Ductal carcinoma in situ of the breast: results of treatment by conservative surgery and definitive irradiation.

PURPOSE: To determine local control, survivorship, and cosmesis in women with ductal carcinoma in situ treated by conservative surgery and radiation therapy. METHODS AND MATERIALS: We retrospectively analyzed the results of treatment in 56 women with in situ carcinoma of the breast, treated between 1976 and 1990 by conservative surgery and irradiation. Two women had bilateral tumors, for a total of 58 breasts at risk. All patients underwent gross excision of the tumor followed by radiation to the entire breast and a sequential boost to the tumor bed. Eight of the 21 evaluable tumors (38%) had inadequate pathologic margins at the time of excision. Routine re-excision was not performed. The median dose to the whole breast and primary tumor site was 5000 cGy and 6940 cGy, respectively. Median follow-up was 61 months (range 27-191 months). RESULTS: Five patients (9%) failed in the breast for an 8-year actuarial local failure rate of 11%. Median time to failure was 34 months. All five patients with local recurrence underwent mastectomy and are alive, without evidence of disease at a mean of 40 months post mastectomy. The 8-year actuarial absolute and cause specific survivals were 89% and 100%, respectively. Cosmetic results were excellent or totally acceptable in 90% of patients. CONCLUSION: Patients with ductal carcinoma in situ treated by excision and irradiation achieved acceptable local control and excellent survival and cosmetic results. Because of the long time course associated with local failure, diligent and protracted follow-up is mandatory.

Status of radiation treatment of prostate cancer at Stanford University.

Over 900 patients have been treated with radiation therapy in the 30-year Stanford prostate study. Overall survival, i.e., scoring death due to all causes, was 45%, 35%, 33%, 20%, and 10% for Stanford stages T0, T1, T2, T3, and T4 (nominal stages A, B1, B2, C) at 15 years; lymph node status was unknown. Disease-specific survival at 15 years was 85%, 64%, 45%, 33%, and 15%, respectively, for the same patients. In 141 patients with restricted nodular disease (lymph node status unknown) equal to or less than one-half of one lobe involved (stage B1), the 15-year overall survival was 50% and identical to the expected survival of an age-matched cohort of males. Potency was preserved in 86% of the patients at 15 months posttreatment, and 50% of the patients maintained erectile potency for 7 years posttherapy. Other sequelae and complications are analyzed. The incidence of second neoplasms did not exceed expectations for an age-matched population.

Selecting initial therapy for prostate cancer. Radiation therapy perspective.

External-beam irradiation of prostatic cancer was introduced at Stanford in 1956. The program has sought to determine the following: whether prostatic carcinoma can be cured by external beam radiation therapy, with what frequency this can be accomplished, which patients are best suited for irradiation, and what technique best accomplishes the irradiation. This report deals with differences and similarities between radiation therapy and surgery, and emphasizes the selection of patients for irradiation.

Radiotherapy of prostatic carcinoma: long- or short-term efficacy (Stanford University experience).

Results of a study that began at Stanford in 1956 demonstrate that long-term, disease-free survival can be achieved following appropriate irradiation in patients with prostatic carcinoma. However, the investigation has also uncovered several powerful prognostic indicators, such as the extent of anatomic involvement, histologic pattern, particularly as described by Gleason; and presence or absence of lymphnode metastases. To illustrate the importance of these parameters, the author presents data that correlate survival with the anatomic extent of the primary tumor and the Gleason pattern scores. Of the staged patients, 64 have been subjected to post-therapeutic biopsy of the prostate 18 months or more following therapy. A correlation also seems to exist among clinical stage, lymph node involvement, and subsequent biopsy status. The implication of this finding in the development of more aggressive therapeutic approaches will be discussed.

External beam radiation salvage for residual or recurrent local tumor following radical prostatectomy.

