Adjuvant CMFVP versus melphalan for operable breast cancer with positive axillary nodes: 10-year results of a Southwest Oncology Group Study.

Four hundred forty-one women with operable breast cancer with histologically positive axillary nodes were randomized to receive either combination cyclophosphamide (60 mg/m2 orally everyday for 1 year); fluorouracil (300 mg/m2 intravenously [IV] weekly for 1 year); methotrexate (15 mg/m2 IV weekly for 1 year); vincristine (0.625 mg/m2 IV for 10 weeks); prednisone (30 mg/m2 orally days 1 to 14, 20 mg/m2 days 15 to 28, 10 mg/m2 days 29 to 42) (CMFVP) or single-agent melphalan (L-PAM) (5 mg/m2 orally every day for 5 days every 6 weeks for 2 years) chemotherapy after a modified or radical mastectomy between January 1975 and February 1978. Patients were stratified according to menopausal status and number of positive nodes (one to three, more than three nodes) before randomization. Seventy-eight patients were ineligible, most (56) because they were registered more than 42 days from surgery. Maximum duration of follow-up is 12 years, with a median of 9.8 years. The treatment arms were balanced with respect to age, menopausal status, and number of positive nodes. Among eligible patients, disease-free survival and survival were superior with CMFVP (P = .002, .005, respectively). At 10 years, 48% of patients treated with CMFVP remain alive and disease-free and 56% remain alive, compared with 35% alive and disease-free and 43% alive on the L-PAM arm. Disease-free survival and survival were significantly better with CMFVP compared with L-PAM only in premenopausal patients and patients with four or more positive nodes. Both regimens were well tolerated, although toxicity was more severe and more frequent with CMFVP. We conclude that after 10 years of follow-up, adjuvant combination chemotherapy with CMFVP is superior to single-agent L-PAM in patients with axillary node-positive primary breast cancer. The major advantage is in premenopausal women and in patients with more than three positive axillary nodes.

A method of radiation treatment for advanced neck node metastases.

Thirty-one advanced cervical node metastases (staged N3 according the U.I.C.C. system; 4 N2A, 27N3A according the A.J.C. system) were treated using a particular schedule consisting in two courses: in the first, only the palpable tumor was irradiated with several low energy beams (3.3 mm Al HVL), using as X ray tube operated at 60 kV; in the second course, the whole lymphatic area was treated with 60 Co and conventional fractionation. Palpable disease received 7500 to 10,500 cGy in a overall time of 45-55 days. The local control rate was 87%, without any severe complication. The four (13%) failures were all related to the lowest dose levels.

Guidelines for radiotherapeutic techniques for cervical metastases from an unknown primary.

Between 1968 and 1980, radiotherapy was part of the treatment of 120 patients with cervical nodes from an unknown primary tumor. Thirteen patients presented with supraclavicular nodes only and 14 presented with massive adenopathy; they are analyzed separately. The remaining 93 patients are analyzed in this report with emphasis on the applied radiotherapeutic techniques. Twenty of the 93 patients received radiation treatment to the neck only, 26 to the naso- and oropharynx and neck, and 47 to the naso-, oro-, and hypopharynx and neck. Fourteen patients subsequently developed a tumor at a primary site or a recurrence of metastases in the neck; in nine patients the disease recurrence was in areas that had not been irradiated. There was an increase in failures above the clavicles in patients who received irradiation to the neck alone. No correlation was found between initial tumor staging and subsequent failure, nor between types of surgical procedures and failure. In 86 of 93 (92.5%) patients there was eventual control of disease above the clavicles; 22 of the 93 patients died of disease, whereas 36 died of other causes. The determinate survival rate for the 93 patients treated with curative intent is 70% at 10 years. Guidelines for selection of techniques based on tumor and patient factors are discussed.

A twenty-year analysis of the results of sleeve resection for primary bronchogenic carcinoma.

