or adenocarcinoma, respectively) showed better tumor response than those treated with lower doses. However, in melanoma satisfactory results (80% or higher response) were observed with doses as low as 2000 rad. This combined therapy has been well tolerated by the normal tissues. In 6% of the patients there was evidence of tumor necrosis with ulceration and in 5% thermal burns which healed after 2 to 3 months, with conservative management. Subcutaneous fibrosis and some skin atrophy developed in about one third of the patients, probably due to the additional doses of irradiation delivered after previous definitive radiotherapy. These preliminary observations suggest enhanced tumor response and control after moderate doses of irradiation and hyperthermia. Efforts must be intensified to develop adequate equipment to satisfactorily produce heat and to measure temperatures in clinical settings, thus paving the way for appropriately designed clinical trials to test the efficacy of hyperthermia in patients with deep seated lesions and advanced primary tumors.

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

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.

Interstitial thermoradiotherapy in the treatment of recurrent/residual malignant tumors

From October 1981-November 1983, a total of 31 recurrent and/or persistent tumors in 29 patients were treated with interstitial radiotherapy in combination with interstitial hyperthermia. All patients had undergone extensive previous treatments by surgery and/or radiation therapy. In the present series, radiation used was administered by iridium 192 implant, with doses varying from 4000–6000 cGy, delivered at the rate of 1000 cGy ± 10%/day. Hyperthermia was delivered by radiofrequency (8 lesions) and microwave (25 lesions) in two sessions, each raising tumor temperature to a minimum of 42°C over 60 minutes. Of 26 lesions with at least one satisfactory heating session, there were 18 (69%) complete responses, five (19%) partial responses, and three with less than 50% regression. None of the five lesions with unsatisfactory heating resulted in complete response. Of the total group, two patients developed a cutaneous sinus and one patient developed a fistula. The detailed methodology and results are presented and recommendations for future improvements are discussed.

Differential effects of in vitro heating on rat sciatic nerve branches and spinal nerve roots

Locally applied heat induces nerve conduction block. Conflicting observations have been made regarding the relation of fiber conduction velocity to heat sensitivity. This study utilized sciatic nerve branches and spinal nerve roots which were heated until a substantial conduction block occurred. The results indicated that sensory fibers conducting at greater than 40 m/s are more heat-sensitive than motor fibers of the same conduction velocity.

A simple technique for alignment of perineal needle template to ultrasound image grid for permanent prostate implants.

Proper alignment of a needle template and ultrasound software grid is required to accurately deliver permanent prostate seed implants optimized using pretreatment volume studies. Correct alignment may also reduce tissue edema, morbidity, and the time and labor required to deliver permanent prostate seed implants. A technique has been developed to rapidly assess (and, if necessary, improve) the alignment using a custom-designed water phantom. Verification of needle positions can be conducted within 1 mm and requires less than ten minutes. We have instituted the technique as a part of our periodic quality assurance program.

Results of a preliminary study of the potential of vasodilators for improving thermotherapy of deep-seated tumours

Administration of the vasodilator hydralazine to a single mongrel dog with a transplanted, superficial transmissible venereal tumour in the abdomen permitted tumour-adjacent normal tissue temperature differences produced in local hyperthermia to be enhanced by nearly 2 degrees C. A preliminary study of tumour and normal tissue perfusion rate in the dog, employing the 15O-labelled water-positron emission tomography technique, suggested that administration of the vasodilator led to a significant reduction in the tumour perfusion rate, consistent with the observed tumour temperature enhancement. Computational studies with a multi-layer, one-dimensional cylindrical model of deep-tumour heating suggest that vasodilator-induced reductions of tumour perfusion rates could significantly increase deep tumour-superficial normal tissue temperature differences produced in deep-tumour thermotherapy.

Physical predictors of adequate hyperthermia with the annular phased array

One hundred and fifty-two hyperthermia sessions in 36 consecutive patients treated with the BSD 1000 annular phased array system (APAS) are reviewed with regard to physical predictors of quality of hyperthermia. Although central tumour temperatures exceeding 42 degrees C were momentarily obtained in 62% of the sessions, it frequently proved difficult to maintain the patient at temperature for prolonged periods of time. The time to reach target temperature was negatively associated with quality of hyperthermia. Thus, of 25 sessions which required over 25 min to attain a temperature of 42 degrees C, only one was adequate (defined as central tumour temperature greater than or equal to 42 degrees C maintained for at least 30 min) as opposed to 28/69 adequate sessions when 42 degrees C was reached in less than 25 min. Physical parameters measured in the first 3 min of the session found to be associated with adequate hyperthermia include an initial rate of temperature rise at the tumour site exceeding 0.4 degrees C/min achieved with a net forward power less than 1500 W. Only three of 57 sessions not meeting these criteria were adequate. Treatment policy recommendations and recommendations for future research are made.

Design and dosimetric characteristics of a high dose rate remotely afterloaded endocavitary applicator system

PURPOSE An applicator is described for endocavitary treatment of rectal cancers using a high dose rate (HDR) remote afterloading system with a single high-intensity 192Ir source as an alternative to the 50 kVp x-ray therapy contact unit most frequently used in this application. METHODS AND MATERIALS The applicator consists of a tungsten-alloy collimator with a 45 degree beveled end, placed in a protoscope with an elliptical cross-section. The resultant 3 cm diameter circular treatment aperture, located in the beveled face of the proctoscope, is irradiated by circular array of dwell positions located about 6.5 mm from the applicator surface. This beveled end allows patients with posterior wall tumors to be treated in the dorsal lithotomy position. The dose-rate distributions about the applicator were determined using a combination of thermoluminescent dosimetry (TLD-100 detectors) and radiochromic film dose measurement techniques along with Monte Carlo dosimetry calculations. TLD-100 (3 x 3 x 0.9 mm3 chips) measurements were used to measure the distribution of dose over the proctoscope surface as well as the central axis dose-rate distribution. Relative radiochromic film measurements were used to measure off-axis ratios (flatness and penumbra width) within the treatment aperture. These data were combined with Monte Carlo simulation results to obtain the final dose distribution. RESULTS The tungsten collimator successfully limits the dose to the tissue in contact with the proctoscope walls to less than 12% of the prescribed dose. These results indicate that the HDR applicator system has slightly more penetrating depth-dose characteristics than the most widely used contact therapy x-ray machine. Flatness characteristics of the two treatment delivery systems are comparable, although the HDR endocavitary applicator has a significantly wider penumbra. Finally, the HDR applicator has a lower surface dose rate (1.5-4 Gy/min of dwell time) compared to 9-10 Gy/min for the x-ray unit. CONCLUSIONS An applicator system has been developed for endocavitary treatment of early stage rectal carcinoma that uses a single-stepping source HDR remote afterloading system as a radiation source. The advantages of the HDR-based system over x-ray therapy contact units currently used in this clinical application are (a) enhanced flexibility in applicator design and (b) widespread availability of single-stepping source HDR remote afterloading systems.

A practical, modular hyperthermia phantom

A catheterized, three-component slab phantom has been fabricated for use in mapping specific absorption rate (SAR) distributions from hyperthermia applicators. A planar array of 21 closely spaced catheters, located at one surface of the 1-cm-thick slab, can be positioned at depths of 0-7 cm below the phantom surface, in 1-cm steps, through appropriate placement and orientation of this slab within the three-slab set. Owing to its modular design, the phantom can be prepared, and also purged of degraded material rapidly and without damage to the catheter tracks.