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.

Prognostic significance of cytokeratin-positive breast cancer metastases.

The most important discriminant in staging carcinoma of the breast is the presence of positive axillary lymph nodes. In this study, we determined if 45 female breast cancer patients originally classified as lymph node-negative by standard light microscopy (SLM) could be more accurately classified by immunohistochemical (IH) examination of their lymph nodes with an anticytokeratin monoclonal antibody cocktail. Identical sections of lymph nodes were sequentially examined by SLM and IH. Eight nodes (1%) in a total of five patients (11%) were positive by SLM. In comparison, 12 nodes (1.5%) in a total of nine patients (20%) were positive by IH. Five nodes were positive by IH and negative by SLM. There was no correlation between IH-detected metastases and tumor size or patient age. The survival curve for patients with IH-detected metastases was significantly worse than that of patients without IH-detected metastases. IH detection methods may be an important adjunct in staging breast cancer patients.

Lymph node involvement as the only prognostic factor in curative resected gastric carcinoma: a multivariate analysis.

The aim of this study was to evaluate the independent influence of clinical and pathological variables on survival of patients with gastric carcinoma using the Cox regression proportional hazard model. Of 156 patients operated on for gastric carcinoma, 46 (29.5%) underwent palliative operation, 24 (15.5%) had a palliative resection, and 86 (55%) had a curative resection. The overall 5-year survival rate was 25 +/- 4%. After curative resection, the 5-year survival rate was 44 +/- 6%. Univariate analysis applied to these patients showed that poor survival was related (p less than 0.01) to: age (over 80 years), absence of epigastric pain, vomiting and dysphagia, total gastrectomy, tumor size (more than 4 cm), lymph node involvement (LNI), invasion through the muscularis propria, absence of intestinal metaplasia near the tumor, and linitis plastica. In multivariate analysis, lymph node involvement was found to be the only independent prognostic factor. The 5-year survival rate was 75.5 +/- 8% without LNI, 28 +/- 10% with proximal LNI, and 7 +/- 6% with distal LNI. Our results suggest that classification into 3 LNI groups is the best staging system for curative resection in gastric carcinoma.

[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.

Prognostic significance of lymphatic permeation in Dukes' B colorectal cancer.

The survival of 78 patients with Dukes' B colorectal carcinoma was evaluated in relation to the presence (36 patients) or absence (42 patients) of tumour cells within lymphatic capillaries. Age-adjusted survival analysis did not reveal a statistically significant difference in survival between these two groups.

Survival of ovarian carcinoma with or without lymph node metastasis.

Because of the limited number of reports concerning the influence of retroperitoneal lymph node metastasis upon survival in patients with ovarian carcinoma, a prospective study was conducted between December 1975 and December 1982 to provide such information. This series consisted of 75 unselected patients with epithelial carcinoma of the ovary in all stages. Thirty-three patients had tumor-positive nodes and 42 had negative nodes. The two groups were compared with regard to stage of disease, grade of tumor, histology of tumor, residual disease after initial operation, finding at second-look laparotomy, and survival. All had initial maximal surgery and biopsy of para-aortic and pelvic nodes: most received postoperative chemotherapy. Follow-up was from 36 months to 10 years. Patients with positive nodes preferentially had more advanced disease (Stage III and IV). Grade 3 tumor, papillary serous cystadenocarcinoma, residual disease greater than 2%, low rate of second-look laparotomy, and death. Patients with negative nodes were connected with earlier disease (Stage I and II), nonserous tumor, minimal residual disease, high rate of second-look laparotomy, and survival. No patient with isolated nodal metastasis to pelvic or para-aortic survived. Only 18.2% with concomitant para-aortic and pelvic node involvements are currently alive, opposed to 64.3% with negative node. The results indicate that tumor-positive nodes in ovarian carcinoma are a poor prognostic factor and current combination chemotherapy is not effective. Alternative treatment for these patients should be considered.

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 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.

Surgery as palliative treatment for distant metastases of melanoma.

Sixty-five patients with distant metastatic melanoma amenable to surgical treatment had excision of 94 metastatic lesions from the brain, lung, abdomen, distant subcutaneous sites, and distant lymph nodes. Relief of symptoms, if present, was obtained after excision of 77% of brain metastases, 100% of lung metastases, 88% of distant lymph node and subcutaneous metastases, and 100% of abdominal metastases. Median survival after excision of brain metastases was 8 months, lung metastases 9 months, abdominal metastases 8 months, and distant subcutaneous and lymph node metastases 15 months. Sixteen per cent of patients lived for 2 years of longer. These results demonstrated that surgery can achieve an effective local disease control in selected patients with distant melanoma metastases and that a few have a relatively long-term survival.

