Richard G. Martin

Management of stage III primary breast cancer with primary chemotherapy, surgery, and radiation therapy

One hundred seventy‐four evaluable patients with noninflammatory Stage III (both operable and inoperable) breast cancer were treated with a combined modality strategy between 1974 and 1985. All patients received combination chemotherapy with 5‐fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide (FAC) as their initial form of therapy. After three cycles of chemotherapy, local treatment in the form of a total mastectomy with axillary dissection, or radiotherapy, or both, was completed. Subsequently, adjuvant chemotherapy was continued. There were 48 patients with Stage IIIA, and 126 patients with Stage IIIB disease. A complete remission was achieved in 16.7% of the patients, and 70.7% achieved a partial remission after the initial three cycles of FAC. The complete response rate was higher for patients with Stage IIIA, than for patients with Stage IIIB disease. All but six of the 174 patients treated were rendered disease‐free after induction chemotherapy and local treatment. The median follow‐up of this group of patients is 59 months. The 5‐year disease‐free survival rates were 84% for patients with Stage IIIA, and 33% for patients with Stage IIIB disease. The 5‐year survival rate for, patients with Stage IIIA was 84%, and for patients with Stage IIIB 44%. At 10 years, 56% of patients with Stage IIIA and 26% of patients with Stage IIIB disease are projected to be alive. Younger patients, and those with estrogen receptor‐positive tumors, had a trend for better survival than older patients and those with estrogen receptor‐negative tumors. The quality of response to induction chemotherapy correlated prominently with prognosis, as did compliance with treatment. Twenty‐six patients (15.3%) had locoregional recurrence. This multidisciplinary approach to locally advanced breast cancer rendered most patients disease‐free and produced an excellent local control rate. Modifications of this treatment strategy may result in further improvement of survival rates.

Sarcoma of soft tissue: Clinical and histopathologic parameters and response to treatment

Radical dose radiation therapy alone or combined with limited surgery has been employed in the management of 100 patients with primary (71) and recurrent (29) sarcoma of soft tissue. Results of this experience show that a combination of conservative surgery and radiation therapy, based upon radical dose levels and sophisticated techniques, is effective: only 13 of 100 patients showed local regrowth during a followup of 2–12 years. This may be compared with an expected ⩽25 recurrences had treatment been radical surgery (wide resection or amputation). For lesions located on the distal extremities (elbow‐hand, knee‐foot) there were local failures in only 3 of 59 (5%). Further, 75% of patients treated by the improved techniques utilized in the recent 8 years retained a useful limb which is free of pain or edema. Histopathologic grade is demonstrated to be an important indicator of prognosis of local recurrence and of disease‐free survival. Local recurrence rates were 0/23, 9/53, and 4/24 for Grades 1, 2, and 3. Disease‐free survival rates were 19/23 (86%), 27/53 (51%), and 4/24 (17%) for Grades 1, 2, and 3, respectively. Invasion of skin appeared to be a sign of poor prognosis; 8 of 9 such patients developed distant metastases.

Thin-section contrast-enhanced computed tomography accurately predicts the resectability of malignant pancreatic neoplasms☆

A prospective diagnostic study was designed to determine the ability of thin-section contrast-enhanced computed tomography (CT) to predict the resectability of malignant neoplasms of the pancreatic head. Patients with a presumed resectable pancreatic neoplasm referred during a 21-month period were studied with abdominal CT performed at 1.5-mm section thickness and 5-mm slice interval during the bolus phase of intravenous contrast enhancement. CT criteria for resectability included the absence of extrapancreatic disease, no evidence of arterial encasement, and a patent superior mesenteric-portal venous confluence. Of 145 patients evaluated, 42 were considered to have resectable tumors by CT criteria, and 37 (88%) underwent potentially curative pancreaticoduodenectomy. Six patients were found to have a microscopically positive retroperitoneal resection margin; no patient had a grossly positive resection margin. Five (12%) of 42 patients were found at laparotomy to have unresectable, locally advanced or metastatic tumors. Thin-section contrast-enhanced CT is an essential component of the preoperative evaluation for pancreaticoduodenectomy and can prevent needles laparotomy in most patients with locally advanced or metastatic disease.

