Miep A. van der Drift

Only half of the chronic pain after thoracic surgery shows a neuropathic component.

UNLABELLEDnChronic pain is a common complication after thoracic surgery. The cause of chronic post-thoracotomy pain is often suggested to be intercostal nerve damage. Thus chronic pain after thoracic surgery should have an important neuropathic component. The present study investigated the prevalence of the neuropathic component in chronic pain after thoracic surgery. Furthermore, we looked for predictive factors for prevalence and intensity of chronic pain. We contacted 243 patients who underwent a video-assisted thoracoscopy (VATS) or thoracotomy in the period between January 2004 and September 2006 by mail. Patients retrospectively received a questionnaire with the Dutch version of the PainDETECT Questionnaire, a validated screening tool for neuropathic pain. Results were analyzed from 204 patients (144 thoracotomies, 60 VATS). The prevalence of chronic pain was 40% after thoracotomy and 47% after VATS. Definite chronic neuropathic pain was present in 23% of the patients with chronic pain, with an additional 30% having probable neuropathic pain. Greater probability of neuropathic pain (ie, a higher total score of the PainDETECT) correlated with more intense chronic pain. Predictive factors for chronic pain were younger age (P = .01), radiotherapy (P = .043), pleurectomy (P = .04) and more extensive surgery (P < .001).nnnPERSPECTIVEnUp to half the chronic pain after thoracic surgery is not associated with a neuropathic component, which has not been reported to date. More extensive surgery and pleurectomy are predictive factors for chronic pain after thoracic surgery, suggesting a visceral component apart from nerve injury.

Circulating DNA is a non-invasive prognostic factor for survival in non-small cell lung cancer.

INTRODUCTIONnCirculating plasma DNA is present in a considerably higher concentration in lung cancer patients than in controls. Conflicting data are reported about circulating DNA as a prognostic factor. The aim of this study was to prospectively analyse the relationship of circulating plasma DNA with overall survival (OS) of previously untreated non-small cell lung cancer (NSCLC) patients.nnnMETHODSn46 untreated NSCLC patients and 21 controls with a follow-up time of 6.5 years were analyzed. Quantification of baseline circulating plasma DNA was performed by a real-time quantitative polymerase chain reaction (qPCR) targeting the human beta-globin gene. Survival analysis was performed using the Kaplan-Meier method and compared with a Cox-regression analysis.nnnRESULTSnThe median DNA concentration of the patients who died (87%) was significantly higher compared to the patients that survived at the end of follow-up (55ng/ml versus 23ng/ml, p=0.02). In patients with higher DNA concentration overall survival was significantly worse. In this study no relation of DNA concentration with tumour characteristics, age, gender or pulmonary inflammatory conditions was found.nnnCONCLUSIONnIn this study a high circulating plasma DNA concentration at time of diagnosis in NSCLC patients was a prognostic factor for poorer survival. Circulating DNA may be used as a non-invasive biomarker to refine the prognostic profile in NSCLC patients.

Progress in Standard of Care Therapy and Modest Survival Benefits in the Treatment of Non-small Cell Lung Cancer Patients in the Netherlands in the Last 20 Years

Introduction: Lung cancer is the leading cause of cancer mortality worldwide. We analyzed changes in treatment and their potential effect on survival of non-small cell lung cancer (NSCLC) patients in the Netherlands. Methods: All NSCLC patients diagnosed during 1989–2009 (n=147,760) were selected from the population-based Netherlands Cancer Registry. Differences in treatment over time were tested by the Cochran-Armitage trend test. The effects of sex, age, histology, and treatment on relative survival were estimated in multivariable models. Follow-up was completed until January 1, 2010. Results: Between 1989 and 2009, the proportion of younger patients (younger than 75 years) with stage I undergoing surgery increased from 84 to 89% and among elderly (75 years or elder) from 35 to 49%; for stage II, this proportion decreased from 80 to 70% and remained about 25% in respectively younger and older patients. Adjuvant chemotherapy for stage II increased to from 0 to 24% in younger patients but remained less than 5% among the elderly. Chemoradiation increased from 8 to 43% among younger patients with stage III and from 1 to 13% among elderly. In stage IV, chemotherapy in younger patients increased from 10 to 54% and in elderly from 5 to 21%. Five-year relative survival of the total group increased from 14.8 to 17% (especially among females, younger patients, and within each stage), which could be partly explained by changes in treatment and better staging. Conclusions: Over a 20-year period, application of therapy, which is currently considered as standard, has improved. This resulted in small improvements in survival within all stages.

Study protocol of a randomized controlled trial comparing Mindfulness-Based Stress Reduction with treatment as usual in reducing psychological distress in patients with lung cancer and their partners: the MILON study

BackgroundLung cancer is the leading cause of cancer death worldwide and characterized by a poor prognosis. It has a major impact on the psychological wellbeing of patients and their partners. Recently, it has been shown that Mindfulness-Based Stress Reduction (MBSR) is effective in reducing anxiety and depressive symptoms in cancer patients. The generalization of these results is limited since most participants were female patients with breast cancer. Moreover, only one study examined the effectiveness of MBSR in partners of cancer patients. Therefore, in the present trial we study the effectiveness of MBSR versus treatment as usual (TAU) in patients with lung cancer and their partners.Methods/DesignA parallel group, randomized controlled trial is conducted to compare MBSR with TAU. Lung cancer patients who have received or are still under treatment, and their partners are recruited. Assessments will take place at baseline, post intervention and at three-month follow-up. The primary outcome is psychological distress (i.e. anxiety and depressive symptoms). Secondary outcomes are quality of life (only for patients), caregiver appraisal (only for partners), relationship quality and spirituality. In addition, cost-effectiveness ratio (only in patients) and several process variables are assessed.DiscussionThis trial will provide information about the clinical and cost-effectiveness of MBSR compared to TAU in patients with lung cancer and their partners.Trial registrationClinicalTrials.gov NCT01494883.

