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.

Development of an EORTC questionnaire measuring instrumental activities of daily living (IADL) in patients with brain tumours: phase I-III.

PURPOSE: Being able to function independently in society is an important aspect of quality of life. This ability goes beyond self-care, requires higher order cognitive functioning, and is typically measured with instrumental activities of daily living (IADL) questionnaires. Cognitive deficits are frequently observed in brain tumour patients, however, IADL is almost never assessed because no valid and reliable IADL measure is available for this patient group. Therefore, this measure is currently being developed. METHODS: This international multicentre study followed European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group module development guidelines. Three out of four phases are completed: phases (I) generation of items, (II) construction of the item list, and (III) pre-testing. This paper reports the item selection procedures and preliminary psychometric properties of the questionnaire. Brain tumour patients (gliomas and brain metastases), their informal caregivers, and health care professionals (HCPs) were included. RESULTS: Phase I (n = 44 patient-proxy dyads and 26 HCPs) generated 59 relevant and important activities. In phase II, the activities were converted into items. In phase III (n = 85 dyads), the 59 items were pre-tested. Item selection procedures resulted in 32 items. Exploratory factor analysis revealed a preliminary dimensional structure consisting of five scales with acceptable to excellent internal consistency (α = 0.73-0.94) and two single items. For three scales, patients with cognitive impairments had significantly more IADL problems than patients without impairments. CONCLUSION: A phase IV validation study is needed to confirm the psychometric properties of the EORTC IADL-BN32 questionnaire in a larger international sample.

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.

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.

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.

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.

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.

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.

Short-Course External Beam Radiotherapy Versus Brachytherapy for Palliation of Dysphagia in Esophageal Cancer: A Matched Comparison of Two Prospective Trials.

INTRODUCTION: Short-course external beam radiotherapy (EBRT) and intraluminal brachytherapy are both accepted treatments for the palliation of dysphagia in patients with incurable esophageal cancer. We compared the effects of both treatments from two prospective studies. METHODS: We performed a multicenter prospective cohort study of patients with metastasized or otherwise incurable esophageal cancer requiring palliation of dysphagia from September 2016 to March 2019. Patients were treated with EBRT in five fractions of 4 Gy. Data were compared with all patients treated with a single brachytherapy dose of 12 Gy in the SIREC (Stent or Intraluminal Radiotherapy for inoperable Esophageal Cancer) trial, both between the original cohorts and between 1:1 propensity score-matched cohorts. The primary end point was an improvement of dysphagia at 3 months without reintervention. The secondary end points included toxicity and time-to-effect. RESULTS: A total of 115 patients treated with EBRT and 93 patients who underwent brachytherapy were eligible for analysis. In the original cohorts, dysphagia improved after EBRT in 79% of patients compared with 64% after brachytherapy (p = 0.058). Propensity score matching resulted in 69 patients in each cohort well-balanced at baseline. Improvement of dysphagia was observed in 83% after EBRT versus 64% after brachytherapy (p = 0.048). In responding patients, improvement of dysphagia at 2 weeks was observed in 67% after EBRT compared with 35% after brachytherapy, and the maximum effect was reached after 4 weeks in 55% and 33%, respectively. Severe toxicity occurred in 3% of patients after EBRT compared with 13% after brachytherapy. CONCLUSIONS: Short-course EBRT appears at least as effective as brachytherapy in the palliation of dysphagia in patients with esophageal cancer.

Health-related quality of life 3 years after high-dose intensity-modulated radiotherapy with gold fiducial marker-based position verification.

OBJECTIVE: To evaluate the change in quality of life (QoL) 3 years after high-dose intensity-modulated radiotherapy (IMRT) using gold fiducial marker-based position verification in patients with locally advanced prostate cancer. PATIENTS AND METHODS: Between October 2003 and November 2004, 95 patients with locally advanced prostate cancer were treated with 76 Gy IMRT with gold-fiducial marker-based position verification. Before treatment (baseline) and 1, 6 and 36 months after RT the QoL was measured using the RAND-36, the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30(+3)) and the prostate tumour-specific module (EORTC QLQ-PR25). Changes in QoL with time of > or =10 points were considered clinically relevant. RESULTS: After 3 years there was a statistically significant improvement in QoL for emotional role restriction and functioning, change in health, mental health and insomnia, compared with baseline. Emotional role restriction increased by >10 points and was therefore clinically relevant, while all other differences were of <10 points. There was a statistically significant deterioration of QoL after 3 years in physical and cognitive functioning, bowel symptoms/function and sexual activity. Only the sexual activity QoL score changed by 12 points and was therefore the only meaningful deterioration in QoL at 3 years after treatment. CONCLUSION: IMRT and accurate position verification provide the possibility to deliver a high irradiation dose to the prostate without clinically relevant deterioration in long-term QoL, except for a persistent decrease in sexual activity score.

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.

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.

Feasibility of adequate dose coverage in permanent prostate brachytherapy using divergent needle insertion methods.

