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Biomedical subjects

T E Moon

Publications and source records attributed to T E Moon.

At least 37 records · Page 2Linked to original sources
PubMed1990

The risk of developing subsequent nonmelanoma skin cancers.

Data from the Southeast Arizona Skin Cancer Registry collected during 1985 through June 1988 were used in this study. Patients who had a nonmelanoma skin cancer (basal cell or squamous cell carcinoma) removed in 1985 were observed until subsequent nonmelanoma skin cancers developed or until June 30, 1988. Twelve categories of nonmelanoma skin cancers were developed on the basis of the type of first nonmelanoma skin cancer and type of second, third, and fourth nonmelanoma skin cancers. Analyses showed the highest risk of a subsequent nonmelanoma skin cancer developing was within 1 year (36.39%), the rate of developing another nonmelanoma skin cancer depended on type (squamous cell carcinoma, 100%; basal cell carcinoma, 44.23% to 83.65%), and total risk decreased during the 1277 days of the study.

Aged↗
PubMed1989

Cutaneous malignant melanoma. II. The natural history and prognostic factors influencing the development of stage II disease.

The survival history of 259 patients with Stage I cutaneous malignant melanoma who were at risk for developing regional nodal metastases (Stage II) were studied. Eighty-seven of 377 Stage I patients (23%) developed regional nodal metastases (Stage IIB) with 40% 5-year survival. Fifty patients had regional nodal metastases at presentation, with or without a known primary (Stages IIA or IIC, respectively), with a 42% 5-year survival. A step-down multivariate analysis using the Cox regression model revealed four risk factors as being highly significant for predicting a more favorable survival outcome: (1) thinner Breslow thickness (P = 0.0001), (2) pathologic Stage I disease (P = 0.004), (3) no clinical ulceration (P = 0.0004), and (4) being a woman younger than 50 years of age (P = 0.029). These results are discussed in reference to other series.

Age Factors↗
PubMed1989

Interpretation of cancer prevention trials.

Principles and methods to guide interpretation require a different emphasis for cancer trials. Assumptions used to design a trial must be validated and modified during the trial to avoid limitations. To maximize information from such trials, recruitment strategies for commonly free-living subjects, measurements of safety and compliance, and ascertainment with pathologic review of endpoints must be obtained. Consideration of multiple endpoints may provide a better interpretation of cancer prevention for skin, colon, and transient occurrences illustrated by cervical dysplasia or biochemical precursors. A careful definition of the limitations of preventive trials is required. These include the actual size of the intervention groups, completeness and duration of follow-up, and comparison between trial participants and a defined source population. To obtain a valid interpretation with adequate precision of intervention effectiveness, time to endpoints should be evaluated using statistical multivariate methods such as Cox proportional hazard or relative risk models. These permit adjustment for important confounding and risk modifiers such as compliance, dietary intake, and drift in control group. The magnitude of the intervention efficacy and the generalizability of results of the trial will be negatively impacted if the intervention has a delayed (latent) effect. Such delay in intervention effect requires added considerations with possible extension of trial duration. Use of confidence limits for intervention effectiveness provides added insight and improved interpretation of prevention trials. The final component of a cancer prevention trial, as with any study, is to interpret and report its results. Providing a valid interpretation with adequate precision to hypotheses of a cancer prevention trial requires added emphasis on the accuracy of the assumptions made to design the trial and the duration of the trial. Design assumptions regarding compliance to the prescribed interventions, time until the experimental intervention achieves full effect, and the frequency of endpoints directly impact on the number of endpoints observed. Terminating a cancer prevention trial before adequate information is obtained, thus severely flawing its interpretation, requires ongoing awareness. Interpretation of a cancer prevention trial should include several added steps: first, investigators to critically review the actual manner in which the trial was conducted; second, carry out an appropriate analysis of the data; and third, review the results and note exceptions or limitations in the data. The results of the trial should be contrasted with previous studies. Implications of the results to future trials should be considered. Finally, these interpretations should be documented in a written report and made available to the scientific community.

Clinical Trials as Topic↗
PubMed1988

Cutaneous malignant melanoma (Arizona Cancer Center experience). I. Natural history and prognostic factors influencing survival in patients with stage I disease.

