Papers by Bruce Bornstein
International Journal of Radiation Oncology Biology Physics, 1993
We retrospectively reviewed the response rate and the acute and long-term toxicity of combined tr... more We retrospectively reviewed the response rate and the acute and long-term toxicity of combined treatment using radiation therapy, hyperthermia, and chemotherapy in 29 patients with locally or regionally recurrent or advanced adenocarcinoma of the breast who completed at least 4 of the 6 prescribed hyperthermia treatments as part of a Phase I-II trial. Thirty-nine separate byperthermia treatment fields were evaluated. Cisplatin alone or cisplatin with etanidazole or bleomycin was delivered just prior to hyperthermia once weekly. Hyperthermia was delivered to a target minimum tumor temperature of 43°C * 0.5 for 60 min. Following hyperthermia, a 400 cGy fraction of radiation was given. The radiation fraction size on other days was 200 cGy. Twenty-two fields had previously been irradiated and 17 fields had not. Prior chemotherapy had been given in 24 of 29 patients (83%) and hormonal therapy given in 21 (72%). The median follow-up time is 10 months; 16/29 patients (55%) have died of disease. The overall complete response rate for all fields was 53%. Response rate was not related to any clinical factor, radiation dose, microwave or ultrasound technique, type of chemotherapy, or tumor temperatures, but the number of patients in the study population was small. A statistically significant association between the likelihood of complications and the total radiation therapy dose (previous radiation and present radiation) was found. Persistent ulceration lasting greater than 1 month after completing treatment was seen in 67% of previously irradiated fields compared to 21% of fields that had not been previously treated (p = 0.015). Surgical wound repair was needed for 38% of fields with a history of prior irradiation versus 6% of those without prior treatment (p = 0.050). A statistically significant radiation therapy dose response was found for the likelihood of these complications. None of the hyperthermia temperature parameters studied correlated with an increased risk of complication. We conclude that the combination of radiation therapy, hyperthermia, and chemotherapy results in a high rate of complete response. However, in patients who have been treated with prior radiation therapy, this combination may be more locally toxic than treatment with hyperthermia and radiation therapy alone. The precise impact of chemotherapy on the therapeutic index of hyperthermia and radiation therapy remains to be determined in randomized clinical trials.
PubMed, Oct 1, 1995
There is a need for more clinical investigation in advanced local breast cancer. Both chemotherap... more There is a need for more clinical investigation in advanced local breast cancer. Both chemotherapy and endocrine therapy improve disease-free and overall survival and are now a routine part of standard patient care. Dose-intensive chemotherapy should be reserved for younger patients in large, controlled clinical trials. For operable patients, adequate surgical therapy of the breast and axilla remains a standard of care and provides the most important piece of prognostic information (i.e., the number of involved axillary lymph nodes). Tamoxifen treatment of the estrogen receptor-positive postmenopausal patient remains the standard, although chemotherapy may add a further increment to disease-free survival.
PubMed, May 1, 1996
Purpose: Ductal carcinoma in situ (DCIS) is increasingly detected as a nonpalpable lesion on mamm... more Purpose: Ductal carcinoma in situ (DCIS) is increasingly detected as a nonpalpable lesion on mammographic screening performed for the early detection of breast cancer. Because of the growing incidence of mammographically detected DCIS, the present study was undertaken to determine the outcome of treatment of nonpalpable, mammographically detected intraductal carcinoma of the breast using breast-conserving surgery and definitive breast irradiation. Materials and methods: An analysis was performed of 110 women who presented with unilateral, nonpalpable, mammographically detected intraductal carcinoma of the breast and who were treated with breast-conserving surgery and definitive breast irradiation at 10 institutions in Europe and the United States. In all patients, complete gross excision of the primary tumor was performed, and breast irradiation was delivered with definitive intent. When performed, pathologic axillary lymph node staging was node negative (n=29). The median follow-up time was 9.3 years. Results: The 10-year actuarial overall survival rate was 93%, and the 10-year actuarial cause-specific survival rate was 96%. The 10-year actuarial rate of freedom from distant metastases was 96%. There were 15 local recurrences in the treated breast. The actuarial rate of local failure was 7% at 5 years and 14% at 10 years. The histology of the local recurrence was intraductal carcinoma in 9 cases and invasive ductal carcinoma (with or without associated intraductal carcinoma) in 6 cases. The median time to local recurrence was 5.0 years (mean, 5.4; range, 2.1-15.2). With a median follow-up time of 4.4 years after salvage treatment, 14 of the 15 patients with local recurrence were alive without evidence of disease at the time of last follow-up examination. The crude incidence of local recurrence was 7% (3/42) when the final pathology margin of tumor excision was negative, 29% (5/17) when the margin was close or positive, and 14% (7/51) when the margin was unknown. There was no difference in the rate of local recurrence based on pathologic characteristics of the primary tumor. Discussion: Results from the present study demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases at 10 years following the treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Local recurrences within the treated breast were detected early and were treated with salvage for cure. These results support the initial treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Improvements in patient selection have the potential to reduce the risk of local recurrence.
