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Biomedical subjects

G P ten Velde

Publications and source records attributed to G P ten Velde.

At least 19 recordsLinked to original sources

Prospective study on quality of life before and after radical radiotherapy in non-small-cell lung cancer.

PURPOSE: The purpose of this study was to investigate changes in respiratory symptoms and quality of life (QoL) in patients with non-small-cell lung cancer (NSCLC) receiving radical radiotherapy (60 Gy). Additionally, the association between the level of symptom relief and objective tumor response, as well as with radiation-induced pulmonary changes, was investigated. PATIENTS AND METHODS: One hundred sixty-four patients were entered onto this prospective study. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-LC13 were used to investigate changes in QOL: Assessments were performed before radiotherapy and 2 weeks, 6 weeks, 3 months, 6 months, and 12 months after the completion of radiotherapy. RESULTS: The QoL response rates were excellent for hemoptysis (83%); good for chest pain (68%), arm/shoulder pain (63%), and appetite loss (60%); and poor for dyspnea (37%), cough (31%), and fatigue (28%). The QoL response rates for the five functioning scales of the QLQ-C30 varied from 35% for physical and role functioning to 55% for social and cognitive functioning. The response rate for global QoL was 36%. A significant association was found between tumor response and palliation of chest pain, arm/shoulder pain, and physical functioning. During radiotherapy, a significant increase for most general symptoms and a deterioration in functioning and QoL were noted. CONCLUSION: This study is the first to describe palliation and changes in QoL in radically irradiated patients with NSCLC. Radical radiotherapy offers palliation of respiratory symptoms and improved QoL in a substantial proportion of patients with NSCLC who have relatively good prognostic features. Although tumor reduction is associated with palliation of respiratory symptoms, it cannot serve as a surrogate for palliation.

Adult↗

Diagnostic yield of computed tomography and densitometric measurements of the lung in thoracoscopically-defined idiopathic spontaneous pneumothorax.

In the present study, the diagnostic yield of high resolution computed tomography (HRCT) is evaluated in patients with thoracoscopically-verified idiopathic spontaneous pneumothorax (SP). Visual assessment as well as densitometry of lung parenchyma was performed. In eight of the 20 prospectively-evaluated SP patients, emphysema-like (EL) changes such as blebs and bullae could be detected. The SP patients with EL changes were significantly older and were more heavy smokers. Spirometrically-controlled CT lung densitometry showed no differences between the patient group with or without these EL changes. Comparing the densitometric measurements of the patient group with a healthy control group no significant differences in densitometry between both groups were found. In conclusion, this study confirms that HRCT is a reliable method of detecting blebs and bullae in patients with spontaneous pneumothorax. Furthermore CT lung densitometry revealed no parenchymal abnormalities or signs of air trapping in patients with spontaneous pneumothorax.

Adult↗

Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m(2)) or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80 mg/m(2)) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P=.026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.

Adult↗

Quality of life after palliative radiotherapy in non-small cell lung cancer: a prospective study.

PURPOSE: The purpose of this study was to investigate changes in respiratory symptoms and quality of life (QoL) in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC) receiving thoracic radiotherapy. Additionally, the correlation between the level of symptom relief and objective tumor response was investigated. METHODS AND MATERIALS: Sixty-five patients were entered in this prospective study. The EORTC QLQ-C30 and EORTC QLQ-LC13 were used to investigate changes in QoL. Assessments were performed before radiotherapy and 2 weeks, 6 weeks, and 3 months after radiotherapy. RESULTS: The QoL response rates were excellent for hemoptysis (79%); good for arm/shoulder pain (56%), chest wall pain (53%), and cough (49%); moderate for dyspnea (39%); and minimal for the general symptoms fatigue (22%) and appetite loss (11%). The QoL response rates for the five functioning scales of the QLQ-C30 varied from 35% for role functioning to 57% for emotional functioning. Global QoL improved in 37% of the cases. In general, there was a tendency for better palliation of symptoms and improvement of QoL among patients with an objective tumor response than among those without objective tumor response, which was statistically significant for dyspnea (p = 0.02) and social functioning (p = 0.04). CONCLUSIONS: This study confirms that conventional thoracic radiotherapy offers palliation of respiratory symptoms and improved QoL in a substantial proportion of patients with locally advanced and metastatic NSCLC. Tumor reduction is only one of the mechanisms by which palliation of symptoms and improvement of QoL is achieved.

Adult↗

The prognostic impact of quality of life assessed with the EORTC QLQ-C30 in inoperable non-small cell lung carcinoma treated with radiotherapy.

