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Biomedical subjects

E N Atkinson

Publications and source records attributed to E N Atkinson.

70 records · Page 4Linked to original sources

Tumor volume, nodal status, and metastasis in breast cancer in women.

The relationship between primary tumor volume at detection, number of positive nodes, and probability of and time until first distant metastasis was examined for a group of 2,663 women with breast cancer. Time until metastasis was shown to decrease and probability of metastasis to increase as tumor volume and number of nodes increased. Either factor remained significant after correction for the other. Simple proportional hazards models were shown to be inadequate to describe the data. Graphic techniques were used to obtain nonparametric estimates of the forms of the relationships between tumor volume, nodal status, and the time course of the occurrence of metastasis. A simple calculation demonstrated that the average contribution per cell to the probability of metastasis decreased with increasing volume.

Breast Neoplasms↗

Prognosis of surgically determined complete responders in advanced ovarian cancer.

From January 1971 through December 1981, 246 patients with advanced (Stages III and IV) epithelial ovarian cancer underwent second-look laparotomy at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston. Eighty-five of these patients had a complete response (negative second-look laparotomy) following treatment with a variety of chemotherapeutic regimens. Three patients had also received irradiation. Patients were analyzed according to pretreatment characteristics (age, FIGO stage, ascites, pleural effusion, histologic grade, tumor type, type of surgery, residual tumor diameter, initial clinical status) and by the number of biopsy specimens taken at second-look laparotomy. The probability of recurrence and the length of survival following a negative second-look laparotomy are statistically related to these characteristics. Twenty of the 85 patients (24%) developed recurrent disease 5 to 32 months after laparotomy. The estimated 2- and 5-year survival rates are 99% and 85%, respectively. Patients who achieve a surgically determined complete response have an excellent chance for long-term survival.

Adult↗

Microscopic disease at second-look laparotomy in advanced ovarian cancer.

During the 11-year interval from January 1971 to January 1982, 50 of 246 patients with advanced (Stage III and IV) epithelial ovarian carcinoma at second-look laparotomy had biopsy or cytologic evidence of persistent microscopic carcinoma. The stage and grade profile include 46 Stage III and 4 Stage IV patients: 4 borderline, 9 grade 1, 20 grade 2 and 17 grade 3 patients. Following second-look laparotomy, 4 patients received no further therapy, 45 received chemotherapy, and 1 received external radiation. No patient was lost to follow-up, and the median interval off therapy was 24 months. Progressive or recurrent disease has manifest in 12 (24%). No recurrences have developed either in patients younger than age 40 or in patients with grade 1 tumors. Two patients died of leukemia, 1 died of heart disease, and 35 (70%) are alive with no evidence of disease. In patients developing recurrence, the median progression-free interval was 17.5 months, with a range of 6 to 46 months. The median interval of survival following disease progression was 7 months. There was no evidence of progression at 2 years and 5 years in 81% and 70% of patients, respectively. The uncorrected 2- and 5-year survival rates were 96% and 71%, respectively. The 5-year survival rates for grades 1, 2, and 3 were 100%, 79%, and 36%, respectively. Other variables analyzed include number of positive foci, residual tumor volume at initial surgery, cytologic findings at second-look laparotomy, type of chemotherapy, and number of courses of chemotherapy before second-look laparotomy. In summary, patients with only microscopic evidence of disease at second-look surgery have a good probability for extended survival.

Adolescent↗

Confidence limits for probability of response in multistage phase II clinical trials.

Herson (1979, Biometrics 35, 775-783) has given a method for designing one-arm k-stage phase II clinical trials, which permits early termination of the trial if the treatment is apparently ineffective, while retaining acceptable levels of power and significance. This paper gives a method for calculating the confidence limits on the response proportion, conditional on a particular study design.

Drug Evaluation↗

Virus-augmented delayed hypersensitivity skin tests in gynecological malignancies.

Cultured human tumor cells of various histologic origins were infected with PR8/A/34 influenza virus. Nonviable crude membrane extracts were derived from the infected and uninfected cells. The extracts were coded and tested for their ability to produce delayed hypersensitivity skin reactions (DHSR) in allogeneic patients with squamous uterine cervical carcinoma, epithelial ovarian carcinoma, and malignant melanoma. Augmented antigen sensitivity to the virus-modified extracts compared with virus alone or to the unmodified extracts was observed in all patient groups. There was insufficient specificity to delineate a response by individual tumor type and related tumor extract, but some of the observed responses suggested tumor or organ site associations. Cervical carcinoma patients reacted more frequently to the virus-modified cervix extract, which also produced a high frequency of response in patients with ovarian carcinoma and melanoma. Ovarian carcinoma patients demonstrated increased sensitivity to both virus-modified ovarian carcinoma extracts, although 14 of 21 patients also showed responsiveness to one of the unmodified ovarian extracts. Malignant melanoma patients showed increased sensitivity to all virus-modified extracts except one of two derived from the ovarian carcinoma, and demonstrated a significantly augmented response to the virus-modified melanoma extract when the response to this extract was compared with that in ovarian carcinoma patients. The augmented reactions appear to be due to an association of the PR8 virus and as yet undetermined cellular components rather than to the virus alone. The possible involvement of tumor-associated determinants and the clinical significance of this phenomenon require further investigation.

