Robert S. Heusinkveld

Prospects for hyperthermia in human cancer therapy. Part I: hyperthermic effects in man and spontaneous animal tumors.

Systemic hyperthermia in man may occur by accident, as in heat stroke or malignant hyperthermia during general anesthesia, or it may be therapeutically induced (fever therapy). The latter has been used infrequently since the advent of antibiotics, except recently for treatment of cancer. Local or regional heating combined with x irradiation for human cancer therapy has been sporadically reported for over 60 years, but has not found its place in clinical medicine possibly due to technical limitations in heat production and dosimetry. Preliminary results are reported for treatment of spontaneous animal tumors with radiofrequency current fields and x irradiation.

Pacemaker failure due to radiation therapy.

Pacemaker malfunction occurred after a patient was given 3000–3600 rads to an area occupied by an A‐V sequential pacemaker. Analysis of the removed generator showed that there was malfunction of the large scale integrated circuit and the type of damage was consistent with radiation‐induced effects. The newer muJtiprogram‐mable units may be more sensitive to ionizing radiation than those previously available. (PACE, Vol. 5, March‐April, 1982)

External beam radiotherapy in cancer of the prostate: The university of arizona experience

Between 1973 and 1979, 218 patients with adenocarcinoma of the prostate stage A2 through D1 were treated with primary external beam radiotherapy. The majority of the patients (211) received 6000-7000 rad to the prostate using a small (160) or large (58) volume technique. With a minimum follow-up of 36 months and a maximum of 120 months, the control rates of the local tumor were 96%, 95%, 88% and 81% for stage A2, B, C and D1. The corresponding 5-year survivals were 100%, 82%, 60% and 42%. Mild to severe complications were documented in 35 cases (16%). The frequency and severity of the complications correlated with the size of the irradiated volume and history of previous surgery. The use of large fields, to encompass the regional lymphatics, is not associated with improved survival.

Combination chemotherapy of metastatic malignant schwannoma with vincristine, adriamycin, cyclophosphamide, and imidazole carboxamide: a case report.

This report describes a patient with a 15‐year history of schwannoma (peripheral nerve sheath sarcoma) who developed extensive pulmonary metastases associated with hypoxemia. Treatment with chemotherapy consisting of cyclophosphamide, vincristine, Adriamycin, and imidazole carboxamide resulted in a complete remission lasting 17+ months. Malignant schwannoma should probably be regarded as a drug sensitive neoplasm.

Hyperthermia by magnetic induction: II. Clinical experience with concentric electrodes☆

Thirty-one patients with visceral or extensive superficial malignant tumors of various histologies and sites have been evaluated for our hyperthermia protocols employing magnetic induction at 13.56 MHz with concentric electrodes associated with a commercially available device. Response data in patients completing combined hyperthermia and radiation treatment was difficult to analyze because of the short survival of these patients with advanced disease. Acute toxicity, however, was limited to 2/31 patients with minor skin blistering from excessive superficial heating. In this report we focus on clinical thermometric results. In 6/31 (19%) of patients, portions of the tumor achieved greater than or equal to 42.5 degrees C. In 3/31 (10%), nearly all the tumor achieved greater than or equal to 42.5 degrees C. Those tumors successfully heated to greater than or equal to 42.5 degrees C throughout were relatively superficial. In 22/31 (71%), temperature greater than or equal to 42.5 degrees C were not achieved at any measured site. Maximum applied power levels were limited by development of painful superficial hot spots in 21/31 (68%), by diffuse discomfort or systemic intolerance in 9/31 (29%), by maximum power output from the generator in 1/31, or by other factors in 2/31 patients. Some patients had both local and systemic discomfort that limited power levels. Based upon analysis of the thermometric results, we discuss the anatomic sites and tumor depths for which this technique is most applicable.

