Cost-Effectiveness of Reduced Waiting Time for Head and Neck Cancer Patients due to a Lean Process Redesign.

BACKGROUND: Compared with new technologies, the redesign of care processes is generally considered less attractive to improve patient outcomes. Nevertheless, it might result in better patient outcomes, without further increasing costs. Because early initiation of treatment is of vital importance for patients with head and neck cancer (HNC), these care processes were redesigned. OBJECTIVES: This study aimed to assess patient outcomes and cost-effectiveness of this redesign. METHODS: An economic (Markov) model was constructed to evaluate the biopsy process of suspicious lesion under local instead of general anesthesia, and combining computed tomography and positron emission tomography for diagnostics and radiotherapy planning. Patients treated for HNC were included in the model stratified by disease location (larynx, oropharynx, hypopharynx, and oral cavity) and stage (I-II and III-IV). Probabilistic sensitivity analyses were performed. RESULTS: Waiting time before treatment start reduced from 5 to 22 days for the included patient groups, resulting in 0.13 to 0.66 additional quality-adjusted life-years. The new workflow was cost-effective for all the included patient groups, using a ceiling ratio of €80,000 or €20,000. For patients treated for tumors located at the larynx and oral cavity, the new workflow resulted in additional quality-adjusted life-years, and costs decreased compared with the regular workflow. The health care payer benefited €14.1 million and €91.5 million, respectively, when individual net monetary benefits were extrapolated to an organizational level and a national level. CONCLUSIONS: The redesigned care process reduced the waiting time for the treatment of patients with HNC and proved cost-effective. Because care improved, implementation on a wider scale should be considered.

Workshops as a useful tool to better understand care professionals' views of a lean change program.

PURPOSE: For change programs to succeed, it is vital to have a detailed understanding of employees' views regarding the program, especially when the proposed changes are potentially contested. Gaining insight into employee perceptions helps managers to decide how to proceed. The authors conducted two workshops in a radiotherapy institute to assess the benefits and drawbacks, as well as their underlying causes, of a proposed Lean change program. Managers' views on the workshops' usefulness were charted. The paper aims to discuss these issues. DESIGN/METHODOLOGY/APPROACH: Two workshops were organized in which employees predicted positive and negative effects of a Lean program. The workshops combined a structured brainstorm (KJ-technique) and an evaluation of the expected effects. Eight top managers judged the workshops' value on supporting decision making. FINDINGS: In total, 15 employees participated in the workshops. Participants from workshop 2 reported more expected effects (27 effects; 18 positive) than from workshop 1 (14 effects; six positive). However, when effects were categorized, similar results were shown. Three from eight managers scored the results relevant for decision making and four neutral. Seven managers recommended future use of the instrument. Increased employee involvement and bottom-up thinking combined with relatively low costs were appreciated most. PRACTICAL IMPLICATIONS: The workshop could serve as a simple instrument to improve decision making and enhance successful implementation of change programs, as it was expected to enhance employees' involvement and was relatively easy to conduct and cheap. ORIGINALITY/VALUE: The workshop increased insight into employee views, facilitating adaptive actions by healthcare organization managers.

Position statement on ethics, equipoise and research on charged particle radiation therapy.

The use of charged-particle radiation therapy (CPRT) is an increasingly important development in the treatment of cancer. One of the most pressing controversies about the use of this technology is whether randomised controlled trials are required before this form of treatment can be considered to be the treatment of choice for a wide range of indications. Equipoise is the key ethical concept in determining which research studies are justified. However, there is a good deal of disagreement about how this concept is best understood and applied in the specific case of CPRT. This report is a position statement on these controversies that arises out of a workshop held at Wolfson College, Oxford in August 2011. The workshop brought together international leaders in the relevant fields (radiation oncology, medical physics, radiobiology, research ethics and methodology), including proponents on both sides of the debate, in order to make significant progress on the ethical issues associated with CPRT research. This position statement provides an ethical platform for future research and should enable further work to be done in developing international coordinated programmes of research.

The potential benefit of radiotherapy with protons in head and neck cancer with respect to normal tissue sparing: a systematic review of literature.

