Search

Structural brain network topology can be altered in case of a brain tumor, due to both the tumor itself and its treatment. In this study, we explored the role of structural whole-brain and nodal network metrics and their association with cognitive functioning. Fifty WHO grade 2–3 adult glioma survivors (> 1-year post-therapy) and 50 matched healthy controls underwent a cognitive assessment, covering six cognitive domains. Raw cognitive assessment scores were transformed into w-scores, corrected for age and education. Furthermore, based on multi-shell diffusion-weighted MRI, whole-brain tractography was performed to create weighted graphs and to estimate whole-brain and nodal graph metrics. Hubs were defined based on nodal strength, betweenness centrality, clustering coefficient and shortest path length in healthy controls. Significant differences in these metrics between patients and controls were tested for the hub nodes (i.e. n = 12) and non-hub nodes (i.e. n = 30) in two mixed-design ANOVAs. Group differences in whole-brain graph measures were explored using Mann–Whitney U tests. Graph metrics that significantly differed were ultimately correlated with the cognitive domain-specific w-scores. Bonferroni correction was applied to correct for multiple testing. In survivors, the bilateral putamen were significantly less frequently observed as a hub (pbonf < 0.001). These nodes' assortativity values were positively correlated with attention (r(90) > 0.573, pbonf < 0.001), and proxy IQ (r(90) > 0.794, pbonf < 0.001). Attention and proxy IQ were significantly more often correlated with assortativity of hubs compared to non-hubs (pbonf < 0.001). Finally, the whole-brain graph measures of clustering coefficient (r = 0.685), global (r = 0.570) and local efficiency (r = 0.500) only correlated with proxy IQ (pbonf < 0.001). This study demonstrated potential reorganization of hubs in glioma survivors. Assortativity of these hubs was specifically associated with cognitive functioning, which could be important to consider in future modeling of cognitive outcomes and risk classification in glioma survivors. [ABSTRACT FROM AUTHOR]

Objective. Lung cancer (LC) patients suffer from multiple cooccurring symptoms. Interventions that have the potential to impact more than one symptom within a symptom cluster should be identified. The aim of this review was to examine nonpharmacological interventions that were effective in the management of one or more of the following symptoms in LC patients: dyspnea, fatigue, physical functioning (PF), and role functioning (RF). Methods. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used for reporting this systematic review. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (using the PubMed interface), Embase (using the embase.com interface), and Web of Science were used as electronic databases. Randomized controlled studies were included if they assessed the effects of nonpharmacological interventions on dyspnea, fatigue, PF, and/or RF in patients with LC. Studies were evaluated with the Cochrane risk of bias tool, and relevant data were extracted and narratively summarized. Results and Conclusions. In total, 89 articles were included. Search results (until April 2023) show that most evidence was found for exercise interventions, followed by multicomponent, psychoeducational, diet, acupuncture, and other interventions. Studies that had an effect on multiple symptoms were observed to have the most frequent instances of positively affecting dyspnea, followed by PF, fatigue, and RF. [ABSTRACT FROM AUTHOR]

During pregnancy, the use of radiation therapy for cancer treatment is often considered impossible due to the assumed associated fetal risks. However, suboptimal treatment of pregnant cancer patients and unjustifiable delay in radiation therapy until after delivery can be harmful for both patient and child. In non‐pregnant patients, proton‐radiation therapy is increasingly administered because of its favorable dosimetric properties compared with photon‐radiation therapy. Although data on the use of pencil beam scanning proton‐radiation therapy during pregnancy are scarce, different case reports and dosimetric studies have indicated a more than 10‐fold reduction in fetal radiation exposure compared with photon‐radiation therapy. Nonetheless, the implementation of proton‐radiation therapy during pregnancy requires complex fetal dosimetry for the neutron‐dominated out‐of‐field radiation dose and faces a lack of clinical guidelines. Further exploration and standardization of proton‐radiation therapy during pregnancy will be necessary to improve radiotherapeutic management of pregnant women with cancer and further reduce risks for their offspring. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the most lethal cancer, and 85% of cases are classified as non-small cell lung cancer (NSCLC). Metabolic rewiring is a cancer hallmark that causes treatment resistance, and lacks insights into serine/glycine pathway adaptations upon radiotherapy. Methods: We analyzed radiotherapy responses using mass-spectrometry-based metabolomics in NSCLC patient's plasma and cell lines. Efficacy of serine/glycine conversion inhibitor sertraline with radiotherapy was investigated by proliferation, clonogenic and spheroid assays, and in vivo using a serine/glycine dependent NSCLC mouse model by assessment of tumor growth, metabolite and cytokine levels, and immune signatures. Results: Serine/glycine pathway metabolites were significantly consumed in response to radiotherapy in NSCLC patients and cell models. Combining sertraline with radiotherapy impaired NSCLC proliferation, clonogenicity and stem cell self-renewal capacity. In vivo, NSCLC tumor growth was reduced solely in the sertraline plus radiotherapy combination treatment group. Tumor weights linked to systemic serine/glycine pathway metabolite levels, and were inhibited in the combination therapy group. Interestingly, combination therapy reshaped the tumor microenvironment via cytokines associated with natural killer cells, supported by eradication of immune checkpoint galectin-1 and elevated granzyme B levels. Conclusion: Our findings highlight that targeting serine/glycine metabolism using sertraline restricts cancer cell recovery from radiotherapy and provides tumor control through immunomodulation in NSCLC. [ABSTRACT FROM AUTHOR]