Ninety-six patients with primary bronchogenic carcinoma were treated by lobectomy with sleeve resection of the bronchus, over a 20 year period (1958 through 1977). In 80 resections undertaken prior to 1973, a 5 year survival rate of 34 percent was realized, with an operative mortality rate of 7.5 percent. Survival at 10 and 15 years has been assessed. A review of factors influencing survival has been undertaken and the biologic behavior of these pulmonary neoplasms, modified by sleeve resection, has been outlined. Of interest is the high rate of local recurrence accounting for death within 5 years postoperatively and the late incidence in the survivors of second malignancies and other diseases of surgical interest. Sleeve resection represents a surgical alternative in selected cases of bronchogenic carcinoma in which wider resection may be hazardous, and the indications should be extended to include some lesions commonly managed by pneumonectomy.

Lymph node mapping and curability at various levels of metastasis in resected lung cancer.

By means of lymph mapping, the prognosis significance of lymph node metastasis in lung cancer was studied in 270 patients who had undergone radical operations--pulmonary resection combined with complete mediastinal lymph node disection, which is used for patients in whom all cancer could thereby be ablated. Mediastinal lymph node metastasis was found in 64 patients, and 12 patients lived 5 years or more (an absolute 5 year survival rate of 18.8 percent). After radical surgery, there was a significant difference between the prognosis for patients who had metastases to the subcrainal lymph nodes as compared to the prognosis for those who did not. The 5 years survival rates were 9.1 percent and 29.0 percent, respectively. On the other hand, prognosis was not significantly affected by involvement or noninvolvement of the superior mediastinal, paratracheal, tracheobronchial, pretracheal, and the subaortic and para-aortic lymph nodes. No significant difference in survival was detected between patients who were given adjuvant therapy and those who were not. Lymph node mapping gives valuable prognostic information.

Survival with residual tumor on the bronchial margin after resection for bronchogenic carcinoma.

Sixty-four (14.7 percent) of 434 consecutive patients having pulmonary resection for bronchogenic carcinoma were found to have microscopic residual tumor on the cut margins of the resected specimens. These subjects were further subdivided histologically into those with direct extension of the tumor (34 patients), lymphatic permeation (14 patients), clumps of cancer cells in parabronchial tissues (six patients), and the presence of carcinoma in situ change (10 patients). Bronchopleural fistulas developed in eight (12.5 percent) of 64 patients. The operative mortality rate was 15.6 percent, with four of the deaths occurring as the result of bronchopleural fistulas. Thirty-two patients (50 percent) survived 1 year, 21 (32.8 percent) survived 3 years, and 15 (23.4 percent) lived for 5 years or more. The patients with tumor in the submucosal and peribronchial lymphatics had the worst prognosis. 78.6 percent having died within 1 year and the remainder within 3 years. All 5-year survivors were men with squamous cell carcinoma and had relatively small tumors (mean diameter 2.9 cm). No direct relationship between the length of the resected bronchial stump and survival could be established; a short stump did not preclude long survival. The possible factors involved in the relatively high 5 year survival rate in this group of patients and the therapeutic implications of these factors are discussed.

Adenocarcinoma of the uterine cervix: histologic variables associated with lymph node metastasis and survival.

One hundred and two patients were treated for primary adenocarcinoma of the uterine cervix over a ten-year period from 1973 to 1982. Of these, 51 patients underwent initial surgical management that included a pelvic and para-aortic lymphadenectomy with a radical hysterectomy or a surgical staging operation. Clinical lesion size, grade, and depth of stromal invasion were correlated with lymph node metastasis and survival. The incidence of positive lymph nodes was 14.6% for stage I and 40.0% for stage II. Positive lymph nodes were documented in none of 15 patients with lesions smaller than 2 cm, 16.7% (five of 30) with 2 to 4 cm, and 82.3% (five of six) with larger than 4 cm; 5.3% of grade 1 tumors, 11.1% of grade 2, and 50.0% of grade 3. There were no lymph node metastases (zero of six) in patients with a tumor that had a depth invasion of less than 2 mm, whereas positive nodes were found in 11.1% (two of 18) patients with 2 to 5 mm of invasion, 28.6% (two of seven) with 5 to 10 mm, and 57.1% (four of seven) with greater than 10 mm of invasion. Five-year survival was 82.9% for stage I and 42.9% for stage II patients; 91.7% with negative lymph nodes, and 10% with positive nodes (P less than .0001). The size of the primary tumor (P less than .0001), tumor grade (P less than .05), and depth of invasion (P less than .05) correlated with patient survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Staging of breast cancer: a new rationale for internal mammary node biopsy.

