Bruce A. Bornstein

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.

Long-term outcome following breast-conserving surgery and radiation therapy

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, 1870 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/regional (DF/RNF) or local (LR). Local recurrence was defined 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 follow-up 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 overall crude rates of ipsilateral 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 all 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 0.1-0.7%. 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 1-5% over all years. Although the magnitude of the incidence was different, DF/RNF recurrence predominated in years 1-3 for both node-positive and node-negative patients. For the 1968-1982 and 1983-1986 cohorts, the 5-year crude rates of ipsilateral breast recurrence were 8.8 and 5.9%, respectively. CONCLUSIONS 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 follow-up and was highest during years 8 through 10. The 5-year crude rate of ipsilateral 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 significantly (p = 0.13). Any decrease in ipsilateral breast recurrence likely reflects improvements in mammographic and pathologic evaluation, patient selection, and the increased use of reexcision.

Ten‐year results of breast‐conserving surgery and definitive irradiation for intraductal carcinoma (ductal carcinoma in situ) of the breast

An analysis of 259 women with 261 treated breasts from nine institutions in Europe and the United States was performed to determine the 10‐year results of the treatment of intraductal carcinoma of the breast with definitive irradiation. All patients had undergone complete gross excision of the primary intraductal carcinoma, and definitive breast irradiation was delivered in all cases. The median follow‐up time was 78 months (range, 11 to 197 months). The 10‐year actuarial overall survival rate was 94%, and the 10‐year actuarial cause‐specific survival rate (including deaths only from carcinoma of the breast) was 97%. The 10‐year actuarial rate of freedom from distant metastases was 96%. There were 28 failures in the breast, and the 10‐year actuarial rate of local failure was 16%. The pathologic type of local recurrences showed invasive ductal carcinoma in 14 of 28 recurrences (50%) and noninvasive ductal carcinoma in 14 of 28 recurrences (50%). The median time to local failure was 50 months (range, 17 to 129 months). Twenty‐four of 28 patients with local failure were salvaged with additional treatment, generally mastectomy, and 4 of 28 patients with local failure subsequently had distant metastases. Median follow‐up time after salvage treatment of breast recurrence was 29 months (range, 3 to 90 months). Two patients without local failure subsequently had distant metastases, one of which occurred after a node‐positive, contralateral breast carcinoma. These results demonstrate high rates of overall survival, cause‐specific survival, and freedom from distant metastases for the treatment of patients with intraductal carcinoma of the breast. The local recurrences within the treated breast were generally salvaged with additional treatment, although with limited follow‐up. Because of the long natural history of intraductal carcinoma of the breast, prolonged and careful follow‐up of patients after breast‐conservation and definitive irradiation is required. Cancer 68:2337–2344, 1991.

Reduction of cardiac volume in left-breast treatment fields by respiratory maneuvers: a CT study

PURPOSE A previous study of healthy female volunteers suggested that deep inspiratory breath holding can reduce the cardiac volume in the treatment portals for left-breast cancer treatment. The reduction of irradiated cardiac volume may be important considering the reported late cardiac morbidity and mortality and the frequent coexistent use of potentially cardiotoxic chemotherapy in breast cancer patients. In the present study, we evaluated the heart volume in the fields and, thus, the true benefit of this respiratory maneuver in breast cancer patients undergoing CT simulation. MATERIALS AND METHODS Fifteen patients (median age, 53) were studied. For each patient, CT scans were performed both when the patient breathed normally (quiet respiration) and when the patient held her breath after a deep inspiration. Tangential fields were planned using the same medial, lateral, superior, and inferior borders on skin for the normal breathing and the breath-holding configurations. The cardiac and left-lung volumes within the tangential fields were calculated for both breathing configurations. Multiple scan series were performed for the breath-holding configuration to provide a more accurate delineation of the cardiac tissue and to study the reproducibility of the patients position between different cycles of deep inspiration. RESULTS None of the patients had difficulty holding her breath for 20 s. The cardiac volume in the field was reduced (-86 +/- 24%; p < 0.001) when patients held their breath after a deep inspiration compared to when breathing normally. For 7 patients (47%), deep inspiration moved the heart completely out of the radiation fields. The expansion of the lung tissue due to deep inspiration also increased the absolute lung volume in the tangential fields (183 cm(3) vs 97 cm(3), p < 0.001). However, the fractional volume of the left lung in the field was essentially unchanged. For all but 1 patient, the maximum difference between the external body contours from different breath holding cycles was 5 mm and occurred at the lateral aspect of the breast. At the medial aspect, as indicated by the position of the midline marker, the variations were well within the currently accepted tolerance for patient positioning during tangential treatment. CONCLUSIONS Deep-inspiration breath holding substantially reduces cardiac volume in the tangential fields for left-sided breast cancer treatment. The variation between patient positions at different cycles of breath holding was found to be reasonably small. Therefore, it appears feasible to reduce cardiac radiation by treating patients with intratreatment minifractions lasting 10-15 s while patients hold their breath.

