[Show abstract][Hide abstract] ABSTRACT: Objective: Increased tumor metabolism and hypoxia are related to poor prognosis in solid tumors, including non-small cell lung cancer (NSCLC). PET imaging is a non-invasive technique frequently used to visualize and quantify tumor metabolism and hypoxia. The aim of this study was to perform an extensive comparison of tumor metabolism using FDG PET and hypoxia using HX4 PET imaging. Materials/Methods: FDG- and HX4-PET/CT images of 25 NSCLC patients were co-registered. At a global tumor-level, HX4 and FDG parameters were extracted from the gross-tumor-volume. The HX4-high fraction and high volume were defined using a tumor-to-blood ratio>1.4. This study used a SUV>50% of SUVmax for FDG-high fraction and high volume. We evaluated the spatial correlation between HX4 and FDG uptake within the tumor, to quantify the (mis)match between the volumes with high FDG and HX4 uptake. Results: At a tumor-level, significant correlations were observed between FDG and HX4 parameters. For the primary GTV, the HX4-high fraction was three times smaller compared to the FDG-high fraction. In 53% of the primary lesions, less than 1cm3 of the HX4-high-volume was outside the FDG-high volume; for 37% this volume was 1.9-12cm3. Remarkably, a distinct uptake pattern was observed in 11%, with large hypoxic volumes localized outside the FDG-high volume. Conclusion: Hypoxic tumor volumes are smaller than metabolic active volumes. Approximately half of the lesions showed a good spatial correlation between the PET tracers. In the other cases, a (partial)mismatch was observed. The addition of HX4-PET imaging has the potential to individualize patient treatment.
Clinical cancer research : an official journal of the American Association for Cancer Research. 10/2014;
[Show abstract][Hide abstract] ABSTRACT: The importance of a safety culture to maximize safety is no longer questioned. However, achieving sustainable culture improvements are less evident. Evidence is growing for a multifaceted approach, where multiple safety interventions are combined. Lean management is such an integral approach to improve safety, quality and efficiency and therefore, could be expected to improve the safety culture. This paper presents the effects of lean management activities on the patient safety culture in a radiotherapy institute.
European journal of oncology nursing: the official journal of European Oncology Nursing Society 09/2014; · 1.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this review is to investigate the effect of timing of the reconstruction and radiotherapy, with respect to complication rate and cosmetic outcome, with a special focus on the timing of the placement of the definite implant.
European journal of cancer (Oxford, England: 1990) 08/2014; · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To realize safe radiotherapy treatment, processes must be stabilized. Standard operating procedures (SOP's) were expected to stabilize the treatment process and perceived task importance would increase sustainability in compliance. This paper presents the effects on compliance to safety related tasks of a process redesign based on lean principles.
European journal of oncology nursing: the official journal of European Oncology Nursing Society 06/2014; · 1.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this open-label phase I study, the maximum-tolerated dose of cetuximab with concurrent chemoradiotherapy (C-CRT) in stage III non-small-cell lung cancer together with individualized, isotoxic accelerated radiotherapy (RT) was investigated.
Patients with stage III non-small-cell lung cancer, World Health Organization performance status 0-1, forced expiratory volume in 1 second more than 50%, carbon monoxide diffusing capacity more than 50%, weight loss less than 10%, and no severe comorbidity were enrolled. Patients without progression after one to two cycles of gemcitabine-carboplatin were included and treated with cetuximab 400 mg/kg d7 and 250 mg/kg weekly together with RT and cisplatin (50 mg/m d1, 8; 40 mg/m d22)-vinorelbine for 5 weeks. Vinorelbine was escalated in three steps; (1) 10 mg/m d1, 8 and 8 mg/m d22, 29; (2) 20 mg/m d1, 8 and 8 mg/m d22, 29; (3) 20 mg/m d1, 8; 15 mg/m d22, 29. An individualized prescribed RT dose based on normal tissue dose constraints was applied (e.g., mean lung dose 19 Gy). The primary endpoint was the maximum-tolerated dose 3 months after the end of C-CRT; secondary endpoints were toxicity and metabolic response as assessed by positron emission tomography.