Adenocarcinoma↗

Estimation of human tumor growth rate from distribution of tumor size at detection.

Methods are presented for estimating the growth curve of a tumor (up to an unknown scale factor of time) from the distribution of volumes at detection on the basis of two assumptions: 1) the existence of a common growth curve and 2) the assumption that the probability of detecting a tumor in a period of time is proportional to the tumor volume. These methods can accommodate variation between individuals in speed of traversal of the growth curve. The methods are applied to volumes of tumor at detection of a large series of breast cancers. The simplest, adequate description is exponential growth with great individual-to-individual variation in tumor doubling time. The data are consistent with bounded growth (Gompertzian or logistic form) as well as exponential growth. However, there is no evidence that the bound on growth is within the range of the data. The shape of the distribution of volumes does not yield an effective lower limit on such a bound.

Breast Neoplasms↗

Fallopian tube carcinoma.

Seventy-one cases of primary adenocarcinoma of the fallopian tube treated at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston were reviewed. The most common presenting symptoms were abdominal pain, abnormal uterine bleeding, and vaginal discharge. The most common physical finding was a palpable abdominal or pelvic mass. The preoperative diagnosis was correct for two patients. Initial therapy consisted of surgery alone, surgery plus radiation therapy, surgery plus chemotherapy, and a combination of surgery, chemotherapy, and radiation therapy in 10, 32, 21, and eight cases, respectively. The median survival for patients in these treatment groups was 33, 22, 27, and 22 months, respectively; the median survival for all patients was 23 months. No statistically significant differences emerged among the survival curves of patients treated with each of the above regimens.

Adenocarcinoma↗

Vulvar melanoma at the M. D. Anderson Cancer Center: 25 years later.

The purpose of this study was to review the clinical course of patients diagnosed with vulvar melanoma. Charts of patients diagnosed between 1970 and 1997 were reviewed for demographics, lesion characteristics, disease duration and extent, and treatments. Actuarial survival curves were computed by the Kaplan Meier method and compared by Cox proportional hazards regressions. Fifty-one patients (median age 54) with vulvar melanoma presented with a vulvar mass (39%), pain (30%), bleeding (24%), and itching (20%). Anatomical distribution was mucosa of the vulva (65%), vulvar epidermal site (21%), or unspecified vulva (14%), with 20% having multifocal disease at diagnosis. Histologic types were superficial spreading or nodular (50% each). Median lesion characteristics were diameter 2 cm, Breslow index 4.4 mm, and Clark level IV. Distribution of patients per American Joint Committee on Cancer (AJCC) stage was 29%, 50%, 16%, and 7% for stages I, II, III and IV, respectively. Inguinal node metastases were unilateral in 16% and bilateral in 7%. Despite complete surgical resection, 32 patients (63%) recurred. Median survival for all patients was 41 months (range, 5-324), with 91% 5-year survival for patients with stage I and 31% for stage >or= IIA (P = 0.0002). As with cutaneous melanoma, the AJCC classification, Breslow's thickness, and Clark's levels are the major predictors of overall survival (P = 0.0001 each) and disease-free survival (P <or= 0.0001, 0.0004, and 0.0002, respectively). Surgical techniques do not seem to alter the prognosis. Because vulvar melanoma carries a poor prognosis at early stages, the use of adjuvant therapies needs to be studied prospectively in women affected with this disease.

Adult↗

A pilot study for a screening trial of cervical fluorescence spectroscopy.

Fluorescence spectroscopy is a promising technology for detection of epithelial precancers and cancers. In preparation for a multicenter phase II screening trial, a pilot trial was conducted to test data collection and patient examination procedures, use data forms, time procedures, and identify problems with preliminary data analysis. Women 18 years of age and older underwent a questionnaire, a complete history, and a physical examination, including a pan-colposcopy of the lower genital tract. A fiber-optic probe measured fluorescence excitation-emission matrices at 1-3 cervical sites for 58 women. The data collection procedures, data forms, and procedure times worked well, although collection times for all the clinical data take an average of 28 min. The clinical team followed procedures well, and the data could be retrieved from the database at all sites. The multivariate analysis algorithm correctly identified squamous normal tissue 99% of the time and columnar normal tissue only 7%. The assessment of ploidy from monolayer samples was not accurate in this small sample. The study was successful as a pilot trial. We learned who participated, who withdrew, how often abnormalities were present, and that algorithms that have worked extremely well in previous studies do not work as well when a few study parameters are changed. The current algorithm for diagnosis identified squamous normal tissue very accurately and did less well for columnar normal tissue. Inflammation may be an explanation for this phenomenon. Fluorescence spectroscopy is a promising technology for the detection of epithelial precancers and cancers. The screening trial of fluorescence and reflectance spectroscopy was successful.

Adult↗

New tumor markers: CA125 and beyond.

