Do neurocognitive impairments explain the differences between brain tumor patients and their proxies when assessing the patient's IADL?

Background: Neurocognitive impairments are common among brain tumor patients, and may impact patients' awareness of performance in instrumental activities in daily life (IADL). We examined differences between patient- and proxy-reported assessments of the patient's IADL, and whether the level of (dis)agreement is associated with neurocognitive impairments. Methods: Brain tumor patients and their proxies completed the phase 3 version of the EORTC IADL-BN32 questionnaire measuring IADL, and patients completed six neurocognitive measures. Patient-proxy difference scores in IADL were compared between patients who were defined as neurocognitively impaired (≥2 neurocognitive measures ≥2.0 standard deviations below healthy controls) and non-neurocognitively impaired. With multinomial logistic regression analyses we examined if neurocognitive variables were independently associated with patient-proxy disagreement in IADL ratings. Results: Patients (n = 81) did not systematically (P < .01) rate IADL outcomes different than their proxies. Proxies did report more problems on 19/32 individual items and all five scales. This effect was more apparent in dyads with a neurocognitively impaired patient (n = 37), compared to dyads with non-neurocognitively impaired patients (n = 44). Multinomial logistic regression analyses showed that several neurocognitive variables (e.g., cognitive flexibility and verbal fluency) were independently associated with disagreement between patients and proxies on different scales. Conclusion: Neurocognitive deficits seem to play a role in the discrepancies between brain tumor patients and their proxies assessment of patient's level of IADL. Although replication of our results is needed, our findings suggests that caution is warranted in interpreting self-reported IADL by patients with neurocognitive impairment, and that such self-reports should be supplemented with proxy ratings.

Neoadjuvant chemoradiotherapy followed by resection for esophageal cancer: clinical outcomes with the 'CROSS-regimen' in daily practice.

BACKGROUND AND OBJECTIVES: Since the first results of the Dutch randomized CROSS-trial, neoadjuvant chemoradiotherapy (CRT) using carboplatin and paclitaxel followed by resection for primary resectable nonmetastatic esophageal cancer (EC) has been implemented as standard curative treatment in the Netherlands. The purpose of this retrospective study is to evaluate the clinical outcomes of this treatment in daily practice in a large academic hospital. METHODS: Medical records of patients treated for primary resectable nonmetastatic EC between May 2010 and December 2015 at our institution were reviewed. Treatment consisted of five weekly courses of carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) with concurrent external beam radiotherapy (23 fractions of 1.8 Gy), followed by transthoracic or transhiatal resection. Data on survival, progression, acute and late toxicity were recorded. RESULTS: A total of 145 patients were included. Median follow-up was 43 months. Median overall survival (OS) and progression-free survival (PFS) were 35 (95% confidence interval [CI] 29.8-40.2) and 30 (95% CI 19.7-40.3) months, respectively, with corresponding 3-year OS and PFS of 49.6% (95% CI 40.4-58.8) and 45.6% (95% CI 36.6-54.6). Acute toxicity grade ≥3 was observed in 25.5% of patients. Late adverse events grade ≥3 were seen in 24.8%, mostly esophageal stenosis. CONCLUSION: Neoadjuvant CRT followed by resection for primary resectable nonmetastatic EC in daily practice results in a 3-year OS of 49.6% (95% CI 40.4-58.8) and PFS of 45.6% (95% CI 36.6-54.6), compared with 58% (51-65%) and 51% (43-58%) within the CROSS-trial. The slightly poorer survival in our daily practice group might be due to the presence of less favorable patient and tumor characteristics in daily practice, as is to be expected in daily practice. Toxicity was comparable with that in the CROSS-trial and considered acceptable.

Patient-reported outcomes after external beam radiotherapy versus brachytherapy for palliation of dysphagia in esophageal cancer: A matched comparison of two prospective trials.

