Number Of Prospective Clinical Trials Research Articles

The incidence and intensity of postoperative pain and Flare-up following the use of three different intracanal medicaments in teeth with posttreatment apical periodontitis: a randomized clinical trial

ObjectivesThis randomized clinical trial aimed to compare the effect of intracanal medicaments on the incidence of postoperative pain and flare-up with posttreatment apical periodontitis (PTAP) of retreatment cases.Materials and methodsOne hundred twenty patients diagnosed with PTAP with single-rooted teeth with single-canal without spontaneous pain or swellings were included and randomly divided into three groups according to the intracanal medicament used. Intracanal medicaments were placed into the root canals following the removal of previous root canal fillings and re-instrumentation. Calcium hydroxide (Ca (OH)2), chlorhexidine gel (CHX), calcium hydroxide and chlorhexidine gel combinations were used as intracanal medicaments. Postoperative pain scores were recorded at 6 and 12 h and 1, 2, 3, 4, 5, 6, and 7 days using a visual analog scale (VAS). Sensitivity on percussion, spontaneous pain, swelling, antibiotic and analgesic requirements of the patients were evaluated during clinical examinations performed postoperatively after 2 and 7 days.ResultsThere were no statistically significant differences between groups in terms of VAS scores following the intracanal medicament application (p > 0.05). However, compared to the patients of 20–34 and 50–65 age groups, greater VAS scores were observed in patients of 35–49 age groups at 12 h, and 3, 4, 7 days (p < 0.05). Flare-up was observed in only one patient in the CHX gel group, and no flare-up was observed in other groups.ConclusionsSimilar postoperative pain incidence in all experimental groups indicates that all three medicaments are clinically acceptable in inter-appointment management of retreatment cases in terms of post-endodontic pain and flare-up.Clinical relevanceIn this randomized clinical trial, three different intracanal medicaments were utilized in nonsurgical endodontic retreatment and their effect on postoperative pain and flare-up incidence was examined. Thus, this study will be a significant contribution in the decision-making during clinical practice; since there are a limited number of prospective clinical trials in the literature about the severity of pain following retreatment procedures including intracanal medicament use.

MD Anderson Phase III Randomized Preoperative Stereotactic Radiosurgery (SRS) vs. Postoperative SRS for Brain Metastases Trial

Postoperative stereotactic radiation therapy/radiosurgery (SRT/SRS) is being evaluated in comparison to Preoperative SRT for brain metastases (mets) in a limited number of prospective clinical trials. Our objective is to address the significant knowledge gap concerning the logistics of preoperative SRT in comparison to postoperative SRT in a randomized controlled study. Patients with brain mets with at least 1 surgically operable met were randomized (1:1) to Preop vs Postop SRT. In this abstract, we present non-primary endpoint data on the trial concept and logistics of treatment for this data safety monitoring board reviewed study. Patients enrolled had 1-2 lesions resected and <15 lesions treated at time of SRT to best reflect the standard population that receive SRT and surgery at our institution. From 12/2018 to 12/2022, 99 patients with 1-2 operable brain mets were enrolled and randomized to Preop (n = 49) or Postop (n = 50) SRT. Males represented 56% of the cohort compared to females, and <25% were age 18-49 years, while 27%, 29, and 19% respectively were 50-59, 60-69, and > = 70. The most frequent histologies enrolled were lung (29%), renal cell (15%), melanoma (14%), and breast (11%) cancers. The majority of patients (83%) had 1-4 brain mets on their baseline MRI and 91% subsequently had a single lesion resected. Seventy-nine patients completed both SRT and surgery, while 9% received no therapy due to drop out before study therapy initiation. Among patients receiving both therapies in the combined cohort, 68% received a non-invasive stereotactic radiosurgery instrument to the randomized cavity lesion compared to 32% receiving LINAC based SRT. Treatment of the lesion or cavity with single fraction SRT was 51% in the Preop arm vs 31% in the Postop arm. Multi-fraction (3-5 SRT) was 67% in the Postop cohort in contrast to 47% in the Preop cohort. Time from randomization to RT was 5.6 days and 33.7 days in the Preop and Postop cohorts respectively, and for surgery was 10.2 days vs 12.9 days in the Postop vs Preop cohorts. The average time from RT to surgery was 7.3 days in the Preop arm and 23.5 days in the Postop arm (to allow for incisional healing time). In one of the early initiated randomized prospective cohorts of Preop vs Postop SRT, we demonstrated logistical feasibility with an efficient clinical trial workflow for study treatment. Differences in Preop vs Postop logistics reflect clinical practice differences in time-to-treatment. Therapy with various modalities reflected real-world practice and possibly provider preferences in technique when addressing the nature of delineating cavities and changes in cavity volume with regard to fractionation. Independent of the primary outcomes, our data provides insights in the practical management of patients receiving these two modalities of therapy, and further data at the completion of trial will address relevant primary outcomes.