A variety of biomarkers have been developed to monitor growth of ovarian cancer and to detect disease at an early interval. CA125 (MUC16) has provided a useful serum tumor marker for monitoring response to chemotherapy, detecting disease recurrence, distinguishing malignant from benign pelvic masses, and potentially improving clinical trial design. A rapid fall in CA125 during chemotherapy predicts a favorable prognosis and could be used to redistribute patients on multiarmed randomized clinical trials. Several studies now document that CA125 can serve as a surrogate marker for response in phase II trials. Serial measurement of CA125 might also provide a useful marker for monitoring stabilization of disease with cytostatic targeted therapeutic agents. The greatest potential for serum markers may be in detecting ovarian cancer at an early stage. A rising CA125 can be used to trigger transvaginal sonography (TVS) in a small fraction of patients. An algorithm has been developed that calculates risk of ovarian cancer based on serial CA125 values and refers patients at highest risk for TVS. Use of the algorithm is currently being evaluated in a trial with 200,000 women in the UK that will test critically the ability of a two-stage screening strategy to improve survival in ovarian cancer. Whatever the outcome, as 20% of ovarian cancers have little or no expression of CA125, additional serum markers will be required to detect all patients in an initial phase of screening. More than 30 serum markers have been evaluated alone and in combination with CA125 by different investigators. Some of the most promising include: HE4, mesothelin, M-CSF, osteopontin, kallikrein(s), and soluble EGF receptor. Two proteomic approaches have been used: one examines the pattern of peaks on mass spectroscopy and the other uses proteomic analysis to identify a limited number of critical markers that can be assayed by more conventional methods. Both approaches are promising and require further development. Several groups are placing markers on multiplex platforms to permit simultaneous assay of multiple markers with very small volumes of serum. Mathematical techniques are being developed to analyze combinations of marker levels to improve sensitivity and specificity. In the future, serum markers should improve the sensitivity of detecting recurrent disease as well as facilitate earlier detection of ovarian cancer.

Biomarkers, Tumor↗

Fine needle aspiration of the pancreas. In quest of accuracy.

Percutaneous fine needle aspiration (FNA) is the diagnostic method of choice for patients with a pancreatic mass. A positive cytologic diagnosis allows administration of neoadjuvant therapy in patients with resectable disease and avoids laparotomy in patients with locally advanced or metastatic disease. Ninety patients underwent computed tomographically guided FNA of the pancreas, and the results were compared to the final histologic diagnosis. The initial sensitivity for diagnosis of pancreatic adenocarcinoma was 70%. To improve our diagnostic accuracy, 19 independent cytologic criteria were evaluated for each case. Multivariate logistic-regression analysis identified three major criteria (nuclear crowding and overlapping, nuclear contour irregularity, irregular chromatin distribution) and four minor criteria (nuclear enlargement, single epithelial cells, necrosis, mitoses) as the most important predictors of malignancy. In the presence of two or more major or one major and three minor criteria, the sensitivity and specificity for the diagnosis of pancreatic adenocarcinoma were 100%. Objective application of these criteria improved our diagnostic sensitivity to 90%.

Adenocarcinoma↗

Prognostic significance of estrogen receptor expression in ovarian cancer. Immunoreactive Score (IRS) vs. Composition Adjusted Receptor Level (CARL).

An Immunoreactive Score (IRS) was compared to the Composition Adjusted Receptor Level (CARL) evaluating prognostic significance of estrogen receptor (ER) expression in 61 ovarian cancers after > or = 8 years. CARL of ER allowed for calculating individual risk curves in stage III and IV, Grade 2 and 3, serous ovarian carcinoma after surgical debulking to < or = 2 cm residual and platinum based chemotherapy. In overall analysis and in subsets defined by tumor stage, grade or a combination thereof significant prognostic distinction became possible using a cutoff IRS of 4 vs. 0 or vs. scores < or = 3. This study substantiates ER as a prognostic variable in human ovarian cancer and for the first time establishes the value of an IRS.

Female↗

Telomere length in human white blood cells remains constant with age and is shorter in breast cancer patients.

BACKGROUND: Telomeres, which are TTAGGG repeats at the end of the eukaryotic chromosome, are essential for complete DNA replication. Telomere length has been reported to decrease in peripheral WBC, unlike the telomerase activity found in these cells. The purpose of this study was to investigate whether telomere length in WBC is indeed age dependent and could serve as a genetic marker in breast or ovarian cancer. METHODS: Five age groups: 20-29; 30-39; 4049; 50-59 and > or = 60 years were examined. The cancer patients were 18 women with ovarian cancer and 18 women with breast cancer. Southern blot analysis of the DNA from peripheral white blood cells (WBC) was performed using 32P-labeled (TTAGGG)3 probe. Blots were scanned in a phosphoimager and analyzed by computer-assisted image analysis. RESULTS: No statistically significant correlation was observed between telomere length and age in either healthy females or cancer patients. However, significantly shorter median telomere length was found in WBC obtained from breast cancer patients as compared to healthy individuals and ovarian cancer patients. CONCLUSIONS: It is concluded that telomere length in WBC is not age dependent, but is significantly shorter in breast cancer patients.

Adult↗