Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma.

BACKGROUND: Uncontrolled studies have reported encouraging outcomes for patients with high-risk primary breast cancer treated with high-dose chemotherapy and autologous hematopoietic stem cell support. We conducted a prospective randomized trial to compare standard-dose chemotherapy with the same therapy followed by high-dose chemotherapy. PATIENTS AND METHODS: Patients with 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of primary (neoadjuvant) chemotherapy were eligible. All patients were to receive eight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). Patients were stratified by stage and randomly assigned to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support or no additional chemotherapy. Tamoxifen was planned for postmenopausal patients with estrogen receptor-positive tumors and chest wall radiotherapy was planned for all. All P values are from two-sided tests. RESULTS: Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine patients were randomly assigned to FAC and 39 to FAC followed by high-dose chemotherapy. After a median follow-up of 6.5 years, there have been 41 relapses. In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P =.35), and 3-year survival rates were 77% and 58%, respectively (P =.23). Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associated with high-dose chemotherapy. CONCLUSIONS: No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial.

Estrogen replacement therapy after localized breast cancer: clinical outcome of 319 women followed prospectively.

PURPOSE: To determine whether estrogen replacement therapy (ERT) alters the development of new or recurrent breast cancer in women previously treated for localized breast cancer. PATIENTS AND METHODS: Potential participants (n = 319) in a trial of ERT after breast cancer were observed prospectively for at least 2 years whether they enrolled onto the randomized trial or not. Of 319 women, 39 were given estrogen and 280 were not given hormones. Tumor size, number of lymph nodes, estrogen receptors, menopausal status at diagnosis, and disease-free interval at the initiation of the observation period were comparable for the trial participants (n = 62) versus nonparticipants (n = 257) and for women on ERT (n = 39) versus controls (n = 280). Cancer events were ascertained for both groups. RESULTS: Patient and disease characteristics were comparable for the trial participants versus nonparticipants, as well as for the women on ERT versus the controls. One patient in the ERT group developed a new lobular estrogen receptor-positive breast cancer 72 months after the diagnosis of a ductal estrogen receptor-negative breast cancer and 27 months after initiation of ERT. In the control group, there were 20 cancer events: 14 patients developed new or recurrent breast cancer at a median time of 139.5 months after diagnosis and six patients developed other cancers at a median time of 122 months. CONCLUSION: ERT does not seem to increase breast cancer events in this subset of patients previously treated for localized breast cancer. Results of randomized trials are needed before any changes in current standards of care can be proposed.

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.

Impact of systemic treatment on local control for patients with lymph node-negative breast cancer treated with breast-conservation therapy.

PURPOSE: To determine the impact of tamoxifen and chemotherapy on local control for breast cancer patients treated with breast-conservation therapy. PATIENTS AND METHODS: The data from 484 breast cancer patients who were treated with breast-conserving surgery and radiation were analyzed. Only patients with lymph node-negative disease were studied to provide comparative groups with a similar stage of disease and a similar competing risk for distant metastases. Actuarial local control rates of the 277 patients treated with systemic therapy (128, chemotherapy with or without tamoxifen; 149, tamoxifen alone) were compared with the rates for the 207 patients who received no systemic treatment. Only 10% of the patients had positive (2%), close (3%), or unknown margin status (5%). RESULTS: Patients treated with systemic therapy had improved 5-year (97.5% v 89.8%) and 8-year (95.6% v 85.2%) local control rates compared with those that did not receive systemic treatment (P =.004, log-rank test). There was no statistical difference in local control between patients treated with chemotherapy and patients treated with tamoxifen alone (P =.219). Systemic treatment, margin status, young patient age, estrogen and progesterone receptor status, and primary tumor size were analyzed in a Cox regression analysis. The use of systemic treatment was the most powerful predictor of local control: patients who did not receive systemic treatment had a relative risk of local recurrence of 3.3 (95% confidence interval, 1.5 to 7.5; P =.004). CONCLUSION: In this retrospective analysis, systemic therapy appears to contribute to long-term local control in patients with lymph node-negative breast cancer treated with breast-conservation therapy.