Metastases to the axillary nodes, the internal mammary nodes, or both, define a group of patients at very high risk of having systemic micrometastases leading to recurrent disease and death if surgical therapy alone is used. In our review of 7,070 patients with breast cancer in whom both axillary nodes and internal mammary nodes were examined histologically, 5% to 10% had internal mammary node metastases in the absence of axillary node metastases. With the availability of effective systemic therapy that can improve the survival of patients with operable breast cancer who have lymph node metastases, information obtained from internal mammary node biopsies assumes practical significance. Our current policy is to perform internal mammary node biopsies on patients with operable breast cancer who have medial and central primary tumors of any size and lateral primary tumors 2 cm or greater in diameter if a frozen section of the most suspicious node in the axillary dissection shows no histologic evidence of metastasis.

Relationship of cell type and lymph node metastasis to survival after resection of bronchial carcinoma.

In the completed adjuvant chemotherapy lung trials conducted by the Veterans Administration Surgical Group, the cell type was recorded in 2,341 of 2,349 curative resections; extent of lymph node involvement was known in all cases. Nodes were normal in 1,231 patients. Five- and ten-year survival computed by the life-table method was 33.7% and 20.4%, respectively. These rates were significantly greater than the 16.2% and 8.8% recorded in 1,118 patients whose nodes showed metastases. Among patients whose cell type was known, five-year survival in 484 with hilar node involvement was 17.4% and was not significantly different from 20.1% in 364 patients in whom only lobar nodes were involved. The survival was 8.9% in 268 patients with cancer in the mediastinal nodes; this was significantly worse than either of the aforementioned groups. A five-year survival of 26.8% in 1,482 patients with squamous cell carcinoma was greater than the 24.3% in 359 with adenocarcinoma and 22.4% in 500 with undifferentiated cell types, but the differences were not significant. Variations between these groups remained nonsignificant when nodes were normal and were of only borderline significance, at the 5% level, when they showed metastasis. When a curative resection has been accomplished, cell-type as classified in this study has little bearing on long-term survival, whereas the presence of node metastasis as well as its location is of the utmost importance.

Results of total gastrectomy for gastric cancer.

To compare the results of total gastrectomy performed during the last 30 years, we classified 256 patients into four chronologic groups. Despite advances facilitating early detection of gastric cancer, the percentage of patients with stage IV cancer was not significantly different among the four groups. However, operative mortality decreased and curability increased in the two most recent groups. The 5 year survival rate was significantly increased in patients operated on after 1960. Our results show that in Japan, operative mortality and 5 year survival compare favorably with reports from Western countries.

Occult primary adenocarcinoma with axillary metastases.

The medical charts of 20 women with occult primary adenocarcinoma with axillary metastases were reviewed. An extensive radiologic workup in search of the primary lesion had a less than 7 percent positivity rate in the 74 studies carried out. Eleven patients were treated with mastectomy, 5 of whom were found to have carcinoma (49 percent). Four of the 11 patients, all with 14 or more positive axillary lymph nodes, died from breast cancer. Seven patients with no evidence of disease had an average of 4.6 positive axillary lymph nodes. Seven patients did not receive mastectomy, and one died from breast cancer. There was no significant difference in survival between the group treated with mastectomy and the group treated with axillary dissection. We conclude that mastectomy is unnecessary for patients with adenocarcinoma in axillary nodes but no apparent primary tumor.

Factors affecting long-term survival of patients with bronchogenic carcinoma.

From January 1963 to December 1968, 148 patients underwent thoracotomy for bronchogenic carcinoma. In 123 patients either lobectomy or pneumonectomy was performed (resectability rate of 84 per cent). The over-all operative mortality was 3.4 per cent. Forty of the patients undergoing resection (34 per cent) are alive and free of cancer five years after surgery. Tumor size, nodal involvement, cell type, location, symptoms, and extent of surgery were studied in relation to the long-term results. Five year survival was directly related to the size of the tumor and the extent of nodal involvement. No patients with mediastinal nodal involvement or with lesions larger than 7 cm in diameter were among the long-term survivors.

