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Biomedical subjects

B Fowble

Publications and source records attributed to B Fowble.

At least 37 records · Page 2Linked to original sources
PubMed1997

Patterns of dose variability in radiation prescription of breast cancer.

PURPOSE: Comparison of radiation outcome of various treatment protocols is difficult due to the variability of dose prescription. A retrospective analysis of the pattern and intercomparison of dose prescriptions is presented for the treatment of breast cancer. MATERIALS AND METHODS: To represent the clinical practice for breast irradiation with tangential fields, commonly used prescription points were chosen that lie on the perpendicular bisector of the chest wall separation (s) that represents the breast apex height (h). These points are located at 1.5 cm from the posterior beam edge, at the chest wall-lung interface (2-3 cm), at distances of h/3 and h/2, and at the isocenter. One hundred consecutive patients treated with intact breast following excisional biopsy were used in this study. For analysis, treatment planning was carried out without lung correction with a 6 MV beam for all patients, even though some of the patients were treated with high energy beams for dose uniformity. Dose distributions were optimized with wedges and beam weights to provide a symmetrical dose distribution on the central axis plane. The statistical analyses of the different parameters, s, h, maximum dose, and doses at various prescription points were carried out. RESULTS: The maximum dose (hot spot) in breast varied from +5% to +27% above the prescribed dose among the patient population. The hot spot was directly related to s, and appeared to be independent of h and the ratio h/s. Among 55%, 40%, and 5% of the patients, the magnitude of the hot spot was 5-10%, 10-15%, and >15%, respectively. Except for the magnitude of the hot spot, the doses at various prescription points were independent of the breast size. For a prescription point at h/3 or at the lung-chest wall interface, the dose variation within +/- 1% is observed for 90% of the patient population. On the other hand, the average dose variation is about +/- 3% among other protocols with dose prescription point varying up to the h/2 point. With the prescription point at the isocenter, an average and maximum variation of 4-5% and 11% were observed, respectively. The maximum dose inhomogeneity for some patients was significantly higher, i.e. up to +27% even without the lung correction. CONCLUSIONS: A wide variation in prescription dose is observed among the different treatment protocols commonly used in breast treatment. For a total dose of 46-50 Gy delivered at 2 Gy/fraction to the breast, the prescribed dose may vary between 50 and 55 Gy and the hot spot dose per fraction may range between 2.3 and 2.5 Gy depending on the protocol and breast size. Thus dose normalization at hot spot and the isocenter should be discouraged unless the total dose to the breast is modified. A uniform definition of dose prescription for breast treatment is greatly required for intercomparison of clinical data.

Breast Neoplasms↗
PubMed1997

Postmastectomy radiation: then and now.

With the increased use of doxorubicin-based chemotherapy, chemoendocrine therapy, and high-dose chemotherapy with autologous bone marrow transplantation or peripheral blood progenitor-cell reinfusion, the role of postmastectomy radiation in the treatment of stages II-III breast cancer has been challenged. Despite these therapies, 20% to 30% of patients with four or more positive nodes, primary tumor size > or = 5 cm, or pectoral fascia involvement will develop an isolated locoregional recurrence. Postmastectomy radiation decreases the incidence of locoregional recurrence to < or = 10% in these high-risk patients, and modifications in technique can minimize long-term cardiac mortality. A recent meta-analysis has demonstrated a decrease in breast cancer mortality of approximately 10% with postmastectomy radiation, which is similar to the effect of adjuvant systemic therapy in axillary node-positive patients. Future studies are needed to further define the subset of patients who will benefit from postmastectomy radiation and to more precisely quantitate this benefit.

Antineoplastic Agents↗
PubMed1996

The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor-positive early-stage breast cancer.

