Characteristics of married and unmarried adolescent mothers and their partners.
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Biomedical subjects
Publications and source records attributed to L J Peters.
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Between 1960 and 1982, 188 patients were treated for soft tissue sarcomas of the head and neck. These patients had a heterogeneous group of neoplasms whose biologic behavior was determined by histologic classification, differentiation, and size. Histologic classification of these tumors was important and had prognostic significance. Differentiation affected local control and the propensity for distant metastases. Tumor size also contributed to outcome: patients with tumors of more than 5 cm had a worse survival than those with smaller sarcomas. Wide surgical excision with an adequate margin of normal tissue offered the best means of local control. The addition of postoperative radiotherapy was utilized for patients with positive margins or high grade aggressive sarcomas. Finally, despite multimodality therapy, achieving local control and prevention of distant disease in high grade sarcomas remains a major therapeutic challenge.
Several predictors of tumor radiocurability are already integrated into clinical practice, for example, tumor size, gross morphology (that is, infiltrative or exophytic), histologic type and grade. These are nonspecific and relatively imprecise. The aim of research into predictive assays is not only to refine the discrimination of existing predictors, but also to suggest specific experimental approaches for overcoming tumor radioresistance in individual patients. Two broad categories of predictive assays can be defined: direct and indirect measurement of tumor cell survival and/or repair capability following irradiation, and measurement of cellular and extracellular parameters affecting radiosensitivity. The ongoing research at The University of Texas M. D. Anderson Hospital is overviewed to illustrate potential methods for predicting radiocurability.
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Between 1954 and 1981, 72 patients with unresectable soft tissue sarcomas were treated with radiotherapy at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, 57 with photons alone and 15 with neutrons for at least part of the treatment. Twenty-three patients received systemic chemotherapy in addition to radiation therapy. The absolute 2-year and actuarial 5-year tumor control rates were 39 and 29%, respectively. In this heterogeneous series, the malignancy group (based on pathologic diagnosis) was the only factor significantly affecting tumor control probability, which at 5 years was 58% for 12 patients with group I tumors, 32% for 10 patients with group II tumors, and 17% for 50 patients with group III tumors. No relationship between total dose and tumor control probability was found in this group of patients, though the duration of tumor control was longer in those receiving 65 Gy or more. No apparent improvement in tumor control was observed in the subsets of patients receiving fast neutron therapy or combined modality treatment with chemotherapy, but because of the many unmatched variables between the groups, no meaningful comparison of treatment modalities can be made. Distant metastasis were seen more frequently in higher malignancy groups, whereas size or site of tumors did not significantly influence the incidence of distant metastasis. Six patients sustained major complications of radiotherapy, of whom five received total doses in excess of 70 Gy or its estimated biologic equivalent.
Survival in radiation myelopathy has been the subject of analysis. Factors affecting survival are the level of the lesion, the age of the patient, and the latent period of the injury. The influence of age and level of the lesion is compared with the effects of these same parameters in traumatic myelopathy. Patients with cervical cord lesions have more rapid morbidity in both radiation and traumatic myelopathy. For thoracic but not cervical lesions, younger patients have a greater survival expectation than older patients. Patients with shorter latent periods have a more rapid mortality in cervical radiation myelopathy, but no demonstrable effect is seen in thoracic radiation myelopathy.
Late complications of radiation therapy and other cancer therapies may not always be expressed because of the shortened survival of cancer patients. Methods for estimating the true complication rate must account for censoring of the data. Actuarial methods give the time-dependent probability of remaining free of the injury. However, these methods fail when the last surviving patient develops a complication. This study describes a different method for calculating the corrected complication rate. One advantage is that the method does not produce estimates of 100% for the complication rate that occur using the actuarial method when the last survivor suffers a complication. To use the method presented here, the distribution of latent periods of the injury and the survival function for the patients at risk must be identified.
Morphological alterations of parotid and submandibular salivary glands of rhesus monkeys were studied 1-72 h and 16-40 weeks postirradiation (PI) with single photon doses of 2.5-15.0 Gy, or 10.2 Gy given in 6 fractions. Acute degeneration and necrosis of serous cells in both parotid and submandibular glands were clearly expressed by 24 h PI and occurred in a dose-related fashion. In submandibular glands, doses of 12.5 or 15.0 Gy damaged mucous cells, but to a considerably lesser extent than the serous cells in the same glands. No significant sparing was evident with dose fractionation. These observations demonstrate the unique sensitivity of serous cells which appear to undergo interphase cell death after irradiation. The results also show that late atrophy was the direct result of acute loss of serous acini and reflects a lack of regeneration of acinar cells receiving acute injury.
