Gene expression profiling to predict the risk of locoregional recurrence in breast cancer: a pooled analysis.

The 70-gene signature (MammaPrint) has been developed to predict the risk of distant metastases in breast cancer and select those patients who may benefit from adjuvant treatment. Given the strong association between locoregional and distant recurrence, we hypothesize that the 70-gene signature will also be able to predict the risk of locoregional recurrence (LRR). 1,053 breast cancer patients primarily treated with breast-conserving treatment or mastectomy at the Netherlands Cancer Institute between 1984 and 2006 were included. Adjuvant treatment consisted of radiotherapy, chemotherapy, and/or endocrine therapy as indicated by guidelines used at the time. All patients were included in various 70-gene signature validation studies. After a median follow-up of 8.96 years with 87 LRRs, patients with a high-risk 70-gene signature (n = 492) had an LRR risk of 12.6% (95% CI 9.7-15.8) at 10 years, compared to 6.1% (95% CI 4.1-8.5) for low-risk patients (n = 561; P < 0.001). Adjusting the 70-gene signature in a competing risk model for the clinicopathological factors such as age, tumour size, grade, hormone receptor status, LVI, axillary lymph node involvement, surgical treatment, endocrine treatment, and chemotherapy resulted in a multivariable HR of 1.73 (95% CI 1.02-2.93; P = 0.042). Adding the signature to the model based on clinicopathological factors improved the discrimination, albeit non-significantly [C-index through 10 years changed from 0.731 (95% CI 0.682-0.782) to 0.741 (95% CI 0.693-0.790)]. Calibration of the prognostic models was excellent. The 70-gene signature is an independent prognostic factor for LRR. A significantly lower local recurrence risk was seen in patients with a low-risk 70-gene signature compared to those with high-risk 70-gene signature.

Identification of a subgroup of patients with breast cancer and histologically positive axillary nodes receiving adjuvant chemotherapy who may benefit from postoperative radiotherapy.

Risk factors for isolated local-regional (LR) recurrence following mastectomy for breast cancer were analyzed in a review of 627 women entered into Eastern Cooperative Oncology Group (ECOG) adjuvant chemotherapy trials between 1978 and 1982. Premenopausal patients were randomized to cyclophosphamide, methotrexate, and fluorouracil (5-FU) (CMF), cyclophosphamide, methotrexate, 5-FU, and prednisone (CMFP), or cyclophosphamide, methotrexate, 5-FU, prednisone, and tamoxifen (CMFPT). Postmenopausal patients were randomized to observation, CMFP, or CMFPT. Median follow-up time was 4.5 years. At 3 years, 225 patients relapsed and in 70 (31% of failures, 11% of all patients) the initial site was LR without distant metastases. In a multivariate analysis, the risk of an isolated LR recurrence significantly correlated with the number of positive axillary nodes, the primary tumor size, the presence of tumor necrosis, and the number of axillary nodes examined. Factors that significantly discriminated between an isolated LR recurrence and distant metastasis were the number of positive nodes and primary tumor size. Patients with four to seven positive nodes or tumor size greater than or equal to 5 cm had a chance of developing an isolated LR recurrence almost equal to the risk of distant metastases. These findings suggest a potential for improved survival in this subset of patients with the addition of postmastectomy radiation to chemotherapy, and continue to emphasize the presence of a group of patients at high risk for isolated LR recurrence despite adjuvant chemotherapy.

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

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

Recursive partitioning identifies patients at high and low risk for ipsilateral tumor recurrence after breast-conserving surgery and radiation.

PURPOSE: Recursive partitioning analysis (RPA), a method of building decision trees of significant prognostic factors for outcome, was used to determine subgroups at significantly different risk for ipsilateral breast tumor recurrence (IBTR) in early-stage breast cancer. PATIENTS AND METHODS: Nine hundred twelve women underwent breast-conserving surgery, axillary dissection, and radiation. Systemic therapy was chemotherapy with or without tamoxifen in 32%, tamoxifen in 27%, or none in 41%. RPA was used to create a decision tree according to predictive variables that classify patients by IBTR risk, and the Kaplan-Meier method was used to calculate 10-year risks. Median follow-up was 5.9 years. RESULTS: Age was the first split in the partition tree. Patients more than 55 years old had a 4% 10-year IBTR, the only further division being use of tamoxifen or not (2% v 5%, P =.03). For patients

Impact of improved irradiation technique, age, and lymph node sampling on the severe complication rate of surgically staged endometrial cancer patients: a multivariate analysis.

