Biomedical subjects

M Strawderman

Publications and source records attributed to M Strawderman.

31 records · Page 2Linked to original sources

PubMed1998

Effect of dietary vitamin A or N-acetylcysteine on ethylnitrosourea-induced rat gliomas.

It is our hypothesis that low grade gliomas are the glial counterparts of other precancerous lesions such as colon polyps and, therefore, suitable targets for chemoprevention. Steps in the molecular progression of gliomas have been described, indicating that an accumulation of abnormalities is required for progression to a high grade and interruption of this progression might be possible. An animal model of chemical glial carcinogenesis was used to test this hypothesis. Pregnant rats were injected intravenously with ENU (ethylnitrosourea) on the 18th day of gestation to induce gliomas in the offspring, which were randomized to receive control diet, diet supplemented with vitamin A palmitate, or diet supplemented with N-acetylcysteine. Animals exposed to ENU and receiving a control diet developed brain tumors and had a shortened life expectancy compared with rats unexposed to ENU. The animals treated with NAC showed no statistically significant delay in the time to tumor and no change in the histologic grade of the tumors when compared with animals receiving control diet, but the time to death from any cause of NAC treated animals differed significantly from untreated animals. Animals receiving high dose VA had statistically significantly prolonged time to tumor, survived significantly longer than untreated animals, but had no reduction in the total number of tumors or change in the histologic grade of their tumors. The theoretical basis of these results is likely due to the putative mechanism of action of these agents. These data indicate that glioma chemoprevention is possible and deserves further exploration.

Acetylcysteine↗

PubMed1998

Variability in the detection of enlarged mediastinal lymph nodes in staging lung cancer: a comparison of contrast-enhanced and unenhanced CT.

OBJECTIVE: Because CT protocols for staging lung cancer vary and little information exists regarding the diagnostic importance of using i.v. contrast material, our intent was to evaluate intra- and interobserver agreement in the detection of enlarged mediastinal lymph nodes, comparing i.v. contrast-enhanced and unenhanced CT. SUBJECTS AND METHODS: Fifty patients with known or suspected bronchogenic carcinoma underwent unenhanced thoracic CT followed by contrast-enhanced CT. Three observers noted enlarged lymph nodes (> 10 mm in the short axis) and assigned the enlarged nodes to American Thoracic Society nodal station designations. Enlarged lymph nodes were grouped two ways: by assigning the exact number of enlarged lymph nodes found (zero, one, two, three, four or more), and by assigning whether at least one, or no, enlarged mediastinal lymph nodes were found at a station ("one or none"). Agreement levels were determined for inter- and intraobserver interpretations using weighted kappa statistics and the McNemar test. RESULTS: The number of enlarged lymph nodes with enhanced CT was 11% higher than on unenhanced studies (418 versus 377; p = .044). Numbers of enlarged lymph nodes were different for five stations; however, the numbers were small except for the right upper paratracheal station (2R) (contrast-enhanced, 68 enlarged lymph nodes; unenhanced, 44 enlarged lymph nodes; p = .014). With regard to all stations together, intraobserver agreement between contrast-enhanced and unenhanced studies was almost perfect (kappa range, .85-.94), and no difference was found for any observer in the proportion of patients with at least one enlarged lymph node. Interobserver agreement was substantial or almost perfect for the total number of enlarged lymph nodes. For specific stations, the lowest kappa value was .48 at 2R. One observer reported more patients with at least one enlarged lymph node with contrast enhancement at station 2R (p = .031). Greater agreement existed between two observers at station 2R with contrast enhancement versus no enhancement (kappa = .85 versus .48; p = .02). Conclusions matched, and calculations of estimated kappa values gave similar results for determination of the specific number of enlarged lymph nodes at a station and the "one or none" category. CONCLUSION: We found high agreement for intra- and interobserver interpretations for contrast-enhanced and unenhanced CT, although contrast-enhanced CT revealed more enlarged lymph nodes, especially at station 2R.

Adult↗

PubMed1998

Mammographic screening in women more than 64 years old: a comparison of 1- and 2-year intervals.

