Perspectives of bereaved partners of lung cancer patients on the role of mindfulness in dying and grieving: A qualitative study.

BACKGROUND: Mindfulness-Based Stress Reduction (MBSR) has been shown to reduce psychological distress in cancer patients but not their partners. Whether MBSR can support patients and partners in coping with the dying and grieving process is less well examined. AIM: We aimed to gain more insight in the role of mindfulness in the dying and grieving process from the perspective of the partner after the patient's death. DESIGN: As part of a pilot study or subsequent randomized controlled trial, partners had participated together with the patient in MBSR. After the patient's death partners were invited for qualitative in-depth interviews. Data from the interviews was analyzed using the grounded theory approach. SETTING/PARTICIPANTS: Interviews were conducted with 11 partners in their homes, on average 11 months after the patient's death (SD = 7.8). RESULTS: Mindfulness helped couples to allow and regulate difficult thoughts and feelings, which in turn helped them to accept the patient's impending death. It also facilitated them to enjoy things together and communicate more openly. For a few couples, however, participation was physically too burdensome or emotionally too confrontational. During the partners' grieving process, mindfulness helped allowing difficult thoughts and feelings, and taking the time to grieve, which helped them to take good care of themselves, giving them faith in the future. CONCLUSION: The present study showed that MBSR can facilitate lung cancer patients and their partners in accepting the forthcoming death and openly communicating about this, which can support a peaceful death and healthy grieving process.

Effectiveness and feasibility of a mindful leadership course for medical specialists: a pilot study.

BACKGROUND: Medical specialists experience high levels of stress. This has an impact on their well-being, but also on quality of their leadership. In the current mixed method study, the feasibility and effectiveness of a course Mindful Leadership on burnout, well-being and leadership skills of medical specialists were evaluated. METHODS: This is a non-randomized controlled pre-post evaluation using self-report questionnaires administered at 3 months before (control period), start and end of the training (intervention period). Burn-out symptoms, well-being and leadership skills were assessed with self-report questionnaires. Semi-structured interviews were used to qualitatively evaluate barriers and facilitators for completion of the course. RESULTS: From September 2014 to June 2016, 52 medical specialists participated in the study. Of these, 48 (92%) completed the course. Compared to the control period, the intervention period resulted in greater reductions of depersonalization (mean difference = - 1.2, p = 0.06), worry (mean difference = - 4.3, p = 0.04) and negative work-home interference (mean difference = - 0.2, p = 0.03), and greater improvements of mindfulness (mean difference = 0.5, p = 0.04), life satisfaction (mean difference = 0.4, p = 0.01) and self-reported ethical leadership (mean difference = 0.1, p = 0.02). Effect sizes were generally small to medium (0.3 to 0.6) and large for life satisfaction (0.8). Appreciation of course elements was a major facilitator and the difficulty of finding time a major barrier for participating. CONCLUSIONS: A 'Mindful Leadership' course was feasible and not only effective in reducing burnout symptoms and improving well-being, but also appeared to have potential for improving leadership skills. Mindful leadership courses could be a valuable part of ongoing professional development programs for medical specialists.

Are Mindfulness and Self-Compassion Related to Psychological Distress and Communication in Couples Facing Lung Cancer? A Dyadic Approach.

Lung cancer patients and their spouses report high rates of distress. Due to the increasing popularity of and evidence for mindfulness-based interventions in cancer, mindfulness and self-compassion have been identified as potentially helpful skills when coping with cancer. This dyadic study examined how mindfulness and self-compassion are related to psychological distress and communication about cancer in couples facing lung cancer. Using the actor-partner interdependence model, self-reported mindfulness, self-compassion, psychological distress and communication about cancer were analyzed in a cross-sectional sample of 88 couples facing lung cancer. Regarding psychological distress, no difference was found between patients and spouses. In both partners, own levels of mindfulness (B = -0.19, p = .002) and self-compassion (B = -0.45, p < .001) were negatively related to own distress levels. At a dyadic level, own self-compassion was less strongly associated with distress if the partner reported high self-compassion (B = 0.03, p = .049). Regarding communication about cancer, patients reported to communicate more openly with their partner than with spouses. However, after controlling for gender, this difference was no longer significant. In both partners, own self-compassion (B = 0.03, p = .010) was significantly associated with own communication while mindfulness was not. A trend showed that mindfulness of the partner was related to more open communication in the individual (B = 0.01, p = .080). These findings give a first indication that mindfulness and self-compassion skills may go beyond the individual and could impact couple functioning. Future research should examine whether couples facing (lung) cancer may benefit from programs in which mindfulness and self-compassion are cultivated.

