Biomedical subjects

Susan L Tucker

Publications and source records attributed to Susan L Tucker.

61 records · Page 4Linked to original sources

PubMed2002

International prognostic index-based outcomes for diffuse large B-cell lymphomas.

BACKGROUND: We present the results of doxorubicin-based chemotherapy with or without involved-field radiotherapy for patients with diffuse large B-cell lymphoma (DLBCL) according to the international prognostic index (IPI). METHODS: From September 1988 through December 1996, 294 patients with Stage I-IV Working Formulation large B-cell or T-cell lymphomas were treated prospectively on two protocols at our center. Diagnoses were reclassified subsequently according to the new World Health Organization classification. Two-hundred and twenty-four patients had DLBCL, including 24 patients with primary mediastinal large B-cell lymphoma. Treatment consisted of a median of six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy with or without involved-field radiotherapy (median dose, 39.6 Gy). RESULTS/CONCLUSIONS: The median length of follow-up among surviving patients was 5.0 years. Patient subgroups differed from each other in terms of progression-free (P = 0.003), cause-specific (P = 0.003), and overall (P = 0.001) survival rates when analyzed by IPI. Five-year progression-free, cause-specific, and overall survival rates for 212 patients with an IPI of 0-2 were 73%, 84%, and 82%, respectively, versus only 37%, 33%, and 32% for 12 patients with an IPI of 3-4. To improve our results, we are conducting clinical trials with young DLBCL patients and with patients who are older than 60 years. The young DLBCL patients, who have more than two adverse prognostic features, are receiving high-dose chemotherapy and autologous stem cell rescue. The patients who are older than 60 years, regardless of IPI, are receiving rituximab immunotherapy and liposomal CHOP chemotherapy with or without involved-field radiotherapy.

Adolescent↗

PubMed2002

Assessment of histologic features and expression of biomarkers in predicting pathologic response to anthracycline-based neoadjuvant chemotherapy in patients with breast carcinoma.

BACKGROUND: There is significant variability in the response of tumors to neoadjuvant chemotherapy, and the underlying mechanism for this variability is unknown. In this study, the authors investigated the roles of tumor nuclear grade, mitotic activity, and biomarker expression profiles in predicting the pathologic response of breast tumors to preoperative chemotherapy. METHODS: Eighty-two patients with breast carcinoma participated in two clinical trials and were treated with neoadjuvant chemotherapy, which consisted of either a conventional dose of fluorouracil, doxorubicin, and cyclophosphamide (FAC) or dose-escalated FAC. The mean age of the patients was 46 years (range, 24-69 years). Nuclear grade, mitotic activity, and biomarker profile (Her2-neu and mitosin expression patterns) in pretreatment tumors were correlated with the postchemotherapy pathologic response. RESULTS: Twelve patients (15%) had a complete pathologic response (CPR), 23 patients (28%) had a near complete response (NCR), and 47 patients (57%) had significant residual disease present either at the primary site or in the axillary lymph nodes. The authors found that the nuclear grade and mitotic activity of pretreatment tumors were correlated significantly with CPR and NCR (P = 0.002 and P = 0.004). Mitosin also was correlated significantly with CPR and NCR (P = 0.028). A higher percentage of patients with Her2-neu-positive tumors had a CPR or an NCR (P = 0.152). CPR and NCR were not correlated significantly with disease stage (P = 0.186) or lymph node positivity (P = 0.498). CONCLUSIONS: The current results indicate that tumor nuclear grade and tumor proliferative activity (mitotic activity and mitosin immunostaining) of pretreatment tumors in patients with breast carcinoma may serve as important indicators for the pathologic responsiveness of tumors to neoadjuvant, anthracycline-based chemotherapy.

Adult↗

PubMed2002

Evidence of haplotype insufficiency in human cells containing a germline mutation in BRCA1 or BRCA2.

