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S Hetelekidis

Publications and source records attributed to S Hetelekidis.

16 recordsLinked to original sources
PubMed2000

The relation between the presence and extent of lobular carcinoma in situ and the risk of local recurrence for patients with infiltrating carcinoma of the breast treated with conservative surgery and radiation therapy.

BACKGROUND: When found in an otherwise benign biopsy, lobular carcinoma in situ (LCIS) has been associated with an increased risk of development of a subsequent invasive breast carcinoma. However, the association between LCIS and the risk of subsequent local recurrence in patients with infiltrating carcinoma treated with conservative surgery and radiation therapy has received relatively little attention. METHODS: Between 1968 and 1986, 1625 patients with clinical Stage I-II invasive breast carcinoma were treated at the Joint Center for Radiation Therapy at Harvard Medical School with breast-conserving surgery (CS) and radiation therapy (RT) to a total dose to the primary site of > or =60 grays. Analysis was limited to 1181 patients with infiltrating ductal carcinoma, infiltrating lobular carcinoma, or infiltrating carcinoma with mixed ductal and lobular features who, on review of their histologic slides, had sufficient normal tissue adjacent to the tumor to evaluate for the presence of LCIS and also had a minimum potential follow-up time of 8 years. The median follow-up time was 161 months. RESULTS: One hundred thirty-seven patients (12%) had LCIS either within the tumor or in the macroscopically normal adjacent tissue. The 8-year crude risk of recurrence was not significantly increased for patients with LCIS associated with invasive ductal, invasive lobular, or mixed ductal and lobular carcinoma. Among the 119 patients with associated LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%, compared with 12% for the 1062 patients without associated LCIS. For the 70 patients with moderate or marked LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%. The extent of LCIS did not affect the risk of recurrence. The risks of contralateral disease and of distant failure were similarly not affected by the presence or extent of LCIS. CONCLUSIONS: Breast-conserving therapy involving limited surgery and radiation therapy is an appropriate method of treating patients with invasive breast carcinoma with or without associated LCIS. Neither the presence nor the extent of LCIS should influence management decisions regarding patients with invasive breast carcinoma. [See editorial counterpoint and reply to counterpoint on pages 978-81 and 982-3, this issue.]

Breast Neoplasms↗
PubMed2000

The significance of extracapsular extension of axillary lymph node metastases in early-stage breast cancer.

PURPOSE: To investigate if extracapsular extension (ECE) of axillary lymph node metastases predicts for a decreased rate of disease-free survival or an increased rate of regional recurrence of breast carcinoma. METHODS: The study population consisted of 368 patients with T1 or T2 breast cancer and pathologically-positive lymph nodes treated with breast-conserving therapy between 1968 and 1986. The median number of sampled lymph nodes was 10. Median follow-up time for the surviving patients was 139 months (range 70-244). Twenty percent of the patients were treated with supraclavicular RT, and 64% received both axillary and supraclavicular RT, with a median dose to the nodes of 45 Gy. The following factors were evaluated: presence of ECE, number of sampled lymph nodes (LN), number of involved LN, size of primary tumor, histologic grade of tumor, presence of lymphatic vessel invasion (LVI), presence of an extensive intraductal component (EIC), radiation dose, use of adjuvant chemotherapy, and age of patient. Recurrences were reported as the 5-year crude sites of first failure, and were divided into breast recurrences (LR), regional nodal failure (RNF, defined as isolated axillary, supraclavicular, or internal mammary recurrence), and distant metastases (DM). RESULTS: One hundred twenty-two patients (33%) had ECE and 246 patients did not. The median number of LN with ECE was 1 (range 1-10) and 20% of patients had ECE in > or =4 LN. Patients with ECE tended to be older (median age 51 vs. 47, p = 0.01), and had a higher number of involved LN (median 3 vs. 2, p = 0.005) than patients without ECE. Forty-three percent of patients with ECE had > or =4 involved LN compared to 15% of patients without ECE (p<0.0001). Models of ECE and the above factors revealed no significant correlation between ECE and either disease-free or overall survival. There was no statistically significant increase in local, regional nodal, or distant failures in patients with ECE as compared to patients without ECE. CONCLUSION: In this population of patients with nodal involvement, the presence of ECE correlates with the number of involved LN but does not appear to add predictive power to models of local, regional, or distant recurrence when the number of positive LN is included.