PURPOSE: Clinical studies concerning head and neck cancer patients treated with protons reporting on radiation-induced side effects are scarce. Therefore, we reviewed the literature regarding the potential benefits of protons compared with the currently used photons in terms of lower doses to normal tissue and the potential for fewer subsequent radiation-induced side effects, with the main focus on in silico planning comparative (ISPC) studies. MATERIALS AND METHODS: A literature search was performed by two independent researchers on ISPC studies that included proton-based and photon-based irradiation techniques. RESULTS: Initially, 877 papers were retrieved and 14 relevant and eligible ISPC studies were identified and included in this review. Four studies included paranasal sinus cancer cases, three included nasopharyngeal cancer cases, and seven included oropharyngeal, hypopharyngeal, and/or laryngeal cancer cases. Seven studies compared the most sophisticated photon and proton techniques: intensity-modulated photon therapy versus intensity-modulated proton therapy (IMPT). Four studies compared different proton techniques. All studies showed that protons had a lower normal tissue dose, while keeping similar or better target coverage. Two studies found that these lower doses theoretically translated into a significantly lower incidence of salivary dysfunction. CONCLUSION: The results of ISPC studies indicate that protons have the potential for a significantly lower normal tissue dose, while keeping similar or better target coverage. Scanned IMPT probably offers the most advantage and will allow for a substantially lower probability of radiation-induced side effects. The results of these ISPC studies should be confirmed in properly designed clinical trials.

When to wait for more evidence? Real options analysis in proton therapy.

PURPOSE: Trends suggest that cancer spending growth will accelerate. One method for controlling costs is to examine whether the benefits of new technologies are worth the extra costs. However, especially new and emerging technologies are often more costly, while limited clinical evidence of superiority is available. In that situation it is often unclear whether to adopt the new technology now, with the risk of investing in a suboptimal therapy, or to wait for more evidence, with the risk of withholding patients their optimal treatment. This trade-off is especially difficult when it is costly to reverse the decision to adopt a technology, as is the case for proton therapy. Real options analysis, a technique originating from financial economics, assists in making this trade-off. METHODS: We examined whether to adopt proton therapy, as compared to stereotactic body radiotherapy, in the treatment of inoperable stage I non-small cell lung cancer. Three options are available: adopt without further research; adopt and undertake a trial; or delay adoption and undertake a trial. The decision depends on the expected net gain of each option, calculated by subtracting its total costs from its expected benefits. RESULTS: In The Netherlands, adopt and trial was found to be the preferred option, with an optimal sample size of 200 patients. Increase of treatment costs abroad and costs of reversal altered the preferred option. CONCLUSION: We have shown that real options analysis provides a transparent method of weighing the costs and benefits of adopting and/or further researching new and expensive technologies.

Do we have enough evidence to implement particle therapy as standard treatment in lung cancer? A systematic literature review.

BACKGROUND: The societal burden of lung cancer is high because of its high incidence and high lethality. From a theoretical point of view, radiotherapy with beams of protons and heavier charged particles, for example, carbon ions (C-ions), should lead to superior results, compared with photon beams. In this review, we searched for clinical evidence to justify implementation of particle therapy as standard treatment in lung cancer. METHODS: A systematic literature review based on an earlier published comprehensive review was performed and updated through November 2009. RESULTS: Eleven fully published studies, all dealing with non-small cell lung cancer (NSCLC), mainly stage I, were identified. No phase III trials were found. For proton therapy, 2- to 5-year local tumor control rates varied in the range of 57%-87%. The 2- and 5-year overall survival (OS) and 2- and 5-year cause-specific survival (CSS) rates were 31%-74% and 23% and 58%-86% and 46%, respectively. Radiation-induced pneumonitis was observed in about 10% of patients. For C-ion therapy, the overall local tumor control rate was 77%, but it was 95% when using a hypofractionated radiation schedule. The 5-year OS and CSS rates were 42% and 60%, respectively. Slightly better results were reported when using hypofractionation, 50% and 76%, respectively. CONCLUSION: The present results with protons and heavier charged particles are promising. However, the current lack of evidence on the clinical (cost-)effectiveness of particle therapy emphasizes the need to investigate the efficiency of particle therapy in an adequate manner. Until these results are available for lung cancer, charged particle therapy should be considered experimental.