The BRCA1 and BRCA2 gene products are thought to play important roles in the processing of DNA damage. To assess whether heterozygous mutations in these genes are associated with cellular radiosensitivity, we performed an in vitro radiation clonogenic survival assay on dermal fibroblasts obtained from 8 sequence-proven BRCA heterozygotes (6 BRCA1, 2 BRCA2). These data were compared to results obtained from a previous set of 17 prospectively studied cancer patients who had a negligible risk for a BRCA mutation. In addition, results from radiation-induced chromatid break assay performed on lymphocytes obtained from 9 BRCA heterozygotes (8 BRCA1, 1 BRCA2) were compared to results from a control group of 18 women with no cancer history. Results from both assays suggested that cells containing a heterozygous mutation in BRCA1 or BRCA2 were more radiosensitive than controls. For the fibroblast studies, the mean surviving fraction at 2 Gy (SF2) for carriers was 0.279 vs. 0.348 for the control set (p = 0.007). For the lymphocyte studies, the mean number of chromatid breaks after 125 cGy of radiation was 0.79 breaks per cell for the carriers vs. 0.45 for the controls (p = 0.0005). There was no apparent difference in the radiosensitivity between cells with BRCA1 vs. BRCA2 mutations (p = 0.769), although the small sample size minimizes the certainty of this observation. These preliminary results are consistent with a relationship between a germline mutation in BRCA1 or BRCA2 and a hypersensitivity to radiation. This phenotype could possibly predispose to an increased risk of radiation-induced mutagenesis and carcinogenesis.

BRCA1 Protein↗

PubMed2002

Results with chemotherapy comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone followed by radiotherapy with or without prechemotherapy surgical debulking for patients with bulky, aggressive lymphoma.

BACKGROUND: The authors performed a case-control analysis of local control, progression free survival, and overall survival in patients with Stage I-II aggressive lymphomas measuring > or = 7 cm in greatest dimension who were treated initially with or without surgical debulking: All patients then received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) based chemotherapy followed by involved field radiotherapy. METHODS: From May 1975 through May 1996, 50 patients were treated with (n = 25 patients) or without (n = 25 patients) resection of > 80% of their bulky lymphomas. Chemotherapy consisted of 3-12 cycles of CHOP. In general, patients who underwent debulking received three cycles of chemotherapy, whereas patients who did not undergo debulking received at least six cycles of chemotherapy. The total radiotherapy dose was 40.8 grays (Gy) +/- 4.2 Gy (mean +/- standard deviation). RESULTS: The median follow-up was 62 months. Patients who underwent debulking were similar prognostically to patients who did not. There was a trend toward improved local control (5 year rates: 96% vs. 80%; P = 0.10) and overall survival (5 year rates: 83% vs. 71%; P = 0.18) in patients who underwent debulking compared with patients who did not, respectively. Progression free survival was significantly better for patients who underwent debulking compared with patients who did not (5 year rates: 88% vs. 62%, respectively; P = 0.04). CONCLUSIONS: Because this study was retrospective, selection bias may account for the observed difference in progression free survival. Because it is unlikely that a trial randomizing patients with bulky, aggressive lymphoma to surgery will be conducted, the authors' current efforts are focused on escalation of the total radiotherapy dose as a possibly less costly and less morbid approach toward improving progression free survival for these patients.

Aged↗

PubMed2002

Predictors of local-regional recurrence after neoadjuvant chemotherapy and mastectomy without radiation.

PURPOSE: To define clinical and pathologic predictors of local-regional recurrence (LRR) for patients treated with neoadjuvant chemotherapy and mastectomy without radiation. PATIENTS AND METHODS: We analyzed the outcome of the 150 breast cancer cases treated on prospective institutional trials with neoadjuvant chemotherapy and mastectomy without postmastectomy radiation. Clinical stage at diagnosis was I in 1%, II in 43%, IIIA in 23%, IIIB in 25%, and IV in 7%. No patient had inflammatory breast cancer. RESULTS: The median follow-up period of surviving patients was 4.1 years. The 5- and 10-year actuarial rates of LRR were both 27%. Pretreatment factors that positively correlated with LRR were increasing T stage (P <.0001) and increasing combined clinical stage (P <.0001). Pathologic and treatment factors that positively correlated with LRR were size of the residual primary tumor (P =.0048), increasing number of involved lymph nodes (P <.0001), and no use of tamoxifen (P =.0013). The LRR rate for the 18 patients with a pathologic complete response of both the primary tumor and lymph nodes (pCR) was 19% (95% confidence interval, 6% to 48%). In a forward stepwise Cox logistic regression analysis, clinical stage IIIB or greater (hazard ratio of 4.5, P <.001), pathologic involvement of four or more lymph nodes (hazard ratio of 2.7, P =.008), and no use of tamoxifen (hazard ratio of 3.9, P =.027) independently predicted for LRR. CONCLUSION: Advanced disease at presentation and positive lymph nodes after chemotherapy predict for clinically significant rates of LRR. Achievement of pCR does not preclude the need for postmastectomy radiation if warranted by the pretreatment stage of the disease.

