Twice-daily fractionation schemes for advanced head and neck cancer.

Eighty-five patients with advanced squamous cell carcinoma of the head and neck were treated with twice-a-day fractionation schedules between April 1972 and December 1980. Two types of treatment were distinguished: hyperfractionation, by which 65 patients (Group I) were treated at a weekly dose rate of 1100 to 1200 rad (10 fractions of 110 to 120 rad) in 5 to 6 1/2 weeks for either advanced primary disease (Group 1A) and/or advanced neck metastases (Group IB); and accelerated treatment, used to treat 20 patients (Group 2) who had fast-growing and usually massive neck nodes, at a weekly dose rate of 1300 to 1500 rad in 7 to 10 fractions, to a total dose of 6100 to 8000 rad in 4 to 6 weeks. The radiation portals for patients in Group 2 excluded the mucosa of mouth and throat for part of the treatment. The local control rate at 1 year in Groups 1A and 1B was 41 and 54%, respectively; the incidence of complications was 17%, 5% of them fatal. The local control rate in Group 2 was 80%. Seven patients in this group underwent a neck dissection 6 to 8 weeks following irradiation. Four specimens were negative for tumor. In two, only necrotic tumor cells were identified, and in one specimen morphologically intact tumor cells were seen. There were no fatal complications.

Dosimetric evaluation of a pencil-beam algorithm for electrons employing a two-dimensional heterogeneity correction.

The accuracy of a pencil-beam algorithm for electrons employing a two-dimensional heterogeneity correction is demonstrated by comparing calculation with measurement. Ionization measurements have been made in a water phantom for a variety of non-standard geometries. Geometries to demonstrate the effect of an extended treatment distance, a sloping skin surface, and an irregular skin surface have been selected. Additionally, thermoluminescent dosimeters have been used to measure distributions in tissue-substitute phantoms, which were designed from individual patient computerized tomographic scans. Three patient scans have been selected: (1) diffuse hystiocytic lymphoma of the left buccal mucosa and retromolar trigone; (2) squamous cell carcinoma of the nose at the columnella ; and (3) carcinoma of the maxillary antrum. Results demonstrate the algorithm's ability to simultaneously account for the isodose shifting as a result of internal heterogeneities and for sidescatter non-equilibrium caused by lateral discontinuities of the skin surface and internal anatomy. The algorithm is shown to generally be accurate to within +/- 4% in the treatment volume or +/- 4 mm in regions of sharp dose gradients as found in the penumbra and distal edge of the beam. Examples of greater disagreement are shown and their physical interpretation discussed.

Non-Hodgkin's lymphoma of the tonsil. A clinicopathologic study of 65 cases.

Sixty-five patients presenting to M. D. Anderson Hospital and Tumor Institute with Stages IE and IIE primary tonsillar lymphoma between 1954 and 1981 were reviewed. All cases were non-Hodgkin's lymphomas, with the majority being diffuse large cell lymphoma (85%). Initial therapy was radiotherapy alone in 54 patients, radiotherapy combined with chemotherapy in 8 patients, and chemotherapy alone in 3 patients. Stage was the most important prognostic factor, with 86% and 41% 5-year survivals for Stages IE and IIE, respectively (P = 0.006). Lymphangiography was crucial in staging patients with clinically positive cervical lymph nodes because 94% of clinically staged IIE patients developed recurrent disease, in comparison with only 50% of lymphangiogram-staged IIE patients. The incidence of large cell lymphoma was so high as to preclude analysis of survival by histologic type. From this limited series, radiotherapy alone would appear to be sufficient initial therapy for Stage IE patients, whereas Stage IIE patients probably benefit from the addition of prophylactic chemotherapy. Relapses were most common in nonirradiated lymph-node-bearing areas, with the majority presenting in the first 2 years following initial therapy. The salvage of relapsing patients has been disappointing, with the best hope residing in combination chemotherapy.

Misonidazole combined with large-fraction pelvic irradiation in the treatment of patients with advanced pelvic malignancies. Preliminary report of an ongoing RTOG phase I-II study.