OBJECTIVE: The purpose of our study was to determine if annual mammographic screening was superior to biennial screening in women more than 64 years old by examining differences in various prognostic indicators. MATERIALS AND METHODS: We reviewed the records of 119 consecutive women 65 years old and older with 120 cases of breast cancer who had a previous normal screening evaluation for breast cancer that included mammography and physical examination 8-30 months before diagnosis. A search of the computerized tumor registry, clinical records, and breast imaging records from November 1988 to April 1995 provided our cases. Screening intervals were defined as 6-18 months (annual) and 19-30 months (biennial). Mammographic, histologic, and clinical features were reviewed. Disease severity (DS) levels were assigned to each tumor as follows: DS-1 included minimal disease (ductal carcinoma in situ [TisNO], T1aN0, and T1bN0 tumors), DS-2 included all T1cN0 tumors, DS-3 included tumors larger than 2 cm in diameter with lymph nodes that were negative for cancer, and DS-4 included all metastatic disease. Statistically significant differences were calculated using the Wilcoxon rank sum test, Fisher's exact test, and the chi-square test. RESULTS: Ninety-three tumors were found in the group of patients who were annually screened, and 27 were found in the group of patients who were screened biennially. The women who underwent yearly screening mammography had significantly smaller invasive tumors (average, 10.7 mm; median, 9.5 mm versus 16.5 mm and 15.0 mm, respectively; p = .0086). The women who were screened annually also had significantly less advanced disease than women screened biennially (annually screened patients versus biennially screened patients: DS-1, 72% versus 44%; DS-2, 23% versus 37%; DS-3, 2% versus 11%; DS-4, 3% versus 7%; p = .0071). The group of patients screened annually had fewer cases of lymph node metastases (3% versus 8%; p = .12) and three times as many cases of ductal carcinoma in situ (22% versus 7%, p = .10). CONCLUSION: Annual screening mammography revealed significantly smaller tumors and less advanced cases of cancer than biennial screening, providing inferential support for annual mammographic screening of women more than 64 years old.

Age Factors↗

PubMed1997

The conservative management of Paget's disease of the breast with radiotherapy.

BACKGROUND: The purpose of this study was to evaluate the feasibility of breast-conserving therapy involving limited surgery and definitive radiotherapy as a treatment for Paget's disease, and to determine the disease free and overall survival associated with this approach. METHODS: The authors retrospectively reviewed the charts of all patients treated during the period 1980-1994 for Paget's disease of the breast who did not present with a palpable mass or mammographic density. Through a collaborative review, 30 cases were identified. A biopsy confirming the presence of typical Paget's cells was performed on all patients. All patients received external beam radiotherapy to the breast, with a median dose of 50 gray (Gy). Ninety-seven percent received a boost to the remaining nipple or tumor bed, with a median dose to the tumor bed of 61.5 Gy. RESULTS: The median follow-up for surviving patients was 62 months. Three patients (10%) developed a recurrence in the breast as the only site of first failure, and 2 additional patients (7%) experienced failure in the breast as a component of first failure. The median time to local failure was 69 months. The 5- and 8-year actuarial estimates of local failure as the only site of first failure were 9% (95% confidence interval [CI], 0-20%) and 16% (95% CI, 0-31%), respectively. Of the 5 patients with local failures, 3 were among 22 patients (14%) who underwent complete resection of the nipple or nipple-areola complex, compared with 2 failures among 6 patients (33%) after partial resection (P = 0.29). There were no failures among 2 patients who had a biopsy only. Four of 5 local failures were salvaged by mastectomy, and 3 of these patients were free of disease after a median follow-up of 52 months. The 5- and 8-year estimates of disease free survival for the overall series were both 95% (95% CI, 87-100%); cause specific overall survival was 100% at 8 years. CONCLUSIONS: Breast-conserving therapy involving complete resection of the nipple-areola complex followed by definitive radiotherapy is a viable alternative to mastectomy in the treatment of Paget's disease. High rates of disease free and cause specific survival, in addition to adequate local control, justify consideration of a conservative approach.

Adult↗

PubMed1997

A phase II trial of oral estramustine and oral etoposide in hormone refractory prostate cancer.