Diagnosing Peripheral Lung Cancer: The Additional Value of the Ras-Association Domain Family 1A Gene Methylation and Kirsten Rat Sarcoma 2 Viral Oncogene Homolog Mutation Analyses in Washings in Nondiagnostic Bronchoscopy

BACKGROUNDnThe diagnostic yield of bronchoscopy in patients with endoscopically nonvisible (peripheral) tumors varies from 40% to 56%. Increasingly, molecular markers in bronchial washings are being investigated to improve the diagnostic yield. The aim of this study was to analyze the diagnostic value of the Ras association domain family 1A gene (RASSF1A) methylation analysis in washings in nondiagnostic bronchoscopy in the analysis of patients with suspected lung cancer who had peripheral tumors. Furthermore, the additional diagnostic value of Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutations with RASSF1 methylation was analyzed.nnnMETHODSnFrom a prospectively collected series, 129 patients with lung cancer and 28 control subjects were analyzed retrospectively regarding the methylation status of the promoter region of the RASSF1A gene by quantitative methylation-specific polymerase chain reaction and KRAS point mutations by using the sensitive Point-EXACCT method.nnnRESULTSnA total of 40% of the lung cancer patients had peripheral tumors, and 17 patients had a nondiagnostic bronchoscopy. In these patients, RASSF1A methylation was detected in the washings of four patients (24%), and KRAS mutations were detected in the washings of two patients (12%). In total, 29% of the false-negative or doubtful cytology results were accompanied by RASSF1A methylation or KRAS mutation results that were highly suggestive of malignancy. The proportion of RASSF1A methylation was significantly higher in central and larger tumors. No relevant RASSF1A methylation was detected in control samples.nnnCONCLUSIONSnOur data suggest that the molecular analysis of two biomarkers in nondiagnostic bronchial washings may better guide diagnostic procedures in patients with suspected lung cancer.

Neuropathic Pain Components in Patients with Cancer: Prevalence, Treatment, and Interference with Daily Activities

Pain and neuropathic symptoms impact quality of life of patients with cancer. To obtain more insight in the prevalence, severity, and treatment of neuropathic symptoms in patients with cancer and their interference with daily activities, we conducted a cross‐sectional study at the outpatient clinic of a Dutch university hospital.

Modest Improvements of Survival for Patients with Small Cell Lung Cancer Aged 45 to 59 Years Only, Diagnosed in the Netherlands, 1989 to 2008

Introduction: Lung cancer was a major epidemic in the last decades; 10 to 15% of lung cancer consists of small cell lung cancer (SCLC). Several changes in the diagnostic and treatment procedures took place during the last 20 years. This article focuses on trends in incidence, treatment, and survival of SCLC observed since the 1990s. Methods: All cases with SCLC diagnosed in 1989 to 2009 in the Netherlands were included (n = 34,100). Follow-up was complete until January 1, 2010. Results: The proportion of patients with extensive disease increased from 47 to 63%. The proportion of patients with limited disease receiving chemoradiation increased from 22% in 1989 to 2003 to 72% in 2004 to 2009 among those younger than 45 to 59 years, from 15 to 58% among those aged 60 to 74 years, and from 7 to 27% among those 75 years or older. Among patients with extensive disease, the proportion receiving chemotherapy remained stable over time (84, 75, and almost 50% for the above mentioned age groups, respectively). Significant improvements in 1-year relative survival occurred for patients aged 45 to 59 years, but not for the other age groups. Relative survival has significantly increased for both stage groups. Conclusion: Improved staging resulted in improved survival for both stage groups, whereas survival of the total group has only significantly improved for patients aged 45 to 59 years. The latter is possibly related with improved treatment strategies. As survival is still very poor, prevention of lung cancer remains important.

Encouraging results in older patients receiving chemotherapy: a retrospective analysis of treatment guideline adherence in daily practice.

Objective:u2003 A retrospective study was performed to determine whether patients over 60u2003years old who received chemotherapy were treated according to the existing treatment guidelines and to investigate the reasons for dose reductions or treatment delay.

The Clinical Value of Lymphatic Micrometastases in Patients with Non-small Cell Lung Cancer

Introduction: In early stage non-small cell lung cancer (NSCLC), presence of lymphatic micrometastases and isolated tumor cells, primarily detected by immunohistochemistry, is suggested to be a prognostic factor. However, there is no consensus whether immunohistochemistry should be used routinely in lymph node assessment. The goal of our study was to determine whether recurrent disease is associated with the presence of lymphatic micrometastases and/or isolated tumor cells, at the time of the lung resection. Methods: We retrospectively analyzed the prevalence of lymphatic micrometastases and/or isolated tumor cells in two groups of patients, who underwent a curative resection for early stage NSCLC. Group I had a follow-up of 5 years without recurrent disease. Group II consisted of a matched group of patients with recurrent disease. Patients were originally classified as having negative mediastinal lymph nodes. All lymph nodes obtained by mediastinoscopy and thoracotomy were re-examined by serial sectioning and immunohistochemistry. Results: Micrometastases and/or isolated tumor cells were found in one of 16 patients in group I, which was significantly different from six of 16 patients in group II. (Fisher exact test, 4.6; p, 0.04; risk ratio, 2.4). Serial sectioning and immunohistochemistry did not change N-stage for the single patient in group I, in contrast to all six patients in group II. Conclusion: Presence of lymphatic micrometastases and/or isolated tumor cells is associated with distant recurrence in patients with early stage NSCLC. We recommend the routine use of serial sectioning and immunohistochemistry in lymph node assessment to improve the accuracy of staging.