Comorbidity and outcomes of concurrent chemo- and radiotherapy in limited disease small cell lung cancer.

BACKGROUND: Many patients with limited disease small cell lung cancer (LD SCLC) suffer from comorbidity. Not all patients with comorbidity are offered standard treatment, though there is little evidence for such a policy. The aim of this study was to investigate whether patients with comorbidity had inferior outcomes in a LD SCLC cohort. MATERIAL AND METHODS: We analyzed patients from a randomized study comparing two three-week schedules of thoracic radiotherapy (TRT) plus standard chemotherapy in LD SCLC. Patients were to receive four courses of cisplatin/etoposide and TRT of 45 Gy/30 fractions (twice daily) or 42 Gy/15 fractions (once daily). Responders received prophylactic cranial irradiation (PCI). Comorbidity was assessed using the Charlson Comorbidity Index (CCI), which rates conditions with increased one-year mortality. RESULTS: In total 157 patients were enrolled between May 2005 and January 2011. Median age was 63 years, 52% were men, 16% had performance status 2, and 72% stage III disease. Forty percent had no comorbidity; 34% had CCI-score 1; 15% CCI 2; and 11% CCI 3-5. There were no significant differences in completion rates of chemotherapy, TRT or PCI across CCI-scores; or any significant differences in the frequency of grade 3-5 toxicity (p = 0.49), treatment-related deaths (p = 0.36), response rates (p = 0.20), progression-free survival (p = 0.18) or overall survival (p = 0.09) between the CCI categories. CONCLUSION: Patients with comorbidity completed and tolerated chemo-radiotherapy as well as other patients. There were no significant differences in response rates, progression-free survival or overall survival - suggesting that comorbidity alone is not a reason to withhold standard therapy in LD SCLC.

Randomized phase II trial comparing twice daily hyperfractionated with once daily hypofractionated thoracic radiotherapy in limited disease small cell lung cancer.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy (TRT) is recommended for limited disease small cell lung cancer (LD SCLC). Twice daily TRT is well documented, but not universally implemented - probably mainly due to inconvenience and concerns about toxicity. A schedule of three-week hypofractionated TRT is a commonly used alternative. This is the first randomized trial comparing twice daily and hypofractionated TRT in LD SCLC. MATERIAL AND METHODS: Patients received four courses of cisplatin/etoposide (PE) and were randomized to TRT of 42 Gy in 15 fractions (once daily, OD) or 45 Gy in 30 fractions (twice daily, BID) between the second and third PE course. Good responders received prophylactic cranial irradiation of 30 Gy in 15 fractions. RESULTS: 157 patients were enrolled between May 2005 and January 2011 (OD: n = 84, BID: n = 73). Median age was 63 years, 52% were men, 84% had performance status 0-1, 72% had stage III disease and 11% non-malignant pleural effusion. The treatment arms were well balanced. The response rates were similar (OD: 92%, BID: 88%; p = 0.41), but more BID patients achieved a complete response (OD: 13%, BID: 33%; p = 0.003). There was no difference in one-year progression-free survival (PFS) (OD: 45%, BID: 49%; p = 0.61) or median PFS (OD: 10.2 months, BID: 11.4 months; p = 0.93). The median overall survival in the BID arm was 6.3 months longer (OD: 18.8 months, BID: 25.1 months; p = 0.61). There were no differences in grade 3-4 esophagitis (OD: 31%, BID: 33%, p = 0.80) or pneumonitis (OD: 2%, BID: 3%, p = 1.0). Patients on the BID arm reported slightly more dysphagia at the end of the TRT. CONCLUSION: There was no difference in severe toxicity between the two TRT schedules. The twice daily schedule resulted in significantly more complete responses and a numerically longer median overall survival, but no firm conclusions about efficacy could be drawn from this phase II trial.

Low oxygen saturation and mortality in an adult cohort: the Tromsø study.