Long-term results of combined-modality therapy for locally advanced breast cancer with ipsilateral supraclavicular metastases: The University of Texas M.D. Anderson Cancer Center experience.

PURPOSE: To determine outcomes in local-regional control, disease-free survival, and overall survival in patients with locally advanced breast cancer (LABC) who present with ipsilateral supraclavicular metastases and who are treated with combined-modality therapy. PATIENTS AND METHODS: Seventy patients with regional stage IV LABC, which is defined by our institution as LABC with ipsilateral supraclavicular adenopathy without evidence of distant disease, received treatment on three prospective trials of neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil, or cyclophosphamide, doxorubicin, vincristine, and prednisone. Patients then received local therapy that consisted of either total mastectomy and axillary lymph node dissection (ALND) or segmental mastectomy and ALND before or after irradiation. Patients with no response to neoadjuvant chemotherapy were treated with surgery and/or radiotherapy. After completion of local therapy, chemotherapy was continued for four to 15 cycles, followed by radiotherapy. Patients older than 50 years who had estrogen receptor-positive tumors received tamoxifen for 5 years. RESULTS: Median follow-up was 11.6 years (range, 4.8 to 22.6 years). Disease-free survival rates at 5 and 10 years were 34% and 32%, respectively. The median disease-free survival was 1.9 years. Overall survival rates at 5 and 10 years were 41% and 31%, respectively. The median overall survival was 3.5 years. The overall response rate (partial and complete responses) to induction chemotherapy was 89%. No treatment-related deaths occurred. CONCLUSION: Patients with ipsilateral supraclavicular metastases but no other evidence of distant metastases warrant therapy administered with curative intent, ie, combined-modality therapy consisting of chemotherapy, surgery, and radiotherapy. Patients with ipsilateral supraclavicular metastases should be included in the stage IIIB category of the tumor-node-metastasis classification because their clinical course and prognosis are similar to those of patients with stage IIIB LABC.

Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation.

PURPOSE: The objective of this study was to determine locoregional recurrence (LRR) patterns after mastectomy and doxorubicin-based chemotherapy to define subgroups of patients who might benefit from adjuvant irradiation. PATIENTS AND METHODS: A total of 1,031 patients were treated with mastectomy and doxorubicin-based chemotherapy without irradiation on five prospective trials. Median follow-up time was 116 months. Rates of isolated and total LRR (+/- distant metastasis) were calculated by Kaplan-Meier analysis. RESULTS: The 10-year actuarial rates of isolated LRR were 4%, 10%, 21%, and 22% for patients with zero, one to three, four to nine, or >/= 10 involved nodes, respectively (P <.0001). Chest wall (68%) and supraclavicular nodes (41%) were the most common sites of LRR. T stage (P <.001), tumor size (P <.001), and >/= 2-mm extranodal extension (P <.001) were also predictive of LRR. Separate analysis was performed for patients with T1 or T2 primary disease and one to three involved nodes (n = 404). Those with fewer than 10 nodes examined were at increased risk of LRR compared with those with >/= 10 nodes examined (24% v 11%; P =.02). Patients with tumor size greater than 4.0 cm or extranodal extension >/= 2 mm experienced rates of isolated LRR in excess of 20%. Each of these factors continued to significantly predict for LRR in multivariate analysis by Cox logistic regression. CONCLUSION: Patients with tumors >/= 4 cm or at least four involved nodes experience LRR rates in excess of 20% and should be offered adjuvant irradiation. Additionally, patients with one to three involved nodes and large tumors, extranodal extension >/= 2 mm, or inadequate axillary dissections experience high rates of LRR and may benefit from postmastectomy irradiation.

Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy.