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Acute and chronic salivary gland dysfunction are common sequelae of radiotherapy for head and neck cancer; but the associated morphologic changes, especially of the acute damage, have received relatively little study. For investigation of the morphologic characteristics of acute radiation injury to parotid glands, rhesus monkeys were studied 1-72 hours after parotid irradiation with single doses of 2.5-15.0 Gy. The acute damage from all doses was clearly expressed by 24 hours. Histologically, parotid glands irradiated with 2.5 or 5.0 Gy had random degeneration and necrosis of the serous acinar cells. Doses of 7.5-15.0 Gy produced widespread degeneration along with necrosis of whole acini. Serous cell damage was accompanied by neutrophilic inflammation that subsided after 24 hours to become replaced by plasma cell and lymphocytic infiltrates. Parotid glands receiving 7.5-15.0 Gy were atrophic at 16-22 weeks after irradiation and showed no recovery by 40 weeks. Although parotid acinar cells are well-differentiated nondividing cells, these observations show that they express lethal radiation injury in interphase within hours of receiving a radiation dose as low as 2.5 Gy. This is unlike most mammalian cells that express radiation injury during mitosis. Chronic atrophy is a consequence of this direct, irreversible, and early injury, rather than the result of radiation-induced changes in the vasculature.
The saliva of patients undergoing radiation therapy for head and neck cancer contains increased acidic mucosubstances associated with a reduced serous component. To assess the morphologic features of the acute radiation damage in serous versus mucous acinar cells, the mixed serous/mucous submandibular glands of 18 rhesus monkeys were studied 1-72 hours after irradiation with single doses of 2.5-15.0 Gy. Selective degeneration and necrosis of serous cells was observed with doses of 2.5-7.5 Gy. Doses of 10.0-15.0 Gy caused widespread destruction of whole serous acini, but only isolated mucous cells were affected. The lesions were clearly expressed by 24 hours. Transient exudation of neutrophils was replaced by plasma cells and lymphocytes. Examination at 16, 22 and at 40 weeks revealed that late atrophy was caused solely by loss of serous acini in glands treated with 7.5 and 10.0 Gy. Although both serous and mucous acini were reduced in glands treated with 12.5 and 15.0 Gy, the atrophy was mainly due to loss of serous acini. The finding that serous cells are more vulnerable to radiation injury than mucous cells provides a morphologic explanation for early and late changes in saliva composition after salivary gland irradiation.
Dependency on tumor type of tumor growth retardation caused by the radiation-induced damage of tumor bed stroma, a phenomenon known as the tumor bed effect (TBE), was investigated using two mammary carcinomas designated MCA-4 and MCA-K and two fibrosarcomas designated FSA and NFSA, all syngeneic to C3Hf/Kam mice. Inoculations of tumor cells were given s.c. into the right hind thighs of mice either treated or not treated 1 day earlier with graded doses of gamma-rays; tumor latency and growth rate were determined. Tumor latency was prolonged and tumor growth was retarded, but the magnitude of these two features of TBE greatly depended on radiation dose and tumor type. TBE began to appear at doses of 5-10 Gy and then sharply increased as the dose of radiation was increased up to between 20 and 30 Gy, at which point a plateau was achieved. TBE was also significant after 40 and 60 Gy total dose given in daily fractions of 2 Gy 5 times per week, a schedule commonly used in radiotherapy treatment of cancer patients. Carcinomas exhibited more pronounced TBE than fibrosarcomas, with NFSA showing only minimal TBE. Radiation-inactivated MCA-4 and FSA cells admixed with viable MCA-4 cells reduced tumor latency, but not the tumor growth delay, of resulting MCA-4 tumors in preirradiated legs. In contrast, admixture of irradiated NFSA and viable MCA-4 cells abolished growth delay but did not influence tumor latency of the TBE phenomenon. Thus the type of a tumor growing in the irradiated tissue is a very important factor that determines the expression of TBE.
Wedge biopsy of the caudal borders of the parotid or submandibular salivary glands of rhesus monkeys avoids major nerves, ducts, and blood vessels. This is a minor surgical procedure that provides adequate material for in vitro studies and causes no significant postoperative complications. Gross and light microscopic anatomy of the rhesus and human salivary glands are similar. We have concluded that rhesus monkeys are good models for human salivary diseases, including radiation sialoadenitis.
Several predictors of tumor radiocurability are already integrated into clinical practice, e.g., tumor size, gross morphologic features (i.e., infiltrative or exophytic), histologic type, and grade. These are relatively imprecise, however, and none is specific. The aim of research into predictive assays is not only to refine the discrimination of existing predictors but also to suggest specific experimental approaches for overcoming tumor radioresistance in individual patients. Two broad categories of predictive assays can be defined: direct and indirect measurements of tumor cell survival and/or repair capability following irradiation and measurement of cellular and extracellular parameters affecting radiosensitivity. Examples from ongoing research at the University of Texas M. D. Anderson Hospital using one technique from each category (the micronucleus assay and flow cytometric analysis of tumor cell proliferation kinetics and ploidy) are used to illustrate potential methods of selecting patients for fast neutron radiotherapy.