The authors have studied the natural history of 377 patients with Stage I cutaneous malignant melanoma followed at the Arizona Cancer Center, Tucson. Two hundred eight patients, or 55%, remained free of metastatic disease after a median follow-up of 30 months. The survival at 5, 8, and 10 years was 69, 65, and 63%, respectively. Natural breakpoints in Breslow thickness for survival occurred at 0.85, 1.95, and 4.00 mm. These are not significantly different from those found by other investigators. A step-down multivariate analysis using the Cox regression model yielded four factors as highly significant in predicting survival: Breslow thickness (P less than 0.001), an age/sex interaction (P = 0.0012), clinical ulceration (P = 0.0039), and a prophylactic node dissection (P = 0.019). No predictive value for a BANS or non-BANS location was detected. These results are discussed in reference to other large series which describe the natural history of cutaneous melanoma.

Arizona↗
PubMed1988

The effect of prior adjuvant chemotherapy on survival in metastatic breast cancer.

Some adjuvantly treated patients develop recurrent breast cancer and little is known about the effect of prior adjuvant chemotherapy on subsequent response rates to systemic therapy or on overall survival. We describe our retrospective comparison of 179 patients who received doxorubicin containing adjuvant chemotherapy and developed recurrent breast cancer on University of Arizona Cancer Center clinical trials with 202 non-adjuvantly treated patients entered onto clinical protocols for recurrent or metastatic breast cancer during the same period. Adjuvant failures had a shorter median survival from the date of onset of recurrent disease (18 months versus 28 months, P less than 0.001), a lower response rate to initial combination chemotherapy (38% versus 69%, P = 0.001), and a high incidence of CNS involvement at the time of relapse (11%). In patients having recurrent or metastatic breast cancer, a history of prior adjuvant chemotherapy appears to identify a subgroup who will have a higher incidence of CNS involvement, a lower response rate to chemotherapy and a shorter survival with metastatic disease. These findings may help explain the failure of improved relapse free survival seen in many adjuvant chemotherapy trials to result in improved overall survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Comparison of different trials of adjuvant chemotherapy in stage II breast cancer using a natural history data base.

Prognostic factors and treatment were analyzed for 2,578 patients to assess the impact of various forms of adjuvant chemotherapy on the natural history of operable stage II (node-positive) breast cancer. The outcome after surgery alone (or with radiotherapy) was determined in 1,014 patients in the natural history data base (NHDB). Adjuvant chemotherapy consisted of L-phenylalanine mustard (L-PAM; 130 patients); cyclophosphamide, methotrexate, and 5-fluorouracil (CMF; 645 patients); doxorubicin and cyclophosphamide (AC; 241 patients); CMF plus vincristine and prednisone (CMFVP; 263 patients); and 5-fluorouracil plus AC (FAC; 285 patients). L-PAM had minimal effect on relapse-free survival (RFS) compared to the NHDB, but all combination chemotherapy programs significantly improved RFS and survival compared to the NHDB. In women with 1-3 positive nodes, all combination chemotherapy programs produced similar results. In women with 4-9 positive nodes, the FAC regimen appeared to be associated with superior RFS compared to other programs, but all were superior to the NHDB. In women with 10 or more positive nodes, FAC was the only regimen associated with improved RFS. The use of a NHDB and known pretreatment characteristics, such as nodal status and tumor size, permits comparison of patients at similar risk of recurrence of breast cancer who have received adjuvant chemotherapy and provides leads for evaluation in future prospective clinical trials.

Adult↗
PubMed1987

Development and use of a natural history data base of breast cancer studies.

Pretreatment information, type of treatment, and longitudinal follow-up on 1,971 patients with operable breast cancer were used to establish a breast cancer natural history data base (NHDB). Data were available for 957 patients with stage I (node-negative) breast cancer and 1,014 stage II (node-positive) patients. In women with negative nodes, information was available on 759 patients treated at the Milan National Cancer Institute and 188 patients treated at the Royal Marsden Hospital. After adjustment for differences in the distribution of patient prognostic factors, relapse-free survival and overall survival were not significantly different. Of the 1,014 node-positive patients, 540 were treated at the Milan National Cancer Institute, 258 at the Royal Marsden, and 216 at the M. D. Anderson Hospital. Relapse-free survival and overall survival did not significantly differ between Milan patients and those treated at the Royal Marsden Hospital. However, M. D. Anderson Hospital patients did have significantly better relapse-free and overall survival. In each institution, outcome was consistently most dependent on the number of involved axillary lymph nodes and tumor size. Also, similar patterns of survival were observed for each of the institutions. The development of an NHDB can be of value in the identification and evaluation of consistency of prognostic factors, permitting improved comparisons between clinical trials. The development of such a natural history data base (NHDB) provides a reference for assessing the impact of different adjuvant chemotherapy programs, and aids in the design of new protocols.