Health-related quality of life in patients surviving non-small cell lung cancer.

BACKGROUND AND AIMS: The EuroQol 5D (EQ-5D) is a standardised instrument for measuring health-related quality of life (HRQoL). It provides a utility score for health, and a self-rating of HRQoL (EQ-VAS). In this study, the EQ-5D was used to assess HRQoL in survivors of non-small cell lung cancer (NSCLC). The influence of tumour stage, adverse events, initial treatment and presence of recurrence was examined. METHODS: Patients treated for NSCLC were sent a questionnaire, consisting of the EQ-5D, EQ-VAS and questions regarding adverse events. Tumour stage, date and type of initial treatment, and presence of recurrence were derived from patient files once patients had completed the questionnaire and informed consent form. Influencing factors were examined by exploring subgroups and using multiple regression analysis. RESULTS: Of the 374 patients contacted, 260 (70%) returned a completed questionnaire. The EQ-VAS generated an average self-rated health of 69 (SD 18). The mean utility score was 0.74 (SD 0.27). Respondents with severe adverse events (dyspnoea grade ≥ 3) had statistically significantly lower utility scores than respondents without severe adverse events (median 0.52 vs 0.81; p <0.001). Subgroups based on a patient's initial treatment modality revealed statistically significantly different utility scores (p=0.010). CONCLUSION: The results of the present study provide original data on HRQoL during survival of NSCLC. Adverse events were found to have a considerable impact on HRQoL. This stresses the need to search for treatment modalities that not only improve survival, but also reduce adverse events.

Combined use of hyperthermia and radiation therapy for treating locally advanced cervical carcinoma.

BACKGROUND: Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells. It was introduced into clinical oncology practice several decades ago. Positive clinical results, mostly obtained in single institutions, resulted in clinical implementation albeit in a limited number of cancer centres worldwide. Because large scale randomised clinical trials (RCTs) are lacking, firm conclusions cannot be drawn regarding its definitive role as an adjunct to radiotherapy in the treatment of locally advanced cervical carcinoma (LACC). OBJECTIVES: To assess whether adding hyperthermia to standard radiotherapy for LACC has an impact on (1) local tumour control, (2) survival and (3) treatment related morbidity. SEARCH STRATEGY: The electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 1, 2009) and Cochrane Gynaecological Cancer Groups Specialised Register, MEDLINE, EMBASE, online databases for trial registration, handsearching of journals and conference abstracts, reviews, reference lists, and contacts with experts were used to identify potentially eligible trials, published and unpublished until January 2009. SELECTION CRITERIA: RCTs comparing radiotherapy alone (RT) versus combined hyperthermia and radiotherapy (RHT) in patients with LACC. DATA COLLECTION AND ANALYSIS: Between 1987 and 2009 the results of six RCTs were published, these were used for the current analysis. MAIN RESULTS: 74% of patients had FIGO stage IIIB LACC. Treatment outcome was significantly better for patients receiving the combined treatment (Figures 1 to 3). The pooled data analysis yielded a significantly higher complete response rate (relative risk (RR) 0.56; 95% confidence interval (CI) 0.39 to 0.79; p < 0.001), a significantly reduced local recurrence rate at 3 years (hazard ratio (HR) 0.48; 95% CI 0.37 to 0.63; p < 0.001) and a significanly better overall survival (OS) at three years following the combined treatment with RHT(HR 0.67; 95% CI 0.45 to 0.99; p = 0.05). No significant difference was observed in treatment related acute (RR 0.99; 95% CI 0.30 to 3.31; p = 0.99) or late grade 3 to 4 toxicity (RR 1.01; CI 95% 0.44 to 2.30; p = 0.96) between both treatments. AUTHORS' CONCLUSIONS: The limited number of patients available for analysis, methodological flaws and a significant over-representation of patients with FIGO stage IIIB prohibit drawing definite conclusions regarding the impact of adding hyperthermia to standard radiotherapy. However, available data do suggest that the addition of hyperthermia improves local tumour control and overall survival in patients with locally advanced cervical carcinoma without affecting treatment related grade 3 to 4 acute or late toxicity.

