Leslie E. Botnick

Cosmetic results following primary radiation therapy for early breast cancer

In order to assess the cosmetic results of treatment, the results in 239 patients with early breast cancer treated by primary radiation treatment without adjuvant chemotherapy were reviewed. Four patients had bilateral cancers, making a total of 243 breasts available for analysis. Follow‐up ranged from 24 to 78 months with a median of 33 months. The parameters measured were breast edema, retraction, telangiectasia, arm edema, and the overall cosmetic appearance. The cosmetic results declined over the first 3 years after treatment, but then stabilized. At 5 years, the overall cosmetic results were judged by physicians as excellent in 77%, good in 9%, fair in 9%, and poor in 5%. A fair or poor cosmetic result was highly correlated with the development of moderate or severe breast retraction. Telangiectasia was uncommonly the only cause of a fair or poor cosmetic result. Breast and arm edema were rarely noted to be significant, but were more common in patients who underwent axillary dissection. In 210 cases, a supplementary boost dose of radiation was delivered to the primary tumor area, and in 33 cases a boost was not used. This boost consisted of an interstitital iridium‐192 implant in 204 cases and either high‐energy photons or electrons in the remainder. At 4 years, no patient treated without a boost had a fair or poor result compared with 22% who received a boost (P = 0.13). The conclusion is that, in general, primary radiation treatment provides highly satisfactory cosmetic results for patients with early breast cancer.

ANTI-B1 MONOCLONAL ANTIBODY AND COMPLEMENT TREATMENT IN AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR RELAPSED B-CELL NON-HODGKIN'S LYMPHOMA

Eight patients with relapsed B-cell non-Hodgkins lymphoma were treated with intensive chemoradiotherapy and reconstituted with autologous bone marrow rendered free of tumour cells by the B-cell-specific monoclonal antibody anti-B1 and complement. Before the autologous marrow transplantation patients were induced with chemotherapy, radiotherapy, or both, into a minimum disease state with less than 5% bone-marrow involvement with tumour. All patients treated achieved a complete clinical response and had stable haematological engraftment by 8 weeks. No significant acute or chronic toxic effects have occurred. B cells could be detected by 2 months after transplantation and normal immunoglobulin levels were achieved by 6 months. Six of eight patients are disease free in unmaintained remission more than 20, 19, 10, 8, 5, and 3 months after transplantation.

Intraductal carcinoma of the breast: results of treatment with excisional biopsy and irradiation.

Between 1976 and 1983, 40 women with intraductal carcinoma of the breast without invasion underwent excisional biopsy and irradiation as an alternative to mastectomy. The median age was 53 years (range, 28 to 77 years) and the median follow-up time since initiation of radiation was 44 months (range, 14 to 97 months). Twenty-seven patients presented with a palpable mass; in 13 patients the tumor was detected only by mammography. A limited axillary dissection was performed in 13 patients, and all lymph nodes removed were negative. Treatment was administered to the breast and adjacent chest wall to a dose of 4,600 to 5,000 rad, with 26 patients also receiving a boost dose of 1,000 to 2,000 rad to the site of the primary. Four patients have developed a recurrence in the treated breast, at 17, 19, 35, and 63 months after the beginning of radiation therapy. The 5-year actuarial rate of local recurrence is 10%. Three of the recurrences were in those four patients who presented with a nipple discharge and a central primary. In two cases, the recurrence consisted of only intraductal carcinoma; in the other two, both intraductal and invasive cancer were found. All four patients with recurrence underwent mastectomy and are well without evidence of distant metastases at 1, 12, 15, and 15 months since mastectomy. Cosmetic results were excellent. No patient has developed distant metastases. Since the number of patients treated is small and the period of follow-up is short, one must be cautious in the interpretation of these results. Nonetheless, the treatment of intraductal carcinoma of the breast by excision and irradiation appears to give acceptable local control and excellent survival when suitable precautions of patient selection and evaluation are taken.

Primary radiation therapy for early breast cancer: The experience at the joint center for radiation therapy

Abstract The results of primary radiation therapy in 176 consecutive patients with clinical Stage I and II carcinoma of the breast were reviewed. Median follow-up time was 47 months. The overall breast relapse rate was 7%. Patients undergoing interstitial implantation had a significantly lower breast relapse rate (1%) than patients not undergoing implantation (11 %). Breast relapse was more common in patients undergoing incisional or needle biopsy (17 %), compared to patients treated after excisional biopsy (5 %). In patients undergoing excisional biopsy, but not interstitial implantation, breast relapse was related to external beam dose. Twelve percent of the patients who received less than 1600 ret dose relapsed in the breast, compared to none of the 19 patients who received more than 1700 ret dose. These results imply that supplemental irradiation to the primary tumor area is required following excisional biopsy of a primary breast cancer when 4500–5000 rad is delivered to the entire breast.

An evaluation of long-term survival and treatment complications in children with Hodgkin's disease

Between April 1969 and July 1977, 83 patients, 16 years or younger, with pathologically staged IAIIIB Hodgkins disease were seen and treated at the Joint Center for Radiation Therapy. The five‐year actuarial relapse‐free and overall survivals were 82 and 95%, respectively, with a median follow‐up from diagnosis of 65 months. Relapse occurred in 6/50 Stage IA–IIA, 2/9 Stage IIB, 4/9 Stage IIIA, and 3/15 Stage IIIB patients. Of patients who relapsed, 11/15 are currently disease‐free following retreatment with chemotherapy. Nine patients with Stage IV disease were also evaluated. Four of seven patients initially treated with chemotherapy remain free of disease. Forty‐two patients in this study were treated with mantle and para‐aortic irradiation alone, thus avoiding the risk of sterility associated with pelvic irradiation or MOPP chemotherapy while retaining a high probability for long‐term diseasefree survival. Complications of radiation therapy included growth retardation and thyroid function abnormalities in some patients. Standing height measurements were normal regardless of age at initial treatment, however, 16 of 23 patients 3–12 years old at initial treatment had sitting heights measuring more than one standard deviation below the mean. Intraclavicular distances were shortened in some patients and examples are shown. Thyroid stimulating hormone levels were elevated in 21 of 37 patients evaluated. Radiation therapy, without adjuvant chemotherapy remains an important treatment approach for children with early stage Hodgkins disease.

