Long-term results of combined-modality therapy in resectable non-small-cell lung cancer.

PURPOSE: Assessment of long-term results of combined-modality therapy for resectable non-small-cell lung cancer is hampered by insufficient follow-up and small patient numbers. To evaluate this, we reviewed our collective experience. PATIENTS AND METHODS: This study was a retrospective chart review recording demographics, tumor stage, treatment, and outcome of consecutive patients undergoing surgery. Survival was analyzed by Kaplan-Meier, and prognostic factors were analyzed by log-rank and Cox regression. RESULTS: From January 1993 to December 1999, 470 patients were treated, with follow-up in 446: 27 stage I, 55 stage II, 316 stage III, 43 stage IV (solitary M1), and five uncertain. Chemotherapy was mitomycin/vinblastine/cisplatin (174 patients [39.0%]), carboplatin/paclitaxel (148 [33.2%]), and other combination (124 [27.8%]); 75 patients (16.8%) received induction radiation. Resection was complete in 77.4%, incomplete in 8.3%, attempted but with gross residual disease afterward in 1.8%, and not performed in 12.6%. Pathologic complete response occurred in 20 patients (4.5%). With median follow-up of 31.0 months for patients still alive, median and 3-year survival for pathologic stages 0, I, II, III, and IV were more than 90 months, 73%; 42 months, 52%; 23 months, 35%; 16 months, 28%; and 16 months, 23% (P <.001). In a multivariate analysis, age, complete resection, pathologic stage, and pneumonectomy, but not induction regimen, significantly influenced survival. CONCLUSION: Although pathologic complete response outside the protocol setting is low, survival of this large patient cohort is comparable to that of patients in published combined-modality trials. Survival is significantly influenced by patient age, complete resection, pathologic stage, and pneumonectomy. These results can help guide standard clinical practice and emphasize the need for novel induction regimens.     

Migraine preventive medications: a reappraisal

Newer acute care migraine medications demonstrate improved rapidity of action, consistent effectiveness, excellent safety profiles, and rarely cause rebound headaches. Their use could decrease the need for migraine-preventive medication. The present analysis derives a formula that can be used by practitioners to determine the cost-effectiveness of various migraine-preventive medications relative to selected acute-care medications. We propose a measure called the cost-equivalent number (CEN), the number of headaches per month at which the cost of the preventive medication equals the cost savings in acute-care treatment realized by using the preventive medication. The use of the CEN individualizes the decision of whether to use a migraine-preventive medication, weighing both the efficacy and cost of the preventive medication against the cost of the acute-care medication. A CEN lower than the migraine frequency suggests that use of a preventive medication will be cost-effective.     

Yield of brain 18F-FDG PET in evaluating patients with potentially operable non-small cell lung cancer.

The American College of Surgeons Oncology Group recently completed a trial evaluating the role of PET with 18F-FDG in patients with documented or suspected non-small cell lung cancer. Subjects underwent standard imaging to exclude metastatic disease before PET. Here, we report the yield of brain PET in evaluating, for potential intracranial metastases, patients who have undergone previous brain CT or MRI with negative findings. METHODS: A total of 287 evaluable patients who had been registered from 22 institutions underwent whole-body 18F-FDG PET, including dedicated PET of the brain, after routine staging procedures had found no suggestion of metastatic disease. Patients were followed postoperatively for disease-free and overall survival, with a minimum follow-up of 6 mo. Patients with specific brain abnormalities identified by PET were further examined, and the findings were evaluated along with the results of CT and MRI, clinical management, and follow-up. RESULTS: In 4 patients, PET found focal 18F-FDG uptake in the brain suggestive of metastatic disease; however, metastatic disease was excluded clinically in all 4 by negative findings on further brain imaging. All 4 patients remained alive at follow-up (mean duration, 10.5 mo; range, 6-16 mo). CONCLUSION: In patients with suspected or proven non-small cell lung cancer considered resectable by standard imaging, including routine preoperative contrast-enhanced CT or MRI of the brain, PET of the brain provides no additional information regarding metastatic disease.     