Adult↗
PubMed1986

The role of lymphangiography in vulvar carcinoma.

The records of all patients with vulvar carcinoma seen at Washington University School of Medicine between 1970 and 1983 were reviewed to determine the role of lymphangiography in the management of patients with vulvar malignancy. Forty-three patients were identified who had a preoperative lymphangiogram followed by radical vulvectomy and lymph node dissection. Thirty-two films were available for review. Seventy-seven sets of lymph nodes were obtained from the 32 patients. Overall diagnostic accuracy was 42 of 77 (54.5%), with a sensitivity of three of 19 (15.7%) and a specificity of 39 of 59 (66.1%). Corresponding values for inguinal nodes were 26 of 57 (45.6%), two of 16 (12.5%), and 24 of 41 (58.5%), respectively. Accuracy rates for pelvic nodes were 16 of 21 (76.2%) with a sensitivity rate of one of three (33%) and a specificity of 15 of 18 (83%). Negative scans were more likely to be accurate than positive scans, 88.6% versus 30%. While a negative lymphangiogram may be helpful in predicting the absence of metastases, its poor specificity limits its widespread usefulness.

Carcinoma↗
PubMed1986

Adjuvant chemotherapy of axillary node-negative carcinoma of the breast using doxorubicin and cyclophosphamide.

One hundred fifty-six women with axillary node-negative breast cancer and primary tumors less than or equal to 5 cm in diameter (T1N0 or T2N0) were treated with a brief course of postoperative adjuvant chemotherapy consisting of doxorubicin and cyclophosphamide. Treatment was well tolerated and toxicity was minimal. With a median follow-up time of 58 months, there has been 1 relapse among 58 patients with T1 primary lesions and 15 relapses among 98 patients with T2 primary tumors. When compared with a matched historical control group receiving surgery alone, significant improvement was apparent in disease-free survival among the patients who received adjuvant chemotherapy. Prospective controlled trials are needed if we are to confirm this favorable experience with adjuvant chemotherapy in the treatment of women with node-negative breast cancer.

Adult↗
PubMed1985

Chemohormonal therapy for advanced breast cancer with tamoxifen, adriamycin, and cyclophosphamide (TAC).

Combined chemohormonal therapy is an attractive therapeutic strategy for the treatment of Stage IV breast cancer. Between 1977 and 1979, the authors evaluated a new chemohormonal therapy program in 63 evaluable women with advanced breast cancer who previously had not received cytotoxic chemotherapy or tamoxifen. The chemohormonal therapy consisted of 21- to 28-day cycles of tamoxifen (10 mg orally twice daily), Adriamycin (doxorubicin) (40 mg/m2 intravenously on day 1) and cyclophosphamide (200 mg/m2 orally on days 3-6) (TAC). Objective responses were observed in 82% of the patients (22% complete response, 60% partial response). With a median follow-up of 104 weeks (2 years), the median relapse-free survival for the 52 responding patients was 80 weeks. The median survival for the entire group of 63 patients was 118 weeks. Eleven pretreatment patient characteristics were evaluated via univariate and multivariate analysis to determine their effect on response and survival. Prognostic factors with a significant association with longer survivals were as follows: a lack of soft tissue involvement, a lack of pleural involvement, and a long disease-free interval (DFI). Estrogen receptor (ER)-unknown patients, being composed primarily of postmenopausal patients with a long DFI and single-organ involvement (primarily bone), comprised 62% of the patient population and achieved a survival similar to the smaller number of ER-positive patients and was superior to the survival of ER-negative patients. Toxicities were recorded on all patients and overall the treatment was well tolerated. Combined chemohormonal therapy with TAC resulted in a high objective response rate and a long median survival. This study would support additional trials of chemohormonal therapy in patients with ER-positive tumors or in those whose tumors are likely to be ER-positive (e.g., postmenopausal patients with long DFIs).

Aged↗
PubMed1985

Similar self-renewal properties for different sizes of human primary melanoma colonies replated in agar.

Clonogenic assays currently define colonies as multicellular growth units above an arbitrarily designated cutoff size rather than by the biological function of different-sized growth units. To define the cutoff size between clusters and colonies in terms of the biological function of the cells within the growth units, we directly measured the self-renewal and proliferative capacity of cells from different-sized melanoma colonies. Primary colonies formed from cells of two patients were removed, pooled according to size, and replated, and the frequency and size distribution of the secondary colonies were analyzed. Cells from primary melanoma colonies that resulted from four to eight population doublings had similar extensive proliferative and self-renewal characteristics. The results demonstrated that self-renewal was not limited to cells in large colonies and suggested that the cutoff may be below 16 cells/growth unit. These data support the use of relatively small multicellular growth units to define colonies and measure highly proliferative human melanoma tumor cells. In addition, these methods may allow the determination of the cutoff size for other tumor types in terms of the biological function of cells rather than arbitrarily designating a cutoff size.

