A phase III randomized-controlled, single-blind trial to improve quality of life with stereotactic body radiotherapy for patients with painful bone metastases (ROBOMET)

Background Bone metastases represent an important source of morbidity in cancer patients, mostly due to severe pain. Radiotherapy is an established symptomatic treatment for painful bone metastases, however, when conventional techniques are used, the effectiveness is moderate. Stereotactic body radiotherapy (SBRT), delivering very high doses in a limited number of fractions in a highly conformal manner, could potentially be more effective and less toxic. Methods This is a phase III, randomized-controlled, single-blind, multicenter study evaluating the response rate of antalgic radiotherapy for painful bone metastases and the acute toxicity associated with this treatment. A total of 126 patients will be randomly assigned to receive either the standard schedule of a single fraction of 8.0 Gy delivered through three-dimensional conformal radiotherapy or a single fraction of 20.0 Gy delivered through SBRT. Primary endpoint is pain response at the treated site at 1 month after radiotherapy. Secondary endpoints are pain flare at 24-48-72 h after radiotherapy, duration of pain response, re-irradiation need, acute toxicity, late toxicity, quality of life and subsequent serious skeletal events. In a supplementary analysis, patient-compliance for a paper-and-pencil questionnaire will be compared with an electronic mode. Discussion If a dose-escalated approach within the context of single fraction stereotactic body radiotherapy could improve the pain response to radiotherapy and minimize acute toxicity, this would have an immediate impact on the quality of life for a large number of patients with advanced cancer. Potential disadvantages of this technique include increased pain flare or a higher incidence of radiation-induced fractures. Trial registration: The Ethics committee of the GZA Hospitals (B099201732915) approved this study on September 4th 2018. Trial registered on Clinicaltrials. gov (NCT03831243) on February 5th 2019

Challenges in rectal cancer radiotherapy: optimizing target volume delineation and response prediction.

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The role of diffusion-weighted MRI and (18)F-FDG PET/CT in the prediction of pathologic complete response after radiochemotherapy for rectal cancer: A systematic review

After neoadjuvant radiochemotherapy (RCT) for locally advanced rectal cancer, 15-27% of the patients experience a pathological complete response (pCR). This observation raises the question as to whether invasive surgery could be avoided in a selected cohort of patients who obtain a clinical complete response after preoperative RCT. In this respect, there has been growing interest in functional imaging techniques to improve clinical response assessment. This systematic review focuses on the role of diffusion-weighted imaging (DWI) and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the prediction of pCR after RCT for rectal cancer. A total of 14 publications on DWI and 25 on (18)F-FDG PET/CT were retrieved. Pooled analysis of individual patient data shows both imaging modalities have a low positive predictive value in the prediction of pCR (mean PPV of 54% and 39% for DWI- and (18)F-FDG PET/CT-based parameters respectively). Especially pre-RCT imaging is unable to predict pCR with overall accuracies of 68-72% for DWI and 44% for (18)F-FDG PET/CT. Qualitative DWI assessment 5-10weeks after the end of RCT may outperform apparent diffusion coefficient (ADC)-based DWI-parameters (overall accuracy of 87% vs. 74-78%). Although few data are available, early changes in FDG-uptake seem promising in the prediction of pCR and the role of (18)F-FDG PET/CT during RCT should be further investigated. Quantitative and qualitative (18)F-FDG PET/CT measurements are equally effective in the assessment of pCR after RCT. The major strength of DWI and (18)F-FDG PET/CT lies in the identification of non-responders who are not candidates for organ preservation. Up to now, DWI and (18)F-FDG PET/CT are not accurate enough to safely select patients for organ-sparing strategies. Future research must focus on the integration of functional imaging with clinical data and molecular biomarkers.publisher: Elsevier articletitle: The role of diffusion-weighted MRI and 18F-FDG PET/CT in the prediction of pathologic complete response after radiochemotherapy for rectal cancer: A systematic review journaltitle: Radiotherapy and Oncology articlelink: http://dx.doi.org/10.1016/j.radonc.2014.11.026 content_type: article copyright: Copyright © 2014 Elsevier Ireland Ltd.status: publishe