Most patients receive whole breast radiotherapy in a supine position. However, two randomised trials showed lower acute toxicity in prone position. Furthermore, in most patients, prone positioning reduced doses to the organs at risk. To confirm these findings, we compared toxicity outcomes, photographic assessment, and dosimetry between both positions using REQUITE data. REQUITE is an international multi-centre prospective observational study that recruited 2069 breast cancer patients receiving radiotherapy. Data on toxicity, health-related quality of life (HRQoL), and dosimetry were collected, as well as a photographic assessment. A matched case control analysis compared patients treated prone (n = 268) versus supine (n = 493). Exact matching was performed for the use of intensity-modulated radiotherapy, boost, lymph node irradiation, chemotherapy and fractionation, and the nearest neighbour for breast volume. Primary endpoints were dermatitis at the end of radiotherapy, and atrophy and cosmetic outcome by photographic assessment at two years. At the last treatment fraction, there was no significant difference in dermatitis (p =.28) or any HRQoL domain, but prone positioning increased the risk of breast oedema (p <.001). At 2 years, patients treated in prone position had less atrophy (p =.01), and higher body image (p <.001), and social functioning (p <.001) scores. The photographic assessment showed no difference in cosmesis at 2 years (p =.22). In prone position, mean heart dose (MHD) was significantly lower for left-sided patients (1.29 Gy vs 2.10 Gy, p <.001) and ipsilateral mean lung dose (MLD) was significantly lower for all patients (2.77 Gy vs 5.89 Gy, p <.001). Prone radiotherapy showed lower MLD and MHD compared to supine position, although the risk of developing breast oedema during radiotherapy was higher. At 2 years the photographic assessment showed no difference in the cosmetic outcome, but less atrophy was seen in prone-treated patients and this seems to have a positive influence on the HRQoL domain of body image. [ABSTRACT FROM AUTHOR]

Simple Summary: As survival rates for cancer increase and most patients exceed the age of 65 years, more emphasis has gone to possible cognitive sequelae, which could be explained by accelerated brain aging. We conducted a systematic literature review to summarize the existing risks of cognitive decline, imaging-based indication of neurotoxicity, as well as developing a neurodegenerative disease in older cancer survivors. Evidence was found for functional and structural brain changes. Cognitive decline was mainly found in memory functioning. Individual risk factors included cancer types (brain, hormone-related cancers), treatment (anti-hormonal therapy, chemotherapy, cranial radiotherapy), genetic predisposition (APOE, COMT, BDNF), increasing age, comorbidities (frailty, baseline cognitive reserve, functional decline), and psychological (distress, depression, anxiety, post-traumatic stress disorder, sleeping problems, fatigue) and social factors (loneliness, caregiver support, socioeconomic status). Further research is needed to provide a more detailed and profound picture of accelerated neurocognitive aging in specific older subpopulations and targeted interventions. As survival rates increase, more emphasis has gone to possible cognitive sequelae in older cancer patients, which could be explained by accelerated brain aging. In this review, we provide a complete overview of studies investigating neuroimaging, neurocognitive, and neurodegenerative disorders in older cancer survivors (>65 years), based on three databases (Pubmed, Web of Science and Medline). Ninety-six studies were included. Evidence was found for functional and structural brain changes (frontal regions, basal ganglia, gray and white matter), compared to healthy controls. Cognitive decline was mainly found in memory functioning. Anti-hormonal treatments were repeatedly associated with cognitive decline (tamoxifen) and sometimes with an increased risk of Alzheimer's disease (androgen deprivation therapy). Chemotherapy was inconsistently associated with later development of cognitive changes or dementia. Radiotherapy was not associated with cognition in patients with non-central nervous system cancer but can play a role in patients with central nervous system cancer, while neurosurgery seemed to improve their cognition in the short-term. Individual risk factors included cancer subtypes (e.g., brain cancer, hormone-related cancers), treatment (e.g., anti-hormonal therapy, chemotherapy, cranial radiation), genetic predisposition (e.g., APOE, COMT, BDNF), age, comorbidities (e.g., frailty, cognitive reserve), and psychological (e.g., depression, (post-traumatic) distress, sleep, fatigue) and social factors (e.g., loneliness, limited caregiver support, low SES). More research on accelerated aging is required to guide intervention studies. [ABSTRACT FROM AUTHOR]