BACKGROUND AND PURPOSE: The purpose of this study is to investigate the feasibility of adequate dose coverage in permanent prostate brachytherapy using divergent needle insertion methods. These methods can be useful in magnetic resonance imaging (MRI) guided needle insertion techniques to avoid pubic arch interference. METHODS AND MATERIALS: MRI data were collected from 10 patients with T1-T2 prostate cancer. An inverse planning algorithm based on simulated annealing was used to optimize the dose distribution for three needle insertion methods: divergent needles with a single rotation point, divergent needles with a double rotation point, and current parallel needle insertion method. The dose constraints were based on our clinical criteria and the recent ESTRO/EAU/EORTC recommendations. RESULTS: If the planning target volume (PTV) surrounded the prostate and only intraprostatic seeds were allowed, the mean PTV volume that received 100% of the prescribed dose (V(100)) was 99% for all needle insertion methods. If the PTV was increased to the prostate with a 3mm margin, the mean PTV V(100) equalled 94%, 95%, and 94% for the single rotation point, double rotation point and current parallel needle insertion method, respectively. If in the latter case the tips of the seeds were placed 3mm outside the apex and base of the prostate, the mean PTV V(100) was 96% for all needle insertion methods. CONCLUSION: This planning study shows that it is feasible to generate an adequate dose coverage using divergent needle insertion methods.

Automatic segmentation of the prostate in 3D MR images by atlas matching using localized mutual information.

An automatic method for delineating the prostate (including the seminal vesicles) in three-dimensional magnetic resonance scans is presented. The method is based on nonrigid registration of a set of prelabeled atlas images. Each atlas image is nonrigidly registered with the target patient image. Subsequently, the deformed atlas label images are fused to yield a single segmentation of the patient image. The proposed method is evaluated on 50 clinical scans, which were manually segmented by three experts. The Dice similarity coefficient (DSC) is used to quantify the overlap between the automatic and manual segmentations. We investigate the impact of several factors on the performance of the segmentation method. For the registration, two similarity measures are compared: Mutual information and a localized version of mutual information. The latter turns out to be superior (median DeltaDSC approximately equal 0.02, p < 0.01 with a paired two-sided Wilcoxon test) and comes at no added computational cost, thanks to the use of a novel stochastic optimization scheme. For the atlas fusion step we consider a majority voting rule and the "simultaneous truth and performance level estimation" algorithm, both with and without a preceding atlas selection stage. The differences between the various fusion methods appear to be small and mostly not statistically significant (p > 0.05). To assess the influence of the atlas composition, two atlas sets are compared. The first set consists of 38 scans of healthy volunteers. The second set is constructed by a leave-one-out approach using the 50 clinical scans that are used for evaluation. The second atlas set gives substantially better performance (DeltaDSC=0.04, p < 0.01), stressing the importance of a careful atlas definition. With the best settings, a median DSC of around 0.85 is achieved, which is close to the median interobserver DSC of 0.87. The segmentation quality is especially good at the prostate-rectum interface, where the segmentation error remains below 1 mm in 50% of the cases and below 1.5 mm in 75% of the cases.

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.

Health-related quality of life in patients with locally advanced prostate cancer after 76 Gy intensity-modulated radiotherapy vs. 70 Gy conformal radiotherapy in a prospective and longitudinal study.

PURPOSE: To compare quality of life (QoL) after 70 Gy conformal radiotherapy with QoL after 76 Gy intensity-modulated radiotherapy (IMRT) in patients with locally advanced prostate carcinoma. METHODS AND MATERIALS: Seventy-eight patients with locally advanced prostate cancer were treated with 70 Gy three-field conformal radiotherapy, and 92 patients received 76 Gy IMRT with fiducial markers for position verification. Quality of life was measured by RAND-36, the European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30(+3)), and the prostate-specific EORTC QLQ-PR25, before radiotherapy (baseline) and 1 month and 6 months after treatment. Quality of life changes in time (baseline vs. 1 month and baseline vs. 6 months) of > or =10 points were considered clinically relevant. RESULTS: Differences between the treatment groups for QoL changes over time occurred in several QoL domains. The 76-Gy group revealed no significant deterioration in QoL compared with the 70-Gy group. The IMRT 76-Gy group even demonstrated a significantly better change in QoL from baseline to 1 month in several domains. The conformal 70-Gy group revealed temporary deterioration in pain, role functioning, and urinary symptoms; for the IMRT 76-Gy group a better QoL in terms of change in health existed after 1 month, which persisted after 6 months. For both treatment groups temporary deterioration in physical role restriction occurred after 1 month, and an improvement in emotional role restriction occurred after 6 months. Sexual activity was reduced after treatment for both groups and remained decreased after 6 months. CONCLUSIONS: Intensity-modulated radiotherapy and accurate position verification seem to provide a possibility to increase the radiation dose for prostate cancer without deterioration in QoL.

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.