Between September 2007 and October 2010, 25 patients (12 men, 13 women, mean age 59 years) were included. The mean RT dose was 62 ± 6.6 Gy. The vinorelbine dose could be escalated to dose level 3. Twelve of 25 patients experienced greater than or equal to grade 3 toxicity (esophagitis 3, rash 1, diarrhea 1, cough 1, dyspnea 1, vomiting 1, and pulmonary embolism 1). No dose-limiting toxicities were observed. One patient with a complete pathological response in dose level 3 developed a fatal hemoptysis 4 months after RT. Metabolic remissions were observed in 19 of 22 patients.
C-CRT with cetuximab and cisplatin-vinorelbine is safe to deliver at full dose. The recommended phase II dose is therefore cetuximab 400 mg/m d7 and 250 mg/m weekly, cisplatin 50 mg/m d1, 8; 40 mg/m d22 and vinorelbine 20 mg/m d1, 8; 15 mg/m d22, 29 for 5 weeks together with RT.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2014; 9(5):710-6. · 4.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
To date studies do not agree on the effects of irradiation on bone mineral density. The aim of this study was to investigate changes in mandibular bone mineral density after irradiation in various doses with and without surgery.
Materials and Methods
The investigators implemented a descriptive animal experiment. The sample was composed of sixteen female Göttingen minipigs, randomly assigned into four groups, and were irradiated with equivalent doses of 0, 25, 50 and 70 Gray to the mandibular region. Three months after irradiation, mandibular left premolars and molars were removed and dental implants were placed. CT-scans were made before and 6 months after irradiation. The measured bone density was related to a bone phantom to calculate the bone mineral density quotient (BMDQ). The outcome variable was BMDQ. Other study variables were irradiation dose, and operation. Descriptive and univariate analyses were computed and the p value was set at 0,05.
In the left hemimandible, compared to the control group a significant decrease in BMDQ was observed 0,01 (0Gy), -0,01 (25Gy), -0,06 (50Gy), and -0,11 (70Gy) (p=0,023). The right hemimandible compared to the control group, also showed significant decrease in BMDQ -0,02 (0Gy), -0,08 (25Gy), -0,09 (50Gy), and -0,11 (70Gy) (p=0,007).
This study presents a large animal model to simulate tissue reactions induced by various doses of irradiation in the mandible. We found a significant decrease in BMDQ after irradiation, but no significant correlation could be found between the irradiation dose and a decrease in BMDQ.
Journal of Oral and Maxillofacial Surgery 05/2014; · 1.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
Both bone and brain are frequent sites of metastasis in non-small cell lung cancer (NSCLC). Conflicting data exist whether EGFR mutant (+) patients are more prone to develop brain metastases or have a better outcome with brain metastases compared to EGFR/KRAS wild type (WT) or KRAS+ patients. For bone metastases this has not been studied.
In this retrospective case-control study all EGFR+ (exon 19 and 21) patients diagnosed at two pathology departments were selected (2004/2008 to 2012). For every EGFR+ patient a consecutive KRAS+ and WT patient with metastatic NSCLC (mNSCLC) was identified. Patients with another malignancy within 2 years of mNSCLC diagnosis were excluded. Data regarding age, gender, performance score, histology, treatment, bone/brain metastases diagnosis, skeletal related events (SRE) and subsequent survival were collected.
189 patients were included: 62 EGFR+, 65 KRAS+, 62 WT. 32%, 35% and 40% respectively had brain metastases (p = 0.645). Mean time to brain metastases was 20.8 [±12.0], 10.8 [±9.8], 16.4 [±10.2] months (EGFR + -KRAS+ p = 0.020, EGFR + -WT p = 0.321). Median post brain metastases survival was 12.1 [5.0-19.1], 7.6 [1.2-14.0], 10.7 [1.5-19.8] months (p = 0.674). 60%, 52% and 50% had metastatic bone disease (p = 0.528). Mean time to development of metastatic bone disease was 13.4 [±10.6], 23.3 [±19.4], 16.4 [±9.6] months (p = 0.201). Median post metastatic bone disease survival was 15.0 [10.6-20.3], 9.0 [5.2-12.9], 3.2 [0.0-6.9] months (p = 0.010). Time to 1st SRE was not significantly different.
Incidence of brain and bone metastases was not different between EGFR+, KRAS+ and WT patients. Post brain metastases survival, time from mNSCLC diagnosis to metastatic bone disease and 1st SRE did not differ either. Post metastatic bone disease survival was significantly longer in EGFR+ patients. Although prevention of SRE's is important for all patients, the latter finding calls for a separate study for SRE preventing agents in EGFR+ patients.
