BACKGROUND:Although short-course radiotherapy is an effective treatment for patients with painful bone metastases, pain is not always sufficiently controlled. We therefore investigated the additional effect of a nurse-led pain education program on pain control and quality of life (QoL). PATIENTS AND METHODS:In this multicenter study, patients with solid tumor bone metastases and a worst pain intensity of ≥5 on a 0-10 numeric rating scale (NRS) were randomized between care as usual (control-group) and care as usual plus the Pain Education Program (PEP-group). PEP consisted of a structured interview and personalized education with follow-up phone calls. Patients completed the Brief Pain Inventory, EORTC QLQ-C15-PAL and BM22 at week 0, 1, 4, 8 and 12. The primary outcome was pain control, defined as the number of patients whose worst pain intensity was <5 on a 0-10 NRS after 12 weeks. Secondary outcomes were time to reach control of pain (NRS < 5), mean worst pain and average pain, and QoL at weeks 1, 4, 8 and 12. RESULTS:Of 308 included patients, 182 (92 PEP-group) completed 12 weeks follow-up. At 12 weeks, more patients in the PEP-group (71%) compared to the control-group (52%) reported pain control (P =.008). In the PEP-group, pain control was reached earlier than in the control-group (median 29 days versus 56 days; P =.003). Mean worst and average pain decreased in both groups but decreased more in the PEP-group. QoL did not differ between the groups. CONCLUSION:The addition of PEP to care as usual for patients treated with radiotherapy for painful bone metastases resulted in less pain and faster pain control.

Purpose: In the Netherlands, oesophageal cancer (EC) patients are selected for intensity modulated pro-ton therapy (IMPT) using the expected normal tissue complication probability reduction (DNTCP) when treating with IMPT compared to volumetric modulated arc therapy (VMAT). In this study, we evaluate the robustness of the first EC patients treated with IMPT in our clinic in terms of target and organs-at-risk (OAR) dose with corresponding NTCP, as compared to VMAT. Materials and Methods: For 20 consecutive EC patients, clinical IMPT and VMAT plans were created on the average planning 4DCT. Both plans were robustly evaluated on weekly repeated 4DCTs and if target cov-erage degraded, replanning was performed. Target coverage was evaluated for complete treatment tra-jectories with and without replanning. The planned and accumulated mean lung dose (MLD) and mean heart dose (MHD) were additionally evaluated and translated into NTCP. Results: Replanning in the clinic was performed more often for IMPT (15x) than would have been needed for VMAT (8x) (p = 0.11). Both adaptive treatments would have resulted in adequate accumulated target dose coverage. Replanning in the first week of treatment had most clinical impact, as anatomical changes resulting in insufficient accumulated target coverage were already observed at this stage. No differences were found in MLD between the planned dose and the accumulated dose. Accumulated MHD differed from the planned dose (p < 0.001), but since these differences were similar for VMAT and IMPT (1.0 and 1.5 Gy, respectively), the DNTCP remained unchanged. Conclusion: Following an adaptive clinical workflow, adequate target dose coverage and stable OAR doses with corresponding NTCPs was assured for both IMPT and VMAT. (c) 2022 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 177 (2022) 197-204 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

There is no consensus yet for the best treatment regimen in patients with recurrent rectal cancer (RRC). This study aims to evaluate toxicity and oncological outcomes after re-irradiation in patients with RRC in our center. Clinical (cCR) and pathological complete response (pCR) rates and radicality were also studied. Between January 2010 and December 2018, 61 locally advanced RRC patients were treated and analyzed retrospectively. Patients received radiotherapy at a dose of 30.0–30.6 Gy (reCRT) or 50.0–50.4 Gy chemoradiotherapy (CRT) in cases of no prior irradiation because of low-risk primary rectal cancer. In both groups, patients received capecitabine concomitantly. In total, 60 patients received the prescribed neoadjuvant (chemo)radiotherapy followed by surgery, 35 patients (58.3%) in the reRCT group and 25 patients (41.7%) in the long-course CRT group. There were no significant differences in overall survival (p = 0.82), disease-free survival (p = 0.63), and local recurrence-free survival (p = 0.17) between the groups. Patients in the long-course CRT group reported more skin toxicity after radiotherapy (p = 0.040). No differences were observed in late toxicity. In the long-course CRT group, a significantly higher cCR rate was observed (p = 0.029); however, there was no difference in the pCR rate (p = 0.66). The treatment of RRC patients with re-irradiation is comparable to treatment with long-course CRT regarding toxicity and oncological outcomes. In the reCRT group, less cCR was observed, although there was no difference in pCR. The findings in this study suggest that it is safe and feasible to re-irradiate RRC patients.