BACKGROUND: Oxygen saturation has been shown in risk score models to predict mortality in emergency medicine. The aim of this study was to determine whether low oxygen saturation measured by a single-point measurement by pulse oximetry (SpO2) is associated with increased mortality in the general adult population. METHODS: Pulse oximetry was performed in 5,152 participants in a cross-sectional survey in Tromsø, Norway, in 2001-2002 ("Tromsø 5"). Ten-year follow-up data for all-cause mortality and cause of death were obtained from the National Population and the Cause of Death Registries, respectively. Cause of death was grouped into four categories: cardiovascular disease, cancer except lung cancer, pulmonary disease, and others. SpO2 categories were assessed as predictors for all-cause mortality and death using Cox proportional-hazards regression models after correcting for age, sex, smoking history, body mass index (BMI), C-reactive protein level, self-reported diseases, respiratory symptoms, and spirometry results. RESULTS: The mean age was 65.8 years, and 56% were women. During the follow-up, 1,046 (20.3%) participants died. The age- and sex-adjusted hazard ratios (HRs) (95% confidence intervals) for all-cause mortality were 1.99 (1.33-2.96) for SpO2 ≤ 92% and 1.36 (1.15-1.60) for SpO2 93-95%, compared with SpO2 ≥ 96%. In the multivariable Cox proportional-hazards regression models that included self-reported diseases, respiratory symptoms, smoking history, BMI, and CRP levels as the explanatory variables, SpO2 remained a significant predictor of all-cause mortality. However, after including forced expiratory volume in 1 s percent predicted (FEV1% predicted), this association was no longer significant. Mortality caused by pulmonary diseases was significantly associated with SpO2 even when FEV1% predicted was included in the model. CONCLUSIONS: Low oxygen saturation was independently associated with increased all-cause mortality and mortality caused by pulmonary diseases. When FEV1% predicted was included in the analysis, the strength of the association weakened but was still statistically significant for mortality caused by pulmonary diseases.

How Do Elderly Poor Prognosis Patients Tolerate Palliative Concurrent Chemoradiotherapy for Locally Advanced Non-Small-Cell Lung Cancer Stage III? A Subset Analysis From a Clinical Phase III Trial.

BACKGROUND: In a phase III trial of patients with unresectable, locally advanced, stage III non-small-cell lung cancer (NSCLC) with a poor prognosis, palliative concurrent chemoradiotherapy (CRT) provided a significantly better outcome than chemotherapy alone, except among performance status (PS) 2 patients. In the present subgroup analysis, we evaluated the effect on patients aged ≥ 70 years (42% of all included) compared with patients aged < 70 years enrolled in the trial. PATIENTS AND METHODS: All patients received 4 courses of intravenous carboplatin and oral vinorelbine. The experimental arm also received radiotherapy (42 Gy in 15 fractions). The included patients were required to have large tumors (> 8 cm), weight loss (> 10% within the previous 6 months) and/or PS 2. RESULTS: The overall survival was increased among the CRT patients in both age groups, but the difference was significant only in patients aged < 70 years (median survival, 14.8 vs. 9.7 months; P = .001; age ≥ 70 years, median survival, 10.2 vs. 9.1 months; P = .09). Patients aged ≥ 70 years experienced better preserved health-related quality of life (QOL) and significantly less hematologic toxicity. The 2- and 3-year survival was significantly increased in both age groups receiving CRT. CONCLUSION: Elderly patients aged ≥ 70 years with unresectable, stage III, locally advanced, NSLCL and a poor prognosis can tolerate CRT with the doses adjusted to age and palliative intent. These results indicate that CRT can provide both survival and QOL benefits in elderly patients, except for those with PS 2 or worse. The male predominance in the ≥ 70-year-age group and the reduced chemotherapy intensity for the patients aged > 75 years might explain the lack of significant survival improvement among those patients aged ≥ 70 years.

Low FEV1, smoking history, and obesity are factors associated with oxygen saturation decrease in an adult population cohort.