On target methods to induce abscopal phenomenon for Off-Target effects: From happenstance to happenings.

Although the "abscopal phenomenon" has been described several decades ago, this phenomenon lately has been obtaining momentous traction with the dawn of immune-based therapies. There has been increased cross talk among radiation oncologists, oncologists and immunologists and consequently a surge in the number of prospective clinical trials. This must be coupled with translation work from these clinical trials to aid in eventual identification of patients who may benefit. Abscopal effects may be induced by local and systemic methods, conventional radiotherapy, particle radiation, radionucleotide methods, cryoablation and brachytherapy. These approaches have all been reported to be stimulate abscopal effect. Immune induction by immune checkpoint therapy, immune adjuvants, cellular therapy including CAR and NK cell therapies may generate systemic abscopal response. With increasing recognition of this effect, there remains a lot of work to explore the modalities of inducing abscopal responses and ultimate prediction or prognostication on stratifying who may benefit. Ultimately, there is an urgent need for prospective studies and data to tease apart which one of these modalities can be applied to the appropriate candidate, to the appropriate cancer at the appropriate setting. This review seeks to elucidate readers on the different modalities of radiation, systemic therapies and other techniques rarely explored to potentiate the abscopal effect from a mere coincidence to a finite occurrence.

An Updated Review of Subglottic Stenosis: Etiology, Evaluation, and Management.

Purpose of ReviewTo assimilate the newly published literature regarding subglottic stenosis (SGS), including basic science and translational research on mechanisms of etiology, clinical diagnostics, and therapeutic treatments.Recent FindingsThe role of inflammation in development of iatrogenic and idiopathic SGS (iSGS) is continuing to be studied. The IL-23/IL-17A inflammatory axis appears to be a potential mechanism for development of iSGS. Additionally, as anticipated in an inflammatory milieu, PD-1/PD-L1 expression is upregulated. If the PD-1/PD-L1 axis is important in SGS pathogenesis, then it may represent a potential target for immunotherapeutic inhibition, given its success in cancer treatment. In terms of surgical management, prospective studies show that endoscopic approaches have more frequent recurrence compared to open techniques.SummarySGS arises from various etiologies, and further understanding of its pathogenesis can aid in the development of novel therapies. It is imperative to obtain a thorough history for each patient presenting with respiratory complaints, as misdiagnosis can delay proper treatment. Endoscopic and open surgical techniques continue to be investigated in a growing number of prospective clinical trials to determine optimal treatment protocols. In-office injections are gaining popularity and show promise in the treatment of SGS.

SS-1 Therapeutic challenges for glioblastoma: Temozolomide and its issues?

