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Biomedical subjects

L J Peters

Publications and source records attributed to L J Peters.

At least 163 records · Page 9Linked to original sources
PubMed1988

Radiation dose and second cancer risk in patients treated for cancer of the cervix.

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

Female↗
PubMed1988

Proliferation kinetics of a murine fibrosarcoma during fractionated irradiation.

Accelerated growth of tumor clonogens during the course of fractionated irradiation has been considered one of the major causes of radiation treatment failure. Alterations in clonogen growth rate could occur through three basic mechanisms: changes in cell-loss factor, changes in cell-cycle time, and recruitment of previously quiescent cells into the proliferative pool. This study was designed to assess changes in the cell-cycle time of clonogens of a murine fibrosarcoma during fractionated irradiation using an artificial pulmonary micrometastasis model. Lung colonies of various ages (4 h, 1 day, or 4 days) were exposed to single doses of irradiation ranging from 5-13 Gy; the fraction of surviving colonies was used to determine the preirradiation growth kinetics. The growth kinetics during fractionated irradiation was derived from colony-survival data of 4-day-old micrometastasis exposed to single doses or to 2, 5, 9, and 15 fractions separated by 4, 12, or 24-h intervals. The size of dose fractions used ranged from 1.7 to 14 Gy. The estimated clonogen doubling times before irradiation and during overall treatment periods of up to 14 days were 0.71 and 1.1 days, respectively. This significant (P less than 0.0001) increase in the doubling time was most likely a consequence of lengthening of the overall cell-cycle time of the clonogens by radiation-induced division delay. This observation suggests that accelerated growth, when it occurs in some tumors during fractionated treatment, is the result of a decreased cell-loss factor or recruitment of quiescent cells, but not a shortening of the cell-cycle time of the clonogens.

Animals↗
PubMed1987

Adjuvant chemotherapy for advanced nasopharyngeal carcinoma.

The outcome of therapy is reported in 34 previously untreated patients with advanced-stage (AJC IV) nasopharyngeal carcinoma treated with combination chemotherapy (cisplatin and non-cisplatin based) and sequential radiation therapy. Sixty-nine patients treated with radiotherapy alone were used as a control group. The control group was matched for T and N stage grouping but differed in that 45% had keratinizing squamous carcinoma, 14.5% had nonkeratinizing squamous carcinoma, and 40.6% had undifferentiated carcinoma, compared with 18%, 50%, and 32.4%, respectively in the combined-treatment group. Seventeen of 21 patients (81%) who received chemotherapy followed by radiotherapy achieved complete remission (CR), whereas 11 of 13 patients (85%) who received radiotherapy followed by chemotherapy achieved CR (P = NS). Patients treated by radiotherapy alone had a 91% CR rate. The combined treatment yielded a relapse-free rate of 78% versus 44% for the radiotherapy group (P = 0.001). Median survival in the combined-treatment group has not been reached (111+ months), compared with 67 months in the group receiving radiotherapy alone (P = 0.04). The recurrence rate at the primary site and in regional nodes was more frequent in the radiotherapy group (36%), compared with the combined-therapy group (7%) (P = 0.004), but the occurrence of distant metastases was similar in each group (P = 0.41). The acute toxicity of the treatment was well tolerated. The major long-term toxic effect experienced by patients in the combined-therapy group was soft tissue fibrosis. These data suggest that a prospective trial comparing chemotherapy and radiotherapy versus radiotherapy alone is warranted.

Adolescent↗
PubMed1987

Cervical carcinoma DNA content, S-fraction, and malignancy grading. II. Comparison with clinical staging.

In an attempt to achieve more biologically meaningful subclassification of squamous cell cervical cancers and ultimately more reliable prediction of tumor behavior, we have studied the tumor pretreatment DNA content (i.e., DNA index), cell-cycle S-fraction, and histomorphologic malignancy grading properties for tumors having similar and different clinical staging. The tumor DNA index, %S-phase cells, and average malignancy grades were statistically tested against known clinical predictive variables for 90 primary squamous cell carcinomas of the uterine cervix studied prior to radiotherapy. We observed that the biological and morphological tumor properties of cervical cancers broadly overlapped between different stages of disease and for other clinical criteria including the gross morphology, lymph node status, and intravenous positivity. No significant differences were detected in the DNA indices, %S, or malignancy grades between the stages of disease or the other clinical criteria. It was concluded that: the gross clinical staging criteria inadequately reflected the tumor biological properties; and that the possibility exists for refining prognosis by use of the biological and morphological noncodependent tumor parameters to supplement staging criteria; and the use of cell-cycle cytokinetic and malignancy grading criteria in addition to tumor DNA index is superior to DNA index (or DNA content) alone for identifying biologically different cervical cancers.