Estrogen receptor: A prognostic factor in breast cancer

Two‐hundred‐seventeen women with primary breast carcinoma had an estrogen receptor determination tested by both the dextran‐coated charcoal assay and sucrose density gradient. The results were correlated with the disease‐free interval, survival, response to hormone therapy or chemotherapy, and site of recurrent disease. The disease‐free interval (DFI) was significantly longer in premenopausal patients with estrogen receptor positive (ER+) determination compared with premenopausal patients with estrogen receptor negative (ER‐) determinations, irrespective of nodal involvement (P < 0.05). There was no difference between the postmenopausal patients.

Management of patients with sarcoma of soft tissue in an extremity

Results of management of 57 patients with sarcoma of soft tissue on an extremity by radical dose radiation therapy are presented. These patients had been treated 2 to 10 years previously at the University of Texas M.D. Anderson Hospital. Forty‐six patients were seen after simple excision (no palpable tumor at time of our examination), while 11 patients were treated for the primary or a recurrent tumor. The recommended surgical treatment was amputation in all patients of this study sample. Radiation therapy technique was complex; dose level was 6300–7000 rads or the equivalent in 61/2‐7 weeks. Local control has been achieved in 50 of 57 patients. For the 46 patients with lesions in the elbow‐hand or knee‐foot regions, local control has been 100%. In contrast, 7 of 11 tumors located in the proximal extremities (upper arm or thigh) have recurred locally. A useful limb has been retained for 2 to 10 years in 34 of the cases. The more refined techniques of therapy now being employed yield a good functional result in nearly all cases. Metastasis‐free survival at 2 to 10 years is 58%. This figure depends not only upon histologic type but apparently also on histologic grade: 26 of 36 (72%) for Grades 1 and 2 but only 7 of 17 (41%) for Grade 3.

Treatment of soft tissue sarcomas by preoperative irradiation and conservative surgical resection

From 1970-1984, 114 patients with soft-tissue sarcomas received preoperative irradiation at U.T.M.D. Anderson Hospital. Two patients refused surgery and two had progressing disease and therefore did not proceed to surgery; in the remaining 110 patients, conservative surgical resections were performed 3-6 weeks following irradiation. Analysis of survival by histologic type, age, primary size, and histologic grade revealed a significant negative correlation with grade 3 and to a lesser extent to primary size greater than 15 cm. Eleven patients failed within the radiation portal for the primary, four in conjunction with distant metastases. Of the remaining seven, four were salvaged by further surgery for an ultimate primary-only failure rate of three. Distant metastasis occurred in 35 patients and was the major mechanism of treatment failure in this experience. Adjunctive chemotherapy was not used for the majority of patients and it remains to be seen if its routine employment in large, high-grade, lesions will diminish the deaths caused by distant metastases.

Radiotherapy for anal cancer: Experience from 1979–1987

Seventy patients with squamous cell carcinoma or cloacogenic carcinoma of the anus treated from 1979-1987 were reviewed. Five groups were analyzed: (a) local excision (LE) with postoperative radiotherapy (n = 9); (b) abdominoperineal resection (APR) with either pre- or postoperative radiotherapy (n = 22); (c) definitive radiotherapy alone (n = 8); (d) radiotherapy with continuous 5-Fluorouracil (5-FU) infusion (chemoradiation) (n = 25); and (e) patients treated for recurrent disease (n = 6). Abdomino-perineal resection and radiotherapy resulted in an actuarial local control (LC) rate of 90% and an overall 5-year survival rate of 77% (median follow-up, 48 months). All patients in Group 1 and 5/8 patients in Group 3 had locally controlled disease and were disease-free. The chemoradiation protocol resulted in a complete clinical response rate of 75% (18/24, one patient died during treatment) assessed 4-6 weeks after treatment. The colostomy-free local control rate with chemoradiation is 67% (16/24). Local control was 50% for all stages receiving 45-49 Gy and 90% for those patients receiving greater than or equal to 55 Gy but was not correlated with total 5-FU dose. Abdomino-perineal resection was performed to salvage six patients with persistent disease and two with recurrent disease, resulting in an overall local control rate of 92% (22/24). The actuarial survival was 96% (median follow-up, 14 months; range, 1-30). The acute complications of radiotherapy included diarrhea and perineal skin reactions that were increased by 5-FU infusion. However, diarrhea can be ameliorated by a modified treatment technique that reduces irradiation to the small intestine. For the entire patient group, minor late complications occurred in 23%, and major complications occurred in 9%.