PURPOSE: The purpose of this study was to assess the prognostic significance of pretreatment quality of life (QoL) scores and symptom scores in a group of patients treated with high dose radiotherapy. MATERIAL AND METHODS: A total of 198 patients treated with external irradiation (>/=60 Gy) were included. In all these patients, baseline QoL was assessed using the EORTC QLQ-C30. The prognostic significance of a number of non-QoL and QoL parameters with regard to survival was estimated in both univariate and multivariate analyses. RESULTS: In a multivariate model including the non-QoL parameters, performance status, weight loss and N-classification were independent prognostic factors for survival. After entering the QoL parameters in the model, global QoL was the strongest prognostic factor, while performance status lost its significance. Subsequently, a significant interaction term was found between N-classification and global QoL, indicating that global QoL was an independent prognostic factor but that the effect varied as a function of N-status. In N+ patients, the median survival in the group with low scores for global QoL was 4.5 months, which was significantly worse (P<0.0001) compared with the high score group in which the median survival was 12.9 months. CONCLUSION: Global QoL is a strong prognostic factor for survival in patients with NSCLC who have pathological lymph nodes at presentation and who are treated with radical or curative radiotherapy.

Activities of Daily Living↗

Asymptomatic brain metastases (BM) in small cell lung cancer (SCLC): MR-imaging is useful at initial diagnosis.

PURPOSE: In this study we evaluated the usefulness of MR-imaging in the detection of asymptomatic brain metastases (BM) at the initial diagnosis in patients with small cell lung cancer (SCLC) and studied the follow-up of these patients. PATIENTS AND METHODS: One-hundred and twenty-five patients with SCLC were investigated with MR-imaging. RESULTS: In 112 patients with normal neurological findings, MR-imaging of the brain demonstrated BM in 17 patients (15%). Six of these 17 patients were therefore upgraded to extensive disease (ED). Two of these 17 patients died during chemotherapy because of progressive disease and 3 patients became neurologic symptomatic with progressive disease on MR-imaging of the brain. After completion of chemotherapy a repeated MR-imaging of the brain in the remaining 12 patients showed 1 complete remission, 4 partial remission and 7 progressive disease of the BM. CONCLUSION: This study showed that at presentation an unexpectedly high percentage of SCLC patients had asymptomatic BM on MR-imaging. We propose that MR-imaging of the brain should be included in the staging of SCLC patients as well for staging, prognosis and therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Pretreatment quality of life of inoperable non-small cell lung cancer patients referred for primary radiotherapy.

This study examined the association between the most important prognostic factors in non-small cell lung carcinoma (NSCLC) and self-reported pretreatment quality of life (QoL) and the impact of the presence, severity and changes in respiratory symptoms on general symptoms and QoL. The study included 262 patients. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-LC13 were used to assess symptoms and QoL before radiotherapy. Patients with inoperable NSCLC showed major differences in self-reported QoL as a function of clinical prognostic factors. A significant association was found between World Health Organization (WHO) performance status and QoL but not other prognostic factors. Dyspnoea was the only respiratory symptom associated significantly with general symptoms, physical and psychosocial functioning and QoL. Furthermore, changes in dyspnoea were associated significantly with changes in physical and role functioning, global QoL and fatigue as assessed 6 weeks after radiotherapy. These results indicate that palliation of dyspnoea may have a significant beneficial effect on QoL and that palliation of other respiratory symptoms is not necessarily associated with improvement of general symptoms, physical and psychological functioning or global QoL.

Adult↗

Clinical value of DNA image cytometry in effusions with atypia.

Malignant cells in serosal effusions provide essential information about the extent of malignant disease. The main aim of this study was to examine the additional diagnostic value of DNA image cytometry for cases with uncertainty in the cytological diagnosis. In addition, the feasibility of automated nuclei detection was investigated. Out of 457 cases, 33 samples in 32 patients were diagnosed with "atypia" (probably benign) and 21 as "suspicious for malignancy." DNA image cytometry was performed on these 54 cases and on an additional group of 14 cytologically malignant cases. The results show that automatic classification is useful for separation of control cells, i.e., lymphocytes and neutrophilic granulocytes from other mononuclear cells. In 21 cases an insufficient number of control cells were measured. Seventy-two percent of the cytologic malignant cases were aneuploid. In contrast, in none of the cases with "atypia" and in only 2 of the cases "suspicious for malignancy" was aneuploidy present (2 of the remaining 32, 6%). From the cases with follow-up, a malignancy in the pleural fluid was present in 2 out of 17 cases with "atypia" and in 5 out of 10 with a "suspicious for malignancy" cytologic diagnosis, respectively. In conclusion, the additional diagnostic value of DNA image cytometry in cases with a cytological diagnosis of "atypia" or "suspicious for malignancy" is limited. Diagn. Cytopathol. 1999;21:112-116.

