A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer.

BACKGROUND: This open-label phase III study assessed the addition of Toll-like receptor 9-activating oligodeoxynucleotide PF-3512676 to gemcitabine/cisplatin chemotherapy in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomized (1:1) to receive six or fewer 3-week cycles of i.v. gemcitabine (1250 mg/m2 on days 1 and 8) and cisplatin alone (75 mg/m2 on day 1, control arm) or combined with s.c. PF-3512676 0.2 mg/kg on days 8 and 15 of each chemotherapy cycle and weekly thereafter until progression or unacceptable toxicity (experimental arm). No crossover was planned. The primary end point was overall survival (OS). RESULTS: A total of 839 patients were randomized. Baseline demographics were well balanced. Median OS (11.0 versus 10.7 months; P=0.98) and median progression-free survival (PFS) (both 5.1 months) were similar between groups. Grade≥3 hematologic adverse events (AEs), injection-site reactions, and influenza-like symptoms were more frequently reported among patients receiving PF-3512676. At the first-interim analysis, the Data Safety Monitoring Committee recommended study discontinuation. Administration of PF-3512676 was halted based on efficacy futility and increased grade≥3 AEs (experimental arm). CONCLUSIONS: Addition of PF-3512676 to gemcitabine/cisplatin chemotherapy did not improve OS or PFS but did increase toxicity.

A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease.

BACKGROUND: This study compared irinotecan plus cisplatin (IP) with etoposide plus cisplatin (EP) in small-cell lung cancer patients with extensive disease. PATIENTS AND METHODS: Patients were randomly assigned to receive cisplatin 80 mg/m(2) and either irinotecan 65 mg/m(2), days 1 and 8 or etoposide 100 mg/m(2), days 1-3, every 3 weeks. RESULTS: Baseline characteristics were balanced between patients receiving IP (N = 202) or EP (N = 203). Median overall survival was nonsignificantly superior for patients receiving IP versus EP, 10.2 versus 9.7 months [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.65-1.01, P = 0.06] and 1- and 2-year survival rates were 41.9% versus 38.9% and 16.3% versus 8.2%, respectively. Noninferiority of IP versus EP was established, upper bound of the 95% CI of HR 1.01 (prespecified margin IP/EP <1.25). Overall response (39.1% versus 46.6%) and time to tumor progression (5.4 versus 6.2 months) were not superior for IP. Grade 3/4 vomiting (10.9% versus 4.4%) and diarrhea (15.4% versus 0.5%) were more common in the IP versus EP arm; grade 3/4 neutropenia was more frequent in the EP (59.6%) versus IP arm (38.1%). CONCLUSIONS: Our data demonstrate the noninferiority of IP versus EP for survival in primarily Western patients with SCLC-ED. A meta-analysis is required to finally assess the role of irinotecan in this setting.

Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL).

BACKGROUND: Bevacizumab, the anti-vascular endothelial growth factor agent, provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer. We report the final overall survival (OS) analysis from the phase III AVAiL trial. PATIENTS AND METHODS: Patients (n = 1043) received cisplatin 80 mg/m(2) and gemcitabine 1250 mg/m(2) for up to six cycles plus bevacizumab 7.5 mg/kg (n = 345), bevacizumab 15 mg/kg (n = 351) or placebo (n = 347) every 3 weeks until progression. Primary end point was progression-free survival (PFS); OS was a secondary end point. RESULTS: Significant PFS prolongation with bevacizumab compared with placebo was maintained with longer follow-up {hazard ratio (HR) [95% confidence interval (CI)] 0.75 (0.64-0.87), P = 0.0003 and 0.85 (0.73-1.00), P = 0.0456} for the 7.5 and 15 mg/kg groups, respectively. Median OS was >13 months in all treatment groups; nevertheless, OS was not significantly increased with bevacizumab [HR (95% CI) 0.93 (0.78-1.11), P = 0.420 and 1.03 (0.86-1.23), P = 0.761] for the 7.5 and 15 mg/kg groups, respectively, versus placebo. Most patients ( approximately 62%) received multiple lines of poststudy treatment. Updated safety results are consistent with those previously reported. CONCLUSIONS: Final analysis of AVAiL confirms the efficacy of bevacizumab when combined with cisplatin-gemcitabine. The PFS benefit did not translate into a significant OS benefit, possibly due to high use of efficacious second-line therapies.

Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and i.v. vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer.

BACKGROUND: The study compared the efficacy of a first-line treatment with day 1 i.v. vinorelbine (NVBiv) and day 8 oral vinorelbine (NVBo) versus docetaxel (DCT) in a cisplatin-based combination in advanced non-small-cell lung cancer, in terms of time to treatment failure (TTF), overall response, progression-free survival (PFS), overall survival (OS), tolerance and quality of life (QoL). METHODS: Patients were randomly assigned to receive cisplatin 80 mg/m2 with NVBiv 30 mg/m2 on day 1 and NVBo 80 mg/m2 on day 8 every 3 weeks, after a first cycle of NVBiv 25 mg/m2 on day 1 and NVBo 60 mg/m2 on day 8 (arm A) or cisplatin 75 mg/m2 and DCT 75 mg/m2 on day 1 every 3 weeks (arm B), for a maximum of six cycles in both arms. RESULTS: From 2 February 2004 to 1 January 2006, 390 patients were entered in a randomised study and 381 were treated. The patient characteristics are as follows (arms A/B): metastatic (%) 80.5/84.8; patients with three or more organs involved (%) 45.3/40.8; median age 59.4/62.1 years; male 139/146; squamous (%) 34.2/33.5; adenocarcinoma (%) 41.6/39.3; median TTF (arms A/B in months) [95% confidence interval (CI)]: 3.2 (3.0-4.2), 4.1 (3.4-4.5) (P = 0.19); overall response (arms A/B) (95% CI): 27.4% (21.2% to 34.2%), 27.2% (21.0% to 34.2%); median PFS (arms A/B in months) (95% CI): 4.9 (4.4-5.9), 5.1 (4.3-6.1) (P = 0.99) and median OS (arms A/B in months) (95% CI): 9.9 (8.4-11.6), 9.8 (8.8-11.5) (P = 0.58). The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B, respectively. Main haematological toxicity was grade 3-4 neutropenia: 24.4% (arm A) and 28.8% (arm B). QoL as measured by the Lung Cancer Symptom Scale was similar in both arms. CONCLUSIONS: Both arms provided similar efficacy in terms of response, time-related parameters and QoL, with an acceptable tolerance profile. In the current Global Lung Oncology Branch trial 3, NVBo was shown to be effective as a substitute for the i.v. formulation. This can relieve the burden of the i.v. injection on day 8 and can optimise the hospital's resources and improve patient convenience.

A case-control study of lifestyle and lung cancer associations by histological types.

The objective of the study was to investigate the contribution of dietary factors and physical exercise to the variation in the risk of lung cancer and its major histological types among men and women in the Czech Republic, and reveal interactions between smoking and diet/physical exercise, if any. In a hospital based case-control study, data collected by in-person interviews from 1096 microscopically confirmed lung cancer cases (587 women, 509 men) and 2966 controls were analyzed using unconditional logistic regression stratified by appropriate factors. Among all nonsmoking women protective effects were observed for black tea (OR=0.69), among all smoking women for wine (OR=0.71), physical exercise (OR=0.64) and vitamin supplements (OR=0.71). Among all men, inverse associations were found in smokers between lung cancer risk and frequent intake of fruits (OR=0.69) or moderate intake of spirits (OR=0.64), and a direct association for fat foods (OR=1.68). Comparing the effects of diet/physical activity on lung cancer risk among nonsmokers versus smokers, interactions with smoking appeared for the intake of black tea and milk/dairy products among women, and for moderate intake of spirits in men. When the effects of diet/physical exercise on risk were analyzed by major cell types in women, the intake of wine and physical exercise were inversely associated with the risk of both adenocarcinoma and small cell cancer, the intakes of fruits and vitamin supplements were inversely associated with the risk of squamous cell cancer. In men, the intake of fat foods was directly associated with the risk of squamous cell cancer, while the frequent intake of apples was inversely associated with the risk of both squamous- and small cell cancers. In men an inverse association with the risk of squamous cell cancer was found for the intake of other fruits. These data suggest that diet/physical exercise may affect the risk of lung cancer and major cell types, and that interactions between some dietary items and smoking may occur. Lung cancer is a multifactorial disease, since smoking, its main determinant, and other environmental and lifestyle factors interact with one another and with genetic factors to cause the disease.