Does a central review platform improve the quality of radiotherapy for rectal cancer? Results of a national quality assurance project

Background and purpose Quality assurance (QA) for radiation treatment has become a priority since poorly delivered radiotherapy can negatively influence patient outcome. Within a national project we evaluated the feasibility of a central review platform and its role in improving uniformity of clinical target volume (CTV) delineation in daily practice. Material and methods All Belgian radiotherapy departments were invited to participate and were asked to upload CTVs for rectal cancer treatment onto a secured server. These were centrally reviewed and feedback was given per e-mail. For each five consecutive patients per centre, the overlap parameter dice coefficient (DC) and the volumetric parameters volumetric ratio (RV) and commonly contoured volume (VCC) were calculated. Results Twenty departments submitted 1224 eligible cases of which 909 were modified (74.3%). There was a significant increase in RV and VCC between the first ten patients per centre and the others. This was not seen for DC. Statistical analysis did not show a further significant improvement in delineation over the entire review period. Conclusion Central review was feasible and increased the uniformity in CTV delineation in the first ten rectal cancer patients per centre. The observations in this study can be used to optimize future QA initiatives. © 2014 Elsevier Ireland Ltd. All rights reserved

Can clinical factors be used as a selection tool for an organ-preserving strategy in rectal cancer?

BACKGROUND: Rectal cancer patients who achieve a good response to chemoradiotherapy (CRT), may be offered less invasive surgery or even no surgery at all. Implementation of such a policy, however, requires precise patient selection. This study identifies pretreatment clinical factors that are associated with pathological complete response (pCR) and ypT0-1N0 and evaluates their performance as a selection tool for organ-preserving strategies. MATERIAL AND METHODS: Patients with rectal cancer treated with CRT and total mesorectal excision between January 2000 and December 2014 were retrospectively included. Following clinical characteristics were extracted from the medical files: age, gender, body mass index, ASA score, cT-stage, cN-stage, distance from the anal verge, pretreatment carcinoembryonic antigen (CEA), pretreatment hemoglobin and distance from the mesorectal fascia. Univariable and multivariable binary logistic regression models were used to predict pCR and ypT0-1N0. The discriminative ability of the prediction models was evaluated by receiver operating characteristic analysis. RESULTS: A total of 620 patients were included of whom 120 experienced a pCR (19%) and 170 patients achieved ypT0-1N0 response (27%). A low pretreatment CEA, a high pretreatment hemoglobin and a high cN-stage were associated with pCR in multivariable analysis. A low pretreatment CEA, a low cT-stage and a high cN-stage were associated with ypT0-1N0. After cross validation, the area under the curve for the pCR and ypT0-1N0 prediction model equaled 0.609 and 0.632, respectively. CONCLUSION: Despite their statistical significance, the value of pretreatment clinical variables in the prediction of pCR and ypT0-1N0 is very limited. To safely select patients for organ preservation, other strategies need to be explored.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=ionc20status: publishe

Synthesis of Coumarin Derivatives and Sensing Heavy Metal Ions in Aqueous Solution

