Eligibility for concurrent chemotherapy and radiotherapy of locally advanced lung cancer patients: a prospective, population-based study.

BACKGROUND: Patients with stage III non-small-cell lung cancer (NSCLC) and limited disease small-cell lung cancer are excluded from concurrent chemoradiation mostly on the basis of comorbidity and age. The purpose of this prospective study was to get insight in what proportion of patients with locally advanced lung cancer would be suitable for concurrent chemoradiation. PATIENTS AND METHODS: From 2002 to 2005, all patients with a pathological diagnosis of lung cancer and with locally advanced disease in the Maastricht Cancer Registry, the Netherlands, comorbidity were prospectively assessed. Patients were regarded as noneligible for concurrent chemoradiation if they had one or more important comorbidity or were 75 years or older. RESULTS: In all, 711 patients were included, 577 with NSCLC and 134 with SCLC. Overall, 166 patients (23.3%) were 75 years or older. Of the 526 patients <75 years, comorbidities were as follows: 278 (52.9%) 0, 188 (35.7%) 1, and 56 (11.4%) 2 or more. In all, 408/686 (59%) of the whole patient group were considered as ineligible for concurrent chemoradiation. CONCLUSIONS: More than half of patients with stage III lung cancer were theoretically not eligible for concurrent chemoradiation. Less toxic alternatives are needed for these patients.

Impact of fatigue on overall quality of life in lung and breast cancer patients selected for high-dose radiotherapy.

BACKGROUND: Although studies show that cancer patients consider fatigue as an important problem, few, if any, studies have quantified the impact of fatigue on overall quality of life (QoL) in cancer patients. In the present study, we evaluated the relative impact of different QoL domains/subscales, including fatigue, on overall QoL in cancer patients preceding radiotherapy. PATIENTS AND METHODS: Sixty-four patients with lung or breast cancer selected for high-dose radiotherapy on the primary tumour completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Multivariate models were fitted to define the impact of QLQ-C30 subscales, including fatigue, on overall QoL. RESULTS: Of all QLQ-C30 subscales, fatigue showed by far the strongest univariate correlation with overall QoL (r = -0.76, P < 0.001); correlations for functioning subscales (r = 0.44-0.55) and symptom subscales (r = -0.31 to -0.45) were considerably lower. In multivariate analyses, adjusting for potential confounders, fatigue was the only subscale that independently contributed to overall QoL (standardized regression coefficient-0.57, P < 0.001). CONCLUSION: Our results indicate that, of all QoL domains/subscales, fatigue is by far the predominant contributor to patient-perceived overall QoL in both lung and breast cancer patients preceding high-dose radiotherapy.

Maximal neutropenia during chemotherapy and radiotherapy is significantly associated with the development of acute radiation-induced dysphagia in lung cancer patients.

BACKGROUND: Acute dysphagia is a distressing dose-limiting toxicity after concurrent chemoradiation or high-dose radiotherapy for lung cancer. We therefore identified factors associated with the occurrence of acute dysphagia in lung cancer patients receiving radiotherapy alone or combined with chemotherapy. PATIENTS AND METHODS: Radiotherapy, chemotherapy and patient characteristics were analyzed using ordinal regression analysis as possible predictors for acute dysphagia (CTCAE 3.0) in 328 lung cancer patients treated with curative intent. RESULTS: The most significant association was seen between the maximal grade of neutropenia during chemoradiation and dysphagia, with an odds ratio increasing from 1.49 [95% confidence interval (CI) 0.63-3.54, P = 0.362] for grade 1-2 neutropenia to 19.7 (95% CI 4.66-83.52, P < 0.001) for patients with grade 4 neutropenia. Twice-daily schedule, mean esophageal dose and administration of chemotherapy were significant predictive factors. By combining these factors, a high-performance predictive model was made. On an individual patient level, 64% of patients were correctly classified and only 1.2% of patients were misclassified by more than one grade. CONCLUSIONS: The maximal neutrophil toxicity during concurrent chemotherapy and radiotherapy is strongly associated with the development of acute dysphagia. A multivariate predictive model was developed.

[Protons and ions in the treatment of cancer; a systematic review of the literature]. / Protonen en ionen in de behandeling van kanker; systematisch literatuuroverzicht.