PURPOSE: To assess patient and tumor characteristics associated with a complete pathologic response (pCR) in both the breast and axillary lymph node specimens and the outcome of patients found to have a pCR after neoadjuvant chemotherapy for locally advanced breast cancer (LABC). PATIENTS AND METHODS: Three hundred seventy-two LABC patients received treatment in two prospective neoadjuvant trials using four cycles of doxorubicin-containing chemotherapy. Patients had a total mastectomy with axillary dissection or segmental mastectomy and axillary dissection followed by four or more cycles of additional chemotherapy. Patients then received irradiation treatment of the chest-wall or breast and regional lymphatics. Median follow-up was 58 months (range, 8 to 99 months). RESULTS: The initial nodal status, age, and stage distribution of patients with a pCR were not significantly different from those of patients with less than a pCR (P>.05). Patients with a pCR had initial tumors that were more likely to be estrogen receptor (ER)-negative (P<.01), and anaplastic (P = .01) but of smaller size (P<.01) than those of patients with less than a pCR. Upon multivariate analysis, the effects of ER status and nuclear grade were independent of initial tumor size. Sixteen percent of the patients in this study (n = 60) had a pathologic complete primary tumor response. Twelve percent of patients (n = 43) had no microscopic evidence of invasive cancer in their breast and axillary specimens. A pathologic complete primary tumor response was predictive of a complete axillary lymph node response (P<.01 ). The 5-year overall and disease-free survival rates were significantly higher in the group who had a pCR (89% and 87%, respectively) than in the group who had less than a pCR (64% and 58%, respectively; P<.01). CONCLUSION: Neoadjuvant chemotherapy has the capacity to completely clear the breast and axillary lymph nodes of invasive tumor before surgery. Patients with LABC who have a pCR in the breast and axillary nodes have a significantly improved disease-free survival rate. However, a pCR does not entirely eliminate recurrence. Further efforts should focus on elucidating the molecular mechanisms associated with this response.

Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer.

PURPOSE: To compare prospectively the antitumor activity of single-agent paclitaxel to the three-drug combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC) as neoadjuvant therapy in patients with operable breast cancer. PATIENTS AND METHODS: Patients with T1-3N0-1M0 disease were randomized to receive either paclitaxel (250 mg/m(2)) as 24-hour infusion or FAC in standard doses at every-3-week intervals. Each patient was treated with four cycles of preoperative chemotherapy. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after four cycles of induction chemotherapy. RESULTS: A total of 174 patients were registered, and 87 were randomized to each arm of the study. Clinical response, ie, complete and partial responses, was similar in both arms of the study. Three patients in the FAC arm and one patient in the paclitaxel subgroup had progressive disease. The extent of residual disease by intent-to-treat analysis at the time of surgery was similar between the two arms of the study. CONCLUSION: The results of this prospective study demonstrated that single-agent paclitaxel as neoadjuvant therapy has significant antitumor activity, and this was clinically comparable to FAC. Similar fractions of patients had clinical complete and partial responses, and very few patients had no response to either therapy. The value of alternate non-cross-resistant therapies as used in this protocol on the clinical course of this disease would require longer follow-up.

Postmastectomy irradiation: rationale for treatment field selection.

The goal of postmastectomy irradiation is to eliminate residual viable tumor in tissue remaining after standard mastectomy. Because this subclinical disease is, by definition, not detectable by current technology, the choice of patients and treatment volumes for postmastectomy irradiation must be inferred from a variety of data sources. The absolute risk of locoregional recurrence is related to the stage of disease, the extent of lymphatic involvement, and other treatment received. Patterns of failure analyses consistently identify the chest wall as the most important target for treatment with radiation therapy in high-risk patients. When patients with multiple locoregional sites of recurrence are included, the chest wall may be involved in as many as 60% to 80% of patients. The second most common place for locoregional failure is the undissected lymphatics of the paraclavicular region. The cumulative probability of failure in this region ranges from 10% to 35% of the patients treated for locoregional recurrence. Microscopic tumor metastases in the internal mammary chain are theorized to represent a potential source for distant metastases. Each of the prospective trials of postmastectomy irradiation that have shown survival benefit included the internal mammary chain within their target volume. Nonetheless, local failure in the internal mammary nodes is an uncommon finding. Similarly, after a level I and II axillary dissection, axillary failure is a minor component of local recurrence risk, and it is probable that only a subset of patients may benefit from axillary irradiation.

Prospective randomized trial of paclitaxel alone versus 5-fluorouracil/doxorubicin/cyclophosphamide as induction therapy in patients with operable breast cancer.