Background: Optimal treatment for thymoma with pleural dissemination (TPD) remains unclear. Extended radical resection is the cornerstone for local treatment but the need for pleuro-pneumonectomy is debatable. Cytoreductive surgery with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) provides an alternative strategy to reduce tumor load and prevent pleural recurrence. Objective: The aim of this review was to provide an overview of current literature regarding HITHOC for TPD. Methods: A systematic literature review (PRISMA) was performed in the EMBASE, MEDLINE, Cochrane and Web of Science databases, resulting in 154 papers selected for screening (PROSPERO: CRD42020208242). Title, abstract, and full-text screening resulted in 13 papers subjected to structured data extraction and methodological quality assessment. One additional case from our department was included. Inclusion criteria were original research reporting on patients diagnosed with TPD; oncological outcome reporting; intraoperative HITHOC; and papers written in English, Dutch or German. Methodological quality was assessed using the Risk-of-Bias (RoB)-2 Tool and the Newcastle–Ottawa scale. Results: HITHOC for TPD was reported in 171 cases. HITHOC-related mortality was absent and morbidity was reported in three cases. Intrathoracic perfusion of a platinum-derivative, often combined with other chemotherapeutic drugs at >40°C for 60 min or longer was always used. Post-HITHOC recurrence was reported in 37/120 cases (31%). In patients with a minimal 1-year follow-up, average time to recurrence was 68.5 months. Conclusion: Combining cytoreductive surgery and HITHOC is feasible and safe for TPD. The strong heterogeneity in the literature impedes proper outcome analysis. More research is needed to better understand the additional benefit of HITHOC in the TPD setting. [ABSTRACT FROM AUTHOR]

Objective: As preservation of cognitive functioning increasingly becomes important in the light of ameliorated survival after intracranial tumor treatments, identification of eloquent brain areas would enable optimization of these treatments. Methods: This cohort study enrolled adult intracranial tumor patients who received neuropsychological assessments pre-irradiation, estimating processing speed, verbal fluency and memory. Anatomical magnetic resonance imaging scans were used for multivariate voxel-wise lesion-symptom predictions of the test scores (corrected for age, gender, educational level, histological subtype, surgery, and tumor volume). Potential effects of histological and molecular subtype and corresponding WHO grades on the risk of cognitive impairment were investigated using Chi square tests. P-values were adjusted for multiple comparisons (p <.001 and p <.05 for voxel- and cluster-level, resp.). Results: A cohort of 179 intracranial tumor patients was included [aged 19–85 years, median age (SD) = 58.46 (14.62), 50% females]. In this cohort, test-specific impairment was detected in 20–30% of patients. Higher WHO grade was associated with lower processing speed, cognitive flexibility and delayed memory in gliomas, while no acute surgery-effects were found. No grading, nor surgery effects were found in meningiomas. The voxel-wise analyses showed that tumor locations in left temporal areas and right temporo-parietal areas were related to verbal memory and processing speed, respectively. Interpretation: Patients with intracranial tumors affecting the left temporal areas and right temporo-parietal areas might specifically be vulnerable for lower verbal memory and processing speed. These specific patients at-risk might benefit from early-stage interventions. Furthermore, based on future validation studies, imaging-informed surgical and radiotherapy planning could further be improved. [ABSTRACT FROM AUTHOR]

Introduction: We hypothesized that increasing the pelvic integral dose (ID) and a higher dose per fraction correlate with worsening fatigue and functional outcomes in localized prostate cancer (PCa) patients treated with external beam radiotherapy (EBRT). Methods: The study design was a retrospective analysis of two prospective observational cohorts, REQUITE (development, n=543) and DUE-01 (validation, n=228). Data were available for comorbidities, medication, androgen deprivation therapy, previous surgeries, smoking, age, and body mass index. The ID was calculated as the product of the mean body dose and body volume. The weekly ID accounted for differences in fractionation. The worsening (end of radiotherapy versus baseline) of European Organisation for Research and Treatment of Cancer EORTC) Quality of Life Questionnaire (QLQ)-C30 scores in physical/role/social functioning and fatigue symptom scales were evaluated, and two outcome measures were defined as worsening in ≥2 (WS2) or ≥3 (WS3) scales, respectively. The weekly ID and clinical risk factors were tested in multivariable logistic regression analysis. Results: In REQUITE, WS2 was seen in 28% and WS3 in 16% of patients. The median weekly ID was 13.1 L·Gy/week [interquartile (IQ) range 10.2-19.3]. The weekly ID, diabetes, the use of intensity-modulated radiotherapy, and the dose per fraction were significantly associated with WS2 [AUC (area under the receiver operating characteristics curve) =0.59; 95% CI 0.55-0.63] and WS3 (AUC=0.60; 95% CI 0.55-0.64). The prevalence of WS2 (15.3%) and WS3 (6.1%) was lower in DUE-01, but the median weekly ID was higher (15.8 L·Gy/week; IQ range 13.2-19.3). The model for WS2 was validated with reduced discrimination (AUC=0.52 95% CI 0.47-0.61), The AUC for WS3 was 0.58, Conclusion: Increasing the weekly ID and the dose per fraction lead to the worsening of fatigue and functional outcomes in patients with localized PCa treated with EBRT. [ABSTRACT FROM AUTHOR]