BACKGROUND AND PURPOSE:A radical resection of locally advanced rectal cancer (LARC) or recurrent rectal cancer (RRC) can be challenging. In case of increased risk of an R1 resection, intra-operative brachytherapy (IOBT) can be applied. We evaluated the clinical selection strategy for IOBT. MATERIALS AND METHODS:Between February 2007 and May 2018, 132 LARC/RRC patients who were scheduled for surgery with IOBT standby, were evaluated. By intra-operative inspection of the resection margin and MR imaging, it was determined whether a resection was presumed to be radical. Frozen sections were taken on indication. In case of a suspected R1 resection, IOBT (1 × 10 Gy) was applied. Histopathologic evaluation, treatment and toxicity data were collected from medical records. RESULTS:Tumour was resected in 122 patients. IOBT was given in 42 patients of whom 54.8% (n = 23) had a histopathologically proven R1 resection. Of the 76 IOBT-omitted R0 resected patients, 17.1% (n = 13) had a histopathologically proven R1 resection. In 4 IOBT-omitted patients, a clinical R1/2 resection was seen. In total, correct clinical judgement occurred in 72.6% (n = 88) of patients. In LARC, 58.3% (n = 14) of patients were overtreated (R0, with IOBT) and 10.9% (n = 5) were undertreated (R1, without IOBT). In RRC, 26.5% (n = 9) of patients were undertreated. CONCLUSION:In total, correct clinical judgement occurred in 72.6% (n = 88). However, in 26.5% (n = 9) RRC patients, IOBT was unjustifiedly omitted. IOBT is accompanied by comparable and acceptable toxicity. Therefore, we recommend IOBT to all RRC patients at risk of an R1 resection as their salvage treatment.

Objective: Neoadjuvant chemoradiotherapy followed by surgery establishes a considerable pathologic complete response (pCR) in EC. The aim was to determine site of residual tumor and its prognostic impact. Summary Background Data: High rates of residual tumor in the adventitial region even inside the radiation fields will influence current decision-making. Methods: We evaluated resection specimens with marked target fields from 151 consecutive EC patients treated with carboplatin/paclitaxel and 41.4Gy between 2009 and 2018. Results: In radically resected (R0) specimens 19.8% (27/136) had a pCR (ypT0N0) and 14% nearly no response (tumor regression grade: tumor regression grade 4–5). Residual tumor commonly extended in or restricted to the adventitia (43.1%; 47/109), whereas 7.3% was in the mucosa (ypT1a), 16.5% in the submucosa (ypT1b) and 6.4% only in lymph nodes (ypT0N+). Macroscopic residues in R0-specimens of partial responders (tumor regression grade 2-3: N = 90) were found in- and outside the gross tumor volume (GTV) in 33.3% and 8.9%, and only microscopic in- and outside the clinical target volume in 58.9% and 1.1%, respectively. Residual nodal disease was observed proximally and distally to the clinical target volume in 2 and 5 patients, respectively. Disease Free Survival decreased significantly if macroscopic tumor was outside the GTV and in ypT2-4aN+. Conclusions: After neoadjuvant chemoradiotherapy, pCR and ypT1aN0 were seen in a limited number of R0 resected specimens (19.8% and 7.3%, respectively), whereas 6.4% had only nodal disease (yT0N+). Disease Free Survival decreased significantly if macroscopic residue was outside the GTV and in responders with only nodal disease. Therefore, we should be cautious in applying wait and see strategies.

