Karen J. Halverson

Factors influencing cosmetic results after conservation therapy for breast cancer

PURPOSE Host, tumor, and treatment-related factors influencing cosmetic outcome are analyzed for patients receiving breast conservation treatment. METHODS AND MATERIALS Four-hundred and fifty-eight patients with evaluable records for cosmesis evaluation, a subset of 701 patients treated for invasive breast cancer with conservation technique between 1969 and 1990, were prospectively analyzed. In 243 patients, cosmetic evaluation was not adequately recorded. Cosmesis evaluation was carried out from 3.7 months to 22.3 years, median of 4.4 years. By pathologic stage, tumors were 62% T1N0, 14% T1N1, 15%, T2N0, and 9% T2N1. The majority of patients were treated with 4-6 MV photons. Cosmetic evaluation was rated by both patient and physician every 4-6 months. A logistic regression analysis was completed using a stepwise logistic regression. P-values of 0.05 or less were considered significant. Excellent cosmetic scores were used in all statistical analyses unless otherwise specified. RESULTS At most recent follow-up, 87% of patients and 81% of physicians scored their cosmetic outcome as excellent or good. Eighty-two percent of physician and patient evaluations agreed with excellent-good vs. fair-poor rating categories. Analysis demonstrated a lower proportion of excellent cosmetic scores when related to patient age > 60 years (p = 0.001), postmenopausal status (p = 0.02), black race (p = 0.0034), and T2 tumor size (p = 0.05). Surgical factors of importance were: volume of resection > 100 cm3 (p = 0.0001), scar orientation compliance with the National Surgical Adjuvant Breast Project (NSABP) guidelines (p = 0.0034), and > 20 cm2 skin resected (p = 0.0452). Extent of axillary surgery did not significantly affect breast cosmesis. Radiation factors affecting cosmesis included treatment volume (tangential breast fields only vs. three or more fields) (p = 0.034), whole breast dose in excess of 50 Gy (p = 0.0243), and total dose to tumor site > 65 Gy (p = 0.06), as well as optimum dose distribution with compensating filters (p = 0.002). Daily fraction size of 1.8 Gy vs. 2.0 Gy, boost vs. no boost, type of boost (brachytherapy vs. electrons), total radiation dose, and use of bolus were not significant factors. Use of concomitant chemotherapy with irradiation impaired excellent cosmetic outcome (p = 0.02). Use of sequential chemotherapy or adjuvant tamoxifen did not appear to diminish excellent cosmetic outcomes (p = 0.31). Logistic regression for excellent cosmetic outcome analysis was completed for age, tumor size, menopausal status, race, type of surgery, volume of breast tissue resected, scar orientations, whole breast radiation dose, total radiation dose, number of radiation fields treated, and use of adjuvant chemotherapy. Significant independent factors for excellent cosmetic outcome were: volume of tissue resected (p = 0.0001), type of surgery (p = 0.0001), breast radiation dose (p = 0.005), race (p = 0.002), and age (p = 0.007). CONCLUSIONS Satisfactory cosmesis was recorded in 81% of patients. Impaired cosmetic results are more likely with improper orientation of tylectomy and axillary incisions, larger volume of breast resection, radiation dose to the entire breast in excess of 50.0 Gy, and concurrent administration of chemotherapy. Careful selection of treatment procedures for specific patients/tumors and refinement in surgical/irradiation techniques will enhance the cosmetic results in breast conservation therapy.

Regional nodal management and patterns of failure following conservative surgery and radiation therapy for stage I and II breast cancer.

PURPOSE To determine the incidence, pattern of regional nodal failure, and treatment sequelae as determined by the extent of lymphatic irradiation. METHODS AND MATERIALS The records of 511 patients with 519 Stage I and II breast cancers treated with breast conserving surgery with or without axillary dissection and irradiation were reviewed. The extent of nodal irradiation was at the discretion of the attending radiation oncologist and varied considerably over the years. Management of the axilla consisted of axillary dissection alone in 351, axillary dissection and supplemental irradiation in 74, irradiation alone in 75, and simply observation in 21 patients. RESULTS Overall, axillary recurrence was uncommon (1.2%), but was slightly more frequent after irradiation alone (2.7%) than after surgery alone (0.3%), p = 0.14. There was no benefit for supplemental axillary irradiation after an axillary dissection yielding negative or 1 to 3 positive nodes. In the 21 patients in whom the axilla was observed, axillary recurrence was not observed. Supraclavicular failures were rare in women with negative or 1 to 3 positive axillary lymph nodes (0.5%), and not significantly affected by elective irradiation. Internal mammary node recurrence was seen in only one patient, and was not significantly influenced by elective internal mammary irradiation. Both arm and breast edema were significantly more common in women having breast and nodal irradiation than after breast irradiation alone. These sequelae were not influenced significantly by the number of lymph nodes obtained in the axillary dissection specimen. Radiation pneumonitis was seen with increased frequency with more extensive nodal radiotherapy. Pneumonitis was not found to be affected by the administration or sequencing of chemotherapy. CONCLUSION There is little justification for axillary or supraclavicular irradiation following an axillary dissection which yields negative or minimally involved (1 to 3 positive) lymph nodes. There were too few patients with extensive axillary node metastases (> or = 4 positive) in our series to draw conclusions about the optimal extent of nodal irradiation in this subset. Elective internal mammary lymph node irradiation increases technical complexity, does not appear to be advantageous, and when combined with supraclavicular irradiation places the patient at highest risk for pneumonitis.

