Albert L. Wiley

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.

Primary irradiation, surgery or combined therapy in squamous cell carcinoma of the larynx: A comparison of treatment results from two centers

We compared two groups of patients with squamous cell carcinoma of the larynx. Group 1 consisted of 483 patients treated from 1958 through 1978. Primary surgery was selected in 41% pre- or postoperative radiation therapy in 16% and primary radiation therapy in 43%. Group 2 consisted of 247 patients treated from 1978 through 1983. Primary surgery was selected in only 1.6%, pre- or postoperative radiation therapy in 23%, and primary radiation therapy, with surgery in reserve for residual or recurrent carcinoma, in 76%. Although the results were comparable for patients with early stage tumors in the two groups, significantly higher local-regional tumor control rates and corrected survival rates were recorded for patients with advanced tumors in group 2. More patients survived with a cancer-free functional larynx, the surgical salvage rates were higher, the complication rates and the death rates lower in group 2 compared to group 1.

18F-5-fluorouracil studies in humans and animals☆

Abstract Studies in animals showing that 18 F from 18 F-5-fluorouracil ( 18 F-FU) concentrated in various transplanted tumors suggested to us that 18 F-FU might be a useful tumor scanning agent in patients with cancer. We synthesized 18 F-FU from radioactive fluorine gas produced on the University of Wisconsin Tandem Van de Graaf accelerator and studied 16 patients with a variety of malignant tumors. Patients were given 1.4–4.0 mCi of 18 F-FU intravenously and studied with a rectilinear scanner two hours later. In two of seven patients with gastrointestinal cancer there was positive uptake of 18 F in tumor locations. Two patients with head and neck cancer had positive scans. Seven other patients with non-gastrointestinal cancers were studied; in two 18 F concentrated at the tumor site. We have shown that in 16 patients with cancer, sufficient uptake of 18 F occurred in six to provide a positive rectilinear scan. These results suggest that 18 F-FU might be a useful tumor scanning agent. Further investigation is necessary to confirm that positive scans represent increased concentrations of 18 F in tumor tissue.

Clinical and theoretical aspects of the treatment of surgically unresectable retroperitoneal malignancy with combined intra-arterial actinomycin-d and radiotherapy

A small pilot series (eight patients) of surgically unresectable retroperitoneal tumors treated with radiotherapy and a selective, prolonged, continuous intraarterial infusion of actinomycin‐D is discussed, in addition to the possible theoretical advantages for this therapy. For such tumors, there is a very low probability of obtaining local control with conventional radiotherapy alone. However, on the basis of recent knowledge from radiobiology and molecular biology, the technique is a rational attempt to improve the local control probability. Geographic miss with radiotherapy portals is another major cause for local failure with such tumors. We also emphasize the importance of detailed tumor localization procedures. The local responses, some of the local controls, the palliation achieved, and the lack of significant morbidity with this technique have been encouraging. We therefore consider it worthy of further clinical investigation.

Quantitation of Tumor Volumes and Response to Therapy with Ultrasound B-Scans

A technique employing serial ultrasonic B-scans and a computer for measuring volumes of internal anatomical structures is described. Phantom studies indicate that this method is accurate to within 5% for phantom volumes in the 200–2000 cm3 range. The technique was applied to monitor the spleen-tumor volume in a patient with chronic lymphocytic leukemia and the liver-tumor volume in a patient with retroperitoneal rhabdomyosarcoma. The data suggest that the method is clinically useful for determining normal organ and tumor volumes and for evaluating response to therapy.

Neoadjuvant chemoradiation therapy in patients with surgically treated esophageal cancer.

Over the past 10 years, 232 patients were treated at the East Carolina School of Medicine for cancer of the esophagus. Of these, 73 received neoadjuvant chemoradiation therapy and subsequent surgical resection. The results in this group suggest improved cancer control, with 18 patients (25%) remaining free of recurrence 3 years after treatment, compared with 11 out of 159 patients (7%) in the group that was not treated with neoadjuvant therapy (p < 0.0001). The 5-year recurrence-free survival with neoadjuvant chemoradiotherapy and surgery was 16% (12/73) compared with 3% (5/159) with other types of therapy. Two protocols of neoadjuvant chemoradiotherapy with subsequent surgery were compared: I: Split-course, once-a-day radiotherapy and concomitant cisplatinum/5-fluorouracil followed by esophagectomy. II: Accelerated, twice-a-day radiotherapy with concomitant triple chemotherapy using cisplatinum/5-fluorouracil/vinblastine followed by transhiatal extrathoracic esophagectomy. The survival rate was similar in the two groups of patients but the complication rate was higher in group II. Neoadjuvant chemoradiation therapy and the techniques of transhiatal esophagectomy may have contributed to the improved results in the treatment of esophageal carcinoma. Accelerated radiotherapy with triple chemotherapy was more toxic and did not give better survival rates than split-course, once-a-day, conventional, fractionated-protracted radiotherapy combined with two drugs.Over the past 10 years, 232 patients were treated at the East Carolina School of Medicine for cancer of the esophagus. Of these, 73 received neoadjuvant chemoradiation therapy and subsequent surgical resection. The results in this group suggest improved cancer control, with 18 patients (25%) remaining free of recurrence 3 years after treatment, compared with 11 out of 159 patients (7%) in the group that was not treated with neoadjuvant therapy (p < 0.0001). The 5-year recurrence-free survival with neoadjuvant chemoradiotherapy and surgery was 16% (12/73) compared with 3% (5/159) with other types of therapy. Two protocols of neoadjuvant chemoradiotherapy with subsequent surgery were compared: I: Split-course, once-a-day radiotherapy and concomitant cisplatinum/5-fluorouracil followed by esophagectomy. II: Accelerated, twice-a-day radiotherapy with concomitant triple chemotherapy using cisplatinum/5-fluorouracil/vinblastine followed by transhiatal extrathoracic esophagectomy. The survival rate was similar in the two groups of patients but the complication rate was higher in group II. Neoadjuvant chemoradiation therapy and the techniques of transhiatal esophagectomy may have contributed to the improved results in the treatment of esophageal carcinoma. Accelerated radiotherapy with triple chemotherapy was more toxic and did not give better survival rates than split-course, once-a-day, conventional, fractionated-protracted radiotherapy combined with two drugs.

