Biomedical subjects
Publications and source records attributed to A L Wiley.
Primary anterior mediastinal malignant teratoma is an uncommon tumor. A 17-year-old girl presented with an advanced tumor extending parasternally. Therapy consisted of intraarterial iododeoxyuridine and irradiation followed by surgical resection after failing multidrug therapy. The patient is without evidence of disease 23 years after therapy.
Since subclinical hepatic metastases are frequently present at time of diagnosis of pancreatic carcinoma, any meaningful effort to improve survival must include 'prophylactic' liver therapy in addition to treatment of the pancreatic primary. We report the results of a prospective, unrandomized clinical trial of a 2-week liver and pancreas infusion (by hepatic artery) of 5-fluorouracil (5-FU) and pancreatic irradiation to 50-60 Gy, combined with prophylactic irradiation of the liver with approximately 20 Gy. Of 21 evaluable patients, 17 completed therapy without excessive toxicity and had a median survival of 50 weeks. Contrary to historical controls, the liver in our series was rarely the first site of failure (6%), suggesting that the combination of hepatic artery 5-fluorouracil and 20 Gy liver radiation may suppress subclinical (microscopic) liver metastases without significant hepato-toxicity. When radiation doses to the pancreas were increased above 50 Gy there was improvement in primary tumor control, although failure in the pancreatic bed remained the most common site of failure. Future clinical investigation of this form of combined therapy for eradication of micro-metastasis in the liver, combined with more aggressive local pancreatic therapy, would seem appropriate.
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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.
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.
The local control rates in patients with squamous cell carcinoma of the tongue, treated between 1958 and 1972, were determined by retrospective analysis of the records of 339 patients at the Norwegian Radium Hospital and of 164 patients at the University of Wisconsin Hospitals. The correlation between the clinical stage and the local control rate was good in Norway, less striking in Wisconsin. As the tumor grew in size it generally became increasingly difficult to control. Irradiation and surgery appeared relatively satisfactory in patients with tumors in early stages, but were often inadequate in the advanced tumors. The differences observed between Norway and Wisconsin were statistically significant only for the tumors of the base of the tongue and T2N0, T3N0 and TxN1 tumors of the anterior two-thirds of the tongue.
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"Tumor equivalent" phantoms containing inorganic salts (KH2PO4, CH3COOK, NaCl and Kl) were scanned on an EMI 5005 body scanner at 140 kVp, 28 mA; 120 kVp, 33 mA; and 81 kVp, 42 mA. Significant signal gain for the detection of higher atomic number elements by multiple energy scanning was noted. Certain sarcomas are known to accumulate high Z elements. Accordingly, excised specimens of various histologies of human sarcomata (chondrosarcoma, liposarcoma, and malignant fibrous histiocytoma) were scanned at 140 kVp and 81 kVp. Using selected areas of interest in the computed tomographic (CT) image to direct the in vitro biopsy of various regions of excised tumors, interesting correlations between the CT number variation and the respective, high Z elemental composition variation, as determined by thermal neutron activation analysis were observed. Further investigation with phantoms and excised sarcomata at 62 kVp and 42 mA suggested that dual energy CT scanning (at 140 kVp and 62 kVp) may be a method of monitoring "effective Z" and heavy element compositional changes. The authors are also attempting to develop these same low kilovoltage techniques as a method for the noninvasive clinical monitoring of an antisarcoma chemotherapeutic agent, cis-diammineaichloroplatinum (11).