PURPOSE: To evaluate the impact of tamoxifen on breast recurrence, cosmesis, complications, overall and cause-specific survival in women with Stage I-II breast cancer and estrogen receptor positive tumors undergoing conservative surgery and radiation. METHODS AND MATERIALS: From 1982 to 1991, 491 women with estrogen receptor positive Stage I-II breast cancer underwent excisional biopsy, axillary dissection, and radiation. The median age of patient population was 60 years with 21% < 50 years of age. The median follow-up was 5.3 years (range 0.1 to 12.8). Sixty-nine percent had T1 tumors and 83% had histologically negative axillary nodes. Re-excision was performed in 49% and the final margin of resection was negative in 64%. One hundred fifty-four patients received tamoxifen and 337 patients received no adjuvant therapy. None of the patients received adjuvant chemotherapy. RESULTS: There were no significant differences between the two groups for age, race, clinical tumor size, histology, the use of re-excision, or median total dose to the primary. Patients who received tamoxifen were more often axillary node positive (44% tamoxifen vs. 5% no tamoxifen), and, therefore, a greater percentage received treatment to the breast and regional nodes. The tamoxifen patients less often had unknown margins of resection (9% tamoxifen vs. 22% no tamoxifen). The 5-year actuarial breast recurrence rate was 4% for the tamoxifen patients compared to 7% for patients not receiving tamoxifen (p = 0.21). Tamoxifen resulted in a modest decrease in the 5-year actuarial risk of a breast recurrence in axillary node-negative patients, in those with unknown or close margins of resection, and in those who underwent a single excision. Axillary node-positive patients had a clinically significant decrease in the 5-year actuarial breast recurrence rate (21 vs. 4%; p = 0.08). The 5-year actuarial rate of distant metastasis was not significantly decreased by the addition of adjuvant tamoxifen in all patients or pathologic node-negative patients. Pathologically node-positive patients had a significant decrease in distant metastasis (35 vs. 11%; p = 0.02). There were no significant differences in cause-specific survival for patients receiving tamoxifen when compared to observation (95% no tamoxifen vs. 89% tamoxifen; p = 0.24). Similar findings were noted for pathologically node-negative patients. However, axillary node-positive patients receiving tamoxifen had an improvement in 5-year actuarial cause-specific survival (90% tamoxifen vs. 70% no tamoxifen; p = 0.10). Cosmesis (physician assessment) was good to excellent in 85% of the tamoxifen patients compared to 88% of the patients who did not receive tamoxifen. CONCLUSION: The addition of tamoxifen to conservative surgery and radiation in women with Stage I-II breast cancer and estrogen receptor positive tumors resulted in a modest but not statistically significant decrease in the 5-year actuarial risk of a breast recurrence. Tamoxifen significantly decreased the 5-year actuarial risk of distant metastasis in axillary node-positive patients and there was a trend towards improvement in cause-specific survival that was not statistically significant. Tamoxifen did not decrease the 5-year actuarial rate of distant metastasis in axillary node negative, patients and in this group, there was no improvement in cause-specific survival. Tamoxifen did not have an adverse effect on cosmesis or complications.

Adult↗
PubMed1996

Fifteen-year results of breast-conserving surgery and definitive breast irradiation for the treatment of ductal carcinoma in situ of the breast.

PURPOSE: To determine the 15-year outcome for women with ductal carcinoma in situ (DCIS, intraductal carcinoma) of the breast treated with breast-conserving surgery followed by definitive breast irradiation. PATIENTS AND METHODS: An analysis was performed of 270 intraductal breast carcinomas in 268 women from 10 institutions in Europe and the United States. In all patients, breast-conserving surgery included complete gross excision of the primary tumor followed by definitive breast irradiation. When performed, pathologic axillary lymph node staging was node-negative (n=86). The median follow-up time was 10.3 years (range, 0.9 to 26.8). RESULTS: The 15-year actuarial overall survival rate was 87%, and the 15-year actuarial cause-specific survival rate was 96%. The 15-year actuarial rate of freedom from distant metastases was 96%. There were 45 local recurrences in the treated breast, and the 15-year actuarial rate of local failure was 19%. The median time to local failure was 5.2 years (range, 1.4 to 16.8). A number of clinical and pathologic parameters were evaluated for correlation with local failure, and none were predictive for local failure (all P > or = .15). CONCLUSION: The results from the present study demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases following the treatment of DCIS of the breast using breast-conserving surgery and definitive breast irradiation. These results support the use of breast-conserving surgery and definitive breast irradiation for the treatment of DCIS of the breast.

