Barbara Fineberg

Plasmacytoma. Treatment results and conversion to myeloma

Forty‐six cases of solitary plasmacytoma were reviewed for response to radiation and progression to multiple myeloma. Cases were classified as solitary plasmacytomas of bone (SPB) (32 cases) or extramedullary plasmacytomas (EP) (14 cases). There was an overall 93% response rate of the tumor to radiation therapy: 62% had a complete response after radiation therapy, whereas 31% had a partial response. Conversion to multiple myeloma was influenced by the type of plasmacytoma; 53% of the patients with SPB converting to myeloma versus 36% of the patients with EP. Time from diagnosis to conversion for patients with SPB showed no evidence of plateau, with conversion continuing to occur even after 17 years. The median survival time for patients after conversion to myeloma was 14.5 months and was not affected by time to conversion. Serum protein level, presence of monoclonal gammopathy, and size of primary lesion were of some prognostic significance in predicting conversion to myeloma. Adjuvant chemotherapy did not affect the incidence of conversion but did appear to delay conversion to myeloma. Seven patients in whom multiple sequential solitary plasmacytomas developed formed a distinct subset, with a median time to a second plasmacytoma of 63 months. In three of these patients, conversion to myeloma occurred subsequently. This study supports the idea of EP having a lower incidence of conversion to myeloma and a different natural history from SPB, with SPB likely to be multiple myeloma in evolution. Cancer 1992; 69:1513‐1517.

Prognostic indicators in patients with isolated local–regional recurrence of breast cancer

A retrospective review was undertaken of 129 patients with isolated local‐regional recurrence of breast cancer following radical or modified radical mastectomy. The overall survival and disease‐free survival for these patients five years from the time of local‐regional recurrence was 36 and 13%, respectively. The clinical stage at initial diagnosis, the number of histologically positive nodes at mastectomy, menopauseal status, and the location of the recurrence (chest wall vs. nodal) were all found to have no significant effect on survival or disease‐free survival. On the other hand, the number of recurrences, the size of the largest recurrence, and the time interval between mastectomy and recurrence (disease‐free interval) had definite prognostic significance. A single recurrence, the size of the largest recurrence being ≥ 1 cm, and a disease‐free interval of longer than 24 months predicted a good prognosis; on the other hand, multiple recurrences, the size of the largest recurrence being <1 cm, and a disease‐free interval of less than 24 months predicted a bad prognosis. Eighty‐one percent of the patients ultimately developed distant metastases; the incidence of distant metastases was the same for patients with factors predicting a good prognosis as it was for those with factors predicting a bad prognosis. The time to appearance of distant metastases, however, was significantly longer in the former group of patients than in the latter. The information from this analysis should be useful in designing future clinical trials involving patients with isolated local‐regional recurrence of breast cancer.

Analysis of failures following local treatment of isolated local-regional recurrence of breast cancer

Abstract Obe hundred fifty-seven patients with local-regional recurrence of breast cancer but without co-existing distant metastases were reviewed. The incidence of failure to control the local-regional recurrence was essentially the same whether the recurrence was treated with radiotherapy alone (62% ), surgery alone (76% ), or with a combination of the two (60 % ). A detailed analysis of the failures occurring in the patients treated with radiotherapy, with or without surgery, showed that most of the failures were because of a) inadequate doses of irradiation, b) the use of fields that were too small, and c) the lack of elective irradiation to the chest wall and supraclavicular fossa. Of the 100 patients with uncontrolled local-regional disease, 62% developed clinical symptoms that markedly impaired the quality of life. All of these symptoms were directly caused by the uncontrolled local-regional disease. Specific recommendations for the treatment of isolated local-regional recurrence are made.

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.

RADIATION THERAPY FOR GLIOMAS OF THE OPTIC NERVE AND CHIASM

Thirty-three patients with optic glioma seen over a 30-year period were reviewed. Five patients (15%) had tumor confined to the optic nerve, 8 patients (24%) had optic nerve and chiasmal involvement, and the remaining 20 patients (61%) had invasion of contiguous structures as well as chiasmal involvement. Eleven patients (33%) had a history of neurofibromatosis. Two-thirds of the patients had either a biopsy or a partial resection of the tumor, with the remaining one-third being clinically diagnosed. All patients received irradiation to local fields. The median dose was 5040 cGy in 160 cGy fractions. Of patients alive at last follow-up, the median time of follow-up was 12.3 years. The 5-, 10-, and 15-year overall actuarial survivals were 94, 81, and 74%, respectively. Univariate and multivariate analysis were performed on the following clinical variables: extent of primary tumor, extent of surgery, dose of radiation, gender, race, age, and presence or absence of neurofibromatosis. Extension of the primary lesion to the optic chiasm and age less than or equal to 15 years were the only two variables to have statistically significantly inferior 15-year progression free survivals by multivariate analysis. Eighteen (55%) patients had treatment related complications with most involving the pituitary gland. We conclude that postoperative radiotherapy is beneficial in patients with chiasmal involvement and those with incomplete resections. A minimum tumor dose of 4000 cGy is recommended.

Breast Reconstruction in Women Treated with Radiation Therapy for Breast Cancer: Cosmesis, Complications, and Tumor Control

The records of 55 patients who had breast cancer treated by mastectomy, irradiation, and breast reconstruction were reviewed for cosmetic outcome, complications, and tumor control. Median follow-up was 35 months. Local control rates were 95 percent in patients treated for high risk factors or breast conservation and 85 percent in patients treated for recurrent breast cancer. Acceptable cosmetic results were obtained in only 42 percent of patients. The incidence of complications was 55 percent. Transverse rectus abdominis muscle (TRAM) reconstructions gave superior cosmetic results compared with all other types of reconstructions. The timing of reconstruction in relation to mastectomy or radiation therapy did not significantly influence cosmetic outcome, although other factors suggest that delayed reconstruction may give better results. A majority of patients were satisfied with cosmetic outcome.