Lung cancer (Amsterdam, Netherlands) 04/2014; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Radiation-esophagitis and weight loss are frequently observed toxicities in patients treated with concurrent chemo-radiotherapy (CT-RT) for non-small cell lung cancer (NSCLC) and might be related. The purpose was to investigate whether weight loss already starts early after initiation of CT-RT and precedes radiation-esophagitis.
In a retrospective cohort, weight and esophagitis grade ≥2 were assessed during the first weeks of (CT-)RT in patients treated with concurrent (n = 102) or sequential (n = 92) therapy. In a prospective validation study, data on body weight, esophagitis grade ≥2, nutritional intake and muscle strength were obtained before, during and following CT-RT.
In the retrospective cohort, early weight loss was observed in concurrently treated patients (p = 0.002), independent of esophagitis ≥ grade 2. Early weight loss was also observed in the prospective cohort (p = 0.003) and was not accompanied by decreases in nutritional intake. In addition lower limb muscle strength rapidly declined (p = 0.042). In the later weeks of treatment, further body weight loss occurred (p < 0.001) despite increased nutritional supplementation and body weight was only partly recovered after 4 weeks post CT-RT (p = 0.003).
Weight loss during concurrent CT-RT for NSCLC starts early and prior to onset of esophagitis, requiring timely and intense nutritional rehabilitation.
Journal of cachexia, sarcopenia and muscle. 01/2014;
[Show abstract][Hide abstract] ABSTRACT: Purpose
To realize safe radiotherapy treatment, processes must be stabilized. Standard operating procedures (SOP's) were expected to stabilize the treatment process and perceived task importance would increase sustainability in compliance. This paper presents the effects on compliance to safety related tasks of a process redesign based on lean principles.
Compliance to patient safety tasks was measured by video recording of actual radiation treatment, before (T0), directly after (T1) and 1.5 years after (T2) a process redesign. Additionally, technologists were surveyed on perceived task importance and reported incidents were collected for three half-year periods between 2007 and 2009.
Compliance to four out of eleven tasks increased at T1, of which improvements on three sustained (T2). Perceived importance of tasks strongly correlated (0.82) to compliance rates at T2. The two tasks, perceived as least important, presented low base-line compliance, improved (T1), but relapsed at T2. The reported near misses (patient-level not reached) on accelerators increased (P < 0.001) from 144 (2007) to 535 (2009), while the reported misses (patient-level reached) remained constant.
Compliance to specific tasks increased after introducing SOP's and improvements sustained after 1.5 years, indicating increased stability. Perceived importance of tasks correlated positively to compliance and sustainability. Raising the perception of task importance is thus crucial to increase compliance. The redesign resulted in increased willingness to report incidents, creating opportunities for patient safety improvement in radiotherapy treatment.
[Show abstract][Hide abstract] ABSTRACT: This study tests whether using a screening instrument improves referral to psychosocial care providers (e.g. psychologist) and facilitates patient-radiotherapist communication.
A cluster randomized controlled trial was used. Fourteen radiotherapists were randomly allocated to the experimental or control group and 568 of their patients received care in accordance with the group to which their radiotherapist was allocated. Patients in the experimental group were asked to complete a screening instrument before and at the end of the radiation treatment period. All patients were requested to complete questionnaires concerning patient-physician communication after the first consultation and concerning psychosocial care 3 and 12 months post-intervention.
Patients who completed the screening instrument were referred to social workers at an earlier stage than patients who did not (P<0.01). No effects were observed for numbers of referred patients, or for improved patient-radiotherapist communication.
Our results suggest that a simple screening procedure can be valuable for the timely treatment of psychosocial problems in patients. Future efforts should be directed at appropriate timing of screening and enhancing physicians' awareness regarding the importance of identifying, discussing and treating psychosocial problems in cancer patients.