BACKGROUND: Worsening of pulmonary diseases is associated with a decrease in oxygen saturation (SpO2). Such a decrease in SpO2 and associated factors has not been previously evaluated in a general adult population. AIM: We sought to describe SpO2 in a sample of adults, at baseline and after 6.3 years, to determine whether factors predicting low SpO2 in a cross-sectional study were also associated with a decrease in SpO2 in this cohort. METHODS: As part of the Tromsø Study, 2,822 participants were examined with pulse oximetry in Tromsø 5 (2001/2002) and Tromsø 6 (2007/2008). Low SpO2 by pulse oximetry was defined as an SpO2 ≤ 95%, and SpO2 decrease was defined as a ≥ 2% decrease from baseline to below 96%. RESULTS: A total of 139 (4.9%) subjects had a decrease in SpO2. Forced expiratory volume in 1 second (FEV1) <50% of the predicted value and current smoking with a history of ≥ 10 pack-years were the baseline characteristics most strongly associated with an SpO2 decrease in multivariable logistic regression (odds ratio 3.55 [95% confidence interval (CI) 1.60-7.89] and 2.48 [95% CI 1.48-4.15], respectively). Male sex, age, former smoking with a history of ≥ 10 pack-years, body mass index ≥ 30 kg/m(2), and C-reactive protein ≥ 5 mg/L were also significantly associated with an SpO2 decrease. A significant decrease in FEV1 and a new diagnosis of asthma or chronic obstructive pulmonary disease during the observation period most strongly predicted a fall in SpO2. A lower SpO2 decrease was observed in those who quit smoking and those who lost weight, but these tendencies were not statistically significant. CONCLUSION: A decrease in SpO2 was most strongly associated with severe airflow limitation and a history of smoking. Smoking cessation and reducing obesity seem to be important measures to target for avoiding SpO2 decreases in the general population.

Poor prognosis patients with inoperable locally advanced NSCLC and large tumors benefit from palliative chemoradiotherapy: a subset analysis from a randomized clinical phase III trial.

INTRODUCTION: Poor prognosis patients with bulky stage III locally advanced non-small-cell lung cancer may not be offered concurrent chemoradiotherapy (CRT). Following a phase III trial concerning the effect of palliative CRT in inoperable poor prognosis patients, this analysis was performed to explore how tumor size influenced survival and health-related quality of life (HRQOL). METHODS: A total of 188 poor prognosis patients recruited in a randomized clinical trial received four courses intravenous carboplatin day 1 and oral vinorelbine day 1 and 8, at 3-week intervals. The experimental arm (N = 94) received radiotherapy with fractionation 42 Gy/15, starting at the second chemotherapy course. This subset study compares outcomes in patients with tumors larger than 7 cm (N = 108) versus tumors 7 cm or smaller (N = 76). RESULTS: Among those with tumors larger than 7 cm, the median overall survival in the chemotherapy versus CRT arm was 9.7 and 13.4 months, respectively (p = 0.001). The 1-year survival was 33% and 56%, respectively (p = 0.01). Except for a temporary decline during treatment, HRQOL was maintained in the CRT arm, regardless of tumor size. Among those who did not receive CRT, patients with tumors larger than 7 cm experienced a gradual decline in the HRQOL. The CRT group had significantly more esophagitis and hospitalizations because of side effects regardless of tumor size. CONCLUSION: In patients with poor prognosis and inoperable locally advanced non-small-cell lung cancer, large tumor size should not be considered a negative predictive factor. Except for performance status 2, patients with tumors larger than 7 cm apparently benefit from CRT.

Predictors of oxygen saturation ≤95% in a cross-sectional population based survey.

BACKGROUND: Pulse oximetry has become an important tool in evaluating, and monitoring pulmonary diseases, but the knowledge about arterial oxygen saturation (SpO(2)) values in a general population is limited. The aim of this study was to describe the distribution of low pulse oximetry values in a general adult population and their association with certain predictors. METHODS: A cross-sectional population based survey was performed in Tromsø, Norway, in 2007-2008. Valid SpO(2) and pre-bronchodilator spirometry was recorded in 6317 participants aged 38-87 years (57% women). Resting SpO(2) ≤95% was defined as an abnormal value. Predictors of SpO(2) ≤95% with p < 0.05 were entered into a binary multivariable logistic regression. RESULTS: The prevalence of SpO(2) ≤95% was 6.3%. The strongest predictors in the logistic regression were increased body mass index (BMI) (OR of BMI ≥35 = 6.2, CI(4.2, 9.2)), and reduced forced expiratory volume in 1 s (FEV(1)) % predicted (OR of FEV1% predicted <50 = 4.1, CI(2.5, 6.7)), followed by increased age, male gender, and smoking (p < 0.001). Other significant predictors were elevated C-reactive protein (CRP) (p < 0.005), former smoking, breathlessness and elevated hemoglobin (p < 0.01). CONCLUSION: Airflow limitation and other known signs of pulmonary diseases were, as expected, strongly associated with decreased oxygen saturation. Obesity was also a strong predictor of low SpO(2), and should be included among possible explanations when low SpO(2) values are encountered.