Treatment of advanced cancer of the cervix with transperineal interstitial irradiation

A pilot study using transperineal interstitial implantation to the parametrium in patients with locally advanced carcinoma of the cervix or with distorted anatomy is presented. Twenty-one consecutive patients (2 cervical stump Stage IB, 3 Stage IIB, 15 Stage IIIB, 1 Stage IVA) received one (12) or two (9) implants following 40-45 Gy whole pelvis external irradiation. In addition 8 patients underwent staging laparotomies concurrently with the first implant procedure. Control of the pelvic tumor was accomplished in 18 of 21 patients (85%) with a mean follow-up of 26 months (range 15 to 48 months). Seven patients (33%) developed long term complications (fistula 3, superficial necrosis of the vagina 1, severe proctitis or cystitis 3). Six of the complications occurred in 8 patients (75%) who had radioactive sources placed on the surface of the vaginal obturator as a substitute for the lack of tandem. In contrast, only 1 in the remaining 13 patients (8%) who did not have obturator sources placed, developed long term complications.

Control of radiation-induced diarrhea with cholestyramine

Cholestyramine is a non-absorbable ion-exchange resin which specifically binds bile salts. We have treated seven patients with acute or chronic radiation-induced diarrhea that was refractory to the usual methods of control with cholestyramine. In each case, the diarrhea was controlled with cholestyramine. This observation supports previous experimental work with animals which indicated that bile salts contribute to the genesis of radiation-induced diarrhea. Cholestyramine is well-tolerated, but should not be administered with certain oral medications. The results of this small series are preliminary, but point the way toward a more extensive clinical trial to define the usefulness of cholestyramine in the treatment of refractory acute or chronic radiation-induced diarrhea.

Effect of Protein Modification on Erythrocyte Membrane Mechanical Properties

Cross-linking of membrane proteins in normal erythrocytes and corresponding erythrocyte ghosts by the bifunctional reagent glutaraldehyde results in progressive increase in force required for membrane deformation as measured by uniaxial extension in glass micropipettes. The qualitative similarity of behavior in ghosts containing less than 0.5% of the original hemoglobin indicates that modification of membrane proteins is responsible for the altered elasticity. The monofunctional agent parachloromercuribenzoic acid, which penetrates the membrane to affect sulfhydryl groups caused quantitatively less conspicuous change in the membrane elasticity and resistance to local membrane failure during the experimental membrane fragmentation process. Reduction of the erythrocyte membrane’s spectrin content appears to reduce hyperelasticity and tensile strength whereas removal of integral protein such as glycophorin had no effect. In the senescent erythrocyte in which increased protein aggregation has been postulated as a function of aging, membrane elasticity is altered; these cells’ membranes behave like those of the glutaraldehyde model. ATP-depleted cells, in which protein aggregation occurs, previously were interpreted to have reduced membrane deformability with Ca++ accumulation; membranes’ normal elastic behavior was observed. These observations in model systems support the hypothesis that membrane protein aggregation, determined by the phosphorylation state of spectrin and actin may affect intrinsic membrane properties of hyperelasticity and tensile strength.

Enhanced radiation reaction following combination chemotherapy for small cell carcinoma of the lung, possibly secondary to VP16-213

Abstract A new combined radiation-chemotherapy protocol for the treatment of small cell lung carcinoma has produced unexpectedly severe normal tissue injury during radiation therapy. Thirteen of 23 patients who received radiation treatment plus combination chemotherapy [Vincristine, Adriamycin, Cyclophosphamide and VP16-213 (epipodophyllotoxin)] developed severe epithelial reactions from relatively low radiation doses. Prior experience with combination of radiation and chemotherapy leads us to implicate VP16-213 as the agent responsible for the enhanced radiation reactions.

Comprehensive radiotherapy for advanced Hodgkin's disease refractory to chemotherapy.

Seven patients with advanced nodular sclerosing Hodgkins disease who relapsed after initial intensive combination chemotherapy were selected for individualized pathologic restaging and comprehensive radiotherapy. One patient failed to respond completely to mantle-field irradiation and no further staging or radiotherapy was undertaken. Six other patients underwent staging laparotomy and received total nodal irradiation including prophylactic lung irradiation (5 cases) and hepatic irradiation (3 cases). Irradiation was well tolerated. Complete remission was achieved by 5 patients and 2 continue in remission 29+ and 32+ months after beginning of irradiation. Five of the 7 patients remain alive. This study indicates that comprehensive irradiation is a relatively well tolerated and effective treatment for carefully selected patients with advanced Hodgkins disease who have relapsed after combination chemotherapy. For selected patients, pathologic restaging and comprehensive radiotherapy can be considered as an alternative to further chemotherapy.