Glioblastoma (GBM), the most malignant form (WHO grade IV) of gliomas, remains incurable despite recent advances in medical technologies and molecular knowledge, with 5-year survival rate being just beyond 10%, thus undoubtedly leaving unmet needs to develop effective therapeutics to improve outcome. Current standard of care for patients with newly diagnosed GBM is maximum safe resection of the enhancing tumor bulk, followed by involved-field radiotherapy with temozolomide (TMZ) given concomitantly and as an adjuvant therapy thereof with or without Tumor-Treating Fields (TTF). The efficacy of TMZ for GBM was proved in 2005 by a randomized phase III trial (EORTC25981) for the first time ever in history, since then, however, any other agents have failed to show benefit to improve survival until now. O6-methylguanine-DNA methyltransferase (MGMT), a specific DNA repair enzyme, has been shown to restore the cytotoxic O6-methylguanine lesion induced by TMZ to normal, responsible for a major reason of TMZ resistance. Expression of MGMT is tightly regulated by methylation of the promoter region of the MGMT gene, where promoter methylation results in suppression of its expression. Accordingly, the promoter methylation of the MGMT gene (meth-MGMT) has been consistently associated with a better response to and outcome by TMZ treatment, and furthermore a favorable prognostic factor for patients with newly diagnosed GBM in a number of prospective clinical trials. In this line, efforts have been made to overcome TMZ resistance including intensifying dose schedulings of TMZ, one of which has been currently tested in a multi-institutional prospective phase III trial in Japan (JCOG1308C). TMZ has also been investigated in lower grade gliomas. A major issue in treating lower grade glioma with TMZ is potential development of the hypermutated tumors by virtue of O6-methylguanine-induced mutagenesis. The clinical and molecular consideration related to TMZ in glioma treatment will be presented.

Abstract 1117: XenoSarc: Patient-derived xenograft (PDX) models of soft tissue sarcoma (STS) and their histopathological and molecular characterization

Abstract Background: STS constitutes a rare family of mesenchymal tumors with more than 70 subtypes classified by WHO (2013). The limited treatment options available for advanced STS underline the need for reliable preclinical models, especially from ultra-rare subtypes, to test novel therapeutic strategies. Methods: A panel of PDX models was established by subcutaneous implantation of fresh tumor specimens in immunodeficient, athymic nude NMRI mice. Once tumor growth was observed, pieces of tumor were re-transplanted to next generations of mice. At each passage tumor fragments were collected for histopathological and molecular characterization. A model was considered “established” after observing stable histological and molecular features for at least two passages. Furthermore, ex-mouse tumor tissue samples were stored, further characterized by immunocytology and flow cytometry and cultured to be used for in vitro drug testing. Results: Between September 2011 and November 2019, 375 STS samples from 325 consenting patients treated at the University Hospitals, Leuven, Belgium have been transplanted. A total of 56 PDX models were established, maintaining the histopathological and molecular features of the original tumor. Detailed clinical information about the donor patient and tumor characteristics (including sensitivity to standard and experimental agents), is known for every model. At present the XenoSarc platform includes ready to use models of dedifferentiated liposarcoma (11 models), gastrointestinal stromal tumor (8), myxofibrosarcoma (8), leiomyosarcoma (7), malignant peripheral nerve sheath tumor (3), synovial sarcoma (2), pulmonary artery intimal sarcoma (2), epithelioid hemangioendothelioma (1), mesenchymal chondrosarcoma (1), pleomorphic rhabdomyosarcoma (1), CIC-rearranged round cell sarcoma (1), myxoinflammatory fibroblastic sarcoma (1), rhabdomyosarcoma not otherwise specified (NOS) (1), telangiectatic extraskeletal osteosarcoma (1), extraskeletal osteosarcoma (1) and high-grade undifferentiated pleomorphic sarcoma (7). These models are well-characterized, including molecular information on copy number changes (by low-coverage whole genome sequencing), gene expression profile (by RNA-Seq) and targeted sequencing to detect mutations in genes involved in tumorigenesis. In addition, we have constructed tissue microarrays (TMA) from the xenografts which are used for target identification and model selection for preclinical studies. We are using the xenografts for in vivo testing of novel agents, including targeted and cytotoxic (pro-)drugs, and results already served as rationale for a number of prospective clinical trials. A total of 27 other xenografts are still in early stages of engraftment, not yet fulfilling our criteria of an “established” model. Conclusion: The XenoSarc platform offers a lot of opportunities for studying the biology of a variety of important sarcoma subtypes including ultra-rare entities, and has proven efficiency for early drug screening in STS in preparation of clinical testing of novel compounds. The platform is well maintained and continuously expanded, and available to collaborators from academia and industry. Citation Format: Agnieszka Wozniak, Britt Van Renterghem, Jasmien Cornillie, Yannick Wang, Che-Jui Lee, Jasmien Wellens, Ulla Vanleeuw, Madita Nysen, Daphne Hompes, Friedl Sinnaeve, Hazem Wafa, Baki Topal, Tom Verbelen, Maria Debiec-Rychter, Raf Sciot, Patrick Schöffski. XenoSarc: Patient-derived xenograft (PDX) models of soft tissue sarcoma (STS) and their histopathological and molecular characterization [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1117.