Combined use of hyperthermia and radiation therapy for treating locally advanced cervix carcinoma.

BACKGROUND: Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells. It was introduced into clinical oncology practice several decades ago. Positive clinical results, mostly obtained in single institutions, resulted in clinical implementation albeit in a limited number of cancer centres worldwide. Because large scale randomised clinical trials (RCTs) are lacking, firm conclusions cannot be drawn regarding its definitive role as an adjunct to radiotherapy in the treatment of locally advanced cervix carcinoma (LACC). OBJECTIVES: To assess whether adding hyperthermia to standard radiotherapy for LACC has an impact on (1) local tumour control, (2) survival and (3) treatment related morbidity. SEARCH STRATEGY: The electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 1, 2009) and Cochrane Gynaecological Cancer Groups Specialised Register, MEDLINE, EMBASE, online databases for trial registration, handsearching of journals and conference abstracts, reviews, reference lists, and contacts with experts were used to identify potentially eligible trials, published and unpublished until January 2009. SELECTION CRITERIA: RCTs comparing radiotherapy alone (RT) versus combined hyperthermia and radiotherapy (RHT) in patients with LACC. DATA COLLECTION AND ANALYSIS: Between 1987 and 2009 the results of six RCTs were published, these were used for the current analysis. MAIN RESULTS: 74% of patients had FIGO stage IIIB LACC. Treatment outcome was significantly better for patients receiving the combined treatment (Figures 4 to 6). The pooled data analysis yielded a significantly higher complete response rate (relative risk (RR) 0.56; 95% confidence interval (CI) 0.39 to 0.79; p < 0.001), a significantly reduced local recurrence rate (hazard ratio (HR) 0.48; 95% CI 0.37 to 0.63; p < 0.001) and a significantly better overall survival (OS) following the combined treatment with RHT(HR 0.67; 95% CI 0.45 to 0.99; p = 0.05). No significant difference was observed in treatment related acute (RR 0.99; 95% CI 0.30 to 3.31; p = 0.99) or late grade 3 to 4 toxicity (RR 1.01; CI 95% 0.44 to 2.30; p = 0.96) between both treatments. AUTHORS' CONCLUSIONS: The limited number of patients available for analysis, methodological flaws and a significant over-representation of patients with FIGO stage IIIB prohibit drawing definite conclusions regarding the impact of adding hyperthermia to standard radiotherapy. However, available data do suggest that the addition of hyperthermia improves local tumour control and overall survival in patients with locally advanced cervix carcinoma without affecting treatment related grade 3 to 4 acute or late toxicity.

Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head and neck cancer.

BACKGROUND: Tumour hypoxia increases tumour invasiveness and has a negative impact on response to therapy. Hypoxic tumours are also associated with severely anaemic individuals. It has therefore been hypothesised that correcting anaemia, by increasing haemoglobin levels using erythropoietin, improves tumour oxygenation and consequently the patient's prognosis. OBJECTIVES: To assess whether combined treatment with radiotherapy and erythropoietin (RT plus EPO) is better than standard radiotherapy (RT alone) for the treatment of head and neck cancer patients. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; mRCT and additional sources for published and unpublished trials. The date of the most recent search was 24 February 2009. SELECTION CRITERIA: Two independent authors assessed identified studies according to the eligibility criteria: RCTs which delivered radiotherapy combined with or without erythropoietin, in patients of any age with head and neck cancer of any stage or type. In addition, trials administering concomitant iron therapy among one or both arms were also eligible. DATA COLLECTION AND ANALYSIS: For statistical analysis of survival data, we computed a weighted estimate of the typical treatment effect across studies. We used Chi(2) heterogeneity tests to test for statistical heterogeneity among trials and performed the statistical analyses using Review Manager 5.0. MAIN RESULTS: Five RCTs with a total of 1397 patients were included. Pooled data yielded a significantly worse overall survival (OS) for RT plus EPO as compared to RT alone (Peto odds ratio 0.73; 95% confidence interval (CI) 0.58 to 0.91; P = 0.005, five trials). For local regional tumour control (LRTC) analyses resulted in a small but non-significant difference between the RT alone group and the RT plus EPO group (RR 0.92; 95% CI 0.81 to 1.03; P = 0.15, four trials). In addition, the local regional progression free survival (LRPFS) measured in four studies was significantly different between groups (Peto odds ratio 0.63; 95% CI 0.49 to 0.80; P = 0.0002, four trials), in favour of the RT alone group. Two studies used supplemental iron in the RT plus EPO group and not in the RT alone group. When excluding these studies from the analyses, the statistically (non-) significant differences in OS, LRTC and LRPFS are maintained. AUTHORS' CONCLUSIONS: There are strong suggestions that RT plus EPO has a negative influence on outcome as opposed to RT alone. However, the target haemoglobin concentration, which was higher than recommended in four of the five included RCTs, may have had a significant role. Nevertheless, based on these findings EPO should not be administered as an addition to RT outside the experimental setting for patients with head and neck cancer.