Objectives To assess the complementary value of human epidermal growth factor receptor 2 (HER2)-related biological tumor markers to clinico-radiomic models in predicting complete response to neoadjuvant chemoradiotherapy (NCRT) in esophageal cancer patients. Methods Expression of HER2 was assessed by immunohistochemistry in pre-treatment tumor biopsies of 96 patients with locally advanced esophageal cancer. Five other potentially active HER2-related biological tumor markers in esophageal cancer were examined in a sub-analysis on 43 patients. Patients received at least four of the five cycles of chemotherapy and full radiotherapy regimen followed by esophagectomy. Three reference clinico-radiomic models based on 18 F-FDG PET were constructed to predict pathologic response, which was categorized into complete versus incomplete (Mandard tumor regression grade 1 vs. 2–5). The complementary value of the biological tumor markers was evaluated by internal validation through bootstrapping. Results Pathologic examination revealed 21 (22%) complete and 75 (78%) incomplete responders. HER2 and cluster of differentiation 44 (CD44), analyzed in the sub-analysis, were univariably associated with pathologic response. Incorporation of HER2 and CD44 into the reference models improved the overall performance ( R 2 s of 0.221, 0.270, and 0.225) and discrimination AUCs of 0.759, 0.857, and 0.816. All models exhibited moderate to good calibration. The remaining studied biological tumor markers did not yield model improvement. Conclusions Incorporation of HER2 and CD44 into clinico-radiomic prediction models improved NCRT response prediction in esophageal cancer. These biological tumor markers are promising in initial response evaluation. Key Points • A multimodality approach, integrating independent genomic and radiomic information, is promising to improve prediction of γpCR in patients with esophageal cancer. • HER2 and CD44 are potential biological tumor markers in the initial work-up of patients with esophageal cancer. • Prediction models combining 18 F-FDG PET radiomic features with HER2 and CD44 may be useful in the decision to omit surgery after neoadjuvant chemoradiotherapy in patients with esophageal cancer.

Objectives Mindfulness and self-compassion are related to psychological well-being and can be regarded as personal resources. It is, however, unclear whether these resources are always beneficial (direct effect) or only in stressful circumstances (buffer effect). We therefore examined whether mindfulness and self-compassion are equally or more strongly related to depressive symptoms and affect in cancer patients, compared to healthy controls. Methods Using a case-control design, 245 cancer patients were matched to 245 healthy controls (without chronic somatic comorbidities). Both groups filled out questionnaires concerning mindfulness (Five Facet Mindfulness Questionnaire), self-compassion (Self-Compassion Scale), depressive symptoms (Center for Epidemiologic Studies Depression Scale), and affect (Positive and Negative Affect Scale). Using correlation and regression analyses, we examined within both groups the associations for mindfulness (i.e., total score and five facets) and self-compassion (i.e., total score, two factors and six facets) with depressive symptoms and affect. Results Mindfulness and self-compassion were equally strongly related to depressive symptoms and affect in cancer patients versus healthy controls. Mindfulness facets Act with awareness and Non-judgment were strongly related to depressive symptoms, negative affect, and the negative self-compassion factor. In contrast, mindfulness facets Describe and Observe were strongly related to positive affect and the positive self-compassion factor. When distinguishing the six self-compassion facets, Isolation and Mindfulness were strongly related to depressive symptoms, Over-identification to negative affect, and Mindfulness to positive affect. Conclusions Results suggest that mindfulness and self-compassion are basic human personal resources associated with psychological functioning, regardless of the presence or absence of stressful life experiences.

Background: Clinical nodal (cN) staging is a key element in treatment decisions in patients with esophageal cancer (EC). The reliability of cN status regarding the effect on response and survival after neoadjuvant chemoradiotherapy (nCRT) with esophagectomy was evaluated in determining the up- and downstaged pathological nodal (pN) status after surgery alone. Material and methods: From a prospective database, we included all 395 EC patients who had surgery with curative intent with or without nCRT between 2000 and 2015. All patients were staged by a standard pretreatment protocol: 16-64 mdCT, 18 F-FDG-PET or 18 F-FDG-PET/CT and EUS ± FNA. After propensity score matching on baseline clinical tumor and nodal (cT/N) stage and histopathology, a surgery-alone and nCRT group (each N = 135) were formed. Clinical and pathological N stage was scored as equal (cN = pN), downstaged (cN > pN) or upstaged (cN < pN). Prognostic impact on disease free survival (DFS) was assessed with multivariable Cox regression analysis (factors with p value <.1 on univariable analysis). Results: The surgery-alone and nCRT group did not differ in cT/N status. Pathologic examination revealed equal staging (32 vs. 27%), nodal up (43 vs. 16%) and downstaging (25 vs. 56%), respectively (p < .001). Nodal up-staging was common in cT3-4a tumors and adenocarcinomas in the surgery-alone group, while nodal downstaging was found in half of cT1-2 and cT3-4 regardless of tumortype after nCRT. Prognostic factors for DFS were pN (p = .002) and lymph-angioinvasion (p = .016) in surgery-alone, and upper abdominal cN metastases (p = .012) and lymph node ratio (p = .034) in the nCRT group. Conclusions: Despite modern staging methods, correct cN staging remains difficult in EC. Nodal overstaging (cN > pN) occurred more often than understaging impeding an adequate assessment of pathologic complete response and prognosis after nCRT.