International Journal of Hyperthermia, Nov 1, 2005
Purpose/Objective(s): Hyperthermia offers potential therapeutic advantage in combination with rad... more Purpose/Objective(s): Hyperthermia offers potential therapeutic advantage in combination with radiation for treatment of prostate cancer. A phase 2 study was initiated at the Dana-Farber Cancer Institute (DFCI 94-153) to provide a preliminary assessment of efficacy of transrectal ultrasound hyperthermia in combination with radiation ± androgen suppression in treatment of locally advanced prostate cancer. The long-term results of this completed trial are now presented. Materials/Methods: Patients with clinical $T2b, N0, M0 disease by 1992 AJCC staging criteria who consented to participation on this IRB approved study received 3D conformal radiation therapy in combination with 2 trans-rectal ultrasound hyperthermia treatments at least 1 week apart during the first 4 weeks of radiation. After 4 patients were accrued, in light of changing practice patterns, 6 months of androgen suppression was allowed. Hyperthermia was administered with a 16 element trans-rectal ultrasound applicator with rectal wall, normal tissue, and intra-prostatic temperature monitoring performed during all treatments. The study was designed to have 80% power to detect a 20% absolute improvement in the 2-year disease-free survival rate observed on the short-term androgen supression arm in RTOG Trial 92-02, from 65% to 85%. Results: Thirty-seven patients received a total of 72 hyperthermia treatments between September, 1997 and April, 2002. A favorable long-term toxicity profile noted with this treatment regiment was previously reported. The mean cumulative equivalent minutes at 43 C as measured by 90% of the intraprostatic temperature sensors (CEM T 90 43 C) for all 37 patients was 8.4 minutes. 1992 AJCC clinical stage: T2b 20, T2c 8, T3a 4, T3b 4, and T3c 1 patients. Median Gleason score was 7 (range, 6-9), and median PSA was 11.4 (2-65) ng/nl. All patients completed radiation therapy with median dose of 6700 cGy as normalized to 95%. Thirtyone patients received androgen suppression initiated within 3 months prior to radiation. All but 2 of these patients received 6 months of therapy. PSA failure was defined using the ASTRO consensus definition. Failure was also defined by clinical or pathologic evidence of local or distant disease recurence, or at the time of initiation of salvage androgen suppression irregardless of PSA. With a median follow-up of 60 months (15-84 months), 65% of patients remain free from failure. Three patients developed metastatic disease of which one patient died of prostate cancer 30 months after treatment. Absolute rate of disease-free survival at 2 years, the primary study endpoint, was 73% (90% CI, 59%-85%) which compares favorably with a rate of 64% for similar patients on the 4 month androgen suppression arm of RTOG 92-02 that served as the comparison group for this study. Using Phoenix criteria (nadir +2) for biochemical failure, 89% of patients were progression-free at 2 years (90% CI, 77%-96%). Conclusions: Transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer appears promising. Further study of hyperthermia in primary treatment of prostate cancer in combination with optimal radiation and systemic therapies is warranted.