Purpose: COVID-19 reached Belgium in February and quickly became a major public health challenge. It is of importance to evaluate the actual impact of COVID-19 on patients and staff in Belgian radiotherapy departments (RTDs). This was evaluated through a weekly national survey sent to departments measuring key factors that were affected by the pandemic. Materials and Methods: The Belgian SocieTy for Radiation Oncology (BeSTRO) together with the Belgian College for physicians in Radiation Oncology invited all 26 RTD to participate in a survey that started on March 2nd and was re- submitted weekly for 4 months to assess variations in time. The survey focused on: (1) the COVID-19 status of patients and staff; (2) the management of clinically suspected COVID patients and COVID positive patients; (3) the impact of COVID-19 on RTD activities; (4) its impact in radiotherapy indications and fractionation schemes. Results: Seventy-three percent of 26 RTDs completed the first survey and 57% responded to all weekly surveys. In the RTD staff, 24 members were COVID-positive of whom 67% were RTTs. Over the study period, the number of patients treated dropped by a maximum of 18.8% when compared to March 2nd. In 32.3% of COVID-positive and 54% of COVID suspected patients, treatment was continued without any interruptions. Radiotherapy indications were adapted within the 1st weeks of the survey in 47.4% of RTD, especially for urological and breast tumors. Fractionation schemes were changed in 68.4% of RTD, mainly for urological, breast, gastro-intestinal, and lung tumors. Conclusions: Between March and June 2020, the COVID-19 pandemic resulted in an important decrease in treatment activity in RTD in Belgium (18.8%). The COVID-19 infection status of patients influenced the continuity of the radiotherapy schedule. Changes in indications and fractionation schedules of radiotherapy were rapidly incorporated in the different RTD. [ABSTRACT FROM AUTHOR]

Purpose: Patients with a benign meningioma often have a long survival following the treatment of their meningioma. Since radiotherapy is frequently part of the treatment, long-term side effects are of considerable concern. A controversial long-term side effect of radiotherapy is stroke. Due to its severity, it is important to know the frequency of this side effect. The aim of this study was to assess the stroke incidence and risk factors among patients receiving radiotherapy for their benign meningioma. Methods: We performed a retrospective database study of patients who underwent primary or adjuvant radiotherapy for their benign meningioma at University Hospitals Leuven from January 2003 to December 2017. Results: We included 169 patients with a median age of 51 years (range 22–84). Every patient received fractionated radiotherapy using photons with a median dose of 56 Gy (range 54–56) in fractions of 2 Gy (range 1.8–2). The median follow-up was 5.3 years (range 0.1–14). The cumulative stroke incidence function showed an incidence of 11.6% after 9 years of follow-up, translating to a stroke incidence per year of 1.29%. We found two significant risk factors for stroke: medically treated arterial hypertension (p = 0.005) and history of previous stroke or transient ischemic attack (p < 0.001). 5-year local control and overall survival rates were respectively 97.4% and 91.2%. Other late grade III/IV toxicities occurred in 16.0% (27/169) of patients. Conclusion: Our study shows a higher incidence of stroke in patients who received radiotherapy for their benign meningioma compared to the general population. [ABSTRACT FROM AUTHOR]

Background: REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) is an international prospective cohort study. The purpose of this project was to analyse a cohort of patients recruited into REQUITE using a deep learning algorithm to identify patient-specific features associated with the development of toxicity, and test the approach by attempting to validate previously published genetic risk factors. Methods: The study involved REQUITE prostate cancer patients treated with external beam radiotherapy who had complete 2-year follow-up. We used five separate late toxicity endpoints: ≥grade 1 late rectal bleeding, ≥grade 2 urinary frequency, ≥grade 1 haematuria, ≥ grade 2 nocturia, ≥ grade 1 decreased urinary stream. Forty-three single nucleotide polymorphisms (SNPs) already reported in the literature to be associated with the toxicity endpoints were included in the analysis. No SNP had been studied before in the REQUITE cohort. Deep Sparse AutoEncoders (DSAE) were trained to recognize features (SNPs) identifying patients with no toxicity and tested on a different independent mixed population including patients without and with toxicity. Results: One thousand, four hundred and one patients were included, and toxicity rates were: rectal bleeding 11.7%, urinary frequency 4%, haematuria 5.5%, nocturia 7.8%, decreased urinary stream 17.1%. Twenty-four of the 43 SNPs that were associated with the toxicity endpoints were validated as identifying patients with toxicity. Twenty of the 24 SNPs were associated with the same toxicity endpoint as reported in the literature: 9 SNPs for urinary symptoms and 11 SNPs for overall toxicity. The other 4 SNPs were associated with a different endpoint. Conclusion: Deep learning algorithms can validate SNPs associated with toxicity after radiotherapy for prostate cancer. The method should be studied further to identify polygenic SNP risk signatures for radiotherapy toxicity. The signatures could then be included in integrated normal tissue complication probability models and tested for their ability to personalize radiotherapy treatment planning. [ABSTRACT FROM AUTHOR]