The objective of this study was to compare the antitumor activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with that of the 5-fluorouracil/doxorubicin/cyclophosphamide (FAC) combination by evaluating the extent of residual disease in the breast and regional lymph nodes of patients with breast cancer following four cycles of induction chemotherapy. Patients with histologically confirmed invasive but noninflammatory carcinoma of the breast stages T2-3, N0-1, M0 were eligible to enter the study. Patients were treated with four cycles of either FAC or single-agent paclitaxel before local therapy. Following local therapy, treatment of the two arms was identical. Of 104 operable breast cancer patients who were treated with either regimen, 78 were evaluable for response to preoperative chemotherapy and had undergone local therapy. Age, TNM classification, and estrogen receptor status of the patients were similar in the two groups. Following induction chemotherapy, the extent of disease in the breast and the distribution and number of positive nodes were similar between the two treatment arms. Disease progressed in two patients in the FAC arm and in none in the paclitaxel arm during the induction phase of therapy. A higher fraction of patients had neutropenic fever during the paclitaxel treatment. Initial data from this ongoing randomized study show that paclitaxel alone has comparable anticancer activity with FAC in patients with early breast cancer. The degree of cytoreduction was similar with both induction therapies.

Radiation therapy for unresectable soft tissue sarcomas.

Between 1954 and 1981, 72 patients with unresectable soft tissue sarcomas were treated with radiotherapy at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, 57 with photons alone and 15 with neutrons for at least part of the treatment. Twenty-three patients received systemic chemotherapy in addition to radiation therapy. The absolute 2-year and actuarial 5-year tumor control rates were 39 and 29%, respectively. In this heterogeneous series, the malignancy group (based on pathologic diagnosis) was the only factor significantly affecting tumor control probability, which at 5 years was 58% for 12 patients with group I tumors, 32% for 10 patients with group II tumors, and 17% for 50 patients with group III tumors. No relationship between total dose and tumor control probability was found in this group of patients, though the duration of tumor control was longer in those receiving 65 Gy or more. No apparent improvement in tumor control was observed in the subsets of patients receiving fast neutron therapy or combined modality treatment with chemotherapy, but because of the many unmatched variables between the groups, no meaningful comparison of treatment modalities can be made. Distant metastasis were seen more frequently in higher malignancy groups, whereas size or site of tumors did not significantly influence the incidence of distant metastasis. Six patients sustained major complications of radiotherapy, of whom five received total doses in excess of 70 Gy or its estimated biologic equivalent.

Does radiotherapy have a role in hemangiopericytoma management? Report of 14 new cases and a review of the literature.

From 1948 to 1984, 14 adult patients received radiation therapy as a part of their treatment for hemangiopericytoma at the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston. In addition to radiation therapy 11 patients were treated with surgery, with or without chemotherapy--5 as primary management and 6 after recurrence following surgical excision. Although 9 of these 11 patients had macroscopic and 1 had definite microscopic disease at the time of irradiation, none suffered local recurrence and 9 have survived from 3.5 years to 20 years free of disease. Two of the 11 patients died of distant metastases. Two patients completed treatment for palliation and 1 of them survived for 2 years after treatment. The results suggest that postoperative radiation therapy should be considered as an integral part of the primary treatment of hemangiopericytoma.

Irradiation of prosthetically augmented breasts: a retrospective study on toxicity and cosmetic results.

Eleven patients with subcutaneous prosthetic breast implants were followed 3-16 years after mammary irradiation. Radiation doses ranged between 45 Gy and 50 Gy to the whole breast, supplemented in five cases with 10-21 Gy scar boost. Evaluation of the cosmetic results revealed a good score in three patients, moderate to fair in three, and poor in five. Of the five patients who had poor postirradiation cosmesis, three had fibrotic changes and encapsulation of the prostheses prior to the irradiation, and two received their irradiation 1 month after the reconstruction. In most of the patients, the nonirradiated breast was augmented with a prosthesis and both breasts could be followed for comparison. The irradiated side usually looked and felt on palpation worse than the nonirradiated, but both breasts exhibited a steady deterioration in appearance over time. The patients who enjoyed better cosmetic results after irradiation had better breast appearance before the radiotherapy. Of three patients treated with lower doses (45 Gy/4.5-5 weeks), two enjoyed good cosmesis. Both patients who received irradiation immediately after reconstructive surgery had poor cosmetic results. Three observations could be made: (a) when the implanted breast was free of fibrotic changes, radiotherapy produced acceptable results, (b) whenever feasible, 45 Gy/5 weeks seemed preferable over higher doses, (c) irradiation immediately after the reconstructive surgery appeared to produce poorer cosmetic results.