External beam radiation therapy was used as a means of salvage in 32 patients with either incomplete excision or palpable local recurrence following radical prostatectomy. Patients were divided into 2 groups consisting of 13 patients who were referred within 4 months of incomplete excision (group 1) and 19 who were referred only after palpable local recurrence had developed (group 2). The 5 and 10-year actuarial survival free of disease in group 1 was 57 per cent, compared to 40 and 20 per cent for group 2 (p equals 0.05). Fourteen patients with an elevated pre-radiation therapy serum acid phosphatase level and/or bladder invasion had an especially poor prognosis, with a median survival free of disease of only 2.4 years. Ten complications were recorded in 5 patients (16 per cent), which were slightly higher than experienced in irradiated patients without a previous radical operation. The data support the contention that external beam radiation therapy may offer a means of post-radical prostatectomy salvage for selected patients with incomplete excision or palpable local recurrence. The best results were obtained in patients who were referred within 4 months of prostatectomy because of incomplete excision rather than waiting for palpable local recurrence to develop.

Impact of adjuvant chemotherapy on cosmesis and complications in stages I and II carcinoma of the breast treated by biopsy and radiation therapy.

Cosmesis and complication rates were examined in patients with early stage carcinoma of the breast treated by biopsy and radiation therapy with and without adjuvant chemotherapy in an attempt to determine the effect of chemotherapy upon these parameters. Between April 1, 1975 and June 1, 1980, 51 patients were treated with radiation therapy and adjuvant chemotherapy (XRT + ACT) and 83 patients with radiotherapy alone (XRT). Chemotherapy usually consisted of cytoxan, methotrexate and 5-fluorouracil for 6 or 12 cycles. Minimum follow-up was 36 months. Cosmetic results deteriorated with time in both groups but to a greater extent in the XRT + ACT group. At 36 months, excellent cosmetic results were obtained in 73 of the 83 patients (88%) in the XRT group compared to 37 of 51 patients (73%) in the XRT + ACT group (p = less than .05). Comparison of the two treatment groups revealed that complication rates were significantly increased in the XRT + ACT group. Of the 51 patients in the XRT + ACT group, 21 patients (41%) suffered complications compared to 8 (10%) of the 83 patients in the XRT group (p = less than .001). This difference in complication rates resulted primarily from an increased incidence in the XRT + ACT group of wet desquamation in the electron beam portal used to treat the internal mammary lymph nodes and a trend towards a higher incidence of spontaneous nonpathologic rib fractures, myositis and arm edema. An increased incidence of nonbreast primary cancers was not seen. Our preliminary conclusions are that adjuvant chemotherapy has a negative impact upon cosmesis and complication rates in patients being treated with definitive radiotherapy. However, cosmetic results remain satisfactory and complication rates are maintained at an acceptable level. Continued close follow-up will be required before definitive conclusions can be reached as to the overall incidence and severity of the changes noted.

The effect of postoperative and primary radiation therapy on delivered dose of adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy in breast cancer.

The dose of adjuvant chemotherapy for breast cancer may be an important factor in the success of the treatment program. In a retrospective analysis, the authors determined whether patients who were irradiated either postoperatively (N = 29) or as part of primary treatment (N = 13) received a lower dose of adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy than patients who were not irradiated (N = 42). The 84 evaluable patients received either cyclical or weekly CMF. Radiation therapy included the chest wall or breast and regional lymph nodes. The mean percentage of maximum chemotherapy dose delivered (59.9% versus 73.5%; P less than 0.001), mean percent prescribable or theoretical maximum dose (83.1% versus 91.3%; P less than 0.001), and mean leukocyte count (3.9 versus 4.5; P less than 0.01) during therapy were statistically significantly lower in irradiated patients. The lower delivered chemotherapy dose in irradiated patients was not related to the radiation dose to the thoracic spine. The authors conclude that radiation therapy to the chest wall or breast and regional lymph nodes reduces the dose of adjuvant CMF that can be delivered.

Biopsy and definitive radiation therapy in Stage I and II adenocarcinoma of the female breast: analysis of cosmesis and the role of electron beam supplementation.