Isolated local-regional recurrence of breast cancer following mastectomy: Radiotherapeutic management

Two hundred twenty-four patients with their first, isolated local-regional recurrence of breast cancer were irradiated with curative intent. Patients who had previous chest wall or regional lymphatic irradiation were not included in the study. With a median follow-up of 46 months (range 24 to 241 months), the 5- and 10-year survival for the entire group were 43% and 26%, respectively. Overall, 57% of the patients were projected to be loco-regionally controlled at 5 years. The 5-year local-regional tumor control was best for patients with isolated chest wall recurrences (63%), intermediate for nodal recurrences (45%), and poor for concomitant chest wall and nodal recurrences (27%). In patients with solitary chest wall recurrences, large field radiotherapy encompassing the entire chest wall resulted in a 5- and 10-year freedom from chest wall re-recurrence of 75% and 63% in contrast to 36% and 18% with small field irradiation (p = 0.0001). For the group with recurrences completely excised, tumor control was adequate at all doses ranging from 4500 to 7000 cGy. For the recurrences less than 3 cm, 100% were controlled at doses greater than or equal to 6000 cGy versus 76% at lower doses. No dose response could be demonstrated for the larger lesions. The supraclavicular failure rate was 16% without elective radiotherapy versus 6% with elective radiotherapy (p = 0.0489). Prophylactic irradiation of the uninvolved chest wall decreased the subsequent re-recurrence rate (17% versus 27%), but the difference is not statistically significant (p = .32). The incidence of chest wall re-recurrence was 12% with doses greater than or equal to 5000 cGy compared to 27% with no elective radiotherapy, but again was not statistically significant (p = .20). Axillary and internal mammary failures were infrequent, regardless of prophylactic treatment. Although the majority of patients with local and/or regional recurrence of breast cancer will eventually develop distant metastases and succumb to their disease, a significant percentage will live 5 years. Therefore, aggressive radiotherapy should be used to provide optimal local-regional control.(ABSTRACT TRUNCATED AT 400 WORDS)

SURVIVAL FOLLOWING LOCOREGIONAL RECURRENCE OF BREAST CANCER: UNIVARIATE AND MULTIVARIATE ANALYSIS

Although prognostic variables for locoregional recurrence of breast cancer have been evaluated by univariate analysis, multifactorial analysis has not been previously performed. In the present study, survival following chest wall and/or regional lymphatic recurrence was determined in 230 patients with locoregionally recurrent breast cancer without evidence of distant metastases treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology and affiliated hospitals. Multifactorial analysis demonstrated that the site of recurrences correlated most strongly with overall survival (p = 0.001). The 5-year actuarial overall survival was 44-49% for patients with isolated chest wall, axillary, and internal mammary lymph node recurrence. Patients with either supraclavicular, multiple lymphatic, or concomitant chest wall and lymphatic recurrence had an 21-24% 5-year overall survival. The 5-year disease-free survival was 28-37% for patients with chest wall, axillary, or internal mammary recurrences compared to 4-13% for those with supraclavicular, chest wall and lymphatic, or those with multiple sites of lymphatic recurrence. Disease-free interval from mastectomy to recurrence was also found to be a significant prognostic factor for overall survival (p = 0.005). Fifty percent of patients with a disease-free interval of at least 2 years survived 5 years following locoregional relapse, compared to 35% for those with disease-free interval of less than 2 years. In the subset of patients with small chest wall recurrences (excised or less than 3 cm) and a disease-free interval of at least 2 years, the 5-year overall and disease-free survivals were 67% and 54%, respectively. These results suggest that subsets of patients with locoregional recurrence of breast cancer can survive for long periods of time. The conventional wisdom that chest wall and/or regional nodal recurrence following mastectomy uniformly confers a dismal prognosis is not necessarily true.