International Journal of Radiation Oncology Biology Physics, Dec 1, 1989
A Phase I-II trial testing the addition of systemic cisplatin (CDDP) to local hyperthermia and ra... more A Phase I-II trial testing the addition of systemic cisplatin (CDDP) to local hyperthermia and radiation was conducted to determine the dose of cisplatin that is tolerable once weekly for 6 weeks and to estimate the therapeutic potential of this trimodality combination in patients with locally advanced malignancies. Cisplatin at 20 mg/m* (4 patients), 30 mg/m* (8 patients), and 40 mg/m* (12 patients) was given rapidly (over 5-10 min) i.v. after prehydration with 1 liter of normal saline. After approximately two-thirds of the cisplatin dose had been delivered, microwave hyperthermia was begun and continued for 60 min; the target minimum tumor temperature was 43°C. Following hyperthermia, a 400 cGy fraction of radiati.on was delivered to the tumor. On other days during the treatment weeks, additional 200 cGy fractions were given to total doses of 6,000-6600 cGy in patients with full radiation tolerance or 2400-3600 cGy in patients with limited radiation tolerance. The 24 patients in this trial had a median age of 57 years and the predominant sites/tumor types were head and neck/squamous cell carcinoma (9) and chest wall/breast adenocarcinoma (9). Seventeen of the 24 treated tumors (70%) had previously been irradiated. Eighteen patients (75%) had received prior chemotherapy and nine patients (38%) had previously been treated with cisplatin. Bone marrow suppression was dose limiting in patients heavily pretreated with chemotherapy and chest wall radiation. No significant toxicities were observed at the 20 and 30 mg/m* dose levels, but 5 of the 12 patients (42%) treated at 40 mg/m* required modification of the cisplatin dose because of blood count suppression in four patients and mild renal dysfunction in one patient. Each of the patients with bone marrow suppression, however, had been heavily pretreated except for one patient with thrombocytopenia due to hypersplenism. Nausea and vomiting were mild with use of a standard, multiagent antiemetic regimen. Twelve patients (50%) attained a complete regression (CR) and 12 patients (50%) a partial regression (PR). Complete regression appeared to correlate with smaller tumor volumes (115 cc for CR versus 199 cc for PR patients) and higher tumor temperatures (4.6 average minimum equivalent minutes at 43°C in CR versus 2.0 min in PR patients). Local toxicities included second degree bums in 12 patients (50%) and third degree burns in 6 (25%), but all burns healed in 4-12 weeks without surgical intervention. There was no significant increase in acute radiation reactions. This protocol proved feasible and effective, although time consuming. A cisplatin dose of 30 mg/m* i.v. weekly for 6 weeks appears tolerable even in heavily pretreated patients. The dose of cisplatin that is tolerable in untreated patients is at least 40 mg/m* weekly for 6 weeks and may well be higher but has yet to be determined. Cisplatin, Hyperthermia and radiation. INTRODUCIION Many clinical studies (6) have indicated that local hyperthermia adds significantly to the ability of radiation therapy to control human tumors. Dewhirst et al. (1), Luk et al. (5), and Sim et al. (9) have shown that the probability of attaining a complete regression (CR) with hyperthermia and radiation treatment is related to: (a) the tumor size, (b) the total dose of radiation therapy used, and (c) the ability to achieve adequate temperature elevations in the tumor. There remain, however, a substantial number of patients, depending on these factors, who do not achieve This work was presented at the 30th Annual Meeting of the
Journal of Cellular Physiology, Nov 1, 1989
Heat shock has a profound influence on the metabolism and behavior of eukaryotic cells. We have e... more Heat shock has a profound influence on the metabolism and behavior of eukaryotic cells. We have examined the effects of heat shock on the release from cells of arachidonic acid and its bioactive eicosanoid metabolites, the prostaglandins and leukotrienes. Heat shock (42-45") increased the rate of arachidonic acid release from human, rat, murine, and hamster cells. Arachidonate accumulation appeared to be due, at least partially, to stimulation of a phospholipase AL activity by heat shock and was accompanied by the accumulation of lysophosphatidylinosilol and lysophosphdlidylcholitie in membranes. Induction of arachidonate release by heat did not appear to be mediated by an increase in cell Ca++. stimulation oi arachidonate release by heat shock in hamster fibroblasts was quantitatively similar to the receplor-mediated effects of c1 thrombin and bradykinin. The effects of heat shock and a thrombin on arachidonate release were inhibited by glucocorticoids. Increased arachidonate release in heat-shocked cells was accompanied by the accelerated accumulation of cyclooxygenase products prostaglandin EL and prostaglandin FZct and by 5-Iipoxygenase metabolite leukotriene B4. Elevated concentrations of arachidonic acid and metabolites may he involved in the cytotoxic effects of hyperthermia, in homeostatic responses to heat shock, and in vascular and inflammatory reactions to stress.