PURPOSE: Limited information is available regarding factors that predispose to complications following postoperative pelvic radiotherapy (RT) for endometrial cancer. To address this issue, patients with clinically staged I/II endometrial cancer who received postoperative RT following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) with or without lymph node sampling (LNS) were studied. PATIENTS AND METHODS: From 1960 through 1990, 235 patients with adenocarcinoma of the endometrium received postoperative RT after surgical staging. Multiple factors were evaluated to determine associations with severe complications. Pretreatment factors included age, stage, comorbidities. Treatment-related factors consisted of LNS, total RT dose, volume of RT fields, dose per fraction, total number of RT fields, number of RT fields treated per day, machine energy, and addition of vaginal implant. RESULTS: The 5-year actuarial risk of a severe complication was 5.5%. Factors associated with an increased risk of complications in univariate analysis included age more than 65 years (11% v 2%), use of only one portal per day (40% v 3%), use of anteroposterior/posteroanterior fields (23% v 4%), total dose > or = 50 Gy (8% v 2%), and LNS (11% v 3%). In a multivariate analysis, only older age, LNS, and the use of one field per day were significant. Increased risks associated with a total dose > or 50 Gy and the anteroposterior/posteroanterior technique were entirely attributable to the use of one field per day. A subanalysis among patients who had adequate RT techniques (eg, multiple fields treated per day) showed a significant increase in complications (7% v 1%) for those with and without LNS, respectively. CONCLUSIONS: Severe complications associated with adjuvant RT for endometrial cancer were increased among patients who were older or underwent LNS or received suboptimal RT technique. Pelvic RT using proper methods can be delivered with acceptable risks.

Postmenopausal hormone replacement therapy: effect on diagnosis and outcome in early-stage invasive breast cancer treated with conservative surgery and radiation.

PURPOSE: To compare the pretreatment characteristics and outcome of postmenopausal women with stage I-II breast cancer treated with conservative surgery and radiation who had a history of hormone replacement therapy (HRT) with those who had never received HRT. MATERIALS AND METHODS: From 1979 to 1993, 485 postmenopausal women underwent excisional biopsy, axillary dissection, and radiation for stage I-II breast cancer. The median follow-up was 5.9 years. One hundred forty-one patients reported a history of HRT. The median length of use was 5 years. Three hundred forty-four patients reported no history of HRT. RESULTS: Statistically significant differences between the two groups were observed for median age (HRT 60 years v no HRT 64 years; P =.0009), median weight (HRT 142 lbs v no HRT 152 lbs; P =.004), clinical tumor size < or = 2 cm (HRT 77% v no HRT 66%; P =.02), and the use of re-excision (HRT 62% v no HRT 49%; P =.01). The method of detection by mammogram only (HRT 52% v no HRT 42%; P =.06) was of borderline statistical significance. The HRT patients had a statistically significant increased cumulative incidence of ipsilateral breast tumor recurrence (8% v 2%; P =.02), a statistically significant decreased cumulative incidence of distant metastases (HRT 6% v no HRT 17%; P =.01), and a borderline statistically significant improvement in cause-specific survival at 10 years (HRT 92% v no HRT 86%; P =.07). Postmenopausal women with a history of HRT did not have an increased risk of contralateral breast cancer or second non-breast cancer malignancy. CONCLUSION: This study failed to identify an adverse effect of HRT on breast cancer mortality in patients with stage I-II disease treated with conservative surgery and radiation.

Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group.