BACKGROUND AND PURPOSE: A matched comparison of external beam radiotherapy (EBRT) versus brachytherapy recently demonstrated that EBRT appears at least as effective for palliating dysphagia in patients with incurable esophageal cancer. The aim of this analysis was to compare patient-reported outcomes (PROs) after EBRT versus brachytherapy. MATERIALS AND METHODS: In a multicenter prospective cohort study, patients with incurable esophageal cancer requiring palliation of dysphagia were included to undergo EBRT (20 Gy in 5 fractions). This EBRT cohort was compared to the single-dose 12 Gy brachytherapy cohort of the previously reported SIREC-trial. Propensity score matching was applied to adjust for baseline imbalances. The primary endpoint of dysphagia improvement was reported previously. PROs were secondary outcomes and assessed at baseline and 3 months after treatment using EORTC QLQ-C30 and QLQ-OES18 questionnaires. RESULTS: A total of 115 enrolled EBRT patients and 93 brachytherapy patients were eligible. After matching, 69 well-balanced pairs remained. At follow-up, significant deteriorations in functioning (i.e. physical, role, social), pain, appetite loss, and trouble with taste were observed after brachytherapy. In the EBRT group, such deterioration was observed only for role functioning, while significant improvements in trouble with eating and pain were found. Between-group comparison showed mostly comparable PRO changes, but significantly favored EBRT with regard to nausea, vomiting, pain, and appetite loss. CONCLUSION: Short course EBRT results in similar or better PROs at 3 months after treatment compared to single-dose brachytherapy for the palliation of malignant dysphagia. These findings further support its use and inclusion in clinical practice guidelines.

Gross Tumor Delineation in Esophageal Cancer on MRI Compared With 18F-FDG-PET/CT.

PURPOSE: Current delineation of the gross tumor volume (GTV) in esophageal cancer relies on computed tomography (CT) and combination with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). There is increasing interest in integrating magnetic resonance imaging (MRI) in radiation treatment, which can potentially obviate CT- or FDG-PET/CT-based delineation. The aim of this study is to evaluate the feasibility of target delineation on T2-weighted (T2W) MRI and T2W including diffusion-weighted MRI (T2W + DW-MRI) compared with current-practice FDG-PET/CT. METHODS: Ten observers delineated primary esophageal tumor GTVs of 6 patients on FDG-PET/CT, T2W-MRI, and T2W + DW-MRI. GTVs, generalized conformity indices, in-slice delineation variation (root mean square), and standard deviations in the position of the most cranial and caudal delineated slice were calculated. RESULTS: Delineations on MRI showed smaller GTVs compared with FDG-PET/CT-based delineations. The main variation was seen at the cranial and caudal border. No differences were observed in conformity indices (FDG-PET/CT, 0.68; T2W-MRI, 0.66; T2W + DW-MRI, 0.68) and in-slice variation (root mean square, 0.13 cm on FDG-PET/CT; 0.10 cm on T2W-MRI; 0.14 cm on T2W + DW-MRI). In the 2 tumors involving the gastroesophageal junction, addition of DW-MRI to T2W-MRI significantly decreased caudal border variation. CONCLUSIONS: MRI-based target delineation of the esophageal tumor is feasible with interobserver variability comparable to that with FDG-PET/CT, despite limited experience with delineation on MRI. Most variation was seen at cranial-caudal borders, and addition of DW-MRI to T2W-MRI may reduce caudal delineation variation of gastroesophageal junction tumors.

Effectiveness of several external beam radiotherapy schedules for palliation of esophageal cancer.