The cosmetic and functional outcome in 130 patients with Stages I and II carcinoma of the breast treated by biopsy and radiation therapy were evaluated. The cosmetic outcome was excellent in 107 patients (82%), acceptable in 17 patients (13%), and unacceptable in six patients (5%). Complete axillary dissection (CAD) was more morbid than limited axillary dissection (LAD) as a means of preradiotherapy staging of the axilla. The former was more often associated with breast edema, hematoma formation, and subsequent development of arm edema than the latter. A multivariate analysis revealed that the four most dominant variables associated with the attainment of an excellent cosmetic outcome were: 1) the performance of a conservative biopsy procedure; 2) small breast size (cup size A and B); 3) the use of electron energies equal to or less than 12 MeV; and 4) the presence of primary tumors less than or equal to 4 cm in diameter when adjusted for breast size. Postexternal beam supplementation to the area of the primary tumor was accomplished with electrons in 107 patients (82%) and with interstitial implantation in 23 patients (18%). Excellent cosmetic results were achieved in 97 of the 107 patients (91%) treated with electrons. The use of electrons appears to produce local control and cosmesis equal to that of interstitial implantation if specific indications and guidelines are followed, and is superior to implantation in certain clinical settings.

Biopsy and definitive radiation therapy in stages I and II carcinoma of the female breast.

One hundred-twenty patients with Stages I and II carcinoma of the female breast were treated by biopsy followed by definitive radiation therapy without mastectomy. The breast received 4500-5000 cGy (rad) using a 6 MV linear accelerator followed by a supplement to the area of the primary tumor of 2000 cGy (rad) using electrons in 99 patients (83%) and interstitial implantation in 21 patients (17%). Local recurrence was not recorded in the 43 patients with Stage I disease, while three of 77 patients (4%) with Stage II disease suffered a local recurrence. The actuarial five-year relapse-free survival was 91% and 60% in Stages I and II respectively. Cosmetic results were considered excellent by both physician and patient in the majority of cases. Axillary dissection was the recommended method of staging the axilla but was noted to be more morbid than axillary sampling. Electrons may be as effective as interstitial implantation as a means of supplementation following external beam therapy if specific guidelines are followed.

An evaluation of lymphography in localized carcinoma of the prostate.

Lymph node biopsies were positive in 20% (7/35) of stage T1 and T2 (stage B) tumors and 64% (21/33) of stage T3 (stage C) tumors in 69 previously untreated and unselected patients with apparently localized carcinoma of the prostate. One patient with a To (stage A) tumor had no evidence of lymph node metastasis. Prospective analysis demonstrated an overall lymphographic accuracy of 78%, sensitivity of 57% and specificity of 92%. The detection of lymph node metastases in the lymphogram is limited by the frequency of microscopic metastasis and the frequency of benign changes within pelvic lymph nodes in this older patient population. Diagnostic criteria for metastatic disease which gives a low incidence of false-positive interpretations should be maintained, since relaxing the criteria will not necessarily improve the detection rate of metastases and would decrease specificity.

Evaluation of extended-field radiotherapy for prostatic neoplasm: 1976 progress report.

These observations show that short-term, disease-free survival is (a) excellent (86.5%) in patients with negative lymph node biopsies, (b) greatly diminished (30%) in patients with positive para-aortic and pelvic lymph node biopsies, and (c) intermediate (71.5%) in patients with positive pelvic lymph node biopsies only in the pelvic region following extended-field radiation therapy of carcinoma of the prostate.

Operative staging of apparently localized adenocarcinoma of the prostate: results in fifty unselected patients. I. Experimental design and preliminary results.