Adult↗

Additional value of K-ras point mutations in bronchial wash fluids for diagnosis of peripheral lung tumours.

The purpose of this study was to examine the additional diagnostic value of K-ras point mutations in the clinical diagnosis of peripheral lung tumours. To this end, bronchial wash fluids obtained during bronchoscopy from patients suspected of having lung cancer were studied. Only those patients were investigated for whom the cytological diagnosis was not conclusive for malignancy. As a control group, patients without lung cancer were investigated. The method of "point mutation detection using the exonuclease amplification coupled capture technique" (Point-EXACCT) for analysis of K-ras codon 12 was performed in bronchial wash fluids and the corresponding tumour tissue, if available. K-ras point mutations were identified in 4 out of 19 (21%) bronchial wash fluids from patients without a decisive diagnosis of malignancy. The diagnosis of malignancy was further based on cytological examination of bronchial brush specimens, perthoracic needle aspiration, histological investigation of biopsy and resection specimens, needle aspiration of a lymph node in the neck and pleural fluid examination. Four of the patients who were K-ras-positive yielded positive malignant tissue via bronchoscopy even though the bronchial wash was negative for malignancy. The bronchial wash was positive for K-ras in two of the four patients whose tumour tissue demonstrated the K-ras mutations. Analysis of bronchial wash fluids from 11 patients without lung cancer revealed no K-ras codon 12 mutations. In conclusion, K-ras point mutations can be identified in bronchial wash fluids obtained during bronchoscopic procedures. K-ras can be used as a biomarker in the clinical diagnosis of lung cancer and may serve as an adjunct to cytology in lung cancer diagnosis.

Aged↗

Is the chest radiograph a reliable tool in the assessment of tumor response after radiotherapy in nonsmall cell lung carcinoma?

BACKGROUND: The purpose of this study was to evaluate whether the chest radiograph is a reliable tool to assess response to radiotherapy. MATERIALS AND METHODS: Pre- and post-treatment chest radiographs and computed tomographs (CT) of 63 patients with nonsmall cell lung cancer (NSCLC) treated by radiotherapy were reviewed by four observers with regard to suitability for tumor measurement, and response. Suitability for tumor measurement was expressed as the number of measurable diameters. In addition, the consequences to clinical outcome were studied by survival analysis. RESULTS: The CT turned out to be more suited for tumor measurement before as well as after radiotherapy, resulting in an increase of the number of measurable cases. The number of measurable cases with CT was 52 (83%) as compared to 28 (44%) with chest radiography. Especially in case of centrally localized tumors, the presence of an atelectasis, or squamous cell carcinoma, CT contributed to a higher rate of measurable cases. The interobserver agreement with regard to response using chest radiograph was good (mean kappa = 0.74). In 25 of 28 cases (89%) measurable with CT as well as with chest radiograph, response was equally classified. When CT was used, the median survival of the responders was 14.2 months as compared to 6.8 months of the nonresponders. When chest radiograph was used, the median survival of these groups was 12.0 and 6.6 months respectively, which was not significantly different when response was assessed by CT. CONCLUSION: We conclude that CT is more suited for tumor measurement because more measurable lesions can be found and more evaluable lesions on chest radiograph become measurable on CT. The chest radiograph does have a valuable role to play in those lesions that are measurable because of the good interobserver agreement with regard to the response classification, the high overall agreement between CT and chest radiograph in case of measurable cases, and the lack of important differences with regard to survival.

Adult↗

Effects of medroxyprogesterone acetate on food intake, body composition, and resting energy expenditure in patients with advanced, nonhormone-sensitive cancer: a randomized, placebo-controlled trial.

BACKGROUND: Anorexia and cachexia are well-known sequelae of cancer that contribute to morbidity and mortality. In several studies in patients with non-hormone-sensitive tumors, synthetic progestogens were shown to exert beneficial effects on appetite and weight loss. The current study was undertaken to investigate the effects of medroxyprogesterone acetate (MPA) on food intake, body composition, and resting energy expenditure (REE). METHODS: Fifty-four patients with non-hormone-sensitive cancer, generally characterized by substantial weight loss and hypermetabolism, received either MPA, 500 mg, or placebo twice daily for 12 weeks (double-blind study). Food intake was measured by dietary history, body composition was assessed by deuterium dilution (fat mass, fat-free mass), and REE was obtained by indirect calorimetry. RESULTS: Compared with placebo, 12 weeks of MPA led to an increase in energy intake (between-group difference, 426 kcal/day; P = 0.01) that was significantly associated (r = 0.68, P = 0.003) with an increase in fat mass (between-group difference, 2.5 kg; P = 0.009). Fat-free mass was not significantly influenced. REE increased during MPA treatment: at 6 weeks, the between-group difference in change was 135 kcal/day (P = 0.009); after 12 weeks, this difference was 93 kcal/ day (P = 0.07). CONCLUSIONS: The authors conclude that MPA is able to stimulate increased food intake significantly and to reverse fat loss concomitantly in patients with non-hormone-sensitive cancer.