Background: Our aim is to report treatment efficacy and toxicity of patients treated by robotic (Cyberknife®) stereotactic body radiotherapy (SBRT) for oligorecurrent lung metastases (ORLM). Additionally we wanted to evaluate influence of tumor, patient and treatment related parameters on local control (LC), lung and distant progression free- (lung PFS/Di-PFS) and overall survival (OS).Methods: Consecutive patients with up to 5 ORLM (confirmed by FDG PET/CT) were included in this study. Intended dose was 60Gy in 3 fractions (prescribed to the 80% isodose volume). Patients were followed at regular intervals and tumor control and toxicity was prospectively scored. Tumor, patient and treatment data were analysed using competing risk- and Cox regression.Results: Between May 2010 and March 2016, 104 patients with 132 lesions were irradiated from primary lung carcinoma (47%), gastro-intestinal (34%) and mixed primary histologies (19%). The mean tumor volume was 7.9 cc. After a median follow up of 22 months, the 1, 2 and 3 year LC rate (per lesion) was 89.3, 80.0 and 77.8% respectively. The corresponding (per patient) 1, 2 and 3 years lung PFS were 66.3, 50.0, 42.6%, Di-PFS were 80.5, 64.4, 60.6% and OS rates were 92.2, 80.9 and 72.0% respectively. On univariable analysis, gastro-intestinal (GI) as primary tumor site showed a significant superior local control versus the other primary tumor sites. For OS, significant variables were primary histology and primary tumor site with a superior OS for patients with metastases of primary GI origin. LC was significantly affected by the tumor volume, physical and biologically effective dose coverage. Significant variables in multivariable analysis were BED prescription dose for LC and GI as primary site for OS. The vast majority of patients developed no toxicity or grade 1 acute and late toxicity. Acute and late grade 3 radiation pneumonitis (RP) was observed in 1 and 2 patients respectively. One patient with a centrally located lesion developed grade 4 RP and died due to possible RT-induced pulmonary hemorrhage.Conclusions: SBRT is a highly effective local therapy for oligorecurrent lung metastases and could achieve long term survival in patients with favourable prognostic features. [ABSTRACT FROM AUTHOR]

View large Download slide View large Download slide OBJECTIVES Combined modality treatment (CMT) for malignant pleural mesothelioma (MPM) remains a matter of debate regarding the choice of surgical procedure: extrapleural pneumonectomy (EPP) or pleurectomy/decortication. METHODS We performed a prospective interventional cohort study between 2003 and 2014. All consecutive patients with any histological MPM subtype, ≤70 years old, World Health Organization performance status ≤1, medically fit for pneumonectomy and stage cT1-2cN0-2cM0 (TNM7) or lower were included. Eligibility for CMT was discussed by the multidisciplinary tumour board. Our local CMT protocol consisted of induction chemotherapy, followed by EPP and hemithoracic radiotherapy. Induction chemotherapy consisted of 3 cycles of cisplatin (75 mg/m2 day 1) and pemetrexed (500 mg/m2 day 1), each administered once every 3 weeks. If non-progressive, EPP was performed followed by hemithoracic radiotherapy (most frequently, intensity-modulated radiotherapy; dose 54 Gy/1.8 Gy ± boost). Feasibility and long-term survival analyses were performed. Overall survival and disease-free survival (DFS) were calculated from histological confirmation of a diagnosis of MPM. RESULTS Out of 197 patients, 97 started with CMT (79 epithelioid, 15 mixed and 3 sarcomatoid tumours, based on histological analysis). Clinical TNM was IA (n  = 9)/IB (n  = 8)/II (n  = 57)/III (n  = 23). A total of 76 patients underwent surgery (EPP: n  = 56; exploratory thoracotomy: n  = 20). The in-hospital mortality rate was 3.6%. Out of 56 patients who underwent surgery, 47 completed the entire CMT protocol. The intent-to-treat median and 5-year OS were 22.4 [95% confidence interval (CI) = 15.5–27.9] months and 11.2% (95% CI = 6.9–23.4). In patients who completed the CMT protocol (n  = 47), these values were 33.2 (95% CI = 23.0–45.0) months and 24.2% (95% CI = 13.4–43.8). The intent-to-treat median and 5-year DFS were 15.6 (95% CI = 14.0–17.3) months and 9.9% (95% CI = 5.1–19.2), 19.8 (95% CI = 16.8–27.7) months and 17.2% (95% CI = 8.6–34.1) in those who had the full CMT. The Cox proportional hazards model showed a significantly lower DFS in positive lymph nodes (HR 2.79, 95% CI=1.35-5.78; P =0.006). In 30 (64%) patients with epithelioid type MPM without positive lymph nodes (pN0) after EPP, the 5-year DFS was 27.0% (95% CI=14.1-51.7). CONCLUSIONS CMT with EPP for MPM is feasible, with an acceptable surgical mortality rate, and results in a 5-year survival rate of 24%. Careful patient selection (staging and physical performance) is extremely important. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Current guidelines recommend preoperative invasive mediastinal staging in centrally located tumours with negative mediastinum on positron emission tomography-computed tomography, based on a 20-30% prevalence of occult mediastinal disease (pN2-3). However, a uniform definition of central tumour location is lacking. Our objective was to determine the best definition in predicting occult pN2-3. METHODS: A single-institution database was queried for patients with (suspected) non-small-cell lung cancer staged cN0 after positron emission tomography-computed tomography and referred to invasive staging and/or primary surgery. We evaluated 5 definitions: inner 1/3, inner 2/3, contact with bronchovascular structures, <_2 cm from bronchus or endobronchial visualization. RESULTS: Between 2005 and 2015, 813 patients were eligible (cT1: 42%, cT2: 28%, cT3: 17% and cT4: 11%). Invasive mediastinal staging and resection were performed in 30% and 97% of patients, respectively. Any nodal upstaging (pN+) was found in 21% of patients, of whom pN2-3 was found in 8%. Central tumour location demonstrated 4 times higher odds for any pN+ [for inner 1/3 vs outer 2/3, odds ratio 3.90 (95% confidence interval 2.24-6.77), P < 0.001], whereas no significantly different odds was observed for pN2-3. The discriminative ability for pN+ was not significantly different between the several definitions. CONCLUSIONS: The prevalence of occult pN2-3 was only 8% when modern fusion positron emission tomography-computed tomography imaging pointed at clinical N0 non-small-cell lung cancer. None of the 5 verified definitions of centrality was predictive for occult pN2-3. However, each definition of centrality was related to any pN+ at a prevalence of 21%, without significant differences in discriminative ability between definitions. These data question whether indication for preoperative invasive mediastinal staging should be based on centrality alone. [ABSTRACT FROM AUTHOR]