The design and details of a prospective, randomized study protocol involving bipedal lymphography, and exploratory laparotomy with selective node biopsy in patients with apparently localized adenocarcinoma of the prostate are presented. The analysis includes the results of selected diagnostic tests, and an assessment of the accuracy of clinical vs. surgical staging in 50 unselected patients. Lymphatic metastases were found at the time of diagnostic laparotomy in 18 of the 50 patients (36%). Both increasing size (advanced T stage) and decreasing differentiation of the primary tumor were associated with an increased incidence of lymph node metastases. Of 25 patients with T1 and T2 tumors (Stage B), and 25 patients with T3 tumors (Stage C), lymphatic dissemination was found in 20 and 52%, respectively. Eleven of 20 patients (55%) with poorly differentiated tumors had lymph node metastasis, compared with only 2 or 11 patients (18%) with well-differentiated tumors. Twelve patients had a change in their clinical stage following exploratory laparotomy; in eight the stage was increased and in four it was decreased. Of 18 patients with lymphatic metastases, some of which were extensive and most of which were associated with increased serum acid phosphatase values, no evidence of concurrent bony or visceral dissemination was found. Although preliminary, this finding should stimulate the search for effective treatment in these patients who were previously thought to be incurable on the basis of probable vascular dissemination.

Gallium-67 citrate scanning in Hodgkin's disease and non-Hodgkin's lymphoma.

Gallium-67 citrate scintigraphy was performed in 33 patients with Hodgkin's disease and 25 patients with non-Hodgkin's lymphoma. Three hundred twenty-eight sites of potential involvement were investigated. Confirmation of involvement was made by physical examination, roentgenographic evaluation and histopathologic examination of tissue obtained at diagnostic laparotomy. The results of scintigraphy correlated with all other clinicopathologic data in only 35% of patients, the true-positive rate being significantly higher above the diaphragm (61%) than below (40%). The overall true-positive and true-negative rates were 53 and 90%, respectively. A significant correlation existed between tumor histology and scanning accuracy; the true-positive rate in Hodgkin's disease was 74% compared to only 13% in patients with lymphocytic lymphoma. A similar variation of 67Ga concentration with tumor histology was also noted in 70 tissue specimens obtained from 28 patients at the time of diagnostic laparotomy or biopsy. The routine use of 67Ga-citrate to detect splenic involvement with tumor appeared to be precluded by the low true-positive and high false-negative rates of 57 and 27%, respectively. Gallium-67-citrate scintigraphy may be useful as an adjunct to established clinical staging procedures in untreated patients and in the detection of recurrent disease in treated patients. Our data indicate it is not sifficiently reliable to replace established methods presently used for clinical staging.

Bladder cancer: results of radiation therapy in 384 patients.

Between 1957 and 1972, 384 patients with bladder cancers were treated initially with megavoltage radiation therapy. Actuarial five-year survival ranged from 35 to 42% for Stages A and B1 tumors, and was 35, 22 and 7%, respectively, for Stages B2, C and D carcinomas. Approximately 30-40% of deeply invasive tumors confined to the bladder can be controlled with radiation therapy alone, directed solely to the bladder itself.

External beam radiation therapy of primary carcinoma of the prostate.

During the past 10 years, some 15 publications have appeared in the English literature on the definitive radiotherapy of prostatic cancer. The long-term followup required for rational assessment of the treatment of prostatic cancer is not yet available for most of these studies. However, in the Stanford series, the direct disease-free survival at 5 years for patients with disease localized to the prostate is 70%; at 10 years, 42%. The direct disease-free survival at 5 years for patients with extracapsular extension in 36%, and at 10 years, 29%. Recently, mapping of potential lymph node metastases has been studies by several authors.Early results of extended-field irradiation required for regional treatment are presented.

External-bean megavoltage radiation therapy in the treatment of post-radical prostatectomy residual or recurrent tumor preliminary results.

High dose, external-beam megavoltage radiation therapy was administered to 21 patients because of incomplete excision (11 patients) or palpable local recurrence (10 patients) following radical prostatectomy. Of the 21 patients 8 were alive without clinical evidence of cancer for 29 to 97 months after radiation therapy. The best survival was in the 11 patients referred because of incomplete excision. Of these 11 patients 9 were alive, 6 without cancer, and 2 were dead of intercurrent disease without evidence of cancer. Of the 10 patients with palpable local recurrence 2 were alive without evidence neoplasm, while 2 died of intercurrent disease without cancer. Acute treatment-associated symptoms occurred in 11 of the 21 patients. Generally, these symptoms were mild and responded to conservative, symptomatic management. Two serious complications were recorded.