The Lean method as a clinical pathway facilitator in patients with lung cancer.

INTRODUCTION: Patient flow during workup for lung cancer is often difficult to influence because of delay at many levels: patient delay, doctors' delay and waiting time for X-ray and CT scan, referral to specialist, and waiting time for chemotherapy and radiotherapy or surgery. A mean workup time of 4 months is not unusual. OBJECTIVES: To improve quality and shorten the workup time for patients with lung cancer. METHODS: It was decided to employ a program designed by the Toyota car industry, the Lean process, as a tool to improve workup time. A Lean process implicates all levels of an institution with project and focus groups having workshops to analyse present status and suggest improvements. RESULTS: Since introducing the Lean project, we have decreased the workup time from a mean of 64 days to 16 days, and the median time from diagnosis to surgery was reduced from 26.5 days to 15 days. CONCLUSION: It is feasible to improve patient flow for patients with lung cancer by employing the Lean method as a pathway instrument.

Lead poisoning as possible cause of deaths at the Swedish House at Kapp Thordsen, Spitsbergen, winter 1872-3.

OBJECTIVE: To investigate cause of death in 17 sealers who died in the Swedish house in Kapp Thordsen, Spitsbergen, during the winter of 1872-3. DESIGN: Analysis of skeletal samples from one sealer's grave. SETTING: Field trip to Spitsbergen to exhume skeletal remains. SUBJECTS: One of 17 sailors who died in 1872-3. RESULTS: No objective signs of scurvy were found. The concentration of lead in the bone samples was 102.05 microg/g. CONCLUSIONS: The high concentrations of lead indicate that this man died from lead poisoning, probably from food tins. The absence of macroscopic signs of scurvy supports this theory.

Pulmonary function in long-term survivors of testicular cancer.

PURPOSE: Long-term toxicity after cancer treatment has gained increasing clinical attention. We evaluated pulmonary function in long-term survivors of testicular cancer (TC). PATIENTS AND METHODS: The pulmonary function of 1,049 TC survivors treated during 1980 to 1994 at three university hospitals in Norway was assessed by spirometry and a questionnaire (1998 to 2002). The patients were categorized into five treatment groups, as follows: surgery only (n = 202); radiotherapy only (n = 449); chemotherapy (cisplatin < or = 850 mg; n = 306); chemotherapy (cisplatin > 850 mg [higher-dose group]; n = 62); and chemotherapy and pulmonary surgery (cis/pulmsurg; n = 30). Spirometry variables included forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). Actual values and percentages of predicted normal values (FVC%pred and FEV1%pred, respectively) are reported. Restrictive lung disease was defined as FEV1/FVC > or = 70% and FVC%pred less than 80%. RESULTS: Median observation time was 11.2 years (range, 5 to 21 years). Compared with the surgery group, the higher-dose or cis/pulmsurg groups had considerably lower age-adjusted FVC (higher-dose: beta = -.37; P = .001; cis/pulmsurg: beta = -.58; P < .001), FEV1 (higher-dose: beta = -.24; P = .014; cis/pulmsurg: beta = -.55; P < .001), FVC%pred (higher-dose: beta = -8.3; cis/pulmsurg: beta = -10.5; bothP < .001), and FEV1%pred (higher-dose: beta = -6.8; P = .003; cis/pulmsurg: beta = -12.4; P < .001). Adjustment for total testosterone, body mass index, smoking, and physical activity did not change these associations. Eight percent of all patients had restrictive lung disease, and the highest prevalence was in the higher-dose group (17.7%) and the cis/pulmsurg (16.7%) group. Compared with patients who underwent surgery only, these groups had odds ratio for restrictive disease of 3.1 (95% CI, 1.3 to 7.3) and 2.5 (95% CI, 0.8 to 7.6), respectively. CONCLUSION: Large doses of cisplatin-based chemotherapy and combined chemotherapy/pulmonary surgery are significantly associated with decreased pulmonary function several years after TC treatment.

Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer.

PURPOSE To compare pemetrexed/carboplatin with a standard regimen as first-line therapy in advanced non-small-cell lung cancer NSCLC. PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC and performance status of 0 to 2 were randomly assigned to receive pemetrexed 500 mg/m(2) plus carboplatin area under the curve (AUC) = 5 (Calvert's formula) on day 1 or gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin AUC = 5 on day 1 every 3 weeks for up to four cycles. The primary end point was health-related quality of life (HRQoL) defined as global quality of life, nausea/vomiting, dyspnea, and fatigue reported on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the lung cancer-specific module LC13 during the first 20 weeks. Secondary end points were overall survival and toxicity. Results Four hundred thirty-six eligible patients were enrolled from April 2005 to July 2006. Patients who completed the baseline questionnaire were analyzed for HRQoL (n = 427), and those who received > or = one cycle of chemotherapy were analyzed for toxicity (n = 423). Compliance of HRQoL questionnaires was 87%. There were no significant differences for the primary HRQoL end points or in overall survival between the two treatment arms (pemetrexed/carboplatin, 7.3 months; gemcitabine/carboplatin, 7.0 months; P = .63). The patients who received gemcitabine/carboplatin had more grade 3 to 4 hematologic toxicity than patients who received pemetrexed/carboplatin, including leukopenia (46% v 23%, respectively; P < .001), neutropenia (51% v 40%, respectively; P = .024), and thrombocytopenia (56% v 24%, respectively; P < .001). More patients on the gemcitabine/carboplatin arm received transfusions of RBCs and platelets, whereas the frequencies of neutropenic infections and thrombocytopenic bleedings were similar on both arms. CONCLUSION Pemetrexed/carboplatin provides similar HRQoL and survival when compared with gemcitabine/carboplatin with less hematologic toxicity and less need for supportive care.

Chemotherapy and quality of life in NSCLC PS 2 patients.

INTRODUCTION: Nearly 40% of patients with advanced NSCLC are in performance status (PS) 2. These patients have a shorter life expectancy than PS 0/1 patients and they are underrepresented in clinical trials. Data on how platinum-based combination chemotherapy affects Health Related Quality of Life (HRQOL) of patients with PS 2 are scarce and the treatment of this important group of patients is controversial. METHODS: A national multicenter phase III study on platinum based chemotherapy to 432 advanced NSCLC patients included 123 patients with PS 2. To explore the treatment impact on HRQOL, the development of HRQOL during the first nine weeks were compared between PS 2 and PS 0/1 patients. We used the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Standardized area under the curve for all HRQOL items, and HRQOL responses classified as better, stable or worse, were compared between the groups. RESULTS: Whereas the demographic data at baseline were well balanced between the groups, the PS 2 patients had significantly worse function and more severe symptoms than the PS 0/1 patients. In response to combination chemotherapy, the PS 2 patients had a more profound improvement of global QOL, cognitive function, fatigue, dyspnea, sleeping problems and appetite loss in comparison to the PS 0/1 group. CONCLUSIONS: PS 2 NSCLC patients seem to achieve valuable HRQOL benefits from platinum-based combination therapy. Prospective clinical studies with predefined HRQOL outcomes in PS 2 patients are needed to confirm these findings.

A prospective phase II study: high-dose pemetrexed as second-line chemotherapy in small-cell lung cancer.