Concomitant hyperthermia and radiation therapy for treating locally advanced rectal cancer.

BACKGROUND: Surgery has been the treatment of choice for patients with rectal cancer. For locally advanced cancer results were poor, with high rates of locoregional recurrences and poor overall survival data. Adding (chemo)radiotherapy upfront improved results mainly in locoregional control. Adding hyperthermia to radiotherapy preoperatively might have an equivalent beneficial effect. OBJECTIVES: To quantify the potential beneficial effect of thermo radiation compared to chemo-radiation with respect to pathological complete responses, overall survival and toxicity in rectal cancer therapy. SEARCH STRATEGY: We identified the relevant phase II and III randomised controlled trials in any language trough electronic searches May 2007 of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2007), the Cochrane Colorectal Cancer Groups Specialised Register, MEDLINE (from 1966), EMBASE (from 1974), CINAHL (from 1982). Furthermore, various trial databases were searched for the identification of recent completed and ongoing trials (metaRegister of Controlled Trials, Cancer Research UK, Cancer.gov, The Eastern Cooperative Oncology Group Trials Database). All studies identified until May 2007 were considered for inclusion in the present study. SELECTION CRITERIA: Only phase II and III randomised controlled clinical trials were included in the analysis. DATA COLLECTION AND ANALYSIS: All identified studies were assessed by two independent reviewers. A weighted estimate of the treatment effect was computed for 2, 3, 4 and 5-year survival, for local tumour recurrence, severe acute and late toxicity and complete tumour response (CR). CR was defined either clinically by disappearance of all pretreatment signs of local tumour or pathologically by microscopically free margins. The risk ratio (RR) and hazard ratio (HR) were used. Analyses were performed with the Reference Manager (RevMan). MAIN RESULTS: Six RCTs published between 1990 and 2007 were identified. A total number of 520 patients was treated, 258 in the radiotherapy only arm (RT) and 262 in the radiotherapy-hyperthermia arm (RHT). Four studies (424 patients) reported overall survival (OS) rates. After 2 years, OS was significantly better in the RHT group (HR 2.06; 95% CI 1.33-3.17; p=.001), but this difference disappeared after a longer period (3, 4 and 5 year OS). All but one studies reported CR rates. A significant higher CR rate was observed in the RHT group (RR 2.81; 95% CI 1.22-6.45; p=.01). Only 2 studies reported on acute toxicity. In these 2 studies no significant differences were observed between the RT and the RHT group. Late toxicity data were not reported. AUTHORS' CONCLUSIONS: Further studies are needed to compare chemoradiation versus thermoradiation versus chemoradiation plus hyperthermia in well selected/conducted and quality controlled randomised trials.

Particle therapy in lung cancer: where do we stand?