Proton therapy and the European Particle Therapy Network: The past, present and future

Proton therapy is delivered to selected cancer patients presenting with rare tumours, for which a dose escalation paradigm and/or a reduced dose-bath to the organs at risk is pursued. It is a costly treatment with an additional cost factor of 2–3 when compared to photon radiotherapy. Notwithstanding the 180′000 patients treated with protons, scars robust clinical evidence is available to justify the administration of this treatment modality. The European Particle Therapy Network (EPTN) was created in 2015 to answer the critical European needs for cooperation among protons and carbon ions centres in the framework of clinical research networks. EPTN with other European groups will launch a number of prospective clinical trials that could be practice changing if positive. Alternative way to generate clinical data could be provided by alternative methodologies, such as the Dutch model-based approach, or could be provided by European infrastructure projects.

Strategies to Prevent Cardiotoxicity.

Cardiovascular disease is a leading cause of death among cancer survivors. While the field of cardiology as a whole is driven by evidence generated through robust clinical trials, data in cardio-oncology is limited to a relatively small number of prospective clinical trials with heterogeneous groups of cancer patients. In addition, many pharmaceutical trials in oncology are flawed from a cardiovascular perspective because they exclude patients with significant cardiovascular (CV) history and have wide variation in the definitions of CV events and cardiotoxicity. Ultimately, oncology trials often underrepresent the possibility of cardiovascular events in a "real world" population. Thus, the signal for CV toxicity from a cancer treatment is often not manifested until phase IV studies; where we are often caught trying to mitigate the CV effects rather than preventing them. Most of the data about cardiotoxicity from cancer therapy and cardioprotective strategies has been developed from our experience in using anthracyclines for over 50years with dramatic improvement in cancer survivorship. However, as we are in an era where cancer drug discovery is moving at lightning pace with increasing survival rates, it is imperative to move beyond anthracyclines and commit to research on the cardiovascular side effects of all aspects of cancer therapy with a focus on prevention. We emphasize the role of pre-cancer treatment CV assessment to anticipate cardiac issues and ultimately optimizing CV risk prior to cancer therapy as an opportunity to mitigate cardiovascular risk from cancer therapy.

CXCR4 mutational status does not impact outcomes in patients with Waldenström macroglobulinemia treated with proteasome inhibitors.

CXCR4 mutational status does not impact outcomes in patients with Waldenström macroglobulinemia treated with proteasome inhibitors.

XenoSarc: A comprehensive platform of patient-derived xenograft (PDX) models of soft tissue sarcoma (STS) for early drug testing.