Stem cell depletion: An explanation of the late effects of cytotoxins

Abstract It is proposed that both the acute and the late effects of radiation and cytotoxic chemotherapy are due to cell depletion of the major target cell renewel tissues such as the skin, gastro-intestinal mucosa and bone marrow. Acute effects depend on the balance between cell killing and compensatory cellular replication of both the stem and proliferative compartments. The development of late effects requires that stem cells have only a limited proliferative capacity. Compensation for extensive or repeated cell killing may exhaust this capacity resulting in eventual tissue failure. This can be observed clinically as mucosal or skin ulceration and bone marrow aplasia.

A long lasting proliferative defect in the hematopoietic stem cell compartment following cytotoxic agents

Abstract We have reported a significant proliferative defect caused by busulfan and L-phenylalanine mustard (L-PAM) while cyclophosphamide and 5-fluorouracil (5-FU) did not cause such a defect as measured by serial transplantation of bone marrow up to 110 weeks after drug administration. If the proliferative capacity of the initial colony-forming units (CFU-S) as expressed by the ratio (Rs) of the number of CFUs recovered (after 14 days) compared to the number seeding the hind limb prior to transplantation is determined, one finds that the R S correlates with the defect in serial transplantation. Thus, damage to the proliferative capacity of the hematopoietic stem cell caused by chemotherapeutic agents can be expressed in terms of R S , a measure of the self-renewal potential of the stem cell compartment. If R S is assessed after a single drug injection, the pattern of the rise and decline of R S with time following injection offers an efficient method of classifying drug injury to the CFU-S compartment. Busulfan was found to be the most damaging since it killed the most primitive stem cells preferentially. 5-FU was found to be the least damaging to the proliferative capacity of the stem cell compartment while BCNU and cyclophosphamide damaged it in an intermediate way. Therefore, busulfan would be expected to be most damaging to the normal hematopoietic tissue, followed by BCNU, cyclophosphamide and 5-FU in descending order of risk.

Stages I--III Hodgkin's disease in children: results of staging and treatment.

Fifty‐two children with clinical stages I‐III Hodgkins disease were evaluated for disease extent between April 1969 and March 1975. All underwent laparotomy and splenectomy. Two patients with liver involvement were excluded. Thirty of 31 patients with pathologically staged IA‐IIA disease have been in continuous complete remission after mantle and para‐aortic irradiation. There have been no extensions into the untreated pelvis. Fourteen of 15 patients with pathologic stages IIB and IIIB disease show no evidence of relapse after TNI and MOPP. Three of four patients with stage IIIA disease developed nodal relapse after irradiation; all are alive without evidence of disease after re‐irradiation (3) and MOPP (2). Thus 45 of 50 patients (90%) have remained continuously free of disease after completion of the planned treatment, and overall 49 of 50 (98%) are alive without evidence of disease. Such results justify continuation of our staging and treatment philosophy in children with Hodgkins disease.

An evaluation of total nodal irradiation as treatment for stage III a Hodgkin's disease

Between April 1969 and December 1974, 37 patients with surgically staged III A Hodgkins disease were treated with total nodal irradiation (TNI). Their probability of relapse‐free survival at 7 years is 51% and overall survival 82% with the majority of patients remaining disease free after retreatment with MOPP (10 of 16). In contrast, 21 stage III B patients treated with TNI and MOPP chemotherapy over the same time period have a relapse‐free survival of 74% and overall survival of 91%. Because of superior results in treating stage III B patients with combined modality treatment, we feel that a relapse‐free survival of 51% may not justify continuation of TNI as the only modality of treatment for patients with stage III A disease, and we have initiated a trial of combined radiation therapy and MOPP chemotherapy in these patients. The most effective treatment of stage III A Hodgkins disease, however, remains uncertain and depends both on the ultimate risk of combined modality treatment and the success of retreatment following relapse after radiation.

Axillary sampling in the definitive treatment of breast cancer by radiation therapy and lumpectomy

Between January, 1967 and July, 1980, 176 women who were referred to the Joint Center for Radiation Therapy (JCRT) for definitive breast irradiation underwent low axillary dissection. A typical operative technique is described. The dissection stops short of the axillary vein although the vein is usually visualized. One hundred thirty-two axillae were thought to be N0 or N1a. Forty-six axillae were felt to be N1b. Seventeen percent of the T1 N0 patients had pathologically positive nodes. Twenty-seven percent of the T2 N0 patients had positive nodes. When 5 or less nodes were removed at axillary sampling the incidence of nodal involvement was very low. There were no differences in nodal positivity when comparing upper quadrant to lower or central lesions. Lateral lesions appeared to have higher positivity rates compared with either medial or central lesions. Ninety-four percent of axillae with N1b lesions were pathologically confirmed. The complication rate for this procedure was low. There were 5 transient non-surgical complications and 1 cellulitis resulting in a frozen shoulder, which required corrective surgery. There were no cases of moderate or severe arm edema. Axillary sampling is compared to axillary dissection as a diagnostic procedure. Axillary sampling may underestimate the true pathologic positive rate, but diagnostic accuracy appears excellent if level 1 and 2 nodes are sampled.