Effect of furosemide on fully established low pressure pulmonary edema

It has been shown that furosemide, via nondiuretic vascular effects, reduces pulmonary shunt and lung water during the development of oleic acid permeability edema. We studied this effect in a fully established stable model of oleic acid permeability edema. Sixteen anesthetized mongrel dogs, mechanically ventilated with a FIO2 of 0.5, were studied 24 hr after induction of pulmonary capillary leak by intravenous oleic acid (0.06 cc/kg). After stabilization of pulmonary capillary wedge pressure (PCWP) in the range of 0.5-3 mm Hg, bilateral ureteral ligation was performed. Furosemide (2 mg/kg) was then administered intravenously to eight dogs (treated group). An equivalent volume of saline was given to eight control dogs (control group). Pulmonary artery (PAP) and capillary wedge pressures (PCWP), thermodilution cardiac output (Qt), thermal dye lung water (LW), venous admixture (Qva/Qt), arterial and mixed venous blood gases (PaO2, MVO2) were then measured at hourly intervals for 4 hr. During this period of time, central hemodynamics (PCWP, PAP, Qt) remained stable in both groups. Indices of gas exchange and edema formation (Qva/Qt, LW, PaO2) did not change significantly in either control or treated animals. We conclude that furosemide, previously shown to reduce pulmonary shunt and lung water in the early phase of oleic acid permeability edema, does not have any effect once the pulmonary injury is well-established.     

Ras oncogene point mutation: an infrequent event in bronchioloalveolar cancer.

Ras oncogene point mutation, primarily activating the K-ras gene, has been reported in approximately one third of lung adenocarcinomas. This identifies a subset of early stage tumors clinically associated with smoking and an aggressive clinical course. Because of these findings, this study was undertaken to determine the occurrence of ras point mutations in bronchioloalveolar carcinoma. This uncommon form of lung adenocarcinoma is usually indolent but can sometimes present as a rapidly growing, multifocal tumor. Twenty tumor samples obtained at thoracotomy were examined for H-ras, K-ras, and N-ras oncogene mutational activation involving codons 12, 13, or 61. This was performed by an oligonucleotide hybridization technique following polymerase chain reaction amplification of these specific sequences. K-ras point mutation involving codon 12 was observed in two tumors, but not in the adjacent histologically benign lung tissue. These mutations were confirmed by direct sequencing of these polymerase chain reaction products. Both patients were smokers, had stage I tumors, and remain disease-free at 27 and 40 months postoperatively. No H-ras or N-ras point mutations were found. These findings suggest that ras activation is an infrequent event in bronchioloalveolar carcinoma. We speculate that ras activation is not a common transformational event in this form of lung adenocarcinoma.     

Preoperative F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value predicts survival after lung cancer resection.

PURPOSE: A retrospective review of surgically treated lung cancer patients imaged preoperatively by F-18 fluorodeoxyglucose-positron emission tomography ([(18)F]FDG-PET) to determine if the primary tumor standardized uptake value (SUV) predicts survival. PATIENTS AND METHODS: Non-small-cell lung cancer or carcinoid pT1-4, N0-2, M0 patients treated by R0 surgical resection alone were imaged with computed tomography scan and PET within 90 days before surgery. Prognostic variables were assessed by log-rank test; survival was assessed by the method of Kaplan and Meier. RESULTS: One hundred consecutive patients (48 men, 52 women) were retrospectively reviewed. Median follow-up for surviving patients was 28 months (range, 16 to 81 months). Median maximal SUV (SUV(MAX)) was 9. The 2-year survival for patients with SUV(MAX) more than 9 was 68% and for those with SUV(MAX) less than 9, it was 96% (P <.01, log-rank test). In a multivariate analysis including pathologic tumor size, involved nodes, histology, and SUV(MAX), only tumor size (T) more than 3 cm and SUV(MAX) more than 9 and their interaction were significant predictors of survival (P =.01, 0.02, and < 0.01, respectively). The 3-year survivals for patients with both T less than 3 cm and SUV(MAX) less than 9 was 97%; for those with T less than 3 cm and SUV(MAX) more than 9, it was 94%; for those with T more than 3 cm and SUV(MAX) less than 9, it was 93%; and for those with T more than 3 cm and SUV(MAX) more than 9, it was 47% (P <.01). CONCLUSION: In surgically managed lung cancer patients, SUV is a predictor of overall survival after resection. The addition of SUV(MAX) to pathologic tumor size identifies a subgroup of patients at highest risk for death as a result of recurrent disease after resection.