Carcinoma, Squamous Cell↗
PubMed1987

The tumor bed effect: dependence of tumor take, growth rate, and metastasis on the time interval between irradiation and tumor cell transplantation.

Experiments were designed to investigate the influence of time interval between leg irradiation and tumor cell transplantation on 3 different aspects of the tumor bed effect (TBE): tumor take, growth rate, and metastasis formation. MCA-4 tumor cells were injected subcutaneously into the legs of syngeneic C3Hf/Kam mice that had been locally irradiated with 30 Gy gamma rays 1, 50, 100, or 200 days previously. Interim TD50 values were higher in the day 1, 50, and 100 preirradiated mice than in controls for about 100 days after tumor cell transplantation. However, the final TD50 values determined 220 days after cell transplantation were marginally lower than controls in the day 1, and 50 preirradiated groups. TD50 values in the day 200 preirradiated group were similar to those of controls at all times after tumor cell injection. Retardation of tumor growth rate was observed in all preirradiated groups, but with a progressive decrease in effect as the time between irradiation and tumor cell injection was increased. In the day 200 preirradiated group it was noted that the degree of tumor growth rate retardation decreased as the number of injected tumor cells was increased. The incidence of lung metastases when the "primary" tumor reached a size of 20 mm was higher than in controls in mice irradiated 1, 50, and 100 days before tumor cell injection, but not in the 200-day preirradiated group. Thus, in this tumor system TBE influences tumor take, growth rate, and lung metastasis formation differently; but for all parameters, the effect decayed with increasing time between irradiation and tumor cell transplantation.

Animals↗
PubMed1987

Results of irradiation in the squamous cell carcinomas of the anterior faucial pillar-retromolar trigone.

Between January 1966 and August 1981, 159 patients with previously untreated squamous cell carcinomas of the anterior faucial pillar or retromolar trigone received definitive radiation therapy at The University of Texas M. D. Anderson Hospital and Tumor Institute. All except 11 patients were treated by external radiation including combination of electron beams with high-energy photons or 60Co to doses ranging from 60 Gy to 75 Gy. In the N0 patients, as a rule, only the ipsilateral subdigastric nodes were treated electively to a dose of 50 Gy. The 5-year determinate survival rate for the overall group was 83%. The cumulative recurrence rate showed that 92% of the patients had recurrence by 2 years. Therefore, all patients except those who died with no evidence of local disease less than 2 years after treatment were evaluated for local control. The failure rate for the evaluable patients was 29% for T1 lesions, 30% for T2 lesions, 24% for T3 lesions, and 40% for T4 lesions. After salvage surgery, which consisted of intraoral resection in one-third of the patients and of a composite operation in the other two-thirds, the ultimate failure rate was 0% for T1 lesions, 6% for T2 lesions, 8% for T3 lesions, and 20% for T4 lesions. Whereas stage was a poor indicator for treatment outcome, there was a significantly higher failure rate for infiltrative and/or ulcerated lesions (35%) than for exophytic or superficial lesions (15%). Histologic grade was of no prognostic significance, nor was there any significant difference in the failure rate for lesions originating on the anterior faucial pillar versus that for lesions on the retromolar trigone. Following radiotherapy, 30% of the patients developed some degree of bone exposure but only 5.6% (9 patients) required a segmental mandibular resection. The probability of bone exposure was not dose related and more likely reflected tumor location on the mucoperiosteum. Of the whole group, 16 patients (10%) experienced a neck failure with 8 ultimate failures after salvage surgery. Among the 16 patients who had neck failures, 13 were originally staged N0; 6 of these patients had failures that occurred in the electively treated ipsilateral subdigastric area, but the field was too small to cover the nodes adequately. Aspects of the radiotherapy techniques with combined electron and photon beams that may influence the treatment outcome are discussed.