Axilla↗
PubMed2000

The influence of infiltrating lobular carcinoma on the outcome of patients treated with breast-conserving surgery and radiation therapy.

BACKGROUND: The role of conservative surgery and radiation therapy (CS and RT) in the treatment of patients with infiltrating ductal carcinoma is well established. However, the efficacy of CS and RT for patients with infiltrating lobular carcinoma is less well documented. The goal of this study was to examine treatment outcome after CS and RT for patients with infiltrating lobular carcinoma and to compare the results to those of patients with infiltrating ductal carcinoma and patients with mixed ductal-lobular histology. METHODS: Between 1970 and 1986, 1624 patients with Stage I or II invasive breast cancer were treated with CS and RT consisting of a complete gross excision of the tumor and > or = 6000 cGy to the primary site. Slides were available for review for 1337 of these patients (82%). Of these, 93 had infiltrating lobular carcinoma, 1089 had infiltrating ductal carcinoma, and 59 had tumors with mixed ductal and lobular features; these patients constitute the study population. The median follow-up time for surviving patients was 133 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. Additional histologic features assessed for patients with infiltrating lobular carcinoma included histologic subtype, multifocal invasion, stromal desmoplasia, and the presence of signet ring cells. RESULTS: Five and 10-year crude results by site of first failure were similar for patients with infiltrating lobular, infiltrating ductal, and mixed histology. In particular, the 10-year crude local recurrence rates were 15%, 13%, and 13% for patients with infiltrating lobular, infiltrating ductal, and mixed histology, respectively. Ten-year distant/regional recurrence rates were 22%, 23%, and 20% for the three groups, respectively. In addition, the 10-year crude contralateral breast cancer rates were 4%, 13% and 6% for patients with infiltrating lobular, infiltrating ductal and mixed histology, respectively. In a multiple regression analysis which included established prognostic factors, histologic type was not significantly associated with either survival or time to recurrence. CONCLUSIONS: Patients with infiltrating lobular carcinoma have a similar outcome following CS and RT to patients with infiltrating ductal carcinoma and to patients with tumors that have mixed ductal and lobular features. We conclude that the presence of infiltrating lobular histology should not influence decisions regarding local therapy in patients with Stage I and II breast cancer.

Aged↗
PubMed2000

Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence.

PURPOSE: To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy. PATIENTS AND METHODS: The study population comprised 533 patients with International Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of invasive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed. Median follow-up time was 127 months. RESULTS: At 8 years, patients with close margins and those with negative margins both had a rate of local recurrence (LR) of 7%. Patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%. In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease. Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%). CONCLUSION: Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy.

Adult↗
PubMed1999

Predictors of local recurrence following excision alone for ductal carcinoma in situ.

BACKGROUND: The treatment of ductal carcinoma in situ (DCIS) remains controversial, particularly in regard to the selection of patients who may be appropriately treated with wide excision alone. To help identify such patients, the authors assessed prognostic factors for local recurrence in patients with DCIS treated with excision alone. METHODS: The study population consisted of 59 patients diagnosed with DCIS between 1985 and 1990. All had been treated with excision alone, had their histologic slides available for re-review by a study pathologist, and had negative margins of excision on review. The median age at diagnosis was 54 years, and the median follow-up time was 95.5 months. Ninety-six percent presented with mammographic findings only; all patients had a reexcision. The size of the DCIS was assessed by the total number of low-power fields (LPF) in which DCIS was present (median LPF = 5). RESULTS: Ten patients experienced a local recurrence (LR) at 5-132 months (median, 37 months) after excision. The actuarial 5-year LR rate was 10%. Four of the recurrences were invasive carcinomas, and 6 were DCIS. No patients have developed metastatic disease or have died of disease. Lesion size >5 LPF was the only significant prognostic factor for local recurrence on univariate analysis (3% vs. 17% for < or = 5 vs. > or = 5 LPF, P = 0.02) and in proportional hazards models. Although patients with nuclear Grade 3 lesions had a higher LR rate than those with nuclear Grade 1 and 2 lesions (18% vs. 6% and 5%, respectively) and patients with close margins (< or = 1 mm) had a higher LR rate than patients with negative margins (>1 mm) (25% vs. 8%), these differences did not reach statistical significance. Among the 19 cases with margins negative by more than 1 mm, lesion size < or = 5 LPF, and nuclear Grade 1 or 2, there were no LRs; by contrast, the remaining 40 patients had a 5-year actuarial LR rate of 15% (P = 0.08). CONCLUSIONS: Lesion size was the only statistically significant prognostic factor for local recurrence in this series of patients with DCIS treated with excision alone. Other factors, such as margin status and nuclear grade, may also be useful in the identification of patients with DCIS who can be managed with excision alone. However, the most reliable and reproducible method of assessing these factors and the best way to combine them have not been determined.

