High dose radiation therapy and chemotherapy as induction treatment for stage III nonsmall cell lung carcinoma.

BACKGROUND: The current study was conducted to review the authors' experience in treating consecutive patients with American Joint Committee on Cancer (1997 revision) Stage III nonsmall cell lung carcinoma with aggressive preoperative chemoradiation followed by surgical resection. METHODS: The records of all patients who received preoperative chemoradiation were evaluated. Patients received 2 cycles of concurrent cisplatin and etoposide with 5940 centigrays of radiation therapy. They then were reevaluated to determine whether they were surgical candidates. If so, resection of the primary tumor with mediastinal lymph node dissection was performed 4-6 weeks after the completion of preoperative treatment. After adequate healing, an additional four cycles of cisplatin/etoposide or carboplatin/paclitaxel was given. RESULTS: Forty-two patients received preoperative chemoradiation, 33 of whom underwent surgical resection (79%), including 9 patients who underwent pneumonectomies. Complete pathologic responses were observed in 27% of these patients. Postoperative complications were noted in 21% of the patients and included persistent air leak, supraventricular arrhythmia, and empyema. There were no reported treatment-related deaths. The median follow-up was 26 months. The overall 5-year survival rate for all patients was 36.5% and was 45. 3% for patients who underwent resection. A trend toward increased 5-year survival was observed in patients who had a complete pathologic response (57.1%). Univariate analysis revealed the N stage classification to be significant for predicting a complete response. Patterns of failure revealed the brain to be the most common site of first recurrence (50%) and the only site of recurrence in 36% of patients. There was only one case of local failure. CONCLUSIONS: Preoperative chemoradiation using high radiation doses is feasible with acceptable toxicity. The results of the current study suggest an increased complete pathologic response rate and increased overall survival rate compared with reports in the published literature.

Management of microcalcifications that develop at the lumpectomy site after breast-conserving therapy.

PURPOSE: To design a decision tree according to time from irradiation and site, morphology, and number of microcalcifications for the rational treatment of patients with microcalcifications at the lumpectomy site after breast-conserving therapy (BCT), to minimize performance of biopsy. MATERIALS AND METHODS: From a database of 504 women selected to receive BCT, those developing probably benign microcalcifications within 3 years of BCT received close follow-up with mammography. Patients developing fewer than four probably benign microcalcifications more than 3 years after treatment were offered mammography or biopsy. If microcalcifications appeared malignant or patients developed four or more microcalcifications after 3 years, biopsy was performed. RESULTS: Twenty-eight patients (29 breasts [5.7%]) developed microcalcifications confined to the lumpectomy site. Fifteen patients (15 breasts) developed microcalcifications within 3 years of BCT and were followed up with mammography. Thirteen patients (14 breasts) developed microcalcifications confined to the lumpectomy site after more than 3 years. Among the latter group, microcalcifications appeared malignant in four breasts, and biopsy specimens revealed three recurrences. The remaining 10 breasts were followed up with mammography. No patient undergoing mammographic follow-up without biopsy has had clinical evidence of local failure throughout the follow-up period. CONCLUSION: Follow-up mammography is an option when benign-appearing microcalcifications develop at the lumpectomy site depending on time of appearance and number; it is the primary recommendation when these microcalcifications develop within 3 years after treatment.

Lectinlike interactions of Fusobacterium nucleatum with human neutrophils.

Fusobacterium nucleatum expresses lectinlike adherence factors which mediate binding to a variety of human tissue cells. Adherence is selectively inhibited by galactose, lactose, and N-acetyl-D-galactosamine. In this study, adherence of F. nucleatum to human peripheral blood polymorphonuclear neutrophils (PMNs) was investigated. The results indicated that the fusobacteria adhered to live and metabolically inactivated or fixed PMNs. Adherence of F. nucleatum resulted in activation of PMNs as determined by PMN aggregation, membrane depolarization, increased intracellular free Ca2+, superoxide anion production, and lysozyme release. Transmission electron micrographs showed that F. nucleatum was phagocytized by the PMNs. Microbicidal assays indicated that greater than 98% of F. nucleatum organisms were killed by PMNs within 60 min. Adherence to and activation of PMNs by F. nucleatum were inhibited by N-acetyl-D-galactosamine or lactose greater than galactose, whereas equal concentrations of glucose, N-acetyl-D-glucosamine, mannose, and fucose had little or no effect on F. nucleatum-PMN interactions. Pretreatment of the fusobacteria with heat (80 degrees C, 20 min) or proteases inhibited adherence to and activation of PMNs, but superoxide production was also stimulated by heated bacteria. The results indicate that interaction of F. nucleatum with PMNs is lectinlike and is probably mediated by fusobacterial proteins which bind to other human tissue cells. Adherence of F. nucleatum to PMNs in the absence of serum opsonins, such as antibodies and complement, may play an important role in PMN recognition and killing of F. nucleatum in the gingival sulcus and in the subsequent release of PMN factors associated with tissue destruction.