Carcinoma of the Tongue in Norway and Wisconsin I. Incidence and Prognosis Related to Sex and Age

The records of 503 patients with carcinoma of the tongue diagnosed between 1958 and 1972 were reviewed. The preponderance of tongue carcinoma among men was confirmed both in The Norwegian Radium Hospital (NRH) and the University of Wisconsin Hospitals (UW), but it was relatively more frequent among women in NRH and in UW than in southern Europe. More women had on presentation less advanced tumors at NRH than at UW. The incidence of tongue carcinoma in Norway increased steadily with age for both sexes. The sex ratio did not change in Norway such as in England, Canada and the United States. Tumor of the posterior one-third of the tongue was relatively infrequent in women both in NRH and UW, in agreement with reports from other countries. The length of survival was analysed and no significant sex difference was demonstrated. The younger patients had less advanced tumors and a better prognosis.

Intraarterial iododeoxyuridine infusion combined with irradiation. A pilot study.

The halogenated pyrimidine, iododeoxyuridine (IUdR), enhances cytotoxicity of ionizing irradiation experimentally. Continuous intraarterial infusion of IUdR was combined with irradiation to maximize drug concentration in tumor and reduce potential systemic toxicity. Percutaneous tumor-specific artery catheterization was utilized in five patients, with delivery of IUdR (20 mg/kg/day) by continuous infusion 5 days prior to irradiation treatments and continued for 10–14 days. Infusion vessels included the internal mammary, the internal iliac, the renal, the common femoral, and the bronchial arteries. Conventional radiotherapy fields, fractionation, and total doses were utilized, and therapy was well tolerated. Low-grade leukopenia and thrombocytopenia was observed several weeks following infusion. A clinically nonsignificant skin reaction was observed within the irradiation fields 2–3 weeks after initiation of irradiation in several patients. No alopecia or stomatitis was observed. This study minimizes initial hepatic dehalogenation of IUdR when given by intraarterial administration. Two patients have been free of disease for over 20 years, with no long-term toxicity from IUdR therapy.

Role of dicentric analysis in an overarching biodosimetry strategy for use following a nuclear detonation in an urban environment.

AbstractIn the moments immediately following a nuclear detonation, casualties with a variety of injuries including trauma, burns, radiation exposure, and combined injuries would require immediate assistance. Accurate and timely radiation dose assessments, based on patient history and laboratory testing, are absolutely critical to support adequately the triage and treatment of those affected. This capability is also essential for ensuring the proper allocation of scarce resources and will support longitudinal evaluation of radiation-exposed individuals and populations. To maximize saving lives, casualties must be systematically triaged to determine what medical interventions are needed, the nature of those interventions, and who requires intervention immediately. In the National Strategy for Improving the Response and Recovery for an Improvised Nuclear Device (IND) Attack, the U.S. Department of Homeland Security recognized laboratory capacity for radiation biodosimetry as having a significant gap for performing mass radiation dose assessment. The anticipated demand for radiation biodosimetry exceeds its supply, and this gap is partly linked to the limited number and analytical complexity of laboratory methods for determining radiation doses within patients. The dicentric assay is a key component of a cytogenetic biodosimetry response asset, as it has the necessary sensitivity and specificity for assessing medically significant radiation doses. To address these shortfalls, the authors have developed a multimodal strategy to expand dicentric assay capacity. This strategy includes the development of an internet-based cytogenetics network that would address immediately the labor intensive burden of the dicentric chromosome assay by increasing the number of skilled personnel to conduct the analysis. An additional option that will require more time includes improving surge capabilities by combining resources available within the country’s 150 clinical cytogenetics laboratories. Key to this intermediate term effort is the fact that geneticists and technicians may be experts in matters related to identifying chromosomal abnormalities related to genetic disorders, but they are not familiar with dosimetry for which training and retraining will be required. Finally, long-term options are presented to improve capacity focus on ways to automate parts of the dicentric chromosome assay method.

Fast neutrons and Π-1 mesons in cancer therapy

Radiotherapy is unique as a medical specialty in that it depends upon physical sources of energy deposition within tissues to bring about profound and complex biological changes for the purpose of eradicating cancerous growths. Thus, it has the broadest interface with both physical and biological sciences of any clinical discipline. It is for this reason that progress in radiotherapy is continually stimulated by advances in bothphysical and biological sciences. In recent years, increasing attention has been focused on high energy particle radiations as possible additions to the therapeutic armamentarium, in an effort to improve the results obtainable with x and y radiations. The purpose of this paper is to discuss how some accelerator produced radiations, fast neutrons and Π mesons, might be of potential value to radiotherapy.