Adult↗
PubMed1998

No long-term increase in cardiac-related mortality after breast-conserving surgery and radiation therapy using modern techniques.

PURPOSE: To determine whether left-breast irradiation using modern techniques after breast-conserving surgery leads to an increased risk of cardiac-related mortality. METHODS: Between 1968 and 1986, 1,624 patients were treated for unilateral stage I or II breast cancer at the Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA, with conservative surgery and breast irradiation. Seven hundred forty-five patients with a potential follow-up of at least 12 years were analyzed. Clinical, pathologic, and treatment characteristics were compared between the 365 patients (49%) who received left-sided irradiation and the 380 patients (51%) who received right-sided irradiation. The relationship between left-sided breast irradiation and the risk of nonbreast cancer- and cardiac-related mortality was examined. RESULTS: There was no significant difference in the distribution of clinical, pathologic, or treatment characteristics between the two groups, with the exception of a small difference in pathologic tumor size (medians, left, 2.0 cm, right, 1.5 cm; P = .007). At 12 years, a majority of patients still were alive. Slightly more patients with left-sided tumors had died of breast cancer (31% v 27%; P = NS). Equivalent proportions from each group died of nonbreast cancer causes (11%), including nine patients (2%) from each group who died from cardiac causes. The risk of cardiac mortality did not increase as time after treatment increased for patients who received left-sided irradiation compared with right-sided irradiation. A model that controlled for clinical, pathologic, and treatment differences showed no significant increase in any category of cause of death (breast, cardiac, or other) for patients who received left-sided irradiation. CONCLUSION: These results suggest that modern breast radiotherapy is not associated with an increased risk of cardiac-related mortality within at least the first 12 years after treatment.

Breast Neoplasms↗
PubMed1998

Family history and treatment outcome in young women after breast-conserving surgery and radiation therapy for early-stage breast cancer.

PURPOSE: To evaluate the safety and efficacy of breast-conserving therapy for young women with a family history (FH) suggestive of inherited breast cancer susceptibility. MATERIALS AND METHODS: A total of 201 patients aged 36 or younger at diagnosis treated with breast-conserving surgery and radiation therapy (> or = 60 Gy) for early-stage breast cancer were categorized by FH. FH was considered positive in 29 patients who, at the time of diagnosis, had a mother or sister previously diagnosed with breast cancer before age 50 or ovarian cancer at any age. Clinical, pathologic, and demographic variables; sites of first failure; disease-free survival; and overall survival (OS) were compared between FH-positive and -negative groups. Median follow-up time was 11 years. RESULTS: Patient and tumor features were similar between those with and without an FH. Regression analysis of sites of first failure at 5 years demonstrated a risk ratio (RR) of 5.7 for opposite breast cancer for FH-positive patients. Rates of local, regional, and distant failure and disease-free survival or OS did not differ between FH-positive and -negative patients. Age at diagnosis and Ashkenazi heritage were not significantly predictors of patterns of failure. CONCLUSION: Breast-conserving surgery combined with radiation therapy is not associated with a higher rate of local recurrence, distant failure, or second (non-breast) cancers in young women with an FH suggestive of inherited breast cancer susceptibility compared with young women without an FH. However, their increased risk of opposite breast cancer should be taken into account when considering breast conservation as a treatment option.

Adult↗
PubMed1996

Relationship of tumor grade to other pathologic features and to treatment outcome of patients with early stage breast carcinoma treated with breast-conserving therapy.