Psychosocial screening can be enhanced by effective radiotherapist-patient communication.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Long-term survival can be obtained with local treatment of lung metastases from colorectal cancer. However, it is unclear as to what the optimal local therapy is: surgery, radiofrequency ablation (RFA) or stereotactic radiotherapy (SBRT). METHODS: A systematic review included 27 studies matching with the a priori selection criteria, the most important being ⩾50 patients and a follow-up period of ⩾24months. No SBRT studies were eligible. The review was therefore conducted on 4 RFA and 23 surgical series. RESULTS: Four of the surgical studies were prospective, all others were retrospective. No randomized trial was found. The reporting of data differed between the studies, which led to difficulties in the analyses. Treatment-related mortality rates for RFA and surgery were 0% and 1.4-2.4%, respectively, whereas morbidity rates were reported inconsistently but seemed the lowest for surgery. CONCLUSION: Due to the lack of phase III trials, no firm conclusions can be drawn, although most evidence supports surgery as the most effective treatment option. High-quality trials comparing currently used treatment modalities such as SBRT, RFA and surgery are needed to inform treatment decisions.
Cancer Treatment Reviews 06/2013; · 6.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aimed at validating the previously published association between TGF-β1 single nucleotide polymorphisms and a reduced risk for radiation-induced lung toxicity. We were not able to confirm the reported association, neither using maximum dyspnea score nor after correction for baseline dyspnea score.
Radiotherapy and Oncology 11/2012; · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND PURPOSE: For stereotactic body radiotherapy (SBRT), typically a scheme of 60Gy in 3-8 fractions is applied, producing local tumour control rates around 90%. The dose specification is in one point only and ignores possible underdosages at the edge of the planning target volume (PTV). We investigated the doses at the edge of the PTV and correlated this with local tumour control with the aim to shed light on the radiation dose needed to eradicate stage I NSCLC. MATERIALS AND METHODS: Published data on the freedom from local progression (FFLP) data from SBRT and accelerated high-dose conventional radiotherapy series for stage I NSCLC with a follow up of at least 30months were included. The EQD(2,T) was calculated from the dose at the periphery of the PTV. RESULTS: Fifteen studies for SBRT (1076 patients) showed a median FFLP of 88.0±10.4% with a median EQD(2,T) of 76.9±17.4Gy. The median FFLP was 87.6±6.0% for the accelerated schedules with an EQD(2,T) of 86.9±39.1Gy, respectively. No significant relation was found between FFLP and the EQD(2,T) (p=0.23). CONCLUSIONS: Several fractionated and accelerated schedules with equal biological doses achieve the same tumour control rates as SBRT. Lower, but more uniform doses to the whole PTV may be sufficient to achieve similar control rates, with the possibility to deliver SBRT in adapted schedules, beneficial to centrally located tumours in the vicinity of critical structures like the oesophagus and great vessels.
Radiotherapy and Oncology 10/2012; · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:: Stage IV non-small-cell lung cancer (NSCLC) patients with oligometastases (< 5 metastatic lesions) may experience long-term survival when all macroscopic tumor sites are treated radically, but no prospective data on NSCLCs with synchronous oligometastases are available. METHODS:: A prospective single-arm phase II trial was conducted. The main inclusion criteria were pathologically proven NSCLC stage IV with less than five metastases at primary diagnosis, amendable for radical local treatment (surgery or radiotherapy). The study is listed in clinicaltrials.gov, number NCT01282450. RESULTS:: Forty patients were enrolled, 39 of whom were evaluable (18 men, 21 women); mean age was 62.1 ± 9.2 years (range, 44-81). Twenty-nine (74%) had local stage III; 17 (44%) brain, seven (18%) bone, and four (10%) adrenal gland metastases. Thirty-five (87%) had a single metastatic lesion. Thirty-seven (95%) of the patients received chemotherapy as part of their primary treatment. Median overall survival (OS) was 13.5 months (95% confidence interval 7.6-19.4); 1-, 2-, and 3-year OS was 56.4%, 23.3%, and 17.5%, respectively. Median progression-free survival (PFS) was 12.1 months (95% confidence interval 9.6-14.3); 1-year PFS was 51.3%, and both 2- and 3-year PFS was 13.6%. Only two patients (5%) had a local recurrence. No patient or tumor parameter, including volume and F-deoxyglucose uptake was significantly correlated with OS or PFS. The treatment was well tolerated. CONCLUSION:: In this phase II study, long-term PFS was found in a subgroup of NSCLC patients with synchronous oligometastases when treated radically. Identification of this favorable subgroup before therapy is needed.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2012; 7(10):1547-1555. · 4.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The goal was to provide a quantitative evaluation of the accuracy of three different fixation systems for stereotactic radiotherapy and to evaluate patients' acceptance for all fixations.