OBJECTIVE: To provide an overview of the present role of proton and ion therapy, also referred to as 'charged particle therapy', in the treatment of cancer. DESIGN: Systematic literature study. METHOD: Systematic electronic searches were carried out in 12 databases according to the Cochrane Collaboration criteria, without restriction as to year of publication or study design. Manual searches of bibliographies and journals were also performed. The inclusion criteria were: at least 20 patients and a follow-up of at least 2 years. In addition, experts on the subject were consulted by correspondence for their opinion. RESULTS: The search identified 36 relevant articles on proton therapy and 15 on ion therapy. Based on prospective and retrospective studies, proton irradiation emerged as the treatment of choice for ocular tumours, chordomas and skull-base tumours. For prostate cancer, the results were comparable with the best results of photon therapy. Ion therapy was still in an experimental phase. CONCLUSION: According to the current literature, proton therapy is looked upon as the preferred treatment modality for certain rare tumours, such as ocular tumours, chordoma, and skull-base tumours. However, charged particle therapy as a whole, and especially ion therapy, is not supported as the treatment of choice for cancer by published evidence. Nevertheless, the potential theoretical benefit of this treatment is great.

Systematic review and meta-analysis of randomised, controlled trials of the timing of chest radiotherapy in patients with limited-stage, small-cell lung cancer.

BACKGROUND: We undertook a systematic review and literature-based meta-analysis to determine whether the timing of chest radiotherapy may influence the survival of patients with limited-stage small-cell lung cancer (LS-SCLC). MATERIALS: Eligible randomised controlled clinical trials were identified according to the Cochrane Collaboration Guidelines, comparing different timing of chest radiotherapy in patients with LS-SCLC. Early chest irradiation was defined as beginning within 30 days after the start of chemotherapy. RESULTS: Considering all seven eligible trials, the overall survival at 2 or 5 years was not significantly different between early or late chest radiotherapy. When only trials were considered that used platinum chemotherapy concurrent with chest radiotherapy, a significantly higher 5-year survival was observed when chest radiotherapy was started within 30 days after the start of chemotherapy (2-year survival: OR: 0.73, 95% CI 0.51-1.03, P = 0.07; 5-year survival: OR: 0.64, 95% CI 0.44-0.92, P = 0.02). This was even more pronounced when the overall treatment time of chest radiotherapy was less than 30 days. CONCLUSIONS: There are indications that the 5-year survival rates of patients with LS-SCLC are in favour of early chest radiotherapy, with a significant difference if the overall treatment time of chest radiation is less than 30 days.

Early versus late chest radiotherapy for limited stage small cell lung cancer.

BACKGROUND: It is standard clinical practice to combine chemotherapy and chest radiotherapy in treating patients with limited-stage small cell lung cancer. However, the best way to integrate both modalities is unclear. OBJECTIVES: To establish the most effective way of combining chest radiotherapy with chemotherapy for patients with limited-stage small cell lung cancer in order to improve long-term survival. SEARCH STRATEGY: The electronic databases MEDLINE, EMBASE, Cancerlit and the Cochrane Central Register of Controlled Trials (CENTRAL), reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished. SELECTION CRITERIA: Randomised controlled clinical trials comparing different timing of chest radiotherapy in patients with limited-stage small cell lung cancer. DATA COLLECTION AND ANALYSIS: Seven randomised trials were reviewed. There were differences in the timing and the overall treatment time of chest radiotherapy, the overall treatment time of , and the type of chemotherapy used. MAIN RESULTS: No significant differences in the 2-year and the 5-year survival were found, whether chest radiotherapy was delivered within 30 days after the start of chemotherapy or later. When the only study that delivered chest radiotherapy during cycles of non-platinum chemotherapy was excluded, a trend for the 5-year survival was observed (RR:0.93, p=0.07) in favour of early radiation, but not for the 2-year survival. Survival at 5 years, but not at 2 years, was significantly better for those having early chest radiotherapy delivered in an overall treatment time of less than 30 days compared with a longer treatment time (RR: 0.90, p=0.006). These results, however, should be interpreted with caution because the largest trial has follow-up data at three years, but not later. It remains to be seen what the effect of longer follow up will be for 5-year survival rates. Local tumour control was not significantly different between early and late chest radiotherapy. The incidence of severe pneumonitis or severe oesophagitis was not significantly different for early versus late thoracic radiotherapy. However, a trend for a higher chance to develop pneumonitis when early chest radiotherapy was delivered during non-platinum based chemotherapy was observed. AUTHORS' CONCLUSIONS: At present, it is uncertain whether the timing of chest radiotherapy as such is important for survival. The optimal integration of chemotherapy and chest radiotherapy in patients with limited-stage small cell lung cancer is unknown. Therefore, further research is needed to establish the most effective combination of radiotherapy and chemotherapy in this disease.