OBJECTIVE:In line with screening guidelines, cancer survivors were consecutively screened on depressive symptoms (as part of standard care), with those reporting elevated levels of symptoms offered psychological care as part of a trial. Because of the low uptake, no conclusions could be drawn about the interventions' efficacy. Given the trial set-up (following screening guidelines and strict methodological quality criteria), we believe that this observational study reporting the flow of participation, reasons for and characteristics associated with nonparticipation, adds to the debate about the feasibility and efficiency of screening guidelines. METHODS:Two thousand six hundred eight medium- to long-term cancer survivors were consecutively screened on depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9). Those with moderate depressive symptoms (PHQ-9 ≥ 10) were contacted and informed about the trial. Patient flow and reasons for nonparticipation were carefully monitored. RESULTS:One thousand thirty seven survivors (74.3%) returned the questionnaire, with 147 (7.6%) reporting moderate depressive symptoms. Of this group, 49 survivors (33.3%) were ineligible, including 26 survivors (17.7%) already receiving treatment and another 44 survivors (30.0%) reporting no need for treatment. Only 25 survivors (1.0%) participated in the trial. CONCLUSION:Of the approached survivors for screening, only 1% was eligible and interested in receiving psychological care as part of our trial. Four reasons for nonparticipation were: nonresponse to screening, low levels of depressive symptoms, no need, or already receiving care. Our findings question whether to spend the limited resources in psycho-oncological care on following screening guidelines and the efficiency of using consecutive screening for trial recruitment in cancer survivors.

Purpose To assess the value of baseline and restaging fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) radiomics in predicting pathologic complete response to neoadjuvant chemotherapy and radiation therapy (NCRT) in patients with locally advanced esophageal cancer. Materials and Methods In this retrospective study, 73 patients with histologic analysis-confirmed T1/N1-3/M0 or T2-4a/N0-3/M0 esophageal cancer were treated with NCRT followed by surgery (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study regimen) between October 2014 and August 2017. Clinical variables and radiomic features from baseline and restaging 18F-FDG PET were selected by univariable logistic regression and least absolute shrinkage and selection operator. The selected variables were used to fit a multivariable logistic regression model, which was internally validated by using bootstrap resampling with 20 000 replicates. The performance of this model was compared with reference prediction models composed of maximum standardized uptake value metrics, clinical variables, and maximum standardized uptake value at baseline NCRT radiomic features. Outcome was defined as complete versus incomplete pathologic response (tumor regression grade 1 vs 2-5 according to the Mandard classification). Results Pathologic response was complete in 16 patients (21.9%) and incomplete in 57 patients (78.1%). A prediction model combining clinical T-stage and restaging NCRT (post-NCRT) joint maximum (quantifying image orderliness) yielded an optimism-corrected area under the receiver operating characteristics curve of 0.81. Post-NCRT joint maximum was replaceable with five other redundant post-NCRT radiomic features that provided equal model performance. All reference prediction models exhibited substantially lower discriminatory accuracy. Conclusion The combination of clinical T-staging and quantitative assessment of post-NCRT 18F-FDG PET orderliness (joint maximum) provided high discriminatory accuracy in predicting pathologic complete response in patients with esophageal cancer. © RSNA, 2018 Online supplemental material is available for this article.