屬離子在生物體內扮演極重要的角色，過量或不足均會影響機能的正常，因此如何感測生物體內的金屬離子變成一項不可或缺的研究目的，而具有螢光的化學感測器可作為分析生物體內重要元素的工具。本研究的目的在於利用香豆素(coumarin)衍生物經由光誘導電子轉移機制(Photoinduced Electron Transfer, PET)設計出對特定金屬離子有專一感測能力的螢光感測器。此外，也藉由分子結構上的設計來增加感測器的水溶性，提高未來應用在生物體內的實用性。 如下圖所示，CDC-O利用雜氮冠醚作為金屬離子辨識單元，並且利用兩個羧酸基來增加其水溶性，由實驗可知對鉛離子具有選擇性使螢光增強。CDC-S則是把冠醚中的氧原子改成了硫原子，期望會對較軟性的金屬具有辨識效果，實驗結果顯示果然如預期的對比鉛離子較軟的汞離子具有選擇性。此外，CDC-Asp則是利用天冬胺酸(aspartic acid)為辨識單元，希望利用胺基增加與金屬離子的辨識結合位置，此外，天冬胺酸也是已知對汞離子具有辨識能力的接收端，實驗證明也如預期的對汞離子具有選擇性而使螢光增強。CDC-DPA則是以會與鋅離子作選擇性結合的二吡啶甲基胺作為分子辨識單元，成為一水溶性鋅離子螢光探針。As more critical environment pollution around the world, top consumers in the food chains, such as human, might be expected to accumulate environmental contaminants, especially the toxic heavy metal ions, thus research for sensing heavy metal ions has attracted more concern, particularly for water-soluble probes. Herein we report a series of coumarin-based fluorescent metal ion probes, ketoaminocoumarin is selected as a signal transducing-unit owing to its high photostability and visible excitation wavelength, the fluorescent enhancement can be rationalized via inhibition of photoinduced electron transfer. CDC-O and CDC-S have a dicarboxylate pseudocrown receptor designed to satisfy the size and charge requirements of the metal cation, and improve water compatibility of water. We use sulfer atom in the receptor unit of CDC-S, wish it would sense softer metal ions than CDC-O does. We also use aspartic acid and dipicolylamine as the molecular recognition unit for CDC-Asp and CDC-DPA, which are reported receptor and selectively for mercury and zinc ions

Completeness of Reporting Oligometastatic Disease Characteristics in Literature and Influence on Oligometastatic Disease Classification Using the ESTRO/EORTC Nomenclature

PURPOSE There is increasing evidence for the integration of locally ablative therapy into multimodality treatment of oligometastatic disease (OMD). To support standardised data collection, analysis, and comparison, a consensus OMD classification based on fundamental disease and treatment characteristics has previously been established. This study investigated the completeness of reporting the proposed OMD characteristics in literature and evaluated whether the proposed OMD classification system can be applied to the historical data. METHODS AND MATERIALS A systematic literature review was performed in Medline, Embase, and Cochrane, searching for prospective and retrospective studies, where stereotactic body radiation therapy was a treatment component of OMD. Reporting of the OMD characteristics as described in the European Organisation for Research and Treatment of Cancer/European Society for Radiotherapy and Oncology classification was analyzed, feasibility to retrospectively classify the proposed OMD states was investigated, and the effect of the categorization on overall survival (OS) was evaluated. RESULTS Our study shows incomplete reporting of the proposed OMD characteristics. The most fully reported characteristic was type of involved organs (88/95 studies); history of cancer progression was the least reported (not mentioned in 50/95 studies). Retrospective OMD classification of existing literature was only possible for 7 of the95 studies. With respect to categorization as de novo, repeat, or induced OMD, homogeneous patient cohorts were observed in 21 of the 95 studies, most frequently de novo OMD in 20 studies. Differences in OS at 2, 3, or 5 years were not statistically significant between the different states. OS was significantly influenced by primary tumor histology, with superior OS observed for prostate cancer and worst OS observed for non-small cell lung cancer. CONCLUSIONS The largely incomplete reporting of the proposed OMD characteristics hampers a retrospective classification of existing literature. To facilitate future comparison of individual studies, as well as validation of the OMD classification, comprehensive reporting of OMD characteristics using standardised terminology is recommended, as proposed by the European Organisation for Research and Treatment of Cancer/European Society for Radiotherapy and Oncology classification system and following European Society for Radiotherapy and Oncology -American Society for Radiation Oncology consensus