Aged↗

Massive haemoptysis after radiotherapy in inoperable non-small cell lung carcinoma: is endobronchial brachytherapy really a risk factor?

BACKGROUND AND PURPOSE: This retrospective study was conducted to investigate whether endobronchial brachytherapy (EBB) is a risk factor for massive haemoptysis in patients primarily treated by a combination of EBB and external irradiation (XRT) for NSCLC. MATERIALS AND METHODS: The records of 938 patients with inoperable NSCLC who were treated with XRT and/or EBB were reviewed. The patients were divided into five groups as follows: group XRT, treated by XRT alone (n = 421); group XRTelig, treated by XRT but eligible for EBB (n = 419); group XRTEBB, primarily treated with EBB+XRT (n = 62); group EBBrec, treated by EBB for recurrence after XRT (n = 23); and group EBB, treated by EBB alone (n = 13). EBB was delivered using HDR. Patients with bronchoscopy-proven endobronchial tumour in the proximal airways, i.e. the trachea, the main bronchus or lobar bronchus were considered eligible for EBB. RESULTS: One hundred one out of 938 patients (10.8%) died from massive haemoptysis. The incidence was 4.3% in group XRT, 13.1% in group XRTelig and 25.4% in group XRTEBB. The differences between groups XRT and XRTelig as well as between groups XRTelig and XRTEBB were statistically significant (P<0.01). The incidence of massive haemoptysis depended significantly on the fraction size of brachytherapy. When two fractions of 7.5 Gy or a single fraction of 10 Gy were used, 11.1% of the patients died from massive haemoptysis. However, when a single dose of 15 Gy was used, 47.8% died from massive haemoptysis. In the multivariate analysis, a single dose of 15 Gy EBB was the most important prognostic factor for massive haemoptysis. CONCLUSION: XRT+EBB as primary treatment for NSCLC does not lead to a higher risk of massive haemoptysis as compared to XRT alone when fraction sizes for EBB of 7.5 or 10 Gy are used. However, the risk of massive haemoptysis increases dramatically when a fraction size of 15 Gy is used.

Adolescent↗

The enhanced inflammatory response in non-small cell lung carcinoma is not reflected in the alveolar compartment.

An inflammatory response has been observed in lung cancer both locally and systemically. The aim of the present study was to investigate whether the alveolar compartment was involved in the inflammatory response in non-small cell lung carcinoma (NSCLC). Both inflammatory mediators in bronchoalveolar lavage fluid (BALF) and cytokines produced by alveolar macrophages (AM) were investigated. Twenty patients with newly detected NSCLC and nine control subjects were studied. The patients had not been treated with chemotherapy, radiotherapy or with systemic or inhaled corticosteroids. All patients and control subjects were current smokers or stopped smoking recently. BAL was performed in the affected lung as well as in the contralateral lung of NSCLC patients, and only unilaterally in control subjects. Comparable results were demonstrated for the levels of the of the inflammatory mediators TNF-a, Interleukin (IL)-6, IL-8, both soluble TNF receptors and the soluble adhesion molecules E-selectin and intercellular adhesion molecule (ICAM)-1 between the affected lung and the contralateral lung in the NSCLC population as well as between the NSCLC population and the control subjects. Moreover, no significant differences in cytokine profiles of AM were found between AM obtained from the affected lung and from the contralateral lung. Although BAL is a useful tool in the diagnostic procedure for NSCLC, the present findings suggest that BAL does not reflect the enhanced inflammatory state, as reported in plasma and in the interstitial compartment around the tumour cells in NSCLC.

Analysis of Variance↗

Role of recombinant interferon-gamma maintenance in responding patients with small cell lung cancer. A randomised phase III study of the EORTC Lung Cancer Cooperative Group.