Carcinoma, Squamous Cell↗
PubMed1987

Technique for verifying treatment fields using portal images with diagnostic quality.

The image quality of portal films for megavoltage photon beams, when using the double-exposure technique, is poor compared to diagnostic quality, X ray images. A technique is described to record on a single film a megavoltage portal image superimposed upon a diagnostic X ray image, which provides the radiotherapist with "diagnostic quality" portal images. The technique uses a commercially available X ray tube mounted on the head of a 60Co unit. The alignment procedure, which uses a leveling device to ensure that the X ray focal spot and 60Co source are at the same location for each exposure, is confirmed by registering on film the image of an alignment marker. An evaluation of film-screen combination showed therapy verification film in a rare earth intensifying screen cassette to be best suited for this technique. The relationship between off-axis dose and the penumbral region of the portal image has been evaluated and should be useful in the interpretation of portal verification film relative to the treatment volume.

Cobalt Radioisotopes↗
PubMed1987

Palliative radiotherapy of a mouse mammary carcinoma.

A mouse mammary carcinoma was exposed to one of three palliative treatment schemes: rapid, split, and extended. Tumors were treated at either 4 mm diameter or 8 mm diameter to compare the responses of small and large tumors to the three treatment schemes. In addition, acute skin reaction and late skin contracture were assessed. The results were: (1) The rapid treatment resulted in the greatest tumor response for 4 and 8 mm tumors but it also caused the most severe normal tissue reaction. (2) Lengthening the overall treatment time to 5 weeks (extended treatment) resulted in the poorest response for both large and small tumors. (3) The split course technique was almost as effective as the rapid course in treating small tumors, but its effectiveness was reduced if treatment was delayed until the tumor reached 8 mm in diameter. (4) The survival of mice with 4 mm tumors clearly depended upon the type of radiation schedule used, with the rapid treatment being superior. (5) If treatment was delayed until the tumors were large (8 mm diameter), there was no survival advantage between the three treatment schedules. (6) Palliation and survival were better when the tumor was treated when it was small, suggesting that palliation may be better if treatment is given early or electively.

Animals↗
PubMed1987

Inter-tumor heterogeneity and radiation dose-control curves.

This communication presents a theoretical analysis of the influence of inter-tumor heterogeneity on clinical radiation dose-response curves. Any clinically defined group of tumors consists of individuals each having a unique individual dose-control relation (I-TCP/D). This I-TCP/D relation is steep and is based on Poisson statistics. The population as a whole possesses a heterogeneous dose-control relation (H-TCP/D relation) that is a resultant of the weighted summation of the I-TCP/D curves, each weighted according to its relative frequency in the population. This summation leads to an H-TCP/D curve that is considerably flatter than the steep portion of any I-TCP/D curve. For any specified radiation regimen, three subclasses of tumors exist in any population: the stochastic fraction, which consists of those tumors whose individual tumor control probability lies between 99% and 1% and individual outcome is probabilistic; the refractory fraction, which consists of those tumors each of which has no prospect for control with the specified treatment; and the sensitive fraction, which consists of tumors each of which is absolutely controllable with the specific treatment. Based on plausible parameters, it is estimated that, for tumors associated with an overall tumor control probability of approximately 50%, some 70-85% of failures come from a predictably radioresistant fraction. To optimize and improve the radiation therapy of tumors with unsatisfactory local control, it is necessary to predictably identify the location of each individual in one of the three subclasses.

Dose-Response Relationship, Radiation↗
PubMed1987

An explanatory hypothesis for early- and late-effect parameter values in the LQ model.

The isoeffect equation derived from the linear-quadratic (LQ) model of cell survival contains linear and quadratic terms in dose. Experimental studies have shown that higher-order terms may also be present. These terms have been previously attributed to the fact that the LQ model may be the first two terms in a power series approximation to a more complex model. This study shows that higher-order terms are introduced as a result of heterogeneity in the response of the cell population being irradiated. This heterogeneity is modeled by assuming that the parameters alpha and beta in the LQ model are distributed according to a bivariate normal distribution. Using this distribution, the expected value of cell survival contains third- and fourth-order terms in dose. These terms result in the previously observed downward curvature of Fe plots. Furthermore, these higher-order terms introduce bias in the estimated values of alpha and beta, if only the linear and quadratic terms of the LQ model are used, and higher-order terms are ignored. The bias is such that the estimated value of alpha/beta is substantially increased. Thus the higher values of alpha/beta observed for early effects as compared to late effects may be due to greater heterogeneity of response in early-responding tissues than in later-responding tissues. This differential effect is maintained even if the two cell populations have the same average values of alpha and beta.