The Predictive Value of Early In-Treatment 18F-FDG PET/CT Response to Chemotherapy in Combination with Bevacizumab in Advanced Nonsquamous Non-Small Cell Lung Cancer.

18F-FDG PET/CT is potentially applicable to predict response to chemotherapy in combination with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC). Methods: In 25 patients with advanced nonsquamous NSCLC, 18F-FDG PET/CT was performed before treatment and after 2 wk, at the end of the second week of first cycle carboplatin-paclitaxel and bevacizumab (CPB) treatment. Patients received up to a total of 4 cycles of CPB treatment. Maintenance treatment with bevacizumab monotherapy was continued until progressive disease without significant treatment-related toxicities of first-line treatment. In the case of progressive disease, bevacizumab was combined with erlotinib. SUV corrected for lean body mass (SUL and SULpeak) were obtained. PERCIST were used for response evaluation. These semiquantitative parameters were correlated with progression-free survival and overall survival (OS). Results: Metabolic response, defined by a significant reduction in SULpeak of 30% or more after 2 wk of CPB, was predictive of progression-free survival and OS. For partial metabolic responders (n = 19), the median OS was 22.8 mo. One-year and 2-y OS were 79% and 47%, respectively. Nonmetabolic responders (n = 6) (stable metabolic disease or progressive disease) showed a median OS of 4.4 mo (1-y and 2-y OS was 33% and 0%, respectively) (P < 0.001). Conclusion:18F-FDG PET/CT after 1 treatment cycle is predictive of outcome to first-line chemotherapy with bevacizumab in patients with advanced nonsquamous NSCLC. This enables identification of patients at risk of treatment failure, permitting treatment alternatives such as early switch to a different therapy.

The suitability of the Hospital Anxiety and Depression Scale, Distress Thermometer and other instruments to screen for psychiatric disorders in both lung cancer patients and their partners.

BACKGROUND: Lung cancer patients and their partners report high rates of distress. Although distress is of importance, psychiatric disorders might be more important in terms of prognostic value and additional psychological treatment. This study examined the suitability of the Hospital Anxiety and Depression Scale (HADS), Distress Thermometer (DT), Beck Depression Inventory (BDI-II) and State subscale of State Trait Anxiety Inventory (STAI-S) to screen for psychiatric disorders in lung cancer patients and partners. METHODS: A consecutive sample of lung cancer patients and partners completed the screening instruments. The Structured Clinical Interview DSM-IV (SCID-I) was used to diagnose psychiatric axis I disorders. RESULTS: In 144 patients, overall ability of HADS total score (HADS-T) screening for patients with psychiatric disorders was good, whereas DT appeared less suitable. In 98 partners, the performance of HADS-T was good. Although no instrument was successful in identifying psychiatric disorders, HADS-T came closest with a fair performance in patients and partners. LIMITATIONS: Several patients and partners declined participation because they perceived participation as too distressing. As decliners possibly have the highest rates of disorders, our findings might underestimate the prevalence of psychiatric disorders. A low prevalence negatively affects the positive predictive value and complicates efficient screening for psychiatric disorders. CONCLUSION: The HADS-T appears to be a suitable screening instrument for ruling out those lung cancer patients and partners without a psychiatric disorder. Regarding identifying those with a psychiatric disorder, HADS-T should be used to refer both patients and partners for further diagnostics and treatment to a psychiatrist/psychologist.

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

BACKGROUND: 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. METHODS: A cross-sectional study among outpatients with cancer. To identify pain, its intensity, quality, and interference with daily activities, the Brief Pain Inventory (BPI) was used. Neuropathic symptoms were identified with the Douleur Neuropathique (DN4) interview and pain characteristics with the McGill Pain Questionnaire (MPQ). Pain medication and adjuvant analgesics were also collected with a prestructured questionnaire. Descriptives, chi-squared tests, t-tests, and a logistic regression analysis were conducted. RESULTS: 892 patients completed the questionnaires. Twenty-three percent (n = 204) reported moderate to severe pain, and 19% (n = 170) scored positive on neuropathic symptoms (DN4 ≥ 3). Particularly in patients with a rating on a numeric rating scale (NRS) < 5, existence of neuropathic symptoms significantly increased interference with daily activities. Of patients with neuropathic symptoms, 8% received adjuvant pain treatment. Receiving curative treatment, using a systemic drug with neurotoxicity, having had an operation, and having had a lymph node dissection independently contributed to having neuropathic symptoms. CONCLUSIONS: This study shows that over 40% of the patients with moderate to severe pain also have neuropathic symptoms, causing increased interference with daily activities. Most of these patients do not receive adjuvant analgesics. There is a need to improve management of neuropathic symptoms in patients with cancer.