Agar↗
PubMed1985

Clinical-biologic patterns of metastatic melanoma and their effect on treatment.

We have identified three distinct groups of patients with metastatic malignant melanoma that differ in their clinical behavior and responsiveness to therapy. These include a favorable group of patients with lymph node or skin metastases, an intermediate prognostic group with lung or bone metastases, and a poor prognostic group with brain or gastrointestinal involvement. These three groups differed in their predicted objective response to therapy, in their likelihood to achieve a complete remission, and in their median survival.

Analysis of Variance↗
PubMed1984

Kinetics of clonogenic melanoma cell proliferation and the limits on growth within a bilayer agar system.

Accurate descriptions of the kinetics of cell growth in semi-solid agar clonogenic systems have been difficult because the number of cells in colonies of different sizes is largely unknown. We stained and removed tumor cell colonies from agar, directly counted their cells, and established equations to quantitate the number of cells within colonies of different sizes. We used these equations to quantitate, in terms of cell number and volume, the total amount and kinetics of clonogenic cell proliferation from biopsies of human melanoma and cell lines of several different tumor types. Daily observations of cells in agar and serial photography indicated a 0- to 4-day delay in the onset of proliferation in agar followed by rapid growth and then abrupt cessation of proliferation. We quantified the extent of proliferation of cells from melanoma biopsies of seven patients and 11 cell lines after they were allowed to proliferate in agar until they stopped. Approximately 10% of cells divided one to five times while only 0.01% divided six to nine times. The total number of cells within the colonies at the end of growth was different while the total volume of cells within the colonies per plate was similar; approximately 10(9) microns 3 cellular volume per plate represents an upper limit for proliferation within the closed, nonrefed bilayer agar system. Previous replating studies using the same biopsy cells have shown that clonogenic melanoma cells can self-renew and have more proliferative capacity than that expressed during primary colony formation. Thus, the clonogenic assay only measured initial proliferative capacities. Furthermore, variable delays in the onset of proliferation may contribute to the heterogeneity of colony size within clonogenic assays.

Agar↗
PubMed1984

Evaluation of an automated image analysis system for counting human tumor colonies.

The Omnicon FAS II image analysis system was applied to counting tumor colonies grown in a soft agar human tumor clonogenic assay with a detailed protocol designed to assess the instrument's sensitivity, specificity, precision, and accuracy. Comparisons of technician and instrument counts were done on a blinded basis. Sensitivity studies (which used metal microspheres) yielded a correlation coefficient (r) of 0.999 between technicians and the counter. A field-by-field analysis of the instrument's specificity for identifying individual objects correctly as tumor colonies rather than artifacts (as identified by the technician) was excellent (r = 0.95). In the precision studies (determined with repeated automated counting of the same samples for five days), the median coefficient of variation was less than 7%. Accuracy was evaluated on cultures of fresh biopsies from 30 human cancers obtained for drug sensitivity testing as well as on a series of tumor cell lines. The correlation between the mean number of colonies counted by the technicians and by the colony counter was greater than 0.91. Similar comparisons of mean percent survival of tumor colony-forming cells after drug exposure between technician and machine were also quite acceptable (r = 0.85). We conclude that the colony counter provided sufficient reliability to be applied to counting human tumor colonies grown in vitro. In addition, the colony counter performed the Petri dish counts ten times faster than experienced technicians and without associated operator fatigue.

Animals↗
PubMed1984

Chronic solar ultraviolet damage associated with malignant melanoma of the skin.

A retrospective study of 226 cases of cutaneous malignant melanoma (CMM) was done to determine if patients with CMM showed evidence of chronic solar ultraviolet radiation damage, i.e., a past history of actinic keratosis (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC) anywhere on the patient's skin, and solar elastosis (SE) at the site of a CMM. This statistical analysis consisted of 119 clinical records and 158 pathology slides after all cases of lentigo CMM were deleted. CMM showed no statistical correlation with AK, BCC, SCC, or SE. This supports the idea that it is not the chronic solar-ultraviolet radiation exposure that causes CMM.

Adult↗