BACKGROUND: From a theoretical point of view, charged particles should lead to superior results compared to photons. In this review, we searched for clinical evidence that protons or C-ions are really beneficial to patients with lung cancer. METHODS: A systematic literature review based on an earlier published comprehensive review was performed and updated until November 1st 2007. RESULTS: Ten fully published series, all dealing with non-small cell lung cancer (NSCLC), mainly stage I, were identified. No phase III trials were found. On proton therapy, 2-5 year local tumor control rates varied between 87% and 57%. The 2 year/5 year overall survival and 2 year/5 year cause specific survival varied between 31-74%/23% and 58-86%/46%, respectively. Late side effects were observed in about 10% of the patients. For C-ion therapy, the local tumor control rate was 77%, while 95% when using a hypofractionated radiation schedule. The 5 year overall survival and cause specific survival rates were 42% and 60%, respectively. Slightly better results were reported when using hypofractionation, 50% and 76%, respectively. The reported late side effects for C-ions were 4%. CONCLUSION: The results with charged particles, at least for stage I disease, seem to be promising. A gain can be expected in reduction of late side effects, especially after treatment with C-ions. Available data demonstrate that particle therapy in general is a safe and feasible treatment modality. Although current results are promising, more evidence is required before particle therapy can become internationally the standard treatment for (subsets of) lung cancer patients.

Determinants of overall quality of life in preterminal cancer patients.

Recently, a few studies reported that fatigue was a predominant contributor to patient-perceived overall QoL in patients with different types of cancer in a relatively early stage of disease. In the present study, we aimed to investigate whether fatigue is also a major contributor to overall QoL in preterminal cancer patients. Ninety-eight preterminal cancer patients, mainly lung (44%) and gastrointestinal cancer (25%), with an estimated life expectancy of 1-6 months were included. QoL domains as well as overall QoL were measured using the EORTC QLQ-C30 questionnaire. Data were analysed by Pearson's correlations and multivariate modelling. Fatigue showed the strongest correlation with overall QoL (r = -0.63, p < 0.001), followed in decreasing order by role functioning (r = 0.53), physical functioning (r = 0.47), social functioning (r = 0.44), nausea (r = -0.37), cognitive functioning (r = 0.33), appetite loss (r = -0.31), dyspnea (r = -0.26) and emotional functioning (r = 0.24). Multivariate analysis confirmed that the fatigue scale paid by far the highest individual contribution to overall QoL (standardized regression coefficient (SRC): -0.41, p = 0.002), followed by social functioning (SRC: 0.18, p = 0.05). None of the other domains or symptom scales contributed independently to overall QoL. Our results clearly demonstrate that, in preterminal cancer patients, fatigue is a major contributor of overall QoL, corroborating reports in cancer patients in earlier disease stages.

Cost-effectiveness of particle therapy: current evidence and future needs.

PURPOSE: Questions are being raised regarding the cost of particle therapy (PT), and with them criticism that PT is too expensive to allow the expected gain in effectiveness. This paper aims to get more insight in the cost and cost-effectiveness of particle therapy and to discuss a future strategy that allows for critical assessment of this health technology. MATERIAL AND METHODS: A systematic literature review based on an earlier published comprehensive review was performed and updated until June 1st 2008. Besides, current business plans of PT projects were examined. Additionally, results retrieved from a cost-simulation tool developed under auspice of the ENLIGHT were discussed. RESULTS: The current literature on cost-effectiveness of PT is scarce, non-comparable, and largely not performed according to standard health technology assessment criteria. Besides, different perspectives for cost evaluations have been used, making it difficult to compare and to determine the relative impact in terms of costs for this new treatment modality. CONCLUSIONS: Evidence on the cost-effectiveness of PT is scarce. Adequate reimbursement is necessary to support such innovative yet costly treatments. For now, model-based economic evaluations performed at least from a health care perspective may help us to gain evidence-based insight into cost-effectiveness.

A Factorial Survey on Safety Behavior Providing Opportunities to Improve Safety.