BACKGROUND: Although histologic grade has previously been described as a predictor of distant failure, it is uncertain whether histologic grade should be used to decide which patients should undergo axillary lymph node dissection and whether grade should be considered as a selection factor for breast-conserving therapy. METHODS: The authors retrospectively analyzed data from 1081 patients with American Joint Committee on Cancer Stage I or II infiltrating ductal carcinoma treated with breast-conserving therapy at the Joint Center for Radiation Therapy between 1970 and 1986. All patients had pathology slides reviewed by one of two study pathologists. Using the Elston modification of the Bloom-Richardson grading system, patients were divided by histologic grade into 3 groups (219 with Grade I, 482 with Grade II, and 380 with Grade III). The median follow-up time for 716 survivors was 134 months. The incidence of various pathologic features was examined with respect to histologic grade. In addition, the 10-year crude rates of failure (by first site) were examined as they related to grade. A polychotomous logistic regression model was used to determine the effect of grade on local and distant failure. RESULTS: High grade tumors tended to be larger, to exhibit more mononuclear cellular reaction and necrosis, and were more likely to be estrogen receptor negative. Patients with high grade tumors were also younger than those with lower grade tumors. The incidence of an extensive intraductal component and lymphatic vessel invasion did not vary significantly by histologic grade. The incidence of pathologic lymph node metastases also did not vary by grade, even when stratified by tumor size. In both univariable and multivariable analyses, the 10-year crude rate of local recurrence was not related to histologic grade (P = 0.44). Distant recurrence rates, however, were significantly higher as grade increased (p = 0.002). CONCLUSIONS: Higher histologic grade predicted an increased incidence of distant recurrence, but not a greater likelihood of axillary lymph node metastases or local recurrence after breast-conserving therapy. The authors conclude that grade should not be used to make decisions regarding local management.

Breast Neoplasms↗
PubMed1994

Biosynthesis and processing by phorbol ester of the cells surface-associated precursor form of heparin-binding EGF-like growth factor.

Human MDA MB 231 cells were found to synthesize mostly the cell surface-associated precursor form of heparin-binding EGF-like growth factor (HB-EGF), a 27-kDa protein. Evidence for this form of HB-EGF included increased fluorescence intensity when cells were analyzed by flow cytometry using anti-HB-EGF antibodies, lack of HB-EGF in conditioned medium, and sensitivity to diphtheria toxin, for which HB-EGF is the receptor. Phorbol ester treatment of cells resulted, within 30 minutes, in loss of cell surface 27 kDA HB-EGF, lack of interaction with anti-HB-EGF antibodies, accumulation of active 21 kDa HB-EGF in conditioned medium, and the acquisition of diphtheria toxin resistance. It was concluded that cell surface-associated HB-EGF is the precursor of a bioactive growth factor, is biologically active as the receptor for diphtheria toxin, and is susceptible to rapid processing.

Diphtheria Toxin↗
PubMed1994

Surgery, radiation, and combination therapy in the treatment of childhood craniopharyngioma--a 20-year experience.

The records of 61 children treated for primary craniopharyngioma at the Children's Hospital in Boston and The Joint Center for Radiation Therapy from 1970 to 1990 were reviewed to determine if any information could be obtained regarding the efficacy of surgery versus radiotherapy or a combination of these modalities for this tumor. A select group of 9 children treated without biopsy by radiation therapy alone were all alive without disease progression at follow-up. Although 9 of the 15 children who underwent surgery alone had tumor recurrence, 7 of the 37 children treated with radiotherapy following surgery have also recurred. Treatment morbidity occurred in all groups, but the 10-year actuarial survival for all patients was 91%. Early postoperative imaging and pre- and posttreatment endocrine and neuropsychologic evaluations need to be carried out in all prospective studies of the treatment of craniopharyngioma in children.

Adolescent↗
PubMed1993

20-year experience in childhood craniopharyngioma.