Adult↗
PubMed1995

Factors associated with a positive reexcision after excisional biopsy for invasive breast cancer.

BACKGROUND: Breast-conserving therapy followed by adjuvant radiotherapy represents an alternative to mastectomy as a treatment for invasive breast cancer. When excisional biopsy has been performed outside the parent institution, reexcision is often performed, with tumor being identified in 32% to 62% of the subsequent specimens. We analyzed not only the factors associated with a positive reexcision but also those factors associated with final surgical margins that are positive for tumor. METHODS: Between 1978 and 1991, 956 female patients with American Joint Committee on Cancer clinical stage I or II breast cancer were treated with breast-conserving therapy where a total of 420 patients underwent reexcision after an initial excisional biopsy. Several factors were analyzed to determine their association with a positive reexcision, the status of the final surgical margin, and the nature of the disease present within the reexcision specimen. RESULTS: Factors that correlated with a positive reexcision in both univariate and multivariate analysis were clinical tumor size, method of detection, the pathologic status of the axillary lymph nodes, and the histologic appearance. Those factors associated with finding invasive disease at the time of reexcision were clinical tumor size, clinical presentation, and nodal status. The single factor associated with finding residual in situ disease at the time of reexcision was histologic appearance of the primary tumor. A final positive margin was associated with method of tumor detection, age of the patient, and the presence of axillary lymph node metastases. CONCLUSIONS: The most significant factors associated with a positive reexcision are clinical tumor size, method of tumor detection, pathologic nodal status, and histologic appearance. Patients with larger tumors or those that are detected by physical examination, as well as invasive lobular carcinomas, may require a more generous initial resection to achieve negative surgical margins and avoid the likelihood of reexcision.

Adult↗
PubMed1993

The role of mastectomy in patients with stage I-II breast cancer presenting with gross multifocal or multicentric disease or diffuse microcalcifications.

PURPOSE: Women with Stage I-II invasive breast cancer who present with gross multicentric disease or diffuse microcalcifications have a significant risk of breast recurrence when treated with conservative surgery and radiation. The purpose of this report is to present the results of mastectomy in this group of patients. METHODS AND MATERIALS: Between 1982 and 1989, 88 patients with clinical Stage I-II breast cancer who presented with clinical and mammographic evidence of gross multicentric disease or diffuse microcalcifications underwent modified radical mastectomy. Median followup was 4 years for the 57 patients with gross multicentric disease and 5.6 years for 31 patients with diffuse microcalcifications. At the time of mastectomy, 42% of patients were found to have positive axillary nodes. Following mastectomy, 15 patients received post mastectomy radiation and 35 patients received adjuvant systemic chemotherapy. RESULTS: When compared to a group of 1295 patients with unifocal, Stage I-II breast cancer, treated with conservative surgery and radiation during the same time period, patients with gross multicentric disease and diffuse microcalcifications had a significantly higher incidence of > or = 4 positive nodes, patients with gross multicentric disease had a lower incidence of positive resection margins following mastectomy and patients with diffuse microcalcifications were younger. The 5-year actuarial risk of an isolated local-regional recurrence was 8% for patients with gross multicentric disease or diffuse microcalcifications and 7% for patients with unifocal disease. Patients with gross multicentric disease or diffuse microcalcifications and > or = 4 positive axillary nodes who did not receive post mastectomy radiation had an increased risk for local regional recurrence. There were no significant differences in the 5-year actuarial overall or relapse-free survival (88% and 73% gross multicentric disease, 97% and 86% diffuse microcalcifications and 90% and 79% unifocal disease), freedom from distant metastasis (76% gross multicentric disease, 90% diffuse microcalcifications, 86% unifocal disease) or incidence of contralateral breast cancer (10% gross multicentric disease, 13% diffuse microcalcifications, 8% unifocal disease) among the three groups. CONCLUSION: The present study demonstrates no increased risk of local-regional recurrence in patients with gross multicentric disease or diffuse microcalcifications undergoing mastectomy in contrast to the increased risk of breast recurrence in patients with gross multicentric disease undergoing conservative surgery and radiation. Indications for post mastectomy radiation include > or = 4 positive nodes or close or positive surgical margins. Despite a significantly higher incidence of > or = 4 positive nodes, patients with gross multicentric disease and diffuse microcalcifications have a 5-year actuarial overall and relapse-free survival comparable to a group of patients with unifocal disease treated with conservative surgery and radiation.