Mindfulness-Based Stress Reduction for lung cancer patients and their partners: Results of a mixed methods pilot study.

BACKGROUND: Lung cancer patients and partners show high rates of impaired quality of life and heightened distress levels. Mindfulness-Based Stress Reduction has proven to be effective in reducing psychological distress in cancer patients. However, studies barely included lung cancer patients. AIM: We examined whether Mindfulness-Based Stress Reduction might be a feasible and effective intervention for patients with lung cancer and partners. DESIGN: Mindfulness-Based Stress Reduction is a training in which mindfulness practices are combined with psycho-education to help participants cope with distress. In this mixed methods pilot study, questionnaires on psychological distress and quality of life were administered before, directly after and 3 months after the Mindfulness-Based Stress Reduction training, in combination with semi-structured interviews. SETTING/PARTICIPANTS: Patients with lung cancer and partners were recruited at one tertiary care academic medical centre. A total of 19 lung cancer patients and 16 partners participated in the Mindfulness-Based Stress Reduction training. RESULTS: Most patients were diagnosed with advanced stage lung cancer. Vast majority completed the training. Those receiving anti-cancer treatment did not miss more sessions than patients who were not currently treated. Patients and partners felt positive about participating in a peer group and with their partner. Among participants no significant changes were found in psychological distress. Caregiver burden in partners decreased significantly after following Mindfulness-Based Stress Reduction. The qualitative analysis showed that the training seemed to instigate a process of change in participants. CONCLUSION: The Mindfulness-Based Stress Reduction training seemed to be feasible for patients with lung cancer and their partners. A randomized controlled trial is needed to examine the effectiveness of Mindfulness-Based Stress Reduction in reducing psychological distress in lung cancer patients and partners.

Glucose metabolism in NSCLC is histology-specific and diverges the prognostic potential of 18FDG-PET for adenocarcinoma and squamous cell carcinoma.

INTRODUCTION: Biological features of non-small-cell lung carcinomas (NSCLCs) are important determinants for prognosis. In this study, differences in glucose metabolism between adeno- and squamous cell NSCLCs were quantified using the hypoxia and glycolysis-related markers glucose transporter 1 (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 (MCT1) and 4 (MCT4) vasculature, and 18-fluoro-2-deoxyglucose (FDG)-uptake. Relevance of these markers for disease-free survival (DFS) was analyzed. METHODS: Patients with curatively resected stage I to II and resectable stage IIIA, cN0-1 adeno- or squamous cell NSCLC, of whom fresh-frozen lung resection biopsies and pretreatment FDG-positron emission tomography (PET) scans were available, were included in this study (n = 108). FDG-uptake was quantified by calculating total lesion glycolysis (TLG). Metabolic marker expression was measured by immunofluorescent staining (protein) and quantitative polymerase chain reaction (messenger ribonucleic acid [mRNA]). Patients were retrospectively evaluated for DFS. RESULTS: mRNA and protein expression of metabolic markers, with the exception of MCT4, and TLG were higher in squamous cell carcinomas than in adenocarcinomas, whereas adenocarcinomas were better vascularized. Adenocarcinomas had a worse DFS compared with squamous cell carcinomas (p = 0.016) based on the potential to metastasize. High TLG was associated with a worse DFS only in adenocarcinomas. CONCLUSION: Our findings suggest that the adenocarcinomas exhibit glycolysis under normoxic conditions, whereas squamous cell carcinomas are exposed to diffusion-limited hypoxia resulting in a very high anaerobic glycolytic rate. Although squamous cell carcinomas have a higher FDG-uptake, in general regarded as a poor prognostic factor, adenocarcinomas have a higher metastatic potential and a worse DFS. These findings show that FDG-PET should be interpreted in relation to histology. This may improve the prognostic potential of FDG-PET and may aid in exploiting FDG-PET in treatment strategies allied to histology.

Methylation analysis in spontaneous sputum for lung cancer diagnosis.