The level of entrepreneurship and commercialization of inventions at universities in the United S... more The level of entrepreneurship and commercialization of inventions at universities in the United States varies widely. This study attempts to uncover the factors that may explain the differences in the attitude toward entrepreneurship and commercialization found at academic institutions. To this end nineteen interviews with faculty researchers, inventors, entrepreneurs, venture capitalists, technology transfer officers, and others were conducted. The different perceptions toward entrepreneurship and commercialization at the Massachusetts Institute of Technology, Harvard University, and Harvard Medical School and its associated research hospitals were examined with particular care. A BSTRA CT.
Cancer, Oct 1, 1996
Although histologic grade has previously been described as a predictor of distant failure, it is ... more 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. 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. 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). 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.
Cancer, Sep 30, 2010
Background-A phase 2 study was done to assess efficacy of transrectal ultrasound hyperthermia wit... more Background-A phase 2 study was done to assess efficacy of transrectal ultrasound hyperthermia with radiation +/− androgen suppression for treatment of locally advanced prostate cancer. Long-term results of this trial are now presented. Methods-Patients with clinical T2b-T3b, N0, M0 disease (1992 AJCC criteria) received radiation plus 2 transrectal ultrasound hyperthermia treatments. Subsequent to the first 4 patients, 6 months of androgen suppression was allowed. The study was designed to assess absolute improvement in 2-year disease-free survival rate as compared with the short-term androgen suppression arm in RTOG 92-02. Results-Thirty-seven patients received a total of 72 hyperthermia treatments. Mean CEM T90 43°C was 8.4 minutes. 1992 AJCC clinical stage: T2b 19, T2c 8, T3a 5, and T3b 5 patients. Median Gleason score was 7 (range, 6-9), and median PSA was 13.3 (2-65) ng/nl. Thirty-three patients received androgen suppression. With a median follow-up of 70 months (18-110 months) 7 year overall survival is 94% with 61% of patients failure free (ASTRO definition). Absolute rate of disease free survival at 2 years, the primary study endpoint, was significantly improved (84%) when compared with a rate of 64% for similar patients on the 4 month androgen suppression arm of RTOG 92-02. Using Phoenix criteria (PSA nadir +2) for biochemical failure, 89% of patients were failure free at 2 years. Conclusions-Hyperthermia combined with radiation for treatment of locally advanced prostate cancer appears promising. Further study of hyperthermia in treatment of prostate cancer with optimal radiation and systemic therapies is warranted.
Journal of Clinical Oncology, Mar 1, 1996
To determine the 15-year outcome for women with ductal carcinoma in situ (DCIS, intraductal carci... more 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. 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). 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). 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.
Surgical Oncology Clinics of North America, Oct 1, 1995
International Journal of Radiation Oncology Biology Physics, Apr 1, 1993
Purpose: To determine the risk of local-regional failure following post-mastectomy radiotherapy a... more Purpose: To determine the risk of local-regional failure following post-mastectomy radiotherapy and the incidence of complications associated with such treatment. Methods and Materials: We retrospectively analyzed the results in 309 patients with Stage I-III invasive breast cancer treated with post-mastectomy radiation therapy between 1975 and 1985. The median radiotherapy dose was 45 Gy in 1.8 to 2.25 Gy fractions. One hundred forty-seven (48%) of the patients received adjuvant systemic chemotherapy with 115 (78%) of these receiving a CMF-based or doxorubicin-containing regimen. The median follow-up time of surviving patients was 130 months (range, 28 to 191 months) after mastectomy. Results: Seventeen patients (6%) developed a local-regional failure at an interval of 4 to 87 months after radiotherapy. Moderate or severe complications related to radiotherapy and requiring treatment were uncommon. Symptomatic radiation pneumonitis occurred in four patients (1.3%), arm edema in 18 (5.8%), and brachial plexopathy in 2 (0.6%). Conclusion: We conclude that post-operative radiotherapy is a safe and effective means of reducing local-regional failure following mastectomy. The efficacy of post-mastectomy radiotherapy in improving survival should be addressed in new large randomized controlled studies.
Breast Cancer Research and Treatment, 2000
Background: The role of conservative surgery and radiation therapy (CS and RT) in the treatment o... more 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 ≥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 l3% 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.
Cancer, Mar 1, 2000
When found in an otherwise benign biopsy, lobular carcinoma in situ (LCIS) has been associated wi... more 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. 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. 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. 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.]