OBJECTIVES: We previously demonstrated that the combination of oral estramustine (15 mg/kg/day) and oral etoposide (50 mg/m2/day) is effective first-line therapy for the treatment of hormone refractory prostate cancer. We initiated a new Phase II trial utilizing a lower dose of estramustine (10 mg/kg/day) and allowing previous chemotherapy treatment. METHODS: Estramustine (10 mg/kg/day) and etoposide (50 mg/m2/day) were administered orally for 21 of 28 days. Sixty-two patients were enrolled with a minimum of 26 weeks of follow-up. RESULTS: Of 15 patients with measurable soft tissue disease, 8 (53%) had a partial response (PR). Seven of these 8 patients also demonstrated a decrease in baseline prostate-specific antigen (PSA) of more than 50%. The median survival of all patients was 56 weeks. Of 47 patients with disease limited to the bone, 16 (34%) had a PR to therapy based on decrease in pretreatment PSA of more than 50%. Overall, 24 (39%) of 62 patients demonstrated a decrease in pretreatment PSA levels of at least 50% from baseline. Twenty-two patients received previous chemotherapy. There were no differences in survival or disease response in patients treated with previous chemotherapy compared with untreated patients. Pretreatment hemoglobin, PSA, alkaline phosphatase and lactate dehydrogenase levels were not significant prognostic factors, but performance status was an important predictor of survival. CONCLUSIONS: We conclude that the combination of oral estramustine (10 mg/kg/day) and oral etoposide (50 mg/m2/day) is an active regimen for hormone refractory prostate cancer.

Administration, Oral↗

PubMed1997

Volume and dose parameters for survival of non-small cell lung cancer patients.

BACKGROUND AND PURPOSE: To determine the effect of tumor volume and dose factors derived from 3-D treatment planning dose distributions on survival outcome for non-small cell lung cancer patients. MATERIALS AND METHODS: Seventy-six consecutive patients diagnosed with medically inoperable or locally advanced, unresectable non-small cell lung cancer planned with 3-D treatment planning between 1986 and 1992 were the subject of this retrospective study. Patient characteristics and dosimetric parameters were analyzed for influence on overall survival and local progression-free survival (LPFS) using univariate and multivariate analysis. RESULTS: Nodal stage and stage were the most significant factors for overall survival and LPFS duration on both univariate and multivariate analysis. We found a wide range of primary tumor volume sizes for each stage. Patients with tumor volumes <200 cm3 had longer survival (P = 0.047). In an analysis stratifying patients into four groups by tumor volume (<200 cm3 versus >200 cm3) and nodes (negative versus positive), patients in the group with no nodal disease and <200 cm3 tumor volumes survived longer than patients in any other group (P = 0.046). No dose factors were statistically significant for longer survival. Longer LPFS was seen for (a) isocenter dose >70 Gy (P = 0.055) for the overall group of patients, (b) within a subgroup with no nodal disease and >73 Gy (P = 0.054), and (c) within a subgroup with no nodal disease and tumor volume <200 cm3 receiving >73 Gy (P = 0.086). CONCLUSIONS: Several findings from the volume and dosimetric analysis in this study are noteworthy. Stage was found to be a poor predictor of primary tumor volume size. Also, tumor volume size (<200 cm3) in conjunction with nodal status (negative nodes) had an impact on survival though there was a mix of stage (I, IIIa, IIIb) in this group of patients. Finally, dose appears to influence local control (LPFS) for the overall group of patients and when tumor volumes are <200 cm3. Our data indicate that outcome following radiation may be better predicted by a staging system that takes into account tumor volume and nodal spread rather than a system that is largely based on anatomic location of disease. Dose prescription for lung cancer treatment might better be written based on tumor volume size.

Carcinoma, Non-Small-Cell Lung↗

PubMed1997

Breast conservation and prolonged chemotherapy for locally advanced breast cancer: the University of Michigan experience.

PURPOSE: To determine whether breast conservation and prolonged neoadjuvant chemotherapy have efficacy in locally advanced breast cancer (LABC), as measured by survival and rate of breast conservation. MATERIALS AND METHODS: Eighty-nine patients with stage III disease were enrolled at the University of Michigan (UM) onto a prospective nonrandomized trial. Patients received nine 21-day cycles of neoadjuvant chemohormonal therapy that consisted of doxorubicin 30 mg/m2 and cyclophosphamide 750 mg/m2 intravenously on day 1, conjugated estrogens 0.625 mg orally twice daily on days 6 to 8, methotrexate 40 mg/m2 and fluorouracil 500 mg/m2 intravenously on day 8, and tamoxifen 10 mg orally twice daily on days 9 to 14. Patients with a negative biopsy received radiation only, while those with residual disease underwent mastectomy and postoperative radiotherapy. Eight more cycles of chemohormonal therapy were administered after local-regional therapy. RESULTS: The clinical response rate to neoadjuvant therapy was 97%, 28% of patients had a complete pathologic response evaluated at biopsy. Five-year overall and disease-free survival probabilities were 54% and 44%, respectively. The median disease-free survival time was 2.4 years. The 5-year actuarial rates of local-regional control with local failure as only first failure were 82% and 78% following radiotherapy, and mastectomy and radiotherapy, respectively (P = .99). CONCLUSION: Prolonged neoadjuvant chemohormonal therapy and biopsy-driven local therapy have efficacy in LABC, with 28% of patients being candidates for breast conservation and a 5-year overall survival rate of 54%.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

A two-step intervention of increase mammography among women aged 65 and older.