37 Background: STS is a family of rare, heterogeneous tumors with &gt; 70 subtypes. There is an urgent need for reliable preclinical models, especially for orphan subtypes of STS, given the limited treatment options. Methods: A panel of PDX models was established by s.c. implantation of fresh tumor specimens in athymic NMRI mice. Growing pieces of tumor were re-transplanted to next generations of mice. At each passage fragments were collected for histological/molecular characterization. A model was considered “established” after observing stable features for at least 2 passages. Ex-mouse tissue samples were stored, characterized by immunohistochemistry/flow cytometry and used for in vitro drug testing. Results: Between 2011-2019, 329 samples from 301 consenting patients were transplanted; 56 models are established, 16 additional models are in early passaging. Clinical information about donor and tumor (including sensitivity to standard and experimental agents) is available. The platform includes models of dedifferentiated lipo- (10 models), myxofibro- (8), leiomyo- (7), synovial (2), intimal (2), CIC-positive round cell (1), mesenchymal chondro- (1), extraskeletal osteo- (1), myxoid lipo- (1), myxoinflammatory fibroblastic (1), rhabdomyo- (2) and high-grade undifferentiated pleomorphic sarcoma (7), as well as GIST (8), MPNST (4) and epithelioid hemangioendothelioma (1). Models are well-characterized, with molecular information on copy number changes (low-coverage whole genome sequencing) and gene expression profile (RNA-Seq) available. We also constructed tissue microarrays from the xenografts which are used for target identification and model selection for preclinical studies. Xenografts are available for in vivo testing of novel agents, and results already served as a rationale for a number of prospective clinical trials. Conclusions: XenoSarc offers opportunities for studying the biology of a variety of sarcoma subtypes including ultra-rare entities and is a valuable tool for early drug screening in preparation of clinical STS trials. The platform is well maintained and continuously expanded, and available to collaborators from academia and industry.

The Diagnosis and Treatment of Primary CNS Lymphoma.

Primary central nervous system lymphoma is a diffuse large B-celllymphoma with exclusive manifestation in the central nervous system (CNS), leptomeninges, and eyes. Its incidence is 0.5 per 100 000 persons per year.Currently, no evidence-based standard of care exists. This review is based on pertinent publications (2000-2017) retrieved by aselective search in PubMed. The clinical and neuroradiological presentation of primary CNS lymphoma isoften nonspecific, and histopathological confirmation is obligatory. The disease, if left un- treated, leads to death within weeks or months. If the patient's general condition permits, treatment should consist of a high-dose chemotherapy based on methotrexate (HD- MTX) combined with rituximab and other cytostatic drugs that penetrate the blood-brain barrier. Long-term survival can be achieved in patients under age 70 by adding non- myeloablative consolidation chemotherapy or high-dose chemotherapy with autologous stem cell transplantation (HD-AST) to the induction therapy. Clinical trials comparing the efficacy and toxicity of these two treatment strategies are currently underway. Con- solidation whole-brain radiotherapy is associated with the risk of severe neurotoxicity and should be reserved for patients who do not qualify for systemic treatment. Some 30% of patients are refractory to primary treatment, and at least 50% relapse. In patients who are still in good general condition, relapse can be managed with HD-AST. Re- exposure to conventional HD-MTX-based polychemotherapy is another option, if the initial response was durable. The 5-year survival rate of all treated patients is 31%,according to registry data. Current recommendations for the treatment of primary CNS lymphomaare based on only a small number of prospective clinical trials. Patients with this disease should be treated by interdisciplinary teams in experienced centers, andpreferably as part of a controlled trial.

The clinical Outcome of One-stage High Tibial Osteotomy and Anterior Cruciate Ligament Reconstruction. A Current Concept Systematic and Comprehensive Review.

