Gerald A. King

Induction and repair of DNA double-strand breaks

Induction and repair of DNA double-strand breaks (DSBs) was measured using a pulsed-field gel electrophoresis system. A cell line of methotrexate-resistant EMT-6 cells that contain numerous double-minutes (DMs) 3 million base pairs in size was employed. The electrophoretic mobility of these DMs depends on whether they have zero, one, or more than one DSB. With no DSBs the DMs remain as circles and are trapped in the origin of electrophoresis, but with one DSB the DMs migrate as a discrete band and can be detected easily through hybridization with a gene-specific probe. Using a clamped homogeneous electrical field apparatus, the induction of DSBs in the 1.5 to 12 Gy X-ray dose range is studied and is shown to be linear. Double-strand break repair following 7.5 Gy is studied, and is shown to be exponential. The kinetics of both induction and repair of DSBs induced in DM DNA was compared to the induction and repair of DSBs in chromosomal DNA and is shown to be similar. The kinetics of repair of DSBs following 7.5 Gy for cells embedded in agarose and cells in suspension is shown to be similar.

Complications of High Dose Preoperative Irradiation for Advanced Laryngeal-Hypopharyngeal Cancer

The authors studied 162 patients with advanced cancer of the laryngopharynx who were treated over the same period of time by standard techniques. High dose preoperative supervoltage irradiation to 5000 rads/5 weeks through large opposed lateral fields and a lower anterior neck field is not accompanied by a prohibitive increase in mortality or morbidity for patients with stage III-IV largynogopharyngeal cancer. Rescue surgery for recurrence after definitive irradiation can be accomplished.

Irradiation of Primary Brain-Stem Tumors

Of 40 patients treated for brain-stem tumors, 20 had lesions of the thalamus and midbrain (group A) and 20 had lesions of the pons and medulla (group B). Performance status measured 1 month after irradiation improved in 16 of 20 group A and 11 of 20 group B patients and was a valuable prognostic factor. The survival rate at 5 years was 40% (8/20) in group A and 30% (6/20) in group B. All recurrences appeared within 3 years and were predominantly locoregional. Treatment factors, including dose and field size, are analyzed.

Induction and repair of DNA double-strand breaks in the same dose range as the shoulder of the survival curve

We have used pulsed-field gel electrophoresis (PFGE) to test two hypotheses that have been proposed to explain the survival curves with shoulders which are characteristic of low-LET ionizing radiation: (1) Neutral elution studies of the induction of double-strand breaks (DSBs) have suggested that ionizing radiation might induce DSBs in a nonlinear fashion at low doses. (2) Based on analogies to enzyme kinetics, DSB repair might be saturating in the shoulder region. We quantified DSB induction and survival resulting from doses between 0 and 5 Gy spanning the shoulder region of the survival curve. We found that DSB induction was linear at all doses tested down to 0.5 Gy, the limits of sensitivity. Therefore, nonlinear DSB induction cannot account for the shape of the survival curve. To determine whether the DSB repair system was saturated in the shoulder region, we quantified the rate of DSB repair as a function of dose of X rays between 1.25 and 20 Gy. The repair of DSBs was exponential with half-times of repair constant for doses below 10 Gy, and averaged 28 min. We determined the initial rate of repair from the exponential repair kinetics for each dose. The initial rate of repair after radiation treatment increased linearly with dose up to at least 10 Gy. Therefore, saturating DSB repair cannot explain the shoulder of the survival curve.

Lead as surface bolus for high-energy photon and electron therapy

Dose distributions were evaluated under thin sheet lead used as surface bolus for 4- and 10-MV photons and 6- and 9-MeV electrons using a parallel-plate ion chamber and film. A narrow, significantly low dose region (-17%) was noted for 4-MV photons, whereas a 6% increase in dose was present for 10-MV photons. The dose was elevated 15%-22% near the surface of electron fields with lead bolus, but depth dose relationships were similar to soft-tissue-equivalent (STE) bolus. Investigation of partial-field bolus (2-cm-diam circle) documented reduced doses due to lack of lateral electron equilibrium for 10-MV photons, which was less evident using lead, and large edge effects (up to 30%) for electrons using either lead or STE bolus. Dose distributions on sloped surfaces with electron fields were similar for lead and STE; both require thickness adjustment to achieve a desired effective thickness normal to the surface. Lead bolus has been used successfully in clinical practice for photons.

High Dose Preoperative Irradiation for Advanced Laryngeal-Hypopharyngeal Cancer

Combined therapy, consisting of 5000 rads delivered in five weeks followed by total laryngectomy ± radical neck dissection, was compared with treatment by irradiation (6000–7000 rads) with surgical salvage when clinically possible for radiation failure. Patients were categorized according to site of primary cancer (glottic, supraglottic and pyriform sinus) and staged (T, N, M). Survival was equally good in the two programs for glottic and supraglottic lesions, N0 or N1. The combined treatment program was judged superior for supraglottic and pyriform sinus lesions, N2 or N3.

Combination Chemotherapy and Radiotherapy in Smalt-Cell Carcinoma of the Lung

A combination of chemotherapy (Cytoxan, vincristine, and CCNU) and radiation therapy was used to treat 37 patients with small-cell carcinoma of the lung. There was 49% complete remission and an overall 76% objective response with an overall median survival of 12.5 months and 17 months for those showing a complete response. No serious morbidity was observed.

Ventricular uptake during brain scanning. A case report of ventricular lymphomatosis.

Visualization of the cerebral ventricles during radionuclide brain scanning is rarely reported. A case demonstrating the lateral ventricles by brain scanning with 99mCc-stannous glucoheptonate in a patient with lymphoma is presented.

High dose preoperative irradiation for advanced laryngeal—hypopharyngeal cancer

Combined therapy, consisting of 5000 rads delivered in five weeks by total laryngectomy +/- radical neck dissection, was compared with treatment by irradiation (6000-7000 rads) with surgical salvage when clinically possible for radiation failure. Patients were categorized according to site of primary cancer (glottic, supraglottic and pyriform sinus) and staged (T, N, M). Survival was equally good in the two programs for glottic and supraglottic lesions, N0 or N1. The combined treatment program was judged superior for supraglottic and pyriform sinus lesions, N2 or N3.

Local excision and radiotherapy for cancer of the oral tongue. A preliminary report.

A GROUP OF 18 PATIENTS WITH SQUAMOUS CELL carcinoma of the mid one-third of the tongue was treated by local resection and planned postoperative radiotherapy between 1976 and 1980. Tumors 0.5 cm or greater in thickness were included; no patients had cervical ad-enopathy. Six were categorized as T1, 10 as T2 and two as T3. In eight patients, histologie review showed tumor extension at or near the resection margin, despite a tumor-free margin at frozen section, while in 10 patients the margins were clear. Local tumor control was achieved in 16 patients (89%). Two failures were evident within 3 months after completion of treatment. The relatively short follow-up of such a small series limits the conclusions from this preliminary study, but the excellent results thus far merit further study.