Results of treating ductal carcinoma In situ of the breast with conservative surgery and radiation therapy

To determine the frequency, pattern, and time course of tumor recurrence in the breast, the outcome of 38 women with ductal carcinoma in situ (DCIS) treated with conservative surgery and radiation therapy between 1976 and 1985 was studied. Surgery typically consisted of local excision without evaluation of the microscopic margins of resection. The median radiation dose to the tumor site was 6400 cGy. With a median follow‐up time of 81 months, eight patients (21%) have experienced a recurrence in the breast. The time course to recurrence was protracted in some cases, with failures occurring at 17, 27, 43, 63, 71, 83, 92, and 104 months. The 5‐year and 8‐year actuarial rates of tumor recurrence in the breast were 8% and 27%, respectively. Seven patients had a recurrence at or near the primary tumor site, four with invasive carcinoma, and one had an invasive recurrence at a site elsewhere in the breast. No clinical or pathologic factor was significantly associated with an increased risk of recurrence, but the number of patients in the study population was small. The authors reached the following conclusions for patients with DCIS treated with conservative surgery and radiation therapy without careful mammographic and pathologic evaluation: (1) recurrence in the breast may be seen in at least one fifth of the patients; (2) recurrence typically occurs at or near the primary site; and (3) recurrence can occur long after treatment. Careful mammographic and pathologic assessment may be useful in reducing the local recurrence rate and should be considered essential if patients are considered for conservative surgery and radiation therapy.

Can simulation measurements be used to predict the irradiated lung volume in the tangential fields in patients treated for breast cancer

A simple method of estimating the amount of lung irradiated in patients with breast cancer would be of use in minimizing lung complications. To determine whether simple measurements taken at the time of simulation can be used to predict the lung volume in the radiation field, we performed CT scans as part of treatment planning in 40 cases undergoing radiotherapy for breast cancer. Parameters measured from simulator films included: (a) the perpendicular distance from the posterior tangential field edge to the posterior part of the anterior chest wall at the center of the field (CLD); (b) the maximum perpendicular distance from the posterior tangential field edge to the posterior part of the anterior chest wall (MLD); and (c) the length of lung (L) as measured at the posterior tangential field edge on the simulator film. CT scans of the chest were performed with the patient in the treatment position with 1 cm slice intervals, covering lung apex to base. The ipsilateral total lung area and the lung area included within the treatment port were calculated for each CT scan slice, multiplied by the slice thickness, and then integrated over all CT scan slices to give the volumes. The best predictor of the percent of ipsilateral lung volume treated by the tangential fields was the CLD. Employing linear regression analysis, a coefficient of determination r2 = 0.799 was calculated between CLD and percent treated ipsilateral lung volume on CT scan. In comparison, the coefficients for the other parameters were r2 = 0.784 for the MLD, r2 = 0.071 for L, and r2 = 0.690 for CLD x L. A CLD of 1.5 cm predicted that about 6% of the ipsilateral lung would be included in the tangential field, a CLD of 2.5 cm about 16%, and a CLD of 3.5 cm about 26% of the ipsilateral lung, with a mean 90% prediction interval of +/- 7.1% of ipsilateral lung volume. We conclude that the CLD measured at the time of simulation provides a reasonable estimate of the percent of the ipsilateral lung treated by the tangential fields. This information may be of value in evaluating the likelihood of pulmonary complications from such treatment and in minimizing toxicity.

Locally advanced rectal carcinoma: pelvic control and morbidity following preoperative radiation therapy, resection and intraoperative radiation therapy

PURPOSE To determine the impact of intraoperative radiation therapy (IORT) combined with preoperative external beam irradiation and surgical resection in patients with locally advanced, unresectable rectal carcinoma. METHODS AND MATERIALS Between 1982 and 1993, 40 patients with locally advanced colorectal cancer unresectable at initial presentation were treated with preoperative external beam radiation therapy (median dose 50.4 Gy). Thirty patients received concurrent 5-fluorouracil. Twenty-seven patients had primary tumors and 13 had recurrent disease; 1 patient had a solitary hepatic metastasis at the time of surgery. Four to 6 weeks after radiation, surgical resection was undertaken, and if microscopic or gross residual disease was encountered, IORT was delivered to the tumor bed. Patients with an unevaluable or high-risk margin were also considered for IORT. IORT was delivered through a dedicated 300-kVp orthovoltage unit. The median dose of IORT was 12.5 Gy (range 8-20). The dose was typically prescribed to a depth of 1-2 cm. The median follow-up was 33 months (range 5-100). RESULTS Thirty-three patients were able to undergo a curative resection (83%). Five patients had gross residual disease despite aggressive surgery. Seven patients did not receive IORT: six because of clear margins, and one with gross disease that could not be treated for technical reasons. The remainder of the patients (26) received IORT to the site of pelvic adherence. The crude local control rates for patients following complete resection with negative margins were 92% for patients treated with IORT and 33% for patients without IORT. IORT was ineffective for gross residual disease. Pelvic control was none of four in this setting. The crude local control rate of patients with primary cancer was 73% (16 of 22), as opposed to 27% (3 of 11) for these with recurrent cancer. The 5-year actuarial overall survival and local control rates for patients undergoing gross complete resection and IORT were 64% and 75%, respectively. Seventeen of the 26 patients (65%) who received IORT experienced pelvic complications, as opposed to two patients (28%) who did not receive IORT. The incidence of complications was similar in the patients with primary versus recurrent disease. All cases were successfully treated with the placement of a posterior thigh myocutaneous flap. Of note, no pelvic osteoradionecrosis was seen in this series. CONCLUSION Patients with locally advanced carcinoma of the rectum were aggressively treated with combined modality therapy consisting of preoperative external beam radiotherapy, surgery, and IORT. The pelvic control rate was 82% for patients with minimal residual disease. IORT failed to control gross residual disease. The incidence of pelvic wound healing problems was 65% in this series; however, a reconstructive procedure which replaced irradiated tissue with a vascularized myocutaneous flap was successful in treating this complication. We believe that IORT has therapeutic merit in the treatment of locally advanced rectal cancer, particularly in the setting of minimal residual disease.

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.

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.

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

AbstractBackground: 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 feature 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.

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.