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.

Can dogs smell lung cancer? First study using exhaled breath and urine screening in unselected patients with suspected lung cancer.

BACKGROUND: On the basis of our own experience and literature search, we hypothesised that a canine olfactory test may be useful for detecting lung cancer in an unselected population of patients suspected to have lung cancer. MATERIAL AND METHODS: We conducted a prospective study of 93 patients consecutively admitted to hospital with suspected lung cancer. Exhaled breath and urine were sampled before the patients underwent bronchoscopy. The canine olfactory test was performed in a double-blinded manner. Sensitivity and specificity were outcome measures. RESULTS: With 99% sensitivity, the olfactory test demonstrated that dogs have the ability to distinguish cancer patients from healthy individuals. With an intensified training procedure, the exhaled breath and urine tests showed sensitivity rates of 56-76% and specificity rates of 8.3-33.3%, respectively, in our heterogeneous study population. CONCLUSION: Although the olfactory test appears to be a promising tool for the detection of cancer, the main challenge is to determine whether the test can sufficiently discriminate between patients at risk, patients with benign disease, and patients with malignant disease. We need to gain a deeper understanding of this test and further refine it before applying it as a screening tool for lung cancer in clinical settings.

[Occupational lung cancer in Sør-Trøndelag county]. / Arbeidsbetinget lungekreft i Sør-Trøndelag.

BACKGROUND: Lung cancer can be caused by occupational exposure. This is not always recognised or reported, and not all patients receive the benefits to which they are entitled. MATERIAL AND METHOD: We collected occupational case histories for patients from Sør-Trøndelag county with a first-time diagnosis of lung cancer. The number of reported cases of occupationally related lung cancer was collected from the Norwegian Labour Inspection Authority, and information on approval of occupational illness was collected from the Norwegian Labour and Welfare Authority (NAV). RESULTS: 105 patients with lung cancer took part in the study, 73 men and 32 women. Among the men, altogether 12 cases (16%) were assessed as likely and 16 (22%) as possibly occupationally related. Among the women, none of the cases were assessed as occupationally related. The reporting frequency from the health regions to the Norwegian Labour Inspection Authority varied from 1.7% to 5.1%. Altogether 9 out of 11 likely cases and 5 out of 12 possible cases of occupationally related lung cancer were granted injury compensation by the Norwegian Labour and Welfare Authority. INTERPRETATION: In this study, we found that approximately 20% of the cases of lung cancer in men are occupationally related, and that the underreporting of occupationally related lung cancer appears to be considerable. The obligation of doctors to report to the Norwegian Labour Inspection Authority should be made better known. Most likely, more patients would have had their lung cancer verified as an occupational illness and could have received injury compensation if they had been aware of the opportunity to apply for this.

Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004-2007.

BACKGROUND: The authors consider whether differences in stage at diagnosis could explain the variation in lung cancer survival between six developed countries in 2004-2007. METHODS: Routinely collected population-based data were obtained on all adults (15-99 years) diagnosed with lung cancer in 2004-2007 and registered in regional and national cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Stage data for 57 352 patients were consolidated from various classification systems. Flexible parametric hazard models on the log cumulative scale were used to estimate net survival at 1 year and the excess hazard up to 18 months after diagnosis. RESULTS: Age-standardised 1-year net survival from non-small cell lung cancer ranged from 30% (UK) to 46% (Sweden). Patients in the UK and Denmark had lower survival than elsewhere, partly because of a more adverse stage distribution. However, there were also wide international differences in stage-specific survival. Net survival from TNM stage I non-small cell lung cancer was 16% lower in the UK than in Sweden, and for TNM stage IV disease survival was 10% lower. Similar patterns were found for small cell lung cancer. CONCLUSIONS: There are comparability issues when using population-based data but, even given these constraints, this study shows that, while differences in stage at diagnosis explain some of the international variation in overall lung cancer survival, wide disparities in stage-specific survival exist, suggesting that other factors are also important such as differences in treatment. Stage should be included in international cancer survival studies and the comparability of population-based data should be improved.