BACKGROUND AND PURPOSE: Although external beam radiotherapy (EBRT) is frequently used for palliative treatment of patients with incurable esophageal cancer, the optimal schedule for symptom control is unknown. This retrospective study evaluated three EBRT schedules for symptom control and investigated possible prognostic factors associated with second intervention and overall survival (OS). MATERIAL AND METHODS: Patients with esophageal cancer treated with EBRT with palliative intent between January 2009 and December 2015 were evaluated. Univariate and multivariate Cox regression models estimated the effect of treatment schedule (20 Gy in 5 fractions, 30 Gy in 10 fractions or 39 Gy in 13 fractions) on OS. To study the effect of prognostic factors on time to second intervention (repeat EBRT, intraluminal brachytherapy or stent placement) a competing risk model with death as competing event was used. RESULTS: 205 patients received 20 Gy (31%), 30 Gy (38%) or 39 Gy (32%). Improvement of symptoms was observed in 72% with no differences between schedules. Median OS after 20 Gy, 30 Gy and 39 Gy was 4.6 months (95%CI 2.6-6.6), 5.2 months (95%CI 3.7-6.7) and 9.7 months (95%CI 6.9-12.5), respectively. Poor performance status (HR 2.25 (95%CI 1.53-3.29)), recurrent esophageal cancer (HR 1.69 (95%CI 1.15-2.47)) and distant metastasis (HR 1.73 (95%CI 1.27-2.35)) were significantly related to worse OS. Treatment with 30 Gy and 39 Gy was related to longer time to second intervention compared to 20 Gy (adjusted cause specific HR 0.50 (95%CI 0.25-0.99) and 0.27 (95%CI 0.13-0.56), respectively). CONCLUSIONS: Palliative EBRT provides good symptom control in patients with symptomatic esophageal cancer. A higher dose schedule was related to a longer time to second intervention. Hence, selection based on life expectancy is vital to prevent unnecessary long treatment schedules in patients with expected short survival, and limit the chance of second intervention when life expectancy is longer.

Functional and cognitive impairment, social functioning, frailty and adverse health outcomes in older patients with esophageal cancer, a systematic review.

BACKGROUND: Older patients with esophageal cancer are at high risk of adverse health outcomes, but the association of geriatric assessment with adverse health outcomes in these patients has not been systematically evaluated. The aim of this systematic review was to study the association of functional and cognitive impairment, social environment and frailty with adverse health outcomes in patients diagnosed with esophageal cancer. METHODS: We searched Pubmed, Embase, Web of Science and Cochrane Library for original studies reporting on associations of functional or cognitive impairment, social environment and frailty with adverse outcomes (mortality, functional or cognitive decline, adverse events during treatment, prolonged length of hospitalization (LOS) and health related quality of life (HRQoL)) after follow-up in patients with esophageal cancer. RESULTS: Of 1.391 identified citations, nineteen articles were included that reported on 53 associations. The median sample size of the included studies was 110 interquartile range (IQR 91-359). Geriatric conditions were prevalent: between 14 and 67% of the included participants were functionally impaired, around 42% had depressive symptoms and between 5 and 23% did not have a partner. In nineteen of 53 (36%) associations functional or cognitive impairment or frailty were significant associated with adverse health outcomes, but the studies were small. In four out of six (67%) associations with the largest sample size (n ≥ 359), functional impairment or social environment were significant associated with adverse health outcomes. CONCLUSION: Functional and cognitive impairment, depression and social isolation are prevalent in patients with esophageal cancer, and associate with adverse health outcomes. Geriatric measurements may guide decision-making and customize treatments, but more large studies are needed to explore the clinical usability.

Long-term health-related quality of life after pancreatic resection for malignancy in patients with and without severe postoperative complications.

BACKGROUND: Surgery for pancreatic cancer yields significant morbidity and mortality risks and survival is limited. Therefore, the influence of complications on quality of life (QoL) after pancreatic surgery is important. This study compares QoL in patients with and without severe complications after surgery for pancreatic (pre-)malignancy. METHODS: This prospective cohort study scored complications after pancreatic surgery according to the Clavien-Dindo system and the definitions of the International Study Group of Pancreatic Surgery. QoL was measured by the RAND36 questionnaire, the European Organization for Research and Treatment of Cancer core questionnaire (QLQ-C30) and the pancreas specific QLQ-PAN26. QoL in patients with severe complications was compared with QoL in patients with no or mild complications over a period of 12 months. Analysis was performed with linear mixed models for repeated measurements. RESULTS: Between March 2012 and July 2016, 137 patients were included. Sixty-eight patients (50%) had at least 1 severe complication. There were no statistically significant and clinically relevant differences between both groups in QoL up to 12 months after surgery. CONCLUSION: In this study, no differences in QoL between patients with and without severe postoperative complications were encountered during the first 12 months after surgery for pancreatic (pre-)malignancy. TRIAL REGISTRATION: http://www.clinicaltrials.gov Identifier: NCT02175992.