This study was undertaken to determine if recombinant interferon-gamma (rIFN-gamma) given every other day as maintenance therapy could prolong the survival of patients with small cell lung cancer (SCLC) who achieved a complete or nearly-complete response to induction therapy. A secondary endpoint was to assess the toxicity of alternate day doses of this treatment. One hundred and seventy seven patients in complete or nearly-complete response following chemotherapy with or without thoracic radiotherapy were studied. Patients were randomised to receive either rIFN-gamma 4 million units (0.2 mg) subcutaneously every other day for 4 months or observation. One hundred and twenty of the 127 registered patients were eligible; 59 patients received IFN and 61 patients without maintenance therapy were followed. Alternate day IFN was reasonably well tolerated by the majority of patients, but in 12% substantial non-haematological toxicity (including flu-like syndrome) occurred. One of 3 patients with pneumonitis died after having received 3.6 mg IFN. The median survival time from the date of randomisation was 8.9 months for the IFN arm and 9.9 months for the observation arm. rIFN-gamma at the dose and schedule used in this study failed to prolong response duration and survival in SCLC patients in complete or nearly-complete response. The toxicity seen with every other day doses of IFN was less than that reported with daily dosing. The hypothesis that this agent may increase the deleterious effects of radiation on normal lung tissue was supported by the development of pneumonitis in 3 cases of whom 1 had a fatal outcome. The results do not warrant further studies with rIFN-gamma on maintaining response in SCLC.

Antineoplastic Agents↗

Efficacy and safety of prophylactic cranial irradiation in patients with small cell lung cancer.

BACKGROUND: Prophylactic cranial irradiation (PCI) as part of the treatment regimen for patients with limited stage small cell lung cancer (SCLC) remains controversial. The present study was performed to analyze the efficacy and safety of PCI in patients with limited stage SCLC who achieved complete remission. PATIENTS AND METHODS: Between 1983 and 1993, thirty-nine patients with limited stage SCLC who had shown complete remission after chemotherapy were enrolled prospectively into the non-randomized study. Eighteen of them received PCI (PCI+), while 21 did not (PCI-). Pretreatment CT or MRI of the brain was performed in all patients. Patients were prospectively evaluated by a neurologist at regular intervals. RESULTS: Three PCI+ patients and seven PCI- patients developed brain metastases. The frequencies of brain metastases were not significantly different between the groups (Fisher's exact test, p = 0.207), but brain metastases in PCI+ patients tended to occur later (log rank, p = 0.008). Overall survival was significantly longer in PCI+ patients (log rank, p < 0.001). Early toxicity consisted of headache, nausea, fatigue, concentration problems and alopecia. These symptoms and signs were mild and usually reversible within a few months. Late toxicity was studied in patients whose survival exceeded two years. Seven PCI+ patients survived for more than two years, while no PCI- patients survived for more than two years. Memory problems were seen in six of the seven patients. These problems were non-disabling and, once established, remained stable for months to years. The most prominent radiologic abnormalities were cortical atrophy and leukoencephalopathy, found in four of the five patients who underwent radiologic follow-up examination. CONCLUSIONS: This non-randomized study suggests that PCI may be effective by decreasing the frequency of brain metastases and by increasing the brain metastasis-free survival and overall survival, with a minor risk of clinical and radiologic neurotoxicity.

Adult↗

The effects of treatment with chemotherapy on energy metabolism and inflammatory mediators in small-cell lung carcinoma.

A disturbed energy balance has been demonstrated in lung cancer patients. Both an enhanced resting energy expenditure (REE) and a decreased energy intake contribute to weight loss. Enhanced systemic levels of inflammatory mediators were found to be related to the enhanced REE in lung cancer. The aim of the present study was to investigate energy metabolism and systemic levels of inflammatory mediators in small-cell lung carcinoma (SCLC) patients before and after treatment with chemotherapy. Hypermetabolism and an enhanced inflammatory response have already been demonstrated in SCLC by our group before. Twelve newly diagnosed SCLC patients were consecutively included in the study. REE was measured by indirect calorimetry and body composition was determined by bioelectrical impedance (BIA) before and 1 month after treatment. To assess the inflammatory state the acute-phase proteins, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP), both soluble tumour necrosis factor (TNF) receptors, (sTNF-R)-55 and sTNF-R75, and soluble intercellular adhesion molecule (sICAM)-1 were measured in plasma before and 1 month after treatment. CRP was assessed by turbidemetry, whereas the other inflammatory parameters were measured by enzyme-linked immunosorbent assay (ELISA). A significant reduction in REE was found irrespective of therapeutic outcome, whereas body weight and body composition remained stable. The acute-phase proteins CRP and LBP were reduced significantly after treatment with chemotherapy, whereas both sTNF receptors and sICAM-1 remained enhanced. No correlation, however, existed between the decrease in REE and the decrease in the acute-phase proteins. In conclusion, chemotherapeutic treatment attenuates the tumour-related metabolic derangements and acute-phase response.

Adult↗