Patients with an anterior cruciate ligament-deficient varus-angulated knee may need not only an isolated high tibial osteotomy (HTO), but also an additional anterior cruciate ligament reconstruction (ACLR). A number of prospective clinical trials have been published considering the combination of HTO and ACL reconstruction. Our aim was to investigate whether one-stage combined HTO and ACL reconstruction is an effective, well-established technique with long-term results in the treatment of varus-angulated knees with ACL deficiency. A systematic review was conducted by two independent reviewers by searching the MEDLINE/PubMed and the Cochrane Database of Systematic Reviews. These databases were queried with the term 'combined high tibial osteotomy anterior cruciate ligament reconstruction' and 'simultaneous high tibial osteotomy anterior cruciate ligament reconstruction'. From the initial 41 studies we finally chose and assessed 6 studies were eligible according to our inclusion-exclusion criteria. The vast majority of the patients were treated with hamstrings autograft (85.6% of the patients), whereas a small minority had a patellar Bone-to-Bone autograft (12.8% of the patients) and 3 patients received a patellar allograft. High tibial open wedge osteotomy was performed in 116 patients (57.4%) and closed wedge in 86 patients (42.6%). The mean pre-operative angle of the patients included in our review was 6.6º varus, while the mean final post-operative angle was found to be 1.3º valgus. All 6 studies illustrated improved post-operative IKDC with the use of one-stage HTO and ACLR, whereas the reoperation rate was very low. Despite the lack of high quality studies, it seems that one-stage HTO and ACLR is a safe and effective procedure for treatment of patients suffering from symptomatic varus osteoarthritis in combination with anterior knee instability.

Complete response after chemoradiotherapy for rectal cancer: what is the reasonable approach?

With the increasing use of preoperative treatment rather than upfront surgery, it has become evident that the response of rectal carcinoma to standard chemoradiotherapy (CRT) shows a great variety that includes histopathologiocally confirmed complete tumor regression in 10–30% of cases. Adaptive strategies to avoid radical surgery, either by local excision or non-operative management, have been proposed in these highly responsive tumors. A growing number of prospective clinical trials and experiences from large databases, such as the European Registration of Cancer Care (EURECCA) watch-and-wait database, or the recent Oncological Outcome after Clinical Complete Response in Patients with Rectal Cancer (OnCoRe) project, will provide more information on its safety and efficacy, and help to select appropriate patients. Future studies will have to establish appropriate inclusion criteria and optimize CRT regimens in order to maximize the number of patients achieving complete response. Standardized re-staging procedures have to be investigated to improve the prediction of a sustained complete response, and long-term close follow-up with thorough documentation of failure patterns and salvage therapies will have to prove the oncological safety of this approach.

Coronary Artery Chronic Total Occlusion

Coronary artery chronic total occlusion (CTO) is defined as an occluded coronary artery segment without anterograde flow for at least three months. It can be classified as a “true” or “functional” CTO based on flow characteristics. In “true” CTO, there is no anterograde flow. In “functional” CTO, there is minimal anterograde flow through the occluded segment of the coronary artery. CTO is a common finding during coronary angiography and its prevalence may vary depending on the reported literature. Among patients without previous coronary artery bypass grafting (CABG), CTO is found in about 20–30% of the patients. CTO may develop insidiously over a period of time and involve a complex interplay between intracellular and extracellular factors, smooth muscle and foam cells, calcification, and neovascularization. There is a growing body of evidence to support that CTO revascularization may improve clinical outcome when compared to medical management. Both the European and American cardiovascular societies support CTO revascularization with a class 2a recommendation (level of evidence B). Historically, due to low procedural success rate, apparent inefficient resource utilization, potential increase in complication rates and uncertain clinical benefits, only about 10–20% of patients with CTO are treated with percutaneous coronary intervention (PCI). Recent advances using novel and innovative techniques with dedicated equipment have significantly improved the procedural success rate for CTO PCI to about 90% in the hands of experienced operators. With increasing interest in CTO PCI coupled with increased educational effort, CTO PCI likely will become more accessible to patients in need of CTO revascularization. Ongoing advancement in innovative techniques and equipment will continue to improve procedural success rates and reduce procedural complication rate for CTO PCI. Furthermore, there are a number of prospective clinical trials on the horizon which should help define the clinical benefits and limitations of CTO PCI in the near future.

Management of Neovascular Age-related Macular Degeneration: A Review on Landmark Randomized Controlled Trials.