PURPOSE: To investigate the efficacy and tolerability of high-dose pemetrexed as second-line chemotherapy in small cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with verified SCLC who had received one prior chemotherapy regimen, aged 18-75 years, WHO Performance Status 0-2, no clinical signs of brain metastases and measurable disease were eligible. Patients received pemetrexed 900 mg/m(2) IV every 3 weeks. Four courses were planned for all patients. Patients with relapse later than 3 months since last course of first-line chemotherapy were defined as "sensitive", those with relapse within 3 months as "refractory". Toxicity was graded using the CTCAE v3.0. RESULTS: 36 patients were accrued, 34 received study treatment. Median age was 61 (range 43-74), 18 (53%) males and 16 (47%) females. Mean number of courses administered was 2.5. One patient (3%) had partial response, three (9%) had stable disease and 29 (85%) progressed. One patient (3%) was not evaluable for response. Median TTP (n=33) was 7.7 weeks ("sensitive": 8.4 weeks, "refractory": 5.1 weeks). Median OS (n=34) was 17.6 weeks ("sensitive": 22.6 weeks, "refractory": 15.3 weeks). Of grade 3-4 haematological toxicity, anemia was observed in 2 (6%) patients, leukopenia in 6 (18%), granulocytopenia in 9 (27%) and thrombocytopenia in 3 (9%). Febrile neutropenia occurred in 6 (18%) patients. There were no treatment related deaths. CONCLUSION: High-dose pemetrexed monotherapy to patients with recurrent SCLC yielded moderate toxicity, but limited treatment efficacy.

Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial.

PURPOSE: A Japanese randomized trial showed superior survival for patients with extensive-disease (ED) small-cell lung cancer (SCLC) receiving irinotecan plus cisplatin compared with etoposide plus cisplatin. The present trial evaluated the efficacy of irinotecan plus carboplatin (IC) compared with oral etoposide plus carboplatin (EC). PATIENTS AND METHODS: Patients with ED SCLC were randomly assigned to receive either IC, which consisted of carboplatin (area under the curve = 4; Chatelut formula) and irinotecan (175 mg/m2) intravenously both on day 1, or EC, which consisted of carboplatin as in IC and etoposide (120 mg/m(2)/d) orally on days 1 through 5. Courses were repeated every 3 weeks with four cycles planned. Doses were reduced by one third in patients with a WHO performance status (PS) of 3 to 4 and/or age older than 70 years. Primary end point was overall survival (OS). Secondary end points were quality of life (QOL) and complete response (CR) rate. RESULTS: Of 220 randomly assigned patients, 209 were eligible for analysis (IC, n = 105; EC, n = 104). Thirty-five percent were older than 70 years, and 47% had a PS of 2 to 4. The groups were well balanced with respect to prognostic factors. OS was inferior in the EC group (hazard ratio = 1.41; 95% CI, 1.06 to 1.87; P = .02). Median survival time was 8.5 months for IC compared with 7.1 months for EC. One-year survival rate was 34% for IC and 24% for EC. CR was seen in 18 IC patients compared with seven EC patients (P = .02). There were no statistically significant differences in hematologic grade 3 or 4 toxicity. Grade 3 or 4 diarrhea was more common in the IC group. QOL differences were small, with a trend toward prolonged palliation with the IC regimen. CONCLUSION: IC prolongs survival in ED SCLC with slightly better scores for QOL.

Treatment outcome in performance status 2 advanced NSCLC patients administered platinum-based combination chemotherapy.

BACKGROUND: There is no consensus regarding chemotherapy to patients with advanced NSCLC (ANSCLC) and performance status (PS) 2. Using data from a national multicenter study comparing two third-generation carboplatin-based regimens in ANSCLC patients, we evaluated the outcome of PS 2 patients. PATIENTS AND METHODS: The 123 PS 2 patients were compared to 309 PS 0/1 patients regarding survival, quality of life (QOL) and treatment toxicity. RESULTS: PS 2 patients had lower haemoglobin, lower global QOL and more pain, nausea/vomiting and dyspnea at inclusion. 68% of PS 2 patients received three chemotherapy courses vs. 85% in the PS 0/1 group (P<0.01). Median and 1-year survival were lower in the PS 2 group, 4.5 vs. 8.9 months and 10% vs. 37% (P<.01). More PS 2 patients needed blood transfusions (P=0.03) and hospitalization (P<0.01). In contrast, PS 2 patients had better relief of pain and dyspnea, and tended to a better global QOL and did not experience more leucopoenia, infections or bleeding. CONCLUSIONS: Despite shorter survival, treatment toxicity was acceptable and PS 2 patients achieved better improvement of pain and dyspnea and tended to better global QOL when compared to PS 0/1 patients.

Reduced pulmonary function is associated with lower levels of endogenous total and free testosterone. The Tromsø study.