111 Background: Although essential in treatment decision making, clinical nodal (cN) staging in esophageal cancer (EC) remains difficult. We assessed the rate of nodal up- and downstaging and its prognostic value on 5-year disease-free survival (DFS) in EC patients treated with surgery-alone or with neoadjuvant chemoradiotherapy (nCRT). Methods: For this retrospective study, we included 395 EC patients who underwent a curative esophagectomy with or without nCRT between 2000 and 2015. The surgery-alone and nCRT group were matched on clinical T-stage (cT), cN-stage, and histopathological type using propensity score matching ( n=270). Staging consisted of PET with CT, or PET/CT, and endoscopic ultrasonography (n = 235). We compared cN and pathological N-stage (pN) and scored correct, down- and upstaging. The prognostic value of nodal up- and downstaging and localization of node metastases on 5-year DFS were assessed with multivariate Cox regression analysis (factors with a P-value <0.1 on univariate analysis). Results: Nodal upstaging (43.0% vs. 16.3%), correct staging (31.9% vs. 28.1%) and downstaging (25.2% vs. 55.6%) differed between the surgery-alone and nCRT group ( P<0.001). Nodal upstaging was commonly present in adenocarcinoma and cT3-4a tumors. Independent prognostic factors for DFS were pN ( P=0.002) and lymph-angioinvasion ( P=0.016) in the surgery and cN metastasis under the diaphragm ( P=0.012) and lymph node ratio ( P=0.034) in the nCRT group. Conclusions: In esophageal cancer, clinical lymph node staging is still insufficient with >25% nodal downstaging. This inaccuracy might impede assessment of true nodal response to nCRT, affording dubious decisions for a ‘wait-and-see’ strategy.

203 Background: Radiotherapy (RT) is an effective treatment for painful bone metastases, although pain is not always sufficiently controlled. Pain management education may improve patient empowerment and, consequently, reduce pain intensity. The effect of nurse-led education (NLE) in patients undergoing RT for painful bone metastases was investigated as compared to care as usual (CAU). Primary endpoint was pain intensity at 12 weeks, secondary outcome was quality of life (QoL). Methods: In this multicentre, randomised phase 3 study, patients referred for short schedule RT, with uncontrolled pain (a score of ≥5 on a 0-10 numeric rating scale (NRS)), were randomised between NLE or CAU before start of RT. The NLE consisted of a structured interview including assessment of pain knowledge, verbal and written education on all aspects of pain and follow-up phone calls at 1, 4, 8 & 12 weeks to address pain-related questions. Patients in CAU received leaflets on RT, cancer pain and opioid use. Patient characteristics were assessed at baseline. Pain intensity and QoL were evaluated with the Brief Pain Inventory, EORTC QLQ-C15-PAL and EORTC QLQ-BM22 at baseline, and week 1, 4, 8 & 12. Power calculation showed that there were 89 patients per arm needed to detect a 10% difference in number of patients with a NRS < 5 at 12 weeks(1-sided α = 0.05; β 0.8). Results: Between May 2011-April 2016, 354 patients were randomised (176 NLE, 178 CAU), 38 were excluded (30 NRS < 5 at baseline, 7 no short schedule RT, 1 missing informed consent). At twelve weeks, 185 (NLE 95) had completed follow-up (72 stopped filling out questionnaires, 59 died prematurely). Baseline characteristics were similar in both groups; mean age 65 years, 56% men. At week 12, more patients in NLE than in CAU had controlled pain (NRS < 5; respectively 66% and 52%, p = 0.036). Moreover, patients in NLE reached faster a pain score < 5 than patients in CAU (31 versus 54 days respectively, p = 0.026). On all time points, no significant differences in QoL were found between both groups. Conclusions: Controlled pain, i.e. a pain intensity < 5, was reached faster and by more patients with painful bone metastases undergoing RT by the addition of nurse-led pain education. Clinical trial information: NCT01358539.

Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUVmax in 18F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18F-FDG PET/CT–derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18F-FDG PET and CT. The current most accurate prediction model with SUVmax as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model’s performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2–5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18F-FDG PET–derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUVmax model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion: The predictive values of the constructed models were superior to the standard method (SUVmax). These results can be considered as an initial step in predicting tumor response to nCRT in locally advanced EC. Further research in refining the predictive value of these models is needed to justify omission of surgery.