Clinical implementation of 3D printing in the construction of patient specific bolus for electron beam radiotherapy for non-melanoma skin cancer.

BACKGROUND AND PURPOSE: Creating an individualized tissue equivalent material build-up (i.e. bolus) for electron beam radiation therapy is complex and highly labour-intensive. We implemented a new clinical workflow in which 3D printing technology is used to create the bolus. MATERIAL AND METHODS: A patient-specific bolus is designed in the treatment planning system (TPS) and a shell around it is created in the TPS. The shell is printed and subsequently filled with silicone rubber to make the bolus. Before clinical implementation we performed a planning study with 11 patients to evaluate the difference in tumour coverage between the designed 3D-print bolus and the clinically delivered plan with manually created bolus. For the first 15 clinical patients a second CT scan with the 3D-print bolus was performed to verify the geometrical accuracy. RESULTS: The planning study showed that the V85% of the CTV was on average 97% (3D-print) vs 88% (conventional). Geometric comparison of the 3D-print bolus to the originally contoured bolus showed a high similarity (DSC=0.89). The dose distributions on the second CT scan with the 3D print bolus in position showed only small differences in comparison to the original planning CT scan. CONCLUSIONS: The implemented workflow is feasible, patient friendly, safe, and results in high quality dose distributions. This new technique increases time efficiency.

Dynamic contrast-enhanced MRI for treatment response assessment in patients with oesophageal cancer receiving neoadjuvant chemoradiotherapy.

PURPOSE: To explore and evaluate the potential value of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in oesophageal cancer. MATERIAL AND METHODS: Twenty-six patients underwent DCE-MRI before, during (week 2-3) and after nCRT, but before surgery (pre/per/post, respectively). Histopathologic tumour regression grade (TRG) was assessed after oesophagectomy. Tumour area-under-the-concentration time curve (AUC), time-to-peak (TTP) and slope were calculated. The ability of these DCE-parameters to distinguish good responders (GR, TRG 1-2) from poor responders (noGR, TRG⩾3), and pathologic complete responders (pCR) from no-pCR was assessed. RESULTS: Twelve patients (48%) showed GR of which 8 patients (32%) pCR. Analysis of AUC change throughout treatment, AUCper-pre, was most predictive for GR, at a threshold of 22.7% resulting in a sensitivity of 92%, specificity of 77%, PPV of 79%, and a NPV of 91%. AUCpost-pre was most predictive for pCR, at a threshold of -24.6% resulting in a sensitivity of 83%, specificity of 88%, PPV of 71%, and a NPV of 93%. TTP and slope were not associated with pathologic response. CONCLUSIONS: This study demonstrates that changes in AUC throughout treatment are promising for prediction of histopathologic response to nCRT for oesophageal cancer.

Diffusion-weighted magnetic resonance imaging for the prediction of pathologic response to neoadjuvant chemoradiotherapy in esophageal cancer.

PURPOSE: To explore the value of diffusion-weighted magnetic resonance imaging (DW-MRI) for the prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer. MATERIAL AND METHODS: In 20 patients receiving nCRT for esophageal cancer DW-MRI scanning was performed before nCRT, after 8-13 fractions, and before surgery. The median tumor apparent diffusion coefficient (ADC) was determined at these three time points. The predictive potential of initial tumor ADC, and change in ADC (ΔADC) during and after treatment for pathologic complete response (pathCR) and good response were assessed. Good response was defined as pathCR or near-pathCR (tumor regression grade [TRG] 1 or 2). RESULTS: A pathCR after nCRT was found in 4 of 20 patients (20%), and 8 patients (40%) showed a good response to nCRT. The ΔADCduring was significantly higher in pathCR vs. non-pathCR patients (34.6%±10.7% [mean±SD] vs. 14.0%±13.1%, p=0.016), as well as in good vs. poor responders (30.5%±8.3% vs. 9.5%±12.5%, p=0.002). The ΔADCduring was predictive of residual cancer at a threshold of 29% (sensitivity of 100%, specificity of 75%, PPV of 94%, and NPV of 100%), and for poor pathologic response at a threshold of 21% (sensitivity of 82%, specificity of 100%, PPV of 100%, and NPV of 80%). CONCLUSIONS: In this exploratory study, the treatment-induced change in ADC during the first 2-3weeks of nCRT for esophageal cancer seemed highly predictive of histopathologic response. Larger series are warranted to verify these results.