Journal of Clinical Oncology, Apr 1, 1998
To determine whether left-breast irradiation using modern techniques after breast-conserving surg... more To determine whether left-breast irradiation using modern techniques after breast-conserving surgery leads to an increased risk of cardiac-related mortality. 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. 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. 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.
International Journal of Radiation Oncology Biology Physics, Sep 1, 1995
Purpose: To examine the long-term pattern and frequency of recurrences after breast-conserving th... more Purpose: To examine the long-term pattern and frequency of recurrences after breast-conserving therapy and whether the outcome was influenced by the era of treatment. Methods and Materials: From 1968 to 1986,187O patients with unilateral Stage I or II breast cancer were treated at the Joint Center for Radiation Therapy. Of these, 1628 underwent gross tumor excision and received a dose of > 60 Gy to the tumor bed and constituted the study population. Patients were classified as without evidence of disease, dead from other causes (DOC), or by their first site of recurrence. First sites of recurrent disease were categorized as distant/regionai (DF/RNF) or local (LR). Local recurrence was detined as the detection of any invasive or in situ carcinoma occurring in the ipsilateral breast and was further categorized as: true recurrence (TR), marginal miss (MM), skin recurrence (S), or elsewhere in the breast (E). Median follow-up in survivors was 116 months. Eighty patients (4.9%) were lost to followup at 3-175 months. The population was divided into two time cohorts: 1968-1982 (n = 810), with a median follow-up time of 143 months, and 1983-1986 (n = 792), with a median follow-up time of 95 months. Results: The overaii crude rates of ipsilaterai breast recurrence were 7.4 and 13.3% at 5 and 10 years, respectively. Crude rates at 5 and 10 years were 5.7 and 9.3% for TR/MM and were 0.9 and 2.8% for E recurrences, respectively. The annual incidence rates for ail LR ranged from 0.5-2.4% and was relatively constant after the first year. The annual incidence rates for TR/MM ranged from 0.4 to 1.9%, whereas for E recurrences the range was O.l-0.7%. The crude rates of DF/RNF were 16.6 and 23.1% at 5 and 10 years, respectively. The annual incidence rates for DF/RNF ranged from l-5% over ail years. Although the magnitude of the incidence was different, DF/RNF recurrence predominated iu years l-3 for both nodepositive and node-negative patients. For the 1968-1982 and 1983-1986 cohorts, the 5-year crude rates of ipsiiaterai breast recurrence were 8.8 and 5.9%, respectively. Conclusion: Distant and regional nodal failures were the predominant form of recurrence. The annual incidence rate of LR was relatively constant over the first decade. True recurrence/marginal miss was the most frequent type of ipsilateral breast recurrence and was highest during years 2 through 7. The risk of a recurrence elsewhere in the breast increased with longer foiiow-up and was highest during years 8 through 10. The 5-year crude rate of ipsiiateral breast recurrence appeared lower in the 1983-1986 patient cohort compared to the 1968-1982 patient cohort (8.8% vs. 5.9%), but the distributions of site of first failure did not differ signiticantly (p = 0.13).. Any decrease in ipsilaterai breast recurrence likely reflects improvements in mammographic and pathologic evaluation, patient selection, and the increased use of reexcision.
Circulation, Nov 18, 1997
Background Late cardiac morbidity and mortality have been reported among left-breast cancer survi... more Background Late cardiac morbidity and mortality have been reported among left-breast cancer survivors treated with radiation therapy. Radiation-induced cardiotoxicity is affected by the volume of myocardium included in the radiation portals. We hypothesize that simple respiratory maneuvers may alter the position of the heart relative to the portals without altering the radiation dose delivered to the breast. Methods and Results Fourteen healthy female adult volunteers underwent cardiac MRI to determine the cardiac volume included in the typical left-breast radiation field during respiratory maneuvers. Cardiac volume within the radiation portals was assessed from a transverse stack of 14 1-cm-thick contiguous slices covering the entire heart, obtained during breath holding at end-tidal volume (baseline), deep inspiration, and forced expiration. Thirteen subjects (92%) had inclusion of a portion of the heart within the radiation portals at end-tidal volume (median, 20.9 cm 3 ; range, 1.3 to 88.4 cm 3 ). In these subjects, inspiration decreased the cardiac volume included within the radiation portals (median change: −10.7 cm 3 [−40.2%], P <.001 versus end-tidal volume), whereas expiration increased the cardiac volume included (median change: 4.0 cm 3 [21.5%]; P <.001 versus end-tidal volume). Conclusions Inclusion of a portion of the heart in the left-breast radiation field is common. The use of simple inspiratory maneuvers significantly decreases cardiac volume within the radiation portals. Such an approach during delivery of radiation therapy may allow for preservation of radiation dosage to the breast while reducing cardiac involvement and subsequent mortality.