In the last decade, a number of prospective clinical trials with carefully designed study protocols have been conducted for the treatment of neovascular age-related macular degeneration (AMD). These landmark clinical trials such as ANCHOR and MARINA and, more recently, the Comparison of AMD Treatment Trials and VIEW studies have revolutionized the management of neovascular AMD. While AMD continues to remain a leading cause of severe visual loss worldwide, advances in pharmacotherapeutics have led to substantial improvements in the outcome of these patients. The introduction of anti-vascular endothelial growth factor agents has resulted in improvement of visual outcomes and has had a positive impact on the quality of life among elderly population. While the contemporary management of neovascular AMD has been successful in tremendously reducing the visual morbidity, the financial burden of therapy has increased exponentially. To overcome these challenges, newer pharmacologic agents are evaluated for their efficacy and safety in AMD. Ground-breaking advances in bench to bedside research have led to discovery of new pathways that appear to be viable targets for preventing visual loss in AMD. In this review, study designs and results of landmark clinical trials in AMD from the past decade have been summarized.

Peripheral Nerve Stimulation: Advances in the Field

The prevalence of chronic pain is increasing in the United States. Fortunately, a growing body of evidence continues to enhance our understanding of pain pathways and provide new avenues for clinical treatment of pharmacologic-resistant pain disorders. Specifically, the field of neurostimulation is garnering momentum with peripheral nerve stimulation (PNS) being one of the largest areas of interest over the last decade. PNS potentially offers clinicians an alternative treatment modality when conventional management options fail. The current body of literature is dominated by case series and reports; however, there is an increasing number of prospective clinical trials being conducted in recent years. As applications continue to expand, further evaluation of its utility, efficacy, and safety is needed.

Evolving clinical evidence for selective internal radiation therapy in hepatocellular carcinoma

*Correspondence: Professor Pierce Chow MBBS MMed, FAMS, FRCSE, PhD, DukeNUS Graduate Medical School, 8 College Road, Singapore 169857. Tel: +65 6326 6450; fax: +65 6220 9323. E-mail address: pierce.chow@duke-nus.edu.sg (P. Chow); Prof. Dr. J. Ricke, Direktor, Klinik fur Radiologie und Nuklearmedizin, Universitatsklinikum Magdeburg AoR, Leipziger Strasse 44, 39120 Magdeburg, Germany. Tel.: +39 1 67 13030. E-mail address: Jens.ricke@med.ovgu.de (J. Ricke). Professor V. Vilgrain, Radiologie, Hopital Beaujon, 100, boulevard du General Leclerc, Clichy Cedex 9211, France. E-mail address: valerie.vilgrain@bjn.aphp.fr (V. Vilgrain). treatment. 2 However, for patients with inoperable local disease, both sorafenib and locoregional treatments are recommended in the absence of a recognised firstline treatment. 2 The current evidence indicates that for patients with intermediate (BCLC stage B) HCC, median overall survival is ~14 months with sorafenib 3,4 (level 1 evidence) and ~17 months with the locoregional treatment, selective internal radiation therapy (SIRT) (level 2 evidence). 5,6 In the light of the encouraging data with SIRT in inoperable HCC, a number of prospective clinical trials are currently being conducted both in the Asia-Pacific as well as in Europe. The results of these trials will define the role of SIRT in the management of HCC.

Gemcitabine for the treatment of advanced nonsmall cell lung cancer

Gemcitabine is a pyrimidine nucleoside antimetabolite agent which is active in several human malignancies, including nonsmall cell lung cancer (NSCLC). Because of its acceptable toxicity profile, with myelosuppression being the most common adverse event, gemcitabine can be safely combined with a number of cytotoxic agents, including platinum derivatives and new-generation anticancer compounds. In fact, the combination of gemcitabine and cisplatin is a first-line treatment for patients with advanced NSCLC, pharmacoeconomic data indicating that it represents the most cost-effective regimen among platinum-based combinations with third-generation cytotoxic drugs. The drug has been investigated in the context of nonplatinum-based regimens in a number of prospective clinical trials, and might provide a suitable alternative for patients with contraindications to platinum. Recently, gemcitabine-based doublets have been successfully tested in association with novel targeted agents with encouraging results, providing further evidence for the role of the drug in the treatment of NSCLC. In the last few years several attempts have been pursued in order to identify molecular predictors of gemcitabine activity, and recent data support the feasibility of genomic-based approaches to customize treatment with the ultimate goal of improving patient outcome.

