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

AbstractBackgroundIn 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 MethodsAll 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.ResultsThe 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.ConclusionElderly 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

Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: a randomised trial by the Norwegian Lung Cancer Study Group

Background: The palliative role of chemoradiation in the treatment of patients with locally advanced, inoperable non-small-cell lung cancer stage III and negative prognostic factors remains unresolved. Methods: Patients not eligible for curative radiotherapy were randomised to receive either chemoradiation or chemotherapy alone. Four courses of intravenous carboplatin on day 1 and oral vinorelbin on days 1 and 8 were given with 3-week intervals. Patients in the chemoradiation arm also received radiotherapy with fractionation 42 Gy/15, starting at the second chemotherapy course. The primary end point was overall survival; secondary end points were health-related quality of life (HRQOL) and toxicity. Results: Enrolment was terminated due to slow accrual after 191 patients from 25 Norwegian hospitals were randomised. Median age was 67 years and 21% had PS 2. In the chemotherapy versus the chemoradiation arm, the median overall survival was 9.7 and 12.6 months, respectively (Po0.01). One-year survival was 34.0% and 53.2% (Po0.01). Following a minor decline during treatment, HRQOL remained unchanged in the chemoradiation arm. The patients in the chemotherapy arm reported gradual deterioration during the subsequent months. In the chemoradiation arm, there were more hospital admissions related to side effects (Po0.05). Conclusion: Chemoradiation was superior to chemotherapy alone with respect to survival and HRQoL at the expense of more hospital admissions due to toxicity

Improving treatment in patients with lung cancer : Results from two multicentre randomised studies

Paper II and IV are reprinted with kind permission of Elsevier, sciencedirect.co

Expression and clinical significance of the proliferation marker minichromosome maintenance protein 2 (Mcm2) in diffuse astrocytomas WHO grade II

Background The WHO classification system for astrocytomas is not considered optimal, mainly because of the subjective assessment of the histopathological features. Few prognostic variables have been found that stratify the risk of clinical progression in patients with grade II astrocytoma. For that reason there is a continuous search for biomarkers that can improve the histopathological diagnosis and prognostication of these tumours. Aim This study was designed to investigate the prognostic significance of the proliferative marker Mcm2 (minichromosome maintenance protein 2) in diffuse astrocytomas WHO grade II and correlate the findings with histopathology, mitoses, and Ki67/MIB-1 immunostaining. Method 61 patients with histologically verified grade II astrocytoma (WHO 2007) were investigated. Paraffin sections were immunostained with anti-Mcm2, and the Mcm2 proliferative index (PI) was determined as the percentage of immunoreactive tumour cell nuclei. Results Mcm2 PI was not associated with any histopathological features but correlated significantly with mitotic count and Ki67/MIB-1 PI (p0.05). Conclusions In our hands Mcm2 immunostaining has no advantage over Ki67/MIB-1 in the evaluation of grade II astrocytomas. Larger studies are needed to fully clarify the prognostic role of this biomarker. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/171500279194403

Pemetrexed as Second-Line Treatment in Malignant Pleural Mesothelioma after Platinum-Based First-Line Treatment

Introduction:Pemetrexed is active as first-line treatment of malignant pleural mesothelioma. The objective was to evaluate its activity as second-line treatment.Methods:Patients had disease progression of malignant pleural mesothelioma after previous platinum-based regimens without pemetrexed. Treatment was pemetrexed alone or pemetrexed combined with carboplatin. Pemetrexed dosing was 500 mg/m2 and carboplatin was AUC (area under the curve) 5 once every 3 weeks.Results:Thirty-nine patients were included: 28 Danish patients received pemetrexed (three patients received pemetrexed as third-line treatment), whereas 11 Norwegian patients received pemetrexed plus carboplatin. Most patients were men (90%), had epithelial subtype (85%), and International Mesothelioma Interest Group stages III to IV (77%). Median age was 62 years (range, 30–77). The median number of treatment courses was six (range, 1–23). Common Toxicity Criteria grade 3 to 4 toxicity occurred only with respect to leukocytopenia (pemetrexed: 14% of patients; pemetrexed plus carboplatin: 9%) and thrombocytopenia (pemetrexed: 7%; pemetrexed plus carboplatin: 18%). One patient receiving pemetrexed died of sepsis. Partial response rates were 21% and 18%, the median time to progression was 21 weeks (range, 4–92) and 32 weeks (range, 4–128+), and the median survival was 42 weeks (range, 4–99) and 39 weeks (range, 10–128+) with pemetrexed and pemetrexed plus carboplatin, respectively.Conclusions:Pemetrexed was generally well tolerated with noteworthy activity in malignant pleural mesothelioma after previous platinum-based treatment and may be considered for second-line treatment

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