The article offers information on the standards of care in high-dose radiotherapy for treatment of localized non-small cell lung cancer (NSCLC). Topics discussed include the importance of stereotactic body radiotherapy (SBRT) in treatment of early stage NSCLC, the risk associated with the use of this treatment method, and the use of radiotherapy for the treatment of stage III NSCLC.

Purpose: Prolonged postoperative ileus (PPOI) after colorectal resection significantly impacts patients' recovery and hospital stay. Because treatment options for PPOI are limited, it is necessary to focus on prevention strategies. The aim of this study is to investigate risk factors associated with PPOI in patients undergoing colorectal surgery. Methods: Data from all consecutive patients who underwent colorectal resection in our department were retrospectively analyzed from a prospective database over a 9-month period. PPOI was defined as the necessity to insert a nasogastric tube in a patient who experienced nausea and two episodes of vomiting with absence of bowel function. Multivariable analysis was performed considering a prespecified list of 16 potential preoperative risk factors. Results: A total of 523 patients (mean age 59 years; 52.2% males) were included, and 83 patients (15.9%) developed PPOI. Statistically significant independent predictors of PPOI were male sex (OR 2.07; P = 0.0034), open resection (OR 4.47; P < 0.0001), conversion to laparotomy (OR 4.83; P = 0.0015), splenic flexure mobilization (OR 1.72; P = 0.063), and rectal resection (OR 2.72; P = 0.0047). Discriminative ability of this prediction model was 0.72. Conclusions: Therapeutic strategies aimed to prevent PPOI after colorectal resection should focus on patients with increased risk. Patients and medical staff can be informed of the higher PPOI risk, so that early treatment can be started. [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: Mucosal damage is an important and debilitating side effect when treating head and neck cancer patients with (chemo-)radiation. The aim of this randomized clinical trial was to investigate whether the addition of a neutral, supersaturated, calcium phosphate (CP) mouth rinse benefits the severity and duration of acute mucositis in head and neck cancer patients treated with (chemo)radiation.Materials and Methods: A total of 60 patients with malignant neoplasms of the head and neck receiving (chemo)radiation were included in this study. Fifty-eight patients were randomized into two treatment arms: a control group receiving standard of care (n = 31) and a study group receiving standard of care + daily CP mouth rinses (n = 27) starting on the first day of (chemo-)radiation. Oral mucositis and dysphagia were assessed twice a week using the National Cancer Institute common toxicity criteria scale version 3, oral pain was scored with a visual analogue scale.Results: No significant difference in grade III mucositis (59 vs. 71 %; p = 0.25) and dysphagia (33 vs. 42 %, p = 0.39) was observed between the study group compared to the control group. Also no significant difference in time until development of peak mucositis (28.6 vs. 28.7 days; p = 0.48), duration of peak mucositis (22.7 vs. 24.6 days; p = 0.31), recuperation of peak dysphagia (20.5 vs 24.2 days; p = 0.13) and occurrence of severe pain (56 vs. 52 %, p = 0.5).Conclusion: In this randomized study, the addition of CP mouth rinse to standard of care did not improve the frequency, duration or severity of the most common acute toxicities during and early after (chemo)radiation. There is currently no evidence supporting its standard use in daily practice. [ABSTRACT FROM AUTHOR]

