Mary Jane Oswald

Prognostic implications of age in breast cancer patients treated with tumorectomy and irradiation or with mastectomy

Conservation breast treatment is of particular interest to young women, but whether saving the breast carries a penalty in shorter survival or local-regional recurrent disease has not been well-established. At The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston, 1161 patients treated prior to 1983 with Stage I or II breast cancer were reviewed. Of these patients, 378 were treated with tumorectomy plus irradiation, and 783 were treated with radical or modified radical mastectomy. The two patient groups were compared relative to local-regional disease recurrence and overall and disease-free survivals. Local recurrences in the breast appear to be more frequent in patients less than or equal to 35 years of age treated with tumorectomy and irradiation than in patients older than 35 years, but in patients aged less than or equal to 50 or greater than 50 or less than or equal to 35 or greater than 35 years, there was no significant statistical difference between tumorectomy and irradiation or mastectomy nor was there a difference in disease-free survival. Overall survival rates favored patients treated by tumorectomy and irradiation.

Results of irradiation in the treatment of locoregional breast cancer recurrence

A retrospective review is presented of 255 patients with chest wall and/or regional nodal recurrent breast cancer treated between January 1956 through December 1981 at the University of Texas M. D. Anderson Hospital; 61 patients had such massive or diffuse disease that only palliative irradiation was given, and 194 patients were treated with curative intent and form the basis of this report. All patients treated with radical irradiation received ⩾ 4500 rad, and 65% of the patients received boost therapy through reduced fields. Thirty‐two percent of patients were treated only to a single recurrent site, 11% of two sites, and 57% to the chest wall and regional nodes. Failure to control recurrent disease within or on the border of the irradiated field occurred in 27% of patients. Of 62 patients treated to the local recurrence site, 27% had further recurrences in adjacent unirradiated sites. The patients with the greatest success for tumor control (78%) and survival at 5 years (48% diseasefree) are those patients with histologically negative nodes at time of mastectomy and a single chest wall recurrence. Possible prognostic factors are discussed: initial clinical stage, age of the patient, axillary histology at the time of mastectomy, disease‐free interval between mastectomy and recurrence, number and size of recurrences, and prior chest wall recurrence.

Palliative radiotherapy for brain metastases in renal carcinoma

Between 1968 and 1985, 46 patients with renal cell carcinoma metastatic to the brain parenchyma were treated with radiation. Thirty‐nine received whole‐brain radiation, mostly 30 Gy in ten fractions. Symptoms improved in 30% of evaluable patients. Partial regression of metastases was documented in two of 11 available sequential computed tomographs (CT) of the brain. Seven patients were treated with surgery and postoperative radiation. In five the excision was complete and associated with clinical improvement. All 46 patients have subsequently died. The median survival time of the entire group was 8 weeks. The ten patients who improved after radiotherapy survived for a median of 17 weeks. Two additional patients were treated in 1986 with fast neutrons; both had a documented maintained complete response. Brain metastasis in renal carcinoma carries a poor prognosis. It is usually unresponsive to conventional photon therapy. In selected cases an alternative treatment with surgery or neutron therapy should be considered.

Postoperative adjuvant radiotherapy for adenocarcinoma of the rectum and rectosigmoid

One hundred five patients treated with potentially curative surgery and adjuvant postoperative radiotherapy for adenocarcinoma of the rectum and rectosigmoid from 1973 through 1981 were reviewed. Radiation therapy was given with 18-25 MeV X rays in doses of 40-50 Gy in 5 weeks (midline dose) using AP-PA fields in 97 patients. A boost of 6 to 10 Gy was directed to the area of maximum risk by anterior-posterior or perineal fields in 71 patients. Local failure occurred in 15 patients and was documented pathologically in 8 patients, or clinically or radiologically in 7 patients. The local recurrences according to the Modified Astler-Coller staging criteria were: B1: 0% (0/3); B2: 4% (1/24); B3: 31% (4/13); C1: 8% (1/12); C2: 18% (8/45); C3: 20% (1/5). Local failure after adjuvant radiotherapy versus surgery alone was compared. The comparison of local failure of combined treatment versus surgery alone, from our institution, is as follows: B2-4% vs 13%, B3-31% vs 26%, C2-18% vs 30%, and C3-20% vs 49%. Sixty-one patients (58.1%) have been followed for 5 years, with a median of 73 months and a minimum of 24 months. The actuarial 5-year survival (disease-free) for the entire group is 55% and is not statistically different for the groups with negative or positive nodes. Fourteen patients (13%) required surgery for small bowel complications; four others (4%) had symptomatic small bowel obstruction treated with conservative therapy only. Small bowel obstruction occurred in 4 of 16 (25%) treated with radiation fields above L5, whereas those treated below L5 had an 11% incidence. Postoperative adjuvant radiotherapy can increase local tumor control compared to surgery alone. The small bowel complication rate in this series most likely reflects AP-PA treatment technique and can be decreased by the use of multiple fields with maximum shielding of the small intestine.