Primary human glioblastomas - prognostic value of clinical and histopathological parameters.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant human brain tumor with a poor prognosis. The diagnosis of GBM is based on histological features, however, few studies have evaluated their prognostic relevance in light of the latest WHO classification of 2007. AIM: In this study we have evaluated the prognostic value of several clinical and histological characteristics encountered in human GBMs according to the WHO 2007 criteria. MATERIAL AND METHODS: 199 patients with primary GBM consecutively operated and histologically reviewed according to the 2007 WHO scheme, were included. Several clinical and histological features were recorded and related to survival. RESULTS: Mean age of the GBM patients at diagnosis was 62 years (range 21 - 84). Male/female ratio was 1.3/1, and the median survival was 8.0 months (95% CI: 7.1 - 9.0 months). In a multivariate COX analysis age, WHO performance score, subcortical localization, extent of surgery, radiation treatment, chemotherapy, and the presence of large necrosis had individual effect on overall survival (p < 0.05). In addition, females, tumors with angiocentric growth, with pseudopalisades, or without lymphocyte infiltration were related to shorter survival in univariate analyses (p < 0.05). CONCLUSION: Our findings confirm the strong prognostic value of age, treatment, performance score, and localization for glioblastoma patients. Amongst the histopathological features only large necrosis was an independent prognostic factor.

[Recurrence and survival after surgical treatment of lung cancer]. / Residiv og overlevelse etter kirurgisk behandling for lungekreft.

BACKGROUND: 2500 new cases of lung cancer are diagnosed in Norway annually. Patients with limited disease can be operated, but many will die from the disease despite surgical treatment. The aim of the study was to review survival and recurrence, and factors which affect survival, in patients operated for lung cancer. MATERIAL AND METHODS: The risk of death and recurrence of disease was assessed retrospectively in patients who had non-small lung cancer and were operated at St. Olavs University Hospital, Trondheim in the period 1994-2001. Patient data were retrieved from medical records and a database with records from thoracosurgical procedures. RESULTS: 190 patients (30 % women) were included in the study. Average observation time after surgery was 58.3 months (range 21-99). Adenocarcinoma was the most common histological cancer type and occurred in 57.9 % of women and 39.1 % of the men (p = 0.02). The 30-day mortality rate was 3.2 % and the 60-day rate was 4.7 %. Recurrence of the disease was found in 45.8 %, among them median time to recurrence was 9 months after the operation. 5-year survival was 42 %, as analysed by the Kaplan-Meier estimate, and survival was best for early stages of the disease. 5-year survival was better for women (53.3 %) than men (36.8 %), p = 0.05. Prognostic factors for survival, estimated by Hazard ratio for death with Cox multiple regression analysis, were sex, age at the time of operation, type of operation, tumour diameter and postoperative N-stage. INTERPRETATION: Postoperative mortality and survival corresponded to data in the literature. Early stage lung cancer can be cured with surgical treatment. Our study confirms an increase in the incidence of adenocarcinoma among lung cancer patients during the last decades. Female sex is a positive prognostic factor for survival, as is young age, small tumor size, standard lobectomy, and absence of lymph node metastases.

Major Durable Response of Pembrolizumab in Chemotherapy Refractory Small Cell Bladder Cancer: A Case Report.

Small cell carcinoma of the urinary bladder is a rare subtype (incidence of 1-9/1,000,000), characterized by an aggressive behavior with early metastasis and poor prognosis. Chemotherapy, radiation, and surgery are the usual treatment options, but to date, no accepted standard treatment exists. Since small cell bladder cancer shares similar clinicopathological features with small cell lung cancer, the same type of chemotherapy has been used. Recently, immune checkpoint inhibitors have shown effect in small cell lung cancer, but data regarding small cell bladder cancer is insufficient. Here we present a case where a 73-year-old male with chemorefractory metastatic small cell bladder cancer received a successful treatment with immune checkpoint inhibitor pembrolizumab resulting in a major durable response and no side effects. To our knowledge, this is the second case report on successful treatment of the rare subtype of small cell bladder cancer with an immune checkpoint inhibitor, supporting the use of pembrolizumab as a therapeutic option for small cell bladder cancer. Serum neuron-specific enolase was a useful biomarker both for chemo- and immunotherapy response.

