Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27.

PURPOSE: Experience with sentinel node biopsy (SNB) after neoadjuvant chemotherapy is limited. We examined the feasibility and accuracy of this procedure within a randomized trial in patients treated with neoadjuvant chemotherapy. PATIENTS AND METHODS: During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27, several participating surgeons attempted SNB before the required axillary dissection in 428 patients. All underwent lymphatic mapping and an attempt to identify and remove a sentinel node. Lymphatic mapping was performed with radioactive colloid (14.7%), with lymphazurin blue dye alone (29.9%), or with both (54.7%). RESULTS: Success rate for the identification and removal of a sentinel node was 84.8%. Success rate increased significantly with the use of radioisotope (87.6% to 88.9%) versus with the use of lymphazurin alone (78.1%, P = .03). There were no significant differences in success rate according to clinical tumor size, clinical nodal status, age, or calendar year of random assignment. Of 343 patients who had SNB and axillary dissection, the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients (56.0%). Of the 218 patients with negative sentinel nodes, nonsentinel nodes were positive in 15 (false-negative rate, 10.7%; 15 of 140 patients). There were no significant differences in false-negative rate according to clinical patient and tumor characteristics, method of lymphatic mapping, or breast tumor response to chemotherapy. CONCLUSION: These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy.     

Systemic therapy in patients with node-negative breast cancer. A commentary based on two National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials

OBJECTIVE: To determine whether in the previous National Surgical Adjuvant Breast and Bowel Project (NSABP) studies of node-negative breast cancer there were either cohorts of patients with a prognosis favorable enough to preclude using systemic therapy or subsets of patients who failed to benefit from the treatments. DESIGN: Randomized clinical trials with stratification after surgery. SETTING: NSABP trials at institutions in the United States and Canada. PATIENTS: Data were collected on 731 eligible patients (Protocol B-13) with estrogen-receptor-negative tumors who randomly received either no therapy after surgery or sequential methotrexate and fluorouracil (M----F) followed by leucovorin. Data were also collected on 2834 patients (Protocol B-14) with estrogen-receptor-positive tumors who randomly received either placebo or tamoxifen treatment. The percentage of patients surviving disease-free was determined through 4 years of follow-up using life-table estimates. INTERVENTIONS: Protocol B-13 patients received 12 courses of M----F given intravenously on days 1 and 8 every 4 weeks. Leucovorin therapy was begun 24 hours after M----F administration. Protocol B-14 patients received 5-year treatment with either tamoxifen (10 mg twice daily by mouth) or placebo. RESULTS: When the outcome of untreated patients in either trial was related to the stratification variables, women were found to have a disease-free survival of less than 80% through 4 years of follow-up. This percentage is apt to decrease because the probability of treatment failure increases with time. In both trials, all subsets of women benefited from M----F or tamoxifen therapy. CONCLUSIONS: The disease-free survival of all cohorts of node-negative patients with estrogen-receptor-negative or estrogen-receptor-positive tumors was poor enough to justify systemic treatment. The benefits of the therapies used are insufficient to eliminate the need for assessing putatively better regimens.     

Toxicity assessment of contaminated soils from an antitank firing range

Explosives are released into the environment at production and processing facilities, as well as through field use. These compounds may be toxic at relatively low concentrations to a number of ecological receptors. A toxicity assessment was carried out on soils from an explosive-contaminated site at a Canadian Forces Area Training Center. Toxicity studies on soil organisms using endpoints such as microbial processes (potential nitrification activity, dehydrogenase activity, substrate-induced respiration, basal respiration), plant seedling and growth (Lactuca sativa and Hordeum vulgare), and earthworm (Eisenia andrei) growth and reproduction were carried out. Results showed that 1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX) was the principal polynitro-organic compound measured in soils. Soils from the contaminated site decreased microbial processes and earthworm reproduction; whereas plant growth was not significantly reduced. Toxicity to aquatic organisms and genotoxicity were also assessed on soil elutriates using Microtox (Vibrio fischeri), growth inhibition of algae (Selenastrum capricornutum), and SOS Chromotest (Escherichia coli). Results indicated that soil elutriates were generally not toxic to bacteria (Microtox) and algae. However, genotoxicity was found in a number of soil elutriate samples. Thus, the explosive-contaminated soils from the antitank firing range may represent a hazard for the soil organisms. Nevertheless, the global toxicity might have partially resulted from HMX as well as from other (not identified) contaminants such as heavy metals.     