Actuarial Analysis↗
PubMed1993

A new technique for positioning tangential fields.

PURPOSE: A technique that eliminates the use of a mechanical "breast-bridge" for positioning tangential fields for treatment of the intact breast or chest wall has been developed. METHODS AND MATERIALS: Treatment set-up parameters are determined using measuring capabilities (gantry angles and source-skin distances) available on a standard simulator unit. A programmable scientific calculator is used to determine field geometry from polar coordinates for various points on the patient's skin. The calculator program determines the field size, a depth and lateral shift from a skin reference point to the isocenter for the tangential fields, and the gantry angles. The program provides additional information which facilitates the simulation process: First, the coordinates of the isocenter for the tangential fields are expressed relative to couch coordinates for an initial arbitrary isocenter so that the "auto go to" capability available on some simulators can be used. Second, the coordinates of the medial and lateral entry points can be edited when the first set of tangents are not accepted. This part of the program allows quick and efficient adjustment of the fields to obtain adequate treatment volume coverage and a minimum of irradiated lung or heart. RESULTS: Simulation of more than 300 patients has shown the technique to be a practical and efficient method for positioning tangential fields for breast or chest wall irradiation. CONCLUSION: The technique described here takes full advantage of the capabilities of the new generation of computer controlled simulators, and offers an alternative to previous methods employing a mechanical "breast-bridge."

Breast Neoplasms↗
PubMed1993

neu(c-erbB-2/HER2) and the epidermal growth factor receptor (EGFR) in breast cancer.

One hundred and eighty thousand new cases of invasive breast cancer were diagnosed in 1992 within the United States. This disease affects approximately 1 out of 8 women in the US. Chemotherapy and/or hormonal therapy have shown some improved disease-free and/or overall survival rates. Unfortunately, this type of therapy is not directed specifically to the malignant cells, and systemic toxicities are observed. In order to develop site-specific treatment, the biology of the disease must be understood such that certain genes or their products which are involved in the pathogenesis of the disease can be targeted. Two structurally related tyrosine kinase growth factors, the epidermal growth factor receptor (EGFR) and c-erbB-2 (neu) have been identified in human breast cancer tissue and, in many instances, may function as oncogenes. The clinical data related to these two growth factor receptors as prognostic factors for the disease have been critically evaluated. Several problems with the critical studies were identified, and solutions were proposed to clarify the conflicting results reported in the studies which have attempted to examine whether c-erbB-2 (neu), in particular, is a prognostic indicator for breast cancer. In addition, data related to the structure of, ligands for and interaction between the proteins have been reviewed and presented with respect to their role in breast cancer development. A more thorough understanding of the genetic changes which contribute to the development of breast cancer will lead to more specific and less toxic treatment for this disease.

Breast Neoplasms↗
PubMed1993

Tumor necrosis is a prognostic predictor for early recurrence and death in lymph node-positive breast cancer: a 10-year follow-up study of 728 Eastern Cooperative Oncology Group patients.