OBJECTIVES: This study evaluated a two-step intervention for mammography screening among older women. METHODS: Four hundred and sixty women, identified from physician practices, were randomized to a control or a two-step intervention (physician letter and peer counseling call) group. Women in the intervention group who obtained a mammogram received a grocery coupon. RESULTS: Over the 12 months of the study, more women in the intervention group than in the control group obtained mammograms (38% vs 16%). The most dramatic difference was in the higher odds that women in the intervention group would obtain a mammogram within 2 months (odds ratio = 10.5). CONCLUSIONS: The intervention significantly increased screening mammography. Future efforts must be multifaceted and incorporate the unique concerns of older women.

Aged↗

PubMed1996

Ejaculation increases the serum prostate-specific antigen concentration.

OBJECTIVES: To determine the effect of ejaculation on the serum prostate-specific antigen (PSA) concentration in men at risk for developing prostate cancer. METHODS: A prospective, community-based study was conducted in which 64 men, aged 49 to 79 years, underwent a serum PSA determination immediately before ejaculation (baseline) and at 1 hour, 6 hours, and 24 hours following ejaculation. The serum PSA also was measured 48 hours and 1 week after ejaculation if the concentration had not returned to the baseline value by the previous time interval. All subjects abstained from ejaculation for a minimum of 7 days prior to the study and until the PSA concentration returned to the baseline level. Absolute and relative change in serum PSA concentration, as well as the time to return to baseline PSA concentration following ejaculation, were assessed. RESULTS: The serum PSA concentration increased following ejaculation in 87% of the subjects. The mean baseline PSA was 1.8 ng/mL (median, 0.7 ng/mL). The mean absolute PSA change +/- standard deviation 1 hour, 6 hours, 24 hours, and 48 hours after ejaculation was 0.8 +/- 1.32 ng/mL, 0.3 +/- 0.66 ng/mL, 0.2 +/- 0.33 ng/mL, and 0.4 +/- 0.40 ng/mL, respectively. The mean relative PSA change +/- standard error 1 hour, 6 hours, 24 hours, and 48 hours after ejaculation was 41 +/- 4%, 9 +/- 1.5%, 8 +/- 1.3%, and 10 +/- 2.3%, respectively. The absolute and relative changes in PSA concentration noted 1 hour, 6 hours, and 24 hours after ejaculation were statistically significant (P = 0.0001). A strong correlation was observed between absolute change in PSA and baseline serum PSA, at each time interval (1 hour: r = 0.68, 6 hours: r = 0.77, 24 hours: r = 0.70; P < 0.0001) after ejaculation. Similarly, a significant correlation was noted between absolute change in PSA and patient age at each time interval (1 hour: r = 0.37, 6 hours: r = 0.38; P = 0.002, 24 hours: r = 0.55; P < 0.0001). Ninety-two percent of subjects returned to baseline by 24 hours (95% confidence interval (Cl) = 83% to 97%), whereas 97% of subjects returned to baseline by 48 hours (95% Cl = 89% to 99%). CONCLUSIONS: Ejaculation causes a significant increase in the serum PSA concentration in men between 49 and 79 years of age that may persist for up to 48 hours. This change appears to correlate with age and baseline PSA. It is recommended that men abstain from ejaculation for 48 hours prior to having a serum PSA determination.

Age Factors↗

PubMed1996

Chemotherapy followed by accelerated fractionated radiation for larynx preservation in patients with advanced laryngeal cancer.