Breast conservation therapy for intraductal carcinoma of the breast

PURPOSE Between 1979 and 1987, 76 women with 77 ductal carcinomas in-situ of the breast were evaluated by The Radiation Oncology Center after breast conservation surgery. METHODS AND MATERIALS Seventy breasts (91%) had tylectomy and irradiation and seven breasts (9%) had tylectomy alone. Median follow-up was 4.0 years, with a range of 2-10 years. Fifty patients (65%) had occult lesions discovered by mammography with a median mammographic size of 0.9 cm. The twenty-six patients with presenting symptoms had a median clinical tumor size of 1.95 cm. All patients had local excision of the primary tumor. Of 15 patients who had axillary dissections, one had nodal metastasis. Seventy breasts were irradiated. Seven patients refused radiotherapy. RESULTS Overall 5-year actuarial survival was 99%; 5-year actuarial disease-free survival was 89%; the 5-year actuarial intramammary tumor control rate for irradiated patients was 93% vs. 57% for patients not irradiated (p < 0.001). Comedocarcinoma had a 5-year actuarial tumor control rate of 75%, 88% in the irradiated group as compared to 98% for all other histologic subtypes of ductal carcinoma in situ (p < 0.03). All six patients with local failure were successfully salvaged by further surgery. Multivariate analysis revealed significant factors in local control to be (a) radiotherapy, (b) comedocarcinoma histology, and (c) menopausal status. CONCLUSIONS Although the number of patients treated is small, and follow-up time is limited, these early results support the contention that the treatment of ductal carcinoma in situ by excision and irradiation is an acceptable alternative to mastectomy. We urge caution in treating patients with the comedocarcinoma subtype and counsel these patients to have more treatment than excision alone.

Irradiation alone or combined with hyperthermia in the treatment of recurrent carcinoma of the breast in the chest wall: a nonrandomized comparison

Tumour response and control (freedom from local relapse) were compared in two non-randomized groups of patients with recurrences from carcinoma of the breast (95 per cent in the chest wall and 5 per cent in the axillary or supraclavicular lymph nodes) receiving treatment at the Mallinckrodt Institute of Radiology. One group, comprising 48 patients treated between March 1978 and December 1984, received varying doses of irradiation (2000-4000 cGy in fractions of 400 cGy every 72 h) followed by local microwave hyperthermia (41-43 degrees C, 30-60 min). Irradiation was usually delivered with electrons ranging from 9 to 16 MeV. Hyperthermia was administered with 915 MHz external microwaves. The second group of 116 patients, with lesions similar to those treated with hyperthermia and irradiation, were treated with irradiation alone between January 1964 and December 1984. Doses of irradiation ranged from 2000 to 6000 cGy, usually delivered in daily fractions of 200-300 cGy TD. Irradiation was administered with Cobalt-60, 4 MeV photons or electrons (9-13 MeV) and occasionally with superficial X-rays. Patients with lesions 1-3 cm in diameter treated with irradiation and hyperthermia exhibited a complete tumour response rate of 80 per cent (12/15) while patients receiving irradiation alone had a complete response rate of 33 per cent (P = 0.04, Fisher exact test, two tail). The complete response rate for tumours larger than 3 cm treated with irradiation and heat was 65 per cent (13/20) compared to 42 per cent (18/43) for lesions receiving irradiation alone (P = 0.1, Fisher exact test, two tail).(ABSTRACT TRUNCATED AT 250 WORDS)

Radiotherapy and breast reconstruction: clinical results and dosimetry

Immediate or delayed reconstruction using implants or autologous tissue transfer is increasingly offered to women undergoing mastectomy for breast cancer. Some patients require radiotherapy for prevention of local/regional relapse, and some for post-surgical local/regional recurrence. Others with augmented breasts may opt for conservative surgery and irradiation. At Washington University, 70 breast cancers were irradiated in 66 patients following mastectomy with reconstruction (N = 61) or wide local excision of an augmented breast (N = 5). Two patients elected to have a second reconstruction after an unsatisfactory initial result. Thus, 72 breasts were evaluated after radiotherapy for tumor control, complications, cosmesis, and patient satisfaction. Locoregional failure occurred in only five patients, one following adjuvant radiotherapy after mastectomy with reconstruction and four following radiotherapy for recurrent breast cancer within a reconstructed breast. Grade 2 or 3 complications occurred in 34 patients (51%). The complication rate was highest in autologous tissue transfer reconstructions. Cosmetic results were evaluated good/excellent in 49% by physicians and 67% by patients. Immediate reconstructions had fewer good/excellent physician evaluations (32%) compared with reconstructions performed at least 6 weeks after radiotherapy (55%). Transverse rectus abdominis flaps had the best cosmesis scores, followed by permanent silicone prostheses, tissue expanders, latissimus dorsi, and gluteal flaps. Only 48% of patients would choose to have the same reconstructive procedure again. Phantom interface dosimetry with a parallel plate chamber and TLD measurements was performed. Radiotherapy and reconstruction are not incompatible, but careful consideration of their relative timing and technique appear to be important in optimizing cosmesis while minimizing complications.