Archival, paraffin-embedded, pathology specimens representing pretreatment tissue biopsies from 73 patients with epidermoid carcinoma of the head and neck were analyzed for DNA Index and %S-phase cells by flow cytometry and were scored for quantitative histomorphology. The DNA fluorescence/light scatter size patterns derived from paraffin-embedded specimens were shown to be essentially the same as those from mechanically disaggregated, ethanol-fixed cells obtained from the same tissue specimen. Patterns ranged from lymphocyte-like to highly abnormal DNA Index cytokinetic patterns. The DNA Index values ranged from 0.70 to 3.50 (median 1.42), with an aneuploidy frequency of 63/73 (86%). DNA distribution %S ranged from 4% to 45% (mean 19), with the microscopic malignancy grading showing broad heterogeneity (mean 2.1, range 1.0-3.0, where 1.0-1.7 = well differentiated, 1.8-2.3 = moderately differentiated, 2.4-3.0 = poorly differentiated). Cross-comparison of these data showed that (1) the tumor %S was dependent on DNA Index (higher %S at higher ploidy), (2) low to high malignancy tumors were randomly distributed between diploid/near diploid tumors and high-degree DNA abnormality tumors, and (3) proliferative activity values broadly overlapped between low to high malignancy scored tumors. However, those carcinomas characterized by high DNA Index (greater than or equal to 1.50) and high %S-phase fractions (greater than or equal to 20) had a five fold higher incidence of high-degree malignancy, invasive tumors than diploid/near diploid (%S less than or equal to 19) tumors.
The effect of tumor bed irradiation (TBX) on subsequent tumor response to treatment with cyclophosphamide (CY) or further irradiation was studied in mice. Using the growth delay assay, the therapeutic response was enhanced by prior TBX: for example, in mice receiving 3000 rad TBX 1 day before fibrosarcoma cell inoculation, the growth delay from 8 to 12 mm produced by CY (150 mg/kg) was 18.8 days compared with 9.4 days without prior TBX. This effect was independent of time between TBX and tumor cell inoculation over the range 1-56 days. When tumor cure experiments were performed, however, the effect of prior TBX was to decrease significantly the proportion of tumors controlled by either CY or irradiation and to make the dose-response curve for radiocurability less steep. These data are best interpreted by postulating that TBX increases the environmental heterogeneity of tumors growing in preirradiated sites, with an overall net decrease in the cell kill achieved by a given dose of CY or radiation. This results in increased resistance to cure and a lack of dose response. However, the TBX also causes slower regrowth of surviving cells, so that an increase in tumor growth delay is realized. Thus, although eradication of postirradiation recurrences by chemotherapy is compromised, their palliation may actually be enhanced.
A retrospective review of 248 patients with squamous cell carcinoma of the supraglottic larynx was undertaken to determine the relationship between the probability of control of the primary lesion, the extent of neck nodal disease at initial presentation, and its ultimate control. All patients were treated at the U.T. M. D. Anderson Hospital between 1960 and 1980, and had a minimum of 3 years follow-up. The primary lesion was staged T1 in 38 patients, T2 in 132, T3 in 50 and T4 in 28. The initial volume of neck nodal disease was scored on a scale of 0 (no palpable nodes) to 9 (bilateral neck nodes greater than 6 cm in diameter). All primary lesions were treated definitively with megavoltage radiation therapy. Treatment to the neck varied according to the extent of lymph node involvement. There was no significant difference in the range of total radiation doses delivered to the primary lesion, stage for stage, in patients who presented with clinically negative or positive nodes, or in those with controlled versus uncontrolled neck disease. Analysis of the probability of primary tumor control was made by life table methods because of the poorer survival expectation in node positive patients. For T1 and T2 primary lesions, any positive node decreased the probability of primary tumor control (p = 0.06). For T3 and T4 lesions, a single node less than 3 cm in diameter did not worsen the chance of primary tumor control, but any greater degree of lymph node involvement did (p = 0.03). For both T stage groupings, the probability of primary tumor control at 5 years decreased progressively with increasing neck nodal disease. Primary tumor control probability was also significantly associated with control of the neck disease, independent of the modality of neck treatment. No correlation could be demonstrated between the histological grade of the primary tumor and initial lymph node status or tumor control probability. Possible interpretations of this manifestation of biological heterogeneity are discussed.
The concomitant boost technique is a variant of accelerated fractionation whereby the boost is delivered as a second daily fraction during the basic treatment course to reduce the total duration of treatment. From April 1972 through June 1983, 53 patients with advanced squamous cell carcinoma of various sites in the head and neck region were treated for cure at U.T. M. D. Anderson Hospital with this technique. In 12 patients, the concomitant boost was used because of rapid recurrence following surgical resection either before or after initiation of planned postoperative radiotherapy; the remaining patients had rapidly growing untreated or recurrent disease in the primary site, neck, or both. In most cases, the concomitant boost was delivered in fractions of 120-150 cGy, separated by 3-6 h from the basic daily treatment of 180-200 cGy. The boost treatments were given 2-3 times a week for 3-5 weeks, delivering an average of about 17 Gy in 12 fractions. Two different treatment techniques were used. Patients with predominantly neck disease (30) were treated with glancing AP and PA fields or with appositional electron beam portals to spare the mucous membranes, while those with advanced or rapidly progressive primary lesions, with or without nodal disease (23), received their concomitant boost through lateral photon or high energy electron beams to include the primary tumor site. As expected, the acute mucosal reactions were most severe in the latter group, but only three patients required interruption of treatment because of severe mucositis.(ABSTRACT TRUNCATED AT 250 WORDS)