25 Background: The optimal sequence of endoscopic ultrasonography (EUS) and positron emission tomography with computed tomography (PET/CT) in esophageal cancer (EC) is a matter of debate. The use of EUS with fine needle aspiration (FNA) after PET/CT seems to increase the efficacy of curative intended neoadjuvant or definitive chemoradiotherapy. Retrospectively, we assessed the impact of EUS in the PET/CT upfront model on the treatment decision making in EC patients. Methods: In the period 2009 to 2015, 298 EC patients were staged with hybrid PET/CT or PET with CT, and EUS if applicable, in a non-specific order to assess curability (T1-4a,N0-3M0). We determined the feasibility of EUS and whether the initial or additional EUS changed the primary decision suspicious incurable (T4b and M+) into curable disease or added extra nodal information leading to up/downstaging or exhibit suspected nodes at different lymph node stations. In addition, we assessed if EUS changed the radiation area (i.e. lymph nodes > 3.5 cm from the defined radiation target volumes) in the PET/CT “upfront model”. Results: EUS was complete in 185 (62.1%) and incomplete due to stricture from a relative obstructing tumor in 59 (19.8%) patients. Fifty-four patients (18.1%) did not receive EUS because of stenosis (n = 46; 15.4%), patient dependent reasons (n = 4; 1.3%) or other reasons (n = 4; 1.3%). EUS after hybrid PET/CT or PET with CT (n = 244) gave additional information in 166 patients (68.0%); it changed the curability in 4 (1.6%), lead to nodal up and downstaging in respectively, 81 (33.2%) and 27 (11.1%) patients, changed the number of or lymph node station of suspected lymph nodes in an additional 58 patients (n = 23.8%), and FNA gave additional information in 34 (13.9%) patients. EUS after PET/CT ”upfront” changed the treatment plan in 90 patients (36.9%), including alteration in the radiation field (86; 35.2%) and curability (4; 1.6%). Conclusions: EUS gave additional information after PET/CT “up front” and altered the radiation field in about one third of the EC patients, suggesting a better yield of “EUS on indication” after PET/CT upfront.

BACKGROUND: The purpose of this study was to provide more insight in the course of cytokine concentrations related to pathologic response (pR) and complications after neoadjuvant chemoradiotherapy (NCRT) and esophagectomy in esophageal cancer patients.METHODS: Patients treated with NCRT followed by transthoracic esophagectomy (n = 35) or transthoracic esophagectomy alone (n = 8) were included. Eight different cytokine concentrations were determined during NCRT, esophagectomy, and the first postoperative week.RESULTS: Platelet-activating factor before NCRT was associated with pR (P = .011) and remained elevated in patients with a better response. Concentrations of intestinal fatty acid-binding protein and angiopoietin 1 (Ang-1) were different between patients with and without NCRT. Decreased concentrations of Ang-1 on the third postoperative day were associated with postoperative complications (P = .046).CONCLUSIONS: In this observational study, elevated platelet-activating factor concentrations before NCRT were associated with pR. NCRT is associated with decreased Ang-1 concentrations, whereas reduced Ang-1 concentrations were associated with postoperative complications. (C) 2016 Elsevier Inc. All rights reserved.

Background and purposeNeoadjuvant chemoradiotherapy (nCRT) improves survival in esophageal cancer (EC) patients, but the response to treatment is heterogeneous and little is known regarding prognostic and predictive markers in these patients. CD44, SOX2 and SHH have been implicated in resistance to CRT, possibly through an association with a cancer stem cell phenotype.Material and methods101 EC patients treated with nCRT and surgery were included. Sufficient pre-treatment biopsy material was present in 71 patients, of which 53 patients were non-complete responders on nCRT (nCR). Protein expression was examined using immunohistochemistry (IHC). Prognostic factors were determined using Cox regression analysis for disease free survival (DFS) and cause specific survival (CSS) in the complete cohort, the pre-treatment biopsies group and post-treatment nCR group.ResultsLow CD44 expression in the nCR group was an independent prognostic factor for both DFS and CSS (DFS HR 2.81, p=0.002 and CSS HR 3.48, p=0.002). Absent SOX2 expression in pretreatment biopsies was related to systemic recurrence (p=0.029) while low SHH in pretreatment biopsies was an independent prognostic factor for a poor DFS (HR 2.27, p=0.036). No relation between marker expression and response to nCRT was observed.ConclusionsLow expression of CD44 and SHH are associated with a poor survival outcome in EC patients treated with nCRT.