OBJECTIVES: Lung cancer is the most fatal cancer in the developed world due to presence of metastases at time of diagnosis. The aim of this study is to examine DNA hypermethylation in sputum compared to sputum cytology for the diagnosis of lung cancer. A novel risk analysis is introduced, using the distinction between diagnostic and risk markers. METHODS: Two independent sets were randomly composed from a prospectively collected sputum bank (Set 1: n = 98 lung cancer patients, n = 90 controls; Set 2: n = 60 lung cancer patients, n = 445 controls). Sputum cytology was performed for all samples. The following DNA hypermethylation markers were tested in both sets: RASSF1A, APC and cytoglobin (CYGB). Two statistical analyses were conducted: multivariate logistic regression and a risk classification model based on post-test probabilities. RESULTS: In multivariate analysis, RASSF1A was the best of the three markers in discriminating lung cancer cases from controls in both sets (sensitivity 41-52%, specificity 94-96%). The risk model showed that 36% of lung cancer patients were defined as "high risk" (≥ 60% chance on lung cancer) based on RASSF1A hypermethylation in Set 1. The model was reproducible in Set 2. Risk markers (APC, CYGB) have less diagnostic value. Sensitivity of cytology for lung cancer diagnosis was 22%. RASSF1A hypermethylation yielded a sensitivity of 45%. The combined sensitivity for RASSF1A with cytological diagnosis increased to 52% with similar specificity (94%). CONCLUSION: In a diagnostic setting, hypermethylation analysis in sputum is possible when a diagnostic marker is used. However, risk markers are insufficient for this purpose.

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.

BACKGROUND: Lung 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/DESIGN: A 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. DISCUSSION: This trial will provide information about the clinical and cost-effectiveness of MBSR compared to TAU in patients with lung cancer and their partners.

[Maternal pulmonary oedema due to the use of atosiban in cases of multiple gestation]. / Maternaal longoedeem bij gebruik van atosiban bij meerlingzwangerschap.

BACKGROUND: Nifedipine is used as a first choice tocolytic agent in many Dutch hospitals, but its use is discouraged in multiple gestations. Atosiban, a selective oxytocin receptor antagonist that rarely causes systemic side effects, is used as an alternative. CASE DESCRIPTION: A 32-year-old primigravida with spontaneous triplet pregnancy was admitted at 33 3/7 weeks for threatened preterm labour. For tocolysis, atosiban was administered for 48 hours together with betamethasone for foetal lung maturation. One day after treatment with atosiban she developed dyspnoea caused by pulmonary oedema. After a caesarean section and furosemide treatment the pulmonary oedema resolved. Analysis showed that atosiban was a likely cause of the pulmonary oedema. CONCLUSION: Every patient with multiple gestation is at increased risk of pulmonary oedema. Any tocolytic agent may elicit that response, even the relatively safe atosiban.

Safety and efficacy of sequential chemotherapy with carboplatin plus gemcitabine followed by weekly paclitaxel in advanced non-small cell lung cancer.

BACKGROUND: Improving survival in non-small cell lung cancer (NSCLC) will require new strategies or new drugs. Sequential administration of conventional non-cross-resistant cytotoxic drugs offers an opportunity to increase drug diversity while maintaining dose intensity. This Phase II trial was designed to assess the efficacy and feasibility of such a regimen in advanced NSCLC. METHODS: Patients with NSCLC stage IIIB or IV received as first-line treatment four cycles of carboplatin (AUC 5) (day 1) plus gemcitabine 1000 mg/m(2) (days 1 and 8) every 3 weeks. Thereafter, treatment continued with 12 weekly cycles of paclitaxel 80 mg/m(2). RESULTS: In total, 46 patients were included. Median age was 59.6 years (range 41.3-74.3 years) and 93.5 % (n = 43) had Eastern Cooperative Oncology Group performance score of 0 or 1. All but 6 had stage IV disease, and 13 (28.3 %) had squamous cell carcinomas. Thirty-six (78 %) patients completed 4 cycles of carboplatin-gemcitabine and 35 patients received at least 1 cycle of paclitaxel, of whom 16 (46 % of total) patients completed 12 cycles of paclitaxel. The overall objective response rate was 49 %. Sixteen (37 %) patients had a response to carboplatin-gemcitabine, increasing to 21 (49 %) patients after administration of paclitaxel. Of the 13 assessable patients who showed a partial response (PR) on carboplatin-gemcitabine, 12 (92 %) patients showed also a PR on paclitaxel. Of 19 assessable patients with stable disease (SD) on carboplatin-gemcitabine, 4 (21 %) had a PR and 13 (68 %) SD on paclitaxel. Toxicity was moderate: 24 % stopped because of toxicity. CONCLUSION: Sequential chemotherapy with carboplatin-gemcitabine and weekly paclitaxel is active and feasible in advanced NSCLC patients.