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.

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.

[Adjuvant chemotherapy in addition to radical surgical treatment of regional lymph node metastases in malignant melanoma]. / Adjuvante Polychemotherapie zusätzlich zur radikalen operativen Behandlung regionaler Lymphknotenmetastasen beim malignen Melanom.

Thirty-three patients with malignant melanoma and regional lymph node metastases who underwent lymph node dissection were additionally given polychemotherapy with carmustine, hydroxycarbamide and dacarbazine immediately before surgery and up to five times postoperatively. Twenty-nine patients were only treated surgically. These two groups were comparable as regards prognostic criteria, in particular tumour size, ulceration and the number of lymph nodes affected, although the individual follow-up periods varied considerably. The group given chemotherapy showed better results than the control group undergoing surgery alone. The log rank test yielded a significant difference (P less than 0.05) with respect to the probability of relapse-free survival but not as regards probability of survival time. Patients with ulcerated primary melanomas and with a large number of affected lymph nodes had a less favourable prognosis. The major side effects of chemotherapy were transient nausea and bone marrow depression.

The surgical approach to primary malignant melanoma.

Surgical excision is the only curative treatment for malignant melanoma. Excisional biopsy of the suspected lesion allows for adequate tissue diagnosis and microstaging and does not alter ten year survival periods. Wide local excision with a resection margin of 3 centimeters is recommended for all but the most superficial (less than 0.76 millimeters) lesions. Nodal and systemic metastases and long term survival are unaffected by the size of the resection margin. The role of prophylactic lymphadenectomy for Stage I melanoma remains controversial. The results of both prospective and retrospective studies have demonstrated an improved survival after prophylactic lymphadenectomy for patients with intermediate thickness (0.76 to 3.9 millimeters or Clark's level III to IV, or both) lesions. Patients with ulcerated lesions and lesions in the BANS distribution, even when superficial, might benefit from elective lymphadenectomy. At least quarterly follow-up examination is recommended for those patients who undergo wide excision alone. Therapeutic lymphadenectomy is indicated for the treatment of Stage II melanoma. The results of ongoing prospective randomized studies will clarify the role of fascia removal, resection margins and prophylactic lymphadenectomy in the treatment of malignant melanoma.

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)

Relationship between lymph node metastases and prognosis in patients irradiated postoperatively for carcinoma of the uterine cervix.

Three hundred and ten patients with squamous cell carcinoma of the uterine cervix received postoperative radiation therapy and the relationship between the extent of lymph node metastases and the prognosis was analysed. Patients with lymph node metastases showed a markedly lower five-year survival rate (42.1%) than those without such metastases (91.9%). The prognosis for patients with lymph node metastases was inversely correlated to the number of nodes involved. Bilateral lymph node involvement or lymph node involvement above the bifurcation of the iliac artery gave a much poorer prognosis than unilateral involvement or involvement only below the bifurcation.

Therapeutic groin dissection in malignant melanoma.

In a retrospective review of therapeutic dissections of the groin, 22 patients underwent radical groin dissection and seven were alive at five years, whereas 26 patients underwent a superficial groin dissection and two were alive at five years, p less than 0.05. Involvement of the deep nodes is not always equivalent with systemic disease. A radical groin dissection should be used to eradicate the disease locally. The survival rate for the patients following groin dissection correlated significantly with the disease-free interval prior to occurrence of inguinal lymphadenopathy.

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.

Metastases in malignant melanoma.

A study has been made of 76 cases of metastatic melanoma presenting over a ten year period. Of this group, 64.5 per cent developed clinical metastases within 12 months of presentation with the primary disease while 80 per cent had developed metastases by three years. Fifty per cent of our patients had ulcerated lesions, and most patients had thick lesions on histological examination. The site of the first metastasis occurred in the regional lymph nodes in 65 per cent and in viscera in 22 per cent. Subsequent clinical metastases were widespread and their distribution is recorded. Of those patients with nodal involvement, 75 per cent had only one node involved in histological examination. Only 14 of the 76 patients are alive and of these nine are alive without disease. The surviving patients had regional node, intransit or local metastases present. Disease beyond these areas was fatal. We have recorded the therapeutic modalities used without attempting to study them objectively.