Prognostic evaluation of regional lymph node morphology colorectal cancer.

Histologic sections from 143 patients treated with surgery for infiltrating adenocarcinoma of the distal large bowel were studied with emphasis on the morphologic characteristics of the regional lymph nodes. Lymph nodes were classified into four groups designated lymphocyte predominance, germinal center predominance, lymphocyte depletion, and unstimulated. Results were correlated with the extent of disease and five year survival data. There was no significant association between the histologic pattern of the lymph nodes and the extent of the primary lesion. There was a higher survival rate in patients whose nodes showed germinal center predominance (71 per cent) compared with those whose nodes showed lymphocyte predominance or the unstimulated pattern (both 54 per cent), but these results were not statistically significant.

Synchronous bilateral neck dissection.

The type of treatment used to control evident or possible metastatic cancer in the cervical region remains in dispute. When clinically positive lymph nodes are present in both sides of the neck, treatment to both sides is mandatory. If surgery is elected as the primary treatment, the neck dissection can be done bilaterally, either in one or two stages. Synchronous bilateral radical neck dissection has been associated with a high morbidity rate. It was the purpose of this paper to report the indications, complications, and results in a series of 179 synchronous bilateral neck dissections done between 1967 and 1979. In all except one instance, the internal jugular vein was saved on one or both sides. The mortality rate was 3.4 percent. Patients with histologically positive lymph nodes that were present bilaterally were found to have a reasonable prospect for cure. The rate of recurrence was related more to the inability to control the primary cancer than to treatment failure in the neck.

The prognostic significance of metastatic cervical lymph nodes.

The ability to predict accurately the clinical course of a patient with a malignancy is critically important to the patient's subsequent management. It has been well documented that the presence of metastatic nodal disease is associated with decreased patient survival. Survival data from a group of 242 head and neck cancer patients from the University of Iowa were analyzed to determine the significance of specific characteristics of metastatic lymph nodes. Evaluation of absolute numbers and percentages of positive nodes or node size generally was not useful. However, involvement of the posterior triangle nodes, noncontiguous nodal sites, or multiple sites was associated with a worse prognosis. When that was accurate enough to be of help to the clinician in prognostication. The single most important feature seems to be documentation of the presence of metastatic nodal disease, rather than particular features (i.e., number, size) of the metastatic nodes.

The violated neck: cervical node biopsy prior to definitive treatment.

The intent of this study was to determine whether open neck biopsy for patients with squamous cell carcinoma metastatic to the neck influenced the biologic course of the disease or the response to treatment. One hundred ninety-two patients, treated over a 10-year period at M.D. Anderson Hospital and Tumor Institute, were reviewed; 102 of the 139 patients, whose primary site of disease was identified prior to definitive treatment, were matched with a control group of 204 patients. The results showed no significant difference in wound complications, neck recurrence, distant metastases, and 5-year survival. Also, time interval from the biopsy to subsequent treatment and the type of node biopsy did not appear to have any significant detrimental effect. On the basis of these findings, we conclude that, although it is important to refrain from proceeding with an open biopsy until a complete head and neck evaluation has been done, violation of the neck does not signify a poorer prognosis--provided adequate treatment is subsequently given.

[Supraclavicular lymph node metastasis from carcinoma of the uterine cervix after radiotherapy--analysis of 219 patients].

From Mar. 1958 to Dec. 1985, 13547 patients with cervical cancer in stages I-III were treated by radiotherapy in our hospital. Supraclavicular lymph node metastasis developed in 219 (1.62%), 83.1% on the left, 7.7% on the right and 9.13% bilateral. 61.2% of the metastasis occurred within 2 years and 86.75% within 5 years after radiotherapy. The majority of these patients (88.3%, 191/215), except 4 who are still being followed, had died within 1.5 years of metastasis with a mean survival of 9.3 months. If radiotherapy in adequate dose is given to the supraclavicular metastatic area, the mean survival can be prolonged for 3.7 months. The prognosis is very poor for these patients no matter what the clinical stage is or when the metastasis develops. The more advanced clinical stage, the higher metastasis rate (P less than 0.001). In this series, 47/219 (21.5%) were found to have concurrent metastasis to the other organs.