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.

Assessing quality of life in a randomized clinical trial: correcting for missing data.

BACKGROUND: Health-related quality of life is a topic of current interest. This paper considers a randomized phase III study of radiation therapy with concurrent chemotherapy (docetaxel) versus radiation therapy alone in non-small cell lung cancer, stage III A/B. Longitudinal data on quality of life have been obtained through repeated administration of a multi-item questionnaire (EORTC QLQ-C30) developed by the European Organisation for Research and Treatment of Cancer. Missingness in the data is owing to patients having failed to complete the questionnaire at some of the scheduled filling-in times. METHODS: We have analysed a monotone (in terms of missingness) subset of the data as regards estimation of the mean score of a summary measure of self-reported quality of life in a hypothetical drop-out-free population at different points in time. Missingness is a difficult issue of great importance. We have therefore chosen to compare three different methods that are relatively easy to implement: the linear-increments method, the inverse-probability-weighting method and the Markov-process method. Single imputation has been applied in a supplementary analysis to fill in for all the non-consecutive missing score values prior to the execution of the estimation procedure. RESULTS: For the response in focus, the observed mean score at a certain time is larger than the estimated mean scores, which implies that the true mean score is easily overestimated unless the missingness is appropriately adjusted for. Comparison of the treatment arms shows a significant difference in mean score at the end of treatment. CONCLUSION: Use of proper methodology developed for analysing data subject to missingness is necessary to reduce potential estimation bias. The quality of life of patients receiving radiation therapy with concurrent chemotherapy (docetaxel) appears somewhat worse than that of patients receiving radiation therapy alone in the period during which treatment is given. The conclusions are robust for the choice of statistical methods.

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.

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.

Survival in Limited Disease Small Cell Lung Cancer According to N3 Lymph Node Involvement.

BACKGROUND/AIM: There are several definitions of limited disease (LD) in small cell lung cancer (SCLC), differing with respect to N3 disease accepted. We analyzed patients from a randomized trial comparing two schedules of thoracic radiotherapy (TRT) in LD SCLC to investigate whether there were survival differences between N3 subcategories (n=144). PATIENTS AND METHODS: Patients with a baseline CT scan available were analysed. Patients received four courses of cisplatin/etoposide and TRT of 45 Gy/30 fractions (twice daily) or 42 Gy/15 fractions (once daily). RESULTS: Median overall survival (OS) was 23.3 months in the whole cohort. N3-patients (n=37) had shorter survival than those with N0-2 (16.7 vs. 33.0 months; p<0.001). There were no significant OS-differences between the N3 subcategories, but patients with metastases to two or more N3 regions had shorter survival than other N3 patients (13.4 vs. 19.9 months; p=0.011). CONCLUSION: There were no survival differences between the N3 subcategories, suggesting that all N3 disease should be considered as LD.

Tumour size reduction after the first chemotherapy-course and outcomes of chemoradiotherapy in limited disease small-cell lung cancer.

OBJECTIVES: Concurrent chemotherapy and thoracic radiotherapy (TRT) is recommended for limited disease small-cell lung cancer (LD SCLC). TRT should start as early as possible, often meaning with the second course due to patient referral time and the fact that TRT planning takes time. Early assessment of response to the first course of chemotherapy may be a useful way to individualise treatment. The aims of this study were to assess tumour size reduction after the first chemotherapy-course, and whether this reduction was associated with outcomes in LD SCLC. MATERIAL AND METHODS: A randomised trial comparing twice-daily (45Gy/30 fractions) with once-daily (42Gy/15 fractions) TRT, given concurrently with four courses of cisplatin/etoposide (n=157) was the basis for this study. Tumour size was assessed on CT scans at baseline and planning scans for TRT according to RECIST 1.0. RESULTS: CT scans were available for 135 patients (86%). Ninety-four percent had a reduction in tumour size after the first chemotherapy-course. The median reduction in sum of diameters (SOD) of measurable lesions was ÷16mm (÷84 to +10mm), corresponding to ÷18% (÷51 to +12%). Eighty-two percent had stable disease, 18% partial response. Reduction in SOD was significantly associated with complete response at first follow-up (OR: 1.05, 95% CI 1.01-1.09; p=0.013), PFS (HR: 0.97, 95% CI 0.96-0.99; p=0.001), and overall survival (HR: 0.98, 95% CI 0.96-1.00; p=0.010). CONCLUSION: Response from the first course of chemotherapy had a significant positive association with outcomes from chemoradiotherapy, and might be used to stratify and randomise patients in future studies.