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.

BACKGROUND: The 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. METHODS: From 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. RESULTS: A 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. CONCLUSIONS: Our data suggest that the molecular analysis of two biomarkers in nondiagnostic bronchial washings may better guide diagnostic procedures in patients with suspected lung cancer.

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 1990 s. 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.

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.

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

OBJECTIVE: A retrospective study was performed to determine whether patients over 60 years old who received chemotherapy were treated according to the existing treatment guidelines and to investigate the reasons for dose reductions or treatment delay. MATERIAL AND METHODS: Three hundred and seven patients aged over 60 years old and diagnosed with colon, breast or lung cancer between 1998 and 2008 who were treated with chemotherapy in the Radboud University Medical Center were included. From the medical records we recorded the number of and the reasons for dose reductions and delays. We calculated the relative dose intensity (RDI) received. RESULTS: RDI did not decrease significantly with age. However patients over 65 years of age had a higher probability of receiving a suboptimal dose intensity, even when treated with curative intent. There was no correlation between toxicity and age, however the comorbidity score increased with age. The average received RDI was higher in patients diagnosed more recently. CONCLUSION: Despite increased comorbidity, older patients receiving chemotherapy were generally treated according to protocol without high incidence of severe toxicity. We saw improvement of RDI over the time period investigated. The participation of geriatricians in multidisciplinary oncology teams could help to optimize therapy decisions for patients with comorbidity.

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.

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

INTRODUCTION: Circulating 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. METHODS: 46 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. RESULTS: The 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. CONCLUSION: In 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.

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

UNLABELLED: Chronic 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). PERSPECTIVE: Up 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.

A prospective study of the timing and cost-effectiveness of bronchial washing during bronchoscopy for pulmonary malignant tumors.

STUDY OBJECTIVES: The value of obtaining washings during fiberoptic bronchoscopy in the workup of lung cancer is controversial. Moreover, the optimal timing of washing relative to biopsy and brushing is not known. In this study, the diagnostic yields of washings before and after biopsy and brushings were compared. The different diagnostic strategies were assessed in terms of yield and costs. DESIGN: A prospective study performed from 2001 to 2003 in a secondary care medical center. MEASUREMENTS AND RESULTS: Two hundred twenty-one patients underwent flexible bronchoscopy, and the diagnostic yield of washings before biopsy and brushing (strategy I) and after biopsy and brushing (strategy II) specimens were assessed. Using the known probabilities and costs for various bronchoscopic procedures, the expected utility of a number of diagnostic strategies was estimated. Patients (147 men and 74 women) were included in the study in whom a definite cytologic or histologic diagnosis of pulmonary malignancy had been made. The diagnostic yield of strategy I was 72% for visible tumors and 36% for nonvisible tumors. For strategy II, the diagnostic yield was 74% for visible tumors and in 42% for nonvisible tumors. The comparison of strategies I and II for both visible and nonvisible tumors revealed that 176 cases were concordant (80%); in 19 cases (9%) the cytologic analysis of washings in strategy I was positive for malignancy and negative in strategy II. In 26 cases (12%) washings in strategy II were positive and negative in strategy I (p = 0.37). An analysis of the diagnostic yield of both washings in visible tumors and nonvisible tumors showed no significant difference. In 13 patients, a diagnosis of malignancy was established only by washings (6%). Confining the laboratory investigations of washings or brush samples to those cases in which the initial findings of the biopsies are negative (the two-stage procedure) is more cost-effective than examining all biopsy, brushing, and washing specimens. In patients with visible tumors, brushing or washing in addition to biopsy is equally cost-effective; in patients with nonvisible tumors, biopsy combined with washing is the preferred option. CONCLUSIONS: No difference in the diagnostic yield could be demonstrated for washings before or after biopsies and brushings. Although the additional diagnostic yield of washing and brushing during bronchoscopy is relatively low, it is cost-effective to use these procedures in the diagnostic workup of patients who are clinically suspected of having a pulmonary malignancy.