Results of radiation therapy for limited small-cell lung cancer

Results of radiotherapy were reviewed in 68 patients with limited small-cell lung cancer from the aspect of local control. Thirty-one patients achieved CR (46%), while the other 31 remained at PR. The 1-, 2-, 3-, and 5-year cumulative survival rates were 57%, 28%, 21%, and 16%, respectively, for 15 months in MST. Thirty-six patients developed local recurrence (53%) and 46 had distant metastasis (68%). The thirty-one patients with CR had a 43% 2-year-survival rate and 23 months in MST. The remaining 37 patients (PR + NC) had respective figures of 13% and 13 months (p < 0.025). There was no statistically significant difference between radiation dose and local thoracic failure among the patients. Of the 31 patients with CR, 28 had achieved CR at 45Gy (17 received 55Gy or more, and 11 less than 55Gy). In the former, the local control rate, 2-year-survival and MST were 94%, 53% and 44 months, while in the latter these were 45%, 27% and 17 months, respectively. Thirty-five patients were irradiated by the shrinking field technique according to tumor reduction; however, this technique did not influence the treatment results. To obtain better results, it is first necessary to achieve CR at initial chemo-radiotherapy. As to irradiation, randomized trials between 50Gy and 60Gy would require patients with CR at 45Gy.     

Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide

BACKGROUND: For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic radiotherapy improves survival, but the best ways of integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily accelerated thoracic radiotherapy has potential advantages over once-daily radiotherapy. METHODS: We studied 417 patients with limited small-cell lung cancer. All the patients received four 21-day cycles of cisplatin plus etoposide. We randomly assigned these patients to receive a total of 45 Gy of concurrent thoracic radiotherapy, given either twice daily over a three-week period or once daily over a period of five weeks. RESULTS: Twice-daily treatment beginning with the first cycle of chemotherapy significantly improved survival as compared with concurrent once-daily radiotherapy (P=0.04 by the log-rank test). After a median follow-up of almost 8 years, the median survival was 19 months for the once-daily group and 23 months for the twice-daily group. The survival rates for patients receiving once-daily radiotherapy were 41 percent at two years and 16 percent at five years. For patients receiving twice-daily radiotherapy, the survival rates were 47 percent at two years and 26 percent at five years. Grade 3 esophagitis was significantly more frequent with twice-daily thoracic radiotherapy, occurring in 27 percent of patients, as compared with 11 percent in the once-daily group (P<0.001). CONCLUSIONS: Four cycles of cisplatin plus etoposide and a course of radiotherapy (45 Gy, given either once or twice daily) beginning with cycle 1 of the chemotherapy resulted in overall two- and five-year survival rates of 44 percent and 23 percent, a considerable improvement in survival rates over previous results in patients with limited small-cell lung cancer.     

Surgical treatment for lung cancer invading thoracic aorta

There are two situations when antibiotic prophylaxis is recommended. The first is associated with procedures known to be followed by high rates of bacteraemia, involving organisms prone to cause endocarditis. These include oesophageal dilatation, variceal sclerotherapy and laser therapy in the upper gastrointestinal tract. As bacteraemia following these procedures is usually harmless in average risk patients antibiotic prophylaxis is recommended only for a patient with a lesion susceptible to endocarditis or one who is at increased risk of symptomatic bacteraemia due to neutropenia or immunosuppression. In most cases parenteral amoxycillin and gentamicin is recommended plus metronidazole for neutropenic patients. Vancomycin or teicoplanin replace amoxycillin in a case of allergy. The second situation concerns procedures with a high incidence of local infection or which may lead to serious sepsis. These include therapeutic retrograde cholangiopancratography and percutaneous endoscopic gastrostomy where antibiotic prophylaxis is recommended even in average risk patients. Several antibiotics are recommended including oral ciprofloxacin or parenteral gentamicin or quinolone for ERCP and amoxycillin for PEG or cephalosporin or ureidopenicillin for both.     

Results of initial surgery and adjuvant chemotherapy in treating small-cell lung cancer

The changes in the intestinal mucosal permeability were observed by quantitatively assessing plasma to luminal clearance of 99mTc-labeled DTPA, and the influence of platelet activating factor (PAF) on it was investigated. The results showed that intestinal permeability was significantly elevated after severe burn and was positively correlated with increase in PAF in the intestinal tissue (r = 0.94, P < 0.01). PAF antagonist therapy could significantly attenuate postburn intestinal mucosal permeability. It is concluded that PAF is one of the important factors causing increased intestinal permeability after severe burn.     