Adjuvant chemotherapy for advanced nasopharyngeal carcinoma.

The outcome of therapy is reported in 34 previously untreated patients with advanced‐stage (AJC IV) nasopharyngeal carcinoma treated with combination chemotherapy (cisplatin and non‐cisplatin based) and sequential radiation therapy. Sixty‐nine patients treated with radiotherapy alone were used as a control group. The control group was matched for T and N stage grouping but differed in that 45% had keratinizing squamous carcinoma, 14.5% had nonkeratinizing squamous carcinoma, and 40.6% had undifferentiated carcinoma, compared with 18%, 50%, and 32.4%, respectively in the combined‐treatment group. Seventeen of 21 patients (81%) who received chemotherapy followed by radiotherapy achieved complete remission (CR), whereas 11 of 13 patients (85%) who received radiotherapy followed by chemotherapy achieved CR (P = NS). Patients treated by radiotherapy alone had a 91% CR rate. The combined treatment yielded a relapse‐free rate of 78% versus 44% for the radiotherapy group (P = 0.001). Median survival in the combined‐treatment group has not been reached (111+ months), compared with 67 months in the group receiving radiotherapy alone (P = 0.04). The recurrence rate at the primary site and in regional nodes was more frequent in the radiotherapy group (36%), compared with the combined‐therapy group (7%) (P = 0.004), but the occurrence of distant metastases was similar in each group (P = 0.41). The acute toxicity of the treatment was well tolerated. The major long‐term toxic effect experienced by patients in the combined‐therapy group was soft tissue fibrosis. These data suggest that a prospective trial comparing chemotherapy and radiotherapy versus radiotherapy alone is warranted.

Acute and late toxicity associated with sequential bleomycin-containing chemotherapy regimens and radiation therapy in the treatment of carcinoma of the nasopharynx☆

Between 1975 and 1984, 33 patients with squamous cell carcinoma of the nasopharynx received adjuvant chemotherapy before and/or after definitive radiotherapy at UT M. D. Anderson Hospital. The favored chemotherapy regimens during this time were BCMF (bleomycin, cyclophosphamide, methotrexate, and 5-FU) and PMB (cisplatinum, methotrexate, and bleomycin). Total radiation doses to the primary site averaged 65 Gy for T1 and T2 lesions and 70 Gy for T3 and T4 lesions. Neck nodes were given boost treatments to a maximum of 70 Gy, depending on the extent of the disease. The outcome of treatment in these patients was compared to that of a stage-matched group of 71 patients treated during the same time period with radiotherapy alone. However, the groups were not matched with regard to histologic subtypes: 45% of the radiation-only group had prognostically unfavorable keratinizing squamous carcinomas (WHO 1) compared with 18% of the combined modality group. Overall disease-free survival at 5 years was 63% in the combined modality group and 44% in the radiation only group (p = 0.15). Both acute reactions and late treatment complications were much more frequent and severe in patients receiving combined modality treatment. In patients treated with chemotherapy prior to radiation therapy, 10/20 (50%) experienced severe acute toxicity (RTOG Grade 3 or 4) versus 9/71 (13%) in the radiotherapy-only group. Severe late normal tissue injury occurred in 15/33 (45%) of the combined modality group versus 5/71 (7.0%) in the control group. The majority of the late complications in the adjuvant chemotherapy group consisted of severe soft tissue and muscle fibrosis. The average total bleomycin dose in the patients with severe late soft tissue and muscle fibrosis was 336 mg. The actuarial risk of developing a severe late complication by 2 years after treatment was 68% in the combined modality group versus 8% in the radiation-therapy-only group (p = .001). The probability of remaining both disease-free and complication-free at 5 years was 40% in the radiation-only group and 22% in the combined-modality group (p = 0.08). Comparison of these results with other published reports emphasizes the importance of late toxicity data in assessing the ultimate value of combined modality therapy.

Bilateral breast cancer in patients with initial stage I and II disease.

Between January 1947 and the end of 1976, of 2076 patients with Stages I and II breast cancer treated at M. D. Anderson Hospital, 126 received treatment for cancer in both breasts. Records of 94 patients who had only one cancer treated at U. T. M. D. Anderson Hospital and in whom staging and treatment details were not available and records of the patients who developed local, regional, or systemic failure prior to the diagnosis of the second breast were excluded. Of 126 patients with bilateral breast cancer, 39 had simultaneous tumors (both cancers diagnosed within six months) and 87 had consecutive tumors. The disease‐free 20‐year survival rate shows no significant difference between patients with unilateral tumors and those with bilateral simultaneous or consecutive tumors. Analysis by radiotherapy modality or surgery alone shows, if anything, a lower incidence of cancer in the second breast in the irradiated patients, indicating that in patients with Stage I or Stage II lesions, the doses of radiation given in the management of the first breast cancer were not conducive to the development of a cancer in the remaining breast.

Relationship between lymph nodal status and primary tumor control probability in tumors of the supraglottic larynx.

