Biomedical subjects

B Haffty

Publications and source records attributed to B Haffty.

10 recordsLinked to original sources

PubMed2001

Mammographically detected ductal carcinoma in situ of the breast treated with breast-conserving surgery and definitive breast irradiation: long-term outcome and prognostic significance of patient age and margin status.

PURPOSE: This study was performed to determine the long-term outcome for women with mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast treated with breast-conserving surgery followed by definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed of 422 mammographically detected intraductal breast carcinomas in 418 women from 11 institutions in North America and Europe. All patients were treated with breast-conserving surgery followed by definitive breast irradiation. The median follow-up time was 9.4 years (mean, 9.4 years; range, 0.1-19.8 years). RESULTS: The 15-year overall survival rate was 92%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 94%. There were 48 local failures in the treated breast, and the 15-year rate of any local failure was 16%. The median time to local failure was 5.0 years (mean, 5.7 years; range, 1.0-15.2 years). Patient age at the time of treatment and final pathology margin status from the primary tumor excision were both significantly associated with local failure. The 10-year rate of local failure was 31% for patient age < or = 39 years, 13% for age 40-49 years, 8% for age 50-59 years, and 6% for age > or = 60 years (p = 0.0001). The 10-year rate of local failure was 24% when the margins of resection were positive, 9% when the margins of resection were negative, 7% when the margins of resection were close, and 12% when the margins of resection were unknown (p = 0.030). Patient age < or = 39 years and positive margins of resection were both independently associated with an increased risk of local failure (p = 0.0006 and p = 0.023, respectively) in the multivariable Cox regression model. CONCLUSIONS: The 15-year results from the present study demonstrated high rates of overall survival, cause-specific survival, and freedom from distant metastases following the treatment of mammographically detected ductal carcinoma in situ of the breast using breast-conserving surgery and definitive breast irradiation. Younger age and positive margins of resection were both independently associated with an increased risk of local failure. The 15-year results in the present study serve as an important benchmark for comparison with other treatment modalities. These results support the use of breast-conserving surgery and definitive breast irradiation for the treatment of appropriately selected patients with mammographically detected ductal carcinoma in situ of the breast.

Adult↗

PubMed2001

Salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ of the breast.

BACKGROUND: The purpose of the current study is to evaluate the outcome of salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. METHODS: An analysis was performed of 42 patients with local only first failure (n = 41) or local-regional only first failure (n = 1) after breast-conserving surgery and radiation treatment had been given for DCIS of the breast. Surgical treatment at the time of local recurrence included mastectomy (n = 37; 88%) or excision (n = 5; 12%). Adjuvant systemic therapy at the time of local recurrence was chemotherapy (n = 3; 7%), tamoxifen (n = 8; 19%), both (n = 1; 2%), none (n = 29; 69%), or unknown (n = 1; 2%). The median interval from the time of initial treatment to local recurrence was 4.8 years (range = 1.0-15.2 yrs). The median follow-up after salvage treatment was 4.5 years (range = 0.2-12.8 yrs). RESULTS: At the time of the local recurrence, 22 patients (52%) had invasive ductal carcinoma, 18 patients (43%) had DCIS, 1 patient (2%) had invasive lobular carcinoma, and 1 patient (2%) had angiosarcoma. After salvage treatment, the rate of overall survival and the rate of cause specific survival for all 42 patients were 92% at both 5- and 8-years after treatment. The rate of freedom from distant metastases was 89% at 5 and 8 years. Favorable prognostic factors after salvage treatment were DCIS as the histology of the local recurrence and mammography only as the method of detection of the local recurrence. CONCLUSIONS: The results of salvage treatment in the current study demonstrated that local recurrences were salvaged with high rates of survival and freedom from distant metastases. These results support the use of breast-conserving surgery and radiation for initial management of DCIS of the breast.

Adult↗

PubMed2000

Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations.