A randomized phase III trial comparing standard and high-dose pemetrexed as second-line treatment in patients with locally advanced or metastatic non-small-cell lung cancer.

BACKGROUND: This phase III randomized trial compared pemetrexed 500 mg/m(2) (P500) with pemetrexed 900 mg/m(2) (P900) to determine whether higher dosing benefits non-small-cell lung cancer (NSCLC) patients as second-line therapy. PATIENTS AND METHODS: Patients with locally advanced or metastatic NSCLC, previously treated with platinum-based chemotherapy, were randomly assigned to receive i.v. P500 or P900 every 3 week. RESULTS: Accrual was terminated with 588/600 patients enrolled because an interim analysis indicated a low probability of improved survival and numerically greater toxicity on the P900 arm. P900 patients were permitted to continue treatment at P500. No statistical difference was observed between the treatment arms (P500 versus P900) for median survival {6.7 versus 6.9 months, hazard ratio [HR] = 1.0132 [95% confidence interval (CI) 0.837-1.226]}, progression-free survival [2.6 versus 2.8 months, HR = 0.9681 (95% CI 0.817-1.147)], or best overall tumor response [7.1% versus 4.3% (P = 0.1616)]. The incidence of drug-related grade 3/4 toxicity was typically <5% on both treatment arms, but was numerically higher on the P900 arm for most toxicity categories. CONCLUSIONS: P900 did not improve any efficacy measure over P500. P500 i.v. every 3 week remains the standard pemetrexed dose for second-line treatment of platinum-pretreated advanced NSCLC.

Interactions between smoking and other exposures associated with lung cancer risk in women: diet and physical activity.

UNLABELLED: The objective of the study is to estimate the differences in the impact of diet and physical exercise on lung cancer risk in female nonsmokers vs. smokers, and reveal interactions, if any. In a hospital based case-control study, data collected by in-person interviews from 569 female lung cancer cases and 2120 controls were analyzed using unconditional logistic regression stratifying by appropriate factors. Protective effects were observed for intake of milk/dairy products (OR=0.57, 95%CI 0.35-0.94), vegetables (OR=0.60, 95%CI 0.40-0.91), apples (OR=0.69), wine (OR=0.77), and physical exercise (OR=0.59, 95%CI 0.42-0.83) among smokers only, while no similar effects were found among nonsmokers. In contrast, the intake of black tea was associated with a protective effect (OR=0.66, 95%CI 0.47-0.94) among nonsmokers only. Comparing the effects of dietary items and physical activity on lung cancer risk among nonsmokers versus smokers, statistically significant effect modifications were found for black tea (P 0.005), and milk/dairy products (P 0.047). Borderline effect modifications emerged for physical exercise (P 0.077). CONCLUSIONS: These results indicate protective effects of some components of healthful diet and physical exercise among smokers, and of the intake of black tea among nonsmokers. The observed interactions of the impact of black tea, milk/dairy products and physical activity upon lung cancer risk in women at different levels of the smoking habit deserve further studies.

Clinical correlations of potential activity markers in systemic sclerosis.