Implication of ATP and sodium in arachidonic acid incorporation by placental syncytiotrophoblast brush border and basal plasma membranes in the human

The human placental syncytiotrophoblast is the main site of exchange of nutrients and minerals between the mother and her fetus. In order to characterize the placental transport of some fatty acids, we studied the incorporation of arachidonic acid, a fetal primordial fatty acid, in purified bipolar syncytiotrophoblast brush border (BBM) and basal plasma membranes (BPM) from human placenta. The basal arachidonic acid incorporation in BBM and BPM was time dependent and reached maximal values of 0.75+/-0.10 and 0.48+/-0.18 pmol/mg protein, respectively, after 2.5 min. The presence of adenosine triphosphate (ATP) (3 m m) increases significantly the maximal incorporation of arachidonic acid by sixfold (4.75+/-0.35 pmol/mg) and ninefold (4.40+/-0.84 pmol/mg) in BBM and BPM, respectively. Moreover, an increase in the arachidonic acid incorporation was also obtained in the presence of sodium where the values achieved 7.68+/-0.98 (10x) and 6.53 pmol/mg (13.6x) for BBM and BPM, respectively. We also showed that the combination of both Na(+)and ATP increases significantly the maximal incorporation of arachidonic acid in BPM to 7.89+/-0.15 pmol/mg protein, while in BBM it did not modify its incorporation (8.18+/-0.25 pmol/mg protein), as compared to the presence of sodium alone. Our results demonstrate that arachidonic acid is incorporated by both placental syncytiotrophoblast membranes, and is ATP and sodium-linked. However, different mechanisms seem to be involved in this fatty acid incorporation through BBM and BPM, since the presence of Na(+)or ATP increased it, while the association of these two elements increased it only in BPM. We also demonstrated by osmolarity experiments that both membranes bind arachidonic acid, potentially involving one or more fatty acids binding proteins.     

Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02

Between March 1984 and July 1988, 1,158 patients with Dukes' A, B, and C carcinoma of the colon were entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-02. Patients were randomized to either no further treatment following curative resection or to postoperative fluorouracil (5-FU) and heparin administered via the portal vein. Therapy began on day of operation and consisted of constant infusion for 7 successive day. Average time on study was 41.8 months. A comparison between the two groups of patients indicated both an improvement in disease-free survival (74% v 64% at 4 years, overall P = .02) and a survival advantage (81% v 73% at 4 years, overall P = .07) in favor of the chemotherapy-treated group. When compared with the treated group, patients who received no further treatment had 1.26 times the risk of developing a treatment failure and 1.25 times the likelihood of dying after 4 years. Particularly significant was the failure to demonstrate an advantage from 5-FU in decreasing the incidence of hepatic metastases. The liver was the first site of treatment failure in 32.9% of 82 patients with documented recurrences in the control group and in 46.3% of 67 patients who received additional treatment. Therapy is administered via a regional route to affect the incidence of recurrence within the perfused anatomic boundary. Since, in this study, adjuvant portal-vein 5-FU infusion failed to reduce the incidence of hepatic metastases, it may be concluded that its use thus far is not justified. It may also be speculated that the disease-free survival and survival advantages (the latter of borderline significance) are a result of the systemic effects of 5-FU.     

Pulmonary complications of multimodality therapy for esophageal carcinoma

Thirty patients with cancer of the esophagus were treated with multimodality therapy. We studied the incidence of pulmonary complications in these patients. The value of chest radiographs and sequential measurements of carbon monoxide diffusing capacity (DLco) in predicting pulmonary toxicity was determined. Patients were divided into two groups, according to treatment. Patients in group I (n = 16) received two cycles of chemotherapy (bleomycin 15 units/m2, cisplatinum 120 mg/m2, vincristine 2 mg) and radiotherapy (50 Gy). Based on the presence of interstitial lesions on chest radiographs in five patients the incidence of pulmonary toxicity was 32%. In four of these five patients such an appearance was preceded by a drop in DLco: this was documented in 8 of the 16 patients. Nine patients of group I underwent esophagectomy and four (44%) developed adult respiratory distress syndrome (ARDS). In group II (n = 14) the tumor was resected without other treatment and four (29%) of these patients developed ARDS. The incidence of ARDS in both groups demonstrates that pulmonary complications are mainly related to surgical manipulation and to preexisting lung disease. Preoperative radiotherapy and chemotherapy may be associated factors. Sequential measurements of DLco are more sensitive for detecting pulmonary damage than chest radiographs and should be used to predict pulmonary toxicity.     

Small-cell carcinoma of the rectum

Small-cell carcinoma of the rectum is a rare tumor. We treated a patient with small-cell carcinoma of the rectum with radiation and multidrug regimen being used for small-cell carcinoma of the lung. Within two months of chemotherapy, the primary lesion, as evaluated by rectoscopy, biopsy, and CT scan, had resolved completely. The patient was in complete remission for 12 months after initiation of chemotherapy and died of widespread metastases. At autopsy, no residual tumor was found in the rectum. This case stresses the importance of ultrastructural study in the differential diagnosis of small-cell cancer of the rectum and the fact that this tumor can be treated in the same fashion as for small-cell carcinoma of the lung with multidrug chemotherapy and radiation therapy to achieve local control.