Hypofractionated palliative radiotherapy (17 Gy per two fractions) in advanced non-small-cell lung carcinoma is comparable to standard fractionation for symptom control and survival: a national phase III trial.

PURPOSE: To investigate whether the effect of hypofractionated thoracic radiotherapy (TRT) is comparable to more standard fractionated radiotherapy (RT) in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 421 patients with locally advanced stage III or stage IV NSCLC tumors were included. Inclusion criteria were inoperable, disease too advanced for curative radiotherapy, and chest symptoms or central tumor threatening the airways. Patients were randomly assigned to three arms: A, 17 Gy per two fractions (n = 146); B, 42 Gy per 15 fractions (n = 145); and C, 50 Gy per 25 fractions (n = 130). Four hundred seven patients were eligible for the study; 395 patients (97%) participated in the health-related quality-of-life (HRQOL) study. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-lung cancer-specific module (LC13) were used to investigate airway symptom relief and changes in HRQOL. Assessments were performed before TRT and until week 54. Clinicians' assessments of symptom improvement were at 2, 6, and 14 weeks after completion of TRT. The patients were observed for a minimum of 3 years. Results Baseline prognostic data were equally distributed in the treatment groups. Patient compliance with respect to the HRQOL investigation was minimum 74%. HRQOL and symptom relief were equivalent in the treatment arms. No significant difference in survival among arms A, B, and C was found, with median survival 8.2, 7.0, and 6.8 months, respectively. CONCLUSION: Our data indicate that protracted palliative TRT renders no improvement in symptom relief, HRQOL, or survival when compared with short-term hypofractionated treatment in advanced NSCLC.

Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up.

PURPOSE: To investigate whether chemotherapy with etoposide and cisplatin (EP) is superior to cyclophosphamide, epirubicin, and vincristine (CEV) in small-cell lung cancer (SCLC). PATIENTS AND METHODS: A total of 436 eligible patients were randomized to chemotherapy with EP (n = 218) or CEV (n = 218). Patients were stratified according to extent of disease (limited disease [LD], n = 214; extensive disease [ED], n = 222). The EP group received five courses of etoposide 100 mg/m(2) intravenously (IV) and cisplatin 75 mg/m(2) IV on day 1, followed by oral etoposide 200 mg/m(2) daily on days 2 to 4. The CEV group received five courses of epirubicin 50 mg/m(2), cyclophosphamide 1,000 mg/m(2), and vincristine 2 mg, all IV on day 1. In addition, LD patients received thoracic radiotherapy concurrent with chemotherapy cycle 3, and those achieving complete remission during the treatment period received prophylactic cranial irradiation. RESULTS: The treatment groups were well balanced with regard to age, sex, and prognostic factors such as weight loss, and performance status. The 2- and 5-year survival rates in the EP arm (14% and 5%, P =.0004) were significantly higher compared with those in the CEV arm (6% and 2%). Among LD patients, median survival time was 14.5 months versus 9.7 months in the EP and CEV arms, respectively (P =.001). The 2- and 5-year survival rates of 25% and 10% in the EP arm compared with 8% and 3% in the CEV arm (P =.0001). For ED patients, there was no significant survival difference between the treatment arms. Quality-of-life assessments revealed no major differences between the randomized groups. CONCLUSION: EP is superior to CEV in LD-SCLC patients. In ED-SCLC patients, the benefits of EP and CEV chemotherapy seem equivalent, with similar survival time and quality of life.

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.