Objectives: Mucosal damage is an important and debilitating side effect when treating head and neck cancer patients with (chemo-)radiation. The aim of this randomized clinical trial was to investigate whether the addition of a neutral, supersaturated, calcium phosphate (CP) mouth rinse benefits the severity and duration of acute mucositis in head and neck cancer patients treated with (chemo)radiation. Materials and methods: A total of 60 patients with malignant neoplasms of the head and neck receiving (chemo)radiation were included in this study. Fifty-eight patients were randomized into two treatment arms: a control group receiving standard of care ( n = 31) and a study group receiving standard of care + daily CP mouth rinses ( n = 27) starting on the first day of (chemo-)radiation. Oral mucositis and dysphagia were assessed twice a week using the National Cancer Institute common toxicity criteria scale version 3, oral pain was scored with a visual analogue scale. Results: No significant difference in grade III mucositis (59 vs. 71 %; p = 0.25) and dysphagia (33 vs. 42 %, p = 0.39) was observed between the study group compared to the control group. Also no significant difference in time until development of peak mucositis (28.6 vs. 28.7 days; p = 0.48), duration of peak mucositis (22.7 vs. 24.6 days; p = 0.31), recuperation of peak dysphagia (20.5 vs 24.2 days; p = 0.13) and occurrence of severe pain (56 vs. 52 %, p = 0.5). Conclusion: In this randomized study, the addition of CP mouth rinse to standard of care did not improve the frequency, duration or severity of the most common acute toxicities during and early after (chemo)radiation. There is currently no evidence supporting its standard use in daily practice. [ABSTRACT FROM AUTHOR]

Purpose: In 10-24% of patients with rectal cancer who are treated with neoadjuvant chemoradiation, no residual tumor is found after surgery (ypT0). When accurately selected, these complete responders might be considered for less invasive treatments instead of standard surgery. So far, no imaging method has proven reliable. This study was designed to assess the accuracy of diffusion-weighted MRI (DWI) in addition to standard rectal MRI for selection of complete responders after chemoradiation. Methods: A total of 120 patients with locally advanced rectal cancer from three university hospitals underwent chemoradiation followed by a restaging MRI (1.5T), consisting of standard T2W-MRI and DWI (b0-1000). Three independent readers first scored the standard MRI only for the likelihood of a complete response using a 5-point confidence score, after which the DWI images were added and the scoring was repeated. Histology (ypT0 vs. ypT1-4) was the standard reference. Diagnostic performance for selection of complete responders and interobserver agreement were compared for the two readings. Results: Twenty-five of 120 patients had a complete response (ypT0). Areas under the ROC-curve for the three readers improved from 0.76, 0.68, and 0.58, using only standard MRI, to 0.8, 0.8, and 0.78 after addition of DWI ( P = 0.39, 0.02, and 0.002). Sensitivity for selection of complete responders ranged from 0-40% on standard MRI versus 52-64% after addition of DWI. Specificity was equally high (89-98%) for both reading sessions. Interobserver agreement improved from κ 0.2-0.32 on standard MRI to 0.51-0.55 after addition of DWI. Conclusions: Addition of DWI to standard rectal MRI improves the selection of complete responders after chemoradiation. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the use of FDG-PET/CT before, during and after chemoradiotherapy (CRT) and diffusion-weighted magnetic resonance imaging (DW-MRI) before CRT for the prediction of pathological response (pCR) in rectal cancer patients. Material and methods. Twenty-two rectal cancer patients treated with long course CRT were included. An FDG-PET/CT was performed prior to the start of CRT, after 10 to 12 fractions of CRT and five weeks after the end of CRT. The tumor was delineated using a gradient based delineation method and the maximal standardized uptake values (SUVmax) were calculated. A DW-MRI was performed before start of CRT. Mean apparent diffusion coefficients (ADC) were determined. The ΔSUVmax during and after CRT and the initial ADC values were correlated to the histopathological findings after total mesorectal excision (TME). Results. ΔSUVmax during and after CRT significantly correlated with the pathological response to treatment (during CRT: ΔSUVmax = 59% ± 12% for pCR vs. 25% ± 27% if no pCR, p=0.0036; post-CRT: 90% ± 11 for pCR vs. 63% ± 22 if no pCR p=0.013). ROC curve analysis revealed an optimal threshold for ΔSUVmax of 40% during CRT and 76% after CRT. The initial ADC value was also significantly correlated with pCR (0.94 ± 0.12 × 10−3 mm2/s for pCR vs. 1.2 ± 0.24 × 10−3 mm2/s, p=0.002) and ROC curve analysis revealed an optimal threshold of 1.06 × 10−3 mm2/s. Combining the provided ΔSUVmax thresholds during and after CRT increased specificity of the prediction (sensitivity 100% and specificity 94%). The combination of the thresholds for the initial ADC value and the ΔSUVmax during CRT increased specificity of the prediction to a similar level (sensitivity of 100% and specificity of 94%). Conclusions. The combination of the different time points and the different imaging modalities increased the specificity of the response assessment both during and after CRT. [ABSTRACT FROM AUTHOR]