PURPOSE: To assess patterns of failure and how selected prognostic and treatment factors affect the risks of locoregional failure (LRF) after mastectomy in breast cancer patients with histologically involved axillary nodes treated with chemotherapy with or without tamoxifen without irradiation. PATIENTS AND METHODS: The study population consisted of 2,016 patients entered onto four randomized trials conducted by the Eastern Cooperative Oncology Group. The median follow-up time for patients without recurrence was 12.1 years (range, 0.07 to 19.1 years). RESULTS: A total of 1,099 patients (55%) experienced disease recurrence. The first sites of failure were as follows: isolated LRF, 254 (13%); LRF with simultaneous distant failure (DF), 166 (8%); and distant only, 679 (34%). The risk of LRF with or without simultaneous DF at 10 years was 12.9% in patients with one to three positive nodes and 28.7% for patients with four or more positive nodes. Multivariate analysis showed that increasing tumor size, increasing numbers of involved nodes, negative estrogen receptor protein status, and decreasing number of nodes examined were significant for increasing the rate of LRF with or without simultaneous DF. CONCLUSION: LRF after mastectomy is a substantial clinical problem, despite the use of chemotherapy with or without tamoxifen. Prospective randomized trials will be necessary to estimate accurately the potential disease-free and overall survival benefits of postmastectomy radiotherapy for patients in particular prognostic subgroups treated with presently used and future systemic therapy regimens.

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.

Radiotherapeutic considerations in the treatment of primary breast cancer.

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

Postmastectomy radiation in patients with one to three positive axillary nodes receiving adjuvant chemotherapy: An unresolved issue.

The rationale for postmastectomy radiation is based on the prevention of locoregional recurrence in the chest wall, regional lymphatics, or both. The randomized trials of postmastectomy radiation in patients with one to three positive nodes receiving adjuvant chemotherapy have shown a proportional reduction in locoregional recurrence rates of two thirds. The absolute benefit, however, varies with the magnitude of the risk in patients who do not receive radiation. The survival benefit from radiation is best explained by the prevention of an isolated locoregional recurrence, which could serve as a source of fatal distant metastases and parallels the difference in the total incidence of distant metastases. The current dilemma is to identify patients with one to three positive nodes who have had an adequate axillary dissection and remain at substantial risk for a locoregional recurrence despite adjuvant chemotherapy. The routine use of postmastectomy radiation in all axillary node-positive patients requires further evaluation.

Hypopituitarism following radiation therapy of pituitary adenomas.

Pituitary function was evaluated before and after supervoltage radiotherapy for a pituitary adenoma in 35 patients; 22 had had prior surgical treatment, and 13 had not. For comparison, pituitary function was also followed concurrently in another 10 patients whose pituitary adenomas were treated surgically, but who did not receive subsequent radiotherapy. Following radiotherapy, deficiencies of adrenal, thyroid, and gonadal function developed in 67, 55, and 67 percent of the patients who had previously been treated surgically during a mean of 4.2 years of observation, and in 55, 15, and 50 percent of the patients who did not have prior surgery during the subsequent five years. In contrast, in patients who had previously been treated surgically and who did not receive radiation, deficiencies of these hormones developed in only 13, 13, and 0 percent during four years of observation. It is concluded that supervoltage radiotherapy for pituitary adenoma, especially when preceded by surgical treatment, frequently produces, during the ensuing four to five years, deficiencies of pituitary hormones that had been secreted normally prior to irradiation.

Radiotherapy for the prevention of local-regional recurrence in high risk patients post mastectomy receiving adjuvant chemotherapy.