A systematic review: effectiveness of rectal emptying preparation in prostate cancer patients.

While the importance of a consistent rectal volume during radiation therapy planning and treatment for patients receiving radiation therapy to the prostate is recognized, there is no clear guidance as to the most effective method. This review examines the evidence for the efficacy of rectal preparations. Eighteen papers were found where the primary aim was to investigate a rectal emptying intervention and included 5 different strategies. These included evacuation techniques, dietary interventions, laxatives, and enemas and were either investigated alone or in combination. There is no robust evidence to recommend one rectal emptying strategy over another. Further investigation in adequately powered clinical trials is advised.

Effect of magnesium oxide on interfraction prostate motion and rectal filling in prostate cancer radiotherapy: analysis of a randomized clinical trial.

PURPOSE: To investigate whether magnesium oxide reduces the interfraction motion of the prostate and the amount of rectal filling and rectal gas, which influences prostate position during radiotherapy for prostate cancer. PATIENTS AND METHODS: From December 2008 to February 2010, 92 prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. In a previous study, we investigated the effect on intrafraction motion and did not find a difference between the treatment arms. Here, we compared the interfraction prostate motion between the two treatment arms as well as the amount of rectal filling and rectal air pockets using pretreatment planning computed tomography and magnetic resonance imagingscans. RESULTS: There was no statistically significant difference between the treatment arms in translation and rotation of the prostate between treatment fractions, except for the rotation around the cranial caudal axis. However, the difference was less than 1° and therefore considered not clinically relevant. There was no significant difference in the amount of rectal filling and rectal air pockets between the treatment arms. CONCLUSION: Magnesium oxide is not effective in reducing the interfraction prostate motion or the amount of rectal filling and rectal gas during external-beam radiotherapy. Therefore, magnesium oxide is not recommended in clinical practice for these purposes.

Quantification of esophageal tumor motion on cine-magnetic resonance imaging.

PURPOSE: To quantify the movement of esophageal tumors noninvasively on cine-magnetic resonance imaging (MRI) by use of a semiautomatic method to visualize tumor movement directly throughout multiple breathing cycles. METHODS AND MATERIALS: Thirty-six patients with esophageal tumors underwent MRI. Tumors were located in the upper (8), middle (7), and lower (21) esophagus. Cine-MR images were collected in the coronal and sagittal plane during 60 seconds at a rate of 2 Hz. An adaptive correlation filter was used to automatically track a previously marked reference point. Tumor movement was measured in the craniocaudal (CC), left-right (LR), and anteroposterior (AP) directions and its relationship along the longitudinal axis of the esophagus was investigated. RESULTS: Tumor registration within the individual images was typically done at a millisecond time scale. The mean (SD) peak-to-peak displacements in the CC, AP, and LR directions were 13.3 (5.2) mm, 4.9 (2.5) mm, and 2.7 (1.2) mm, respectively. The bandwidth to cover 95% of excursions from the mean position (c95) was also calculated to exclude outliers caused by sporadic movements. The mean (SD) c95 values were 10.1 (3.8) mm, 3.7 (1.9) mm, and 2.0 (0.9) mm in the CC, AP, and LR dimensions. The end-exhale phase provided a stable position in the respiratory cycle, compared with more variety in the end-inhale phase. Furthermore, lower tumors showed more movement than did higher tumors in the CC and AP directions. CONCLUSIONS: Intrafraction tumor movement was highly variable between patients. Tumor position proved the most stable during the respiratory cycle in the end-exhale phase. A better understanding of tumor motion makes it possible to individualize radiation delivery strategies accordingly. Cine-MRI is a successful noninvasive modality to analyze motion for this purpose in the future.

Innovative techniques in evaluating the esophagus; imaging of esophageal morphology and function; and drugs for esophageal disease.