A total of 16 consecutive patients with brain tumours undergoing fractionated stereotactic radiotherapy (SCRT) were enrolled after informed consent (Clinical trials.gov: NCT00181350). Fixation systems evaluated were the BrainLAB® mask, with and without custom made bite-block (fixations S and A) and a homemade neck support with bite-block (fixation B) based on the BrainLAB® frame. The sequence of measurements was evaluated in a randomized manner with a cross-over design and patients' acceptance by a questionnaire.
The mean three-dimensional (3D) displacement and standard deviations were 1.16 ± 0.68 mm for fixation S, 1.92 ± 1.28 and 1.70 ± 0.83 mm for fixations A and B, respectively. There was a significant improvement of the overall alignment (3D vector) when using the standard fixation instead of fixation A or B in the craniocaudal direction (p = 0.037). Rotational deviations were significantly less for the standard fixation S in relation to fixations A (p = 0.005) and B (p = 0.03). EPI imaging with off-line correction further improved reproducibility. Five out of 8 patients preferred the neck support with the bite-block.
The mask fixation system in conjunction with a bite-block is the most accurate fixation for SCRT reducing craniocaudal and rotational movements. Patients favoured the more comfortable but less accurate neck support. To optimize the accuracy of SCRT, additional regular portal imaging is warranted.
Strahlentherapie und Onkologie 12/2011; 188(1):84-90. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Psychosocial problems in cancer patients are often unrecognized and untreated due to the low awareness of the existence of these problems or pressures of time. The awareness of the need to identify psychosocial problems in cancer patients is growing and has affected the development of screening instruments. This study explored the usefulness and feasibility of using a screening instrument (SIPP: Screening Inventory of Psychosocial Problems) to identify psychosocial problems in cancer patients receiving curative radiotherapy treatment (RT).
The study was conducted in a radiation oncology department in The Netherlands. Several methods were used to document the usefulness and feasibility of the SIPP. Data were collected using self-report questionnaires completed by seven radiotherapists and 268 cancer patients.
Regarding the screening procedure 33 patients were offered to consult a psychosocial care provider (e.g. social worker, psychologist) during the first consultation with their radiotherapist. Of these patients, 31 patients suffered from at least sub-clinical symptoms and two patients hardly suffered from any symptoms. Patients' acceptance rate 63.6% (21/33) was high. Patients were positive about the content of the SIPP (mean scores vary from 8.00 to 8.88, out of a range between 0 and 10) and about the importance of discussing items of the SIPP with their radiotherapist (mean score = 7.42). Radiotherapists' perspectives about the contribution of the SIPP to discuss the different psychosocial problems were mixed (mean scores varied from 3.17 to 4.67). Patients were more positive about discussing items of the SIPP if the radiotherapists had positive attitudes towards screening and discussing psychosocial problems.
The screening procedure appeared to be feasible in a radiotherapy department. In general, patients' perspectives were at least moderate. Radiotherapists considered the usefulness and feasibility of the SIPP generally to be lower, but their evaluations were mixed. A positive attitude to using screening instruments like the SIPP needs to be encouraged among radiotherapists, as this may not only improve the usefulness of a screening instrument, but also patients' satisfaction with care.
[Show abstract][Hide abstract] ABSTRACT: A pre-operative CT scan with contrast enhancement (CE) has recently been proposed to improve tumorbed delineation in breast conserving therapy. However, it is not clear whether CE is required for visualization of a known breast tumor. The main aims of this study were to compare the sensitivity of a CE-CT scan with a native CT scan (i.e. without CE) and to identify characteristics predictive for the requirement of CE.
Both a CE-CT and a native CT were made in 58 breast cancer patients (age 37-75 yr), prior to breast conserving surgery. Visibility of the tumor on CT was scored by three observers (clearly visible/doubtful/not visible). Age, tumor size, palpable tumor yes/no, histology, and visibility on mammography were analyzed with respect to the visibility of the tumor on the native CT.
The sensitivity for tumor detection was better for CE-CT (95%) than for native CT (83%) (p<0.001). Only mammographic visibility scores appeared to be significantly correlated with the visibility of the tumor on the native CT (p=0.013).
In most patients CE is not required to visualize a known breast tumor. Mammographic visibility is a good parameter to decide on the use of CE.
Radiotherapy and Oncology 07/2011; 100(2):271-5. · 4.52 Impact Factor