From 1977 to 1986, 63 patients at high risk for isolated local-regional recurrence following mastectomy and adjuvant chemotherapy received post-operative radiotherapy. All patients had operable primary tumors (T1-3a). For entire group the mean and median number of positive nodes were 10 and 8, respectively. Radiotherapy consisted of 4500 to 5000 rad to the chest wall and regional nodes. Chemotherapy consisted of CMF +/- prednisone (45 patients), CAF (16 patients), and other variable regimens (2 patients). Relapse occurred in 23 patients with only two patients experiencing an isolated local-regional recurrence. In 3 patients local-regional recurrence appeared simultaneously with or following distant metastases and in 18 patients the pattern of failure was distant metastases alone. With a median follow-up of 28 months (range 9-87 mo.), 40 patients are alive without disease, 9 are alive with disease, and 14 have died with disease. The 4-year actuarial overall survival is 67% and the 4-year actuarial disease-free survival is 47%. The 4-year actuarial probability of an isolated local-regional recurrence is 5%. Complications related to the radiation included a 9% incidence of moderate to severe arm edema. This study demonstrates the ability of radiation to reduce the incidence of local-regional recurrence in a previously identified high risk group of patients and has produced encouraging survival results with minimal morbidity.

Use of the prone position in radiation treatment for women with early stage breast cancer.

PURPOSE: The prone position has been advocated for women with large pendulous breasts undergoing breast-conserving treatment with radiation therapy. However, there is no information in the literature regarding the coverage of the target volume with this technique. The purpose of this study was to evaluate the effectiveness of the prone treatment position in including at least the biopsy cavity with a 2-cm margin. METHODS AND MATERIALS: Eleven consecutive patients who underwent CT simulation in the prone position were included in this study. Patients underwent CT simulation in the prone position using a flat platform containing an aperture for the breast to hang through in a dependent fashion. CT slices were 5-mm thick taken at 3-mm intervals. The biopsy cavity was localized and outlined on sequential CT images using the surgical clips (when present) as well as the residual seroma. A 2-cm margin was included around the biopsy cavity to define the minimal target volume (mTV). Lateral fields were used for treatment planning. The beam arrangements were considered adequate if the mTV was totally included in the lateral fields. RESULTS: Median age of the patient population was 55 years. Bra sizes ranged from 36A-44DD. The majority of patients had mammographically detected T1 lesions. Median volume of the biopsy cavity was 48 cm3. Five of 11 (45%) patients underwent reexcision of the biopsy cavity, and 6 of 11 (55%) had surgical clips placed in the biopsy cavity. Overall, 8 of 11 (73%) patients did not have the entire mTV included in the lateral opposed tangential fields in the prone position. This was especially true in patients whose biopsy cavity extended down to the chest wall. There were no other clinical factors that could predict for the adequacy of coverage in the prone position. CONCLUSION: Special attention must be paid to the location of the surgical clips to determine the proximity of the biopsy cavity to the chest wall, or CT simulation should be performed to determine the exact location of the biopsy cavity prior to selecting patients with large pendulous breasts for treatment in the prone position.

Definitive irradiation for early stage breast cancer: The University of Pennsylvania experience.

From 1977 to 1984, 552 breast cancers in 548 women were treated with definitive irradiation following breast-conserving surgery at the Hospital of the University of Pennsylvania and the Fox Chase Cancer Center. All patients had invasive carcinoma and were AJC clinical Stage I or II. Pathologic axillary lymph node staging was known for all cases. The 5-year actuarial survival for the entire group was 93% with an NED survival of 81%. The 5-year survival for clinical Stage I and II patients was 97 and 87%, respectively, with a corresponding NED survival of 87 and 73%, respectively. For pathologic Stage I and II patients, the corresponding survival figures were 97 and 89%, respectively, with NED survival rates of 86 and 76%, respectively. The overall 5-year actuarial local failure rate was 6%, and the rate of local only as the first failure was 3%. The overall local-regional failure rate was 13% with a local-regional only first failure rate of 8%. These results compare favorably with other reported series and contribute a substantial number of patients to the increasing experience with definitive irradiation following breast-conserving procedures. The relatively low incidence of breast recurrence may be related to the emphasis on integrating the surgical, pathologic, and radiotherapeutic aspects of treatments, as well as the emergence of a re-excision policy for patients at high risk to have residual tumor.

A new technique for positioning tangential fields.

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

Ten-year results of the treatment of early-stage breast carcinoma in elderly women using breast-conserving surgery and definitive breast irradiation.