This paper reporting on techniques for esophageal evaluation and imaging and drugs for esophageal disease includes commentaries on endoscopy techniques including dye-based high-resolution and dye-less high-definition endoscopy; the shift from CT to MRI guidance in tumor delineation for radiation therapy; the role of functional lumen imaging in measuring esophageal distensibility; electrical stimulation of the lower esophageal sphincter (LES) as an alternative to fundoduplication for treatment of gastroesophageal reflux disease (GERD); the morphological findings of reflux esophagitis and esophageal dysmotility on double-contrast esophagography; the value of videofluoroscopy in assessing protecting mechanisms in patients with chronic reflux or swallowing disorders; targeting visceral hypersensitivity in the treatment of refractory GERD; and the symptoms and treatments of nighttime reflux and nocturnal acid breakthrough (NAB).

Imaging strategies in the management of oesophageal cancer: what's the role of MRI?

OBJECTIVES: To outline the current role and future potential of magnetic resonance imaging (MRI) in the management of oesophageal cancer regarding T-staging, N-staging, tumour delineation for radiotherapy (RT) and treatment response assessment. METHODS: PubMed, Embase and the Cochrane library were searched identifying all articles related to the use of MRI in oesophageal cancer. Data regarding the value of MRI in the areas of interest were extracted in order to calculate sensitivity, specificity, predictive values and accuracy for group-related outcome measures. RESULTS: Although historically poor, recent improvements in MRI protocols and techniques have resulted in better imaging quality and the valuable addition of functional information. In recent studies, similar or even better results have been achieved using optimised MRI compared with other imaging strategies for T- and N-staging. No studies clearly report on the role of MRI in oesophageal tumour delineation and real-time guidance for RT so far. Recent pilot studies showed that functional MRI might be capable of predicting pathological response to treatment and patient prognosis. CONCLUSIONS: In the near future MRI has the potential to bring improvement in staging, tumour delineation and real-time guidance for RT and assessment of treatment response, thereby complementing the limitations of currently used imaging strategies. KEY POINTS: • MRI's role in oesophageal cancer has been somewhat limited to date. • However MRI's ability to depict oesophageal cancer is continuously improving. • Optimising TN-staging, radiotherapy planning and response assessment ultimately improves individualised cancer care. • MRI potentially complements the limitations of other imaging strategies regarding these points.

A double-blind placebo-controlled randomized clinical trial with magnesium oxide to reduce intrafraction prostate motion for prostate cancer radiotherapy.

PURPOSE: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. METHODS AND MATERIALS: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in ≥ 50% of the fractions an intrafraction motion outside a range of 2 mm. Secondary outcome measures included quality of life and acute toxicity. RESULTS: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. CONCLUSIONS: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.

Single blind randomized phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a randomized controlled trial.

BACKGROUND: The treatment results of external beam radiotherapy for intermediate and high risk prostate cancer patients are insufficient with five-year biochemical relapse rates of approximately 35%. Several randomized trials have shown that dose escalation to the entire prostate improves biochemical disease free survival. However, further dose escalation to the whole gland is limited due to an unacceptable high risk of acute and late toxicity. Moreover, local recurrences often originate at the location of the macroscopic tumor, so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control. A reduction of distant metastases and improved survival can be expected by reducing local failure. The aim of this study is to investigate the benefit of an ablative microboost to the macroscopic tumor within the prostate in patients treated with external beam radiotherapy for prostate cancer. METHODS/DESIGN: The FLAME-trial (Focal Lesion Ablative Microboost in prostatE cancer) is a single blind randomized controlled phase III trial. We aim to include 566 patients (283 per treatment arm) with intermediate or high risk adenocarcinoma of the prostate who are scheduled for external beam radiotherapy using fiducial markers for position verification. With this number of patients, the expected increase in five-year freedom from biochemical failure rate of 10% can be detected with a power of 80%. Patients allocated to the standard arm receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in the experimental arm receive 77 Gy to the entire prostate and an additional integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions. The secondary outcome measures include treatment-related toxicity, quality of life and disease-specific survival. Furthermore, by localizing the recurrent tumors within the prostate during follow-up and correlating this with the delivered dose, we can obtain accurate dose-effect information for both the macroscopic tumor and subclinical disease in prostate cancer. The rationale, study design and the first 50 patients included are described. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov: NCT01168479.