PURPOSE: Recent laboratory data suggest a role for BRCA1/2 in the cellular response to DNA damage. There is a paucity of clinical data, however, examining the effect of radiotherapy (RT), which causes double-strand breaks, on breast tissue from BRCA1/2 mutation carriers. Thus the goals of this study were to compare rates of radiation-associated complications, in-breast tumor recurrence, and distant relapse in women with BRCA1/2 mutations treated with breast-conserving therapy (BCT) using RT with rates observed in sporadic disease. PATIENTS AND METHODS: Seventy-one women with a BRCA1/2 mutation and stage I or II breast cancer treated with BCT were matched 1:3 with 213 women with sporadic breast cancer. Conditional logistic regression models were used to compare matched cohorts for rates of complications and recurrence. RESULTS: Tumors from women in the genetic cohort were associated with high histologic (P =.0004) and nuclear (P =.009) grade and negative estrogen (P=.0001) and progesterone (P=.002) receptors compared with tumors from the sporadic cohort. Using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity scoring, there were no significant differences in acute or chronic morbidity in skin, subcutaneous tissue, lung, or bone. The 5-year actuarial overall survival, relapse-free survival, and rates of tumor control in the treated breast for the patients in the genetic cohort were 86%, 78%, and 98%, respectively, compared with 91%, 80%, and 96%, respectively, for the sporadic cohort (P = not significant). CONCLUSION: There was no evidence of increased radiation sensitivity or sequelae in breast tissue heterozygous for a BRCA1/2 germline mutation compared with controls, and rates of tumor control in the breast and survival were comparable between BRCA1/2 carriers and controls at 5 years. Although additional follow-up is needed, these data may help in discussing treatment options in the management of early-stage hereditary breast cancer and should provide reassurance regarding the safety of administering RT to carriers of a germline BRCA1/2 mutation.

Adult↗

PubMed1998

Breast reconstruction in previously irradiated patients using tissue expanders and implants: a potentially unfavorable result.

There exists a paucity of definitive information on the suitability of implant reconstructions in previously irradiated breast cancer patients. This controversial topic prompted a review of our prosthetic reconstructions in this select group of patients. A retrospective study of patients treated between 1976 and 1993 with lumpectomy and radiation therapy for early breast cancer revealed 67 patients with local recurrences. Nine of these patients (10 breasts) underwent a two-stage prosthetic reconstruction following a salvage mastectomy. The average age was 47.9 years. The mean dose of irradiation was 6,070 cGy. The average interval from radiation therapy to placement of a tissue expander was 4.6 years. In one patient (10%) the tissue expander extruded. The average follow-up for 8 patients (9 breasts) who underwent exchange to a permanent prosthesis was 5.1 years. In four reconstructions (40%) there was an uneventful postoperative course. Two cases (20%) were difficult to expand and the final result lacked projection. One patient (10%) developed an infection requiring removal of the permanent prosthesis. Two patients (20%) developed Baker class III or IV capsular contractures. Overall, in our group of 10 implant reconstructions, 60% of the patients resulted in either a complication or an unfavorable result.

Breast Implantation↗

PubMed1997

Modified total lymphoid irradiation and low dose corticosteroids in progressive multiple sclerosis.

In a double-blind prospective randomized trial, we assessed the efficacy and safety of modified total lymphoid irradiation (TLI) plus low dose prednisone (TLI-LDP) as compared to sham TLI plus identical prednisone therapy (sham TLI-LDP) in 46 patients with progressive forms of multiple sclerosis (MS). No significant difference existed between groups at study entry in patient age, sex, duration of MS, or disability status. However, following treatment, significantly fewer TLI patients showed a sustained one point decline in the Expanded Disability Status Scale, the primary study endpoint, as compared to the sham TLI group using the Kaplan-Meier Product-limit survival analysis, (P<0.005). Risk for relapse requiring treatment with intravenous methylprednisolone was reduced by 54% in the TLI-treated group (P<0.05). Significantly fewer TLI-LDP patients had gadolinium enhancing plus new T2-weighted lesions (P=0.018) when compared to the sham group post-treatment. There was also a substantial and significant decrease in blood lymphocytes in the TLI-LDP group when compared to either pretreatment values or to sham TLI-LDP through at least 12 months post-therapy. Side effects secondary to TLI were generally mild and well-tolerated. These results further support the hypothesis that TLI and systemic immunosuppression have a beneficial effect in progressive forms of MS.

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↗

PubMed1994

Salvage treatment for local recurrence following breast-conserving surgery and definitive irradiation for ductal carcinoma in situ (intraductal carcinoma) of the breast.

PURPOSE: The purpose of the present study is to evaluate the outcome of salvage treatment for local recurrence in the breast following the initial treatment of ductal carcinoma in situ (intraductal carcinoma) with breast-conserving surgery and definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed of 42 local failures in the breast that occurred following the initial treatment of ductal carcinoma in situ (intraductal carcinoma) with breast-conserving surgery and definitive breast irradiation. At the time of the local recurrence, 23 cases (55%) showed invasive ductal carcinoma, and 19 cases (45%) showed intraductal carcinoma, one with associated Paget's disease. The surgical treatment at the time of local recurrence included mastectomy (n = 39), excision (n = 2), or other (n = 1). Adjuvant systemic therapy at the time of local recurrence included chemotherapy (n = 2), hormonal treatment (n = 7), both (n = 1), or none (n = 32). The median follow-up after salvage treatment was 3.7 years (mean = 4.0 years; range = 0.1-9.5 years). RESULTS: The 5-year actuarial outcome following salvage treatment for the 42 local recurrences showed an overall survival rate of 78% and a cause-specific survival rate of 84%. The 5-year actuarial rate of freedom from distant metastases was 86%. None of the patients with histology of the local recurrence of intraductal carcinoma or with detection of the local recurrence with mammographic findings only developed distant metastatic disease after salvage treatment. The 5-year actuarial rate of freedom from chest wall recurrence following salvage mastectomy was 92%. All three of the patients who developed chest wall recurrence following salvage mastectomy also developed distant metastatic disease. CONCLUSIONS: These results demonstrate that local recurrences following the initial treatment of ductal carcinoma in situ with breast-conserving surgery and definitive breast irradiation can be salvaged with high rates of survival, freedom from distant metastases, and freedom from chest wall recurrence. The results of salvage treatment support the use of breast-conserving surgery and definitive breast irradiation for the initial management of ductal carcinoma in situ of the breast.