OBJECTIVES: To realize safe, high-quality treatment, employees should behave according to patient safety standards. Periodic measurement of safety behavior could provide management-relevant information to adjust the implementation of interventions and maximize improvement. Therefore, we constructed a factorial survey measuring safety awareness and intentions for behavior. METHODS: Cross-sectional results of the factorial survey were compared with results from the Hospital Survey on Patient Safety Culture, distributed in MAASTRO radiotherapy in 2010 to 2011. Respondents were presented 20 scenarios about incidents, randomly varying on work pressure, person causing incident, whether patient level was reached, severity of harm, notification by patient, and management support. After each scenario, questions were asked about safety awareness and behavior. χ and multilevel regression analyses were used. RESULTS: Response rates were 64% (n = 54) for the culture survey and 62% (n = 52) for the factorial survey on intentions. The culture survey reflected positive opinions regarding nonpunitive response and incident reporting, in accordance with high scores (factorial survey) on safety awareness (9.0; scale, 1-10) and reporting intentions (8.7). Whether an incident reached the patient level predicted safety awareness and intentions for safety behavior (ß = -1.3/-3.08) most strongly. Severity of harm showed minimal additional effects (ß = -0.24/-0.42). CONCLUSIONS: The factorial survey presented practical information on safety awareness and intentions for behavior. Therefore, it created additional opportunities for improving safety interventions. Because behavior is expected to change before values, one could hypothesize that factorial surveys would be more sensitive to change than culture surveys. Longitudinal research should further study the surveys' sensitivity to measure changes.

Timing of chest radiotherapy in patients with limited stage small cell lung cancer: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: We undertook a systematic review and literature-based meta-analysis to determine whether the timing of chest radiotherapy may influence the survival of patients with limited stage small cell lung cancer (LS-SCLC). OBJECTIVES: To establish the most effective way of combining chest radiotherapy with chemotherapy for patients with limited-stage small cell lung cancer in order to improve long-term survival. MATERIALS: Eligible studies were identified according to the Cochrane Collaboration Guidelines and were randomised controlled clinical trials comparing different timing of chest radiotherapy in patients with LS-SCLC. Early chest irradiation was defined as beginning within 30 days after the start of chemotherapy. RESULTS: Seven randomised trials were eligible. The overall survival at 2 years or at 5 years was not significantly different between early or late chest radiotherapy. When only trials were considered that used platinum chemotherapy concurrent with chest radiotherapy, significantly higher 2 and 5-year survival rates were observed when chest radiotherapy (RT) was started within 30 days after the start of chemotherapy (2-year survival: HR: 0.73, 95% CI 0.57-0.94, p=0.01; 5-year survival: HR: 0.65, 95% CI 0.45-0.93, p=0.02). This was even more pronounced when the overall treatment time of chest radiotherapy was less than 30 days. In studies that did not show a survival advantage by early chest radiation, a lower dose-intensity of chemotherapy in the early vs. late arm was observed. CONCLUSIONS: When platinum-based chemotherapy concurrently with chest RT is used, the 2- and 5-year survival rates of patients with LS-SCLC may be in favour of early chest radiotherapy, with a significant difference if the overall treatment time of chest radiation is less than 30 days.

A systematic literature review of the clinical and cost-effectiveness of hadron therapy in cancer.

BACKGROUND: In view of the continued increase in the number of hadron (i.e. neutron, proton and light or heavy ion) therapy (HT) centres we performed a systematic literature review to identify reports of the efficacy of HT. METHODS: Eleven databases were searched systematically. No limit was applied to language or study design. Established experts were contacted for unpublished data. Data on outcomes were extracted and summarised in tabular form. RESULTS: Seven hundred and seventy three papers were identified. For proton and heavy ion therapy, the number of RCTs was too small to draw firm conclusions. Based on prospective and retrospective studies, proton irradiation emerges as the treatment of choice for some ocular and skull base tumours. For prostate cancer, the results were comparable with those from the best photon therapy series. Heavy ion therapy is still in an experimental phase. CONCLUSION: Existing data do not suggest that the rapid expansion of HT as a major treatment modality would be appropriate. Further research into the clinical and cost-effectiveness of HT is needed. The formation of a European Hadron Therapy Register would offer a straightforward way of accelerating the rate at which we obtain high-quality evidence that could be used in assessing the role of HT in the management of cancer.

Radiation-induced bullous pemphigoid: a systematic review of an unusual radiation side effect.