Erlotinib-induced rash spares previously irradiated skin.

BACKGROUND: Erlotinib is an epidermal growth factor receptor inhibitor prescribed to patients with locally advanced or metastasized non-small cell lung carcinoma after failure of at least one earlier chemotherapy treatment. Approximately 75% of the patients treated with erlotinib develop acneiform skin rashes. CASE REPORT: A patient treated with erlotinib 3 months after finishing concomitant treatment with chemotherapy and radiotherapy for non-small cell lung cancer is presented. Unexpectedly, the part of the skin that had been included in his previously radiotherapy field was completely spared from the erlotinib-induced acneiform skin rash. CONCLUSION: The exact mechanism of erlotinib-induced rash sparing in previously irradiated skin is unclear. The underlying mechanism of this phenomenon needs to be explored further, because the number of patients being treated with a combination of both therapeutic modalities is increasing. The therapeutic effect of erlotinib in the area of the previously irradiated lesion should be assessed.

Influence of antiflatulent dietary advice on intrafraction motion for prostate cancer radiotherapy.

PURPOSE: To evaluate the effect of an antiflatulent dietary advice on the intrafraction prostate motion in patients treated with intensity-modulated radiotherapy (IMRT) for prostate cancer. METHODS AND MATERIALS: Between February 2002 and December 2009, 977 patients received five-beam IMRT for prostate cancer to a dose of 76 Gy in 35 fractions combined with fiducial markers for position verification. In July 2008, the diet, consisting of dietary guidelines to obtain regular bowel movements and to reduce intestinal gas by avoiding certain foods and air swallowing, was introduced to reduce the prostate motion. The intrafraction prostate movement was determined from the portal images of the first segment of all five beams. Clinically relevant intrafraction motion was defined as ≥50% of the fractions with an intrafraction motion outside a range of 3 mm. RESULTS: A total of 739 patients were treated without the diet and 105 patients were treated with radiotherapy after introduction of the diet. The median and interquartile range of the average intrafraction motion per patient was 2.53 mm (interquartile range, 2.2-3.0) without the diet and 3.00 mm (interquartile range, 2.4-3.5) with the diet (p < .0001). The percentage of patients with clinically relevant intrafraction motion increased statistically significant from 19.1% without diet to 42.9% with a diet (odds ratio, 3.18; 95% confidence interval, 2.07-4.88; p < .0001). CONCLUSIONS: The results of the present study suggest that antiflatulent dietary advice for patients undergoing IMRT for prostate cancer does not reduce the intrafraction movement of the prostate. Therefore, antiflatulent dietary advice is not recommended in clinical practice for this purpose.

Health-related quality of life up to six years after (125)I brachytherapy for early-stage prostate cancer.

PURPOSE: Health-related quality of life (HRQOL) after prostate brachytherapy has been extensively described in published reports but hardly any long-term data are available. The aim of the present study was to prospectively assess long-term HRQOL 6 years after (125)I prostate brachytherapy. METHODS AND MATERIALS: A total of 127 patients treated with (125)I brachytherapy for early-stage prostate cancer between December 2000 and June 2003 completed a HRQOL questionnaire at five time-points: before treatment and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTCQLQ-C30), and the tumor-specific EORTC prostate cancer module (EORTC-PR25). A change in a score of >/=10 points was considered clinically relevant. RESULTS: Overall, the HRQOL at 6 years after (125)I prostate brachytherapy did not significantly differ from baseline. Although a statistically significant deterioration in HRQOL at 6 years was seen for urinary symptoms, bowel symptoms, pain, physical functioning, and sexual activity (p <.01), most changes were not clinically relevant. A statistically significant improvement at 6 years was seen for mental health, emotional functioning, and insomnia (p <.01). The only clinically relevant changes were seen for emotional functioning and sexual activity. CONCLUSION: This is the first study presenting prospective HRQOL data up to 6 years after (125)I prostate brachytherapy. HRQOL scores returned to approximately baseline values at 1 year and remained stable up to 6 years after treatment. (125)I prostate brachytherapy did not adversely affect patients' long-term HRQOL.