Long-range results for breast cancer patients treated by radical mastectomy and postoperative radiation without adjuvant chemotherapy: an update.

Between 1963 and 1977, 941 patients with carcinoma of the breast received, at the University of Texas M.D. Anderson Cancer Center, peripheral lymphatic irradiation alone or with chest wall irradiation after a radical or modified radical mastectomy. None of the patients received adjuvant chemotherapy. The incidence of patients with histologically involved axillary nodes was 70%. The lymphatics of the apex of the axilla, of the supraclavicular area, and of the internal mammary chain were irradiated in patients with histologically positive axillary nodes and/or in patients with central or inner quadrant primaries regardless of the axillary status. When in 1963 an electron beam became available, chest wall irradiation has been added to the peripheral lymphatics irradiation, primarily when there was a heavy infestation of the axillary nodes. The disease-free survival curves tend to flatten out at 10 years. At 10 and 20 years, the disease-free survival rates are respectively 55% and 50% for all patients, 44% and 40% for all patients with positive nodes, 56% and 48% for the patients with one to three positive nodes, and 33% and 30% for the patients with four or more positive nodes. The comparison of the mortality curves between the general population and the breast cancer patients seems to indicate a cured fraction, since the curves become parallel at 17 years. The highest incidence of failures is between 0 and 5 years, still a significant incidence between 5 and 10 years, but after 10 years the incidence of failures is relatively small.

Evaluation of a total scalp electron irradiation technique.

A dosimetric evaluation of a total scalp electron-beam irradiation technique that uses six stationary fields was performed. The initial treatment plan specified a) that there be a 3-mm gap between abutted fields and b) that the field junctions be shifted 1 cm after 50% of the prescribed dose had been delivered. Dosimetric measurements were made at the scalp surface, scalp-skull interface, and the skull-brain interface in an anthropomorphic head phantom using both film and thermoluminescent dosimeters (TLD-100). The measurements showed that the initial technique yields areas of increased and decreased dose ranging from -50% to +70% in the region of the field junctions. To reduce regions of nonuniform dose, the treatment protocol was changed by eliminating the gap between the coronal borders of abutted fields and by increasing the field shift from 1 cm to 2 cm for all borders. Subsequent measurements showed that these changes in treatment protocol resulted in a significantly more uniform dose to the scalp and decreased variation of doses near field junctions (-10% to +50%).

The influence of pathologic tumor characteristics on locoregional recurrence rates following mastectomy.

PURPOSE: The objective of this study was to evaluate the influence of pathologic factors other than tumor size and number of involved axillary nodes on the risk of locoregional recurrence (LRR) following mastectomy. PATIENTS AND METHODS: We reviewed the medical records of 1031 patients treated with mastectomy and doxorubicin-based chemotherapy without radiation on 5 prospective clinical trials. Median follow-up was 116 months (range, 6-262 months). RESULTS: Patients with gross multicentric disease were at increased risk of LRR (37% at 10 years). However, patients with multifocal disease and those with microscopic multicentric disease did not experience higher rates of LRR than those with single lesions (17% at 10 years). Patients with lymph-vascular space invasion (LVSI) or involvement of the skin or nipple also experienced high rates of LRR (25%, 32%, and 50%, respectively). The presence of close (<5 mm) or positive margins was associated with an increased risk of LRR (45%). The increased risk of LRR observed for patients with pectoral fascial invasion (33%) was not reduced when negative deep margins were obtained. On multivariate analysis, the presence of 4 or more involved axillary nodes, tumor size of greater than 5 cm, close or positive surgical margins, and gross multicentric disease were found to be independent predictors of LRR (all, p < 0.01). In a separate analysis including only patients with 1-3 involved axillary nodes, microscopic invasion of the skin or nipple, pectoral fascial invasion, and the presence of close or positive margins were significant predictors of LRR. CONCLUSION: In addition to the extent of primary and nodal disease, other factors that predict for high rates of LRR include the presence of LVSI, involvement of the skin, nipple or pectoral fascia, close or positive margins, or gross multicentric disease. These factors predict for high LRR rates regardless of the number of involved axillary nodes.