PURPOSE: The optimal management of breast cancer in elderly women is not well established. Therefore, the present study was undertaken to evaluate the outcome of breast cancer in elderly women treated with breast-conserving surgery and definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed of 558 women age > or = 50 years treated with breast-conserving surgery and definitive breast irradiation for Stages I-II invasive carcinoma of the breast. Of the 558 total women, there were 173 elderly women > or = 65 years and a comparison group of 385 women age 50-64 years. Treatment for all women included complete gross excision of the primary tumor, pathologic axillary lymph node staging, and definitive breast irradiation. Adjuvant systemic chemotherapy was used in 18% (102 out of 558) of the overall group. Adjuvant tamoxifen was used in 17% (94 out of 558) of the overall group. The median follow-up after treatment was 6.2 years (mean = 6.4 years; range = 0.1-15.4 years). RESULTS: Elderly patients age > or = 65 years and patients age 50-64 years were both found to have tumors with adverse prognostic features, including clinical T2 lesions (43 vs. 34%, respectively; p = 0.055), estrogen receptor negativity (9 vs. 16%, respectively; p = 0.13), and progesterone receptor negativity (17 vs. 21%, respectively; p = 0.50). Pathologic axillary lymph node staging showed that 24% of the elderly women were node positive, including 8% with four or more positive nodes, which was not different from women age 50-64 years (p = 0.23). There was no difference between the two age groups for the rate of deaths from breast cancer at 10 years (13 vs. 13%, respectively; p = 0.71). However, there was a significant difference between the two age groups for the rate of deaths from intercurrent disease at 10 years (11 vs. 2%, respectively; p = 0.0006). There were no differences between the two age groups for the 10-year rates of overall survival (77 vs. 85%, respectively; p = 0.14), relapse-free survival (64 vs. 70%, respectively; p = 0.16), freedom from distant metastases (83 vs. 78%, respectively; p = 0.45), or local failure (13 vs. 12%, respectively; p = 0.60). CONCLUSIONS: These results have shown that breast carcinomas in elderly women are not indolent and have a number of adverse prognostic features. Breast-conserving surgery and definitive breast irradiation in elderly women age > or = 65 years achieves good outcomes for survival, freedom from distant metastases, and local control, which are comparable to women age 50-64 years. The causes of deaths in elderly women age > or = 65 years are from both breast cancer and intercurrent disease. Breast-conserving surgery and definitive breast irradiation should continue to be considered as a standard treatment option for appropriately selected elderly women with early-stage breast cancer.

Age as a prognostic factor for patients treated with definitive irradiation for early stage breast cancer.

From 1977 to 1986, 88 breast cancers in 86 women age less than or equal to 35 years were treated with definitive irradiation following breast-conserving surgery. The records of these cases were reviewed and compared to 808 breast cancers in 798 women age greater than or equal to 36 years treated similarly during the same time period. All women had AJC clinical Stages I or II invasive carcinoma of the breast and had undergone an axillary surgical staging procedure to determine pathologic lymph node staging prior to receiving definitive radiotherapy. There was no statistical difference between the younger and older women in terms of 5-year actuarial overall survival (94% vs. 90%), NED survival (78% vs. 81%) or relapse-free survival (70% vs. 77%). Although the younger women tended to have an earlier pattern of failure, the difference between the actuarial percentage of failures at 5 years for the two age groups was not significantly different for local only first failure (9% vs. 5%), regional only first failure (6% vs. 3%), and local and regional only first failure (0% vs. 1%). Subset analyses also did not show a difference between the younger and older patients. Although longer follow-up will be needed to confirm these observations, our 5-year results show that younger patients less than or equal to age 35 do not have an adverse outcome in terms of survival, local control, or regional control when compared with older patients greater than or equal to age 36. Potential candidates for definitive irradiation following breast-conserving surgery should not be excluded for treatment solely on the basis of younger age less than or equal to 35 years.

Frequency, sites of relapse, and outcome of regional node failures following conservative surgery and radiation for early breast cancer.

