Carcinoma of the major and minor salivary glands: analysis of treatment results and sites and causes of failures.
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Biomedical subjects
Publications and source records attributed to K K Fu.
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Between January 1957 and June 1974, 173 patients with carcinoma of the supraglottic larynx were treated by an integrated approach at the University of California in San Francisco. The policy was to use radiotherapy or surgery alone for Stage I and II disease, radiotherapy combined with either supraglottic laryngectomy or total laryngectomy for resectable Stage III and IV disease, and radiotherapy alone for advanced unresectable disease. Control of the disease in the primary site was achieved in 92% of T1a, 88% of T1b, 80% of T2, 79% of T3 and 56% of T4 lesions. Of the 36 patients with late Stage I and resectable Stages III and IV disease treated by combined preoperative radiotherapy and supraglottic or total laryngectomy, the primary lesion was controlled in 33 (92%). Recurrent disease in the primary site after radiotherapy alone, when detected early, was usually controlled by subsequent surgery, whereas recurrent disease after surgery was not controlled by radiotherapy. Preservation of a functioning vocal apparatus was achieved in 44% of the patients whose primary lesion was controlled. Control of cervical lymph node metastasis was achieved in 71% of N1, 38% of N2, and 25% of N3 disease. No disease recurred in the radically dissected neck which received preoperative radiotherapy. Radiotherapy also reduced the incidence of subsequent neck disease in patients without cervical lymph node metastasis initially from 23% to 14%.
In order to determine the modification of radiation effects on critical normal tissues which occurs with combinations of radiation and cancer chemotherapy, a review of laboratory and clinical data has been carried out. Information on 10 different normal tissues is available. It is clear that the antibiotic cancer chemotherapeutic agents are the most likely to enhance radiation injury, with increased levels reported in all tissues except the central nervous system. The second most common type of injury with combination therapy appears to occur with drugs causing injury to the normal tissue on their own, such as adriamycin in the heart and methotrexate in the central nervous system. Quantification of the dose-effect factor is only available on a limited number of tissues, and, primarily, in experimental animals. From these limited data, it is clear that dose-effect factors between 1.1 and 1.8 are seen, indicating that radiation doses must be reduced by 10-80% for the same level of injury when combined with chemotherapy. The augmentation of radiation damage by cancer chemotherapeutic agents is a serious problem in a wide range of tissues, but a problem which can be dealt with by accurate knowledge as to the dose-effect factor and appropriate modification of the radiation treatment.
In a retrospective computer dosimetry analysis of 58 patients with carcinoma of the oral tongue treated with interstitial radium implants alone or in combination with external irradiation, dose and volume appear to be the most important factors in both local control and the incidence of necrosis; in the dose rate range commonly used in clinical interstitial radiotherapy, dose rate has no significant effect. The optimal minimum tumor doses for local control vary with the size of the primary lesion: 6,000 rads for T1 lesions and 6,500 rads for T2 lesions treated with interstitial radium implants alone and 7,500 rads for lesions treated with interstitial radium implants in combination with external irradiation. For lesions treated with implants plus external irradiation, greater local control was achieved when most of the dose was delivered through the interstitial implants. For a given volume, the incidence of necrosis was directly proportional to the degree of overdosage; for a given dose, the incidence of necrosis was directly proportional to the volume receiving the dose.
EMT6 tumors were exposed to neon ions in vivo and in vitro in the plateau and spread-out Bragg peak regions of the beam. The RBE in vivo was 1.7-2.1 in the plateau region and 2.6-2.9 in the Bragg peak; the OER was 2.0 and 1.4, respectively. Neon ions have great potential in the radiotherapy of tumors because of their decreased OER and excellent depth-dose distribution in tissue.