Adult↗

PubMed1994

Mitomycin C: a prototype bioreductive agent.

Hypoxic cells of solid tumors represent a therapeutically resistant population that limits the curability of many solid tumors by x-irradiation and by most chemotherapeutic agents. The oxygen deficit, however, creates an environment conducive to reductive processes that results in a major exploitable difference between normal and neoplastic tissues. Mitomycin C (MC) can be reductively activated by a number of oxidoreductases, in a process required for the production of its therapeutic effects. This enzymatic reduction results in preferential activation of MC under hypoxia and, in most instances, the production of greater toxicity to oxygen-deficient cells than to their oxygenated counterparts. DNA appears to be the most important target of the reactive species generated from MC, with both mono- and bis-adducts of DNA being formed in drug-treated cells. The demonstration that MC, used to kill the hypoxic fraction, in combination with x-irradiation, to eradicate the oxygenated portion of the tumor, produced enhanced cytodestructive effects on solid tumors of animals has led to the clinical evaluation of the mitomycin antibiotics in combination with x-rays in patients with cancers of the head and neck. The findings from these clinical trials have demonstrated the utility of directing a concerted therapeutic attack on the hypoxic fraction of solid tumors as an approach toward enhancing the curability of localized neoplasms by x-irradiation.

Animals↗

PubMed1993

The effect of advanced age on the efficacy of radiation therapy for early breast cancer, local prostate cancer and grade III-IV gliomas.

PURPOSE: This study was undertaken to determine the effect of advanced age on radiation therapy outcomes for early breast cancer, local prostate cancer and Grade 3-4 gliomas of the brain. METHODS AND MATERIALS: Radiation therapy outcomes for three malignancies (N = 1,401) were determined for a geriatric cancer population defined as 70 years of age or older and compared to a non-geriatric cancer population defined as less than 70 years of age. The three patient groups studied were: (a) primary breast cancer patients with clinical Stage I or II disease treated with lumpectomy and radiation therapy (N = 994), (b) local prostate cancer patients with Stage A2, B, or C disease treated with radical radiation therapy (N = 294), and (c) patients with Grade 3-4 gliomas of the brain treated with high dose radiation therapy (N = 113). RESULTS: For Stage I and II breast cancer, there was no statistically significant difference in the overall 10-year survival rates (63% vs. 73%), 10-year cause-specific disease-free survival rates (70% vs. 63%), and 10-year local breast recurrence free survival rates (76% vs. 79%) comparing the geriatric cancer population to the non-geriatric cancer population. For local prostate cancer, there was no statistically significant difference in the 10-year survival rates (38% vs. 41%) or in the 10-year cause-specific disease-free survival rates (58% vs. 52%) in the geriatric population compared with the non-geriatric population. On the other hand, the use of high dose radiation therapy for malignant gliomas resulted in statistically significant inferior 1-year (18% vs. 38%) and 2-year (0% vs. 10%) survival rates for the geriatric population versus the non-geriatric population. CONCLUSION: This study strongly supports the use of standard radiation therapy programs for early breast and prostate cancer patients age 70 years or more. However, our study raises questions about the efficacy of radiation therapy in patients over the age of 70 years with Grade 3-4 gliomas.

Age Factors↗

PubMed1978

"Paradoxical" reduction in postexercise ejection time and increased transthoracic impedance.

Despite decreasing heart rate, left ventricular ejection time (LVET) transiently falls immediately following bicycle exercise. In seven normal, untrained subjects LVET decreases at 15 s postexercise corresponded (r = 0.78) with an increase in transthoracic electrical impedance (Z) consistent with decreased venous return to the thorax. Because the determinants of LVET are stroke volume (SV) and ejection rate, the deltaZ implies that decreased SV contributed to the "paradoxical" fall in LVET.

Adult↗