A retrospective review of 248 patients with squamous cell carcinoma of the supraglottic larynx was undertaken to determine the relationship between the probability of control of the primary lesion, the extent of neck nodal disease at initial presentation, and its ultimate control. All patients were treated at the U.T. M. D. Anderson Hospital between 1960 and 1980, and had a minimum of 3 years follow-up. The primary lesion was staged T1 in 38 patients, T2 in 132, T3 in 50 and T4 in 28. The initial volume of neck nodal disease was scored on a scale of 0 (no palpable nodes) to 9 (bilateral neck nodes greater than 6 cm in diameter). All primary lesions were treated definitively with megavoltage radiation therapy. Treatment to the neck varied according to the extent of lymph node involvement. There was no significant difference in the range of total radiation doses delivered to the primary lesion, stage for stage, in patients who presented with clinically negative or positive nodes, or in those with controlled versus uncontrolled neck disease. Analysis of the probability of primary tumor control was made by life table methods because of the poorer survival expectation in node positive patients. For T1 and T2 primary lesions, any positive node decreased the probability of primary tumor control (p = 0.06). For T3 and T4 lesions, a single node less than 3 cm in diameter did not worsen the chance of primary tumor control, but any greater degree of lymph node involvement did (p = 0.03). For both T stage groupings, the probability of primary tumor control at 5 years decreased progressively with increasing neck nodal disease. Primary tumor control probability was also significantly associated with control of the neck disease, independent of the modality of neck treatment. No correlation could be demonstrated between the histological grade of the primary tumor and initial lymph node status or tumor control probability. Possible interpretations of this manifestation of biological heterogeneity are discussed.

Results of irradiation in the squamous cell carcinomas of the anterior faucial pillar-retromolar trigone☆

Between January 1966 and August 1981, 159 patients with previously untreated squamous cell carcinomas of the anterior faucial pillar or retromolar trigone received definitive radiation therapy at The University of Texas M. D. Anderson Hospital and Tumor Institute. All except 11 patients were treated by external radiation including combination of electron beams with high-energy photons or 60Co to doses ranging from 60 Gy to 75 Gy. In the N0 patients, as a rule, only the ipsilateral subdigastric nodes were treated electively to a dose of 50 Gy. The 5-year determinate survival rate for the overall group was 83%. The cumulative recurrence rate showed that 92% of the patients had recurrence by 2 years. Therefore, all patients except those who died with no evidence of local disease less than 2 years after treatment were evaluated for local control. The failure rate for the evaluable patients was 29% for T1 lesions, 30% for T2 lesions, 24% for T3 lesions, and 40% for T4 lesions. After salvage surgery, which consisted of intraoral resection in one-third of the patients and of a composite operation in the other two-thirds, the ultimate failure rate was 0% for T1 lesions, 6% for T2 lesions, 8% for T3 lesions, and 20% for T4 lesions. Whereas stage was a poor indicator for treatment outcome, there was a significantly higher failure rate for infiltrative and/or ulcerated lesions (35%) than for exophytic or superficial lesions (15%). Histologic grade was of no prognostic significance, nor was there any significant difference in the failure rate for lesions originating on the anterior faucial pillar versus that for lesions on the retromolar trigone. Following radiotherapy, 30% of the patients developed some degree of bone exposure but only 5.6% (9 patients) required a segmental mandibular resection. The probability of bone exposure was not dose related and more likely reflected tumor location on the mucoperiosteum. Of the whole group, 16 patients (10%) experienced a neck failure with 8 ultimate failures after salvage surgery. Among the 16 patients who had neck failures, 13 were originally staged N0; 6 of these patients had failures that occurred in the electively treated ipsilateral subdigastric area, but the field was too small to cover the nodes adequately. Aspects of the radiotherapy techniques with combined electron and photon beams that may influence the treatment outcome are discussed.

Results in patients with breast cancer treated by radical mastectomy and postoperative irradiation with no adjuvant chemotherapy.

In 1963 an electron beam became available, making irradiation of the chest wall technically easy. In addition to peripheral lymphatic irradiation in patients with positive axillary nodes and/or the tumor in the inner quadrants or centrally located, patients with tumor larger than 5 cm or with grave signs and/or a significant incidence of positive axillary nodes received chest wall irradiation. None of the patients has received elective chemotherapy. Disease‐free survival rates at ten years are 54% for the overall group, 79% for the patients with negative nodes, 44% for patients with positive nodes, 61% for patients with 1–3 positive nodes, and 33% for patients with four or more positive nodes. The incidence of peripheral lymphatic failures is low as well as the incidence of failures on the chest wall in the patients having had chest wall irradiation. With the availability of electron beam and adjustments in doses, complications are nonexistent. The incidence of treatment failures, local‐regional, or distant, that have appeared by ten years are compared with the incidence of failures that were experienced by the placebo patients in the clinical trial of the NSABP of thio‐TEPA versus placebo. The clearly lesser incidence of treatment failures in the U.T.M.D. Anderson Hospital patients either suggests that postoperative irradiation may have survival benefits or that the data of the NSABP series are not representative of all series.