Brachytherapy or electron beam boost in conservation therapy of carcinoma of the breast: A nonrandomized comparison

PURPOSE The results of breast-conservation therapy using breast irradiation and a boost to the tumor excision site with either electron beam or interstitial 192Ir implant are reviewed. METHODS AND MATERIALS A total of 701 patients with histologically confirmed Stage T1 and T2 carcinoma of the breast were treated with wide local tumor excision or quadrantectomy and breast irradiation. The breast was treated with tangential fields using 4 or 6 MV photons to deliver 48 to 50 Gy in 1.8 to 2 Gy daily dose, in five weekly fractions. In 80 patients the regional lymphatics were irradiated. In 342 patients with Stage T1 and 107 with Stage T2 tumors, boost to the primary tumor excision site was delivered with 9 MeV and, more frequently, with 12 MeV electrons. In 91 patients with Stage T1 and 38 patients with Stage T2 tumors an interstitial 192Ir implant was performed. Tumor control, disease-free survival, cosmesis, and morbidity of therapy are reviewed. Minimum follow-up is 4 years (median 5.6 years; maximum, 24 years). RESULTS The overall local tumor recurrence rates were 5% in the T1 and 11% in the T2 tumor groups. There was no significant difference in the breast relapse rate in patients treated with either electron beam or interstitial 192Ir boost. Regional lymph node recurrences were 1% in patients with T1 and 5% with T2 tumors. Distant metastases were recorded in 5% of the T1 and 23% of the T2 groups. The 10-year actuarial disease-free survival rates were 87% for patients with T1 and 75% with T2 tumors. Disease-free survival was exactly the same in patients receiving either electron beam or interstitial 192Ir boost. Cosmesis was rated as excellent/good in 84% of patients with T1 tumors treated with electron beam and 81% of patients treated with interstitial implant, and 74 and 79% respectively, in patients with T2 tumors. CONCLUSIONS Breast-conservation therapy is an effective treatment for patients with T1 and T2 carcinoma of the breast. There is no difference in local tumor control, disease-free survival, cosmesis, or morbidity in patients treated with either electron beam or interstitial 192Ir implant boost. Clinical trials in progress will further elucidate this controversial subject.

Management of the axilla in patients with breast cancers one centimeter or smaller.

Very small breast cancers are being diagnosed with increased frequency, and, until recently, little information regarding the incidence of axillary lymph node metastases in these most favorable tumors was available. Moreover, scarce data exist regarding axillary failure in this cohort as a function of initial treatment, be it surgery, radiation, or simply observation. In the present study, limited to women with invasive cancers measuring no more than 10 mm, the incidence of pathologically positive axillary nodes was 12.3%. The incidence of nodal metastases was influenced by tumor size (albeit not quite significantly. p = .08); not one patient with a tumor ≤ 5 mm had axillary node metastases. compared to 14.7% in those with cancers 6 to 10 mm. The histologic grade and tumor location were also important in predicting nodal positivity. The incidence of positive nodes was 38% in those with poorly differentiated cancers, compared to 8% and 7% in women with well and moderately differentiated cancers, respectively, p = .03. Axillary nodal positivity was seen in 17% of outer quadrant vs 3% of central and inner quadrant primaries. p < .01. The axilla was managed with surgery alone (76%). radiation alone (6%). surgery and radiation (6%), or simply observation (10%). With a median follow-up of 55 months, not one patient has suffered a nodal recurrence, and in our experience, survival free of distant relapse was not adversely affected by the omission of axillary surgery.

Locoregional Recurrence of Breast Cancer: A Retrospective Comparison of Irradiation Alone Versus Irradiation and Systemic Therapy

The role of systemic therapy in addition to irradiation for locoregional recurrence of breast cancer is controversial. In the absence of prospective randomized trials, treatment decisions must be based on retrospective studies. We retrospectively analyzed 230 patients treated for locoregionally recurrent breast cancer between 1964 and 1986. Forty-seven were premenopausal, 173 were postmenopausal, and the menopausal status was unknown in 10 patients. Each patient treated with radiotherapy (RT) and chemotherapy or with RT and hormonal therapy was matched with a control patient treated with RT alone. The addition of hormonal therapy to radiation therapy significantly improved the 5-year overall survival (50 versus 28%), disease-free survival (37 versus 26%), and distant metastases-free survival (45 versus 29%). No improvement in locoregional control was observed. In contrast, chemotherapy did not confer such survival benefits, but there was a trend towards improvement in 5-year locoregional control (68 versus 50%), p = 0.08. Our data support the use of hormonal therapy along with RT at the time of locoregional recurrence of breast cancer. Although our data suggest that chemotherapy is not routinely indicated, controlled clinical trials are needed to define which subsets of patients, if any, benefit from systemic therapy.