PURPOSE: Larynx preservation in advanced, resectable laryngeal cancer may be achieved using induction chemotherapy (CT) followed in responding patients by definitive radiation (RT). To address potential accelerated repopulation of clonogenic tumor cells during the prolonged total treatment time, we studied the feasibility of accelerated fractionated RT after CT. METHODS: Patients with advanced laryngeal cancer received two cycles of cisplatin 100 mg/m2 and fluorouracil (5-Fu) 1,000 mg/m2/d for 5 days. Responding patients received a third cycle after which those who had complete response or tumor down-staging to T1 proceeded with accelerated RT: 70.4 Gy delivered over 5.5 weeks. Patients who achieved a lesser response to CT underwent total laryngectomy and postoperative RT. RESULTS: Thirty-three patients were accrued. Three died during the course of CT and two declined definitive treatment after CT. Twenty-one patients had a major response to CT, 20 of whom received accelerated RT. Median weight loss during RT was 11%. Late severe morbidity was observed in five patients (25%). All four patients who underwent salvage laryngectomy after accelerated RT experienced major postoperative complications. The locoregional failure rate was 25%. The larynx was preserved in 48% of the total study population and in 80% of the patients irradiated according to the study protocol. CONCLUSION: Accelerated RT after CT as delivered in this study may increase both acute and long-term morbidity rates compared with studies using standard RT after CT. It did not seem to improve local/regional tumor control or survival despite stringent patient selection criteria.

Adult↗

PubMed1993

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis.

PURPOSE: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.

Adult↗

PubMed1993

Prognostic factors for treatment outcome in autotransplantation of intermediate-grade and high-grade non-Hodgkin's lymphoma with cyclophosphamide, carmustine, and etoposide.

PURPOSE: We examined a consecutive series of 78 patients with non-Hodgkin's lymphoma treated on prospective protocols with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (CBV) plus autotransplantation to determine prognostic factors for time to treatment failure. PATIENTS AND METHODS: Patients with relapsed, refractory, or poor-risk intermediate- and high-grade non-Hodgkin's lymphoma were treated with CBV with autologous marrow or peripheral-blood progenitor cell support. Patient characteristics before transplantation were examined in univariate analyses by the log-rank test and simultaneously in a Cox proportional hazards regression analysis. A best-predictive model was determined from those variables significant (P < .10) in the univariate test. RESULTS: In univariate analysis, intermediate-grade and immunoblastic lymphoma, responsiveness to pretransplant salvage chemotherapy, and transplantation after primary therapy (first complete response [CR] or partial response [PR]) were associated with prolonged time to treatment failure. In proportional hazards multiple regression analysis, intermediate-grade and immunoblastic histology, responsive disease, and autotransplantation in first CR or PR were positive prognostic factors, and these characteristics are the basis of the best-predictive model for prolonged time to failure. Actuarial 3-year failure-free survival of patients with stable or responding disease at autotransplant was 54%. CONCLUSION: CBV is an effective conditioning regimen in intermediate-grade and immunoblastic non-Hodgkin's lymphoma. Patients with these histologies transplanted while responding to primary therapy, or those with stable disease or disease responding to salvage therapy at the time of autotransplant, are most likely to benefit. Patients with lymphoblastic lymphoma or diffuse undifferentiated lymphoma did poorly with CBV and should be offered alternative therapy.

Adolescent↗

PubMedDate not supplied

A bcl-x(S) adenovirus demonstrates therapeutic efficacy in an ascites model of human breast cancer.

OBJECTIVES: To determine whether a Bcl-x(S) adenoviral vector has therapeutic potential in an ascites model of human breast cancer in nude mice. METHODS: Advanced ascites were developed by injecting mice intraperitoneally (IP) with MDA-MB-231 human breast carcinoma cells. Mice received sequential IP injections of the Bcl-x(S) virus or a control lac-Z adenovirus. A third group of mice received no virus. Tumor burden and survival were monitored. Histopathology and necropsies were performed on mice. RESULTS: A single injection of the Bcl-x(S) adenovirus produced no systemic or local toxicity and no abnormal histopathology in normal mice. However, abdominal organs within these mice were transduced with the Bcl-x(S) vector. Adenoviral gene transduction efficiency in MDA-MB-231 ascites was 36+/-6.40% (n = 3). Percent weight change differences revealed that ascites bearing mice injected three times with the Bcl-x(S) vector showed a statistically significant decrease in tumor burden compared with lac-Z-injected mice (n = 7; P = .012 on days 10-15 after the first injection). Mice injected with the Bcl-x(S) vector had significantly greater survival relative to lac-Z-injected mice (n = 7; P = .0004). Bcl-x(S) protein expression was detected in aspirates of mice injected with the Bcl-x(S) vector but not the lac-Z vector. Necropsies revealed that ascites bearing mice injected with Bcl-x(S) vector lacked carcinoma in the peritoneal cavity compared with control mice. CONCLUSION: The Bcl-x(S) adenovirus can reduce tumor burden and increase survival in an ascites model of advanced stage breast cancer.

Adenoviridae↗