In the head and neck, squamous cell carcinoma is one of the most common tumour types. Currently, the primary imaging modalities for initial locoregional staging are computed tomography and—to a lesser extent—magnetic resonance imaging, whilst [18F]fluorodeoxyglucose (FDG) positron emission tomography has additional value in the detection of subcentimetric metastatic lymph nodes and of tumour recurrence after chemoradiotherapy (CRT). However, dependency on the morphological and size-related criteria of anatomical imaging and the limited spatial resolution and FDG avidity of inflammation in metabolic imaging may reduce diagnostic accuracy in the head and neck. Diffusion-weighted magnetic resonance imaging (DWI) is a noninvasive imaging technique that measures the differences in water mobility in different tissue microstructures. Water mobility is likely influenced by cell size, density, and cellular membrane integrity and is quantified by means of the apparent diffusion coefficient. As such, the technique is able to differentiate tumoural tissue from normal tissue, inflammatory tissue and necrosis. In this article, we examine the use of DWI in head and neck cancer, focussing on technique optimization and image interpretation. Afterwards, the value of DWI will be outlined for clinical questions regarding nodal staging, lesion characterization, differentiation of post-CRT tumour recurrence from necrosis and inflammation, and predictive imaging towards treatment outcome. The possible consequences of adding DWI towards therapeutic management are outlined. [ABSTRACT FROM AUTHOR]

Simple Summary: Over the last 5 years, immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of non-small cell lung cancer (NSCLC) as either monotherapy or in combination with chemo- and/or radiotherapy. However, despite these advances, outcome still remains poor for most patients and there is still a lot of room to improve prognosis in these patients. To date, we have no tools that allow us to identify the patients that will benefit from chemo- and/or radiotherapy combined with immunotherapy, what treatment-induced immune changes can be expected, and what are the most optimal treatment combinations. Therefore, prognostic and predictive immunological biomarkers are urgently needed. This prospective exploratory study aimed to identify potential prognostic and predictive immune-related proteins that are associated with progression-free survival in patients with stage I/III NSCLC. The results of this trial provide a good starting point to implement blood-based immune profiling analyses in future clinical trials. Radiotherapy (RT) and chemotherapy can induce immune responses, but not much is known regarding treatment-induced immune changes in patients. This exploratory study aimed to identify potential prognostic and predictive immune-related proteins associated with progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). In this prospective study, patients with stage I NSCLC treated with stereotactic body radiation therapy (n = 26) and patients with stage III NSCLC treated with concurrent chemoradiotherapy (n = 18) were included. Blood samples were collected before (v1), during (v2), and after RT (v3). In patients with stage I NSCLC, CD244 (HR: 10.2, 95% CI: 1.8–57.4) was identified as a negative prognostic biomarker. In patients with stage III NSCLC, CR2 and IFNGR2 were identified as positive prognostic biomarkers (CR2, HR: 0.00, 95% CI: 0.00–0.12; IFNGR2, HR: 0.04, 95% CI: 0.00–0.46). In addition, analysis of the treatment-induced changes of circulating protein levels over time (Δv2/v3−v1) also identified CXCL10 and IL-10 as negative predictive biomarkers (CXCL10, HR: 3.86, 95% CI: 1.0–14.7; IL-10, HR: 16.92 (2.74–104.36)), although serum-induced interferon (IFN) response was a positive prognostic. In conclusion, we identified several circulating immunogenic proteins that are correlated with PFS in patients with stage I and stage III NSCLC before and during treatment. [ABSTRACT FROM AUTHOR]

Background: Gene expression of specific therapeutic targets in non-malignant lung tissue might play an important role in optimizing targeted therapies. This study aims to identify different expression patterns of fifteen genes important for targeted therapy in non-small cell lung cancer (NSCLC).Methods: We prospectively collected tissue of NSCLC and non-malignant lung tissue from 25 primary resected patients. RNA-sequencing and 450 K methylation array profiling was applied to both NSCLC and non-malignant lung tissue and data were analyzed for 14 target genes. We analyzed differential expression and methylation as well as expression according to patient characteristics like smoking status, histology, age, chronic obstructive pulmonary disease, C-reactive protein (CRP) and gender. TCGA data served as a validation set.Results: Nineteen men and 6 women were included. Important targets like PD-L2 (p = 0.035), VEGFR2 (p < 0.001) and VEGFR3 (p < 0.001) were downregulated (respective fold changes = 1.8, 3.1, 2.7, 3.5) in tumor compared to non-malignant lung tissue. The TCGA set confirmed these findings almost universally. PD-L1 (p < 0.001) became also significantly downregulated in the TCGA set. In NSCLC, MUC1 (p = 0.003) showed a higher expression in patients with a CRP < 5 mg/L compared to > 5 mg/L. In the TCGA data but not in our primary data, PD-L1 & 2 were both borderline more expressed in tumors of active smokers vs. tumors of ex-smokers (p = 0.044 and 0.052).Conclusions: Our results suggest a lower PD-L1 & 2 and VEGFR expression in NSCLC vs. non-malignant lung tissue. Specific patient characteristics did not seem to change the overall expression differences as they were in line with the overall results. This information may contribute to the optimization of targeted treatments. [ABSTRACT FROM AUTHOR]