Multimodality therapy for stage III non-small-cell lung cancer.

The treatment of stage III non-small-cell lung cancer has evolved over the last two decades, with combined-modality therapy the current standard of care. As a result, intermediate and long-term survival has improved for patients in this common stage category, compared to the poor outcomes achieved with the historical standard of once-daily radiation therapy alone. This review summarizes two decades of clinical research regarding bimodality and trimodality approaches for the heterogenous stage subsets within the stage III designation, discusses the rationale and status of prophylactic brain irradiation, and concludes with perspectives on progress and future directions. Chemotherapy plus radiotherapy given concurrently is the optimal treatment for the group of patients with advanced stage III disease. The potential role of a surgical resection following chemotherapy (with or without radiation) in this setting is still controversial. The only subsets for which trimodality treatments are clearly preferred include T4N0-1 disease and superior sulcus tumors. The other major stage III subgroup has a minimal disease burden with low tumor volume and/or microscopic N2 disease, thus technically could undergo a surgical resection upfront. Induction chemotherapy before surgery may yield a survival advantage, although the phase III trials in this area are not conclusive. Given the marked survival benefit from adjuvant chemotherapy after surgery in even earlier stages of non-small-cell lung cancer, the proper sequence of surgery and chemotherapy (before v after surgery) remains an important unresolved question in this subgroup. Furthermore, how to incorporate radiation therapy, as well as whether it should be given at all in this subset of patients, are other important issues actively under study in ongoing trials.

The treatment and prevention of deep vein thrombosis in the preoperative management of patients who have neurologic diseases.

All patients with neurologic diseases should receive perioperative VTE prophylaxis. The choice of mechanical, pharmacologic, or combined modalities of prophylaxis depends on both the underlying risk factors and surgical VTE risks. Prophylaxis and treatment options must be individualized to the patient. Prevention of VTE will help minimize the need for therapeutic treatment. Options for treatment include both inpatient and outpatient regimens using UFH or LMWH. In patients with an absolute or relative contraindication to anticoagulation, an IVC filter is an appropriate management strategy. Perioperative bridging therapy should be considered in patients with high or moderate risks for recurrent VTE.

Pre-irradiation 9-amino [20s] camptothecin (9-AC) in patients with newly diagnosed glioblastoma multiforme.

PURPOSE: To evaluate the efficacy of 9-amino [20s] camptothecin (9-AC) given before radiation therapy to patients with newly diagnosed glioblastoma multiforme (GBM). METHODS: Eligible patients had newly diagnosed GBM who had residual measurable contrast-enhancing tumor. The trial was a phase 2 trial of 9-AC at 1100 microg/m2 /24 h infused over 72 h every two weeks for up to six cycles in patients with newly diagnosed GBM before radiation therapy. RESULTS: Fourteen patients entered the study and all were evaluable. All of the patients had progressive disease by imaging criteria after at least two cycles of 9-AC (1 month). The median overall survival was 7.5 months (range 1.5-18 months). The most common adverse event was transient lymphopenia (grade 3-4). One patient developed grade 4 neutropenic fever that resolved after three days of diagnosis. CONCLUSIONS: 9-AC lacks activity against glioblastoma multiforme (GBM). Further studies looking at the efficacy of 9-AC in GBM may be futile.