PURPOSE: The management of craniopharyngioma is controversial, and surgery alone is frequently advocated. The purpose of this study was to assess the long-term impact of various treatments in childhood craniopharyngioma. METHODS AND MATERIALS: Sixty-one children < or = 21 years of age at diagnosis were treated for craniopharyngioma at Children's Hospital and the Joint Center for Radiation Therapy in Boston from 1970 to 1990. The median age was 7.5 years (range 10 months-21 years). There were 33 females and 28 males. The median follow-up was 10 years (range 2-20.5 years). Neuroimaging was available for detailed review in 53. Nine children were treated with radiotherapy alone, 15 were treated with surgery alone, and 37 were treated with both surgery and radiotherapy. All patients in the radiotherapy and surgery plus radiotherapy groups were treated with megavoltage radiation with a median dose of 5464 cGy. RESULTS: All nine of the children treated with radiation therapy alone are alive; none have recurred. Nine of the 15 children treated with surgery alone have recurred (p = 0.007 Fisher exact test). Two are alive with disease, and seven are alive without disease after treatment at relapse with radiation therapy, surgery, or both. Seven of the 37 patients treated with surgery plus radiotherapy have recurred. Three of the seven patients are dead of disease, three patients are alive with disease, and one patient is alive without disease after further treatment. The 10-year actuarial overall survival was 91% for all patients. The 10-year actuarial freedom from progression for the surgery group was 31% compared with 100% for patients treated with radiation therapy only (log rank p = 0.01), and 86% for patients treated with surgery plus radiotherapy at diagnosis (p = 0.001). There were two treatment related deaths, both in the surgery plus radiotherapy group. A higher incidence of visual loss and diabetes insipidus was associated with the use of aggressive surgery. The size of the tumor at presentation correlated with an increased risk of recurrence; 5 of 6 patients with tumors > or = 5 cm experienced recurrences while only 6 of 30 recurred when the tumor was < 5 cm. CONCLUSIONS: Overall survival in childhood craniopharyngioma is excellent. However, patients treated with surgery alone have a significantly worse freedom from progression when compared to patients treated with surgery and radiation therapy or radiation therapy alone.

Actuarial Analysis↗
PubMed1988

Radiotherapy in the treatment of pituitary adenomas.

Between 1970 and 1985, 145 patients were treated for pituitary adenomas and 126 patients were available for analysis. Sixty patients were treated with surgery alone (Group I), 54 were treated with surgery and radiation therapy (Group II), and 12 received irradiation only without tissue diagnosis (Group III). Extent of tumor was evaluated by CT scan, PEG, and surgical reports. There were 22 microadenomas in Group I and only 1 microadenoma in Group II. The mean follow-up was 6.4 years, 85% (51/60) of patients in Group I, 93% of patients in Group II, and only 50% of those treated with irradiation alone achieved tumor control. With subsequent salvage treatment, overall tumor control in Group I was 97%. The mean time to recurrence was 3.7 years (Group I), 4.5 years (Group II), and 4 years (Group III). In summary, combined treatment is effective to decrease the chance of local recurrence of pituitary adenomas. Nevertheless, because of successful salvage treatment after surgical failure, overall outcome is similar. Without persistent symptom after surgery or large residual tumor in or near the critical structures, postoperative irradiation can be deferred until tumor regrowth.

Adenoma↗
PubMed1984

Disposition and anticoagulant activity of biologically active heparin fragments in the rat.

The disposition of biologically active [35S]heparin fragments was studied in both normal and uremic rats after an i.v. dose of 1 mg/kg. In normal animals, the amount of radioactivity in the blood rapidly decreased with a half-life of less than 2 min whereas the anticoagulant activity showed a half-life of 30 min. By 5 hr, only 0.4% of the initial radioactivity was present in the blood whereas no anticoagulant activity could be detected. The heparin fragments were rapidly excreted: by 5 hr, 85% of the initial dose was excreted into the urine, whereas only 1% of the radioactivity was present in the feces. In contrast, 55% of the initial dose of the same amount of radioactive heparin was excreted into the urine after 5 hr. By 5 hr, 5.2% of the heparin fragments was organ-associated and 3.1% was present in the skin, muscle and bone. One week after injection, 3.9% of the radioactivity was still present in the body. In uremic animals, the radioactivity in the blood decreased to 12% of the initial dose by 5 hr whereas 13.5% was organ-associated and 64% was present in the skin, muscle and bone. Comparison of heparin with di- or hexasac-charide fragments indicated that both the clearance in the blood and the excretion into the urine are size-dependent. By 5 hr, the body burden of heparin is approximately five times higher than it is after the same dose of heparin fragments.

Animals↗
PubMedDate not supplied

Management of ductal carcinoma in situ.

The increased use of screening mammography in the past two decades has led to a marked increase in the number of patients diagnosed with ductal carcinoma in situ. Treatment has traditionally involved mastectomy, but this approach has come under increasing scrutiny, and the treatment of ductal carcinoma in situ has become one the most controversial areas in the field of breast disease. This article reviews current concepts regarding the diagnosis, natural history, and treatment of ductal carcinoma in situ.

Breast Neoplasms↗