Cell Cycle↗
PubMed1987

Patterns of recurrence from head and neck cancer. An immunologic perspective.

The influence of pretreatment natural killer (NK) cell activity on patterns of disease recurrence in patients with head and neck cancer was studied. One hundred eighty-three patients were followed prospectively for disease recurrence following definitive therapy (median disease-free follow-up = 15 months). Pretreatment peripheral blood NK cell activity against K562 target cells was measured for each patient and expressed in lytic units (LU). The risk of death caused by recurrent disease was greatest in those patients with peripheral blood NK cell activity less than 60 LU (P less than 0.05). The site of recurrence could also be distinguished by LU value. As a percentage of total recurrences, locally recurrent disease was predominant in the patients with NK function greater than 60 LU whereas distant metastases predominated in the group of patients with peripheral blood NK cell activity less than 60 LU. These patterns were maintained when patients were stratified by clinical N stage (N = 0 versus N+), T stage (T-1 or T-2 versus T-3 or T-4), and treatment regimen (surgery alone versus surgery and postoperative radiation therapy). Natural killer cell activity appears to have prognostic significance, both for disease-free survival and for site of recurrence independent of clinical stage. The indications for multimodality therapy for patients with head and neck cancer when stratified by NK cell function need to be clarified.

Combined Modality Therapy↗
PubMed1987

Anatomy of the major lacrimal gland of rhesus monkeys (Macaca mulatta).

The major lacrimal gland of rhesus monkeys is impalpable within the fatty connective tissue of the upper lateral quadrant of the orbit. Acini of the lacrimal glands are composed of both sparsely and heavily granulated cells that histochemically resemble serous acinar cells of the submandibular salivary gland. The cytoplasmic granules are strongly periodic acid-Schiff (PAS)-positive, and some are also stained by alcian blue for acidic mucosubstances. The lacrimal gland has a simple duct system of intralobular ducts and interlobular excretory ducts. Lymphocytes and plasma cells are common in the periductal stroma. Major lacrimal glands of rhesus monkeys are suitable for comparative and correlative studies of lacrimal and salivary diseases and radiation responses.

Animals↗
PubMed1987

Radiation dose and leukemia risk in patients treated for cancer of the cervix.

To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.

Adult↗
PubMed1986

Patterns of recurrence in malignant mixed müllerian tumor of the uterus.

Of 120 patients treated definitively at University of Texas System Cancer Center, M. D. Anderson Hospital for malignant mixed müllerian tumor of the uterus, 67 had their tumors recur. These patients were analyzed for recurrence pattern and response of recurrence to treatment. The most frequent sites of recurrence were the lung and abdomen, accounting for 66% of all first-site recurrences and 80% of all first-site distant metastases. Locoregional recurrences were much less frequent, accounting for 18% of recurrences. There was no apparent change in recurrence pattern with the addition of adjuvant chemotherapy. The effect of adjuvant radiation could not be assessed, because 95% of patients treated surgically received adjunctive radiation. The survival after treatment of recurrence was shortest for patients with bone, brain, or liver metastases (median, 4 months). There were four long-term survivors (more than 36 months). Patients with resectable recurrences had the highest response rates. Response to chemotherapy alone was uniformly poor (6% response rate).

Female↗
PubMed1986

Reye's syndrome in adults. A case report and review of the literature.

Adult Reye's syndrome (ARS) is an infrequently diagnosed condition that typically affects patients younger than age 35 years. We describe a 61-year-old man with ARS occurring after influenza B-USSR infection and aspirin use. The diagnosis of ARS was confirmed by oil-red-O stain of liver biopsy tissue and subsequent electron microscopy. We review the literature on ARS and compare the clinical features and management of ARS with pediatric Rye's syndrome. This case is of interest to practitioners treating adult patients because it demonstrates that the patient population at risk for Reye's syndrome is broader than generally believed.

Aspirin↗