Between October 1979 and January 1982, a total of 39 cases were entered on a nonrandomized phase I-II protocol for the evaluation of misonidazole combined with radiation in the treatment of patients with advanced pelvic malignancies of multiple gynecological and gastrointestinal origin. Patients were treated with pelvic irradiation using a dose of 1000 rad in one fraction every 4 weeks for a total of three treatments. Oral misonidazole at a dose of 4 g/m2, was administered 4-6 hours prior to the radiation treatment (total dose, 12 g/m2). Of the 39 patients entered, 25 have completed the three doses of radiation and have had at least one follow-up after the third treatment. Eight patients have had insufficient follow-up information for evaluation and five patients did not complete three doses of radiation but have follow-up. One patient was excluded from the study. Among the 30 patients with follow-up, there were four complete responses (13.3%) and seven partial responses (23.3%). Two patients showed no response, and 17 experienced progression of disease. Follow-up time ranged from 2 to 16 months. The most frequent toxicity in the study has been nausea and vomiting. There were eight cases of neurotoxicity reported: ototoxicity grade 1 (one patient), peripheral neuropathy grades 1 and 2 (six patients), and C.N.S. toxicity grade 2 (one patient). Toxicity from radiation was difficult to separate from the presenting symptomatology. In the 30 patients with follow-up information, eight cases of abdominal sequelae were seen with five of them major complications (perforation, obstruction, and abscess). Early information from the study indicates the following: The most frequent morbidity at this point is acute nausea and vomiting. This level of nausea is consistent with the protocol dose of misonidazole. From the evaluable patients, 5/30 (17%) have developed major bowel problems requiring surgery. At the time of this report, this protocol remains open for case accession.

Hypothalamic, pituitary and thyroid dysfunction after radiotherapy to the head and neck.

One hundred-ten patients who had nasopharyngeal cancer and paranasal sinus tumors and were free of the primary disease were studied one to 26 years following radiotherapy. There were 70 males and 40 females ranging in age from 4 to 75 years, with a mean age of 36.5 years. During therapy both the hypothalamus and the anterior pituitary gland were in the field of irradiation. The radiation dose to the hypothalamus and the anterior pituitary gland was estimated to be 400 to 7500 rad with a median dose of 5618 rad to the anterior pituitary gland and a median dose of 5000 rad to the hypothalamus. We found evidence of endocrine deficiencies in 91 of the 110 patients studied. Seventy-six patients showed evidence of one or more hypothalamic lesions and 43 patients showed evidence of primary pituitary deficiency. Forty of the 66 patients who received radiotherapy to the neck for treatment or prevention of lymph node metastasis showed evidence of primary hypothyroidism. The range of the dose to the thyroid area was 3000 to 8800 rad with a median of 5000 rad. One young adult woman who developed galactorrhea and amenorrhea 2 years following radiotherapy showed a high serum prolactin level, but had normal anterior pituitary function and sella turcica. She regained her menses and had a normal pregnancy and delivery following bromocriptine therapy. These results indicate that endocrine deficiencies after radiotherapy for tumors of the head and neck are common and should be detected early and treated. Long-term follow-up of these patients is indicated since complications may appear after the completion of radiotherapy.

Anatomical coverage in elective irradiation of the neck for squamous cell carcinoma of the oral tongue.

From January 1954 through December 1978, 146 patients with squamous cell carcinoma of the oral tongue and clinically negative neck had their primary lesion controlled with irradiation. Metastases to the neck developed later in: 27 of 76 patients (36%) treated by interstitial implantation; nine of 27 patients (33%) who received 2,000 rad in five fractions to the upper neck prior to the implant; eight of 19 (42%) patients who received 5,000 rad through an upper ipsilateral neck field prior to the implant; four of 24 patients (16.6%) who received 5,000 rad through bilateral portals to the upper neck with or without irradiation of the lower neck. In the 43 ipsilateral neck failures, 23 were in the upper jugular chain, (posterior subdigastric nodes), 12 in the mid-jugular, three in the lower jugular, and four in the more anterior part of the subdigastric area. There was one failure in the posterior cervical chain, and five contralateral neck failures. A review of the treatment charts showed that the patients who had an ipsilateral upper neck field only, had smaller portals because the irradiation was tailored to produce shrinkage of the primary tumor prior to needling. To include adequate coverage of the posterior subdigastric nodes (upper jugular), the bodies of the vertebrae must be seen on the simulator films. Also the junction of the subdigastric and the mid-jugular lymphatics must be covered. Although there were only three failures in the lower jugular nodes, it is technically easier to treat the upper mid-jugular nodes through an anterior appositional portal to the lower neck. A dose of 5,000 rad must be given since 2,000 rad, even if delivered in five fractions, gives a failure rate as if there had been no irradiation to the neck.

Effect of pulmonary function of split-course radiation therapy for carcinoma of the lung.

A group of patients treated with radiation therapy for bronchogenic carcinoma were evaluated with serial pulmonary function testing. The patients were treated with a split-course technique with 60-Cobalt. A total of 30 patients with unresectable carcinoma have been studied. Measurements of vital capacity (V.C.) and forced expiratory volume at one second (F.E.V.1) were made prior to therapy; at the beginning and end of the split; upon completion of therapy; and thereafter at 1, 2, and 6 months post therapy. The percentage changes in V.C. and F.E.V.1 from pretreatment values are plotted against time. A trend to improve throughout the treatment course is suggested by these results. Twelve patients have been studied at six-month follow-up: eight of the patients showed less than a 10% reduction from pretreatment V.C. and F.E.V.1 and had no respiratory impairment; of the other four patients, three had evidence of progression of disease in the thorax.