International Journal of Radiation Oncology Biology Physics, Oct 1, 2005
Purpose/Objective(s): Hyperthermia offers potential therapeutic advantage in combination with rad... more Purpose/Objective(s): Hyperthermia offers potential therapeutic advantage in combination with radiation for treatment of prostate cancer. A phase 2 study was initiated at the Dana-Farber Cancer Institute (DFCI 94-153) to provide a preliminary assessment of efficacy of transrectal ultrasound hyperthermia in combination with radiation ± androgen suppression in treatment of locally advanced prostate cancer. The long-term results of this completed trial are now presented. Materials/Methods: Patients with clinical $T2b, N0, M0 disease by 1992 AJCC staging criteria who consented to participation on this IRB approved study received 3D conformal radiation therapy in combination with 2 trans-rectal ultrasound hyperthermia treatments at least 1 week apart during the first 4 weeks of radiation. After 4 patients were accrued, in light of changing practice patterns, 6 months of androgen suppression was allowed. Hyperthermia was administered with a 16 element trans-rectal ultrasound applicator with rectal wall, normal tissue, and intra-prostatic temperature monitoring performed during all treatments. The study was designed to have 80% power to detect a 20% absolute improvement in the 2-year disease-free survival rate observed on the short-term androgen supression arm in RTOG Trial 92-02, from 65% to 85%. Results: Thirty-seven patients received a total of 72 hyperthermia treatments between September, 1997 and April, 2002. A favorable long-term toxicity profile noted with this treatment regiment was previously reported. The mean cumulative equivalent minutes at 43 C as measured by 90% of the intraprostatic temperature sensors (CEM T 90 43 C) for all 37 patients was 8.4 minutes. 1992 AJCC clinical stage: T2b 20, T2c 8, T3a 4, T3b 4, and T3c 1 patients. Median Gleason score was 7 (range, 6-9), and median PSA was 11.4 (2-65) ng/nl. All patients completed radiation therapy with median dose of 6700 cGy as normalized to 95%. Thirtyone patients received androgen suppression initiated within 3 months prior to radiation. All but 2 of these patients received 6 months of therapy. PSA failure was defined using the ASTRO consensus definition. Failure was also defined by clinical or pathologic evidence of local or distant disease recurence, or at the time of initiation of salvage androgen suppression irregardless of PSA. With a median follow-up of 60 months (15-84 months), 65% of patients remain free from failure. Three patients developed metastatic disease of which one patient died of prostate cancer 30 months after treatment. Absolute rate of disease-free survival at 2 years, the primary study endpoint, was 73% (90% CI, 59%-85%) which compares favorably with a rate of 64% for similar patients on the 4 month androgen suppression arm of RTOG 92-02 that served as the comparison group for this study. Using Phoenix criteria (nadir +2) for biochemical failure, 89% of patients were progression-free at 2 years (90% CI, 77%-96%). Conclusions: Transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer appears promising. Further study of hyperthermia in primary treatment of prostate cancer in combination with optimal radiation and systemic therapies is warranted.
International Journal of Radiation Oncology Biology Physics, 1997
International Journal of Radiation Oncology Biology Physics, 1991
Five patients (11%) were unable to complete the planned therapy secondary to acute toxicity. The ... more Five patients (11%) were unable to complete the planned therapy secondary to acute toxicity. The three year actuarial survival and recurrence free survival rates for the entire group are 32% and 26% respectively. The survival and recurrence free survival rates for the group with microscopic residual disease at 48% and 51% are significantly better than those for the patients with macroscopic residual disease-18% and 5% (p<O.OOS) respectively. Patients with disease limited to pelvis only have a recurrence free survival of 56% compared to 10% when the upper abdomen was involved (p<O.OOl). The abdomino pelvic cavity was the fiit site of failure in 27 of 30 patients failing. Eight patients (18%) experienced bowel complications, of whom five needed surgical intervention. Conclusion: WART with a pelvic boost is feasible with acceptable acute and late toxicity. It is effective in patients with minima1 residual disease.
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Papers by Bruce Bornstein