Men with chronic obstructive pulmonary disease have reduced endogenous testosterone levels. Little is known, however, about the relationship between pulmonary function and endogenous testosterone levels in a general population. In the present study we have examined the cross-sectional associations between sex hormones measured by immunoassay and pulmonary function assessed with spirometry and oxygen saturation in 2,197 men participating in the fifth Tromsø study. The data were analyzed by univariate correlations, multiple linear regression analyses and analyses of variance and covariance. Total and free testosterone were positively and independently associated with forced vitality capacity, FVC (% of predicted) (P = 0.001 and P = 0.006, respectively) and forced expiratory volume in 1 second, FEV(1 )(% predicted) (P = 0.033 and P = 0.002, respectively), and men with severe pulmonary obstruction (FEV(1) % of predicted < 50) had lower free testosterone levels (P = 0.005). In this cross-sectional data from Tromsø, a reduction in pulmonary function was associated with lower levels of total and free testosterone. We suggest that the reduction of total and free testosterone could be due to an alteration of the hypothalamic-pituitary response.

Palliative thoracic radiotherapy in locally advanced non-small cell lung cancer: can quality-of-life assessments help in selection of patients for short- or long-course radiotherapy?

PURPOSE: Patient-assessed health-related quality-of-life (HRQOL) scores, together with demographic and clinical factors in stage III non-small cell lung cancer (NSCLC) patients, are important prognostic factors for survival and may be helpful in determining thoracic radiotherapy (TRT) strategy. METHODS: In a previously published randomized trial, 301 patients were treated with different palliative radiotherapy schedules, comparing short-term hypofractionated TRT (arm A: 17 Gy/2 fractions [n = 105]) with more protracted TRT (arm B: 42 Gy/15 fractions [n = 104]); arm C: 50 Gy/25 fractions [n = 92]). Baseline HRQOL, demographic, and clinical data were available for all patients. All possible prognostic factors from univariate analysis were entered into the Cox multivariate regression model to identify variables of independent prognostic relevance. RESULTS: Overall survival was similar, whereas long-term survival was restricted to higher-dose radiotherapy with 3-year survival rates of 1, 8, and 6% (p = 0.40) and 5-year survival rates of 0, 4, and 3% (p = 0.12) in arms A, B, and C, respectively. In univariate analysis, Karnofsky performance status, use of analgesics, and weight loss were highly significant non-HRQOL factors (p < 0.001), and physical function, appetite loss, cough, and pain were the most powerful HRQOL factors (p < 0.001). In multivariate analysis, appetite loss appeared as the most powerful independent prognostic indicator. In the group of patients treated with protracted fractionation (n = 196), the 2-, 3-, and 5-year survival rates in patients with no appetite loss (n = 95) were 22% (21/95), 12% (11/95), and 8% (8/95) compared with 3% (3/101), 1% (1/101), and 1% (1/101) in patients with appetite loss present at baseline (n = 101). CONCLUSION: In addition to performance status and weight loss, patient-reported appetite loss should be assessed in stage III NSCLC patients before administrating TRT; such assessment is a valuable tool for selecting patients to normofractionated or lower-dose hypofractionated palliative TRT.

Immediate or delayed radiotherapy in advanced non-small cell lung cancer (NSCLC)? Data from a prospective randomised study.

BACKGROUND AND PURPOSE: To compare the course of symptoms and health-related quality-of-life (HRQOL) after immediate thoracic radiotherapy (TRT) between symptomatic (S) and non-symptomatic (NS) patients with advanced NSCLC. PATIENTS AND METHODS: 407 stage III/IV patients were initially treated with immediate TRT within a randomised phase III trial comparing different fractionation schedules. At inclusion, patients were prospectively stratified according to presence (S) or absence (NS) of tumour-related chest/airway symptoms to facilitate comparison between these groups. The EORTC QLQ-C30 and LC-13 were used for symptom and HRQOL assessments at baseline and at regular intervals up to 1 year (N=395). RESULTS: NS patients had significantly more favourable baseline characteristics when compared to S patients with a median survival of 11.8 versus 6.0 months (P<0.0001), respectively. At baseline, S patients demonstrated HRQOL scores inferior to those of NS patients (P<0.01) for most scales. Until week 14, NS patients developed more symptoms while S patients experienced symptom relief in most scales. After week 14, no significant differences could be observed between the groups. CONCLUSION: This study indicates that immediate TRT, given to patients with minimal/none chest symptoms, does not prevent development of disease-related symptoms and diminished HRQOL. A wait-and-see policy appears to be acceptable.

