David Elkon

Optimum dose of radiotherapy for chemodectomas of the middle ear

Abstract Forty patients with chemodectomas of the middle ear were seen at the University of Virginia Hospital from 1932 to 1978. Surgery, post-operative radiotherapy or radiotherapy alone were the treatment modalities employed depending on the extent of the disease. These have been reviewed with regard to the clinical presentation and results of treatment with long term follow-up of 1–30 years. An attempt was made to determine the optimum dose of radiotherapy based on our data and reported cases in the literature. The majority of patients complaining of tinnitus, otalgia and pulsation obtained significant if not complete relief of symptoms. Cranial nerve defects, however, often persisted after therapy. Tumor was considered to be controlled if there was no increase in its size or progression of symptoms. Tumor control was obtained in eight of 10 early patients but only in two of seven more patients with advanced disease with total resection. Control rate with post-operative radiotherapy after subtotal resection was 85%. Radiotherapy alone was used for inoperable or recurrent tumors and control was obtained in 88 % of them. In addition to our data, the radiation dose used in over 200 patients reported in the literature were analyzed. There was only a 2% recurrence rate in patients who received 4000 rad/4 weeks or higher. Twenty-two percent of patients treated with less than 4000 rad developed recurrence. The tendency is to use a lower dose of postoperative treatment and a higher dose for gross inoperable tumors. 4000 rad/4 weeks seems to be adequate for control of postoperative residual disease and no more than 5000 rad/5 weeks are required even for advanced inoperable cases. By keeping the dose below 5000 rad/5 weeks, the incidence of complications such as brain necrosis is greatly decreased.

The Use of Strontium-90 in the Treatment of Carcinoma in Situ of the Conjunctiva

Four patients with carcinoma in situ were treated with strontium-90 beta ray application. The dose used was 4,500 rads after surgical removal or with small recurrent tumor and 7,000 rads for primary treatment. All patients were disease-free at follow-up periods of 48 to 320 months after treatment. One patient required superficial x-ray treatment for recurrent disease. No serious complications developed with the treatment and no progressive cataracts have occurred.

Olfactory esthesioneuroblastoma—variables predictive of tumor control and recurrence

This report surveys the world literature concerning prognostic variables for patients with esthesioneuroblastoma, an uncommon tumor arising from the olfactory epithelium. Specific sites of local and regional tumor extension, recurrence of disease after treatment, distant metastasis, and patient age were all found to be related to patient prognosis. There is a higher cure rate for patients treated after 1966, indicating an improvement in treatment methods. Also, the results indicate that in more recent years patients are being diagnosed and treated with less advanced disease. A statistical procedure, discriminant analysis, was employed, which permits the oncologist to predict patient outcome accurately. The discriminant function equation was 87% correct in identifying patients with tumor control (for a minimum period of 36 months) or recurrence and was 84% correct in classifying patients free of disease for at least 60 months or with recurrence. The statistical procedures employed in this report can be extended to other tumors and survival criteria.

Cancer of the posterior hypopharyngeal wall.

Thirty-five patients with cancer of the posterior pharyngeal wall treated at the University of Virginia Hospital since 1956 have been reviewed. A minimum follow-up of five years was available in all patients. These have been analyzed by stage and treatment modality, and the crude and determinate three and five year survival figures presented. In contradistinction to results reported for other hypopharyngeal sites, radiotherapy alone has proved the most effective treatment in the posterior wall, particularly for T1 and T2, NO lesions, where the crude and determinate survival after 5 years were 45 and 50% respectively. For advanced lesions no treatment approach has approved efficacious, although 2 or 10 (20%) patients treated initally by radiotherapy alone survived disease free for 3 years with subsequent surgical removal of residual nodal disease.

Does local X-irradiation of a tumor increase the incidence of metastases

KHT sarcomas were implanted into the right rear legs of C3H mice. Animals receiving no treatment died at 32 days with a 67% incidence of metastatic tumors. A dose of 6000 rads in ten fractions over 12 days, starting ten days after implant, delivered to the primary tumor (with the remainder of the body shielded) produced 55% local tumor control. However, 83% of the mice with local tumor control, subsequently developed metastatic lesions. Amputation of the tumor‐bearing leg either prior to the start of radiation treatment, at the end of treatment or at intervals during treatment or sham treatment, indicated that 1) metastases occurred predominantly during the initial three radiation fractions and 2) the increased incidence of metastases following irradiation was a result of the manipulations associated with the irradiation and not the irradiation per se. Irradiation did not change the distribution of organ sites involved with metastatic tumors compared to untreated or sham‐treated tumors.