PURPOSE: The Eastern Cooperative Oncology Group (ECOG) entered 766 patients onto two prospectively randomized surgical adjuvant clinical trials for lymph node-positive breast cancer (T1-3N1M0). Ninety-five percent (n = 728) of eligible patients have complete information on the prognostic covariables under study (tumor necrosis [TN], tumor size, number of positive lymph nodes, age) and a median follow-up duration of 10.3 years. METHODS: TN was defined as confluent cell death in invasive areas of primary cancers, visible at 4 x objective lens magnification. Cox proportional hazards models were used to estimate presence versus absence of TN effects on clinical outcomes over full cross-stratification of variables, including delivery of chemotherapy versus observation only. Time-varying effects were modeled using spline functions of time, and by fixing proportional hazards models separately in the time periods 0 to 2 and 2+ years. RESULTS: Presence of TN was an independent predictor for time to recurrence (TTR) (P = .007) and for survival (P = .0003) in the overall 10-year follow-up period. Presence of TN was also an independent predictor for TTR and for survival (each P < .0001) in the period 0 to 2 years after diagnosis. Spline function time-modeling calculations showed different hazard ratios in the TN-present (TN+) versus TN-absent (TN-) groups for both TTR and survival (each P < .0001). This difference is changing over time (P = .0001 for TTR, P = .0005 for survival). Once a patient has been disease-free beyond 2 years after diagnosis, presence or absence of TN is irrelevant to future prognosis. CONCLUSION: Confluent TN of any dimension in invasive areas of lymph node-positive breast cancer is an independent predictor for early recurrence and death from the disease.

Breast Neoplasms↗
PubMed1992

Conservative surgery and radiation therapy in black women with early stage breast cancer. Patterns of failure and analysis of outcome.

Between 1977 and 1986, 75 black and 615 white women with American Joint Committee (AJC) Stages I and II breast cancer were treated with excisional biopsy, axillary dissection, and radiation therapy for breast conservation. Cyclophosphamide, methotrexate, and 5-fluorouracil, with and without prednisone and tamoxifen, was given to 92% of premenopausal, 83% of perimenopausal, and 63% of postmenopausal node-positive women; 20 of 106 (19%) postmenopausal node-positive women received tamoxifen only. The clinical characteristics of the similarly treated patients were compared. The 5-year actuarial local only first failure rate was 5% for black women and 6% for white women (P = 0.53). Regional only failure as the first site of failure was 9% for blacks versus 1% for whites (P = 0.002), with regional recurrence as any component of first failure being 16% for blacks and 4% for whites (P = 0.001). The supraclavicular fossa was identified as the primary site of regional recurrence in black patients with either pathologically positive or negative axillae. Distant metastases as the only site of first failure were significantly greater in the black population with a 20% 5-year actuarial failure rate versus 11% in white patients (P = 0.01). The 5-year actuarial overall survival for the black patients was 82% versus 91% for the white patients (P = 0.01), with no-evidence-of-disease (NED) survival being 64% and 83% (P = 0.0002) and relapse-free survival (RFS) being 61% and 77% (P = 0.01), respectively. Black patients younger than 40 years of age or with pathologically positive axillary nodes had significantly worse NED, RFS, and overall survival compared with similarly staged white patients. Cosmetic results were analyzed at 3 and 5 years after completion of therapy. Although significantly fewer black patients had an excellent-to-good cosmetic result at 3 years compared with white patients, the results were not significantly different at 5 years. These results show that appropriately selected black patients with early stage breast cancer have excellent local control after conservative surgery and radiation therapy and should continue to be offered breast preservation as an alternative to mastectomy. Patterns of failure, however, demonstrated higher regional and distant recurrence rates and lower NED, RFS, and overall survival rates in most subsets of black patients reviewed.

Age Factors↗
PubMed1992

Breast recurrence and survival related to primary tumor location in patients undergoing conservative surgery and radiation for early-stage breast cancer.