Study of treatment variation in the radiotherapy of head and neck tumors using a fiber-optic on-line radiotherapy imaging system

On-line radiotherapy imaging systems allow convenient daily acquisition of portal images for treatment verification. The information can also be used to study treatment variability. Using a prototype fiber-optic imaging system, we have measured the treatment variation of 17 head and neck patients. Daily digital portal images were acquired for the on-cord left and right lateral fields. Treatment variations were quantified using the Cumulative Verification Image Analysis (CVIA) method developed at our institute. In the CVIA method, daily portal images were aligned according to three anatomical points predefined on a digitized simulation, or prescription, image. After each image alignment, the block position was cumulated in a bit-map and superimposed on the prescription image to give a cumulative verification summary image. Iso-frequency distributions, or contours, of the block overlap were calculated and examined with respect to the prescription treatment area. The range of the treatment variation was large for the 17 patients. On average, separation of the 0% to 100% block overlap contours was about 10 mm, and the 20% to 80%, 5 mm. The block overlap contours were also used to calculate the frequency with which the prescription area as defined on the simulation film had been treated. The fraction of the prescription area treated depended on the accuracy of the treatment setup and patient repositioning, as expected. At best, approximately 95% of the prescribed area was irradiated 100% of the time during the entire course of radiotherapy. At worst, approximately 70% of the prescribed area was irradiated 100% of the time. These results demonstrate that despite immobilization, large setup variation can still occur. Presenting treatment variation data as population averages does not reflect on the large variation that may be observed in the individual patient.

Age as a prognostic factor for breast and regional nodal recurrence following breast conserving surgery and irradiation in stage I and II breast cancer.

PURPOSE To evaluate the association between age and breast/regional nodal relapse following breast conserving surgery and irradiation. METHODS AND MATERIALS The results of treatment in 511 patients with 519 Stage I and II breast cancers treated at Mallinkrodt Institute of Radiology and affiliated hospitals between 1958 and 1988 were reviewed. RESULTS Seventy women, of whom 96% had axillary dissections, were 39 years of age or younger. These young patients were more likely to have chemotherapy (p < 0.0001), and tumor bed reexcision (p < 0.01), and less likely to have an undissected axilla (p < 0.01), or estrogen receptor positive tumor (p = 0.02) than the older women (> 40 years). Although breast recurrence tended to appear earlier in the younger patients (12% at 5 years for those < 40 years vs. 6% at 5 years for those older), by 7 years the breast failure rate for the two groups was the same (12%), p = 0.13. In the 37 women 35 years of age or younger, the actuarial rate of breast recurrence was 9% at 7 years. Compared to other series in the literature, in which cancers were grossly excised without regard to the microscopic margins of resection, and reexcision was not routinely performed, young women treated with breast conserving surgery and irradiation at our institution frequently underwent reexcision of the tumor bed (57%), and had negative pathologic margins of resection (75%). Regional nodal relapse was in general uncommon, and not seen with increased frequency in the youngest cohort. CONCLUSION Our experience suggests that young age is not a contraindication to breast conserving surgery and irradiation. Although breast cancers in this cohort may have certain features rendering them prone to local failure, we believe this risk can be mitigated by appropriate patient selection and optimal surgical resection.

The cumulative verification image analysis tool for offline evaluation of portal images

PURPOSE Daily portal images acquired using electronic portal imaging devices contain important information about the setup variation of the individual patient. The data can be used to evaluate the treatment and to derive correction for the individual patient. The large volume of images also require software tools for efficient analysis. This article describes the approach of cumulative verification image analysis (CVIA) specifically designed as an offline tool to extract quantitative information from daily portal images. METHODS AND MATERIALS The user interface, image and graphics display, and algorithms of the CVIA tool have been implemented in ANSCI C using the X Window graphics standards. The tool consists of three major components: (a) definition of treatment geometry and anatomical information; (b) registration of portal images with a reference image to determine setup variation; and (c) quantitative analysis of all setup variation measurements. The CVIA tool is not automated. User interaction is required and preferred. Successful alignment of anatomies on portal images at present remains mostly dependent on clinical judgment. Predefined templates of block shapes and anatomies are used for image registration to enhance efficiency, taking advantage of the fact that much of the tools operation is repeated in the analysis of daily portal images. RESULTS The CVIA tool is portable and has been implemented on workstations with different operating systems. Analysis of 20 sequential daily portal images can be completed in less than 1 h. The temporal information is used to characterize setup variation in terms of its systematic, random and time-dependent components. The cumulative information is used to derive block overlap isofrequency distributions (BOIDs), which quantify the effective coverage of the prescribed treatment area throughout the course of treatment. Finally, a set of software utilities is available to facilitate feedback of the information for treatment plan recalculation and to test various decision strategies for treatment adjustment. CONCLUSIONS The CVIA tool provides comprehensive analysis of daily images acquired with electronic portal imaging devices. Its offline approach allows characterization of the nature of setup variation for the individual patient that would have been difficult to deduce using only a few daily or weekly portal images. Distribution of the tool will help establish an important database of setup variation from many clinics. The information derived from CVIA can also serve as the foundation to integrate treatment verification, treatment planning, and treatment delivery.