Second-line chemotherapy in recurrent small cell lung cancer. Results from a crossover schedule after primary treatment with cisplatin and etoposide (EP-regimen) or cyclophosphamide, epirubicin, and vincristin (CEV-regimen).

PURPOSE: To evaluate the benefit of crossover chemotherapy with etoposide and cisplatin (EP) versus cyclophosphamide, epirubicin, vincristine (CEV) at relapse after primary treatment with the opposite regimen in patients with small cell lung cancer (SCLC). Further, to compare the crossover group with patients not receiving chemotherapy. PATIENTS AND METHODS: Among 286 patients diagnosed with relapse after first-line chemotherapy, 120 patients received second-line chemotherapy and 166 patients received best supportive care. Fifty-six patients received EP after previous treatment with CEV, 52 received CEV after EP, and 12 patients were re-treated with the same regimen. Possible prognostic factors in the crossover group were identified at time for first-line chemotherapy and at relapse. The EP therapy comprised five courses of etoposide 100 mg/m(2) IV and cisplatin 75 mg/m(2) IV on day 1, followed by oral etoposide 200 mg/m(2) daily on day 2-4. The CEV-regimen was five courses of epirubicin 50 mg/m(2), cyclophosphamide 1000 mg/m(2), and vincristine 2 mg, all IV on day 1. RESULTS: Patients administered second-line chemotherapy lived significantly longer with median survival 5.3 months compared to 2.2 months in patients with best supportive care only (P<0.001). The best supportive care patients had significantly worse PS status and more resistant disease. The crossover treatment group was well balanced regarding possible prognostic factors prior to initial treatment and at recurrence. No difference in survival was found (P=0.71). Univariate analysis revealed PS at recurrence, objective tumour response from initial chemotherapy, disease stage at first-line, LDH-, NSE-, and ALP at first-line to be significant prognostic factors for survival in the second-line setting. In a multivariate analysis, only PS at time of recurrence remained an independent prognostic factor (P<0.0001). CONCLUSION: Patients administered second-line chemotherapy had significantly longer survival than patients administered best supportive care. However, this difference can be explained by more negative prognostic factors in the best supportive care group. No survival difference between EP and CEV crossover chemotherapy was found. Multivariate analysis revealed PS at time of relapse as the only independent predictor of survival in the crossover recurrent SCLC group.

Pancreatic polypeptide is increased in patients with advanced malignant disease.

BACKGROUND: Augmented secretion of pancreatic polypeptide (PP) has been demonstrated in patients with severe systemic diseases or endocrine tumors. The aim of this study was to evaluate PP and autonomic neuropathy in patients with advanced malignant disease. MATERIALS AND METHODS: Basal PP assessments and five cardiovascular tests for autonomic function were used. Twenty patients, including 11 patients with lung cancer (69 yrs +/- 11, mean +/- SD) and 10 healthy age-matched controls, were studied. RESULTS: PP levels were significantly higher in the patients than in the controls (pmol/L 107.0 +/- 111.4 versus 28.2 +/- 13.4, p<0.05). In the parasympathetical tests, the patients showed significantly decreased heart rate response to the Valsalva manoeuvre (ratio 1.20 +/- 0.19 versus 1.46 +/- 0.23, p<0.005). Also, in the sympathetical tests, the blood pressure response to standing up was significantly decreased (mmHg -3.84 +/- 17.53 versus 10.80 +/- 8.89, p<0.05). The heart rate response to standing up and deep breathing as well as the blood pressure response to sustained handgrip, did not differ significantly between the groups. In spite of the apparent autonomic dysfunction among cancer patients with advanced malignant disease, PP levels were significantly higher in these patients when compared with healthy controls. CONCLUSION: PP levels were significantly higher in patients with advanced cancer than controls, regardless of autonomic dysfunction in the cancer patients. This finding supports the hypothesis that PP may, in some cancer patients, be a marker of advanced malignant disease.