In 204 patients with squamous cell carcinoma of the oral tongue treated with radiation therapy, the most significant prognostic factors appeared to be the presence of neck lymph node metastasis on presentation and the status of the disease three months after treatment. The most common site of failure was the primary lesion, either alone or with neck disease. External irradiation alone was seldom successful. Use of peroral cone irradiation or interstitial implants, either alone or in combination with external irradiation, achieved good local control in early lesions. When the primary tumor was uncontrolled by radiation therapy, salvage with surgery was rare. When failure occurred in the neck alone, radical neck dissection was successful in the majority of cases.
Continuous irradiation in vivo at dose rates ranging form 0.54 to 274 rads per minute was performed in mice using the EMT6 tumor, the gut clone system, and the bone-marrow CFU system. A progressive increase in D0 and decrease in ñ were seen with decreasing dose rates in the EMT6 tumor and the gut clone system. The D0 showed little change in the bone-marrow CFU system. These findings are related to the D2-D1 values obtained from split-dose experiments at conventional dose rates. The results do not fit the various mathematical models proposed for correlating the effects of continuous low-dose-rate irradiation and acute exposure.
Forty-two patients with recurrent nasopharyngeal carcinoma in the primary site and/or neck nodes were treated at the University of California, San Francisco, between 1940 and 1974. Sixty-nine per cent of the recurrences appeared within 3 years and 83% within 5 years after initial treatment. Retreatment included external radiotherapy and/or intercavitary radium or cobalt beads in the majority of cases. The actuarial survival rate was 41% at 5 years after first recurrence. Survival rates increased proportionally with increasing time between initial treatment and recurrence. There was no statistically significant difference in survival rates with respect to age, sex, race, or histology. Local soft-tissue or bone necrosis developed in 9 patients, but both conditions were tolerated well.
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The signals that determine body part identity in vertebrate embryos are largely unknown, with some exceptions such as those for teeth and digits. The vertebrate face is derived from small buds of tissue, facial prominences, that surround the embryonic oral cavity. In chicken embryos, the skeleton of the upper beak is derived from the frontonasal mass and maxillary prominences. Here we show that bone morphogenetic proteins (Bmps) and the vitamin A derivative, retinoic acid (RA), are used to specify the identity of the frontonasal mass and maxillary prominences. Implanting two beads adjacent to the stage-15 presumptive maxillary field, one soaked in the Bmp antagonist Noggin and one soaked in RA, induces a duplicate set of frontonasal mass skeletal elements in place of maxillary bones. We also show that the duplicated beak is due to transformation of the maxillary prominence into a second frontonasal mass and not due to ectopic migration of cells or splitting of the normal frontonasal mass. Thus the levels of Bmp and RA determine whether specific regions of the face form maxillary or frontonasal mass derivatives.
Clinical investigations for cancer of the head and neck, primarily tumors of the upper respiratory and digestive tracts, have been one of the most important components of the Radiation Therapy Oncology Group (RTOG) since its inception 30 years ago. Emphasis from the very beginning to the present time has been on altered fractionation. Studies of hypoxic cell sensitizers were also explored for many years. More recently, combinations of radiation therapy with cytotoxic chemotherapeutic agents, either sequentially or concurrently, have been a major focus. Although the majority of the trials have been for unresectable tumors, surgical adjuvant radiation therapy alone or combined with chemotherapy has also been an important activity. Combined modality trials emphasizing organ conservation have been carried out within the last decade. The RTOG represents a national and international resource for studies of cancer of the head and neck. Its results influence the care of patients and the clinical research environment.
Forty-two patients with inoperable stage III or IV head and neck epithelial tumors were entered in a phase I pilot study to evaluate the toxicity and efficacy of combined radiotherapy and bleomycin for advanced head and neck cancers. Twenty-three patients (52%) achieved complete remissions and 18 patients (42%) had greater than 50% regression. Most patients tolerated bleomycin at a dose of 5 units twice a week, with a full course of radiotherapy delivered at 1809 rads/day, 5 days/week. Although the complete remission rate appears to be higher than with radiotherapy alone and 13 of the 23 complete remissions (57%) lasted greater than 1 year, methods of prolonging the duration of remission need to be developed.