BACKGROUND: Percutaneous radiotherapy (RT) may cause a range of acute and late side effects of the skin within the irradiated area. In rare cases radiotherapy can cause bullous pemphigoid (BP). BP is reported to occur mainly within irradiated fields following radiation treatment. Exceptionally, BP may arise during RT. It is unclear which mechanism exactly triggers BP following megavoltage irradiation and whether there is a potential association with hormonal anticancer treatment. METHODS: A systematic literature based review was performed. Publications reporting histologically confirmed BP and a treatment with RT were retrieved based on a standardized query using electronic databases. A standardized quality assessment was applied. RESULTS: Out of 306 potentially relevant publications 21 were identified to be relevant and included in this review. An association between RT and BP was reported in 27 patients. The majority developed BP after RT and a median dose of 50 Gy. Four patients developed BP during RT after a minimal dose of 20 Gy. CONCLUSIONS: BP induced by RT was observed predominantly in patients with breast cancer. In all reported cases, there is a clear relationship with RT. Therefore, BP may be considered as RT-induced side effect. RT can induce a BP following a minimal dose of 20 Gy. New biological agents may play a role in the future treatment of BP.

Psychometric properties of the revised Piper Fatigue Scale in Dutch cancer patients were satisfactory.

OBJECTIVE: To examine the psychometric properties of the revised Piper Fatigue Scale (PFS) in Dutch cancer patients. STUDY DESIGN AND SETTING: Participants were 64 patients with lung (any stage, nonsurgery) and breast (any stage) cancer, selected for curative high-dose radiotherapy (> or =50 Gy). Prior to radiotherapy, patients completed the revised PFS (translated into Dutch), the Multidimensional Fatigue Inventory (MFI), and the Rotterdam Symptom Checklist (RSCL). Reliability and construct and criterion validity of the PFS were investigated. RESULTS: Overall, the structure of the Dutch revised PFS appeared appropriate, with corrected item-subscale correlations being higher than the correlations of the same item with the three other subscales; furthermore, internal consistency was excellent (Cronbach's alpha > or =0.90). Lung cancer patients were significantly more tired then breast cancer patients, supporting construct validity. Criterion validity was also satisfactory, with highest correlations of PFS total fatigue with the MFI subscale general fatigue (0.84) and RSCL overall quality of life score (0.74). Internal consistency was similar in Dutch and U.S. breast cancer patients; fatigue scores were lower on several PFS subscales in the Dutch study population. CONCLUSION: Psychometric properties of the Dutch version of the revised PFS, as tested in cancer patients prior to radiotherapy, were satisfactory.

Safer radiation therapy treatment resulting from an equipment transition: A mixed-methods study.

PURPOSE: To realize individualized safe radiation therapy, reliable treatment equipment is essential in combination with a system-level improvement approach. We hypothesized that implementation of a system that integrated all required treatment equipment would result in improved safety and stability of the irradiation treatment process. METHODS AND MATERIALS: Seven accelerators, portal imaging, and the treatment planning software were replaced by an integrated system that included 6 accelerators. The number of reported safety incidents and root causes were recorded between 2010 and 2014. Time series analysis was performed, and quantitative results were explored by structured interviews. Additionally, downtime was recorded. RESULTS: From January 2010 to July 2014, 5085 incidents were reported. Reports related to the accelerators decreased from 33% (2010) to 20% (2013-2014) of total reports, whereas the number of delivered fractions per accelerator increased by 20% (2010: 643 per month; 2013: 795 per month). Reports related to portal imaging decreased from 16.5 reports per month (2010) to 3.1 (2013-2014). Of these portal imaging reports, 316 had at least 1 technical cause in 2010, which decreased to 13 in 2013-2014. Interviewees attributed the decreased reporting to the equipment transition, not to decreased safety awareness. Downtime decreased by 46%, from 5.4% in 2010 to 2.9% in 2013. CONCLUSIONS: The number of reported accelerator- and portal imaging-related incidents decreased significantly, whereas safety awareness remained stable. In addition, accelerator downtime decreased, possibly resulting in less rescheduling of patients and fewer disruptions of work processes. Therefore, we conclude that the risk for serious safety incidents and patient harm decreased after implementation of the new integrated system.