Effect of hyperthermia on murine myeloid precursors.

Murine bone marrow was exposed to hyperthermia temperatures of 41.5 to 45.5°C. The proliferation capacity of myeloid progenitor and committed precursors was assayed in vivo utilizing spleen colony formation and diffusion chamber (DC) techniques. The survival of both pluripotential (CFU‐S) and committed myeloid (CFU‐DG) stem cells decreased exponentially with an increase in the heating period. Progression from CFU‐S to CFU‐DG significantly altered thermal sensitivity in the temperature range examined. Proliferation of mature granulocyte‐monocytes (G‐M) in DC is more thermostable than their stem cell precursors. Heat inactivation energies (enthalpies) of CFU‐S and CFU‐DG were derived from the slope of the heating time survival curves. Enthalpy of CFU‐S is 300 kcal/mole below 43° and 105 kcal/mole above 43°. The enthalpy of CFU‐DG is 250 and 145 kcal/mole below and above 43°, respectively.

The influence of ICRF-159 and levamisole on the incidence of metastases following local irradiation of a solid tumor.

Courses of irradiation consisting of 6000 rad in ten equal fractions over 12 days delivered to KHT sarcomas in mice controlled 55% of the local tumors but 83% of the mice died from metastases. Three strategies to reduce the risk of metastatic spread were tested. The fractionation scheme was changed to deliver the same total dose using a large initial fraction followed by seven equal portions with the same overall time. ICRF‐159 was used with the intention of partially synchronizing the tumor growth fraction in a radiosensitive state of the growth cycle and of promoting normalization of the tumor vasculature. Levamisole was used to stimulate the immune system. The combination of ICRF‐159 with the eight‐fraction radiation course proved to be effective for both increasing local control and decreasing the incidence of metastases. The addition of levamisole did not improve the results obtained with a combination of ICRF‐159 and irradiation.

Effect of ultrasound-induced hyperthermia and cis-diamminedichloride platinum II on murine renal function.

Murine renal function was evaluated after ultrasound‐induced kidney hyperthermia (42.5°C and 46,5%deg; C for 35 minutes) and the administration of cis‐diamminedichloride platinum II (8 mg/kg). A quantitative immunonephelometric technique was employed to determine urinary total protein (TP) and albumin (Alb) 1–180 days post‐treatment. Hyperthermia of 46.5°C elevated urinary TP excretion significantly more than that of 42.5°C cis‐diamminedichloride platinum (Cis DDP) administration greatly increased urine TP with a peak mean TP concentration of 488 μg/ml, four days after Cis DDP (normal range was 26–48 μg/ml). This returned to normal by day 14. The TP excretion after 42.5°C hyperthermia with concurrent Cis DDP was similar to Cis DDP alone, implying there was no potentiation of early or late Cis‐DDP‐induced renal damage by hyperthermia. Late mouse mortality was greater (P = 0.08) after Cis DDP alone, than Cis DDP with 42.5°C hyperthermia. There was a statistically significant increase (P < 0.05) in the Alb/TP exccetion ratio after the addition of 42.5°C hyperthermia to Cis DDP, implying an alteration in the site or nature of the Cis DDP renal lesion by hyperthermia.

Anatomic localization of radioactive gold seeds of the prostate by computer-aided tomography.

Abstract Anatomic localization of radioactive gold seeds, used for the treatment of malignant tumors of prostate, has been achieved using computerized tomography. Three illustrative cases are presented showing how the radiation dose distribution can be determined in relation to the location of the tumor. Areas of underdosage can then be corrected for supplemental external beam therapy.

CT scanning and interstitial therapy

Computerized tomography is of considerable value in determining tumor volume at many anatomic sites that are otherwise difficult to visualize. The ability to define volume accurately by means of a CT scan can be employed in interstitial radiotherapy. First, CT scan information may be used to plan the implant volume by defining the tumor location and extent prior to implantation of radioactive materials. Second, radioactive sources and/or afterloading devices can be localized after implantation by means of a CT scan. Third, follow-up of tumors to assess both tumor regression and recurrence is facilitated.