Computer-aided diagnosis in breast tomosynthesis and chest CT.

Computer-aided diagnosis (CAD), in the general sense, includes computer-aided detection and characterization of abnormalities on medical images. The usefulness of CAD for assisting radiologists in detection of breast cancer in screening mammography has been demonstrated by a number of prospective clinical trials in recent years. The development of CAD in other areas is also being actively pursued by researchers. In this talk, the recent work in two areas of CAD, digital breast tomosynthesis (DBT) and chest computed tomography (CT), in the CAD Research Laboratory at the University of Michigan will be reviewed. DBT is a new modality under development for breast imaging. The quasi-3D information in DBT alleviates the problem of overlapping tissue in mammography and holds the promise to improve the sensitivity for cancer detection. DBT image analysis can be performed in the 3D reconstructed volume of the 2D projection view (PV) images. DBT image quality depend on the image acquisition parameters, reconstruction method and parameters. The flexibility in image processing approaches makes CAD development for DBT interesting and challenging. out early experiences in the development of image segmentation and features extraction technique for mass detection and characterization in DBT will be discussed. The performances of the CAD systems using the 2D, 3D, and combined 2D and 3D approaches will be compared. CT has been shown to be superior to chest x-ray in detection of small lung nodules and thus lung cancer screening with CT is still being debated, many research groups are developing CAD methods for detection and characterization of lung nodules in chest CT scans. The specific prescreening, segmentation, and feature extraction techniques designed for our lung nodule detection and characterization systems will be discussed. The effects of CAD on radiologists' accuracy in nodules detection and characterization in CT scans will be demonstrated by results of observer ROC studies. There are similarities in the approaches to developing CAD methods in 3D image volumes such as DBT and CT, these experiences will facilitate the development of CAD systems for other diseases in 3D modalities.

Gait analysis methods in rehabilitation.

IntroductionBrand's four reasons for clinical tests and his analysis of the characteristics of valid biomechanical tests for use in orthopaedics are taken as a basis for determining what methodologies are required for gait analysis in a clinical rehabilitation context.Measurement methods in clinical gait analysisThe state of the art of optical systems capable of measuring the positions of retro-reflective markers placed on the skin is sufficiently advanced that they are probably no longer a significant source of error in clinical gait analysis. Determining the anthropometry of the subject and compensating for soft tissue movement in relation to the under-lying bones are now the principal problems. Techniques for using functional tests to determine joint centres and axes of rotation are starting to be used successfully. Probably the last great challenge for optical systems is in using computational techniques to compensate for soft tissue measurements. In the long term future it is possible that direct imaging of bones and joints in three dimensions (using MRI or fluoroscopy) may replace marker based systems.Methods for interpreting gait analysis dataThere is still not an accepted general theory of why we walk the way we do. In the absence of this, many explanations of walking address the mechanisms by which specific movements are achieved by particular muscles. A whole new methodology is developing to determine the functions of individual muscles. This needs further development and validation. A particular requirement is for subject specific models incorporating 3-dimensional imaging data of the musculo-skeletal anatomy with kinematic and kinetic data.Methods for understanding the effects of interventionClinical gait analysis is extremely limited if it does not allow clinicians to choose between alternative possible interventions or to predict outcomes. This can be achieved either by rigorously planned clinical trials or using theoretical models. The evidence base is generally poor partly because of the limited number of prospective clinical trials that have been completed and more such studies are essential. Very recent work has started to show the potential of using models of the mechanisms by which people with pathology walk in order to simulate different potential interventions. The development of these models offers considerable promise for new clinical applications of gait analysis.