BW 1023U90: a new GRP receptor antagonist for small-cell lung cancer cells

Gastrin-releasing peptide (GRP) receptor antagonists were synthesized and their ability to interact with small-cell lung cancer (SCLC) cells determined. [125I] BW1023U90, bound with high affinity (Kd = 2 nM) to a single class of sites (Bmax = 55 fmol/mg protein) using SCLC cell line NCI-H345. [125I] BW1023U90 binding was time dependent and reversible even at 37 degrees C as the ligand was minimally internalized. Specific [125I] BW1023U90 binding was inhibited with high affinity by GRP as well as bombesin (BB) but not neuromedin B (NMB). BW1023U90 inhibited the ability of BB to elevate cytosolic Ca2+ and increase the growth of SCLC cells. A BW1023U90 analogue, BW2258U89 (10 micrograms/day, SC) slowed SCLC xenograft format on in nude mice and [125I] BW 1023U90 localized to SCLC tumors 1 h after injection into nude mice. BW2258U89 (4% by weight) was placed in microspheres and slowly released over a 3-week period in nude mice bearing SCLC xenografts. The microspheres containing BW2258U89 strongly inhibited SCLC growth in vivo. A radioimmunoassay was developed for the GRP receptor antagonists and the rabbit antiserum cross-reacted totally with BW2258U89 or BW1023U90. BW2258U89 immunoreactivity (5 nM) was detected in the plasma of nude mice containing the microspheres after 1 week. These data suggest that GRP receptor antagonists bind to receptors on SCLC tumors.     

Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake

The effect of oral ubiquinone (Q10) intake on the in vivo response of tumors to single dose radiotherapy was examined. The human small-cell lung cancer (SCLC) line CPH 054A, which is sensitive to relatively low doses of X-radiation, was grown as subcutaneous transplants in the flanks of nude nu/nu mice. When macroscopical growth was established, groups of mice received either 10, 20 or 40 mg/kg Q10 in 30 mL soy oil intragastrically daily on 4 consecutive days. Controls received either 30 mL of pure soy oil or nothing. Three h after the last dose half of the tumors in each group received a single radiation dose of 5 Gy, using a 300 kV therapeutic unit. The macroscopic growth pre- and posttreatment was analyzed according to a transformed Gompertz algorithm using the software program GROWTH. Treatment with Q10 or soy oil alone had no effect on tumor growth compared with untreated controls. Groups of tumors that received Q10 and radiotherapy had a significantly lower specific growth delay (SGD) than the radiotherapy-only groups. This effect was significant at 40 mg/kg and borderline at 20 mg/kg, whereas at 10 mg/kg no radioprotection was seen. We conclude that systemic Q10 reduces the response to single dose tumor irradiation inxenotransplanted human SCLC tumors.     

Phase II trial of raltitrexed ('Tomudex') in advanced small-cell lung cancer

Raltitrexed, a thymidylate synthase inhibitor, was given to 21 patients with advanced small-cell lung cancer, at a dose of 3 mg m(-2) as a 15-min intravenous infusion at 21-day intervals. All of the patients had extensive disease and 17 had received prior therapy. Patients with disease refractory to primary chemotherapy were excluded. Forty-one treatment cycles were given (median two, range one to four). The drug was well tolerated. No objective tumour response was documented. The patients had chemoresistant disease, as shown by a response in only one of ten patients who went on to receive alternative cytotoxic regimens. We conclude that raltitrexed given in this schedule is inactive as second line therapy for small-cell lung cancer.     

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis

PURPOSE: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.     

A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major complications associated with total knee arthroplasty. The American College of Chest Physicians recommends twice-daily, fixed-dose low-molecular-weight heparin (LMWH) as routine prophylaxis in this patient population. This study represents a cost analysis of ardeparin and enoxaparin, the two LMWHs currently available for this indication in the United States. Costs for treating DVT, PE, and major bleeding episodes were derived from values reported in the literature. Both ardeparin and enoxaparin were found to produce significant cost savings when used routinely as DVT prophylaxis after knee replacement surgery compared with no prophylaxis. Based on the currently available data, enoxaparin 40 mg once daily appears to be the least costly LMWH for routine pharmacoprophylaxis of DVT in patients undergoing knee replacement surgery.     

Long-term remission after brachytherapy with external irradiation for locally advanced lung cancer

Three cases are reported who received brachytherapy with external irradiation for inoperable lung cancer and have shown long-term remission. The diseases were adenoid cystic carcinoma, recurrent adenocarcinoma and squamous cell carcinoma. The associated symptoms were severe cough and dyspnea in all 3 cases. They received 60 Gy of external irradiation. After an interval of 2 weeks, 6 Gy at a radius of 1 cm from the center of the source was delivered by iridium-192. They received 2-4 fractions at 1-week intervals. On termination of brachytherapy, complete response was observed in all cases. In 1 case, bronchial stenosis due to radiation-induced fibrosis was observed, but was successfully treated by bronchial stent. Cough and dyspnea disappeared, and all patients have been rendered asymptomatic for the last 2 years. Local disease was well controlled in 2 cases; however, minimal local recurrence was observed after a 2-year follow-up in 1 case.     

Limbic encephalitis and SIADH revealing small-cell anaplastic lung cancer: MRI and immunologic findings

Paraneoplastic limbic encephalitis (PLE) is a manifestation of clinico pathological entity encephalo-myelo-neuropathy associated with anti-neuronal antibodies type 1 (ANNA-1 also called anti-Hu). Isolated PLE is rare. We reported a case of PLE in a 61-year-old heavy smoker man. An inappropriate antidiuretic hormone secretion syndrome was associated. Cranial MRI showed hyperintensity in amygdalo-hippocampic regions on T2 weighted sequences which appeared hypointense on T1-weighted sequences without gadolinium enhancement. Anti-Hu antibodies were absent in serum and in CSF. Despite chemotherapy, he died 18 months after disease onset. Our patient presented PLE without myelonouropathy and without ANNA-1 which suggests a different immunopathology.