Adult↗

PubMedDate not supplied

Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy.

PURPOSE: The relevance of apoptosis to breast cancer response to chemotherapy is unclear. We investigated whether changes in tumor cell apoptosis and Bcl-2 expression immediately after chemotherapy correlated with response to breast cancer treatment. PATIENTS AND METHODS: Serial core biopsies of 25 breast cancer primary tumors were performed at either two or three time points: before treatment (N = 24) and approximately 24 hours (N = 22) and/or 48 hours (N = 19) after the initiation of the first cycle of chemotherapy. Apoptosis levels were quantified by use of a fluorescent terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) stain, and Bcl-2 and Bax were measured by semiquantitative immunohistochemical assays. All calculated P values were two sided. RESULTS: The apoptosis level at 48 hours was significantly higher in the tumors with pathological complete response or < 1 cm of residual disease (median, 22%; range, 6%-51%) than in the tumors with > 1 cm residual disease (median, 7%; range, 1%-36%); Mann-Whitney test. This difference was also present in the subgroup of 16 tumors treated with docetaxel/doxorubicin chemotherapy (25% vs 4%, respectively). A decrease in Bcl2 expression after chemotherapy relative to the expression from the pretreatment sample also correlated with disease response. Specifically, three of the nine tumors with a decrease in Bcl-2 had a pathological complete response, compared with 0 of the 15 tumors with stable levels of Bcl-2 (Fisher's exact test). There was no relationship between serial measurements of Bax and response. DISCUSSION: These data suggest that apoptosis may play an important role in determining breast cancer response to chemotherapy and that the level of treatment-induced apoptosis may have some value as a predictive marker.

Adult↗

PubMedDate not supplied

Molecular response of follicular lymphoma to cyclophosphamide, doxorubicin, vincristine, prednisone C(H)OP or COP-based therapy as measured by polymerase chain reaction evidence of translocation (14;18)(q32;q21).

PURPOSE: Existing data suggest that conventional C(H)OP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen may not be intensive enough to achieve molecular response, as measured by polymerase chain reaction (PCR) evidence of translocation (14;18)(q32:q21) for follicular lymphoma. This study was undertaken to study the molecular response rate of follicular lymphoma to C(H)OP-based therapy and to analyze prognostic factors for molecular response. PATIENTS AND METHODS: Twenty patients with pretreatment PCR evidence of t(14;18)(q32; q21) and at least one posttreatment PCR analysis after the initiation of the treatment with C(H)OP with or without radiation therapy constituted the basis for this analysis. The random effects logistic model was used to analyze the data. The following factors were investigated for their relationship to molecular response: gender, age, beta2-microglobulin, use of radiation therapy, Ann Arbor stage, and international Prognostic Index for malignant lymphoma. RESULTS: Median follow-up was 56 months (range, 23-153 months). A total of 135 PCR results were available, 33 from bone marrow and 102 from peripheral blood. Overall, there was a clear and steady decreasing trend toward loss of PCR positivity with increasing time aftertreatment. By univariate analysis, stage > or = 3, stage = 4, International Prognostic Index > or = 2, and no radiation therapy were adverse factors for molecular response. On multivariate analysis, Ann Arbor stage IV and no radiation therapy were independent risk factors for PCR positivity, both for the peripheral blood data analyzed alone and for all data combined. DISCUSSION: It is possible to achieve molecular response with C(H)OP with or without radiation therapy in patients with follicular lymphoma. Response rate depends on the Ann Arbor stage and radiation therapy.

Adult↗