The objectives of the project were the following: (1) to establish a group of patients with a confirmed diagnosis of systemic sclerosis (Ssc), (2) to perform a detailed entrance examination of each patient, (3) to determine concentrations of potential activity markers, and (4) to make a comprehensive examination of each patient 1 year after inclusion into the study. A total of 49 patients were examined, 36 with a limited form of SSc, 9 with diffuse SSc, and 4 with other forms of SSc. We determined plasma or serum levels of the N-terminal propeptide of procollagen type III (NPIIIP), interleukin-6 (IL-6), soluble receptor for interleukin-2 (sIL-2r), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), von Willebrand factor antigen (vWFAg), and big endothelin-1 (BET-1) using commercial kits, and urinary excretion of pyridinoline (PYR) and deoxypyridinoline (D-PYR) using high-performance liquid chromatography. Correlations of these markers with selected clinical data were calculated. The mean levels of all potential activity markers were increased compared with normal values, but differences were not significant. The levels of NPIIIP, D-PYR, and IL-6 were normal. The measured values after 1 year did not differ from the entry values. At entry, NPIIIP concentrations correlated with the finger-to-palm distance, and D-PYR corresponded with findings on a simplified health assessment questionnaire (FQ). IL-6 levels correlated with the leukocyte count, sIL-2r with the FQ, and ET-1 with the diffuse lung capacity for carbon monoxide. In general, we found only a few clinical correlates of potential activity markers. Our data confirmed the correlations of collagen metabolism markers with skin involvement and FQ, as was reported previously. Larger studies in this field are needed.

Low mutational rate of K-ras codon 12 in singular bronchoscopy specimens in suspected lung cancer.

Mutations of the K-ras gene are found in a subset of non-small- cell lung carcinomas (NSCLC). The aim of our study was to determine the K-ras codon 12 mutation in the first, singular bronchoscopy specimen in parallel with the cytological examination for the diagnosis of lung cancer. Samples were obtained by diagnostic bronchoscopy in 140 patients with suspected lung tumors. The analysis of K-ras mutations was carried out by a sensitive two-step mutation- enriched polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. This method has been confirmed earlier to be positive for mutated tumor cells and negative for normal lung parenchyma and bronchus. Of the 140 patients with suspected cancer, 93 were diagnosed as NSCLC by cytology or histology in either the same specimen used for the detection of K-ras mutation or in later biopsies. However, only four K-ras codon 12 mutations were detected in the first bronchoscopic material: one in adenocarcinoma, two in squamous cell tumors, and one mutation was found in a patient with dysplasia which was diagnosed later as a squamous cell carcinoma. Our findings indicate that although the K-ras (codon 12) mutation is a gene lesion infrequently detectable in a singular specimen taken at the first bronchoscopy examination in cases of clinically suspected lung cancer, the detection of this mutation can help to confirm the cytological diagnosis of NSCLC or may be even diagnostic in cytologically negative cases.

Dietary habits and lung cancer risk among non-smoking women.

A case-control study was conducted to investigate the relationship between diet and the risk of lung cancer among women non-smokers and to compare with women smokers in the same population. Data collected by personal interviews from 435 microscopically confirmed cases and 1710 controls were analysed using unconditional logistic regression. In addition to results for all study subjects, associations between diet and lung cancer risk were compared between two highly contrasting groups: smokers (odds ratio (OR) 7.03) and non-smokers (OR 1.00). A protective effect of frequent (daily or several times per week) black tea drinking appeared among non-smoking women (OR 0.65, 95% confidence interval (CI) 0.43-0.99). Among smoking women, protective effects were observed for frequent intake of milk/dairy products (OR 0.56, 95% CI 0.32-0.96), coffee (OR 0.47, 95% CI 0.25-0.88), and wine consumption (daily or weekly OR 0.60, 95% CI 0.37-0.98; monthly OR 0.60, 95% CI 0.39-0.94). Inverse associations with the risk appeared for physical exercise for smokers only, and for the body mass index both among non-smoking and smoking women. Some items of diet may contribute to variation in risk among women in the Czech Republic; their importance seems to vary in relation to their status in smoking, the dominant factor in the aetiology of lung cancer.

Lung cancer risk among nonsmoking women in relation to diet and physical activity.