Between 1970 and 1986, 990 patients underwent excisional biopsy and radiation for clinical Stage I or II breast cancer. A limited axillary dissection (levels I and II) was performed in 914 of these patients. The median follow-up was 40 months from the initiation of radiation. Thirty-one patients developed a regional node failure as their first site of recurrence either with (12 patients) or without (19 patients) simultaneous distant metastases. The median interval to recurrence was 27 months (range 4-59). The 5-year actuarial rate for an isolated regional node recurrence (without simultaneous distant metastases) was 3%. The most common site for a regional node failure was the axilla (17 patients) followed by the supraclavicular nodes (13 patients). Salvage therapy was effective for an axillary +/- breast failure with 10/14 patients alive with no evidence of disease. Prognosis was related to the site of recurrence as well as the presence or absence of distant metastases. The 5-year actuarial survival from initial treatment for all patients with a regional node failure was 63% with a 3-year actuarial survival of 57% from diagnosis of recurrence. Regional node failure was related to the number of axillary nodes removed at the time of dissection and patient age.

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

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

Effect of low-density lateral interfaces on soft-tissue doses.

PURPOSE: Doses at the interface between tissue and low-density inhomogeneities with the interface positioned perpendicular to the beam direction have been well studied. When the inhomogeneity lies parallel to the beam direction (i.e., a lateral interface), the resulting dose distribution is not as well known. Lateral lung-soft-tissue interfaces are common in many fields used to treat malignancies in the thorax region including tangential breast fields and anteroposterior fields for lung and esophageal cancer. The purpose of this study was to evaluate the dose distribution along lateral interfaces and to determine the implications for treatment. METHODS AND MATERIALS: A polystyrene and cork slab phantom was irradiated from the side to simulate treatment fields with lateral lung-soft-tissue interfaces. The beam was positioned with the isocenter in polystyrene and the field edge in cork. Cork slabs (0.6-2.5 cm) were used to simulate different thicknesses of lung between the field edge and the target volume. Measurements were made using a parallel plate ionization chamber. With the chamber position held constant, polystyrene slabs were added between the cork and the chamber to study the dose distribution in the interface region. Interface doses were studied as a function of the amount of cork in the field, field size, beam energy (6-18 MV), and depth. RESULTS: Doses in the interface region were lower by as much as 10% compared to doses in a homogeneous phantom. For a given cork width and field size, the magnitude of the underdose increased by several percent as the x-ray energy increased from 6 to 18 MV. The underdose at the interface was 5% for 6 MV and 8% for 18 MV X-rays with a 1-cm cork width. For a 2.5-cm cork width, underdoses of 2.5% and 3% at distances up to 2.5 and 4 mm lateral to the interface were observed for 6- and 18-MV X-rays, respectively. However, doses right at the interface were 1% greater for 6 MV and 3% less for 18 MV than doses in a homogeneous phantom. For a given cork width, the interface doses were not significantly dependent on field width but decreased by an additional 2-3% as the length decreased to 4 cm. Additional decreases were also observed when the measurement depth decreased to 3 cm. With a 1-cm width of cork in the field, a lateral distance of 3-4 mm from the interface was necessary to ensure doses of at least 98% of the homogenous dose with 6-MV X-rays. A lateral distance of 6-7 mm was necessary for 10- and 18-MV X-rays. CONCLUSION: Underdosing will occur in the soft tissues adjacent to low-density inhomogeneities. The magnitude depends primarily on the width of the inhomogeneity seen in the treatment field, but also on field size, depth, and beam energy. For treatment fields with a lateral lung interface, a segment of tissue approximately 3-4 mm thick for 6 MV and 6-7 mm thick for higher-energy beams may be underdosed. Lung widths of > or = 1.75 cm as observed on film will generally guarantee doses of at least 96% of those calculated with no inhomogeneity corrections. High-energy beams are often used to treat sites in the thorax or breast to improve dose homogeneity throughout the treatment volume. Potential underdosing due to the presence of lung should be considered and may require a decrease in beam energy or an increase in the margin between the target volume and the field edge to ensure adequate treatment.