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To study the effects of upper mantle radiation therapy on pulmonary function, forced expiratory volume in one second (FEV1), vital capacity (VC), inspiratory capacity (IC), diffusing capacity for CO (DLCO) and diffusion per unit of alveolar volume (DL/VA were determined in 28 patients with Hodgkin's disease, stages 1--3, before therapy and at regular intervals thereafter. Within the first year of follow-up there were significant declines in DLCO, VC, and IC, whereas there were no significant changes in FEV1 or DL/VA. DLCO showed the greatest decline in the largest number of subjects (22/28). Eleven of the 22 had 20 to 60 percent decline of DLCO from baseline. The maximum mean decline in DLCO was -12.7 +/- 3 percent at the 87th +/- 3 days from initiation of therapy postradiation sustained through the 150th day and improving to pretreatment value (+/- 5 percent) by the 8th to 12th month. The changes in DLCO seemed to be independent of the radiation dose ranges evaluated, clinically apparent intrathoracic lymphoma, postradiation radiographic abnormalities and respiratory symptoms. We concluded that impairment in diffusing capacity and loss of vital capacity will develop in most patients receiving upper mantle radiation therapy, indicating that pulmonary reaction occurs despite lung shielding. The functional losses were prolonged and occasionally severe, but were transient and subclinical in most but not all cases. A case of fatal radiation pneumonitis affecting the lung beyond the field of irradiation is reported.
A 10 kG magnetic field has been used to modify the conventional electron beam isodose distributions. Isodose curves of modified distributions for single and multiple beams measured in a polystyrene phantom are presented. The results suggest a potential use of this technique to achieve dose distributions adjusted to the various tumor contours and corrected for heterogeneity effects.
The treatment of advanced base of tongue carcinoma with concurrent radiation therapy and 5-fluorouracil versus radiation therapy alone is compared. Although the results are inconclusive, it is noteworthy that all the 5-year survivors were patients given combined treatment. Important questions regarding optimization of time-dose relationships with combined therapy were generated. Accordingly, 18F-5 fluorouracil was synthesized in an attempt to answer some of these questions.
In 1961, a randomized study was begun at the University of Wisconsin Medical Center in which the treatment of advanced squamous cell carcinoma of the head and neck with radiation therapy was compared with combined treatment with radiation therapy and 5-Fluorouracil. One hundred and thirty-six patients with primary lesions in the oral cavity, the base of the tongue, and the oropharynx were analyzed. Both local control and survival were better in the combined treatment group than in the group with radiation therapy alone. However, in only the oral cavity patient population was the difference statistically significant. Both acute and late complications were also increased in this group of patients who received combined treatment.
As an attemp to improve the quantitative and qualitative evaluation of neoplastic neck nodes, we are evaluating ultrasound B-scans. Clinical examples are presented to demonstrate how "B-scans" may be used to evaluate lymph node size and response to therapy. Qualitatively, such scans may also be of value as a means of establishing lymph node boundaries and position with respect to other neck structures.
A small pilot series (eight patients) of surgically unresectable retroperitoneal tumors treated with radiotherapy and a selective, prolonged, continuous intra-arterial 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.
One primary goal of preoperative radiotherapy for hypernephroma is to reduce the volume of tumor and, therefore, improve the possibility of resection. It is important that this goal be accomplished promptly so that 4 to 6 weeks after radiation therapy nephrectomy can be attempted. A longer waiting period may allow fibrosis of the normal surrounding tissues and make surgery more difficult. In addition, longer waiting periods could theoretically increase the probability of metastasis. Therefore, we plan to continue clinical investigation on the use of combined intra-arterial actinomycin D and radiotherapy as a possible useful means of improving the possibility of prompt surgical resection, since theoretically this regimen may be a method of increasing the effective radiation dose to the hypernephroma without increasing the effective radiation dose to surrounding normal tissue, such as bowel. The method may also have merit as an improved means of palliating selected patients with metastases who are symptomatic from a bulky primary hypernephroma.
A system employing an opaque projector mounted on a steel-framed cart was constructed to provide full-scale enlargement of ultrasound echograms for use in radiation therapy planning. Anatomical outlines from the enlarged echograms are traced directly into a minicomputer. Life-sized isodose curves for a selected treatment plan are overlayed on the enlarged echogram to produce a permanent record for treatment field adjustments and retrospective analysis.
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