Recurrence-free survival time for surgically treated soft tissue sarcoma patients. Multivariate analysis of five prognostic factors.

A staging system, based upon the experience of 1215 patients, was published by the American Joint Committee Task Force on Soft Tissue Sarcoma in 1977. A subset of these patients, 594, was selected to study recurrence‐free survival time. The authors found 331 patients with a recurrence within 5 years (100 local only, 123 metastatic only, and 108 local + metastatic); median months to recurrence was 9.7. Within 5 years, recurrence was clearly associated with mortality: among the 331 patients who experienced a recurrence, 245 died, whereas only 31 died among the 263 who had no recurrence. To further evaluate the utility of the published staging system, a multivariate analysis of five factors was carried out for 297 of the 594 patients (patients with unknown information for any one of these factors were excluded). Factors in addition to grade that exerted a significant influence on recurrence were: direct extension, symptoms, and location of tumor when survival was measured to the first of any recurrence, and tumor size, measuring survival to the first metastatic recurrence. It is therefore recommended that these factors be taken into account in staging this disease. Estimates of probable recurrence‐free survival time based upon the multivariate model (Weibull) are also presented.

Adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide, with or without Bacillus Calmette‐Guerin and with or without irradiation in operable breast cancer a prospective randomized trial

Between May 1977 and April 1980, 238 patients with operable breast cancer were treated with adjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) chemotherapy. All patients were randomized to receive FAC alone or FAC with nonspecific immunotherapy with Bacillus Calmette‐Guerin (BCG) vaccine. A randomization for routine postoperative irradiation was included in the study in May 1978. At the median follow‐up of 33 months, 53 patients had developed recurrent disease. Up to the present time, there have been no significant differences in the disease‐free survival of patients treated with FAC alone from those treated with FAC + BCG (P = 0.21). The disease‐free survival for patients treated with and without routine postoperative irradiation was similar (P = 0.99). Disease‐free survival of premenopausal and postmenopausal women was similar. The overall estimate of disease‐free survival was 72% at 3 years.

Adjuvant therapy of breast cancer with or without additional treatment with alternate drugs

Three hundred ten patients with Stage II or Stage III breast cancer were entered on an adjuvant protocol consisting of a combination of 5‐fluorouracil, doxorubicin, cyclophosphamide, vincristine, and prednisone (FACVP). In the second phase of the study, patients with estrogen receptor‐negative tumors received sequential courses of methotrexate and vinblastine. Other patients, who were estrogen receptor‐positive or unknown, were randomized to receive either tamoxifen alone or tamoxifen plus methotrexate and vinblastine. AH therapy was completed within 1 year. The estimated disease‐free rate at 5 years was 68% among patients with Stage II disease and 52% for patients who had Stage III disease. Among patients with estrogen receptor‐positive tumors, disease‐free survival was significantly prolonged in patients who received methotrexate and vinblastine in addition to tamoxifen (P = 0.04). However, this difference was less pronounced when all randomized patients (including those whose estrogen receptor status was unknown) were included in the comparison. Although most patients experienced moderate to severe granulocytopenia, infectious complications were infrequent. One patient died of septicemia. Congestive heart failure developed in two patients, one of whom had a history of myocardial infarction and congestive heart failure.