BACKGROUND:The aim of this prospective study was to determine the proportion of locoregional recurrences (LRRs) that could have been prevented if radiotherapy treatment planning for oesophageal cancer was based on PET/CT instead of CT.MATERIALS AND METHODS:Ninety oesophageal cancer patients, eligible for high dose (neo-adjuvant) (chemo)radiotherapy, were included. All patients underwent a planning FDG-PET/CT-scan. Radiotherapy target volumes (TVs) were delineated on CT and patients were treated according to the CT-based treatment plans. The PET images remained blinded. After treatment, TVs were adjusted based on PET/CT, when appropriate. Follow up included CT-thorax/abdomen every 6months. If LRR was suspected, a PET/CT was conducted and the site of recurrence was compared to the original TVs. If the LRR was located outside the CT-based clinical TV (CTV) and inside the PET/CT-based CTV, we considered this LRR possibly preventable.RESULTS:Based on PET/CT, the gross tumour volume (GTV) was larger in 23% and smaller in 27% of the cases. In 32 patients (36%), >5% of the PET/CT-based GTV would be missed if the treatment planning was based on CT. The median follow up was 29months. LRRs were seen in 10 patients (11%). There were 3 in-field recurrences, 4 regional recurrences outside both CT-based and PET/CT-based CTV and 3 recurrences at the anastomosis without changes in TV by PET/CT; none of these recurrences were considered preventable by PET/CT.CONCLUSION:No LRR was found after CT-based radiotherapy that could have been prevented by PET/CT. The value of PET/CT for radiotherapy seems limited.

Background. Neoadjuvant chemoradiotherapy (CRT) improves locoregional control and overall survival in esophageal cancer patients. Although adverse events are relatively low during neoadjuvant CRT, severe postoperative adverse effects may occur, leading to morbidity and even mortality. We investigated the impact of a more frequently used neoadjuvant CRT regimen of 41.4 Gy/5 weeks radiotherapy with concurrent carboplatin and paclitaxel (CROSS schedule) on the postoperative course.Methods. Between 2006 and 2012, a total of 96 esophageal cancer patients (staged cT1N+/T2-4a/N0-3 and M0) were treated according to the above neoadjuvant scheme. To reduce bias in this single-center study, we performed a propensity score-matched analysis with patients who underwent surgery alone (n = 230) from a prospectively maintained database (n = 326).Results. Baseline characteristics between both groups were equally distributed in the matched cohort. In the neoadjuvant treated group, significantly more patients were diagnosed with pneumonia (27.1 vs. 51.0 %; p = 0.001), pleural effusion (12.5 vs. 24.0 %; p = 0.040), and arrhythmia (20.4 vs. 34.4 %; p = 0.008). In addition, in the multivariate analysis, neoadjuvant CRT was significantly associated with an increased risk of pneumonia (p = 0.001, odds ratio 2.896), pleural effusion (p = 0.041, odds ratio 2.268), and arrhythmia (p = 0.023, odds ratio 2.215). Despite these outcomes, no differences were detected in duration of intensive care unit or hospital stay. Short-term mortality did not differ between both groups.Conclusions. We observed an increase of cardiopulmonary complications in the neoadjuvant CRT group, without any effect on hospital or intensive care unit stay and mortality. Further research is warranted on the limitation of chemoradiation-induced cardiopulmonary toxicity.

BACKGROUND:Neoadjuvant chemoradiotherapy (CRT) in esophageal cancer (EC) patients may increase the formation of thromboembolic events (TEEs). We analyzed the incidence and impact of TEEs in EC patients treated with platinum-based CRT.METHODS:A total of 336 patients with EC underwent an esophagectomy, of which 110 patients received neoadjuvant CRT (41.4 Gy with concurrent Carboplatin/Paclitaxel). Patients were matched based on pre- and perioperative characteristics.RESULTS:Preoperatively, 9 (8.2%) patients with neoadjuvant CRT (P = .004) were diagnosed with TEEs. Despite delay until surgery (P = .021), the postoperative course did not differ. In multivariate analysis, a history of deep vein thrombosis (P = .005) and neoadjuvant CRT (P = .004) were identified as risk factors. Postoperatively, there were no differences in TEEs (P = .560) observed. In multivariate analysis, a history of pulmonary embolism (P = .012) was identified as a risk factor for postoperative TEEs.CONCLUSIONS:Preoperatively, EC patients treated with neoadjuvant CRT have an increased risk to develop a TEE, especially those with a previous history of TEE. After surgery no increased incidence was observed. We recommend secondary prophylaxis during neoadjuvant treatment in this high-risk group.