To investigate the relationship between diet, physical activity, and the risk of lung cancer among female nonsmokers, and to compare it with female smokers in the same population, we conducted a case-control study. Data collected by personal interviews from 419 cases and 1593 controls were analyzed using unconditional logistic regression. As expected, among 130 nonsmoking cases, adenocarcinoma was the predominant cell type (49.2%), followed by squamous cell (20.2%) and small cell cancers (10.5%). The corresponding figures for 289 smoking cases were 29.3%, 27.5%, and 28.2%, respectively. Excess lung cancer risk was associated with consumption of red meat among nonsmokers (OR=2.20, 95%CI 1.07--4.51). Protective effects were observed for vegetables (OR=0.61, 95%CI 0.39--0.96), apples (OR=0.67, 95%CI 0.48--0.95), milk/dairy products (OR=0.54, 95%CI 0.32--0.93), coffee (OR=0.56, 95%CI 0.34--0.91), and wine (OR=0.69, 95%CI 0.49--0.98) among smokers only, and for black tea (OR=0.67, 95%CI 0.46--0.99) among nonsmokers only. An inverse association with risk emerged for physical exercise (or sport, walking), among smokers only. Some items of diet and physical activity appear to be important factors contributing to variation in lung cancer risk among women in the Czech Republic, however, their effects in nonsmokers may differ from those in smokers.

Vinorelbine alternating oral and intravenous plus carboplatin in advanced non-small-cell lung cancer: results of a multicentre phase II study.

BACKGROUND: Vinorelbine and carboplatin are both active agents in the treatment of non-small-cell lung cancer (NSCLC). Vinorelbine has recently been developed in an oral formulation, which is as active as the intravenous (i.v.) form. PATIENTS AND METHODS: Fifty-two chemonaive patients with unresectable localised or metastatic NSCLC received i.v. vinorelbine 25 mg/m(2) plus carboplatin (AUC 5) on day 1 and oral vinorelbine 60 mg/m(2) on day 8 (or day 15 if neutrophils <1500/mm(3)) every 3 weeks in an open-label, multicentre phase II study. RESULTS: A total of 224 cycles were given, with the median number per patient of four (range one to eight). Eight responses out of 52 enrolled patients were documented and validated by an independent panel review, yielding a response rate of 18.2% [95% confidence interval (CI) 6.8-29.6%] in the evaluable population. This response rate was balanced by a high rate of disease control (78.9% in the intention-to treat population and 90.9% in the evaluable population). The median progression-free and median survival were 5.1 months (95% CI 4.3-8.1) and 9.3 months (95% CI 6.8-11.4), respectively. Overall, the safety profile of the combination regimen alternating i.v. and oral vinorelbine appeared similar to that expected for each individual agent. Some lung cancer-specific items (pain, dyspnoea) improved or were stabilised by assessment using the EORTC QLQ-C30 and QLQ-LC13 questionnaires. CONCLUSIONS: The combination of carboplatin with an alternating regimen of i.v./oral vinorelbine is a well tolerated regimen with a low level of toxicity and a low rate of serious adverse events. A high rate of disease control (partial response + no change) was achieved. Progression-free survival and overall survival fell within the expected range. This regimen is convenient and safe for the treatment of patients with locally advanced or metastatic NSCLC patients.

Bronchial carcinoid tumors: long-term outcome after surgery.