Radiation induced osteochondroma in long-term survivors of childhood cancer.

The records of 200 long term survivors of childhood cancer where reviewed. Radiation induced osteochondromata were detected in 12 patients (6%). Radiation had been administered in doses ranging from 1250 R (approximately 1500 rad) to 5500 rad between the ages of 8 months and 11 1/2 years. Radiation-induced osteochrondromata were detected 3 to 13 1/2 years later, with a median of 5 years. The osteochrondomata were single in 7 patients and multiple (2-4) in 5. Two occurred at sites of previous thoracotomy. Factors related to radiation induced osteochondromata are discussed.

Spinal cord dose reduction using an anterior 13 MeV electron field situated between a split anterior 60Co supraclavicular field.

As part of the treatment for lymphoma, disease involving the supraclavicular region has been treated with megavoltage 60Co photons to a midline dose of 30 to 45 Gy through an anterior involved field and a supplementary posterior field when necessary. The spinal cord was shielded with a 5 cm lead block during treatment to the posterior field. A typical 40 Gy treatment results in a dose to the lower cervical and upper thoracic spinal cord in the range of 22 to 26 Gy, a level that could compromise subsequent mediastinal treatment in the event of a relapse. To reduce this cord dose, the midportion of the anterior supraclavicular 60Co To reduce this cord dose, the midportion of the anterior supraclavicular 60Co field was replaced with a high-energy (13 MeV) electron port, which reduces the dose to the cord to below 6 Gy in the average adult patient. This modification of the routine supraclavicular treatment allows greater flexibility in future treatment in the event of a mediastinal relapse.

The role of limited surgery with irradiation in primary treatment of ductal in situ breast cancer.

The results of management of ductal carcinoma in situ with limited surgery and radiotherapy are presented at a median follow-up of 92 months. In 44 treated breasts the actuarial 10-year loco-regional control rate was 91%, four patients having recurred. Each loco-regional failure was due to invasive carcinoma and three of the affected patients have developed metastases. No patient developed metastases without previous clinically-evident invasive loco-regional disease. The 10-year disease-specific survival rate was 96%. Previous publications have shown that the 25% or greater risk of local failure after limited excision of ductal carcinoma in situ can be reduced by irradiation of the breast. Our results demonstrate that good loco-regional control is maintained in the longer term.

Locally advanced breast cancer treated with neutron beams: long-term follow-up in 28 patients.

Between 1972 and 1978, 28 patients with locally advanced breast cancer were treated, 15 with neutron beams only and 13 with mixed neutron and photon beams. Half the patients had inflammatory cancer. For neutrons only, doses ranged between 13.35-25.34 nGy. In mixed-beam regimens, the prescribed total dose ranged between 62 and 76 Gy photon equivalent. Nine patients (32%) had a complete response without local recurrence for the duration of their survival ranging from 1 to 14+ years; 18 patients had a partial response (64%); and one patient had no change. Late toxicity was high: of 24 patients who received tangential breast irradiation, 5 (21%) had ulceration of the breast or chest wall, or both. In four patients, mastectomy and skin grafts were necessary for repair. In only one patient did the skin necrosis heal without corrective surgery. Twelve patients received axillary neutron irradiation, resulting in severe edema in four patients, and brachial plexopathy in six patients. Radiation-induced complications progressed steadily for the duration of the patients' survival after the neutron irradiation. The high complication rate encountered is attributed to high doses resulting from an under estimation of the relative biological effect of the neutron beam for late effects, and to the poor physical and geometrical characteristics of the neutron beam.