Between 1977 and 1986, 886 pts with Stage I and II breast cancer underwent excisional biopsy, axillary dissection and radiation. Median follow-up was 5 years (range 2 months-13 years). The patients were divided into four groups according to the primary tumor location: 1) outer (495 patients), 2) inner (202 patients), 3) central (119 patients), and 4) subareolar (70 patients). Subareolar tumors were defined as those immediately beneath the nipple-areolar complex or within 2 cm of the areolar margin. The comparability of the groups was assed in terms of clinical T stage, patient age, histology, final pathologic margin status, estrogen and progesterone receptor status, pathologic nodal status, and use of adjuvant chemotherapy. There were no significant differences among the four groups in the distribution of these factors except for the pathologic nodal status (outer 38% positive nodes, inner 24%, central 23%, subareolar 31%) p = .0004. There were no significant differences in 5 year actuarial overall survival (91% vs 86% vs 92% vs 91%, p = .34), relapse-free (75% vs 74% vs 80% vs 79%, p = .77), or NED survival (82% vs 78% vs 87% vs 84%, p = .29) for the four groups. A separate analysis for pathologic node negative and node positive patients revealed similar findings. For node-negative patients, the 5 year actuarial overall survival was 93% vs 88% vs 94% vs 91% (p = .20), the relapse-free survival was 78% vs 76% vs 82% vs 79% (p = .49), and the NED survival was 86% vs 81% vs 88% vs 86% (p = .46). For node-positive patients, the 5 year actuarial overall survival was 87% vs 82% vs 84% vs 90% (p = .59), relapse-free survival was 69% vs 66% vs 77% vs 80% (p = .78), and NED survival was 75% vs 68% vs 85% vs 80% (p = .66). Patterns of first failure were also not significantly different among the four groups: local only first failure (7% vs 4% vs 5% vs 8%, p = .49), any local first failure, i.e., +/- simultaneous distant metastases (8% vs 5% vs 5% vs 9%, p = .61), regional only (2% vs 1% 1% vs 0%, p = .65), any regional (4% vs 3% vs 3% vs 3%), or distant metastases (11% vs 17% vs 9% vs 10%, p = .16). A separate analysis of node negative and node positive patients revealed similar findings.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Radiotherapeutic considerations in the treatment of primary breast cancer.

Patients who are candidates for conservative surgery and radiation include those with a primary tumor size of less than 4-5 cm, without evidence of gross multicentricity or diffuse microcalcifications. Patients with an extensive intraductal component may be appropriate candidates, provided that margins of resection are negative. Focally positive margins of resection in patients without an extensive intraductal component are not a contraindication, provided that a boost dose of radiation is employed; young age is also not a contraindication to conservative treatment. The optimal radiotherapy technique includes a total dose to the breast of 4500-5000 cGy with a daily fraction size of less than 250 cGy and a weekly dose of more than 800 cGy. The role of boost treatment in patients with negative margins of resection is currently under investigation. Boost treatment is essential in patients with positive margins. A direct photon-beam field to treat the internal mammary nodes should be avoided, especially in patients receiving chemotherapy. The subset of patients for whom the addition of radiation following an excisional biopsy does not result in a decreased risk of breast cancer recurrence remains to be defined and is currently being evaluated in several prospective randomized trials. The optimal sequencing of adjuvant chemotherapy and primary radiotherapy has not been determined.

Biopsy↗
PubMed1990

Breast recurrence following conservative surgery and radiation: patterns of failure, prognosis, and pathologic findings from mastectomy specimens with implications for treatment.

Between 1978 and 1986, 1030 women with clinical Stage I or II breast cancer underwent excisional biopsy, axillary dissection (948 patients), and definitive irradiation. Sixty-five patients developed a recurrence in the treated breast, 9 of which were associated with simultaneous (8) or antecedent (1) distant metastases. Detection was by mammography alone in 29%, physical exam alone in 50%, and both in 21%. The median interval to recurrence was 34 months. Overall, 65% of the recurrences were in the vicinity of the original tumor; however, as the interval to recurrence increased, the percentage of operable recurrences in a separate quadrant increased. For those recurring after 5 years, 54% were in a separate quadrant. Ninety-five percent of the recurrences unassociated with distant metastases were operable and pathology revealed non-invasive cancer only in 10%. Fifty-two patients underwent salvage mastectomy. Thirteen patients had no residual tumor following excisional biopsy at the time of mastectomy. None of the following factors were predictive for no residual tumor: initial age, method of detection, interval to recurrence, location of recurrence, or histology. Local-regional control following mastectomy was 95%. The 5-year actuarial overall and disease-free survivals for salvage mastectomy patients were 84% and 59%, respectively. The only significant prognostic factor for survival was the initial clinical tumor size, which was related to the extent of the recurrence. Based on the inability to identify factors which would predict for a localized recurrence pathologically, we recommend mastectomy as the preferred surgical treatment for an isolated breast recurrence. Adjuvant chemotherapy may be beneficial in patients with an unfavorable prognosis.

Adult↗