The objective of the present study was to evaluate clinical condition and results of surgical treatment of patients with typical and atypical bronchial carcinoids. The study was based on retrospective analysis of a total of 96 patients (mean age 47.3 year, age range 21-76, 44 men and women 52), who were surgically treated for bronchial carcinoid between 1985-2001. We assessed symptomatology of the disease, type of surgical intervention, tumor histology and staging, and postoperative 5-year and 10 year survival rates. The main sign of disease was respiratory inflammation. The carcinoid syndrome was not found in any patient. Most patients (n=68) were operated for central form of the tumor. The micromorphological tumor diagnosis was established prior to surgery in 76.5% patients with the central form of carcinoid. Surgical treatment included lobectomy (n=49), bronchoplastic procedure (n=14), sleeve lobectomy (n=9), atypical resection and segmentectomy (n=11), pneumonectomy (n=7) and tumor enucleation (n=5). Histological analysis revealed typical carcinoid in 77 cases (80.2%) and atypical carcinoid in 19 (19.8%). Lymph nodes (N1 and/or N2) were examined by histology in 84 patients and lymph node metastases were found in 13 (19.4%) of 67 patients with typical carcinoid and in 5 cases (29.4%) of 17 with atypical carcinoid. In the postoperative period on patient died from embolism to the arteria pulmonalis. Postoperative complications (atelectasis, prolonged air leak, bronchopleural fistula) were observed in 11.4% of patients. Tumor relapse occurred only in two patients with typical carcinoid. Postoperative 5-year and 10-year rates amounted to 98.6% and 87.3%, respectively, in typical carcinoid 94.5% and 73.5% in atypical carcinoid. The survival rates of patients with typical and atypical bronchial carcinoids were not significantly different (p>0.05). The surgical management is the treatment of choice in bronchial carcinoids. Results of this study indicate that the 5-year survival in patients with either histological type of bronchial carcinoid is excellent and the prognosis of operated patients is very good even in the case of regional lymph nodes infiltration by the tumors.

Disseminated Nocardia asteroides infection in an immunocompetent woman following an arm injury.

A case of disseminated infection with Nocardia asteroides in a 55-year-old immunocompetent woman after mild trauma to the arm is reported. Secondary dissemination was identified in the skin, right kidney, liver, peritoneal cavity, lungs and thigh. The patient was successfully treated with surgical drainage and a 9-week course of antibiotics including cefotaxime, amikacin, chloramphenicol, trimethoprim/sulfamethoxazole (TMP/SMX) and doxycycline. The administration of TMP/SMX in combination with doxycycline was clinically beneficial despite in vitro resistance.

[Resection of the trachea for cicatrical stenosis]. / Trachealresektion bei Narbenstenosen.

UNLABELLED: Tracheal stenosis represents a serious complication of tracheostomy or of endotracheal intubation. The objective of this article was to evaluate the results of resective therapy of patients with tracheal stenosis. METHODS: In 41 patients treated by tracheal resection for tracheal stenosis the diagnosis was established by bronchoscopy, tracheal tomography or CT. The following parameters were evaluated: the reasons for artificial pulmonary ventilation, basic parameters of stenosis (site of stenosis, length, diameter), the relationship between the duration of cannulation and asymptomatic interval, and postoperative complications. RESULTS: The most frequent reason for cannulation was trauma (n = 23), most patients were cannulated for 4-5 weeks (n = 16), the symptoms of stenosis appeared mostly within 4-5 weeks (n = 11) after decannulation. The asymptomatic interval was longer in patients with longer periods of cannulation (p < 0.01) than in patients with a shorter cannulation period. The most frequent site of stenoses was the medium third of the trachea (n = 22). The longest resected section measured 60 mm. In 3 patients (7.3 %) a tracheoesophageal fistula was found together with the stenosis. In 3 patients (7.3 %) restenosis appeared. Tracheocutaneous fistula with osteomyelitis of the sternum developed in one patient. Granulation tissue on the anastomosis site (n = 4, 9.7 %) was treated by laser or disappeared spontaneously. None of the patients died within 30 days after operation. CONCLUSION: Resection is the optimum therapeutic method for tracheal stenosis with low postoperative mortality and a small number of postoperative complications. Successful tracheal resection is a definitive solution in comparison with stent placement.

Diet and the risk of lung cancer among women. A hospital-based case-control study.

Variation in diet has been suspected to be one of cofactors related to geographic variation in lung cancer risk, namely for women, or other population groups with a low exposure to cigarette smoking. The study has been designed to obtain more insight into possible associations between diet and lung cancer risk among women in a country with a Central European socioeconomic background. In a hospital-based case-control study personal interviews of 282 female lung cancer cases and 1120 female controls were done using a structured standard questionnaire. Cigarette smoking was the most important factor associated with excess risk for lung cancer among women. Significantly increased risk was found both among current smokers (OR = 9.22), and ex-smokers (OR = 7.11). Positive dose-response gradients (p < 0.001) were observed between lung cancer risk and the daily number of cigarettes, duration of smoking, and number of pack-years. For squamous-, small- and large-cell cancers combined, significant associations of lung cancer risk with the consumption of red meat and poultry (OR = 2.33, and OR = 8.67, respectively), and an inverse association with the consumption of vegetables (OR = 0.55) were found. No such variations in risk were observed for adenocarcinoma, including the bronchioalveolar cancer type. For all lung cancer types combined, coffee drinking showed a significant inverse association with lung cancer risk risk (OR = 0.66). While smoking is the major risk for lung cancer, diet may have a contributory role. Variations in the intake of some components of diet, namely red meat, poultry, vegetables, and coffee may contribute to understanding variations in the risk of lung cancer among Czech women.

Management of inoperable carcinoma of the breast by curative radiotherapy and chemo-hormonotherapy.

BACKGROUND: The aim of this study was to evaluate local control and its relation to survival in patients with locally advanced breast cancer treated with curative irradiation and systemic therapy. PATIENTS AND METHODS: 240 patients with unresectable breast cancer were treated with curative radio- and chemo- or hormonotherapy from 1990-1995. The frequency of distant dissemination and the overall survival of patients with and without complete local control were compared. RESULTS: Complete local control was achieved in 63% of patients. Complete local control correlated with decrease of distant metastases and increase of survival in comparison with patients without complete local control. CONCLUSION: Radiotherapy without surgery provides insufficient local control in patients with locally advanced breast cancer. Complete local control is an important factor for prevention of distant dissemination and for survival.

A case-control study of lung cancer among Czech women.

Few data are available to explain the continuing increase in lung cancer mortality among Czech women. The study was designed to examine the role of active smoking and other known or suspected factors. Data collected by personal interviews during the 15 months of a hospital-based case control study are reported. A total of 140 microscopically confirmed cases and 280 frequency-matched controls were analysed using multiple logistic regression. Cigarette smoking was the most important factor associated with excess risk for lung cancer among women. Significantly increased risk was found both among current smokers (OR=11.20, 95% CI 5.9-21.2), and ex-smokers (OR=10.02, 95% CI 5.5-18.4). Positive dose-response gradients (P<0.001) were observed between lung cancer risk and the daily number of cigarettes, duration of smoking, number of pack-years, inhaling, and grade of nicotine dependence assessed by the Fagerström test (Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO. Br J Addict 1991;86:1119-1470; Pomerleau OF. In: Bolliger CT, Fagerström KO, editors. The Tobacco Epidemic. Basle: Karger, 1997: 122-131). Exposure to environmental smoke was associated with elevated lung cancer risk (OR=3.58, for lifetime non-smokers exposed both in childhood and in adult age). Physical exercise and body mass index were inversely associated with lung cancer risk. For the category of physical exercise of more than 5 h per week, the odds ratio was 0.38, compared to subjects admitting no physical exercise. For body mass index, the odds ratio for the highest (compared to the lowest) quartile was 0.50. Chronic cough and phlegm (at least 3 months per year) were associated with excess risk (OR=6.07) only if their duration was less than 2 years before diagnosis of lung cancer, and, therefore, they were suspected of being more likely early symptoms of preclinical lung cancer rather than its cause. Our results support the statement that cigarette smoking is by far the most important cause of the on-going epidemic of lung cancer among Czech women, and are consistent with the concept of a balance between risk and protective factors whose eventual maintenance or alteration determine the development of disease (as suggested by Rylander R, Axelsson G, Andersson L, Liljequist T, Bergman B. Lung Cancer 1996;14(Suppl 1): S75-S83). Concerted control of smoking appears to be an urgent priority in lung cancer prevention among women, including specific approaches targeted on the female population.